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EFFECTS OF MIXTURES OF PHTHALATES, PESTICIDES AND TCDD ON SEXUAL DIFFERENTIATON IN RATS: A RISK FRAMEWORK BASED UPON DISRUPTION OF COMMON DEVELOPING SYSTEMS
Citation:
GRAY, L. E. EFFECTS OF MIXTURES OF PHTHALATES, PESTICIDES AND TCDD ON SEXUAL DIFFERENTIATON IN RATS: A RISK FRAMEWORK BASED UPON DISRUPTION OF COMMON DEVELOPING SYSTEMS. Presented at Society of Toxicology Annual Meeting (SOT), Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
The author was invited to present this work in a special Symposium at the 2011 Annual Society of Toxicology Meeting
Description:
Since humans are exposed to more than one chemical at a time, concern has arisen about the effects of mixtures of chemicals on human reproduction and development. We are conducting studies to determine the 1) classes of chemicals that disrupt sexual differentiation via different mechanisms of toxicity, 2) effects associated with in utero phthalate, pesticide and 2,3,7,8 dioxin (TCDD) exposures, and 3) how mixtures of phthalates behave when combined with pesticides or TCDD. In the mixture studies, we have examined the postnatal development of male rat offspring after in utero exposure to 1) pairs of AR antagonists, 2) pairs of phthalates, 3) phthalates with AR antagonists, 4) five phthalates, 5) seven chemicals (four pesticides and three phthalates), 6) ten chemicals (four pesticides and six phthalates) and 7) the potent Ah receptor agonist TCDD plus a phthalate. We also have examined the effects of some of these chemicals on fetal male rat hormone levels and testicular gene expression levels. Results of these studies demonstrate that dose addition models generally provide the most accurate predictions of the observed effects of these mixtures on male rat sexual differentiation. For example, when ten chemicals were administered in utero, 100% of the males displayed reproductive tract malformations as predicted by dose addition models, whereas response addition models predicted that none of the males would be malformed. Our data indicate that cumulative risk assessments based upon disruption of common fetal targets or systems during development more accurately predicts mixture effects than does one based upon mechanisms of toxicity. This abstract does not necessarily reflect EPA policy. This abstract does not necessarily reflect EPA policy. NTP, NIEHS/EPA Interagency Cooperative Research Agreement HHS Y1-ES-8014-01; EPA RW75922