基于PBPK模型评价三氯乙烯的职业暴露健康风险

Health Risk Assessment of Occupational Exposure to Trichloroethylene Based on PBPK Model

三氯乙烯(TCE)作为脱脂和清洗剂被广泛应用于五金、电镀和电子等行业。TCE的职业暴露会产生一系列健康风险,包括过敏症和致癌等。2012年TCE被美国环保局(US EPA)和国际癌症研究机构列为1类致癌物。采用吸附管采样-热脱附/气相色谱-质谱法分析了大连市某企业车间生产工况下空气中TCE浓度。基于生理学的药代动力学(PBPK)模型预测了呼吸暴露途径下TCE在职业工人体内组织中的动态分布、代谢产物生成情况和致癌风险。TCE在不同组织中预测的最大浓度呈现出脂肪>肠>充分灌注室>支气管>非充分灌注室>肝脏>静脉血>动脉血的趋势。预测的与致癌有关的代谢产物最大浓度表现为三氯乙酸>二氯乙酸>三氯乙醛>S-二氯乙烯基-L-半胱氨酸。在监测的TCE水平(39.2±24.4)μg·m^3下,暴露8 h·d^1,连续暴露20年,基于外暴露评价的职业工人致癌风险均值为1.31×10^5,该暴露水平下,基于PBPK模型预测的TCE内暴露与外暴露计算的致癌风险水平相近,但基于具有致癌性主要代谢产物的内暴露致癌风险值是外暴露风险值的1.17~1.73倍。TCE的暴露水平越高,基于内暴露方法和外暴露方法的致癌风险评价结果差异越大。敏感性分析表明,心输出血流量和充分灌注室血流量对PBPK模型输出结果具有重要影响。不确定性分析表明,模型参数变化会显著地影响PBPK模型输出结果,但变异在可接受水平。本研究结果说明,评价TCE暴露对人的致癌风险需要考虑其在体内的分布和代谢过程。

Trichloroethylene(TCE)has been used as a degreasing and cleaning agent in the hardware,electroplating,and electronic industries.Occupational exposure to TCE produces a range of health risks,including hypersensitivity syndrome and carcinogenicity.In 2012,TCE was classified as a Group 1 carcinogen to humans by the US Environmental Protection Agency(USEPA)and the International Agency for Research on Cancer.TCE air levels from manufacturing process of an enterprise in Dalian were analyzed by adsorption tube sampling and thermal desorption coupled with gas chromatography/mass spectrometry.The dynamic distribution,metabolite production and carcinogenic risk of TCE in tissue levels of occupational workers by inhalation exposure were predicted with physiologically based pharmacokinetic(PBPK)model.The predicted maximal tissue levels of TCE presented an accumulation trend of fat tissue>gut tissue>richly perfused tissue>tracheo-bronchial tissue>poorly perfused tissue>liver tissue>venous blood>arterial blood.The predicted maximal levels of metabolites with carcinogenicity presented an accumulation trend of trichloroacetate>dichloroacetate>chloral>S-(1,2-dichlorovinyl)-L-cysteine.The estimated mean cancer risk of occupational workers was 1.31×10^-5 based on external exposure at the monitored TCE level of(39.2±24.4)μg·m^-3 with an exposure duration of 8 h·d-^1 for 20 years.Under the detected exposure level,comparable risks were estimated by the internal tissue levels of TCE based on PBPK model and by the external exposure level of TCE,however,1.17 to 1.73 times of risk values were estimated based on internal exposure to the main carcinogenic metabolites than that of external exposure to TCE.The higher the exposure level of TCE,the greater the discrepancy between the assessment results of carcinogenic risk from internal exposure and external exposure methods.Sensitivity analysis showed that values of cardiac output and blood flow of richly perfused tissue highly affected the predicted results by PBPK model.Uncertainty analysis presented that the variation of model parameters significantly affected the output of cancer risk assessment.Nonetheless the variation was acceptable.It was indicated that it was necessary to consider in vivo distribution and metabolism of TCE in the assessment of the carcinogenic risk for human being.