Exposure to neonicotinoid insecticides and their characteristic metabolites: Association with human liver cancer.

Neonicotinoid insecticides (NEOs) are commonly applied for pest control in China and around the world. Previous studies reported that NEOs are hepatotoxic to mammals. However, limited studies have explored the associations between NEOs exposure and liver disease. In the present study, we detected six parent NEOs (p-NEOs), including acetamiprid, thiacloprid, dinotefuran, clothianidin, imidacloprid, and thiamethoxam, and five characteristic metabolites (m-NEOs), including 5-hydroxy-imidacloprid, olefin-imidacloprid, N-desmethyl-acetamiprid, 1-methyl-3-(tetrahydro-3-furylmethyl) guanidine and 1-methyl-3-(tetrahydro-3-furyl methyl) urea, in blood samples collected from healthy donors (n = 100; females vs. males: 45 vs. 55; age: 22-91 years) and liver cancer patients (n = 274; females vs. males: 118 vs. 156; age: 11-88 years) in one hospital from Guangzhou city, South China. NEOs were frequently detected (61%-94%) in blood samples, with median concentrations ranging from 0.19 ng/mL to 1.28 ng/mL and 0.20 ng/mL to 2.03 ng/mL for healthy and liver cancer populations, respectively. olefin-imidacloprid was the most abundant NEOs in healthy and liver cancer populations, accounting for 23.4% and 20.7%, respectively. Significant positive correlations among most m-NEOs concentrations were found, and associations between m-NEOs and their corresponding p-NEOs were positively correlated. These findings indicated that the sources of m-NEOs were both endogenous and exogeneous. Females had higher median concentrations of NEOs and their metabolites than males. Moreover, the α-fetoprotein values and blood concentrations of target analytes (r = 0.428-0.601, p < 0.05) were positively correlated. Meanwhile, associations between the concentrations of p-NEOs and m-NEOs and liver cancer were found (odds ratio = 2.33-9.02, 95% confidence interval = 0.31-22.7, p < 0.05), indicating that human exposure to NEOs and their metabolites might increase the odds of liver cancer prevalence. Our work provided a new insight into the hepatotoxicity of NEOs and their metabolites, and human health risks of exposure to these pollutants warranted further studies.