O. Agboola, MSc1, M. Gully, MSc1, T. Wong, MD, FRCPC1, U. Auguste, MD, MSc2, M. Lem, MD, MHSc, FRCPC2, and T. Mersereau, MSc, BScN2
1 Community Acquired Infections Division, CIDPC, Public Health Agency of Canada, Ottawa, ON
2 Communicable Disease Control Division, FNIHB, Health Canada, Ottawa, ON
OBJECTIVES: To describe the epidemiology of sexually transmitted infections and sexual risk behaviours among Aboriginal Street Youth (SY) population in selected cities across Canada.
DESIGN: The Enhanced Surveillance of Canadian Street Youth (E-SYS) is a repeated cross-sectional survey carried out in 1999, 2001 and 2003. SY aged 15-24 years inclusive, who had spent at least three consecutive nights away from home, were recruited in seven cities across Canada. Information was collected in a nurse-administered questionnaire; blood and/or urine samples were also collected for STIs/HIV testing.
RESULTS: 1656 SY were recruited in 2003; 601 (36.3%) were Aboriginal youth. Of these 601, 60% were male and 40% were female; the average age was 19 years with 59% younger (15-19 years) and 41% older (20-24 years) youth.
The prevalence rates of STIs were significantly higher in Aboriginal SY than in general population youth of the same age range - chlamydia (14% vs. <1%), gonorrhoea (4.7% vs.0.09%) and infectious syphilis (0.4 vs. <.01%).
Approximately half (50%) reported not using any form of protection at their last sexual encounter. The average number of sex partners in the past three months was 4; most reported high-risk partners who trade sex (10%), are injected drug users (9%), and were high on drugs during sex (40%). Compared with non-Aboriginal SY, more Aboriginal SY reported having traded sex ever (24% vs. 22.6%), and in the past 3 months (41.3% vs.35.6%).
CONCLUSIONS: High-risk behaviours are common among SY and increase the risk of contracting and transmitting STIs. These findings show that there is an urgent need to develop intensive and long-term services that provide alternatives to the sex trade as means of meeting economic needs among the Aboriginal SY population. Knowing the factors that put SY at risk for STIs/HIV is imperative in identifying areas for intervention and establishing harm reduction measures.
R. Aranda-Rodriguez1, B. Koudjonou1, C. Kubwabo1, B. Jay1, B. Stewart1, and J. Harvie1
1 Chemistry Research Division, Environmental Health Science Bureau, Health Canada, Ottawa, ON
OBJECTIVES: Health Canada has been conducting research studies focussing on disinfection by-products (DBPs) produced by drinking water (DW) treatment plants across Canada. Research focuses on method development, stability of compounds, seasonal and spatial variations in the distribution systems.
DESIGN: Five methods have been developed at the Chemistry Research Division (CRD) to include up to 40 drinking water contaminants. Surveys have been conducted at various drinking water facilities using different source waters and purification strategies to gather information on the occurrence of DPBs in the distribution systems.
OUTPUTS/RESULTS
Neutral-extractable DBPs: The consolidated approach developed at the CRD (derived from US EPA 551.1 method) allows for the determination of 25 target compounds including trihalomethanes (THMs), haloacetonitriles (HAN), haloacetaldehydes (HAs), halonitromethanes (HNMs).
THMs: Findings -from surveys, in-house and inter-laboratory studies- support the need to standardize sample collection procedures for THM analysis. For some systems, the Purge-and-Trap technique overestimates THMs, partly due to conversion of some DBPs.
HAs highly contribute to the pool of DBPs (HA/THM: 10-45% w/w) and may degrade to corresponding THMs at typical DW conditions.
HNMs are stable in water at our sampling conditions (pH 4.5, 4°C); however, brominated HNMs readily degrade to less brominated HNMs.
Acid-extractable DBPs: Haloacetic acids. The method developed for HAA allows the detection of eight haloacetic acids. Tribromoacetic acid is unstable in water and was not found in Canadian DW. In general, HAAs contributes more than THMs to the DBPs.
Other DBPs
n-Nitrosodimethylamine (NDMA): The method adapted at the CRD allows the detection of NDMA at 0.5 ng/L. Levels lower than 2.5 ng/L (below the Ontario Drinking Water Objective, 9 ng/L) were found in selected samples collected in 2005.
Mutagen X (MX) or 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone. The method adapted at the CRD allows the detection of MX at 7.7 ng/L. A pilot study conducted in the Ottawa region revealed the presence of MX in DW samples at an average concentration of 31.1 ng/L.
IMPACTS/OUTCOMES/CONCLUSION: The CRD research findings have been instrumental in the derivation of drinking water DBPs guidelines. In the new Canadian Guideline for Drinking Water, released in May 2006, the maximum acceptable concentration for THMs is set at 0.1 mg/L, including 0.016 mg/L for bromodichloromethane. The guidelines for chloral hydrate and haloacetic acids are in preparation.
K. Basu1
1 Microsimulation Modelling and Data Analysis, Applied Research and Analysis Directorate, HPB, Health Canada, Ottawa, ON
OBJECTIVE: To analyze the characteristics of family physicians (FPs) offering home visits and the circumstances of their patients.
DESIGN: The physicians' supply of services is modeled using a negative binomial regression where the number of home visits is the dependent variable and physician's age groups, practice settings, sex, and payment modes are the independent variables.
For the purpose of analyzing the patients who required home visits, we estimated a Logit Model where home visit (yes/no) is considered as a dependent variable and the dummies for age group, sex, location (rural/urban), the most responsible diagnosis, and years as the explanatory variables.
OUTPUTS/RESULTS: The study shows that 10% of the FPs provide over 50% of the total home visit services. Patients who received home visits are predominantly elderly female living in the rural areas with terminal or chronic diseases. Services in the rural areas have a higher likelihood of receiving a home visit. The physicians who made home visits are more likely to be male, older, under fee-for-service pay mode, and in solo practice setting.
IMPACTS/OUTCOMES/CONCLUSIONS: The FP home visit is drawing more attention today as a complement to home care services. In the first four decades of the twentieth century, home visits by physicians were more commonplace. Over time, the introduction of technology, the growth of third party payers, the intrusiveness of treatments in general, favoured the controlled context of office based or hospital care. However, there is still a large number of home visits needed by patients who are likely to be old and suffering from severe chronic diseases and unable to go to the FP office on their own.
Integration of home care and primary care should be considered by policy makers.
X.-L. Cao1, V. Casey1, B. Tague1, S. Seaman1, and A. Becalski1
1 Food Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: To investigate: 1) the levels of benzene in beverages containing benzoate salts on the Canadian market; and, 2) the formation of benzene from the possible precursors - benzoate salts and ascorbic acid.
DESIGN: Beverage samples spanned a wide range of domestic and imported products and consisted of carbonated and non-carbonated drinks, cocktail mixes, low alcohol (0.5% alcohol vol.) drinks, sports/energy drinks and which were packaged in a variety of glass, plastic and aluminum containers. The majority of the drinks were selected because benzoate salt and/or ascorbic acid were listed on their product labels. A few cranberry drink products were also included since they are known to contain benzoic acid as a natural constituent.
A simple and rugged method based on isotope dilution headspace gas chromatography-mass spectrometry (GC-MS) in a selected ion monitoring (SIM) mode was developed. Model experiments on solutions containing benzoate and ascorbic acid were performed. Formation of benzene in soft drink products under extreme environmental conditions during transportation and storage was also investigated.
OUTPUTS/RESULTS: Of the 124 soft drink products tested (samples of two products were purchased in two different lots), more than 80% did not contain benzene or its levels were below method reporting limit of 1 μg/L. There were six products (< 5%) with benzene levels close to or above the Canadian maximum contaminant level (MCL) of 5 μg/L for benzene in drinking water, and four products (~3%) with benzene levels close to or above the World Health Organization (WHO) guideline for benzene in drinking water (10 μg/L). The highest concentration of benzene, 23 μg/L, was found in a soft drink product for children. The formation of benzene from precursors was positively correlated with temperature in model reactions.
IMPACTS/OUTCOMES/CONCLUSIONS: Our findings were disseminated to manufacturers and stakeholders, to assist in reformulations of products to avoid excessive formation of benzene and to confirm the effectiveness of their mitigation strategies.
J. Bertinato, PhD1, E. Swist1, and M.R. L'Abbé, PhD1
1 Nutrition Research Division, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Marginal copper (Cu) deficiency from consuming diets low in copper or high in zinc (Zn) (zinc reduces copper absorption) may be more prevalent than previously thought. A better understanding of the intracellular trafficking of copper is necessary to accurately assess health risks associated with marginal copper deficiency and set precise Dietary Reference Intakes for copper and zinc. To date, a number of copper transporters and chaperones have been shown to play important roles in maintaining copper balance within cells when copper is in excess or scarce. The primary objective of this study was to begin to elucidate the function of human copper transporter 2 (Ctr2).
DESIGN: Ctr2 expression in rat and human tissues was determined by Western blot. Human Ctr2 was expressed in COS-7 cells (monkey kidney) as a green fluorescent protein (GFP) fusion protein (GFP-Ctr2) by transient transfection. GFP-Ctr2 localization was determined by direct fluorescence in live cells. Copper content and copper chaperone for Cu/Zn superoxide dismutase (CCS) expression in GFP or GFP-Ctr2 expressing cells was determined by graphite furnace atomic absorption spectrometry and Western blot, respectively.
OUTPUTS/RESULTS: In rat tissues, Ctr2 was abundantly expressed in placenta and heart, while in human tissues Ctr2 was highly expressed in ovary, pancreas, small intestine and heart. GFP-Ctr2 localized to the membrane of large vesicles reminiscent of vacuoles. Cos-7 cells expressing GFP-Ctr2 accumulated 2-3-fold more copper than cells transfected to express GFP alone. Increased copper content in GFP-Ctr2 expressing cells was inversely correlated with CCS expression level.
IMPACT/OUTCOMES/CONCLUSIONS: Together, these data suggest that Ctr2 activity influences cellular copper levels in COS-7 cells and Ctr2 functions to deliver copper to CCS. These are the first data demonstrating a role for Ctr2 in copper trafficking in mammalian cells.
G. Bondy, PhD1, I. Curran, PhD1, L. Coady1, C. Armstrong1, M. Parenteau2, M. Barker, DVM, MSc1, V. Liston1, L. Hierlihy1, and J. Shenton, PhD1
1 Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, ON
2 Animal Resources Division, Food Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Perfluorooctanesulfonate (PFOS) has numerous industrial applications and is widely disseminated in the environment. Although the structurally related contaminant perfluorooctanoic acid (PFOA) has been shown to be immunomodulatory in laboratory animals, similar studies have not been conducted with PFOS. To address this gap, rats were exposed to PFOS in feed and changes in immune parameters were assessed.
DESIGN: Rats were exposed to PFOS for 28 days at levels ranging from 2 to100 mg/kg in feed. The following endpoints were measured post-necropsy: spleen and thymus weights, blood lymphocyte phenotype, total immunoglobulins, spleen lymphocyte proliferation, histopathology of immune tissues.
RESULTS: At the highest PFOS dose, thymus weights were lower in male and female rats and spleen weights were lower in female rats. In male rats, circulating T and Thelper (TH) lymphocytes (expressed as % of total lymphocytes) increased with dose, while % B lymphocytes decreased. In female rats total white blood cell numbers were elevated along with elevated total T, TH and TSuppressor (TS) cells; % T and TH lymphocytes increased and % B lymphocytes decreased with increasing PFOS in diet. Lymphocyte proliferative responses to the T cell mitogen Con A and the B cell mitogen LPS were not altered. Serum IgG levels were elevated in male rats, while serum IgM levels were elevated in females. Increased incidence of thymic lymphocyte apoptosis was more prevalent in male than female rats in the highest PFOS dose group.
CONCLUSIONS: While splenic and thymic atrophy and decreased B lymphocytes in PFOS-treated rats were indicative of immunosuppression, elevated T lymphocytes and increased serum immunoglobulins were indicative of immunostimulation. To determine the functional significance of these changes, an immune challenge assay has recently been completed to assess the effects of PFOS on cellular and immune responses to keyhole limpet hemocyanin. When analyses are completed, these studies will indicate whether human exposure to PFOS may influence immune function. In the longer term, the data will contribute to hazard assessments for PFOS in foods and other matrices.
R.M. Wilson, MSc1, S. Petrovic, MSc2, and O. Bose3
1 SNC-Lavalin Morrow Environmental, Burnaby, BC
2 Contaminated Sites Division, HECSB, Health Canada, Burnaby, BC
3 Safe Environments Programme, HECSB, Health Canada, Edmonton, AB
OBJECTIVES: Human health risk assessment (HHRA) of chemicals in air presents separate challenges as opposed to the assessment of chemicals in food, water, soil and other sources. Consequently, an approach for HHRA of chemicals in air is developed according to Health Canada policy. This air quality HHRA approach will provide guidance for new developments or risk management/remediation for contaminated sites under federal jurisdiction in Canada. In addition, the purpose of this project is to develop screening level air concentrations for the protection of human health for a list of chemicals composed in Health Canada's Federal Contaminated Site Risk Assessment in Canada (2004) Part II Guidance.
DESIGN: The risk assessment approach used to achieve the objectives of this project is primarily based on the standard Preliminary Quantitative Risk Assessment (PQRA) approach described by Health Canada (2004) for contaminated sites but modified for assessment of chemicals in air. The steps that are used to develop Air Screening Concentrations for the protection of human health include:
OUTPUTS/RESULTS: Screening level air concentrations for the protection of human health are developed for 95 chemicals. Information on key issues and methods related to guidance on HHRA of chemicals in air are also provided.
IMPACTS/OUTCOMES/CONCLUSIONS: The guidance for information developed through this project should help standardize air quality assessments for federal sites through prescribing standard exposure pathways, receptor characteristics, toxicological reference values, and other parameters required to quantitatively assess the potential chemical exposures and risks from chemicals that may occur in air. It will also help to ensure all relevant data are presented in air quality HHRA reports.
D. Breznan, MSc1,2, V. Chauhan, PhD1,3, P. Goegan, MSc1, J.R. Brook, PhD4, and R. Vincent, PhD1,2
1 Inhalation Toxicology and Aerobiology Section, HECSB, Health Canada, Ottawa, ON
2 University of Ottawa, Faculty of Medicine, Department of BMI, Ottawa, ON
3 Consumer and Clinical Radiation Protection Bureau, HECSB, Health Canada, Ottawa, ON
4 Atmospheric Environment Service, Environment Canada, Downsview, ON
OBJECTIVES: To examine the effects of respirable particles on the respiratory burst of primary rat alveolar macrophages.
DESIGN: Alveolar macrophages were isolated from rat lungs by bronchoalveolar lavage and incubated (2h) with aqueous suspensions of urban particles (Ottawa, EHC-93; St-Louis, SRM-1648; Washington, SRM-1649), fine PM2.5 (southern Ontario, VERP), minerals (titanium dioxide, silicon dioxide) and metals [iron(III)oxide, iron (II/III)oxide, nickel(II)oxide, copper(II)oxide]. The cells were stimulated with phorbol 12-myristate 13-acetate (PMA, 40 minutes), yeast cell fragments (zymosan, 5 hours), or bacterial cell wall lipopolysaccharide (S. typhimurium) plus interferon-gamma (LPS+IFN, 5 hours). The respiratory burst during exposure to particles and during stimulation was determined from luminol-enhanced chemiluminescence.
RESULTS: EHC-93 and silicone dioxide initiated a respiratory burst, while VERP and the soluble fraction of EHC-93 (EHC-93sol) decreased baseline production of reactive oxygen species. Overall, pre-exposure of the macrophages to particles suppressed the respiratory burst induced by PMA, zymosan, or LPS+IFN. VERP, EHC-93sol and metals including iron oxides and copper(II)oxide were potent suppressors of the effects of the burst inducers. Using the XTT reduction assay, concentration-dependent decreases in cell viability were detected in cells exposed to the urban particles and to most metals, copper(II)oxide being most toxic. VERP and EHC-93sol had no effect on cell viability despite their pronounced effect on the respiratory burst. Inhibition by particles of the respiratory burst in response to agents that mimic pathogens indicates that the effect is not through direct cytotoxicity of the particles.
CONCLUSIONS: Macrophages undergo a differential respiratory burst upon exposure to respirable particles of varying composition and origin, illustrating a role for the physico-chemical characteristics of particles as modulators of the respiratory burst in primary rat alveolar macrophages. Subsequent challenge of the cells with compounds that mimic contact with pathogens reveals that particles can compromise the functional integrity of the cells, rendering them potentially less competent with respect to microbial clearance. This provides an insight into potential detrimental effects of particles to human health due to perturbation of normal immune responses, for example in individuals undergoing infection.
