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Environmental and Workplace Health

Second Report on Human Biomonitoring of Environmental Chemicals in Canada

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Results of the Canadian Health Measures Survey Cycle 2 (2009-2011)

April 2013

ERRATUM

8.4 Cesium

Tables 8.4.1 - 8.4.4
Data in these tables have been updated. Original data published in the PDF version of this report erroneously included 84 cases of non-response that have now been removed.

16.1 Overview

Table 16.1.1
9-Hydroxyfluorene 1689-64-1
3-Hydroxyfluoranthene 17798-09-3
1-Hydroxyphenanthrene 2433-56-9

Appendix B - Limits of Detection

Metals and Trace Elements in Blood
Zinc 0.0007 mg/L 0.1 mg/L

Appendix C - Conversion Factors

Adjustment Factor
a Creatinine CF from mg/dL→μmol/L

Table of Contents

1 Introduction

This Second Report on Human Biomonitoring of Environmental Chemicals in Canada presents national data on concentrations of environmental chemicals in Canadians. These data were collected as part of the Canadian Health Measures Survey (CHMS), an ongoing national direct health measures survey. Statistics Canada, in partnership with Health Canada and the Public Health Agency of Canada, launched the CHMS in 2007 to collect health and wellness data and biological specimens on a nationally representative sample of Canadians. Biological specimens were analyzed for indicators of health status, chronic and infectious diseases, nutritional status and environmental chemicals.

The CHMS biomonitoring component measures many environmental chemicals and/or their metabolites in blood and urine of survey participants. For the purposes of this report, an environmental chemical is defined as a chemical substance, either human-made or natural, that is present in the environment and to which humans may be exposed through media such as air, water, food, soil, dust, or consumer products.

The first Report on Human Biomonitoring of Environmental Chemicals in Canada was published in August 2010 and included baseline data for 80 environmental chemicals measured in cycle 1 (Health Canada, 2010). Data for cycle 1 of the CHMS were collected between March 2007 and February 2009 from approximately 5,600 Canadians aged 6 to 79 years at 15 sites across Canada.

The second report contains data from cycle 2 collected between August 2009 and November 2011 from approximately 6,400 Canadians aged 3 to 79 years at 18 sites across Canada. Cycle 2 includes 91 environmental chemicals of which 42 were also measured in cycle 1. A summary of the environmental chemicals measured in cycle 1 and cycle 2 of the CHMS is presented in Table 1.1. For a detailed list of the environmental chemicals measured in cycle 2, see Table 3.4.1.

Table 1.1 Summary of chemicals measured in cycle 1 (2007-2009) and cycle 2 (2009-2011) of the Canadian Health Measures Survey.
Chemicals Cycle 1
(2007-2009)
Cycle 2
(2009-2011)
Organochlorines Yes No
Polybrominated flame retardants Yes No
Polychlorinated biphenyls Yes No
Metals and trace elements Yes Yes
Chlorophenols Yes Yes
Environmental phenols and triclocarban Yes Yes
Nicotine metabolite Yes Yes
Perfluoroalkyl substances Yes Yes
Pesticides Yes Yes
Phthalate metabolites Yes Yes
Benzene metabolites  No Yes
Polycyclic aromatic hydrocarbon metabolites No Yes

Collection for cycle 3 of the CHMS began in January 2012 and will be completed in late 2013. Planning for future cycles is under way.

In this report, the general CHMS survey design and implementation are described, with emphasis on the biomonitoring component. These sections are followed by descriptive summaries for each chemical, outlining the chemical's identity, common uses, occurrence in the environment, potential sources of exposure in the human population, toxicokinetics in the body, health effects, regulatory status, and existing Canadian biomonitoring data.

Data tables specific to each chemical follow each summary; the tables are broken down by age group and sex, and contain descriptive statistics on the distribution of blood and/or urine concentrations in the sample population. For the 50 new environmental chemicals measured in cycle 2, tables present baseline data for the Canadian population. For chemicals that were measured in both cycle 1 and cycle 2, data from both cycles are presented together in tables to allow for ease of comparison. Data for chemicals that were only measured in cycle 1 (Table 1.1) can be found in the first Report on Human Biomonitoring of Environmental Chemicals in Canada (Health Canada, 2010).

References

Health Canada. (2010). Report on Human Biomonitoring of Environmental Chemicals in Canada: Results of the Canadian Health Measures Survey Cycle 1 (2007-2009). Minister of Health, Ottawa, ON. Retrieved September 1, 2011, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/chms-ecms/index-eng.php

2 Objectives

The primary purpose of the Second Report on Human Biomonitoring of Environmental Chemicals in Canada is to provide human biomonitoring data to scientists and health and environment officials to aid in assessing exposure to environmental chemicals and in developing policies to reduce exposure to toxic chemicals for the protection of the health of Canadians.

Some specific uses of the information presented in this report include the following:

  • to establish baseline concentrations of chemicals in Canadians that could allow for comparisons with subpopulations in Canada and with other countries;
  • to establish baseline concentrations of chemicals to track trends in Canadians over time;
  • to provide information for setting priorities and taking action to protect the health of Canadians and to protect Canadians from exposure to environmental chemicals;
  • to assess the effectiveness of health and environmental risk management actions intended to reduce exposures and health risks from specific chemicals;
  • to support future research on the potential links between exposure to certain chemicals and specific health effects; and
  • to contribute to international monitoring programs, such as the Stockholm Convention on Persistent Organic Pollutants.

3 Survey Design

The Canadian Health Measures Survey (CHMS) was designed as a cross-sectional survey to address important data gaps and limitations in existing health information in Canada. Its principal objective is to collect national-level baseline data on important indicators of Canadians' health status, including those pertaining to exposures to environmental chemicals. This information is important in understanding exposure to risk factors, detecting emerging trends in risk factors and exposures, and advancing health surveillance and research in Canada. Detailed descriptions of the CHMS rationale, survey design, sampling strategy, mobile examination centre (MEC) operations and logistics, as well as ethical, legal, and social issues for cycle 2, have been published previously (Giroux et al., 2013; Statistics Canada, 2013).

3.1 Target Population

Cycle 2 of the CHMS targets the population aged 3 to 79 years living at home and residing in the 10 provinces and three territories. People living on reserves or in other Aboriginal settlements in the provinces, residents of institutions, full-time members of the Canadian Forces, persons living in certain remote areas, and persons living in areas with a low population density were excluded.

3.2 Sample Size and Allocation

To meet the objective of producing reliable estimates at the national level by age group and sex, cycle 2 of the CHMS required a minimum sample of at least 5,700 participants. The participants were distributed among six age groups (3-5, 6-11, 12-19, 20-39, 40-59, and 60-79 years) and sex (except for 3-5 years), for a total of 11 groups. For the 3 to 5 year old age group, the survey was not designed to provide estimates for the individual sexes.

3.3 Sampling Strategy

To meet the requirements of the CHMS, a multi-stage sampling strategy was used.

3.3.1 Sampling of Collection Sites

The CHMS required participants to report to a mobile examination centre and be able to travel to the centre within a reasonable period of time. The Canadian Labour Force Survey sampling frame (Statistics Canada, 2008) was used to create 257 collection sites across the country. A geographic area with a population of at least 10,000 and a maximum participant travel distance of 100 kilometres (50 kilometres in urban areas and 100 kilometres in rural areas) were required for the location of collection sites. Areas not meeting these criteria were excluded. Nonetheless, the CHMS covers 96.3% of the Canadian population aged 3 to 79 years (Statistics Canada, 2013).

A larger number of collection sites would have optimized the precision of the estimates. However, the logistical and cost constraints associated with the use of MECs restricted the number of collection sites to 18. The 18 collection sites were selected from within the five standard regional boundaries used by Statistics Canada (Atlantic, Quebec, Ontario, Prairies [including Yellowknife], and British Columbia [including Whitehorse]); they were allocated to these regions in proportion to the size of the population. Although not every province and territory in Canada had a collection site, the CHMS sites were chosen to represent the Canadian population, east to west, including larger and smaller population densities. The collection sites selected for cycle 2 of the CHMS are listed in Table 3.3.1.1.

Table 3.3.1.1 Canadian Health Measures Survey cycle 2 (2009-2011) collection sites
Atlantic Quebec Ontario Prairies British Columbia
  • St. John's, N.L.
  • Colchester and Pictou Counties, N.S.
  • Laval
  • South Montérégie
  • Gaspésie
  • North Shore Montréal
  • Central and East Ottawa
  • South of Brantford
  • Southwest Toronto
  • East Toronto
  • Kingston
  • Oakville
  • Edmonton, Alta.
  • Winnipeg, Man.
  • Calgary, Alta.
  • Richmond
  • Central and East Kootenay
  • Coquitlam

3.3.2 Dwelling and Participant Sampling

The 2006 Canadian Census was used as the frame to select dwellings. Within each site, dwellings with known household composition at the time of the 2006 Census, updated with the most recent information from administrative files, were stratified by age of household residents at the time of the survey, with the six age-group strata corresponding to the CHMS cycle 2 age groups (3-5, 6-11, 12-19, 20-39, 40-59, 60-79 years). Within each site, a simple random sample of dwellings was selected in each stratum. Each selected dwelling was then contacted and asked to provide a list of current household members; this list was used to select the survey participants. One or two people were selected, depending on the household composition.

3.4 Selection of Environmental Chemicals

To determine the list of environmental chemicals to be included in cycle 2 of the CHMS, a national consultation process was initiated by Health Canada from May to June 2008. The primary mechanism of consultation was through a questionnaire distributed to key participants with expertise or interest in human biomonitoring of environmental chemicals; the purpose was to define specifically what should be measured in blood and urine samples in cycle 2 in the Canadian population. Key participants included various internal Health Canada branches and programs as well as a number of external groups, including other federal departments, provincial/territorial health and environment departments, industry groups, environment and health non-governmental organizations, and academics. Through this consultation, over 310 different chemicals and metabolites were nominated.

Selection was based on health risks; evidence of human exposure; existing data gaps; commitments under national and international treaties, conventions, and agreements; availability of standard laboratory analytical methods; and current and anticipated health policy development and implementations.

The following criteria were used as a general guide for identifying and selecting the environmental chemicals to include in the CHMS:

  • seriousness of known or suspected health effects related to the substance;
  • need for public health actions related to the substance;
  • level of public concern about exposures and possible health effects related to the substance;
  • evidence of exposure of the Canadian population to the substance;
  • feasibility of collecting biological specimens in a national survey and associated burden on survey participants;
  • availability and efficiency of laboratory analytical methods;
  • costs of performing the test; and
  • parity of selected chemicals with other national and international surveys and studies.

In addition, environmental chemicals from cycle 1 considered to be high priorities were carried forward into cycle 2. Ultimately, the list was narrowed by the volume of biospecimens available from survey participants to conduct the analyses. Blood volume is generally limited, and it is also required for analyses of chronic and infectious diseases and nutritional biomarkers. Thus, fewer environmental chemicals were measured in blood than in urine.

Some analytes were measured because the analytical method used, such as that used for the metals, provided results for additional chemicals with little or no additional biospecimen volume and cost; these included essential nutrients such as copper, molybdenum, selenium, and zinc, all of which are required for maintenance of good health. A full list of the chemicals measured in CHMS cycle 2 is presented in Table 3.4.1.

Table 3.4.1 Chemicals measured in the Canadian Health Measures Survey cycle 2 (2009-2011) including those also measured in cycle 1 (2007-2009).
  Cycle 1
(2007-2009)
Cycle 2
(2009-2011)
Metals and trace elements
Antimony Yes Yes
Arsenic (total) Yes Yes
Cadmium Yes Yes
Copper Yes Yes
Lead Yes Yes
Mercury Yes Yes
Manganese Yes Yes
Molybdenum Yes Yes
Nickel Yes Yes
Selenium Yes Yes
Uranium Yes Yes
Vanadium Yes Yes
Zinc Yes Yes
Arsenic (speciated)
Arsenate No Yes
Arsenite No Yes
Arsenocholine and arsenobetaine No Yes
DMA (Dimethylarsinic acid) No Yes
MMA (Monomethylarsonic acid) No Yes
Cesium No Yes
Cobalt No Yes
Fluoride No Yes
Silver No Yes
Thallium No Yes
Tungsten No Yes
Chlorophenols
2,4-DCP (2,4-Dichlorophenol) Yes Yes
2,5-DCP (2,5-Dichlorophenol) No Yes
2,4,5-TCP (2,4,5-Trichlorophenol) No Yes
2,4,6-TCP (2,4,6-Trichlorophenol) No Yes
PCP (Pentachlorophenol) No Yes
Environmental phenols and triclocarban
Bisphenol A Yes Yes
Triclocarban No Yes
Triclosan No Yes
Nicotine metabolite
Cotinine Yes Yes
Perfluoroalkyl substances
PFHxS (Perfluorohexane sulfonate) Yes Yes
PFOA (Perfluorooctanoic acid) Yes Yes
PFOS (Perfluorooctane sulfonate) Yes Yes
PFBA (Perfluorobutanoic acid) No Yes
PFBS (Perfluorobutane sulfonate) No Yes
PFDA (Perfluorodecanoic acid) No Yes
PFHxA (Perfluorohexanoic acid) No Yes
PFNA (Perfluorononanoic acid) No Yes
PFUnDA (Perfluoroundecanoic acid) No Yes
Pesticides
2,4-D (2,4-Dichlorophenoxyacetic acid) Yes Yes
Organophosphate metabolites
DEDTP (Diethyldithiophosphate) Yes Yes
DEP (Diethylphosphate) Yes Yes
DETP (Diethylthiophosphate) Yes Yes
DMDTP (Dimethyldithiophosphate) Yes Yes
DMP (Dimethylphosphate) Yes Yes
DMTP (Dimethylthiophosphate Yes Yes
Pyrethroid metabolites
cis-DBCA (cis-3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid) Yes Yes
cis-DCCA (cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid) Yes Yes
trans-DCCA (trans- 3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid) Yes Yes
4-F-3-PBA (4-Fluoro-3-phenoxybenzoic acid) Yes Yes
3-PBA (3-Phenoxybenzoic acid) Yes Yes
Atrazine metabolites
AM (Atrazine mercapturate) No Yes
DEA (Desethylatrazine) No Yes
DACT (Diaminochlorotriazine) No Yes
Carbamate metabolites
Carbofuranphenol No Yes
2-Isopropoxyphenol No Yes
Phthalate metabolites
MBzP (Mono-benzyl phthalate) Yes Yes
MnBP (Mono-n-Butyl phthalate) Yes Yes
MCPP (Mono-3-carboxypropyl phthalate) Yes Yes
MCHP (Mono-cyclohexyl phthalate) Yes Yes
MEHP (Mono-2-ethylhexyl phthalate) Yes Yes
MEHHP (Mono-(2-ethyl-5-hydroxyhexyl) phthalate) Yes Yes
MEOHP (Mono-(2-ethyl-5-oxohexyl) phthalate) Yes Yes
MEP (Mono-ethyl phthalate) Yes Yes
MiNP (Mono-isononyl phthalate) Yes Yes
MMP (Mono-methyl phthalate) Yes Yes
MOP (Mono-n-Octyl phthalate) Yes Yes
MiBP (Mono-isobutyl phthalate) No Yes
Benzene metabolites
t,t-MA (trans,trans-Muconic acid) No Yes
Phenol No Yes
S-PMA (S-Phenylmercapturic acid) No Yes
PAH (polycyclic aromatic hydrocarbon) metabolites
Benzo[a]pyrene metabolite
3-HydroxyBenzo[a]pyrene No Yes
Chrysene metabolites
2-Hydroxychrysene No Yes
3-Hydroxychrysene No Yes
4-Hydroxychrysene No Yes
6-Hydroxychrysene No Yes
Fluoranthene metabolite
3-Hydroxyfluoranthene No Yes
Fluorene metabolites
2-Hydroxyfluorene No Yes
3-Hydroxyfluorene No Yes
9-Hydroxyfluorene No Yes
Naphthalene metabolites
1-Hydroxynaphthalene No Yes
2-Hydroxynaphthalene No Yes
Phenanthrene metabolites
1-Hydroxyphenanthrene No Yes
2-Hydroxyphenanthrene No Yes
3-Hydroxyphenanthrene No Yes
4-Hydroxyphenanthrene No Yes
9-Hydroxyphenanthrene No Yes
Pyrene metabolite
1-Hydroxypyrene No Yes

Owing to the high cost of laboratory analyses, some environmental chemicals were not measured for all CHMS participants. Two subsamples were selected for environmental chemicals: one to measure perfluoroalkyl substances in plasma among 12 to 79 year olds and one to measure several environmental chemicals in urine among 3 to 79 year olds (Table 3.4.2). Further details on the subsampling for environmental chemicals are available in Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 2 (Statistics Canada, 2013) and in Giroux et al.'s sampling strategy overview (Giroux et al., 2013).

Table 3.4.2 Environmental chemicals measured by age group
Measure Matrix Target sample size Age (years)
3-5 6-11 12-19 20-39 40-59 60-79
Metals and trace elements Urine, blood 5,700 Yes Yes Yes Yes Yes Yes
Arsenic (speciated) Urine 2,500 Yes Yes Yes Yes Yes Yes
Fluoride Urine 2,500 Yes Yes Yes Yes Yes Yes
Benzene metabolites Urine 2,500 Yes Yes Yes Yes Yes Yes
Chlorophenols Urine 2,500 Yes Yes Yes Yes Yes Yes
Environmental phenols and triclocarban Urine 2,500 Yes Yes Yes Yes Yes Yes
Nicotine metabolite Urine 5,700 Yes Yes Yes Yes Yes Yes
Perfluoroalkyl substances Plasma 1,500 No No Yes Yes Yes Yes
Atrazine metabolites Urine 2,500 Yes Yes Yes Yes Yes Yes
Carbamate metabolites Urine 2,500 Yes Yes Yes Yes Yes Yes
2,4-D Urine 2,500 Yes Yes Yes Yes Yes Yes
Organophosphate metabolites Urine 2,500 Yes Yes Yes Yes Yes Yes
Pyrethroid metabolites Urine 2,500 Yes Yes Yes Yes Yes Yes
Phthalate metabolites Urine 2,500 Yes Yes Yes Yes Yes Yes
PAH metabolites Urine 2,500 Yes Yes Yes Yes Yes Yes

3.5 Ethical Considerations

Personal information collected through the CHMS is protected under the federal Statistics Act (Canada, 1970-71-72). Under the Act, Statistics Canada is obliged to safeguard and to keep in trust the information it obtains from the Canadian public. Consequently, Statistics Canada has established a comprehensive framework of policies, procedures, and practices to protect confidential information against loss, theft, unauthorized access, disclosure, copying, or use; this includes physical, organizational, and technological measures. The steps taken by Statistics Canada to safeguard the information collected in the CHMS have been described previously (Day et al., 2007).

Ethics approval for all components of the CHMS was obtained from Health Canada's Research Ethics Board. Informed written consent for the MEC portion of the CHMS was obtained from participants older than 14 years of age. For younger children, a parent or legal guardian provided written consent, and the child provided assent. Participation in this survey was voluntary, and participants could opt out of any part of the survey at any time.

A strategy was developed to communicate results to survey participants with the advice and expert opinion of the CHMS Laboratory Advisory Committee, the Physician Advisory Committee, l'Institut national de santé publique du Québec (the reference laboratory performing the environmental chemical analyses), and Health Canada's Research Ethics Board (Day et al., 2007). For the environmental chemicals, only results for lead, mercury, cadmium, and fluoride were actively reported to participants. However, participants could receive all other test results upon request to Statistics Canada. More information on reporting to participants, including the ethical challenges encountered, can be found in Haines et al. (2011).

References

Canada. (1970-71-72). Statistics Act. c. 15, s. 1. Retrieved August 7, 2012, from www.statcan.gc.ca/about-apercu/act-loi-eng.htm

Day, B., Langlois, R., Tremblay, M., & Knoppers, B.M. (2007). Canadian Health Measures Survey: Ethical, legal and social issues. Health Reports, Special Issue Supplement 18, 37---51.

Giroux, S., Labrecque, F., & Quigley, A. (2013). Sampling documentation for cycle 2 of the Canadian Health Measures Survey Cycle 2. Methodology Branch Working Paper, to be published April, 2013.

Haines, D.A., Arbuckle, T.E., Lye, E., Legrand, M., Fisher, M., Langlois, R., & Fraser, W. (2011). Reporting results of human biomonitoring of environmental chemicals to study participants: A comparison of approaches followed in two Canadian studies. Journal of Epidemiology and Community Health, 65 (3), 191-198.

Statistics Canada. (2008). Methodology of the Canadian Labour Force Survey (Catalogue 71-256-X). Minister of Industry, Ottawa, ON.

Statistics Canada. (2013). Canadian Health Measures Survey (CHMS) data user guide: Cycle 2. Ottawa, ON. Available upon request (infostats@statcan.gc.ca)

4 Fieldwork

Fieldwork for the Canadian Health Measures Survey (CHMS) took place over a period of 2.5 years from August 2009 to November 2011. Data were collected sequentially at 18 sites across Canada. The sites were ordered to take into account seasonality by region and the temporal effect, subject to operational and logistical constraints.

Statistics Canada mailed an advance letter and brochure to households that were selected as outlined in section 3.3.2 (Dwelling and Participant Sampling). The mailing informed potential participants that they would be contacted for the survey's data collection.

Data was collected from consenting survey participants through a household personal interview, using a computer-assisted method, and a visit to a mobile examination centre (MEC) for physical measures. The field team consisted of household interviewers and the CHMS MEC staff, including trained health professionals who performed the physical measures testing (Statistics Canada, 2013b).

Participants were first administered a household questionnaire in their home. Using a computer application, the interviewer randomly selected one or two participants and conducted separate 45- to 60-minute health interviews (Statistics Canada, 2013b). The interviews collected demographic and socioeconomic data and information about lifestyle, medical history, current health status, the environment, and housing conditions.

Within approximately 2 weeks after the home visit, participants visited the MEC. Each MEC consisted of two trailers linked by an enclosed pedestrian walkway. One trailer served as a reception containing an administration area and an examination room; the other contained additional examination rooms and a laboratory. The MEC operated 7 days a week in order to complete approximately 350 visits at each site over 5 to 6 weeks and to accommodate participants' schedules (Statistics Canada, 2013b). MEC appointments averaged about 2.5 hours. A parent or legal guardian accompanied children under 14 years of age. To maximize response rates, participants who were unable or unwilling to go to the MEC were offered the option of a home visit by members of the CHMS MEC staff to perform some of the physical measures and the biospecimen collection portion of the survey (Statistics Canada, 2013b).

At the start of the MEC visit, participants signed consent/assent forms prior to any testing and in most cases provided a urine sample immediately thereafter. For logistical purposes, spot samples were collected rather than 24-hour urine samples. The urine samples were collected using the first catch urine, as opposed to the mid-stream urine collected in cycle 1, in order to optimize new infectious disease testing introduced in cycle 2. Also new for cycle 2, guidelines were provided to participants asking them to abstain from urinating 2 hours prior to their MEC visit. Samples were collected in 120 mL urine specimen containers. Trained health professionals took physical health measurements such as height, weight, blood pressure, lung function, and physical fitness. A series of screening questions were administered to determine their eligibility for the various tests, including phlebotomy (blood collection), based on pre-existing exclusion criteria (Statistics Canada, 2013b). Blood specimens were drawn by a certified phlebotomist; the maximum amount depended upon the age of the participant. The approximate volume drawn from participants aged 3-5 years was 22.0 mL; 6-11 years, 28.5 mL; 12-13 years, 48.8 mL; 14-19 years, 52.8 mL; and 20-79 years, 72.8 mL.

All blood and urine specimens collected in the MEC were processed and aliquotted in the MEC. Biospecimens were stored temporarily in two freezers at -20ºC until shipping. Once a week, the specimens were shipped on dry ice to the reference laboratory for analyses. Standardized operating procedures were developed for the collection of blood and urine specimens, processing and aliquoting procedures, as well as for shipping biospecimens to ensure adequate data quality and to standardize data collection. A priority sequence for laboratory analyses was established in the event that an insufficient volume of biospecimen was collected for complete analyses of the environmental chemicals as well as for analyses of infectious diseases, nutritional status, and chronic diseases. Details on the collection tubes, aliquot volumes, and priority testing are presented in Table 4.1.

Table 4.1 Urine and blood collection procedure for the environmental chemicals (in order of testing priority) measured in cycles 2 (2009-2011) of the Canadian Health Measures Survey
Measure Matrix Collection Tube
(size and typeTable 5 footnote a)
Aliquot VolumeTable 5 footnote b

Table 5 footnotes

Table 5 footnote 1

Becton Dickinson Vacutainers were used for the collection of blood; VWR urine specimen containers were used for the collection of urine.

Return to table 5 footnote a referrer

Table 5 footnote 2

Optimum sample volume sent to the reference laboratory

Return to table 5 footnote b referrer

Table 5 footnote 3

EDTA: ethylenediaminetetraacetic acid

Return to table 5 footnote c referrer

Table 5 footnote 4

Participants 3-5 years of age

Return to table 5 footnote d referrer

Table 5 footnote 5

Participants 6-79 years of age

Return to table 5 footnote e referrer

Metals and trace elements Whole Blood 4.0 mL Lavender EDTATable 5 footnote c 1.8 mL
Perfluoroalkyl substances Plasma

4.0 or 10.0 mL

Lavender EDTATable 5 footnote c

2.4 mL

Environmental phenols and triclocarban, organophosphate metabolites,

2,4-dichlorophenoxyacetic acid (2,4-D), carbamate metabolites, chlorophenols

Urine 120 mL urine specimen container 1.0 mL
Metals and trace elements 1.8 mL
Creatinine and nicotine metabolite 1.0 mL
Phthalate metabolites 4.0 mL
Pyrethroid metabolites 12 mL
Polycyclic aromatic hydrocarbon metabolites, atrazine metabolites, benzene metabolites 20 mL
Arsenic (speciated) 4.0 mL
Fluoride 1.0 mLTable 5 footnote d or 1.8 mLTable 5 footnote e

To maximize the reliability and validity of the data and to reduce systematic bias, the CHMS developed quality assurance and quality control protocols for all aspects of the fieldwork. Quality assurance for the MEC covered staff selection and training, instructions to respondents (pre-testing guidelines), and issues related to data collection. All staff had appropriate education and training for their respective positions. To ensure consistent measurement techniques, procedure manuals and training guides were developed in consultation with, and reviewed by, experts in the field. Quality control samples were done at each site, consisting of three field blanks (deionized water for most analytes) and blind commercial control samples when available for an analyte. These control samples were done on the following chemicals:

  • all metals in blood and urine (not including urinary speciated arsenic, blood copper, blood and urinary molybdenum, silver, and uranium);
  • organophosphate metabolites;
  • chlorophenols (not including 2,4-dichlorophenol and 2,4,5-trichlorophenol);
  • pyrethroid metabolites (not including 4-fluoro-3-phenoxybenzoic acid and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid);
  • 1-hydroxypyrene;
  • benzene metabolites;
  • cotinine; and
  • creatinine.

Blind commercial controls were not done for certain chemicals (including phthalates, some PAHs, environmental phenols and triclocarban, 2,4-D, and some metals) because commercial controls were not readily available.

The quality control samples were sent to the laboratory with a regular specimen shipment. Results were sent to Statistics Canada's CHMS headquarters, along with all other respondent results, where they were assessed to determine the accuracy of the methodology based on the defined analyte concentration. If required, feedback was provided quickly to the reference laboratory for review and remedial action.

During the MEC visit a sub-sample of participants were also asked to collect indoor air samples from their households using an indoor air sampler. Participants were asked to place the indoor air sampler in their household for 7 days in order to measure a number of volatile organic contaminants. One indoor air sampler was given per selected household, along with a pencil, postage-paid envelope and information sheet. After the 7 day collection period was over, participants mailed their indoor air sampler in the envelope provided to CASSEN Testing Laboratories where all indoor air analyses were performed.

A complete list of the substances measured in the indoor air samples is available in the Canadian Health Measures Survey (CHMS) Content Summary for Cycles 1, 2 and 3 (Statistics Canada, 2013a). Further details on the indoor air study are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 2 (Statistics Canada, 2013b). Data from the indoor air samplers are available upon request by contacting Statistics Canada at info@statcan.gc.ca.

Detailed descriptions of the CHMS MEC operations and logistics have been described previously in Bryan et al. (2007) and are presented in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 2 (Statistics Canada, 2013b).

References

Bryan, S.N., St-Denis, M. & Wojtas, D. (2007). Canadian Health Measures Survey: Operations and logistics. Health Reports, Special Issue Supplement 18, 53-70.

Statistics Canada. (2013a). Canadian Health Measures Survey (CHMS) content summary for cycles 1, 2 and 3. Ottawa, ON. Available upon request (infostats@statcan.gc.ca).

Statistics Canada. (2013b). Canadian Health Measures Survey (CHMS) data user guide: Cycle 2. Ottawa, ON. Available upon request (infostats@statcan.gc.ca).

5 Laboratory Analyses

Laboratory analyses of environmental chemicals and creatinine were performed at the Centre de toxicologie du Québec of l'Institut national de santé publique du Québec (INSPQ), city of Québec. INSPQ followed standardized operating procedures that were developed for every assay and technique performed in its laboratory. The laboratory, which is accredited under ISO 17025, used numerous internal and external quality control programs. The limit of detection for each method is presented in Appendix B.

Internal quality control measures within INSPQ included the use of calibration standards, laboratory blanks, and other in-house reference materials. External quality control measures included participation in inter-laboratory comparison studies for most analytes. Quality assurance reviews were conducted on laboratory data in order to identify inconsistencies in results, such as assay drifting.

The methods used in the analyses of the environmental chemicals and creatinine are described below.

5.1 Metals and Trace Elements

5.1.1 Blood Analyses

Blood samples were diluted in a basic solution containing octylphenol ethoxylate and ammonia. They were analyzed for cadmium, cobalt, copper, lead, manganese, molybdenum, total mercury, nickel, selenium, silver, uranium, and zinc by inductively coupled plasma-mass spectrometry (ICP-MS) (Perkin Elmer Sciex, Elan DRC II). Matrix matched calibration was performed using blood from a non-exposed individual (INSPQ, 2009a).

5.1.2 Urine Analyses

Urine samples were diluted in 0.5% nitric acid and analyzed for antimony, total arsenic, cadmium, cesium, cobalt, copper, lead, manganese, molybdenum, nickel, selenium, silver, thallium, tungsten, uranium, vanadium, and zinc by ICP-MS (Perkin Elmer Sciex, Elan DRC II). Matrix matched calibration was performed using urine from non-exposed individuals (INSPQ, 2009b).

5.1.2.1 Arsenic (speciated)

Urine samples were diluted in ammonium carbonate and analyzed for arsenite (+3 oxidation state), arsenate (+5 oxidation state), monomethylarsonic acid, dimethylarsinic acid, and arsenocholine and arsenobetaine combined using ultra performance liquid chromatography (UPLC) on a Waters Acquity UPLC (Galaxie software) coupled to ICP-MS on a Varian 820-MS (Varian ICP-MS Expert software package version 2.1) (INSPQ, 2009c).

5.1.2.2 Fluoride

Fluoride in urine samples were analyzed using Orion pH meter with fluoride ion selective electrode (Orion Research Inc.) (INSPQ, 2009d).

5.2 Benzene Metabolites

Benzene metabolites (trans,trans-muconic acid and S-phenylmercapturic acid) were extracted from urine by hydrophilic-lipophilic-balanced solid-phase extraction using the automated Janus workstation. The extracts were evaporated to dryness, reconstituted in the mobile phase, and analyzed using UPLC on a Waters Acquity UPLC coupled to tandem mass spectrometry on a Waters Quattro Premier XE (MassLynx software) in the multiple reaction monitoring (MRM) mode operated in negative ion mode (INSPQ, 2009e).

Urinary phenol was hydrolyzed in β-glucuronidase enzyme and again in mild acid. The samples were then derivatized with pentafluorobenzyl bromide at 80ºC for 2 hours. The derivatized products were extracted with a mixture of dichloromethane-hexane. Evaporated extracts were redissolved and analyzed by gas chromatography on an Agilent 6890 or 7890 coupled to tandem mass spectrometry on a Waters Quattro Premier XE (MassLynx software) operating in MRM mode following negative ion chemical ionization (INSPQ, 2009f).

5.3 Chlorophenols

Urinary chlorophenols (2,4-dichlorophenol, 2,5-dichlorophenol, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol, and pentachlorophenol) were hydrolyzed in β-glucuronidase enzyme and again in mild acid. The samples were then derivatized with pentafluorobenzyl bromide at 80ºC for 2 hours. The derivatized products were extracted with a mixture of dichloromethane-hexane. Evaporated extracts were redissolved and analyzed by gas chromatography on an Agilent 6890 or 7890 coupled to tandem mass spectrometry on a Waters Quattro Premier XE (MassLynx software) operating in MRM mode following negative ion chemical ionization (INSPQ, 2009f).

5.4 Environmental Phenols and Triclocarban

Urinary bisphenol A, triclocarban, and triclosan were hydrolyzed in β-glucuronidase enzyme and again in mild acid. The samples were then derivatized with pentafluorobenzyl bromide at 80ºC for 2 hours. The derivatized products were extracted with a mixture of dichloromethane-hexane. Evaporated extracts were redissolved and analyzed by gas chromatography on an Agilent 6890 or 7890 coupled to tandem mass spectrometry on a Waters Quattro Premier XE (MassLynx software) operating in MRM mode following negative ion chemical ionization (INSPQ, 2009f). Free and hydrolyzed forms of bisphenol A were measured together by this procedure.

5.5 Nicotine Metabolite

Cotinine was recovered from urine samples by solid-phase extraction using an automated Janus workstation. Deuterated cotinine was used as the internal standard. The extract was then redissolved in the mobile phase, and analyzed using UPLC on a Waters Acquity UPLC coupled to tandem mass spectrometry on a Waters Quattro Premier XE (MassLynx software) in MRM mode with an ion source in positive ion mode (INSPQ, 2009g).

5.6 Perfluoroalkyl Substances

Perfluoroctane sulfonate, perfluorooctanoic acid, perfluorohexane sulfonate, perfluorononanoic acid, perfluorobutanoic acid, perfluorobutane sulfonate, perfluorohexanoic acid, perfluorodecanoic acid, and perfluoroundecanoic acid were extracted from plasma samples with methyl-tert butyl ether after forming an ion pair with tetrabutylammonium hydrogensulfate. Extracts were evaporated to dryness and dissolved in 200 µL of the mobile phase. They were analyzed by UPLC on a Waters Acquity UPLC coupled to tandem mass spectrometry on a Waters Quattro Premier XE (MassLynx software) in MRM mode with an electrospray ion source in the negative ion mode (INSPQ, 2009h).

5.7 Pesticides

5.7.1 Atrazine Metabolites

Urinary pyrethroid metabolites (4-fluoro-3-phenoxybenzoic acid; cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid; cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid; trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid; 3-phenoxybenzoic acid) were hydrolyzed in ß-glucuronidase enzyme. The samples were then acidified and extracted with hexane. Extracts were derivatized and extracted a second time with a mixture of isooctane-hexane. Evaporated extracts were dissolved in hexane and analyzed by gas chromatography on an Agilent 6890 N coupled to mass spectrometry on an Agilent 5973 N operated in the single ion monitoring mode following negative chemical ionization (Agilent MSD Chem software) (INSPQ, 2009j).

5.7.2 Carbamate Metabolites, 2,4-Dichlorophenoxyacetic Acid, and Organophosphate Metabolites

Urinary carbamate metabolites (carbofuranphenol and 2-isopropoxyphenol), 2,4-dichlorophenoxyacetic acid, and organophosphate metabolites (diethyl phosphate, dimethyl phosphate, diethyl thiophosphate, dimethyl thiophosphate, diethyl dithiophosphate, and dimethyl dithiophosphate) were hydrolyzed in β-glucuronidase enzyme and again in mild acid. The samples were then derivatized with pentafluorobenzyl bromide at 80ºC for 2 hours. The derivatized products were extracted with a mixture of dichloromethane-hexane. Evaporated extracts were redissolved and analyzed by gas chromatography on an Agilent 6890 or 7890 coupled to tandem mass spectrometry on a Waters Quattro Micro-GC (MassLynx software) operating in MRM mode following negative ion chemical ionization (INSPQ, 2009f).

5.7.3 Pyrethroid Metabolites

Urinary pyrethroid metabolites (4-fluoro-3-phenoxybenzoic acid; cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid; cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid; trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid; 3-phenoxybenzoic acid) were hydrolyzed in β-glucuronidase enzyme. The samples were then acidified and extracted with hexane. Extracts were derivatized and extracted a second time with a mixture of isooctane-hexane. Evaporated extracts were dissolved in hexane and analyzed by gas chromatography on an Agilent 6890 N coupled to mass spectrometry on an Agilent 5973 N operated in the single ion monitoring mode following negative chemical ionization (Agilent MSD Chem software) (INSPQ, 2009j).

5.8 Phthalate Metabolites

Urine samples were spiked with the internal standard solution and phthalate metabolites (mono-benzyl phthalate, mono-butyl phthalate, mono-3-carboxypropyl phthalate, mono-cyclohexyl phthalate, mono-2-ethylhexyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-ethyl phthalate, mono-isobutyl phthalate, mono-isononyl phthalate, mono-methyl phthalate, and mono-n-octyl phthalate) were hydrolyzed at 37°C for 90 minutes with b-glucuronidase enzymatic solution in an ammonium acetate buffer at a pH of 6.5. The samples were acidified with phosphoric acid and extracted using strong anion-exchange solid-phase extraction columns using an automated Janus workstation. Phthalate metabolites were eluted using 2% formic acid in acetonitrile solution, evaporated to dryness, reconstituted in deionized water and analyzed by UPLC on a Waters Acquity UPLC coupled to tandem mass spectrometry on a Waters Quattro Premier XE (MassLynx software) in MRM mode following electrospray ionization in negative ion mode (Waters Acquity UPLC, Waters Quattro Premier XE, MassLynx software) (INSPQ, 2009k).

During the course of the phthalate analyses for cycle 1, INSPQ identified accuracy issues with the commercial "certified" standard solutions that were used to develop calibration curves (Langlois et al., 2012). Therefore, all pertinent data from cycle 1 have been adjusted using compound-specific correction factors derived from the accuracy investigation. Information regarding the development of the compound-specific correction factors will be presented in a future publication.

5.9 Polycyclic Aromatic Hydrocarbon Metabolites

Polycyclic aromatic hydrocarbon metabolites (3-hydroxybenzo[a]pyrene, 2-hydroxychrysene, 3-hydroxychrysene, 4-hydroxychrysene, 6-hydroxychrysene, 3-hydroxyfluoranthene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxynaphthalene, 2-hydroxynaphthalene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, and 1-hydroxypyrene) in urine samples were hydrolyzed using b-glucuronidase enzymatic solution and extracted with an organic solvent at neutral pH. The extracts were evaporated and derivatized with N-methyl-N-(trimethylsilyl)-

trifluoroacetamide and analyzed using gas chromatography on an Agilent 7890 coupled to mass spectrometry on an Agilent 7000B triple-quad tandem mass spectrometry operated in MRM mode with an ion source in electron ionization mode (Agilent MassHunter software) (INSPQ, 2011).

5.10 Creatinine

Creatinine was measured in urine using the colorimetric end-point Jaffe method. An alkaline solution of sodium picrate reacts with creatinine in urine to form a red Janovski complex using Microgenics DRI Creatinine-Detect reagents (#917). The absorbance was read at 505 nm on a Hitachi 917 chemistry autoanalyzer (INSPQ, 2008).

References

INSPQ (Institut national de santé publique du Québec). (2008). Analytical method for the determination of urine creatinine on Hitachi 917 (C-530), condensed version. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009a). Analytical method for the determination of metals and iodine in blood by inductively coupled plasma mass spectrometry (ICP-MS),DRC II (M-572), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009b). Analytical method for the determination of metals in urine by inductively coupled plasma mass spectrometry (ICP-MS), DRC II (M-571), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009c). Analytical method for the determination of arsenic species in urine by ultra performance liquid chromatography coupled to argon plasma induced mass spectrometry (HPLC-ICP-MS) (M-585), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009d). Analytical method for the determination of fluoride in urine (M-186), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009e). Analytical method for the determination of benzene metabolites in urine by UPLC-MS-MS (E-460), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009f). Analytical method for the determination of bisphenol A, triclosan, triclocarban and pesticide metabolites in urine by GC-MS-MS (E-454), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009g). Analytical method for the determination of cotinine in urine by HPLC-MS-MS robotic workstation method (C-550), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009h). Analytical method for the determination of perfluorinated compounds (PFCs) in plasma by HPLC-MS-MS (E-456), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009i). Analytical method for the determination of triazine metabolites in urine by UPLC-MS-MS (E-459), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009j). Analytical method for the determination of pyrethroids metabolites in urine by GC-MS (EC-426), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2009k). Analytical method for the determination of phthalate metabolites (phthalate monoesters) in urine by HPLC-MS-MS (E-453), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

INSPQ (Institut national de santé publique du Québec). (2011). Analytical method for the determination of polycyclic aromatic hydrocarbons (PAHs) in urine by GC-MS-MS (E-465), condensed version for CHMS. Laboratoire de toxicologie, Québec, QC.

Langlois, É., Leblanc, A.,Simard, Y., & Thellen, C. (2012). Accuracy investigation of phthalate metabolite standards. Journal of Analytical Toxicology, 36 (4), 270-279.

6 Statistical Data Analyses

Descriptive statistics on the concentrations of environmental chemicals in blood and urine of Canadians, aged 3 to 79 years, were generated using the Statistical Analysis System software (SAS Institute Inc., version 9.2, 2008) and the SUDAAN®(SUDAAN Release 10.0, 2008) statistical software package.

The Canadian Health Measures Survey (CHMS) is a sample survey, meaning that the participants represent many other Canadians not included in the survey. In order for the results of the survey to be representative of the entire population, sample weights were generated by Statistics Canada and incorporated into all estimates presented in this report (e.g. geometric means). Survey weights were used to take into account the unequal probability of selection into the survey as well as non-response. Further, to account for the complex survey design of the CHMS, the set of bootstrap weights included with the data set was used to estimate the 95% confidence intervals (CIs) for all means and percentiles (Rao et al., 1992; Rust & Rao, 1996).

For each chemical measured in cycle 2, data tables are presented. Data from cycle 1 are also provided within the tables for those substances measured in both cycles. In the first Report on Biomonitoring of Environmental Chemicals in Canada all results were reported to two decimal places. For cycle 2 of the CHMS, the reporting protocol changed and the results were reported to two significant digits. For consistency, cycle 1 data was adjusted to two significant digits prior to generating the descriptive statistics and data from both cycles is presented to two significant digits. Therefore, the descriptive statistics presented in this report for cycle 1 may differ from those presented in the first report. The differences are not significant and the values presented in the first report are still considered to be accurate.

The data tables include the sample size (n); percentage of results that fall below the limit of detection (LOD); geometric mean (GM); the 10th, 50th, 75th, and 95th percentiles; and associated 95% CIs. Three steps were involved in the calculation of the GM and associated 95% CIs. First, the log of each variable was calculated. Second, the mean and 95% CIs for the log transformed variables were calculated using bootstrap weights. Finally, the GM and associated 95% CIs were calculated by taking the antilog of the log transformed mean and associated 95% CIs. For each chemical, results are presented for the total population as well as by age group and sex (except for 3-5 year olds). For each chemical that was measured in both cycle 1 and cycle 2 of the CHMS, a summary table is provided that compares results for the aggregate of all age groups common to both cycles and for that same aggregate population separated by sex. Measurements that fell below the LOD for the laboratory analytical method were assigned a value equal to half the LOD. If the proportion of results below the LOD was greater than 40%, GMs were not calculated. Percentile estimates that are less than the LOD are reported as <LOD. Appendix B contains a table of LOD values for each chemical, specific to each cycle. A table of conversion factors is provided in Appendix C to assist in the comparison of data from other studies that report different units.

Chemicals measured in either whole blood or plasma are presented as weight of chemical per volume of whole blood or plasma (e.g. µg chemical/L blood or plasma).

For urine measurements, concentrations are presented as weight of chemical per volume of urine (e.g. µg chemical/L urine) and adjusted for urinary creatinine (e.g. µg chemical/g creatinine). Urinary creatinine is a chemical by-product generated from muscle metabolism; it is frequently used to adjust for urine concentration (or dilution) in spot urine samples because its production and excretion are relatively constant over 24 hours owing to homeostatic controls (Barr et al., 2005; Boeniger et al., 1993; Pearson et al., 2009). If the chemical measured behaves similarly to creatinine in the kidney, it will be filtered at the same rate, thus expressing the chemical per gram of creatinine helps adjust for the effect of urinary dilution as well as some differences in renal function and lean body mass (Barr et al., 2005; CDC, 2009; Pearson et al., 2009). Creatinine is primarily excreted by glomerular filtration; therefore, creatinine adjustment may not be appropriate for compounds that are excreted primarily by tubular secretion in the kidney (Barr et al., 2005; Teass et al., 2003). In addition, creatinine excretion can vary due to age, sex and ethnicity; therefore, it may not be appropriate to compare creatinine-adjusted concentrations between different demographic groups (e.g. children with adults) (Barr et al., 2005). Where urinary creatinine values were missing or <LOD, the estimate of that participant's creatinine-adjusted chemical was not calculated and was also set to missing.

Descriptive statistics are presented for creatinine (mg/dL) in Appendix D. These include n; % <LOD; GM; the 10th, 50th, 75th, and 95th percentiles; and associated 95% CIs for the total population as well as by age group and gender. Measurements that fell below the LOD for the laboratory analytical method were assigned a value equal to half the LOD.

Specific gravity was also measured in all urine samples at the mobile examination centre, immediately following sample collection. Urinary specific gravity is the ratio of densities between urine and pure water and can be used to adjust for variations in urine output, similar to urinary creatinine adjustment. Urinary specific gravity adjustment has not been done for any of the chemicals presented in this report; however, specific gravity data are available upon request by contacting Statistics Canada at info@statcan.gc.ca should they wish to perform this adjustment for their own data analyses.

Under the Statistics Act, Statistics Canada is required to ensure participant confidentiality. Therefore, estimates based on a small number of participants are suppressed. Following suppression rules for the CHMS, any estimate based on fewer than 10 participants is suppressed in this report. To avoid suppression, estimates at the 95th percentile require at least 200 participants, estimates at the 10th percentile require at least 100 participants, estimates at the 75th percentile require at least 40 participants, estimates at the 50th percentile require at least 20 participants, and estimates of the geometric mean require at least 10 participants.

Estimates from a sample survey inevitably include sampling errors. Measuring the possible scope of sampling errors is based on the standard error of the estimates drawn from the survey results. To get a better indication of the size of the standard error, it is often more useful to express the standard error in terms of the estimate being measured. The resulting measure, called the coefficient of variation (CV), is obtained by dividing the standard error of the estimate by the estimate itself, and it is expressed as a percentage of the estimate (Statistics Canada, 2013). Statistics Canada employs the following guidelines for releasing estimates based on their CV, which have been followed in this report:

  • When a CV is between 16.6% and 33.3%, an estimate can be considered for general unrestricted release but is accompanied by a warning cautioning subsequent users of the high sampling variability associated with the estimate. These estimates are identified by the superscript letter E.
  • When a CV is greater than 33.3%, Statistics Canada recommends not releasing the estimate because conclusions based on these data will be unreliable and most likely invalid. These estimates will not be published and will instead be replaced by the letter F.

Further details on the sample weights and data analysis are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 2 (Statistics Canada, 2013).

References

Barr, D.B., Wilder, L.C., Caudill, S.P., Gonzalez, A.J., Needham, L.L., & Pirkle, J.L. (2005). Urinary creatinine concentrations in the U.S. population: Implications for urinary biologic monitoring measurements. Environmental Health Perspectives, 113 (2), 192-200.

Boeniger, M.F., Lowry, L.K., & Rosenberg, J. (1993). Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: A review. American Industrial Hygiene Association Journal, 54 (10), 615-627.

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Pearson, M., Lu, C., Schmotzer, B., Waller, L., & Riederer, A. (2009). Evaluation of physiological measures for correcting variation in urinary output: Implications for assessing environmental chemical exposure in children. Journal of Exposure Science and Environmental Epidemiology, 19 (3), 336-342.

Rao, J., Wu, C., & Yue, K. (1992). Some recent work on resampling methods for complex surveys. Survey Methodology, 18 (2), 209-217.

Rust, K.F. & Rao, J.N.K. (1996). Variance estimation for complex surveys using replication techniques. Statistical Methods in Medical Research, 5 (3), 283-310.

Statistics Canada. (2013). Canadian Health Measures Survey (CHMS) data user guide: Cycle 2. Ottawa, ON. Available upon request (infostats@statcan.gc.ca)

Teass, A., Biagini, R., DeBord, G., & DeLon Hull, R. (2003). Application of biological monitoring methods. NIOSH Manual of Analytical Methods, NIOSH Publication Number 2003-154 (3rd Supplement).

7 Considerations for Interpreting the Biomonitoring Data

The Canadian Health Measures Survey (CHMS) was designed to provide estimates of environmental chemical concentrations in blood or urine for the Canadian population as a whole. The first cycle of the survey covered approximately 96.3% of the Canadian population aged 6 to 79 years. The second cycle included children as young as 3 years of age and covered approximately 96.3% of the Canadian population up to 79 years of age. The survey was not designed to permit breakdown of data by collection site. In addition, the CHMS design did not target specific exposure scenarios; consequently, it did not select or exclude participants on the basis of their potential for low or high exposures to environmental chemicals.

Biomonitoring can estimate how much of a chemical is present in a person, but it cannot say what health effects, if any, may result from that exposure. The ability to measure environmental chemicals at very low concentrations has advanced in recent years. However, the presence alone of a chemical in a person's body does not necessarily mean that it will cause a health effect. Factors such as the dose, the toxicity of the chemical, and the duration and timing of exposure are important to determine whether potential adverse health effects may occur. For chemicals such as lead or mercury, research studies have provided a good understanding of the health risks associated with different concentrations in blood. However, for many chemicals, further research is needed to understand the potential health effects, if any, from different blood or urine concentrations. Furthermore, small amounts of certain chemicals, such as manganese and zinc, are essential for the maintenance of good health and would be expected to be present in the body. In addition, the way in which a chemical will act in the body will differ among individuals and cannot be predicted with certainty. Certain populations (children, pregnant women, the elderly or immuno-compromised people) may be more susceptible to the effects of exposure.

The absence of a chemical does not necessarily mean a person has not been exposed. It may be that the technology is not capable of detecting such a small amount, or that the exposure occurred at an earlier point in time allowing for the chemical to be eliminated from the person's body before measurement took place.

Biomonitoring cannot tell us the source or route of the exposure. The amount of chemical measured indicates the total amount that has entered the body through all routes of exposure (ingestion, inhalation, and skin contact) and from all sources (air, water, soil, food, and consumer products). The detection of the chemical may be the result of exposure to a single source or multiple sources. In addition, in most cases biomonitoring cannot distinguish between natural and anthropogenic sources. Many chemicals (lead, mercury, cadmium, and arsenic) occur naturally in the environment and are also present in human-made products.

Metals are the only chemicals measured in urine as the parent compounds. Almost all other chemicals are measured as metabolites. For many chemicals, parent compounds may be broken down (i.e. metabolized) in the body into one or more metabolites. For example, the pyrethroid insecticide cyfluthrin is broken down into several metabolites. Some metabolites are specific to one parent compound whereas others are common to several parent compounds. Several urinary metabolites are also formed in the environment (e.g. dialkyl phosphate metabolites). Their presence in urine does not necessarily mean that an exposure to the parent chemical has occurred; rather, exposure could be to the metabolite itself in media such as food, water, or air.

Factors that contribute to the concentrations of chemicals measured in blood and urine include the quantity entering the body through all routes of exposure, absorption rates, distribution to various tissues in the body, metabolism, and excretion of the chemical and/or its metabolites from the body. These processes depend on both the characteristics of the chemical, including its solubility in fat (or lipophilicity), its pH, its particle size, and the characteristics of the individual being exposed, such as age, diet, health status, and race. For these reasons, the way in which a chemical will act in the body will differ among individuals and cannot be predicted with certainty.

This report includes temporal data for substances measured in both cycle 1 (2007-2009) and cycle 2 (2009-2011) and baseline data for substances introduced to the survey in cycle 2. Results from future cycles of CHMS can be compared with the baseline data from cycle 1 and cycle 2 in order to begin to examine trends in Canadians' exposures to selected environmental chemicals. It is important to note that there were some sampling and analytical modifications between cycles that may have contributed some variation in results for those substances measured in both cycle 1 and cycle 2. The limits of detection (LOD) for certain analytical methods changed from cycle 1 to cycle 2. Although the LOD values did not change by a large margin, this difference should be noted when comparing data from cycles 1 and 2. A list of LOD values from cycles 1 and 2 is provided in Appendix B. In addition, the urine collection protocol and guidelines were changed in cycle 2, and this may have resulted in a shift in creatinine levels when cycle 1 and cycle 2 are compared. This, in turn, could affect creatinine-adjusted levels of some chemicals.

Urinary creatinine concentrations can also be affected by variables such as age, sex and ethnicity resulting in differences among demographic groups within a single cycle (Mage et al., 2004). In particular, creatinine excretion per unit bodyweight increases substantially with increasing age in children (Aylward et al., 2011; Remer et al., 2002). As a result, it is acceptable to compare creatinine-adjusted concentrations among similar demographic groups (e.g. children with children, adults with adults) but not among two different demographic groups (e.g. children with adults) (Barr et al., 2005).

More in-depth statistical analyses of the CHMS biomonitoring data, including time trends, exploring relationships among environmental chemicals, other physical measures, and self-reported information are beyond the scope of this report, and may be performed in the future. The CHMS data are being made available to scientists upon request by contacting Statistics Canada at info@statcan.gc.ca and will be a resource for additional scientific analysis.

References

Aylward, L.L., Lorber, M., & Hays, S.M. (2011). Urinary DEHP metabolites and fasting time in NHANES. Journal of Exposure Science and Environmental Epidemiology, 21, 615-624.

Barr, D.B., Wilder, L.C., Caudill, S.P., Gonzalez, A.J., Needham, L.L., & Pirkle, J.L. (2005). Urinary creatinine concentrations in the U.S. population: Implications for urinary biologic monitoring measurements. Environmental Health Perspectives, 113 (2), 192-200.

