人体经皮给予双酚 A 的药代动力学。
Pharmacokinetics of bisphenol A in humans following dermal administration.
机构信息
U.S. Environmental Protection Agency (US EPA), Office of Research and Development, Center for Public Health and Environmental Assessment (CPHEA), Chemical Pollutant Assessment Division (CPAD), 1200 Pennsylvania Avenue, NW (8623R), Washington, DC 20460, USA.
German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
出版信息
Environ Int. 2020 Nov;144:106031. doi: 10.1016/j.envint.2020.106031. Epub 2020 Aug 13.
BACKGROUND
Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA following dermal exposure.
OBJECTIVE
To examine the absorption, distribution, metabolism and excretion of BPA in humans following dermal administration.
METHODS
We dermally administered deuterated BPA (d6-BPA) to 10 subjects (6 men and 4 women) at a dose of 100 µg/kg over a 12-hour period and conducted blood and urine analysis from the beginning of dosing through a three- or six-day period. We present time-course serum and urine concentrations of total and unconjugated ("free") d6-BPA and used this information to calculate terminal half-life and area under the curve.
RESULTS AND CONCLUSIONS
Detectable serum levels of total d6-BPA were observed at 1.4 h after the start of dosing, and a maximum serum concentration (C) of 3.26 nM was observed. Free d6-BPA was detectable in serum 2.8 h after start of dermal administration, with C of 0.272 nM. Beginning at approximately seven hours and continuing to 12 h (which corresponds to cessation of exposure), the concentration of free and total serum d6-BPA plateaued. The terminal half-lives of total d6-BPA and free d6-BPA in the body were 21.4 ± 9.81 h and 17.6 ± 7.69 h, respectively. Elimination from the body was rate-limited by kinetics in the dermal compartment. Free d6-BPA was a greater percentage of the area under the curve of total serum BPA (8.81%) compared to the 0.56% observed in our previously published oral study. Recovery of total d6-BPA in urine was <2% of the applied dose after six days. Analysis of the area under the curve for dermal and oral administration revealed that 2.2% of the dermal dose became systemically available. These data are in line with prior studies indicating how pharmacokinetics of BPA differ following oral and dermal exposures. Dermal exposure resulted in a longer apparent half-life and higher free:total d6-BPA ratio compared to oral.
背景
人类接触双酚 A（BPA）的情况非常普遍。本研究旨在解决人们在经皮暴露于 BPA 后，其体内药代动力学的不确定性问题。
目的
研究经皮给予 BPA 后 BPA 在人体中的吸收、分布、代谢和排泄情况。
方法
我们以 100μg/kg 的剂量，在 12 小时内对 10 名受试者（6 名男性和 4 名女性）进行了氘代 BPA（d6-BPA）的经皮给药，并在给药开始后 3 天或 6 天内进行了血液和尿液分析。我们呈现了总 d6-BPA 和未结合（“游离”）d6-BPA 的血清浓度时间曲线，并利用这些信息计算了终末半衰期和曲线下面积。
结果与结论
在开始给药后 1.4 小时可检测到总 d6-BPA 的血清水平，最大血清浓度（C）为 3.26 nM。游离 d6-BPA 在经皮给药后 2.8 小时即可检测到，C 为 0.272 nM。从大约 7 小时开始，直到 12 小时（即暴露停止），游离和总血清 d6-BPA 的浓度趋于稳定。总 d6-BPA 和游离 d6-BPA 在体内的终末半衰期分别为 21.4±9.81 小时和 17.6±7.69 小时。体内的消除受到皮肤隔室动力学的限制。游离 d6-BPA 在总血清 BPA 的曲线下面积中占 8.81%，高于我们之前发表的口服研究中观察到的 0.56%。六天后，尿液中回收的总 d6-BPA 不足应用剂量的 2%。对经皮和口服给药的曲线下面积进行分析表明，2.2%的经皮剂量可系统吸收。这些数据与先前的研究结果一致，表明 BPA 的药代动力学在口服和经皮暴露后存在差异。与口服相比，经皮暴露导致更长的表观半衰期和更高的游离：总 d6-BPA 比值。
Zotero 插件