Experimental study on cross‐reactivity of α‐arbutin toward p‐phenylenediamine and hydroquinone in guinea pigs

Hydroquinone (HQ) has been used as a skin‐lightening cosmetic ingredient, while it has been known that HQ shows sensitizing potential and cross‐reactivity toward a strong sensitizer, p‐phenylenediamine (PPD). α‐Arbutin, a glycoside of HQ (4‐hydroxyphenyl α‐D‐glucopyranoside), is used worldwide as a skin‐lightening agent. The aim of this study was to evaluate the cross‐reactivity of α‐arbutin toward PPD and HQ. All tests were performed using the guinea pig maximization test. In experiments on the cross‐reactivity of α‐arbutin or HQ to PPD, six animals in each group were induced with PPD at 0.1% by i.d. injection and at 1.0% by topical application. The animals were challenged with α‐arbutin, HQ or PPD (as a positive control) at concentrations of 0.01%, 0.05% and 0.1%. In experiments on the cross‐reactivity of α‐arbutin to HQ, four animals in each group were induced with HQ at 2% by i.d. injection and at 1% by topical application. The animals were challenged with α‐arbutin or HQ (as a positive control) at concentrations of 0.2%, 2% and 20%. The cross‐reactivity toward PPD was observed with HQ (4/6) only at 0.1% challenge. However, α‐arbutin showed no apparent cross‐reactivity to either PPD or HQ even at their highest challenge concentrations. Potent sensitization was observed with PPD (6/6) even at 0.01% challenge and with HQ (3/4) at 0.2%. In conclusion, glycosylation of HQ remarkably reduced the sensitization potency of HQ and the cross‐reactivity of HQ to PPD.