Associations between neonicotinoids and liver function measures in US adults National Health and Nutrition Examination Survey 2015-2016

Background: Toxicological studies indicate that neonicotinoids may be associated with disruptions in liver function due to an increase in oxidative stress. There are scant epidemiological studies investigating the chronic hepatotoxic effects of neonicotinoids. Objective: To examine the association between detectable concentrations of parent neonicotinoids and neonicotinoid metabolites with liver function markers among US adults, and whether sex modifies this association. Methods: National Health and Nutrition Examination Survey 2015-2016 data were used to estimate associations between detectable neonicotinoids and serum alkaline phosphatase (ALP), alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transaminase (GGT), albumin, total bilirubin, total protein, and Hepatic Steatosis Index (HSI) using multiple linear regression. Results: Detectable levels of N-desmethyl-acetamiprid were associated with a decrease in GGT (beta = -3.54 unit/l; 95% confidence interval [CI] = -6.48, -0.61) and detectable levels of 5-hydroxy-imidacloprid were associated with a decrease in HSI (beta = -1.11; 95% CI = -2.14, -0.07). Sex modified the association between any parent neonicotinoid and ALP (P-int = 0.064) and the association between clothianidin and ALP (P-int = 0.019), with a pattern of positive associations in males and inverse associations in females, though stratified associations did not reach statistical significance. Sex also modified the association between 5-hydroxy-imidacloprid and total protein (P-int = 0.062), with a significant positive association in females (beta = 0.14 g/dl; 95% CI = 0.03, 0.25) and a null association in males. Conclusion: Detectable concentrations of neonicotinoid metabolites were inversely associated with GGT and HSI in US adults. Evidence suggests neonicotinoids may influence liver function differently depending on sex. Future research is recommended to replicate the findings as the study was limited in its cross-sectional nature and inability to examine continuous neonicotinoid concentrations with liver function.