Boerleider R Z, Olie J D N, van Eijkeren J C H, Bos P M J, Hof B G H, de Vries I, Bessems J G M, Meulenbelt J, Hunault C C
National Poisons Information Center, University Medical Center Utrecht (UMCU), P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80178, 3508 TD Utrecht, The Netherlands.
National Poisons Information Center, University Medical Center Utrecht (UMCU), P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Toxicol Lett. 2015 Jan 5;232(1):21-7. doi: 10.1016/j.toxlet.2014.10.010. Epub 2014 Oct 13.
Physiologically based pharmacokinetic (PBPK) models may be useful in emergency risk assessment, after acute exposure to chemicals, such as dichloromethane (DCM). We evaluated the applicability of three PBPK models for human risk assessment following a single exposure to DCM: one model is specifically developed for DCM (Bos) and the two others are semi-generic ones (Mumtaz and Jongeneelen).
We assessed the accuracy of the models' predictions by simulating exposure data from a previous healthy volunteer study, in which six subjects had been exposed to DCM for 1h. The time-course of both the blood DCM concentration and percentage of carboxyhemoglobin (HbCO) were simulated.
With all models, the shape of the simulated time course resembled the shape of the experimental data. For the end of the exposure, the predicted DCM blood concentration ranged between 1.52-4.19mg/L with the Bos model, 1.42-4.04mg/L with the Mumtaz model, and 1.81-4.31mg/L with the Jongeneelen model compared to 0.27-5.44mg/L in the experimental data. % HbCO could be predicted only with the Bos model. The maximum predicted % HbCO ranged between 3.1 and 4.2% compared to 0.4-2.3% in the experimental data. The % HbCO predictions were more in line with the experimental data after adjustment of the Bos model for the endogenous HbCO levels.
The Bos Mumtaz and Jongeneelen PBPK models were able to simulate experimental DCM blood concentrations reasonably well. The Bos model appears to be useful for calculating HbCO concentrations in emergency risk assessment.
基于生理的药代动力学（PBPK）模型可能有助于在急性接触二氯甲烷（DCM）等化学品后的应急风险评估。我们评估了三种PBPK模型在单次接触DCM后用于人体风险评估的适用性：一种模型是专门为DCM开发的（Bos模型），另外两种是半通用模型（Mumtaz模型和Jongeneelen模型）。
我们通过模拟先前一项健康志愿者研究中的暴露数据来评估模型预测的准确性，在该研究中，六名受试者接触DCM 1小时。模拟了血液中DCM浓度和碳氧血红蛋白（HbCO）百分比的时间进程。
使用所有模型时，模拟时间进程的形状与实验数据的形状相似。在接触结束时，Bos模型预测的DCM血液浓度范围为1.52 - 4.19mg/L，Mumtaz模型为1.42 - 4.04mg/L，Jongeneelen模型为1.81 - 4.31mg/L，而实验数据中的范围为0.27 - 5.44mg/L。只有Bos模型能够预测HbCO百分比。预测的最大HbCO百分比范围在3.1%至4.2%之间，而实验数据中的范围为0.4% - 2.3%。在根据内源性HbCO水平对Bos模型进行调整后，HbCO百分比预测与实验数据更相符。
Bos、Mumtaz和Jongeneelen PBPK模型能够较好地模拟实验性DCM血液浓度。Bos模型似乎可用于在应急风险评估中计算HbCO浓度。