V. Chauhan, PhD1, A. Mariampillai, BSc1, G.B. Gajda, PhD1, A. Thansandote, PhD1, and J.P. McNamee, PhD1
1 Consumer and Clinical Radiation Protection, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: With the rapid expansion of mobile telephones, the possible health risks of exposure to radiofrequency (RF) fields has become a great public concern. Although the majority of the research conducted to date suggests that mobile phones pose no risk towards carcinogenesis, there are still concerns that RF field exposure may induce stress responses and alter cellular functions. Several studies involving either animals or cell cultures have reported no biological consequences attributable to RF fields. The current study was undertaken to evaluate gene expression changes in three human immune cell-lines following RF field exposure.
DESIGN: HL-60, TK6 and Mono-Mac-6 (MM6) cells were exposed to intermittent (5 minutes on, 10 minutes off) 1.9 GHz pulse-modulated RF fields at average specific absorption rates (SARs) of 1 and 10 W/kg at 37 ± 0.5°C for 6 hours. Concurrent negative and positive (heat-shock for 1 hour at 43°C) controls were conducted with each experiment. Immediately following RF field exposure (T=6 hours) and 18 hours post-exposure (T=24 hours), cell pellets were collected from each of the culture dishes and analyzed for transcript levels of proto-oncogenes (c-jun, c-myc and c-fos) and the stress-related genes (heat shock proteins (HSP) HSP27 and HSP70B) by quantitative RT-PCR.
RESULTS: No significant effects were observed in mRNA expression of HSP27, HSP70, c-jun, c-myc or c-fos between the sham and RF-exposed groups, in either of the two cell-lines at either 6 hours or 18 hours post-exposure. However, the positive control group displayed a significant elevation in the expression of HSP27, HSP70, c-fos and c-jun in both cell-lines at T=6 hours and 24 hours, relative to the sham and negative control groups.
CONCLUSIONS: This study found no evidence that exposure of cells to non-thermalizing levels1.9 GHz pulse-modulated RF fields can cause any detectable change in stress-related gene expression. This knowledge will strengthen the scientific justification for risk assessment decisions for existing and future Health Canada radiation safety guidelines.
J. Chen, PhD1, B.L. Tracy, PhD1, and D. Moir, PhD1
1 Radiation Protection Bureau, HECSB, Health Canada, Ottawa, ON
OBJECTIVE: Recent studies on the link between lung cancer and residential exposure to radon gas have lead Health Canada to recommend that the Canadian radon guideline for dwellings be lowered from 800 to 200 Bq/m3. This project seeks to development a set of radon maps of Canada for effective communication of radon risk.
DESIGN: All available measurements of radon in homes and public buildings are being combined through GIS software to develop maps of varying scales and levels of detail to address the needs of a national radon program. Other types of data (e.g., geological formations, soil types, and aerial radiation surveys) are being utilized to fill in blank spaces in the maps.
OUTPUTS/RESULTS: The following maps have already been produced:
IMPACTS/OUTCOMES/CONCLUSIONS: These maps will aid government planners in deciding where to focus resources in a nation-wide radon testing and mitigation program. They will also serve as a guide to homeowners on the likelihood of a radon hazard in their locality and on the degree of importance they should assign to radon testing of their homes.
G. Coleman, BSc1, P.S. Shwed, PhD1, A.F. Tayabali, PhD1, G. Arvanitakis, BSc2, D. Johnston, PhD2, and V.L. Seligy, PhD1
1 Safe Environments Program, HECSB, Health Canada, Ottawa, ON
2 Product Safety Program, HECSB, Health Canada, Ottawa, ON
OBJECTIVE: The Domestic Substance List (DSL) of the Canadian Environmental Protection Act (CEPA 1999) includes micro-organisms (MOs) which are considered "existing" and therefore do not require notification and assessment before manufacturing or importing into Canada. Because many DSL MOs have not undergone a screening-level risk assessment (SLRA), and in several cases even lack details about their identity and virulence potential, we have characterized them for key traits deemed to be important for input into risk assessment models and monitoring their release.
DESIGN: Only DSL bacteria available from the American Type Culture Collection (ATCC) were tested. Replica tests on them included: purity and taxon assignment by colony and cell type morphology and Gram staining, fatty acid methyl ester (FAME) profiling by MIDI-Sherlock Microbial Identification system (Agilent Technology), and screens for expression of enterotoxin, hemolysin-cytotoxin-like activity using mammalian cells, and resistance to antibiotics (10 classes), and growth preference for mammalian cell physiologic conditions.
RESULTS: Cytotoxic, enterotoxic, and hemolytic assays identified the same DSL MOs, enabling a ranking of 'toxic' potential relative to Bacillus cereus14579. A FAME library was developed and refined using DSL strains grown on clinical and environmental selection media to link data with proprietary databases (MIDI). Power to resolve identity, heterogeneity (in some DSL MOs) and virulence hierarchy of strains was further enhanced by linking to MIC antibiotic data and multi-variate analysis. Only DSL B.cereus14579 and Bt13367 killed mucosal cells (HT29) and macrophage cells (J774A.1). However, the latter exhibited normal phagocytic and killing activity with all other DSL MOs.
CONCLUSIONS/IMPLICATIONS: The multi-indicator screen provides a comprehensive package of data for SLRA of 19, ATCC available DSL bacteria. Only a few merit the highest priority for further assessment by in vivo tests. However, some others need further investigation because they elicit unusual responses in our immune cell model.
J. Crosthwait, BSc1, P.S. Shwed, PhD1, A.F. Tayabali, PhD1, and V.L. Seligy, PhD1
1 Safe Environments Program, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: Bacillus thuringiensis (Bt) is considered a genetic member of a group containing B. cereus (Bc) and B. anthracis (Ba). We are characterizing Bt strains of biotechnology interest using microarray-based technology and have detected by DNA hybridization several virulence factors characteristic of Bc or Ba strains. The current study involves the validation of these observations by isolating and cloning different virulence genes, in particular hemolysins, and characterizing their expression in Bt commercial products derived from Bt israelensis (Bti) and Bt kurstaki (Btk) strains.
DESIGN: Microarray hybridizations of Bs, Bc, Bti and Btk genomic DNAs were performed on oligonucleotide arrays designed from the B. anthracis A2012 genome and validated with those from Bc14579. PCR primers to screen Bt strains were for Bc genes [hemolysin II (hlyII) and hemolysin BL (hbl) enterotoxin operon (hblA, hblC, hblD)]. Amplified products were cloned into plasmid vectors for sequencing and expression. To identify other potential virulence genes, genomic libraries were made using Bti and Btk. Blood agar plates were used to screen for hemolytic activity in all clones.
RESULTS: Putative sequences for different classes of virulence factors, including several different hemolysins, lipases and toxins were identified by scoring Bti and Btk microarrays. PCR amplification from Bti and Btk showed that the Bc hblA-hblC-hblD operon is conserved on a 5.7kb amplicon and nucleotide sequencing evidence indicated >97% identity. An amplicon of 1.7kb, homologous to Bc hlyII was also obtained from Bti. When cloned into E. coli, transformants showed hemolytic activity.
OUTCOMES: The identification of Bt virulence factors related to Bc and Ba, by functional cloning (hemolytic expression), enables analysis of virulence genes and their elimination in new commercial Bt strains. Also, the build of antibody-based probes will allow for rapid screening and quantification of toxicity/pathogenicity potential of these and other related microbes and their by-products, including new commercial formulations.
I. Curran, PhD1, G. Bondy, PhD1, V. Liston1, L. Hierlihy1, L. Coady1, and S. Gurofsky1
1 Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Perfluorooctanesulfonate is a widely disseminated environmental contaminant due to its usage in commercial fluorochemical applications. Analyses of wildlife at different trophic levels of the food chain indicate that PFOS is bioaccumulative. PFOS is the dominant fluorochemical compound found to bioaccumulate in northern biota. To address potential health effects, rats were exposed to PFOS in feed and clinical and toxicological endpoints were monitored and assessed.
DESIGN: Male and female rats were exposed for 28 days to PFOS in feed ranging from 2 to 100 mg/kg feed. The following endpoints were measured post-necropsy: weights of liver, kidney, brain, thymus, spleen, adrenals, heart and in males testes; histopathology of liver, kidney, brain and heart; 26 clinical chemistry endpoints were performed on serum and basic hematology on whole blood. Hepatic gene expression was evaluated, as this is a known target organ.
OUTPUTS/RESULTS: At necropsy liver weights were significantly increased while heart and kidney weights were significantly decreased in a dose-dependent manner. Clinical changes included significantly decreased serum cholesterol and triglyceride levels in males and females, consistent with the known hypolipodemic effects of PFOS. Hematological changes were observed several endpoints for female rats but not males. Analyses of hepatic gene expression indicated that there were significant dose-related increases in markers of peroxisome expression in males and females.
IMPACTS/OUTCOMES/CONCLUSIONS: Comparison of hepatic gene expression between livers from PFOS treated male rats and archived samples treated with ciprofibrate (a known peroxisome proliferator used as a positive control) found significant differences. Weight changes in heart were also not typical of other reported hypolipodemic compounds. PFOS does induce peroxisome proliferation typically observed in rats, but also indicates a distinct mode of action from other peroxisome proliferators. Upon completion, these studies will be used to assess whether human exposure to PFOS in foods or other matrices will influence human health.
G. Zhou1, C. Parfett1, C. Healy1, M. Wade2, and A. McMahon2
1 Mutagenesis Section, Bureau of Environmental Health Research, HECSB, Health Canada, Ottawa, ON
2 Systemic Toxicology and Pharmacokinetics Section, Bureau of Environmental Health Research, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: In previous microarray studies, we examined three promoters (nongenotoxic/epigenotoxic carcinogens) of morphological transformation in pluripotent mesenchymal C3H/10T1/2 cell cultures: xanthine substrate with xanthine oxidase (XXO); 12-O-tetradecanoylphorbol-13-acetate (TPA), benzoyl peroxide (BPO). Many operative and checkpoint genes in the pathway of DNA replication and DNA repair (mismatch, recombinational) were found down-regulated significantly. In this investigation, we conducted RNA interference to observe whether physiologically-relevant cause-and-effect relationships exist between DNA repair-related gene knockdown and DNA instability.
DESIGN: C3H 10T 1/2 cells were transfected with DsRed reporter plasmids. The DsRed constructs have tandem repeat sequences inserted upstream of the DsRed coding sequence that put the DsRed sequence out of frame.
Chemically synthesized small interference RNAs (siRNA) were transfected into cultures. Time course and dose-responses of gene silencing were performed using RT-PCR. The knockdown cultures were subsequently exposed to 9-amino-acridine (9AA). Frame-shift mutations that resulted in red fluorescent revertants were determined by flow cytometry.
OUTPUTS/RESULTS: Mre11 was examined as a representative of DNA repair genes. Efficient mRNA knockdown (50% ~ 90%) was detected with different gene-specific sequence siRNAs. The chemical treatments induced a statistically significant, dose-dependent response in both siRNA-silenced cells and negative control cells. Mutation rates observed, however, were significantly greater in cells transfected with gene-specific siRNA than in cells transfected with the negative control oligo.
IMPACTS/OUTCOMES/CONCLUSIONS: Results from the experiments reveal that the decreased expression of DNA repair-related genes such as Mre11 might lead DNA instability. Nongenotoxic/epigenotoxic carcinogens may act (at least in part) by eliciting changes to expression of many genes, which create disruption to metabolic and regulatory pathways controlling DNA structure, synthesis and repair thereby resulting in decreased genomic stability.
B. Dixon1, L. Parrington1, T. Coklin1, A. Cook2, F. Pollari2, R. Friendship3, and J.M. Farber1
1 Microbiology Research Division, Bureau of Microbial Hazards, HPFB, Health Canada, Ottawa, ON
2 C-EnterNet, Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Guelph, ON
3 Department of Population Medicine, University of Guelph, ON
OBJECTIVES: To determine the presence and genotypes of Giardia duodenalis and Cryptosporidium spp. in Canadian swine.
DESIGN:
OUTPUTS/RESULTS: 64/122 (52.5%) of the swine manure samples were found to be PCR positive for Giardia. Similarly, 67/122 (54.9%) were PCR positive for Cryptosporidium. Slightly lower positive rates were determined by epifluorescence microscopy. Sequencing data demonstrated the presence of the zoonotic genotypes, Giardia duodenalis Assemblage A and Cryptosporidium parvum (bovine).
IMPACTS/OUTCOMES/CONCLUSIONS: While the prevalence of both Giardia and Cryptosporidium was relatively high in the pooled swine manure, and zoonotic genotypes were identified, further study will be required to demonstrate a risk of transmission to humans. It is anticipated that human stool samples submitted to public health laboratories in the same area will be made available in the future for similar molecular characterization.
M. Ducharme1, and M. Connolly1
1 Health Supply and Demand Analysis Division, Applied Research and Analysis Directorate, HPB, Health Canada, Ottawa, ON
OBJECTIVES: To understand why incidence rates of CVD are higher in rural areas of Canada.
DESIGN: In a previous study, we found that incidence rates of AMI and stroke tend to be higher in rural areas than in urban areas in Ontario and British Columbia, contrary to the popular belief that it is healthier to live in rural areas. We found no articles in the literature that explicitly explained why CVD rates are higher in rural areas in Canada. Therefore, in this study, we build a framework of potential factors (e.g., risk factors, access issues, service delivery, etc.) to explain the differences. We identify empirical evidence for each factor and compile the results to produce a potential explanation for the higher rural CVD rates. These results can serve as a basis for later studies.
RESULTS: Our preliminary results indicate that some factors are specific to CVD and other factors apply to all diseases and are a function of rurality (e.g., access issues). For example, we find that there is a higher prevalence of CVD risk factors, such as smoking and obesity, in rural areas than in urban areas. We also find that people in rural areas do not have the same access to health services as those in urban areas, affecting the prevention and treatment of CVD. There are fewer physicians, longer distances to hospitals and specialists, and different practice and referral patterns.
CONCLUSIONS: Because rural areas face higher levels of both CVD and its risk factors, health promotion and prevention programs could be designed to address these differences. Rural areas also face unique difficulties in accessing care and appropriate treatments in a timely fashion. This could be improved with different health human resource allocation and innovative service delivery methods, such as telehealth.
G. Dufresne1, A. Fouquet1, and A. Robichaud1
1 Food Directorate, Québec Region Laboratory, HPFB, Health Canada, Longueuil, PQ
OBJECTIVES: Develop a specific, sensitive and multi-residues quantitative method for the determination of sulfonamide, quinolone (QN) and fluoroquinolone (FQ) antibacterials in fish and shrimp. Limit of detection are between 0.1 and 0.8 ppb in tissue.
DESIGN: Tissues are extracted in Ethyl alcohol-acetic acid solvent. The extract is diluted in aqueous HCl, defatted with hexane and passed on a cation-exchange SPE cartridge to retain the analytes. Analytes are eluted using NH4OH/methanol and concentrated before injection. Measurement is carried out using a capillary HPLC system with a 1.0 x 150 mm phenyl-hexyl column, coupled to a triple-quad mass spectrometer operating in ESI+ mode. Two injection runs are performed; one for FQs+QNs, and one for sulfas. Surrogate-recovery compounds and internal standards are used. Calibration is made by matrix-matched standards.
OUTPUT/RESULTS: Eight FQ compounds, four QN, 18 sulfonamides (sulfas) and two potentiators of sulfas, trimethoprim and ormethoprim were determined. The method has been validated for shrimp tissues at 1.25, 3.0 and 10 ng/g (ppb). It has been validated for FQs and QNs in salmon and trout, and showed to work for sulfas in those commodities using incurred samples. Recovery ranges from 50% (sulfacetamide) to 100 % (flumequine) with RSD ranging from 3 to 20%. Limit of detections are from 0.1 to 0.8 ppb. Shrimp from Asia are most often found positive; the compounds found (always below 10 ppb) are: enrofloxacin, flumequin, sulfadimethoxine, sulfamethazine, and sulfamethoxazole.
IMPACTS/OUTPUT/CONCLUSIONS: Although concentrations found are very low, many of the compounds found in imported fish are not permitted for use on animals in Canada.
S. Farnworth, MSc1, M.J. Cooper, PhD1, L. Dumais, DtP1, W.M.N. Ratnayake, PhD2, and B.E. McDonald, PhD3
1 Nutrition Evaluation Division, Food Directorate, HPFB, Health Canada, Ottawa, ON
2 Nutrition Research Division, Food Directorate, HPFB, Health Canada, Ottawa, ON
3 University of Manitoba, Winnipeg, MB
OBJECTIVES: Recently there has been significant interest surrounding TFAs in Canada since they have been negatively associated with cardiovascular disease (CVD). Part of the mandate of a joint Health Canada and Heart and Stroke Foundation of Canada Task Force was to develop recommendations and strategies for reducing TFAs in foods to the lowest levels possible. As part of the process, a focused literature review was undertaken to assess the strength of the scientific evidence regarding the replacement of TFAs with various alternatives. Thus, our objective was to evaluate the evidence on the impact of replacing TFAs with different types of fatty acids including monounsaturated, polyunsaturated, saturated (SFA), and specific SFAs on CVD outcomes.
