Rees D C, Wood R W, McCormick J P, Cox C
Scand J Work Environ Health. 1985 Aug;11(4):301-6. doi: 10.5271/sjweh.2219.
Toxicokinetic experiments with toluene that rely on data pooled from several animals have typically provided estimates of rate constants based on single exponential functions; in the present study a within-subject design was used to describe the time course of toluene in the blood to see if additional exponential terms could be resolved. Each rat was exposed for 2 h to either 1 000, 1 780, or 3 000 ppm of toluene. Blood samples were drawn at different times from indwelling jugular cannulae, and blood toluene concentrations were determined by vapor phase equilibrium chromatography. There was substantial variability between the peak blood values of the animals at each exposure concentration. Nonlinear regression was used to determine regression parameters for data drawn from individual animals. A bi-exponential function was found to minimize significantly the residual sum of squares observed during elimination. However, only a single exponential function could be resolved reliably during uptake. The mean half-time during uptake was approximately 34 min; the two half-times for elimination averaged approximately 6 and 90 min. Because of between-subject variability, a more accurate description of the time course of toluene uptake and elimination can be provided by kinetic studies that use a within-subject design.
以往依赖多只动物汇总数据进行的甲苯毒代动力学实验，通常基于单指数函数给出速率常数的估计值；在本研究中，采用了个体内设计来描述血液中甲苯的时程，以确定是否能分辨出额外的指数项。每只大鼠暴露于1000、1780或3000 ppm的甲苯中2小时。在不同时间从颈静脉留置套管采集血样，采用气相平衡色谱法测定血液中甲苯浓度。在每个暴露浓度下，动物的血液峰值之间存在很大差异。使用非线性回归来确定从个体动物获取的数据的回归参数。发现双指数函数能显著最小化消除过程中观察到的残差平方和。然而，在摄取过程中只能可靠分辨出单指数函数。摄取过程中的平均半衰期约为34分钟；消除过程的两个半衰期平均约为6分钟和90分钟。由于个体间的变异性，采用个体内设计的动力学研究能更准确地描述甲苯摄取和消除的时程。
