RESUMO
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 (ß = -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 (ß = -1.11; 95% CI = -2.14, -0.07). Sex modified the association between any parent neonicotinoid and ALP (Pint = 0.064) and the association between clothianidin and ALP (Pint = 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 (Pint = 0.062), with a significant positive association in females (ß = 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.
RESUMO
BACKGROUND: Toxicology studies suggest that neonicotinoids may be associated with adiposity development via thyroid hormone disruption and increased oxidative stress. Prior epidemiological studies report mixed results for the association between neonicotinoids and adiposity measures. OBJECTIVE: To examine the association between detectable concentrations of parent neonicotinoids (imidacloprid, acetamiprid, clothianidin) and neonicotinoid metabolites (5-hydroxy-imidacloprid, N-desmethyl-acetamiprid) with adiposity measures among US adults, and whether sex modifies the associations for neonicotinoid metabolites with adiposity. METHODS: National Health and Nutrition Examination Survey (NHANES) 2015-2016 data was utilized to estimate covariate-adjusted associations between detectable neonicotinoids and fat mass index (FMI), lean mass index (LMI), waist circumference, body fat percentage, and body mass index (BMI) using multiple linear regression. We estimated incidence rate ratios (IRRs) for overweight or obese status with detectable neonicotinoid concentrations using Poisson's modified regression. Sampling strategies were accounted for in the regression models. RESULTS: Detectable levels of acetamiprid were associated with a decrease in FMI (ß = -3.17 kg/m2, 95% CI [-4.79, -1.54]), LMI (ß = -3.17 kg/m2, 95% CI [-5.17, -1.17]), body fat percentage (ß = -4.41, 95% CI [-8.20, -0.62]), waist circumference (ß = -9.80 cm, 95% CI [-19.08, -0.51]), and BMI (ß = -3.88kg/m2, 95% CI [-7.25, -0.51]) among adults. In contrast, detectable levels of 5-hydroxy-imidacloprid were associated with greater rates of being overweight/obese (IRR = 1.11, 95% CI [1.04, 1.18)) and increased LMI (ß = 0.67 kg/m2, 95% CI [0.04, 1.29]). Sex modified the association between N-desmethyl-acetamiprid and LMI (pint = 0.075) with a positive association among males (ß = 1.14 kg/m2, 95% CI [0.38, 1.90]), and an insignificant inverse association in females. Sex also modified the association for N-desmethyl-acetamiprid with FMI (pint = 0.095) and body fat percentage (pint = 0.072), with suggestive evidence showing positive associations for males and inverse associations for females. CONCLUSION: Detectable concentrations of acetamiprid were inversely associated with adiposity, while there were mixed findings for 5-hydroxy-imidacloprid. Findings suggest sex differences, though results are not clear with regard to the directionality of the association by sex.
