Farrar D, Allen B, Crump K, Shipp A
Clement Associates, Inc., Ruston, LA 71270.
Toxicol Lett. 1989 Dec;49(2-3):371-85. doi: 10.1016/0378-4274(89)90044-1.
Physiologically-based pharmacokinetic (PBPK) models may be used to predict the concentrations of parent chemical or metabolites in tissues, resulting from specified chemical exposures. An important application of PBPK modeling is in assessment of carcinogenic risks to humans, based on animal data. The parameters of a PBPK model may include metabolic parameters, blood/air and tissue/blood partition coefficients, and physiological parameters, such as organ weights and blood flow rates. Uncertainty in estimates of these parameters results in uncertainty regarding tissue concentrations and resulting risks. Data are reviewed relevant to the quantification of these uncertainties, for a PBPK model-based risk assessment for tetrachloroethylene. Probability distributions are developed to express uncertainty in model parameters, and uncertainties are propagated by a sequence of operations that simulates processes recognized as contributing to estimates of human risk. Distributions of PBPK model output and human risk estimates are used to characterize uncertainty resulting from uncertainty in model parameters.
基于生理学的药代动力学（PBPK）模型可用于预测特定化学物质暴露后，母体化学物质或代谢产物在组织中的浓度。PBPK建模的一个重要应用是基于动物数据评估对人类的致癌风险。PBPK模型的参数可能包括代谢参数、血/气和组织/血分配系数，以及生理参数，如器官重量和血流速率。这些参数估计中的不确定性导致了组织浓度和由此产生的风险的不确定性。回顾了与这些不确定性量化相关的数据，用于基于PBPK模型的四氯乙烯风险评估。开发概率分布以表达模型参数中的不确定性，并通过一系列模拟被认为有助于估计人类风险的过程的操作来传播不确定性。PBPK模型输出和人类风险估计的分布用于表征模型参数不确定性导致的不确定性。
