{"title":"Estimation of time to compromised tenability in fires: is it time to change paradigms?","authors":"Juergen Pauluhn","doi":"10.1016/j.yrtph.2020.104582","DOIUrl":null,"url":null,"abstract":"<div><p>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 LCt<sub>01</sub> × 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 LCt<sub>01</sub> × 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 LCt<sub>01</sub> × 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.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"111 ","pages":"Article 104582"},"PeriodicalIF":3.0000,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.yrtph.2020.104582","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regulatory Toxicology and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0273230020300088","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, LEGAL","Score":null,"Total":0}
引用次数: 4
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.
期刊介绍:
Regulatory Toxicology and Pharmacology publishes peer reviewed articles that involve the generation, evaluation, and interpretation of experimental animal and human data that are of direct importance and relevance for regulatory authorities with respect to toxicological and pharmacological regulations in society. All peer-reviewed articles that are published should be devoted to improve the protection of human health and environment. Reviews and discussions are welcomed that address legal and/or regulatory decisions with respect to risk assessment and management of toxicological and pharmacological compounds on a scientific basis. It addresses an international readership of scientists, risk assessors and managers, and other professionals active in the field of human and environmental health.
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1.Factors influencing human sensitivity
2.Exposure science related to risk assessment
3.Alternative toxicological test methods
4.Frameworks for evaluation and integration of data in regulatory evaluations
5.Harmonization across regulatory agencies
6.Read-across methods and evaluations
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