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Mixture interactions of xenoestrogens with endogenous estrogens.
WILSON, V. S. Mixture interactions of xenoestrogens with endogenous estrogens. Presented at 6th Copenhagan Workshop on Endocrine Disruptors, Copenhagan, DENMARK, April 26 - 29, 2011.
Understanding the behavior of mixture interactions of estrogenic compounds with each other and also of xenoestrogens with endogenous estrogens will allow a better assessment of the potential risk associated with exposure to these chemicals individually or as mixtures.
There is growing concern of exposure to fish, wildlife, and humans to water sources contaminated with estrogens and the potential impact on reproductive health. These environmental estrogens originate from various sources including concentrated animal feedlot operations (CAFO), municipal waste, agricultural runoffs, industrial effluents and pharmaceuticals. Estrogenic compounds from such sources occur as part of complex environmental mixtures and, furthermore, exposure to xenoestrogens occurs against a backdrop to physiological levels of endogenous estrogens. Only a few studies, however, have evaluatedestrogenmixtureinteractions. Using an in vitro transcriptional activation assay, we evaluated estrogenic compounds individually and as environmentally relevant mixtures. Mixtures were evaluated for additive effects using both the concentration addition model (CA) and estrogen equivalence model (EEQ). Studies included 1) the interaction of xenoestrogens with the endogenous hormone, 17B-estradiol (E2). Specifically binary (8x8 factorial design) and ternary (4x4x4 factorial) mixtures of estrogen (E2) with bisphenol A and/or, bisphenol AF were evaluated; 2) a mixture of seven estrogens reportedly identified in public water systems (fixed ray design); 3) mixtures that each mirrored primary estrogens found in swine, poultry or dairy animal feedlot effluents (fixed ray design); and 4) a ternary mixture (4x4x4 factorial design) of estrogens found in hormone replacement therapy and/or oral contraceptives. In each of these cases mixtures were evaluated over a broad range of concentrations. In all cases, both the CA and EEQ models accurately predicted the observed responses. Understanding the behavior of mixture interactions of estrogenic compounds with each other and also of xenoestrogens with endogenous estrogens will allow a better assessment of the potential risk associated with exposure to these chemicals individually or as mixtures. Disclaimer: This abstract does not necessarily reflect USEPA policy.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION
REPRODUCTIVE TOXICOLOGY BRANCH