Mage, D.T., Allen, R., Gondy, G., Smith, W., Barr, D.B., & Needham, L.L. (2004). Estimating pesticide dose from urinary pesticide concentration data by creatinine correction in the Third National Health and Nutrition Examination Survey. Journal of Exposure Analysis and Environmental Epidemiology, 14 (6), 457-465.

Remer, T., Neubert, A., & Maser-Gluth, C. (2002). Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research. American Journal of Clinical Nutrition, 75, 561-569.

8 Metal and Trace Element Summaries and Results

8.1 Antimony

Antimony (CASRN 7440-36-0) is a naturally occurring element present in the Earth's crust at an average concentration of approximately 0.00002% (Emsley, 2001). It is classified as a metalloid, exhibiting both metallic and non-metallic characteristics. It can exist as a pure metal as well as in various oxidation states and forms (ATSDR, 1992). The trivalent (+3) form is the most stable and is commonly found in antimony compounds including antimony trioxide and antimony trisulphide (ATSDR, 1992).

Antimony is released naturally into the environment as a result of weathering of rocks, runoff from soils, emissions from volcanic eruptions, sea spray, and forest fires (Health Canada, 1997). Primary anthropogenic releases of antimony occur through industrial processes. Antimony may enter surface water by way of effluents from mining and manufacturing operations, as well as through industrial and municipal leachate discharges. Atmospheric releases are the result of stack dust outputs from industrial sources such as coal-fired power plants, inorganic chemical plants, and metal smelters (Health Canada, 1997).

Antimony is used in the production of semi-conductors, and infrared detectors and diodes, and as an additive in paint pigments, glass, and ceramic products (Health Canada, 1997; NTP, 2005). It is also used as a component in alloys for batteries, cable sheathing, plumbing solder, ammunition and fireworks, and flame retardant and anti-friction materials (ATSDR, 1992; Health Canada, 1997; NTP, 2005). Some forms of antimony are used in pharmaceutical products or to induce vomiting following poisonings (WHO, 2003).

Canadians are exposed to antimony mainly through ingestion of food, but also to some extent from water, air (including tobacco smoke), dust, or direct dermal contact with consumer products containing antimony (Environment Canada & Health Canada, 2010). The absorption, distribution and excretion of antimony depend on both the route of administration and its oxidation state. The available data suggest an average intestinal absorption of less than 10% (ATSDR, 1992). Following ingestion in animals, the liver, kidney, bone, lung, spleen, and thyroid are the major sites of accumulation outside the gastrointestinal tract (Health Canada, 1997). After inhalation, tissue distribution studies show that the trivalent form accumulates more rapidly in the liver than the pentavalent form, whereas pentavalent antimony is found preferentially in the skeleton. Clearance and retention of antimony depend mainly on solubility (NTP, 2005). Inhaled antimony trioxide is retained in the lung with long half-lives for lung clearance (Garg et al., 2003). Once absorbed, antimony is relatively rapidly cleared from other tissues with an estimated elimination half-life of 3 to 4 days (Kentner et al., 1995). In humans, urine is the primary route of excretion with pentavalent antimony tending to be more readily excreted in the urine than the trivalent form (Elinder & Friberg, 1986; Health Canada, 1997). Antimony is most commonly measured in blood and urine, and this measurement is reflective of exposure to antimony and antimony-related compounds, such as antimony trioxide (ATSDR, 1992).

The levels of antimony to which the general population is exposed are not expected to cause any adverse health effects (ATSDR, 1992). Acute oral and inhalation exposure to high doses of antimony may cause gastrointestinal effects in humans whereas chronic exposure to low doses of antimony compounds is primarily associated with myocardial effects (Health Canada, 1997). The International Agency for Research on Cancer has classified antimony trioxide as Group 2B, a possible human carcinogen, and antimony trisulphide as Group 3, not classifiable as to its carcinogenicity to humans (IARC, 1989).

As part of the Chemicals Management Plan under the Canadian Environmental Protection Act, 1999, antimony trioxide was identified as a high-priority substance and a final screening assessment was published in September 2010 (Canada, 1999; Canada, 2011a; Environment Canada & Health Canada, 2010). The assessment concluded that antimony trioxide is not of concern to the environment or to human health at current levels of exposure (Environment Canada & Health Canada, 2010). Antimony and its compounds are included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Drugs Act (Canada, 1985; Health Canada, 2011). The leachable antimony content in a variety of consumer products is regulated under the Canada Consumer Product Safety Act (Canada, 2010a). These regulated consumer products include paints and other surface coatings on cribs, toys, and other products for use by a child in learning or play situations (Canada, 2010b; Canada, 2011b).

Considering both toxicity and analytical capabilities, a Canadian drinking water quality guideline has been developed that sets out the maximum acceptable concentration of antimony (Health Canada, 1997). Currently, there are no guidelines for antimony trioxide in drinking water in Canada because of insufficient data for its presence in drinking water (Environment Canada & Health Canada, 2010).

In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric mean of antimony in whole blood was 5.40 µg/L (INSPQ, 2004). Urinary antimony concentrations were less than the detection limit of 0.12 µg/L in over 50% of the participants (INSPQ, 2004).

Antimony was measured in the urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented as both µg/L (Tables 8.1.1, 8.1.2, and 8.1.3) and µg/g creatinine (Tables 8.1.4, 8.1.5, and 8.1.6). Finding a measurable amount of antimony in urine is an indicator of exposure to antimony or antimony-containing compounds and does not necessarily mean that an adverse health effect will occur.

6 Data Tables: 8.1.1 to 8.1.6

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1992). Toxicological profile for antimony. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved January 12, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=332&tid=58

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2010a). Canada Consumer Product Safety Act. SC 2010, c. 21. Retrieved February 20, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-1.68/index.html

Canada. (2010b). Cribs, Cradles and Bassinets Regulations. SOR/2010-261. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2010-261/index.html

Canada. (2011a). Chemical substances website. Retrieved January 12, 2012, from www.chemicalsubstances.gc.ca

Canada. (2011b). Toys Regulations. SOR/2011-17. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2011-17/index.html

Elinder, C.G. & Friberg, L. (1986). Antimony. Handbook on the toxicology of metals. Elsevier, New York, NY.

Emsley, J. (2001). Nature's building blocks: An A-Z guide to the elements. Oxford University Press, Oxford.

Environment Canada & Health Canada. (2010). Screening assessment for the challenge: Antimony trioxide (antimony oxide). Ottawa, ON. Retrieved January 12, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=9889ABB5-1

Garg, S.P., Singh, I.S., & Sharma, R.C. (2003). Long term lung retention studies of 125Sb aerosols in humans. Health Physics, 84 (4), 457-468.

Health Canada. (1997). Guidelines for Canadian drinking water quality: Guideline technical document - Antimony. Minister of Health, Ottawa, ON. Retrieved January 12, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/antimony-antimoine/index-eng.php

Health Canada. (2011). List of prohibited and restricted cosmetic ingredients ("hotlist"). Minister of Health, Ottawa, ON. Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

IARC (International Agency for Research on Cancer). (1989). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 47: Some organic solvents, resin monomers and related compounds, pigments and occupational exposures in paint manufacture and painting. Summary of data reported and evaluation. World Health Organization, Geneva.

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

Kentner, M., Leinemann, M., Schaller, K.-H., Weltle, D., & Lehnert, G. (1995). External and internal antimony exposure in starter battery production. International Archives of Occupational and Environmental Health, 67 (2), 119-123.

NTP (National Toxicology Program). (2005). Antimony trioxide: Brief review of toxicological literature. Department of Health and Human Services, Research Triangle Park, NC. Retrieved January 12, 2012, from http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Antimonytrioxide.pdf

WHO (World Health Organization). (2003). Antimony in drinking-water: Background document for development of WHO guidelines for drinking-water quality. WHO, Geneva. Retrieved January 12, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/0304_74/en/index.html

8.2 Arsenic

Arsenic (CASRN 7440-38-2) is a naturally occurring element making up a small fraction (0.00015%) of the Earth's crust (ATSDR, 2007; Emsley, 2001). It is classified as a metalloid, exhibiting properties of both a metal and a non-metal. Arsenic is commonly found as an inorganic sulphide complexed with other metals (CCME, 1997). Arsenic also forms stable organic compounds in its trivalent (+3) and pentavalent (+5) states. Common organic arsenic compounds include monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine, and arsenocholine (WHO, 2001).

Arsenic may enter lakes, rivers, or groundwater naturally through erosion and weathering of soils, minerals, and ores (Health Canada, 2006). The primary anthropogenic sources of arsenic are the smelting of metal ores, the use of arsenical pesticides, and the burning of fossil fuels (WHO, 2001). In Canada, smelting of gold ores is the primary anthropogenic source of arsenic (Environment Canada & Health Canada, 1993).

Arsenic is used in the manufacture of transistors, lasers and semi-conductors, and in the processing of glass, pigments, textiles, paper, metal adhesives, ceramics, wood preservatives, ammunition, and explosives. Historical uses of arsenic include application of lead arsenate as a pesticide in apple orchards and vineyards and arsenic trioxide as a herbicide (ATSDR, 2007; Health Canada, 2006). Chromated copper arsenate was formerly used as a wood preservative in residential construction projects, such as playground structures and decks; however, it is now used only for industrial purposes and for domestic wood foundations (Health Canada, 2005). Organic arsenical herbicides, such as MMA and DMA, are no longer registered for use in Canada (Environment Canada, 2008; EPA, 2006; Health Canada, 2012).

The public can be exposed to arsenic through food, drinking water, soil, and ambient air (Environment Canada & Health Canada, 1993). Food is the major source of intake with total arsenic concentrations being highest in seafood (IARC, 2012). Inorganic arsenic is the predominant form found in meats, dairy products, and cereal; organic arsenic, including arsenobetaine and arsenocholine, predominates in seafood, fruit, and vegetables (CDC, 2009; IARC, 2012). Exposure may also arise from indoor house dust; levels in dust can exceed levels in soil (Rasmussen et al., 2001). Further, exposure to arsenic may be elevated in populations residing in areas where industrial or natural sources occur.

Inorganic arsenic is readily absorbed, up to 95%, in the gastrointestinal tract; however, absorption may be much lower for highly insoluble forms of arsenic (ATSDR, 2007). Following oral ingestion, inorganic arsenic appears rapidly in blood circulation where it binds primarily to hemoglobin. Within 24 hours, it is found mainly in the liver, kidney, lung, spleen, and skin. Skin, bone, and muscle represent the major storage sites. In cases of chronic exposure, arsenic will preferentially accumulate in tissues rich in keratin or sulfhydryl functional groups, such as hair, nails, skin, and other protein-containing tissues (Human Biomonitoring Commission, 2003). Metabolism of inorganic arsenic involves an initial reduction of pentavalent to trivalent arsenic followed by oxidative methylation to monomethylated, dimethylated, and trimethylated products including MMA and DMA (WHO, 2011). Methylation facilitates the excretion of inorganic arsenic from the body because the end-products MMA and DMA are readily excreted in urine (WHO, 2001). Arsenobetaine and other organic forms of arsenic found in seafood are readily and rapidly absorbed from the gastrointestinal tract, do not undergo significant metabolism, and are predominantly and rapidly eliminated in urine (WHO, 2001).

Biomarkers of arsenic exposure include the levels of arsenic or its metabolites in blood, hair, nails, and urine (WHO, 2001). Measurements of speciated metabolites in urine expressed either as inorganic arsenic or as the sum of metabolites (inorganic arsenic + MMA + DMA) are generally accepted as the most reliable indicator of recent arsenic exposure (ATSDR, 2007; WHO, 2001). Measurements of arsenic in urine have been used to identify recent arsenic ingestion or above-average exposures in populations living near industrial point sources of arsenic (ATSDR, 2007). Blood arsenic levels are not as well correlated with drinking water concentrations and speciation of the chemical forms of arsenic in blood is difficult (Valentine et al., 1979; WHO, 2001).

Chronic ingestion of drinking water contaminated with inorganic arsenic has been associated with decreased lung function, non-cancer skin effects, and cardiovascular effects including increased incidence of high blood pressure and circulatory problems (ATSDR, 2007; Environment Canada & Health Canada, 1993). In addition, increased incidences of skin cancer and various cancers of the internal organs have been associated with chronic ingestion of inorganic arsenic-contaminated drinking water (Health Canada, 2006). Much of the evidence comes from an epidemiological study conducted in southwestern Taiwan (Chen et al., 1985; Health Canada, 2006; Tseng, 1977; Wu et al., 1989). Arsenic and inorganic arsenic compounds are classified as carcinogenic to humans by Health Canada and other international agencies (EPA, 1998; Health Canada, 2006; IARC, 2012).

Although the majority of assessments on the toxicity of arsenic have concentrated on the inorganic forms, recent studies have highlighted the potential for organic arsenic compounds, in particular the pentavalent DMA, to exert carcinogenic effects (Cohen et al., 2006; IARC, 2012; Schwerdtle et al., 2003). The International Agency for Research on Cancer (IARC) has classified the methylated arsenic metabolites MMA and DMA as Group 2B, possibly carcinogenic to humans (IARC, 2012). IARC has also evaluated arsenobetaine and other organic arsenic compounds and found them to be not classifiable as to their carcinogenicity to humans (Group 3) (IARC, 2012).

Health Canada and Environment Canada concluded that arsenic in Canada may be harmful to the environment and may constitute a danger to human life or health (Environment Canada & Health Canada, 1993). Inorganic arsenic compounds are listed on Schedule 1, List of Toxic Substances, under the Canadian Environmental Protection Act, 1999 (CEPA 1999). The Act allows the federal government to control the importation, manufacture, distribution, and use of inorganic arsenic compounds in Canada (Canada, 1999; Canada, 2000). Risk management actions under CEPA 1999 have been developed to control releases of arsenic from thermal electric power generation, base-metal smelting, wood preservation, and steel manufacturing processes (Environment Canada, 2010). Arsenic and its compounds are included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011). The Food and Drug Regulations prohibit the sale in Canada of drugs for human use containing arsenic or any of its salts or derivatives (Canada, 2012). Further, the leachable arsenic content in a variety of consumer products is regulated under the Canada Consumer Product Safety Act (Canada, 2010a). These regulated consumer products include paints and other surface coatings on cribs, toys, and other products for use by a child in learning or play situations (Canada, 2010b; Canada, 2011).

Health Canada has developed a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of arsenic (Health Canada, 2006). The guideline was developed based on the incidence of internal (lung, bladder, and liver) cancers in humans and the ability of currently available treatment technologies to remove arsenic from drinking water (Health Canada, 2006). Arsenic is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply. The concentration of arsenic in some foods is regulated by Health Canada under the Food and Drug Regulations; current food tolerances are in the process of being updated (Canada, 2012).

In a study carried out in British Columbia to assess the levels of trace elements in 61 non-smoking adults aged 30 to 65 years, the geometric mean concentration and 95th percentile of total arsenic in urine were 27.8 µg/g creatinine and 175.5 µg/g creatinine, respectively (Clark et al., 2007). In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric mean of total arsenic in urine was 12.73 µg/L and in whole blood was 0.95 µg/L (INSPQ, 2004).

Total arsenic was measured in the urine of all Canadian Health Measures Survey (CHMS) participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented as both µg/L (Tables 8.2.1.1, 8.2.1.2, and 8.2.1.3) and µg/g creatinine (Tables 8.2.1.4, 8.2.1.5, and 8.2.1.6).

Arsenite (+3), arsenate (+5), and methylated metabolites of arsenic (MMA and DMA) were measured individually in the urine of all CHMS cycle 2 (2009-2011) participants aged 3 to 79 years. The data are presented as both μg/L and μg/g creatinine (Tables 8.2.2.1 to 8.2.5.4).

The organoarsenic compounds, arsenobetaine and arsenocholine, were measured together in the urine of all CHMS cycle 2 (2009-2011) participants aged 3 to 79 years. The data are presented as both μg/L and μg/g creatinine (Tables 8.2.6.1, 8.2.6.2, 8.2.6.3, and 8.2.6.4).

Finding a measurable amount of arsenic in urine is an indicator of exposure to arsenic and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary speciated arsenic, methylated arsenic metabolites, and organoarsenic compounds in the Canadian population.

8.2.1 Arsenic (total)

6 Data Tables: 8.2.1.1 to 8.2.1.6

8.2.2 Arsenite

4 Data Tables: 8.2.2.1 to 8.2.2.4

8.2.3 Arsenate

4 Data Tables: 8.2.3.1 to 8.2.3.4

8.2.4 Monomethylarsonic Acid (MMA)

4 Data Tables: 8.2.4.1 to 8.2.4.4

8.2.5 Dimethylarsinic Acid (DMA)

4 Data Tables: 8.2.5.1 to 8.2.5.4

8.2.6 Arsenocholine and Arsenobetaine

4 Data Tables: 8.2.6.1 to 8.2.6.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2007). Toxicological profile for arsenic. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 30, 2012, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=22&tid=3

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2000). Order adding a toxic substance to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part II: Official Regulations, 134 (7). Retrieved June 11, 2012, from www.gazette.gc.ca/archives/p2/2000/2000-03-29/html/sor-dors109-eng.html.

Canada. (2010a). Canada Consumer Product Safety Act. SC 2010, c. 21. Retrieved February 20, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-1.68/index.html

Canada. (2010b). Cribs, Cradles and Bassinets Regulations. SOR/2010-261. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2010-261/index.html

Canada. (2011). Toys Regulations. SOR/2011-17. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2011-17/index.html

Canada. (2012). Food and Drug Regulations. C.R.C., c. 870. Retrieved July 24, 2012, from http://laws-lois.justice.gc.ca/PDF/C.R.C.,_c._870.pdf

CCME (Canadian Council of Ministers of the Environment). (1997). Canadian soil quality guidelines for the protection of environmental and human health - Arsenic (inorganic). Winnipeg, MB. Retrieved April 30, 2012, from http://ceqg-rcqe.ccme.ca/download/en/257/

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Chen, C.-J., Chuang, Y.-C., Lin, T.-M., & Wu, H.-Y. (1985). Malignant neoplasms among residents of a blackfoot disease-endemic area in Taiwan: High-arsenic well water and cancers. Cancer Research, 45, 5895-5899.

Clark, N.A., Teschke, K., Rideout, K., & Copes, R. (2007). Trace element levels in adults from the west coast of Canada and associations with age, gender, diet, activities, and levels of other trace elements. Chemosphere, 70 (1), 155-164.

Cohen, S.M., Arnold, L.L., Eldan, M., Lewis, A.S., & Beck, B.D. (2006). Methylated arsenicals: The implications of metabolism and carcinogenicity studies in rodents to human risk assessment. Critical Reviews in Toxicology, 36 (2), 99-133.

Emsley, J. (2001). Nature's building blocks: An A-Z guide to the elements. Oxford University Press, Oxford.

Environment Canada. (2008). A case against arsenic-based pesticides. Minister of Environment, Ottawa, ON. Retrieved May 2, 2012, from www.ec.gc.ca/EnviroZine/default.asp?lang=En&n=B9657723-1

Environment Canada. (2010). List of toxic substances managed under CEPA (Schedule 1): Inorganic arsenic compounds. Minister of Environment, Ottawa, ON. Retrieved September 13, 2012 from www.ec.gc.ca/toxiques-toxics/Default.asp?lang=En&n=98E80CC6-1&xml=40B2B1A3-9B61-40EE-8746-CD949298CD0D

Environment Canada & Health Canada. (1993). Priority substances risk assessment report: Arsenic and its compounds. Minister of Supply and Services Canada, Ottawa, ON. Retrieved April 30, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/psl1-lsp1/arsenic_comp/index-eng.php

EPA (U.S. Environmental Protection Agency). (1998). Integrated Risk Information System (IRIS): Arsenic, inorganic. Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH. Retrieved April 30, 2012, from www.epa.gov/ncea/iris/subst/0278.htm

EPA (U.S. Environmental Protection Agency). (2006). Revised reregistration eligibility decision for MSMA, DSMA, CAMA, and cacodylic acid. Office of Prevention, Pesticides and Toxic Substances, Washington, DC. Retrieved May 1, 2012, from www.epa.gov/opp00001/reregistration/REDs/organic_arsenicals_red.pdf

Health Canada. (2005). Fact sheet on chromated copper arsenate (CCA) treated wood. Minister of Health, Ottawa, ON. Retrieved April 30, 2012, from www.hc-sc.gc.ca/cps-spc/pubs/pest/_fact-fiche/cca-acc/index-eng.php

Health Canada. (2006). Guidelines for Canadian drinking water quality: Guideline technical document - Arsenic. Minister of Health, Ottawa, ON. Retrieved April 30, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/arsenic/index-eng.php

Health Canada. (2009). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2011). List of prohibited and restricted cosmetic ingredients ("hotlist"). Minister of Health, Ottawa, ON. Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

Health Canada. (2012). Pesticide product information database. Minister of Health, Ottawa, ON. Retrieved April 20, 2012, from www.pr-rp.hc-sc.gc.ca/pi-ip/index-eng.php

Human Biomonitoring Commission (2003). Substance monograph: Arsenic - Reference value in urine. German Federal Environmental Agency, Germany. Retrieved April 30, 2012, from www.umweltdaten.de/gesundheit-e/monitor/39e.pdf

IARC (International Agency for Research on Cancer). (2012). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 100C: Arsenic, metals, fibres, and dusts. World Health Organization, Geneva.

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

Rasmussen, P.E., Subramanian, K.S., & Jessiman, B.J. (2001). A multi-element profile of house dust in relation to exterior dust and soils in the city of Ottawa, Canada. Science of the Total Environment, 267 (1-3), 125-140.

Schwerdtle, T., Walter, I., Mackwin, I., & Hartwig, A. (2003). Induction of oxidative DNA damage by arsenite and its trivalent and pentavalent methylated metabolites in cultured human cells and isolated DNA. Carcinogenesis, 24 (5), 967-974.

Tseng, W. (1977). Effects and dose-response relationships of skin cancer and blackfoot disease with arsenic. Environmental Health Perspectives, 19, 109-119.

Valentine, J.L., Kang, H.K., & Spivey, G. (1979). Arsenic levels in human blood, urine, and hair in response to exposure via drinking water. Environmental Research, 20 (1), 24-32.

WHO (World Health Organization). (2001). Environmental health criteria 224: Arsenic and arsenic compounds. WHO, Geneva. Retrieved January 4, 2012, from www.inchem.org/documents/ehc/ehc/ehc224.htm

WHO (World Health Organization). (2011). Guidelines for drinking-water quality, fourth edition. WHO, Geneva. Retrieved March 9, 2012, from www.who.int/water_sanitation_health/publications/2011/dwq_guidelines/en/index.html

Wu, M.M., Kuo, T.L., Hwang, Y.H., & Chen, C.J. (1989). Dose-response relation between arsenic concentration in well water and mortality from cancer and vascular diseases. American Journal of Epidemiology, 130, 1123-1132.

8.3 Cadmium

Cadmium (CASRN 7440-43-9) is among the least abundant metals in the Earth's crust at an average concentration of approximately 0.00001% (Emsley, 2001). It is a naturally occurring soft, silvery white, blue-tinged metal. Cadmium often occurs in zinc ores (Health Canada, 1986). Common forms include soluble and insoluble species that may also be found as particulate matter in the atmosphere (ATSDR, 2008; CCME, 1999).

Cadmium is released to the environment as a result of natural processes, including forest fires, volcanic emissions, and weathering of soil and bedrock (Morrow, 2000). The main anthropogenic sources of atmospheric cadmium are industrial base-metal smelting and refining processes, and combustion processes such as coal-fired electrical plants and waste incineration where cadmium is released as a by-product (CCME, 1999).

Cadmium is primarily used in the manufacture of nickel-cadmium batteries (USGS, 2012). It is also used in industrial coatings and electroplating, in pigments, and as a stabilizer in polyvinyl chloride plastics. Cadmium is present in metal alloy sheets, wires, rods, solders, and shields for various industrial applications (Environment Canada & Health Canada, 1994). It is also sometimes used as a pigment in ceramic glazes. Cadmium may also be present in fertilizers as the result of recycling of by-products and waste materials for land application. It is frequently an impurity in galvanized pipes and can leach into drinking water (Health Canada, 1986).

In smokers, inhalation of cigarette smoke is the major source of cadmium exposure (Environment Canada & Health Canada, 1994; IARC, 2012). For non-smoking adults and children, the largest source of cadmium exposure is through the ingestion of food (IARC, 2012). Ambient air is a minor source of exposure with intakes estimated to be two to three orders of magnitude lower than food, although cadmium compounds are more readily absorbed following inhalation than ingestion (Friberg, 1985). Other minor sources of exposure include ingestion of drinking water, soil, or dust (ATSDR, 2008; Environment Canada & Health Canada, 1994).

Absorption of dietary cadmium into the bloodstream depends on an individual's nutritional status and the levels of other components of the diet such as iron, calcium, and protein. The average gastrointestinal absorption of dietary cadmium is estimated at 5% in adult men and 10% or higher in women (CDC, 2009). About 25% to 60% of inhaled cadmium is absorbed through the lungs (ATSDR, 2008). Absorbed cadmium accumulates mainly in the kidney and liver, with approximately one-third to one-half of the total body burden accumulating in the kidney (CDC, 2009). The biological half-life of cadmium in the kidney has been estimated to be approximately 10 to 12 years (Amzal et al., 2009; Lauwerys et al., 1994). Only a small proportion of absorbed cadmium is eliminated, mainly in the urine and feces with small amounts also eliminated through hair, nails, and sweat.

Cadmium can be measured in blood, urine, feces, liver, kidney, and hair among other tissues. Cadmium concentrations in urine best reflect cumulative exposure and the concentration of cadmium in the kidney, although slight fluctuations occur with recent exposures (CDC, 2009). Concentrations in blood reflect both recent and cumulative exposures (CDC, 2009). Blood cadmium concentrations are about twice as high in smokers compared with non-smokers; concentrations can also be elevated following occupational exposures (ATSDR, 2008).

Oral exposure to high doses of cadmium may cause severe gastrointestinal irritation and kidney effects (ATSDR, 2008). Chronic exposure via inhalation has been associated with effects in the lungs, including emphysema, and in the kidneys (ATSDR, 2008). The kidney is the critical organ that exhibits the first adverse effects following both oral and inhalation exposure (Lauwerys et al., 1994).

Cadmium and its compounds have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer, based on various data including associations between occupational inhalation exposure and lung cancer (IARC, 2012). There is insufficient evidence to determine whether or not cadmium is carcinogenic following oral exposure (ATSDR, 2008).

Health Canada and Environment Canada concluded that inorganic cadmium compounds are a concern for human health (Environment Canada & Health Canada, 1994). Inorganic cadmium compounds are listed on Schedule 1, List of Toxic Substances, under the Canadian Environmental Protection Act, 1999 (CEPA 1999). The Act allows the federal government to control the importation, manufacture, distribution, and use of inorganic cadmium compounds in Canada (Canada, 1999; Canada, 2000). Risk management actions under CEPA 1999 have been developed to control releases of cadmium from thermal electric power generation, base-metal smelting, and steel manufacturing processes (Environment Canada, 2010).

In Canada, the leachable cadmium content in a variety of consumer products is regulated under the Canada Consumer Product Safety Act (Canada, 2010a). Consumer products regulated for leachable cadmium content include glazed ceramics and glassware, as well as paints and other surface coatings on cribs, toys, and other products for use by a child in learning or play situations (Canada, 1998; Canada, 2010b; Canada, 2011; Health Canada, 2009a). In addition, since children's jewellery items containing high levels of cadmium have been found on the Canadian marketplace, a guideline limit for total cadmium in children's jewellery was proposed by Health Canada in 2011 (Health Canada, 2011a). Cadmium and its compounds are included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011b). On the basis of health considerations, Health Canada has developed a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of cadmium (Health Canada, 1986). Cadmium is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009b). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric means for cadmium in urine and whole blood were 0.54 µg/L and 0.69 µg/L, respectively (INSPQ, 2004).

Cadmium was measured in the whole blood and urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as μg/L (Tables 8.3.1, 8.3.2, and 8.3.3) and in urine as both µg/L (Tables 8.3.4, 8.3.5, and 8.3.6) and µg/g creatinine (Tables 8.3.7, 8.3.8, and 8.3.9). Finding a measurable amount of cadmium in blood or urine is an indicator of exposure to cadmium and does not necessarily mean that an adverse health effect will occur.

9 Data Tables: 8.3.1 to 8.3.9

References

Amzal, B., Julin, B., Vahter, M., Wolk, A., Johanson, G., & Akesson, A. (2009). Population toxicokinetic modeling of cadmium for health risk assessment. Environmental Health Perspectives, 117 (8), 1293-1301.

ATSDR (Agency for Toxic Substances and Disease Registry). (2008). Draft toxicological profile for cadmium. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved January 12, 2012, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=48&tid=15

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1998). Glazed Ceramics and Glassware Regulations. SOR/98-176. Retrieved February 20, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-98-176/page-1.html

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2000). Order adding a toxic substance to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part II: Official Regulations, 134 (7). Retrieved June 11, 2012, from www.gazette.gc.ca/archives/p2/2000/2000-03-29/html/sor-d

Canada. (2010a). Canada Consumer Product Safety Act. SC 2010, c. 21. Retrieved February 20, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-1.68/index.html

Canada. (2010b). Cribs, Cradles and Bassinets Regulations. SOR/2010-261. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2010-261/index.html

Canada. (2011). Toys Regulations. SOR/2011-17. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2011-17/index.html

CCME (Canadian Council of Ministers of the Environment). (1999). Canadian soil quality guidelines for the protection of environmental and human health - Cadmium. Winnipeg, MB. Retrieved January 24, 2012, from http://ceqg-rcqe.ccme.ca/download/en/261/

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Emsley, J. (2001). Nature's building blocks: An A-Z guide to the elements. Oxford University Press, Oxford.

Environment Canada. (2010). List of toxic substances managed under CEPA (Schedule 1): Inorganic cadmium compounds. Minister of Environment, Ottawa, ON. Retrieved September 13, 2012 from www.ec.gc.ca/toxiques-toxics/Default.asp?lang=En&n=98E80CC6-1&xml=B1F78D6F-21C9-470B-AB05-FFCB5B215D3C

Environment Canada & Health Canada. (1994). Priority substances list assessment report: Cadmium and its compounds. Minister of Supply and Services Canada, Ottawa, ON. Retrieved January 24, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/psl1-lsp1/cadmium_comp/index-eng.php

Friberg, L. (1985). Cadmium and health: A toxicological and epidemiological appraisal. CRC Press, Boca Raton, FL.

Health Canada. (1986). Guidelines for Canadian drinking water quality: Guideline technical document - Cadmium. Minister of Health, Ottawa, ON. Retrieved January 24, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/cadmium/index-eng.php

Health Canada. (2009a). Notice regarding Canada's legislated safety requirements related to heavy metal content in surface coating materials applied to children's toys. Minister of Health, Ottawa, ON. Retrieved January 24, 2012, from www.hc-sc.gc.ca/cps-spc/advisories-avis/info-ind/heavy_met-lourds-eng.php

Health Canada. (2009b). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2011a). Draft proposal for Cadmium guideline in children's jewellery. Minister of Health, Ottawa, ON. Retrieved July 23, 2012, from www.hc-sc.gc.ca/cps-spc/legislation/consultation/_2011cadmium/draft-ebauche-eng.php

Health Canada. (2011b). List of prohibited and restricted cosmetic ingredients ("hotlist"). Minister of Health, Ottawa, ON. Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

IARC (International Agency for Research on Cancer). (2012). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 100C: Arsenic, metals, fibres, and dusts. World Health Organization, Geneva.

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

Lauwerys, R.R., Bernard, A.M., Roels, H.A., & Buchet, J.P. (1994). Cadmium: Exposure markers as predictors of nephrotoxic effects. Clinical Chemistry, 40 (7), 1391-1394.

Morrow, H. (2000). Cadmium and cadmium alloys. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc, Mississauga, ON.

USGS (U.S. Geological Survey). (2012). Mineral commodity summaries 2012. Reston, VA. Retrieved April 16, 2012, from http://minerals.usgs.gov/minerals/pubs/mcs/2012/mcs2012.pdf

8.4 Cesium

Cesium (CASRN 7440-46-2) is a naturally occurring rare alkali metal present in the Earth's crust at an average concentration of approximately 0.0001% (ATSDR, 2004). In its pure form, cesium is a silvery white, soft, and ductile metal. Pure cesium metal is not expected to be found in the environment as it ignites spontaneously in air and reacts vigorously with water to form cesium hydroxide (Ferguson & Gorrie, 2011). There are 11 major radioactive isotopes of cesium, the two most important of which are cesium 134 and cesium 137. In the environment, cesium is naturally present as a stable non-radioactive isotope in various ores and to a lesser extent in soil. Unlike pure cesium, cesium compounds do not react violently in air and are generally very water soluble.

Cesium can be naturally released into the environment through weathering and erosion of cesium-containing minerals (ATSDR, 2004). In addition to natural sources, cesium is released into the atmosphere through human activities such as mining and manufacturing (ATSDR, 2004). Radioactive forms of cesium are produced as by-products during the operation of nuclear power plants and from the use of nuclear weapons (ATSDR, 2004).

Cesium has very few industrial applications. Its principal use is in formate brines used for oil and gas drilling and exploration (IARC, 2001). Cesium compounds are used in research and development, and are used commercially in biomedical, chemical, and electronic applications (USGS, 2012). Radioactive cesium isotopes are used to treat prostate and other cancers, and a number of industries rely on cesium 137 as a component in industrial gauges and for the sterilization of food, sewage, and surgical equipment. Non-radioactive cesium chloride is sometimes used as a natural health product for self-treatment of cancer, although its use as a therapeutic agent is not authorized in Canada (Painter et al., 2008).

In the general population, exposure to cesium can occur via ingestion of food and drinking water, inhalation of ambient air, and dermal contact (ATSDR, 2004). Oral ingestion of food items is the greatest source of internal exposure for both naturally occurring and radioactive cesium (ATSDR, 2004).

Following ingestion, cesium is almost completely absorbed by the intestine. Absorbed cesium undergoes widespread distribution in the body. The majority of absorbed cesium is excreted via urine with a small portion released in feces (ATSDR, 2004). Recent exposure can be evaluated by measuring cesium concentrations in urine (ATSDR, 2004).

Health effects in humans associated with exposure to high levels of stable cesium include nausea, diarrhea, and loss of appetite (Neulieb, 1984). Several reports of cardiac effects have also been associated with repeated oral intake of cesium chloride for unauthorized therapeutic use (Painter et al., 2008). Results from a number of animal studies have shown a relatively low acute toxicity of cesium and its compounds (ATSDR, 2004).

The primary health effects of exposure to radioactive cesium are related to the emission of ionizing radiation, a human carcinogen (IARC, 2001; IARC, 2012). The International Agency for Research on Cancer determined that there is sufficient evidence in laboratory animals to classify the cesium 137 radioisotope as Group 1, carcinogenic to humans (IARC, 2001).

On the basis of health considerations, Health Canada has developed a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of cesium 137 (Health Canada, 2009a; Health Canada, 2012). Health Canada has also calculated maximum acceptable concentrations for cesium 131, cesium 134, and cesium 136 (Health Canada, 2009a). However, because these isotopes are not expected to be found in Canadian drinking water sources, the concentrations represent the theoretical level at which potential health effects could occur and have been calculated for information purposes only (Health Canada, 2009a). Cesium is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009b). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply. In addition, Health Canada has developed cesium radionuclide action levels for various foods (Health Canada, 2000).

Cesium was measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 8.4.1, 8.4.2, 8.4.3, and 8.4.4). Finding a measurable amount of cesium in urine is an indicator of exposure to cesium and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary cesium levels in the Canadian population.

4 Data Tables: 8.4.1 to 8.4.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2004). Toxicological profile for cesium. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=578&tid=107

Ferguson, W. & Gorrie, D. (2011). Cesium and cesium compounds. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc, Mississauga, ON.

Health Canada. (2000). Canadian guidelines for the restriction of radioactively contaminated food and water following a nuclear emergency. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/emergency-urgence/index-eng.php

Health Canada. (2009a). Guidelines for Canadian drinking water quality: Guideline technical document - Radiological parameters. Minister of Health, Ottawa, ON. Retrieved July 11, 2011, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/radiological_para-radiologiques/index-eng.php

Health Canada. (2009b). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2012). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

IARC (International Agency for Research on Cancer). (2001). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 78: Ionizing radiation, Part 2, some internally deposited radionuclides. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (2012). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 100D: Radiation. World Health Organization, Geneva.

Neulieb, R. (1984). Effects of oral intake of cesium chloride: A single case report. Pharmacology Biochemistry and Behavior, 21 (Supplement 1), 15-16.

Painter, D., Berman, E., & Pilon, K. (2008). Cesium chloride and ventricular arrhythmias. Canadian Adverse Reaction Newsletter, 18 (4), 3-4.

USGS (U.S. Geological Survey). (2012). Mineral commodity summaries 2012. Reston, VA. Retrieved April 16, 2012, from http://minerals.usgs.gov/minerals/pubs/mcs/2012/mcs2012.pdf

8.5 Cobalt

Elemental cobalt (CASRN 7440-48-4) is a hard, silvery grey metal with magnetic properties. It is present in the Earth's crust at an average concentration of approximately 0.0025%, and occurs naturally in various mineral forms (ATSDR, 2004). Cobalt minerals occur in nature in other metal deposits (particularly copper and nickel) generally as sulfides, oxides, or arsenides (IARC, 1991). It has several radioisotopes, two of which are commercially important: cobalt 57 and cobalt 60. Cobalt is an essential trace element required for the maintenance of good health in humans.

Cobalt is naturally released into the environment through leaching from soil, airborne dust, sea spray, volcanic eruptions, and forest fires (ATSDR, 2004). Significant quantities of cobalt are also released as by-products of the mining industry. Other anthropogenic sources of cobalt include burning of fossil fuels, smelting and refining of cobalt ores, and processing of cobalt alloys (ATSDR, 2004).

In Canada, cobalt is primarily used in industrial raw materials (Environment Canada & Health Canada, 2011). Elemental cobalt is a component in alloys that are used to manufacture gas turbines for aircraft engines and hard metals for tools. Cobalt is also used to manufacture pigments and fertilizers and as a drying agent in paint, varnishes, and inks. Cobalt compounds are used as catalysts in oil and gas refining and in the synthesis of polyester and other materials. They are also used in the manufacture of battery electrodes, steel-belted radial tires, car airbags, diamond polishing wheels, and magnetic recording media. Cobalt 60 is used as a source of gamma rays for food irradiation, sterilization of medical and consumer products, and radiation treatment of cancer, whereas the use of cobalt 57 is limited to medical and scientific research (ATSDR, 2004; Richardson, 2003).

Cobalt exposure in the general population occurs primarily through food and to a lesser degree through drinking water and air (ATSDR, 2004). Soluble cobalt compounds are absorbed via oral or pulmonary routes. Absorption of cobalt via the gastrointestinal tract varies considerably (18% to 97% of the given dose), based on the type and dose of cobalt compound and the nutritional status of the subjects (ATSDR, 2004). The majority of absorbed cobalt is excreted through urine within several days. However, a small amount of the element may be retained in the body with a biological half-life varying between 2 and 15 years (IARC, 2006). As a component of vitamin B12, cobalt is found in most body tissues with the highest concentrations observed in the liver (ATSDR, 2004). Urinary cobalt can be used as a biomarker of recent exposure to soluble cobalt compounds (CDC, 2009).

As an essential trace element, cobalt has a functional role in vitamin B-12; this vitamin helps the body form red blood cells and metabolize carbohydrates, fats, and proteins. Vitamin B12 deficiency results in the development of pernicious anemia. The cobalt in vitamin B 12 does not exchange with cobalt in the blood and no other essential functions for cobalt are known. On account of its essentiality, Health Canada has recommended minimum and maximum daily intake levels of cobalt in the form of vitamin B12 (Health Canada, 2007).

Adverse health effects have been traced to elevated levels of cobalt compounds from non-occupational exposures. Cobalt sulphate and cobalt chloride were used in the 1950s and 1960s in the United States, Canada, and Europe as a foam stabilizer in beer. During that time, several cases of lethal cardiomyopathy were documented in heavy beer drinkers (Alexander, 1972). Altered thyroid function associated with cardiomyopathy has also been observed following cobalt exposure over a period of a few weeks (ATSDR, 2004; Roy et al., 1968).

Several cancer studies for workers in hard-metal production facilities provide evidence of an increased lung cancer risk related to exposure to hard-metal dust containing cobalt and tungsten carbide (IARC, 2006; IPCS, 2006). In 1991, the International Agency for Research on Cancer (IARC) has classified cobalt and its compounds as Group 2B, possibly carcinogenic to humans, based on inadequate evidence linking exposure and lung cancer in humans but with limited or sufficient evidence in animals for some specific cobalt compounds (IARC, 1991). In 2006, IARC evaluated the exposure of cobalt metal with tungsten carbide as Group 2A, probably carcinogenic to humans (IARC, 2006). Cobalt metal without tungsten carbide as well as cobalt salts were also re-evaluated in 2006 and continue to be classified as Group 2B, based on inadequate evidence of carcinogenicity in humans (IARC, 2006).

As part of the Chemicals Management Plan under the Canadian Environmental Protection Act, 1999, elemental cobalt, cobalt chloride, and cobalt sulphate were identified as high-priority substances; the final screening assessment was published in 2011 (Canada, 1999; Environment Canada & Health Canada, 2011). The assessment concluded that levels of cobalt normally found in the Canadian environment are not considered harmful to human health (Environment Canada & Health Canada, 2011). This assessment is the starting point for an assessment of all sources of environmental cobalt that is currently in preparation as part of the Chemicals Management Plan; a draft assessment is expected to be published in 2014.

Radioactive isotopes of cobalt are used by industry and in research. These radionuclides are not expected to be found in Canadian drinking water sources, and exposure to the general public is limited to rare cases of accidental loss, theft, or damage of contained sources (Health Canada, 2009a; IARC, 2012). The health effects of exposure to radioactive cobalt are related to the emission of ionizing radiation, a human carcinogen (IARC, 2012).

Health Canada has developed Canadian drinking water quality guidelines that set out the maximum acceptable concentrations of cobalt 57 and cobalt 60. Because these isotopes are not expected to be found in Canadian drinking water sources, the concentrations represent the theoretical level at which potential health effects could occur and have been calculated for information purposes only (Health Canada, 2009a). Cobalt is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009b). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply. In addition, Health Canada has developed cobalt radionuclide action levels for various foods (Health Canada, 2000).

In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric means for cobalt in urine and whole blood were below the detection limits of 0.35 µg/L and 0.18 µg/L, respectively (INSPQ, 2004).

Cobalt was measured in the whole blood and urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented in blood as μg/L (Tables 8.5.1 and 8.5.2) and in urine as both µg/L and µg/g creatinine (Tables 8.5.3, 8.5.4, 8.5.5, and 8.5.6). Finding a measurable amount of cobalt in blood or urine is an indicator of exposure to cobalt and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for blood and urinary cobalt in the Canadian population.

6 Data Tables: 8.5.1 to 8.5.6

References

Alexander, C.S. (1972). Cobalt-beer cardiomyopathy: A clinical and pathologic study of twenty-eight cases. The American Journal of Medicine, 53 (4), 395-417.

ATSDR (Agency for Toxic Substances and Disease Registry). (2004). Toxicological profile for cobalt. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=373&tid=64

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Environment Canada & Health Canada. (2011). Screening assessment for the challenge: Cobalt (elemental cobalt); cobalt chloride; sulfuric acid, cobalt (2+) salt (1:1) (cobalt sulfate); sulfuric acid, cobalt salt (cobalt sulfate). July 11, 2011, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=8E18277B-1

Health Canada. (2000). Canadian guidelines for the restriction of radioactively contaminated food and water following a nuclear emergency. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/emergency-urgence/index-eng.php

Health Canada (2007). Multi-vitamin/mineral supplement monograph. Minister of Health, Ottawa, ON. Retrieved July 11, 2011, from www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/multi_vitmin_suppl-eng.php

Health Canada. (2009a). Guidelines for Canadian drinking water quality: Guideline technical document - Radiological parameters. Minister of Health, Ottawa, ON. Retrieved July 11, 2011, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/radiological_para-radiologiques/index-eng.php

Health Canada. (2009b). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

IARC (International Agency for Research on Cancer). (1991). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 52: Chlorinated drinking-water; chlorination by-products; some other halogenated compounds; cobalt and cobalt compounds. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (2006). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 86: Cobalt in hard metals and cobalt sulfate, gallium arsenide, indium phosphide and vanadium pentoxide. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (2012). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 100D: Radiation. World Health Organization, Geneva.

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

IPCS (International Programme on Chemical Safety). (2006). Concise international chemical assessment document 69: Cobalt and inorganic cobalt compounds. World Health Organization, Geneva. Retrieved July 11, 2011, from www.who.int/ipcs/publications/cicad/cicad69%20.pdf

Richardson, H.W. (2003). Cobalt compounds. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc, Mississauga, ON.

Roy, P.E., Bonenfant, J.L., & Turcot, L. (1968). Thyroid changes in cases of Quebec beer drinkers myocardosis. American Journal of Clinical Pathology, 50, 234-239.

8.6 Copper

Copper (CASRN 7440-50-8) is a base metal present in the Earth's crust at an average concentration of approximately 0.005% (ATSDR, 2004). Pure copper is a reddish, lustrous, malleable, and ductile metal, whereas many copper compounds have a blue-green colour (CCME, 1999). Copper is an essential trace element required for the maintenance of good health in humans.

Copper occurs naturally in rock, soil, sediment, water, plants, and animals (CCME, 1999). It is released from natural sources including volcanoes, decaying vegetation, and forest fires (ATSDR, 2004). It is also released from anthropogenic sources such as mining, farming, manufacturing operations, and combustion of fuels and other copper-containing materials.

Copper is mined extensively for use in the manufacture of brass, bronze, gunmetal, and nickel alloys (ATSDR, 2004). Copper alloys are used in sheet metal, piping, and electrical conductors. Copper and copper alloys are also used in cooking utensils, coins, anti-fouling paint, dental amalgams, plumbing fixtures and pipes, and architectural applications such as roofing, guttering, and flashing. In addition, copper compounds are important chemicals in the textile, petroleum refining, wood preservative, and agricultural industries (ATSDR, 2004; CCME, 1999; IPCS, 1998).

For the general population, most exposure to copper originates from the ingestion of food (ATSDR, 2004). Additional exposure may result from inhalation of dust particles and ingestion of drinking water (CCME, 1999).

Approximately 24% to 60% of copper is absorbed following oral ingestion; absorption is affected by a number of factors, including age, the amount of copper in the diet, and the presence of other metals (ATSDR, 2004; IPCS, 1998). Following ingestion, absorbed copper is bound to plasma protein carriers and transported to the liver. Copper is then redistributed from the liver to other tissues where it is stored bound to metallothionein and amino acids (ATSDR, 2004). Elimination of copper is biphasic with a biological half-life in the plasma of 2.5 and 69 days for the first and second phases, respectively (ATSDR, 2004). Bile is the major excretory route for copper; up to 70% of orally ingested copper may be excreted in the feces. Normally 0.5% to 3.0% of daily copper intake is excreted in the urine (ATSDR, 2004). Exposure to copper can lead to increased copper concentrations in whole blood, serum, urine, feces, hair, and the liver. Concentrations in serum have been observed to decrease rapidly after exposure, indicating that they may reflect only recent exposures (ATSDR, 2004).

As an essential trace element, copper is required for growth and proper functioning of many physiological processes, including cellular respiration, iron metabolism, antioxidant defence, connective tissue development, and neurotransmitter production (IPCS, 1998). Overt copper deficiency is relatively rare, but has been associated with effects such as anaemia, neutropenia, and bone abnormalities (IPCS, 1998).

High doses of copper may result in adverse effects, although chronic and acute toxic effects from copper are rare in the general population (ATSDR, 2004). Hemodialysis patients, individuals with the genetic disorder Wilson's disease, and those with chronic liver disease may be more susceptible to copper toxicity (IPCS, 1998). High copper intake can result in liver damage; however, this is observed almost exclusively in patients with Wilson's disease and in children with Indian childhood cirrhosis and idiopathic copper toxicosis (IOM, 2001). Acute oral exposure to copper has been associated with nausea, vomiting, and diarrhea (ATSDR, 2004; Olivares et al., 2001). When inhaled, copper is a respiratory tract irritant (ATSDR, 2004).

The International Agency for Research on Cancer has not reviewed copper for its carcinogenic potential (ITER, 2010). The United States Environmental Protection Agency has concluded that human and animal data were inadequate to assess the carcinogenicity of copper and copper compounds (EPA, 1988).

Maximum levels for copper in dietary supplement formulations (tablets, capsules, etc.) have been established in Canada (Health Canada, 2007). The sale and use of copper-containing pesticides is regulated in Canada by the Pest Management Regulatory Agency (PMRA) under the Pest Control Products Act (Canada, 2006). In 2009, PMRA initiated a re-evaluation of a number of copper-based active ingredients in pesticide products with agricultural or antimicrobial uses (Health Canada, 2009a). Based on this re-evaluation, PMRA has proposed to conclude that pesticides containing these forms of copper do not present unacceptable risks to human health when used according to label directions and provided that risk-reduction measures are implemented (Health Canada, 2009a).

Tolerable upper intake levels for copper, based on liver damage as the critical adverse effect, have been developed by the Institute of Medicine and adopted by Health Canada (Health Canada, 2010; IOM, 2001). Health Canada has also established an aesthetic objective for copper in drinking water, based on palatability and staining of laundry and plumbing fixtures (Health Canada, 1992). This guideline was deemed protective of adverse health effects, but a health-based value has not been established (Health Canada, 1992). Copper is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009b). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

In a study carried out in British Columbia to assess the levels of trace elements in 61 non-smoking adults aged 30 to 65 years, the geometric mean and 95th percentile values of copper in urine were 10.67 µg/g creatinine and 19.66 µg/g creatinine, respectively (Clark et al., 2007).

Copper was measured in the whole blood and urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as μg/L (Tables 8.6.1, 8.6.2, and 8.6.3) and in urine as both µg/L (Tables 8.6.4, 8.6.5, and 8.6.6) and µg/g creatinine (Tables 8.6.7, 8.6.8, and 8.6.9). Finding a measurable amount of copper in blood or urine is an indicator of exposure to copper and does not necessarily mean that an adverse health effect will occur. Because copper is an essential trace element, its presence in biological fluids is expected.

9 Data Tables: 8.6.1 to 8.6.9

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2004). Toxicological profile for copper. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved March 26, 2012, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=206&tid=37

Canada. (2006). Pest Control Products Act. SC 2002, c. 28. Retrieved May 30, 2012, from http://laws-lois.justice.gc.ca/eng/acts/P-9.01/

CCME (Canadian Council of Ministers of the Environment). (1999). Canadian soil quality guidelines for the protection of environmental and human health - Copper. Winnipeg, MB. Retrieved March 26, 2012, from http://ceqg-rcqe.ccme.ca/download/en/263/

Clark, N.A., Teschke, K., Rideout, K., & Copes, R. (2007). Trace element levels in adults from the west coast of Canada and associations with age, gender, diet, activities, and levels of other trace elements. Chemosphere, 70 (1), 155-164.

EPA (U.S. Environmental Protection Agency). (1988). Integrated Risk Information System (IRIS): Copper. Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH. Retrieved March 26, 2012, from www.epa.gov/ncea/iris/subst/0368.htm

Health Canada. (1992). Guidelines for Canadian drinking water quality: Guideline technical document - Copper. Minister of Health, Ottawa, ON. Retrieved March 26, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/copper-cuivre/index-eng.php

Health Canada. (2007). Multi-vitamin/mineral supplement monograph. Minister of Health, Ottawa, ON. Retrieved July 11, 2011, from www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/multi_vitmin_suppl-eng.php

Health Canada. (2009a). Consultation document on copper pesticides - Proposed re-evaluation decision - PRVD2009-04. Minister of Health, Ottawa, ON. Retrieved June 7, 2012, from www.hc-sc.gc.ca/cps-spc/pest/part/consultations/_prvd2009-04/copper-cuivre-eng.php#whatcopper

Health Canada. (2009b). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2010). Dietary reference intakes. Minister of Health, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/fn-an/nutrition/reference/table/index-eng.php

IOM (Institute of Medicine). (2001). Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press, Washington, DC.

IPCS (International Programme on Chemical Safety). (1998). Environmental health criteria 200: Copper. World Health Organization, Geneva. Retrieved March 26, 2012, from www.inchem.org/documents/ehc/ehc/ehc200.htm

ITER (International Toxicity Estimates for Risk). (2010). ITER database: Copper (CAS 7440-50-8). National Library of Medicine, Bethesda, MD. Retrieved May 15, 2012, from www.toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?iter

Olivares, M., Araya, M., Pizarro, F., & Uauy, R. (2001). Nausea threshold in apparently healthy individuals who drink fluids containing graded concentrations of copper. Regulatory Toxicology and Pharmacology, 33 (3), 271-275.

8.7 Fluoride

Fluorine (CASRN 16984-48-8) is the 13th most abundant element, occurring naturally in the Earth's crust at an average concentration of about 0.09% (ATSDR, 2003). It is widely distributed and naturally occurring, but it is rarely found in nature because it reacts readily with most organic and inorganic substances. Fluorides are formed when fluorine reacts with metals. Four inorganic fluorides of environmental importance are calcium fluoride (fluorspar and fluorite), sodium fluoride, sulphur hexafluoride, and hydrogen fluoride (Cotton & Wilkinson, 1988; Mackay & Mackay, 1989).

Fluorides are found in rocks, coal, clay, and soil. Gases and particles produced from volcanic eruptions and minerals leached from bedrock release inorganic fluorides into the environment (ATSDR, 2003; CCME, 2002). In addition to these natural sources, inorganic fluorides are released through human activities such as phosphate fertilizer production, chemical production, and aluminum smelting (Environment Canada & Health Canada, 1993).

