Interactive Effects of Endocrine Disruptors: Thyroid Hormone Homeostasis as a Target for Environmental Contaminants. Kevin M. Crofton, US EPA, ORD, NHEERL, Neurotoxicology Division. MD-74B Research Triangle Park, NC 27711, phone 919-541-2672, fax 919-541-4849, email crofton.kevin@epa.gov Michael DeVito Acting Branch Chief PKB/ETD/NHEERL, MD-74, Research Triangle Park, NC 27711, phone 919-5410061 A wide range of chemicals alter serum thyroid hormone (TH) concentrations. These structurally diverse chemicals act through multiple mechanisms. Major uncertainties in our understanding of the toxicity of chemicals that alter TH concentrations are: 1) the dose-response relationships between alterations in TH concentrations and developmental toxicity, 2) the effects of mixtures of chemicals with different mechanisms of action, and 3) the relevance of data from animal models when extrapolating risk to other species. This project is a multidisciplinary approach to address a number of uncertainties in the risk assessment of chemicals that alter serum TH concentrations. The project attempts to describe the quantitative and qualitative relationships between the short-term screens and endpoints of concern, such as the potential for developmental neurotoxicity. In addition, the project attempts to develop biomarkers for thyroid responsiveness that will provide for the development of screens and allow for a better understanding of the doseresponse relationship for adverse effects. These findings will examine the relevance of the current animal model for predicting the effects of thyroid hormone disruption on human health. These data will provide risk assessors with information on the potential effects of cumulative exposures to chemicals that alter THs. An increased understanding of species differences in the effects of xenobiotics on TH homeostasis will help to decrease the uncertainty when extrapolating data from species to species.