基于配体络合常数的毒代-毒效动力学(TK-TD)模型预测不同pH下镉和铅在斑马鱼幼鱼体内的积累和毒性

Prediction of Accumulation and Toxicity of Cadmium and Lead in Zebrafish Larvae at Different pH Using A Toxicokinetic-toxicodynamic(TKTD)Model Based on Ligand Complex Constant

复杂多变的水化学条件影响重金属生物有效性和毒性,进一步影响水质基准的制定,需要建立既考虑水化学条件又考虑时间过程的毒代动力学-毒效动力学(toxicokinetics-toxicodynamics, TK-TD)模型去实时地模拟金属的生物蓄积性及产生的毒性。本研究将生物配体模型(biotic ligand model, BLM)中氢离子与配体络合常数(K_(HBL))引入TK-TD模型,尝试建立预测水环境不同pH条件下金属毒性的理论模型框架,分别预测镉(Cd)和铅(Pb)在染毒溶液pH为4.5、5.5和6.5下在斑马鱼幼鱼体内的积累和急性毒性,并验证该模型框架的有效性和合理性。结果表明,Pb的最大吸收速率(J_(max))比Cd大约3倍。Cd的致死速率(kk)是Pb的4倍。Cd和Pb的安全阈值(threshold)之间相差30倍。染毒溶液中H+浓度增加可显著抑制Cd和Pb在斑马鱼幼鱼体内的累积量。基于KHBL的TK-TD模型可以较好地预测染毒溶液不同pH(pH=4.5、5.5和6.5)条件下,非必需元素Cd和Pb在斑马鱼幼鱼体内的累积量及产生的毒性。

The complex and ever-changing hydro-chemical conditions affect the bioavailability and toxicity of heavy metals,which further affects the formulation of water quality standards.There is a high demand for develo-ping a toxicokinetic-toxicodynamic(TK-TD)model that considers both hydro-chemical conditions and time proces-ses to simulate the bioaccumulation and toxicity of heavy metals in real-time.This study attempts to establish a the-oretical model framework for predicting the toxicity of heavy metals under different pH conditions in the aquatic environment.Additionally,the present work involves the introduction of hydrogen ion-ligand complex constant(K_(HBL))in the biotic ligand model(BLM)into a TK-TD model,by predicting the accumulation and acute toxicity of cadmium(Cd)and lead(Pb)in zebrafish(Daniorerio)larvae that are exposed to the aquatic environment of vari-ous pH levels(4.5,5.5,and 6.5).Also,the verification of the effectiveness and rationality of the corresponding model frameworks was carried out in this work.Results showed that the maximum uptake rate(J_(max))of Pb was three times higher than that of Cd.The killing rate kk of Pb is four times lower than that of Cd in the zebrafish lar-vae.The safe threshold variation between Cd and Pb was found to be 30-fold.Further,the increased H+concentra-tion in poisoning solutions can significantly inhibit the accumulation of Cd and Pb in zebrafish larvae.In conclu-sion,the KHBL-refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb in zebrafish larvae at pH 4.5,5.5,and 6.5.