SKIN SENSITIZATION THRESHOLDS - DETERMINATION IN PREDICTIVE MODELS

For many years, test methods for the prospective identification of ski n sensitizing chemicals have been widely available. However, although these techniques have permitted the identification of the great majori ty of skin sensitizers, their use in assessing the relative potency of a particular chemical as a human contact allergen has not been well d escribed. A primary reason for this is the inherent difficulty of such an exercise. A complex phenomenon involving interactions between the vehicle, the allergen, the skin and its inflammatory responses takes p lace during the induction and elicitation of sensitization. All these factors can have a profound effect on the threshold values determined for a skin sensitizer. Consequently, whether the assessment is conduct ed in humans or in animal models, a threshold concentration is always a function of the method of measurement as much as the potency of the allergen. Although an exhaustive review has not been carried out, this paper considers the attempts that have been made to assess relative p otency by the measurement of dose-response relationships and the deter mination of induction and elicitation thresholds in both animal models and in humans. The latter has special relevance for regulatory toxico logy and this matter is given particular attention in this article. Fi nally, recommendations are made: (a) that threshold concentrations for skin sensitizers should be determined on a case by case basis in rela tion to the likely mode of skin contact; (b) where the data are used i n comparisons of skin sensitization potency, then there should be stan dardization of the method used for the determinations. (C) 1997 Elsevi er Science Ltd.