Risk assessment in combustion toxicology: Should carbon dioxide be recognized as a modifier of toxicity or separate toxicological entity?

To characterize the accumulated hazards associated with the inhalation of gases typical of combustion products, a time-integrated value known as the fractional effective dose (FED) is used. This FED is maintained by the International Organization for Standardization (ISO) and made publicly available as the Standard ISO 13571. The current FED calculation related to asphyxiant gases is based on non-human primate data to estimate the 50% probability of humans to be incapacitated or not being able to execute any escape paradigm from fires. The objective of this paper was to compare two to calculate FEDs of the most common mixture of asphyxiant fire gases CO, HCN, and CO2. The first was based on the current ISO 13571 (draft) standard, the alternative second method applied the conceptual principles established for the derivation of Acute Emergency Response Planning Guideline values. The alternative approach applied one third of the non-lethal threshold concentration (LC01) as the most suitable and robust Point of Departure (POD) to estimate the threshold characterizing 'impairment of escape' in the absence of post-exposure mortality. The hyperventilation correction factor for CO2 of ISO 13571 was replaced by a separate term that accounts for the inherent acute toxicity of CO2. This analysis supports the conclusion that the current ISO 13571 standard misjudges the impact of the acute toxicity elicited by concentrations of CO2 exceeding ≈6%. While underestimating the hazards attributable to CO2, the hyperventilation adjustment factor suggested by this standard is biased to markedly overestimate the hazards assigned to CO and HCN in fire effluents.