Hydrogen fluoride is one of the most commonly used fluoride compounds; it is a component in the production of refrigerants, herbicides, pharmaceuticals, aluminum, plastics, high-octane gasoline, electrical components, and fluorescent light bulbs (ATSDR, 2003). In water, hydrogen fluoride becomes hydrofluoric acid, which is used in the metal and glass manufacturing industries (ATSDR, 2003). Calcium fluoride is used in the production of steel, aluminum, glass, and enamel, and as the raw material for the production of hydrofluoric acid and hydrogen fluoride (CCME, 2002). Sodium fluoride is often added to drinking water and dental products to prevent dental cavities. Toothpastes are the most commonly used dental product that contain fluoride (Health Canada, 2010a). Other fluoride-containing dental products available to consumers include fluoride supplements, fluoride mouth rinses, and dental floss. Sodium fluoride is also used as a preservative in wood and glues and in the production of glass, enamel, steel, and aluminum (CCME, 2002). Sulphur hexafluoride is used extensively in electrical switch gear such as power circuit breakers, compressed gas transmission lines, and various components in electrical substations (CCME, 2002).

Fluoride compounds are ubiquitous in the environment; however, the major sources of exposure to the general population are water, food, beverages, and dental products (Health Canada, 2010a). Following ingestion of soluble fluoride salts and inhalation of gaseous hydrogen fluoride, fluoride is rapidly and efficiently absorbed (ATSDR, 2003). Once absorbed, fluoride is rapidly distributed throughout the body via the bloodstream (ATSDR, 2003). In infants, about 80% to 90% of the total absorbed fluoride is retained in bones and teeth with the level dropping to about 60% in adults (Fawell et al., 2006). The remaining fluoride in adults and infants is excreted through urine (ATSDR, 2003). The biological half-life of fluoride is on the order of several hours (ATSDR, 2003; NRC, 2006). Urine and blood analyses are the most common tests for fluoride exposure (ATSDR, 2003).

The primary adverse effects associated with chronic excess fluoride intake are dental and skeletal fluorosis (IOM, 1997). Exposure to excessive levels of fluoride over a very long period of time can lead to skeletal fluorosis characterized by dense bones, joint pain, and limited range of joint movement (ATSDR, 2003). Dense bones are often more brittle or fragile than normal bones and there is an increased risk of bone fractures in older adults. Dental fluorosis is a dose-response effect caused by fluoride ingestion during tooth formation that becomes apparent upon eruption of the teeth. The effects of dental fluorosis can range from mild discolouration of the tooth surface to severe staining, enamel loss, and pitting (NRC, 2006).

Health Canada found that the weight of evidence from existing scientific data does not support an association between fluoride and increased risks of cancer, and has classified fluoride in Group VI, unclassifiable with respect to carcinogenicity in humans (Health Canada, 2010a). Similarly, the International Agency for Research on Cancer has classified fluorides (inorganic, used in drinking water) as Group 3, not classifiable as to its carcinogenicity to humans (IARC, 1987).

Health Canada and Environment Canada have reviewed and assessed inorganic fluorides under the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999). The screening assessment concluded that levels of inorganic fluorides normally found in the Canadian environment are not considered harmful to human health but are a concern for the environment (Environment Canada & Health Canada, 1993). Inorganic fluorides are listed on Schedule 1, List of Toxic Substances, under CEPA 1999. The Act allows the federal government to control the importation, manufacture, distribution, and use of inorganic fluorides in Canada (Canada, 1999; Canada, 2000).

Health Canada does not consider fluoride to be an essential element and recommends that fluoride requirements be based only on the beneficial effect on dental caries (Health Canada, 2010a). Young children tend to swallow toothpaste during brushing, so guidelines have been established that strive to balance the health risks with the health benefits of fluoride use. In general, toothpaste use is not recommended for children under the age of 3 and for children 3 to 6 years old, Health Canada recommends supervision during brushing and use of only a small amount of fluoridated toothpaste (Health Canada, 2010b).

Health Canada recently completed a review of the health risks associated with fluoride in drinking water in which moderate dental fluorosis was chosen as the endpoint of concern for fluoride (Health Canada, 2010a). Although moderate dental fluorosis is not a health concern and is not considered to be a toxicological endpoint, Health Canada considers it to be an adverse effect based on its potential aesthetic concern. The current Canadian drinking water quality guideline developed by Health Canada sets out the maximum acceptable concentration of fluoride (Health Canada, 2010a). This guideline is considered to be protective against all potential adverse health effects including those related to cancer, immunotoxicity, reproductive/developmental toxicity, genotoxicity, and/or neurotoxicity (Health Canada, 2010a). For communities wishing to fluoridate their water supply, Health Canada has determined an optimal concentration of fluoride in drinking water to promote dental health while protecting against adverse effects (Health Canada, 2010b). Tolerable upper intake levels for fluoride, which account for its potential toxicity, have been developed by the Institute of Medicine and adopted by Health Canada (Health Canada, 2010c; IOM, 1997).

The concentration of fluoride in some foods and prepackaged water and ice is regulated by Health Canada under the Food and Drug Regulations (Canada, 2012). Food tolerances for fluoride currently exist for edible bone meal and fish protein as well as prepackaged ice or water, including those represented as mineral or spring water (Canada, 2012).

The first cycle (2007-2009) of the Canadian Health Measures Survey (CHMS) included a National Oral Health Component supported by Health Canada (Health Canada, 2010d). In addition to many other dental considerations, dental fluorosis was measured in children ranging from 6 to 12 years old. The results from cycle 1 of the CHMS found that 60% of children had teeth considered normal, 24% had enamel with white flecks or spots where the cause was questionable, 12% had one or more teeth with fluorosis classified as very mild, and 4% had fluorosis classified as mild. The prevalence of moderate or severe fluorosis was too low to allow reporting (less than 0.3%).

Fluoride was measured in the urine of all CHMS cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 8.7.1, 8.7.2, 8.7.3, and 8.7.4). Finding a measurable amount of fluoride in urine is an indicator of exposure to fluoride and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary fluoride in the Canadian population.

4 Data Tables: 8.7.1 to 8.7.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2003). Toxicological profile for fluorides, hydrogen fluoride, and fluorine. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved July 13, 2011, from www.atsdr.cdc.gov/ToxProfiles/tp11.pdf

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2000). Order adding a toxic substance to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part II: Official Regulations, 134 (7). Retrieved June 11, 2012, from www.gazette.gc.ca/archives/p2/2000/2000-03-29/html/sor-dors109-eng.html.

Canada. (2012). Food and Drug Regulations. C.R.C., c. 870. Retrieved July 24, 2012, from http://laws-lois.justice.gc.ca/PDF/C.R.C.,_c._870.pdf

CCME (Canadian Council of Ministers of the Environment). (2002). Canadian water quality guidelines for the protection of aquatic life - Inorganic fluorides. Winnipeg, MB. Retrieved July 13, 2011, from http://ceqg-rcqe.ccme.ca/download/en/180/

Cotton, F.A. & Wilkinson, G. (1988). Advanced inorganic chemistry. John Wiley & Sons, New York, NY.

Environment Canada & Health Canada. (1993). Priority substances list assessment report: Inorganic fluorides. Minister of Supply and Services Canada, Ottawa, ON. Retrieved August 30, 2011, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/psl1-lsp1/fluorides_inorg_fluorures/index-eng.php

Fawell, J., Bailey, K., Chilton, J., Dahi, E., Fewtrell, L., & Magara, Y. (2006). Fluoride in drinking-water. World Health Organization, London.

Health Canada. (2010a). Guidelines for Canadian drinking water quality: Guideline technical document - Fluoride. Minister of Health, Ottawa, ON. Retrieved July 13, 2011, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2011-fluoride-fluorure/index-eng.php

Health Canada. (2010b). It's your health - Fluorides and human health. Minister of Health, Ottawa, ON. Retrieved August 31, 2011, from www.hc-sc.gc.ca/hl-vs/iyh-vsv/environ/fluor-eng.php

Health Canada. (2010c). Dietary reference intakes. Minister of Health, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/fn-an/nutrition/reference/table/index-eng.php

Health Canada. (2010d). Report on the findings of the oral health component of the Canadian Health Measures Survey 2007-2009. Minister of Health, Ottawa. Retrieved September 1, 2011, from www.fptdwg.ca/English/e-documents.html

IARC (International Agency for Research on Cancer). (1987). IARC monographs on the evaluation of carcinogenic risks to humans - Overall evaluations of carcinogenicity: An updating of IARC monographs volumes 1 to 42. World Health Organization, Geneva.

IOM (Institute of Medicine). (1997). Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. The National Academies Press, Washington, DC.

Mackay, K.M. & Mackay, R.A. (1989). Introduction to modern inorganic chemistry. Prentice Hall, Englewood Cliffs, NJ.

NRC (National Research Council). (2006). Fluoride in drinking water: A scientific review of EPA's standards. Committee on Fluoride in Drinking Water, National Academies Press, Washington, DC.

8.8 Lead

Lead (CASRN 7439-92-1) is a naturally occurring element present in the Earth's crust at an average concentration of approximately 0.0014% (Emsley, 2001). It is a base metal and can exist in various oxidation states and in both inorganic and organic forms (ATSDR, 2007). Inorganic forms include substances such as elemental lead, lead sulphate, lead carbonates and oxycarbonates, lead oxides, and lead halides. Organic lead compounds include tetra-alkyl, trialkyl, and dialkyl lead compounds.

Lead is found in bedrock, soils, sediments, surface water, groundwater, and sea water (Health Canada, 2012a). It enters the environment from a variety of natural and anthropogenic sources. Natural processes include soil weathering, erosion, and volcanic activity (ATSDR, 2007; IARC, 2006). Lead released from industrial emissions can be a major source of environmental contamination, especially near point sources such as smelters or refineries (ATSDR, 2007). Historical use of leaded motor fuels has contributed to the ubiquitous distribution of lead throughout the globe (WHO, 2000).

In North America, tetraethyl and tetramethyl lead were used as anti-knock additives in motor vehicle fuels up until the 1990s. Presently in Canada, lead use in gasoline is limited to fuels for piston engine aircrafts and racing fuels for competition vehicles (Health Canada, 2013a). Lead is currently used in the refining and manufacturing of products such as lead acid automotive batteries, lead shot and fishing weights, sheet lead, lead solder, some brass and bronze products, and some ceramic glazes (ATSDR, 2007; WHO, 2000). Other uses of lead include dyes in paints and pigments. It is also used in scientific equipment, as a stabilizer in plastics, in military equipment and ammunition, and in medical equipment as radiation shields (ATSDR, 2007; WHO, 2000). Lead is also used in the manufacturing of cable sheathing, circuit boards, chemical baths and storage vessel linings, chemical transmission pipes, electrical components, and polyvinyl chloride (Health Canada, 2013a).

Everyone is exposed to trace amounts of lead through food, drinking water, soil, household dust, air, and some consumer products. Over the past 30 years, lead exposure has declined by over 70% in Canada (Bushnik et al., 2010; Health Canada, 2011a; Health Canada, 2013a). The substantial decrease in lead is attributed mainly to the phase-out of leaded gasoline, reduction of lead content in lead-based paints, and the elimination of lead solder in food cans (Health Canada, 2011a). Today, the main route of exposure for the general adult population is from ingestion of food and drinking water (ATSDR, 2007; Health Canada, 2013a). For infants and children, the primary route of exposure is food, drinking water, and the ingestion of non-food items containing lead such as house dust, lead-based paint, soil, and products (Health Canada, 2013a). Lead can enter the water supply from old lead service connections (pipes) or lead solder in the plumbing in homes. Other potential sources of exposure include products that may contain lead, such as costume jewellery, art supplies, leaded crystal, and glazes on ceramics and pottery; working on a hobby that involves the use of lead or lead solder, such as making stained glass, ceramic glazing, lead shot or lead fishing weights, and furniture refinishing; living in or frequently visiting older buildings that contain deteriorating lead paint or that are undergoing renovation activities; and behaviours such as smoking (Health Canada 2011a).

Approximately 3% to 10% of ingested lead is absorbed into blood in adults; the amount absorbed can increase to up to 40% to 50% in children (Health Canada, 2013a). Nutritional iron and calcium deficiencies in children appear to increase lead absorption (Health Canada, 2013a). Once absorbed by the human body, lead circulates in the bloodstream and either accumulates in tissues, particularly bone, or is excreted from the body. Some lead may also be absorbed into soft tissues such as the liver, kidneys, pancreas, and lungs. Bones account for approximately 70% of the total body burden of lead in children and more than 90% of the total body burden in human adults (EPA, 2006). Lead stored in bone can be remobilized and released back into circulating blood. Under certain conditions such as pregnancy, lactation, menopause, andropause, extended bed rest, hyperparathyroidism, and osteoporosis, lead can be mobilized at an increased rate (Health Canada, 2013a).

During pregnancy, lead stored in maternal bone becomes a source of fetal exposure (Rothenberg et al., 2000). Lead can also be present in breast milk and is transferred from lactating mothers to infants (ATSDR, 2007; EPA, 2006). The half-life for lead in blood is approximately 30 days, whereas the half-life for lead accumulated in the body, such as in bone, is around 10 to 30 years (ATSDR, 2007; Health Canada, 2007; Health Canada, 2013a). Excretion of absorbed lead, independent of the route of exposure, occurs primarily in urine and feces (ATSDR, 2007). Blood lead is the preferred indicator of human exposure to lead, although other matrices such as urine, bone, and teeth have also been used (ATSDR, 2007; CDC, 2009).

Lead is considered a cumulative general poison, with infants, toddlers, children, and fetuses being most susceptible to adverse health effects (WHO, 2011). Following acute exposure, a variety of metabolic processes may be affected. Very high exposure may result in vomiting, diarrhea, convulsions, coma, and death. Severe cases of lead poisoning are rare in Canada (Health Canada, 2007). Symptoms of chronic exposure to relatively low levels of lead are often not apparent (ATSDR, 2007). Chronic low-level exposure may affect both the central and peripheral nervous systems (Health Canada, 2013a). Chronic low-level exposure to lead has also been associated with effects on neurodevelopment, the cardiovascular system, kidneys, the reproductive system, and other health endpoints (ATSDR, 2007; Health Canada, 2013a). Cognitive and neurobehavioural effects have been recognized as major concerns for children exposed to lead. In infants and children, neurodevelopmental effects are most strongly associated with lead exposure, specifically the reduction of intelligence quotient (Lanphear et al., 2005) and attention-related behaviours (Health Canada, 2013a). Based on available data, no threshold has yet been identified for the effects of lead exposure on cognitive function and neurobehavioural development (CDC, 2012; EPA, 2006; Health Canada, 2013a). Developmental neurotoxicity has been associated with the lowest levels of lead exposure to date (Health Canada, 2013a). The International Agency for Research on Cancer classifies inorganic lead compounds as Group 2A, probably carcinogenic to humans (IARC, 2006).

Lead is listed on Schedule 1, List of Toxic Substances, under the Canadian Environmental Protection Act, 1999 (CEPA 1999). The Act allows the federal government to control the importation, manufacture, distribution, and use of lead and lead compounds in Canada (Canada, 1999; Health Canada, 2007). CEPA 1999 restricts the use of lead in gasoline and controls its release from secondary lead smelters, steel manufacturing, and mining effluents (Environment Canada, 2010). The use of lead in toys, children's jewellery and other products intended for children, glazed ceramics and glass foodware, and other consumer products representing a potential risk of lead exposure is restricted under the Canada Consumer Product Safety Act and its associated regulations (Canada, 2010a; Canada, 2010b; Health Canada, 2012a). Lead and its compounds are included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011c).

On the basis of health considerations, Health Canada has developed a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of lead (Health Canada, 1992); this guideline is planned for review by Health Canada in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water (Health Canada, 2013b). Health Canada has also published guidance on controlling corrosion in drinking water distribution systems to help control the leaching of metals, including lead, that results from corrosion (Health Canada, 2009a). The concentration of lead in some foods is regulated by Health Canada under the Food and Drug Regulations; the current food tolerances are in the process of being updated (Canada, 2012; Health Canada, 2011b). Lead is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009b). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

In 1994, the Federal-Provincial-Territorial Committee on Environmental and Occupational Health recommended a blood lead intervention level of 10 μg/dL as guidance for low-level exposure to lead (CEOH, 1994). Recent scientific assessments indicate that chronic health effects are occurring in children at blood lead levels below 10 μg/dL and that there is sufficient evidence that blood lead levels below 5 μg/dL are associated with adverse health effects (Health Canada, 2013a). Update of evidence for low-level effects of lead and blood-lead intervention levels and strategies (CEOH, 1994) is currently under review by the federal, provincial, and territorial jurisdictions through the Committee on Health and Environment.

In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric means for lead in whole blood and urine were 2.15 μg/dL and 0.12 μg/dL, respectively (INSPQ, 2004). Higher lead levels have been found in some northern communities; a geometric mean blood level of 3.9 μg/dL was measured from 917 adults aged 18 to 74 years in Nunavik, Quebec, in 2004 (Dewailly et al., 2007). More recently, a study conducted in Hamilton on 643 children aged 0 to 6 years reported a geometric mean blood lead level of 2.21 μg/dL (Richardson et al., 2011). A number of other studies that measured blood lead levels have been conducted in various locations in Canada over the years. In a recent report by Health Canada, blood lead levels were reported for various locations, age groups, and years. The reported geometric means ranged from 0.7 to 5.6 μg/dL for various age groups within the Canadian population (Health Canada, 2013a).

Lead was measured in the whole blood and urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as μg/dL (Tables 8.8.1, 8.8.2, and 8.8.3) and in urine as both μg/L (Tables 8.8.4, 8.8.5, and 8.8.6) and µg/g creatinine (Tables 8.8.7, 8.8.8, and 8.8.9). Finding a measurable amount of lead in blood and urine does not necessarily mean that an adverse health effect will occur.

9 Data Tables: 8.8.1 to 8.8.9

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2007). Toxicological profile for lead. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved March 27, 2012, from www.atsdr.cdc.gov/toxprofiles/tp13.html

Bushnik, T., Haines, D., Levallois, P., Levesque, J., Van Oostdam, J., & Viau, C. (2010). Lead and bisphenol A concentrations in the Canadian population. Health Reports, 21 (3), 7-18.

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2010a). Canada Consumer Product Safety Act. SC 2010, c. 21. Retrieved February 20, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-1.68/index.html

Canada. (2010b). Consumer Products Containing Lead (Contact with Mouth) Regulations. SOR/2010-273. Retrieved March 27, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2010-273/page-1.html

Canada. (2012). Food and Drug Regulations. C.R.C., c. 870. Retrieved July 24, 2012, from http://laws-lois.justice.gc.ca/PDF/C.R.C.,_c._870.pdf

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

CDC (Centers for Disease Control and Prevention). (2012). CDC response to Advisory Committee on Childhood Lead Poisoning Prevention recommendations in "Low level lead exposure harms children: a renewed call for primary prevention." Department of Health and Human Services, Atlanta, GA. Retrieved November 13, 2011, www.cdc.gov/nceh/lead/acclpp/cdc_response_lead_exposure_recs.pdf

CEOH (Federal-Provincial Committee on Environmental and Occupational Health). (1994). Update of evidence for low-level effects of lead and blood-lead intervention levels and strategies - final report of the working group. Minister of Health, Ottawa, ON.

Dewailly, É., Ayotte, P., Pereg, D., Déry, S., Dallaire, R., Fontaine, J., & Côté, S. (2007). Exposure to environmental contaminants in Nunavik: Metals. Institut national de santé publique du Québec, Nunavik Regional Board of Health and Social Services, Québec, QC. Retrieved March 27, 2012, from www.inspq.qc.ca/pdf/publications/661_esi_contaminants.pdf

Emsley, J. (2001). Nature's building blocks: An A-Z guide to the elements. Oxford University Press, Oxford.

Environment Canada. (2010). List of toxic substances managed under CEPA (Schedule 1): Lead. Minister of Environment, Ottawa, ON. Retrieved September 13, 2012 from www.ec.gc.ca/toxiques-toxics/Default.asp?lang=En&n=98E80CC6-1&xml=D048E4B9-B103-4652-8DCF-AC148D29FB7D

EPA (U.S. Environmental Protection Agency). (2006). Air quality criteria for lead - Volume I and II. U.S. Environmental Protection Agency, Washington, DC. Retrieved March 27, 2012, from http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=158823

Health Canada. (1992). Guidelines for Canadian drinking water quality: Guideline technical document - Lead. Minister of Health, Ottawa, ON. Retrieved March 27, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/lead-plomb/index-eng.php

Health Canada. (2007). Lead and health. Minister of Health, Ottawa, ON. Retrieved March 27, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/lead-plomb-eng.php

Health Canada. (2009a). Guidance on controlling corrosion in drinking water distribution systems. Minister of Health, Ottawa, ON. Retrieved May 22, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/corrosion/index-eng.php

Health Canada. (2009b). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2011a). It's your health - Lead and human health. Minister of Health, Ottawa, ON. Retrieved March 27, 2012, from www.hc-sc.gc.ca/hl-vs/iyh-vsv/environ/lead-plomb-eng.php

Health Canada. (2011b). Food Directorate updated approach for managing dietary exposure to lead. Minister of Health, Ottawa, ON. Retrieved July 25, 2012, from www.hc-sc.gc.ca/fn-an/securit/chem-chim/environ/lead_strat_plomb_strat-eng.php

Health Canada. (2011c). List of prohibited and restricted cosmetic ingredients ("hotlist"). Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

Health Canada. (2013a). Final human health state of the science report on lead. Minister of Health, Ottawa, ON. Retrieved March 1, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/dhhssrl-rpecscepsh/index-eng.php

Health Canada. (2013b). Risk management strategy for lead. Minister of Health, Ottawa, ON. Retrieved March 1, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/prms_lead-psgr_plomb/index-eng.php

IARC (International Agency for Research on Cancer). (2006). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 87: Inorganic and organic lead compounds. World Health Organization, Geneva.

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

Lanphear, B.P., Hornung, R., Khoury, J., Yolton, K., Baghurst, P., Bellinger, D.C., Canfield, R.L., Dietrich, K.N., Bornschein, R., Greene, T., Rothenberg, S.J., Needleman, H.L., Schnaas, L., Wasserman, G., Graziano, J., & Roberts, R. (2005). Low-level environmental lead exposure and children's intellectual function: An international pooled analysis. Environmental Health Perspectives, 113 (7), 894-899.

Richardson, E., Pigott, W., Craig, C., Lawson. M., & Mackie, C. (2011). North Hamilton child blood lead study public health report. Hamilton Public Health Services, Hamilton, ON. Retrieved May 22, 2012, from www.hamilton.ca/NR/rdonlyres/453D1F95-87EE-47D2-87AB-025498737337/0/Sep26EDRMS_n216098_v1_BOH11030_Child_Blood_Lead_Prevalence_Stud.pdf

Rothenberg, S.J., Khan, F., Manalo, M., Jiang, J., Cuellar, R., Reyes, S., Acosta, S., Jauregui, M., Diaz, M., Sanchez, M., Todd, A.C., & Johnson, C. (2000). Maternal bone lead contribution to blood lead during and after pregnancy. Environmental Research, 82 (1), 81-90.

WHO (World Health Organization). (2000). Air quality guidelines for Europe, second edition. WHO, Geneva. Retrieved March 27, 2012, from www.euro.who.int/en/what-we-publish/abstracts/air-quality-guidelines-for-europe

WHO (World Health Organization). (2011). Lead in drinking-water: Background document for development of WHO guidelines for drinking-water quality. WHO, Geneva. Retrieved May 22, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/lead/en/

8.9 Manganese

Manganese (CASRN 7439-96-5) is the 12th most abundant element, occurring naturally in the Earth's crust at an average concentration of approximately 0.1% (Health Canada, 1987). Pure manganese is silver in colour, but manganese in the environment is always found combined with other elements in a variety of minerals. Manganese can exist in both organic and inorganic forms. Organic manganese compounds do not occur in nature but are manufactured for specific uses (ATSDR, 2008). Manganese is an essential trace element required for the maintenance of good health in humans.

Manganese is ubiquitous in the environment, naturally occurring in air, soil, water, and biological organisms, including food. Natural sources of manganese include erosion and volcanic activity (ATSDR, 2008). Manganese is released to the air from anthropogenic sources including mining operations, coke ovens, and iron, steel, and power plants. Historical use of a manganese-containing additive, methylcyclopentadienyl manganese tricarbonyl (MMT), in leaded gasoline has contributed to the atmospheric concentrations of manganese (ATSDR, 2008).

Metallic manganese is used principally in steel production to improve hardness and strength. Other uses of manganese compounds include production of dry-cell batteries, fireworks, matches, animal feed to supply essential trace minerals, porcelain and glass-bonding materials, and fertilizers. Potassium permanganate is commonly used in water and waste-treatment plants as a disinfectant and anti-algal agent, but is also used for metal cleaning, tanning, and bleaching (ATSDR, 2008). The predominant application of organic manganese was in petroleum refineries as an octane enhancer, namely MMT, in use prior to 2004 (Health Canada, 2010a). Other organic manganese compounds, such as maneb or mancozeb, are used as fungicides for fruits and vegetables and in seed treatment; maneb is no longer being registered for use in Canada (Health Canada, 2012). Another organic manganese compound, mangafodipir trisodium, is used as a contrast agent in magnetic resonance imaging (ATSDR, 2008).

Food is the main source of manganese exposure for the majority of the population (ATSDR, 2008). Manganese is found in trace amounts in all plant and animal tissues. Manganese intake from drinking water and air is substantially lower than intake from food (ATSDR, 2008).

The main routes of absorption for manganese are the respiratory and gastrointestinal tracts. Approximately 3% to 5% of orally ingested manganese is absorbed from the gastrointestinal tract and enters systemic circulation (ATSDR, 2008). Conversely, inhaled manganese enters systemic circulation directly, making the manganese available for distribution to and accumulation in body tissues, including the brain (Health Canada, 2010a). Half-lives are influenced by both age and route of exposure. The ubiquitous presence of manganese in foods along with the essential nature of this element has resulted in the development of homeostatic control mechanisms for dietary manganese. Under conditions of high dietary manganese, adaptive changes include reduced gastrointestinal absorption of manganese, enhanced manganese liver metabolism, and increased biliary and pancreatic excretion of manganese (Davis et al., 1993; Dorman et al., 2001; Dorman et al., 2002). Biliary excretion is the main excretory pathway with the manganese in bile being excreted in the feces along with unabsorbed dietary manganese (Davis et al., 1993; Malecki et al., 1996). Urinary excretion of manganese is low (Davis & Greger, 1992).

Concentrations in blood and urine can be used to evaluate exposure to manganese (ATSDR, 2008). Whole blood is preferred rather than plasma or serum because slight hemolysis of samples can significantly increase plasma or serum manganese concentrations (IOM, 2001). Concentrations in blood tend to reflect the overall body burden of manganese, whereas concentrations in urine are more stable responding only to significant fluctuations in manganese intake (IOM, 2001).

As an essential trace element, manganese is involved in the formation of bone, in cellular protection from free radical damage, and in amino acid, cholesterol, and carbohydrate metabolism (ATSDR, 2008; IOM, 2001). Manganese deficiency in humans is rare; however, excessive exposure can cause neurological effects (ATSDR, 2008).

The adverse health effects from overexposure to manganese depend on the route of exposure, the chemical form (solubility), the age of the individual at exposure, and the individual's nutritional status (iron content). Very high concentrations of manganese in air, such as those associated with occupational exposures, can result in metal fume fever, pneumonitis, and manganism (a condition resembling Parkinson's disease) (Health Canada, 1987). Exposure to moderately high levels of manganese in air can result in subtle neurological effects such as poorer fine-motor skills (Health Canada, 2010a). The United States Environmental Protection Agency has classified manganese as Group D, not classifiable as to human carcinogenicity, based on an absence of human data and inadequate animal data (EPA, 1996). The International Agency for Research on Cancer has not published an evaluation of the carcinogenicity of manganese (ITER, 2010).

Tolerable upper intake levels for manganese, which account for its potential toxicity, have been developed by the Institute of Medicine and adopted by Health Canada (Health Canada, 2010b; IOM, 2001). These levels only account for intake from pharmacological agents and do not include intake from diet. Manganese is included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply. An aesthetic objective for manganese in drinking water, based on palatability and the staining of laundry and plumbing fixtures, was established by Health Canada; this guideline was also deemed protective of adverse health effects (Health Canada, 1987). On the basis of health considerations, Health Canada has also established a manganese reference concentration in air (Health Canada, 2010a).

In a study carried out in British Columbia to assess the levels of trace elements in 61 non-smoking adults aged 30 to 65 years, the geometric mean and 95th percentile values of manganese in blood were 10.75 µg/L and 14.94 µg/L, respectively (Clark et al., 2007). In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric mean for manganese in whole blood was 9.33 µg/L (INSPQ, 2004). In a 1996 study of manganese levels in a non-occupationally exposed adult population in southwest province of Quebec, blood samples were obtained from 297 subjects between the age of 20 and 69 years (Baldwin et al., 1999). The geometric mean blood manganese level for this population was 7.1 µg/L. Blood manganese levels were also measured in children, aged 2 to 17 years, in Montréal (Dupont & Tanaka, 1985). Twenty-nine children were tested in 1976 and 24 children were tested in 1984 with mean blood manganese levels of 14.4 µg/L and 14.0 µg/L, respectively.

Manganese was measured in the whole blood and urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as μg/L (Tables 8.9.1, 8.9.2, and 8.9.3) and in urine as both µg/L (Tables 8.9.4, 8.9.5, and 8.9.6) and µg/g creatinine (Tables 8.9.7, 8.9.8, and 8.9.9). Finding a measurable amount of manganese in blood or urine is an indicator of exposure to manganese and does not necessarily mean that an adverse health effect will occur. Because manganese is an essential trace element, its presence in biological fluids is expected.

9 Data Tables: 8.9.1 to 8.9.9

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2008). Draft toxicological profile for manganese. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 5, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=102&tid=23

Baldwin, M., Mergler, D., Larribe, F., Belanger, S., Tardif, R., Bilodeau, L., & Hudnell, K. (1999). Bioindicator and exposure data for a population based study of manganese. Neurotoxicology, 20 (2-3), 343-354.

Clark, N.A., Teschke, K., Rideout, K., & Copes, R. (2007). Trace element levels in adults from the west coast of Canada and associations with age, gender, diet, activities, and levels of other trace elements. Chemosphere, 70 (1), 155-164.

Davis, C.D. & Greger, J.L. (1992). Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. American Journal of Clinical Nutrition, 55 (3), 747-752.

Davis, C.D., Zech, L., & Greger, J.L. (1993). Manganese metabolism in rats: An improved methodology for assessing gut endogenous losses. Proceedings of the Society for Experimental Biology and Medicine, 202 (1), 103-108.

Dorman, D.C., Struve, M.F., James, A., McManus, B.E., Marshall, M.W., & Wong, B.A. (2001). Influence of dietary manganese on the pharmacokinetics of inhaled manganese sulfate in male CD rats. Toxicological Sciences, 60 (2), 242-251.

Dorman, D.C., Struve, M.F., & Wong, B.A. (2002). Brain manganese concentrations in rats following manganese tetroxide inhalation are unaffected by dietary manganese intake. Neurotoxicology, 23 (2), 185-195.

Dupont, C.L. & Tanaka, Y. (1985). Blood manganese levels in children with convulsive disorder. Biochemical Medicine, 33 (2), 246-255.

EPA (U.S. Environmental Protection Agency). (1996). Integrated Risk Information System (IRIS): Manganese. Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH. Retrieved April 16, 2012, from www.epa.gov/iris/subst/0373.htm#carc

Health Canada. (1987). Guidelines for Canadian drinking water quality: Guideline technical document - Manganese. Minister of Health, Ottawa, ON. Retrieved April 11, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/manganese/index-eng.php

Health Canada. (2009). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2010a). Human health risk assessment for inhaled manganese. Minister of Health, Ottawa, ON. Retrieved May 24, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/air/manganese-eng.php

Health Canada. (2010b). Dietary Reference Intakes. Minister of Health, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/fn-an/nutrition/reference/table/index-eng.php

Health Canada. (2012). Pesticide product information database. Retrieved April 20, 2012, from www.pr-rp.hc-sc.gc.ca/pi-ip/index-eng.php

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

IOM (Institute of Medicine). (2001). Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press, Washington, DC.

ITER (International Toxicity Estimates for Risk). (2010). ITER database: Manganese (CAS 7439-96-5). National Library of Medicine, Bethesda, MD. Retrieved May 24, 2012, from www.toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?iter

Malecki, E.A., Radzanowski, G.M., Radzanowski, T.J., Gallaher, D.D., & Greger, J.L. (1996). Biliary manganese excretion in conscious rats is affected by acute and chronic manganese intake but not by dietary fat. Journal of Nutrition, 126 (2), 489-498.

8.10 Mercury

Mercury (CASRN 7439-97-6) is a naturally occurring soft, silvery white metal present in the Earth's crust at an average concentration of approximately 0.000005% (Emsley, 2001). It is the only metal that is a liquid at room temperature. Mercury exists in elemental, inorganic, and organic forms (CCME, 1999). Elemental and certain organic forms of mercury have relatively high vapour pressures and, as a result, can be present as a vapour in air (ATSDR, 1999). The most common organic mercury compounds in nature are methylmercury (monomethylmercury) and dimethylmercury. Mercury can be converted among its elemental, inorganic, and organic forms by a variety of processes including biological transformation (Environment Canada, 2010).

Mercury is found throughout the environment, including remote Arctic regions because of its persistence, mobility, and tendency to accumulate in colder climates. Natural sources include volcanic activity and natural erosion of mercury-containing deposits (Environment Canada & Health Canada, 2010). Metabolism of inorganic mercury by micro-organisms in the environment creates organic mercury (methylmercury) that can bioaccumulate in terrestrial and aquatic food chains (ATSDR, 1999). Anthropogenic sources of inorganic mercury include metal mining and smelting; combustion of fossil fuels, particularly coal; incineration of municipal wastes; cement production; and sewage sludge and waste water (UNEP, 2002). Inorganic mercury may also be released to the environment following disposal of products containing mercury.

Mercury has unique properties that have made it useful in certain products such as wiring devices, switches, and scientific measuring devices including vacuum gauges and thermometers (ATSDR, 1999). Today it has been phased out of most products manufactured in Canada; however, many products that contain mercury are still imported into the Canadian marketplace (Canada, 2011a). Inorganic mercury is still found in some medical devices, such as thermostats and X-ray tubes, and in button-cell batteries used in small electronic and hearing aids. Mercury vapour is also present in many lamps and lights including all fluorescent lamps, mercury vapour lamps, metal halide lamps, and sodium vapour lamps (Environment Canada, 2010). Use of mercury-containing light bulbs is increasing because of widespread replacement of incandescent bulbs with compact fluorescent bulbs. Mercury is also used as an industrial catalyst and in laboratory reagents, disinfectants, embalming solutions, and some pharmaceuticals. A significant use of inorganic mercury is in dental amalgam, which is composed of approximately 50% mercury, but it contributes only minimally to the total daily exposure of Canadians to mercury (Health Canada, 2007; IMERC, 2010).

Mercury exposure for the general population is primarily due to methylmercury, and occurs through the consumption of fish and seafood (Health Canada, 2007). To a much lesser extent, the general population is exposed to inorganic mercury from such sources as dental amalgams (Health Canada, 2007). The general population may also be exposed to elemental mercury via inhalation of vapours in ambient air, ingestion of drinking water and food, or through dental and medical treatments (ATSDR, 1999).

Approximately 95% of organic mercury is absorbed from the gastrointestinal tract following oral ingestion, whereas elemental mercury is poorly absorbed through the digestive tract or the skin (ATSDR, 1999). Following absorption, organic mercury is distributed to all tissues, including hair, with highest accumulation in the kidneys (ATSDR, 1999). Organic mercury is demethylated in the body to inorganic mercury that accumulates primarily in the liver and kidneys. Previous studies have shown that inorganic mercury constitutes 14% to 26% of total blood mercury (Kingman et al., 1998; Oskarsson et al., 1996; Passos et al., 2007). Methylmercury is estimated to have a biological half-life of approximately 50 days. The majority of mercury in the body is excreted via feces, with a small amount excreted as inorganic mercury in urine (ATSDR, 1999).

Exposure to mercury is commonly evaluated using mercury concentrations in blood and urine, although hair also may be used as a biomarker of exposure (ATSDR, 1999). Blood concentrations primarily reflect recent exposures to mercury (ATSDR, 1999). Typically, blood and urine mercury levels are reported as total mercury comprising both inorganic and organic mercury. The concentration of total mercury in blood is accepted as a reasonable measure of methylmercury exposure. Based on a review of existing data from other countries, the World Health Organization has estimated that the average total blood mercury concentration for the general population is approximately 8 μg/L (WHO, 1990). In individuals who consume fish daily, methylmercury concentrations in blood can be as high as 200 μg/L (WHO, 1990).

Mercury is known to be toxic to humans with the effects depending on the form and the exposure route. Chronic oral exposure to low levels of methylmercury may not result in any observable symptoms (Health Canada, 2007). The primary effects associated with oral exposure to organic mercury compounds are neurological effects and developmental neurotoxicity (UNEP, 2002). Symptoms of organic mercury toxicity include a tingling sensation in the extremities; impaired peripheral vision, hearing, taste, and smell; slurred speech; muscle weakness and an unsteady gait; irritability; memory loss; depression; and sleeping difficulties (UNEP, 2002). Exposure of a fetus or young child to organic mercury can result in effects on the development of the nervous system, affecting fine-motor function, attention, verbal learning, and memory (ATSDR, 1999; Health Canada, 2007). Exposure to elemental mercury may be hazardous, depending upon the levels of exposure, because the vapour that can be released from this form is readily absorbed into the body through inhalation. Inhalation of mercury vapour may cause respiratory, cardiovascular, kidney, and neurological effects. Exposure to inorganic mercury from dental amalgams has not been associated with neurologic effects in children or adults (Bates et al., 2004; Bellinger et al., 2007; DeRouen et al., 2006; Factor-Litvak et al., 2003). Health Canada concluded that mercury exposure from dental amalgams does not pose a health impact for the general population (Health Canada, 1996).

The International Agency for Research on Cancer (IARC) determined that methylmercury compounds are possibly carcinogenic to humans (Group 2B), based on animal data showing a link to certain cancers, particularly renal cancer (IARC, 1993). Elemental mercury and inorganic mercury compounds were classified by IARC as Group 3, not classifiable as to their carcinogenicity to humans (IARC, 1993).

The United Nations Environment Programme (UNEP) Global Risk Assessment for Mercury concluded that there was sufficient evidence of adverse impacts from mercury to warrant further international action to reduce the risks to human health and the environment (UNEP, 2002). International negotiations are taking place under UNEP toward a global legally binding instrument, the intent of which is to reduce atmospheric emissions, supply, trade, and demand for mercury, and to find environmentally sound solutions for storage of mercury and mercury-containing wastes.

In Canada, mercury and its compounds are listed as toxic substances on Schedule 1 of the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Canada, 2012a). Existing and planned actions to manage the risks from mercury are summarized in the Government of Canada's Risk Management Strategy for Mercury (Environment Canada & Health Canada, 2010). These risk management actions include several Canada-wide standards that have been established to reduce the releases of mercury to the environment (CCME, 2000; CCME, 2005; CCME, 2006; CCME, 2007).

The Surface Coating Materials Regulations, in effect under the Canada Consumer Product Safety Act, restrict the level of mercury in all surface coating materials advertised, sold or imported into Canada (Canada, 2005). In addition, the Toys Regulations prohibit any compound of mercury in the surface coating material that is applied to a product that is used by a child in learning or play situations (Canada, 2011b). In 2011, a regulation was proposed under CEPA 1999 with prohibitions on the import, manufacture, sale, and offer for sale of mercury-containing products that are not currently regulated under other legislation (Canada, 2011a). Mercury and its compounds are also included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011). The Food and Drug Regulations prohibit sale in Canada of drugs for human use containing mercury or any of its salts or derivatives except in some specific instances, including those where it is present as a preservative (Canada, 2012b).

On the basis of health considerations, Health Canada has developed a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of mercury (Health Canada, 1986; Health Canada, 2012a). Health Canada has also adopted a provisional tolerable daily mercury intake level for adults developed by the World Health Organization (WHO, 1972). For women who are or may become pregnant and for young children, Health Canada has developed a provisional tolerable daily intake level for mercury (Health Canada, 2002; Health Canada, 2007). Health Canada has also established a total mercury blood guidance value of 20 µg/L for the general adult population (Health Canada, 2004). For children (<18 years of age), pregnant women, and women of childbearing age (<50 years of age), a provisional methylmercury guidance value of 8 µg/L has recently been proposed for the protection of the developing nervous system (Legrand et al., 2010). Health Canada has also established maximum contaminant concentrations for mercury in fish (Health Canada, 2012b) and provides consumption advice for consumers (Health Canada, 2008).

In a study carried out in British Columbia to assess the levels of trace elements in 61 non-smoking adults aged 30 to 65 years, the geometric mean and 95th percentile concentrations of total mercury in blood were 2.94 µg/L and 7.26 µg/L, respectively (Clark et al., 2007). In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric mean of total mercury in whole blood was 0.74 µg/L (INSPQ, 2004).

Total mercury was measured in the whole blood of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as µg/L (Tables 8.10.1, 8.10.2, and 8.10.3). Finding a measurable amount of mercury in blood is an indicator of exposure to mercury and does not necessarily mean that an adverse health effect will occur.

3 Data Tables: 8.10.1 to 8.10.3

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1999). Toxicological profile for mercury. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved March 30, 2012, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=115&tid=24

Bates, M.N., Fawcett, J., Garrett, N., Cutress, T., & Kjellstrom, T. (2004). Health effects of dental amalgam exposure: A retrospective cohort study. International Journal of Epidemiology, 33 (4), 894-902.

Bellinger, D.C., Daniel, D., Trachtenberg, F., Tavares, M., & McKinlay, S. (2007). Dental amalgam restorations and children's neuropsychological function: The New England Children's Amalgam Trial. Environmental Health Perspectives, 115 (3), 440-446.

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2005). Surface Coating Materials Regulations. SOR/2005-109. Retrieved April 3, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2005-109/index.html

Canada. (2011a). Proposed regulations respecting products containing certain substances listed in Schedule 1 to the Canadian Environmental Protection Act, 1999. April 2, 2012, from www.gazette.gc.ca/rp-pr/p1/2011/2011-02-26/html/reg4-eng.html

Canada. (2011b). Toys Regulations. SOR/2011-17. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2011-17/index.html

Canada. (2012a). Order adding a toxic substance to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part II: Official Regulations, 146(21). Retrieved October, 2012, from gazette.gc.ca/rp-pr/p2/2012/2012-10-10/html/sor-dors186-eng.html

Canada. (2012b). Food and Drug Regulations. C.R.C., c. 870. Retrieved July 24, 2012, from http://laws-lois.justice.gc.ca/PDF/C.R.C.,_c._870.pdf

CCME (Canadian Council of Ministers of the Environment). (1999). Canadian soil quality guidelines for the protection of environmental and human health - Mercury (inorganic). Winnipeg, MB. Retrieved March 30, 2012, from http://ceqg-rcqe.ccme.ca/download/en/270/

CCME (Canadian Council of Ministers of the Environment). (2000). Canada-wide standards for mercury emissions. Québec, QC. Retrieved March 30, 2012, from www.ccme.ca/assets/pdf/mercury_emis_std_e1.pdf

CCME (Canadian Council of Ministers of the Environment). (2005). Canada-wide standards for mercury (mercury emissions, mercury-containing lamps, and mercury for dental amalgam waste): A report on progress. Winnipeg, MB. Retrieved March 30, 2012, from www.ccme.ca/assets/pdf/joint_hg_progress_rpt_e.pdf

CCME (Canadian Council of Ministers of the Environment). (2006). Canada-wide standards for mercury emissions from coal-fired electric power generation plants. Winnipeg, MB. Retrieved March 30, 2012, from www.ccme.ca/assets/pdf/hg_epg_cws_w_annex.pdf

CCME (Canadian Council of Ministers of the Environment). (2007). Canada-wide standards for mercury - A report on compliance and evaluation (mercury from dental amalgam waste), a report on progress (mercury emissions and mercury-containing lamps). Winnipeg, MB. Retrieved April 2, 2012, from www.ccme.ca/assets/pdf/2007_joint_hg_rpt_1.0_e.pdf

Clark, N.A., Teschke, K., Rideout, K., & Copes, R. (2007). Trace element levels in adults from the west coast of Canada and associations with age, gender, diet, activities, and levels of other trace elements. Chemosphere, 70 (1), 155-164.

DeRouen, T.A., Martin, M.D., Leroux, B.G., Townes, B.D., Woods, J.S., Leitao, J., Castro-Caldas, A., Luis, H., Bernardo, M., Rosenbaum, G., & Martins, I.P. (2006). Neurobehavioral effects of dental amalgam in children: A randomized clinical trial. Journal of the American Medical Association, 295 (15), 1784-1792.

Emsley, J. (2001). Nature's building blocks: An A-Z guide to the elements. Oxford University Press, Oxford.

Environment Canada. (2010). Mercury and the environment. Retrieved August 30, 2012, from www.ec.gc.ca/mercure-mercury/

Environment Canada & Health Canada. (2010). Risk management strategy for mercury. March 30, 2012, from www.ec.gc.ca/Publications/default.asp?Lang=En&xml=9B24BD24-7D0B-4A1E-BFE0-53DC4137ED90

Factor-Litvak, P., Hasselgren, G., Jocobs, D., Begg, M., Kline, J., Geier, J., Mervish, N., Schoenholtz, S., & Graziano, J. (2003). Mercury derived from dental amalgams and neuropsychologic function. Environmental Health Perspectives, 111 (5), 719-723.

Health Canada. (1986). Guidelines for Canadian drinking water quality: Guideline technical document - Mercury. Minister of Health, Ottawa, ON. Retrieved May 18, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/mercury-mercure/index-eng.php

Health Canada. (1996). The safety of dental amalgam. Minister of Health, Ottawa, ON. Retrieved August 22, 2012, from www.hc-sc.gc.ca/dhp-mps/md-im/applic-demande/pubs/dent_amalgam-eng.php

Health Canada (2002). Toxicological reference doses for trace elements. Minister of Health, Ottawa, ON.

Health Canada. (2004). Mercury - Your health and the environment. Minister of Health, Ottawa, ON. Retrieved April 3 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/mercur/index-eng.php

Health Canada. (2007). Human health risk assessment of mercury in fish and health benefits of fish consumption. Minister of Health, Ottawa, ON. Retrieved August 28, 2012, from www.hc-sc.gc.ca/fn-an/pubs/mercur/merc_fish_poisson-eng.php

Health Canada. (2008). Consumption advice: Making informed choices about fish. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/securit/chem-chim/environ/mercur/cons-adv-etud-eng.php

Health Canada. (2011). List of prohibited and restricted cosmetic ingredients ("hotlist"). Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

Health Canada. (2012a). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

Health Canada. (2012b). Canadian standards (maximum levels) for various chemical contaminants in foods. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/securit/chem-chim/contaminants-guidelines-directives-eng.php

IARC (International Agency for Research on Cancer). (1993). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 58: Beryllium, cadmium, mercury, and exposures in the glass manufacturing industry. World Health Organization, Geneva.

IMERC (Interstate Mercury Education and Reduction Clearinghouse). (2010). Fact sheet - Mercury use in dental amalgam. Northeast Waste Management Officials' Association, Boston, MA. Retrieved April 3, 2012, from www.newmoa.org/prevention/mercury/imerc/factsheets/dental_amalgam.cfm

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

Kingman, A., Albertini, T., & Brown, L.J. (1998). Mercury concentrations in urine and whole blood associated with amalgam exposure in a US military population. Journal of Dental Research, 77 (3), 461-471.

Legrand, M., Feeley, M., Tikhonov, C., Schoen, D., & Li-Muller, A. (2010). Methylmercury blood guidance values for Canada. Canadian Journal of Public Health, 101 (1), 28-31.

Oskarsson, A., Schütz, A., Skerfving, S., Hallén, I.P., Ohlin, B., & Lagerkvist, B.J. (1996). Total and inorganic mercury in breast milk and blood in relation to fish consumption and amalgam fillings in lactating women. Archives of Environmental Health, 51 (3), 234-241.

Passos, C.J.S., Mergler, D., Lemire, M., Fillion, M., & Guimaraes, J.R.D. (2007). Fish consumption and bioindicators of inorganic mercury exposure. Science of the Total Environment, 373 (1), 68-76.

UNEP (United Nations Environment Programme). (2002). Global mercury assessment. UNEP Chemicals, Geneva. Retrieved April 2, 2012, from www.chem.unep.ch/mercury/Report/Final%20Assessment%20report.htm

WHO (World Health Organization). (1972). WHO food additive series 52: Methylmercury (addendum). WHO, Geneva. Retrieved April 4, 2012, from www.inchem.org/documents/jecfa/jecmono/v52je23.htm

WHO (World Health Organization). (1990). Environmental health criteria 101: Methylmercury. WHO, Geneva. Retrieved April 4, 2012, from www.inchem.org/documents/ehc/ehc/ehc101.htm

8.11 Molybdenum

Molybdenum (CASRN 7439-98-7) is a naturally occurring element found throughout the Earth's crust at an average concentration of approximately 0.00015% (Emsley, 2001). It commonly exists in combination with other elements and does not occur as a free metal in nature. Molybdenum is an essential trace element required for the maintenance of good health in humans (IOM, 2001).

Molybdenum is found naturally in soil, sediment, surface water, groundwater, plants, animals, and humans. It may be released to the environment through natural processes such as the weathering of soil or ores from igneous and sedimentary rock (CCME, 1999). Anthropogenic sources include combustion of coal, municipal sewage sludge, and industrial and mining operations (CCME, 1999). The use of fertilizers is also an important anthropogenic source of molybdenum to aquatic systems.

The primary use of molybdenum is in the steel industry as a component of steel alloys to increase strength, durability, resistance to corrosion (Steifel, 2010). Other uses include electrical contacts, spark plugs, X-ray tubes, filaments, screens, grids for radio valves, glass-to-metal seals, nonferrous alloys, and pigments (WHO, 2011). It is also used in pigments for ceramics, inks, and paints (CDC, 2009). Molybdenum compounds are used in agriculture for the treatment of seeds and in the formulation of fertilizers to prevent molybdenum deficiency in crops (WHO, 2011).

Ingestion of food, and to a lesser degree drinking water, is the main route of exposure for the general population (WHO, 2011). Intake of molybdenum via air is considered an insignificant exposure source (WHO, 2011).

Absorption of dietary molybdenum from the gastrointestinal tract depends on the chemical form and ranges from 30% to 70% (WHO, 2011). Following gastrointestinal absorption, molybdenum rapidly appears in the blood and most organs with the highest concentrations found in the liver, kidney, and bone (WHO, 2011). However, there is no apparent bioaccumulation of molybdenum in human tissues (WHO, 2011). Molybdenum is primarily excreted in the urine, and urinary levels are a direct reflection of the dietary molybdenum intake level (IOM, 2001; Turnlund et al., 1995).

As an essential trace element, molybdenum is required as a cofactor for several enzymes and to aid in metabolizing proteins (EPA, 1993; WHO, 2011). Molybdenum deficiency is normally observed only in people with metabolic defects (IOM, 2001). On account of its essentiality, Health Canada has established recommended dietary allowances for molybdenum (Health Canada, 2010; IOM, 2001).

Toxicity data for molybdenum in humans are limited, and the adverse effects observed in laboratory animals are either not relevant for humans or have not been observed in humans (IOM, 2001). However, chronic exposure to high levels of molybdenum has been associated with gout-like symptoms in humans, including high uric acid concentrations and joint pain (EPA, 1993). Neither the International Agency for Research on Cancer nor Health Canada has published an evaluation of the carcinogenicity of molybdenum (ITER, 2010).

Tolerable upper intake levels for molybdenum, which account for its potential toxicity, have been developed by the Institute of Medicine and adopted by Health Canada (Health Canada, 2010; IOM, 2001). Because molybdenum generally occurs at very low concentrations in drinking water, the World Health Organization considers it unnecessary to set a formal guideline value, but has provided a health-based value for guidance purposes (WHO, 2011). Currently, Health Canada has not set a guideline for molybdenum in drinking water (Health Canada, 2012).

In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric means for molybdenum in whole blood and in urine were 1.14 µg/L and 44.25 µg/L, respectively (INSPQ, 2004). In a study carried out in British Columbia to assess the levels of trace elements in 61 non-smoking adults aged 30 to 65 years, the geometric mean concentration for molybdenum in blood was 1.47 µg/L (Clark et al., 2007). In urine, the geometric mean and 95th percentile molybdenum values were 49.5 µg/g creatinine and 159.8 µg/g creatinine, respectively (Clark et al., 2007).

Molybdenum was measured in the whole blood and urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as µg/L (Tables 8.11.1, 8.11.2, and 8.11.3) and in urine as both µg/L (Tables 8.11.4, 8.11.5, and 8.11.6) and µg/g creatinine (Tables 8.11.7, 8.11.8, and 8.11.9). Finding a measurable amount of molybdenum in blood or urine is an indicator of exposure to molybdenum and does not necessarily mean that an adverse health effect will occur. Because molybdenum is an essential trace element required for the maintenance of health, its presence in biological fluids is expected.

9 Data Tables: 8.11.1 to 8.11.9

References

CCME (Canadian Council of Ministers of the Environment). (1999). Canadian water quality guidelines for the protection of aquatic life - Molybdenum. Winnipeg, MB. Retrieved July 30, 2012, from http://ceqg-rcqe.ccme.ca/download/en/195/

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Clark, N.A., Teschke, K., Rideout, K., & Copes, R. (2007). Trace element levels in adults from the west coast of Canada and associations with age, gender, diet, activities, and levels of other trace elements. Chemosphere, 70 (1), 155-164.

Emsley, J. (2001). Nature's building blocks: An A-Z guide to the elements. Oxford University Press, Oxford.

EPA (U.S. Environmental Protection Agency). (1993). Integrated Risk Information System (IRIS): Molybdenum. Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH. Retrieved April 4, 2012, from www.epa.gov/iris/subst/0425.htm

Health Canada. (2010). Dietary reference intakes. Minister of Health, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/fn-an/nutrition/reference/table/index-eng.php

Health Canada. (2012). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

IOM (Institute of Medicine). (2001). Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press, Washington, DC.

