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Toxicokinetics of a Urinary Metabolite of Tebuconazole Following Controlled Oral and Dermal Administration in Human Volunteers

Toxicokinetics of a Urinary Metabolite of Tebuconazole Following Controlled Oral and Dermal Administration in Human Volunteers

A Oerlemans, L F M Verscheijden, J G J Mol, R C H Vermeulen, J Westerhout, N Roeleveld, F G M Russel, P T J Scheepers

Arch Toxicol. 2019 Sep;93(9):2545-2553.

PMID: 31359083

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP212267646	Hydroxytebuconazole		212267-64-6	Price

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