Percutaneous Absorption of climbazole: In Vitro Data from Human Skin

Climbazole is an antifungal substance used as an active ingredient or antimicrobial preservative in pharmaceuticals and personal care products. It is classified by the EU as an acute toxicant (Category 4), and ECHA has recently confirmed its endocrine disruptor concern. Data on climbazole s skin permeability, and consequently its occupational risks, are limited.<br/>
The aim of this study was to generate percutaneous absorption data in line with OECD guidelines to support occupational exposure assessment. In vitro experiments using [14C]-labelled climbazole were conducted on freshly excised human skin samples placed in Franz diffusion cells, monitoring absorption over 20 hours. The absorption profile data were used to calculate key parameters, including steady-state flux, lag time, and skin permeability coefficient (Kp). The dose distribution across various compartments, including the skin, was evaluated. The individual skin layers were isolated by sequential tape-stripping, followed by epidermis-dermis separation to more precisely measure radioactivity levels. This information was used to predict the potential for further absorption of the dose retained within the skin. The presence of climbazole metabolites in the receptor fluid was also investigated.<br/>
The Kp was determined to be 4.7 x 10-3 cm/h, which classes climbazole as a "fast" penetrant. Significant dermal absorption was measured, with 57% of the applied dose absorbed, highlighting potential occupational risks. Climbazole is mainly absorbed with biotransformation: 67% of the absorbed dose was detected as metabolites. These new percutaneous absorption data will enhance the assessment of the occupational risks associated with dermal exposure to climbazole.