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Triclosan exposure modulates estrogen-dependent responses in the rat uterotrophic assay.
Citation:
STOKER, T E., L. ZORRILLA, AND E K. GIBSON. Triclosan exposure modulates estrogen-dependent responses in the rat uterotrophic assay. Presented at 2009 SOT Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
This study was conducted to examine the estrogenic activity of the biocide triclosan.
Description:
Our previous studies in the juvenile rat indicated that the biocide triclosan may alter steroid hormone levels. Here, we hypothesize that triclosan possesses estrogenic activity. In the first study, we evaluated the potential estrogenicity of triclosan using the immature rat uterotrophic assay. Female Wistar rats (19 days old) were gavaged for 3 consecutive days with corn oil, 3 ug/kg ethinyl estradiol (EE) or 1.17 to 300 mg/kg triclosan either alone or in combination with EE. Six hours following the last dose, the uteri were weighed and processed for subsequent histological evaluation. Uterine weight was increased in the EE group as compared to the control, but was not affected by triclosan alone. However, there was a significant dose-dependent increase in the triclosan 4.69 to 300 mg/kg co-treated with EE as compared to the EE alone, indicating a potentiation of the estrogen response on uterine weight (NOEL=2.34 mg/kg). In addition, this result was correlated with a dose response increase in degree of columnar differentiation of the luminal epithelium of the uteri in the females receiving co-treatment with EE. In a second experiment, an in vitro cell-based estrogen receptor (ER) transcriptional activation (TA) assay using the T47D-Bluc cell line was used to determine if triclosan altered estrogen receptor activation. Triclosan concentrations of .003 to 10μM were evaluated in this assay. All concentrations of triclosan were completely soluble and cytoxicity was not observed after 24 hour incubation. Triclosan alone did not have agonistic or antagonistic activity in the ER TA assay. In addition, co-incubations of triclosan and various concentrations of estradiol resulted in a response comparable to estradiol alone, indicating that the parent compound does not potentiate ER TA. It is possible that one of the metabolites of triclosan may be responsible for the observed effect. In conclusion, there appears to be a potentiating effect of triclosan on estrogen mediated uterine response in the weanling female rat. Current studies are evaluating other potential modes of action for the effect, such as effects on estrogen metabolism. This abstract does not reflect EPA policy.