Depigmentation with tert-butyl hydroquinone using black guinea pigs.
tert-Butyl hydroquinone (TBHQ) has important and functional uses in consumer and commercial applications, some of which involve human exposure primarily through dermal contact. To assist in the safety evaluation of TBHQ, this study was conducted to determine whether TBHQ would produce changes in skin pigmentation after repeated dermal application to black guinea pigs. Hydroquinone (HQ) and hydroquinone monomethyl ether (HQMME) were used as positive controls. TBHQ and HQ were tested at concentrations of 0.1, 1.0 and 5.0%, while HQMME was tested at a concentration of 10.0%. Groups of five males and five females were dosed with TBHQ, HQ, or the vehicle (hydrophilic ointment) daily (M-F) for 13 weeks. In addition, animals (five males, five females) treated with HQMME received 13 doses over a 3-week period. The application site was evaluated weekly for degree of pigmentation loss and irritation. Twenty-four hours after final application, sites were evaluated for depigmentation, irritation and hyperpigmentation. Subsequently, the application site was depilated and re-evaluated for the same endpoints. Repetitive exposure to concentrations of 1.0% and 5.0% TBHQ and HQ were slightly to moderately irritating, while 0.1% of each of these test materials produced only weak irritant responses. No irritant responses to hydrophilic ointment were observed and HQMME produced weak irritant responses after 2 weeks. Neither 0.1% TBHQ nor HQ produced depigmentation, while 20% of animals dosed with 1.0% TBHQ and 30% of animals dosed with 1.0% HQ had spotty or uniform loss of pigment at the site of treatment. Approximately 40% of animals dosed with 5% TBHQ or HQ were depigmented at the treatment site at the final evaluation. HQMME produced complete depigmentation of the skin and hair in all animals. Hyperpigmentation of the treatment site was observed in 80-100% of animals in all groups (with the exception of HQMME-treated animals, treated for only 3 weeks), which may be attributable to the use of hydrophilic ointment as the vehicle, the application procedure, or simply clipping hair from the skin. Thus, this study showed that TBHQ causes depigmentation in black guinea pigs at concentrations of 1% or greater, but that a no-effect threshold for this endpoint exists at a concentration between 0.1 and 1.0%.
Patrick
E
E
Department of Dermatology, University of California Medical Center, San Francisco 94143, USA.
Juberg
D R
DR
O'Donoghue
J
J
Maibach
H I
HI
D000279:Administration, Cutaneous; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006873:Hydroquinones / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D012880:Skin Pigmentation / Q000187:drug effects*
D000840:Anisoles; D000975:Antioxidants; D006873:Hydroquinones; C009760:mequinol; C018855:2-tert-butylhydroquinone; C031927:hydroquinone