Skin sensitization potency and cross-reactivity of p-phenylenediamine and its derivatives evaluated by non-radioactive murine local lymph node assay and guinea-pig maximization test

Background: p-Phenylenediamine (PPD)-related chemicals have been used as Antioxidants in rubber products, and many cases of contact dermatitis caused by these chemicals have been reported.

Objective: The aim of this study was to investigate relative sensitizing potency and cross-reactivity among PPD derivatives.

Methods: Five PPD derivatives, p-aminodiphenylamine (PADPA), N,N'-diphenyl-p-phenylenediamine (DPPD), N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (DMBPPD), N-(1-methylheptyl)-N'-phenyl-p-phenylenediamine (MHPPD), and the core chemical PPD were evaluated for their sensitizing potency and cross-reactivity using the non-radioactive murine local lymph node assay (LLNA) and the guinea-pig maximization test (GPMT).

Results: PPD and all the derivatives were identified as primary sensitizers in both tests. The order of potency in the LLNA was as follows: IPPD and PADPA > PPD > DMBPPD and MHPPD > DPPD. In the GPMT, all six groups of Animals sensitized with one of these chemicals cross-reacted to four Other derivatives. Specifically, the five groups that have a common basic PADPA structure, that is PADPA, DPPD, IPPD, DMBPPD, and MHPPD, all reacted to each Other at almost the same scores, while none of them reacted to PPD.

Conclusions: The cross-reactivity profile found in the study was to some extent different from that in previous human data, where distinction between cross-reaction and concomitant primary sensitization is not always clear.