SUPPORT CONTRACT FOR THE NTP INTERAGENCY CENTER

包括协调对多机构感兴趣的拟议测试方法的技术评估，并就其有用性向适当的联邦机构提供建议。ICCVAM还协调有关验证、接受和国家/国际毒理学测试方法统一的跨机构问题。NICEATM管理并为ICCVAM提供操作和科学支持，并与ICCVAM合作开展相关的验证活动，如同行评审和联邦机构感兴趣的测试方法研讨会。如资源允许，独立验证研究由NICEATM协调。NICEATM和ICCVAM的目标是促进比现有方法更能预测人类、动物和生态影响的新测试方法的科学验证和监管接受，包括在科学可行的情况下改进（减轻疼痛和痛苦）、减少和替代动物使用的方法。为了实现这一目标，NICEATM与ICCVAM合作评估多机构感兴趣的新测试方法。召集独立的同行审查小组，就测试方法的有用性和局限性达成科学共识，并为特定的人类健康和/或生态风险评估目的提供信息。召开专家研讨会和专家小组会议，以评估评估特定毒性的现有方法的充分性，确定需要改进或新方法的领域，评估拟议的验证研究，评估方法的临时验证状态，并为进一步评估或改进各种测试方法的有用性所需的研究，开发和验证研究提出建议。2005年10月31日，ICCVAM收到了来自美国人道协会（HSUS）的提名，要求对肉毒杆菌毒素效价检测的小鼠LD50测定法的替代检测方法进行评估，并优先进行预验证和验证工作。这一进程的第一步是由icvam组织一个研讨会，与ECVAM和其他适当的利益攸关方协调，以确保拥有相关协议和测试数据的个人和组织的合作。在本次研讨会之后，HSUS建议ICCVAM与合适的合作伙伴合作，验证一种或多种替代检测方法，以替代小鼠LD50检测。针对这一提名，委员会建议应高度优先考虑举办一次讲习班。ICCVAM在2005年12月12日的SACATM会议上提出了这一建议。咨委会赞同委员会的建议，即应高度优先重视一个讲习班。2006年5月举办了一个讲习班。NICEATM主任应邀参加由欧共体资助的综合项目ACuteTox联盟的顾问委员会。该联盟由来自学术界、工业界、中小型企业、政府机构和国际组织的35个合作伙伴组成，包括欧洲委员会联合研究中心、欧洲体外测试工业平台、欧洲体外毒理学学会和欧洲共识替代品平台。NICEATM代表参加了2005年10月26-28日在西班牙阿利坎特举行的ACuteTox联盟会议，并介绍了NICEATM/ECVAM体外细胞毒性测定验证研究的现状。ICCVAM/NICEATM成员于2005年11月17日和18日在马里兰州巴尔的摩参加了一个名为“美国采用替代毒理学方法的进展和障碍”的研讨会。本次研讨会的目的是总结在美国监管评估框架和决策程序中实施新的、修订的和替代的毒理学测试方法的进展

include coordinating technical evaluations of proposed test methods of multi-agency interest and providing recommendations regarding their usefulness to appropriate Federal agencies. ICCVAM also coordinates cross-agency issues on validation, acceptance, and national/international harmonization of toxicological test methods. NICEATM administers and provides operational and scientific support for the ICCVAM, and collaborates with ICCVAM to carry out related validation activities such as peer reviews and workshops for test methods of interest to Federal agencies.Independent validation studies are coordinated by NICEATM as resources permit. The goal of NICEATM and ICCVAM is to promote the scientific validation and regulatory acceptance of new test methods that are more predictive of human, animal, and ecological effects than currently available methods, including methods that will refine (lessen pain and distress), reduce, and replace animal use whenever scientifically feasible.To achieve this goal, NICEATM collaborates with ICCVAM to evaluate new test methods of multi-agency interest.Independent peer review panels are convened to develop scientific consensus on the usefulness and limitations of test methods and to generate information for specific human health and/or ecological risk assessment purposes. Expert workshops and expert panel meetings are convened to evaluate the adequacy of current methods for assessing specific toxicities, to identify areas in need of improved or new methods, to evaluate proposed validation studies, to evaluate the interim validation status of methods, and to develop recommendations for research, development, and validation studies needed to further evaluate or improve the usefulness of various test methods.On October 31, 2005, ICCVAM received a nomination from the Humane Society of the United States (HSUS) requesting that alternative test methods to the mouse LD50 assay for Botulinum toxin potency testing be assessed and prioritized for prevalidation and validation efforts.An initial step in this process was for ICCVAM to organize a workshop that would be coordinated with ECVAM and other appropriate stakeholders to secure the cooperation of individuals and organizations that possess relevant protocols and test data.Following this workshop, HSUS proposes that ICCVAM work with appropriate partners to validate one or more of the alternative assays as a replacement of the mouse LD50 test.In response to this nomination, ICCVAM recommended that a workshop should be given a high priority. ICCVAM presented this recommendation to SACATM at their December 12, 2005 meeting.SACATM endorsed the ICCVAM recommendation that a workshop should be given a high priority.A workshop is took place in May 2006. The Director of NICEATM was invited to participate on the advisory board of the ACuteTox Consortium, an integrated project funded by the EC. The Consortium consists of 35 partners from academia, industry, partners from small and medium enterprises, governmental institutions, and partners from international organizations, including the Joint Research Centre of the European Commission, the European In Vitro Testing Industrial Platform, the European Society of Toxicology In Vitro and the European Consensus-Platform for Alternatives.A NICEATM representative participated in the ACuteTox Consortium meeting held in Alicante, Spain on October 26-28, 2005, and gave a presentation on the status of the NICEATM/ECVAM Validation Study of In Vitro Cytotoxicity Assays. ICCVAM/NICEATM members participated in a workshop, Progress and Barriers to Incorporating Alternative Toxicological Methods in the U.S., on November 17 and 18, 2005 