Standard health risks from volatile organic compounds (VOCs) are generally interpreted at ambient environmental conditions. The aim of this study was to develop a strategy for using physiologically based pharmacokinetic (PBPK) modeling to compare known risks in the general population to calculated risks in pilots experiencing pressure-based stressors. PBPK models facilitate these comparisons by prediction of how target-tissue specific doses are altered when a stressor, such as high altitude, produces changes in physiological parameters. Cardiac output, regional blood flow, and alveolar ventilation rate following acute exposure to altitude ranging from moderate to extremely high were estimated from published data from 52 groups of human subjects. Scenarios where pilots might inhale toluene, 1,2,4-trimethylbenzene (1,2,4-TMB), or cyclohexane during routine military flight training were simulated. At the recommended Threshold Limit Values (TLV), arterial blood concentrations were predicted to be higher for exposure at 15000 ft (4572 m) than at sea level. The differences were greater for toluene and TMB, which have higher blood: air and fat: blood partition coefficients than less lipophilic cyclohexane. In summary, quantitative approaches to internal dosimetry prediction that take advantage of existing knowledge of physiological changes induced by occupational stressors possess potential as tools in performing a human health risk assessment.

挥发性有机化合物（VOC）的标准健康风险通常在周围环境条件下进行解释。这项研究的目的是开发一种策略，该策略使用基于生理的药代动力学（PBPK）模型将一般人群中的已知风险与飞行员在遭受基于压力的压力的情况下计算出的风险进行比较。PBPK模型通过预测当应激源（例如高海拔）产生生理参数变化时靶组织特定剂量的变化而有助于这些比较。根据52组人类受试者的公开数据，估计了急性暴露于中度至极高高度后的心脏输出，局部血流量和肺泡通气率。飞行员可能会吸入甲苯，1,2,4-三甲基苯（1,2,4-TMB），模拟常规军事飞行训练中的环己烷或环己烷。在建议的阈值限制（TLV）下，预计在15000英尺（4572 m）处暴露的动脉血浓度会比在海平面上更高。甲苯和TMB的血液，空气和脂肪：血液分配系数较高，而亲脂性环己烷较少，差异更大。总之，利用现有的由职业压力源引起的生理变化知识的内部剂量学预测的定量方法，具有进行人类健康风险评估的潜力。甲苯和TMB的血液，空气和脂肪：血液分配系数较高，而亲脂性环己烷较少，差异更大。总之，利用现有的由职业压力源引起的生理变化的知识进行内部剂量学预测的定量方法，具有进行人类健康风险评估的潜力。甲苯和TMB的差异更大，后者的血液：空气和脂肪：血液分配系数高于亲脂性环己烷少。总之，利用现有的由职业压力源引起的生理变化知识的内部剂量学预测的定量方法，具有进行人类健康风险评估的潜力。