Exposure to organophosphate, pyrethroid, and neonicotinoid insecticides and dyslexia: Association with oxidative stress

Organophosphates (OPPs), pyrethroids (PYRs), and neonicotinoids (NNIs) are three major classes of insecticides used worldwide. They might compromise child neurodevelopment. However, few studies have explored the association between exposure to them and dyslexia. The present study aimed to investigate the association between dyslexia and exposure to the three classes of insecticides, as well as explore the potential role of oxidative stress in the association. A total of 355 dyslexic children and 390 controls were included in this study. The exposure biomarkers were determined by liquid chromatography-tandem mass spectrometry. Specifically, the exposure biomarkers included three typical metabolites of OPPs, three of PYRs, and nine of NNIs. Additionally, three typical oxidative stress biomarkers, namely, 8-hydroxy-2 ' -deoxyguanosine (8-OHdG) for DNA damage, 8hydroxyguanosine (8-OHG) for RNA damage, and 4-hydroxy-2-nonenal-mercapturic acid (HNEMA) for lipid peroxidation were measured. The detection frequencies of the urinary biomarkers ranged from 83.9% to 100%. Among the target metabolites of the insecticides, a significant association was observed between urinary 3,5,6trichloro-2-pyridinol (TCPy, the metabolite of chlorpyrifos, an OPP insecticide) and dyslexia. After adjusting for potential confounding variables, children in the highest quartile of TCPy levels had an increased odds of dyslexia (odds ratio [OR], 1.68; 95% confidence interval [CI]: 1.03, 2.75] in comparison to those in the lowest quartile. Among the three oxidative stress biomarkers, urinary HNEMA concentration showed a significant relationship with dyslexia. Children in the highest quartile of HNEMA levels demonstrated an increased dyslexic odds in comparison to those in the lowest quartile after multiple adjustments (OR, 1.64; 95% CI: 1.01, 2.65). Mediation analysis indicated a significant effect of HNEMA in the association between urinary TCPy and dyslexia, with an estimate of 17.2% (P < 0.01). In conclusion, this study suggested the association between urinary TCPy and dyslexia. The association could be attributed to lipid peroxidation partially.