10 min

30 min

1 h

4 h

8 h

1,700 ppm

600 ppm

330 ppm

150 ppm

130 ppm

End Point/Concentration/Rationale: The derivation of AEGL-3 values was based on observations in humans. Analysis of lethal cases reported by Nelson (2006a) indicated that most lethal poisoning cases occurred at COHb levels higher than 40% and that survival of CO-exposed humans were likely to be seen at levels below 40%. Thus, 40%COHb level seems a reasonable threshold for lethality. This level is supported by experimental studies suggest that a COHb of about 34-56% does not cause lethal effects in healthy individuals. Further support come from the studies by Kizakevich et al. (2000), Stewart et al. (1970), and Nielsen (1971) that reported headache as the only symptom when subjects were exposed to 20-33% COHb. The point of departure of 40% COHb is also supported by studies in animals reporting minimum lethal COHb levels in rats and mice of about 50-70% (E.I. du Pont de Nemours and Co., 1981; Rose et al., 1970). Further support comes from published cases of myocardial infarction that measured COHb levels after transport to the hospital: 52.2% (Marius-Nunez 1990), 30%, 22.8% (Atkins and Baker 1985), 21% (Ebisuno et al., 1986), 15.6% (Grace and Platt 1981).

Uncertainty Factors/Rationale:

Total uncertainty factor: 3

Interspecies: Not applicable.

Intraspecies: 3

An intraspecies uncertainty factor of 3 was supported by information on effects, such as myocardial infarction and stillbirths, reported in more susceptible subpopulations.

Modifying Factor: Not applicable.

Animal to Human Dosimetric Adjustment: Not applicable.

Time Scaling: A mathematical model (Coburn et al. 1965; Peterson and Stewart 1975) was used to calculate exposure concentrations in air resulting in a COHb of 40% at the end of exposure periods of 10 and 30 min and 1, 4 and 8 h.

Data Adequacy: AEGL-3 values were based on 40% COHb levels derived from the analysis of clinical cases of lethal and nonlethal poisoning. The AEGL-3 values derived using an intraspecies uncertainty factor of 3 (corresponding to an COHb of about 15%) are supported by the available case reports of lethal effects (myocardial infarction, stillbirths) in more susceptible subpopulations. Lethal effects from myocardial infarction in hypersusceptible patients with coronary artery disease at even lower CO concentrations, which could be at the upper end of the range of CO concentrations found inside buildings and in ambient air outside, cannot be excluded.



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