Exposure assessment of neonicotinoid insecticides and their metabolites in Chinese women during pregnancy: A longitudinal study.

Neonicotinoid insecticides (NNIs) are the most widely used insecticides globally and ubiquitous in the environment, which has led to widespread human exposure. However, studies on internal exposure levels of NNIs and their metabolites in pregnant women are scarce. In this study, we measured nine parent NNIs and ten main metabolites in 1224 urine samples donated by 408 pregnant women at three trimesters. In the urine samples, the unadjusted vs. specific gravity (SG) adjusted median concentrations and detection frequencies (DFs) of desmethyl-acetamiprid (DM-ACE; 1.01 vs. 1.08 ng/mL; DF: 99.7%), 5-hydroxy-imidacloprid (5-hydroxy-IMI; 0.54 vs. 0.56 ng/mL; 98.5%), imidacloprid-olefin (IMI-olefin; 0.41 vs. 0.44 ng/mL; 99.3%), and desnitro-imidacloprid (DN-IMI; 0.12 vs. 0.12 ng/mL; 90.4%) were higher than their corresponding parent NNIs, acetamiprid (ACE; <0.01 vs. <0.01 ng/mL; 26.4%) and imidacloprid (IMI; 0.04 vs. 0.04 ng/mL; 69.9%). The unadjusted and SG-adjusted median concentrations of clothianidin (CLO), thiamethoxam (THM), and desmethyl-clothianidin (DM-CLO) were 0.05 vs. 0.07, 0.05 vs. 0.06, and 0.04 vs. 0.05 ng/mL, with the DFs of 61.0%, 57.5%, and 75.7%, respectively. The cumulative exposure level, imidacloprid-equivalent total NNIs (IMI), was generated by the relative potency factor approach considering the toxic effects of NNIs and their metabolites. The unadjusted IMI varied from 0.17 ng/mL (SG-adjusted: 0.20) to 1969 ng/mL (SG-adjusted: 1817) with a median of 14.1 ng/mL (SG-adjusted: 14.1). A decreased trend was observed in urinary NNIs and their metabolites throughout the three trimesters. Maternal age, educational level, and household income were related to the concentrations of NNIs and their metabolites. DM-ACE, 5-hydroxy-IMI, and IMI-olefin were significantly lower in winter than in autumn; DN-IMI, THM, CLO, and DM-CLO were significantly higher in both summer and autumn than in winter. The maximum estimated daily intake of IMI [34.8 μg/kg-body weight (bw)/d] was lower than the chronic reference dose of IMI (57 μg/kg-bw/d) currently recommended by the United States Environmental Protection Agency. Human health risk of exposure to NNIs and their main metabolites warranted further studies.