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，包括评估急性吸入毒性潜力，是国际商业中使用的化学物质的强制性国际监管要求。急性吸入毒性或刺激潜力是建立化学物质和化学混合物的安全处理，包装，标记和运输的程序，以及对紧急暴露情况的反应。最近制定的立法包括欧盟（EU）注册，化学药品（覆盖范围）计划的标签和授权以及美国EPA高生产量（HPV）化学挑战将大大增加对吸入毒性信息的需求。本赠款提案的目的是验证Epiairway体外人类气道模型，以预测体内人类吸入毒性危害危害潜力，因为验证替代方法验证委员会（ICCVAM）和欧洲替代方法验证中心（ECVAM）指南。 I期实验产生了几个预测模型，这些模型将在当前II期项目中进一步测试。在II期验证项目中，将使用一百种具有体内人类或动物吸入毒性数据的化学物质，并立即确定由NIOSH建立的生命或健康（IDLH）浓度危险的化学物质。该方法的实验室间可传递性还将在4个实验室中使用从II阶段研究期间测试的原始100个选择的30种化学物质进行评估。然后，研究数据将提交独立统计分析，最终结果和报告将提交给监管机构（即ICCVAM），以支持监管接受。在当前第二阶段提案中要验证的技术将纠正实施全球吸入毒性测试化学物质以及迫切需要的技术能力，但目前不存在的技术能力的关键障碍。开发的方法将提供一种变革性的技术，该技术将促进从体内啮齿动物到体外人类吸入毒理学测试的范式转变，在仇恨国家研究委员会报告中设想的“ 21世纪的毒性测试：一种愿景和战略”。公共卫生相关性：危害评估，包括评估急性吸入毒性潜力，是对国际商务中使用的化学物质的强制性国际监管要求。急性吸入毒性或刺激潜力是建立化学物质和化学混合物的安全处理，包装，标记和运输的程序，以及对紧急暴露情况的反应。在当前第二阶段提案中要验证的技术将解决对化学药品的吸入毒性测试实施全球要求的关键障碍，并提供急需的技术能力，但目前不存在。