title: Evaluation of the utility of the lifetime mouse bioassay in the identification of cancer hazards for humans.
abstract: Limited testing resources, the need to limit animal use, and the demand for better knowledge about carcinogenic hazards require that the carcinogenicity testing paradigm based on lifetime cancer bioassays in rats and mice should be as efficient and reliable as possible. We have therefore reevaluated the rodent bioassay, particularly for nongenotoxic chemicals and conducted a rigorous examination of the 710 substances listed in the Carcinogenic Potency Database (CPDB) that were tested in both mice and rats. The CPDB is a web-based database that provides access to the literature and the results of 6540 bioassays on 1547 chemicals that have been published in the general literature through 2001 and by the National Cancer Institute/National Toxicology Program through 2004. Only three chemicals (o-benzyl-p-chlorophenol, Elmiron®, p-tolylurea) were identified as unequivocally non-genotoxic, mouse non-liver carcinogens. A careful analysis showed that their carcinogenicity in mice is irrelevant for assessment of human cancer hazards. This is consistent with data showing, with a few well-known exceptions, that non-genotoxic carcinogens in rodents are considered to be non-carcinogenic to humans. As a result, we propose that the inclusion of the mouse bioassay in the standard assessment scheme for non-genotoxic chemicals is no longer necessary.
authors: Science Strategies, LLC, 1001 East Market Street, Suite 202, Charlottesville, VA 22902, USA. Electronic address: tom@sciencestrategies.com.
authors: Thomas G
authors: TG
authors: Osimitz
authors: Wiebke
authors: W
authors: Droege
authors: Alan R
authors: AR
authors: Boobis
authors: Brian G
authors: BG
authors: Lake
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000032:analysis / Q000633:toxicity*; D004249:DNA Damage; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020407:Internet; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced; D051381:Rats
chemical_list: D002273:Carcinogens
keywords: Ames mutagenicity assay; BCP; CAR; CPDB; Cancer bioassay; Carcinogenic Potency Database; DNA; EAFUS; EU; European Union; Everything Added to Food in the United States; FDA; Genotoxicity; HSDB; Hazardous Substances Data Bank; Human relevance; IARC; IPCS; International Agency for Research on Cancer; International Programme on Chemical Safety; MTD; Maximum Tolerated Dose; Mode of action; NCI; NTP; National Cancer Institute; National Toxicology Program; Non-genotoxic carcinogens; OECD; OSTP; Organisation for Economic Co-operation and Development; PPARα; QSAR; REACH; Registration, Evaluation, Authorisation and Restriction of Chemical Substances; TD50; TSCA; Toxic Substances Control Act; U.S. Office of Science and Technology Policy; USEPA; United States Environmental Protection Agency; United States Food and Drug Administration; constitutive androstane receptor; deoxyribonucleic acid; median toxic dose value; o-benzyl-p-chlorophenol; peroxisome proliferator-activated receptor alpha; quantitative structure–activity