DESIGN: We conducted focussed literature searches in Medline and Current Contents databases to identify primary research articles published between 1999 and 2005. Additionally, studies had to be published in English and conducted in adult human subjects (age > 17 years). Key search terms included: dietary fat, fatty acids, and cholesterol. All eligible studies were then assessed for methodological quality.
RESULTS: There were 491 titles and abstracts that were screened from the database searches and from articles suggested by Task Force members. Upon further screening, 144 of these articles were reviewed for their relevancy to the topic, of which 42 were deemed appropriate. Studies were then evaluated for methodological quality and grouped according to the research question(s) they were answering, i.e., which fatty acids were being compared. Although there is general agreement that TFAs in the diet should be limited due to the adverse effects on the risk factors for CVD, results from this focussed review did not identify a specific SFA that could be used as a possible replacement for TFAs.
CONCLUSIONS: This focused review provides the foundation for continued investigation on the impact of replacing TFAs with alternatives such as monounsaturated, polyunsaturated, and saturated fatty acids on CVD outcomes.
D. Page1, G. Lacroix1, P.J. Lalonde2, and M. Feeley3
1 Food Research Division, Bureau of Chemical Safety, HPFB, Health Canada, Ottawa, ON (ret'd)
2 Product Safety Programme, HECSB, Health Canada, Ottawa, ON
3 Chemical Health Hazard Assessment Divison, Bureau of Chemical Safety, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: To measure the extractable BPA content in a random sample of PC baby bottles. Following detection of BPA, bottles will be subjected to standard migration simulations in order to quantify possible leaching of BPA.
DESIGN: 1 cm2 sections of baby bottle (thread and main body) were completely dissolved in dichloromethane and then extracted into a methanol fraction. Following filtration, the BPA content was analyzed using a HPLC fitted with a UV detector. For the leaching experiments, baby bottles were filled with a 50% ethanol solution (milk simulant) and subjected to various combinations of time periods at room temperature (22°C), refrigeration (4°C) or in an oven (70°C).
OUTPUTS/RESULTS: BPA could be detected at concentrations ranging from 4.2-60.5 µg/g following organic solvent extraction of the PC bottles. Only blank amounts of BPA were detected during leaching studies at either room temperature and/or refrigeration. However, when the bottles were subjected to temperatures of 70°C, time dependent increases in BPA could be detected in the ethanol solution, but at much lower amounts (ppb) than with the extraction studies.
IMPACTS/OUTCOMES/CONCLUSIONS: Results from the extraction studies indicate that BPA could be detected in PC bottles. This was as expected considering BPA and carbonyl chloride are the main reaction materials used in the production of various polycarbonate plastics and synthetic resins. Leaching studies indicated that low concentrations of BPA could migrate into a milk simulant but only under conditions of extreme use. Under normal conditions, it is estimated that the daily intake of BPA from PC baby bottles would be in the range of 1-10 ng/kg bw/day or 1000-fold lower than the current most conservative tolerable daily intake. Overall, these results suggest there are no BPA-safety concerns with PC baby bottles.
J. Flight, MA1, and S. Racine, M.Ps.1
1 Drug Strategy and Controlled Substances Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: Youth are a focus of Canada's Drug Strategy. Street youth, in particular, are at high risk of harms due to a myriad of factors of which substance use is an important one. In this presentation, street youth's substance use and associated risk factors are examined.
DESIGN: Results are based on the Public Health Agency of Canada's Enhanced Surveillance of Canadian Street Youth (E-SYS), a comprehensive study monitoring street youth, aged 15 to 24 years of age, since 1999. Various outreach means were used to recruit 4728 street youth over three phases of data collection (1999, 2001, 2003). In-person interviews covered demographics, lifestyle, substance use, sexual practices, attitudes and knowledge of risk behaviours and family history. Results are contrasted with those of general population youth (Canadian Addiction Survey, Canadian Tobacco Use Monitoring Survey).
OUTPUTS/RESULTS: When examining alcohol, street youth presented similar rates and patterns of use as general population youth, but comparability is weak across surveys. Street youth had higher rates of use of non-injection drugs (including cannabis) as well as higher rates of daily use of tobacco (average 80% vs. 30%). About 20% of street youth reported injection drug use, while this behaviour is too low to be reportable in general population youth.
IMPACTS/OUTCOMES/CONCLUSIONS: Street youth are different from general population youth. This study increases our knowledge about this population, which is not reached through standard monitoring activities. Furthermore, it provides social workers and other care providers with an enhanced knowledge about street youth's substance involvement and associated risks and harms and enables improvements to programs and services aimed at them.
M.L. Gagnon, BSc1, M. Meier1, and P.A. White, PhD1
1 Safe Environments Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: The objectives of this study are to employ in vitro bioassays including the Salmonella mutagenicity test, as well as the DR- and ER-CALUX assays, to assess the comparative toxicological properties of diesel engine emissions.
DESIGN: Diesel emissions were collected by Environment Canada's Emission Research and Measurement Division using specialized facilities and equipment. Particulate material generated under different test conditions was collected on 70mm Pallflex® filters upstream of a polyurethane foam (PUF) plug. The soluble organic material was extracted from the filters and the PUF plugs using pressurized fluid extraction and separated into polar aromatics and non-polar neutral fractions. (Geno)toxicity of the individual fractions was evaluated using the Salmonella mutagenicity assay as well as the DR- and ER-CALUX assays.
OUTPUT/RESULTS: Standard reference material (SRM 2975) generated by a heavy-duty forklift, was used to validate the performance of the three assays. Both fractions of this material yielded significant positive results in the Salmonella mutagenicity assay, and are currently being evaluated with the DR- and ER-CALUX assays. Archived material of delivery vehicle emissions generated using a variety of fuels and driving cycles have been extracted and fractionated and testing is currently underway. Additional emission samples, representing heavy-duty trucks operated with alternative fuels, are currently being collected.
IMPACTS/OUTCOMES/CONCLUSIONS: Research has clearly demonstrated that traffic related air pollution contributes to an enhanced risk of adverse health effects including renal failure and pulmonary diseases. Because mobile sources are the leading cause of air pollution in many urban areas, it is imperative to develop strategies that minimize human exposure and risk. The results obtained to date indicate that diesel emissions contain substances that are mutagenic and have the potential to induce dioxin- and estrogen-like responses. The results of current and future analyses will provide an ability to evaluate diesel combustion technology, and identify scenarios that minimize exposure and the risk of adverse health effects.
J. Grose, BSc, BA1, and K. Basu, PhD2
1 Health Accountability and Performance Reporting Division, Applied Research and Analysis Directorate, HPB, Health Canada, Ottawa, ON
2 Microsimulation Modelling and Data Analysis Division, Applied Research and Analysis Directorate, HPB, Health Canada, Ottawa, ON
OBJECTIVES: Study the effects on self-rated health status of spiritual values and participating in religious activity. Do spiritual/religious people live happier lives? Is it necessary to be religiously active to enjoy this effect, if any, or is being spiritual in and of itself sufficient? In future research, should spirituality or religiosity be treated as control variables, just as significant as the standard age, sex, income, education, marital status and province variables?
METHODS: Using the Canadian Community Health Survey (CCHS) 2002 1.2 Mental Health and Well-being, study the relationships between mental health, physical health, religious activities and being spiritual.
The independent variables used were:
SPVB_1: Spiritual values play an important role: "Do spiritual values play an important role in your life?" (Yes/No)
SPVB_7: The self-perception of being very or somewhat religious: "In general, would you say that you are very religious, religious, not very religious, not religious at all?" This was collapsed to very religious or religious vs. not very religious or not at all religious.
The dependent variables used were:
SCRBDPHY: Self-rated physical health: "In general, would you say your health is (excellent, very good, good, fair, poor)?" This was collapsed to excellent or very good vs. good, fair or poor.
SCRBDMEN: Self-rated mental health: "In general, would you say your mental health is (excellent, very good, good, fair, poor)?" This was collapsed to excellent or very good vs. good, fair or poor.
RESULTS: Logistic regressions revealed that, after controlling for age, sex, income, education, marital status and province:
CONCLUSIONS:
Those who are religious are more likely to be both physically and mentally healthy.
Those who are spiritual are more likely to be both physically and mentally healthy.
Policy Implications and Next Steps
Clearly in our pluralistic society the Government of Canada has no business urging people to be more religious or spiritual. However in future studies of health, whether physical or mental, investigators may wish to consider including religiosity and/or spirituality with standard control variables.
Still to be explored is the cause and effect relationship, if any, between spirituality/ religiosity and self-rated physical/mental health. Does being spiritual or religious lead to an improvement in one's physical and mental health? Does being physically and mentally healthy lead to an increased level of spirituality or religiosity? Is there a confounding variable? A longitudinal study following the spirituality/religiosity and physical/mental health of subjects might help answer these questions.
N. Hidiroglou1, and K. Sarafin1
1 Nutrition Research Division, HPFB, Health Canada, Ottawa, ON
INTRODUCTION: Vitamin D is receiving considerable interest in both the scientific and public arena in its role in health and chronic disease outcomes. Vitamin D status including deficiency and insufficiency is an emerging issue in many parts of the world including Canada. Vitamin D has been suggested to play a role in health/disease beyond its classical function in bone health. Some emerging areas include its potential role in autoimmune disease, cardiovascular disease and cancer.
OBJECTIVES: Health Canada Laboratories (Ottawa) are re-establishing their analytical capabilities to quantify Vitamin D and its metabolites in biological samples by: 1) High Pressure Liquid Chromatography and; 2) Radioimmunoassay technique in biological samples.
METHODOLOGY: The best marker for vitamin D status is serum 25 (OH-D) and thus was used in the analytical methodology work up.
For the HPLC method, 25-OH Vitamin D was extracted from serum by a liquid-liquid organic solvent extraction. Extract was removed and cleaned by passing through a solid phase extraction cartridge. The eluent was dried and re-dissolved into the HPLC mobile phase for analysis by HPLC-PDA (photodiode array detection). The HPLC analysis was done isocratically with acetonitrile on a reverse-phase column.
For the RIA, total Vitamin D status was measured for comparison by radioimmunoassay (RIA) utilizing a commercial kit (Diasorin Inc). The RIA is based on an antibody with specificity to 25-OH-Vitamin D.
OUTPUT/RESULTS: A high correlation coefficient (r value > 0.95) was found between the HPLC and RIA method for serum vitamin D (25-OH-D). Serum vitamin D (25-OH-D) recovery data obtained from HPLC analysis was in the range of 80-105%. To further validate the HPLC and RIA vitamin D techniques, quality control serum samples are routinely obtained from DEQAS (International Vitamin D Quality Control Assessment Scheme, based in the UK) for vitamin D analysis. Our data obtained to date are well within the targeted vitamin D levels.
IMPACTS/OUTCOMES/CONCLUSIONS: This technical capacity will allow for in-house and external collaborations on vitamin D nutrition regulatory research issues such as food fortification practices, bioavailability, nutritional status, safety and health/disease issues. In addition, with the development of these assays will directly support the Nutrition Research Division (NRD's) participation in the upcoming Canadian National Health Measures Survey (Fall 2006). The NRD will provide analytical and scientific expertise related to various markers of nutritional status including vitamin D.
M. Hill1, R. Gandia1, G. White1, and G. Hammond2
1 New Substances Assessment and Control Bureau, HECSB, Health Canada, Ottawa, ON
2 New Substances Programme, Environment Canada, Ottawa, ON
OBJECTIVES: Develop an integrated approach for the management of perfluorinated carboxylic acids (PFCAs) and their precursors in order to protect human health and the environment from adverse effects of PFCAs.
DESIGN: In 2004, four fluorotelomer-based substances intended for use as stain/water repellants for textiles, carpets, stone and tile, as sizing agents for paper products with food contact applications, and as levelling agents in coatings, were notified pursuant to subsection 81(1) of the Canadian Environmental Protection Act (CEPA), 1999. The assessments were based upon information submitted by the notifiers, studies published in the scientific literature, and information otherwise available to the Departments of Health and Environment.
OUTPUTS/RESULTS: The substances were suspected of being toxic under section 64 of CEPA, 1999, and were subject to temporary prohibitions. The assessment conclusions were based upon information indicating the substances would ultimately be a source of PFCAs. Members of the PFCA class are known to be persistent and suspected to be bioaccumulative, subject to long-range transport and associated with adverse effects in laboratory animals. Particular concern exists for PFCAs with longer chain lengths, as these have shown greater potential for bioaccumulation. A literature review in 2006 corroborated the occurrence of PFCAs in environmental compartments that directly impact human exposure such as indoor air, dust, food and drinking water. Biomonitoring clearly demonstrates the presence of PFCAs in human blood globally. Detection of PFCAs in seminal plasma, breast milk and umbilical cord blood raises new concerns regarding routes of human exposure and potential effects.
IMPACTS/OUTCOMES/CONCLUSIONS: An Action Plan is being considered to address PFCAs and precursors. The plan includes an approach to address the substances currently prohibited and similar new substances in the future, as well as members of this class already in commerce. It encourages engagement of the research community and international regulators in contributing to assessment and management issues.
R. Huang1, B. Junkins1, and M. Vigneault1
1 Food Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVE: An important indicator in the development of nutrition focused health policies is the proportion of a targeted population whose usual intakes of a nutrient fail to meet their individual requirements. While this proportion is simple to define in principle, an accurate calculation requires a comprehensive understanding of the joint distribution of individual usual intakes and requirements for each nutrient. Such detailed information is usually missing, so that approximate methods must be employed. This study aims to compare the sensitivity to underlying assumptions of two different approaches to estimating nutrient inadequacy, namely the full probability approach and the Estimated Average Requirement (EAR) cut-point method.
DESIGN: This analysis is based on data derived from the Federal / Provincial Food and Nutrition Surveys (1990 - 1999) which encompasses a total of 20 373 respondents. We analyzed five nutrients - Magnesium, Vitamin C, Vitamin B12, Riboflavin and Thiamin. These nutrients provided a sufficiently varied challenge to the assumption estimation procedures to form a basis for sensitivity analysis. For each nutrient, a distribution of usual intakes was derived and combined with information on requirements consistent with the full probability approach. Next, nutrient inadequacy was calculated based on the two proposed approaches and differences were analyzed, accounting for uncertainties in estimation.
OUTPUTS/RESULTS: The EAR cut-point method is the simpler method but requires rather strict conditions on the underlying joint distribution of usual intakes and requirements. While the full probability approach uses a more detailed analysis, it too incorporates a number of important assumptions. This analysis demonstrates the deviation of the distribution of usual intakes from the assumptions inherent in the EAR cut-point method have important impacts on the resulting estimated levels of nutrient inadequacy.
IMPACTS/OUTCOMES/CONCLUSIONS: This study shows the importance of establishing an appropriate methodology in estimating the key health related measures in establishing effective policy.
X. Jin, PhD1, E. Lok, BSc1, S. Gill, PhD1, D. Caldwell, DVM1, M. Taylor1, K. Kapal1, L.M.H. Chan, PhD2, and R. Mehta, PhD1
1 Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, ON
2 Community Health Program, University of Northern British Columbia, Prince George, BC
OBJECTIVES: Human exposure to methylmercury through consumption of contaminated fish and marine mammals has become an increasing concern in the Arctic. Fish and marine mammals as important components of Northern traditional diet are rich in protein, polyunsaturated fatty acids, selenium (Se), vitamin E (VE) and fiber. This study was conducted to investigate the effects of dietary Se plus VE ([Se+VE]) on acute toxicity of methylmercury in male SD rats.
DESIGN: Male SD rats were fed starch-based casein diet alone, or casein diet supplemented with a high level of Se (3 mg/kg diet) plus a low level of VE (250 mg/kg diet) for 28 days. The rats were then gavaged with 0, or 3 mg MeHg/kg body weight (BW) for 14 consecutive days. Body weights were recorded. At necropsy, target organs were weighed, and blood and urine samples were collected and analyzed for hematology, biochemistry, and oxidative stress endpoints.
RESULTS: MeHg significantly decreased body weight, red blood cell counts, hematocrit, and hemoglobin concentration, and increased relative kidney weight, to a similar degree with or without [Se+VE] supplementation. However, MeHg significantly increased relative spleen weight and monocyte counts, and decreased relative liver weight to a greater degree in the rats fed casein diet alone than casein plus [Se+VE] diet. MeHg significantly increased serum lipase and creatinine and urinary 8-hydroxydeoxyguanosine in rats fed casein diet alone, but not in rats fed casein plus [Se+VE] diet.
CONCLUSIONS: Dietary supplementation with a high level of Se plus a low level of VE improved performance of some toxicological endpoints in rats, but did not attenuate the effects of MeHg on other endpoints. Results of this study will contribute towards characterizing the beneficial effects of dietary constituents in managing health risks associated with mercury exposure.
