Thomas R S, Bigelow P L, Keefe T J, Yang R S
Department of Environmental Health, Colorado State University, Fort Collins 80523, USA.
Am Ind Hyg Assoc J. 1996 Jan;57(1):23-32. doi: 10.1080/15428119691015188.
By using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation, the interindividual variability in the concentrations of chemicals in a worker's exhaled breath and urine were estimated and compared with existing biological exposure indices (BEIs). The PBPK model simulated an exposure regimen similar to a typical workday, while exposure concentrations were set to equal the ambient threshold limit values (TLVs) of six industrial solvents (benzene, chloroform, carbon tetrachloride, methylene chloride, methyl chloroform, and trichloroethylene). Based on model predictions incorporating interindividual variability, the percentage of population protected was derived using TLVs as the basis for worker protection. Results showed that current BEIs may not protect the majority or all of the workers in an occupational setting. For instance, current end-expired air indices for benzene and methyl chloroform protect 95% and less than 10% of the worker population, respectively. Urinary metabolite concentrations for benzene, methyl chloroform, and trichloroethylene were also estimated. The current BEI recommendation for phenol metabolite concentration at the end-of-shift sampling interval was estimated to protect 68% of the worker population, while trichloroacetic acid (TCAA) and trichloroethanol (TCOH) concentrations for methyl chloroform exposure were estimated to protect 54% and 97%, respectively. The recommended concentration of TCAA in urine as a determinant of trichloroethylene exposure protects an estimated 84% of the workers. Although many of the existing BEIs considered appear to protect a majority of the worker population, an inconsistent proportion of the population is protected. The information presented in this study may provide a new approach for administrative decisions establishing BEIs and allow uniform application of biological monitoring among different chemicals.
通过使用基于生理学的药代动力学（PBPK）模型并结合蒙特卡洛模拟，估算了工人呼出气体和尿液中化学物质浓度的个体间变异性，并与现有的生物接触指数（BEIs）进行了比较。PBPK模型模拟了类似于典型工作日的暴露方案，同时将暴露浓度设定为等于六种工业溶剂（苯、氯仿、四氯化碳、二氯甲烷、甲基氯仿和三氯乙烯）的环境阈限值（TLVs）。基于纳入个体间变异性的模型预测，以TLVs作为工人保护的基础，得出了受保护人群的百分比。结果表明，当前的BEIs可能无法保护职业环境中的大多数或所有工人。例如，当前苯和甲基氯仿的终末呼气指数分别仅能保护95%和不到10%的工人。还估算了苯、甲基氯仿和三氯乙烯的尿代谢物浓度。当前针对轮班结束采样间隔时苯酚代谢物浓度的BEI建议估计可保护68%的工人，而甲基氯仿暴露时三氯乙酸（TCAA）和三氯乙醇（TCOH）的浓度估计分别可保护54%和97%的工人。作为三氯乙烯暴露决定因素的尿液中TCAA的推荐浓度估计可保护约84%的工人。尽管所考虑的许多现有BEIs似乎能保护大多数工人，但受保护人群的比例并不一致。本研究中提供的信息可能为制定BEIs的行政决策提供一种新方法，并允许在不同化学物质之间统一应用生物监测。
