ABSTRACT: BACKGROUND:Neonicotinoids are used for insect control in agriculture, landscaping, and on household pets. Neonicotinoids have become popular replacements for organophosphate and carbamate insecticides, and use is on the rise. OBJECTIVES:To assess human exposure to neonicotinoid insecticides in a representative sample of the U.S. general population 3 years and older from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). METHODS:We used online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry after enzymatic hydrolysis of conjugates to quantify in 3038 samples the urinary concentrations of six neonicotinoid biomarkers: four parent compounds (acetamiprid, clothianidin, imidacloprid, thiacloprid) and two metabolites (N-desmethyl-acetamiprid, 5-hydroxy-imidacloprid). We calculated distribution percentiles, and used regression models to evaluate associations of various demographic parameters and fasting time with urinary concentrations above the 95th percentile (a value selected to represent higher than average concentrations) of neonicotinoid biomarkers. RESULTS:Weighted detection frequencies were 35% (N-desmethyl-acetamiprid), 19.7% (5-hydroxy imidacloprid), 7.7% (clothianidin), 4.3% (imidacloprid), and <0.5% (acetamiprid, thiacloprid). The weighted frequency of having detectable concentrations of at least one of the six biomarkers examined was 49.1%. The 95th percentile concentrations for N-desmethyl-acetamiprid, 5-hydroxy imidacloprid, and clothianidin were 1.29, 1.37, and 0.396??g/L, respectively. For people who fasted <8?h, regardless of race/ethnicity and sex, 3-5 year old children were more likely to have N-desmethyl-acetamiprid concentrations above the 95th percentile than adolescents (adjusted odds ratio (OR)?=?3.12; 95% confidence interval [CI], (0.98-9.98)) and adults (adjusted OR?=?4.29; 95% CI, (2.04-9.0)); and children 6-11 years of age were more likely than adults to have N-desmethyl-acetamiprid concentrations above the 95th percentile (adjusted OR?=?2.65; 95% CI, (1.2-5.84)). Asians were more likely than non-Asians to have concentrations above the 95th percentile of N-desmethyl-acetamiprid (adjusted OR?=?1.94; 95% CI, (1.08-3.49)) and 5-hydroxy-imidacloprid (adjusted OR?=?2.25; 95% CI, (1.44-3.51)). Samples collected during the summer were more likely to have metabolite concentrations above the 95th percentile than those collected in the winter (adjusted OR 1.55 for N-desmethyl-acetamiprid, and 2.43 for 5-hydroxy-imidacloprid). CONCLUSIONS:The detection of neonicotinoid metabolites more frequently and at much higher concentrations than the corresponding parent compounds suggests that the metabolites may be suitable biomarkers to assess background exposures. About half of the U.S. general population 3 years of age and older was recently exposed to neonicotinoids. Compared to other age ranges and ethnicities, young children and Asians may experience higher exposures. At present, reasons for such differences remain unknown.
