Longitudinal Health Risk Assessment of Neonicotinoid Exposure and Its Association with Dietary Sources in School-Aged Children: A Prospective Cohort Study

Neonicotinoid insecticides (NNIs) are globally pervasive, and toxicological evidence indicates potential adverse effects from low-dose exposure in non-targeted organisms. Humans may be exposed to NNIs through multiple pathways, such as ingestion and inhalation, with dietary intake recognized as the dominant exposure route. However, longitudinal evidence characterizing evolving exposure patterns in rural children remains scarce. We evaluated temporal trends and dietary determinants of NNI exposure among 643 children at ages 7, 10, and 14 years in the Sheyang Mini Birth Cohort Study. Twelve NNIs and six metabolites in urine samples were measured using UPLC-HRMS; estimated daily exposure doses and hazard index (HI) were calculated, and linear mixed models were used to evaluate dietary determinants of NNI exposure. Widespread exposure was observed (ΣNNIs detection: 98.8-100%), and although cumulative risks remained below safety thresholds, both medians and upper bounds of HI increased with age (0.0007 to 0.0074; 0.2045 to 0.4054). Notably, exposure composition shifted, with declining imidacloprid and emerging dominance of clothianidin (CLO) and thiamethoxam (THM). Fruit and vegetable intakes were positively associated with ΣNNIs, whereas cereals, poultry, and eggs showed inverse associations, with more pronounced effects observed in boys. These findings indicated persistent yet evolving exposure risks in school-aged children, highlighting fruits and vegetables as major contributors. Although current toxicological risk appears low, the transition toward CLO and THM-compounds with limited chronic toxicity data-underscores the need for continued biomonitoring and targeted exposure mitigation.