Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products

Center for Health and the Environment, University of California, Davis, CA 95616, USA.
Toxicology and Applied Pharmacology (Impact Factor: 3.63). 07/2007; 221(3):278-84. DOI: 10.1016/j.taap.2007.03.015
Source: PubMed

ABSTRACT To identify the androgenic potency of commonly used antimicrobials, an in vitro androgen receptor-mediated transcriptional activity assay was employed to evaluate the androgenic/antiandrogenic activity of parabens and selected other antimicrobials containing a phenolic moiety. This cell-based assay utilizes a stably transfected cell line that lacks critical steroid metabolizing enzymes and is formatted in a 96-well format. At a concentration of 10 microM, methyl-, propyl- and butyl-4-hydroxybenzoate (parabens) inhibited testosterone (T)-induced transcriptional activity by 40%, 33% and 19%, respectively (P<0.05), while 4-hydroxybenzoic acid, the major metabolite of parabens, had no effect on T-induced transcriptional activity. Triclosan inhibited transcriptional activity induced by T by more than 92% at a concentration of 10 microM, and 38.8% at a concentration of 1.0 microM (P<0.05). Thirty-four percent of T-induced transcriptional activity was inhibited by thymol at 10 microM (P<0.05). Cell proliferation and/or cytotoxicity were not observed in any of the treatments. None of the compounds appeared to be androgenic when tested individually without T. The data presented in this report demonstrate that some widely used antimicrobial compounds have antiandrogenic properties and warrant further investigation to fully understand their potential impact on human reproductive health.

