The progressive alteration of urine metabolomic profiles of rats following long-term and low-dose exposure to permethrin.

Permethrin is a type of widely used pyrethroid pesticide. Although acute toxicity of permethrin has been well-characterised, the non-acute toxicity of permethrin upon long-term exposure at low dose has been seldom studied yet. The current study investigates the time-course change of the metabolomic profiles of urine following the low level long-term exposure of permethrin and identified biomarkers of the chronic toxicity of permethrin. Male Wistar rats were administrated orally with permethrin (75 mg/kg body weight/day, 1/20 LD) daily for consecutive 90 days. The urine samples from day 30, day 60, and day 90 after the first dosing were collected and analysed by H NMR spectrometry. Serum biochemical analysis was also carried out. Permethrin caused significant changes in the urine metabolites such as taurine, creatinine, acetate, lactate, dimethylamine, dimethylglycine, and trimethylamine--oxide. These biological markers indicated prominent kidney and liver toxicity induced by permethrin. However, there was no change in serum biochemical parameters for the toxicity, indicating that metabolomic approach was much more sensitive in detecting the chronic toxicity. The time-course alteration of metabolomic profiles of the urine based on H NMR reflects the progressive development of the chronic toxicity with the long-term low-level exposure of permethrin.