Benignus V A, Boyes W K, Bushnell P J
U.S. Environmental Protection Agency, Human Studies Division, Research Triangle Park, North Carolina 27711, USA.
Toxicol Sci. 1998 Jun;43(2):186-95. doi: 10.1006/toxs.1998.2458.
The literature on behavioral effects of exposure to toluene is difficult to assess due, in part, to a wide variety of exposure conditions employed and outcomes measured. This study investigated whether previous experiments would be more consistent with each other if toluene exposure parameters were expressed not as concentration and duration, but as estimated amount of toluene in tissues. A physiologically based pharmacokinetic (PBPK) model was used to estimate concentration of toluene in arterial blood (CaTOL) from published studies in rats and humans exposed acutely to toluene vapor. Data for rats were selected from studies of avoidance behavior using both rate of responding and measures of successful responding. Data for humans were from studies of choice reaction time (CRT). Behavioral measures were converted to proportion of baseline to place them on a common scale across experiments. A meta-analysis was done to fit dose-effect curves using CaTOL and the rescaled effects. Results demonstrated that effects were an orderly function of CaTOL and were not influenced by concentration or duration of exposure, except as exposure influenced CaTOL. In rats, response rates first increased, reached a peak, and then declined as CaTOL increased. Successful avoidance in rats and CRT in humans always declined as CaTOL increased. In rats, response rates were increased by 10% at CaTOL approximately 13 ml/L. In humans, reaction times increased by 10% at CaTOL approximately 3 ml/L. Cross-species comparisons were made with the following caveats: PBPK uncertainties, few human data, and poor task comparability.
关于接触甲苯的行为影响的文献难以评估，部分原因在于所采用的接触条件和所测量的结果多种多样。本研究调查了如果甲苯接触参数不是以浓度和持续时间来表示，而是以组织中甲苯的估计量来表示，以往的实验是否会彼此更一致。使用基于生理的药代动力学（PBPK）模型，根据已发表的大鼠和急性接触甲苯蒸气的人类研究，估计动脉血中甲苯的浓度（CaTOL）。大鼠的数据选自在回避行为研究中使用反应率和成功反应测量的研究。人类的数据来自选择反应时（CRT）研究。行为测量值被转换为基线比例，以便在不同实验中放在一个共同的尺度上。进行了一项荟萃分析，使用CaTOL和重新标度后的效应来拟合剂量-效应曲线。结果表明，效应是CaTOL的有序函数，除了接触影响CaTOL外，不受接触浓度或持续时间的影响。在大鼠中，随着CaTOL的增加，反应率先增加，达到峰值，然后下降。在大鼠中，成功回避和人类的CRT总是随着CaTOL的增加而下降。在大鼠中，当CaTOL约为13 ml/L时，反应率增加了10%。在人类中，当CaTOL约为3 ml/L时，反应时间增加了10%。进行了跨物种比较，但有以下注意事项：PBPK的不确定性、人类数据较少以及任务可比性较差。
