Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
RTI International, Discovery Sciences, Research Triangle Park, NC, USA.
Toxicol Appl Pharmacol. 2020 Nov 1;406:115207. doi: 10.1016/j.taap.2020.115207. Epub 2020 Aug 24.
Bisphenol S (BPS) is a component of polyether sulfone used in a variety of industrial applications and consumer products. We investigated the plasma toxicokinetic (TK) behavior of free (unconjugated parent) and total (parent and conjugated) BPS in rats and mice following a single gavage administration (34, 110, or 340 mg/kg). In male rats, BPS was rapidly absorbed with free BPS maximum concentration (C) reached at ≤2.27 h. Elimination of free BPS in male rats was dose-dependent with estimated half-lives of 5.77-11.9 h. C and area under the concentration versus time curve (AUC) increased with dose although the increase in AUC was more than dose proportional. In male rats, total BPS C was reached ≤2.77 h with both C (≥ 10-fold) and AUC (≥ 15-fold) higher than free BPS demonstrating rapid and extensive conjugation of BPS. In male mice, the increase in C and AUC of free BPS was dose-proportional; C was higher and AUC was lower than in male rats. BPS was cleared more rapidly in male mice (half-life 2.86-4.21 h) compared to male rats (half-life 5.77-11.9 h). Similar to rats, total BPS C (≥ 6-fold) and AUC (≥ 12-fold) were higher than corresponding free BPS. Oral bioavailability of free BPS was low to moderate (rats, ≤ 21%; mice, ≤ 19%). There were some species differences in TK parameters of free and total BPS and limited sex difference in rats and mice. In addition, there were dose-related effects of plasma TK parameters in rats.
双酚 S（BPS）是聚醚砜的一种成分，用于各种工业应用和消费产品。我们研究了大鼠和小鼠单次灌胃（34、110 或 340mg/kg）后游离（未共轭母体）和总（母体和共轭）BPS 的血浆毒代动力学（TK）行为。在雄性大鼠中，BPS 被迅速吸收，游离 BPS 的最大浓度（C）在≤2.27h 时达到。雄性大鼠游离 BPS 的消除呈剂量依赖性，半衰期估计为 5.77-11.9h。C 和浓度-时间曲线下面积（AUC）随剂量增加而增加，尽管 AUC 的增加超过了剂量比例。在雄性大鼠中，总 BPS 的 C 在≤2.77h 时达到，C（≥10 倍）和 AUC（≥15 倍）均高于游离 BPS，表明 BPS 迅速广泛地发生了共轭。在雄性小鼠中，游离 BPS 的 C 和 AUC 增加与剂量呈比例；C 更高，AUC 更低。与雄性大鼠相比，雄性小鼠的 BPS 清除速度更快（半衰期 2.86-4.21h）。与大鼠相似，总 BPS 的 C（≥6 倍）和 AUC（≥12 倍）均高于相应的游离 BPS。游离 BPS 的口服生物利用度较低至中等（大鼠，≤21%；小鼠，≤19%）。游离和总 BPS 的 TK 参数在种属间存在差异，在大鼠和小鼠中性别间差异有限。此外，大鼠的血浆 TK 参数存在剂量相关性。