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Available from: Shirley J Gee, Sep 22, 2014
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    • "The hormonal activity of triclosan has not been clearly established, due to the conflicting results from different investigations. There is evidence of weak estrogenic (Chen et al. 2007;Svobodova et al. 2009) and androgenic activity (Chen et al. 2007), estrogen receptor antagonism (Ahn et al. 2008), and anti-androgenic properties (Chen et al. 2007). The excretion half-life of triclosan has been estimated as 11 hours for urine and 21 hours for plasma (Sandborgh-Englund et al. 2006). "
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    ABSTRACT: This first of its kind proof of concept rodent study examines the relationship between oral doses of three widely used personal care product ingredients (diethyl phthalate (DEP), methyl paraben (MPB), triclosan) and urine and serum concentrations of their respective biomarkers. Using female Sprague-Dawley rats, we carried out two rounds of experiments with oral gavage doses selected in reference to EPA NOAEL: 1735 (DEP), 1050 (MPB), 50 (triclosan) mg/kg/day. Administered doses ranged from 0.005-173 mg/kg/day, 10-100,000 times below NOAEL for each chemical. Controls for MBP and triclosan experiments were animals treated with olive oil (the vehicle) only; controls for DEP serum experiments were animals treated with the lowest MBP and triclosan doses. Doses were administered for five days with five rats in each treatment group. Urine and blood serum, collected on the last day of exposure, were analyzed for biomarkers. Relationships between oral dose and biomarker concentrations were assessed using linear regression. Biomarkers were detected in all control urine samples at parts-per-billion levels suggesting a low endemic environmental exposure of the three chemicals that could not be controlled even with all precaution measures undertaken. Among exposed animals, urinary concentrations of all three biomarkers were orders of magnitude higher than those in serum. A consistently positive linear relationship between oral dose and urinary concentration was observed (R(2)>0.80); the relationship was inconsistent in serum. Our study highlights the importance of careful consideration of the oral dose used in animal experiments and provides useful information in selecting doses for future studies.
    Environmental Health Perspectives 06/2015; DOI:10.1289/ehp.1409586 · 7.98 Impact Factor
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    • "Suzuki et al. (2013) reported that AR antagonist activities were frequently found in indoor dust from Japan, the United States, Vietnam, the Philippines, and Indonesia, and several flame retardants exhibited antiandrogenic activity in the AR-CALUX assay. In addition, several synthetic compounds widely used in our daily lives, such as triclosan, parabens, and phthalates have been shown to elicit antiandrogenic or antithyroid hormonal activities (Chen et al., 2007; Shen et al., 2009; Christen, 2012), and these compounds have been detected in indoor dust as well (Bornehag et al., 2005; Fan et al., 2010). Quantification of these potential AR and TR antagonists may be useful in characterizing major AR/TR antagonist contaminants in indoor dust from Taiwan. "
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    ABSTRACT: ABSTRACT Indoor dust serves as a potential sink for various synthetic chemicals used in our daily lives, while exposure to theseanthropogenic contaminants via dust contact, ingestion, or inhalation may pose potential threats to human health. In thisstudy, in vitro biological assays were used to investigate the endocrine disrupting activity and genotoxicity in dust samples collected from a university located in southern Taiwan. Contents of polycyclic aromatic hydrocarbons (PAHs) in indoor dust were also analysed by gas chromatography mass spectrometry. Our results showed that significant aryl hydrocarbon receptor (AhR) agonist, antiandrogenic, antithyroid hormonal, and genotoxic activities were found in dust samples. In particular, high AhR agonist activities were found in indoor dust collected from computer room and laboratory (16112 and 9686 ng benzo(a)pyrene equivalent/g dust dry weight), whereas AhR agonistic PAHs were responsible for only a small percentage of the bioassay-derived activities. Higher antiandrogenic and genotoxic activities were found in indoor dust from office and classroom, respectively, suggesting that contaminants varied in different indoor dust samples. After fractionating by high performance liquid chromatography, AhR agonist activities were detected in several fractions of indoor dust from computer room and laboratory, indicating the presence of unknown AhR agonist contaminants in these indoor dust samples. Further isolation and identification of novel AhR agonistic and antiandrogenic contaminants is necessary to protect the environment and human health.
    Aerosol and Air Quality Research 06/2015; DOI:10.4209/aaqr.2015.06.0404 · 2.66 Impact Factor
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    • "reported that a 1,000 and 10,000 molar excess of TCS inhibited the binding of [ 3 H] testosterone to recombinant androgen receptor (AR) protein by about 49% and 77%, respectively, suggesting that TCS binds specifi cally with low affi nity to the AR. However, several AR reporter cell-based assays, such as transfected human embryonic kidney cells, transfected mouse mammary tumor cells, and yeast-based bioluminescent screens have failed to demonstrate agonistic activity of TCS (Chen et al. 2007, Gee et al. 2008, Svobodov á et al. 2009) although anti-androgenic activity of TCS was observed (Chen et al. 2007, Gee et al. 2008). On the other hand, Christen et al. (2010) observed in MDA-kb2, human breast cancer cells stably expressing an AR-response construct that TCS produced partial androgenic activity between 10 nM and 1 μ M, achieving about 50% of that attained by 0.5 nM dihydrotestosterone (DHT). "
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    ABSTRACT: This review examines the mammalian and human literature pertaining to the potential endocrine disruptive effects of triclosan (TCS). Dietary exposure to TCS consistently produces a dose-dependent decrease in serum thyroxine (T4) in rats without any consistent change in TSH or triiodothyronine (T3). Human studies reveal no evidence that the TCS exposure through personal care product use affects the thyroid system. TCS binds to both androgen and estrogen receptors in vitro with low affinity and evokes diverse responses (e.g., agonist, antagonist, or none) in steroid receptor transfected cell-based reporter assays. Two of three studies in rats have failed to show that TCS exposure suppresses male reproductive function in vivo. Three of four studies have failed to show that TCS possesses estrogenic (or uterotrophic) activity in rats. However, two studies reported that, while TCS lacks estrogenic activity, it can amplify the action of estrogen in vivo. The in vitro, in vivo, and epidemiologic studies reviewed herein show little evidence that TCS adversely affects gestation or postpartum development of offspring. Furthermore, previously reported toxicity testing in a variety of mammalian species shows little evidence that TCS adversely affects thyroid function, male and female reproductive function, gestation, or postpartum development of offspring. Finally, doses of TCS reported to produce hypothyroxinemia, and occasional effects on male and female reproduction, gestation, and offspring in animal studies are several orders of magnitude greater than the estimated exposure levels of TCS in humans. Overall, little evidence exists that TCS exposure through personal care product use presents a risk of endocrine disruptive adverse health effects in humans.
    Critical Reviews in Toxicology 06/2014; 44(6):1-21. DOI:10.3109/10408444.2014.910754 · 6.41 Impact Factor
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