E.A. Sigal1, J.A. Archbold2, G.M. Ferguson1, C.E. Bacigalupo1, D.R.J. Moore1, G.M. Richardson3, and H. Jones-Otazo4
1 Cantox Environmental Inc., Mississauga, ON
2 Environmental Protection Office, Toronto Public Health, Toronto, ON
3 Environmental Protection Office, Toronto Public Health, Toronto, ON
4 Safe Environments Programme, HECSB, Health Canada, Toronto, ON
OBJECTIVES: This research explores the development and application of probabilistic Estimated Daily Intakes (EDI) for use in the derivation of Canadian Soil Quality Guidelines. Probabilistic methods may be used to account for and communicate uncertainty and variability in estimates of exposure to provide more useful information to the risk manager. Probabilistic EDI distributions of nickel (Ni), vanadium (V) and beryllium (Be) were developed to characterize inter-individual variability expected within the Canadian population.
DESIGN: Probability density functions (PDFs) were developed using a 1-Dimentional Monte Carlo Analysis (MCA) approach. This approach combined point estimate values (i.e., the 95% upper confidence limit on the arithmetic mean for media concentration) with log normal PDFs (describing the inter-individual variability among Canadian receptor characteristics and intake rates) to estimate the EDI distributions for Ni, V and Be.
OUTPUTS/RESULTS: With the exception of infants, the EDI rates of Ni, V and Be for all Canadian receptor age classes were driven by the daily consumption of general food stuffs. The infant EDIs were driven by the consumption of human breast milk or infant formula. The incidental soil ingestion pathways appear significant to the overall EDI of V for the toddler, and to the overall EDI of Be for the infant and toddler.
IMPACTS/OUTCOMES/CONCLUSIONS: This research highlights the pathways and assumptions that appear to shape the EDI PDFs, and provides a discussion of some of the general observations, conclusions and recommendations with regards to the derivation and application of probabilistic analyses that were used to estimate EDI rates of Ni, V and Be. The methods and discussion presented are applicable to other types of chemicals in the Health Canada database.
1 Department of Biochemistry, University of Waterloo, Waterloo, ON
2 Department of Biochemistry, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: To review the recent scientific publications on corrosion, biocompatibility and wear of three orthopaedic alloys.
DESIGN: More than seventy scientific publications were reviewed. The corrosion, biocompatibility and wear topics were summarized, outlining the current understanding from the available data.
OUTPUTS/RESULTS: The results of this review were presented to Health Canada evaluators of medical devices. Also, the information will be formatted and posted on a corrosion intranet site to assist in pre-market evaluation of orthopaedic implants. Some examples of the information for biocompatibility are: Cr6+, which is released from stainless steel prostheses, is highly toxic and may inhibit a number of metabolic processes. Both chromium and its compounds, and nickel and its compounds are potent carcinogens in animals. Titanium has low toxicity and accumulates in tissues adjacent to the implant in giant cells and is not excreted.
IMPACT/CONCLUSIONS: Safety and efficacy of medical devices used in Canada depend heavily on the pre-market review process. The results of the scientific literature review provide the evaluators with an up to date knowledge on the corrosion, biocompatibility and wear of orthopaedic implants.
L. Fishman1, and J. Karov, PhD2
1 Department of Mechanical Engineering, University of Ottawa, Ottawa, ON
2 Department of Biochemistry, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: To assess the effect of High Molecular Weight Polyethylene (UHMWPE) articulation against orthopaedic implants on the corrosion of orthopaedic implants.
DESIGN: Fifteen samples were prepared from three main orthopaedic implants: stainless steel, Co -Cr-Mo alloy and Ti-Al-V alloys (five samples for each alloy). Corrosion experiments were carried out on a Gamry 105 corrosion system coupled with in-house built wear apparatus. Each sample was subjected to several corrosion tests under base (no articulation) and wear (UHMWPE articulation) conditions that simulate the electrolytic environment and the stresses found in vivo. One sample from each alloy group was also tested under wear with a ceramic pin to simulate third body wear and to provide reference.
OUTPUTS/RESULTS: Articulation of UHMWPE against Stainless Steel alloy had the following effects: The corrosion potential Eo increased (-364mV to -287mV), the corrosion current was not affected. The Tafel slope of anodic polarization was steeper, indicating the presence of a more effective passive layer. In cycling experiments, the articulation of UHMWPE shifted Eb (the breakdown potential) and Ep (the protection potential) to higher values (922mV and -173mV to1033mV and -105 mV respectively). Articulation of UHMWPE against Co-Cr -Mo alloy lowered the Eo to a more active level and reduced the corrosion current (-238mV to -428mV, 0.76μA to 0.25μA). The Tafel slope of anodic polarization was steeper indicating the presence of a more effective passive layer. In cyclic experiments the break down potential (Eb) was lowered from 622mV to 444mV while Ep the protection potential was not affected. UHMWPE articulation against Ti alloy increased the Eo to more noble values (-295mV to -183mV). The corrosion current increased by more than two orders of magnitude under UHMWPE articulation (0.254μA to 67μA).
IMPACT/CONCLUSIONS: Biocompatibility of orthopaedic implants is strongly dependent on their corrosion characteristics. The relatively small change in corrosion parameters suggest that the articulation does not remove the passive layer but may modify it possibly by compressing locally the oxide layer and/ or depositing a thin layer of UHMWPE. Our results help to estimate the UHMWPE articulation effect on the implant biocompatibility.
S. Katamay1, K. Esslinger1, I. Sirois1, E. Jones-McLean1, C. Martineau1, B. Junkins2, M. Vigneault2, L. Robbins3, A. Kennedy3, and J. Johnston4
1 Office of Nutrition Policy and Promotion, HPFB, Health Canada, Ottawa, ON
2 Bureau of Biostatistics and Computer Applications, Food Directorate, HPFB, Health Canada, Ottawa, ON
3 Cross-Sectoral Food Industry Affairs Division, Food Value Chain Bureau, Agriculture and Agri-Food Canada ON
4 Nutrition Evaluation Division, Bureau of Nutritional Sciences, Food Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Develop a dietary pattern applicable to the Canadian population that will result in acceptable nutrient outcomes and likely contribute to reduced risk of chronic diseases.
DESIGN: To develop the dietary pattern a statistical modelling approach was employed. Food composites were used to provide a first estimate of the number of servings of each food group required to meet defined nutrient outcomes across 16 age and sex groups. The number of servings of each food composite group was then used to inform the creation of 500 test diets using foods reported in four Federal - Provincial nutrition surveys. These test diets yielded distributions of nutrient content, which were then assessed for adequacy using methods recommended in Dietary Reference Intakes: Applications in Dietary Assessment. Adjustments to the dietary pattern were made as necessary to achieve a low prevalence of inadequate nutrient content. The pattern was also assessed using lower income and vegetarian food choices.
The summary of two large systematic reviews provided additional information to the developed pattern to ensure it was consistent with epidemiological evidence around chronic disease prevention and foods, in particular.
OUTPUTS/RESULTS: This innovative evidence-based approach resulted in a final pattern that achieves satisfactory results across most nutrients assessed and is consistent with evidence linking diet to reduced risk of chronic diseases. Any person following the food intake pattern has a high probability of meeting their nutrient requirements as well as a low probability of nutrient excess. This approach provides rationale for specific messaging on whole grains, orange vegetables, dark green vegetables, fluid milk, lower-fat meat and dairy, unsaturated oils and fat, and fish.
IMPACTS/OUTCOMES/CONCLUSIONS: This integrated approach builds on enhanced assessment methods recommended through Dietary Reference Intakes and goes beyond consideration of nutrients alone.
I. Kennedy, PhD1, L. Avon, MSc1, and G. Malis, MSc1
1 Environmental Assessment Division, PMRA, Health Canada, Ottawa, ON
OBJECTIVES: Estimating concentrations of pesticides in water is an integral part of the risk assessment process conducted by the Pest Management Regulatory Agency (PMRA). The transformation rates of those pesticides in soil, water and sediment are key parameters for the PRZM (Pesticide Root Zone Model) and EXAMS (Exposure Analysis Modelling System) models used for calculating concentration estimates. In cases where data are not available in one of these media, PMRA currently assumes the pesticide does not transform in that medium. To provide more realistic concentration estimates, it is desirable to estimate a transformation rate from the rates measured in other media. For example, in the United States, the US Environmental Protection Agency (EPA) estimates the water transformation rate as half the soil transformation rate. Here we aim to provide guidance on estimating transformation rates from the rates in other media.
DESIGN: Evaluation of pesticides for registration in Canada requires measurements of pesticide transformation in soil, water and sediment. The PMRA thus has a database of measured values for transformation rates in these three media for a large number of pesticides. We compiled and compared measurements of transformation rates in all three media and calculated distributions of rates given the rates in other media.
OUTPUTS/RESULTS: The analysis indicates there is no consistent ratio between transformation rates in different media to allow accurate extrapolations across the media. However, it is possible to estimate bounds on the unknown rates, and these bounds can be used to choose defendable values for transformation rates to be used in modeling.
IMPACTS/OUTCOMES/CONCLUSIONS: The results are used to provide estimated transformation rates to use where data is missing, with the intention to produce values that are conservative but within a range we would expect given available data.
S. Kirby, MSc1, L. Avon, MSc1, D. François, MSc1, C. Hart, PhD1, H. Mulye, PhD1, T. Kuchnicki, PhD1, H. Simmons, MSc1, R. Sebastien, PhD1, J. Villeneuve, MSc1, J.D. Whall, MSc1, and P. Delorme, PhD1
1 Environmental Assessment Division, PMRA, Health Canada, Ottawa, ON
OBJECTIVE: Like all science, risk assessment methods and approaches must reflect current knowledge and available methods. In the case of environmental risk assessments of pesticides, approaches to aquatic assessments have not changed significantly in the past 15 years. In order to incorporate advances in knowledge on the fate, effects and risk characterization the Pest Management Regulatory Agency (PMRA) is revising the approach it uses for aquatic assessments and is proposing a new framework.
DESIGN: The proposed framework uses a science-based tiered approach that considers both the inherent toxicity of the pesticide as well as the potential for exposure to that pesticide. Initial tiers (screening levels) use a deterministic approach with conservative exposure scenarios and using conservative effects endpoints. This approach allows those uses that do not pose any significant risk to the environment to be screened out in an efficient manner. The screening level also allows for the identification of taxonomic groups not at risk. Subsequent tiers of the risk assessment focus on refining exposure estimates using more sophisticated fate models with specific regional scenarios. Further refinements for higher tiers are considered on a cases by case basis and can include refinement of model inputs, considerations of additional effects data when available, or the use of probabilistic assessment methods.
OUTPUTS/RESULTS: Results of these changes provide a more scientifically sound risk characterization, reflecting a more modern approach.
OUTCOMES: Efficiency in the risk assessment process can be gained through the early identification uses or taxonomic groups with little or negligible risk. The approach also allows for greater flexibility in risk characterization as needed for specific products.
S.A. Kulkarni, PhD1, J.C.C. Yu, PhD2, J. Zhu, PhD1
1 Chemistry Research Division, HECSB, Health Canada, Ottawa, ON
2 Department of Chemistry, Sam Houston State University, Texas, USA
OBJECTIVES: Investigation of toxicological properties of selected indoor mycotoxins using in silico predictions.
DESIGN: Numerous mycotoxins can be produced by molds under certain conditions. In indoor environment mycotoxins have been found from molds growing on building materials. Our project focused on the prediction of potential toxic effects of approximately fifteen known indoor relevant mycotoxins. QSAR models such as TOPKAT, MCASE and DEREK were run on each of these mycotoxins to obtain information on various toxicological endpoints including carcinogenicity and mutagenicity. Since limited experimental toxicity data are available for comparative assessments therefore, the model predictions were interpreted on the basis of the domains of applicability of individual models with respect to the individual mycotoxins. The indoor relevant mycotoxins will be ranked by their potential toxicity in order to elucidate the major group of hazardous compounds produced by indoor molds.
OUTPUTS/RESULTS: The present study included indoor mycotoxins such as Sterigmatocystin, T-2 toxin, Satratoxin G and H, Diacetoxyscirpenol, Deoxynivalenol, Verrucarol, T-2 tetraol, Citrinine, Fumagillin, Verruculogen, Penitrem A, Roquefortine C, Gliotoxin, Malformins, Mycophenolic acid, etc. CASETOX carcinogenicity model predicts high probabilities for mycotoxins such as Sterigmatocystin, T-2 toxin, Satratoxin G and H, and low probabilities for Roquefortine C, Gliotoxin, Malformins, Mycophenolic acid. On the other hand, the Ames mutagenicity models of both CASETOX and TOPKAT predict higher probability for Sterigmatocystin and lower probabilities for Penitrem, Diacetoxyscirpenol, Citrinine, Fumagillin and Mycophenolic acid. Predictions for some of the mycotoxins are found to be in agreement with the experimental data.
IMPACTS/OUTCOMES/CONCLUSIONS: The presence of mycotoxins is believed to be responsible for some of the adverse health effects including both acute and chronic. The experimental results of toxicities of indoor related mycotoxins are however, sporadically reported. Whereas the guidelines for monitoring highly toxic compounds occurring in the indoor setting would be the most relevant and of great interest to general public and indoor hygienists, our model prediction of toxicities of indoor-relevant mycotoxins will not only provide the likelihood of their health impacts in the event of exposure but also serve as a reference for the development of guidelines in monitoring indoor air quality. The model prediction of toxicities would also contribute to the establishment of investigation guidelines for the researchers working in the area of indoor air quality. Additionally, this study will help evaluate the predictability of the QSAR models for mycotoxins.
C. Gourgue-Jeannot1, M.L. Kalmokoff2, J. Kwan1, M. McAllister1, E. Kheradpir3, B.J. Lampi1, and S.P.J. Brooks1
1 Bureau of Nutritional Research, Food Directorate, HPFB, Health Canada, Ottawa, ON
2 Atlantic Food and Horticulture Research Centre, Agriculture and Agri-Food Canada, Kentville, NS
3 Bureau of Microbial Hazards, Food Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Determine the effect of dietary fructooligosacchardies (FOS) on faecal bacterial populations using a combination of molecular biology and culturing methods.
DESIGN: Two groups of seven 28-42 days old control BB rats were fed either Purina 5001 rat chow (control) or chow containing 5% w/w FOS. Fresh faecal samples were collected, pooled and homogenized at different time points. Analysis was conducted by: 1) culturing on specific media; 2) PCR amplifying DNA using universal primers directed against the full 16S rRNA gene, shotgun cloning and sequencing; or, 3) Denaturing Gradient Gel Electrophoresis (DGGE) after amplification of the 16S gene V2-3 region.
OUTPUTS/RESULTS: A greater diversity of inulin-utilising bacterial species in FOS-fed (vs. controls) was observed when bacteria were cultured using chicory inulin as the sole carbohydrate source, although inulin-utilizing species were identified in controls and experimental rats. The majority of species fell within the Clostridium coccoides group and Clostridium leptum subgroup and some were related to butyrate producing bacteria isolated from other animals. No Bifidobacteria were isolated. Shotgun cloning and DGGE analysis revealed a profound change in the faecal population that took approximately 12 days to stabilize. The final population contained only 12% of the clones found in control rats. The greatest change occurred in the low G + C Gram-positive bacteria where only three phylotypes were identical with those previously identified in the control. Estimates of species diversity in control and FOS-fed rats suggested FOS induced a reduction of about 50%.
IMPACTS/OUTCOMES/CONCLUSIONS: These results show that fermentable carbohydrates can exert a profound effect on the bacterial community of the lower bowel and that FOS does not stimulate Bifidobacteria exclusively but provides substrate for a wide variety of bacteria. This result is hardly surprising, given the diversity of bacteria in the gut and the niche that these bacteria occupy.
M.W. Latendresse, MA1, A. Diener, PhD1, J. Snider, MSc1, and M.J. Kaiserman, PhD, MBA1
1 Office of Research, Surveillance and Evaluation, Tobacco Control Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVE: To assess tobacco use and smoking related behaviours of school aged children in grades five through nine using the Youth Smoking Survey (YSS). It is generally recognized that this is the population most at risk for trying tobacco products.
METHODS: The YSS is a national survey sponsored by Health Canada and conducted by the Centre for Behavioural Research and Program Evaluation and their consortium of pan-Canadian researchers and students. This classroom-based survey was first conducted in 1994 and again in 2002. The most recent implementation of the YSS provided data for 2004-05. The YSS utilized a two-stage stratified clustered design with schools as the primary sampling units and classes as the secondary units. In 2004-05 data from a total of 29 243 students located in all 10 Canadian provinces was collected. The total response rate for Canadian school boards approached for participation in the YSS 2004/05 remained elevated at 73.8.
RESULTS: In 2002, there was a significant decline in the percentage of ever cigarette smokers (23%) among youth in grades five to nine, compared to 1994 (40%). YSS 2002 data indicated that smoking prevalence increases with grade (7% in grade five to 42% in grade nine). YSS 2004-05 data is embargoed until September 6, 2006 and results from this survey will be presented at the conference.
