ICCVAM VALIDATION AND REGULATORY ACCEPTANCE OF TOXICOLOGICAL TEST METHODS A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods http://iccvam.niehs.nih.gov/parts/iccvam.html (1 of 2) [2000/10/20 7:53:24 AM] ICCVAM NIH PUBLICATION NO: 97-3981 National Institute of Environmental Health Sciences Research Triangle Park, North Carolina 27709 National Institutes of Health U.S. Public Health Service Department of Health and Human Services March 1997 NIEHS (National Institute of Environmental Health Sciences), Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods, NIH Publication No. 97-3981, NIEHS, Research Triangle Park , North Carolina, U.S.A., 1997. TABLE OF CONTENTS http://iccvam.niehs.nih.gov/parts/iccvam.html (2 of 2) [2000/10/20 7:53:24 AM] TOC TABLE OF CONTENTS Acronyms/Abbreviations ICCVAM Agency Representatives and Participants ICCVAM Workgroups Acknowledgements Preface Executive Summary I. Introduction II. Validation of Test Methods III. Regulatory Acceptance of Toxicological Test Methods IV. Future Directions and Implementation V. Appendixes Appendix A - Glossary Appendix B - Comparison of Selected Agency Processes for Test Method Acceptance Appendix C - International Organizations Concerned with Toxicological Testing Appendix D - References and Selected Bibliography of Related Publications Appendix E - NRC Risk Assessment Paradigms Appendix F - 1993 NIH Revitalization Act, Sections 1301 and 205 Appendix G - Federal Register Notice, December 7, 1994 Appendix H - December 11-12, 1995, NTP Workshop http://iccvam.niehs.nih.gov/parts/toc.html [2000/10/20 7:54:16 AM] ACRONYMS/ABBREVIATIONS ACRONYMS/ABBREVIATIONS AAMI Association for the Advancement of Medical Instrumentation AOAC Association of Official Analytical Chemists International APHIS Animal and Plant Health Inspection Service/USDA ARS Agricultural Research Service/USDA ASTM American Society for Testing and Materials ATSDR Agency for Toxic Substances and Disease Registry/DHHS CBER Center for Biologics Evaluation and Research/FDA CDC Centers for Disease Control and Prevention/DHHS CDER Center for Drug Evaluation and Research/FDA Comprehensive Environmental Response, Compensation, and Liability Act CERCLA (Superfund)/EPA CFSAN Center for Food Safety and Applied Nutrition/FDA CPSC Consumer Product Safety Commission CRADA Collaborative Research and Development Agreement CVM Center for Veterinary Medicine/FDA DFS Division of Food Safety/CFSAN/FDA DHHS Department of Health and Human Services DLPAD/NIH Division of Legislative Policy Analysis and Development DMS Division of Microbiological Studies/CFSAN/FDA DOD Department of Defense DOE Department of Energy DOI Department of the Interior DOL Department of Labor DOT Department of Transportation DTR Division of Toxicological Research/CFSAN/FDA EEC European Economic Council EPA Environmental Protection Agency FDA Food and Drug Administration/DHHS FFDCA Federal Food, Drug, and Cosmetics Act/FDA FIFRA Federal Insecticide, Fungicide, and Rodenticide Act/OPP/EPA GLP Good Laboratory Practice Regulations ICCVAM Ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods International Conference on Harmonization of Technical Requirements for Registration ICH of Pharmaceuticals for Human Use ISO International Organization for Standardization IRAG Ad hoc Interagency Regulatory Alternatives Group MAD Mutual Acceptance of Data Principles/OECD NCI National Cancer Institute/NIH NCTR National Center for Toxicological Research/FDA http://iccvam.niehs.nih.gov/parts/ACRONYM.html (1 of 2) [2000/10/20 7:54:25 AM] ACRONYMS/ABBREVIATIONS NIEHS National Institute of Environmental Health Sciences/NIH NIH National Institutes of Health/DHHS NIOSH National Institute for Occupational Safety and Health/CDC NLM National Library of Medicine/NIH NRC National Research Council NTIS National Technical Information Service NTP National Toxicology Program/DHHS OECD Organization for Economic Cooperation and Development OLAR Office of Laboratory Animal Research/NIH OPPT Office of Pollution Prevention and Toxics/EPA OPP Office of Pesticide Programs/EPA ORD Office of Research and Development/EPA OSHA Occupational Safety and Health Administration/DOL OSRS Office of Special Research Skills/CFSAN/FDA SAB Science Advisory Board/EPA SAP Scientific Advisory Panel/FIFRA/EPA SOP Standard Operating Procedures TASARC Tri-Agency Superfund Applied