An approach to the development of quantitative models to assess the effects of exposure to environmentally relevant levels of endocrine disrupters onhomeostasis in adults

The workshop "Characterizing the Effects of Endocrine Disrupters on Human H ealth at Environmental Exposure Levels" was held to provide a forum for dis cussions and recommendations of methods and data needed to improve risk ass essments of endocrine disrupters. This article was produced by a working gr oup charged with determining the basic mechanistic information that should be considered when designing models to quantitatively assess potential risk s of environmental endocrine disrupters in adults. To reach this goal, we i nitially identified a set of potential organ system toxicities in males and females on the basis of known and/or suspected effects of endocrine disrup ters on estrogen, androgen. and thryoid hormone systems. We used this integ rated, systems-level approach because endocrine disrupters have the potenti al to exert toxicities at many levels and by many molecular mechanisms. Bec ause a detailed analysis of all these untoward effects was beyond the scope of this workshop, we selected the specific end point of testicular functio n for a more detailed analysis. The goal was to identify the information re quired to develop a quantitative model(s) of the effects of endocrine disru pters on this system while focusing on spermatogenesis, sperm characteristi cs, 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 w as to gather the information needed to develop models in the adult organism containing functional homeostatic mechanisms, and for this reason we did n ot consider possible developmental toxicities. Homeostatic mechanisms have the potential to ameliorate or lessen the effects of endocrine disrupters, but these pathways are also potential target sites for the actions of these chemicals.