RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE

Subcommittee on the Toxicity of Diisopropyl Methylphosphonate

Committee on Toxicology

Board on Environmental Studies and Toxicology

Commission on Life Sciences

National Research Council

NATIONAL ACADEMY PRESS
Washington, D.C.



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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE Subcommittee on the Toxicity of Diisopropyl Methylphosphonate Committee on Toxicology Board on Environmental Studies and Toxicology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C.

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE NATIONAL ACADEMY PRESS 2101 Constitution Ave., N.W. Washington, D.C. 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This project was supported by Contract No. DAMD 17-89-C-9086 and DAMD 17-99-C-9049 between the National Academy of Sciences and the U.S. Department of Defense. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project. International Standard Book Number 0-309-07255-7 Additional copies of this report are available from: National Academy Press 2101 Constitution Ave., NW Box 285 Washington, DC 20055 800-624-6242 202-334-3313 (in the Washington metropolitan area) http://www.nap.eduCopyright 2000 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE THE NATIONAL ACADEMIES National Academy of Sciences National Academy of Engineering Institute of Medicine National Research Council The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE SUBCOMMITTEE ON THE TOXICITY OF DIISOPROPYL METHYLPHOSPHONATE JOHN A. MOORE (Chair), Center for Evaluating Risks to Human Reproduction, Alexandria, Virginia MELVIN E. ANDERSEN, Colorado State University, Fort Collins PETER L. DEFUR, Virginia Commonwealth University, Richmond PAUL M.D. FOSTER, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina SIDNEY GREEN, Howard University, Washington, DC DAVID H. MOORE, Battelle Memorial Institute, Bel Air, Maryland Staff SUSAN N.J. PANG, Project Director KATE KELLY, Editor MIRSADA KARALIC-LONCAREVIC, Information Specialist LEAH L. PROBST, Senior Project Assistant EMILY L. SMAIL, Project Assistant Sponsor: U.S. Department of Defense

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE COMMITTEE ON TOXICOLOGY BAILUS WALKER, JR. (Chair), Howard University Medical Center and American Public Health Association, Washington, DC MELVIN E. ANDERSEN, Colorado State University, Fort Collins, Colorado GERMAINE M. BUCK, University of Buffalo, State of New York ROBERT E. FORSTFR II, University of Pennsylvania, Philadelphia PAUL M.D. FOSTER, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina WILLIAM E. HALPERIN, National Institute for Occupational Safety and Health, Cincinnati, Ohio CHARLES H. HOBBS, Lovelace Respiratory Research Institute and Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico SAMUEL KACEW, University of Ottawa, Ottawa, Ontario NANCY KERKVLIET, Oregon State University, Corvallis FLORENCE K. KINOSHITA, Hercules Incorporated, Wilmington, Delaware MICHAEL J. KOSNETT, University of Colorado Health Sciences Center, Denver MORTON LIPPMANN, New York University School of Medicine, Tuxedo ERNEST E. MCCONNELL, ToxPath, Inc., Raleigh, North Carolina THOMAS E. MCKONE, Lawrence Berkeley National Laboratory and University of California, Berkeley HARIHARA MEHENDALE, University of Louisiana, Monroe DAVID H. MOORE, Battelle Memorial Institute, Bel Air, Maryland GÜNTER OBERDÖRSTER, University of Rochester, Rochester, New York JOHN L. O'DONOGHUE, Eastman Kodak Company, Rochester, New York GEORGE M. RUSCH, AlliedSignal, Inc., Morristown, New Jersey MARY E. VORE, University of Kentucky, Lexington ANNETTA P. WATSON, Oak Ridge National Laboratory, Oak Ridge, Tennessee LAUREN ZEISE, California Environmental Protection Agency, Oakland Staff KULBIR S. BAKSHI, Program Director SUSAN N.J. PANG, Program Officer ABIGAIL E. STACK, Program Officer RUTH E. CROSSGROVE, Publications Manager KATHRINE J. IVERSON, Manager Toxicology Information Center EMILY L. SMAIL, Project Assistant

