Study on the characterization of pesticide modes of action similarity and the multi-endpoint combined toxicity of pesticide mixtures to Caenorhabditis elegans

With the widespread use of pesticides, the coexistence of multiple low-residue pesticides in environmental media has increased significantly, and the cocktail effect caused by this phenomenon has garnered increasing attention. However, owing to the scarcity of information regarding the modes of action (MOAs) of chemicals, the application of concentration addition (CA) models for evaluating and predicting the toxicity of mixture with similar MOAs is limited. Additionally, the joint toxicity laws of complex mixture systems to different toxicity endpoints in organisms remain unclear, and effective methods to test the mixture toxicity on lifespan and reproductive inhibition are lacking. Therefore, in this study, the similarity of pesticide MOAs was characterized using molecular electronegativity-distance vector (MEDV-13) descriptors based on eight pesticides (aldicarb, methomyl, imidacloprid, thiamethoxam, dichlorvos, dimethoate, methamidophos and triazophos). Additionally, the methods of lifespan and reproduction inhibition microplate toxicity analysis of elegans (EL-MTA and ER-MTA) were established to test the lifespan and reproduction inhibition toxicity of Caenorhabditis elegans. Finally, a unified scale synergistic-antagonistic heatmap (SAHscale) method was proposed to explore the combined toxicity of the mixtures on the lifespan, reproduction, and mortality of nematodes. The results showed that the MEDV-13 descriptors could effectively characterize the similarity in MOAs. The lifespan and reproductive ability of Caenorhabditis elegans were significantly inhibited when the pesticide exposure concentration was one order of magnitude lower than the lethal dose. The sensitivity of lifespan and reproductive endpoints to mixtures was dependent on the concentration ratio. The same rays in the mixture had consistent toxicity interactions on the lifespan and reproductive endpoints of Caenorhabditis elegans. In conclusion, we demonstrated the feasibility of MEDV-13 in characterizing the similarity of MOAs, and provided a theoretical basis for exploring the mechanism of chemical mixtures by studying their apparent toxicity of mixtures on nematode lifespan and reproduction endpoints.

Automated summary

With the widespread use of pesticides, the cocktail effect caused by the coexistence of multiple low-residue pesticides in the environment has become a concern. However, limited information on the modes of action (MOAs) of chemicals hinders the application of concentration addition (CA) models in evaluating and predicting the toxicity of mixtures with similar MOAs. This study characterized the similarity of pesticide MOAs using MEDV-13 descriptors and established methods to test the toxicity of mixtures on the lifespan and reproduction of Caenorhabditis elegans. The results showed consistent toxicity interactions of the mixtures on the nematode's lifespan and reproductive endpoints.