邻苯二甲酸酯暴露的大鼠尿液生物标志物研究

建立了检测尿液中邻苯二甲酸酯类化合物(PAEs)共同水解产物邻苯二甲酸(PA)的分析方法;通过雄性成年SD大鼠代谢试验,检测了邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二(2-乙基己基)酯(DEHP)单独暴露、以及联合暴露条件下大鼠尿液中PA总量,并分析了PA与暴露总量之间的关系.结果显示,随着暴露剂量的增大,尿液中排出的PA总量也不断增大;DBP单独暴露、DEHP单独暴露以及两者联合暴露时尿液PAEs代谢物平均排泄总量占摄入量的百分比分别为65.04%、55.00%和38.35%;大鼠尿液中PA的摩尔总量与DBP、DEHP、以及两者联合暴露的摩尔量之间的相关系数分别为0.92(P0.01)、0.56(P0.01)、0.93(P0.01).尿液水解后的PA能够反映PAEs类物质的总暴露水平,将来可能作为一种潜在的暴露生物标志物用于人群的PAEs暴露监测.

Urine biomarker of exposure to phthalate in rat

A high performance liquid chromatographic (HPLC) method was developed for the determination of phthalic acid (PA) in urine after alkaline hydrolysis of the phthalate metabolites to PA. The content of the total PA in male adult SD rat urine was measured after separated or combined exposure to dibutyl phthalate (DBP) and di 2-ethyl hexyl phthalate (DEHP), and then the relationships between exposed PAEs molar quantities and the molar concentration of the urine PA were analyzed by linear regression. The results showed that the total amount of urine PA increased as the exposure increased. The mean percentage of PAEs intake excreted in the urine was found to be 65.04% for DBP exposure alone and 55.00% for DEHP exposure alone and 38.35% for combined exposure to the two. The contents of urinary PA were well correlated with PAEs exposure levels with the correlation coefficient being 0.92 for DBP(P<0.01), 0.56 for DEHP (P<0.01) and 0.93 for combined DPB and DEHP (P<0.01). The findings suggested that PA in urine after alkaline hydrolysis of the phthalate metabolites could evaluate the total exposure level of PAEs, which may be a valid exposure biomarker of PAEs used in risk surveillance of human exposure to PAEs in future.