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Threats to Sources of Drinking Water and Aquatic Ecosystem Health in Canada

5. Endocrine Disrupting Substances

Intensive agriculture is one of the major causes of endocrine disruption in the Canadian environment.Mark Servos,1 Peter Delorme,2 Glen Fox,3 Roger Sutcliffe4 and Michael Wade5

1Environment Canada, National Water Research Institute, Burlington, ON
2Health Canada, Pest Management Regulatory Agency, Ottawa, ON
3Environment Canada, National Wildlife Research Centre, Hull, QC
4Environment Canada, Commercial Chemicals Evaluation Branch, Hull, QC
5Health Canada, Environmental and Occupational Toxicology Division, Healthy Environments and Consumer Safety Branch, Ottawa, ON

 


Current Status

There is growing concern internationally about environmental risks posed by endocrine disrupting substances (EDS). These chemicals include a wide variety of environmental contaminants that can exert a diverse array of effects on growth, development and reproduction in biota. The effects may occur at extremely low concentrations and be expressed in following generations well after the original environmental exposure. These subtle effects may be extremely difficult to detect, even though they may have significant impacts on populations and ecosystems. Although reproduction and development are major endpoints for environmental and human health assessments in many federal government programs, current assessment approaches may not be adequate to detect subtle impacts mediated through disruption of endocrine systems. Development of screening and testing programs for endocrine disrupters in the United States, and international agencies such as the OECD, have been initiated and may have a profound influence on how Canada will address this issue in the future. It is critical that Canada be proactive, identify and address knowledge gaps from a Canadian perspective, and anticipate international developments that may influence Canadian policy.

Concerns over the potential impacts of substances that disrupt endocrine function in biota in the Canadian environment led to CEPA 1999 making research on "hormone disrupting substances" a Ministerial duty for both Environment Canada and Health Canada (CEPA 1999 article 3, subsection 44[3]). Numerous drugs, pesticides, industrial chemicals, metals and natural compounds detected in the environment may alter the normal function of endocrine systems (National Academy of Sciences 1999; Di Giulio and Tillitt 1999; Kendall et al. 1998). Recent studies have implicated some of these substances in the alteration of aspects of growth, reproduction and development of animal species, including humans in Canada and other areas of the globe (Foster 2001; McMaster 2001). It has been suggested that such changes may be associated with adverse responses in individuals or populations of organisms, although further research is needed to substantiate this linkage (Munkittrick 2001; Van Der Kraak 2001; National Academy of Sciences 1999). Chemicals suspected of having endocrine disrupting capability include a wide variety of chemical classes and mixtures (Hewitt and Servos 2001); thus there are implications for a large number of activities and programs in the federal government (Servos et al. 2000a).

Trends

The EDS issue has evolved rapidly and there is increasing public pressure to take action to reduce the potential risk of EDS in the Canadian environment. The uncertainty surrounding the potential for serious and nonreversible effects has resulted in the EDS issue being linked to the debate over the precautionary principle in Canada as well as other jurisdictions (Commission of the European Communities 1999, 2000). CEPA 1999 commits the government to implementing the weight-of-evidence approach as well as the precautionary principle in decision making (Preamble CEPA 1999; paragraph 2[1][a]). It has been recognized that we must be proactive so that we reduce uncertainty and make decisions based on sound science (Servos and Luce 1997; Servos et al. 2000a). The EDS issue presents new challenges for scientific assessments of industrial chemicals (Sutcliffe 2001; Servos 2001), pesticides (Moase and Delorme 2001) and the Canadian environment (Munkittrick 2001).

There are also numerous international activities related to the EDS issue that have implications for Canada. The requirement in the United States to develop an approach for screening and testing for endocrine disrupting substances by the summer of 2000 has resulted in numerous activities in that country (US EPA 1997). The OECD, in which Canada is an active partner, has initiated a program to harmonize testing and screening on EDS (OECD 2000). The EU has recently published a strategy for endocrine disrupting substances and published a list of potential endocrine disrupting substances for further testing in the immediate future (Commission of the European Communities 1999). It is expected that EDS will continue to be a high-profile international issue.

Emerging Issues

Prompted by the urgency and complexity of the question, the Five Natural Resources Departments Working Group on Endocrine Disrupting Substances (5-NR EDS WG) hosted a multi-depart-mental, multi-sector workshop to address emerging issues associated with scientific assessment of EDS in the Canadian environment. The Workshop's agenda placed a major emphasis on reviewing the current status of science on the EDS issue in Canada, but also considered how the issue fits within the regulatory framework of the federal government. The following is a summary of the major conclusions, research priorities and recommendations from the workshop held at the Grandview Inn in Huntsville, Ontario, February 13-17, 2000 (Servos et al. 2000a).