ITER (International Toxicity Estimates for Risk). (2010). ITER database: Molybdenum (CAS 7439-98-7). National Library of Medicine, Bethesda, MD. Retrieved July 31, 2012, from www.toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?iter

Steifel, E.I. (2010). Molybdenum and molybdenum alloys. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc., Mississauga, ON.

Turnlund, J.R., Keyes, W.R., Peiffer, G.L., & Chiang, G. (1995). Molybdenum absorption, excretion, and retention studied with stable isotopes in young men during depletion and repletion. American Journal of Clinical Nutrition, 61 (5), 1102-1109.

WHO (World Health Organization). (2011). Molybdenum in drinking-water: Background document for development of WHO guidelines for drinking-water quality. WHO, Geneva. Retrieved April 5, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/molibdenum/en/

8.12 Nickel

Nickel (CASRN 7440-02-0) is a naturally occurring metal present in the Earth's crust at an average concentration of approximately 0.0075% (Environment Canada & Health Canada, 1994). In its pure form, nickel is hard and silvery white, and it occurs most frequently in combination with sulphur, arsenic, and antimony. Nickel is a very reactive base metal that forms various divalent compounds, including nickel sulphate, nickel oxide, nickel sulphide, nickel subsulphide, and nickel carbonate (Natural Resources Canada, 2012). Studies have suggested that nickel may be an essential trace element required to support biochemical processes in humans.

Nickel is found in many types of rock and released into the environment as a result of natural processes including the weathering of geological deposits (Environment Canada & Health Canada, 1994). Environmental releases of nickel also result from human activities such as fuel combustion, waste incineration, mining, smelting, refining, and other metal operations (Environment Canada & Health Canada, 1994).

Owing to its unique physical properties, nickel is commonly combined with other metals, including iron, copper, chromium, and zinc to form alloys (ATSDR, 2005). Nickel alloys are used in metal coins, jewellery, and heat exchangers. Nickel compounds are used in nickel plating, batteries, ceramic colouring, and as catalysts to increase rates of chemical reactions. Nickel is also a component of stainless steel that has widespread application in a variety of home, medical, and industrial settings (ATSDR, 2005; CCME, 1999).

The main source of nickel exposure for the general population is food (ATSDR, 2005). Drinking water is also a source of nickel exposure. Additional nickel exposure can occur through dermal contact with products such as jewellery, which often contain nickel alloys. Dermal contact can also occur through the use of nickel-containing products such as household cleaning and bleaching agents; cosmetics, where nickel is generally present as an impurity; and medical products including joint implants, intrauterine devices, and acupuncture needles (ATSDR, 2005; Basketter et al., 2003). Nickel exposure can also occur from inhalation of cigarette smoke (ATSDR, 2005). In the general non-smoking population, inhalation is a minor source of nickel intake (ATSDR, 2005).

Nickel and nickel compounds are absorbed from the respiratory tract and, to a lesser extent, from the gastrointestinal tract and skin (ATSDR, 2005; WHO, 1991). Approximately 20% to 35% of inhaled nickel is absorbed into the blood from the respiratory tract, whereas only 1% to 10% of ingested nickel is absorbed, depending largely on the composition of the diet (ATSDR, 2005; WHO, 1991). Nickel has been measured in a variety of organs including the lungs, thyroid, adrenals, kidneys, heart, liver, brain, spleen, and pancreas (ATSDR, 2005). Nickel is excreted in urine and feces, and has an estimated elimination half-life of 17 to 48 hours (Nieboer & Fletcher, 2001). Nickel can be measured in urine, serum, whole blood, feces, hair, sweat, and breast milk; urine is the most commonly used matrix for biological monitoring of nickel (Sunderman Jr., 1993).

Based on studies in laboratory animal species, nickel is proposed to be an essential element in humans (Environment Canada & Health Canada, 1994). However, there have been no studies to determine the nutritional importance of nickel in humans or to demonstrate its biochemical function (IOM, 2001). The Institute of Medicine has concluded that there is insufficient data to establish recommended dietary allowances or adequate intakes (Health Canada, 2010; IOM, 2001).

Although there may be benefits from small doses of nickel, exposure to high levels may result in adverse health effects. These effects depend on the route of exposure and, in the case of inhalation, the species of nickel. At high concentrations, acute oral exposure can cause gastrointestinal effects; chronic inhalation exposure has led to chronic bronchitis and reduced lung function in humans (ATSDR, 2005). Allergic reactions to nickel are the most common adverse effect and can lead to severe contact dermatitis. The condition can be painful but is not life threatening, and it can be managed by avoiding extended contact between the skin and nickel-containing jewellery, buttons, belt buckles, and similar items (ATSDR, 2005).

Health Canada has classified metallic nickel as Group VI, unclassifiable with respect to carcinogenicity in humans; however, oxidic, sulphidic and soluble nickel are classified as Group I, carcinogenic to humans, for inhalation exposure (Environment Canada & Health Canada, 1994). Similarly, the International Agency for Research on Cancer has classified nickel compounds as Group 1, carcinogenic to humans, and metallic and alloy nickel as Group 2B, possibly carcinogenic to humans (IARC, 1990; IARC, 2012)

Health Canada and Environment Canada assessed nickel and its various compounds, and concluded that metallic nickel was not a concern for human health at current levels of exposure (Environment Canada & Health Canada, 1994). However, the oxidic, sulphidic, and soluble nickel groups (primarily nickel sulphate and nickel chloride), as a whole, are entering the environment in a quantity or concentration or under conditions that may constitute a danger in Canada to human life or health. Oxidic, sulphidic, and soluble inorganic nickel compounds are listed on Schedule 1, List of Toxic Substances, under the Canadian Environmental Protection Act, 1999 (CEPA 1999). The Act allows the federal government to control the importation, manufacture, distribution, and use of oxidic, sulphidic, and soluble inorganic nickel compounds in Canada (Canada, 1999; Canada, 2000). Risk management actions under CEPA 1999 have been developed to control releases of oxidic, sulphidic, and soluble inorganic nickel compounds from thermal electric power generation, base-metal smelting, and steel manufacturing processes (Environment Canada, 2010). Tolerable upper intake levels for nickel, which account for its potential toxicity, have been developed by the Institute of Medicine and adopted by Health Canada (Health Canada, 2010; IOM, 2001). Nickel is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric means of nickel in whole blood and urine were <0.59 µg/L and 1.78 µg/L, respectively (INSPQ, 2004).

Nickel was measured in the whole blood and urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as µg/L (Tables 8.12.1, 8.12.2, and 8.12.3) and in urine as both µg/L (Tables 8.12.4, 8.12.5, and 8.12.6) and µg/g creatinine (Tables 8.12.7, 8.12.8, and 8.12.9). Finding a measurable amount of nickel in blood or urine is an indicator of exposure to nickel and does not necessarily mean that an adverse health effect will occur.

9 Data Tables: 8.12.1 to 8.12.9

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2005). Toxicological profile for nickel. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 16, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=245&tid=44

Basketter, D.A., Angelini, G., Ingber, A., Kern, P.S., & Menné, T. (2003). Nickel, chromium and cobalt in consumer products: Revisiting safe levels in the new millennium. Contact Dermatitis, 49 (1), 1-7.

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2000). Order adding a toxic substance to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part II: Official Regulations, 134 (7). Retrieved June 11, 2012, from www.gazette.gc.ca/archives/p2/2000/2000-03-29/html/sor-d

CCME (Canadian Council of Ministers of the Environment). (1999). Canadian soil quality guidelines for the protection of environmental and human health - Nickel. Winnipeg, MB. Retrieved April 16, 2012, from http://ceqg-rcqe.ccme.ca/download/en/272/

Environment Canada. (2010). List of toxic substances managed under CEPA (Schedule 1): Oxidic, sulphidic, and soluble inorganic nickel compounds. Minister of Environment, Ottawa, ON. Retrieved September 13, 2012 from www.ec.gc.ca/toxiques-toxics/Default.asp?lang=En&n=98E80CC6-1&xml=8EFADF28-533F-4CDB-9C8E-EBB3F7557ADF

Environment Canada & Health Canada. (1994). Priority substances list assessment report: Nickel and its compounds. Minister of Supply and Services Canada, Ottawa, ON. Retrieved April 16, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/psl1-lsp1/compounds_nickel_composes/index-eng.php

Health Canada. (2009). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2010). Dietary reference intakes. Minister of Health, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/fn-an/nutrition/reference/table/index-eng.php

IARC (International Agency for Research on Cancer). (1990). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 49: Chromium, nickel and welding. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (2012). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 100C: Arsenic, metals, fibres, and dusts. World Health Organization, Geneva.

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

IOM (Institute of Medicine). (2001). Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press, Washington, DC.

Natural Resources Canada. (2012). Preliminary estimate of the mineral production of Canada, by province, 2011. Minister of Natural Resources, Ottawa, ON. Retrieved April 18, 2012, from http://mmsd.mms.nrcan.gc.ca/stat-stat/prod-prod/2011-eng.aspx

Nieboer, E. & Fletcher, G.G. (2001). Toxicological profile and related health issues: Nickel (for physicians). McMaster University, Hamilton, ON.

Sunderman Jr., F.W. (1993). Biological monitoring of nickel in humans. Scandinavian Journal of Work, Environment and Health, 19 (Supplement 1), 34-38.

WHO (World Health Organization). (1991). Environmental health criteria 108: Nickel. WHO, Geneva. Retrieved April 16, 2012, from www.inchem.org/documents/ehc/ehc/ehc108.htm

8.13 Selenium

Selenium (CASRN 7782-49-2) is a naturally occurring trace mineral distributed widely in the environment and present in the Earth's crust at concentrations averaging 0.000009% (Schamberger, 1984). Selenium is present in the environment in the inorganic form as selenide, selenate, and selenite but rarely as elemental selenium. Selenium is an essential trace element required for the maintenance of good health in humans.

Selenium in its organic form is found in trace quantities in most plants and animal tissues (Schamberger, 1984). Elevated levels of selenium in the environment may occur naturally from weathering of base-metal deposits and soils (CCME, 2009). Selenium is also released to the environment as a result of anthropogenic activities such as mining or metallurgical processes (CCME, 2009). Other sources of anthropogenic selenium emissions include incinerator stacks, burning coal and oil, and large-scale combustion processes.

Historically, the primary use of selenium was in the electronics industry in the form of arsenic triselenide, used as a photoreceptor for photocopiers (USGS, 2001). Because selenium has various electrical and conductive properties, it is also used in light meters, photoelectric and solar cells, semiconductors, and arc-light electrodes. It is also used as a colourizing and decolourizing agent for glass, and to reduce solar heat for architectural glass (USGS, 2004). Selenium is also present in stainless steel, enamels, inks, rubber, batteries, explosives, fertilizers, animal feed, pharmaceuticals, and shampoos (ATSDR, 2003).

The Canadian population is exposed to selenium compounds in food, ambient air, drinking water, soil, and natural health products. More than 99% of the total daily intake of selenium is estimated to occur through the diet (CCME, 2009). Absorption of selenium depends on the chemical form; organic forms are absorbed more readily (>90%) than inorganic forms (>50%) (IOM, 2000). Absorption also depends on the overall exposure level; absorption increases when selenium levels in the body are low (IOM, 2000). Once inside the body, selenium generally concentrates in the liver and kidneys regardless of the initial chemical form. It can also be found in nails and hair (IOM, 2000). Selenium elimination is triphasic with biological half-lives of approximately 1 day, 1 week, and 3 months (ATSDR, 2003). Approximately 50% to 80% of absorbed selenium is eliminated in the urine (Marier & Jaworski, 1983). Selenium levels in the body following both short- and long-term exposure can be determined through blood and urine tests (IOM, 2000). Human breath can also be used as a biomarker for selenium exposure when large amounts of selenium are being excreted (IOM, 2000).

As an essential trace element, selenium is required as a component of several proteins and enzymes in the body (ATSDR, 2003; Health Canada, 2010). Selenium aids in the defence of oxidative stress, the regulation of thyroid hormone action, and the regulation of the redox status of vitamin C and other molecules (IOM, 2000). Selenium deficiency seldom causes overt illness in isolation; however, it may lead to biochemical changes that predispose to illness associated with other stresses (IOM, 2000). On account of its essentiality, Health Canada has established recommended dietary allowances for selenium (Health Canada, 2010; IOM, 2000).

There is a narrow therapeutic window for selenium, and detrimental health effects can occur when ingested at levels greater than the tolerable upper intake level (Health Canada, 2010; IOM, 2000). The level at which selenium toxicity occurs is difficult to determine because it is affected by the types of protein in the diet, levels of vitamin E, and the forms of selenium to which the individual is exposed (Health Canada, 1992). Acute oral intake of selenium can result in nausea, vomiting, and diarrhea. Chronic levels of high selenium (10 to 20 times more than the recommended dietary allowances) can cause selenosis, a disease that results in hair loss, nail brittleness, and neurological abnormalities (ATSDR, 2003; IOM, 2000; WHO, 2011). Based on the available data, there is no evidence in humans of reproductive effects or developmental abnormalities (ATSDR, 2003). The International Agency for Research on Cancer has determined that selenium is not classifiable as to its carcinogenicity to humans (Group 3) (IARC, 1999). The role of selenium in other chronic diseases such as diabetes, hypertension, and cardiovascular disease is a subject of ongoing debate (Boosalis, 2008).

As part of the Chemicals Management Plan under the Canadian Environmental Protection Act, 1999, selenium-containing substances were identified as a priority group based on ecological concern (Canada, 1999; Canada, 2011a). Health Canada and Environment Canada are preparing a draft screening assessment report for publication in 2014-2015 (Canada, 2011b). Selenium and its compounds (except selenium sulfide) are included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011). In Canada, the leachable selenium content in a variety of consumer products is regulated under the Canada Consumer Product Safety Act (Canada, 2010a). Consumer products regulated for selenium content include paints and other surface coatings on cribs, toys, and other products for use by a child in learning or play situations (Canada, 2010b; Canada, 2011c). Health Canada has also set a maximum level for selenium in natural health products in Canada (Health Canada, 2007). Health Canada has developed a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of selenium on the basis of health considerations; this guideline is currently under review (Health Canada, 1992). Tolerable upper intake levels for selenium, which account for its potential toxicity, have been developed by the Institute of Medicine and adopted by Health Canada (Health Canada, 2010; IOM, 2000). Selenium is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric means for selenium in urine and whole blood were 63.19 µg/L and 221.17 µg/L, respectively (INSPQ, 2004).

Selenium was measured in the whole blood and urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as µg/L (Tables 8.13.1, 8.13.2, and 8.13.3) and in urine as both µg/L (Tables 8.13.4, 8.13.5, and 8.13.6) and µg/g creatinine (Tables 8.13.7, 8.13.8, and 8.13.9). Finding a measurable amount of selenium in blood or urine is an indicator of exposure to selenium and does not necessarily mean that an adverse health effect will occur. Because selenium is an essential trace element, its presence in biological fluids is expected.

9 Data Tables: 8.13.1 to 8.13.9

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2003). Toxicological profile for selenium. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 16, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=153&tid=28

Boosalis, M.G. (2008). The role of selenium in chronic disease. Nutrition in Clinical Practice, 23 (2), 152-160.

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2010a). Canada Consumer Product Safety Act. SC 2010, c. 21. Retrieved February 20, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-1.68/index.html

Canada. (2010b). Cribs, Cradles and Bassinets Regulations. SOR/2010-261. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2010-261/index.html

Canada. (2011a). The substance groupings initiative. Retrieved April 19, 2012, from www.chemicalsubstanceschimiques.gc.ca/group/index-eng.php

Canada (2011b). Announcement of planned actions to assess and manage, where appropriate, the risks posed by certain substances to the health of Canadians and the environment. Canada Gazette, Part I: Notices and Proposed Regulations, 145 (41). Retrieved August 28, 2012, from www.gazette.gc.ca/rp-pr/p1/2011/2011-10-08/html/notice-avis-eng.html

Canada. (2011c). Toys Regulations. SOR/2011-17. Retrieved January 25, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-2011-17/index.html

CCME (Canadian Council of Ministers of the Environment). (2009). Canadian soil quality guidelines for the protection of environmental and human health - Selenium. Winnipeg, MB. Retrieved April 16, 2012, from http://ceqg-rcqe.ccme.ca/download/en/341/

Health Canada. (1992). Guidelines for Canadian drinking water quality: Guideline technical document - Selenium. Minister of Health, Ottawa, ON. Retrieved April 16, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/selenium/index-eng.php

Health Canada. (2007). Multi-vitamin/mineral supplement monograph. Minister of Health, Ottawa, ON. Retrieved July 11, 2011, from www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/multi_vitmin_suppl-eng.php

Health Canada. (2009). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2010). Dietary reference intakes. Minister of Health, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/fn-an/nutrition/reference/table/index-eng.php

Health Canada. (2011). List of prohibited and restricted cosmetic ingredients ("hotlist"). Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

IARC (International Agency for Research on Cancer). (1999 ). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 9: Some aziridines, N-, S- and O-mustards and selenium. World Health Organization, Geneva.

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

IOM (Institute of Medicine). (2000). Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. The National Academies Press, Washington, DC.

Marier, J.R. & Jaworski, J.F. (1983). Interactions of selenium. National Research Council Canada Associate Committee on Scientific Criteria for Environmental Quality, Ottawa, ON.

Schamberger, R.J. (1984). Selenium. Biochemistry of the essential ultratrace elements. Plenum Press, New York, NY.

USGS (U.S. Geological Survey). (2001). 2001 minerals yearbook: Volume I - Metals and minerals. Reston, VA. Retrieved July 26, 2012, from http://minerals.usgs.gov/minerals/pubs/commodity/myb/index.html

USGS (U.S. Geological Survey). (2004). 2004 minerals yearbook: Volume I - Metals and minerals. Reston, VA. Retrieved August 22, 2012, from http://minerals.usgs.gov/minerals/pubs/commodity/selenium/index.html

WHO (World Health Organization). (2011). Selenium in drinking-water: Background document for development of WHO guidelines for drinking-water quality. WHO, Geneva. Retrieved April 16, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/selenium/en/

8.14 Silver

Silver (CASRN 7440-22-4) is a rare naturally occurring element found in the Earth's crust at an average concentration of approximately 0.000007% (Emsley, 2001). In its pure form, silver is a white lustrous metal with physical properties including ductility, electrical conductivity, malleability, and reflectivity. Natural silver is found in the environment in its pure form and in ores such as argentite, horn silver, chlorargyrite, and pyrargyritein.

Silver is naturally released into the environment through weathering and erosion of rocks and soil. Anthropogenic sources of silver include base-metal smelting, metal mining, cement manufacturing, burning of fossil fuels, hazardous waste sites, sewage, and silver-iodine cloud seeding (WHO, 2002). Photographic processing and materials were once the primary sources for environmental releases of silver; however, with the advent of digital photography, this use of silver has declined (USGS, 2012). Recent applications of nanosilver as an antimicrobial in a wide variety of products from household appliances to personal-care products are a potentially significant new source of release (Luoma, 2008).

Silver has been traditionally used in coins and medals, industrial applications, jewellery, silverware, and photography (USGS, 2011). Historically, in Canada, the major uses of silver were photography and coin production (Health Canada, 1986). Current industrial applications of silver include batteries, brazing and soldering, automobile catalytic converters, electronics and circuit boards, electroplating, hardening bearings, inks, mirrors, and solar cells (USGS, 2011). Soluble silver compounds are toxic to some bacteria, viruses, algae, and fungi. The antimicrobial properties of silver have led to the development of various applications including its use in bandages for wound care, cell-phone covers to reduce the spread of bacteria, clothing to minimize odour, water purification, and wood treatment to resist mould (USGS, 2011).

Silver exposure occurs primarily through food and drinking water, although exposure can also come from air (ATSDR, 1990). Because many silver salts are sparingly soluble, dissolved silver concentrations in natural waters are very low (Health Canada, 1986).

Based on a variety of mammalian data, the World Health Organization has estimated that approximately 10% of ingested silver is absorbed (WHO, 2003). Absorption of silver compounds from dermal exposure is much less efficient than from inhalation or ingestion because silver compounds are not readily absorbed through intact skin (ATSDR, 1990). Once absorbed, silver is stored primarily in liver and skin and in smaller amounts in other organs (WHO, 2003). Laboratory studies have indicated that silver is excreted following a triphasic profile with biological half-lives of a few hours, several days, and weeks to months (ATSDR, 1990). The majority of absorbed silver is excreted within a week predominantly through feces with a smaller amount through urine (ATSDR, 1990). The most common tests for silver exposure are through sampling of feces and blood (ATSDR, 1990). Urine can also be sampled; however, silver has not always been detected in urine samples from workers with known exposure to the metal, and as such is not as reliable a biomarker as feces and blood (ATSDR, 1990).

No reports of adverse health effects have been associated with exposure to silver at levels normally encountered in diets (Health Canada, 1986). There is human evidence of chronic toxicity following use of silver compounds as therapeutic agents (Health Canada, 1986). Ingestion of excessive quantities or prolonged administration of silver-containing compounds may result in argyria, a condition characterized by blue-grey discoloration of the skin, eyes, and mucous membranes (Health Canada, 1986).

Silver is not regarded as having any carcinogenic effects in humans (ATSDR, 1990). Evidence linking ingested silver or silver compounds with carcinogenic, mutagenic, or teratogenic effects is lacking, and silver has not been classified with respect to its carcinogenicity by the International Agency for Research on Cancer or Health Canada (Health Canada, 1986).

Health Canada has concluded that daily intake of silver from food and water is considerably below the level at which adverse effects would occur; therefore, a maximum acceptable concentration in drinking water has not been specified (Health Canada, 1986).

Silver was measured in the whole blood and urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented in blood as μg/L (Tables 8.14.1 and 8.14.2) and in urine as both µg/L and µg/g creatinine (Tables 8.14.3, 8.14.4, 8.14.5, and 8.14.6). Finding a measurable amount of silver in blood or urine is an indicator of exposure to silver and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for blood and urinary silver in the Canadian population.

6 Data Tables: 8.14.1 to 8.14.6

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1990). Toxicological profile for silver. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved September 6, 2011, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=539&tid=97

Emsley, J. (2001). Nature's building blocks: An A-Z guide to the elements. Oxford University Press, Oxford.

Health Canada. (1986). Guidelines for Canadian drinking water quality: Guideline technical document - Silver. Minister of Health, Ottawa, ON. Retrieved September 6, 2011, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/silver-argent/index-eng.php

Luoma, S.N. (2008). Silver nanotechnologies and the environment: Old problems or new challenges? Project on Emerging Nanotechnologies, Washington, DC.

USGS (U.S. Geological Survey). (2011). Mineral commodity summaries 2011. Reston, VA. Retrieved July 11, 2011, from http://minerals.usgs.gov/minerals/pubs/mcs/2011/mcs2011.pdf

USGS (U.S. Geological Survey). (2012). Mineral commodity summaries 2012. Reston, VA. Retrieved April 16, 2012, from http://minerals.usgs.gov/minerals/pubs/mcs/2012/mcs2012.pdf

WHO (World Health Organization). (2002). Silver and silver compounds: Environmental aspects. WHO, Geneva. Retrieved September 6, 2011, from www.who.int/ipcs/publications/cicad/en/cicad44.pdf

WHO (World Health Organization). (2003). Silver in drinking-water: Background document for development of WHO guidelines for drinking-water quality. WHO, Geneva. Retrieved September 6, 2011, from www.who.int/water_sanitation_health/dwq/chemicals/silver.pdf

8.15 Thallium

Thallium (CASRN 7440-28-0) is a blue-white, soft, malleable, naturally occurring metal present in the Earth's crust at an average concentration of approximately 0.00007% (USGS, 2011). It is ubiquitous in the environment and primarily occurs in the sulphide ores of a number of trace metals including copper, lead, and zinc. Thallium can also combine with other substances such as sulphide, chloride, and bromide to form salts, most of which are soluble in water (ATSDR, 1992).

Thallium is naturally released into the environment through weathering processes (CCME, 1999a). In addition to natural sources, thallium is released into the environment through anthropogenic emissions and waste materials from the combustion of fossil fuels, cement production, base-metal mining, and smelting (USGS, 2011). The major sources of thallium in drinking water are leaching from ore-processing sites and discharge from electronics, glass, and drug factories.

Thallium is used in alloys, electrodes, low-melting and highly refractive glass, cardiac imaging, electroplating, and as a high-temperature superconducting compound (CCME, 1999a). Historically, thallium was used in pesticides, but accidental poisonings and misuse have led to the ban or restriction of this use in most countries including Canada (CCME, 1999b). Thallium salts were also previously used as a depilatory agent and in the treatment of tuberculosis, malaria, and venereal diseases. However, as a consequence of adverse effects related to thallium, these uses have been discontinued (WHO, 1996).

Although only trace amounts of thallium are found in the environment, its presence is widespread, and humans are exposed daily via food and to a lesser degree through air and water (ATSDR, 1992). Thallous compounds have high solubility in water and are transported relatively easily into the environment through water. This fact is of concern because conventional water treatment strategies do little to remove thallium from water (Peter & Viraraghavan, 2005).

Thallium can be absorbed following ingestion, inhalation, or dermal contact. Following inhalation, it is generally assumed that up to 100% of lung-deposited thallium is absorbed (WHO, 1996). Similarly, studies suggest that thallium is completely absorbed following ingestion (ATSDR, 1992). Once absorbed, thallium is rapidly distributed throughout the body and accumulates in bones, kidneys. and eventually in the central nervous system (Peter & Viraraghavan, 2005). Thallium is primarily excreted in urine and to a lesser extent in feces, with a biological half-life of 3 to 8 days (ATSDR, 1992; Peter & Viraraghavan, 2005). Urinary thallium levels can be used as biomarkers of recent thallium exposure (CDC, 2009).

Thallium is a highly toxic element and is considered more acutely toxic than mercury, cadmium, lead, zinc, or copper. Adverse effects of acute thallium exposure include gastroenteritis, polyneuropathy, and alopecia (Peter & Viraraghavan, 2005). Based on human case reports and animal studies, the nervous system is considered the target organ of thallium (EPA, 2009). Information regarding the effects of low-level chronic exposure to thallium is limited. Some human data from the mining industry suggest that workers chronically exposed to thallium experienced headaches, anorexia, and pain in the arms, thighs, and abdomen (Peter & Viraraghavan, 2005).

Presently, there are no studies that evaluate the carcinogenic potential of thallium in animals and no sufficient evidence from workers occupationally exposed to thallium (EPA, 2009). Based on available data, thallium is not considered mutagenic or teratogenic, and data available on the reproductive effects of thallium on humans are limited (Peter & Viraraghavan, 2005). The International Agency for Research on Cancer considers the evidence for the carcinogenicity of thallium as unclassifiable.

As part of the Chemicals Management Plan under the Canadian Environmental Protection Act, 1999, thallium chloride is a priority for future assessment based on ecological concern (Canada, 1999; Environment Canada, 2011). There is currently no Canadian guideline for thallium in drinking water (Health Canada, 2012). Thallium is included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

In a biomonitoring study carried out in the region of the city of Québec with 500 participants aged 18 to 65 years, the geometric mean of thallium in urine was 0.21 µg/L (INSPQ, 2004).

Thallium was measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 8.15.1, 8.15.2, 8.15.3, and 8.15.4). Finding a measurable amount of thallium in urine is an indicator of exposure to thallium and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary thallium in the Canadian population.

4 Data Tables: 8.15.1 to 8.15.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1992). Toxicological profile for thallium. U.S. Department of Health and Human Services. Retrieved January 3, 2012, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=309&tid=49

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

CCME (Canadian Council of Ministers of the Environment). (1999a). Canadian water quality guidelines for the protection of aquatic life - Thallium. January 3, 2012, from http://ceqg-rcqe.ccme.ca/download/en/215/

CCME (Canadian Council of Ministers of the Environment). (1999b). Canadian soil quality guidelines for the protection of environmental and human health - Thallium. January 3, 2012, from http://ceqg-rcqe.ccme.ca/download/en/282/

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Environment Canada. (2011). Status of prioritized substances. Minister of the Environment. Retrieved August 9, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=7CCD1F11-1

EPA (U.S. Environmental Protection Agency). (2009). Integrated Risk Information System (IRIS): Thallium (I), soluble salts. Office of Research and Development, National Center for Environmental Assessment. Retrieved May 4, 2012, from www.epa.gov/ncea/iris/subst/1012.htm

Health Canada. (2009). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2012). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

Peter, A.L.J. & Viraraghavan, T. (2005). Thallium: A review of public health and environmental concerns. Environment International, 31 (4), 493-501.

USGS (U.S. Geological Survey). (2011). Mineral commodity summaries 2011. Retrieved July 11, 2011, from http://minerals.usgs.gov/minerals/pubs/mcs/2011/mcs2011.pdf

WHO (World Health Organization). (1996). Environmental health criteria 182: Thallium. WHO. Retrieved January 4, 2012, from www.inchem.org/documents/ehc/ehc/ehc182.htm

8.16 Tungsten

Tungsten (CASRN 7440-33-7) is a steel grey metal present in the Earth's crust at average concentrations ranging from 0.00001% to 0.00024% (ATSDR, 2005). In its pure form the metal can be easily shaped, but in the presence of impurities it is often brittle and hard. Tungsten is relatively stable in the environment (Langard, 2001). Five stable and 28 radioactive isotopes of tungsten are currently known. In nature, tungsten occurs in minerals combined with other elements but not as a pure metal.

Tungsten particles are released into the atmosphere by both natural and anthropogenic sources. Tungsten is naturally present in soils and sediments and is released to air and water through soil erosion and leaching from soil and rocks (ATSDR, 2005). Anthropogenic sources include emissions from metal milling and processing, waste and fuel burning, mining operations, and fertilizer application (ATSDR, 2005). Military training and combat operations also release tungsten during the use of tungsten-containing weaponry (ATSDR, 2005).

The major uses of tungsten include the production of cutting and wear-resistance materials, mill products, alloy additives, super alloys, and tungsten chemicals (Langard, 2001). Commercial applications of tungsten, primarily in the tungsten carbide form, include uses as a component in cutting, forming, mining, and drilling tools (ATSDR, 2005). Tungsten metal powder is used for the production of filament wire, welding rods, and coating oil-well tools. Tungsten alloys have also been increasingly used in military weaponry as a replacement for depleted uranium and lead-based munitions (EPA, 2010; Health Canada, 2008). Tungsten metal is also a component in the production of golf clubs, counterbalance weights, lamp filaments, furnace elements, glass-melting equipment, high-speed rotors, and aerospace applications, including rocket nozzles. Tungsten compounds may be used as a part of pigments, printing inks, waxes, glasses, and cigarette filters as well as fireproofing agents in textiles (ATSDR, 2005).

The general population can be exposed to trace amounts of tungsten in food, drinking water, and air (ATSDR, 2005). Exposure to tungsten-containing compounds, rather than to tungsten itself, may occur during the use of tungsten, its alloys, and compounds. Based on limited surface-water data, the estimated daily intake from drinking water is expected to be negligible (ATSDR, 2005).

Following ingestion or inhalation, approximately half of soluble tungsten compounds are absorbed into the blood stream (ATSDR, 2005). The majority of absorbed tungsten is rapidly released in the urine (ATSDR, 2005). Studies in animals indicate that bone is the main reservoir for tungsten following long-term distribution in the body (Langard, 2001). The presence of tungsten in the blood, urine, or feces serves as a biomarker of exposure to tungsten or tungsten compounds, with urinary levels reflective of recent exposure (ATSDR, 2005; CDC, 2009).

The toxicity of ingested tungsten in humans is unknown (ATSDR, 2005). Data following inhalation exposure are available only for occupational exposures in the hard-metal industry. It is unclear, however, whether the illnesses observed stem from exposure to tungsten alone or rather cobalt mixed with tungsten carbide (ATSDR, 2005). No other significant adverse health effects have been associated with acute or chronic inhalation, oral, or dermal exposure to tungsten or tungsten compounds in humans (ATSDR, 2005). In laboratory animals, there is limited evidence associating oral or inhalation tungsten exposure with reproductive and developmental effects (ATSDR, 2005). Skin and eye irritations have also been observed in animals following exposure to tungsten chloride (ATSDR, 2005).

The International Agency for Research on Cancer (IARC) concluded that cobalt metal with tungsten carbide is probably carcinogenic to humans (Group 2A) (IARC, 2006). Evidence for the carcinogenicity of tungsten alone is lacking and it has not been classified with respect to its carcinogenicity by IARC (ITER, 2010).

Health Canada has not established a drinking water quality guideline for tungsten (Health Canada, 2012).

Tungsten was measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 8.16.1, 8.16.2, 8.16.3, and 8.16.4). Finding a measurable amount of tungsten in urine is an indicator of exposure to tungsten and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary tungsten in the Canadian population.

4 Data Tables: 8.16.1 to 8.16.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2005). Toxicological profile for tungsten. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved January 6, 2012, from www.atsdr.cdc.gov/toxprofiles/tp186.pdf

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

EPA (U.S. Environmental Protection Agency). (2010). Emerging contaminant fact sheet - Tungsten. U.S. Environmental Protection Agency, Washington, DC. Retrieved January 24, 2012, from www.epa.gov/fedfac/documents/emerging_contaminant_tungsten.pdf

Health Canada. (2008). Environmental and workplace health - Depleted uranium (Health Canada information sheet). Minister of Health, Ottawa, ON. Retrieved January 18, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/radiation/uranium-eng.php

Health Canada. (2012). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

IARC (International Agency for Research on Cancer). (2006). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 86: Cobalt in hard metals and cobalt sulfate, gallium arsenide, indium phosphide and vanadium pentoxide. World Health Organization, Geneva.

ITER (International Toxicity Estimates for Risk). (2010). ITER database: Tungsten (CAS 7440-33-7). National Library of Medicine, Bethesda, MD. Retrieved May 4, 2012, from www.toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?iter

Langard, S. (2001). Chromium, molybdenum, and tungsten. Patty's Toxicology. John Wiley & Sons, Inc., Mississauga, ON.

8.17 Uranium

Pure uranium (CASRN 7440-61-1) is a silvery white, lustrous, weakly radioactive metal present at an average concentration in the Earth's crust of approximately 0.0002% (ATSDR, 2011). Uranium is not a stable element and undergoes radioactive decay, producing radioactive products as well as alpha and gamma radiation. Natural uranium is a mixture of three radioactive isotopes: uranium 238 (99.3%), uranium 235 (approximately 0.7%), and uranium 234 (0.005%) (WHO, 2003).

Uranium occurs naturally in variable, yet small, amounts in rock, soil, water, and air. It is naturally introduced into the atmosphere through the weathering of rock and soil (ATSDR, 2011). In addition to natural sources, uranium is released from anthropogenic sources such as uranium mining and milling, improper disposal of mill tailings, uranium processing, and burning of coal (ATSDR, 2011). Mining and milling operations can also alter the normal distribution of naturally occurring radioactive materials, possibly increasing the potential for human exposure. The use of depleted uranium ammunition during military training and combat operations can also lead to localized release of depleted uranium to soil at those locations (ATSDR, 2011).

Enriched uranium, containing a higher content of uranium 235 than natural uranium, is used primarily as a fuel in nuclear power reactors; it can also be a component of nuclear weapons (ATSDR, 2011). Depleted uranium is the by-product of the enrichment process and has a lower content of uranium 235 compared with natural uranium resulting in low radioactivity. Because of its high density, depleted uranium is used for military ammunition and armour-penetrating military ordnance (ATSDR, 2011). Civilian uses include aviation guidance devices and radiation shielding material for medical purposes. Historically, depleted uranium was also used in dentistry and to produce coloured ceramics and glasses (ATSDR, 2011).

Uranium intake is primarily through the ingestion of food, although drinking water and house dust can also be significant sources (CCME, 2007). The concentration of uranium in drinking water is highly variable and appears to depend on the source of the water (CCME, 2007).

Uranium compounds, such as uranium oxides, are not readily absorbed following oral ingestion and inhalation. Following ingestion, a small fraction (<5%) of ingested uranium rapidly appears in the bloodstream and is subsequently rapidly cleared. The vast majority of ingested uranium is excreted through the feces, and urine to a lesser extent, within a few days (ATSDR, 2011). Following inhalation, insoluble uranium compounds can remain in the lungs for years, whereas soluble forms enter the blood stream where they become concentrated in the bones and kidneys (CCME, 2007). The biological half-life in bone is approximately 11 days and in kidneys is 2 to 6 days (ATSDR, 2011). The most common test for uranium exposure is through urine because traces can remain for months after exposure, although urine tests are less accurate for low exposure levels (ATSDR, 2011). Other possible methods to determine if an individual has been exposed include testing blood and hair and measuring radiation levels within the body or on the skin.

Uranium can have health effects owing to both its chemical toxicity and the radiological toxicity of the radionuclides involved. Chemical toxicity effects are the same regardless of isotopic composition (Health Canada, 2008). Thus, the chemical toxicities of natural, depleted, and enriched uranium are identical. Based on human case reports and animal studies, the kidney is the organ primarily affected by the chemical toxicity of uranium following oral and inhalation exposure (ATSDR, 2011; Health Canada, 2008). Uranium chemical toxicity may also target the respiratory tract (inhalation only), neurological system, reproductive system, and the developing organism (ATSDR, 2011).

Because natural and depleted uranium are only weakly radioactive, health effects due to radioactivity, such as carcinogenicity, are generally observed only at much higher levels than those that can result in chemical toxicity (Health Canada, 2008). Health Canada has classified uranium as Group V, inadequate data for evaluation of carcinogenicity; the chemical carcinogenicity of uranium has been observed only from inhalation of highly insoluble or enriched uranium compounds and not from oral exposure (Health Canada, 2001). The International Agency for Research on Cancer determined that there was inadequate evidence in humans and limited evidence in laboratory animals for carcinogenicity of natural uranium (IARC, 2001). These evaluations consider only potential chemical carcinogenicity; radiation is considered carcinogenic.

A Canadian drinking water quality guideline has been developed that sets out the maximum acceptable concentration of uranium, considering both the toxicity and the cost of treating water to meet the guideline using currently available technologies (Health Canada, 2001; Health Canada, 2009a). Uranium is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009b). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

Uranium was measured in the whole blood and urine from all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as µg/L (Tables 8.17.1, 8.17.2, and 8.17.3) and in urine as both µg/L (Tables 8.17.4, 8.17.5, and 8.17.6) and µg/g creatinine (Tables 8.17.7, 8.17.8, and 8.17.9). Finding a measurable amount of uranium in blood or urine is an indicator of exposure to uranium and does not necessarily mean that an adverse health effect will occur.

9 Data Tables: 8.17.1 to 8.17.9

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2011). Draft toxicological profile for uranium. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 19, 2012, from www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=440&tid=77

CCME (Canadian Council of Ministers of the Environment). (2007). Canadian soil quality guidelines for the protection of environmental and human health - Uranium. Winnipeg, MB. Retrieved April 19, 2012, from http://ceqg-rcqe.ccme.ca/download/en/285/

Health Canada. (2001). Guidelines for Canadian drinking water quality: Guideline technical ocument - Uranium. Minister of Health, Ottawa, ON. Retrieved April 19, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/uranium/index-eng.php

Health Canada. (2008). Environmental and workplace health - Depleted uranium (Health Canada information sheet). Minister of Health, Ottawa, ON. Retrieved January 18, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/radiation/uranium-eng.php

Health Canada. (2009a). Guidelines for Canadian drinking water quality: Guideline technical document - Radiological parameters. Minister of Health, Ottawa, ON. Retrieved July 11, 2011, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/radiological_para-radiologiques/index-eng.php

Health Canada. (2009b). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

IARC (International Agency for Research on Cancer). (2001). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 78: Ionizing radiation, Part 2, some internally deposited radionuclides. World Health Organization, Geneva.

WHO (World Health Organization). (2003). Fact sheet 257: Depleted uranium. World Health Organization, Geneva. Retrieved April 19, 2012, from www.who.int/mediacentre/factsheets/fs257/en/

8.18 Vanadium

Vanadium (CASRN 7440-62-2) is a naturally occurring element present in the the Earth's crust at an average of approximately 0.01%. It is present in iron ores, phosphate rock, and crude oil deposits (ATSDR, 2009). Vanadium is usually found combined with other elements and can exist in six different oxidation states, acting as either a metal or non-metal.

Vanadium is generally associated with organic matter; it can be found in crude oil and various refined petroleum products, particularly heavy fuel oil. Lesser natural sources of vanadium include erosion and weathering of rock-bearing minerals, sea spray, and volcanic emissions (ATSDR, 2009). Anthropogenic sources of vanadium include petroleum refineries, electrical power generation plants, and the pulp and paper industry through the burning of fossil and wood fuels (Environment Canada & Health Canada, 2010).

Vanadium is used mainly as an alloy additive in the production of various steels to increase strength, hardness, wear resistance, and ductility. Some vanadium is used to produce ferrovanadium alloys for aircraft engines and nonferrous titanium alloys. In addition, vanadium is used in the manufacture of phthalic anhydride and sulphuric acid, as a catalyst in processes such as petroleum cracking, and in the production of pesticides, dyes, inks, and pigments (Vanadium Investing News, 2011). The vanadium redox-flow battery is an emerging technology that may be used to store electricity generated by large-scale wind and solar farms (Vanadium Investing News, 2011). Vanadium may also be found in various commercial nutritional supplements and multivitamins (Health Canada, 2007).

The main source of vanadium for the general population is through food, although exposure can also come from air, drinking water, soil, and household dust (ATSDR, 2009). When it is used as a supplement, this use can account for much of the exposure to vanadium (Pennington & Jones, 1987).

Vanadium can be absorbed following inhalation, oral, or dermal exposure, with dermal absorption being less efficient than inhalation or oral absorption. Long-term distribution of vanadium in the body is independent of the route of exposure, with bones being the main reservoir. Ingested vanadium is mainly excreted through the feces; the kidneys are the main route for elimination of absorbed vanadium (ACGIH, 2001). Tissue elimination occurs with half-lives ranging from 3 to 15 days (ATSDR, 2009). Absorption of ingested vanadium is less than 5%, thus most ingested vanadium is found in the feces (IOM, 2001). Urinary vanadium can be a biomarker of exposure to absorbed vanadium and vanadium-related compounds, such as vanadium oxide (ATSDR, 2009). However, because the relationship between external exposure and urine concentrations is variable, urinary vanadium provides only a qualitative indication of external exposure (ILO, 1998).

Vanadium is believed to have beneficial effects at low doses; however, its role in the body remains unclear (IOM, 2001). The Institute of Medicine (IOM) has concluded that data are insufficient to establish recommended dietary allowances (IOM, 2001). There is evidence in humans of mild gastrointestinal effects and hematological effects, such as anemia, following ingestion of vanadium compounds (ATSDR, 2009). Renal toxicity has been observed in animals following ingestion of vanadium compounds, but these effects have not been seen in humans (IOM, 2001). Acute inhalation exposure to vanadium, particularly vanadium pentoxide, has been associated with respiratory irritation (ATSDR, 2009).

The International Agency for Research on Cancer recently evaluated the carcinogenicity of vanadium pentoxide and has classified it as Group 2B, a possible human carcinogen, based on inadequate human data but sufficient evidence of respiratory cancers in rodent inhalation studies (IARC, 2006).

As part of the Chemicals Management Plan under the Canadian Environmental Protection Act, 1999 (CEPA 1999), vanadium pentoxide was identified as a priority substance (Canada, 1999; Canada, 2011). The final screening assessment was published in September 2010 and concluded on the basis of carcinogenicity that there may be a probability of harm at any level of exposure (Environment Canada & Health Canada, 2010). Applying a precautionary approach, it was concluded that vanadium pentoxide may be entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health (Environment Canada & Health Canada, 2010). In 2010, vanadium pentoxide was listed as a toxic substance on Schedule 1 of the CEPA 1999 (Canada, 2010a). To manage the risks posed by vanadium pentoxide, existing programs will be used to reduce particulate emissions from combustion of certain fossil fuels (Canada, 2010b).

Health Canada has adopted tolerable upper intake levels for vanadium developed by the Institute of Medicine based upon renal toxicity as the critical adverse effect (Health Canada, 2007; IOM, 2001). There is currently no Canadian guideline for vanadium in drinking water (Health Canada, 2012).

Vanadium was measured in the urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented as both µg/L (Tables 8.18.1, 8.18.2, and 8.18.3) and µg/g creatinine (Tables 8.18.4, 8.18.5, and 8.18.6). Finding a measurable amount of vanadium in urine is an indicator of exposure to vanadium and does not necessarily mean that an adverse health effect will occur.

6 Data Tables: 8.18.1 to 8.18.6

References

ACGIH (American Conference of Industrial Hygienists). (2001). Documentation of the biological exposure indices. ACGIH, Cincinnati, OH.

ATSDR (Agency for Toxic Substances and Disease Registry). (2009). Draft toxicological profile for vanadium. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 20, 2012, from www.atsdr.cdc.gov/ToxProfiles/tp58.pdf

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2010a). Order adding a toxic substance to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part I: Notices and Proposed Regulations, 144 (44). Retrieved August 28, 2012, from www.gazette.gc.ca/rp-pr/p1/2010/2010-10-30/html/reg1-eng.html

Canada. (2010b). Vanadium pentoxide. Retrieved June 7, 2012, from www.chemicalsubstanceschimiques.gc.ca/challenge-defi/summary-sommaire/batch-lot-9/1314-62-1-eng.php

Canada. (2011). Chemical substances website. Retrieved January 12, 2012, from www.chemicalsubstances.gc.ca

Environment Canada & Health Canada. (2010). Screening assessment for the challenge: Vanadium oxide (vanadium pentoxide). Ottawa, ON. Retrieved April 24, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=62A2DBA9-1

Health Canada. (2007). Multi-vitamin/mineral supplement monograph. Minister of Health, Ottawa, ON. Retrieved July 11, 2011, from www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/multi_vitmin_suppl-eng.php

Health Canada. (2012). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

IARC (International Agency for Research on Cancer). (2006). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 86: Cobalt in hard metals and cobalt sulfate, gallium arsenide, indium phosphide and vanadium pentoxide. World Health Organization, Geneva.

ILO (International Labour Organization). (1998). Encyclopaedia of occupational health and safety. ILO, Geneva.

IOM (Institute of Medicine). (2001). Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press, Washington, DC.

Pennington, J.A.T. & Jones, J.W. (1987). Molybdenum, nickel, cobalt, vanadium, and strontium in total diets. Journal of the American Dietetic Association, 87 (12), 1644-1650.

Vanadium Investing News. (2011). Vanadium batteries for sustainable energy. Retrieved April 24, 2012, from http://vanadiuminvestingnews.com/1811/vanadium-batteries-for-sustainable-energy/

8.19 Zinc

Zinc (CASRN 7440-66-6), one of the more common naturally occurring elements, is present in the Earth's crust at an average of approximately 0.0075% (Emsley, 2001). It is a lustrous, bluish white, relatively soft metal in its pure state. Zinc is a base metal that exists naturally in a divalent oxidation state in various inorganic and organic compounds. The most common zinc ore is sphalerite that often exists with the sulphides of other metallic elements (e.g. lead, copper, cadmium, and iron) (EPA, 1976). Zinc is also found as calamine in carbonate sediments; other forms of zinc are usually products of the oxidation of sphalerite (EPA, 1976; Hem, 1970). Zinc is an essential trace element required for the maintenance of good health in humans.

Natural emissions of zinc and its compounds to air are due mainly to windborne soil particles, volcanic emissions, and forest fires (ATSDR, 2005). The major anthropogenic sources of zinc include electroplating, smelting and ore processing, drainage from both active and inactive mining operations, coal and fuel combustion, waste disposal and incineration, iron and steel production, municipal effluents, and the use of zinc-containing fertilizers (ATSDR, 2005).

Zinc is used mainly for galvanizing other metal products, such as iron and steel, to prevent corrosion. Other principal uses include the production of alloys, such as brass and bronze, and the manufacture of dry-cell batteries. Zinc is also used in paints, preservatives, dyes, pesticides, and various cosmetic and pharmaceutical products; in the manufacture of rayons, yarns, inks, matches, tires, and other rubber products; for cementing metals in metallurgical processing; and in ornamental work (CCME, 1999; Health Canada, 1987). Zinc compounds can also be found in products such as vitamin or mineral supplements, sunscreens, deodorants, and anti-dandruff shampoos.

The general population is primarily exposed to zinc at low levels through the ingestion of food. Increased exposure may occur from drinking water from pipes and fittings leaching zinc. Following ingestion, zinc is absorbed via the gastrointestinal tract and then transported to various tissues and organs. In persons with adequate nutritional levels, between 20% and 30% of dietary zinc is absorbed; however, enhanced absorption is known to occur under conditions of zinc deficiency (ATSDR, 2005). Over 85% of the total body zinc is found in skeletal muscle and bone (IOM, 2001). The primary route of excretion from the body is via the gastrointestinal tract; this excretion includes unabsorbed dietary zinc, a small amount from sloughing of intestinal epithelial cells, and zinc from biliary and pancreatic origin. Under normal circumstances, a small amount of zinc may be lost daily in perspiration and in urine (Prasad, 1983). Concentrations of zinc in serum and urine are believed to increase after exposure. Serum zinc levels are commonly used as indicators of population zinc status (Hess et al., 2007). Hair and nail samples have also been suggested to have potential value for monitoring longer-term exposure (ATSDR, 2005).

As an essential trace element, zinc is required as a component of many metalloenzymes and other substances in the body (Health Canada, 1987). It aids in connective tissue formation, the maintenance of healthy skin, immune system functioning, and the metabolism of carbohydrates, fats, and proteins (CCME, 1999; Health Canada, 1987; Health Canada, 2007). Zinc deficiency may lead to dermatitis, anorexia, reduced growth, poor healing of wounds, reduced reproductive ability, reduced mental function, and impairment of the immune system (ATSDR, 2005). Insufficient zinc intake may also have an impact on the carcinogenicity of other chemicals (ATSDR, 2005). On account of its essentiality, Health Canada has established recommended dietary allowances for zinc (Health Canada, 2010; IOM, 2001).

Acute zinc toxicity is usually the result of taking excessive amounts of vitamin or mineral supplements or drinking acidic beverages stored for long periods of time in galvanized containers (WHO, 2003). Acute exposure to large doses of zinc can cause stomach cramps, nausea, and vomiting (ATSDR, 2005). Ingesting high levels of zinc and chronic low-dose exposure can inhibit absorption of copper into the blood stream and cause copper deficiency (ATSDR, 2005; EPA, 2005a; WHO, 2003). Effects of inhaled zinc are generally limited to the respiratory tract and vary depending on the specific chemical composition (ATSDR, 2005). Data demonstrating an increase in cancer incidence following long-term exposure to zinc compounds are insufficient, and zinc has not been classified with respect to its carcinogenicity by the International Agency for Research on Cancer. Based on this lack of information, the United States Environmental Protection Agency has determined that zinc is not classifiable as to its human carcinogenicity (EPA, 2005b).

Health Canada has established maximum recommended levels for zinc in dietary supplement formulations in Canada (Health Canada, 2007). Tolerable upper intake levels for zinc, which account for its potential toxicity, have been developed by the Institute of Medicine and adopted by Health Canada (Health Canada, 2010; IOM, 2001). Health Canada has also developed a Canadian drinking water quality guideline that sets out the aesthetic objective for zinc based upon taste (Health Canada, 1987). Although a health-based guideline has not been established, the aesthetic guideline is deemed protective of adverse health effects. Zinc is also included in the list of various chemicals analyzed as part of Health Canada's ongoing Total Diet Study surveys (Health Canada, 2009). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

In a study carried out in British Columbia to assess the levels of trace elements in 61 non-smoking adults aged 30 to 65 years, the geometric mean concentration and 95th percentile of zinc in urine were 285.43 µg/g creatinine and 607.83 µg/g creatinine, respectively (Clark et al., 2007).

Zinc was measured in the whole blood and urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented in blood as mg/L (Tables 8.19.1, 8.19.2, and 8.19.3) and in urine as both µg/L and µg/g creatinine (Tables 8.19.4, 8.19.5, 8.19.6, 8.19.7, 8.19.8, and 8.19.9). Finding a measurable amount of zinc in blood or urine is an indicator of exposure to zinc and does not necessarily mean that an adverse health effect will occur. Because zinc is an essential nutrient, its presence in biological fluids is expected.

9 Data Tables: 8.19.1 to 8.19.9

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2005). Toxicological profile for zinc. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved March 6, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=302&tid=54

CCME (Canadian Council of Ministers of the Environment). (1999). Canadian soil quality guidelines for the protection of environmental and human health - Zinc. Winnipeg, MB. Retrieved March 7, 2012, from http://ceqg-rcqe.ccme.ca/download/en/288/

Clark, N.A., Teschke, K., Rideout, K., & Copes, R. (2007). Trace element levels in adults from the west coast of Canada and associations with age, gender, diet, activities, and levels of other trace elements. Chemosphere, 70 (1), 155-164.

Emsley, J. (2001). Nature's building blocks: An A-Z guide to the elements. Oxford University Press, Oxford.

EPA (U.S. Environmental Protection Agency). (1976). Quality criteria for water. U.S. Environmental Protection Agency, Washington, DC. Retrieved March 8, 2012, from http://water.epa.gov/scitech/swguidance/standards/current/upload/2009_01_13_criteria_redbook.pdf

EPA (U.S. Environmental Protection Agency). (2005a). Toxicological review of zinc and compounds - In support of summary information on the Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency, Washington, DC. Retrieved January 24, 2012, from www.epa.gov/iris/toxreviews/0426tr.pdf

EPA (U.S. Environmental Protection Agency). (2005b). Integrated Risk Information System (IRIS): Zinc. Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH. Retrieved June 8, 2012, from www.epa.gov/iris/subst/0426.htm

Health Canada. (1987). Guidelines for Canadian drinking water quality: Guideline technical document - Zinc. Minister of Health, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/zinc/index-eng.php

Health Canada. (2007). Multi-vitamin/mineral supplement monograph. Minister of Health, Ottawa, ON. Retrieved July 11, 2011, from www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/multi_vitmin_suppl-eng.php

Health Canada. (2009). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2010). Dietary reference intakes. Minister of Health, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/fn-an/nutrition/reference/table/index-eng.php

Hem, J.D. (1970). Study and interpretation of the chemical characteristics of natural water. U.S. Geological Survey, Washington, DC. Retrieved March 8, 2012, from http://pubs.usgs.gov/wsp/1473/report.pdf

Hess, S.Y., Peerson, J.M., King, J.C., & Brown, K.H. (2007). Use of serum zinc concentration as an indicator of population zinc status. Food & Nutrition Bulletin, 28 (3), S403-429.

