Pharsight, Montreal, Quebec, Canada.
Inhal Toxicol. 2009 Nov;21(13):1077-91. doi: 10.3109/08958370902744848.
This study proposes to estimate carboxyhaemoglobin (COHb) levels in the blood of men and women of various ages exposed to common concentrations of carbon monoxide (CO) using a model with only one free parameter while integrating alveoli-blood and blood-tissue CO exchanges. The model retained is essentially that of Coburn et al. (1965) with two important additions: an alveoli compartment for the dynamics of CO exchanges between alveoli and blood, and a compartment for the significant amounts of CO bound to heme proteins in extravascular spaces. The model was validated by comparing its simulations with various published data sets for the COHb time profiles of volunteers exposed to known CO concentrations. Once the model was validated, it was used to simulate various situations of interest for their impact on public health. This approach yields reliable estimations of the time profiles of COHb levels resulting from different levels of CO exposure over various periods of time and under various conditions (resting, exercise, working, and smoking). The non-linear kinetics of CO, observed experimentally, were correctly reproduced by simulations with the model. Simulations were also carried out iteratively to determine the exposure times and CO concentrations in ambient air needed to reach the maximum levels of COHb recommended by Health Canada, the U.S. Environmental Protection Agency (EPA), and the World Health Organisation (WHO) for each age group of the general population. The lowest CO concentrations leading to maximum COHb levels of 1.5, 2, and 2.5% were determined.
本研究旨在通过一个仅具有一个自由参数的模型来估算不同年龄段的男性和女性在暴露于常见一氧化碳(CO)浓度下血液中的碳氧血红蛋白(COHb)水平,同时整合肺泡-血液和血液-组织之间的 CO 交换。所保留的模型本质上是 Coburn 等人(1965 年)的模型,有两个重要的补充:一个肺泡腔室用于模拟肺泡和血液之间 CO 交换的动力学,以及一个腔室用于模拟大量与血管外空间中的血红素蛋白结合的 CO。通过将模型模拟与志愿者暴露于已知 CO 浓度时的各种已发表的 COHb 时间曲线数据集进行比较,对模型进行了验证。在验证模型后,使用它来模拟各种感兴趣的情况,以评估其对公共卫生的影响。这种方法可对不同 CO 暴露水平在不同时间段和不同条件(休息、运动、工作和吸烟)下导致的 COHb 水平时间曲线进行可靠估计。模型模拟正确再现了实验中观察到的 CO 的非线性动力学。还进行了迭代模拟,以确定达到加拿大卫生部、美国环境保护署(EPA)和世界卫生组织(WHO)为每个年龄段的一般人群推荐的 COHb 最高水平所需的暴露时间和环境空气中的 CO 浓度。确定了导致 COHb 水平达到 1.5%、2%和 2.5%的最高水平的最低 CO 浓度。