Investigations into Health Effects Caused by Exposure to indoor air reaction prod

与室内空气质量相关的健康问题是主要的职业和环境问题。据报道，一些对健康的影响包括：眼睛和喉咙干燥，鼻炎，嗜睡，头痛，胸闷，喘息和哮喘。工作相关哮喘(WRA)是已报告的较严重的不良健康影响之一，可表现为肺刺激、过敏性哮喘或先前存在的哮喘的恶化。接触化学品可能会导致哮喘和其他不利的健康影响，但不幸的是，与室内环境相关的危险还没有得到很好的理解或很好的描述。接触混合化学物质，如颗粒物和含氧有机物种，包括具有生物活性的氧化挥发性有机化合物(VOC)，都会导致这些症状。消费者清洁产品和空气清新剂含有松油醇等化学物质，松油醇可以与臭氧发生反应，形成各种二次污染物，可能会导致上述症状。这些二次污染物包括含氧的有机化学品，如醛、酮、羧酸和二羰基。不幸的是，这些挥发性反应产物可能无法被传统的采样方法检测到，并导致对室内环境的不准确暴露评估。关于接触复杂混合物的知识有限，特别是VOCs和其他室内空气污染物之间潜在相互作用产生的二次产物。将动物暴露在化学反应产物(如臭氧与柠檬烯)中的研究表明，与单独接触反应物的动物相比，反应产物对暴露于动物的呼吸频率有显著影响。与接触母体化合物相比，小鼠暴露在臭氧和柠檬烯氧化产物中1小时，导致上呼吸道刺激和气流受限显着增加。这些发现表明，室内空气化学产生的二次污染物可能会加剧从事工业清洁作业的个人的下呼吸道症状或职业性哮喘。作为这项机构间协议的一部分，开展的研究已经开发并正在努力验证一种新的体外室内空气暴露系统，该系统将有助于进一步表征与职业相关的室内空气化合物对呼吸道的影响。这一新的系统专门用于评估二次污染物(即臭氧+常用的VOCs)，这些二次污染物具有通过室内空气化学反应产生的保守结构，如呼吸道上的二羰基和羧酸。该项目的研究结果预计将澄清这种潜在的联系，并通过更清楚地确定办公室和医疗保健环境中使用的产品产生的室内空气成分如何导致健康影响，来改进工人暴露评估。此外，拟议的研究结果还可能用于干预措施，如化学品选择或替代、建筑物维护程序和改进的暴露评估，这将有助于通过减少或消除WRA的影响和与室内空气暴露有关的其他健康影响来促进安全和健康的工作场所。这项研究将填补在理解和量化工作场所(办公室和医疗保健)暴露于室内化学产生的二次污染物方面的一个重要空白。从这些研究中获得的这些信息将为进一步的风险评估研究提供应调查哪些化学品/混合物的方向。该项目具体实现了NTP的目标：提供对公共卫生关注的物质的毒理学评估，开发和验证具有更高灵敏度和特异度的改进的高通量替代毒理学方法，并允许减少动物使用，并提供将提高对基本健康影响机制的理解的数据，并有助于加强未来室内空气暴露的风险评估的基础。

Indoor air quality-related health issues are major occupational and environmental problems. Some of the reported health effects include: dry eyes and throat, rhinitis, lethargy, headache, chest tightness, wheezing and asthma. Work related asthma (WRA) is one of the more severe adverse reported health effects, and can take the form of pulmonary irritation, allergic asthma, or exacerbation of pre-existing asthma. Asthma and other adverse health effects may result from exposures to chemicals, but unfortunately, the hazards associated with the indoor environment are not well-understood or well-characterized. Exposures of mixed chemical classes, such as particulate matter and oxygenated organic species, including; biologically active oxidized volatile organic compounds (VOC), contribute to these symptoms. Consumer cleaning products and air fresheners contain chemicals such as α-terpineol, which can react with ozone to form a variety of secondary pollutants that may contribute to the symptoms described above. These secondary pollutants include oxygenated organic chemicals, such as aldehydes, ketones, carboxylic acids and dicarbonyls. Unfortunately, these volatile reaction products may go undetected by conventional sampling methods and lead to inaccurate exposure assessments of indoor environments. There is limited knowledge regarding exposure to complex mixtures, particularly the secondary products from potential interactions among VOCs and other indoor air pollutants. Studies exposing animals to products of chemical reactions, such as ozone with limonene, have demonstrated that the reaction products have a significant impact on the breathing rate of exposed animals when compared to animals exposed to the reactants separately. A 1-hour exposure of mice to the oxidation products of ozone and limonene resulted in a significant increase in upper airway irritation and airflow limitation compared to exposure to the parent compounds. These findings suggest that the secondary pollutants generated from indoor air chemistry may exacerbate lower airway symptoms or occupational asthma in individuals involved in industrial cleaning operations. The studies conducted as part of this interagency agreement have developed and are working to validate a novel in vitro indoor air exposure system which will help to further characterize the effects of occupationally relevant indoor air compounds on the respiratory tract. This novel system has been used specifically to evaluate secondary pollutants (i.e. ozone + commonly used VOCs) with conserved structures generated through reactive indoor air chemistry, such as dicarbonyls and carboxcylic acids, on the respiratory tract. Research results from this project are anticipated to clarify this potential association and improve worker exposure assessment by more clearly identifying how indoor air constituents, generated from products used in offices and health care settings may result in health effects. In addition, the proposed research results can also potentially be used in interventions such as chemical selection or substitution, building maintenance procedures, and improved exposure assessment which will help to promote safe and healthy workplaces by reducing or eliminating the impacts of WRA and other health effects associated with indoor air exposure. This research will fill an important gap in the understanding and quantification of workplace (offices and healthcare) exposures to secondary pollutants generated from indoor chemistry. This information gained from these studies will provide direction for which chemicals/mixtures should be investigated for additional risk assessment studies. This project specifically meets the NTP goals of: providing toxicological evaluations on substances of public health concern, developing and validating an improved high throughput alternative toxicology method with increased sensitivity and specificity that also allows for reduced animal usage, and provide data that will improve understanding of fundamental health effect mechanisms and help to strengthen the base for future risk assessment for indoor air exposure.