Endocrine active compounds: From biology to dose response assessment

Endocrine active compounds (EACs) alter signaling processes responsible for regulation and coordination of physiological functions during development and adulthood. The potential that adverse effects of these compounds have gone unrecognized has focused attention on their toxicology. The primary response to this concern has been development of additional hazard identification methods. This review discusses issues for dose response (DR) analyses for EACs, including definitions of adversity, implications of alternative modes of action, the roles homeostatic and developmental regulatory feedback processes play in creating DR behaviors, uses of in vitro data in DR analyses, and induction of effects by natural and synthetic compounds in the context of endogenous hormone background. Current risk assessment guidance applicable to endocrine-mediated effects provide limited default methods for evaluating DR behaviors and making interspecies comparisons. Improved DR methods for EACs will be achieved through the use of mode of action and dosimetry data to better characterize potential human risks.