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Comparison of estrogen mixtures in vitro vs. in vivo
Citation:
Hannas, B., J. Furr, E. Gray, AND V. Wilson. Comparison of estrogen mixtures in vitro vs. in vivo. Presented at Society of Toxicology meeting, March 10 - 14, 2013.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology meeting March 10-14, 2013, San Antonio, TX
Description:
Numerous sources contribute to widespread contamination of drinking water sources with both natural and synthetic estrogens, which isa concern for potential ecological and human health effects. In vitro screening assays are valuable tools for identifying mechanisms of toxicity but in vitro results cannot be directly extrapolated to in vivo exposures since most in vitro assays do not account for metabolism, distribution and excretion or other systemic toxicities. In this study, we highlight some of the limitations associated with using in vitro estrogen transcriptional activation assays for predicting in vivo action of xenoestrogens. In particular, we compared the ability to predict the uterine growth response in the rat to estrogens, administered orally either individually or as mixtures using an in vitro estrogen transcriptional activation (TA) assay (T470-KBIuc cell line). We demonstrated that a binary mixture of BPAF + Methoxychlor in the uterotrophic assay conforms to dose additive (DA) estrogenicity, whereas the degree of estrogenicity of this mixture is underestimated by the TA assay. In contrast, the TA assay responded to a binary mixture of BBP + BPA in a DA manner, whereas, the uterotrophic assay displayed no estrogenic response to this mixture. These data illustrate the limitations associated with making in vivo predictions based on in vitro assay data for compounds that are metabolically inactivated in vivo in the liver, gut or other tissues or activated by the liver in vivo. Ongoing efforts related to this study include characterizing individual dose response curves and mixture estrogenicity for additional estrogens in vitro and in vivo. These data will improve our ability to make predictions from the in vitro assay to the in vivo response to exposure to the compounds. This information is critical forvalid interpretation of in vitro screening assay results. Disclaimer: Abstract does not necessarily reflect U.S.EPA policy.