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Triclosan enhances the uterine response to ethynyl estradiol: A dose response evaluation in the weanling rat
Citation:
Louis, G., D. Hallinger, D. Best, AND T. E. STOKER. Triclosan enhances the uterine response to ethynyl estradiol: A dose response evaluation in the weanling rat. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
These observations may be important for human health, as the potentiation of EE by TCS was observed at doses of EE that are comparable to those used for birth control and post-menopausal management. In addition, pharmaceuticals such as synthetic estrogens are found in environmental water samples. Until the mechanism of this effect is determined, the impact of these effects on human and ecological health remains to be determined
Description:
Triclosan (TCS) is an antimicrobial agent found in personal care products, such as soaps and toothpaste. TCS has been detected in human breast milk, blood and urine and has been reported to decrease thyroxine and testosterone in rats; thus, rising concerns that this endocrine disruptor may adversely affect human health. Previously, we reported that TCS exposure (150mg/kg) to female rats resulted in advanced age of vaginal opening and increased uterine weight, indicative of an estrogenic effect. In the weanling rat, TCS alone had no effect on uterine weight, whereas combined exposures to ethynyl estradiol (EE; 3ug/kg) and TCS (≥4.69mg/kg) potentiated the effect of EE on uterine growth (i.e., increased uterine weight and epithelial cell height). In this study, we further characterized the combined action of TCS and EE by examining uterine growth in the immature rat following EE treatment at pharmaceutically relevant doses (0.125-3ug/kg) combined with a series of TCS doses (2.3-18.75mg/kg). Exposure to EE at doses as low as 0.25ug/lkg significantly increased uterine weight compared to vehicle, but 0.1251ug/kg of EE had no significant effect. However, a combined exposure to either 9.375 or 18.75mg/kg of TCS with EE (0.5-3ug/kg doses) resulted in a significant increase (>25%) in uterine weight compared to those exposed to (their respective doses of) EE alone. Combining higher doses of EE (2-3ug/ kg) with TCS (4.69mg/kg) significantly increased uterine weight compared to those receiving only EE. Thus, TCS enhances the uterine response to EE at concentrations lower than previously shown. These observations may be important for human health, as the potentiation of EE by TCS was observed at doses of EE that are comparable to those used for birth control and post-menopausal management. In addition, pharmaceuticals such as synthetic estrogens are found in environmental water samples. Until the mechanism of this effect is determined, the impact of these effects on human and ecological health remains to be determined. This abstract does not necessarily reflect EPA policy. This research was supported in part by an appointment to the Research Participation Program for the U.S. EPA, Office of Research and Development, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and EPA