in Baltimore, Maryland.The objective of this workshop was to summarize progress in implementing new, revised and alternative toxicological test methods across regulatory evaluation frameworks and decision-making programs in the United States, identify technical,regulatory,economic,orsocietalbarriersandexplore potential bridges to facilitate overcoming such barriers to progress. The workshop produced: Better understanding of current alternatives research and validation efforts in the United States (who, what, objectives of research; availability of resources), enhanced understanding of the environment motivating alternatives research and how this is or is not linked with the regulatory communities who rely on test methods, Identification and understanding of barriers that impede progress, and recommendations to overcome these barriers.The inauguration of the newly established JaCVAM took place November 29 to December 3, 2005 at an international conference held in Tokyo, Japan in conjunction with the JSAAE.Participants included members of the Japanese National Institutes of Health Sciences (NIHS), ECVAM, ICCVAM, NICEATM, and JaCVAM, as well as scientists involved in the field of alternatives in Korea and China.The Chair of ICCVAM was invited to co-chair a plenary session on the establishment of JaCVAM, focusing on the International Partnership on Alternatives.The Director of NICEATM was invited to present a memorial lecture on the Development of Alternative Methods in the U.S. and the Chair of ICCVAM also was invited to present a memorial lecture on International Cooperation of the Validation and Evaluation of Alternative Methods. In June 2005, ECVAM submitted five in vitro human blood cell pyrogenicity tests to the ICCVAM for consideration. These tests were being proposed as replacements for the currently required in vivo rabbit test or an in vitro test that requires the use of hemolymph collected from the Limulus horseshoe crab (Limulus amoebocyte lysate [LAL] test, also referred to as the bacterial endotoxin test [BET]).However, these test methods are similar in that each assay involves the measurement of cytokine levels from either human blood, peripheral blood mononuclear cells (PBMC), or a human monocytoid cell line, as a biomarker of a pyrogenic response.In each assay, cytokine levels are measured with an enzyme-linked immunosorbent assay (ELISA).The five in vitro pyrogenicity test methods are identified as follows:PBMC/IL-6 (The Human PBMC/IL-6 In Vitro Pyrogen Test), WB/IL-1 (The Human Whole Blood/IL-1 In Vitro Pyrogen Test), cryo WB/IL-1 (The Human Whole Blood/IL-1 In Vitro Pyrogen Test: Application of cryopreserved human whole blood), WB/IL-6 (The Human Whole Blood/IL-6 In Vitro Pyrogen Test), and MM6/IL6 (An Alternative In Vitro Pyrogen Test Using the Human Monocytoid Cell Line MONO MAC-6 [MM6]).NICEATM announced the availability of the report entitled, ICCVAM Test Method Evaluation Report:In Vitro Ocular Toxicity Test Methods for Identifying Severe Irritants and Corrosives.The report provides recommendations on the use of four in vitro test methods in a tiered-testing strategy, where positive substances can be classified as ocular corrosives or severe irritants. The four ocular toxicity test methods evaluated are (1) the Bovine Corneal Opacity and Permeability [BCOP] test, (2) the Isolated Chicken Eye [ICE] test, (3) the Isolated Rabbit Eye [IRE] test, and (4) the Hens Egg Test Chorioallantoic Membrane [HET-CAM]. The report includes (a) ICCVAMs final test method recommendations on the use of these four in vitro test methods, (b) test method protocols for use, (c) recommended future optimization and validation studies, (d) reference substances for such studies, and (e) overall recommendations related to all four in vitro test methods. Keywords NICEATM/ICCVAM Five-Year Plan;CongressionalMandate;research;development; translation;validation of new and revised non-animal and other alternative assays;federal testing program;validation status of LLNA; town meeting;pyrogenicity peer review panel;botulinum toxins;ocular corrosives and severe irritants;6th World Congress on Animal Use in the Life Sciences;endocrine disruptor international validation study. SUMMARY:The NIEHS was directed by Public Law 103-43 to develop and validate alternative methods for acute and chronic toxicity testing and to develop criteria and processes for the validation and regulatory acceptance of alternative methods.To implement these directives, the NIEHS, in collaboration with 14 other Federal regulatory and research agencies, established a standing Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in 1997.Public Law 106-545, the ICCVAM Authorization Act of 2000, established ICCVAM as a permanent committee under the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) in 2000.ICCVAM's duties