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Modeling mixtures of environmental estrogens found in U.S. surface waters with an in vitro estrogen mediated transcriptionai activation assay (T47D-KBluc).
Bermudez, D., L. E. GRAY, AND V. S. WILSON. Modeling mixtures of environmental estrogens found in U.S. surface waters with an in vitro estrogen mediated transcriptionai activation assay (T47D-KBluc). Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Mixture modeling of environmental estrogens with an in vitro ER-mediated assay. Resarch compares two additivity prediction models.
There is growing concern of exposure to fish, wildlife, and humans to water sources contaminated with estrogens and the potential impact on reproductive health. Environmental estrogens can come from various sources including concentrated animal feedlot operations (CAFO), municipal waste, agricultural and industrial effluents. Furthermore, U.S. EPA's drinking water contaminant candidate list 3 (CCL3) includes several estrogenic compounds. While these contaminants are currently not subject to any proposed or promulgated national primary drinking water regulations, they are known or anticipated to occur in public water systems and may require future regulation under the Safe Drinking Water Act. Using an in vitro transcriptional activation assay, this study evaluated estrogens from CCL3 both individually and as a seven estrogen mixture (fixed ray design). In addition, mixtures that mirror primary estrogens found in swine, poultry and dairy CAFO effluent (fixed ray design), and a ternary mixture (4x4x4 factorial design) of estrogens found in hormone replacement therapy and/or oral contraceptives were tested. Mixtures were evaluated for additivity using both the concentration addition model (CA) and estrogen equivalence model (EEQ). Log EC50 and Hillslope values were as follows: Estrone, -11.92 M, 1.283; Estradiol-17a, -9.61 M, 1.486; Estradiol-17B, 11.77 M, 1.494; Estriol, -11.14 M, 1.074; Ethinyl Estradiol-17a, -12.63 M, 1.562; Mestranol, 11.08 M, 0.809; Equilin, -11.48 M, 0.946. In all cases, both the CA and EEQ models predicted the observed responses accurately. There was no evidence that any of the mixtures acted synergistically or in an antagonistic manner. Results indicate both additive models are appropriate for modeling estrogen mixtures. This study augments the understanding of estrogen mixture interactions. Abstract does not necessarily reflect EPA policy. NIEHS/EPA Interagency RW75-92285501-1; NCSU/EPA Cooperative Training Agreement CT833235-01-0.