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