CONCLUSIONS/IMPLICATIONS: The YSS is an essential component of Canada's tobacco control monitoring system and provides a backdrop for making evidence based decisions on federal and provincial smoking policies as well as government based programs targeting the reduction of youth smoking. This project is used to monitor the success of the Federal Tobacco Control Strategy to reduce smoking prevalence from 25% to 20% by monitoring the knowledge, attitudes, and behaviours of youth who are at most at risk of trying cigarettes.
M. Legrand, PhD1, and R. Dabeka, PhD1
1 Food Research Division, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Surveys of selected persistent organic pollutants (POPs) in Canadian human milk were undertaken in 1967, 1975, 1981, 1986, and 1992.
DESIGN: The cross sectional surveys recruited between 100 and 500 Canadian mothers from rural and urban centres within five designated regions (Atlantic, Quebec, Ontario, Prairies and British Columbia).
RESULTS: The data served as an indicator of the mother's body burden and infant's dietary exposure, and allowed an assessment of temporal trends. Since 1967, there has been a steady decline in the human milk levels of DDT, dieldrin and heptachlor epoxide. The concentrations of PCBs and hexachlorocyclohexane showed a general downward trend except for a sharp peak in 1982. Dioxins and furans were incorporated in the analysis as of 1981. Between 1981 and 1986, the levels dropped by half and remained constant through 1992.
DISCUSSION AND CONCLUSION: Despite the detection of these POPs in mother's milk, it was recommended that the nutritional, psychological and immunological benefits provided from the milk to the child outweigh the health risks from exposure to these contaminants. In its continual role of safeguarding the health of infants, the Health Products and Food Branch of Health Canada is planning the sixth national human milk survey for environmental, nutritional and immunoprotective analytes to take place in 2007/2008 with a pilot in 2006/2007. National human milk surveys strengthen health risk assessments in infants (including promotion of breastfeeding) and support measures to reduce exposure to environmental contaminants.
G. Levasseur1, J. Fillion1, and M.J. Kaiserman1
1 Tobacco Control Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVE: The objective is to provide the smoker with a personalized and visual way to estimate immediate intake of smoke emissions.
In this study, an exposure wheel using a colour scale is developed. When matched to the smoker's cigarette filter, the colour scale allows for the estimation of tar exposure per cigarette. Then, using the exposure wheel, intake of nicotine and other toxic compounds can be predicted.
DESIGN: The development of the colour scale is based on the assumption that the tar delivered to the smoker is directly linked to the colour of the cigarette filter. Toxic emissions of eight Canadian cigarettes were determined applying different non-standard smoking conditions. Their filter colours in relation with nicotine and tar levels were then studied to develop a colour scale.
Given that the Canadian market is quite homogeneous, consisting mainly of flue-cured tobacco grown in the same geographic area, a mathematical relationship between tar and other toxic emissions present in the smoke can be established.
OUTPUTS/RESULTS: Using the colour scale developed and a chart of 40 toxic emissions, a smoker can compare cigarette filter colour to the colour scale in order to estimate exposure to tobacco toxic emissions.
IMPACTS/OUTCOMES/CONCLUSIONS: Transferred to a handy wheel, it provides an educational tool to reach the smoker, help identify health hazards associated with smoking and make an informed choice.
G. Levasseur1, and M.J. Kaiserman1
1 Tobacco Control Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: The objective of this study is to determine the relationship between pH and nicotine of different tobacco products available on the Canadian market. Knowing that the pH of tobacco can influence the bio-availability of nicotine (higher pH more bio-available nicotine), the pH and nicotine content of different tobacco products are compared to establish their comparative efficiency in terms of nicotine delivery.
DESIGN: pH and alkaloid levels of different tobacco products were measured and compared in whole tobacco using tests mandated by the Tobacco Reporting Regulations (TRR). Tobacco products available on the Canadian market include; Canadian and imported cigarettes, fine cut tobacco, cigar, pipe tobacco and smokeless tobacco.
OUTPUTS/RESULTS: Products from two smokeless tobacco manufacturers were evaluated. It was shown that smokeless tobacco brands from the United State have high pH, between 6 and 8.5, and high nicotine content, 25-30 mg/g. In contrast, chewing tobacco from Sweden have a low pH 5.5 and low nicotine; 10 mg/g. Cigarettes and fine cut tobaccos cluster around a pH of 5 with average nicotine levels between 15 and 20 mg/g. Pipe tobaccos have the lowest observed pHs between 4.7 and 4.9, while nicotine content averaged around 17 mg/g. Cigars have pH levels between 6 and 7 while nicotine contents are low, between 7 and 12 mg/g.
IMPACTS/OUTCOMES/CONCLUSION: Smokeless tobacco products from the United States have a higher nicotine content at a higher pH than the Swedish product. While cigars have low nicotine content, its availability to the smoker is reinforced by a higher pH. Cigarette, fine cut and pipe tobacco present the lowest pH while their nicotine content seems to be at an average level.
X.-Z. Li, PhD1, M. Mehrotra, PhD1, S. Ghimire, PhD1, and L. Adewoye, PhD1
1 Human Safety Division, Veterinary Drugs Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Assess resistance to beta-lactams and the distribution of beta-lactmases, particularly extended-spectrum beta-lactamases (ESBLs), in animal-derived bacteria in order to identify potential issues of public health concern.
DESIGN: Analyze published antimicrobial resistance surveillance and literature data with an emphasis on identification of resistance to extended-spectrum beta-lactams via genotypic and phenotypic approaches (e.g., reported sequences and substrate/inhibitor profiles of beta-lactamases).
OUTPUTS/RESULTS: Beta-lactams are among the most important antimicrobials in human and veterinary medicine. Bacterial resistance to beta-lactams has been increasingly observed in bacteria, including those from animals. Over 400 beta-lactamases have been reported to date and these enzymes contribute predominantly to beta-lactam resistance in gram-negative bacteria such as Escherichia coli and Salmonella spp. A variety of beta-lactamases have been identified in bacteria from food and companion animals. The plasmid-encoded AmpC-like CMY beta-lactamases, which do not belong to ESBLs but mediate resistance to extended-spectrum beta-lactams, are significantly distributed in E. coli and Salmonella spp. from animals worldwide including in Canada and are mainly responsible for the increasing rates of resistance to third generation cephalosporins. Plasmid-encoded ESBLs, once rarely detected in animal-derived bacteria, are increasingly being observed in Asia and Europe, but so far not in Canada. The dominant ESBLs reported in animals are the CTX-M family, which is also increasingly being identified in bacteria from humans. The genes encoding CMY and CTX-M enzymes often coexist with other resistance determinants and can be associated with transposons/integrons, highlighting the potential enrichment of multi-drug resistant bacteria by multiple antimicrobial agents and dissemination of the resistance determinants among bacterial species.
IMPACT/OUTCOMES/CONCLUSIONS: Studies on beta-lactamases from animal-derived bacteria are somewhat an ignored field. The occurrence of ESBLs in animals is an emerging public health and animal health issue. Characterization of the animal-derived beta-lactamase-producing bacteria warrants further investigation of the type and distribution of beta-lactamases of animal origin and their potential impact on human medicine.
K. Lydon-Hassen1, and C. Tikhonov1
1 Environmental Research Division, FNIHB, Health Canada, Ottawa, ON
OBJECTIVES: To qualitatively assess focus group information from First Nations community representatives from six regions across Canada who attended Environmental Contaminants and Traditional Foods Workshops (ECTFWs) between 2002 and 2005.
DESIGN: Results of focus group sessions conducted during six ECTFWs were compiled and analyzed independently by two evaluators to assess commonalities and disparities with respect to consumption of traditional foods and perceptions related to environmental contaminants in First Nations in six regions across Canada. Open ended questions asked about: traditional foods most often consumed; perceived changes in rates of traditional foods consumption over time; accessibility to traditional foods; environmental contaminant concerns; means of addressing concerns and improving risk communication. Reported responses were categorized under these themes as well as additional themes that emerged from each workshop. Evaluators ranked responses from 1-6; 1 indicating an issue cited in 1 workshop and 6 indicating an issue cited in all six workshops. The resulting datasets from each evaluator were compared to enhance reliability. The presentation/poster will report on commonly reported (highest ranked) themes in all regions as well as issues that may be more specific to a region.
OUTPUTS/RESULTS: Over 380 First Nations in six regions were invited to participate in the workshops and 73.5% of these agreed to participate. A total of 392 workshop attendees participated in two focus groups per workshop. There were expected regional and geographical variations in types of traditional foods consumed. A decrease in traditional food consumption in favour of market foods; decreased interest among youth in traditional harvesting; and increasing inaccessibility to traditional foods were commonly reported themes. Identified environmental concerns also varied by region and were often related to local industrial activities. Some additional reported concerns included: waste management sites; water quality; mercury and pesticide contamination.
IMPACTS/OUTCOMES/CONCLUSIONS: This analysis highlighted regional differences as well as several similarities with respect traditional foods consumption rates and environmental concerns among First Nations communities in six regions in Canada. The study has several major limitations and therefore the results should be interpreted with caution. Despite this, given the general lack of current information on these issues, this analysis sheds some light on the importance and perceived factors affecting the consumption of traditional foods among First Nations people across Canada.
R.M. Maertens, MSc1, P.A. White, PhD1, D. Moir, PhD1, W.S. Rickert, PhD2, G. Levasseur, MSc3, G.R. Douglas, PhD1, and S. Desjardins, PhD4
1 Safe Environments Programme, HECSB, Health Canada, Ottawa, ON
2 Labstat International Inc., Kitchener, ON
3 Tobacco Control Program, HECSB, Health Canada, Ottawa, ON
4 Drug Strategy and Controlle Sustances Program, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: Although the prevalence of tobacco use has decreased over the last decade, cannabis use has increased, particularly among youth. In addition, the use of cannabis for medical purposes is currently permitted under certain circumstances in Canada. Smoking cannabis is often perceived as less harmful than smoking tobacco, but solid scientific evidence regarding the comparative risk of adverse effects is lacking. This study examined the toxicological properties of cannabis smoke and Canadian flue-cured tobacco smoke.
DESIGN: Condensates of main- and side-stream smoke from hand-rolled cannabis and tobacco cigarettes were prepared using standard (i.e., ISO) conditions, as well as "extreme" conditions designed to reflect cannabis smoking habits. Biological analyses included cytotoxicity assessment via the Neutral Red Uptake Assay, and mutagenicity testing via the Salmonella Mutagenicity Assay. Chemical analyses included measurements of cannabinoids, tar, TPM, PAHs, and other chemicals commonly tracked in tobacco smoke.
OUTPUTS/RESULT: Cytotoxicity analyses showed a 2-fold lower IC50 value for cannabis smoke condensate, thus indicating greater cytotoxicity than tobacco. Cannabis smoke condensates consistently displayed higher mutagenic activity (1.2-7.5 fold) than the matched tobacco smoke condensates for all smoking conditions. Within the respective tobacco and cannabis results, the side-stream samples demonstrated greater mutagenic activity (1.1-5.0 fold) than the main-stream samples, and no significant differences were observed between the standard and extreme smoking conditions. Chemical analyses indicate that many analytes were more abundant in main-stream tobacco smoke than cannabis smoke. Total PAHs in tobacco smoke are approximately 1.6-fold higher than levels in cannabis smoke. However, cannabis smoke contained higher levels of pyridine, acrylonitrile, 1,3-butadiene, aminonaphthalenes and aminobiphenyls.
OUTCOMES: Epidemiological studies have thus far been inconclusive in demonstrating a link between cannabis smoking and cancer. However, the cytotoxicity and mutagenicity analyses in this study show that the particulate phase of cannabis smoke condensate is potentially more hazardous than tobacco smoke generated under the same conditions. Furthermore, cannabis and tobacco smoke contain qualitatively the same toxic chemicals. Until there is a better understanding of the mechanisms involved and the overall significance of in vitro data with respect to human health and cancer, this information should be taken into account when considering the potential harms associated with smoking cannabis.
B. Marchand1, M. Kaiserman1, and J. Fillion1
1 Tobacco Control Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: Polycyclic aromatic hydrocarbons (PAHs) formed during incomplete combustion of tobacco are considered to be one of the most carcinogenic groups of compounds in tobacco smoke. Data from the chemical analysis of benzo[a]pyrene (B[a]P) in smoke were evaluated for 34 brands sold in Canada in order to estimate the mean daily exposure of Canadian smokers to B[a]P .
DESIGN: The data were extracted from reports submitted by the industry under the Tobacco Reporting Regulations covering the 2004 reporting period including ISO smoking conditions and Canadian Modified conditions. The 34 selected Canadian brands represented over 40% of the sales volume for 2004.
RESULTS: B[a]P ranged between 0.44 ng/cig and 17.9 ng/cig in unburned tobacco, between 1.25 and 12.2 ng/cig in MS smoke (ISO smoking conditions), between 11.7 ng/cig and 23.7 ng/cig in MS (modified smoking conditions) and between 91.5 ng/cig and 163 ng/cig in SS smoke. Based on a smoking rate of 15.2 cig/day, the B[a]P mean daily exposure varied from 0.13 :g/day in MS smoke using ISO conditions to 0.29 :g/day in MS smoke using modified conditions.
CONCLUSIONS: The daily exposure of B[a]P in cigarette smoke is higher than the no significant risk level of the California state and lower than the permitted occupational exposure recommended by the Occupational Safety and Health Administration (OSHA). Tobacco smoke constitutes a non-negligeable source of PAHs such as B[a]P. Tobacco smoke is also a complex mixture containing over 4000 chemicals including over 50 carcinogens and B[a]P represents only one of these carcinogens which have a serious impact on individual/population health.
K. Mattison1, M. Plante1, A. Cook2, F. Pollari2, R. Friendship3, K. Karthikeyan1, S. Bidawid1, and J.M. Farber1
1 Microbial Research Division, Bureau of Microbial Hazards, HPFB, Health Canada, Ottawa, ON
2 C-EnterNet, Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Guelph, ON
3 Department of Population Medicine, Ontario Veterinary College, University of Guelph, ON
OBJECTIVES: To determine the presence and types of norovirus in swine.
DESIGN:
OUTPUTS/RESULTS: 60/122 (49%) swine manure samples were found to be presumptively positive for norovirus. To date, 3 and 17 of these have been confirmed to be human and swine genotypes, respectively. Testing will continue for the remaining samples. All confirmed isolates belong to genogroup II. Several of the swine isolates are novel sequences that have not previously been reported.
IMPACTS/OUTCOMES/CONCLUSIONS: The potential implications for public health remain uncertain. However, some of the norovirus isolated from healthy domestic swine fall into the same genogroup as strains that infect humans. Therefore, there is the potential for zoonotic transmission of noroviral disease if these truly are human pathogens. Continued and expanded active surveillance with full genetic comparison with human isolates will clarify this link. Additionally, both human and swine norovirus genotypes were found in these pooled fecal samples. There is the potential for recombination between these genogroup II strains, resulting in novel viruses. Once again, continuing and expanding the active surveillance of gastrointestinal disease in the Canadian population will enable quantification of this risk.
J. Mei1, C. Wood1, and C.W. Xiao1
1 Nutrition Research Division, Bureau of Nutritional Sciences, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Retinoic acid (RA) is a metabolite of vitamin A and plays important roles in controlling cell growth, differentiation, lipid metabolism and carcinogenesis. Its effects are mediated mainly through its nuclear receptors (RAR). Our previous study had shown that consumption of soy protein isolate (SPI) affected the function of hepatic RAR in rats. However, the potential physiological impact of this intracellular response to SPI remains unclear. This study has examined the effect of dietary SPI on RAR-mediated gene expression of acetyl-CoA carboxylase (ACC), a rate-limiting enzyme involved in the synthesis of fatty acids, in ex vivo cultured rat liver explants.
DESIGN: Weaning Sprague-Dawley rats were fed diets containing either 20% casein or 20% alcohol-washed SPI for 60 days. Livers were isolated and rapidly cut into approximately 1-mm cubes and cultured in media containing 0, 1, 2.5 or 4 µM RA for 2 hours. ACCα and ACCβ mRNA abundances in the explants were measured by relative semi-quantitative RT-PCR.
OUTPUTS/RESULTS: Incubation with RA increased ACCα mRNA steady-state levels dose-dependently, but had no effect on ACCβ mRNA levels in the liver explants of female rats fed casein. Higher dose of RA (4 µM) significantly attenuated the mRNA abundances of both ACCα (0.66 ± 0.19 vs. 1.49 ± 0.56, p < 0.05) and ACCβ (1.13 ± 0.48 vs. 0.08 ± 0.05, p < 0.05) in the explants of female rats fed SPI compared to the rats fed casein. However, RA had no significant effect on either ACCα or ACCβ mRNA expression in the liver explants of male rats fed casein or SPI.
IMPACTS/OUTCOMES/CONCLUSIONS: These results suggest that consumption of soy-based products such as soy milk and soy infant formula may have different impact on the physiological functions of vitamin A and its metabolites compared to ingestion of bovine milk proteins. This information is important for the Food Directorate of Health Canada in the evaluation of health safety and nutritional quality of soy products.
