Toxicity risk assessment of pyriproxyfen and metabolites in the rat liver: A vitro study

Pyriproxyfen (PYR) is a type of aromatic juvenile hormone analog and a hygienic insecticide used in agriculture to control insect species. Therefore, assessing the metabolic behavior and toxic effects of PYR in mammals is the best means of evaluating its risks to human health. Previous studies have reported conflicting results regarding the toxicity risks of PYR and its metabolites in rat hepatocytes. We used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to perform a chiral analysis of PYR and its metabolites investigating the enantioselective metabolism of PYR in rat liver microsomes. Our results concluded that the recoveries of PYR, metabolites A and B ranged from 81.13%-111.54 %, with RSD values of 0.01 %-6.52 %. The method limits of detection (LODs) and limits of quantification (LOQs) for PYR, metabolites A and B were in accordance with the analysis requirements. Previous studies have demonstrated the enantioselective metabolism of PYR and the generation of metabolites. Measurements of cell proliferation toxicity to rat hepatocytes, apoptosis and DNA damage induced by PYR and its metabolites in rat hepatocytes indicated that the metabolites reflected higher toxicity potential than PYR in rat hepatocytes. More studies about the molecular mechanism of PYR-induced toxicity are urgently needed in future work.