Assessment of the carcinogenicity associated with oral exposures to hydrogen peroxide J. M. DESESSO *, A. L. LAVIN, S. M. HSIA and R. D. MAVIS Mitretek Systems, McLean, Virginia, USA (Accepted 1 May 2000) SummaryÐConcern regarding hydrogen peroxide (H 2 O 2 ) carcinogenicity arises from its ability to act as a strong oxidizing agent. In short-term genotoxicity tests, H 2 O 2 has given predominantly positive results; however, these assays have been performed using either bacterial strains engineered to be exquisitely sensitive to oxidant damage, or mammalian cells de®cient in antioxidant enzymes. Signi®cantly, the addition of anti- oxidant protective measures (normally present in vivo) to these assay systems protects against H 2 O 2 geno- toxicity. In most whole animal studies, H 2 O 2 exposure neither initiates nor promotes tumors. In mice, however, 0.4% H 2 O 2 in drinking water was reported to induce hyperplastic lesions of the duodenum and to erode areas in the glandular stomach epithelium. Owing to the chemistry of dilute H 2 O 2 solutions and the anatomy/physiology of the gastrointestinal tract, it is unlikely that orally ingested H 2 O 2 reaches the duode- num. Instead, greatly decreased water consumption and the resultant abrasion of the luminal lining on ingestion of pelleted dry rodent chow is the most likely cause of the observed gastric and duodenal lesions following H 2 O 2 administration in drinking water. Signi®cantly, when hamsters received high doses of H 2 O 2 by gastric intubation (and water intake was not aected), the gastric and duodenal epithelia appeared normal. In-depth analysis of the available data supports the conclusion that oral ingestion of H 2 O 2 should not be considered a carcinogenic threat. # 2000 Elsevier Science Ltd. All rights reserved Keywords: cancer; duodenum; small intestine; mouse; risk assessment. Abbreviations: CAC=Cancer Assessment Commission; DMBA=dimethylbenz[a]anthracene; DMH= 1,2-dimethylhydrazine dihydrochloride; DNA=deoxyribonucleic acid; ECETOC=European Centre for Ecotoxicology and Toxicology of Chemicals; FDA=United States Food and Drug Administration; GSH=reduced glutathione; GSSG=oxidized glutathione; H 2 O 2 =hydrogen peroxide; IARC=International Agency for Research on Cancer; MAM=methylazoxymethanol; . O 2  =superoxide anion; SCE=sister chromatid exchange; SOD=superoxide dismutase. Introduction First isolated in 1818 (IARC, 1999), hydrogen per- oxide (H 2 O 2 ) is most commonly used as a chemical intermediate in the production of industrial chemicals. It is also used in textile manufacturing, in the bleaching of pulp and paper, and in the potable water treatment process (ECETOC, 1993; Hess, 1995; IARC, 1999). Exposure of the general population to H 2 O 2 occurs mainly as a result of its use in a variety of non-prescription compounds (Harvey, 1990; Hess, 1995; IARC, 1999). Dilute solutions of H 2 O 2 are commonly used as disinfectants. In addi- tion, H 2 O 2 is widely used in dental products such as mouthwash, toothpaste and tooth-whitening sys- tems. This latter use of H 2 O 2 has become the subject of much debate in recent years due to the availability to the consumer of tooth bleaching systems for use without the supervision of a dental professional. Such systems commonly use H 2 O 2 in concentrations of up to 10% or carbamide peroxide (which breaks down to H 2 O 2 and urea in aqueous solutions) in concentrations of up to 22% (10% carbamide per- oxide is approximately equal to 3.5% H 2 O 2 ) (Li, 1996). Although such systems have been shown to be highly ecacious, questions regarding the safety of these products have been raised. H 2 O 2 can produce 0278-6915/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0278-6915(00)00098-3 Food and Chemical Toxicology 38 (2000) 1021±1041 www.elsevier.com/locate/foodchemtox *Corresponding author. Tel: +1-703-610-2130; fax: +1- 703-610-1563; e-mail: jdesesso@mitretek.org