The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

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In recent years much attention has been focused on the potential for a wide range of xenobiotic chemicals to interact with and disrupt the endocrine systems of animal and human populations. An overview of the chemicals that have been implicated as endocrine disruptors is presented. The ubiquity in the environment and associated body burdens of these chemicals in human populations are described. Potential mechanisms of action are reviewed, including the role of specific intracellular receptors and their interactions with endogenous and exogenous materials. The subsequent upregulation or downregulation of physiological processes at critical stages of development is discussed. The potential for joint toxic action and interaction of chemical mixtures is also discussed. The acknowledged role of wildlife populations as sentinels of potential human health effects is reviewed, and the weight of evidence for the role and impact of endocrine disruptors is presented. The implications of exposure to endocrine-disrupting chemicals for human health are reviewed, with special emphasis on the potential for transgenerational effects in at-risk populations. Recommendations for future research include the development of (1) structural activity and in vivo and in vitro functional toxicology methods to screen chemicals for their endocrine-disrupting ability, (2) biomarkers of exposure and effect, and (3) in situ sentinel systems.

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Uncontrolled hazardous-waste sites are a major environmental and public health concern in the United States and elsewhere. The remediation of and public health responses to these sites is mandated by the federal Superfund statute. Approximately 40,000 uncontrolled waste sites have been reported to U.S. federal agencies. About 1,300 of these sites constitute the current National Priorities List (NPL) of sites for remediation. Findings from a national database on NPL sites show approximately 40% present completed exposure pathways, although this figure rose to 80% in 1996. Data from 1992 through 1996 indicate that 46% of sites are a hazard to public health. Thirty substances are found at 6% or more of sites with completed pathways. Eighteen of the substances are known human carcinogens or reasonably anticipated to be carcinogenic. Many of the 30 substances also possess systemic toxicity. The high percentage of sites with completed exposure pathways and the toxicity potential of substances in these pathways show that uncontrolled hazardouswaste sites are a major environmental threat to human health. Findings from the United States' experience in responding to uncontrolled waste sites are relevant to other countries as they address similar environmental and public health concerns.

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