Determination of carboxyhaemoglobin in humans following low-level exposures to carbon monoxide.
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.
Gosselin
Nathalie H
NH
Pharsight, Montreal, Quebec, Canada. ngosseli@pharsight.com
Brunet
Robert C
RC
Carrier
Gaétan
G
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002248:Carbon Monoxide / Q000009:adverse effects* / Q000097:blood; D002263:Carboxyhemoglobin / Q000378:metabolism*; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D008297:Male; D008954:Models, Biological
D015415:Biomarkers; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin