Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. The clinical significance of this is unknown.
Benzoyl peroxide in acetone at doses of 5 and 10 mg administered twice per week induced skin tumors in transgenic Tg.AC mice in a study using 20 weeks of topical treatment.
In a 52 week dermal photocarcinogenicity study in hairless mice, the median time to onset of skin tumor formation was decreased and the number of tumors per mouse increased following chronic concurrent topical administration of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1%/5% with exposure to ultraviolet radiation (40 weeks of treatment followed by 12 weeks of observation).
In a 2-year dermal carcinogenicity study in rats, treatment with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1%/5% at doses of 100, 500 and 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats. The incidence of keratoacanthoma at the treated site of males treated with 2000 mg/kg/day (8 times the highest recommended adult human dose of 2.5 g Clindamycin Phosphate and Benzoyl Peroxide Gel, 1%/5%, based on mg/m2) was statistically significantly higher than that in the sham- and vehicle-controls.
Genotoxicity studies were not conducted with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1%/5%. Clindamycin phosphate was not genotoxic in Salmonella typhimurium or in a rat micronucleus test. Clindamycin phosphate sulfoxide, an oxidative degradation product of clindamycin phosphate and benzoyl peroxide, was not clastogenic in a mouse micronucleus test. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Studies have not been performed with Clindamycin Phosphate and Benzoyl Peroxide Gel, 1%/5% or benzoyl peroxide to evaluate the effect on fertility. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 grams Clindamycin Phosphate and Benzoyl Peroxide Gel, 1%/5%, based on mg/m2) revealed no effects on fertility or mating ability.