The application of physiologically based modeling approaches in evaluating health risks in diverse environments is limited by scarcity of comprehensive reviews detailing how physiological parameters are altered due to stressors. A modern high-performance aviation environment in particular has the potential for simultaneous exposure to chemical and non-chemical stressors which may interact via non-chemical stressor-mediated pharmacokinetic alterations. To support physiologically based pharmacokinetic (PBPK) modeling of in-flight disposition inhaled chemicals, literature review, and synthesis was conducted to determine the impact of gravitational (+Gz) forces on PBPK modeling inputs. Specifically, changes in cardiac output and related parameters heart rate and stroke volume, breathing frequency, tidal volume, and pulmonary and alveolar ventilation rate in vivo were extracted from 36 publications and related mathematically to +Gz intensity. A scenario was simulated where a pilot performing test flights might inhale organic chemicals at the occupational exposure guideline level while experiencing sustained, elevated +Gz. Peak arterial blood concentrations of 1,2,4-trimethylbenzene during a 1 h-flight at +4 Gz were predicted to increase 2-fold relative to would occur on the ground under baseline conditions. This case study demonstrates the potential value of scenario-specific physiological information in assessing changes in risk-relevant internal dosimetry, providing better information for potential risk management actions.

基于生理学的建模方法在评估各种环境中的健康风险中的应用受到缺乏全面评论的限制，因为该评论没有详细说明由于压力因素而如何改变生理参数。现代高性能航空环境尤其具有同时暴露于化学和非化学应激源的潜力，这些应激源可能通过非化学应激源介导的药代动力学改变而相互作用。为了支持飞行中处置化学物质的基于生理的药代动力学（PBPK）建模，进行了文献综述和合成，以确定重力（+ Gz）力对PBPK建模输入的影响。具体来说，心输出量和相关参数的变化（心率和中风量，呼吸频率，潮气量，从36种出版物中提取了体内活性，并在数学上与+ Gz强度相关。模拟了一个场景，在该场景中，进行试飞的飞行员可能会在职业暴露指导水平上吸入有机化学物质，同时经历持续的+ Gz升高。预测在+4 Gz飞行1 h期间，1,2,4-三甲基苯的峰值血药浓度相对于基线条件下在地面上的峰值会增加2倍。本案例研究证明了特定场景的生理信息在评估与风险相关的内部剂量学方面的变化的潜在价值，从而为潜在的风险管理措施提供了更好的信息。