Evaluation of the genotoxic and embryotoxic potential of chlorpyrifos and its metabolites in vivo and in vitro.

The genotoxicity and embryotoxicity of chlorpyrifos (CPF) and two metabolites were evaluated using the chick embryo, Chinese hamster ovary cells, and by examining blastocysts from superovulated cows crossed to chlorpyrifos-treated bulls. Chlorpyrifos and metabolites were dissolved in acetone and administered to 3-day embryos by the air cell method. The LD50 was 1,500 micrograms/embryo when mortality was checked through and including 17 days of development. The metabolites were more embryotoxic than the parent compound, CPF. Chlorpyrifos and metabolites did not increase the sister chromatid exchange (SCE) frequency above background at any dosage in the 3-day chick embryo assay. Similarly, none of these compounds increased SCE frequencies in three-point dosage tests (1, 10, 100 micrograms/ml) using Chinese hamster ovary cells. Controls in these assays consisted of the solvent carrier acetone (7.0 +/- 2.5 SCE/cell) and 8.6 micrograms/ml methyl methane sulfonate (30.5 +/- 7.4 SCE/cell). Studies of bovine blastocysts obtained from superovulated cows crossed with Dursban 44 treated bulls did not reveal evidence of chromosome aberrations or developmental anomalies associated with pesticide application. However, reproductive performance of breeders may be subnormal as a result of severe poisoning. This underscores the limitations of short-term assays and emphasizes the need to perform thorough toxicological assays of a chemical according to actual usage patterns in the species of concern.