Thresholds in contact sensitization: theoretical and practical considerations

The existence of thresholds for both the induction and the elicitation of contact sensitization is an important issue for hazard assessment in this area of toxicology. In this paper, the evidence for such thresholds has been reviewed from both theoretical and practical perspectives. When the mechanisms of skin sensitization are considered, the existence of thresholds can be shown to occur at several stages. They are both quantitative, for example in terms of the degree of protein haptenation and in the sufficiency of the signals for Langerhans cell migration and maturation, as well as qualitative, in terms of the type of immune response that is engaged. Such considerations are evidenced by a substantial body of practical observation. In humans and in animal models of skin sensitization there is abundant evidence for the existence of thresholds for both the induction and the elicitation of reactions. In addition to, and in distinction from, the experimental situation, in the general human population there is extensive evidence for threshold effects. This evidence arises directly from the observation that only a proportion of those who are exposed become sensitized (i.e. are patch test positive), and of that latter group only a proportion develop allergic contact dermatitis.