Radboud Institute for Health Sciences, Radboud University Medical Center, P.O. Box. 9101, 6500 HB, Nijmegen, The Netherlands.
Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Arch Toxicol. 2019 Sep;93(9):2545-2553. doi: 10.1007/s00204-019-02523-5. Epub 2019 Jul 29.
Tebuconazole (TEB) is a widely used triazole fungicide, but the toxicokinetics of its human metabolites are not fully described. For proper interpretation of biological monitoring data, knowledge on the metabolism and elimination of the compound is required. A human volunteer study was performed with the aim to describe the time courses of urinary excretion after controlled oral and dermal administration of TEB. Six healthy volunteers (three males and three females) received on separate occasions a single oral dose of 1.5 mg of TEB and a single dermal dose of 2.5 mg during 1 h. In addition to a pre-exposure urine sample, complete urine voids were collected over 48 h post-administration. The main metabolite hydroxy-tebuconazole (TEB-OH) was quantified in each urine sample. Peak excretion rates after oral and dermal administration were reached after 1.4 and 21 h, mean elimination half-lives were 7.8 and 16 h, and recoveries within 48 h were 38% and 1%, respectively. The time courses of excretion were compared to simulations with an established physiologically based toxicokinetic model for TEB that was extended with a parallel model for TEB-OH. Overall, TEB-OH was rapidly excreted into urine after oral exposure, and renal elimination was considerably slower after dermal exposure. Urinary time courses between individuals were similar. The model predictions were in good agreement with the observed time courses of excretion.
戊唑醇（TEB）是一种广泛使用的三唑类杀菌剂，但人体代谢物的毒代动力学尚未完全描述。为了正确解释生物监测数据，需要了解该化合物的代谢和消除情况。进行了一项人体志愿者研究，旨在描述口服和皮肤给予 TEB 后尿液排泄的时间过程。六名健康志愿者（三名男性和三名女性）分别在一次口服 1.5mg TEB 和 1 小时内单次皮肤给予 2.5mg TEB 的情况下接受了研究。除了暴露前尿液样本外，还在给药后 48 小时内收集了完整的尿液。在每个尿液样本中均定量测定了主要代谢物羟基戊唑醇（TEB-OH）。口服和皮肤给药后的峰值排泄率分别在 1.4 和 21 小时达到，平均消除半衰期分别为 7.8 和 16 小时，48 小时内的回收率分别为 38%和 1%。将排泄时间过程与 TEB 的已建立的基于生理学的毒代动力学模型的模拟进行了比较，该模型扩展了 TEB-OH 的平行模型。总体而言，口服暴露后 TEB-OH 迅速排泄到尿液中，而皮肤暴露后肾脏消除速度明显较慢。个体之间的尿液时间过程相似。模型预测与观察到的排泄时间过程吻合良好。
