Evaluation of cytotoxicity and genotoxicity of pesticide mixtures on lymphocytes

The cytotoxicity and genotoxicity of pesticide mixtures viz. endosulfan + chlorpyrifos, chlorpyrifos + profenofos, and endosulfan + profenofos were evaluated on cultured human peripheral blood lymphocytes using assays for cell viability, and genotoxicity using chromosomal aberrations test and comet assay. The LC50 values for cytotoxicity were 3.50 mu M, 4.18 mu M, and 10.5 mu M for profenofos, endosulfan, and chlorpyrifos respectively. When combined in equimolar concentrations, the LC50 values for cytotoxicity were 1.4 mu M, 1.8 mu M, and 2.0 mu M for endosulfan + chlorpyrifos, chlorpyrifos + profenofos, and endosulfan + profenofos, respectively. Higher concentrations of individual pesticides (0.5-4.0 mu M) but very low concentrations of pesticide mixtures caused significant DNA damage. Additive index values indicated a synergistic effect of toxicity for endosulfan + chlorpyrifos combination (1.12 TTU). The binary mixture of chlorpyrifos + profenofos showed an additive toxicity (0.46 TTU) while an antagonistic effect was observed for endosulfan + profenofos combination. Synergism could be due to these complementary pesticides simultaneously acting in different ways, magnifying their efficacy, whereas an additive interaction would imply that the chemicals are acting by the same mechanism and at the same target. Analysis of toxicity of pesticide mixtures may serve as important biomarker for occupational and household exposure to pesticides, with different modes of action.