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Nira Ben-Jonathan,¹ Ralph L. Cooper,² Paul Foster,³ Claude L. Hughes,⁴ Patricia B. Hoyer,⁵ Diane Klotz,⁶ Michael Kohn,⁶ Dolores J. Lamb,⁷ and George M. Stancel⁸

¹Department of Cell Biology, University of Cincinnati, Cincinnati, Ohio USA;
²National Health Effects and Environmental Research Laboratories, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina USA;
³Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina USA;
⁴Center for Women's Health, Cedars-Sinai Medical Center, Los Angeles, California USA;
⁵Department of Physiology, University of Arizona Health Science Center, Tucson, Arizona USA;
⁶National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina USA;
⁷Department of Urology, Baylor College of Medicine, Houston, Texas USA;
⁸Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School, Houston, Texas USA

Abstract

The workshop "Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels" was held to provide a forum for discussions and recommendations of methods and data needed to improve risk assessments of endocrine disruptors. This article was produced by a working group charged with determining the basic mechanistic information that should be considered when designing models to quantitatively assess potential risks of environmental endocrine disruptors in adults. To reach this goal, we initially identified a set of potential organ system toxicities in males and females on the basis of known and/or suspected effects of endocrine disruptors on estrogen, androgen, and thryoid hormone systems. We used this integrated, systems-level approach because endocrine disruptors have the potential to exert toxicities at many levels and by many molecular mechanisms. Because a detailed analysis of all these untoward effects was beyond the scope of this workshop, we selected the specific end point of testicular function for a more detailed analysis. The goal was to identify the information required to develop a quantitative model(s) of the effects of endocrine disruptors on this system while focusing on spermatogenesis, sperm characteristics, and testicular steroidogenesis as specific markers. Testicular function was selected because it is a prototypical integrated end point that can be affected adversely by individual endocrine disruptors or chemical mixtures acting at one specific site or at multiple sites. Our specific objective was to gather the information needed to develop models in the adult organism containing functional homeostatic mechanisms, and for this reason we did not consider possible developmental toxicities. Homeostatic mechanisms have the potential to ameliorate or lessen the effects of endocrine disruptors, but these pathways are also potential target sites for the actions of these chemicals. Key words: androgen, estrogens, endocrine disruptors, homeostasis, spermatogenesis, testicular steroidogenesis, thyroid hormones. -- Environ Health Perspect 107(suppl 4) :605-611 (1999) .

http://ehpnet1.niehs.nih.gov/docs/1999/suppl-4/605-611ben-jonathan/abstract.html