Priority Substances List Assessment Report for Nonylphenol and its Ethoxylates

1.0 Introduction

The Canadian Environmental Protection Act, 1999 (CEPA 1999) requires the federal Ministers of Environment and of Health to prepare and publish a Priority Substances List (PSL) that identifies substances, including chemicals, groups of chemicals, effluents and wastes, that may be harmful to the environment or constitute a danger to human health. The Act also requires both Ministers to assess these substances and determine whether they are "toxic" as defined in Section 64 of the Act, which states:

... a substance is toxic if it is entering or may enter the environment in a quantity or concentration or under conditions that

1. have or may have an immediate or long-term harmful effect on the environment or its biological diversity;
2. constitute or may constitute a danger to the environment on which life depends; or
3. constitute or may constitute a danger in Canada to human life or health.

Substances that are assessed as "toxic" as defined in Section 64 may be placed on Schedule I of the Act and considered for possible risk management measures, such as regulations, guidelines, pollution prevention plans or codes of practice to control any aspect of their life cycle, from the research and development stage through manufacture, use, storage, transport and ultimate disposal.

Based on an initial screening of readily accessible information, the rationale for assessing nonylphenol (NP) and its ethoxylates (NPEs) provided by the Ministers' Expert Advisory Panel on the Second Priority Substances List (Ministers' Expert Advisory Panel, 1995) was as follows:

NPEs are discharged into the environment primarily from textile and pulp and paper production facilities. They are also used in coal processing, latex paints, grease and lubricating oils, pesticides and industrial detergents. Acute adverse effects have been reported in invertebrates, fish, mammals and algae. There are also concerns that these substances may interfere with endocrine function. An assessment is required to determine exposure levels and the risk they may pose to the environment and human health in Canada.

Descriptions of the approaches to assessment of the effects of Priority Substances on the environment and human health are available in published companion documents. The document entitled "Environmental Assessments of Priority Substances under the Canadian Environmental Protection Act. Guidance Manual Version 1.0 - March 1997" (Environment Canada, 1997a) provides guidance for conducting environmental assessments of Priority Substances in Canada. This document may be purchased from:

• Environmental Protection Publications
  Environmental Technology Advancement Directorate
  Environment Canada
  Ottawa, Ontario
  K1A 0H3

It is also available on the Internet atwww.ec.gc.ca/cceb1/ese/eng/esehome.htm under the heading "Guidance Manual." It should be noted that the approach outlined therein has evolved to incorporate recent developments in risk assessment methodology, which will be addressed in future releases of the guidance manual for environmental assessments of Priority Substances.

The approach to assessment of effects on human health is outlined in the following publication of the Environmental Health Directorate of Health Canada: "Canadian Environmental Protection Act - Human Health Risk Assessment for Priority Substances" (Health Canada, 1994), copies of which are available from:

• Environmental Health Centre
  Room 104
  Health Canada
  Tunney's Pasture
  Ottawa, Ontario
  K1A 0L2

or on the Environmental Health Directorate publications web site (www.hc-sc.gc.ca/ehp/ehd/catalogue/bch.htm). The approach is also described in an article published in the Journal of Environmental Science and Health -Environmental Carcinogenesis & Ecotoxicology Reviews (Meek et al., 1994). It should be noted that the approach outlined therein has evolved to incorporate recent developments in risk assessment methodology, which are described on the Environmental Substances Division web site (www.hc-sc.gc.ca/ehp/ehd/bch/env_contaminants/psap/psap.htm) and which will be addressed in future releases of the approach paper for the assessment of effects on human health.

The search strategies employed in the identification of data relevant to the assessment of potential effects on the environment (prior to December 1998) and on human health (prior to November 1999) are presented in Appendix A. The environmental assessment included data from research commissioned specifically for use in this assessment. These data were obtained following December 1998. Additional literature was considered for the assessment as the authors became aware of its existence. A separate PSL assessment of textile mill effluents was initiated concurrently and the assessment report on textile mill effluents is currently available.