Research Committee TSCA Toxic Substances Control Act/OPPT/EPA UN Transport United Nations Committee of Experts on the Transport of Dangerous Goods USDA United States Department of Agriculture USP United States Pharmacopeia 3Rs Refinement, Reduction, and Replacement (of Animal Use http://iccvam.niehs.nih.gov/parts/ACRONYM.html (2 of 2) [2000/10/20 7:54:25 AM] Agency Representatives and Participants INTERAGENCY COORDINATING COMMITTEE ON THE VALIDATION OF ALTERNATIVE METHODS AGENCY REPRESENTATIVES* AND PARTICIPANTS Agency for Toxic Substances and Disease Registry Christopher DeRosa* William Cibulas Consumer Product Safety Commission Marilyn Wind* Department of Defense Harry Salem* Robert Finch John Frazier Department of Energy James Beall* Marvin Frazier Department of the Interior Barnett Rattner* Eugene Greer Department of Transportation James O'Steen* George Cushmac Environmental Protection Agency Richard Hill (co-chair)* - OPPTS Penelope Fenner-Crisp - OPPTS Angela Auletta - OPPTS Robert MacPhail - ORD Hugh Tilson - ORD Food and Drug Administration David Hattan* - CFSAN William Allaben - NCTR Joy A. Cavagnaro - CBER Joseph Contrera - CDER Sidney Green (to 12/31/95) - CFSAN Anita OÍConnor - Office of Science Leonard Schechtman - CVM Neil Wilcox - Office of Science National Cancer Institute David Longfellow* http://iccvam.niehs.nih.gov/parts/AGENCRE.html (1 of 2) [2000/10/20 7:54:26 AM] Agency Representatives and Participants Victor Fung National Institute of Environmental Health Sciences William Stokes (co-chair)* Errol Zeiger John Bucher National Institute for Occupational Safety and Health Doug Sharpnack* Bryan Hardin David Dankovic National Library of Medicine Vera Hudson* Sidney Siegel Arthur Wykes (to 6/30/95) Occupational Safety and Health Administration Loretta Schuman* United States Department of Agriculture Linda Kahn* - APHIS Helene Guttman* - ARS (to 9/30/95) National Institutes of Health, Office of the Director Louis Sibal - OLAR Christina Blakeslee - DLPAD http://iccvam.niehs.nih.gov/parts/AGENCRE.html (2 of 2) [2000/10/20 7:54:26 AM] ICCVAM Workgroups INTERAGENCY COORDINATING COMMITTEE ON THE VALIDATION OF ALTERNATIVE METHODS WORKGROUPS Validation Workgroup William Allaben, FDA James Beall, DOE William Cibulas, ATSDR Sidney Green, FDA Helene Guttman, USDA David Longfellow, NCI Robert MacPhail, EPA Barnett Rattner, DOI Harry Salem, DOD Doug Sharpnack, NIOSH William Stokes, NIEHS Arthur Wykes, NLM Errol Zeiger, NIEHS (group coordinator) Implementation Workgroup Joy Cavagnaro, FDA (group coordinator) Richard Hill, EPA Penelope Fenner-Crisp, EPA James O'Steen, DOT William Stokes, NIEHS Neil Wilcox, FDA David Hattan, FDA NIEHS Committee Support Loretta F. Brammell, Technical Information Specialist Pamela S. Wigington, Editorial Assistant NIEHS Workshop Support Group Alma Britton Sandra V. Lange Anna Lee Sabell Regulatory Acceptance Workgroup Angela Auletta, EPA (group coordinator) Joy Cavagnaro, FDA Joseph Contrera, FDA Penelope Fenner-Crisp, EPA Victor Fung, NCI Bryan Hardin, NIOSH David Hattan, FDA http://iccvam.niehs.nih.gov/parts/WKGROUP.html (1 of 2) [2000/10/20 7:54:26 AM] ICCVAM Workgroups Richard Hill, EPA Vera Hudson, NLM Anita O'Connor, FDA James O'Steen, DOT Loretta Schuman, OSHA Marilyn Wind, CPSC http://iccvam.niehs.nih.gov/parts/WKGROUP.html (2 of 2) [2000/10/20 7:54:26 AM] Acknowledgments Acknowledgments ICCVAM acknowledges the following individuals who provided information considered in preparing this report or who reviewed and submitted comments on draft versions of the report. Jenan Al-Atrash The Soap & Detergent Association Charles Alden National Institute of Environmental Health Sciences Sarah Amundson Doris Day Animal League Daniel M. Bagley Colgate-Palmolive Paul T. Bailey Stonybrook Laboratories, Inc. Michael Balls European Center for the Validation of Alternative Methods Italy John Bantle Oklahoma State University George Becking World Health Organization Gary Boorman National Institute of Environmental Health Sciences P.A. Botham Zeneca, United Kingdom Klaus Brendel University of Arizona David Bridge National Institute of Environmental Health Sciences Leon H. Bruner Procter & Gamble Company, United Kingdom David J. Brusick Corning Hazleton Thomas Cameron National Cancer Institute http://iccvam.niehs.nih.gov/parts/ACKNOWL.html (1 of 8) [2000/10/20 7:54:27 AM]