Skin sensitization thresholds: determination in predictive models.
For many years, test methods for the prospective identification of skin sensitizing chemicals have been widely available. However, although these techniques have permitted the identification of the great majority of skin sensitizers, their use in assessing the relative potency of a particular chemical as a human contact allergen has not been well described. 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 place 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 conducted 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 potency by the measurement of dose-response relationships and the determination of induction and elicitation thresholds in both animal models and in humans. The latter has special relevance for regulatory toxicology and this matter is given particular attention in this article. Finally, recommendations are made: (a) that threshold concentrations for skin sensitizers should be determined on a case by case basis in relation to the likely mode of skin contact; (b) where the data are used in comparisons of skin sensitization potency, then there should be standardization of the method used for the determinations.
Basketter
D A
DA
Unilever Environmental Safety Laboratory, Sharnbrook, Bedford, UK.
Cookman
G
G
Gerberick
G F
GF
Hamaide
N
N
Potokar
M
M
D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000473:pathology* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D012882:Skin Tests; D018675:Toxicity Tests