Dose metrics in the acquisition of skin sensitization: Thresholds and importance of dose per unit area

Allergic contact dermatitis is a common occupational and environmental health problem and many hundreds of chemicals have been implicated as skin sensitizers. Sensitization is acquired following topical exposure to a contact allergen and induction of a cutaneous immune response of an appropriate magnitude. For effective assessment and management of human health risks there is a need to appreciate the dose metrics that drive the induction of skin sensitization. The available evidence suggests that under most normal conditions of exposure it is the dose per unit area of chemical that has over-riding impact on the effectiveness of sensitization. The exception to this rule is when the area of the application site drops below a certain critical level. Here we review in detail the evidence which supports dose per unit area as being the critical exposure metric in the induction of skin sensitization, and the mechanistic bases for this relationship.