Pollock Tyler, Weaver Rachel E, Ghasemi Ramtin, deCatanzaro Denys
Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Toxicol Appl Pharmacol. 2017 Jun 15;325:18-24. doi: 10.1016/j.taap.2017.04.001. Epub 2017 Apr 5.
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 C-BPA and 17β-estradiol (E). Female and male CF1 mice were each given a subcutaneous injection of oil containing 0 (vehicle), 1, 3, or 9mg BP or PP, then given a dietary supplement containing 50μg/kg C-BPA. Radioactivity was measured in tissues through liquid scintillation counting. Significantly elevated C-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 C-BPA concentrations in the uterus only. In another experiment, female and male CF1 mice were each injected with vehicle, 3mg BP, or 3mg PP, and E was measured in urine 2-12h later. Whereas PP did not affect E, BP significantly elevated E 6-10h after injection in females and 8h after injection in males. These data indicate that BP and PP can alter the pharmacokinetics of BPA in vivo, and that BP can modulate E concentrations. These results are consistent with evidence that parabens inhibit enzymes that are critical for BPA and E metabolism, and demonstrate the importance of considering concurrent exposure to multiple chemicals when determining regulatory exposure limits.
人们经常接触到抗菌防腐剂对羟基苯甲酸丁酯(BP)和对羟基苯甲酸丙酯(PP),以及聚碳酸酯塑料的单体双酚A(BPA)。这些化学物质在人体尿液中能够被可靠检测到,并且可能会相互作用。我们研究了BP或PP的暴露是否会调节结合型双酚A(C-BPA)和17β-雌二醇(E)的浓度。对雌性和雄性CF1小鼠分别皮下注射含0(赋形剂)、1、3或9mg BP或PP的油,然后给予含50μg/kg C-BPA的膳食补充剂。通过液体闪烁计数法测量组织中的放射性。在接受BP处理的两性血清中,以及雌性的肺、子宫和卵巢以及雄性的睾丸和附睾中,观察到C-BPA浓度显著升高。仅用PP处理时,子宫中的C-BPA浓度显著升高。在另一项实验中,对雌性和雄性CF1小鼠分别注射赋形剂、3mg BP或3mg PP,并在2 - 12小时后测量尿液中的E。PP对E没有影响,而BP在雌性注射后6 - 10小时和雄性注射后8小时显著提高了E的水平。这些数据表明,BP和PP可以改变体内双酚A的药代动力学,并且BP可以调节E的浓度。这些结果与对羟基苯甲酸酯抑制对双酚A和E代谢至关重要的酶的证据一致,并证明了在确定监管暴露限值时考虑同时接触多种化学物质的重要性。