IOM (Institute of Medicine). (2001). Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press, Washington, DC.

Prasad, A.S. (1983). Clinical, biochemical and nutritional spectrum of zinc deficiency in human subjects: An update. Nutrition Reviews, 41 (7), 197-208.

WHO (World Health Organization). (2003). Zinc in drinking-water: Background Document for development of WHO guidelines for drinking-water quality. WHO, Geneva. Retrieved March 7, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/zinc/en/

9 Benzene Metabolites Summary and Results

Benzene is a colorless liquid and a highly volatile organic compound that was first isolated and synthesized in the early 1800s (ATSDR, 2007). It is naturally present in ambient air at low concentrations (Health Canada, 2009). Currently, benzene is commercially recovered from both coal and petroleum sources for industrial applications (ATSDR, 2007).

Benzene is released to the environment from natural and anthropogenic sources. It is naturally present at a median concentration of 0.28% by weight in Canadian crude oil, and is formed during the incomplete combustion of organic materials (Drummond, 1991; Environment Canada & Health Canada, 1993). Benzene enters the environment as a result of natural processes including petroleum seepage, weathering of rock and soil, volcanic activity, forest fires, and releases from plant life (Environment Canada & Health Canada, 1993). Anthropogenic sources include the production, storage, use, and transport of isolated benzene, crude oil, and some of its refined products. Examples include evaporative releases from gasoline at service stations and motor vehicle exhaust (Health Canada, 2009). Natural sources are generally considered to be lower contributors than anthropogenic ones to benzene in the environment (Environment Canada & Health Canada, 1993).

Benzene is used widely in industry as a solvent and as an intermediate in the production of a variety of chemicals (Environment Canada & Health Canada, 1993). These chemicals are typically used for the production of end-products including plastics and elastomers, phenol and acetone, and nylon resins (ATSDR, 2007). Benzene is also used at various stages in the manufacturing of synthetic fibres, rubbers, lubricants, dyes, detergents, drugs, and pesticides (ATSDR, 2007).

The general population is exposed to benzene mainly through inhalation of air; higher exposures occur particularly in areas of heavy vehicle traffic and at service stations, and by inhalation of tobacco smoke (ATSDR, 2007). Exposure to benzene in air accounts for an estimated 98% to 99% of total benzene intake for Canadian non-smokers (Health Canada, 2009). In private homes, benzene levels in air have been shown to be higher in homes with attached garages, or where the inhabitants smoke indoors (Héroux et al., 2010; Héroux et al., 2008). Various products containing benzene can also contribute to its presence in indoor air (Environment Canada & Health Canada, 1993). Although low levels of benzene have been detected in tap water and in certain foods and beverages, they do not constitute major sources of exposure for the general population (ATSDR, 2007; Health Canada, 2009).

Following inhalation, benzene is readily absorbed into the blood and is distributed throughout the body concentrating in adipose tissue (EPA, 2002). In the lung and liver, benzene is metabolized into several reactive metabolites including benzene oxide (EPA, 2002; McHale et al., 2012). From benzene oxide, benzene metabolism branches into several alternative metabolic pathways: spontaneous rearrangement produces phenol, a major product; reaction with glutathione ultimately forms S-phenylmercapturic acid (S-PMA); and an iron-catalyzed reaction leads to the formation of trans,trans-muconic acid (t,t-MA) (EPA, 2002). Excretion of benzene occurs primarily as conjugated metabolites, and all benzene metabolites may be conjugated with sulphate or glucuronic acid (EPA, 2002). Phenol, S-PMA, and t,t-MA are considered urinary biomarkers of recent benzene exposure (Boogaard & van Sittert, 1995; Qu et al., 2005; Weisel, 2010). Measurements of t,t-MA and S-PMA are more sensitive and reliable indicators of benzene exposure because urinary phenol may be a result of dietary or environmental exposure to phenol or other phenolic compounds (ATSDR, 2007).

Exposure to benzene is known to cause a number of health effects in humans. Benzene is hematotoxic in humans and laboratory animals, with bone marrow being the principal target organ (EPA, 2002). Available data indicate that metabolites produced in the liver may be carried to bone marrow where benzene toxicity occurs (EPA, 2002). In rodents, chronic inhalation exposure to benzene has been shown to cause leukemia (EPA, 2002). Epidemiologic studies and case studies provide strong evidence of an association between exposure to high levels of benzene and leukemia risk in occupationally exposed humans (EPA, 2002). The International Agency for Research on Cancer has classified benzene as Group 1, carcinogenic to humans (IARC, 2012). A common mode of action has not been established for hematotoxic and carcinogenic effects; however, it is generally accepted that acute myelogenous leukemia and non-cancer effects are caused by one or more reactive metabolites of benzene (ATSDR, 2007; EPA, 2002; McHale et al., 2012; Smith, 2010).

Benzene has become one of the most intensively regulated substances (Capleton & Levy, 2005). Regulations have been put in place for the permissible concentrations of benzene in gasoline as well as for the emission standards for vehicles in Canada (Canada, 1997; Environment Canada, 2012). Benzene is listed on Schedule 1, List of Toxic Substances, under the Canadian Environmental Protection Act, 1999 and is a candidate for a full lifecycle management to prevent or minimize its release into the environment (Canada, 1999; Environment Canada & Health Canada, 1993). In 2000-2001, the Canadian Council of Ministers of the Environment endorsed the Canada-wide standard for benzene requiring industry reduction of total benzene emissions and use of best management practices (CCME, 2000; CCME, 2001). With the implementation of the standard, emissions of benzene in ambient air fell by 67% between 1995 and 2003 (CCME, 2000; CCME, 2001). Benzene is also included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011). Health Canada has established a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of benzene based on cancer endpoints and is considered protective of both cancer and non-cancer effects (Health Canada, 2009). Health Canada is also working on a guidance document for benzene in residential indoor air.

Exposure to benzene was assessed in firefighters in Montréal, Quebec by means of urinary measurements of t,t-MA. Urine samples were collected from 43 firefighters over a period of 20 hours following the end of a fire (Caux et al., 2002). Among the 43 firefighters in this study, only six had t,t-MA concentrations exceeding 1700 µg/g creatinine. This value corresponds to a benzene air concentration almost 1,000 times greater than the average concentration in ambient air (Boogaard & van Sittert, 1995; Environment Canada & Health Canada, 1993).

Benzene metabolites, including phenol, t,t-MA and S-PMA, were measured in the urine of all Canadian Health Measures Survey participants aged 3 to 79 years in cycle 2 (2009-2011). Data are presented as both mg/L and mg/g creatinine for phenol (Tables 9.1.1 to 9.1.4) and as both µg/L and µg/g creatinine for t,t-MA and S-PMA (Tables 9.2.1 to 9.3.4). Finding a measurable amount of phenol, t,t-MA, or S-PMA in urine can be an indicator of exposure to benzene and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary benzene metabolites in the Canadian population.

9.1 Phenol

4 Data Tables: 9.1.1 to 9.1.4

9.2 trans,trans-Muconic Acid (t,t-MA)

4 Data Tables: 9.2.1 to 9.2.4

9.3 S-Phenylmercapturic Acid (S-PMA)

4 Data Tables: 9.3.1 to 9.3.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2007). Toxicological profile for benzene. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved May 22, 2011, from www.atsdr.cdc.gov/toxprofiles/tp3-c6.pdf

Boogaard, P.J. & van Sittert, N.J. (1995). Biological monitoring of exposure to benzene: A comparison between S-phenylmercapturic acid, trans,trans-muconic acid, and phenol. Occupational and Environmental Medicine, 52 (9), 611-620.

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1997). Benzene in Gasoline Regulations. SOR/97-493. Retrieved August 14, 2012, from http://laws-lois.justice.gc.ca/eng/regulations/SOR-97-493/index.html

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Capleton, A.C. & Levy, L.S. (2005). An overview of occupational benzene exposures and occupational exposure limits in Europe and North America. Chemico-Biological Interactions, 43-53, 153-154.

Caux, C., O'Brien, C., & Viau, C. (2002). Determination of firefighter exposure to polycyclic aromatic hydrocarbons and benzene during fire fighting using measurement of biological indicators. Applied Occupational and Environmental Hygiene, 17 (5), 379-386.

CCME (Canadian Council of Ministers of the Environment). (2000). Canada-wide standards for benzene - Phase 1. Québec, QC. Retrieved June 9, 2012, from www.ccme.ca/assets/pdf/benzene_std_june2000_e.pdf

CCME (Canadian Council of Ministers of the Environment). (2001). Canada-wide standards for benzene - Phase 2. Québec, QC. Retrieved June 9, 2012, from www.ccme.ca/assets/pdf/benzene_cws_phase2_e.pdf

Drummond, I. (1991). Industrial hygiene survey report: Benzene content of crude oil and condensate streams. Esso Resources Canada Ltd., Calgary, AB.

Environment Canada. (2012). Guidance document on the benzene in Gasoline Regulations. Minister of the Environment, Ottawa, ON. Retrieved June 8, 2012, from www.ec.gc.ca/lcpe-cepa/default.asp?lang=En&n=4BFBD709-1&offset=2&toc=show

Environment Canada & Health Canada. (1993). Priority substances list assessment report: Benzene. Minister of Supply and Services Canada, Ottawa, ON. Retrieved August 28, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/contaminants/psl1-lsp1/benzene/benzene-eng.pdf

EPA (U.S. Environmental Protection Agency). (2002). Toxicological review of benzene (noncancer effects) - In support of summary information on the Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency, Washington, DC. Retrieved June 8, 2012, from www.epa.gov/iris/toxreviews/0276tr.pdf

Health Canada. (2009). Guidelines for Canadian drinking water quality: Guideline technical document - Benzene. Minister of Health, Ottawa, ON. Retrieved May 24, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/benzene/benzene-eng.pdf

Health Canada. (2011). List of prohibited and restricted cosmetic ingredients ("hotlist"). Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

Héroux, M.-E., Clark, N., van Ryswyk, K., Mallick, R., Gilbert, N.L., Harrison, I., Rispler, K., Wang, D., Anastassopoulos, A., Guay, M., Macneill, M., & Wheeler, A.J. (2010). Predictors of indoor air concentrations in smoking and non-smoking residences. International Journal of Environmental Research and Public Health, 7 (8), 3080-3099.

Héroux, M.-E., Gauvin, D., Gilbert, N.L., Guay, M., Dupuis, G., Legris, M., & Lévesque, B. (2008). Housing characteristics and indoor concentrations of selected volatile organic compounds (VOCs) in Québec City, Canada. Indoor and Built Environment, 17 (2), 128-137.

IARC (International Agency for Research on Cancer). (2012). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 100F: Chemical agents and related occupations. World Health Organization, Geneva.

McHale, C.M., Zhang, L., & Smith, M.T. (2012). Current understanding of the mechanism of benzene-induced leukemia in humans: Implications for risk assessment. Carcinogenesis, 33 (2), 240-252.

Qu, Q., Shore, R., Li, G., Su, L., Jin, X., Melikian, A.A., Roy, N., Chen, L.C., Wirgin, I., Cohen, B., Yin, S., Li, Y., & Mu, R. (2005). Biomarkers of benzene: Urinary metabolites in relation to individual genotype and personal exposure. Chemico-Biological Interactions, 85-95, 153-154.

Smith, M.T. (2010). Advances in understanding benzene health effects and susceptibility. Annual Review of Public Health, 31, 133-148.

Weisel, C.P. (2010). Benzene exposure: An overview of monitoring methods and their findings. Chemico-Biological Interactions, 184 (1-2), 58-66.

10 Chlorophenol Summary and Results

Chlorophenols are the building blocks of many chlorinated aromatic chemicals. There are 19 different chlorophenols that are grouped into five basic types according to the number of chlorine groups (from one to five). In cycle 2 of the Canadian Health Measures Survey (CHMS), five chlorophenols were measured including two dichlorophenols, two trichlorophenols, and pentachlorophenol (Table 10.1).

Table 10.1 Chlorophenols measured in the Canadian Health Measures Survey cycle 2 (2009-2011)
Chlorophenol CASRN
2,4-Dichlorophenol (2,4-DCP) 120-83-2
2,5-Dichlorophenol (2,5-DCP) 583-78-8
2,4,5-Trichlorophenol (2,4,5-TCP) 95-95-4
2,4,6-Trichlorophenol (2,4,6-TCP) 88-06-2
Pentachlorophenol (PCP) 87-86-5

In general, chlorophenols have been used directly as pesticides or as intermediates in the production of pesticides of various types, including bactericides, algicides, molluscides, acaricides (targeting ticks and mites), fungicides, and mould inhibitors (IPCS, 1989). 2,4-DCP and 2,4,5-TCP have been primarily used as intermediates in the production of phenoxy herbicides, specifically 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (ATSDR, 1999). 2,4-D is found in over 150 agricultural and residential products in Canada, whereas 2,4,5-T was removed from the list of herbicides registered for use under the Pest Control Products Act in 1985 (Canada, 2006; Health Canada, 2008; Health Canada, 2012a). PCP is primarily used as a wood preservative in Canada to treat electrical utility poles and cross-arms (Health Canada, 2011). Some chlorophenols have also been used as intermediates in the production of certain dyes and pharmaceuticals and for less specific uses, such as general antiseptics and disinfectants (IPCS, 1989). Chlorophenols are no longer manufactured in Canada but continue to be imported (Health Canada, 1987; Health Canada, 2012b). Currently, 13 pesticide products containing PCP plus related active chlorophenols are registered for use in Canada under the Pest Control Products Act (Canada, 2006; Health Canada, 2012b).

Although some chlorophenols occur naturally, these sources are not significant contributors to overall environmental levels (IPCS, 1989). Significant amounts of chlorophenols can be formed and released into the environment from the chlorination of waste water and drinking water and the incineration of municipal waste (ATSDR, 1999; IPCS, 1989). Chlorophenols may also enter the environment as a result of the degradation of applied pesticides made from chlorophenols (ATSDR, 1999).

People can be exposed to chlorophenols following ingestion of food, inhalation of air, and ingestion of drinking water that has been disinfected with chlorine (ATSDR, 2001; IPCS, 1989). In Canada, food contributes to approximately 40% of the overall exposure to chlorophenols, whereas air (indoor and ambient) and drinking water contribute to approximately 30% and 20%, respectively (Health Canada, 1987). For PCP, food sources are estimated to account for 74% to 89% of total daily intake with air accounting for 10% to 25%; water, soil, and household dust were found to be negligible sources (Coad, 1992). In Canada, concentrations of chlorophenols in drinking water are generally quite low and vary considerably from one location to another (Health Canada, 1987; Sithole & Williams, 1986). Other sources of human exposure to chlorophenols include dermal contact with chlorophenol-containing products such as treated wood (ATSDR, 2001; Health Canada, 1987).

Chlorophenols, including PCP, can be rapidly absorbed following inhalation, ingestion, and dermal contact (ATSDR, 2001; CDC, 2009; Health Canada, 1987; IPCS, 1989). The major metabolic transformation for chlorophenols is through conjugation with sulphate or glucuronate in the liver, prior to excretion in the urine (ATSDR, 2001; IPCS, 1989). Chlorophenol metabolites accumulate most often in the kidney and liver; however, they may also be deposited in the brain and adipose tissue (ATSDR, 2001; IPCS, 1989). Approximately 80% to 90% of chlorophenols are eliminated through the urine in both free and conjugated forms, with smaller amounts eliminated in the feces (IPCS, 1989). A single dose of chlorophenols is virtually eliminated within 1 to several days, although elimination rates appear to be even more rapid for some tissues (IPCS, 1989). Urinary levels of chlorophenols are useful biomarkers of exposure; however, they are not unique to chlorophenol exposure because they are also detectable in urine after exposure to certain pesticides (ATSDR, 1999; ATSDR, 2001).

Chronic health effects that have been reported in those involved in the manufacture of chlorophenols include eye, nose, and airway irritation, dermatitis, chloracne, and porphyria (IPCS, 1989). A few epidemiological studies have shown associations between occupational exposure to chlorophenols and soft tissue sarcoma, malignant lymphoma, and nasal and nasopharyngeal cancer (IPCS, 1989). However, other epidemiology studies have shown no associations, and data from animal studies are equally conflicting (IPCS, 1989). The International Agency for Research on Cancer has classified combined exposure to polychlorophenols (2,4-DCP, 2,4,5-TCP, 2,4,6-TCP, and PCP) as well as PCP alone as Group 2B, possibly carcinogenic to humans (IARC, 1991; IARC, 1999). Health Canada has not classified chlorophenols as to their carcinogenic potential because of the inadequacy of available data; however, 2,4,6-TCP has been classified as Group II, probably carcinogenic (Health Canada, 1987).

As part of the Chemicals Management Plan under the Canadian Environmental Protection Act, 1999 (CEPA 1999), PCP was identified as a high-priority substance; the final screening assessment was published in August 2009 (Canada, 1999; Canada, 2011; Environment Canada & Health Canada, 2009). Although PCP is considered to be inherently toxic to humans, the assessment found no information on non-pesticidal uses or releases of PCP in Canada and concluded that the likelihood of exposure to PCP in Canada resulting from non-pesticidal uses is low (Environment Canada & Health Canada, 2009). To control possible future releases, the Government of Canada published Significant New Activity provisions under CEPA 1999 for this substance. These provisions require that any proposed new manufacture, import, or use, other than those covered under the Pest Control Products Act, be subject to assessment prior to initiation of this activity in Canada (Canada, 2006; Canada, 2009). The Pest Management Regulatory Agency recently completed a re-evaluation of PCP and granted continued registration of PCP for sale and use as a heavy-duty wood preservative in Canada (Health Canada, 2012b). As part of the Chemicals Management Plan under CEPA 1999, 2,4-DCP remains a priority for assessment (Environment Canada, 2011).

Health Canada has established Canadian drinking water quality guidelines that set out the maximum acceptable concentrations of 2,4-DCP, 2,4,6-TCP, and PCP (Health Canada, 1987; Health Canada, 2012c).

In a study carried out in rural and urban areas throughout Saskatchewan, PCP levels were measured in 24-hour urine samples from non-occupationally exposed individuals (Treble & Thompson, 1996). Out of a total of 69 male and female participants 6 to 87 years of age, the average urinary PCP level was 0.75 µg/L and ranged from 0.05 to 3.6 µg/L (Treble & Thompson, 1996).

2,4-DCP, 2,5-DCP, 2,4,5-TCP, 2,4,6-TCP, and PCP were measured in the urine of all CHMS cycle 2 (2009-2011) participants aged 3 to 79 years. Data are presented as both μg/L and μg/g creatinine (Tables 10.1.1 to 10.5.4). Finding a measurable amount of chlorophenols in urine can be an indicator of exposure to chlorophenols and does not necessarily mean that an adverse health effect will occur. These data provide baseline urinary levels for five chlorophenols in the Canadian population.

10.1 2,4-Dichlorophenol (2,4-DCP)

6 Data Tables: 10.1.1 to 10.1.6

10.2 2,5-Dichlorophenol (2,5-DCP)

4 Data Tables: 10.2.1 to 10.2.4

10.3 2,4,5-Trichlorophenol (2,4,5-TCP)

4 Data Tables: 10.3.1 to 10.3.4

10.4 2,4,6-Trichlorophenol (2,4,6-TCP)

4 Data Tables: 10.4.1 to 10.4.4

10.5 Pentachlorophenol (PCP)

4 Data Tables: 10.5.1 to 10.5.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1999). Toxicological profile for chlorophenols. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved May 2, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=941&tid=195

ATSDR (Agency for Toxic Substances and Disease Registry). (2001). Toxicological profile for pentachlorophenol. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved August 15, 2012, from www.atsdr.cdc.gov/toxprofiles/tp51.pdf

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2006). Pest Control Products Act. SC 2002, c. 28. Retrieved May 30, 2012, from http://laws-lois.justice.gc.ca/eng/acts/P-9.01/

Canada (2009). Order 2009-87-03-04 amending the domestic substances list. Canada Gazette, Part II: Official Regulations, 143 (17). Retrieved August 28, 2012, from www.gazette.gc.ca/rp-pr/p2/2009/2009-08-19/html/sor-dors238-eng.html

Canada. (2011). Chemical substances website. Retrieved January 12, 2012, from www.chemicalsubstances.gc.ca

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Coad, S.N.R.C. (1992). PCP exposure for the Canadian general population: A multimedia analysis. Journal of Exposure Analysis and Environmental Epidemiology, 2 (4), 391-413.

Environment Canada. (2011). Status of prioritized substances. Minister of the Environment, Ottawa, ON. Retrieved August 9, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=7CCD1F11-1

Environment Canada & Health Canada. (2009). Screening assessment of six substances on the domestic substances list: Chemical Abstracts Service Registry Number 1582-09-8, 1912-24-9, 1897-45-6, 3691-35-8, 72-43-5, 87-86-5. Ottawa, ON. Retrieved August 15, 2012, from www.ec.gc.ca/lcpe-cepa/documents/substances/pest/sar_pesticides-eng.pdf

Health Canada. (1987). Guidelines for Canadian drinking water quality: Guideline technical document - Chlorophenols. Minister of Health, Ottawa, ON. Retrieved August 15, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/chlorophenols/index-eng.php

Health Canada. (2008). Re-evaluation decision (2,4-dichlorophenoxy) acetic acid [2,4-D]. Re-evaluation document RVD2008-11. Minister of Health, Ottawa, ON. Retrieved May 15, 2012, from www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/rvd2008-11/index-eng.php

Health Canada. (2011). Re-evaluation decision RVD2011-06, heavy duty wood preservatives: Creosote, pentachlorophenol, chromated copper arsenate (CCA) and ammoniacal copper zinc arsenate (ACZA). Minister of Health, Ottawa, ON. Retrieved August 15, 2012, from www.hc-sc.gc.ca/cps-spc/alt_formats/pdf/pubs/pest/decisions/rvd2011-06/RVD2011-06-eng.pdf

Health Canada. (2012a). Public registry, pesticide product information database. Retrieved May 2, 2012, from http://pr-rp.hc-sc.gc.ca/pi-ip/index-eng.php

Health Canada. (2012b). Pesticide label search database. Retrieved April 20, 2012, from www.pr-rp.hc-sc.gc.ca/ls-re/index-eng.php

Health Canada. (2012c). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

IARC (International Agency for Research on Cancer). (1991). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 53: Occupational exposures in insecticide application, and some pesticides. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (1999). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 71: Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. World Health Organization, Geneva.

IPCS (International Programme on Chemical Safety). (1989). Environmental health criteria 93: Chlorophenols other than pentachlorophenol. World Health Organization, Geneva. Retrieved August 15, 2012, from www.inchem.org/documents/ehc/ehc/ehc093.htm

Sithole, B.B. & Williams, D.T. (1986). Halogenated phenols in water at forty Canadian potable water treatment facilities. Journal of the Association of Official Analytical Chemists, 69 (5), 807-810.

Treble, R.G. & Thompson, T.S. (1996). Normal values for pentachlorophenol in urine samples collected from a general population. Journal of Analytical Toxicology, 20 (5), 313-317.

11 Environmental Phenol and Triclocarban Summaries and Results

11.1 Bisphenol A

Bisphenol A (BPA; CASRN 80-05-7) is a synthetic chemical used as a monomer in the production of some polycarbonate plastics and as a precursor for monomers of certain epoxy-phenolic resins (EFSA, 2007). Polycarbonate is used in the manufacture of food and beverage containers such as repeat-use water bottles and storage containers; it was also historically used in infant bottles. Epoxy resins are used as an interior protective lining for food and beverage cans. Additional end-use products containing polycarbonate plastics and resins include medical devices, some dental fillings and sealants, sporting and safety equipment, electronics, and automotive parts (EFSA, 2007; NTP, 2007). BPA is also used in the paper industry to produce thermal paper used for various products including receipts, prescription labels, airline tickets, and lottery tickets (Geens et al., 2011).

BPA does not occur naturally in the environment (Environment Canada & Health Canada, 2008a). Entry into the environment may occur from industrial sources or from product leaching, disposal, and use (CDC, 2009).

The primary route of exposure to BPA for the general public is through dietary intake as a result of various sources including migration from food packaging and repeat-use polycarbonate containers (Health Canada, 2008). Health Canada has recently updated its dietary exposure estimates for BPA following the completion of a number of specific food surveys, including canned foods and beverages, liquid infant formula and Total Diet samples (Health Canada, 2012). Exposure can also occur from contact with environmental media, including ambient and indoor air, drinking water, soil, and dust, and from the use of consumer products (Environment Canada & Health Canada, 2008a). BPA exposure from dental fillings and sealants is short term and considered unlikely to contribute substantially to chronic exposure (WHO, 2011).

In humans, dietary BPA is readily absorbed and undergoes extensive metabolism in the gut wall and the liver (WHO, 2011). Recent studies have also suggested that it may be absorbed and metabolized by the skin following dermal exposure to free BPA in products such as those made from thermal printing papers (Mielke et al., 2011; Zalko et al., 2011). Glucuronidation has been recognized as a major metabolic pathway for BPA, resulting in the BPA-glucuronide conjugate metabolite (EFSA, 2008; FDA, 2008). Conjugation of BPA to BPA-sulphate is shown to be a minor metabolic pathway (Dekant & Völkel, 2008). The BPA-glucuronide metabolite is rapidly excreted in urine with a half-life of less than 2 hours (WHO, 2011). Urinary levels of total BPA, including both conjugated and free unconjugated forms, are commonly used as biomarkers to assess recent exposures (Ye et al., 2005).

Characterization of the potential risk to human health from exposure to BPA includes key effects on the liver and on reproduction, including fertility and developmental effects (EU, 2010; Environment Canada & Health Canada, 2008a). Developmental neurotoxicity studies in animals have suggested that at low levels of exposure in fetuses and newborns, BPA can affect neural development and behaviour (Environment Canada & Health Canada, 2008a; WHO, 2011). Health Canada concluded that there appeared to be sufficient evidence to describe BPA as an endocrine disrupter (Health Canada, 2008). The potential role of BPA and other environmental estrogens in the prevalence of obesity and related metabolic diseases, as well as certain types of cancer, is under intensive debate and investigation among scientific communities (Ben-Jonathan et al., 2009; Carwile & Michels, 2011; Newbold et al., 2009; Soto et al., 2008).

The Government of Canada has conducted a scientific screening assessment of the impact of human and environmental exposure to BPA and determined that it is toxic to human health and the environment as per the criteria set out under the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Canada, 2010). Because of the uncertainty raised in some laboratory animal studies relating to the potential effects of low levels of BPA, a precautionary approach was applied when characterizing risk. Combining the highest potential exposure and potential vulnerability, the risk management strategy for health focused on decreasing exposure to newborns and infants (Environment Canada & Health Canada, 2008b). As of March 2010, under the Canada Consumer Product Safety Act, Health Canada has prohibited the manufacturing, advertisement, sale, or import of polycarbonate baby bottles that contain BPA (Canada, 2010). This precautionary measure protects newborns and infants up to 18 months old (Canada, 2010).

Health Canada is also committed to supporting industry in developing a Code of Practice to reduce levels of BPA in infant-formula can linings (Health Canada, 2010). Health Canada, the United States Food and Drug Administration, and industry have met to initiate this process. Health Canada has committed to facilitating the assessment of proposed industry alternatives to BPA for use in infant-formula and other can coatings, as well as setting stringent migration targets for BPA in infant-formula cans (Health Canada, 2010). Migration targets for canned foods, in general, will be explored. Health Canada will continue to review pre-market submissions for infant-formula packaging to ensure the lowest levels of BPA achievable (Health Canada, 2010). BPA is also included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011). Risk management actions have also been developed under CEPA 1999 with the objective of minimizing releases of BPA in industrial effluents (Canada, 2012).

A provisional tolerable daily intake for BPA, based solely on dietary exposure through food packaging, was established by Health Canada in 1996 and reaffirmed for the general population in 2008 (Health Canada, 2008).

Urinary total BPA (including both free and conjugated forms) was measured in the urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented as both µg/L (Tables 11.1.1, 11.1.2, and 11.1.3) and µg/g creatinine (Tables 11.1.4, 11.1.5, and 11.1.6). Finding a measurable amount of BPA in urine is an indicator of exposure to BPA and does not necessarily mean that an adverse health effect will occur.

6 Data Tables: 11.1.1 to 11.1.6

References

Ben-Jonathan, N., Hugo, E.R., & Brandebourg, T.D. (2009). Effects of bisphenol A on adipokine release from human adipose tissue: Implications for the metabolic syndrome. Molecular and Cellular Endocrinology, 304 (1-2), 49-54.

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2010). Order adding a toxic substance to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part II: Official Regulations, 144 (21). Retrieved August 28, 2012, from http://gazette.gc.ca/rp-pr/p2/2010/2010-10-13/html/sor-dors194-eng.html

Canada. (2010). Canada Consumer Product Safety Act. SC 2010, c. 21. Retrieved February 20, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-1.68/index.html

Canada. (2012). Notice requiring the preparation and implementation of pollution prevention plans with respect to bisphenol A in industrial effluents. Canada Gazette, Part I: Notices and Proposed Regulations, 146 (15). Retrieved August 28, 2012, from http://gazette.gc.ca/rp-pr/p1/2012/2012-04-14/html/sup-eng.html

Carwile, J.L. & Michels, K.B. (2011). Urinary bisphenol A and obesity: NHANES 2003-2006. Environmental Research, 111, 825-830.

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Dekant, W. & Völkel, W. (2008). Human exposure to bisphenol A by biomonitoring: Methods, results and assessment of environmental exposures. Toxicology and Applied Pharmacology, 228 (1), 114-134.

EU (European Union). (2010). Updated European Union risk assessment report: 4,4'-Isopropylidenediphenol (bisphenol A), CAS No: 80-05-7. European Chemicals Bureau. Luxembourg. Retrieved December 14, 2012, from http://esis.jrc.ec.europa.eu/doc/risk_assessment/REPORT/bisphenolareport325.pdf

EFSA (European Food Safety Authority). (2007). Opinion of the scientific panel on food additives, flavourings, processing aids and materials in contact with food on a request from the Commission related to 2,2-bis(4-hydroxyphenyl)propane (bisphenol A), question number EFSA-Q-2005-100. European Food Safety Authority Journal, 428, 1-75.

EFSA (European Food Safety Authority). (2008). Toxicokinetics of bisphenol A. Scientific opinion of the panel on food addictives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission on the toxicokinetics of bisphenol A. European Food Safety Authority Journal, 759, 1-10.

Environment Canada & Health Canada. (2008a). Screening assessment for the challenge: Phenol, 4,4' -(1-methylethylidene)bis- (bisphenol A). Ottawa, ON. Retrieved May 23, 2012, from www.ec.gc.ca/substances/ese/eng/challenge/batch2/batch2_80-05-7_en.pdf

Environment Canada & Health Canada. (2008b). Proposed risk management approach for phenol, 4,4'-(1-methylethylidene) bis (bisphenol A). Retrieved May 24, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=6FA54372-1

FDA (U.S. Food and Drug Administration). (2008). Draft assessment of bisphenol A for use in food contact applications. U.S. Department of Health and Human Services, Washington, DC. Retrieved May 25, 2012, from www.fda.gov/ohrms/dockets/AC/08/briefing/2008-0038b1_01_02_FDA%20BPA%20Draft%20Assessment.pdf

Geens, T., Goeyens, L., & Covaci, A. (2011). Are potential sources for human exposure to bisphenol-A overlooked? International Journal of Hygiene and Environmental Health, 214 (5), 339-347.

Health Canada. (2008). Health risk assessment of bisphenol A from food packaging applications. Minister of Health, Ottawa, ON. Retrieved May 24, 2012, from www.hc-sc.gc.ca/fn-an/securit/packag-emball/bpa/bpa_hra-ers-eng.php

Health Canada. (2010). Bisphenol A. Retrieved June 2, 2012, from www.hc-sc.gc.ca/fn-an/securit/packag-emball/bpa/index-eng.php

Health Canada. (2011). List of prohibited and restricted cosmetic ingredients ("hotlist"). Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

Health Canada. (2012). Health Canada's updated assessment of bisphenol A (BPA) exposure from food sources. Retrieved December 6, 2012, from www.hc-sc.gc.ca/fn-an/securit/packag-emball/bpa/bpa_hra-ers-2012-09-eng.php

Mielke, H., Partosch, F., & Gundert-Remy, U. (2011). The contribution of dermal exposure to the internal exposure of bisphenol A in man. Toxicology Letters, 204, 190-198.

Newbold, R.R., Padilla-Banks, E., & Jefferson, W.N. (2009). Environmental estrogens and obesity. Molecular and Cellular Endocrinology, 304 (1), 84-89.

NTP (National Toxicology Program). (2007). NTP-CERHR Expert Panel report on the reproductive and developmental toxicity of bisphenol-A. Department of Health and Human Services, Research Triangle Park, NC.

Soto, A.M., Vandenberg, L.N., Maffini, M.V., & Sonnenschein, C. (2008). Does breast cancer start in the womb? Basic & Clinical Pharmacology & Toxicology, 102 (2), 125-133.

WHO (World Health Organization). (2011a). Toxicological and health aspects of bisphenol A: Report of joint FAO/WHO expert meeting and stakeholder meeting on bisphenol A. World Health Organization. Retrieved August 2, 2012, from http://whqlibdoc.who.int/publications/2011/97892141564274_eng.pdf

Ye, X., Kuklenyik, Z., Needham, L., & Calafat, A. (2005). Quantification of urinary conjugates of bisphenol A, 2,5-dichlorophenol, and 2-hydroxy-4-methoxybenzophenone in humans by online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry, 383 (4), 638-644.

Zalko, D., Jacques, C., Duplan, H., Bruel, S., & Perdu, E. (2011). Viable skin efficiently absorbs and metabolizes bisphenol A. Chemosphere, 82, 424-430.

11.2 Triclocarban

Triclocarban (CASRN 101-20-2) is a high-production volume synthetic chemical that has been used as an antibacterial agent since the late 1950s (SCCP, 2005). It is used in various consumer and personal-care products including bar and liquid soaps, body washes, toothpastes, deodorants, detergents, and wipes (TCC, 2002; Ye et al., 2011). As of August 2012, no drug products are marketed in Canada with triclocarban as an active medicinal ingredient nor is it an ingredient in any licensed natural health products (Health Canada, 2012a; Health Canada, 2012b).

Triclocarban is not naturally found in the environment. It may be found in surface water owing to the widespread use of triclocarban-containing products and related releases to waste-water systems (Schebb et al., 2011; Ye et al., 2011).

The major route of exposure for the general public is dermal contact with personal-care products containing triclocarban (TCC, 2002). Indirect exposure to triclocarban from ingestion of food or water is expected to be minimal (TCC, 2002).

Following dermal exposure, fairly poor absorption of triclocarban has been observed in humans ranging from less than 1% to 7% (Scharpf Jr. & Hill, 1975; Schebb et al., 2011; Wester et al., 1985). Human metabolism of triclocarban involves either direct glucuronidation or hydroxylation followed by conjugation with glururonic or sulphuric acid (Hiles & Birch, 1978). The majority of triclocarban is excreted in the feces in its conjugated form within 5 days whereas a smaller amount (primarily in conjugated forms) is excreted in the urine within 80 hours (Ahn et al., 2011; Hiles & Birch, 1978; Jeffcoat et al., 1977; Ye et al., 2011). It has been suggested that the level of total triclocarban (conjugated and free) in urine may serve as a biomarker for human exposure (Ye et al., 2011).

In humans, triclocarban has been shown to be minimally irritating to skin and does not display sensitization potential (Maibach et al., 1978; SCCP, 2005). There is some evidence suggesting that it may impair mammalian reproduction by reducing birth weight and survival rate in rats (Nolen & Dierckman, 1979; SCCP, 2005). In some studies at high concentrations, triclocarban has been reported to cause endocrine-modulating effects in rats and in cell-based tests (Ahn et al., 2008; Duleba et al., 2011). A carcinogenicity study in rats demonstrated no evidence of a dose-related increase in tumor incidence at any site (TCC, 2002). To date, triclocarban has not been assessed for carcinogenic potential by the International Agency for Research on Cancer.

As part of the Chemicals Management Plan under the Canadian Environmental Protection Act, 1999, triclocarban was categorized as a priority substance for future assessment based on environmental criteria but not human health (Canada, 1999; Environment Canada, 2011). In 2005, the European Union Scientific Committee on Consumer Products concluded that the use of triclocarban up to a maximum concentration of 1.5% for non-preservative purposes in cosmetic rinse-off hand and body care products does not pose a direct risk to the health of the consumer (SCCP, 2005).

Triclocarban was measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 11.2.1, 11.2.2, 11.2.3, and 11.2.4). Finding a measurable amount of triclocarban in urine is an indicator of exposure to triclocarban and does not necessarily mean that an adverse health effect will occur. These data provide baseline urinary levels for triclocarban in the Canadian population.

4 Data Tables: 11.2.1 to 11.2.4

References

Ahn, K.C., Kasagami, T., Tsai, H.-J., Schebb, N.H., Ogunyoku, T., Gee, S.J., Young, T.M., & Hammock, B.D. (2011). An immunoassay to evaluate human/environmental exposure to the antimicrobial triclocarban. Environmental Science & Technology, 46 (1), 374-381.

Ahn, K.C., Zhao, B., Chen, J., Cherednichenko, G., Sanmarti, E., Denison, M.S., Lasley, B., Pessah, I.N., Kültz, D., Chang, D.P.Y., Gee, S.J., & Hammock, B.D. (2008). In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: Receptor-based bioassay screens. Environmental Health Perspectives, 116 (9), 1203-1210.

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Duleba, A.J., Ahmed, M.I., Sun, M., Gao, A.C., Villanueva, J., Conley, A.J., Turgeon, J.L., Benirschke, K., Gee, N.A., Chen, J., Green, P.G., & Lasley, B.L. (2011). Effects of triclocarban on intact immature male rat. Reproductive Sciences, 18 (2), 119-127.

Environment Canada. (2011). Status of prioritized substances. Minister of the Environment, Ottawa, ON. Retrieved August 9, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=7CCD1F11-1

Health Canada. (2012a). Licensed natural health products database. Retrieved August 9, 2012, from http://webprod3.hc-sc.gc.ca/lnhpd-bdpsnh/start-debuter.do?lang=eng

Health Canada. (2012b). Drug product batabase online query. Retrieved April 20, 2012, from http://webprod3.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp

Hiles, R.A. & Birch, C.G. (1978). The absorption, excretion, and biotransformation of 3,4,4'-trichlorocarbanilide in humans. Drug Metabolism and Disposition, 6 (2), 177-183.

Jeffcoat, A.R., Handy, R.W., Francis, M.T., Willis, S., Wall, M.E., Birch, C.G., & Hiles, R.A. (1977). The metabolism and toxicity of halogenated carbanilides. Biliary metabolites of 3,4,4'-trichlorocarbanilide and 3-trifluoromethyl-4,4'dichlorocarbanilide in the rat. Drug Metabolism and Disposition, 5, 157-166.

Maibach, H., Bandmann, H.-J., Calnan, C.D., Cronin, E., Fregert, S., Hjorth, N., Magnusson, B., Malten, K.E., Meneghini, C.L., Pirilä, V., Wilkinson, D.S., & Johannsen, F.R. (1978). Triclocarban: Evaluation of contact dermatitis potential in man. Contact Dermatitis, 4 (5), 283-288.

Nolen, G.A. & Dierckman, T.A. (1979). Reproduction and teratogenic studies of a 2:1 mixture of 3,4,4'-trichlorocarbanilide and 3-trifluoromethyl-4,4'-dichlorocarbanilide in rats and rabbits. Toxicology and Applied Pharmacology, 51 (3), 417-425.

SCCP (Scientific Committee on Consumer Products). (2005). Opinion on triclocarban for other uses than as a preservative (COLIPA No. P29). Health & Consumer Protection Directorate-General, European Commission, Brussels. Retrieved August 24, 2012, from www.ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_016.pdf

Scharpf Jr., L.G. & Hill, I.D.M.H.I. (1975). Percutaneous penetration and disposition of triclocarban in man: Body showering. Archives of Environmental Health, 30 (1), 7-14.

Schebb, N.H., Inceoglu, B., Ahn, K.C., Morisseau, C., Gee, S.J., & Hammock, B.D. (2011). Investigation of human exposure to triclocarban after showering and preliminary evaluation of its biological effects. Environmental Science & Technology, 45 (7), 3109-3115.

TCC (Triclocarban Consortium). (2002). High production volume (HPV) chemical challenge program data availability and screening level assessment for triclocarban. TCC. Retrieved August 24, 2012, from www.epa.gov/hpv/pubs/summaries/tricloca/c14186tp.pdf

Wester, R.C., Maibach, H.I., Surinchak, J., & Bucks, D.A.W. (1985). Predictability of in vitro diffusion systems: Effect of skin types and ages on percutaneous absorption of triclocarban. Dermatology, 6, 223-226.

Ye, X., Zhou, X., Furr, J., Ahn, K.C., Hammock, B.D., Gray, E.L., & Calafat, A.M. (2011). Biomarkers of exposure to triclocarban in urine and serum. Toxicology, 286 (13), 69-74.

11.3 Triclosan

Triclosan (CASRN 3380-34-5) is a synthetic chemical with wide application as an antimicrobial agent and as a preservative since 1972 (Jones et al., 2000). It is used as a medicinal ingredient in non-prescription drug products and as a non-medicinal ingredient in cosmetics, natural health products, and drug products. In 2011, approximately 1,600 cosmetic and natural health products containing triclosan were reported to be in commerce in Canada (Environment Canada & Health Canada, 2012a). These products include face cream, face and eye makeup, hand cream, deodorant sticks and sprays, fragrances, body lotion, tanning products, skin cleansers, shaving preparations, and shampoos. As of August 2012, an additional 131 products containing triclosan as an active medicinal ingredient are regulated as non-prescription drug products in Canada, including toothpastes, skin cleansers, and moisturizers (Health Canada, 2012a). Triclosan is also used to control the spread of bacteria in household items such as cleaners, textiles, carpets, and cutting boards, and medical devices (Jones et al., 2000). As a material preservative, triclosan is registered under the Pest Control Products Act (Canada, 2006); no domestic class pest-control products containing triclosan are currently registered for use in Canada (Environment Canada & Health Canada, 2012b).

Triclosan does not occur naturally in the environment (Environment Canada & Health Canada, 2012a). Use of triclosan-containing products results in its release to waste-water systems and subsequently surface water (Environment Canada & Health Canada, 2012a). The potential routes of exposure for the general public are oral and dermal contact with products such as toothpastes and cosmetics that contain triclosan, ingestion of drinking water or breast milk, and ingestion of household dust (Environment Canada & Health Canada, 2012b).

Following oral exposures, triclosan is rapidly absorbed and distributed in humans with plasma levels increasing rapidly within 1 to 4 hours (Environment Canada & Health Canada, 2012b). Absorption following dermal exposure to triclosan-containing products ranges from 11% to 17% in humans (Maibach, 1969; Queckenberg et al., 2010; Stierlin, 1972). Only limited absorption (approximately 5% to 10%) occurs under normal conditions of toothpaste use (SCCP, 2009). Following all routes of administration, absorbed triclosan is nearly totally converted to glucuronic and sulfuric acid conjugates (Fang et al., 2010). Triclosan is rapidly eliminated after metabolism with an observed half-life ranging from 9 to 32 hours (SCCP, 2009). About 24% to 83% of absorbed triclosan is excreted in urine, mostly as the glucuronide conjugate (Fang et al., 2010; Sandborgh-Englund et al., 2006). Excretion of triclosan in feces is as the free unchanged compound and represents a smaller portion of the administered dose (10% to 30%) (Environment Canada & Health Canada, 2012b). Currently, there is no evidence of bioaccumulation potential in humans (SCCP 2009). The concentration of triclosan in urine (conjugated and free) can be used as a biomarker of exposure to triclosan (Calafat et al., 2007).

Triclosan is not acutely toxic to mammals, but it can interact with cellular enzymes and receptors (Calafat et al., 2007). The potential effects of these interactions remain unknown. There have been observations of adverse effects of triclosan on thyroid hormone homeostasis resulting from liver toxicity in rodents; however, the overall weight of evidence does not currently support effects of triclosan on thyroid function as a critical effect for risk characterization in humans (Environment Canada & Health Canada, 2012b). Adverse effects on the liver were selected as the toxicological endpoint of concern in the recent human health evaluation of triclosan (Environment Canada & Health Canada, 2012b). To date, triclosan has not been assessed for carcinogenic potential by the International Agency for Research on Cancer; the United States Environmental Protection Agency has classified triclosan as not likely to be carcinogenic to humans (EPA, 2008).

Health Canada and Environment Canada have jointly reviewed triclosan in a preliminary risk assessment and have proposed that it is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health (Environment Canada & Health Canada, 2012b). In the same assessment, Health Canada's Pest Management Regulatory Agency has proposed that the use of pest control products containing triclosan in Canada does not pose an unacceptable risk to human health (Environment Canada & Health Canada, 2012b). However, at current environmental levels, it is proposed that triclosan is an ecological concern and therefore it meets the definition of toxic as set out under section 64 of the Canadian Environmental Protection Act, 1999 (Canada, 1999).

Triclosan is included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011). The cosmetic ingredient hotlist indicates concentration limits of triclosan in mouthwash and other cosmetic products for dental and topical use (Environment Canada & Health Canada, 2012b; Health Canada, 2012b). In addition, the cosmetic ingredient hotlist indicates that oral cosmetic products containing triclosan shall include a label statement indicating that the product is not to be used by children under 12 years of age (Health Canada, 2011). The hotlist also indicates that mouthwashes include a label statement to the effect of "avoid swallowing" (Health Canada, 2011).

Triclosan was measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 11.3.1, 11.3.2, 11.3.3, and 11.3.4). Finding a measurable amount of triclosan in urine is an indicator of exposure to triclosan and does not necessarily mean that an adverse health effect will occur. These data provide baseline urinary levels for triclosan in the Canadian population.

4 Data Tables: 11.3.1 to 11.3.4

References

Calafat, A.M., Ye, X., Wong, L.-Y., Reidy, J.A., & Needham, L.L. (2007). Urinary concentrations of triclosan in the U.S. population: 2003-2004. Environmental Health Perspectives, 116 (3), 303-307.

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2006). Pest Control Products Act. SC 2002, c. 28. Retrieved May 30, 2012, from http://laws-lois.justice.gc.ca/eng/acts/P-9.01/

Environment Canada & Health Canada. (2012a). Risk management scope for triclosan. Ottawa, ON. Retrieved May 25, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=613BAA27-1

Environment Canada & Health Canada. (2012b). Preliminary assessment: Triclosan. Ottawa, ON. Retrieved May 25, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=6EF68BEC-1

EPA (U.S. Environmental Protection Agency). (2008). Cancer assessment document: Evaluation of the carcinogenic potential of triclosan. Office of Prevention, Pesticides and Toxic Substances, Washington, DC.

Fang, J.-L., Stingley, R.L., Beland, F.A., Harrouk, W., Lumpkins, D.L., & Howard, P. (2010). Occurrence, efficacy, metabolism, and toxicity of triclosan. Journal of Environmental Science and Health, Part C, 28 (3), 147-171.

Health Canada. (2011). List of prohibited and restricted cosmetic ingredients ("hotlist"). Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

Health Canada. (2012a). Drug product database online query. Retrieved April 20, 2012, from http://webprod3.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp

Health Canada. (2012b). Natural health products ingredients database. Retrieved August 3, 2012, from http://webprod.hc-sc.gc.ca/nhpid-bdipsn/search-rechercheReq.do

Jones, R.D., Jampani, H.B., Newman, J.L., & Lee, A.S. (2000). Triclosan: A review of effectiveness and safety in health care settings. American Journal of Infection Control, 28 (2), 184-196.

Maibach, H.I. (1969). Percutaneous penetration of Irgasan®CH 3565 in a soap solution. University of California Medical Center, Department of Dermatology, San Francisco, CA.

Queckenberg, C., Meins, J., Wachall, B., Doroshyenko, O., Tomalik-Scharte, D., Bastian, B., Abdel-Tawab, M., & Fuhr, U. (2010). Absorption, pharmacokinetics, and safety of triclosan after dermal administration. Antimicrobial Agents and Chemotherapy, 54 (1), 570-572.

Sandborgh-Englund, G., Adolfsson-Erici, M., Odham, G., & Ekstrand, J. (2006). Pharmacokinetics of triclosan following oral ingestion in humans. Journal of Toxicology and Environmental Health, Part A, 69 (20), 1861-1873.

SCCP (Scientific Committee on Consumer Products). (2009). Opinion on triclosan (COLIPA No. P32). Health & Consumer Protection Directorate-General, European Commission, Brussels.

Stierlin, H. (1972). GP 41 353: Scouting studies to ascertain the cutaneous resorption of GP 41 353 in humans after topical application in a crème excipient. Ciba Geigy Ltd., Basel.

12 Nicotine Metabolite Summary and Results

12.1 Cotinine

Cotinine (CASRN 486-56-6) is the primary metabolite of nicotine, a chemical found naturally in the tobacco plant and present in tobacco products such as cigarettes, cigars, and smokeless tobacco products (e.g.chewing tobacco and snuff). Nicotine is also incorporated into nicotine replacement therapies such as the nicotine gum, patch, lozenge, inhaler, and buccal spray.

Human exposure to nicotine occurs primarily through the use of tobacco products, exposure to environmental tobacco smoke, and the use of nicotine replacement therapies (HSDB, 2009). In addition, infants breast fed by women who smoke may be exposed to nicotine in breast milk (HSDB, 2009).

Inhalation is the most effective intake route with on average 60% to 80% of nicotine absorbed through the lungs (Iwase et al., 1991). Nicotine can also be absorbed through the skin and gastrointestinal tract, but at a much lower efficiency (Karaconji, 2005). Once inside the body, approximately 70% to 80% of nicotine is metabolized into cotinine. It has a half-life of 10 to 20 hours and can remain in the body at detectable levels for up to 4 days (Benowitz & Jacob, 1994; Curvall et al., 1990). Cotinine is considered to be the best biomarker for exposure to tobacco products and tobacco smoke (Brown et al., 2005; CDC, 2009).

Tobacco smoke is a combination of gases, liquids, and breathable particles, some of which are harmful to human health. It contains over 4,000 chemicals, including at least 70 that cause, initiate, or promote cancer, and has been classified by the International Agency for Research on Cancer (IARC) as Group 1, carcinogenic to humans (Health Canada, 2011; IARC, 2004). Exposure to these chemicals also contributes directly to other diseases, such emphysema and heart disease, and an increased risk of asthma (CDC, 2004). Most of these chemicals are formed during the combustion of tobacco; others are found naturally in tobacco and are released as the tobacco burns (CDC, 2004). Smokeless tobaccos, including chewing tobacco and snuff, contain 28 known cancer-causing chemicals and, similar to the tobaccos used in cigarettes, pipes, and cigars, can lead to nicotine dependence and addiction (Health Canada, 2010; IARC, 2007). Smokeless tobacco use causes oral and pancreatic cancer and has been classified by IARC as Group 1, carcinogenic to humans (IARC, 2007). It can also cause serious dental health problems including recession of the gums, tooth loss, and discolouration of the teeth and gums (Walsh & Epstein, 2000). Levels of cotinine in the blood and urine of non-smokers have been correlated with some adverse health effects related to tobacco smoke exposure, and cotinine itself may contribute to the neuropharmacological effects of tobacco smoking (Benowitz, 1996; Crooks & Dwoskin, 1997).

As a result of the adverse health effects associated with tobacco use, the Government of Canada, along with provincial and territorial governments and various municipalities, has taken several steps to reduce the prevalence of tobacco use as well as exposure to tobacco smoke. These steps include prohibitions on the sale of tobacco to youth, requirements to apply health warnings on tobacco packaging, and restrictions on the promotion of tobacco products including the display of tobacco products at retail outlets (Health Canada, 2006). Additional steps include the offer of cessation help along with initiatives to eliminate smoking in workplaces and enclosed public locations (Health Canada, 2006).

In 1992, a biomonitoring study of 232 anglers in two regions of the Great Lakes area of Ontario showed non-smokers to have a median urinary cotinine level of 12.4 µg/g creatinine, whereas smokers had a median urinary cotinine level of 2,583.7 µg/g creatinine (Kearney et al., 1995). A concentration of 50 μg/L urine for cotinine is recommended for determining smoking status; levels greater than this concentration are attributed to smokers (SRNT Subcommittee on Biochemical Verification, 2002).

Cotinine was measured in the urine of all CHMS participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented as both µg/L and µg/g creatinine for non-smokers (Tables 12.1.1 to 12.1.6) and smokers (Tables 12.1.7 to 12.1.10). Survey participants aged 3 to 11 years were assumed to be non-smokers. In this survey, a smoker is defined as someone who is a current daily or occasional smoker and a non-smoker is defined as someone who does not currently smoke and has either never smoked or who was previously a daily or occasional smoker. Finding a measurable amount of cotinine in urine is an indicator of exposure to nicotine and does not necessarily mean that an adverse health effect will occur.

10 Data Tables: 12.1.1 to 12.1.10

References

Benowitz, N.L. (1996). Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiologic Reviews, 18 (2), 188-204.

Benowitz, N.L. & Jacob, P. 3rd (1994). Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clinical Pharmacology and Therapeutics, 56 (5), 483-493.

Brown, K.M., von Weymarn, L.B., & Murphy, S.E. (2005). Identification of N-(hydroxymethyl) norcotinine as a major product of cytochrome P450 2A6, but not cytochrome P450 2A13-catalyzed cotinine metabolism. Chemical Research in Toxicology, 18 (12), 1792-1798.

CDC (Centers for Disease Control). (2004). The health consequences of smoking: A report of the Surgeon General. Department of Health and Human Services, Washington, DC. Retrieved April 12, 2012, from www.cdc.gov/tobacco/data_statistics/sgr/2004/complete_report/index.htm

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Crooks, P.A. & Dwoskin, L.P. (1997). Contribution of CNS nicotine metabolites to the neuropharmacological effects of nicotine and tobacco smoking. Biochemical Pharmacology, 54 (7), 743-753.

Curvall, M., Elwin, C.E., Kazemi-Vala, E., Warholm, C., & Enzell, C.R. (1990). The pharmacokinetics of cotinine in plasma and saliva from non-smoking healthy volunteers. European Journal of Clinical Pharmacology, 38 (3), 281-287.