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY GORDON ORIANS (Chair), University of Washington, Seattle DONALD MATTISON (Vice Chair), March of Dimes, White Plains, New York DAVID ALLEN, University of Texas, Austin INGRID C. BURKE, Colorado State University, Fort Collins WILLIAM L. CHAMEIDES, Georgia Institute of Technology, Atlanta JOHN DOULL, The University of Kansas Medical Center, Kansas City CHRISTOPHER B. FIELD, Carnegie Institute of Washington, Stanford, California JOHN GERHART, University of California, Berkeley J. PAUL GILMAN, Celera Genomics, Rockville, Maryland BRUCE D. HAMMOCK, University of California, Davis MARK HARWELL, University of Miami, Miami, Florida ROGENE HENDERSON, Lovelace Respiratory Research Institute, Albuquerque, New Mexico CAROL HENRY, American Chemistry Council, Arlington, Virginia BARBARA HULKA, University of North Carolina, Chapel Hill JAMES F. KITCHELL, University of Wisconsin, Madison DANIEL KREWSKI, University of Ottawa, Ottawa, Ontario JAMES A. MACMAHON, Utah State University, Logan MARIO J. MOLINA, Massachusetts Institute of Technology, Cambridge CHARLES O'MELIA, Johns Hopkins University, Baltimore, Maryland WILLEM F. PASSCHIER, Health Council of the Netherlands, The Hague KIRK SMITH, University of California, Berkeley MARGARET STRAND, Oppenheimer Wolff Donnelly & Bayh, LLP, Washington, DC TERRY F. YOSIE, American Chemistry Council, Arlington, Virginia Senior Staff JAMES J. REISA, Director DAVID J. POLICANSKY, Associate Director and Senior Program Director for Applied Ecology CAROL A. MACZKA, Senior Program Director for Toxicology and Risk Assessment RAYMOND A. WASSEL, Senior Program Director for Environmental Sciences and Engineering KULBIR BAKSHI, Program Director for the Committee on Toxicology LEE R. PAULSON, Program Director for Resource Management ROBERTA M. WEDGE, Program Director for Risk Analysis

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE COMMISSION ON LIFE SCIENCES MICHAEL T. CLEGG (Chair), University of California, Riverside, PAUL BERG (Vice Chair), Stanford University, Stanford, California FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, D.C. JOANNA BURGER, Rutgers University, Piscataway, New Jersey JAMES E. CLEAVER, University of California, San Francisco DAVID S. EISENBERG, University of California, Los Angeles JOHN L. EMMERSON, Fishers, Indiana NEAL L. FIRST, University of Wisconsin, Madison DAVID J. GALAS, Keck Graduate Institute of Applied Life Science, Claremont, California DAVID V. GOEDDEL, Tularik, Inc., South San Francisco, California ARTURO GOMEZ-POMPA, University of California, Riverside COREY S. GOODMAN, University of California, Berkeley JON W. GORDON, Mount Sinai School of Medicine, New York DAVID G. HOEL, Medical University of South Carolina, Charleston BARBARA S. HULKA, University of North Carolina, Chapel Hill CYNTHIA J. KENYON, University of California, San Francisco BRUCE R. LEVIN, Emory University, Atlanta, Georgia DAVID M. LIVINGSTON, Dana-Farber Cancer Institute, Boston, Massachusetts DONALD R. MATTISON, March of Dimes, White Plains, New York ELLIOT M. MEYEROWITZ, California Institute of Technology, Pasadena ROBERT T. PAINE, University of Washington, Seattle RONALD R. SEDEROFF, North Carolina State University, Raleigh ROBERT R. SOKAL, State University of New York, Stony Brook CHARLES F. STEVENS, The Salk Institute for Biological Studies, La Jolla, California SHIRLEY M. TILGHMAN, Princeton University, Princeton, New Jersey RAYMOND L. WHITE, University of Utah, Salt Lake City Staff WARREN R. MUIR, Executive Director JACQUELINE K. PRINCE, Financial Officer BARBARA B. SMITH, Administrative Associate LAURA T. HOLLIDAY, Senior Program Assistant

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY Toxicological Effects of Methylmercury (2000) Strengthening Science at the U.S. Environmental Protection Agency: Research-Management and Peer-Review Practices (2000) Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000) Modeling Mobile-Source Emissions (2000) Toxicological Risks of Selected Flame-Retardant Chemicals (2000) Copper in Drinking Water (2000) Ecological Indicators for the Nation (2000) Waste Incineration and Public Health (1999) Hormonally Active Agents in the Environment (1999) Research Priorities for Airborne Particulate Matter: I. Immediate Priorities and a Long-Range Research Portfolio (1998); II. Evaluating Research Progress and Updating the Portfolio (1999) Ozone-Forming Potential of Reformulated Gasoline (1999) Risk-Based Waste Classification in California (1999) Arsenic in Drinking Water (1999) Brucellosis in the Greater Yellowstone Area (1998) The National Research Council's Committee on Toxicology: The First 50 Years (1997) Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests (1997) Carcinogens and Anticarcinogens in the Human Diet (1996) Upstream: Salmon and Society in the Pacific Northwest (1996) Science and the Endangered Species Act (1995) Wetlands: Characteristics and Boundaries (1995) Biologic Markers (5 reports, 1989-1995) Review of EPA's Environmental Monitoring and Assessment Program (3 reports, 1994-1995) Science and Judgment in Risk Assessment (1994) Ranking Hazardous Waste Sites for Remedial Action (1994) Pesticides in the Diets of Infants and Children (1993) Issues in Risk Assessment (1993) Setting Priorities for Land Conservation (1993) Protecting Visibility in National Parks and Wilderness Areas (1993) Dolphins and the Tuna Industry (1992) Hazardous Materials on the Public Lands (1992) Science and the National Parks (1992) Animals as Sentinels of Environmental Health Hazards (1991) Assessment of the U.S. Outer Continental Shelf Environmental Studies Program, Volumes I-IV (1991-1993) Human Exposure Assessment for Airborne Pollutants (1991)

