Kumagai S, Matsunaga I, Tabuchi T
Department of Occupational Health, Osaka Prefectural Institute of Public Health, Japan.
Am Ind Hyg Assoc J. 1998 Apr;59(4):242-51. doi: 10.1080/15428119891010505.
Using a physiologically based pharmacokinetic (PBPK) model, the effects of variation of exposure concentration of acetone on three biological indicators--acetone concentrations in blood, urine, and exhaled air--were investigated. The effect of the difference in work load was also examined. It was confirmed that the model could be used to estimate acetone concentrations during fluctuating exposure by comparing simulated acetone concentrations with the corresponding values observed in field surveys. By inputting the exposure situations into the PBPK model, the variabilities of the biological indicators were simulated. The variation of acetone exposure was expressed by seven 1-hour time-weighted averages (CEXPs). The arithmetic means of the CEXPS were 200 and 750 ppm. The geometric standard deviations (GSDs) were 1.5, 2.0, and 3.0, representing low, moderate, and high variations, respectively. Work loads were set at 15 and 50 W. Consequently, there were 12 exposure situations. The acetone concentrations in venous blood (CB) and exhaled alveolar air (CA) at 1 minute after the end of the work shift were selected as biological indicators of exposure because they were predicted to decrease rapidly at the end of exposure and become relatively stable after 1 minute. The acetone concentration in urine excreted during the last 2 hours of the work shift (CU) was also used as a biological indicator. Simulation was repeated 100 times with randomly permuting CEXPs for each situation. The mean values of CB, CU, and CA showed almost no variation regardless of the difference in the GSD of CEXPs. The coefficients of variation increased with the GSD of CEXPs but were less than 0.2. Consequently, these variables were acceptable as biological indicators of daily average exposure for the same work load. However, the difference in work load greatly changed the mean values of CB, CU, and CA, thus making it difficult to use these variables as indicators of daily average exposure for different work loads.
使用基于生理的药代动力学(PBPK)模型,研究了丙酮暴露浓度变化对血液、尿液和呼出气体中丙酮浓度这三个生物学指标的影响。还考察了工作负荷差异的影响。通过将模拟的丙酮浓度与现场调查中观察到的相应值进行比较,证实该模型可用于估计波动暴露期间的丙酮浓度。通过将暴露情况输入PBPK模型,模拟了生物学指标的变异性。丙酮暴露的变化用七个1小时时间加权平均值(CEXPs)表示。CEXPs的算术平均值分别为200和750 ppm。几何标准差(GSDs)分别为1.5、2.0和3.0,分别代表低、中、高变异性。工作负荷设定为15和50 W。因此,共有12种暴露情况。选择工作班次结束后1分钟时静脉血(CB)和呼出肺泡气(CA)中的丙酮浓度作为暴露的生物学指标,因为预计它们在暴露结束时会迅速下降,并在1分钟后变得相对稳定。工作班次最后2小时内排出的尿液中的丙酮浓度(CU)也用作生物学指标。对每种情况,通过随机排列CEXPs重复模拟100次。无论CEXPs的GSD差异如何,CB、CU和CA的平均值几乎没有变化。变异系数随CEXPs的GSD增加,但小于0.2。因此,对于相同的工作负荷,这些变量可作为每日平均暴露的生物学指标。然而,工作负荷的差异极大地改变了CB、CU和CA的平均值,因此难以将这些变量用作不同工作负荷下每日平均暴露的指标。