Estimation of time to compromised tenability in fires: is it time to change paradigms?

IF 3 4区 医学 Q1 MEDICINE, LEGAL Regulatory Toxicology and Pharmacology Pub Date : 2020-03-01 DOI:10.1016/j.yrtph.2020.104582
Juergen Pauluhn
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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.

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火灾中损害可持续性的时间估计:是时候改变范式了吗?
ISO标准13571估计了人们在封闭火灾中受到损害的时间。这被理解为结构设计通过疏散或疏散燃烧建筑物的逃生范例必须可用的时间。与所有应急响应规划值一样,这种一生一次的事件不能轻易地并排验证。因此,风险评估人员必须参考与所关注情景密切相关的基于动物的参考数据。本文中详细的分析使用了急性暴露于一氧化碳(CO)的大鼠的浓度×时间(Cxt)-出发点(pod)矩阵,一氧化碳是最丰富的有毒气体之一。分析的目的是澄清急性大鼠吸入研究中经时间和效果调整的非致死阈值浓度LCt01 × 1/3是否适合用于表征人类任何“逃逸损伤”的模型阈值。将模拟的结果与人类志愿者在800 ppm × 1-h和100 ppm × 8-h下暴露于相似C × t的CO的公开参考数据进行比较。这些暴露时间符合ISO标准13571中考虑的1小时的最大逃逸时间和执行8小时持续时间的职业暴露限制的标准。指示健康成人“逃避障碍”的参考pod依赖于低于引起任何运动功能或心理神经功能丧失的C × t。基于LCt01 × 1/3的大鼠模型结果与基于人类效应的pod比较吻合良好。与已发表的来自人类的证据一致,碳氧血红蛋白(COHb)饱和度——暴露而非效应的生物标志物——无法可靠地预测基于效应的结果。与LCt01 × 1/3阈值方法不同,ISO TS 13571使用的基于cob的中位数方法与人类证据不一致,并且分别高估和低估了co在无毒和剧毒cx下导致失能的相关效力。总之,ISO TS 13571标准关注相关毒性信息的科学进展,并对科学方法进行改进,以充分预测人类风险,这似乎是及时的。
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来源期刊
CiteScore
6.70
自引率
8.80%
发文量
147
审稿时长
58 days
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. Types of peer-reviewed articles published: -Original research articles of relevance for regulatory aspects covering aspects including, but not limited to: 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 -Contemporary Reviews on policy related Research issues -Letters to the Editor -Guest Editorials (by Invitation)
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