Abstract |
88-Kod-Depig-01 was conducted to determine if mono-t--butyl hydroquinone (TBHQ) would produce changes in skin pigmentation or skin irritation after repeated application to the same area of skin. Hydroquinone (HQ), p- methoxyphenol (MMH), and hydrophilic ointment (vehicle in which the chemicals were applied) were tested as controls. TBHQ and HQ were tested at concentrations of 0.1, 1.0 and 5.0%. MMH was tested at 10% concentration. All mixtures were assayed by the sponsor prior to use to verify accuracy of dilution. Test animals were outbred black guinea pigs with darkly pigmented skin as well as black hair. Animals dosed with HQ, TBHQ, or hydrophilic ointment were obtained from ARI Breeding Laboratories, Bridgewater, Mass. Animals dosed with MMH were the offspring of the animals purchased from ARI. Groups of five males and five females were dosed with one of the HQ or TBHQ mixtures or with the vehicle each scheduled working day (M-F) for 13 weeks; they received a total of 63 applications. MMH was added as an additional positive control after the study was underway, five males and five females received 13 doses of MMH. 0.1 ml of the appropriate mixture was spread over the same area, 3.2 cm in diameter, of the shaved flank each day of dosing. The site of application was evaluated for the degree of pigmentation loss and degree of irritation each week during the study. Twenty-four hours after the final application, sites were evaluated for depigmentation, irritation, and hyper pigmentation. The area was depilated with Nair after the evaluation and sites were re-evaluated. The treatment sites were photographed periodically during the study. 1.0 and 5.0% HQ and 1.0 and 5.0% TBHQ were somewhat irritating. Slight inflammatory responses were evident after 3 weeks. The responses of 3 animals dosed with 5.0% HQ were so severe after 7-8 weeks that the site of application was changed. 0.1% HQ and 0.1% TBHQ each produced only weak irritant responses in 2 of 9 animals during the study. No irritant responses to hydrophilic ointment were observed. MMH produced weak irritant responses after 2 weeks. |