The environmental risk assessment of NP and its ethoxylates was developed by members of the Environmental Resource Group, established by Environment Canada. Members were selected on the basis of their expertise, notably in the areas of analytical chemistry, environmental monitoring, environmental chemistry and environmental toxicology. Members of the Environmental Resource Group were:

• D.T. Bennie, National Water Research Institute, Environment Canada
• P. Cureton, Commercial Chemicals Evaluation Branch, Environment Canada
• H.-B. Lee, National Water Research Institute, Environment Canada
• K. Lloyd, Commercial Chemicals Evaluation Branch, Environment Canada
• R.J. Maguire, National Water Research Institute, Environment Canada
• M.R. Servos, National Water Research Institute, Environment Canada.

The environmental risk assessment was led by P. Cureton. In developing the environmental assessment, review articles were consulted where appropriate. However, all original studies that form the basis for determining whether NP and its ethoxylates are "toxic" under Paragraph 64(a) of CEPA 1999 have been critically evaluated by staff of Environment Canada.

The supporting documentation for the environmental assessment (Servos et al., 2000) underwent an external scientific peer review, which was performed by:

• C. Metcalfe, Environmental and Resource Studies, Trent University
• D. Moore, Cadmus Group
• K. Solomon, Centre for Toxicology, University of Guelph

The environmental sections of this Assessment Report, summarizing the supporting documentation, were prepared by D.F.K. Rawn with assistance from N. Davidson and also reviewed by the following internal reviewers at Environment Canada:

• G. Van Der Kraak, Department of Environmental Biology, University of Guelph
• K. Adare, Guidelines and Standards Division, Environment Canada
• D. Dore, Chemicals Control Division Environmental Canada
• D. Dubé, Chemicals Evaluation Division, Environment Canada
• B. Ernst, Air and Toxic Issues, Environment Canada
• J. Haskill, Renewable Resources, Environment Canada
• B. Mander, Chemicals Control Division, Environment Canada
• K. Potter, Guidelines and Standards Division, Environment Canada
• L. Rutherford, Air and Toxic Issues, Environment Canada
• R. Sutcliffe, Chemicals Evaluation Division, Environment Canada
• N. Tremblay, Chemical Control Division, Environment Canada

Although NP/NPEs have toxicological properties that are similar to those of other APs/APEs,¹ other APs/APEs were not considered in this assessment. OP/OPEs, which are used in Canada to a lesser exte nt than NP/NPEs, are present in similar environmental compartments as NP/NPEs. Although this assessment was focused strictly on NP/NPEs, relevant data for OP/OPEs have been reviewed in the environmental supporting documentation (Servos et al., 2000). Because of the toxicological and endocrine effects of these compounds on environmental organisms, their assessment is considered a priority, but the compounds are beyond the scope of this assessment.

The approach to the assessment of the effects of NP/NPEs on human health is necessarily restricted due to the extremely limited database on both exposure and effects for individual components of this complex mixture of a large number of congeners. For example, available data on exposure to NP/NPEs in media to which the general population in Canada is exposed (e.g., air, food, drinking water and consumer products) are insufficient to support other than bounding or reasonable worst-case estimates of intake for the entire class of substances. Moreover, potentially critical effects of NP/NPEs on human health have not been adequately investigated, since only a very limited number of members of this class of substances have been studied and as sensitive frameworks for testing and assessment of some key endpoints (e.g., potential for endocrine disruption) have not yet been developed.

In view of the limitations of the database, an interim screening approach has been adopted for the assessment of risks to human health. In this screening assessment, identified effect levels for NP/NPEs are compared with reasonable worst-case or bounding estimates of exposure for the entire class of substances. Weight of evidence for and adversity of observed effects have generally not been considered at this initial stage. Rather, the adequacy of these rather crude margins of exposure is considered in relation to intake from various sources, including environmental media and consumer products, primarily as a basis for identification of priorities for further work to permit a more defensible assessment of risks from all sources of exposure for the general population. This interim approach has been adopted in recognition that, while more informative data on health effects of these substances are likely to be forthcoming in the near term, the more robust data set on environmental organisms, some of which are directly exposed to discharges of these substances, is currently a more appropriate benchmark against which to assess risks in the general environment.

