Phthalic anhydride: Illustrating a conundrum in chemical allergy

Although a substantial number of chemicals has the ability to bind covalently to proteins and thereby, given sufficient exposure, induce a state of sensitization, only a small minority appear to be able to cause allergic hypersensitivity of the respiratory tract; the great majority being exclusively skin sensitizers. The key mechanistic drivers for the differentiation between skin and respiratory sensitization are already well characterized at the cellular/cytokine level. However, at both the chemical level and in terms of predictive toxicology, matters are much less clear. In the present article, phthalic anhydride is used as an exemplar, since it displays a particularly differentiated profile as a chemical allergen. Whereas most respiratory sensitizers are known also to give rise to delayed skin reactions, evidence for phthalic anhydride suggests that it only causes immediate type allergy. Chemically, phthalic anhydride can be presumed to react similar to other respiratory sensitizing anhydrides; in predictive tests for skin sensitization, phthalic anhydride is clearly positive, a property it has in common with all other chemical respiratory allergens. Thus, in the context of interpreting predictive toxicology tests for skin sensitization, the inference is that negative results demonstrate an absence of both skin- and respiratory-sensitizing capacity.