Background: 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.Methods: Male Wistar rats were administrated orally with permethrin (75 mg/kg body weight/day, 1/20 LD50) 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 1H NMR spectrometry. Serum biochemical analysis was also carried out.Results: Permethrin caused significant changes in the urine metabolites such as taurine, creatinine, acetate, lactate, dimethylamine, dimethylglycine, and trimethylamine-N-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.Conclusion: The time-course alteration of metabolomic profiles of the urine based on 1H NMR reflects the progressive development of the chronic toxicity with the long-term low-level exposure of permethrin.

中文翻译：

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长期和小剂量氯菊酯暴露后大鼠尿代谢组学特征的逐步改变。

背景：氯菊酯是一种广泛使用的拟除虫菊酯农药。尽管苄氯菊酯的急性毒性已被很好地表征，但很少研究长期低剂量接触苄氯菊酯的非急性毒性。当前的研究调查了长期低剂量氯菊酯暴露后尿中代谢组学谱随时间的变化，并鉴定了氯菊酯慢性毒性的生物标志物。方法：雄性Wistar大鼠口服氯菊酯（75 mg / kg）体重/天，连续90天每天1/20 LD50）。收集第一次给药后第30天，第60天和第90天的尿液样品，并通过1H NMR光谱分析。结果：苄氯菊酯引起牛磺酸，牛磺酸等尿液代谢产物的显着变化。肌酐，乙酸盐，乳酸盐，二甲胺，二甲基甘氨酸和三甲胺-N-氧化物。这些生物学标记表明苄氯菊酯可引起显着的肾脏和肝脏毒性。然而，血清中生化参数没有改变，表明该代谢组学方法对检测慢性毒性更为敏感。结论：基于1H NMR的尿液代谢组学谱随时间变化反映了尿毒症的逐步发展。长期低浓度的苄氯菊酯的慢性毒性。