Yang_2025_Environ.Pollut__126404

The widespread use of neurotoxic neonicotinoid pesticides (NEOs) has raised public health concerns. Although studies have revealed that NEOs exist in humans, the lack of suitable biomarkers has prevented us from systematically evaluating the harm of NEOs to human physiological functions. This study assessed the levels of NEOs and their metabolites (m-NEOs) in pairwise serum and urine samples from 144 patients with neurologic disorders and 30 healthy individuals. Correlations between biomarkers reflecting exposure and organ functions were analyzed. Our results revealed that the concentrations of urinary olefin-imidacloprid (Of-IMI) and thiamethoxam (THX) were 52.4 and 19.0 times higher than those in serum in the 15 types of NEOs and their m-NEOs. Notably, N-desmethyl acetamiprid (N-dm-ACE) dominated the levels of NEOs and m-NEOs in urine and serum, with the highest median concentrations being 2.58 ng/mL and 0.183 ng/mL, respectively. The composition profiles of the urinary NEOs and m-NEOs were dependent on sex, age, and disease type. Some biomarkers, i.e., inflammatory parameters, serum albumin (ALB), and cholinesterase (CHE), are closely correlated with the levels of NEOs and m-NEOs. Mediation analysis revealed that these biomarkers significantly mediated the relationships between the degree of exposure of NEOs and neurological impairments. Therefore, biomarkers reflecting the toxicity of NEOs and m-NEOs are urgently needed to evaluate the impairments of individuals with long-term exposure.