J.M. Zielinski, PhD1,2, M.J. Garner, M Sc3, P.R. Band, MD1, D. Krewski, PhD4, H. Jiang, PhD4, J.P. Ashmore, PhD4, W.N. Sont, PhD1,4, M.E. Fair, MSc5, E.G. Letourneau, MD1, and R. Semenciw, MSc6
1 Safe Environments Programme, HECSB, Health Canada, Ottawa, ON
2 Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON
3 Carlington Community and Health Services, Ottawa, ON
4 McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, Ottawa, ON
5 Health Statistics Division, Statistics Canada, Ottawa, ON
6 Public Health Agency of Canada, Ottawa, ON
OBJECTIVES: Medical workers are exposed to chronic low dose ionizing radiation from a variety of sources. Potential cancer risks associated with such exposures have been derived from cohorts experiencing acute high intensity exposure, most notably the Japanese atomic bomb survivors. Since such extrapolations are subject to uncertainty, direct information on the risk associated with chronic low dose occupational exposure to ionizing radiation is needed. We examined possible associations with cancer incidence and mortality in a cohort of medical workers ascertained by the National Dose Registry of Canada (NDR).
DESIGN: Data from the NDR were used to assess the exposure to ionizing radiation incurred between 1951 to 1987 inclusive in a cohort of 67 562 subjects classified as medical workers. Standardized mortality (SMRs) and incidence (SIRs) ratios were ascertained by linking NDR data with those from the Canadian Mortality and the Canadian Cancer Databases respectively. Dosimetry information was obtained from the National Dosimetry Services of the Radiation Protection Bureau of Health Canada. Individual doses were combined to obtain annual doses for each member of the cohort.
OUTPUTS/RESULTS: There were 23 580 male and 43 982 female medical workers in the cohort. During the follow-up period, 1309 incident cases of cancer (509 in males, 800 in females) and 1325 deaths (823 in males, 502 in females) were observed. Mortality from cancer and non-cancer causes was generally below expected compared to the Canadian population. Thyroid cancer incidence was significantly elevated in both males and females, with a combined SIR of 1.74 (90% CI: 1.40-2.10).
IMPACT/OUTCOMES/CONCLUSIONS: Our result of an increased risk of thyroid cancer among medical workers occupationally exposed to ionizing radiation confirms previous reports. Over the last 50 years, radiation protection measures have been effective in reducing occupational exposures of medical workers to ionizing radiation to current very low levels.
M.-C. Nolet1, J. Fillion1, G. Levasseur1, and M.J. Kaiserman1
1 Tobacco Control Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: Evaluate the trends of the Canadian cigarette emissions over the last six years.
DESIGN: The Canadian Tobacco Reporting Regulations (TRR) requires the manufacturers to report every year the levels of 40 emissions under two smoking conditions. TRR allow manufacturers to request a reporting exemption by demonstrating a functional relationship between tar, nicotine and the other emissions (Benchmark) and submits data on various brands to support this request. In addition, Health Canada performs emissions testing on various cigarette brands in order to have additional data. The emissions levels of six brands selected from these two data sets were compared for a period of six years to determine whether there were any trends over time in emissions.
OUTPUTS/RESULTS: A major reduction in tobacco specific nitrosamines (TSNAs) levels is observed. This reduction can be explained by the change in curing process performed by the Canadian tobacco producers. The results indicate that overall, despite this decrease in TSNA, all other emissions show very little change over time. The reasons for this consistency, including source of tobaccos, cigarette engineering and product quality control will be discussed.
CONCLUSIONS/IMPACTS: Any changes in products profile may signal the need to investigate further the impacts on health. It is expected that this analysis will enhance evidence-based decision-making capability in connection with the regulation of tobacco products in Canada.
L. Ntezurubanza, PhD1, V. Assinewe, PhD1, and R. Marles, PhD1
1 Bureau of Clinical Trials and Health Science, Natural Health Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVE: To illustrate the potential roles for ginger containing health natural products in health promotion.
DESIGN: A review of ethnobotanical, chemical and pharmacological studies on ginger.
RESULTS: Today, ginger, Zingiber officinale Roscoe, is an ingredient in more than 50% of traditional herbal remedies described in Eastern and Western pharmacopoeias. There are many naturally occurring varieties of ginger and approximately 50 in India alone. There are striking differences in the essential oil and the oleoresin composition within Zingiber officinale chemotypes. Differing growing conditions and cultivation techniques result in each variety having its own unique aroma, flavour and pharmacological activities. For instance, milder examples tend to be found in China and more pungent ones in Africa. Jamaican ginger, which is used as a spice and a medicine, is one of the most highly valued commercial gingers worldwide.
This variability within rhizome composition may explain its different pharmacological activities, which have included gastrointestinal, cardiovascular, antiarthritic and antirheumatic, antimigraine, antinausea, antipyretic and analgesic, and serotonin-antagonist effects. Ginger has also shown antitumorigenic, antiparasitic and antiviral activities, mutagenicity and thermogenic action.
More recent results indicate the use of ginger for the prevention of nausea and vomiting associated with motion sickness and seasickness, the prevention of pregnancy-induced nausea and vomiting and the prevention of postoperative nausea and vomiting. Other recent results have shown that powdered root ginger could be as effective as an adjuvant to chemotherapy for treating ovarian cancer.
CONCLUSION: Ginger plays a role in the treatment of many ailments.
R. Leblanc1, T. Topolnisky1, B. Pichette1,2, and F. Valcin1
1 Ron Breecher, Golbaltox International. TrevorDiggins-Smith, Frontline Communications
2 Safe Environments Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: To educate GOC staff to develop an effective model that can be utilized to communicate technical health risk information to stakeholders in a way that enhances understanding of complex concepts while addressing stakeholder concerns.
DESIGN: The approach was based on an instructional design model. Best practices in risk communication were reviewed in addition to an environmental analysis of GOC stakeholders in the Contaminated Sites program. The stakeholder analysis included: factors influencing public perceptions of risk; communication challenges regarding technical information; risk communication principles; stakeholder expectations in terms of research dissemination and building capacity for effective communication.
OUTPUTS/RESULTS: The main findings or essential details in support of the impacts/outcomes/conclusions.
Stakeholder demand for effective communication of health risk information from Health Canada has increased significantly. In addition, stakeholder perception and understanding of risk are influenced by many factors, including their capacity to understand scientific concepts; the effects of the risk on individuals' well-being and on that of their community; the type of information they are looking for; and the extent to which stakeholders believe the source of risk information is credible, open and transparent. Risk assessment terminology can be highly technical and inaccessible to stakeholders if the communication model does not take these factors into consideration. Ineffective health risk communication may result in increased stakeholder frustration, and distrust of credible health risk information.
IMPACTS/OUTCOMES/CONCLUSIONS: A summary of the outcomes supported by the results and linked to specific health-related issues where relevant.
The utilization of a health risk communication model based on stakeholder analysis, which identifies that their capacities can enhance the stakeholders ability to understand complicated health risk information as that presented in a health risk assessment. Stakeholder analysis indicates that stakeholders perceive health risk through a filter of psychosocial, emotional and cultural factors.
K.H. Poon1, S.W. Dai1, and R. H. Devlin2
1 Western Region Laboratory, HPFB, Health Canada, BC/Alberta Region, Burnaby, BC
2 West Vancouver Laboratory, Department of Fisheries and Oceans, West Vancouver, BC
OBJECTIVES: Develop a reliable method to quantify as low as 1% of DNA from transgenic fish in a mixed-DNA pool, consisting mainly of wild-type conspecific DNA.
DESIGN: Individuals from one specific line (M77) of the genetically modified coho developed by the West Vancouver Laboratory of the Department of Fisheries and Oceans were used in this study. The transgene construct onMTGH1 (comprising of the metallotionein-B promoter and the type-1 growth hormone gene from sockeye salmon) has been stably incorporated into its genome for several generations. Various amounts of its DNA were mixed into a larger pool of DNA from wild-type coho, and their levels measured by real-time PCR using Taqman chemistry in conjunction with the Delta-Delta Ct method. Primers and probes were carefully designed for three endogenous nuclear genes (RNase P, beta-actin, and 18S rRNA) to serve as candidate reference genes, and their suitability as reference genes for the relative quantification of onMTGH1 assessed.
OUTPUTS/RESULTS: The Delta-Delta Ct method that is conventionally used to study gene expression (i.e., messenger RNA level) by real-time PCR has been successfully adapted for use in the quantification of DNA levels of a transgenic fish in a pool of DNA of its conspecifics. Detailed analysis of the real-time PCR data of the three endogenous genes revealed the significant degree of genetic diversity among the several coho individuals studied, rendering their usefulness as quantitative reference genes limited. However, by carefully matching the genoptypes of individual transgenic and wild coho and the adopting the appropriate reference gene sequences, it is possible to accurately measure as low as 1% of DNA of transgenic coho that has been mixed with a pool of wild coho DNA.
IMPACTS/OUTCOMES/CONCLUSIONS: The limit of quantification established in this study meets the labeling threshold levels set by any country in the world, the most stringent being 0.9% by the European Union. This study provides some useful data from a transgenic animal for discussing the practicality and scientific validity of the "labeling threshold" legislation, which has so far been analyzed only from the perspective of GM crops.
S. Racine, M.Ps.1, J. Flight, M.A.1, and E. Sawka, M.A.2
1 Office of Research and Surveillance, DSCS, HECSB, Health Canada, Ottawa, ON
2 Alberta Alcohol and Drug Abuse Commission, Calgary, AB
OBJECTIVES: The presentation will focus on the results concerning public opinion attitudes and knowledge of Canadians about drugs issues. The themes covered include the following: perceived seriousness of the issue; perceived harms from substance use; and, opinions about cannabis or other illicit drugs.
METHODS: The Canadian Addiction Survey (CAS 2004) is a random digit dialing telephone survey of 13 909 Canadians aged 15 years old and over covering the 10 provinces (the Territories are not included) conducted between December 2003 and April 2004. Results were examined using logistic regressions.
RESULTS: The findings suggest that Canadians agree to a national response to substance use issues that favours a social/medical approach using treatment and prevention but not to the exclusion of enforcement and which is international in scope. However, they seem ambiguous with regards to cannabis, requesting less recourse to the criminal system but still agreeing to other legal actions and associated penalties such as fines.
CONCLUSIONS/IMPLICATIONS: In May 2003, the Government of Canada announced the renewal of Canada's Drug Strategy. One of the priorities identified was the conduct of a general population survey to determine the prevalence and harms associated with alcohol and other drugs use and abuse. In addition to updating our evidence-base on prevalence and harms, this survey allowed Health Canada to query the opinions of Canadians regarding their perception, attitudes and knowledge on these issues and to examine the correspondence with the recommended investments of Canada's Drug Strategy and of the National Framework for Action to Reduce the Harms Associated with Alcohol and Other Drugs and Substances in Canada.
K. Richard, MA1, B. Brands, PhD1, and R. Hanson, MA1
1 Office of Research and Surveillance, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: To explore trends in the methamphetamine market in Canada, the Office of Research and Surveillance undertook a study that examined samples analyzed by the Drug Analysis Service (DAS). This programme is responsible for testing all suspected drug samples sent to their labs by police and customs officials. By exploring data associated with samples seized, it allowed us to add to the knowledge on emerging methamphetamine trends in Canada.
DESIGN: DAS operates four laboratories across Canada. All methamphetamine seizures that were analyzed by DAS from 1988 to 2005 were included in this study. Exploration of DAS samples allows us to determine if cyclical patterns are evident, if methamphetamine is becoming more prevalent, and if the purity content of the substance is consistent over time.
OUTPUT/RESULTS: While, the number of samples containing methamphetamine was relatively low (1.58%) when compared with other substances; Canada did see a significant increase in seizures during this time period. In the past five years, the percentage in the number of samples analyzed that contained methamphetamine has increased from 1.4% in 2000 to 5.8% in 2005. Moreover, there has been a significant increase in the number of samples that contain multiple substances. In 2000, 91% of the samples contained just methamphetamine, while in 2005, this number decreased to 74%. Further, significantly more samples contained methamphetamine (24 163) than was originally suspected by police or customs (13 465).
IMPACTS/OUTCOMES/CONCLUSIONS: These analyses allow us to have a regular and systematic monitoring approach to trends in the illicit drug market and it assists in allowing for early detection of an emerging drug trend. This has serious implications for public health and law enforcement. It should be noted that: only samples that are going to trial are analyzed (cases in which a guilty plea has been entered are not analyzed) and therefore the data under-estimate the total number of illicit drug seizures. Further, it is not known whether the distribution of substances analyzed is similar to the quantities and distribution of illicit drug seizures by police and border services. Finally, the distribution of substances seized is a function of the resource allocation, priorities and effectiveness of police and border service activities. Additional research is needed to determine the extent to which the prevalence of substances seized differs from the prevalence of substances in the illicit drug market.
I. Zverev, MA1
1 Applied Research and Analysis Directorate, HPB, Health Canada, Ottawa, ON
OBJECTIVES: To evaluate the impact of Ontario's Universal Influenza Immunization program.
DESIGN: We use data on the prevalence of influenza, number of influenza tests performed, the number of hospitalizations for influenza and cardiovascular diseases (CVD), as well as drug sales in Ontario and rest of Canada to evaluate the impact of Ontario's Universal Influenza Immunization Program (UIIP).
OUTPUTS/RESULTS: Relative to the Rest of Canada (ROC), Ontario experienced a sharp drop in the number of influenza cases in 2000/01 following the introduction of UIIP. The number of flu cases dropped by 70% following the introduction of UIIP, compared to a 21% decrease in ROC in the same period. The number of hospitalizations for influenza (77% vs. 49%) and CVD (61% vs. 5%) also significantly decreased. Relative contribution of UIIP to the overall reduction in influenza prevalence is difficult to determine due to a corresponding decline in the number of cases in the rest of Canada.
CONCLUSIONS: Introduced in 2000/01, UIIP provides free influenza vaccination to people above the age of 6 month. Ontario is the only jurisdiction to provide a free vaccine to all residents. Programs in other jurisdictions focus on medical staff and specific population groups at high risk of developing influenza-related complications.
Evaluating the effectiveness of UIIP is important for the development of pandemic preparedness for the potential avian influenza outbreak. Limited impact of UIIP on influenza prevalence in Ontario would mean that pandemic preparedness plan would have to focus on means of protecting Canadian population other than vaccinations. On the other hand, if it is clear that UIIP was instrumental in containing influenza outbreaks in Ontario, efforts should be focused on developing vaccine for the H5N1 strain of influenza.
A. Knafla, MSc, DABT1, C. Ott, MSc2, S. Petrovic, MSc3, S. Ramji, MSc3, C. Rowat, MSc3, and D. Schoen, MSc3
1 Equilibrium Environmental Inc., Calgary, AB
2 URS Canada Inc., Vancouver, BC
3 Contaminated Sites Division, Safe Environments Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: Cancer risks are assessed for polycyclic aromatic hydrocarbon (PAH) mixtures using a slope factor for benzo[a]pyrene (B[a]P), and relative potency equivalency factors (PEFs) for other PAHs. In Canada, the Priority Substance List Assessment Report contains PEFs for only 5 PAHs. Analysis of environmental samples have identified significant concentrations of many additional PAHs. The objective of this project was to conduct a literature review of available data for the carcinogenicity of PAHs, and recommend PEFs for them.
DESIGN:
Existing PEFs: Review existing PEFs of other regulatory agencies. If there is consensus on a PEF, recommend this value. If PEFs are within an order of magnitude, recommend the most conservative. If PEFs varied greatly, review the carcinogenicity data and recommend a PEF.
No existing PEFs: If a PAH is reported in environmental mixtures and/or indicates the potential for significant carcinogenic potency, conduct a data review and recommend a PEF.
RESULTS:
Existing PEFs: 20 PAHs were found with pre-existing PEFs and good evidence of genotoxicity/carcinogenicity. Only two were for alkylated PAHs. Nine PEFs (based on consensus), and 11 PEFs (based on analysis of the PEFs and carcinogenicity data) are recommended.
No available PEFs: PEFs are recommended for 33 PAHs with no published PEFs. Of these PAHs, 31 are alkylated, and 14 have potencies equivalent to or greater than B[a]P.
CONCLUSIONS: To promote consistency in the evaluation of carcinogenic PAH mixtures at contaminated sites, Health Canada should, where possible, recommend specific PEFs for individual PAHs. Based on this literature review, 53 PEFs are proposed. No regulatory agency has derived PEFs for several alkylated PAHs often present at contaminated sites. Currently, many of these compounds are simply ignored in risk assessments. Not considering alkylated PAHs in health risk assessments may significantly underestimate the carcinogenic potential of PAH mixtures.
