Associations between concurrent neonicotinoid, pyrethroid, and organophosphate insecticide metabolites and neurocognitive performance in Ecuadorian adolescents.

BACKGROUND: Organophosphate and pyrethroid insecticides can affect children's neurodevelopment and increase inflammation. Limited evidence exists in adolescents, and whether inflammation mediates pesticide-neurobehavior associations. We tested whether concurrent urinary insecticide metabolites decrease neurocognitive performance among adolescents in Ecuadorian agricultural communities. METHODS: We analyzed 520 adolescents (12-17 years), measuring urinary insecticide metabolites and cognitive performance (NEPSY-II); associations were tested with generalized estimating equations, mediation via serum inflammatory biomarkers with structural equation modeling, and mixtures with Partial Least Squares regression. RESULTS: Among organophosphates, para-nitrophenol (PNP) and 3,5,6-Trichloro-2-pyridinol (TCPy) were inversely associated with Social Perception (score difference per 50 % increase [beta coefficients (β)50%] = -0.26 [95 %CI: -1.07, -0.20] and - 0.10 [-0.22, 0.01], respectively). PNP and TCPy also had significant inverse associations with Attention/Inhibitory Control at concentrations >60th percentile (β 50% = -0.26 [95 %CI: -0.51, -0.01] and β 50% = -0.22 [95 %CI: -0.43, -0.00], respectively). The pyrethroid metabolite, 3-phenoxybenzoic acid (3-PBA), was inversely associated with Language (β 50% = -0.13 [95 %CI: -0.19, -0.01]) and had a negative quadratic association with Attention/Inhibitory Control. Neonicotinoid metabolites were positively associated with either Attention/Inhibitory Control or Memory/Learning, although metabolites had low detectability (26 %-37 %). The insecticide mixture was negatively associated with Attention & Inhibitory Control, Language, Visuospatial Processing, Social Perception, and positively with Memory & Learning. No mediation by inflammatory markers in these associations was observed. CONCLUSIONS: Concurrent organophosphate, pyrethroid, and mixtures of all metabolites assessed were associated with lower performance in 4 of 5 cognitive domains in adolescents. Pesticide reduction of people in agricultural settings should be prioritized.