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单次口服后苯并三唑紫外线稳定剂UV-P在人体中的毒代动力学。

Toxicokinetics of benzotriazole UV stabilizer UV-P in humans after single oral administration.

作者信息

Fischer Corinna, Hiller Julia, Leibold Edgar, Göen Thomas

机构信息

Institute and Outpatient Clinic of Occupational, Social, and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestraße 9-11, 91054, Erlangen, Germany.

BASF SE, Carl-Bosch‑Straße 38, 67056, Ludwigshafen Am Rhein, Germany.

出版信息

Arch Toxicol. 2025 Feb;99(2):623-631. doi: 10.1007/s00204-024-03907-y. Epub 2024 Nov 29.

Abstract

UV-P (2-(2H-Benzotriazol-2-yl)-p-cresol) is used as an ultraviolet (UV) light absorber in coating products, paints, adhesives, and sealants. Due to its widespread industrial and consumer uses, human exposure to UV-P is conceivable. In the study presented herein, initial data on its human in vivo metabolism were obtained for three study participants after single oral administration of 0.3 mg of UV-P/kg body weight. Urine and blood samples of two volunteers were collected up to 48 h after exposure. The third study participant donated urine and blood samples up to 72 h. Maximum levels of UV-P in blood of 184 ± 36 µg/l (85 ± 3% as conjugates) were reached 2.4 ± 1.2 h post-exposure. Maximum excretion rates of UV-P in urine of 2896 ± 884 µg/h (completely conjugated) were reached 3.5 ± 1.1 h post-exposure. 37.2 ± 5.4% of the orally administered dose of UV-P was recovered in urine within 48 h post-exposure. The present study provides insight into the complex absorption, distribution, metabolism, and elimination (ADME) processes of benzotriazole UV stabilizers (BUVS). The study also demonstrates differences in the ADME between sterically hindered BUVS, such as UV-327 and UV-328, and sterically unhindered BUVS, such as UV-P, in which the phenolic hydroxyl group is readily accessible for conjugation with glucuronic acid or sulfate.

摘要

UV-P(2-(2H-苯并三唑-2-基)-对甲酚)在涂料产品、油漆、粘合剂和密封剂中用作紫外线(UV)吸收剂。由于其在工业和消费领域的广泛应用,人类接触UV-P是有可能的。在本文所述的研究中,三名研究参与者单次口服0.3毫克UV-P/千克体重后,获得了其人体体内代谢的初始数据。两名志愿者的尿液和血液样本在接触后长达48小时内进行收集。第三名研究参与者在接触后长达72小时内捐献尿液和血液样本。接触后2.4±1.2小时,血液中UV-P的最高水平达到184±36微克/升(85±3%为共轭物)。接触后3.5±1.1小时,尿液中UV-P的最大排泄率达到2896±884微克/小时(完全共轭)。接触后48小时内,尿液中回收了37.2±5.4%的口服剂量UV-P。本研究深入了解了苯并三唑紫外线稳定剂(BUVS)复杂的吸收、分布、代谢和排泄(ADME)过程。该研究还表明,空间位阻型BUVS(如UV-327和UV-328)与空间非位阻型BUVS(如UV-P)在ADME方面存在差异,其中UV-P的酚羟基易于与葡萄糖醛酸或硫酸盐结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e390/11775033/58995b198bff/204_2024_3907_Fig1_HTML.jpg

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