Endocrine Disrupting Substances in the Canadian Environment

There is a concern in Canada that low level and/or multigenerational effects, possibly mediated through disruption of normal endocrine function, are occurring and are currently going undetected. Effects on development and reproduction have been observed in wildlife in Canada, including: deformities and embryo mortality in birds and fish exposed to industrial chemicals or organochlorine insecticides, impaired reproduction and development in fish exposed to pulp and paper mill effluents, abnormal development of molluscs exposed to antifouling substances (TBT) applied to the hulls of ships, depressed thyroid and immune functions in fish-eating birds in the Great Lakes, and feminization of fish exposed to municipal effluents. Available data suggest a potential for these types of effects to occur in humans, although there is only circumstantial evidence that they occur in response to environmental contamination. For example, studies on mother-infant cohorts exposed to environmental contaminants through high consumption of contaminated fish suggest that there can be cognitive and neurobehavioural effects in infants due to prenatal exposure. Some of the effects identified may not occur directly through an endocrine mechanism, or in some cases the mechanism is not yet known; however, this does not diminish the importance of effects or observations. Attention should therefore focus on functional endpoints of growth, reproduction and development during critical life stages, rather than on a specific mode or mechanism such as receptor-mediated responses. In light of relatively recent results, traditional ecosystem monitoring and to some extent human health monitoring programs have not used sufficiently sensitive endpoints related to growth, reproduction and development. Existing monitoring programs should be evaluated and modified to encompass new concerns, identify new issues, and complement mechanistic and toxicology studies.

Risk Assessment and EDS in Canada

Endocrine disrupting substances can be addressed within the existing Canadian legislation and regulatory frameworks. Current risk assessment/management approaches in Canada can be used to identify effects produced via endocrine disrupting mechanisms, but subtle effects on growth, reproduction and development must also be considered. Risk assessment/management approaches require continuous improvement and need to include new tests and approaches as they become available. Both hazard and exposure are important criteria for assessing or prioritizing risks and need to be considered in risk assessments. Additional information required for risk assessments of suspected EDS, which is not normally available, includes: information on sensitive life history stages; identification of windows of sensitivity, including exposure at this stage; possible presence and significance of delayed responses or effects; and significant development of the science of assessing effects of mixtures and mixture interactions. In addition to specific chemicals, a number of sites and sectors have been identified as representing the highest risk and research should be focused in these areas.

Table 1. The following sites and sectors were considered the most important for consideration of EDS impacts in the Canadian environment (Servos et al. 2000a)

Major Sites and Sectors

I. municipal effluents
II. intensive agriculture (including pesticides and livestock production)
III. textile mill effluents
IV. pulp and paper sector (recent dramatic improvement)
V. mining and metals
VI. historically contaminated sites
VII. identified areas of concerns (e.g., Great Lakes AOCs)
VIII. contaminants in the Arctic (including Aboriginal foods)

International Activities and Implications for Canada

International activities will continue to have major implications for the EDS issue in Canada. International harmonization is needed to ensure minimum duplication and maximum benefit to the respective countries dealing with the question, without giving up the ability to set national priorities/concerns differing from those accepted internationally. It is critical that Canada participates in international efforts so that internationally accepted tests are applicable in a Canadian context: i.e., consideration of unique aspects such as climate, population, diet and chemical use patterns.

Application of Sound Science to the EDS Issue

Potential subtle effects on reproduction and development should be considered in our scientific assessments and screens for toxic substances. While in vitro information and studies are useful, they are not currently linked directly to or predictive of in vivo responses; however, this is expected to improve rapidly with additional research. Results of laboratory testing should be related to ecological significance in the environment and possible effects in the environment, especially with respect to sensitive life stages. Functional impacts leading to a negative effect on one or more of survival, growth, development, reproduction, behaviour, immune competence or disease resistance should be monitored and assessed with concern focused at the level of the individual (in vivo) or above.

Large uncertainty is associated with scientific assessments related to the EDS issue and should be considered in developing risk management options. A weight-of-evidence approach based on the most credible information available should be used to make appropriate decisions to protect Canadians and the Canadian environment. Estrogen, androgen, and thyroid hormones are reasonably conserved across vertebrate species. However, there are many species-specific differences in how hormones are regulated and function; thus potential variability in responses of different species and large uncertainty in extrapolation among species are to be expected. Interactions with other chemicals should be considered when possible, despite the complexities and large uncertainties involved. Each federal program may have slightly different requirements but the basic principles for testing and assessment should be the same. A tiered-testing approach that considers both hazard and exposure is advantageous and should be incorporated into Canadian programs once validated and accepted internationally. Collaboration and consultation with stakeholders and the public on the issue must continue.

