Teeguarden Justin G, Twaddle Nathan C, Churchwell Mona I, Yang Xiaoxia, Fisher Jeffrey W, Seryak Liesel M, Doerge Daniel R
Health Effects and Exposure Science, Pacific Northwest National Laboratory, Richland, WA 99352, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 93771, USA.
Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
Toxicol Appl Pharmacol. 2015 Oct 15;288(2):131-42. doi: 10.1016/j.taap.2015.01.009. Epub 2015 Jan 22.
Extensive first-pass metabolism of ingested bisphenol A (BPA) in the gastro-intestinal tract and liver restricts blood concentrations of bioactive BPA to <1% of total BPA in humans and non-human primates. Absorption of ingested BPA through non-metabolizing tissues of the oral cavity, recently demonstrated in dogs, could lead to the higher serum BPA concentrations reported in some human biomonitoring studies. We hypothesized that the extensive interaction with the oral mucosa by a liquid matrix, like soup, relative to solid food or capsules, might enhance absorption through non-metabolizing oral cavity tissues in humans, producing higher bioavailability and higher serum BPA concentrations. Concurrent serum and urine concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were measured over a 24hour period in 10 adult male volunteers following ingestion of 30μg d6-BPA/kg body weight in soup. Absorption of d6-BPA was rapid (t1/2=0.45h) and elimination of the administered dose was complete 24h post-ingestion, evidence against any tissue depot for BPA. The maximum serum d6-BPA concentration was 0.43nM at 1.6h after administration and represented <0.3% of total d6-BPA. Pharmacokinetic parameters, pharmacokinetic model simulations, and the significantly faster appearance half-life of d6-BPA-glucuronide compared to d6-BPA (0.29h vs 0.45h) were evidence against meaningful absorption of BPA in humans through any non-metabolizing tissue (<1%). This study confirms that typical exposure to BPA in food produces picomolar to subpicomolar serum BPA concentrations in humans, not nM concentrations reported in some biomonitoring studies.
摄入的双酚A(BPA)在胃肠道和肝脏中存在广泛的首过代谢,这使得生物活性BPA在人体和非人类灵长类动物血液中的浓度限制在总BPA的1%以下。最近在犬类中证实,摄入的BPA可通过口腔的非代谢组织吸收,这可能导致一些人体生物监测研究中报告的血清BPA浓度较高。我们推测,相对于固体食物或胶囊,像汤这样的液体基质与口腔黏膜的广泛相互作用,可能会增强人体口腔非代谢组织的吸收,从而产生更高的生物利用度和更高的血清BPA浓度。在10名成年男性志愿者摄入30μg d6 - BPA/千克体重的汤后,在24小时内同时测量血清和尿液中d6 - BPA及其葡萄糖醛酸和硫酸盐结合物的浓度。d6 - BPA的吸收很快(t1/2 = 0.45小时),摄入后24小时给药剂量完全消除,这证明不存在BPA的组织储存库。给药后1.6小时血清d6 - BPA的最大浓度为0.43nM,占总d6 - BPA的比例不到0.3%。药代动力学参数、药代动力学模型模拟以及d6 - BPA - 葡萄糖醛酸相对于d6 - BPA明显更快的出现半衰期(0.29小时对0.45小时),证明人体中BPA通过任何非代谢组织的吸收量都没有意义(<1%)。这项研究证实,人类通过食物接触典型的BPA会产生皮摩尔至亚皮摩尔的血清BPA浓度,而不是一些生物监测研究中报告的纳摩尔浓度。