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE Monitoring Human Tissues for Toxic Substances (1991) Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991) Decline of the Sea Turtles (1990) Copies of these reports may be ordered from the National Academy Press (800) 624-6242 (202) 334-3313 www.nap.edu

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY Methods for Developing Spacecraft Water Exposure Guidelines (2000) Review of the U.S. Navy Environmental Health Center's Health-Hazard Assessment Process (2000) Review of the U.S. Navy's Exposure Standard for Manufactured Vitreous Fibers (2000) Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23, and HFC-404a (2000) Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999) Toxicity of Military Smokes and Obscurants, Volume 1 (1997), Volume 2 (1999), Volume 3 (1999) Assessment of Exposure-Response Functions for Rocket-Emission Toxicants (1998) Review of a Screening Level Risk Assessment for the Naval Air Facility at Atsugi, Japan (Letter Report) (1998) Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 (1996) Permissible Exposure Levels for Selected Military Fuel Vapors (1996) Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1 (1994), Volume 2 (1996), Volume 3 (1996), Volume 4 (2000)

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE Preface THERE HAS BEEN a long-standing disagreement between the U.S. Army and the tate of Colorado over the appropriate drinking-water guideline for diisopropyl methylphosphonate (DIMP), a groundwater contaminant at the U.S. Army 's Rocky Mountain Arsenal. The disagreement is over the 100-fold difference between the guideline established by the U.S. Environmental Protection Agency and the one promulgated by Colorado. In response to a request from the Army, the National Research Council (NRC) has conducted an independent evaluation of new studies on the toxicity of DIMP and a re-evaluation of the federal and state drinking-water guidelines for DIMP. This report is intended to provide information to help assess clean-up efforts at the arsenal. This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the NRC's Report Review Committee. The purpose of this independent review is to provide candid and critical comments that assist the NRC in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their participation in the review of this report: Maureen Feuston, Sanofi Pharmaceuticals, Inc., Malvern, Pennsylvania; Curtis

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE Klaassen, University of Kansas Medical Center, Kansas City, Kansas; Loren Koller, Oregon State University, Corvallis, Oregon; and Ernest Eugene McConnell, ToxPath, Inc., Raleigh, North Carolina. Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Harihara Mehendale, University of Louisiana at Monroe, Monroe, Louisiana, appointed by the Commission on Life Sciences, who was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution. We gratefully acknowledge the individuals who provided background material and gave presentations to the subcommittee: Thomas Bucci, Pathology Associates International; Edward Calabrese, University of Massachusetts; Timothy Kilgannon, Rocky Mountain Arsenal; Raj Goyal, Edward La Rock, and Ellen Mangione, Colorado Department of Public Health and Environment; and William Wustenburg, Alternet Medical. We are also grateful for the assistance of the NRC staff in preparing the report. Staff members who contributed to this effort are Carol Maczka, senior program director for the Toxicology and Risk Assessment Program; Kulbir Bakshi, senior program director of the Committee on Toxicology; Kate Kelly, technical editor; Leah Probst and Emily Smail, project assistants; and Mirsada Karalic-Loncarevic, information specialist. We especially wish to recognize the contributions of project director Susan Pang, who coordinated the project and contributed to the preparation of the subcommittee's report. Finally, we would like to thank all the members of the subcommittee for their dedicated efforts throughout the development of this report. John A. Moore, D.V.M. Chair, Subcommittee on the Toxicity of Diisopropyl Methylphosphonate Bailus Walker, Jr., Ph.D., M.P.H. Chair, Committee on Toxicology

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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE Contents     EXECUTIVE SUMMARY   1     INTRODUCTION   3     EVALUATION   5     REFERENCES   27     APPENDIX BIOGRAPHICAL INFORMATION ON THE SUBCOMMITTEE ON THE TOXICITY OF DIISOPROPYL METHYLPHOSPHONATE   31

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