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

In order to define the toxicological risk for the human population derived from the chemical compounds formed during the process of cooking animal meat, which have been described to possess a mutagenic, genotoxic, and carcinogenic activity, an extensive study has been developed on cooked meat extract and two cooked meat mutagens, IQ and MeIQx. The study has been based on toxicokinetics and mouse tissue distribution of the two chemicals, on in vitro and in vivo mutagenicity/genotoxicity analyses (gene mutation, chromosome aberration, micronuclea in mouse bone marrow cells, mice urine and faeces mutagenicity test), as well as in vivo protein and DNA binding. The two chemicals have been found positive for the induction of gene mutation on Salmonella, but not in V-79 Chinese hamster cells; IQ only has been found positive for the induction of chromosome aberrations on CHO cells and cultured human lymphocytes. IQ and MeIQx were negative for the induction of micronuclea in mice treated with 40 mg/kg of the chemicals; the lowest effective administered dose to the mice which produced mutagenic urine was 0.4 mg/kg of IQ and 0.04 mg/kg of MeIQx. A dose of 40 mg/kg of IQ given 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 DNA adducts for the liver were correlated with the dose of the IQ and MeIQx administered to the mice. All the data have been used for defining a possible risk estimate derived to the human population as a consequence of a cooked meat diet.