Metabolic Effects in Rats Following Subchronic Exposure to Chlorpyrifos and Carbaryl

[Objective] To investigate the subchronic toxicity of pesticides chlorpyrifos (CPF) and carbaryl (CAR) at low levels to non-nervous systems and the combined effects of the two pesticides, especially on urinary metabolic profiles. [Methods] Wistar rats were administered orally with CPF and CAR respectively, or in combination for 90 consecutive days. Histopathological examination of liver and kidney, blood biochemical tests, and metabonomic analysis based on the urinary 1H nuclear magnetic resonance spectra were used to investigate the toxic effects. [Results] Increase of creatine, glycine, dimethylglycine, dimethylamine, glutamine, succinate, alanine, lactate, glucose and amino acids was observed in the CPF-treated rats. The categories of main differential urinary metabolites in CAR-treated rats were similar to those in CPF-treated rats, whereas, the changes were of varying degree. When rats were treated with the mixture of CPF and CAR, the levels of urinary metabolites increased in a dose-dependent manner. A combination of low dose of CPF and CAR resulted in an increase in the levels of main urinary metabolites compared to the controls, and the increase in signal intensity of the main metabolites was lower than that in the rats exposed to CPF or CAR respectively. [Conclusion] Subchronic exposure to CPF and CAR respectively, or in combination, could cause disturbance of metabolic function in liver mitochondria and renal insufficiency.