IGF::CL,CT::IGF TITLE: SUPPORT CONTRACT FOR THE NTP NICEATM

IGF::CL,CT::IGF 标题：NTP NICEATM 支持合同

• 批准号: 9156437
• 负责人: DAVID ALLEN
• 金额: $ 19.39万
• 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 2016-05-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9156437
• 关键词: Animals; Authorization documentation; Characteristics; Chemicals; Computer Simulation; Contractor; Contracts; Data; Databases; Development; Documentation; Drug Kinetics; 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 Support; Risk Assessment; Support Contracts; System; Testing; Toxicokinetics; Validation; Work; Writing; adverse outcome; base; flexibility; high throughput screening; in vivo; information gathering; interest; meetings; novel; operation; pharmacodynamic model; research and development; safety testing; screening; text searching; 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. 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 inder 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.

这是一份研究与开发（R&D）合同，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研究支持NTP的活动，特别是NTP的生物分子筛选分支（BSB），Tox 21联盟和替代方法验证机构间协调委员会（ICCVAM）。NICEATM负责确保遵守2000年ICCVAM授权法案（42 U.S.C. 285 l-3）-促进研究、开发、验证、评估、接受和使用新的和替代的测试方法和策略，这些方法和策略比现有的方法和策略更能预测人类健康和生态影响。NICEATM通过执行独立的研发活动、审查拟议的测试方法、组织研讨会和会议以及促进同行评审来履行其使命。 承包商必须获取和应用新的和现有的科学知识，以开发、评估和验证可用于与人类健康直接相关的化学品危害识别和风险评估的新的计算方法。数据开发、分析和评估是这一要求的很大一部分工作。这些方法包括但不限于：暴露建模、基于生理学的药代动力学/药效学（PBPK/PD）建模、反向毒代动力学（R-TK）建模、定量结构-活性关系（QSAR）建模、定量高通量筛选（qHTS）和高含量（HC）数据分析，以及使用体内开发新的综合测试和决策策略（ITDS），体外和/或计算机模拟系统。承包商通常使用来自不同数据类型和多个数据库的信息（例如，ToxRef DB、ToxCastDB、ExpoCastDB、DSSTox、CEBS等）制定和评估上述方法。承包商根据经济合作与发展组织（OECD）3提出的指导方针，为联邦机构感兴趣的新型AOP制定不良结果途径（AOP）。承包商应在新兴科学文献和新颖计算方法的背景下分析拟议AOP的性能特征。 为了探索替代方法的效用，承包商识别、检索并比较新方法产生的数据与已发表文献中传统方法产生的现有数据。使用公共和专有数据库，承包商收集所有相关的生产，使用，接触，和选定的化学品和混合物的毒理学信息，目前包括或考虑纳入Tox 21相关的努力或感兴趣的NTP。承包商审查和评估从文献检索中收集的数据和信息，并根据需要编写全面的书面报告。 为了促进新的和替代的测试方法和策略的研究、开发、验证、接受和使用，NICEATM通过起草支持文件供ICCVAM审查、评论和批准，支持ICCVAM协调对提交和提名的测试方法的评估。此外，还可要求NICEATM协调对新出现的替代方法的验证研究。承包商可以灵活地征求合同组织内没有的专门知识，或征求必要的验证工作。