Rodents chronic/cancer bioassays

COC (2002) Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC). COC statement on ILSI/HESI research programme on alternative cancer models. COC/02/S3, April 2002 Flammang TJ, Von Tungeln LS, Kadlubar FF, Fu PP (1997) Neonatal mouse assay for tumorigenicity. Alternative to the Chronic rodent bioassay. Reg Toxicol Pharmacol 26 230-240... 

Results of chronic MTBE exposure studies are the most widely available of all studies on the ether-like fuel oxygenates (MTBE, ETBE, TAME, DIPE). Evidence from animal bioassays demonstrates that long-term, high-level exposures to MTBE by either ingestion or inhalation cause cancer in rodents. Inhalation exposure to MTBE produced an increased incidence of renal and testicular tumors in male rats and liver tumors in mice. Oral administration of MTBE produced an increased incidence of lymphomas and leukemias in female rats and testicular tumors in male rats. Chronic exposure to ethanol also produces cancers (e.g., esophageal) in laboratory animals. 

Rodent bioassays have shown that chronic APFO (most widely used salt of PFOA) exposure is associated with a variety of tumor types. The mechanisms of APFO tumorigenesis are not clearly understood. The US Environmental Protection Agency (EPA) is currently evaluating the scientific evidence and has not reached any conclusions on the potential significance to humans of the rodent cancer data. 

Genetically modified mice have been useful to show the relationships between the key events in the PPARa MOA. PPARa-null mice provided critical evidence establishing the rodent MOA for PPARa activator-induced hepatocarcinogenesis. Evidence that a particular compound induces key events in wild-type mice but not in mice lacking PPARa would be considered strong support for a PPARa MOA for that particular compound. To date, three chronic bioassays have been conducted in these mice (Hays et al. 2005 Ito et al. 2007 Peters et al. 1997). A greater body of data exists in which precursor events for cancer have been assessed in wild-type and PPARa-nuU mice after acute or subacute exposures. 

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