Validation of an In Vitro Human Airway Model

体外人体气道模型的验证

基本信息

批准号：
8057577
负责人：
PATRICK J HAYDEN
金额：
$ 29.85万
依托单位：
MATTEK CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8057577
关键词：
Acute Address Animals Applications Grants Authorization documentation Biological Assay Breathing Chemicals Commerce Contracts Data Data Set Emergency Situation Equation European European Union Evaluation Goals Government Guidelines Hazard Assessment Hazardous Chemicals Health Human In Vitro Industry Inhalation Toxicology Institutes Interagency Coordinating Committee on the Validation of Alternative Methods International Label Laboratories Letters Life Manufacturer Name Methodology Methods Modeling National Research Council Occupations Phase Procedures Production Protocols documentation Regulation Reporting Research Rodent Safety Services Statutes and Laws Technology Testing Toxic effect Toxicity Tests Validation Vision consumer product hazard in vivo irritation phase 2 study programs research study respiratory response success validation studies

项目摘要

DESCRIPTION (provided by applicant): Hazard assessment, including evaluation of acute inhalation toxicity potential, is a mandatory international regulatory requirement for chemicals utilized in international commerce. Acute inhalation toxicity or irritation potential is an important consideration in establishing procedures for the safe handling, packaging and labeling and transport of chemicals and chemical mixtures, and in formulating responses to emergency exposure situations. Recently enacted legislation including the European Union (EU) Registration, Labeling and Authorization of Chemicals (REACH) program, and the US EPA High production Volume (HPV) Chemical Challenge will dramatically increase the need for inhalation toxicity information. The goal of the present grant proposal is to validate the EpiAirway in vitro human airway model for prediction of in vivo human inhalation toxicity hazard potential following Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and European Center for Validation of Alternative Methods (ECVAM) guidelines. Phase I experiments produced several prediction models that will be further tested in the current Phase II project. One hundred chemicals that have available in vivo human or animal inhalation toxicity data and established immediately Dangerous to Life or health (IDLH) concentrations established by NIOSH will be utilized in the Phase II validation project. Interlaboratory transferability of the method will also be evaluated in 4 laboratories using a subset of 30 chemicals chosen from the original 100 tested during the Phase II study. The study data will then be submitted for independent statistical analysis and the final results and report will be submitted to regulatory agencies (i.e. ICCVAM) in support of regulatory acceptance. The technology to be validated in the current Phase II proposal will address a critical barrier to implementation of worldwide requirements for inhalation toxicity testing of chemicals, and a technical capacity that is urgently needed but that does not presently exist. The methodology developed will provide a transformative technology that will facilitate the paradigm shift from in vivo rodent to in vitro human inhalation toxicology testing envisioned in the resent National Research Council Report "Toxicity Testing in the 21st Century: A Vision and a Strategy". PUBLIC HEALTH RELEVANCE: Hazard assessment, including evaluation of acute inhalation toxicity potential, is a mandatory international regulatory requirement for chemicals utilized in international commerce. Acute inhalation toxicity or irritation potential is an important consideration in establishing procedures for the safe handling, packaging and labeling and transport of chemicals and chemical mixtures, and in formulating responses to emergency exposure situations. The technology to be validated in the current Phase II proposal will address a critical barrier to implementation of worldwide requirements for inhalation toxicity testing of chemicals, and provide a technical capability that is urgently needed but that does not presently exist.

描述（由申请人提供）：危害评估，包括急性吸入毒性潜力的评估，是国际贸易中使用的化学品的强制性国际监管要求。在制定化学品和化学混合物的安全处理、包装、标签和运输程序以及制定紧急暴露情况的应对措施时，急性吸入毒性或潜在刺激性是一个重要的考虑因素。最近颁布的立法，包括欧盟 (EU) 化学品注册、标签和授权 (REACH) 计划以及美国 EPA 高产量 (HPV) 化学品挑战，将大大增加对吸入毒性信息的需求。本拨款提案的目标是根据替代方法验证机构间协调委员会 (ICCVAM) 和欧洲替代方法验证中心 (ECVAM) 的要求，验证 EpiAirway 体外人体气道模型，用于预测体内人体吸入毒性危险潜力）指导方针。第一阶段实验产生了几个预测模型，将在当前第二阶段项目中进一步测试。 II 期验证项目将使用 100 种化学品，这些化学品具有人体或动物体内吸入毒性数据，并立即确定了 NIOSH 确定的危及生命或健康 (IDLH) 浓度。该方法的实验室间可转移性还将在 4 个实验室中使用从第二阶段研究期间测试的原始 100 种化学物质中选出的 30 种化学物质的子集进行评估。然后，研究数据将提交进行独立统计分析，最终结果和报告将提交给监管机构（即 ICCVAM）以支持监管机构的接受。当前第二阶段提案中待验证的技术将解决实施全球化学品吸入毒性测试要求的关键障碍，以及迫切需要但目前不存在的技术能力。所开发的方法将提供一种变革性技术，促进从体内啮齿动物到体外人体吸入毒理学测试的范式转变，这是国家研究委员会最近的报告“21世纪的毒性测试：愿景和战略”中设想的。公共卫生相关性：危害评估，包括急性吸入毒性潜力的评估，是国际贸易中使用的化学品的强制性国际监管要求。在制定化学品和化学混合物的安全处理、包装、标签和运输程序以及制定紧急暴露情况的应对措施时，急性吸入毒性或潜在刺激性是一个重要的考虑因素。当前第二阶段提案中待验证的技术将解决实施全球化学品吸入毒性测试要求的关键障碍，并提供迫切需要但目前尚不存在的技术能力。