对苯二甲酸的毒代动力学研究

通过研究对苯二甲酸 (TPA)在大鼠的毒代动力学 ,为制定生物接触限值 (BEI)提供依据。选清洁级 SD大鼠 8只 ,一次性灌胃染毒 10 0 mg/ kg BW TPA后 ,采用反相高效液相色谱法测定尿 TPA浓度 ,用3P97计算毒代动力学参数。结果显示 ,TPA在体内的毒代动力学行为符合一级吸收二室模型 ,吸收速率常数 ka为 0 .5 1/ h,吸收相半衰期 t1 /2 ka=0 .488h,分布相半衰期 t1 /2 d为 2 .44 6 h,达峰时间 tpeak为 2 .16 h,消除速率常数 K u为 0 .143/ h,消除相半衰期 t1 /2β为 31.5 5 1h,TPA经尿排泄累积量为 10 .0 0 mg,2 4h内约 5 0 %的 TPA由尿排泄 ,48h内约 5 2 % ,72 h内约 5 3%以上的 TPA由尿排泄。结论 :TPA在体内吸收快、消除快 ,主要以原形由尿排泄 ,提示职业人群的工后尿 TPA可作为接触性生物标志物。

Toxicokinetics of terephthalic acid

In order to study the toxicokinetics of terephthalic acid(TPA) in rats, and provide scientific basis for its biological exposed index (BEI), the concentrations of urine TPA in rats after single oral administration in dose of 100 mg/kg BW were determined by high pressure liquid chromatography. The toxicokinetic parameters were computed by using 3P97 program. The results showed that the first-order kinetics and two-compartment model were noted on the elimination of TPA. The main toxicokinetic parameters were as follows: Ka = 0.51/h, T1/2ka = 0.488 h, T1/2 alpha = 2.446 h, Tpeak = 2.160 h, Ku = 0.143/h, T1/2 beta = 31.551 h, Xu(max) = 10.00 mg. The excretion rates of TPA in urine were about 50%, 52% and 53% in 0-24 h, 0-48 h and 0-72 h respectively after administration. TPA is well absorbed when given orally and rapidly eliminated via urine. Urine TPA at the end of work shift should be considered as a biomarker of exposure for the occupational workers.