Factors affecting thresholds in allergic contact dermatitis: safety and regulatory considerations

Although it is now well understood that thresholds exist for both the induction and the elicitation of allergic responses, such as those of allergic contact dermatitis, it must also be appreciated that for any given allergen, these thresholds are not absolute values. They will vary between individuals, and according to the conditions of exposure to the allergen. Therefore, it is necessary for the purposes both of risk assessment and regulatory toxicology to appreciate the variables involved and to adopt strategies that incorporate this understanding. In this short article, the nature of thresholds in allergic contact dermatitis and the factors affecting them are reviewed. In particular, thresholds will vary according to whether skin exposure is transient or prolonged, open or occluded and single or repeated. The condition of the skin, the presence of inflammation and the matrix in which a chemical sensitizer comes into contact with the skin also are important. However, the scale of these variables frequently is quantifiable. Thus, recommendations can be made concerning how these considerations can be embraced by those responsible for safety evaluation and for the shaping of regulations for skin sensitizing chemicals/formulations.