EPA Science Inventory

Examining triclosan-induced estrogenic and androgenic effects on the rat reproductive system

Citation:

Louis, G., D. Hallinger, AND T. Stoker. Examining triclosan-induced estrogenic and androgenic effects on the rat reproductive system. Presented at Triangle Consortium of Reproductive Biology, RTP, NC, March 08, 2014.

Description:

Background: Triclosan (TCS), a widely used antibacterial, has been shown to be an endocrine disruptor. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in female rats co-administered EE (3 μg/kg) and TCS (2 to 18 mg/kg p.o.), whereas TCS alone had no effect. In this study, we further characterized the potentiation of EE by evaluating the effect of co-exposure with lower doses of EE that are more comparable to the concentrations in hormone replacement therapies. We also evaluated the effects of TCS with nonylphenol (NP; a pesticide with ER agonist activity) to determine whether the effects were specific only to co-administration with EE. TCS has been shown to have anti-androgenic activity in vitro and to decrease serum testosterone concentrations in pubertal male rats. Here, we are the first to examine TCS in the Hershberger assay to examine the effects on male accessory sex tissues (AST). Methods: Weanling female rats were gavaged with TCS (2.3, 4.69, 9.375, 18.75 mg/kg) and lower doses of EE (0.125, 0.25, 0.5, 1.0, and 2.0 μg/kg) in the 3-day uterotrophic assay. Separate cohorts were exposed to 100 and 200 mg/kg of NP in the presence and absence of 37 mg/kg TCS, and 3.0 μg/kg EE as positive controls. Young castrated male rats were gavaged with TCS (50 and 200 mg/kg), 0.2 mg/kg testosterone proprionate (TP; an androgen agonist; s.q.), or a combination of TCS and TP in the 10-day Hershberger assay. ASTs (glans penis, Cowper’s glands, LABC, seminal vesicles, and ventral prostate) were dissected and weighed. Results and Conclusions: TCS correspondingly potentiated the uterotrophic effect (in uterine weight) at doses of EE as low as 0.25 μg/kg (>2.3 fold greater than controls). 100 and 200 mg/kg NP induced a significant increase in uterine weight (1.8- and 2-fold, respectively), but to a lesser extent than the EE-induced response (2.8-fold vs. controls). Animals co-treated with TCS and NP showed a significant increase in uterine weight compared to controls (100 mg/kg NP+TCS=1.9-fold; 200 mg/kg NP+TCS=2.1-fold), but this difference was not significant from NP alone. These data demonstrate that TCS potentiated the uterine response to EE at concentrations lower than reported previously and emphasize the significance of considering the concentrations of both chemicals when evaluating the effect of co-exposures in toxicological studies. Furthermore, the lack of effect with TCS on the NP-induced estrogenic effect supports our previous report that TCS does not directly act on the estrogen receptor. In the male Hershberger assay, TCS alone or in combination with TP did not alter the weight of ASTs examined, suggesting that TCS does not have androgenic or anti-androgenic activity. This work does not necessarily reflect EPA policy.

Purpose/Objective:

This poster will be presented at the Triangle Consortium for Reproductive Biology and includes a summary of our research on Triclosan in two short-term in vivo assays. We demonstrate that Triclosan enhances the uterine estrogenic response but has no effects on the androgenic response in the male assay.

URLs/Downloads:

LOUIS TCRB 2014 ABSTRACTFINAL.DOCX

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Completion Date: 03/17/2014
Record Last Revised: 03/17/2014
Record Created: 03/17/2014
Record Released: 03/17/2014
OMB Category: Other
Record ID: 271084

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

TOXICOLOGY ASSESSMENT DIVISION

ENDOCRINE TOXICOLOGY BRANCH