Associations between Neonicotinoid, Pyrethroid, and Organophosphate Insecticide Metabolites and Neurobehavioral Performance in Ecuadorian Adolescents

Abstract Background Organophosphate and pyrethroid insecticides can affect children’s neurodevelopment and increase inflammation. Limited evidence exists among adolescents and on whether inflammation may mediate pesticide–neurobehavior associations. We examined the associations between insecticide metabolite concentrations and neurobehavior among adolescents in Ecuadorian agricultural communities. Methods We included 520 participants aged 11-17 years. We measured urinary insecticide metabolites (mass spectrometry) and neurobehavior (NEPSY-II). Associations were adjusted for socio-demographic and anthropometric characteristics. The associations of insecticide mixtures with neurobehavior were evaluated using PLS regression, and mediation by inflammatory biomarkers (TNF-α, IL-6, CRP, SAA, sICAM-1, sVCAM-1 and sCD-14) was conducted. 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 [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 >60 th 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, 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. The neonicotinoid 5-Hydroxy imidacloprid (OHIM) was positively associated with Memory/Learning (β 50% = 0.20 [95%CI: 0.04, 0.37]). Mixtures of all insecticides were significantly negatively related to all domains, except for Memory/Learning, which was positively associated. No mediation by inflammatory markers on these associations was observed. Conclusions Concurrent organophosphate, pyrethroid, and the mixtures of all metabolites were associated with lower performance in all domains except for Memory/Learning. Neonicotinoids were positively associated with Memory/Learning and Social Perception scores.