Human urinary excretion kinetics of the antimycotic climbazole: Biomonitoring of two new metabolites after oral and dermal dosage.

Climbazole is an antimycotic compound used in cosmetic products as a preservative or as an active ingredient in anti-dandruff (AD) formulations. In this study we provide human toxicokinetic data on climbazole. Using our previously published analytical method, we investigated the urinary excretion of two climbazole metabolites, (OH) 2 -climbazole and cx-OH-climbazole, for 48 h after oral ingestion (n = 5, 49–77 µg/kg bw) and for 72 h after dermal application of either a climbazole-containing rinse-off AD shampoo or a leave-on hair tonic (n = 2×3). In total, 23.9 % (18.0–33.4 %) of the oral dose were excreted as the two abovementioned metabolites over 48 h. In one volunteer, who used an over-the-counter phytopharmaceutical, metabolite excretion was about three times lower and we found influences on diastereoselectivity of (OH) 2 -climbazole formation using a modified analytical method. After dermal application, urinary concentration maxima occurred considerably later than after oral intake. The two different dermal exposure scenarios also revealed a relevance of exposure duration and product formulation on the systemic availability of climbazole. Back-calculated oral-dose-equivalent intakes from the dermal exposures showed a maximum climbazole intake of 18.5 µg/kg bw/d after hair tonic use, or 6.6 µg/kg bw/d after AD shampoo application. • (OH) 2 -climbazole and cx-OH-climbazole identified as suitable exposure biomarkers. • On average 24 % of the dose were recovered in form of the investigated biomarkers within 48 h. • Shifting diastereomeric ratios observed within the investigated excretion period. • Sum parameter recommended as the most robust approach for reverse dosimetry. [ABSTRACT FROM AUTHOR]