Health Canada. (2006). The national strategy: Moving forward - The 2006 progress report on tobacco control. Minister of Health, Ottawa, ON. Retrieved August 16, 2012, from www.hc-sc.gc.ca/hc-ps/alt_formats/hecs-sesc/pdf/pubs/tobac-tabac/prtc-relct-2006/prtc-relct-2006-eng.pdf

Health Canada. (2010). Smokeless tobacco products: A chemical and toxicity analysis. Minister of Health, Ottawa, ON. Retrieved August 16, 2012, from www.hc-sc.gc.ca/hc-ps/alt_formats/hecs-sesc/pdf/pubs/tobac-tabac/smokeless-sansfumee/smokeless-sansfumee-eng.pdf

Health Canada. (2011). Carcinogens in tobacco smoke. Minister of Health, Ottawa, ON. Retrieved August 16, 2012, from www.hc-sc.gc.ca/hc-ps/alt_formats/hecs-sesc/pdf/pubs/tobac-tabac/carcinogens-cancerogenes/carcinogens-cancerogenes-eng.pdf

HSDB (Hazardous Substances Data Bank). (2009). Nicotine, HSDB number: 1107. National Library of Medicine, Bethesda, MD. Retrieved April 12, 2012, from www.toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

IARC (International Agency for Research on Cancer). (2004). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 83: Tobacco smoke and involuntary smoking. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (2007). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 89: Smokeless tobacco and some tobacco-specific N-nitrosamines. World Health Organization, Lyon.

Iwase, A., Aiba, M., & Kira, S. (1991). Respiratory nicotine absorption in non-smoking females during passive smoking. International Archives of Occupational and Environmental Health, 63 (2), 139-143.

Karaconji, I.B. (2005). Facts about nicotine toxicity. Archives of Industrial Hygiene and Toxicology, 56 (4), 363-371.

Kearney, J., Cole, D.C., & Haines, D. (1995). Report on the Great Lakes Anglers Pilot Exposure Assessment Study. Great Lakes Health Effects Program, Health Canada, Ottawa, ON.

SRNT Subcommittee on Biochemical Verification. (2002). Biochemical verification of tobacco use and cessation. Nicotine & Tobacco Research, 4, 149-159.

Walsh, P.M. & Epstein, J.B. (2000). The oral effects of smokeless tobacco. Journal of the Canadian Dental Association, 66 (1), 22-25.

13 Perfluoroalkyl Substances Summary and Results

Perfluoroalkyl substances (PFASs) are members of a structurally related class of persistent organic compounds. This class is characterized by the presence of a perfluoroalkyl chain that is typically four to 14 carbons in length and in which all hydrogen atoms are replaced by fluorine atoms. In cycle 2 of the Canadian Health Measures Survey (CHMS), nine PFASs were measured (Table 13.1).

Table 13.1 Perfluoroalkyl substances measured in the Canadian Health Measures Survey cycle 2 (2009-2011).
Perfluoroalkyl substance CASRN
Perfluorobutanoic acid (PFBA) 375-22-4
Perfluorohexanoic acid (PFHxA) 307-24-4
Perfluorooctanoic acid (PFOA) 335-67-1
Perfluorononanoic acid (PFNA) 375-95-1
Perfluorodecanoic acid (PFDA) 335-76-2
Perfluoroundecanoic acid (PFUnDA) 2058-94-8
Perfluorobutane sulfonate (PFBS) 45187-15-3
Perfluorohexane sulfonate (PFHxS) 108427-53-8
Perfluorooctane sulfonate (PFOS) 45298-90-6

The PFASs most extensively studied and measured in humans are PFOS and PFOA (Dallaire et al., 2009; Hölzer et al., 2008; Kato et al., 2011). PFHxS is another perfluorinated compound that has been measured in humans, but it has not been examined as extensively as PFOS and PFOA. Other PFASs, such as PFBA, PFHxA, PFNA, PFDA, PFUnDA, and PFBS, are measured less frequently in the human population.

PFASs are synthetic chemicals with high chemical and thermal stability and are able to repel both water and oils (Kissa, 2001). These characteristics make them ideal for use in a number of industrial and commercial applications (Kissa, 2001). PFASs are used as stain-repellent, water-repellent, and oil-repellent fabric protectors, in water-repellent and oil-repellent paper coatings, wiper blades, bike-chain lubricant, wire and cable insulation, pharmaceutical packaging, and food packaging (Kissa, 2001). They are also used in engine-oil additives, nail polish, hair curling and straightening products, metal plating and cleaning, fire retardant foams, inks, varnishes, polyurethane production, and vinyl polymerization (Kissa, 2001). Fluoropolymers manufactured using salts of PFASs are used in many industrial and consumer products including surface coatings on textiles and carpets, in personal-care products, and in non-stick coatings on cookware (Indian and Northern Affairs Canada, 2009; Kissa, 2001; Prevedouros et al., 2005).

Worldwide use of PFOS and PFOS-related products has decreased significantly since 2002 when the world's largest producer at the time completed its voluntary phase-out of production (3M, 2012). PFHxS, a known by-product in the production of PFOS, was also phased out as a result. In 2008, replacements for PFOA were introduced, resulting in the subsequent phase-out of PFOA use in the production of fluoropolymers (3M, 2012). Potential replacements for PFOS-based substances include new PFBS-based compounds that are rapidly eliminated from the body with a relatively low bioaccumulation potential and toxicity (Chang et al., 2008; Newsted et al., 2008).

PFASs do not occur naturally in the environment. Entry into the environment occurs through releases during manufacturing and transport, use of consumer products, and the disposal and breakdown of larger PFASs. As a result, PFASs have been detected in a wide array of environmental media (Houde et al., 2006).

Exposure to the general public is widespread through food, drinking water, consumer products, dust, soil, and air (Fromme et al., 2009; Fromme et al., 2007; Hölzer et al., 2008; Kubwabo et al., 2005). PFASs have been analyzed as part of Health Canada's ongoing Total Diet Study surveys; levels in foods that are commercially sold in Canada are low and within a similar range as have been reported in other countries (Health Canada, 2009; Tittlemier et al., 2007; Tittlemier et al., 2006). The contribution of individual pathways and sources of exposure appear to depend on age, dose, and substance. Generally, ingestion of food, drinking water, and house dust are expected to be the main routes of exposure for adults in the general population whereas oral hand-to-mouth contact with consumer products, such as carpets, clothing, and upholstery, is a significant contributor for infants, toddlers, and children (Trudel et al., 2008).

Longer chain PFASs are well absorbed in the body, poorly excreted, and are not extensively metabolized (Harada et al., 2005; Indian and Northern Affairs Canada, 2009; Johnson et al., 1984). Average half-lives of PFOS, PFOA, and PFHxS in humans range from 3 to 9 years (Olsen et al., 2007). However, shorter chain PFASs are eliminated much more quickly; for example, the elimination half-life for PFBA is 72 to 81 hours (ATSDR, 2009). In humans, PFOS and PFOA are found in serum, plasma, kidneys, and the liver (Butenhoff et al., 2006; Fromme et al., 2009; Kärrman et al., 2010). PFASs have also been measured in breast milk and umbilical cord blood (Kärrman et al., 2010; Monroy et al., 2008). PFASs have a strong affinity for the protein fraction in blood and do not typically accumulate in lipids (Kärrman et al., 2010; Martin et al., 2004). Absorbed PFOA and PFOS are ultimately excreted in urine (ATSDR, 2009). Serum levels of PFASs, in particular PFOA and PFOS, can be reflective of cumulative exposure over several years (CDC, 2009). Although both PFOA and PFOS are biomarkers of exposures to themselves, animal studies have indicated that their presence in serum may also result from exposure to and subsequent metabolism of other PFASs (ATSDR, 2009).

The primary concern with PFASs is their persistence in both the environment and the human body (Olsen et al., 2007). Possible linkages between exposure to PFASs and adverse human health effects have been examined in occupational studies and studies of populations exposed to contaminated drinking water (ATSDR, 2009). Although no definitive links have been established, a recent large-scale report in children suggests associations between serum PFASs and thyroid effects (Lopez-Espinosa et al., 2012). In several animal species, the liver has been identified as the primary target organ of toxicity for PFASs regardless of the route of exposure (EPA, 2002; Health Canada, 2006). PFOA has been associated with increased incidence of tumours in rodent bioassays, and PFOA and other PFASs were identified in 2008 as priority agents for future International Agency for Research on Cancer monographs (IARC, 2008).

In 2006, Environment Canada and Health Canada concluded that PFOS was not a concern for human health at current levels of exposure (Health Canada, 2006). However, PFOS and its salts were declared toxic to the environment and its biological diversity, and PFOS was added to Schedule 1 of the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Environment Canada, 2006a). In 2009, PFOS and its salts were added to the Virtual Elimination List under CEPA 1999 (Canada, 2009). Canada is also working through the Convention on Long-Range Transboundary Air Pollution and the Stockholm Convention on Persistent Organic Pollutants under the United Nations to reduce the global production of PFOS (Canada, 2010a).

In 2012, Environment Canada and Health Canada published screening assessments of PFOA and long-chain (C9-C20) perfluorocarboxylic acids (including PFNA, PFDA, and PFUnDA), along with their salts and their precursors (Environment Canada, 2012; Environment Canada & Health Canada, 2012a). The assessments concluded that the substances are an ecological concern, but PFOA and its salts and precursors are not a concern for human life or health (Environment Canada, 2012; Environment Canada & Health Canada, 2012a). Long-chain perfluorocarboxylic acids and their salts and precursors were not considered to be a high priority for assessment of potential risks to human health; as such, no human health assessment was conducted. Based on the assessments, both PFOA and long-chain perfluorocarboxylic acids and their salts and precursors have been added to the List of Toxic Substances in Schedule 1 of CEPA 1999 (Canada, 2012).

A number of risk management actions have been taken in Canada following the Government of Canada's publication of Perfluorinated Carboxylic Acids (PFCAs) and Precursors: An Action Plan for Assessment and Management in 2006 (Environment Canada, 2006b). These actions include regulations prohibiting the manufacture, use, sale, offer for sale, and import of four fluorotelomer-based substances found to be precursors to long-chain perfluorinated carboxylic acids, unless present in certain manufactured items (Canada, 2010b). Additionally in 2010, the voluntary Environmental Performance Agreement Respecting Perfluorinated Carboxylic Acids (PFCAs) and Their Precursors in Perfluorochemical Products Sold in Canada was signed by four companies with the aim of addressing confirmed sources of PFCAs from substances already in Canadian commerce (Environment Canada, 2010).

Globally, there is an initiative to reduce PFOA emissions and product content. In 2006, the United States Environmental Protection Agency and eight major companies in the industry launched the 2010/15 PFOA Stewardship Program. Under this voluntary effort, companies were committed to reduce global facility emissions and product content of PFOA and related chemicals by 95% by 2010, and to work toward eliminating emissions and product content by 2015 (EPA, 2012a). As of 2012, more than 150 replacement chemicals have been developed, and the companies are on track to phase out PFOA and related chemicals by the end of 2015 (EPA, 2012b). Canada's 2010 Environmental Performance Agreement is consistent with the targets and commitments by industry in the United States (Environment Canada, 2010). The European Union and the Australian government have initiated similar policies where PFASs are either prohibited or subject to further toxicity testing for evaluation.

Several human biomonitoring studies in Canada have measured PFASs in serum and plasma (Alberta Health and Wellness, 2008; Hamm et al., 2010; Kubwabo et al., 2004; Monroy et al., 2008; Tittlemier et al., 2004; Turgeon O'Brien et al., 2012). Serum concentrations of some PFASs in children appear to be higher than in adults and may be related to differences in sources and routes of exposure between these two age groups (Calafat et al., 2007a; Calafat et al., 2007b; Kato et al., 2009). In 2002, serum samples from 56 individuals in Ottawa, Ontario, and Gatineau, Quebec, were analyzed for PFOS and PFOA. PFOS was detected in all samples with a mean concentration of 28.8 µg/L and a range of 3.7 to 65.1 µg/L (Kubwabo et al., 2004). The concentration of PFOA was considerably lower, with a mean of 3.4 µg/L and a range from <1.2 to 7.2 µg/L (Kubwabo et al., 2004). In 2004, PFOS was measured in the plasma samples from 883 Nunavik Inuit living in the Canadian Arctic (Dallaire et al., 2009). PFOS was detected in all tested samples, with a geometric mean concentration of 18.68 µg/L (Dallaire et al., 2009). The concentrations of PFASs were measured in 155 Inuit infants attending childcare centres in Nunavik (Turgeon O'Brien et al., 2012). Both PFOS and PFOA were detected in all plasma samples with geometric means of 3.36 µg/L and 1.61 µg/L, respectively.

PFOS, PFOA, and PFHxS were measured in the plasma of all CHMS participants aged 20 to 79 years in cycle 1 (2007-2009) and 12 to 79 years in cycle 2 (2009-2011). PFBA, PFHxA, PFBS, PFNA, PFDA, and PFUnDA were measured in the plasma of all CHMS participants aged 12 to 79 years in cycle 2 (2009-2011). Data for the PFASs are presented as μg/L in plasma (Tables 13.1.1 to 13.9.3). Finding a measurable amount of PFASs in plasma is an indicator of exposure to PFASs and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for plasma levels of PFBA, PFHxA, PFBS, PFNA, PFDA, and PFUnDA in the Canadian population.

13.1 Perfluorobutanoic Acid (PFBA)

2 Data Tables: 13.1.1 to 13.1.2

13.2 Perfluorohexanoic Acid (PFHxA)

2 Data Tables: 13.2.1 to 13.2.2

13.3 Perfluorooctanoic Acid (PFOA)

3 Data Tables: 13.3.1 to 13.3.3

13.4 Perfluorononanoic Acid (PFNA)

2 Data Tables: 13.4.1 to 13.4.2

13.5 Perfluorodecanoic Acid (PFDA)

2 Data Tables: 13.5.1 to 13.5.2

13.6 Perfluoroundecanoic Acid (PFUnDA)

2 Data Tables: 13.6.1 to 13.6.2

13.7 Perfluorobutane Sulfonate (PFBS)

2 Data Tables: 13.7.1 to 13.7.2

13.8 Perfluorohexane Sulfonate (PFHxS)

3 Data Tables: 13.8.1 to 13.8.3

13.9 Perfluorooctane Sulfonate (PFOS)

3 Data Tables: 13.9.1 to 13.9.3

References

3M. (2012). 3M's phase out and new technologies. Retrieved May 29, 2012, from http://solutions.3m.com/wps/portal/3M/en_US/PFOS/PFOA/Information/phase-out-technologies/

Alberta Health and Wellness (2008). Alberta Biomonitoring Program - Chemicals in serum of pregnant women in Alberta. Alberta Health and Wellness, Government of Alberta, Edmonton, AB.

ATSDR (Agency for Toxic Substances and Disease Registry). (2009). Toxicological profile for perfluoroalkyls. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved August 28, 2012, from www.atsdr.cdc.gov/toxprofiles/tp200-c5.pdf

Butenhoff, J.L., Olsen, G.W., & Pfahles-Hutchens, A. (2006). The applicability of biomonitoring data for perfluorooctanesulfonate to the environmental public health continuum. Environmental Health Prespectives, 114 (11), 1776-1782.

Calafat, A.M., Kuklenyik, Z., Reidy, J.A., Caudill, S.P., Tully, J.S., & Needham, L.L. (2007a). Serum concentrations of 11 polyfluoroalkyl compounds in the US population: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Environmental Science & Technology, 41 (7), 2237-2242.

Calafat, A.M., Wong, L.Y., Kuklenyik, Z., Reidy, J.A., & Needham, L.L. (2007b). Polyfluoroalkyl chemicals in the U.S. population: Data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000. Environmental Health Perspectives, 115 (11), 1596-1602.

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Canada. (2009). Regulations adding perfluorooctane sulfonate and its salts to the virtual elimination list. SOR/2009-15. Canada Gazette, Part II: Official Regulations, 143 (3). Retrieved September 17, 2012, from http://canadagazette.gc.ca/rp-pr/p2/2009/2009-02-04/html/sor-dors15-eng.html

Canada. (2010a). Chemical substances: Perfluorooctane sulfonate (PFOS). Retrieved May 29, 2012, from www.chemicalsubstanceschimiques.gc.ca/fact-fait/pfos-eng.php

Canada. (2010b). Regulations amending the prohibition of certain toxic substances regulations, 2005 (four new fluorotelomer-based substances), SOR/2010-211. Canada Gazette, Part II: Official Regulations, 144 (21). Retrieved August 28, 2012, from http://canadagazette.gc.ca/rp-pr/p2/2010/2010-10-13/html/sor-dors211-eng.html

Canada. (2012). Order adding toxic substances to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part I: Notices and Proposed Regulations, 146 (39). Retrieved October 31, 2012, from http://gazette.gc.ca/rp-pr/p1/2012/2012-09-29/html/reg1-eng.html

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Chang, S.-C., Das, K., Ehresman, D.J., Ellefson, M.E., Gorman, G.S., Hart, J.A., Noker, P.E., Tan, Y.-M., Lieder, P.H., Lau, C., Olsen, G.W., & Butenhoff, J.L. (2008). Comparative pharmacokinetics of perfluorobutyrate in rats, mice, monkeys, and humans and relevance to human exposure via drinking water. Toxicological Sciences, 104 (1), 40-53.

Dallaire, R., Ayotte, P., Pereg, D., Déry, S., Dumas, P., Langlois, E., & Dewailly, E. (2009). Determinants of plasma concentrations of perfluorooctanesulfonate and brominated organic compounds in Nunavik Inuit adults (Canada). Environmental Science & Technology, 43 (13), 5130-5136.

Environment Canada. (2006a). Ecological screening assessment report on perfluorooctane sulfonate, its salts and its precursors that contain the C8F17SO2 or C8F17SO3, or C8F17SO2N moiety. Minister of the Environment, Ottawa, ON. Retrieved May 29, 2012, from www.ec.gc.ca/lcpe-cepa/default.asp?lang=En&n=98B1954A-1

Environment Canada. (2006b). Perfluorinated carboxylic acids (PFCAs) and precursors: An action plan for assessment and management. Minister of the Environment, Ottawa, ON. Retrieved August 8, 2012, from www.ec.gc.ca/Publications/default.asp?lang=En&xml=2DC7ADE3-A653-478C-AF56-3BE756D81772

Environment Canada. (2010). Environmental performance agreement respecting perfluorinated carboxylic acids (PFCAs) and their precursors in perfluochemical products sold in Canada. Minister of the Environment, Ottawa, ON. Retrieved May 29, 2012, from www.ec.gc.ca/epe-epa/default.asp?lang=En&n=10551A08-1

Environment Canada. (2012). Ecological screening assessment report: Long-chain (C9-C20) perfluorocarboxylic acids, their salts and their precursors. Minister of the Environment, Ottawa, ON. Retrieved August 29, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=CA29B043-1

Environment Canada & Health Canada. (2012a). Screening assessment: Perfluorooctanoic acid, its salts, and its precursors. Ottawa, ON. Retrieved August 29, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=370AB133-1

Environment Canada & Health Canada. (2012b). Proposed risk management approach for perfluoroactanoic acid (PFOA), its salts, and its precursors and long-chain (C9-C20) perfluorocarboxylic acids (PFCAs), their salts and their precursors. Ottawa, ON. Retrieved August 29, 2012, from www.ec.gc.ca/ese-ees/default.asp?lang=En&n=451C95ED-1

EPA (U.S. Environmental Protection Agency). (2002). Revised draft hazard assessment of perflourooctanoic acid and its salts. U.S. Environmental Protection Agency, Washington DC.

EPA (U.S. Environmental Protection Agency). (2012a). Perfluorooctanoic acid (PFOA) and fluorinated telomers. U.S. Environmental Protection Agency, Washington, DC. Retrieved May 15, 2012, from www.epa.gov/oppt/pfoa/

EPA (U.S. Environmental Protection Agency). (2012b). News release: Industry progressing in voluntary effort to reduce toxic chemicals. Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency, Washington, DC.

Fromme, H., Tittlemier, S.A., Volkel, W., Wilhelm, M., & Twardella, D. (2009). Perfluorinated compounds - Exposure assessment for the general population in western countries. International Journal of Hygiene and Environmental Health, 212 (3), 239-270.

Fromme, H., Schlummer, M., Möller, A., Gruber, L., Wolz, G., Ungewiss, J., Böhmer, S., Dekant, W., Mayer, R., Liebl, B., & Twardella, D. (2007). Exposure of an adult population to perfluorinated substances using duplicate diet portions and biomonitoring data. Environmental Science & Technology, 41 (22), 7928-7933.

Hamm, M.P., Cherry, N.M., Chan, E., Martin, J.W., & Burstyn, I. (2010). Maternal exposure to perfluorinated acids and fetal growth. Journal of Exposure Sciences and Environmental Epidemiology, 20 (7), 589-597.

Harada, K., Inoue, K., Morikawa, A., Yoshinaga, T., Saito, N., & Koizumi, A. (2005). Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species-specific excretion. Environmental Research, 99 (2), 253-261.

Health Canada. (2006). Perfluorooctane sulfonate, its salts and its percursors that contain the C8F17SO2 or C 8F17SO3 moiety. State of the science report for a screening health assessment. Minister of Health, Ottawa. Retrieved September 1, 2011, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/pfos-spfo/index-eng.php

Health Canada. (2009). Questions and answers on perfluorinated chemicals in food. Minister of Health, Ottawa, ON. Retrieved August 8, 2012, from www.hc-sc.gc.ca/fn-an/securit/chem-chim/environ/pcf-cpa/qr-pcf-qa-eng.php

Houde, M., Martin, J.W., Letcher, R.J., Solomon, K.R., & Muir, D.C.G. (2006). Biological monitoring of polyfluoroalkyl substances: A review. Environmental Science & Technology, 40 (11), 3463-3473.

Hölzer, J., Midasch, O., Rauchfuss, K., Kraft, M., Reupert, R., Angerer, J., Kleeschulte, P., Marschall, N., & Wilhelm, M. (2008). Biomonitoring of perfluorinated compounds in children and adults exposed to perfluorooctanoate-contaminated drinking water. Environmental Health Prespectives, 116 (5), 651-657.

IARC (International Agency for Research on Cancer). (2008). IARC monographs on the evaluation of carcinogenic risks to humans - Internal report 08/001: Report of the Advisory Group to Recommend Priorities for IARC Monographs during 2010-2014. World Health Organization, Lyon.

Indian and Northern Affairs Canada (2009). Canadian Arctic contaminants and health assessment report. Indian and Northern Affairs Canada, Ottawa.

Johnson, J.D., Gibson, S.J., & Ober, R.E. (1984). Cholestyramine-enhanced fecal elimination of carbon-14 in rats after administration of ammonium [14C]perfluorooctanoate or potassium [14C]perfluorooctanesulfonate. Fundamental and Applied Toxicology, 4 (6), 972-976.

Kärrman, A., Domingo, J., Llebaria, X., Nadal, M., Bigas, E., van Bavel, B., & Lindström, G. (2010). Biomonitoring perfluorinated compounds in Catalonia, Spain: concentrations and trends in human liver and milk samples. Environmental Science and Pollution Research, 17 (3), 750-758.

Kato, K., Calafat, A.M., Wong, L.Y., Wanigatunga, A.A., Caudill, S.P., & Needham, L.L. (2009). Polyfluoroalkyl compounds in pooled sera from children participating in the National Health and Nutrition Examination Survey 2001-2002. Environmental Science & Technology, 43 (7), 2641-2647.

Kato, K., Wong, L.-Y., Jia, L.T., Kuklenyik, Z., & Calafat, A.M. (2011). Trends in exposure to polyfluoroalkyl chemicals in the U.S. population: 1999-2008. Environmental Science & Technology, 45 (19), 8037-8045.

Kissa, E. (2001). Fluorinated Surfactants and Repellents. Marcel Dekkaer Inc., New York, NY.

Kubwabo, C., Stewart, B., Zhu, J., & Marro, L. (2005). Occurrence of perfluorosulfonates and other perfluorochemicals in dust from selected homes in the city of Ottawa, Canada. Journal of Environmental Monitoring, 7 (11), 1074-1078.

Kubwabo, C., Vais, N., & Benoit, F.M. (2004). A pilot study on the determination of perfluorooctanesulfonate and other perfluorinated compounds in blood of Canadians. Journal of Environmental Monitoring, 6 (6), 540-545.

Lopez-Espinosa, M.J., Mondal, D., Armstrong, B., Bloom, M.S., & Fletcher, T. (2012). Thyroid function and perfluoroalkyl acids in children living near a chemical plant. Environmental Health Perspectives, 120 (7), 1036-1041.

Martin, J.W., Smithwick, M.M., Braune, B.M., Hoekstra, P.F., Muir, D.C., & Mabury, S.A. (2004). Identification of long-chain perfluorinated acids in biota from the Canadian Arctic. Environmental Science & Technology, 38 (2), 373-380.

Monroy, R., Morrison, K., Teo, K., Atkinson, S., Kubwabo, C., Stewart, B., & Foster, W.G. (2008). Serum levels of perfluoroalkyl compounds in human maternal and umbilical cord blood samples. Environmental Research, 108 (1), 56-62.

Newsted, J., Beach, S., Gallagher, S., & Giesy, J. (2008). Acute and chronic effects of perfluorobutane sulfonate (PFBS) on the mallard and northern bobwhite quail. Archives of Environmental Contamination and Toxicology, 54 (3), 535-545.

Olsen, G.W., Burris, J.M., Ehresman, D.J., Froehlich, J.W., Seacat, A.M., Butenhoff, J.L., & Zobel, L.R. (2007). Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environmental Health Perspectives, 115 (9), 1298-1305.

Prevedouros, K., Cousins, I.T., Buck, R.C., & Korzeniowski, S.H. (2005). Sources, fate and transport of perfluorocarboxylates. Environmental Science & Technology, 40 (1), 32-44.

Tittlemier, S.A., Pepper, K., Seymour, C., Moisey, J., Bronson, R., Cao, X.L., & Dabeka, R.W. (2007). Dietary exposure of Canadians to perfluorinated carboxylates and perfluorooctane sulfonate via consumption of meat, fish, fast foods, and food items prepared in their packaging. Journal of Agricultural and Food Chemistry, 55 (8), 3203-3210.

Tittlemier, S.A., Ryan, J.J., and Van Oostdam, J.J. (2004). Presence of anionic perfluorinated organic compounds in serum collected from northern Canadian populations. Organohalogen Compounds, 66, 4009-4014.

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14 Pesticide Summaries and Results

14.1 Atrazine Metabolites

Atrazine (CASRN 1912-24-9) is a synthetic selective herbicide registered for use in Canada for the control of annual broadleaf weeds and grassy weeds in corn (Health Canada, 2003; Health Canada, 2004). It belongs to a group of pesticides known as triazine herbicides that also includes simazine, propazine, and cyanazine (Barr & Needham, 2002; IPCS, 1997). Triazine herbicides were first produced in 1958, and atrazine was introduced into Canada in 1960 (ATSDR, 2003; CCME, 1999). The use of atrazine has decreased significantly in recent years because of environmental concerns; its use is now half of that of 1983 (CCME, 2009; Health Canada, 2003). The following atrazine metabolites were measured as part of this survey: diaminochlorotriazine (DACT; CASRN 3397-62-4), desethylatrazine (DEA; CASRN 6190-65-4), and atrazine mercapturate (AM; CASRN 138722-96-0).

Atrazine is released to the environment as a result of agricultural practices. It is mobile in soil and may enter groundwater through percolation and surface water via direct runoff (ATSDR, 2003; Health Canada, 2007). In the environment, atrazine undergoes dealkylation forming various metabolites, including DEA and DACT (Nelson et al., 2001). Atrazine and its dealkylated metabolites have been found in surface water and groundwater following application of atrazine (WHO, 2009). In areas where atrazine is used extensively, it is one of the most frequently detected pesticides in surface and well water (Health Canada, 1993). Atrazine exposure in the general population occurs primarily through water or air and, in rare instances, food (ATSDR, 2003).

Atrazine is well absorbed orally, metabolized, and then eliminated in the urine over a few days (CDC, 2009). Following absorption, atrazine is metabolized via the glutathione detoxification pathway into mercapturic acid metabolites, such as AM, and via simple dealkylation into dealkylated metabolites, such as DEA and DACT (Barr & Needham, 2002; Barr et al., 2007). In human studies, DACT and AM have been identified as primary metabolites (Barr et al., 2007; Catenacci et al., 1993; Lucas et al., 1993). Dealkylated metabolites are not specific to atrazine and can result from the metabolism of other triazine herbicides such as simazine, propazine, and cyanazine (Barr & Needham, 2002; CDC, 2009; Mendas et al., 2012). These metabolites can be measured in urine and are reflective of recent exposure to triazine herbicides (including atrazine) or the metabolites in the environment (ATSDR, 2003). Atrazine has also been directly measured in urine, but only constituted less than 2% of excreted metabolites (80% were dealkylated metabolites), and therefore is not a good biomarker for exposure (Catenacci et al., 1993). AM is a metabolite specific to atrazine, and urinary levels are a specific biomarker of recent atrazine exposure (CDC, 2009; Mendas et al., 2012).

The bulk of the available toxicity data comes from long-term oral exposure in animals (ATSDR, 2003). In animals, reduced body weight gain, cardiotoxicity, developmental effects, reproductive effects, and neuroendocrine effects have been reported following oral exposure to both atrazine and its dealkylated metabolites (ATSDR, 2006; CDC, 2009; Health Canada, 1993; Health Canada, 2003; WHO, 2011). In humans, nausea and dizziness have been associated with ingestion of an unspecified concentration of atrazine in drinking water (Health Canada, 1993).

Atrazine is not genotoxic and not classifiable as to its carcinogenicity to humans (Group 3) according to the International Agency for Research on Cancer (CDC, 2009; IARC, 1999; WHO, 2009).

The sale and use of atrazine and other triazine herbicides is regulated in Canada under the Pest Control Products Act by the Pest Management Regulatory Agency (PMRA) (Canada, 2006). PMRA completed a re-evaluation of the human health risks related to atrazine in 2004 and determined that all uses of atrazine and its end-use products were not of concern to human health, provided that the proposed mitigation measures were implemented (Health Canada, 2003; Health Canada, 2004). These mitigation measures include a phase-out of use in lowbush blueberries, atrazine-tolerant canola, and in industrial and residential settings (Health Canada, 2003). Health Canada has established maximum residue limits for atrazine in various foods and set an acceptable daily intake for atrazine plus its chlorinated metablites (Health Canada, 2003; Health Canada, 2011). Health Canada has also established a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of the sum of atrazine and its dealkylated metabolites (Health Canada, 1993; Health Canada, 2007; Health Canada, 2012).

There are no existing biomonitoring data on concentrations of atrazine in the Canadian population.

Atrazine metabolites (AM, DACT, and DEA) were measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and are presented as both μg/L and μg/g creatinine (Tables 14.1.1.1 to 14.1.3.4). Finding a measurable amount of atrazine metabolites in urine is an indicator of exposure to atrazine and/or other triazine herbicides and their metabolites in the environment and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary atrazine metabolite levels in the Canadian population.

14.1.1 Atrazine Mercapturate (AM)

4 Data Tables: 14.1.1.1 to 14.1.1.4

14.1.2 Diaminochlorotriazine (DACT)

4 Data Tables: 14.1.2.1 to 14.1.2.4

14.1.3 Desethylatrazine (DEA)

4 Data Tables: 14.1.3.1 to 14.1.3.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2003). Toxicological profile for atrazine. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved May 1, 2012, from www.atsdr.cdc.gov/toxprofiles/tp153.html

ATSDR (Agency for Toxic Substances and Disease Registry). (2006). Interaction profile for toxic substances. Appendix A: Background information for atrazine and deethylatrazine. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved May 14, 2012, from www.atsdr.cdc.gov/interactionprofiles/ip10.html

Barr, D. & Needham, L. (2002). Analytical methods for biological monitoring of exposure to pesticides: A review. Journal of Chromatography B, 778, 5-29.

Barr, D.B., Panuwet, P., Nguyen, J.V., Udunka, S., & Needham, L.L. (2007). Assessing exposure to atrazine and its metabolites using biomonitoring. Environmental Health Perspectives, 115 (10), 1474-1478.

Canada. (2006). Pest Control Products Act. SC 2002, c. 28. Retrieved May 30, 2012, from http://laws-lois.justice.gc.ca/eng/acts/P-9.01/

Catenacci, G., Barbieri, F., Bersani, M., Ferioli, A., Cottica, D., & Maroni, M. (1993). Biological monitoring of human exposure to atrazine. Toxicology Letters, 69 (2), 217-222.

CCME (Canadian Council of Ministers of the Environment). (1999). Canadian water quality guidelines for the protection of aquatic life: Atrazine. Retrieved March 15, 2013, from http://ceqg-rcqe.ccme.ca/download/en/144/

CCME (Canadian Council of Ministers of the Environment). (2009). Source to tap: Atrazine. Retrieved May 15, 2012, from www.ccme.ca/sourcetotap/atrazine.html

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Health Canada. (1993). Guidelines for Canadian drinking water quality: Guideline technical document - Atrazine. Minister of Health, Ottawa, ON. Retrieved May 15, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/atrazine/atrazine-eng.pdf

Health Canada. (2003). Proposed acceptability for continuing registration. Re-evaluation of atrazine. PACR2003-13. Minister of Health, Ottawa, ON.

Health Canada. (2004). Re-evaluation decision document. Atrazine RRD2004-12. Minister of Health, Ottawa, ON.

Health Canada. (2007). Re-evaluation decision cocument: Atrazine (environmental assessment) RVD2007-05. Minister of Health, Ottawa, ON.

Health Canada. (2011). List of maximum residue limits regulated under the Pest Control Products Act. Minister of Health, Ottawa, ON. Retrieved May 15, 2012, from www.hc-sc.gc.ca/cps-spc/pest/part/protect-proteger/food-nourriture/mrl-lmr-eng.php

Health Canada. (2012). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

IARC (International Agency for Research on Cancer). (1999). IARC monographs on the evaluation of carcinogenic risk to humans - 73: Some chemicals that cause tumours of the kidney or urinary bladder and some other substances. World Health Organization, Geneva.

IPCS (Internation Programme on Chemical Safety). (1997). Triazine herbicides. Retrieved May 15, 2012, from www.inchem.org/documents/pims/chemical/pimg013.htl

Kurt-Karakus, P.B., Teixeira, C., Small, J., Muir, D., & Bidleman, T.F. (2011). Current use pesticides in inland lake waters, precipitation and air from Ontario, Canada. Environmental Toxicology and Chemistry, 30 (7), 1539-1548.

Lucas, A.D., Jones, A.D., Goodrow, M.H., Saiz, S.G., Blewett, C., Seiber, J.N., & Hammock, B.D. (1993). Determination of atrazine metabolites in human urine: Development of a biomarker of exposure. Chemical Research in Toxicology, 6 (1), 107-116.

Mendas, G., Vuletic, V., Galic, N., & Drevenkar, V. (2012). Urinary metabolites as biomarkers of human exposure to atrazine: Atrazine mercapturate in agricultural workers. Toxicology Letters, 210, 174-181.

Nelson, H., Lin, J., & Frankenberry, M. (2001). Drinking water exposure assessment for atrazine and various chlorotriazine and hydroxy-triazine degradates. U.S. Environmental Protection Agency, Washington, DC.

WHO (World Health Organization). (2009). Atrazine. In Pesticide Residues in Food - 2007 Evaluations. Part II. Toxicological. World Health Organization. Retrieved May 2, 2012, from http://whqlibdoc.who.int/publications/2009/9789241665230_eng.pdf

WHO (World Health Organization). (2011). Atrazine and its metabolites in drinking water: Background document of WHO guidelines for drinking water quality. Retrieved May 2, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/atrazine/en/

14.2 Carbamate Metabolites

N -Methyl carbamate insecticides, commonly known as carbamates, are a group of synthetic pesticides (Health Canada, 2010; IPCS, 1986). Carbamate insecticides were first introduced in the 1950s as replacements for organochlorine pesticides because they are less persistent in the environment and do not bioaccumulate (Rawn et al., 2004; WHO, 2004). The use of carbamates in Canada has decreased since the mid-1990s with the introduction of pyrethroids and other replacement insecticides (Rawn et al., 2006).

The following carbamate metabolites were measured as part of this survey: carbofuranphenol (CASRN 1563-38-8), 2-isopropoxyphenol (CASRN 4812-20-8), and 1-hydroxynaphthalene (CASRN 90-15-3).

Carbofuranphenol is a metabolite of the carbamate insecticide carbofuran and its derivatives, namely benfuracarb, carbosulfan, and furathiocarb (Kawamoto & Makihata, 2003). In Canada, only carbofuran is currently registered for use; benfuracarb, furathiocarb, and carbosulfan have never been registered for use in Canada (Health Canada, 2009a; Health Canada, 2012a). Carbofuran is used in Canada to control a broad range of insect pests on field, vegetable, and fruit crops primarily by farmers, farmworkers, and professional applicators (Health Canada, 2010; Rawn et al., 2004).

2-Isopropoxyphenol is a specific metabolite of propoxur that has been used internationally as a replacement for dichlorodiphenyltrichloroethane, or DDT, in malaria-vector control (Metcalfe, 1995). In Canada, propoxur is registered under the Pest Control Products Act to control a wide range of insect and arthropod pests (Canada, 2006; Health Canada, 2011a). It is used in and on commercial, industrial, institutional, and residential structures, in transportation vehicles, at outdoor residential sites, on companion animals, and in human habitats and recreational sites (Health Canada, 2011a).

1-Hydroxynaphthalene is a metabolite of the carbamate insecticide carbaryl as well as the polycyclic aromatic hydrocarbon naphthalene, making it difficult to distinguish between these exposures in the general population (Meeker et al., 2007). For information on 1-hydroxynaphthalene, as well as related data tables, see section 16.6 (Naphthalene Metabolites). Carbaryl is a broad spectrum insecticide and a plant growth regulator currently registered for use in agricultural, industrial, forest, and residential areas (Health Canada, 2009b). In Canada, carbaryl is registered for use as an insecticide on food and feed crops, ornamental crops, livestock, forestry sites, industrial sites, as well as commercial turf such as that found on golf courses and sod farms. It is also registered as a plant growth regulator used for apple thinning (Health Canada, 2009b).

Exposure of the general population to carbamates can occur through dermal contact when handling and applying insecticides (EPA, 2012). Although exposure to carbamates can also occur through ingestion of residues present in food and drinking water, this exposure route is less common because residues in treated crops are generally very low (EPA, 2012; Health Canada, 2010).

Carbamates are generally easily absorbed through the skin, mucous membranes, and respiratory and gastrointestinal tracts of mammals (IPCS, 1986). In humans, they are rapidly absorbed, metabolized, and eliminated mainly in urine (IPCS, 1986; WHO, 2004). Urinary levels of carbofuranphenol, 2-isopropoxyphenol, and 1-hydroxynaphthalene reflect recent exposure (CDC, 2009).

Like organophosphates, carbamates inhibit acetylcholinesterase, a key enzyme involved in terminating nerve pulses by degrading the neurotransmitter acetylcholine into the inactive products choline and acetic acid (Fukuto, 1990; IPCS, 1986; Leibson & Lifshitz, 2008; Sogorb & Vilanova, 2002). Carbamates do not require metabolic activation and inhibit acetylcholinesterase by depositing a carbamyl group on the enzyme (Fukuto, 1990; IPCS, 1986; Leibson & Lifshitz, 2008). This interrupts the transmission of nerve impulses and overstimulates the nervous system (IPCS, 1986). An important aspect of carbamate toxicity is the rapid nature of the onset following inhibition of acetylcholinesterase and recovery of effects (EPA, 2007). Acute exposure to high concentrations of carbamates in animals has resulted in salivation, shedding of tears, constriction of pupils, urination, respiratory difficulties, muscular twitching, tremors, cramps, and ataxia (Health Canada, 2009a; IPCS, 1986; WHO, 2004). Adverse health effects observed in humans following short- and long-term exposure include nausea, dizziness, vomiting, headache, sweating, salivation, ataxia, confusion, and breathing difficulties (Health Canada, 2009a; IPCS, 1986). In severe cases, acute toxicity from carbamate exposure can cause potentially fatal respiratory failure (IPCS, 1986). Carbamate metabolites are generally less toxic than their parent compounds (IPCS, 1986). According to the International Agency for Research on Cancer (IARC), carbaryl is not classifiable as to its carcinogenicity to humans (Group 3), whereas naphthalene is possibly carcinogenic to humans (Group 2B) (IARC, 1987; IARC, 2002). Neither carbofuran nor propoxur has been classified by IARC.

The sale and use of carbamate insecticides is regulated in Canada under the Pest Control Products Act by the Pest Management Regulatory Agency (PMRA) (Canada, 2006). In 2002, PMRA initiated a re-evaluation of all N-methyl carbamate active ingredients used in Canada, including carbofuran, carbaryl, and propoxur (Health Canada, 2002). As a result of the re-evaluation, PMRA required phase out of carbofuran products because, under current conditions of use, they pose an unacceptable risk to human health and the environment (Health Canada, 2010). Human health concerns were identified for both occupational and dietary carbofuran exposure (Health Canada, 2010). PMRA has also recently proposed the phase out of certain propoxur uses in Canada, including control of biting flies, pet collars, and all indoor uses of domestic-class products except bait trays (Health Canada, 2011a). It is proposed that propoxur continue to be allowed for commercial use in indoor crack and crevice applications, for domestic and commercial outdoor uses, and for bait trays (Health Canada, 2011a). Certain carbaryl uses in Canada were also proposed for phase out; these uses include turf and residential uses, as well as some agricultural uses (Health Canada, 2009b).

Maximum residue limits have been established in some foods for certain carbamates that have registered food uses (Health Canada, 2010; Health Canada, 2011b; Rawn et al., 2004; Rawn et al., 2006). However, in its recent re-evaluation, PMRA requires that all maximum residue limits for carbofuran be amended or revoked (Health Canada, 2010; Health Canada, 2012b). Health Canada has also set an acceptable daily intake for carbofuran and proposed acceptable daily intakes for propoxur and carbaryl (Health Canada, 2009b; Health Canada, 2010; Health Canada, 2011a). Health Canada has established Canadian drinking water quality guidelines that set out the maximum acceptable concentrations of carbofuran and carbaryl (Health Canada, 2012b). A maximum acceptable concentration has not been established for propoxur.

Carbamate metabolites (carbofuranphenol, 2-isopropoxyphenol and 1-hydroxynaphthalene) were measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years. Data for carbofuranphenol and 2-isopropoxyphenol are presented below as both μg/L and μg/g creatinine (Tables 14.2.1.1 to 14.2.2.4). See section 16.6 (Naphthalene Metabolites) for 1-hydroxynaphthalene data tables. Finding a measurable amount of carbamate metabolites in urine can be an indicator of exposure to carbamates and does not necessarily mean that an adverse health effect will occur. These data provide baseline urinary levels for carbofuranphenol, 2-isopropoxyphenol and 1-hydroxynaphthalene in the Canadian population.

14.2.1 Carbofuranphenol

4 Data Tables: 14.2.1.1 to 14.2.1.4

14.2.2 2-Isopropoxyphenol

4 Data Tables: 14.2.2.1 to 14.2.2.4

References

Canada. (2006). Pest Control Products Act. SC 2002, c. 28. Retrieved May 30, 2012, from http://laws-lois.justice.gc.ca/eng/acts/P-9.01/

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

EPA (U.S. Environmental Protection Agency). (2007). Revised N-methyl carbamate cumulative risk assessment. Retrieved November 7, 2012, from www.epa.gov/oppsrrd1/REDs/nmc_revised_cra.pdf

EPA (U.S. Environmental Protection Agency). (2012). Background and summary of N-methyl carbamate revised cumulative risk assessment. Retrieved June 7, 2012, from www.epa.gov/pesticides/cumulative/carbamate_background.htm

Fukuto, T.R. (1990). Mechanism of action of organophosphorus and carbamate insecticides. Environmental Health Perspectives, 87, 245-254.

Health Canada. (2002). Re-evaluation of selected carbamate pesticides. Re-evaluation note REV2002-06. Minister of Health, Ottawa, ON.

Health Canada. (2009a). Proposed re-evaluation decision: Carbofuran. PRVD2009-11. Minister of Health, Ottawa, ON.

Health Canada. (2009b). Proposed re-evaluation decision: Carbaryl. PRVD2009-14. Minister of Health, Ottawa, ON.

Health Canada. (2010). Re-evaluation decision RVD2010-16: Carbofuran. Minister of Health, Ottawa, ON.

Health Canada. (2011a). Proposed re-evaluation decision PRVD2011-09: Propoxur. Minister of Health, Ottawa, ON.

Health Canada. (2011b). List of maximum residue limits regulated under the Pest Control Products Act. Minister of Health, Ottawa, ON. Retrieved May 15, 2012, from www.hc-sc.gc.ca/cps-spc/pest/part/protect-proteger/food-nourriture/mrl-lmr-eng.php

Health Canada. (2012a). Pesticide label search database. Retrieved April 20, 2012, from www.pr-rp.hc-sc.gc.ca/ls-re/index-eng.php

Health Canada. (2012b). Guidelines for Canadian drinking water quality - Summary table. Minister of Health, Ottawa, ON. Retrieved March 15, 2013, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/2012-sum_guide-res_recom/index-eng.php

IARC (International Agency for Research on Cancer). (1987). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 12: Some carbamates, thiocarbamates and carbazides. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (2002). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 82: Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. World Health Organization, Geneva.

IPCS (International Programme on Chemical Safety). (1986). Carbamate pesticides: A general introduction. Environmental health criteria 64. World Health Organization, Geneva. Retrieved June 12, 2012, from www.inchem.org/documents/ehc/ehc/ehc64.htm

Kawamoto, T. & Makihata, N. (2003). Development of a simultaneous analysis method for carbofuran and its three derivative pesticides in water by GC/MS with temperature programmable inlet on-column injection. Analytical Sciences, 19, 1605-1610.

Leibson, T. & Lifshitz, M. (2008). Organophosphate and carbamate poisoning: review of the current literature and summary of clinical and laboratory experience in southern Israel. Israel Medical Association Journal, 10 (11), 767-770.

Meeker, J.D., Barr, D.B., Serdar, B., Rappaport, S.M., and Hauser, R. (2007). Utility of urinary 1-naphthol and 2-naphthol levels to assess environmental carbaryl and naphthalene exposure in an epidemiology study. Journal of Exposure Science and Environmental Epidemiology, 17, 314-320.

Metcalf, R.L. (1995). Insect control technology. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc., Mississauga, ON.

Rawn, D.F., Roscoe, V., Krakalovich, T., & Hanson, C. (2004). N-methyl carbamate concentrations and dietary intake estimates for apple and grape juices available on the retail market in Canada. Food Additives and Contaminants, 21 (6), 555-563.

Rawn, D.F., Roscoe, V., Trelka, R., Hanson, C., Krakalovich, T., & Dabeka, R.W. (2006). N-methyl carbamate pesticide residues in conventional and organic infant foods available on the Canadian retail market, 2001-03. Food Additives and Contaminants, 23 (7), 651-659.

Sogorb, M.A. & Vilanova, E. (2002). Enzymes involved in the detoxification of organophosphorus, carbamate and pyrethroid insecticides through hydrolysis. Toxicology Letters, 128 (1-3), 215-228.

WHO (World Health Organization). (2004). Carbofuran in drinking water. Background document for development of WHO guidelines for drinking water quality. World Health Organization, Geneva. Retrieved May 25, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/carbofuran.pdf

14.3 2,4-Dichlorophenoxyacetic Acid

The pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) is the most commonly used chemical in the class of phenoxy herbicides. It is a selective synthetic herbicide used for the control of broadleaf weeds in residential, agricultural, and forest environments. 2,4-D was first registered in Canada in 1946 for agricultural and forestry use and has been permitted for use on lawns and turf since the 1960s. 2,4-D is found in over 150 agricultural and residential products in Canada and is often combined with other herbicides and fertilizers (Health Canada, 2012).

2,4-D is a relatively short-lived chemical in terrestrial and aquatic environments, with a half-life of less than 2 weeks, except in anaerobic environments where 2,4-D is persistent (Health Canada, 2007). This highly mobile chemical is susceptible to leaching and runoff from treated areas (Health Canada, 2007).

The primary routes of exposure for the general public are through ingestion of food and drinking water, handling 2,4-D-containing products, and environmental exposure in herbicide-treated areas (Health Canada, 2008).

Following entry into the body, 2,4-D is rapidly absorbed and excreted primarily unchanged in urine (Sauerhoff et al., 1977). Accumulation in tissues is low because 2,4-D has an elimination half-life of 10 to 33 hours (Sauerhoff et al., 1977). 2,4-D has been routinely measured in urine; its presence is proportional to the previous few days of exposure. 2,4-D has been measured in other biological matrices including semen and plasma (Arbuckle et al., 1999; Barr & Needham, 2002).

Long-term exposure to 2,4-D has been associated with effects on the kidneys, nervous system, and body weights in animal studies; the primary target organ for toxicity is the kidney (Health Canada, 2007). Some studies have suggested associations between occupational use of phenoxy herbicides and cancer, including non-Hodgkin's lymphoma and soft tissue sarcomas. However, these studies are complicated by confounding factors and exposures to other pesticides or impurities, and other studies have not shown an association (ATSDR, 1999; Health Canada, 2008; IARC, 1987; IARC, 1999; WHO, 2003a; WHO, 2003b). Recent re-evaluations by the Canadian Pest Management Regulatory Agency (PMRA), the European Union, the United States Environmental Protection Agency, and the World Health Organization did not classify 2,4-D as a human carcinogen (EPA, 2005; European Commission, 2001; Health Canada, 2006; WHO, 2003a).

The sale and use of 2,4-D is regulated in Canada under the Pest Control Products Act by PMRA (Canada, 2006). PMRA evaluates the toxicity of pesticides and potential exposure in order to determine whether a pesticide should be registered for a specific use. In the most recent re-evaluation by PMRA in 2008, it was determined that there were no unacceptable health risks posed to the public from products containing 2,4-D. As part of the registration process, PMRA has established maximum residue limits for 2,4-D in various foods (Health Canada, 2011). Many municipalities and provinces have imposed further restrictions or bans on the use of 2,4-D on lawns to address local concerns regarding the use of pesticides for cosmetic or aesthetic purposes.

Health Canada has set an acceptable daily intake for 2,4-D and established a Canadian drinking water quality guideline that sets out an interim maximum acceptable concentration for 2,4-D (Health Canada, 1993; Health Canada, 2007; Health Canada, 2008; WHO, 2003a).

In 1996, 2,4-D was measured in 24-hour urine samples from Ontario farmers and farm families as part of the Ontario Farm Family Health Study and the Pesticide Exposure Assessment Pilot Study. In the farmers, mean urinary concentrations were 26.6 μg/L (Arbuckle et al., 1999). Geometric mean urinary concentrations ranged from 0.7 to 9.9 μg/L in farm applicators, 0.55 to 0.66 μg/L in women, and 0.7 to 2.9 μg/L in children aged 3 to 18 years (Arbuckle et al., 2004; Arbuckle et al., 2005; Arbuckle & Ritter, 2005). Urinary levels of 2,4-D were measured in morning voids from 123 children aged 3 to 7 years in the province of Quebec in 2003. Only six samples had detectable levels, with a geometric mean and maximum of 13.9 μg/g creatinine and 40 μg/g creatinine, respectively (INSPQ, 2004).

2,4-D was measured in the urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented as both µg/L (Tables 14.3.1, 14.3.2, and 14.3.3) and µg/g creatinine (Tables 14.3.4, 14.3.5, and 14.3.6). Finding a measurable amount of 2,4-D in urine is an indicator of exposure to 2,4-D and does not necessarily mean that an adverse health effect will occur.

6 Data Tables: 14.3.1 to 14.3.6

References

Arbuckle, T.E., Cole, D.C., Ritter, L., & Ripley, B.D. (2004). Farm children's exposure to herbicides: Comparison of biomonitoring and questionnaire data. Epidemiology, 15 (2), 187-194.

Arbuckle, T.E., Cole, D.C., Ritter, L., & Ripley, B.D. (2005). Biomonitoring of herbicides in Ontario farm applicators. Scandinavian Journal of Work, Environment and Health, 31 (Supplement 1), 90-97.

Arbuckle, T.E. & Ritter, L. (2005). Phenoxyacetic acid herbicide exposure for women on Ontario farms. Journal of Toxicology and Environmental Health - Part A, 68 (15), 1359-1370.

Arbuckle, T.E., Schrader, S.M., Cole, D., Hall, J.C., Bancej, C.M., Turner, L.A., & Claman, P. (1999). 2,4-Dichlorophenoxyacetic acid residues in semen of Ontario farmers. Reproductive Toxicology, 13 (6), 421-429.

ATSDR (Agency for Toxic Substances and Disease Registry). (1999). Toxicological profile for chlorophenols. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved May 2, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=941&tid=195

Barr, D.B. & Needham, L.L. (2002). Analytical methods for biological monitoring of exposure to pesticides: A review. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 778 (1-2), 5-29.

Canada. (2006). Pest Control Products Act. SC 2002, c. 28. Retrieved May 30, 2012, from http://laws-lois.justice.gc.ca/eng/acts/P-9.01/

EPA (U.S. Environmental Protection Agency). (2005). Re-registration eligibility decision for 2,4-D. U.S. Environmental Protection Agency. Retrieved June 7, 2012, from www.epa.gov/oppsrrd1/REDs/24d_red.pdf

European Commission. (2001). Review report for the active substance 2,4-D: 7599/VI/97-final. European Commission. Retrieved June 7, 2012, from http://ec.europa.eu/food/plant/protection/evaluation/existactive/list1_2-4-d_en.pdf

Health Canada. (1993). Guidelines for Canadian drinking water quality: Guideline technical document - 2,4-dichlorophenoxyacetic acid. Minister of Health, Ottawa, ON. Retrieved June 11, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/dichlorophenoxyacetic_acid/2_4-dichlorophenoxyacetic_acid-eng.pdf

Health Canada. (2006). Lawn and turf uses of (2,4-dichlorophenoxy)acetic acid [2,4-D]: Interim measures. REV2006-11. Minister of Health, Ottawa, ON. Retrieved May 15, 2012, from www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/rev2006-11/index-eng.php

Health Canada. (2007). Re-evaluation of the agricultural, forestry, aquatic and industrial site uses of (2,4-dichlorophenoxy)acetic acid [2,4-D]. PACR2007-06. Minister of Health, Ottawa, ON.

