Gautham Venugopalan, Rocco Casagrande, Noah Gunther, Rashmi Prasad, Shawn Jackson
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This paper describes an improved multi-module model that addresses these limitations and explores whether facilities using NO should consider adopting measures that can mitigate the simultaneous health effects of both gasses. The model predicts the morbidity (intoxication/injury), mortality (death), and treatment outcomes that may arise following an industrial NO release by first calculating the doses of both NO and NO<sub>2</sub> received by exposed individuals and then applying newly defined toxicity parameters for NO and NO<sub>2</sub> to assign dose-dependent probabilities for the onset of intoxication and/or death and the ability of appropriate treatment(s) to save lives. Modeling results indicate low risk to worker health in the likeliest release scenarios while identifying less likely situations that carry substantially higher risk. Moreover, these results indicate that risks to worker health can be mitigated with simple measures like maintaining reliable alarms, adequate ventilation, and on-site supplies of methylene blue, as well as encouraging quick responses by personnel. With appropriate parameterization, the improved modeling framework is generalizable to any chemical release, especially multi-hazard releases resulting from the conversion of one toxic compound into another under likely environmental conditions. By directly addressing the toxicities of multiple compounds, the improved model presents a more realistic picture of the potential health consequences of a chemical release. 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The model predicts the morbidity (intoxication/injury), mortality (death), and treatment outcomes that may arise following an industrial NO release by first calculating the doses of both NO and NO<sub>2</sub> received by exposed individuals and then applying newly defined toxicity parameters for NO and NO<sub>2</sub> to assign dose-dependent probabilities for the onset of intoxication and/or death and the ability of appropriate treatment(s) to save lives. Modeling results indicate low risk to worker health in the likeliest release scenarios while identifying less likely situations that carry substantially higher risk. Moreover, these results indicate that risks to worker health can be mitigated with simple measures like maintaining reliable alarms, adequate ventilation, and on-site supplies of methylene blue, as well as encouraging quick responses by personnel. 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引用次数: 0
摘要
一氧化氮(NO)和二氧化氮(NO2)这两种气体对人体都有毒,但在半导体制造场所等工业环境中却很常见。由于一氧化氮在环境条件下会自发氧化成二氧化氮,因此在意外释放的情况下,使用一氧化氮的人员实际上可能会接触到这两种气体。遗憾的是,提供给 NO 用户的大多数安全材料都没有涉及相关 NO2 的潜在毒性,而且到目前为止,为预测 NO 释放后的健康后果而开发的模型在评估中都没有适当考虑 NO 和 NO2 的氧化动力学或毒性。本文介绍了一种经过改进的多模块模型,该模型解决了这些局限性,并探讨了使用 NO 的设施是否应考虑采取可减轻这两种气体同时对健康造成的影响的措施。该模型通过首先计算接触者所接受的二氧化氮和二氧化氮的剂量,然后应用新定义的二氧化氮和二氧化氮毒性参数来确定中毒和/或死亡发生的剂量相关概率以及适当治疗的救生能力,从而预测工业二氧化氮释放后可能出现的发病率(中毒/受伤)、死亡率(死亡)和治疗结果。建模结果表明,在最有可能发生释放的情况下,工人的健康风险较低,而在不太可能发生的情况下,风险会大大增加。此外,这些结果表明,可以通过简单的措施来降低对工人健康的风险,如保持可靠的警报、充足的通风和亚甲基蓝的现场供应,以及鼓励工作人员做出快速反应。通过适当的参数设置,改进后的建模框架可适用于任何化学品释放,尤其是在可能的环境条件下一种有毒化合物转化为另一种有毒化合物所导致的多重危害释放。通过直接解决多种化合物的毒性问题,改进后的模型能更真实地反映化学品释放可能对健康造成的影响。这种可通用的多重危害化学品释放建模框架可为 NO 释放事件的准备工作和风险缓解战略提供信息。
Potential consequences of nitric oxide release: An improved model informing worker safety
Both nitric oxide (NO) and nitrogen dioxide (NO2) gasses are toxic to humans but are commonly found in industrial settings such as semiconductor manufacturing sites. Due to the spontaneous oxidation of NO to NO2 under ambient conditions, individuals working with NO may in fact be exposed to both gasses in the case of an accidental release. Unfortunately, most safety materials provided to NO users do not address the potential for associated NO2 toxicity, and, until now, models developed to predict health consequences following a release of NO have not appropriately considered the oxidation kinetics nor the toxicity of both NO and NO2 in their assessments. This paper describes an improved multi-module model that addresses these limitations and explores whether facilities using NO should consider adopting measures that can mitigate the simultaneous health effects of both gasses. The model predicts the morbidity (intoxication/injury), mortality (death), and treatment outcomes that may arise following an industrial NO release by first calculating the doses of both NO and NO2 received by exposed individuals and then applying newly defined toxicity parameters for NO and NO2 to assign dose-dependent probabilities for the onset of intoxication and/or death and the ability of appropriate treatment(s) to save lives. Modeling results indicate low risk to worker health in the likeliest release scenarios while identifying less likely situations that carry substantially higher risk. Moreover, these results indicate that risks to worker health can be mitigated with simple measures like maintaining reliable alarms, adequate ventilation, and on-site supplies of methylene blue, as well as encouraging quick responses by personnel. With appropriate parameterization, the improved modeling framework is generalizable to any chemical release, especially multi-hazard releases resulting from the conversion of one toxic compound into another under likely environmental conditions. By directly addressing the toxicities of multiple compounds, the improved model presents a more realistic picture of the potential health consequences of a chemical release. This generalizable framework for modeling of multi-hazard chemical releases can inform preparedness and risk mitigation strategies for NO release events.
期刊介绍:
Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.