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Currently, very limited information is available in the literature concerning the CO concentration - dose response relationships in humans. The concentration of COHb in the blood at any time will depend on several factors. When in equilibrium with ambient air the COHb content of the blood will depend mainly on the concentrations of inspired CO and O2. If equilibrium cannot be achieved, the COHb concentrations will also depend on the duration of exposure, ventilation (rate and volume) and the COHb originally present before inhalation of contaminated air. The half-time of CO disappearance from blood under normal recovery conditions is known to show considerable variation between individuals. For COHb concentrations of 2-10% the half life is reported to range from 3-5h. The half time can be reduced by inhaling increasing concentration of O2 (breathing 100% O2 he half life has been reported to be shortened by 75%). Further reductions in the half time can be bought about by the elevation of PO2 to 3 atm (~14 fold decrease over that seen when breathing room air).

There are wide ranging, well documented health effects resulting from carbon monoxide (CO) exposure both in the short and long term in humans. Effects include cardiovascular morbidity, central nervous system effects, birth outcomes and developmental effects, respiratory morbidity and mortality. A review and discussion of these health effects has been summarised below (Section 5.10.3) from current documentation (EPA, 2010, EHC, 1999). The conclusions drawn have been based on up to date, relevant human data (epidemiology studies, single/multi city studies, controlled human trials).

Additional information

Cardiovascular morbidity

Compelling evidence of CO-induced effects on the cardiovascular system at carboxyhaemoglobin (COHb) levels relevant to occupational exposure limits demonstrate consistent decreases in the time to onset of exercise-induced angina and ST-segment changes following CO exposures resulting in COHb 2-6%. Findings of epidemiologic studies are coherent with results of the controlled human exposure studies, with all but one of these studies reporting positive associations with CO exposure and evaluated cardiovascular disease outcomes (i.e. myocardial infarction, ischemic heart disease, myocardial infarction). Given the consistent and coherent evidence from epidemiologic and human clinical studies along with biological plausibility provided by CO’s role in limiting oxygens availability, it is concluded that a causal relationship is likely to exist between relevant short term exposures to CO and cardiovascular morbidity. Due to the limited available evidence, it is inadequate to conclude that a causal relationship exists between relevant long-term exposure to CO and cardiovascular morbidity.

Central nervous system effects

Exposure to high levels of CO has long been known to adversely affect the CNS function, with symptoms following acute CO poisoning including headaches, dizziness, cognitive difficulties, disorientation and coma. Inconsistent neural and behavioural effects following exposures resulting in COHb concentrations of 5-20% have been reported back in 2000; however no new human clinical studies have evaluated CNS or behavioural effects of CO. At ambient-level exposures, healthy adults may be protected against CO-induced neurological impairment owing to compensatory responses including increased cardiac output and cerebral blood flow. However, these compensatory mechanisms are likely impaired among certain potentially susceptible groups including individuals with reduced cardiovascular function. Considering the combined evidence from controlled human exposure and toxicological studies, the evidence is suggestive of a causal relationship between relevant short and long-term exposures to CO and CNS effects.

Birth outcomes and developmental effects

The most compelling evidence for CO-induced effects on birth and developmental outcomes is for preterm birth and cardiac birth defects. There is limited epidemiologic evidence that COexposure during pregnancy (e.g. 1st month and 1st trimester) is associated with an increased risk of preterm birth, whilst few studies have examined the effects of CO on birth defects. Two studies in particular found maternal exposure to CO to be associated with an increased risk of cardiac birth defects, which is mirrored in human clinical studies also demonstrating the heart as a target for CO effects. Numerous animal studies (as reported in this submission) provide additional evidence that CO exposure over the duration of gestation have shown skeletal alterations or limb deformities.

There is evidence of ambient CO exposure during pregnancy having a negative effect on foetal growth in epidemiologic studies. Effects reported included small reductions in birth weight, with inconsistent results reported for other metrics such as small for gestational age/intrauterine growth restriction, low birth weight. In general, there is limited epidemiologic evidence that CO is associated with an increased risk of infant mortality during the neonatal or post-natal periods. In support of this limited evidence, data submitted in this submission (Singh and Scott, 1984) provide some evidence that exogenous CO exposure to pups in utero significantly increased postnatal mortality. Overall, there is limited, though positive, epidemiologic evidence for a CO-induced effect on preterm and birth defects and weak evidence for a decrease in birth weight, other measures of foetal growth and infant mortality, suggesting a causal relationship between relevant long term exposures to CO and developmental effects and birth outcomes.  

Respiratory morbidity Epidemiologic studies provide evidence of positive associations between short-term exposure to CO and respiratory related outcomes including pulmonary function, respiratory symptoms, medication use and hospital admissions. However, the majority of these studies did not examine the potential influence on the association between CO and respiratory morbidity. Controlled human exposure studies have not extensively examined the effect of short-term exposure to CO on respiratory morbidity. Although controlled human exposure studies do not provide evidence to support CO-related respiratory health effects, epidemiologic studies show positive associations for CO-induced lung-related outcomes and animal toxicological studies demonstrate the potential for an underlying biological mechanism, which together provide evidence that is suggestive of a causal relationship between relevant short-term exposures to CO and respiratory morbidity.


Evidence from recent multi and single city studies suggests that an association between short-term exposure to CO and mortality exists, but limited evidence is available to evaluate cause-specific mortality outcomes associated with CO exposure. Overall, the epidemiologic evidence is suggestive of a causal relationship between relevant short-term exposures to CO and mortality. Consistent null and negative associations were observed across epidemiologic studies, which included cohort populations encompassing susceptible populations (i.e. post-menopausal women and hypertensive men). This combined with the lack of evidence for respiratory and cardiovascular morbidity outcomes following long term exposure to CO and the absence of a proposed mechanism to explain the progression to mortality provide supportive evidence that there is not likely to be a causal relationship between relevant long-term exposures to CO and mortality.


EHC, 1999. Environmental Health Criteria, 213, International Programme for Chemical Safety, WHO.

EPA, 2010. Integrated Science Assessment for Carbon Monoxide. EPA/600/R-09/019F. January 2010.