Knowledge and Program Needs

Knowledge gaps and research needs were identified in each of the breakout sessions during the workshop and separated into two main themes: EDS in the Canadian environment and risk assessment; and application of sound science to the EDS issue. They were summarized and then prioritized by participant voting (Table 2; see Workshop Proceedings for details; Servos et al. 2000a). It should be underlined that gaps and needs identified were specific to Canada, and considered unique aspects of Canadians and the Canadian environment, our approaches to the management of toxic substances, and our scientific expertise and capacity in this area of research (Table 2).

Canada must continue to support research to address critical knowledge gaps and ensure application of sound science to risk assessment and management of EDS in the Canadian environment. Research should continue to reduce the large uncertainty associated with scientific assessments of these types of substances and effects. Research on the fundamental reproductive and developmental biology of humans, biota and ecosystems is essential to understand and detect subtle effects on growth, reproduction, development (and ultimately effects on populations), mediated through endocrine or other mechanisms and should be encouraged. Canadian research programs should continue to focus on our traditional strengths in field studies, identifying impacts, and defining cause and effect relationships. Replication of international screening and testing activities should be minimized, and Canada should participate in international activities to ensure results are consistent and applicable to the Canadian environment.

Continued coordination and collaboration of research in government, industry, academia, and public interest groups are essential, and interaction among research and regulatory scientists in each of these groups must continue. Programs such as the Toxic Substances Research Initiative (TSRI), the Canadian Network of Toxicology Centres (CNTC) and appropriate internal government and industry programs should be enhanced and focused more on scientific assessment of EDS. Although Canadian scientists make major contributions to the EDS question internationally, the science capacity in Canada to address this issue is limited and should be expanded. Enhanced science-based monitoring programs are required to detect and evaluate the risk to Canadians and the Canadian environment from EDS. Existing monitoring programs should also be enhanced as a mechanism to detect EDS, effects and concerns in the Canadian environment.

Table 2. Knowledge gaps/research needs identified for scientific assessment of endocrine disrupting substances in the Canadian environment

Priority*| EDS in the Canadian Environment and Risk Assessment

  1. Calibrating or benchmarking the ecological relevance of EDS tests--taking them out of the laboratory and assessing their ability to detect impacts/adverse effects of EDS in the Canadian environment.
  2. Improve basic knowledge on the role of hormones in the development of nervous, reproduction and immune systems in human and relevant species
  3. Improve understanding of role and importance of naturally occurring, hormonally active substances in the EDS issue (with regard to testing).
  4. Comprehensive guidance on how to interpret and use scientific data in risk management decision-making frameworks.
  5. Definition of acceptable risk, adverse effect.
  6. Risk communication (need to enhance current activities).
  7. Development and recognition of endpoints for early life stage effects related to organizational changes (e.g., behaviour, immune, endocrine, etc.).
  8. Improve basic knowledge about early specification and development of endocrine and reproductive organ systems from fertilization onwards in vertebrates.
  9. Correct deficiencies in exposure and monitoring data.
  10. Improved understanding of effects of EDS on invertebrates.
  11. Development of mechanistic knowledge on the link between in vitro and in vivo responses.
  12. Understanding link between (screening) test result and adverse effects.

Priority*| Application of Sound Science to the EDS Issue in Canada

  1. Establish connection between lab tests and actual world. Are tests predictive of real world effects? Are things happening in real populations that are not predicted?
  2. Linking screening/testing methods to ecological relevance (especially with respect to sensitive life stages).
  3. Development of a framework for risk assessment of interactions of EDS in mixtures and effluents.
  4. Better knowledge of exposure and dispersal of EDS in the environment.
  5. Better understanding of low dose effects and thresholds.
  6. Ability to separate effects of natural estrogens from effects of anthropogenic chemicals.
  7. Linking biomarker responses with adverse atypical effects (growth, development, reproduction).
  8. Development of a framework regarding public values for risk management decisions.
  9. Enhanced monitoring effort for effects in the environment.
  10. Better knowledge of immune system effects.
  11. Mechanistic studies, including complications from mixed agonists (estrogenic in some tissues, anti-estrogenic in others).
  12. Develop a framework for risk assessment of cumulative exposures and effects rather than single compound approach.

*Priority established by voting of all workshop participants.

The EDS issue is broad in scope and, as a result, is linked directly to numerous other national environmental health issues and initiatives. Its complexity will necessitate a coordinated response from federal government departments, industry, academia and other organizations. Related activities in other jurisdictions, especially the United States, Japan and Europe, will influence development of public opinion and policy in Canada over the next few months and years. The following four areas should form a National Agenda for EDS in the Canadian Environment (Servos et al. 2000b).

