Chronicle of mixture effects: Sensitivity differences in multiple toxicity endpoints of transgenic C. elegans and...

The pesticide, as the typical emerging contaminants, has brought significant benefits to agricultural production due to its widespread use. However, the excessive residue of pesticides in environmental media poses potential risks to both the environment and human health. Therefore, this study focused on three typical pesticide residues (aldicarb (ALD)，methamidophos (MET) and triazophos (TAP)) that were commonly detected in fruits and vegetables, using the DAF-16 transgenic strain of Caenorhabditis elegans (C. elegans) as a model organism. Three binary and one ternary mixture systems were designed using the direct equipartition ray design and the uniform design ray method, resulting in a total of 20 mixture rays. These were used for multi-endpoint toxicity tests on C. elegans. The results indicated that all mixture rays exhibited higher sensitivity at the endpoints of lifespan and reproduction inhibition compared to the mortality endpoint. Furthermore, the sensitivity to lifespan and reproduction inhibition varied across the different mixture rays. The mixture toxicity interaction assessment results indicated that with increasing toxicity effects, a concentration ratio-dependent phenomenon was observed in the toxicity interactions. Furthermore, when the effect level exceeded 30 %, opposite toxicity interaction outcomes (i.e., the shift from antagonism to synergism or vice versa) emerged across different toxicological endpoints. These findings pose significant challenges for the assessment of mixture combined toxicity.