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Modelling defined mixtures of environmental oestrogens found in domestic animal and sewage treatment effluents using an in vitro oestrogen-mediated transcriptional activation assay (T47D-KBluc
Citation:
Bermudez, D., L. E. GRAY, AND V. S. WILSON. Modelling defined mixtures of environmental oestrogens found in domestic animal and sewage treatment effluents using an in vitro oestrogen-mediated transcriptional activation assay (T47D-KBluc. International Journal of Andrology. Blackwell Publishing, Malden, MA, 35(3):397-406, (2012).
Impact/Purpose:
Using an in vitro transcriptional activation assay, estrogens from CCL3 were evaluated both individually and as a seven estrogen mixture (fixed ray design) over a broad range of concentrations, including environmentally relevant concentrations
Description:
There is growing concern that exposure of fish, wildlife, and humans to water sources contaminated with estrogens could potentially impact reproductive health. Environmental estrogens can come from various sources including concentrated animal feedlot operations (CAFO), municipal waste, agricultural runoff, and industrial effluent. 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 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, estrogens from CCL3 were evaluated both individually and as a seven estrogen mixture (fixed ray design) over a broad range of concentrations, including environmentally relevant concentrations. 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 assessed. Mixtures were evaluated for additivity using both a concentration addition model (CA) and estrogen equivalence model (EEQ). Log ECso and Hillslope values for individual estrogens were: Estrone, -11.92 M, 1.283; Estradiol-17a, -9.61 M, 1.486; Estradiol-l Zp, 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 ofthe mixtures acted synergistically or in an antagonistic manner at any concentration. Results indicate both additive models are appropriate for modeling estrogen mixtures. This study augments the understanding of estrogen mixture interactions.
