Citation

Pauluhn J. Regul. Toxicol. Pharmacol. 2020; ePub(ePub): ePub.

Affiliation

Hanover Medical School, Hannover, Germany. Electronic address: juergen.pauluhn@iCLOUD.com.

Copyright

(Copyright © 2020, Elsevier Publishing)

DOI

10.1016/j.yrtph.2020.104582

PMID

31953227

Abstract

The ISO standard 13571 estimates the time to the compromised tenability of people in enclosed fires. This is understood as the time which must be available for the structural design to pass an evacuation, or an escape paradigm for the evacuation of burning buildings. As with all emergency response planning values, such once-in-a-lifetime events cannot readily be validated side-by-side. Consequently, risk assessors must refer to animal-based reference data fitting the scenario of concern closely. The analysis detailed in this paper used the concentration × time (Cxt)-matrix of point of departures (PODs) from rats acutely exposed to carbon monoxide (CO), which is amongst the most abundant toxic fire gases. The objective of the analysis was to clarify whether the time- and effect-adjusted nonlethal threshold concentration LCt₀₁ × 1/3 from acute rat inhalation studies is suited to model thresholds characterizing any 'impairment of escape' in humans. Modeled outcomes are compared with published reference data from human volunteers exposed at the similar C × t's of CO at 800 ppm × 1-h and 100 ppm × 8-h. These exposure durations match the maximum escape duration of 1-h considered in the ISO standard 13571 and standards enforcing occupational exposure limits of 8-h duration. The reference PODs indicative of 'impairment of escape' in healthy adults relied on C × t's below those eliciting any loss of motor function or psychoneurological functions. The comparison of the LCt₀₁ × 1/3 based modeled outcomes from rats match favorably with the effect-based PODs from humans. Consistent with published evidence from humans, carboxyhemoglobin (COHb) saturation-a biomarker of exposure rather than of effect-failed to reliably predict effect-based outcomes. Unlike the LCt₀₁ × 1/3 threshold approach, the COHb-based median approach used by ISO TS 13571 is inconsistent with human evidence and both over- and under-estimates the CO-related potency for causing incapacitation at non-toxic and critically-toxic C × 's, respectively. In summary, it seems timely that the ISO TS 13571 standard pays attention to scientific progress in relevant toxicity information and refinements to scientific methods shown to adequately predict human risks.

Copyright © 2020. Published by Elsevier Inc.

Language: en

Keywords

And effect; Biomarkers of exposure; Carbon monoxide; Carboxyhemoglobin; Combustion toxicology; Haber's rule