Heavy metals and pesticides can be easily enriched in food chains and accumulated in organisms, thus pose significant threat to human health. However, their combined effects for long-term exposure at low dose has not been thoroughly investigated; especially there was no biofluid biomarker available to noninvasively diagnose the toxicosis of the combined exposure of the two chemicals at their low levels. In this study, we investigated the change of urine metabolites of rats with 90-day exposure to heavy metal cadmium (Cd) and/or organophosphorus pesticide chlorpyrifos (CPF) using gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach. Our results showed that the interaction of Cd and CPF mainly displayed an antagonistic effect. We identified the panels of metabolite biomarkers in urine: benzoic acid and mannose were unique biomarkers for Cd exposure; creatinine and N-phenylacetyl glycine were unique biomarkers for CPF exposure; anthranilic acid, ribitol, and glucose were unique biomarkers for Cd plus CPF exposure. Our results suggest that 90-day exposure to Cd and/or CPF could cause a disturbance in energy and amino acid metabolism. And urine metabolomics analysis can help understand the toxicity of low dose exposure to mixed environmental chemicals.

重金属和农药很容易在食物链中富集并在有机体中积累，从而对人类健康构成重大威胁。然而，它们对低剂量长期暴露的综合影响尚未得到彻底研究。尤其是，目前没有生物流体生物标记物可用于无创地诊断两种化学品低浓度联合暴露的毒性。在这项研究中，我们使用基于气相色谱-质谱（GC-MS）的代谢组学方法研究了暴露于重金属镉（Cd）和/或有机磷农药毒死rif（CPF）90天的大鼠尿液代谢产物的变化。我们的结果表明，Cd和CPF的相互作用主要表现出拮抗作用。我们鉴定了尿液中的代谢物生物标志物：苯甲酸和甘露糖是镉暴露的独特生物标记。肌酐和N-苯基乙酰基甘氨酸是CPF暴露的独特生物标志物。邻氨基苯甲酸，核糖醇和葡萄糖是Cd和CPF暴露的独特生物标志物。我们的结果表明90天的Cd和/或CPF暴露可能会导致能量和氨基酸代谢紊乱。尿液代谢组学分析可以帮助了解低剂量暴露于混合环境化学物质的毒性。