Extended one generation reproductive toxicity study of thiamethoxam technical in rats

Thiamethoxam, a second-generation neonicotinoid insecticide was assessed for its systemic and reproductive toxicity, developmental neurotoxicity and immunotoxicity through an extended one generation toxicity study (EOGRTS, OECD No. 443). Wistar rats were exposed to Thiamethoxam at doses of 0, 15, 50 and 150 mg/kg/day by oral intubation. Treatment of males was initiated 2-weeks before cohabitation and continued for 70 consecutive days whereas treatment of females began 2 weeks before cohabitation and continued until weaning of the F1 offspring. In view of reducing the number of animals, but without compromising on parameters to be assessed, cohort 1A was covered in the parental generation. Treatment with Thiamethoxam technical did not reveal any systemic/reproductive toxicity and abnormal changes in the fertility parameters of rats belonging to parental generation. However, males belonging to the F1 generation exhibited delay in the acquisition of balano-preputial separation and, decreased total and ambulatory counts at 50 and 150mg/kg/day. A decrease in the overall width of hippocampus was observed at 150mg/kg/day. The T-cell dependent antibody response (TDAR) functional assay exhibited the ability of Thiamethoxam to mount an antibody (IgM and/or IgG) response up to 150 mg/kg/day in the F1 generation. Based on findings, the No Observed Adverse Effect Level (NOAEL) of Thiamethoxam was 15 mg/kg/day for developmental and neurobehavioral end points and 150 mg/kg/day for reproductive toxicity.