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New in vitro dermal absorption database and the prediction of dermal absorption under finite conditions for risk assessment purposes

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Author: Buist, H.E. · Burgsteden, J.A. van · Freidig, A.P. · Maas, W.J.M. · Sandt, J.J.M. van de
Type:article
Date:2010
Institution: TNO Kwaliteit van Leven
Source:Regulatory Toxicology and Pharmacology, 2-3, 57, 200-209
Identifier: 364402
Keywords: Biology · Biomedical Research · Dermal absorption · Epidermal membranes · Human · In vitro experiments · K<sub>p</sub> · Permeability coefficient · QSAR · Risk assessment · Skin · Stratum corneum/water partition coefficient

Abstract

Most QSARs for dermal absorption predict the permeability coefficient, K<sub>p</sub>, of a molecule, which is valid for infinite dose conditions. In practice, dermal exposure mostly occurs under finite dose conditions. Therefore, a simple model to predict finite dose dermal absorption from infinite dose data (K<sub>p</sub> and lag time) and the stratum corneum/water partition coefficient (K<sub>SC,W</sub>) was developed. To test the model, a series of in vitro dermal absorption experiments was performed under both infinite and finite dose conditions using acetic acid, benzoic acid, bis(2-ethylhexyl)phthalate, butoxyethanol, cortisone, decanol, diazinone, 2,4-dichlorophenol, ethacrynic acid, linolenic acid, octylparaben, oleic acid, propylparaben, salicylic acid and testosterone. For six substances, the predicted relative dermal absorption was not statistically different from the measured value. For all other substances, measured absorption was overpredicted by the model, but most of the overpredictions were still below the European default absorption value. In conclusion, our finite dose prediction model provides a useful and cost-effective estimate of dermal absorption, to be used in risk assessment for non-volatile substances dissolved in water at non-irritating concentrations. © 2010 Elsevier Inc.