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Estimation of time to compromised tenability in fires: is it time to change paradigms?
Regulatory Toxicology and Pharmacology ( IF 3.4 ) Pub Date : 2020-01-15 , DOI: 10.1016/j.yrtph.2020.104582
Juergen Pauluhn 1
Affiliation  

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.

中文翻译:

评估火灾中易损性的时间:是时候改变范例了吗?

ISO标准13571估计了封闭火灾中受损人员的脆弱性所需的时间。这被理解为结构设计通过疏散或逃生模型疏散燃烧建筑物所必须的时间。与所有紧急响应计划值一样,此类千载难逢的事件无法轻易并排验证。因此,风险评估者必须参考适合关注情况的基于动物的参考数据。本文进行的详细分析使用了急性暴露于一氧化碳(CO)的大鼠的出发点(POD)的浓度×时间(Cxt)-矩阵,POS是最丰富的有毒燃气之一。该分析的目的是阐明急性大鼠吸入研究中经时间和作用调整后的非致死阈浓度LCt01×1/3是否适合于模型化阈值,以表征人类的任何“逃生障碍”。将模型化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下暴露的参考数据进行比较。这些暴露持续时间与ISO标准13571和实施8小时持续职业暴露限值的标准中考虑的最大逃生持续时间1-h相匹配。指示健康成年人中“逃生障碍”的参考POD依赖于C×t低于引起运动功能或心理神经功能丧失的那些。来自大鼠的基于LCt01×1/3的建模结果的比较与来自人类的基于效果的POD匹配良好。与人类发表的证据一致,碳氧血红蛋白(COHb)饱和度是暴露而不是效应的生物标志物,因此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COHb的中位数方法与人类证据不一致,并且高估或低估了与CO相关的导致无毒和严重毒性时失能的能力C×的。总而言之,ISO TS 13571标准似乎应及时关注相关毒性信息的科学进展,并应完善对可以充分预测人类风险的科学方法。与人类发表的证据一致,碳氧血红蛋白(COHb)饱和度是暴露而不是效应的生物标志物,因此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COHb的中位数方法与人类证据不一致,并且高估或低估了与CO相关的导致无毒和严重毒性时失能的能力C×的。总而言之,ISO TS 13571标准似乎应及时关注相关毒性信息的科学进展,并应完善对可以充分预测人类风险的科学方法。与人类发表的证据一致,碳氧血红蛋白(COHb)饱和度是暴露而不是效应的生物标志物,因此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COHb的中位数方法与人类证据不一致,并且高估或低估了与CO相关的导致无毒和严重毒性时失能的能力C×的。总而言之,ISO TS 13571标准似乎应及时关注相关毒性信息的科学进展,并应完善对可以充分预测人类风险的科学方法。ISO TS 13571使用的基于COHb的中位数方法与人类证据不一致,并且分别高估和低估了与CO相关的分别导致无毒和严重毒性C×失能的能力。总而言之,ISO TS 13571标准似乎应及时关注相关毒性信息的科学进展,并应完善对可以充分预测人类风险的科学方法。ISO TS 13571使用的基于COHb的中位数方法与人类证据不一致,并且分别高估和低估了与CO相关的导致无毒和严重毒性C×失能的能力。总而言之,ISO TS 13571标准似乎应及时关注相关毒性信息的科学进展,并应完善对可以充分预测人类风险的科学方法。
更新日期:2020-01-15
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