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This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3β‐HSD2, 17β‐HSD1, 17β‐HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism.
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Objectives: Bisphenol A (BPA), a raw material commonly used in the manufacture of resins such as polycarbonate and epoxy, is a possible xenoestrogen that is hypothesized to disrupt the human endocrine system. Humans are widely exposed to BPA. We investigated the urinary concentration of BPA in infertile Japanese women and its possible association with endometriosis. Materials and Methods: We recruited 166 women (aged 20–45) who had complained of infertility and visited a university hospital in Tokyo. The subjects were interviewed and their urine samples were obtained prior to a laparoscopic diagnosis of endometriosis between January 2000 and December 2001. Urinary total BPA concentration in 140 eligible urine samples was then measured using enzymatic deconjugation of glucuronide and sulfate and high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Results: Median (25th–75th percentile) unadjusted and creatinine-adjusted urinary BPA concentrations were 1.6 (0.69–2.8) μg/L and 0.80 (0.45–1.3) μg/g creatinine. No significant monotonic association of endometriosis with urinary BPA concentration was observed. Median urinary BPA concentration in women with stage 0–I endometriosis (0.74 μg/g creatinine) did not significantly differ from that in those with stage II–IV endometriosis (0.93 μg/g creatinine) (p for difference=0.24). Conclusions: This study, based on a larger number of samples than those in previous studies in Japan and using the most reliable analytical method currently available, showed that urinary concentrations of BPA in women who consulted a physician for infertility were not higher than those in other populations. Moreover, no association between urinary BPA concentration and endometriosis was found in this cross-sectional study.
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CreatininaRESUMEN
<p><b>OBJECTIVES</b>Bisphenol A (BPA), a raw material commonly used in the manufacture of resins such as polycarbonate and epoxy, is a possible xenoestrogen that is hypothesized to disrupt the human endocrine system. Humans are widely exposed to BPA. We investigated the urinary concentration of BPA in infertile Japanese women and its possible association with endometriosis.</p><p><b>MATERIALS AND METHODS</b>We recruited 166 women (aged 20-45) who had complained of infertility and visited a university hospital in Tokyo. The subjects were interviewed and their urine samples were obtained prior to a laparoscopic diagnosis of endometriosis between January 2000 and December 2001. Urinary total BPA concentration in 140 eligible urine samples was then measured using enzymatic deconjugation of glucuronide and sulfate and high-performance liquid chromatography isotope-dilution tandem mass spectrometry.</p><p><b>RESULTS</b>Median (25th-75th percentile) unadjusted and creatinine-adjusted urinary BPA concentrations were 1.6 (0.69-2.8) μg/L and 0.80 (0.45-1.3) μg/g creatinine. No significant monotonic association of endometriosis with urinary BPA concentration was observed. Median urinary BPA concentration in women with stage 0-1 endometriosis (0.74 μg/g creatinine) did not significantly differ from that in those with stage II-IV endometriosis (0.93 μg/g creatinine) (p for difference=0.24).</p><p><b>CONCLUSIONS</b>This study, based on a larger number of samples than those in previous studies in Japan and using the most reliable analytical method currently available, showed that urinary concentrations of BPA in women who consulted a physician for infertility were not higher than those in other populations. Moreover, no association between urinary BPA concentration and endometriosis was found in this cross-sectional study.</p>