NICEATM Support Contract: Optional Level of Effort

NICEATM 支持合同：可选的工作级别

• 批准号: 10400625
• 负责人: DAVID ALLEN
• 金额: $ 44.51万
• 依托单位: INTEGRATED LABORATORY SYSTEMS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-05 至 2022-05-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10400625
• 关键词: Animals; Authorization documentation; Characteristics; Chemicals; Contractor; Contracts; Data; Databases; Development; Documentation; Economics; Educational workshop; Ensure; Evaluation; Exposure to; Guidelines; Hazard Identification; Health; Human; In Vitro; Interagency Coordinating Committee on the Validation of Alternative Methods; Knowledge; Literature; Methods; Mission; Modeling; National Toxicology Program; Pathway interactions; Peer Review; Performance; Production; Published Comment; Publishing; Quantitative Structure-Activity Relationship; Reporting; Research Methodology; Research Support; Risk Assessment; Support Contracts; System; Testing; Toxicokinetics; Toxicology; Validation; Work; adverse outcome; diverse data; flexibility; high throughput screening; in silico; in vivo; interest; meetings; novel; operation; pharmacodynamic model; physiologically based pharmacokinetics; research and development; safety testing; screening; validation studies

"This is a Research and Development (R&D) contract to provide scientific and administrative support for the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). NICEATM research supports activities of NTP in general, and specifically, NTP’s Biomolecular Screening Branch (BSB), the Tox21 consortium, and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). NICEATM is responsible for ensuring compliance with the duties and provisions of the ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3) - to promote the research, development, validation, evaluation, acceptance, and use of new and alternative testing methods and strategies that are more predictive of human health and ecological effects than currently available methods and strategies. NICEATM carries out its mission by performing independent R&D activities, reviewing proposed test methods, organizing workshops and meetings, and facilitating peer reviews. Key Words: alternative toxicological strategies; test method validation; computational approaches The Contractor is required to acquire and apply new and existing scientific knowledge to develop, evaluate, and validate novel computational approaches that can be used for chemical hazard identification and risk assessment with direct relevance to human health. Data development, analysis, and evaluation represents a large portion of the work of this requirement. These approaches include, but are not limited to: exposure modeling, physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling, reverse toxicokinetic (R-TK) modeling, Quantitative Structure-Activity Relationship (QSAR) modeling, analysis of quantitative high throughput screening (qHTS) and high content (HC) data, and development of novel Integrated Testing and Decision Strategies (ITDS) using in vivo, in vitro and/or in silico systems. The Contractor routinely utilizes information from diverse data types and multiple databases (e.g., ToxRef DB, ToxCastDB, ExpoCastDB, DSSTox, CEBS, etc.) to develop and evaluate the above listed approaches. The Contractor develops Adverse Outcome Pathways (AOPs), in accordance with guidelines proposed by the Organisation for Economic Co-operation and Development (OECD)3, for novel AOPs of interest to Federal agencies. The Contractor analyzes the performance characteristics of the proposed AOPs in the context of emerging scientific literature and novel computational approaches. To explore the utility of alternative methods, the Contractor identifies, retrieves, and compares data generated from novel methods with extant data from traditional methods found in the published literature. Using public and proprietary databases, the Contractor gathers all relevant production, use, exposure, and toxicological information on selected chemicals and mixtures currently included in or under consideration for inclusion in Tox21-related efforts or of interest to the NTP. The Contractor reviews and evaluates the data and information gathered from the literature searches and prepares comprehensive written reports, as needed. In order to promote the research, development, validation, acceptance, and use of new and alternative testing methods and strategies, NICEATM supports ICCVAM-coordinates evaluations of submitted and nominated test methods by drafting supporting documentation for ICCVAM review, comment, and approval. In addition, NICEATM may be called upon to coordinate validation studies for emerging alternative approaches. The contractor has the flexibility to subcontract for expertise not resident within the contract organization or to subcontract for necessary validation efforts."

“这是一份研发 (R&D) 合同，旨在为国家毒理学计划 (NTP) 替代毒理学方法评估机构间中心 (NICEATM) 提供科学和行政支持。NICEATM 研究总体上支持 NTP 的活动，特别是NTP 生物分子筛选分会 (BSB)、Tox21 联盟和替代方法验证机构间协调委员会(ICCVAM) 负责确保遵守 2000 年 ICCVAM 授权法案 (42 U.S.C. 285l-3) 的职责和规定 - 促进新的和替代测试的研究、开发、验证、评估、验收和使用。 NICEATM 通过开展独立研发活动、审查拟议的测试方法、组织研讨会和会议来履行其使命。并促进同行评审。 关键词：替代毒理学测试方法验证；计算方法 承包商需要获取并应用新的和现有的科学知识来开发、评估和验证可用于与人类健康直接相关的化学危害识别和风险评估的新型计算方法。这些方法包括但不限于：暴露模型、基于生理学的药代动力学/药效学（PBPK/PD）模型、反向毒代动力学（R-TK）模型、定量构效关系（QSAR）。 ) )承包商通常利用来自体内、体外和/或计算机系统的信息进行建模、定量高通量筛选 (qHTS) 和高内涵 (HC) 数据分析，以及开发新型综合测试和决策策略 (ITDS)。不同的数据类型和多个数据库（例如 ToxRef DB、ToxCastDB、ExpoCastDB、DSSTox、CEBS 等）来开发和评估上述方法。根据经济合作与发展组织 (OECD)3 提出的指导方针，针对联邦机构感兴趣的新型 AOP 制定不良结果途径 (AOP)。 承包商将拟议 AOP 的绩效特征结合到一起。新兴科学文献和新颖的计算方法。 为了探索替代方法的实用性，承包商使用公共和专有数据库来识别、检索和比较新方法生成的数据与已发表文献中传统方法的现有数据。目前已纳入或正在考虑纳入 Tox21 相关工作或 NTP 感兴趣的选定化学品和混合物的毒理学信息 承包商审查和评估从文献检索中收集的数据和信息，并根据需要准备全面的书面报告。 。 为了促进新的和替代测试方法和策略的研究、开发、验证、接受和使用，NICEATM 通过起草 ICCVAM 审查、评论和批准添加的支持文档，支持 ICCVAM 协调对提交和提名的测试方法的评估。 ，NICEATM 可能会被要求协调新兴替代方法的验证研究，承包商可以灵活地分包合同组织内不存在的专业知识或分包必要的验证工作。”