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

Abstract Neonicotinoid insecticides (NEOs) are commonly applied for pest control in China and around the world. They have potential toxicity to bees, birds, mammals, and even human being. However, limited studies have explored the associations between NEOs exposure and 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 (5-OH-IMI), olefin-imidacloprid (Of-IMI), 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 (n = 100) and liver cancer (n = 274) populations in 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. Of-IMI 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, 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. This study is the first work to document 5-OH-IMI and DN in blood samples collected from South China.