Skin barrier function for regulatory skin absorption tests and effects on testosterone and sucrose absorption.

In vitro absorption through human skin is a critical component in the safety assessment of chemicals, crop protection products, consumer healthcare products and cosmetics. A barrier integrity assay is used to identify skin samples which are potentially damaged. A retrospective analysis of 9978 electrical resistance (ER) measurements generated in a single laboratory (DTL) over a 15-year period was performed. Skin absorption experiments were performed using two model penetrants, testosterone and sucrose, utilising no ER acceptance criteria, and the results assessed. Using a barrier integrity test, to remove potentially damaged samples, was offset against one that can be used to remove intact skin samples with a poorer barrier function (i.e. false positives). The previously identified barrier integrity limit (10 kΩ for a 2.54 cm2 diffusion cell; Davies et al., 2004) was demonstrated to identify half of all samples tested, many of which would be false positive samples. This retrospective analysis identified 5.0 kΩ (17.5th percentile) as an acceptance criterion for a 2.54 cm2 diffusion cell, whilst not considerably changing results generated in skin absorption studies. This was confirmed from the cumulative absorption of the model penetrants tested. Using this limit would, therefore, provide suitable skin samples for regulatory skin absorption studies.

Further development of an in vitro model for studying the penetration of chemicals through compromised skin.

A new in vitro model based on the electrical resistance properties of the skin barrier has been established in this laboratory. The model utilises a tape stripping procedure in dermatomed pig skin that removes a specific proportion of the stratum corneum, mimicking impaired barrier function observed in humans with damaged skin. The skin penetration and distribution of chemicals with differing physicochemical properties, namely; Benzoic acid, 3-Aminophenol, Caffeine and Sucrose has been assessed in this model. Although, skin penetration over 24h differed for each chemical, compromising the skin did not alter the shape of the time course profile, although absorption into receptor fluid was higher for each chemical. Systemic exposure (receptor fluid, epidermis and dermis), was marginally higher in compromised skin following exposure to the fast penetrant, Benzoic acid, and the slow penetrant Sucrose. The systemically available dose of 3-Aminophenol increased to a greater extent and the absorption of Caffeine was more than double in compromised skin, suggesting that Molecular Weight and Log Pow, are not the only determinants for assessing systemic exposure under these conditions. Although further investigations are required, this in vitro model may be useful for prediction of dermal route exposure under conditions where skin barrier is impaired.