Science Inventory

TRICLOSAN ALTERS THYROID HORMONES HOMEOSTASIS VIA UP-REGULATION OF HEPATIC CATABOLISM.

Citation:

PAUL, K. B., J. M. HEDGE, K. M. CROFTON, AND M. J. DEVITO. TRICLOSAN ALTERS THYROID HORMONES HOMEOSTASIS VIA UP-REGULATION OF HEPATIC CATABOLISM. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.

Impact/Purpose:

Current research tested the hypothesis that triclosan decreases circulating concentrations of T4 via activation of PXR, constitutive androstane receptors (CAR), and subsequent up-regulation of hepatic catabolism of hormones.

Description:

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is a chlorinated phenolic antibacterial compound used in household and hygiene products. The structural similarity of triclosan to thyroid hormones, in vitro studies demonstrating activation of the human pregnane X receptor (PXR) and inhibition of sulfotransferases, and dose-dependent decreases in vivo of total thyroxine (T4) suggests adverse effects on thyroid hormone homeostasis. Current research tested the hypothesis that triclosan decreases circulating concentrations of T4 via activation of PXR, constitutive androstane receptors (CAR), and subsequent up-regulation of hepatic catabolism of hormones. Female Long-Evans rats (24 days old) were exposed po to triclosan (0-1000 mg/kg/day) for four days. Whole blood and liver were collected 24 hr after the last dose. Hepatic microsomal assays measured ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-deethylase (PROD), and uridine diphosphate glucuronyltransferase (UGT) enzyme activities. mRNA expression of UGT 1A1, and sulfotransferases 1C1 were measured by quantitative RT-PCR. Triclosan caused a dose-dependent increase in PROD activity (up to 5-fold at 300 mg/kg/day). There was no biologically relevant change in EROD activity. T4-glucuronidation increased ~2-fold at 100 mg/kg/day. UGT1A1 mRNA expression increased in a dose-dependent manner (up to 2.2-fold at 300 mg/kg/day). These data suggest that triclosan-induced hypothyroxinemia is, at least partially, due to upregulation of hepatic catabolism.

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 03/17/2008
Record Last Revised: 05/12/2008
OMB Category: Other
Record ID: 186008

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

NEUROTOXICOLOGY DIVISION

NEUROBEHAVIORAL TOXICOLOGY BRANCH