The search strategy that served as the basis for identification of relevant data for the human health assessment is outlined in Appendix A. In brief, effects-related studies for this screening assessment were identified primarily from several recent reviews (Talmage, 1994; U.K. Environment Agency, 1998; WHO, 1998). In addition, a number of on-line databases were searched to identify relevant data on exposure and effects of NP/NPEs that were not included in the reviews. Although secondary sources were used to identify many of the available data, the original reports for toxicological studies (except for acute toxicity and genotoxicity) identified in the reviews were acquired in order to confirm the results. In view of the relatively limited database for assessment of the toxicity of NP/NPEs, additional attempts were made to acquire data relevant to exposure and/or effects from representatives of industry, the provinces, and other Canadian federal and international agencies. It has not been possible to determine if studies of Industrial Bio-Test Laboratories Inc., which constitute a subset of the investigations summarized in a 1969 review by Smyth and Calandra, have been validated. While cited in this report, they do not contribute directly to the conclusions drawn (i.e., the critical effect levels were not derived therefrom); moreover, results of these investigations are consistent with those reported by others.

In view of the limited objectives of the screening assessment, the information considered in the health assessment has been restricted principally to that directly relevant to determination of the margin of exposure - i.e., data to serve as the basis of the reasonable worst-case or bounding estimates of exposure and effect levels from repeated-dose studies. Related data, such as those on pharmacokinetics, are not included herein, since they are considered inadequate to meaningfully inform the margin of exposure.

Sections of this Assessment Report and supporting documentation related to human health were prepared by the following staff of Health Canada:

• M.E. Meek
• R. Newhook
• L. Turner

Sections of the supporting documentation on exposure were reviewed by R. Moody of the Product Safety Bureau, Health Canada, and by P. Lau of the Food Packaging Materials and Incidental Additives Section, Food Directorate, Health Canada. Sections of the supporting documentation on reproductive effects, including estrogenicity, were reviewed by M. Wade of the Environmental and Occupational Toxicology Division of Health Canada.

In order to address primarily adequacy of coverage, sections of the effects-related supporting documentation pertaining to human health were reviewed externally by:

• F. Ratpan, Novacor
• S. Sang, World Wildlife Fund Canada
• J.P. Van Miller, Union Carbide

Adequacy of coverage and defensibility of conclusions of the health-related sections of the Assessment Report and the supporting documentation were considered in a written review by:

• J. Christopher, California Environmental Protection Agency
• M. Dourson, Toxicology Excellence for Risk Assessment
• P. Ridgway, U.K. Health and Safety Executive
• R. Rudell, Silent Spring Institute

The health-related sections of the Assessment Report were reviewed and approved by the Health Protection Branch Risk Management meeting of Health Canada.

The entire Assessment Report was reviewed and approved by the Environment Canada/Health Canada CEPA Management Committee.

A draft of the Assessment Report was made available for a 60-day public comment period (April 1 to May 31, 2000) (Environment Canada and Health Canada, 2000). Following consideration of comments received, the Assessment Report was revised as appropriate. A summary of the comments and responses is available on the Internet at:

www.ec.gc.ca/cceb1/eng/final/index_e.html

The text of the Assessment Report has been structured to address environmental effects initially (relevant to determination of "toxic" under Paragraphs 64(a) and (b)), followed by effects on human health (relevant to determination of "toxic" under Paragraph 64(c)). Due to the extensive literature available for NP/NPEs and NPECs, the Assessment Report does not include detailed descriptions of critical studies. These data are, however, reviewed and described in detail in the supporting documentation.

Copies of this Assessment Report are available upon request from:

• Inquiry Centre
  Environment Canada
  Main Floor, Place Vincent Massey
  351 St. Joseph Blvd.
  Hull, Quebec
  K1A 0H3

or on the Internet at:

www.ec.gc.ca/cceb1/eng/final/index_e.html

Unpublished supporting documentation, which presents additional information, is available upon request from:

• Commercial Chemicals Evaluation Branch
  Environment Canada
  14th Floor, Place Vincent Massey
  351 St. Joseph Blvd.
  Hull, Quebec
  K1A 0H3

or

• Environmental Health Centre
  Room 104
  Health Canada
  Tunney's Pasture
  Ottawa, Ontario
  K1A 0L2