NICEATM Support Contract: Optional Level of Effort

这是一份研发(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研究总体上支持NTP的活动，特别是NTP的生物分子筛选处(BSB)、Tox21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.285l-3)的职责和条款--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战略，这些方法和战略比现有的方法和战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审查来履行其使命。 关键词：替代毒理学策略；测试方法验证；计算方法 承包商必须获得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危险识别和风险评估的新的计算方法。数据开发、分析和评估代表了此需求的大部分工作。这些方法包括但不限于：暴露建模、基于生理的药代动力学/药效学(PBPK/PD)建模、反向毒代动力学(R-TK)建模、定量构效关系(QSAR)建模、定量高通量筛选(QHTS)和高含量(HC)数据的分析，以及使用体内、体外和/或硅系统开发新型集成测试和决策策略(ITDS)。承包商通常使用来自不同数据类型和多个数据库(例如，ToxRef DB、ToxCastDB、ExpoCastDB、DSSTox、CEBS等)的信息。开发和评估以上列出的方法。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AOPS制定不利结果路径(AOPS)。承包者在新出现的科学文献和新的计算方法的背景下分析了拟议AOPS的性能特征。 为了探索替代方法的实用性，承包商识别、检索和比较从新方法产生的数据和从出版的文献中找到的传统方法的现有数据。使用公共和专有数据库，承包商收集目前包括在或正在考虑纳入与Tox21相关的工作或NTP感兴趣的选定化学品和混合物的所有相关生产、使用、暴露和毒理学信息。承包商审查和评估从文献搜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、验收和使用，NICEATM支持ICCVAM-通过起草ICCVAM审查、评论和批准的支持文件来协调对提交和提名的测试方法的评估。此外，NICEATM可能被要求协调对新出现的替代方法的验证研究。承包商可以灵活地分包不在合同组织内的专业知识，也可以分包进行必要的验证工作。

"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."