S. Sarma, PhD1, R.A. Devlin, PhD2, and W. Hogg, MD3
1 Microsimulation and Modelling and Data Analysis, Applied Research and Analysis Directorate, HPB, Health Canada, ON
2 Department of Economics, University of Ottawa, ON
3 Department of Family Medicine, University of Ottawa, Ottawa, ON
OBJECTIVES: Recent years have witnessed a shortage of the family physicians in Canada. The dearth of family physicians is a major concern because they are the first point of contact for most Canadians, and are responsible for the lion's share of the management of chronic diseases and the delivery of preventive care. The amount of time family physicians spend in providing direct patient care and the number of patients they treat might be influenced by the method of remuneration. The objective of this study is to analyze the extent that different remuneration schemes and practice settings affect physician output.
DESIGN: We use the Ontario data from the 2004 National Physician Survey and analyze family physicians' patient visits as a function of hours worked providing direct patient care, remuneration schemes, demographic characteristics and practice settings. The theoretical framework underlying this study is a behavioural production function approach. The instrumental variable method of estimation technique is used to account for the endogeneity bias.
OUTPUTS/RESULTS: After controlling for physician demographics and a number of practice characteristics, we find that physicians paid on a fee-for-service are more productive in terms of number of patient visits per week than those who are paid under alternative payment schemes. However, this productivity gain is significantly reduced once we take into account the practice characteristics, especially the illness severity of patient population served in a practice. The group practices are substantially more productive than solo practices.
IMPACTS/OUTCOMES/CONCLUSIONS: Provides evidence supporting the view that remuneration schemes influence physician production of health care services. The results suggest that the productivity associated with fee-for-service be considered against the benefits offered by other practice styles for health policy formulation. The shortage of family physicians can be addressed by producing more of them and by ensuring remuneration and practice settings are optimized.
G. Carrier1,2, M. Bouchard1,2, N. Gosselin1, N. El Majidi1, et D. Schoen3
1 Department of Environmental and Occupational Health, Université de Montréal, Quebec
2 Institut national de santé publique du Québec, Montreal, Quebec
3 Safe Environments Programme, Health Canada, Longueuil, Quebec
This research has three components:
For the first component, the temporal profile kinetics of the body burden are studied using a model that allows for taking into consideration the gender of the study subjects, their age, variation in their weight and body fat, and various exposure scenarios throughout their lifetime. PCBs are grouped into four categories on the basis of the number of chlorine atoms. The exposure scenarios were established on the basis of the published data, which make it possible to estimate over time people's daily intake by age and gender, on the basis of the measured concentrations in food and ambient air in different periods. The model was validated using data from the literature on biomarker measurements in Canadians of both genders at all ages.
The results of the modelling show that a Canadian born in 2000 will, throughout his or her life, be exposed about 5 times less than a Canadian born in 1970, given that the current contamination will decrease much more slowly than did past contamination. It can be deduced that future PCB exposure of Canadians born in the 2000s will never be as high as the exposure of Canadians born before that period. Their risk of being affected by an exposure will therefore be equally lower.
T. Schrader, PhD1, and I. Langlois, BSc1
1 Toxicology Research Division, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: Furan has been isolated from cooked or heated foods, apparently arising through reactions of amino acids, fatty acids, and ascorbic acid. Furan is carcinogenic in lab animals and has been classified as group 2B, possibly carcinogenic to humans. However, although some evidence for furan mutagenicity has been found in mammalian cells, no prokaryotic system has provided a positive response. To examine possible mechanisms for mutagenic activation, furan was incubated with acidified sodium nitrite, a common food preservative, and assayed using the Ames Salmonella test.
DESIGN: Furan, +/- nitrosylation with sodium nitrite in acetic acid buffer, pH 4, was tested for electrophilic activity using the colorimetric 4-(4'-nitrobenzyl)pyridine (NBP) assay. Native and nitrosylated furans were then tested for mutagenicity with the Ames Salmonella test, using strains sensitive to frameshift (TA97, TA98) and base pair (TA100, TA102, TA104) mutations, +/- rat liver S9 for metabolic activation.
OUTPUTS/RESULTS: When tested in the NBP assay up to 100 mg/ml, native furan produced little electrophilicity; however, nitrosylated furan displayed electrophilic activity at 20 µg/ml, the lowest concentration tested. Furan was negative as both a frameshift and base pair mutagen when tested up to 10 mg/plate, but 10 mg/ml of nitrosylated product produced a directly mutagenic species positive in Salmonella strains TA97, TA100, TA102 and TA104. Similar results, although with somewhat lower reverent numbers in TA97 and TA100, were found + S9.
IMPACTS/OUTCOMES/CONCLUSIONS: While furan was negative for both electrophilicity and mutagenicity, nitrosylation produced an electrophilic species with a rather weak direct-acting frameshift mutagenic activity in a run of C's (TA97) and base pair mutagenic activity at GC sites (TA100) as well as AT sites (TA102, TA104). These results demonstrate that dietary interactions can influence the mutagenic activation of food-associated chemical and that such approaches can expand the usefulness of a genetic testing regimen.
V.L. Seligy1, G. Coleman1, J. Crosthwait1, K. Nguyen1, P. Shwed1, A.F. Tayabali1, J. Rancourt2, M. Mulvey3, and G. Rousseau4
1 Environmental Health Science Bureau, HECSB, Health Canada, Ottawa, ON
2 Consumer Products Safety Bureau, HECSB, Health Canada, Ottawa, ON
3 Public Health Agency of Canada, Winnipeg, MB
4 Environmental Monitoring, SOPFIM, Quebec
OBJECTIVES: To examine utility of the nucleic acid (NA) component of microbe-based bioproducts as analyte in tests to assess identification and environmental exposure.
DESIGN: 'Free' (fNA) and intracellular-NA were measured in supernate and pellet fractions of commercial Bt-bioproducts derived from B.thuringiensis (Bt) subspecies israelensis (Bti) and kurstaki (Btk), and cultures of them, and Bt13367 and B.cereus14579(Bc) of the Canadian Environmental Protection Act (CEPA 1999) DSL. Samples from Bt-bioproduct aerial sprays were also analyzed. Detection/quantification methods included colony count, scanning electron microscopy, NA hybridization and PCR methods, using gene probes in single or microarray format.
RESULTS: Bt-bioproducts produced similar-sized pellets (~30-35% w/w) containing comparable masses of spores (~ 1-4x10^10 mL) and proteinaceous-NA aggregates, including parasporal-inclusion bodies (PIBs). Using non-spore disrupting extraction methods, both fractions contained fNA (~40% of total NA; range 0.02-20kb). As PCR templates, fNA was poor compared to spores (~ 10x) and vegetative cells (~50-60x). PCR, Southern blot and microarray assays (> 5000 Bc14579 or Ba A2015 genome features) indicated the fNA was genome related. Analysis of field samples along with calibrated spray droplets and Bt-product dilutions indicated that NA detection was limited (~ 0.1% of live cell values).
CONCLUSIONS/IMPACTS: As an analyte for quantifying environmental release of Bt-Bc-type bioproducts, the NA component has limited use with current NA detection tools. Gene-level detection is reduced by inefficient access to spore DNA, and high content of interfering fermentation residues like fNA. The fNA is clearly genomic in origin. fNA has potential to act on innate immunity via Toll-like receptors during bioproduct exposures, but its degraded state may not mediate significant genetic exchange with feral pathogen counterpart. Some fNA may come from lysed cells, however, given its abundance in Bti/Btk spore-phase cultures, we hypothesize that fNA is genomic residue of non-spore forming daughter cells dedicated to form the insecticide-containing aggregates or PIBs.
M.S. Sevinc, PhD1, V. Kumar, MSc1, M. Abebe, PhD1, S. Mohottalage, PhD1, P. Goegan, MSc1, R. Vincent, PhD1, P. Kumarathasan, PhD1, H.M. Vijay, PhD1, and T. Cyr, PhD2
1 Safe Environments Programme, HECSB, Health Canada, Ottawa, ON
2 Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON
OBJECTIVE: To develop a test kit for mass screening against the allergen Pen b 26 of Penicillium Brevicompactum, a very prevalent indoor allergen
DESIGN: The allergen Pen b 26 of P. brevicompactum was cloned and over-expressed as a 6x His-tagged, N-terminal fusion protein in Escherichia coli. The allergen was purified by his-tag affinity chromatography and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), immuno-blot and mass spectroscopy.
OUTPUTS/RESULTS: Immuno-blot analysis with atopic sera showed that Pen b 26 was an allergen. BLAST search indicated that it had strong homology to 60 S ribosomal P1 proteins, which was also confirmed by immuno-blot analysis using human IgG antibody against ribosomal P proteins. Time-course expression of Pen b 26 fusion protein showed that the concentration of the fusion protein in solution increased with the time after induction with IPTG, being greatest at 3 hours. However, the fusion protein migrated at about 7 kDa higher than the estimated molecular weight of 14.9 kDa of the cloned Pen b 26 on regular SDS-PAGE. The discrepancy between the observed and estimated molecular weights was clarified by mass spectroscopy, which confirmed the size of the estimated molecular weight of Pen b 26 as14.9 kDa. Prevalence of antibodies against Pen b 26 among atopic patients was also studied by immuno-blot analysis. It was found that about 25% of the atopic patients had antibodies against Pen b 26.
IMPACTS/OUTCOMES/CONCLUSIONS: Pen b 26 was identified as 60 S ribosomal P1 protein and a minor allergen of Penicillium brevicompactum was successfully expressed in Escherichia coli. It is now possible to incorporate this cloned allergen into a kit for screening of individuals allergic to Penicillium. In addition, about 50% of the individuals allergic to 60 S ribosomal P proteins have also autoantibodies in their sera and susceptible to autoimmune diseases. Therefore, the kit for screening of Pen b 26 allergen may also be used as a biomarker for screening of individuals susceptible to autoimmune diseases.
P.S. Shwed, PhD1, J. Crosthwait, BSc1, A.F. Tayabali, PhD1, and V.L. Seligy, PhD1
1 Safe Environments Program, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: We are developing genomic and proteomic-based methods and data to establish a baseline for toxicity/pathogenicity testing of Bacillus biotech-organisms regulated under the Canadian Environmental Protection Act (CEPA 1999) and the Pest Control Products Act. Here we report on data derived by gene-based micro array hybridizations and a statistical significance algorithm (SSA) to analyse temporal expression and validate function of select genes using real-time PCR (RT-PCR).
DESIGN: Mouse macrophage cells (J774A.1) were exposed to Bacillus cereus (Bc) group spores, vegetative cells and controls (unexposed cells, Bacillus subtilis or micron-sized latex spheres) for up to 3 hours. Expression of select autoimmune/ inflammatory response genes was monitored using cDNA microarrays and a subset of samples was hybridized to oligonucleotide arrays in order to observe genome wide transcription. Differentially expressed genes were identified using SSA of time course data. Select inflammatory response genes, including the tumour necrosis factor gene were verified by RT-PCR and RNA:probe:capture bead hybridization and detection.
OUTPUTS/RESULTS: Cluster analysis allowed identification of gene groups (homeostasis, chemokines and receptors) that featured similar expression responses to bacterial spores and not latex spheres. Preliminary SSA carried out on data from a live vegetative cell exposure has yielded a significant gene list that includes genes identified by cluster analysis as well as transcription factor receptors and chemokines. Comparison of RT-PCR and RNA: probe: bead hybridization results for select inflammatory response genes show general agreement.
IMPACTS: This analysis significantly augments knowledge on macrophage-like cell exposures and Bc group organisms particularly common early gene responses during uptake. Exposure to Bc, Bti and Btk live vegetative cells induce rapid cytotoxic effects. The development and application of significance analysis coupled with hybridization assays will lead to the identification of significantly expressed genes and rapid validation.
B. Slater1, D. Oudit2, A. Hughes2, M. Taylor3, and L. Hill1
1 Food Liaison, HPFB, Health Canada, Edmonton, AB
2 Bureau of Microbial Hazards, HPFB, Health Canada, Ottawa, ON
3 Foodborne, Waterborne and Zoonotic Infections Division, Public Health Agency of Canada, Guelph, ON
OBJECTIVES: In September 2004, the Calgary Health Region investigated 84 cases of Escherichia coli O157:H7 attributed to the consumption of beef donairs. In order to mitigate the potential health risk in the future, there was a need to characterize the risk factors associated with the consumption of donairs and similar products in Canada.
DESIGN: A Federal/Provincial Working Group was established to collect information and evaluate current Canadian processing, preparation and handling procedures for donairs. The diverse nature of the industry necessitated studying the practices in both restaurants and manufacturing facilities of different sizes and with different food safety controls.
The Working Group also collected current research, reports of food-borne illness, and existing guidance to industry. Data sources included national and international food safety regulators, product manufacturers, and manufacturers of donair broiler machines.
OUTPUTS/RESULTS: The primary risk factors were identified as:
The Working Group determined there is a fundamental absence of control measures in Canada to ensure that E. coli O157:H7, Salmonella spp. and Campylobacter jejuni are not present in donair meat served to consumers by food service operators that cook raw donair cones. Concurrent with this lack of control is an absence of guidance from Canadian regulators on appropriate food safety practices relating to donairs, and concern that existing food safety messages from the industry are neither consistent nor complete.
IMPACTS/OUTCOMES/CONCLUSIONS: This study provides the evidence required to support recommendations from food safety regulators and the Canadian food industry to improve preparation, cooking, cooling, storage and handling of donairs. Information sharing between stakeholders is an effective way to identify and address the risks associated with a food-borne illness outbreak.
J. Stevenson, MA1, and J. Snider, MSc1
1 Office of Research, Surveillance and Evaluation, Tobacco Control Program, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: To monitor self-reported exposure to second-hand smoke (SHS) at home and in places other than the home in Canada.
DESIGN: The Canadian Tobacco Use Monitoring Survey (CTUMS) is an ongoing random digit dialing telephone survey of over 20 000 Canadians 15 years and older.
RESULTS: Based on the CTUMS annual 2005 results, 15% of Canadian households reported at least one person who smoked inside the home everyday or almost everyday (compared to 29% in 1999). Of those households without someone regularly smoking inside the home, 85% did not allow any smoking inside their home (compared to 74% in 2000).
Nine percent of Canadian children aged 0-11 years (382 000 children) were regularly exposed to second hand smoke in Canadian homes in 2005, a reduction from 26% (1.1 million children) in 1999.
Beginning in 2005, exposure to SHS in places other than the home was added to CTUMS. For the first half of 2005, almost 1 in 6 (14%) of Canadians reported being exposed to SHS everyday in places other than their home (e.g., inside a vehicle, in the workplace, at a restaurant/bar/tavern, etc.). The most commonly reported place of SHS exposure was at an entrance to a building (49%).
CONCLUSIONS: It is estimated that exposure to SHS is responsible for 1000 adult non-smoker deaths each year. Monitoring exposure to SHS will provide an indicator of progress made with the advent of provincial smoke free public place bylaws.
C. Stocco, MSc1, D. Wang, PhD2, J. Brook, PhD3, and A. Wheeler, PhD1
1 Air Health Effects Division, Environmental Contaminants Bureau, HECSB, Health Canada, Ottawa, ON
2 Analysis and Air Quality, Environmental Technology Centre, Science and Technology Branch, Environment Canada, Ottawa, ON
3 Meteorological Service of Canada, Air Quality Research, Science and Technology Branch, Environment Canada, Ottawa, ON
OBJECTIVE: As part of a multi-year personal exposure monitoring campaign, 24-hour personal, indoor, and outdoor levels of 188 polar and non-polar volatile organic compounds (VOCs) were obtained for 48 Windsor residents in order to assess their exposure to traffic-related VOCs as a result of their daily routine.
DESIGN: During the winter and summer of 2005 personal, indoor and outdoor locations for 48 participants were monitored. Every 24 hours, for a period of five days in each season, a 1.0 L Summa canister was deployed for personal VOC sampling and 6.0 L Summa canisters were used for indoor and outdoor VOC monitoring. The indoor VOC canister was placed in either the family or living room, while the outdoor VOC canister was located in the backyard, several meters away from the home and from combustion sources. The smaller Summa canister was placed in a backpack that the participants carried everywhere they went. In total, 1350 samples were collected. In order to investigate associations between participant activity and exposure to VOCs, a daily questionnaire and time activity diary were also administered. Samples were analyzed by capillary GC-MS, operated in selected ion monitoring mode.
OUTPUTS/RESULTS: Benzene results indicate that during the winter, mean concentrations for all 48 participants were 1.93±1.30, 2.10±1.88 and 1.03±0.47 µg/m3 for personal, indoor and outdoor locations respectively. During the summer the personal and indoor mean concentrations increased to 2.67±2.76 and 2.92±3.48 µg/m3 and outdoor concentrations were lower at 0.86±0.49 µg/m3.
Time activity diary information revealed that, on average in the winter, participants spent 93% of their time indoors (for example: at home, away from home, and at work), compared to 88% in the summer. Between the two seasons, there did not seem to be any difference in the amount of time spent in transit (vehicle use, walking and taking bus), which accounted for 5.5% of participant time. Further analysis may help us understand the seasonal differences in benzene exposure.
For the 48 participants there is greater inter and intra person variability for indoor and personal exposure to VOCs than is found outdoors. In addition, there seems to be more variability in the summer than in the winter. Preliminary analysis of the data also indicates that in homes where there are attached garages, traffic-related VOCs are higher indoors, and as a result, personal exposure levels are also higher than in homes without attached garages.
