Toxicokinetics, Biotransformation, and Tissue Distribution of Imidaclothiz in Rats.

Imidaclothiz (IMZ), a next-generation neonicotinoid pesticide, has garnered significant attention due to its detection in human samples. In this study, we investigated its toxicokinetics and biotransformation in rats following oral administration. IMZ was rapidly absorbed, reaching peak plasma concentration at 0.75 h, followed by a prolonged elimination phase with minimal decrease between 12 and 48 h. Tissue distribution analysis revealed notable accumulation and slower elimination of IMZ in the kidneys, testes, and muscle. Eleven metabolites were identified, with M227, M231, and M233 being reported for the first time. Notably, metabolite M277 exhibited high relative abundance in the kidneys and liver and was predicted to have high nephrotoxic and hepatotoxic potential. Metabolites M217 and M243 were prominent in the testes, highlighting potential reproductive toxicity concerns. The study provided a comprehensive characterization of IMZ disposition in rats, underscoring its tissue distribution and the organ-specific toxicological risks associated with its key metabolites.