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In vivo and in vitro mixture modeling of endocrine disruptors
Citation:
Bermudez, D., C. Rider, V. S. WILSON, AND L. E. GRAY. In vivo and in vitro mixture modeling of endocrine disruptors. Presented at 14th International Congress of Endocrinology, Kyoto, JAPAN, March 26 - 30, 2010.
Impact/Purpose:
Our in vivo studies have examined the effects of prenatal exposure to chemicals that disrupt the androgen signaling pathway, resulting in abnormal male reproductive development.
Description:
Humans, fish and wildlife are exposed to more than one chemical at a time. There is concern over the potential effects of exposure to mixtures of EDs. We have conducted invitro and in vivo studies to determine how EDs in mixtures interact. Our in vivo studies have examined the effects of prenatal exposure to chemicals that disrupt the androgen signaling pathway, resulting in abnormal male reproductive development. The chemicals include AR antagonists, phthalates, and 2,3,7,8-tetrachlorodibenzodioxin. We have examined the effects of these chemicals on morphology and function of the adult male rat reproductive system and also on fetal male rat hormone levels, and testicular gene expression levels. Results demonstrate that dose addition models accurately predict the effects of these mixtures on male rat sexual differentiation. Xenoestrogens are common in the environment and we are exposed to these, as well as endogenous estrogens. Our in vitro studies addressed how xenoestrogens interact with the endogenous estrogens. To date, we have characterized dose responses of estradiol-17fJ, bisphenol A, te1rabromo-bisphenol A and bisphenol AF with an ER reporter gene assay. Binary and ternary mixtures of these estrogens have been evaluated. In vitro mixtures all behaved in an additive manner. Our studies indicated that the effects of mixtures of EDCs can generally be predicted by dose addition models, but these additive interactions are not limited to chemicals that act via a common mechanism of toxicity in vivo. This abstract does not necessarily reflect EPA policy.