摘要
Following exposure,neonicotinoid insecticides(NEOs)can be metabolized by both Phase Ⅰ and Phase Ⅱ reactions catalyzed by human cytochrome P450 enzymes.However,toxicities of parent NEOs and their metabolites are still unclear,and little is known about biotransformation rates and pathways of NEOs in humans.In this study,98 serum samples collected in China were analyzed for free,conjugated and total forms of six parent NEOs(i.e.,acetamiprid(ACE),imidacloprid(IMI),clothianidin(CLO),thiacloprid(THD),thiamethoxam(THM),and dinotefuran(DIN))and four metabolites(i.e.,N-desmethyl-acetamiprid(N-dm-ACE),1-methyl-3-(tetrahydro-3-furylmethyl)(DIN-U),5-hydroxy-imidacloprid(5-OH-IMI),olefin-imidacloprid(Of-IMI)).NEOs and their metabolites were detected in all serum samples,and the total median concentrations of free,conjugated,and total forms of 10 NEOs were 2.04,2.01,and 5.12 ng/mL,respectively.Conjugated forms of NEOs accounted for only half(53%)of the total forms of NEOs.Based on the profiles of Phase Ⅰ and Phase Ⅱ metabolites of NEOs in serum,it was found that age is a determinant in Phase Ⅰmetabolism of DIN and Phase Ⅱ metabolism of IMI.The Phase Ⅱmetabolites of NEOs are associated with oxidative DNA damage,and the conjugated forms of IMI,DIN,and 5-OH-IMI in serum were significantly positively correlated with oxidative stress.Overall,the amount of NEOs present in conjugated forms in human serum was determined to document the existence of a considerable proportion of free forms of these insecticides.
基金
The Natural Science Foundation of China(Nos.22022612,22036004,and 21677184)
Natural Science Foundation of Guangdong Province,China(Nos.2020A0104006 and 2021A1515010243)are acknowledged for their partial research support.We gratefully acknowledge the donors who contributed blood samples to this study.