Butyl paraben and propyl paraben modulate bisphenol A and estradiol concentrations in female and male mice

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People are routinely exposed to the antimicrobial preservatives butyl paraben (BP) and propyl paraben (PP), as well as the monomer of polycarbonate plastics, bisphenol A (BPA). These chemicals are reliably detected in human urine and potentially interact. We investigated whether BP or PP exposure can modulate the concentrations of 14C-BPA and 17β-estradiol (E2). Female and male CF1 mice were each given a subcutaneous injection of oil containing 0 (vehicle), 1, 3, or 9 mg BP or PP, then given a dietary supplement containing 50 μg/kg 14C-BPA. Radioactivity was measured in tissues through liquid scintillation counting. Significantly elevated 14C-BPA concentrations were observed following BP treatment in blood serum of both sexes, as well as the lungs, uterus, and ovaries of females and the testes and epididymides of males. Treatment with PP significantly elevated 14C-BPA concentrations in the uterus only. In another experiment, female and male CF1 mice were each injected with vehicle, 3 mg BP, or 3 mg PP, and E2 was measured in urine 2–12 h later. Whereas PP did not affect E2, BP significantly elevated E2 6–10 h after injection in females and 8 h after injection in males. These data indicate that BP and PP can alter the pharmacokinetics of BPA in vivo, and that BP can modulate E2 concentrations. These results are consistent with evidence that parabens inhibit enzymes that are critical for BPA and E2 metabolism, and demonstrate the importance of considering concurrent exposure to multiple chemicals when determining regulatory exposure limits.HIGHLIGHTSWe studied whether paraben exposure affects the distribution of oral 14C-BPA.Elevated 14C–BPA was observed in mice given butyl or propyl paraben.We also studied whether paraben exposure affects natural E2 levels in urine.Elevated E2 was observed in mice given butyl, but not propyl, paraben.Parabens may compete for enzymes that are critical for BPA and E2 metabolism.

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