Combined toxicity of nine typical pesticides in binary mixtures on A549 cells

Air pollution caused by pesticide drift poses a significant environmental health risk. The lungs are directly targeted by airborne pesticide exposure via inhalation; however, their inhalation toxicological data are poorly understood. In the present study, we evaluated the combined toxicity and interactions of lambda-cyhalothrin and its binary mixtures with eight insecticides at a concentration ratio of 1:1 in the non-small-cell lung cancer A549 line cells. Cytotoxicity tests showed that the selected pesticide binary mixtures reduced cell viability in a concentration-dependent manner. The combination index (CI) model indicated that the mixtures of lambda-cyhalothrin with acetamiprid, thiamethoxam, or clothianidin exhibited antagonistic effects, while other combinations shifted from antagonism to synergy at a toxicity level of 40%-60%. A synergistic toxicity occurred between lambda-cyhalothrin and emamectin benzoate with CI values of 0.58-0.95, and the obtained benchmark dose limits (BMDLs) value of their binary mixture was greater than 1.5 times more toxic than that of these pesticides individually. Moreover, combined exposure to the binary mixtures produced greater amounts (1.30- to 2.93-fold increase) of reactive oxygen species, malondialdehyde, and lactate dehydrogenase compared with exposure to these pesticides individually. This result suggested that the synergistic cytotoxicity of lambda-cyhalothrin and emamectin benzoate may be driven by excessive oxidative stress. Our findings serve to better understand the complex toxic pesticide interactions that humans face in the environment.