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化学诱导性哮喘以及临床、毒理学、暴露和流行病学研究在监管和危害特征描述方法中的作用。

Chemical-induced asthma and the role of clinical, toxicological, exposure and epidemiological research in regulatory and hazard characterization approaches.

机构信息

Department Environmental Health, University Cincinnati College of Medicine, Cincinnati, OH, United States.

Division of Immunology, Allergy & Rheumatology, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

出版信息

Regul Toxicol Pharmacol. 2017 Nov;90:126-132. doi: 10.1016/j.yrtph.2017.08.018. Epub 2017 Sep 1.

Abstract

Uncertainties in understanding all potential modes-of-action for asthma induction and elicitation hinders design of hazard characterization and risk assessment methods that adequately screen and protect against hazardous chemical exposures. To address this challenge and identify current research needs, the University of Cincinnati and the American Cleaning Institute hosted a webinar series to discuss the current state-of-science regarding chemical-induced asthma. The general consensus is that the available database, comprised of data collected from routine clinical and validated toxicological tests, is inadequate for predicting or determining causal relationships between exposures and asthma induction for most allergens. More research is needed to understand the mechanism of asthma induction and elicitation in the context of specific chemical exposures and exposure patterns, and the impact of population variability and patient phenotypes. Validated tools to predict respiratory sensitization and to translate irritancy assays to asthma potency are needed, in addition to diagnostic biomarkers that assess and differentiate allergy versus irritant-based asthmatic responses. Diagnostic methods that encompass the diverse etiologies of asthmatic responses and incorporate robust exposure measurements capable of capturing different temporal patterns of complex chemical mixtures are needed. In the absence of ideal tools, risk assessors apply hazard-based safety assessment methods, in conjunction with active risk management, to limit potential asthma concerns, proactively identify new concerns, and ensure deployment of approaches to mitigate asthma-related risks.

摘要

理解所有可能导致哮喘的作用模式和引发机制的不确定性,阻碍了危险特征描述和风险评估方法的设计,这些方法无法充分筛选和保护人们免受有害化学物质暴露的影响。为了应对这一挑战并确定当前的研究需求,辛辛那提大学和美国清洁研究所举办了一个网络研讨会系列,讨论关于化学物质诱发哮喘的当前科学状况。人们普遍认为,现有的数据库由常规临床和经过验证的毒理学测试收集的数据组成,不足以预测或确定大多数过敏原暴露与哮喘引发之间的因果关系。需要更多的研究来了解特定化学暴露和暴露模式下哮喘引发和诱发的机制,以及人群变异性和患者表型的影响。除了评估和区分过敏与刺激性哮喘反应的诊断生物标志物外,还需要预测呼吸致敏的验证工具,并将刺激性测定转化为哮喘效力。需要能够评估和区分过敏与刺激性哮喘反应的诊断方法,涵盖哮喘反应的不同病因,并结合强大的暴露测量,以捕捉复杂化学混合物不同的时间模式。在缺乏理想工具的情况下,风险评估人员应用基于危害的安全评估方法,并结合主动风险管理,以限制潜在的哮喘问题,主动识别新问题,并确保采取措施减轻与哮喘相关的风险。

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