Human Health Risk Assessment For Joint Toxicity Of Cu And Zn Based On PBPK Modeling

With the industrial development and economic increasing, heavy metal pollution accidents have happened so frequently across the country, which have severely threatened public health, environmental safety and sustainable development of economy as well as society. In order to protect people’s health, reduce the loss to economy and society and the harm to environment, an effective health risk assessment system with practical measures is urgently needed.There is still a long way to go for the development of health risk assessment and there are so many ways to improve, especially in the aspect of joint toxicity study. Since lacking of basic data, the results of risk assessment are low in accuracy. Or in other cases, because of no further consideration of joint toxicity, the assessment methods can only be applied in a narrow range. Therefore, this study aims to combine joint toxicity study and health risk assessment together to improve the disadvantage of the present methods, hoping to make some helpful and meaningful trials and explorations in this area.The study focuses on the situation in which more than one kind of heavy metal exist and interact in the same environmental area. In the first step, study the joint toxicity of Cu and Zn to check the joint toxicity type. After summarizing the toxic data, an acute toxicity experiment is held to get the experimental data of LC50, enzyme activity and heavy metals concentration in livers. The numbers of AI are all positive and therefore the joint toxicity of Cu and Zn is synergy. The mono factor analysis of variance is taken for the data of SOD and GSH-PX, and the P values are less than0.05. A t-test is also held between the concentration groups, and in95%confidence interval P values are all less than0.05. Both tests results show the joint toxicity has significant influence on the enzyme activity. By analyzing the data of heavy metals in livers, there is a trend of the concentration of Cu and Zn which is growing to the top and then decreasing gradually. Consequently, a conclusion is made that under the experimental condition, the joint toxicity of Cu and Zn is synergy which means when they exist together there will be much more severe toxicity effects to human.Meanwhile a PBPK model was established for the dose-effect analysis. Firstly select organs to build the model construction, then choose the proper mathematical formula to convey the pharmacokinetic and physiological process, and pick the parameters including physiological parameters, partition coefficients and biochemical parameters to run the model. It is important to evaluate the modeling results before applying to the analysis, making sure the model suitable and applicable for the situation in the study. The modeling results show the heavy metals gathering in the livers and kidneys while there are little amount in the blood and heart. After all that the model can be used for exposure period extrapolation and dose extrapolation in the dose-effect analysis.Finally calculate the hazard index of Cu and Zn by interaction-based HI calculation, and evaluate the health risk caused by joint toxicity of Cu and Zn. PBPK model is also used in this step to estimate the concentration of heavy metals in organs on the safe dose exposure.The ideas and methods mentioned above in this study are applied for a case study of a lead and zinc mining area in eastern part of China. Make the assessment of health risks of residents in drinking water exposure, who live around the metal mine. The exposure investigation results are calculated by a model recommended by EPA, which show that the exposure dose for Cu is5.63E-05mg/L while Zn is3.27E-03mg/L. After that the dose-effect analysis by PBPK modeling extrapolation is held, and the data show the metabolism process of Cu and Zn. While calculating the HI, safe dose are selected by the EPA guide, with Cu5.0E-03mg/L and Zn3.0E-01mg/L. The HI results are generally high and during the whole exposure period, the HI value grows to the top and decreases slowly. The highest value is1.08, while the lowest is0.06with the average value0.75. The results show in spite of the exposure doses of both Cu and Zn are lower than safe dose, the hazard indexes are higher than expected. As a result risk alleviation measures including pollution control, cutting exposure routes and receptor protection should be taken to protect residents’health.