The Effects of Triclosan on Puberty and Thyroid Hormones in Male Wistar Rats

Department of Molecular Biomedical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina 27606, USA.
Toxicological Sciences (Impact Factor: 3.85). 11/2008; 107(1):56-64. DOI: 10.1093/toxsci/kfn225
Source: PubMed

ABSTRACT Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is a potent antibacterial and antifungal compound that is widely used in personal care products, plastics, and fabrics. Recently triclosan has been shown to alter endocrine function in a variety of species. The purpose of this study was to determine effects of triclosan on pubertal development and thyroid hormone concentrations in the male rat. Weanling rats were exposed to 0, 3, 30, 100, 200, or 300 mg/kg of triclosan by oral gavage from postnatal day (PND) 23 to 53. Preputial separation (PPS) was examined beginning on PND 33. Rats were killed on PND 53, organ weights were recorded and serum was collected for subsequent analysis. Triclosan did not affect growth or the onset of PPS. Serum testosterone was significantly decreased at 200 mg/kg, however no effects were observed on androgen-dependent reproductive tissue weights. Triclosan significantly decreased total serum thyroxine (T4) in a dose-dependent manner at 30 mg/kg and higher (no observed effect level of 3 mg/kg). Triiodothyronine (T3) was significantly decreased only at 200 mg/kg, but thyroid stimulating hormone was not statistically different at any dose. Liver weights were significantly increased at 100 mg/kg triclosan and above suggesting that the induction of hepatic enzymes may have contributed to the altered T4 and T3 concentrations, but it does not appear to correlate with the T4 dose-response. This study demonstrates that triclosan exposure does not alter androgen-dependent tissue weights or onset of PPS; however, triclosan exposure significantly impacts thyroid hormone concentrations in the male juvenile rat.

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    • "29 h ( SCCP , 2009 ) . Serial measurements of TCS in morning urine have shown relatively high consistency over time ( ICC = 0 . 56 ; ( Lassen et al . , 2013 ) ) . TCS has been shown in animal studies to cause endocrine effects , especially on the levels of thyroid hormones ( Crofton et al . , 2007 ; Dann and Hontela , 2011 ; Kumar et al . , 2009 ; Zorrilla et al . , 2009 ) . The Scientific Committee on Consumer Prod - ucts ( SCCP ) has concluded that the current maximum concentration of 0 . 3% is not safe when the aggregate exposure from all cosmetic products is considered . However , the maximum concentration is considered safe for individual products such as toothpastes , soaps and deodorants , but no"
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    ABSTRACT: Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood. The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6–11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother–child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors. There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 μg/L; ΣDiNP 37.8 μg/L; MBzP 19.9 μg/L; MnBP 76.9 μg/L) than the mothers (ΣDEHP 38.4 μg/L; ΣDiNP 33.8 μg/L; MBzP 12.8 μg/L; MnBP 63.0 μg/L). Conversely, the mother's levels of parabens (MetP 37.8 μg/L; ProP 13.9 μg/L) and MEP (43.4 μg/L) were higher than the children's levels of parabens (MetP 6.8 μg/L; ProP 2.1 μg/L) and MEP (28.8 μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p = < 0.001; MnBP p = 0.001–0.002), which is probably due to higher presence of PVC in floorings and wall coverings in this area, whereas the levels of parabens were higher among the children in the urban area (MetP p = 0.003; ProP p = 0.004) than in the rural area. The levels of high molecular weight phthalates were associated with consumption of certain foods (i.e. chocolate and ice cream) whereas the levels of parabens were associated with use of cosmetics and personal care products.
    Environment International 09/2014; 73C:323-333. DOI:10.1016/j.envint.2014.08.014 · 5.56 Impact Factor
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    • "laevis) tadpoles exposed to 0.8–12.5 ␮g/L TCS showed increased TRˇmRNA levels in the tail fin by 21 days of exposure and the promotion of growth concomitant with increased size and hypertrophy of the thyroid gland by 32 days (Fort et al., 2010, 2011; Helbing et al., 2011a,b). Collectively these studies establish a scientific foundation whereby TCS is observed to affect a critical stage of amphibian development and, with additional evidence garnered on the biological effects of TCS on the thyroid axis in mammals (Paul et al., 2010a,b; Zorrilla et al., 2009), suggest that the increased use of this broad spectrum bactericide and its prevalence as a pollutant in waterways and soils is of concern with respect to normal development of a wide range of non-target vertebrates. "
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    ABSTRACT: The Amphibian Metamorphosis Assay (AMA), developed for Xenopus laevis, is designed to identify chemicals that disrupt thyroid hormone (TH)-mediated biological processes. We adapted the AMA for use on an ecologically-relevant North American species, the Pacific tree frog (Pseudacris regilla), and applied molecular endpoints to evaluate the effects of the antibacterial agent, triclosan (TCS). Premetamorphic (Gosner stage 26-28) tadpoles were immersed for 21 days in solvent control, 1.5μg/L thyroxine (T(4)), 0.3, 3 and 30μg/L (nominal) TCS, or combined T(4)/TCS treatments. Exposure effects were scored by morphometric (developmental stage, wet weight, and body, snout-vent and hindlimb lengths) and molecular (mRNA abundance using quantitative real time polymerase chain reaction) criteria. T(4) treatment alone accelerated development concomitant with altered levels of TH receptors α and β, proliferating cell nuclear antigen, and gelatinase B mRNAs in the brain and tail. We observed TCS-induced perturbations in all of the molecular and morphological endpoints indicating that TCS exposure disrupts coordination of postembryonic tadpole development. Clear alterations in molecular endpoints were evident at day 2 whereas the earliest morphological effects appeared at day 4 and were most evident at day 21. Although TCS alone (3 and 30μg/L) was protective against tadpole mortality, this protection was lost in the presence of T(4). The Pacific tree frog is the most sensitive species examined to date displaying disruption of TH-mediated development by a common antimicrobial agent.
    Aquatic toxicology (Amsterdam, Netherlands) 10/2012; 126C:85-94. DOI:10.1016/j.aquatox.2012.10.010 · 3.45 Impact Factor
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    • "Increased expression of Cyp2b1/2 and Cyp3a1 is consistent with our previous observations from a short-term exposure, which demonstrated that a 4-day TCS exposure resulted in up-regulated expression of both Cyp2b1/2 and Cyp3a1/23 (Paul et al., 2010b). In addition, PROD activity, a marker of Cyp2b activity in the rat, was increased 2–3 fold-control for PND22 dams and PND4 neonates, consistent with previous reports (Paul et al., 2010b; Zorrilla et al., 2009). The lack of effect on PROD activity for GD20 dams was unexpected and may be due to a combination of the mild hypothyroxinemia and their unique metabolic status during pregnancy; several CYPs including Cyp2b2 protein are known to be decreased in rat liver during pregnancy and return to pre-pregnancy levels during lactation (He et al., 2005a,b). "
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    ABSTRACT: This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman(®) qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid hormone-responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300mg/kg/day). Hepatic PROD activity increased 2-3 fold in PND4 pups and PND22 dams, and UGT activity was 1.5 fold higher in PND22 dams only (300mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS-induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the low efficacy of TCS as thyroid hormone disruptor or highlight the possibility that other MOAs may also contribute to the observed maternal and early neonatal hypothyroxinemia.
    Toxicology 05/2012; 300(1-2):31-45. DOI:10.1016/j.tox.2012.05.023 · 3.62 Impact Factor
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