摘要:
环境中同时存在着多种重金属元素,联合暴露与单独暴露时,重金属在体内的蓄积分布情况也可能有所差异。为探究重金属元素(汞、铬、砷、铅)对镉(Cd)在体内分布的影响,建立了大鼠在Cd暴露下的药代动力学(PBPK)模型,并进行了包括Cd在内5种重金属的联合毒性实验,比较了Cd单独给药与重金属混合物给药2种方式下大鼠肝脏、肾脏中的Cd浓度水平。结果表明,联合暴露高(HgCl2 3.67 mg·kg-1,NaAsO2 3.67 mg·kg-1,CdCl2 10.55 mg·kg-1,K2Cr2 O7 6.40 mg·kg-1,Pb(OOCCH3)2·3H2O 133.33 mg·kg-1)、中(HgCl2 0.367 mg·kg-1,NaAsO2 0.367 mg·kg-1,CdCl2 1.055 mg·kg-1,K2Cr2O7 0.640 mg·kg-1,Pb(OOCCH3)2·3H2O 13.333 mg·kg-1)、低(HgCl2 0.0367 mg·kg-1,NaAsO2 0.0367 mg·kg-1,CdCl2 0.1055 mg·kg-1,K2 Cr2O7 0.0640 mg·kg-1,Pb(OOCCH3)2 ·3H2 O 1.3333 mg·kg-1)剂量组大鼠肝脏中Cd浓度分别为13.37、0.78和0.06 μg·g-1;肾脏中Cd浓度分别为14.41、1.64和0.15 μg·g-1。与对照组相比,暴露组中Cd浓度有显著升高,且不同剂量组之间均有显著性差异。同剂量Cd单独暴露的PBPK模拟结果显示,肝脏及肾脏中的Cd浓度水平落在联合毒性实验结果的浓度范围内,初步推断其他4种重金属的联合暴露并没有影响Cd在大鼠肾脏和肝脏中的浓度分布。
Abstract:
The distribution in vivo of metals mixture might be different from that of individual metals. In order to explore the influence of four metals (mercury, chromium, arsenic and lead) on the distribution of cadmium (Cd) in vivo, a physiologically based pharmacokinetic model (PBPK) was constructed to simulate the absorption, distribution, metabolism and excretion (ADME) of Cd in rats exposed to individual Cd. The levels of Cd in liver and kidney exposed to metals mixture were obtained from a joint toxicity experiment. The experiment results showed that the concentrations of Cd in liver in high (HgCl2 3.67 mg·kg-1, NaAsO2 3.67 mg·kg-1, CdCl2 10.55 mg·kg-1, K2Cr2 O7 6.40 mg·kg-1, Pb(OOCCH3)2·3H2O 133.33 mg·kg-1), medium (HgCl2 0.367 mg·kg-1, NaAsO2 0.367 mg·kg-1, CdCl2 1.055 mg·kg-1, K2Cr2O7 0.640 mg·kg-1, Pb(OOCCH3)2·3H2O 13.333 mg·kg-1) and low (HgCl2 0.0367 mg·kg-1, NaAsO2 0.0367 mg·kg-1, CdCl2 0.1055 mg·kg-1, K2 Cr2O7 0.0640 mg·kg-1, Pb(OOCCH3)2 ·3H2 O 1.3333 mg·kg-1) dose groups were 13.37, 0.78 and 0.06 μg·g-1, respectively; and those in kidney were 14.41, 1.64 and 0.15 μg·g-1, respectively. There were significant differences between the control group and exposure groups. The simulated concentrations of Cd in liver and kidney were in the range of the corresponding experimental concentrations. It is preliminarily inferred that the co-exposure with other four heavy metals had no obvious influence on Cd distribution in liver and kidney of rats.