Health Canada. (2008). Re-evaluation decision (2,4-dichlorophenoxy) acetic acid [2,4-D]. Re-evaluation document RVD2008-11. Minister of Health, Ottawa, ON. Retrieved May 15, 2012, from www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/rvd2008-11/index-eng.php

Health Canada. (2011). List of maximum residue limits regulated under the Pest Control Products Act. Minister of Health, Ottawa, ON. Retrieved May 15, 2012, from www.hc-sc.gc.ca/cps-spc/pest/part/protect-proteger/food-nourriture/mrl-lmr-eng.php

Health Canada. (2012). Public registry, pesticide product information database. Retrieved May 2, 2012, from http://pr-rp.hc-sc.gc.ca/pi-ip/index-eng.php

IARC (International Agency for Research on Cancer). (1987). IARC monographs on the evaluation of carcinogenic risks to humans - Overall evaluations of carcinogenicity: An updating of IARC monographs volumes 1 to 42. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (1999). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 71: Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. World Health Organization, Geneva.

INSPQ (Institut national de santé publique du Québec). (2004). Étude sur l'établissement de valeurs de référence d'éléments traces et de métaux dans le sang, le sérum et l'urine de la population de la grande région de Québec. INSPQ, Québec, QC. Retrieved July 11, 2011, from www.inspq.qc.ca/pdf/publications/289-ValeursReferenceMetaux.pdf

Sauerhoff, M.W., Braun, W.H., Blau, G.E., & Gehring, P.J. (1977). The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral administration to man. Toxicology, 8, 3-11.

WHO (World Health Organization). (2003a). 2,4-D in drinking-water: Background document for development of WHO guidelines for drinking-water quality. WHO, Geneva. Retrieved May 15, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/24d/en/

WHO (World Health Organization). (2003b). Chlorophenols in drinking-water: Background document for development of WHO guidelines for drinking-water quality. WHO, Geneva. Retrieved May 15, 2012, from www.who.int/water_sanitation_health/dwq/chemicals/chlorophenols/en/

14.4 Organophosphate Metabolites

Organophosphates are a group of closely related chemicals that are extensively used in Canada as pesticides in agriculture, in the home and garden, and in veterinary practice (Health Canada, 2012a; Health Canada, 2012b; Health Canada, 2012c). This class of pesticides gained popularity in use because organochlorine pesticides were banned in the 1970s. Organophosphate pesticides are less persistent in the environment and less susceptible to pest resistance than the organochlorine pesticides (Wessels et al., 2003). Eighteen organophosphate pesticides were registered for use in Canada during the Canadian Health Measures Survey (CHMS) sampling period (2009-2011) and are listed below in Table 14.4.1 (Health Canada, 2012a).

Organophosphate pesticides have been linked to naturally occurring compounds produced by algae and bacteria; however, their presence in the environment is almost exclusively due to their human use as pesticides (Neumann & Peter, 1987). Despite their rapid degradation in the environment, small amounts can be detected in food and drinking water (Hao et al., 2010; Health Canada, 2003; Health Canada, 2004).

Major uses of organophosphates include as an insecticide on food and feed crops, livestock, and ornamental plants; for insect control in food storage areas, greenhouses, forestry structures, and seed treatment; for control of pet parasites; and for mosquito control (Health Canada, 2012a; Health Canada, 2012b). Although the majority of organophosphates are used as insecticides, bensulide is used as a selective herbicide for the control of weeds in turf and cucumbers (Health Canada, 2012b). In addition to the pesticide uses, dichlorvos and trichlorfon have veterinary drug uses for the control of parasites in livestock (Health Canada, 2012c).

The primary route of exposure for the general public is through ingestion of food previously treated with organophosphate pesticides and drinking water contaminated with agricultural runoff (ATSDR, 1997a; ATSDR, 1997b; ATSDR, 2003). Other routes of exposure include dermal contact and inhalation during the use of products containing organophosphates or during activity in areas previously treated with organophosphates.

After entry into the body, organophosphate pesticides are rapidly metabolized and excreted in urine (Barr & Needham, 2002). Hydrolysis of the parent compound yields various dialkyl phosphate metabolites. Each metabolite is associated with several organophosphate pesticides, and many organophosphates can form more than one of these metabolites (Table 14.4.1). These metabolites also occur in the environment following degradation of the parent compound. Dialkyl phosphate metabolites are not considered toxic, but are considered to be biomarkers of exposure to the parent pesticides and their metabolites in the environment (CDC, 2005; EPA, 1999). In addition to the dialkyl phosphate metabolites, organophosphate parent compounds and other breakdown products can be measured in blood and urine; detection generally reflects exposures over the previous few days (CDC, 2005; EPA, 1999). Some organophosphate pesticides, namely acephate and methamidophos, do not breakdown into dialkyl phosphate metabolites (Barr & Needham, 2002; Wessels et al., 2003).

The following table outlines the dialkyl phosphate metabolites that were measured in urine collected from CHMS participants, and their corresponding organophosphate pesticide parent compounds. There are six dialkyl phosphate metabolites: dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP).

Table 14.4.1 Dialkyl phosphate metabolites measured in the Canadian Health Measures Survey cycle 2 and their parent organophosphate pesticides registered for use in Canada during the cycle 2 sampling period (2009-2011)
Organophosphate pesticide Dialkyl phosphate metabolite (CASRN)
DMP
(813-79-5)
DMTP
1112-38-5)
DMDTP
(765-80-9)
DEP
(598-02-7)
DETP
(2465-65-8)
DEDTP
(298-06-6)
(Bravo et al., 2004; CDC, 2005; Wessels et al., 2003)
Acephate - - - - - -
Azinphos-methyl Yes Yes Yes - - -
Bensulide - - - - - -
Chlorpyrifos - - - Yes Yes -
Coumaphos - - - Yes Yes -
Diazinon - - - Yes Yes -
Dichlorvos Yes - - - - -
Dimethoate Yes Yes Yes - - -
Malathion Yes Yes Yes - - -
Methamidophos - - - - - -
Naled Yes - - - - -
Phorate - - - Yes Yes Yes
Phosalone - - - Yes Yes Yes
Phosmet Yes Yes Yes - - -
Propetemphos - - - - - -
Terbufos - - - Yes Yes Yes
Tetrachlorvinphos Yes - - - - -
Trichlorfon Yes - - - - -

Organophosphates are cholinesterase-inhibiting pesticides that act on the nervous system of insects and mammals by interrupting the transmission of nerve impulses (EPA, 1999). The result is an over-stimulation in the nervous system. Symptoms of acute over-exposure may include headache, dizziness, fatigue, irritation of the eyes or nose, nausea, vomiting, salivation, sweating, and changes in heart rate. Very high exposures can have effects such as paralysis, seizures, loss of consciousness, or even death (ATSDR, 1997a; ATSDR, 1997b; ATSDR, 2003; EPA, 1999). However, typical exposure through the ingestion of organophosphate pesticides in food is generally low. Nevertheless, there is potential for toxic effects resulting from chronic low-dose exposure (Ray & Richards, 2001). Prenatal exposure to organophosphates has been associated with shortened gestation, reduced birth weight, and impaired neurodevelopment in young children (Eskenazi et al., 2007; Bouchard et al., 2011; Rauch et al., 2012). Four of the 18 organophosphate pesticides registered for use in Canada (Table 14.4.1) have been classified by the International Agency for Research on Cancer. Malathion, tetrachlorvinphos, and trichlorfon are not classifiable as to their carcinogenicity to humans (Group 3), whereas dichlorvos is classified as possibly carcinogenic to humans (Group 2B) (IARC, 1987; IARC, 1991).

The sale and use of organophosphate pesticides is regulated in Canada by the Pest Management Regulatory Agency (PMRA) under the Pest Control Products Act (Canada, 2006). PMRA evaluates the toxicity of pesticides and potential exposure in order to determine whether a pesticide should be registered for a specific use. In 1999, PMRA commenced a re-evaluation of the 27 organophosphate pesticides that were registered for use at that time in Canada (Health Canada, 1999). As a result of this review, nine of the pesticides were subsequently discontinued, and certain other pesticides, such as azinphos-methyl, have been restricted to specific uses, with a plan to phase them out when alternatives can be found (Health Canada, 2007). However, the remaining organophosphate pesticides were determined not to pose unacceptable risks to human health or the environment, based on their registered uses. As part of the registration process, PMRA establishes maximum residue limits of pesticides in food, including registered organophosphate pesticides (Health Canada, 2011).

Health Canada has established Canadian drinking water quality guidelines that set out the maximum acceptable concentrations of azinphos-methyl, chlorpyrifos, diazinon, dimethoate, malathion, phorate, and terbufos (Health Canada, 1989a; Health Canada, 1989b; Health Canada, 1989c; Health Canada, 1989d; Health Canada, 1990; Health Canada, 1991; Health Canada, 1995). Several organophosphate pesticides have also been analyzed as part of Health Canada's Total Diet Study surveys (Health Canada, 2009). These surveys provide estimate levels of chemicals that Canadians in different age-sex groups are exposed to through the food supply.

The six dialkyl phosphate metabolites were measured in morning urine voids from 89 children aged 3 to 7 years in a biomonitoring study in the province of Quebec in 2003. The geometric mean and 95th percentile concentrations were 20 µg/g creatinine and 97 µg/g creatinine, respectively, for DMP; 18.8 µg/g creatinine and 210.9 µg/g creatinine, respectively, for DMTP; 2.8 µg/g creatinine and 45.9 µg/g creatinine, respectively, for DMDTP; 4.8 µg/g creatinine and 29 µg/g creatinine, respectively, for DEP; 0.7 µg/g creatinine and 8 µg/g creatinine, respectively, for DETP; and 0.4 µg/g creatinine and 0.4 µg/g creatinine, respectively, for DEDTP (Valcke et al., 2006).

The six dialkyl phosphate metabolites (Table 14.4.1) were measured in the urine of all CHMS participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented as both µg/L and µg/g creatinine (Tables 14.4.1.1 to 14.4.6.6). Finding a measurable amount of organophosphate pesticide metabolites in urine is an indicator of exposure to organophosphate pesticides and/or their metabolites and does not necessarily mean that an adverse health effect will occur.

14.4.1 Dimethylphosphate (DMP)

6 Data Tables: 14.4.1.1 to 14.4.1.6

14.4.2 Dimethylthiophosphate (DMTP)

6 Data Tables: 14.4.2.1 to 14.4.2.6

14.4.3 Dimethyldithiophosphate (DMDTP)

6 Data Tables: 14.4.3.1 to 14.4.3.6

14.4.4 Diethylphosphate (DEP)

6 Data Tables: 14.4.4.1 to 14.4.4.6

14.4.5 Diethylthiophosphate (DETP)

6 Data Tables: 14.4.5.1 to 14.4.5.6

14.4.6 Diethyldithiophosphate (DEDTP)

6 Data Tables: 14.4.6.1 to 14.4.6.6

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1997a). Toxicological profile for chlorpyrifos. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 23, 2012, from www.atsdr.cdc.gov/toxprofiles/tp84.pdf

ATSDR (Agency for Toxic Substances and Disease Registry). (1997b). Toxicological profile for dichlorvos. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 23, 2012, from www.atsdr.cdc.gov/toxprofiles/tp88.pdf

ATSDR (Agency for Toxic Substances and Disease Registry). (2003). Toxicological profile for malathion. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved April 23, 2012, from www.atsdr.cdc.gov/toxprofiles/tp88.pdf

Barr, D. & Needham, L. (2002). Analytical methods for biological monitoring of exposure to pesticides: a review. Journal of Chromatography B, 778, 5-29.

Bouchard, M.F., Chevrier, J., Harley, K.G., Kogut, K., Vedar, M., Calderon, N., Trujillo, C., Johnson, C., Bradman, A., Barr, D.B., & Eskenazi, B. (2011). Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environmental Health Perspectives, 119 (8), 1189-1195.

Bravo, R., Caltabioano, L., Weerasketera, G., Whitehead, R., Fernandez, C., Needham, L., Braman, A., & Barr, D. (2004). Measurement of dialkyl phosphate metabolites of organophosphorus pesticides in human urine using lypophilization with gas chromatography-tandem mass spectrometry and isotope dilution quantification. Journal of Exposure Analysis and Environmental Epidemiology, 14, 249-259.

Canada. (2006). Pest Control Products Act. SC 2002, c. 28. Retrieved May 30, 2012, from http://laws-lois.justice.gc.ca/eng/acts/P-9.01/

CDC (Centers for Disease Control and Prevention). (2005). Third national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA.

EPA (U.S. Environmental Protection Agency). (1999). Organophosphate insecticides. Recognition and management of pesticide poisonings, 5th edition. U.S. Environmental Protection Agency, Washington, DC.

Eskenazi, B., Marks, A., Bradman, A., Harley, K., Barr, D., Johnson, C., Morga, N., & Jewell, N. (2007). Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environmental Health Perspectives, 115 (5), 792-798.

Hao, C., Nguyen, B., Zhao, X., Chen, E., & Yang, P. (2010). Determination of residual carbamate, organophosphate, and phenyl urea pesticides in drinking and surface water by high-performance liquid chromatography/tandem mass spectrometry. Journal of AOAC International, 93 (2), 400-410.

Health Canada. (1989a). Guidelines for Canadian drinking water quality: Guideline technical document - Azinphos-methyl. Ministry of Health, Ottawa, ON. Retrieved June 7, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/azinphos/azinphos-eng.pdf

Health Canada. (1989b). Guidelines for Canadian drinking water quality: Guideline technical document - Chlorpyrifos. Ministry of Health, Ottawa, ON. Retrieved June 7, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/chlorpyrifos/chlorpyrifos-eng.pdf

Health Canada. (1989c). Guidelines for Canadian drinking water quality: Guideline technical document - Diazinon. Ministry of Health, Ottawa, ON. Retrieved June 7, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/diazinon/diazinon-eng.pdf

Health Canada. (1989d). Guidelines for Canadian drinking water quality: Guideline technical document - Malathion. Ministry of Health, Ottawa, ON. Retrieved June 7, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/malathion/malathion-eng.pdf

Health Canada. (1990). Guidelines for Canadian drinking water quality: Guideline technical document - Phorate. Ministry of Health, Ottawa, ON. Retrieved June 7, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/phorate/phorate-eng.pdf

Health Canada. (1991). Guidelines for Canadian drinking water quality: Guideline technical document - Dimethoate. Ministry of Health, Ottawa, ON. Retrieved June 7, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/dimethoate/dimethoate-eng.pdf

Health Canada. (1995). Guidelines for Canadian drinking water quality: Guideline technical document - Terbufos. Ministry of Health, Ottawa, ON. Retrieved June 7, 2012, from www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/water-eau/terbufos/terbufos-eng.pdf

Health Canada. (1999). Re-evaluation of organophosphate pesticides. Minister of Health, Ottawa, ON. Retrieved April 20, 2012, from www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/rev99-01/index-eng.php

Health Canada. (2003). Concentrations (ppb) of pesticide residues in foods from Total Diet Study in Vancouver, 1995. Minister of Health, Ottawa, ON. Retrieved May 28, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/concentration/pesticide_conc_vancouver1995-eng.php

Health Canada. (2004). Concentrations (ppb) of pesticide residues in foods from Total Diet Study in Ottawa, 1995. Minister of Health, Ottawa, ON. Retrieved May 28, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/concentration/pesticide_conc_ottawa1995-eng.php

Health Canada. (2007). Update on re-evaluation of azinphos-methyl. Minister of Health, Ottawa, ON. Retrieved April 20, 2012, from www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/rev2007-08/index-eng.php

Health Canada. (2009). Canadian Total Diet Study. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/surveill/total-diet/index-eng.php

Health Canada. (2011). List of maximum residue limits regulated under the Pest Control Products Act. Retrieved April 20, 2012, from www.hc-sc.gc.ca/cps-spc/alt_formats/pdf/pest/part/protect-proteger/food-nourriture/mrl-lmr-eng.pdf

Health Canada. (2012a). Pesticide label search database. Retrieved April 20, 2012, from www.pr-rp.hc-sc.gc.ca/ls-re/index-eng.php

Health Canada. (2012b). Pesticide product information database. Retrieved April 20, 2012, from www.pr-rp.hc-sc.gc.ca/pi-ip/index-eng.php

Health Canada. (2012c). Drug product database online query. Retrieved April 20, 2012, from www.webprod3.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp

IARC (International Agency for Research on Cancer). (1987). IARC monographs on the evaluation of carcinogenic risks to jumans - Volume 30: Miscellaneous pesticides. World Health Organization, Geneva.

IARC (International Agency for Research on Cancer). (1991). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 53: Occupational exposures in insecticide application, and some pesticides. World Health Organization, Geneva.

Neumann, R. & Peter, H.H. (1987). Insecticidal organophosphates: nature made them first. Cellular and Molecular Life Sciences, 43 (11-12), 1235-1237.

Rauch, S.A., Braun, J.M., Barr, D.B., Calafat, A.M., Khoury, J., Montesano, M.A., Yolton, K., & Lanphear, B.P. (2012). Associations of prenatal exposure to organophosphate pesticide metabolites with gestational age and birthweight. Environmental Health Perspectives, 120 (7), 1055-1060.

Ray, D. & Richards, P. (2001). The potential for toxic effects of chronic, low-dose exposure to organophosphates. Toxicology Letters, 120, 343-351.

Valcke, M., Samuel, O., Bouchard, M., Dumas, P., Belleville, D., & Tremblay, C. (2006). Biological monitoring of exposure to organophosphate pesticides in children living in peri-urban areas of the province of Québec, Canada. International Archives of Occupational and Environmental Health, 79, 568-577.

Wessels, D., Barr, D., & Mendola, P. (2003). Use of biomarkers to indicate exposure to children to organophosphate pesticides: Implication for a longitudinal study of children's environmental health. Environmental Health Perspectives, 111 (16), 1939-1946.

14.5 Pyrethroid Metabolites

Pyrethrins are naturally occurring compounds found in certain chrysanthemum flowers (ATSDR, 2003). They have been used for their insecticidal properties since the early 1800s in Asia to control ticks and various insects, such as fleas and mosquitoes (ATSDR, 2003). Pyrethroids are synthetic versions of pyrethrins that have been structurally altered to improve their efficacy as pesticides by increasing their stability in the environment and their toxicity (ATSDR, 2003; EPA, 2012). Many commercial pyrethroid pesticides currently are registered for use in Canada, as listed in Table 14.5.1 (Health Canada, 2012a).

Pyrethroids enter the environment primarily because of their use as pesticides; however, they break down rapidly and, as a result, only trace amounts of the chemicals are typically found in air, water, soil, and food (ATSDR, 2003). Pyrethroids degrade to carboxylic and phenoxybenzoic metabolites in the environment, and these metabolites have been measured in dust collected from homes and daycare centres (Starr et al., 2008). Pyrethroids bind strongly to soil particles, thus they usually do not leach into the groundwater, but rather remain in the soil (ATSDR, 2003).

Pyrethroid pesticides are used in Canada for insect control on agricultural crops and on turf; in orchards, nurseries, and greenhouses; as a general indoor and outdoor residential insecticide for controlling crawling and flying insect pests; for controlling adult mosquitoes around buildings; in cattle ear tags; for controlling mites in bee colonies; and for flea and tick control on pets (Health Canada, 2004; Health Canada, 2012a). In malaria-endemic zones, pyrethroids are used to impregnate mosquito nets and clothing for the prevention of malaria (Health Canada, 2004). The use of pyrethrins and pyrethroids has increased during the past decade with the declining use of organophosphate pesticides that are more acutely toxic to birds and mammals than the pyrethroids (EPA, 2012).

Permethrin is the most widely used pyrethroid pesticide in Canada and is found in over 250 registered pesticide products (CCME, 2006; Health Canada, 2012a). It is used for a variety of agricultural, livestock, forestry, and residential insect control applications. In addition to the pesticide uses, permethrin is used in medications for the treatment of scabies (Health Canada, 2012b). Cyfluthrin is used as an agricultural and indoor surface insecticide for the control of crawling and flying insect pests (Health Canada, 2012a). Cypermethrin and lambda-cyhalothrin have agricultural and livestock uses. Deltamethrin is used in several agricultural applications, on turf, and in greenhouses; it is also used to treat sleeping areas and clothing in malaria-affected countries (Health Canada, 2004; Health Canada, 2009). D-phenothrin is used primarily in residential settings, whereas fluvalinate-tau is used to control mites in bee colonies (Health Canada, 2009).

The primary routes of exposure for the general population are through the use of products that contain pyrethroids, such as household insecticides and pet sprays, and through the ingestion of pyrethroid residues in food (EPA, 2009a).

Pyrethroid pesticides are rapidly metabolized and eliminated from the body through hydrolysis, oxidation, and conjugation. Following oral ingestion, inhalation, or dermal exposure, pyrethroids are metabolized into carboxylic and phenoxybenzoic acids and excreted with urine. Pyrethroids and metabolites can be measured in blood and urine, and are reflective of recent exposure to the parent compound or the metabolite in the environment (ATSDR, 2003; CDC, 2009; Kuhn et al., 1999; Starr et al., 2008). Urinary metabolites of pyrethroids can be specific to one pyrethroid or common to several pyrethroids. Table 14.5.1 outlines the pyrethroid metabolites measured as part of this survey and their corresponding parent compounds.

Table 14.5.1 Pyrethroid pesticide metabolites measured in the Canadian Health Measures Survey cycle 2 (2009-2011) and their parent pesticide compounds
Pyrethroid pesticide (CASRN) Metabolite (CASRN)
(Barr & Needham, 2002; CDC, 2009; Fortin et al., 2008; Starr et al., 2008)
Cyfluthrin (68359-37-5) 4-F-3-PBA: 4-fluoro-3-phenoxybenzoic acid (77279-89-1)
Deltamethrin (52918-63-5) cis-DBCA: cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (63597-73-9)
Cyfluthrin (68359-37-5)
Permethrin (52645-53-1)
Cypermethrin (52315-07-8)
cis-DCCA: cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (55701-05-8)
Cyfluthrin (68359-37-5)
Permethrin (52645-53-1)
Cypermethrin (52315-07-8)
trans-DCCA: trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (55701-03-6)
Cypermethrin (52315-07-8)
Deltamethrin (52918-63-5)
Permethrin (52645-53-1)
lambda-Cyhalothrin (91465-08-6)
D-Phenothrin (26046-85-5)
Fluvalinate-tau (102851-06-9)
3-PBA: 3-phenoxybenzoic acid (3739-38-6)

Pyrethroids, much like the naturally occurring pyrethrins, primarily affect the nervous system of insects and mammals (Davies et al., 2007). They act on the axons in the peripheral and central nervous systems by prolonging the opening time of small conductance sodium channels, leading to membrane depolarizations and excess excitability. This action causes paralysis in target insect pests, eventually resulting in death. Pyrethroids are over 2,000 times more toxic to insects than mammals because insects have an increased sodium channel sensitivity, a smaller body size, and a lower body temperature (Bradberry et al., 2005). Mammals are also able to quickly metabolize pyrethroids into their inactive forms and eliminate them from the body (Health Canada, 2009).

Adverse effects can include dizziness, nausea, headaches, tremor, salivation, involuntary movements, and seizures; very high exposures may result in unconsciousness (ATSDR, 2003; CDC, 2005). Studies indicate that long-term exposures to low levels of pyrethroids do not cause neurological effects in mammals, primarily because of the rapid metabolism and elimination of these compounds from the body (ATSDR, 2003). Allergic reactions in humans have been reported following exposure to pyrethroids; however, the United States Environmental Protection Agency (EPA) found no clear and consistent pattern of effects reported to indicate conclusively whether there is an association between pyrethroid exposure and asthma and allergies (EPA, 2009b; Moretto, 1991; Salome et al., 2000; Vanden Driessche et al., 2010). The International Agency for Research on Cancer has classified permethrin as Group 3, not classifiable as to its carcinogenicity to humans because of a lack of evidence (IARC, 1991). The EPA has classified permethrin as likely to be carcinogenic in humans by the oral route of exposure (EPA, 2009a).

The sale and use of pyrethroid pesticides is regulated in Canada by the Pest Management Regulatory Agency (PMRA) under the Pest Control Products Act (Canada, 2006). PMRA evaluates the toxicity and potential exposure in order to determine whether a pesticide should be registered for a specific use. As part of this registration process, PMRA specifies maximum residue limits of pesticides in food. Maximum residue limits exist for several pyrethroid pesticides in food including cyfluthrin, cypermethrin, and permethrin (Health Canada, 2011a). Many of the pyrethroids currently registered for use in Canada are under re-evaluation by PMRA (Health Canada, 2011b).

Pyrethroid metabolites were measured in 89 children (6 to 12 years) and 81 adults (18 to 64 years) in the province of Quebec in 2005 (Fortin et al., 2008). Metabolites were identified in urine collected for 12 hours from children and in urine collected for two consecutive 12-hour periods in adults. In children, the median and 95th percentile concentrations were <0.005 µg/L and 0.02 µg/L, respectively, for 4-F-3-PBA; <0.006 µg/L and 0.09 µg/L, respectively, for cis-DBCA; 0.10 µg/L and 0.76 µg/L, respectively, for cis-DCCA; 0.24 µg/L and 4.10 µg/L, respectively, for trans-DCCA; and 0.20 µg/L and 1.54 µg/L, respectively, for 3-PBA. In adults, the median and 95th percentile concentrations were <0.005 µg/L and 0.03 µg/L, respectively, for 4-F-3-PBA; <0.006 µg/L and 0.14 µg/L, respectively, for cis-DBCA; 0.10 µg/L and 1.15 µg/L, respectively, for cis-DCCA; 0.25 µg/L and 3.48 µg/L, respectively, for trans-DCCA; and 0.17 µg/L and 4.23 µg/L, respectively, for 3-PBA (Fortin et al., 2008).

Five pyrethroid metabolites (see Table 14.5.1) were measured in the urine of all Canadian Health Measures Survey participants aged 6 to 79 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). Data from these cycles are presented as both µg/L and µg/g creatinine (Tables 14.5.1.1 to 14.5.5.6). Finding a measurable amount of pyrethroid metabolites in urine is an indicator of exposure to pyrethroid pesticides and does not necessarily mean that an adverse health effect will occur.

14.5.1 4-Fluoro-3-Phenoxybenzoic Acid (4-F-3-PBA)

6 Data Tables: 14.5.1.1 to 14.5.1.6

14.5.2 cis-3-(2,2-Dibromovinyl)-2,2-Dimethylcyclopropane Carboxylic Acid (cis-DBCA)

6 Data Tables: 14.5.2.1 to 14.5.2.6

14.5.3 cis-3-(2,2-Dichlorovinyl)-2,2-Dimethylcyclopropane Carboxylic Acid (cis-DCCA)

6 Data Tables: 14.5.3.1 to 14.5.3.6

14.5.4 trans-3-(2,2-Dichlorovinyl)-2,2-Dimethylcyclopropane Carboxylic Acid (trans-DCCA)

6 Data Tables: 14.5.4.1 to 14.5.4.6

14.5.5 3-Phenoxybenzoic Acid (3-PBA)

6 Data Tables: 14.5.5.1 to 14.5.5.6

References

ATSDR (Agency for Toxic Substances and Disease Registry). (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved May 8, 2012, from www.atsdr.cdc.gov/toxprofiles/tp155.pdf

Barr, D. & Needham, L. (2002). Analytical methods for biological monitoring of exposure to pesticides: A review. Journal of Chromatography B, 778, 5-29.

Bradberry, S.M., Cage, S.A., Proudfoot, A.T., & Vale, J.A. (2005). Poisoning due to pyrethroids. Toxicological Reviews, 24 (2), 93-106.

Canada. (2006). Pest Control Products Act. SC 2002, c. 28. Retrieved May 30, 2012, from http://laws-lois.justice.gc.ca/eng/acts/P-9.01/

CCME (Canadian Council of Ministers of the Environment). (2006). Canadian water quality guidelines for the protection of aquatic life - Permethrin. Retrieved May 8, 2012, from www.ccme.ca/assets/pdf/permethrin_ssd_1.0_e.pdf

CDC (Centers for Disease Control and Prevention). (2005). Third national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA.

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Davies, T.G.E., Field, L.M., Usherwood, P.N.R., & Williamson. M.S. (2007). DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life, 59 (3), 151-162.

EPA (U.S. Environmental Protection Agency). (2009a). Reregistration eligibility decision (RED) for permethrin: Case no. 2510. Office of Pesticide Programs, EPA, Washington, DC. Retrieved May 8, 2012, from www.epa.gov/oppsrrd1/REDs/permethrin-red-revised-may2009.pdf

EPA (U.S. Environmental Protection Agency). (2009b). A review of the relationship between pyrethrins, pyrethroid exposure and asthma and allergies. U.S. Environmental Protection Agency. Retrieved August 22, 2012, from www.epa.gov/oppsrrd1/reevaluation/pyrethrins-pyrethroids-asthma-allergy-9-18-09.pdf

EPA (U.S. Environmental Protection Agency). (2012). Pyrethroids and pyrethrins. U.S. Environmental Protection Agency. Retrieved May 8, 2012, from www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html#epa

Fortin, M., Bouchard, M., Carrier, G., & Dumas, P. (2008). Biological monitoring of exposure to pyrethrins and pyrethroids in a metropolitan population of the province of Québec, Canada. Environmental Research, 107, 343-350.

Health Canada. (2004). Canadian recommendations for the prevention and treatment of malaria among international travellers. Canadian Communicable Disease Report, 30 (S1), 1-62.

Health Canada. (2009). Evaluation of pesticide incident report 2008-5998. Minister of Health, Ottawa, ON. Retrieved May 21, 2012, from www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/epir-edirp2008-5998/index-eng.php

Health Canada. (2011a). List of maximum residue limits regulated under the Pest Control Products Act. Minister of Health, Ottawa, ON. Retrieved April 20, 2012, from www.hc-sc.gc.ca/cps-spc/alt_formats/pdf/pest/part/protect-proteger/food-nourriture/mrl-lmr-eng.pdf

Health Canada. (2011b). Re-evaluation note REV2011-05: Re-evaluation of pyrethroids, pyrethrins and related active ingredients. Minister of Health, Ottawa, ON. Retrieved May 8, 2012, from www.hc-sc.gc.ca/cps-spc/alt_formats/pdf/pubs/pest/decisions/rev2011-05/rev2011-05-eng.pdf

Health Canada. (2012a). Pesticide label search database. Minister of Health, Ottawa, ON. Retrieved April 20, 2012, from www.pr-rp.hc-sc.gc.ca/ls-re/index-eng.php

Health Canada. (2012b). Pesticide product information database. Minister of Health, Ottawa, ON. Retrieved April 20, 2012, from www.pr-rp.hc-sc.gc.ca/pi-ip/index-eng.php

IARC (International Agency for Research on Cancer). (1991). Monographs on the evaluation of carcinogenic risks to humans: Occupational exposures in insecticide application, and some pesticides, vol. 53. World Health Organization, Geneva.

Kuhn, K., Wieseler, B., Leng, G., & Idel, H. (1999). Toxicokinetics of pyrethroids in humans: Consequences for biological monitoring. Bulletin of Environmental Contamination and Toxicology, 62, 101-108.

Moretto, A. (1991). Indoor spraying with the pyrethroid insecticide lambda-cyhalothrin: Effects on spraymen and inhabitants of sprayed houses. Bulletin of the World Health Organization, 69 (5), 591-594.

Salome, C.M., Marks, G.B., Savides, P., Xuan, W., & Woolcock, A.J. (2000). The effect of insecticide aerosols on lung function, airway responsiveness and symptoms in asthmatic subjects. European Respiratory Journal, 16, 38-43.

Starr, J., Graham, S., Stout, D., Andrews, K., & Nishioka, M. (2008). Pyrethroid pesticides and their metabolites in vacuum cleaner dust collected from homes and day-care centers. Environmental Research, 108 (3), 271-279.

Vanden Driessche, K.S.J., Sow, A., Van Gompel, A., & Vandeurzen, K. (2010). Anaphylaxis in an airplane after insecticide spraying. Journal of Travel Medicine, 17 (6), 427-429.

15 Phthalate Metabolites Summary and Results

Diesters of phthalic acid, also called phthalates, are a class of high-production volume industrial chemicals that are used in the manufacture of a variety of consumer products. Table 15.1 lists phthalates commonly found in commerce and their major metabolites measured in cycle 2 of the Canadian Health Measures Survey (CHMS).

Table 15.1 Phthalate metabolites measured in the Canadian Health Measures Survey cycle 2 (2009-2011) and their parent phthalate compounds
Phthalate CASRN Metabolite CASRN
Benzyl butyl phthalate, BBP 85-68-7 Mono-benzyl phthalate, MBzP (some MnBP) 2528-16-7
Di-n-butyl phthalate, DnBP 84-74-2 Mono-n-Butyl phthalate, MnBP 131-70-4
Dicyclohexyl phthalate, DCHP 84-61-7 Mono-cyclohexyl phthalate, MCHP 7517-36-4
Diethyl phthalate, DEP 84-66-2 Mono-ethyl phthalate, MEP 2306-33-4
Di-isobutyl phthalate, DiBP 84-69-5 Mono-isobutyl phthalate, MiBP 30833-53-5
Di-isononyl phthalate, DiNP 28553-12-0,
68515-48-0
Mono-isononyl phthalate, MiNP 519056-28-1
Dimethyl phthalate, DMP 131-11-3 Mono-methyl phthalate, MMP 4376-18-5
Di-n-octyl phthalate, DOP 117-84-0 Mono-n-octyl phthalate, MOP 5393-19-1
Mono-3-carboxypropyl phthalate, MCPP 66851-46-5
Di-2-ethylhexyl phthalate, DEHP 117-81-7 Mono-2-ethylhexyl phthalate, MEHP 4376-20-9
Mono-(2-ethyl-5-oxohexyl) phthalate, MEOHP 40321-98-0
Mono-(2-ethyl-5-hydroxyhexyl) phthalate, MEHHP 40321-99-1

Although some phthalates occur naturally in crude oil and coal, the vast majority are anthropogenic. Phthalates are primarily used as plasticizers to impart flexibility and resilience to plastics (Frederiksen et al., 2007; Graham, 1973). BBP is used in Canada in polyvinyl chloride (PVC) flooring and other materials, in paints and coatings, in adhesive formulations, and in printing inks (Environment Canada & Health Canada, 2000). DEP is the predominant phthalate used in fragrances, cosmetics, and personal-care products (Cosmetic Ingredient Review Expert Panel, 2005; Koniecki et al., 2011). DEHP is added to PVC for use in medical equipment including intravenous bags, blood bags, and various types of tubing (NTP-CERHR, 2006). DMP is used in plastics and consumer products such as insect repellents (Chen et al., 2011). DnBP is used mainly in polyvinyl emulsions, adhesives, and coatings (Environment Canada & Health Canada, 1994a). DCHP is used to stabilize rubbers, resins, and polymers, including nitrocellulose, polyvinyl acetate, and PVC (CDC, 2009). DiNP is used in PVC-based consumer products, inks, paints, and sealants (CDC, 2009). DOP is used in polymer manufacturing, particularly PVC, to make products such as gloves, flooring, and flexible sheets (Environment Canada & Health Canada, 1993). Phthalates, namely BBP, DnBP, DiNP, and DEHP, were also previously used in Canada as plasticizers in the soft vinyl of children's toys and child-care articles.

Phthalates can be released to the environment through air emissions during their manufacture and use, via waste waters from various industries, in municipal sewage, from the incomplete combustion of plastics, and from the use and disposal of consumer products (Environment Canada & Health Canada, 1993; Environment Canada & Health Canada, 1994a; Environment Canada & Health Canada, 1994b; Environment Canada & Health Canada, 2000). Phthalates have been detected in food, water, air, and dust (Clark, 2003).

For the general public, food and the use of consumer products made out of PVC plastics are the primary sources of exposure to phthalates (Fromme et al., 2007; Petersen & Breindahl, 2000; Tsumura et al., 2001; Wormuth et al., 2006). Because phthalates are not chemically bound to plastics used in consumer products, leaching could occur during use of the products.

In laboratory animals, phthalates have been observed to undergo rapid absorption following oral exposure and generally slow absorption following dermal exposure (ATSDR, 1995; ATSDR, 1997; ATSDR, 2001; ATSDR, 2002). In humans, phthalates are rapidly metabolized and do not bioaccumulate (CDC, 2009). Phthalate diesters are converted to their corresponding monoesters in the gastrointestinal tract or saliva prior to absorption (ATSDR, 1995; ATSDR, 1997; ATSDR, 2001; ATSDR, 2002; NRC, 2008). Primary metabolites may undergo further oxidative reactions in the liver to form secondary metabolites (Samandar et al., 2009). Phthalate metabolites can be excreted in urine unchanged or as glucuronic acid conjugates (Samandar et al., 2009). Although the metabolism and excretion of monoester phthalates varies based on a number of factors, they are generally characterized by rapid metabolism and short biological half-lives (ATSDR, 1995; ATSDR, 1997; ATSDR, 2001; ATSDR, 2002; Hauser & Calafat, 2005). Measurement of phthalate metabolites in urine has become the most common approach to assess phthalate exposure in humans and reflects relatively recent exposure (Blount et al., 2000; Calafat & McKee, 2006).

In laboratory animals, exposure to some phthalates adversely affects the male reproductive system. In particular, prenatal exposure to phthalates, such as DnBP, BBP and DEHP, has been shown to disrupt the androgen-mediated development of the male reproductive tract (David, 2006; Foster, 2005; Gray et al., 2000; Howdeshell et al., 2007; Main et al., 2006; Wine et al., 1997). Adverse effects on the testes have also been observed in mature laboratory animals, although these effects occurred at higher doses (David, 2006; Foster, 2005). Other target organs identified in animal studies include the liver and kidneys (David & Gans, 2003; Howdeshell et al., 2007; Main et al., 2006; Wine et al., 1997).

Human data on health effects are still very limited; however, there are multiple studies demonstrating human exposure to phthalates in the human population, including prenatal exposure (Becker et al., 2009; Blount et al., 2000; Marsee et al., 2006; NTP-CERHR, 2003a; NTP-CERHR, 2003b; NTP-CERHR, 2003c; NTP-CERHR, 2003d; NTP-CERHR, 2003e; NTP-CERHR, 2003f; NTP-CERHR, 2006; Silva et al., 2003). Although no causal relationship has been established, several studies suggest an association between urinary phthalate metabolite concentrations and adverse effects on development and reproduction, particularly the male reproductive system (Duty et al., 2005; Jensen et al., 2012; Jurewicz & Hanke, 2011; Liu et al., 2012; Main et al., 2006; Marsee et al., 2006; Philippat et al., 2011; Snijder et al., 2012; Swan et al., 2005). The International Agency for Research on Cancer has classified DEHP as Group 3, not classifiable as to its carcinogenicity to humans (IARC, 2000).

Several phthalates, including DEHP, have been assessed as priority substances by Environment Canada and Health Canada (Environment Canada & Health Canada, 1994b), DnBP (Environment Canada & Health Canada, 1994a), DOP (Environment Canada & Health Canada, 1993; Environment Canada & Health Canada, 2003), and BBP (Environment Canada & Health Canada, 2000). Based on assessments of available data, DnBP and BBP were not considered to be toxic as defined by the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Environment Canada & Health Canada, 1994a; Environment Canada & Health Canada, 2000). Similarly, it was concluded that DOP does not pose an ecological concern, but available data were insufficient to conclude on human health (Environment Canada & Health Canada, 1993). DEHP was declared toxic under CEPA 1999 because it was considered to be a potential danger to human health based on available data (Environment Canada & Health Canada, 1994b). DCHP, DiNP, DiBP, and DMP have been identified as high-priority substances in Canada and will be assessed jointly by Health Canada and Environment Canada as part of the grouping initiative of the Chemicals Management Plan under the CEPA 1999 (Canada, 2011).

DEHP has recently been included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011). Recently, Health Canada has developed and implemented the Phthalates Regulations, on the use of six phthalates (DEHP, DnBP, BBP, DiNP, di-isodecyl phthalate, and DOP) in soft vinyl children's toys and child-care articles (Canada, 2010). This regulation restricts the same six phthalates as regulations in the United States and the European Union.

Eleven monoester phthalate metabolites (MnBP, MEP, MBzP, MCHP, MEHP, MOP, MiNP, MMP, MCPP, MEHHP, and MEOHP) were measured in the urine of all CHMS participants aged 6 to 49 years in cycle 1 (2007-2009) and 3 to 79 years in cycle 2 (2009-2011). MiBP was measured in the urine of all CHMS cycle 2 (2009-2011) participants aged 3 to 79 years. Data from these monoester phthalate metabolites are presented as both µg/L and µg/g creatinine (Tables 15.1.1 to 15.12.6). Finding a measurable amount of monoester phthalate metabolites in urine is an indicator of exposure to diester phthalates and does not necessarily mean that an adverse health effect will occur.

15.1 Mono-Benzyl Phthalate (MBzP)

6 Data Tables: 15.1.1 to 15.1.6

15.2 Mono-n-Butyl Phthalate (MnBP)

6 Data Tables: 15.2.1 to 15.2.6

15.3 Mono-Cyclohexyl Phthalate (MCHP)

6 Data Tables: 15.3.1 to 15.3.6

15.4 Mono-Ethyl Phthalate (MEP)

6 Data Tables: 15.4.1 to 15.4.6

15.5 Mono-Isobutyl Phthalate (MiBP)

4 Data Tables: 15.5.1 to 15.5.4

15.6 Mono-Isononyl Phthalate (MiNP)

6 Data Tables: 15.6.1 to 15.6.6

15.7 Mono-Methyl Phthalate (MMP)

6 Data Tables: 15.7.1 to 15.7.6

15.8 Mono-n-Octyl Phthalate (MOP)

6 Data Tables: 15.8.1 to 15.8.6

15.9 Mono-3-Carboxypropyl Phthalate (MCPP)

6 Data Tables: 15.9.1 to 15.9.6

15.10 Mono-2-Ethylhexyl Phthalate (MEHP)

6 Data Tables: 15.10.1 to 15.10.6

15.11 Mono-(2-Ethyl-5-Oxohexyl) Phthalate (MEOHP)

6 Data Tables: 15.11.1 to 15.11.6

15.12 Mono-(2-Ethyl-5-Hydroxyhexyl) Phthalate (MEHHP)

6 Data Tables: 15.12.1 to 15.12.6

References

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David, R.M. (2006). Proposed mode of action for in utero effects of some phthalate esters on the developing male reproductive tract. Toxicologic Pathology, 34 (3), 209-219.

David, R.M. & Gans, G. (2003). Summary of mammalian toxicology and health effects of phthalate esters. Phtalate Esters: Series Anthropogenic Compounds. Springer, Berlin.

Duty, S.M., Calafat, A.M., Silva, M.J., Ryan, L., & Hauser, R. (2005). Phthalate exposure and reproductive hormones in adult men. Human Reproduction, 20 (3), 604-610.

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Environment Canada & Health Canada. (2000). Priority substances list assessment report: Butylbenzyl phthalate. Minister of Supply and Services Canada, Ottawa, ON. Retrieved March 7, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/psl2-lsp2/butylbenzylphthalate/index-eng.php

Environment Canada & Health Canada. (2003). Follow-up report on a PSL1 substance for which data were insufficient to conclude whether the substance was "toxic" to human health: Di-n-octyl phthalate. Minister of Supply and Services Canada, Ottawa, ON. Retrieved March 7, 2012, from www.ec.gc.ca/substances/ese/eng/psap/assessment/PSL1_di_n_octyl_phthalate_followup.pdf

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Graham, P.R. (1973). Phthalate ester plasticizers: Why and how they are used. Environmental Health Perspectives, 3, 3-12.

Gray, L.E. Jr, Ostby, J., Furr, J., Price, M., Veeramachaneni, D.N., & Parks, L. (2000). Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicological Sciences, 58 (2), 350-365.

Hauser, R. & Calafat, A.M. (2005). Phthalates and human health. Occupational and Environmental Medicine, 62 (11), 806-818.

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Howdeshell, K.L., Furr, J., Lambright, C.R., Rider, C.V., Wilson, V.S., & Gray, L.E. Jr (2007). Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: Altered fetal steroid hormones and genes. Toxicological Sciences, 99 (1), 190-202.

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Jurewicz, J. & Hanke, W. (2011). Exposure to phthalates: Reproductive outcome and children health. A review of epidemiological studies. International Journal of Occupational Medicine and Environmental Health, 24 (2), 115-141.

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Main, K.M., Mortensen, G.K., Kaleva, M.M., Boisen, K.A., Damgaard, I.N., Chellakooty, M., Schmidt, I.M., Suomi, A.M., Virtanen, H.E., Petersen, D.V., Andersson, A.M., Toppari, J., & Skakkebaek, N.E. (2006). Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environmental Health Perspectives, 114 (2), 270-276.

Marsee, K., Woodruff, T.J., Axelrad, D.A., Calafat, A.M., & Swan, S.H. (2006). Estimated daily phthalate exposures in a population of mothers of male infants exhibiting reduced anogenital distance. Environmental Health Perspectives, 114 (6), 805-809.

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NTP-CERHR (National Toxicology Program - Center for the Evaluation of Risks to Human Reproduction). (2003b). NTP-CERHR monograph on the potential human reproductive and developmental effects of di-isodecyl phthalate (DIDP). National Institutes of Health, Research Triangle Park, NC.

NTP-CERHR (National Toxicology Program - Center for the Evaluation of Risks to Human Reproduction). (2003c). NTP-CERHR monograph on the potential human reproductive and developmental effects of di-n-butyl phthalate (DBP). National Institutes of Health, Research Triangle Park, NC.

NTP-CERHR (National Toxicology Program - Center for the Evaluation of Risks to Human Reproduction). (2003d). NTP-CERHR monograph on the potential human reproductive and developmental effects of butyl benzyl phthalate (BBP). National Institutes of Health, Research Triangle Park, NC.

NTP-CERHR (National Toxicology Program - Center for the Evaluation of Risks to Human Reproduction). (2003e). NTP-CERHR monograph on the potential human reproductive and developmental effects of di-n-octyl phthalate (DnOP). National Institutes of Health, Research Triangle Park, NC.

NTP-CERHR (National Toxicology Program - Center for the Evaluation of Risks to Human Reproduction). (2003f). NTP-CERHR monograph on the potential human reproductive and developmental effects of di-n-hexyl phthalate (DnHP). National Institutes of Health, Research Triangle Park, NC.

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16 Polycyclic Aromatic Hydrocarbon Metabolites Summaries and Results

16.1 Overview

Polycyclic aromatic hydrocarbons (PAHs) are a group of more than 100 organic compounds characterized by the presence of two or more fused aromatic rings. The World Health Organization and the United States Environmental Protection Agency have prioritized 16 PAHs because of their toxicity. Table 15.1 lists seven of these priority PAHs and their metabolites measured in cycle 2 of the Canadian Health Measures Survey (CHMS).

Table 16.1.1 Hydroxylated polyaromatic hydrocarbon (PAH) metabolites measured in the Canadian Health Measures Survey cycle 2 (2009-2011) and their parent PAH compounds.
PAH CASRN Hydroxylated PAH metabolites CASRN
Benzo[a]pyrene 50-32-8 3-Hydroxybenzo[a]pyrene 13345-21-6
Chrysene 218-01-9 2-Hydroxychrysene 65945-06-4
3-Hydroxychrysene 63019-39-6
4-Hydroxychrysene 63019-40-9
6-Hydroxychrysene 37515-51-8
Fluorene 86-73-7 2-Hydroxyfluorene 2443-58-5
3-Hydroxyfluorene 6344-67-8
9-Hydroxyfluorene 484-17-3
Fluoranthene 206-44-0 3-Hydroxyfluoranthene 206-44-0
Naphthalene 91-20-3 1-Hydroxynaphthalene 90-15-3
2-Hydroxynaphthalene 135-19-3
Phenanthrene 85-01-8 1-Hydroxyphenanthrene 2443-56-9
2-Hydroxyphenanthrene 605-55-0
3-Hydroxyphenanthrene 605-87-8
4-Hydroxyphenanthrene 7651-86-7
9-Hydroxyphenanthrene 484-17-3
Pyrene 129-00-0 1-Hydroxypyrene 5315-79-7

PAHs are released to the environment from both natural and anthropogenic sources; the contribution from anthropogenic sources is substantially higher than from natural sources (ATSDR, 1995). In Canada, forest fires are the largest natural source of PAHs in the environment (Environment Canada, 2010). Other natural sources include crude oils, coal, and volcanic eruptions. Anthropogenic PAH emissions are predominantly due to the incomplete combustion of organic substances from waste incineration, tobacco smoke, cooking, automobile exhaust, mining and refining operations, oil spills, and the use of creosote-treated products (ATSDR, 1995; ATSDR, 2005; Environment Canada & Health Canada, 1994).

For the general population, the major routes of exposure to PAHs are from diet, smoking, and ambient and indoor air (IARC, 2010; WHO, 2011). Levels in food depend on the source of the food and the method of cooking (ATSDR, 1995). PAHs can be formed when food is charbroiled, grilled, roasted, fried, or baked. Drinking water is considered to be a negligible source of exposure in Canada (Environment Canada & Health Canada, 1994). Vehicle exhaust, tobacco smoke, emissions from wood and charcoal-fired stoves, house dust, and ambient air all contribute to inhalation exposure. Human exposure to PAHs may also occur through skin contact with soot and tars (ATSDR, 1995).

PAHs can be absorbed following inhalation, oral, and dermal exposure. They undergo multi-step metabolism leading to several types of metabolites, including hydroxylated PAHs (Strickland et al., 1996). Elimination occurs through urine and feces, with urinary hydroxylated PAH metabolites observed within a few days of exposure (Viau et al., 1995). These metabolites are excreted both in the free form and as glucuronic acid and sulphate conjugates (Castano-Vinyals et al., 2004).

Several approaches exist to assess human exposure to PAHs. The analysis of urinary hydroxylated PAH metabolites is the most common approach and has been used in several biomonitoring studies (Becker et al., 2003; CDC, 2009). Several urinary hydroxylated PAH metabolites were measured in cycle 2 of the CHMS and are listed along with their parent PAHs in Table 16.1.1.

Evaluating health effects of exposure to individual PAHs in humans is difficult because exposure is generally to multiple PAHs at the same time. Studies in laboratory animals have shown that several PAHs have carcinogenic, mutagenic, and teratogenic potential (IARC, 2010; IARC, 2012). The carcinogenic potency of PAHs appears to differ considerably among exposure routes (ATSDR, 1995). In some, formation of epoxides through metabolic activation of PAHs is considered a key step in eliciting carcinogenic effects (D'Mello et al., 2003). Benzo[a]pyrene, PAH-containing mixtures, such as soot and coal tar, and occupational exposures in PAH-related industries (coal-tar distillation, coal gasification, coke production, aluminium production) have recently been confirmed as carcinogenic to humans by the International Agency for Research on Cancer (IARC) (IARC, 2012). Based on current data, IARC has classified some PAHs, such as chrysene and naphthalene, as possibly carcinogenic to humans (IARC, 2010). Other PAHs, such as fluoranthene, fluorine, phenanthrene, and pyrene, are not classifiable as to their carcinogenicity to humans (IARC, 2010). PAHs also exhibit immunological, hepatic, and reproductive effects in laboratory animals, but generally at doses much higher than those that elicit a carcinogenic response (ATSDR, 1995).

In Canada, PAHs are listed as toxic substances on Schedule 1 of the Canadian Environmental Protection Act, 1999, based on an evaluation of the environmental and health effects of several PAHs, including Benzo[a]pyrene (Canada, 1999; Canada, 2000; Environment Canada & Health Canada, 1994). Several environmental performance agreements, codes of practice, and recommendations have been established to reduce releases of PAHs to the environment from the aluminum and steel manufacturing and wood preservation sectors (Environment Canada, 2010). In order to minimize exposure to PAHs from a specific food product called olive-pomace oil, Health Canada has established a maximum PAH contaminant concentration for the oil (Health Canada, 2012).

In the following sections, some common PAHs (see Table 16.1.1) are discussed, and data on their urinary hydroxylated PAH metabolites and baseline levels found in the Canadian population are presented.

References

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Castaño-Vinyals, G., D'Errico, A., Malats, N., & Kogevinas, M. (2004). Biomarkers of exposure to polycyclic aromatic hydrocarbons from environmental air pollution. Occupational and Environmental Medicine, 61 (4), e12.

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

D'Mello, J.P.F., Guillén, M.D., & Sopelana, P. (2003). Polycyclic aromatic hydrocarbons in diverse foods. Food Safety: Contaminants and Toxins. CAB International, Oxon, UK.

Environment Canada. (2010). Polycyclic aromatic hydrocarbons. Minister of the Environment, Ottawa, ON. Retrieved June 11, 2012, from www.ec.gc.ca/toxiques-toxics/Default.asp?lang=En&n=98E80CC6-1&xml=9C252383-7DB8-4FDB-B811-50FA3C9CE42D

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Health Canada. (2012). Canadian standards (maximum levels) for various chemical contaminants in foods. Minister of Health, Ottawa, ON. Retrieved November 29, 2012, from www.hc-sc.gc.ca/fn-an/securit/chem-chim/contaminants-guidelines-directives-eng.php

IARC (International Agency for Research on Cancer). (2010). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 92: Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. World Health Organization, Lyon.

IARC (International Agency for Research on Cancer). (2012). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 100C: Arsenic, metals, fibres, and dusts. World Health Organization, Geneva.

Strickland, P., Kang, D., & Sithisarankul, P. (1996). Polycyclic aromatic hydrocarbon metabolites in urine as biomarkers of exposure and effect. Environmental Health Prespectives, 104 (Supplement 5), 927-932.

Viau, C., Carrier, G., Vyskocil, A., & Dodd, C. (1995). Urinary excretion kinetics of 1-hydroxypyrene in volunteers exposed to pyrene by the oral and dermal route. Science of the Total Environment, 163 (1-3), 179-186.

