BENZOYL PEROXIDE - AN INTEGRATED HUMAN SAFETY ASSESSMENT FOR CARCINOGENICITY

Topical benzoyl peroxide has been used in the treatment of acne for ov er 30 years, with no reports of adverse effects that could be related to skin carcinogenesis. Two case-control epidemiological studies have found a lack of association between the specific use of benzoyl peroxi de and skin cancer. In addition to these findings in humans, 23 carcin ogenicity studies in rodents with benzoyl peroxide, including 16 emplo ying topical application, have yielded negative results. An increase i n skin carcinomas was reported in 1 study in which benzoyl peroxide in acetone was applied to the skin of SENCAR mice for a 1-year period; h owever, this study did not employ adequate control groups to fully und erstand the unusual findings, and the results were inconsistent with t hose of 6 other similar studies. While benzoyl peroxide is not a compl ete carcinogen in animals and has weak or no mutagenic potential, it h as been found to be a tumor promoter in mouse skin using experimental two-stage models of carcinogenesis. Consistently positive results have been obtained in turner promotion studies in which SENCAR mice were e xposed to initiating doses of potent experimental carcinogens followed by promotion with benzoyl peroxide in acetone. Negative results have been obtained in similar studies with commercial formulations. However , the results of promotion studies with benzoyl peroxide do not carry significant weight for human safety assessment as evidenced by (i) the absence of demonstrated carcinogenicity in humans of a number of rode nt tumor promoters despite long-term human exposure; (ii) the observat ion that tumor promotion in mouse skin occurs only under specific expe rimental conditions and predominantly in highly sensitive strains; (ii i) clinical use scenarios markedly different from the conditions resul ting in tumor promotion in mouse skin; and (iv) the significant physio logical differences between mouse and human skin. Thus, to date, avail able scientific evidence does not allow the results of these rodent pr omotion studies to be meaningfully applied to human safety assessment. As such, significant scientific progress must be made before human sa fety estimations can be derived from rodent promotion data. Based upon lack of activity from 23 animal carcinogenicity studies, the more tha n 30 years of safe clinical use, and negative findings from epidemiolo gical studies, there is no evidence to support an association between benzoyl peroxide and the development of skin cancer in humans. These e pidemiological and animal study findings, along with the general Tack of genotoxic potential, and the absence of potential carcinogenic acti vity from primary metabolites support the conclusion that benzoyl pero xide does not present a carcinogenic risk to humans. (C) 1995 Academic Press, Inc.