Allergenicity Evaluation of N-(1-Methylheptyl)-N'-Phenyl-p-Phenylenediamine and 2-(Thiocyanomethylthio) Benzothiazole by the Guinea Pig Maximization Test

抄録

In order to regulate contact sensitizers in commercial products, not only is identification of chemical allergens essential but also quantitative evaluation of their allergenicity. We have so far reported threshold values of chemical allergens for both induction and challenge phases in the modified guinea pig maximization test (GPMT). In this study, we examined N-(1-methylheptyl)-N'-phenyl-p-phenylenediamine (MHPPD), an antioxidant for rubber products, and 2-(thiocyanomethylthio) benzothiazole (TCMTB), a biocide for plastic and wood products. MHPPD and TCMTB exhibited distinct profiles of contact allergenicity with the GPMT; that is, both could sensitize guinea pigs by the second induction procedure of topical application alone, even without the first induction procedure of intradermal injection. The calculated challenge threshold values for MHPPD and TCMTB were 0.9 and 0.8 ppm, respectively, which were at least one tenth lower than those of chemical allergens previously examined by us. Octanol-water partition coefficients (log p) used as an index of skin permeability were not necessarily higher for MHPPD and TCMTB than those of other allergens, thus, the skin permeability of these compounds did not seem to be related to their ability to cause sensitization by topical application alone or their low challenge threshold values. The results suggest that the sensitizing potential of both compounds is due to their molecular basis. Cross-reactivities among homologues of both allergens were examined to evaluate their antigenic determinants.