WHO (World Health Organization). (2011). Guidelines for drinking-water quality, fourth edition. WHO, Geneva. Retrieved March 9, 2012, from www.who.int/water_sanitation_health/publications/2011/dwq_guidelines/en/index.html

16.2 Benzo[a]pyrene Metabolite

Benzo[a]pyrene is a polycyclic aromatic hydrocarbon (PAH) composed of five fused benzene rings. It is not manufactured in Canada and no industrial uses are known (Health Canada, 1988).

In laboratory rats, about 40% to 60% of benzo[a]pyrene is absorbed following exposure through gavage or diet (Faust, 1994). Based on laboratory studies, approximately 3% of benzo[a]pyrene is expected to be absorbed through skin after 24 hours (Kao et al., 1985). The presence of urinary metabolites in workers exposed occupationally to PAHs in air provides evidence for absorption of benzo[a]pyrene following inhalation (ATSDR, 1995). Its absorption following inhalation is highly dependent on the type of particles onto which it is adsorbed. After absorption, benzo[a]pyrene distributes to several organs including lungs, liver, and intestines (Faust, 1994). Like other PAHs, benzo[a]pyrene is metabolized to various arene epoxides that after rearrangement produce several hydroxylated PAHs and dihydrodiols (Bouchard & Viau, 1996). The metabolite 3-hydroxybenzo[a]pyrene has been used as a biomarker in urine for exposure to benzo[a]pyrene in humans (Chien & Yeh, 2012).

Adverse health effects have been observed in laboratory animals following benzo[a]pyrene exposure via inhalation, oral, and dermal routes. Non-carcinogenic effects have been observed at dose levels on at least an order of magnitude higher than that of carcinogenic effects (ATSDR, 1995; Health Canada, 1988; Jules et al., 2012). The diolepoxides formed during metabolism of benzo[a]pyrene are considered to be the primary carcinogenic agents (IARC, 2012). Although there is no direct evidence for the carcinogenic effects in humans, occupational exposures to benzo[a]pyrene-containing mixtures have been associated with a series of cancers (IARC, 2012). Based on the strong evidence for the carcinogenicity of benzo[a]pyrene in many animal species, and supported by evidence from laboratory and human studies, the International Agency for Research on Cancer has classified benzo[a]pyrene as Group 1, a known human carcinogen (IARC, 2012).

Health Canada has developed a Canadian drinking water quality guideline that sets out the maximum acceptable concentration of benzo[a]pyrene (Health Canada, 1988); this guideline is currently under review.

The benzo[a]pyrene metabolite, 3-hydroxybenzo[a]pyrene, was measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 16.2.1.1, 16.2.1.2, 16.2.1.3, and 16.2.1.4). Finding a measurable amount of 3-hydroxybenzo[a]pyrene in urine is an indicator of exposure to benzo[a]pyrene and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary 3-hydroxybenzo[a]pyrene in the Canadian population.

16.2.1 3-Hydroxybenzo[a]pyrene

4 Data Tables: 16.2.1.1 to 16.2.1.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1995). Toxicological profile for polycyclic aromatic hydrocarbons. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved February 17, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=122&tid=25

Bouchard, M. & Viau, C. (1996). Urinary excretion kinetics of pyrene and benzo(a)pyrene metabolites following intravenous administration of the parent compounds or the metabolites. Toxicology and Applied Pharmacology, 139 (2), 301-309.

Chien, Y.-C. & Yeh, C.-T. (2012). Excretion kinetics of urinary 3-hydroxybenzo[a]pyrene following dietary exposure to benzo[a]pyrene in humans. Archives of Toxicology, 86 (1), 45-53.

Faust, R. (1994). Toxicity profile for benzo[a]pyrene. Oak Ridge National Laboratory, Oak Ridge, TN.

Health Canada. (1988). Guidelines for Canadian drinking water quality: Guideline technical document - Benzo[a]pyrene. Minister of Health, Ottawa, ON. Retrieved June 11, 2012, from www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/benzo_a_pyrene/index-eng.php

IARC (International Agency for Research on Cancer). (2010). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 92: Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. World Health Organization, Lyon.

IARC (International Agency for Research on Cancer). (2012). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 100F: Chemical agents and related occupations. World Health Organization, Lyon.

Jules, G.E., Pratap, S., Ramesh, A., & Hood, D.B. (2012). In utero exposure to benzo(a)pyrene predisposes offspring to cardiovascular dysfunction in later-life. Toxicology, 295 (1-3), 56-67.

Kao, J., Patterson, F.K., & Hall, J. (1985). Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: An in vitro study with Benzo[a]pyrene and testosterone. Toxicology and Applied Pharmacology, 81 (3, Part 1), 502-516.

16.3 Chrysene Metabolites

Chrysene is a polycyclic aromatic hydrocarbon (PAH) composed of four fused benzene rings. There are no known uses of chrysene other than its use as a research chemical (ATSDR, 1995).

Chrysene is highly lipophilic. In animal pharmacokinetic studies, approximately 75% of chrysene was absorbed when administered through oral, inhalation, and dermal routes of exposure; after absorption, it preferentially distributed to adipose tissues (Borges, 1994). Chrysene is metabolized into several mono- and dihydroxychrysene metabolites (CDC, 2009). Chrysene metabolites are excreted predominantly in the feces. However, PAH biomonitoring studies in humans have attempted to measure urinary levels of 1-, 2-, 3-, 4, and 6-hydroxychrysene, and have been able to detect urinary 3- and 6-hydroxychrysene in a small proportion of samples (Nethery et al., 2012).

Data on the systemic toxicity of chrysene in animals and humans are limited (Borges, 1994). In mice, chrysene exposure resulted in an increased incidence of skin papillomas and hepatic and lung tumours (Chang et al., 1983; Wislocki et al., 1986). Based on a limited amount of available carcinogenicity data, the International Agency for Research on Cancer has classified chrysene as Group 2B, possibly carcinogenic to humans (IARC, 2010).

The urinary chrysene metabolites 3- and 6-hydroxychrysene were measured for 73 non-smoking, non-occupationally exposed individuals (aged 16 to 64 years) living approximately 1 km from an aluminum plant in Baie-Comeau, Quebec. These chrysene metabolites were measured as part of a broad set of PAH metabolites. Although the levels of some other urinary PAH metabolites were higher compared with a control group of 71 individuals living at least 11 km from the plant, the urinary concentrations of these chrysene metabolites were below the limit of detection (0.032 µg/L for 3-hydroxychrysene and 0.019 µg/L for 6-hydroxychrysene) for most samples (Bouchard et al., 2009).

The chrysene metabolites, 2-, 3-, 4-, and 6-hydroxychrysene, were measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and are presented as both μg/L and μg/g creatinine (Tables 16.3.1.1 to 16.4.4). Given that chrysene metabolites are predominantly excreted in the feces, their urinary absence alone does not indicate that exposure to chrysene did not occur. Finding a measurable amount of chrysene metabolites in urine is an indicator of exposure to chrysene and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary chrysene metabolites in the Canadian population.

16.3.1 2-Hydroxychrysene

4 Data Tables: 16.3.1.1 to 16.3.1.4

16.3.2 3-Hydroxychrysene

4 Data Tables: 16.3.2.1 to 16.3.2.4

16.3.3 4-Hydroxychrysene

4 Data Tables: 16.3.3.1 to 16.3.3.4

16.3.4 6-Hydroxychrysene

4 Data Tables: 16.3.4.1 to 16.3.4.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1995). Toxicological profile for polycyclic aromatic hydrocarbons. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved February 17, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=122&tid=25

Borges, H.T. (1994). Toxicity summary for chrysene. Oak Ridge Reservation and Environmental Restoration Program, Oak Ridge, TN.

Bouchard, M., Normandin, L., Gagnon, F., Viau, C., Dumas, P., Gaudreau, É., & Tremblay, C. (2009). Repeated measures of validated and novel biomarkers of exposure to polycyclic aromatic hydrocarbons in individuals living near an aluminum plant in Québec, Canada. Journal of Toxicology and Environmental Health, Part A, 72 (23), 1534-1549.

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Chang, R.L., Levin, W., Wood, A.W., Yagi, H., Tada, M., Vyas, K.P., Jerina, D.M., & Conney, A.H. (1983). Tumorigenicity of enantiomers of chrysene 1,2-dihydrodiol and of the diastereomeric bay-region chrysene 1,2-diol-3,4-epoxides on mouse skin and in newborn mice. Cancer Research, 43 (1), 192-196.

IARC (International Agency for Research on Cancer). (2010). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 92: Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. World Health Organization, Lyon.

Nethery, E., Wheeler, A.J., Fisher, M., Sjodin, A., Li, Z., Romanoff, L.C., Foster, W., & Arbuckle, T.E. (2012). Urinary polycyclic aromatic hydrocarbons as a biomarker of exposure to PAHs in air: A pilot study among pregnant women. Journal of Exposure Sciences and Environmental Epidemiology, 22 (1), 70-81.

Wislocki, P.G., Bagan, E.S., Lu, A.Y.H., Dooley, K.L., Fu, P., Han-Hsu, H., Beland, F.A., & Kadlubar, F.F. (1986). Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and benzo[a]pyrene in the newborn mouse assay. Carcinogenesis, 7 (8), 1317-1322.

16.4 Fluoranthene Metabolite

Fluoranthene, also known as benzo[j,k]fluorene, is a polycyclic aromatic hydrocarbon (PAH) with five fused aromatic rings. It is found naturally in the environment in some bacteria, algae, and plants and as a result of anthropogenic releases from incomplete combustion of organic substances (EPA, 1980). Fluoranthene is used in the synthesis of dyes and in biomedical research (Wu et al., 2010).

Limited pharmacokinetic data for fluoranthene are available. Similar to other structurally related PAHs, fluoranthene may be absorbed following oral, inhalation, or dermal exposure (Faust, 1993; Storer et al., 1984). Because of its high lipophilicity, fluoranthene distributes to adipose tissue (EPA, 1980). Metabolism of fluoranthene produces hydroxylated metabolites, and urinary 3-hydroxyfluoranthene is considered an indicator of recent exposures.

Kidney and liver effects were observed in rats orally administered fluoranthene (Faust, 1993). Fluoranthene exposure in mice has resulted in lung tumours (Busby Jr. et al., 1989; IARC, 2010). Dermal exposure in mice to a combination of benzo[a]pyrene and fluoranthene significantly increased the incidence of skin tumours (IARC, 2010). Based on the limited data on fluoranthene carcinogenicity, the International Agency for Research on Cancer has classified fluoranthene as Group 3, not classifiable as to its carcinogenicity to humans (IARC, 2010).

The urinary fluoranthene metabolite, 3-hydroxyfluoranthene, was measured for 73 non-smoking, non-occupationally exposed individuals (aged 16 to 64 years) living approximately 1 km from an aluminum plant in Baie-Comeau, Quebec. The fluoranthene metabolite was measured as part of a broad set of PAH metabolites. Although the levels of some other urinary PAH metabolites were higher compared with a control group of 71 individuals living at least 11 km from the plant, the concentration of 3-hydroxyfluoranthene was below the limit of detection (0.030 µg/L) for most samples (Bouchard et al., 2009).

The fluoranthene metabolite, 3-hydroxyfluoranthene, was measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 16.4.1.1, 16.4.1.2, 16.4.1.3, and 16.4.1.4). Finding a measurable amount of 3-hydroxyfluoranthene in urine is an indicator of exposure to fluoranthene and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary 3-hydroxyfluoranthene in the Canadian population.

16.4.1 3-Hydroxyfluoranthene

4 Data Tables: 16.4.1.1 to 16.4.1.4

References

Bouchard, M., Normandin, L., Gagnon, F., Viau, C., Dumas, P., Gaudreau, É., & Tremblay, C. (2009). Repeated measures of validated and novel biomarkers of exposure to polycyclic aromatic hydrocarbons in individuals living near an aluminum plant in Québec, Canada. Journal of Toxicology and Environmental Health, Part A, 72 (23), 1534-1549.

Busby Jr., W.F., Stevens, E.K., Martin, C.N., Chow, F.L., & Garner, R.C. (1989). Comparative lung tumorigenicity of parent and mononitro-polynuclear aromatic hydrocarbons in the BLU:Ha newborn mouse assay. Toxicology and Applied Pharmacology, 99 (3), 555-563.

EPA (U.S. Environmental Protection Agency). (1980). Ambient water quality criteria for fluoranthene. U.S. Environmental Protection Agency, Washington DC.

Faust, R. (1993). Toxicity profile for fluoranthene. Oak Ridge National Laboratory, Oak Ridge, TN.

IARC (International Agency for Research on Cancer). (2010). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 92: Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. World Health Organization, Lyon.

Storer, J.S., DeLeon, I., Millikan, L.E., Laseter, J.L., & Griffing, C. (1984). Human absorption of crude coal tar products. Archives of Dermatology, 120 (7), 874-877.

Wu, W., Guo, F., Li, J., He, J., & Hua, J. (2010). New fluoranthene-based cyanine dye for dye-sensitized solar cells. Synthetic Metals, 160 (9-10), 1008-1014.

16.5 Fluorene Metabolites

Fluorene is a polycyclic aromatic hydrocarbon (PAH) with three fused aromatic rings. Fluorene and its derivatives are used in the manufacture of dyes, pharmaceuticals, polymer materials, photonics, and basic research (Belfield et al., 1999; Bernius et al., 2000; Mondal et al., 2009).

Animal studies indicate that fluorene is absorbed following oral, inhalation, and dermal exposure (ATSDR, 1995). Metabolism of fluorene produces several hydroxylated metabolites that are further conjugated with glucuronic or sulphonic acids and rapidly eliminated in the urine (Faust, 1994). Several urinary monohydroxy fluorene metabolites, including 2-, 3-, and 9-hydroxyfluorene, have been identified in humans and are considered indicators of recent PAH exposure (Becker et al., 2003; CDC, 2009; Nethery et al., 2012). Urinary 3-hydroxyfluorene may be a good predictive biomarker for specifically assessing inhalation exposure to fluorene (Nethery et al., 2012).

Hematological and liver effects were observed in laboratory animals exposed orally to fluorene (ATSDR, 1995). Data on the carcinogenicity of fluorene in humans have not been identified and the International Agency for Research on Cancer has classified fluorene as Group 3, not classifiable as to its carcinogenicity in humans (IARC, 2010).

The fluorene metabolites, 2-, 3-, and 9-hydroxyfluorene, were measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and are presented as both μg/L and μg/g creatinine (Tables 16.5.1.1 to 16.5.3.4). Finding a measurable amount of fluorene metabolites in urine is an indicator of exposure to fluorene and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary fluorene metabolites in the Canadian population.

16.5.1 2-Hydroxyfluorene

4 Data Tables: 16.5.1.1 to 16.5.1.4

16.5.2 3-Hydroxyfluorene

4 Data Tables: 16.5.2.1 to 16.5.2.4

16.5.3 9-Hydroxyfluorene

4 Data Tables: 16.5.3.1 to 16.5.3.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1995). Toxicological profile for polycyclic aromatic hydrocarbons. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved February 17, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=122&tid=25

Becker, K., Schulz, C., Kaus, S., Seiwert, M., & Seifert, B. (2003). German Environmental Survey 1998 (GerES III): Environmental pollutants in the urine of the German population. International Journal of Hygiene and Environmental Health, 206 (1), 15-24.

Belfield, K.D., Hagan, D.J., Van Stryland, E.W., Schafer, K.J., & Negres, R.A. (1999). New two-photon absorbing fluorene derivatives: Synthesis and nonlinear optical characterization. Organic Letters, 1 (10), 1575-1578.

Bernius, M., Inbasekaran, M., Woo, E., Wu, W., & Wujkowski, L. (2000). Light-emitting diodes based on fluorene polymers. Thin Solid Films, 363 (1-2), 55-57.

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Faust, R.A. (1994). Toxicity summary for fluorene. Oak Ridge Reservation and Environmental Restoration Program, Oak Ridge, Tennessee.

IARC (International Agency for Research on Cancer). (2010). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 92: Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. World Health Organization, Lyon.

Mondal, R., Miyaki, N., Becerril, H.A., Norton, J.E., Parmer, J., Mayer, A.C., Tang, M.L., Brédas, J., McGehee, M.D., & Bao, Z. (2009). Synthesis of acenaphthyl and phenanthrene based fused-aromatic thienopyrazine co-polymers for photovoltaic and thin film transistor applications. Chemistry of Materials, 21 (15), 3618-3628.

Nethery, E., Wheeler, A.J., Fisher, M., Sjodin, A., Li, Z., Romanoff, L.C., Foster, W., & Arbuckle, T.E. (2012). Urinary polycyclic aromatic hydrocarbons as a biomarker of exposure to PAHs in air: A pilot study among pregnant women. Journal of Exposure Sciences and Environmental Epidemiology, 22 (1), 70-81.

16.6 Naphthalene Metabolites

Naphthalene is a polycyclic aromatic hydrocarbon (PAH) with two fused benzene rings. Naphthalene is manufactured and imported into Canada for a wide variety of industrial uses (Environment Canada & Health Canada, 2008). The major consumer products made from naphthalene are moth repellents, in the form of mothballs or crystals, and toilet deodorant blocks. Other commercial use of naphthalene include components of polyvinyl chloride phthalate plasticizers, dyes, resins, leather-tanning agents, and the insecticide carbaryl (EPA, 2008; IARC, 2002).

Naphthalene evaporates easily and is often found in the gaseous phase in ambient air (WHO, 2010). Although diet and smoking are the most important sources of intake for most PAHs, inhalation of ambient and indoor air is the main source of naphthalene exposure for the general population. In Canada, indoor air exposure accounts for more than 95% of the total daily exposure across age groups (Environment Canada & Health Canada, 2008). A recent study identified mothballs and some building materials and furnishings (vinyl and wooden furniture, and painted walls and ceilings) as significant contributors to indoor naphthalene concentrations in Canadian homes (Kang et al., 2012). Other sources of naphthalene in indoor and ambient air include migration of volatile organic compounds from attached garages, during cooking, and from kerosene space heaters and wood stoves (Batterman et al., 2007; Environment Canada & Health Canada, 2008). Food and drinking water are considered minor sources of exposure to naphthalene (NTP, 2002).

Naphthalene is rapidly absorbed and metabolized following oral and inhalation exposures in laboratory animals (Bagchi et al., 2002; NTP, 2002). Naphthalene is also absorbed following dermal application in humans and laboratory animals (Storer et al., 1984; Turkall et al., 1994). Like other PAHs, naphthalene undergoes multi-step metabolism, the result of which includes the production of the hydroxynaphthalene metabolites, 1- and 2-hydroxynaphthalene (WHO, 2010). Urinary levels of hydroxynaphthalene metabolites are reflective of recent exposure and have been measured in several human studies (Bouchard et al., 2009; CDC, 2009; Nethery et al., 2012). Urinary 2-hydroxynaphthalene is a unique biomarker of naphthalene metabolism (CDC, 2009). 1-Hydroxynaphthalene is a metabolite of both naphthalene and the insecticide carbaryl, making it difficult to distinguish between these exposures in the general population. For more information on carbaryl, see section 14.2 (Carbamate Metabolites).

In humans, the most serious effects of acute exposure to naphthalene are reported in individuals with glucose 6-phosphate dehydrogenase deficiency, where hemolytic anemia is the primary adverse effect (WHO, 2010). Reports from occupational exposure and animal studies suggest chronic exposure to naphthalene may lead to the development of lens opacities such as cataracts (WHO, 2010). Respiratory tract lesions have also been observed in laboratory animals following acute and chronic exposures (WHO, 2010). Naphthalene has been observed to induce airway tumours in laboratory animals (NTP, 2002). Increased cell proliferation due to cytotoxicity (cell damage) is considered a key element in the development of airway tumours (WHO, 2010). The International Agency for Research on Cancer has classified naphthalene as Group 2B, possibly carcinogenic to humans (IARC, 2002). The carcinogenicity of naphthalene has been proposed to involve non-genotoxic mechanisms (IARC, 2002). Considering the apparent non-genotoxicity of naphthalene, the World Health Organization favours the assumption of the existence of a threshold and has derived an annual average indoor air guideline for naphthalene (WHO, 2010). The guideline is considered to protect against the carcinogenic and non-carcinogenic effects to the respiratory tract resulting from naphthalene exposure.

On the basis of carcinogenicity as well as non-cancer effects, Health Canada and Environment Canada have concluded that naphthalene is a concern for human health (Environment Canada & Health Canada, 2008). As a result, naphthalene is listed as a toxic substance on Schedule 1 of the Canadian Environmental Protection Act, 1999 (Canada, 1999; Canada, 2010a). In an effort to reduce exposure to naphthalene, several risk management approaches have been taken (Canada, 2010b). In 2010, the Pest Management Regulatory Agency (PMRA) re-evaluated the insecticidal uses of naphthalene. PMRA concluded that pest control products containing naphthalene do not present unacceptable risks to human health when used according to label directions and has granted continued registration (Health Canada, 2010).

Health Canada has introduced new packaging and labelling requirements for naphthalene-containing consumer products (mothballs and moth flakes) in order to minimize exposure (Health Canada, 2012). Naphthalene, 1- hydroxynaphthalene and its salts, and 2-hydroxynaphthalene are all included on Health Canada's list of prohibited and restricted cosmetic ingredients (also known as the Cosmetic Ingredient Hotlist). The Hotlist is an administrative tool to communicate to manufacturers and others that substances on the Hotlist, if used in cosmetics, may cause injury to the health of the user, which is in contravention of the general prohibition against the sale of unsafe cosmetics in the Food and Drugs Act (Canada, 1985; Health Canada, 2011). The Government of Canada is also investigating the development of air quality guidelines for naphthalene levels in residential indoor air (Canada, 2010b).

1-Hydroxynaphthalene and 2-hydroxynaphthalene have been measured in urine as biomarkers of exposure to naphthalene in several studies. In 1999, a study measured the urinary hydroxynaphthalene metabolite concentrations in 60 non-smoking and non-occupational exposed adults (30 exposed and 30 control individuals) between the ages of 18 and 60 years living in the vicinity of a creosote impregnation plant in Delson, Quebec (Bouchard et al., 2001). The geometric means urinary concentrations in residents living near the plant were 3.17 µg/g creatinine for 1-hydroxynaphthalene and 2.47 µg/g creatinine for 2-hydroxynaphthalene. In the control group, geometric mean concentrations were 1.49 µg/g creatinine and 1.38 µg/g creatinine for 1-hydroxynaphthalene and 2-hydroxynaphthalene, respectively (Bouchard et al., 2001). In 144 residents aged 16 to 64 years living near an aluminum plant in Baie-Comeau, Quebec, the geometric mean concentrations ranged from 0.80 to 2.17 µg/g creatinine for 1-hydroxynaphthalene and 1.75 to 3.26 µg/g creatinine for 2-hydroxynaphthalene (Bouchard et al., 2009).

Naphthalene metabolites, 1-hydroxynaphthalene and 2-hydroxynaphthalene, were measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and are presented as both μg/L and μg/g creatinine (Tables 16.6.1.1 to 16.6.2.4). Finding a measurable amount of naphthalene metabolites in urine can be an indicator of exposure to naphthalene or carbaryl (for 1-hydroxynaphthalene) and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary naphthalene metabolites in the Canadian population.

16.6.1 1-Hydroxynaphthalene

4 Data Tables: 16.6.1.1 to 16.5.1.4

16.6.2 2-Hydroxynaphthalene

4 Data Tables: 16.6.2.1 to 16.6.2.4

References

Bagchi, D., Balmoori, J., Bagchi, M., Ye, X., Williams, C.B., & Stohs, S.J. (2002). Comparative effects of TCDD, endrin, naphthalene and chromium (VI) on oxidative stress and tissue damage in the liver and brain tissues of mice. Toxicology, 175 (13), 73-82.

Batterman, S., Jia, C., & Hatzivasilis, G. (2007). Migration of volatile organic compounds from attached garages to residences: A major exposure source. Environmental Research, 104 (2), 224-240.

Bouchard, M., Pinsonneault, L., Tremblay, C., & Weber, J.-P. (2001). Biological monitoring of environmental exposure to polycyclic aromatic hydrocarbons in subjects living in the vicinity of a creosote impregnation plant. International Archives of Occupational and Environmental Health, 74 (7), 505-513.

Bouchard, M., Normandin, L., Gagnon, F., Viau, C., Dumas, P., Gaudreau, É., & Tremblay, C. (2009). Repeated measures of validated and novel biomarkers of exposure to polycyclic aromatic hydrocarbons in individuals living near an aluminum plant in Québec, Canada. Journal of Toxicology and Environmental Health, Part A, 72 (23), 1534-1549.

Canada. (1985). Food and Drugs Act. RSC 1985, c. F-27. Retrieved June 6, 2012, from http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. (1999). Canadian Environmental Protection Act, 1999. SC 1999, c. 33. Retrieved April 2, 2012, from http://laws-lois.justice.gc.ca/eng/acts/C-15.31/index.html

Canada. (2010a). Order adding a toxic substance to Schedule 1 to the Canadian Environmental Protection Act, 1999. Canada Gazette, Part II: Official Regulations, 144 (10). Retrieved August 29, 2012, from www.gazette.gc.ca/rp-pr/p2/2010/2010-05-12/html/sor-dors98-eng.html

Canada. (2010b). Chemical substances: Naphthalene. Retrieved June 11, 2012, from www.chemicalsubstanceschimiques.gc.ca/challenge-defi/summary-sommaire/batch-lot-1/91-20-3-eng.php

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Environment Canada & Health Canada. (2008). Screening assessment for the challenge: Naphthalene (chemical abstracts service registry number 91-20-3). Retrieved May 14, 2012, from www.ec.gc.ca/substances/ese/eng/challenge/batch1/batch1_91-20-3.cfm

EPA (U.S. Environmental Protection Agency). (2008). Reregistration eligibility decision (RED) for naphthalene: List C case no 3058. Retrieved May 14, 2012, from www.epa.gov/oppsrrd1/REDs/naphthalene-red.pdf

Health Canada. (2010). Re-evaluation decision RVD2010-04, Naphthalene. Minister of Health, Ottawa, ON. Retrieved May 8, 2012, from www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/rvd2010-04/index-eng.php

Health Canada. (2011). List of prohibited and restricted cosmetic ingredients ("hotlist"). Retrieved May 25, 2012, from www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/index-eng.php

Health Canada. (2012). New labelling and oackaging requirements for naphthalene-containing mothballs. Retrieved June 11, 2012, from www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2012/2012_46-eng.php

IARC (International Agency for Research on Cancer). (2002). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 82: Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. World Health Organization, Lyon.

Kang, D.H., Choi, D.H., Won, D., Yang, W., Schleibinger, H., & David, J. (2012). Household materials as emission sources of naphthalene in Canadian homes and their contribution to indoor air. Atmospheric Environment, 50 (0), 79-87.

Nethery, E., Wheeler, A.J., Fisher, M., Sjodin, A., Li, Z., Romanoff, L.C., Foster, W., & Arbuckle, T.E. (2012). Urinary polycyclic aromatic hydrocarbons as a biomarker of exposure to PAHs in air: A pilot study among pregnant women. Journal of Exposure Sciences and Environmental Epidemiology, 22 (1), 70-81.

NTP (Natoinal Toxicology Program). (2002). Report on carcinogens background document for naphthalene. US Department of Health and Human Services, Research Triangle Park, NC.

Storer, J.S., DeLeon, I., Millikan, L.E., Laseter, J.L., & Griffing, C. (1984). Human absorption of crude coal tar products. Archives of Dermatology, 120 (7), 874-877.

Turkall, R.M., Skowronski, G.A., Kadry, A.M., & Abdel-Rahman, M.S. (1994). A comparative study of the kinetics and bioavailability of pure and soil-adsorbed naphthalene in dermally exposed male rats. Archives of Environmental Contamination and Toxicology, 26 (4), 504-509.

WHO (World Health Organization). (2010). WHO guidelines for indoor air quality: Selected pollutants. The WHO European Center for Environment and Health, Bonn, Germany. Retrieved May 14, 2012, from www.euro.who.int/__data/assets/pdf_file/0009/128169/e94535.pdf

16.7 Phenanthrene Metabolites

Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) with three fused benzene rings. It is used in the manufacture of dyes, polymer materials, and biomedical research (Mondal et al., 2009).

After oral administration in rats, phenanthrene was found to be absorbed from the gastrointestinal tract (Faust, 1993). It is also absorbed through the skin in humans following dermal exposure (Storer et al., 1984). Metabolism of phenanthrene proceeds through the formation of epoxides that rearrange to form hydroxy and dihydrodiol metabolites (Jacob & Seidel, 2002). Phenanthrene metabolites are primarily excreted in the urine (Faust, 1993).

Urinary hydroxylated phenanthrene metabolites (1-, 2-, 3-, 4-, and 9-hydroxyphenanthrene) have been assessed in several biomonitoring studies and are indicators of recent PAH exposure (Becker et al., 2003; CDC, 2009; Jacob & Seidel, 2002; Nethery et al., 2012). Their relatively high abundance in the urine and the availability of validated analytical methods for their detection and quantification make them good biomarkers for assessing exposure. Additionally, urinary concentrations of monohydroxyphenanthrene metabolites are less sensitive to smoking status than other PAH metabolites; they are therefore better suited for assessing exposures where the study population comprises both smokers and non-smokers (Jacob et al., 1999; Rihs et al., 2005). Urinary 3-hydroxyphenanthrene may be a good predictive biomarker for specifically assessing inhalation exposure to phenanthrene (Nethery et al., 2012).

In animal studies, phenanthrene did not elicit systemic or carcinogenic effects (ATSDR, 1995). The International Agency for Research on Cancer has classified phenanthrene as Group 3, not classifiable as to its carcinogenicity in humans (IARC, 2010).

Phenanthrene metabolites, 1-, 2-, 3-, 4-, and 9-hydroxyphenanthrene, were measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and are presented as both μg/L and μg/g creatinine (Tables 16.7.1.1 to 16.7.5.4). Finding a measurable amount of phenanthrene metabolites in urine is an indicator of exposure to phenanthrene and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary phenanthrene metabolites in the Canadian population.

16.7.1 1-Hydroxyphenanthrene

4 Data Tables: 16.7.1.1 to 16.7.1.4

16.7.2 2-Hydroxyphenanthrene

4 Data Tables: 16.7.2.1 to 16.7.2.4

16.7.3 3-Hydroxyphenanthrene

4 Data Tables: 16.7.3.1 to 16.7.3.4

16.7.4 4-Hydroxyphenanthrene

4 Data Tables: 16.7.4.1 to 16.7.4.4

16.7.5 9-Hydroxyphenanthrene

4 Data Tables: 16.7.5.1 to 16.7.5.4

References

ATSDR (Agency for Toxic Substances and Disease Registry). (1995). Toxicological profile for polycyclic aromatic hydrocarbons. U.S. Department of Health and Human Services, Atlanta, GA. Retrieved February 17, 2012, from www.atsdr.cdc.gov/toxprofiles/tp.asp?id=122&tid=25

Becker, K., Schulz, C., Kaus, S., Seiwert, M., & Seifert, B. (2003). German Environmental Survey 1998 (GerES III): Environmental pollutants in the urine of the German population. International Journal of Hygiene and Environmental Health, 206 (1), 15-24.

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Faust, R.A. (1993). Toxicity summary for phenanthrene. Oak Ridge Reservation and Environmental Restoration Program, Oak Ridge, TN.

IARC (International Agency for Research on Cancer). (2010). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 92: Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. World Health Organization, Lyon.

Jacob, J., Grimmer, G., & Dettbarn, G. (1999). Profile of urinary phenanthrene metabolites in smokers and non-smokers: Biomarkers. Biomarkers, 4 (5), 319-327.

Jacob, J. & Seidel, A. (2002). Biomonitoring of polycyclic aromatic hydrocarbons in human urine. Journal of Chromatography B, 778 (1-2), 31-47.

Mondal, R., Miyaki, N., Becerril, H.A., Norton, J.E., Parmer, J., Mayer, A.C., Tang, M.L., Brédas, J., McGehee, M.D., & Bao, Z. (2009). Synthesis of acenaphthyl and phenanthrene based fused-aromatic thienopyrazine co-polymers for photovoltaic and thin film transistor applications. Chemistry of Materials, 21 (15), 3618-3628.

Nethery, E., Wheeler, A.J., Fisher, M., Sjodin, A., Li, Z., Romanoff, L.C., Foster, W., & Arbuckle, T.E. (2012). Urinary polycyclic aromatic hydrocarbons as a biomarker of exposure to PAHs in air: A pilot study among pregnant women. Journal of Exposure Sciences and Environmental Epidemiology, 22 (1), 70-81.

Rihs, H., Pesch, B., Kappler, M., Rabstein, S., Rossbach, B., Angerer, J., Scherenberg, M., Adams, A., Wilhelm, M., Seidel, A., & Brüning, T. (2005). Occupational exposure to polycyclic aromatic hydrocarbons in German industries: Association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms. Toxicology Letters, 157 (3), 241-255.

Storer, J.S., DeLeon, I., Millikan, L.E., Laseter, J.L., & Griffing, C. (1984). Human absorption of crude coal tar products. Archives of Dermatology, 120 (7), 874-877.

16.8 Pyrene Metabolite

Pyrene is a polycyclic aromatic hydrocarbon (PAH) with four fused benzene rings. Pyrene is used as an intermediate in the synthesis of dyes and fluorescent molecular probes for biomedical research (WHO, 1998).

Pyrene absorption occurs rapidly in the respiratory tract, but more slowly through the gastrointestinal tract and skin (Faust, 1993). After oral administration in rats, pyrene has been found predominantly in the gastrointestinal tract (Mitchell & Tu, 1979). 1-Hydroxypyrene has been identified as the primary metabolite of pyrene (IARC, 2010). In humans, urinary elimination of 1-hydroxypyrene is triphasic with half-lives of 5, 22, and 408 hours (ACGIH, 2005). Monitoring studies of pyrene exposure can measure urinary levels of 1-hydroxypyrene to assess recent and chronic exposures (Becker et al., 2003; CDC, 2009; Hopf et al., 2009; Jongeneelen et al., 1985). Urinary 1-hydroxypyrene may also serve as a useful biomarker for total PAH exposure, given that pyrene is found in most PAH mixtures (Hopf et al., 2009; WHO, 1998).

Subchronic oral exposure to pyrene results in kidney and liver effects in laboratory animals and the liver has been suggested as the main target organ for toxicity (Faust, 1993; TRL, 1989). Pyrene has not been found to be carcinogenic in animals, and the International Agency for Research on Cancer has classified pyrene as Group 3, not classifiable as to its carcinogenicity to humans (IARC, 2010).

1-Hydroxypyrene was measured in the urine of 73 non-smoking, non-occupationally exposed residents (aged 16 to 64 years) living approximately 1 km from an aluminum plant in Baie-Comeau, Quebec. The geometric mean levels ranged from 0.090 to 0.111 µg/g creatinine, compared with 0.048 to 0.077 µg/g creatinine for 71 control individuals living at least 11 km from the plant (Bouchard et al., 2009). Firefighters from Toronto, Ontario, were assessed for their exposure to PAHs from firefighting operations while wearing protective equipment (Caux et al., 2002). Urine was collected from 43 individuals for 20 hours after exposure, and urinary 1-hydroxypyrene levels ranged from <0.043 to 7.00 µg/g creatinine (Caux et al., 2002).

1-Hydroxypyrene was measured in the urine of all Canadian Health Measures Survey cycle 2 (2009-2011) participants aged 3 to 79 years and is presented as both μg/L and μg/g creatinine (Tables 16.8.1.1, 16.8.1.2, 16.8.1.3, and 16.8.1.4). Finding a measurable amount of 1-hydroxypyrene in urine is an indicator of exposure to pyrene and does not necessarily mean that an adverse health effect will occur. These data provide baseline levels for urinary 1-hydroxypyrene in the Canadian population.

16.8.1 1-Hydroxypyrene

4 Data Tables: 16.8.1.1 to 16.8.1.4

References

ACGIH (American Conference of Industrial Hygienists). (2005). Biological exposure indice (BEI): Polycyclic aromatic hydrocarbons (PAHs). ACGIH, Cincinnati, OH.

Becker, K., Schulz, C., Kaus, S., Seiwert, M., & Seifert, B. (2003). German Environmental Survey 1998 (GerES III): Environmental pollutants in the urine of the German population. International Journal of Hygiene and Environmental Health, 206 (1), 15-24.

Bouchard, M., Normandin, L., Gagnon, F., Viau, C., Dumas, P., Gaudreau, É., & Tremblay, C. (2009). Repeated measures of validated and novel biomarkers of exposure to polycyclic aromatic hydrocarbons in individuals living near an aluminum plant in Québec, Canada. Journal of Toxicology and Environmental Health, Part A, 72 (23), 1534-1549.

Caux, C., O'Brien, C., & Viau, C. (2002). Determination of firefighter exposure to polycyclic aromatic hydrocarbons and benzene during fire fighting using measurement of biological indicators. Applied Occupational and Environmental Hygiene, 17 (5), 379-386.

CDC (Centers for Disease Control and Prevention). (2009). Fourth national report on human exposure to environmental chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved July 11, 2011, from www.cdc.gov/exposurereport/

Faust, R.A. (1993). Toxicity summary for pyrene. Oak Ridge Reservation and Environmental Restoration Program, Oak Ridge, TN.

Hopf, N.B., Carreón, T., & Talaska, G. (2009). Biological markers of carcinogenic exposure in the aluminum smelter industry: A systematic review. Journal of Occupational and Environmental Hygiene, 6 (9), 562-581.

IARC (International Agency for Research on Cancer). (2010). IARC monographs on the evaluation of carcinogenic risks to humans - Volume 92: Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. World Health Organization, Lyon.

Jongeneelen, F.J., Anzion, R.B.M., Leijdekkers, C.M., Bos, R.P., & Henderson, P.T. (1985). 1-Hydroxypyrene in human urine after exposure to coal tar and a coal tar derived product. International Archives of Occupational and Environmental Health, 57 (1), 47-55.

Mitchell, C.E. & Tu, K.W. (1979). Distribution, retention, and elimination of pyrene in rats after inhalation. Journal of Toxicology and Environmental Health, 5 (6), 1171-1179.

TRL (Toxicity Research Laboratories). (1989). 13-week Mouse Oral Subchronic Toxicity Study on Pyrene. TRL Study No. 042-012. Toxicity Research Laboratories, Ltd., Muskegon, MI.

WHO (World Health Organization). (1998). Environmental health criteria 202: Selected non-heterocyclic policyclic aromatic hydrocarbons. WHO, Geneva. Retrieved June 11, 2012, from www.inchem.org/documents/ehc/ehc/ehc202.htm

Appendix A: Acronyms and Abbreviations

2,4,5-T
2,4,5-trichlorophenoxyacetic acid
2,4,5-TCP
2,4,5-trichlorophenol
2,4,6-TCP
2,4,6-trichlorophenol
2,4-D
2,4-dichlorophenoxyacetic acid
2,4-DCP
2,4-dichlorophenol
2,5-DCP
2,5-dichlorophenol
3-PBA
3-phenoxybenzoic acid
4-F-3-PBA
4-fluoro-3-phenoxybenzoic acid
AM
atrazine mercapturate
BBP
benzyl butyl phthalate
BPA
bisphenol A
CASRN
Chemical Abstract Services Registry Number
CEPA 1999
Canadian Environmental Protection Act, 1999
CHMS
Canadian Health Measures Survey
CI
confidence interval
cis-DBCA
cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid
cis-DCCA
cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid
CV
coefficient of variation
DACT
diaminochlorotriazine
DnBP
di-n-butyl phthalate
DCHP
dicyclohexyl phthalate
DDT
dichlorodiphenyltrichloroethane
DEA
desethylatrazine
DEDTP
diethyldithiophosphate
DEHP
di-2-ethylhexyl phthalate
DEP
diethyl phthalate
DEP
diethylphosphate
DETP
diethylthiophosphate
DiBP
di-isobutyl phthalate
DiNP
di-isononyl phthalate
DMA
dimethylarsinic acid
DMDTP
dimethyldithiophosphate
DMP
dimethyl phthalate
DMP
dimethylphosphate
DMTP
dimethylthiophosphate
DOP
di-n-octyl phthalate
EDTA
ethylenediaminetetraacetic acid
EPA
United States Environmental Protection Agency
GM
geometric mean
IARC
International Agency for Research on Cancer
ICP-MS
inductively coupled plasma - mass spectrometry
INSPQ
l'Institute national de santé publique du Québec
IOM
Institute of Medicine
LOD
limit of detection
MnBP
mono-n-butyl phthalate
MBzP
mono-benzyl phthalate
MCHP
mono-cyclohexyl phthalate
MCPP
mono-3-carboxypropyl phthalate
MEC
mobile examination centre
MEHHP
mono-(2-ethyl-5-hydroxyhexyl) phthalate
MEHP
mono-2-ethylhexyl phthalate
MEOHP
mono-(2-ethyl-5-oxohexyl) phthalate
MEP
mono-ethyl phthalate
MiBP
mono-isobutyl phthalate
MiNP
mono-isononyl phthalate
MMA
monomethylarsonic acid
MMP
mono-methyl phthalate
MMT
methylcyclopentadienyl manganese tricarbonyl
MOP
mono-n-octyl phthalate
MRM
multiple reaction monitoring
PAH
polycyclic aromatic hydrocarbon
PCP
pentachlorophenol
PFAS
perfluoroalky substance
PFBA
perfluorobutanoic acid
PFBS
perfluorobutane sulfonate
PFDA
perfluorodecanoic acid
PFHxA
perfluorohexanoic acid
PFHxS
perfluorohexane sulfonate
PFNA
perfluorononanoic acid
PFOA
perfluorooctanoic acid
PFOS
perfluorooctane sulfonate
PFUnDA
perfluoroundecanoic acid
PMRA
Pest Management Regulatory Agency
PVC
polyvinyl chloride
S-PMA
S-phenylmercapturic acid
t,t-MA
trans,trans-muconic acid
trans-DCCA
trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid
UNEP
United Nations Environment Programme
UPLC
ultra performance liquid chromatography

Appendix B: Limits of Detection

Laboratory analyses of environmental chemicals and creatinine were performed at the human toxicology laboratory of the Institut national de santé publique du Québec (INSPQ), Québec. INSPQ followed standardized operating procedures that were developed for every assay and technique performed in its laboratory. The laboratory is accredited under ISO 17025. For this report, the limit of detection (LOD) is defined as the minimum concentration of the chemical that is greater than zero and is measured and reported at 99% statistical confidence level. It is estimated based on the United States Environmental Protection Agency protocol (EPA 40 CFR 136).

Limits of Detection
  Cycle 1 Cycle 2

Table 6 footnotes

Table 6 footnote 1

LODs for cycle 1 have been updated from those reported in the first Report on Human Biomonitoring of Environmental Chemicals in Canada.

Return to table 6 footnote a referrer

Metals and Trace Elements in Blood
Cadmium 0.04 µg/L 0.04 µg/L
Cobalt - 0.04 µg/L
Copper 0.6 µg/L 20 µg/L
Lead 0.02 µg/dL 0.1 µg/dL
Manganese 0.05 µg/L 0.5 µg/L
Mercury 0.1 µg/L 0.1 µg/L
Molybdenum 0.1 µg/L 0.1 µg/L
Nickel 0.4 µg/L 0.3 µg/L
Selenium 8 µg/L 20 µg/L
Silver - 0.05 µg/L
Uranium 0.005 µg/L 0.007 µg/L
Zinc 0.0007 mg/L 0.1 mg/L
Metals and Trace Elements in Urine
Antimony 0.02 µg/L 0.02 µg/L
Arsenic, total 0.5 µg/L 0.7 µg/L
Arsenite - 1 µg/L
Arsenate - 1 µg/L
MMA - 1 µg/L
DMA - 1 µg/L
Arsenocholine and arsenobetaine - 2 µg/L
Cadmium 0.09 µg/L 0.07 µg/L
Cesium - 0.1 µg/L
Cobalt - 0.06 µg/L
Copper 0.3 µg/L 0.6 µg/L
Fluoride - 20 µg/L
Lead 0.1 µg/L 0.2 µg/L
Manganese 0.05 µg/L 0.2 µg/L
Molybdenum 0.1 µg/L 1 µg/L
Nickel 0.2 µg/L 0.3 µg/L
Selenium 6 µg/L 4 µg/L
Silver - 0.1 µg/L
Thallium - 0.02 µg/L
Tungsten - 0.2 µg/L
Uranium 0.01 µg/L 0.01 µg/L
Vanadium 0.1 µg/L 0.1 µg/L
Zinc 10 µg/L 10 µg/L
Benzene Metabolites
Phenol - 0.1 mg/L
trans,trans-Muconic acid - 0.8 µg/L
S-Phenylmercapturic acid - 0.08 µg/L
Chlorophenols
2,4-DCP 0.3 µg/L 0.3 µg/L
2,5-DCP - 0.3 µg/L
2,4,5-TCP - 0.5 µg/L
2,4,6-TCP - 1 µg/L
PCP - 0.7 µg/L
Environmental Phenols and Triclocarban
Bisphenol A 0.2 µg/L 0.2 µg/L
Triclocarban - 1 µg/L
Triclosan - 3 µg/L
Nicotine Metabolite
Cotinine 1 µg/L 1 µg/L
Perfluoroalkyl Substances
PFBA - 0.5 µg/L
PFHxA - 0.1 µg/L
PFOA 0.3 µg/L 0.1 µg/L
PFNA - 0.2 µg/L
PFDA - 0.1 µg/L
PFUnDA - 0.09 µg/L
PFBS - 0.4 µg/L
PFHxS 0.3 µg/L 0.2 µg/L
PFOS 0.3 µg/L 0.3 µg/L
Pesticides
Atrazine Metabolites
AM - 0.03 µg/L
DACT - 1 µg/L
DEA - 0.2 µg/L
Carbamate Metabolites
Carbofuranphenol - 0.1 µg/L[KW1]
2-Isopropoxyphenol - 0.05 µg/L
2,4-Dichlorophenoxyacetic Acid
2,4-D 0.2 µg/L 0.2 µg/L
Organophosphate MetabolitesTable 1 footnote a
DMP 0.8 µg/L 1 µg/L
DMTP 0.6 µg/L 0.6 µg/L
DMDTP 0.09 µg/L 0.3 µg/L
DEP 0.5 µg/L 1 µg/L
DETP 0.08 µg/L 0.3 µg/L
DEDTP 0.06 µg/L 0.3 µg/L
Pyrethroid Metabolites
4-F-3-PBA 0.008 µg/L 0.008 µg/L
cis-DBCA 0.006 µg/L 0.006 µg/L
cis-DCCA 0.007 µg/L 0.007 µg/L
trans-DCCA 0.01 µg/L 0.01 µg/L
3-PBA 0.01 µg/L 0.01 µg/L
Phthalate Metabolites
MBzP 0.2 µg/L 0.05 µg/L
MnBP 0.2 µg/L 0.2 µg/L
MCHP 0.2 µg/L 0.09 µg/L
MEP 0.5 µg/L 0.3 µg/L
MiBP - 0.1 µg/L
MiNP 0.4 µg/L 0.3 µg/L
MMP 5 µg/L 5 µg/L
MOP 0.7 µg/L 0.3 µg/L
MCPP 0.2 µg/L 0.06 µg/L
MEHP 0.2 µg/L 0.08 µg/L
MEOHP 0.2 µg/L 0.1 µg/L
MEHHP 0.4 µg/L 0.4 µg/L
Polycyclic Aromatic Hydrocarbon Metabolites
Benzo[a]pyrene Metabolite
3-HydroxyBenzo[a]pyrene - 0.002 µg/L
Chrysene Metabolites
2-Hydroxychrysene - 0.004 µg/L
3-Hydroxychrysene - 0.003 µg/L
4-Hydroxychrysene - 0.003 µg/L
6-Hydroxychrysene - 0.006 µg/L
Fluoranthene Metabolite
3-Hydroxyfluoranthene - 0.008 µg/L
Fluorene Metabolites
2-Hydroxyfluorene - 0.003 µg/L
3-Hydroxyfluorene - 0.001 µg/L
9-Hydroxyfluorene - 0.003 µg/L
Naphthalene Metabolites
1-Hydroxynapththalene - 0.1 µg/L
2-Hydroxynapththalene - 0.05 µg/L
Phenanthrene Metabolites
1-Hydroxyphenanthrene - 0.005 µg/L
2-Hydroxyphenanthrene - 0.003 µg/L
3-Hydroxyphenanthrene - 0.003 µg/L
4-Hydroxyphenanthrene - 0.001 µg/L
9-Hydroxyphenanthrene - 0.004 µg/L
Pyrene Metabolite
1-Hydroxypyrene - 0.002 µg/L
Adjustment Factors
Creatinine 0.3 mmol/L
(4 mg/dL)
0.4 mmol/L
(5 mg/dL)

Appendix C: Conversion Factors

Units of measurement are important. Results are reported here using standard units; however, units can be converted using the conversion factors presented below for comparison of data with other data sets.

Definition of Units
Unit Abbreviation Value
litre L -
decilitre dL 10-1 L
millilitre mL 10-3 L
microlitre µL 10-6 L
gram g -
milligram mg 10-3 g
microgram µg 10-6 g
nanogram ng 10-9 g
picogram pg 10-12 g

Data can be converted from µg/L to µmol/L using the molecular weight (MW) of the chemical using the formula:

X µmol/L = X µg/L x conversion factor (CF), where the CF is equivalent to 1/MW.

Conversion Factors
  MW
(g/mol)
CF
(µg/L ? µmol/L)

Table 1 footnotes

Table 1 footnote 1

Lead CF from µg/dL → µmol/L

Return to table 1 footnote a referrer

Table 1 footnote 2

Zinc CF from mg/L → µmol/L

Return to table 1 footnote b referrer

Table 1 footnote 3

Phenol CF from mg/L → µmol/L

Return to table 1 footnote c referrer

Table 1 footnote 4

Creatinine CF from mg/L→µmol/L

Return to table 1 footnote d referrer

Metals and Trace Elements
Antimony 121.76 0.00821
Arsenic 74.92 0.01335
Arsenite 125.94 0.00794
Arsenate 141.94 0.00705
MMA 139.97 0.00714
DMA 138.00 0.00725
Arsenocholine and arsenobetaine 178.06 0.00562
Cadmium 112.41 0.00890
Cesium 132.91 0.00752
Cobalt 58.93 0. 017
Copper 63.55 0.01574
Fluoride 19.00 0.0526
Lead - blood 207.20 0.0483Table 1 footnote a
Lead - urine 0.00483
Manganese 54.94 0.0182
Mercury 200.59 0.00499
Molybdenum 95.94 0.0104
Nickel 58.69 0.017
Selenium 78.96 0.012 7
Silver 107.87 0.00927
Thallium 204.38 0.00489
Tungsten 183.84 0.00544
Uranium 238.03 0.0042
Vanadium 50.94 0.0196
Zinc - blood 65.39 15.3 Table 1 footnote b
Zinc - urine 0.0153
Benzene Metabolites
Phenol 94.11 10.6Table 1 footnote c
trans,trans-Muconic acid 142.11 0.00704
S-phenylmercapturic acid 239.29 0.00418
Chlorophenols
2,4-DCP 163.00 0.00613
2,5-DCP 163.00 0.00613
2,4,5-TCP 197.45 0.00506
2,4,6-TCP 197.45 0.00506
PCP 266.34 0.00375
Environmental Phenols and Triclocarban
Bisphenol A 228.29 0.00438
Triclocarban 315.58 0.00317
Triclosan 289.54 0.00345
Nicotine Metabolite
Cotinine 176.22 0.00567
Perfluoroalkyl Substances
PFBA 214.04 0.00467
PFHxA 314.05 0.00318
PFOA 414.07 0.00242
PFNA 464.08 0.00215
PFDA 514.08 0.00195
PFUnDA 564.09 0.00177
PFBS 300.10 0.00333
PFHxS 400.11 0.00250
PFOS 500.13 0.00200
Pesticides
Atrazine Metabolites
AM 342.42 0.00292
DACT 145.55 0.00687
DEA 187.63 0.00533
Carbamate Metabolites
Carbofuranphenol 164.20 0.00609
2-Isopropoxyphenol 152.19 0.00657
2,4-Dichlorophenoxyacetic Acid
2,4-D 221.04 0.00452
Organophosphate Metabolites
DMP 126.05 0.00793
DMTP 142.11 0.00704
DMDTP 158.18 0.00632
DEP 154.10 0.00649
DETP 170.17 0.00588
DEDTP 186.24 0.00537
Pyrethroid Metabolites
4-F-3-PBA 232.21 0.00431
cis-DBCA 297.97 0.00336
cis-DCCA 209.07 0.00478
trans-DCCA 209.07 0.00478
3-PBA 214.22 0.00467
Phthalate Metabolites 
MBzP 256.25 0.00390
MnBP 222.24 0.00450
MCHP 248.27 0.00403
MEP 194.18 0.00515
MiBP 222.24 0.00450
MiNP 292.37 0.00342
MMP 180.16 0.00555
MOP 278.34 0.00359
MCPP 252.22 0.00396
MEHP 278.34 0.00359
MEOHP 292.33 0.00342
MEHHP 294.34 0.00340
Polycyclic Aromatic Hydrocarbon Metabolites
Benzo[a]pyrene Metabolite
3-HydroxyBenzo[a]pyrene 268.31 0.00373
Chrysene Metabolites
2-Hydroxychrysene 244.29 0.00409
3-Hydroxychrysene 244.29 0.00409
4-Hydroxychrysene 244.29 0.00409
6-Hydroxychrysene 244.29 0.00409
Fluoranthene Metabolite
3-Hydroxyfluoranthene 218.25 0.00458
Fluorene Metabolites
2-Hydroxyfluorene 182.22 0.00549
3-Hydroxyfluorene 182.22 0.00549
9-Hydroxyfluorene 182.22 0.00549
Naphthalene Metabolites
1-Hydroxynapththalene 144.17 0.00694
2-Hydroxynapththalene 144.17 0.00694
Phenanthrene Metabolites
1-Hydroxyphenanthrene 194.23 0.00515
2-Hydroxyphenanthrene 194.23 0.00515
3-Hydroxyphenanthrene 194.23 0.00515
4-Hydroxyphenanthrene 194.23 0.00515
9-Hydroxyphenanthrene 194.23 0.00515
Pyrene Metabolite
1-Hydroxypyrene 218.25 0.00458
Adjustment Factors
Creatinine 113.18 88.4d

Appendix D: Creatinine

2 Data Tables: D Creatinine (C1) - (C2)