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

Peng Huang; Shu-Shen Liu; Ze-Jun Wang; Ting-Ting Ding; Meng-Ting Tao; Zhong-Wei Gu

doi:10.1016/j.scitotenv.2023.164918

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

Sci Total Environ. 2023 Oct 1:893:164918. doi: 10.1016/j.scitotenv.2023.164918. Epub 2023 Jun 14.

Authors

Peng Huang¹, Shu-Shen Liu², Ze-Jun Wang³, Ting-Ting Ding¹, Meng-Ting Tao¹, Zhong-Wei Gu¹

Affiliations

¹ Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China.
² Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China. Electronic address: ssliuhl@263.net.
³ National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, PR China.

PMID: 37327899
DOI: 10.1016/j.scitotenv.2023.164918

Abstract

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.

Keywords: APTox; Chronic toxicity; Mixture design; Molecular descriptor; Synergistic-antagonistic heatmap.

MeSH terms

Animals
Caenorhabditis elegans
Dimethoate
Dose-Response Relationship, Drug
Nematoda*
Pesticides* / toxicity

Substances

Pesticides
Dimethoate