An experimental approach to identifying the genotoxic risk from cooked meat mutagens

In order to define the toxicological risk to the human population from the chemical compounds formed during the process of cooking animal meat, which have been described as possessing mutagenic, genotoxic and carcinogenic activities, an extensive study was undertaken of cooked meat extract and two cooked meat mutagens, 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) and 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx). The study involved toxicokinetics and mouse-tissue distribution studies of the two chemicals, in vitro and in vivo mutagenicity/genotoxicity analyses (i.e. the detection of gene mutations, chromosome aberrations and micronuclei in mouse bone marrow cells, and mouse urine and faeces mutagenicity tests), as well as in vivo protein and DNA binding assays. IQ and MeIQx were found to be positive for the induction of gene mutations in Salmonella typhimurium TA98, but not in Chinese hamster V79 cells; IQ only was found to be positive for the induction of chromosome aberrations in Chinese hamster ovary cells and cultured human lymphocytes. IQ and MeIQx were negative for the induction of micronuclei in mice treated with 40 mg chemical/kg body weight; the lowest effective dose administered to the mice that produced mutagenic urine was 0.4 mg IQ/kg body weight and 0.04 mg MeIQx/kg. A dose of 40 mg IQ/kg, given orally by gavage to mice, produced an excretion of 1-4% of the applied dose in the urine and 0.1-2% of the applied dose in the faeces, when evaluated chemically or mutagenically. The number of DNA adducts in the liver correlated with the dose of IQ or MeIQx administered to the mice. All the data have been used for defining a possible risk estimate to the human population as a consequence of a cooked meat diet.