Environmental Toxicology and Pharmacology 24 (2007) 194–197 Short communication Short-term in vivo exposure to the water contaminant triclosan: Evidence for disruption of thyroxine  Kevin M. Crofton a,∗ , Katie B. Paul b , Michael J. DeVito c , Joan M. Hedge a a Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. EPA, Research Triangle Park, NC, United States b Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, United States c Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. EPA, Research Triangle Park, NC, United States Received 15 February 2007; received in revised form 23 April 2007; accepted 25 April 2007 Available online 27 April 2007 Abstract Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is a chlorinated phenolic antibacterial compound found as an active ingredient in many personal care and household products. The structural similarity of triclosan to thyroid hormones and recent studies demonstrating activation of the human pregnane X receptor (PXR) and inhibition of diiodothyronine (T 2 ) sulfotransferases, have raised concerns about adverse effects on thyroid homeostasis. The current research tested the hypothesis that triclosan alters circulating concentrations of thyroxine. The hypothesis was tested using a 4-day oral triclosan exposure (0–1000 mg/kg/day) in weanling female Long-Evans rats, followed by measurement of circulating levels of serum total thyroxine (T 4 ). Dose-dependent decreases in total T 4 were observed. The benchmark dose (BMD) and lower bound on the BMD (BMDL) for the effects on T 4 were 69.7 and 35.6mg/kg/day, respectively. These data demonstrate that triclosan disrupts thyroid hormone homeostasis in rats. © 2007 Elsevier B.V. All rights reserved. Keywords: Triclosan; Thyroxine (T 4 ); Thyroid hormone (TH); Endocrine disruptor 1. Introduction Triclosan is a chlorinated phenolic antibacterial compound used as an active ingredient in many personal care and house- hold products (Bhargava and Leonard, 1996; Dayan, 2007). The bactericidal activity of triclosan results from inhibition of the enoyl–acyl carrier protein reductase (ENR) of Gram-negative and Gram-positive bacteria, thereby preventing bacterial lipid biosynthesis (McMurry et al., 1998; Levy et al., 1999; Heath and Rock, 2000). The ubiquitous usage in consumer products has led to widespread environmental contamination evidenced  This work has not been previously published or presented in any manner. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. ∗ Corresponding author at: Neurotoxicology Division, MD-B105-04, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States. Tel.: +1 919 541 2672; fax: +1 919 541 5278. E-mail address: crofton.kevin@epa.gov (K.M. Crofton). by detection of triclosan in wastewater effluent in the US, UK, Japan, and other countries (Kanda et al., 2003; Loraine and Pettigrove, 2006; Nakada et al., 2006). Triclosan has been found in fish exposed to wastewater treatment plant effluents (Adolfsson-Erici et al., 2002), in human breast milk samples (Adolfsson-Erici et al., 2002; Dayan, 2007), and in urine samples from young girls (Wolff et al., 2007). The structural similarity to thyroid hormones (THs, Fig. 1) and evidence for human exposures have increased concern about possible endocrine disrupting effects of triclosan (Veldhoen et al., 2006). Foran et al. (2000) studied the potential estrogenic effects of triclosan in Oryzias latipes (medaka) and concluded that it is not estrogenic, but may be a weak androgen. Vitel- logenin induction, a biomarker for endocrine activity, has been found in medaka and Xenpous laevis (clawed frog) and was attributed to weak estrogenic activity of a triclosan metabolite (Ishibashi et al., 2004). There is also evidence that triclosan may disrupt thyroid mediated development. Exposure of Rana catesbeiana (North American bullfrog) to triclosan resulted in accelerated thyroid hormone-dependent metamorphosis and 1382-6689/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.etap.2007.04.008