Aspects of Regulatory Genotoxicity of Chemicals in Mammalian Cells

Regulatory Genotoxicity Tests are applicable for pharmaceuticals, in general. International Workshop on Stardardisation of Genotoxicity Test Procedures (1993) has given specific guidelines to be considered for mutagenicity or carcinogenicity of a chemical to mammalian cells. Bacterial reverse mutation test, greater than 507o reduction in cell number and 80% toxicity measured by a.sse.ssment of cloning efficiency at highest concentration are the levels of cytotoxicity to be considered. Recent review has pointed that Unscheduled DNA Synthesis Test is also suitable to detect false positive! result. Differences of active metabolites produced in in vivo and in vitro situations can be implied as one parameter for regulatory genotoxicity as genotoxicity is the broad term that refers to any deleterious change in genetic material.

Contamination of the environment with different types of insecticides is one of the greatest concern of human health of these days. It has been estimated by mutagenic tests that some of the common insecticides are strongly genotoxic. Chromosome aberrations, sister chromatid exchanges, gene mutations and death of cells are the common findings of investigations of genotoxicity. Alkylating compounds are always mutagenic and organophosphorous insecticides are the important compounds to be carcinogenic after alkylation. Cytotoxicity of some common insecticides will be discussed here along with the aspects of regulatory genotoxicity tests.