Grantee Research Project Results
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4. Endocrine Disruptors
Evidence has been accumulating that humans and domestic and wild species have suffered adverse health consequences resulting from exposure to environmental chemicals that interact with the endocrine system. These pollutants are collectively referred to as "endocrine disruptors," a term broadly defined as "an exogenous agent that interferes with the production, release, transport, metabolism, binding, action, or elimination of natural hormones in the body responsible for the maintenance of homeostasis and the regulation of developmental processes."
In response to growing public health concerns related to chemicals in the environment which have the potential to act as endocrine disruptors, the Office of Research and Development of the EPA included Endocrine Disruptors as a high priority research issue in the ORD Strategic Plan and has developed an Endocrine Disruptors Research Plan. The plan identifies the need for three broad categories of research: biological-effects studies, exposure studies, and studies on the linkage of exposure and effects. Grant applications are sought in each category. The focus of the research may range from studies on wildlife populations and laboratory organisms, to humans, in both laboratory and field settings.
EPA has developed a three-year plan for the solicitation of research applications from the scientific community. In the forthcoming first year of the plan, research topics of interest include:
- Development and validation of in vivo and in vitro test methods to screen toxicants, singly or in mixtures, for endocrine-disrupting activity in vertebrate and invertebrate species. Methods may employ tissues, cell lines, isolated receptors, and enzymes in vitro, as well as bioassays and hormone measurements in vivo.
- Development of new measurement and analytical methods, including the development of field-portable devices for endocrine disruptors in various media, e.g., air, water, soil.
- Studies in animal models on the modes and mechanisms of action of endocrine disruptors on neuroendocrine, reproductive, immune, and central nervous systems at the molecular, cellular, or functional levels resulting from exposure during development, with emphasis on identification of sensitive subpopulations (age/sex). Studies may include physiologically-based pharmacokinetic (PB-PK), physiologically-based toxicokinetic (PB-TK), and biologically-based dose-response (BBDR) models.
- Development of QSAR models of endocrine disruption mechanisms of action, including receptor binding, enzyme inhibition, etc., for vertebrate and invertebrate species.
- Development of animal models of endocrine disruptor-induced human diseases, including reductions in sperm counts and increased incidences of infertility, testicular cancer, hypospadias, endometriosis, breast cancer, thyroid cancer, and prostate cancer.
- Studies to define the "baseline" endocrine status in wildlife populations and their laboratory surrogates.
- Studies on the role of hormones in sexual differentiation and reproductive development of non-mammalian species and the effects of endocrine disruptors on this process.
- Identification and validation of measurement endpoints, in vivo and in vitro screening methods, and other bioassays indicative of the effects of endocrine disruptors at the level of populations and communities.
- Studies of sites/systems with problems that are known or strongly suspected to be related to endocrine disruptors.
We particularly seek studies that examine endocrine disruptor-related effects in wildlife populations, as well as studies which include significant attention to issues related to the types, levels, sources, and fates of endocrine-disrupting chemicals in the environment. Additional information regarding research needs on endocrine disruptors may be found in the following references:
Ankley, G.T., et al. (1996), Development of a research strategy for assessing the ecological risk of endocrine disruptors. Rev. Toxicol. Series B - Environmental Toxicology, in press.
Kavlock, R.J., et al. (1996), Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the USEPA sponsored workshop, Environmental Health Perspectives 104 (Supplement 4):715-740.
About $3-4 million is expected to be available in fiscal year 1997 for awards in this program area. The projected award range is $100,000 to $200,000/year for up to 3 years.