National Leadership and Communication on the EDS Issue in Canada

A high priority should be placed on providing national leadership at the federal level on the issue of EDS in the environment. The EDS question is related directly to many other priority environmental health issues including Children's Environmental Health, POPs, CEPA, and regulation of pesticides. The issue has also been directly associated in Canada and other countries with the debate on the precautionary principle. A comprehensive and coordinated program of collaborative research, communication and regulation/policy development needs to be established. Federal departments, industry, academia and public interest groups should actively participate and collaborate in an effort to generate the knowledge necessary for scientifically sound assessments, regulations and policies. A national communications program should be established to provide scientists, policy makers and the public with current information on national and international developments and activities.

Establishing a Better Knowledge Base of the Exposure and Effects of EDS in the Canadian Environment

Canadian scientists have played an important role in EDS activities, conducting some of the most comprehensive field studies: e.g., effects of organochlorines in birds, reproductive effects in fish exposed to pulp mill effluents, and effects of chemicals on endocrine-dependent responses such as smoltification. Canadian scientists, especially in the federal government, should utilize and emphasize the traditional strengths of Canadian science and programs in assessing effects on ecosystems to maximize contributions to international efforts. Limitations on available resources dictate that research programs must be focused and prioritized to maximize their effectiveness. Research programs should emphasize development of knowledge and tools to conduct more comprehensive environmental assessments, and apply these tools in field and laboratory studies to determine the extent to which Canadians and the Canadian environment may be affected. Scientists in Canada have considerable expertise in validating the relevance of specific responses and exposures in whole animals and populations (including humans). Emphasis should be placed on determining the relevance and acceptability of internationally recognized EDS responses and tests in the Canadian population and the Canadian environment.

The federal government should give priority to assessing those sites, sectors and populations identified as having the highest potential for adverse effects on functional endpoints related to growth, reproduction or development of biota through disruption of endocrine function, as well as other, not yet fully understood mechanisms. Endocrine disruption should be considered as only one of several mechanisms by which environmental effects can be mediated. Research programs should include both previously identified issues, such as industrial effluents and priority substances, and emerging issues such as intensive agriculture (pesticides and animal wastes), urban exposure (e.g., air, sewage, runoff), and new chemicals. Collaboration and partnerships with universities and industry should be employed to further research mechanisms and other critical areas that will enable scientific assessments of EDS in the Canadian environment.

National and International Harmonization of Screening and Testing Protocols

Development of screening and testing methodologies is recognized as an important research and policy area both within Canada and internationally. Enormous efforts are currently underway in other countries to develop and validate screening and testing methods for EDS. Canadians should participate in and support the efforts of international organizations, especially the OECD, to harmonize internationally accepted screening and testing methods to address this complex global issue. However, this should not be the emphasis of Canadian research programs. Canada should work with a variety of international agencies to validate and calibrate currently proposed tests for use internationally and in Canada, and ensure their applicability to the Canadian population and Canadian environment. Duplication of the efforts of other countries should be actively avoided in order to maximize our contribution to international efforts.

Enhanced Scientific Assessment and Action on Priority Substances

Public perception of the EDS issue has evolved rapidly from scientific interest to seeking action to protect human and ecosystem health. CEPA 1999 requires research on "hormone disrupting substances" and application of both the weight-of-evidence approach and the precautionary principle to management of toxic substances in Canada. Although there are special considerations related to assessment of EDS, they can be addressed within current risk assessment/management frameworks with only minor adjustment for inclusion of new knowledge and testing protocols.

Priority substances such as PCBs, tributyltin, selected pesticides and industrial chemicals shown to have or suspected of having effects on growth, reproduction or development, possibly as a result of alterations of the endocrine system, should continue to be evaluated to determine their risk to the Canadian environment. Canada should act to implement current national or international agreements and protocols (such as the Protocol on Persistent Organic Pollutants) to reduce the exposure of these chemicals to the Canadian environment. Each federal department should take action to reduce the exposure and risk of EDS to Canada and the Canadian environment.

Research on better assessment and management tools for this class of chemicals should be conducted to reduce uncertainty and lead to more effective remedial and risk reduction approaches. As internationally accepted screens and tests are validated and made available in the next two to five years, they should be integrated into the current regulatory framework, which considers both hazard and exposure in characterization of risk and formulation of risk management options. Environmental and human health monitoring programs should be modified and enhanced to build a capability to detect exposure and subtle effects on critical developmental stages of biota and humans.

Acknowledgments

Members of the 5-NR EDS Working Group put considerable effort into this initiative: H. Amys, P. Cureton, G. Cooke, P. Delorme, S. De Silva, G. Fox, R. Garrett, C. Hrenchuk, D. Kreutzeiser, K. Munkittrick, A. Niimi, E. Postlethwaite, M. Servos (co-chair), R. Sutcliffe, E. Topp, L. Toy, H. Vandermeulen, M. Wade (co-chair) and L. Webster.

References

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