IMPACTS/OUTCOMES/CONCLUSIONS: Personal exposure to VOCs appears to be driven by indoor concentrations of VOCs rather than outdoor, which may be of concern as Canadians spend up to 90% of their time in indoor environments.
A.F. Tayabali, PhD1, K.C. Nguyen, BSc1, G. Arvanatakis2, D. Johnston2, M. Navarro, DVM3, S. Popovic3, K. Kittle3, D. Parks3, and V.L. Seligy, PhD1
1 Safe Environments Program, HECSB, Health Canada, Ottawa, ON
2 Product Safety Program, HECSB, Health Canada, Ottawa, ON
3 Animal Resources Division, HPFB, Health Canada, Ottawa, ON
OBJECTIVES: According to the Canadian Environmental Protection Act (CEPA 1999), animate products of biotechnology must be assessed for harmful effects prior to use, import, or manufacture in Canada. In previous work, Domestic Substances List (DSL) bacteria from the Bacillus genus were used as models to screen for potentially harmful effects. Towards this goal, a multi-indicator immunologic strategy was established to test Bacillus inhalation effects in Balb/c mice. These findings showed that spores were cleared efficiently, but 2 hour exposures to washed outgrowths caused shock-like symptoms, neutrophil infiltration, and elevations in proinflammatory cytokines. The objective of the current study is to elaborate on biomarkers indicative of systemic responses and tissue damage during exposure to washed outgrowths.
DESIGN: Outgrowth cultures contain >90% live and dead vegetative bacteria, but also spores and extracellular culture constituents. These were washed of soluble material and used for intratracheal 4 hour exposures to Balb/c mice. Animals were evaluated for physical signs of recovery or distress, pulmonary and serum granulocyte and cytokine levels, as well as liver-expressed acute phase response proteins (serum amyloid A and fibrinogen). Several assays indicative of pulmonary oxidative stress (e.g., lipid peroxidation, DNA adducts) were also used.
OUTPUTS/RESULTS: Four-h shock-like symptoms included hypoactivity, hunched appearance, ruffled fur, respiratory distress, increased lethargy and ocular discharge. Pulmonary granulocytes were elevated by > 3-fold and hepatic and circulatory acute-phase markers were elevated by 1.5 to 4 -fold. Generally, pulmonary cytokine levels were indicative of severity of physical symptoms. For oxidative stress indicators, pulmonary myeloperoxidase was elevated by ~1.5-fold. Of the Bacillus strains tested, B.cereus 14579 and B.thuringiensis 13367 caused most severe effects, whereas effects of B.thuringiensis commercial strains were weak, and those of B.subtilis-inoculated mice were asymptomatic.
IMPACTS/OUTCOMES/CONCLUSIONS: The biomarkers described here are indicative of systemic (hepatic, blood) effects and generally correspond to appearance of physical symptoms. The results show that washed outgrowths of Bc and Bt, but not Bs, could result in health-related issues and should be evaluated further for potential adverse health effects.
P. Tissaaratchy, MA1
1 Health Demand and Supply Analysis Division, Applied Research and Analysis Directorate, HPB, Health Canada, Ottawa, ON
OBJECTIVE: To explore, using recent Canadian survey data, determinants of prolonged waiting times for non-emergency specialized health care services.
DESIGN: A weighted logistic regression model is developed for surgical, diagnostic, and specialist physician services. The relationship between waiting time and socioeconomic status, health status, demography, cancellation, overnight stay, having a family physician, diagnostic condition, and access difficulties is examined.
A prolonged wait is defined as waits exceeding the i) median and ii) third quartile. A relative measure is used to compare characteristics of all patients who faced longer waiting times versus those who did not. (Medically acceptable waiting times apply to select procedures and would not capture all respondent information.)
RESULTS: For surgery, the probability of a prolonged wait is 5.0 times for those with hip/knee problems. Patient cancellation increases by 11.7 times the likelihood of a prolonged wait. For specialist services, patient cancellation increases the likelihood of a prolonged wait by 5.2 times. For diagnostic services, the probability of experiencing a prolonged wait is 5.7 times greater for those reporting difficulty obtaining a hospital bed. The likelihood of experiencing a prolonged wait is 7.0 times greater for those reporting difficulties obtaining an appointment/referral.
CONCLUSIONS: For all services, diagnostic conditions associated with higher mortality rates are associated with the lowest probabilities of a prolonged wait indicating prioritization. For diagnostic services (where private sector options exist), those with the highest income have the lowest probability. Those obtaining diagnostic scans in a public institution have a higher probability than those obtaining scans in private institutions. For surgery, patient cancellation is associated with the highest probability. Procedures requiring an overnight stay are associated with a higher probability. For diagnostic and specialist services, experiencing barriers to access is associated with the highest probability. For surgery and diagnostic services, absence of a family physician is associated with prolonged waiting.
H.M. Vijay, PhD1, V. Kumar, MSc1, M. Abebe, PhD1, M.S. Sevinc, PhD1, and R. Vincent, PhD1
1 Safe Environment Programme, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: 1. To investigate the adjuvant effect of air pollutants on the sensitization of mice to molds and mites. 2. To investigate if air pollution exposure can be related to the prevalence of asthma.
DESIGN: Five groups, each consisting of 6 female BALB/C mice, were immunized as follows: group A was given IP injection of 100 ug of A. alternata mixed with 6 mg of EHC-93; and, group B with the same dose of A. alternata with 6 mg alum. The three control groups C, D, and E were given an IP injection of A. alternata extract, EHC-93 and alum alone, respectively. After four weeks, all the groups were boosted in a similar way except A, B and C, which received 10 ug of the extract. The animals were bled at 7, 14 and 21 days. The strength of the specific antibodies was determined individually by passive cutaneous anaphylaxis (PCA) reaction. Similarly, a second experiment was carried out using D. farinae as an immunizing agent. Total IgE in the sera of the animals was determined by ELISA.
OUTPUTS/RESULTS: Groups A and B gave strong PCA reaction (10x14 mm) indicating EHC-93 is equally as potent adjuvant as alum. The mice immunized with A. alternata alone gave very week reaction and groups D and E were found to be negative. Similar results were found when the animals were immunized with D. farinae. Significant increase in the total IgE was observed in groups A and B.
IMPACTS/OUTCOMES/CONCLUSIONS: EHC-93 appears to exert strong adjuvant activity for the production of specific IgE antibody in BALB/C mice immunized with A. alternata or D. farinae. It could be hypothesized that influence of air pollution in both allergic sensitization and inflammatory response could be gene-environment interaction.
J. Van Oostdam, DVM, MPH1, and M. Walker, PhD2
1 Management of Toxic Substances Division, Safe Environments Programme, HECSB, Health Canada, Ottawa, ON
2 Biostatistics and Epidemiology Division, Safe Environments Programme, HECSB, Health Canada, Ottawa, ON
INTRODUCTION: Canada is participating in the tri-lateral maternal blood contaminant monitoring study of persistent organic pollutants (POPs) and various metals under the North American Commission for Environmental Cooperation (NACEC). Levels of metals such as mercury and lead are likely to be quite low in this population but recent research has indicated that there may be significant health risks to the fetus at lower levels of exposure.
METHODS: This study will examine levels of POPs and heavy metals in the blood of twenty five first birth mothers from five centres across southern Canada. Hospitals and clinics in Halifax, Ottawa, Hamilton, Calgary and Vancouver are recruiting mothers. Samples are being analyzed at one central laboratory for a range of POPs (e.g., PCBs, DDT/DDE, chlordane derivatives, aldrin, dieldrin, hexachlorobenzene, mirex, hexachlorocyclohexane isomers) and various metals (i.e., mercury, lead, cadmium, arsenic). Each mother will complete a demographic and dietary questionnaire.
RESULTS: Comparative results from arctic Canada have found that Inuit mothers from the Baffin Region have significantly higher levels of PCB 153 compared to Caucasian mothers living in arctic Canada (131 vs 16 microgram/kilogram lipid). This regional data from southern Canada will be compared for a number of contaminants including PCBs, mercury, DDE, oxychlordane and other contaminants to the ethnic differences we have seen from arctic Canadian populations. The relationship between demographic characteristics, dietary intakes and contaminant levels will be assessed.
DISCUSSION AND CONCLUSIONS: This study will be the first national assessment of these contaminants in this important segment of the population and will allow initial regional comparisons plus provide information for larger national or regional studies. This information will have direct application for Canada in meeting its monitoring requirements for the Stockholm convention on POPs developed under the United Nations Environment Program, various obligations under NACEC agreements and will be valuable to risk managers and public health officials in Canada.
C. Woodland, MSc1
1 News Substances Assessment and Control Bureau, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: Global awareness of the need to incorporate routine immunotoxicity assessment in the safety evaluation of drugs and chemicals is reflected in the ongoing ICH process of harmonization of testing guidelines for immunotoxicity. In support of this approach, a review of international and domestic research was conducted to assess the potential immunotoxicity of PFCAs (Perfluorinated Carboxylic Acids) on human health, using PFOA (Perfluorooctanoic Acid) as a case study.
DESIGN: A literature review of the effects of PFOA and of the class of compounds to which PFOA belongs (peroxisome proliferators/PPAR [peroxisome proliferator activated receptor] ligands) on the mammalian immune system, with a focus on elucidation of the potential mode of action (MOA) of PFOA immunotoxicity in humans, was performed. Comparisons of in vitro human and animal data and reviews of in vivo animal data and of data generated by the pharmaceutical industry on the PPAR ligand MOA were made. The relative roles of the three PPAR isomeric forms in PFCA immuntoxicity and of peroxisome proliferation in PPAR ligand activation of human PPAR were investigated.
OUTPUTS/RESULTS: The alpha isoform of human PPAR, and possibly the PPAR gamma human isoform, have the potential to mediate PFCA immunotoxicity, as represented by potential PFOA and PPAR ligand immunotoxicity. In vivo assessment of a variety of rodent immunotoxicity endpoints (i.e., lymphocyte subsets, primary humoral response using ELISA and PFC assay, cell cycle effects, organ weight assessment) indicated severe immunosuppression with PFOA treatment. Human PPAR activation was unaccompanied by peroxisome proliferation.
IMPACTS/OUTCOMES/CONCLUSIONS: Concern for the potential of PFCAs, as PPAR ligands, to cause immunosuppression is warranted, particularly in the context of the totality of PPAR ligand pharmaceuticals in the environment. Pharmaceutical PPAR ligands have wide and frequent human use and given the potential for subsequent interactive effects, the potential for PFCA immunotoxicity to human health cannot be dismissed.
B. Adhikari1, C. Robinson1, C. Yung2, and I. Zverev2
1 Health Demand and Supply Analysis Division, Applied Research and Analysis Division, HPB, Health Canada, Ottawa, ON
2 Economic Analysis Unit, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, Ottawa, ON
OBJECTIVES: Is Do It Yourself (DIY) urine dipstick testing a cost-effective method of detecting pre-diabetes and undiagnosed type-2 diabetes in Canadians with risk factors for the disease? Applying markov modelling techniques, we examine the potential economic costs versus benefits of urine dipstick screening for detecting type-2 diabetes.
DESIGN: To examine the effectiveness of DIY urine dipstick testing as a tool for detecting undiagnosed type-2 diabetics, we develop a markov model that allows us to track the diagnoses, treatment and complication paths of a representative cohort of Canadians ages 40-75 screened using urine dipstick testing. Based on individual characteristics of blood pressure, hemoglobin level (Hba1c), age, gender, body mass index (BMI), etc., and treatments, at each time period, we predict the number of individuals who develop type-2 diabetes, and the number of individuals within each complication state. Follow-up diagnosis after DIY screening is based on traditional diabetes clinical screening methods (fasting plasma glucose (FPG) and/or 2-hr oral glucose tolerance tests (OGTT)). Use of the urine dipstick testing is compared against the current status-quo testing and the Canadian Diabetes Association's current recommendations.
DATA: Baseline Characteristics of the Canadian population and cost data are collected from various Canadian and International administrative and survey data sources. Epidemiological and medical literature such as the United Kingdom Prospective Diabetes Study (UKPDS) and the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) were used to provide parameter estimates for transition probabilities between complication states.
OUTPUTS/RESULTS: Differences in detection rates across screening methods, affect the stage at which diabetes is diagnosed as well as subsequent complication rates. Comparing the urine dipstick testing with the current status-quo testing and the recommendation by the Canadian Diabetes Association, the optimal type-2 diabetes screening strategy is determined on the basis of cost-benefit analysis.
IMPACTS/OUTCOMES/CONCLUSIONS: In 1999/2000, an estimated 1.2 M Canadians were diagnosed as diabetic. Another 30% of all diabetes cases were estimated to be undiagnosed. The study will help us determine a cost-effective strategy for detecting type-2 diabetes in Canada.
S. Zhang1, and L. Curtis, PhD2
1 Applied Research and Analysiss Directorate, HPB, Health Canada, Ottawa, ON
2 University of Waterloo
OBJECTIVES: As a greater proportion of the population become computer and Internet savvy, many people are using the Internet to look for health information. This study aims to examine factors associated with the likelihood of using the Internet for health purposes, paying special attention to individuals' unmet health care needs. This study also addresses the relationship between the use of online health resources and health care utilization, measured by physician visits.
DESIGN: We examined two national representative cross-sectional datasets. To determine factors associated with Internet use, logistic regressions are used, with Internet use as the response variable (yes/no). To determine how use of online health information is related health-care utilization, an ordered logit model is used, with family physician visits as the dependent variable, which is categorized into no visit, 1-4 visits, and 5+visits. Additional analysis is also performed to examine specialist visits and psychologist visits using logistic regressions.
RESULTS: As of 2003/04, over 70% of Canadians (15+) used the Internet, and over 40% of them used it to look for health information. Besides individuals' socioeconomic characteristics, individuals' experience with unmet health-care needs is identified as a significant factor associated with use of online health information (OR: 1.50, 95% CI: 1.27-1.77). However, use of online health information does not appear to be associated with a reduction in physician visits. On the contrary, it is found to be associated with an increased likelihood for visits to psychologists (OR: 1.63, P<0.02), specialists (OR: 1.22, P<0.08) and family physicians.
CONCLUSIONS: When consumers' health-care needs cannot be readily met, they are more likely to turn to the Internet for health resources, which implies that the current wait times issue in our health-care system may help create increased demand for Internet health resources. However, consumers' acquisition of online health information does not show an association with a reduced likelihood for physician visits, nor does it appear to be associated with consumers self-rated health knowledge.
J. Zheng1, A. Williams2, A. Yagminas1, C. Parfett1, G. Zhou1, G.R. Douglas1, and C.L. Yauk1
1 Environmental and Occupation Toxicology Division, HECSB, Health Canada, Ottawa, ON
2 Biostatistics and Epidemiology Division, HECSB, Health Canada, Ottawa, ON
OBJECTIVES: To characterize gene expression changes in the livers of phenobarbital-treated mice using oligonucleotide DNA microarrays. To investigate the correlation between blood chemistry, hepatic metabolism and gene expression profiles.
DESIGN: Male B6C3F1 mice (five mice/group) were dosed by oral gavage daily for three days with vehicle or 0.1, 1, 10 and 100 mg/kg/day phenobarbital and sacrificed 4 hours after the last dose. Serum samples were collected to measure standard biochemical markers for hepatotoxicity. Hepatic benzyloxyresorufin O-dealkylase (BROD) and ethoxyresorufin-O-deethylase (EROD) were measured. Total liver RNA was isolated and hybridized to the in-house custom oligonucleotide microarray (ToxArray™), containing 1600 genes predicted to be responsive to toxic exposures. Microarray data were normalized using a composite LOWESS and analyzed in MAANOVA. Selected differentially expressed genes using microarrays were confirmed by real time RT-PCR.
RESULTS: Phenobarbital treatment resulted in a significant (p< 0.05) increase in liver-body weight ratios at the highest dose. BROD activity was significantly elevated approximately 2-fold and 20-fold at 10 and 100 mg/kg/day doses. Consistent with these results, microarray analysis showed that Cyp2b9 and Cyp2b10 genes were significantly induced about 7 and 5-fold at 100 mg/kg/day; 3 and 2.5-fold at 10 mg/kg/day, which were further confirmed using real time RT-PCR. In addition, up to 36 differentially expressed genes were identified in microarray analysis. The predominant pathways represented among the genes that were differentially expressed include xenobiotic metabolism, cell development and differentiation, lipid metabolism, stress response and apoptosis, consistent with the known pathology of phenobarbital exposure.
CONCLUSIONS/IMPACTS: Our results demonstrate a correlation between biochemical endpoints and gene expression changes induced by phenobarbital, suggesting that microarray technology may be used as a tool for elucidating the mechanism of chemical-induced toxicity, predicting the adverse effects of environmental toxins and improving the process of risk assessment and safety evaluation. Further validation using other chemicals with known pathology is currently underway.