Copper in Drinking Water

COMMITTEE ON COPPER IN DRINKING WATER

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

COMMISSION ON LIFE SCIENCES

NATIONAL RESEARCH COUNCIL

NATIONAL ACADEMY PRESS
WASHINGTON, D.C.



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Copper in Drinking Water Copper in Drinking Water COMMITTEE ON COPPER IN DRINKING WATER BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY COMMISSION ON LIFE SCIENCES NATIONAL RESEARCH COUNCIL NATIONAL ACADEMY PRESS WASHINGTON, D.C.

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Copper in Drinking Water 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 Cooperative Agreement No. CR827277-01 between the National Academy of Sciences and the U.S. Environmental Protection Agency. 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. Library of Congress Card Catalog Number 00-102668 International Standard Book Number 0-309-06939-4 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.edu Copyright 2000 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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Copper in Drinking Water 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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Copper in Drinking Water COMMITTEE ON COPPER IN DRINKING WATER RICHARD BULL (Chair), Battelle Pacific Northwest Division, Richland, Wash. MICHAEL ASCHNER, Wake Forest University, Winston-Salem, N.C. GEORGE BREWER, University of Michigan, Ann Arbor, Mich. EDWARD HARRIS, Texas A&M University, College Station, Tex. CARL KEEN, University of California, Davis, Calif. KARL KELSEY, Harvard University, Boston, Mass. F. WILLIAM SUNDERMAN, JR., Middlebury College, Middlebury, Vt. JOYCE TSUJI, Exponent, Bellevue, Wash. LAUREN ZEISE, California Environmental Protection Agency, Oakland, Calif. Staff CAROL A. MACZKA, Project Director MICHELLE C. CATLIN, Postdoctoral Research Associate RUTH E. CROSSGROVE, Editor JUDITH L. ESTEP, Senior Program Assistant LAURA T. HOLLIDAY, Senior Program Assistant MIRSADA KARALIC-LONCAREVIC, Information Specialist Sponsor: U.S. Environmental Protection Agency

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Copper in Drinking Water BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY GORDON ORIANS (Chair), University of Washington, Seattle, Wash. DONALD MATTISON (Vice Chair), March of Dimes, White Plains, N.Y. DAVID ALLEN, University of Texas, Austin, Tex. INGRID C. BURKE, Colorado State University, Fort Collins, Colo. WILLIAM L. CHAMEIDES, Georgia Institute of Technology, Atlanta, Ga. JOHN DOULL, The University of Kansas Medical Center, Kansas City, Kan. CHRISTOPHER B. FIELD, Carnegie Institute of Washington, Stanford, Calif. JOHN GERHART, University of California, Berkeley, Calif. J. PAUL GILMAN, Celera Genomics, Rockville, Md. BRUCE D. HAMMOCK, University of California, Davis, Calif. MARK HARWELL, University of Miami, Miami, Fla. ROGENE HENDERSON, Lovelace Respiratory Research Institute, Albuquerque, N.M. CAROL HENRY, Chemical Manufacturers Association, Arlington, Va. BARBARA HULKA, University of North Carolina, Chapel Hill, N.C. JAMES F. KITCHELL, University of Wisconsin, Madison, Wisc. DANIEL KREWSKI, University of Ottawa, Ottawa, Ont. JAMES A. MACMAHON, Utah State University, Logan, Utah MARIO J. MOLINA, Massachusetts Institute of Technology, Cambridge, Mass. CHARLES O'MELIA, Johns Hopkins University, Baltimore, Md. WILLEM F. PASSCHIER, Health Council of the Netherlands KIRK SMITH, University of California, Berkeley, Calif. MARGARET STRAND, Oppenheimer Wolff Donnelly & Bayh, LLP, Washington, D.C. TERRY F. YOSIE, Chemical Manufacturers Association, Arlington, Va. 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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Copper in Drinking Water COMMISSION ON LIFE SCIENCES MICHAEL T. CLEGG (Chair), University of California, Riverside, Calif. PAUL BERG (Vice Chair), Stanford University, Stanford, Calif. FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, D.C. JOANNA BURGER, Rutgers University, Piscataway, N.J. JAMES E. CLEAVER, University of California, San Francisco, Calif. DAVID EISENBERG, University of California, Los Angeles, Calif. JOHN EMMERSON, Fishers, Ind. NEAL FIRST, University of Wisconsin, Madison, Wisc. DAVID J. GALAS, Keck Graduate Institute of Applied Life Science, Claremont, Calif. DAVID V. GOEDDEL, Tularik, Inc., South San Francisco, Calif. ARTURO GOMEZ-POMPA, University of California, Riverside, Calif. COREY S. GOODMAN, University of California, Berkeley, Calif. JON W. GORDON, Mount Sinai School of Medicine, New York, N.Y. DAVID G. HOEL, Medical University of South Carolina, Charleston, S.C. BARBARA S. HULKA, University of North Carolina, Chapel Hill, N.C. CYNTHIA KENYON, University of California, San Francisco, Calif. BRUCE R. LEVIN, Emory University, Atlanta, Ga. DAVID LIVINGSTON, Dana-Farber Cancer Institute, Boston, Mass. DONALD R. MATTISON, March of Dimes, White Plains, N.Y. ELLIOT M. MEYEROWITZ, California Institute of Technology, Pasadena, Calif. ROBERT T. PAINE, University of Washington, Seattle, Wash. RONALD R. SEDEROFF, North Carolina State University, Raleigh, N.C. ROBERT R. SOKAL, State University of New York, Stony Brook, N.Y. CHARLES F. STEVENS, The Salk Institute, La Jolla, Calif. SHIRLEY M. TILGHMAN, Princeton University, Princeton, N.J. RAYMOND L. WHITE, University of Utah, Salt Lake City, Utah 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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Copper in Drinking Water OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY 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) 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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Copper in Drinking Water Preface In 1991, the U.S. Environmental Protection Agency (EPA) promulgated a maximum contaminant level goal (MCLG) of 1.3 mg/L for copper in drinking water. Some states and municipalities have difficulty maintaining copper levels below the MCLG primarily because of the characteristics of their water. On the basis of recent data from epidemiological studies, questions have been raised about the validity of the science on which the MCLG is based and whether that level is appropriate. In response to those questions, the U.S. Congress requested that the National Research Council (NRC) independently evaluate the toxicological, epidemiological, and exposure data on copper and determine whether EPA's MCLG is scientifically valid. In this report, the Committee on Copper in Drinking Water of the NRC reviews the validity of the scientific basis for EPA's MCLG. The committee reviewed the available toxicological, epidemiological, and exposure data (from food and water) and evaluated the appropriateness of the critical study, end points of toxicity, and uncertainty factors used by EPA in the derivation of the MCLG for copper. The committee was also asked to identify data gaps and make recommendations for future research. 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 for reviewing NRC and Institute of Medicine reports. The purpose of this independent review is to provide candid and critical comments that will assist the NRC in making the published report as sound as possible and to ensure that the

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Copper in Drinking Water report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscripts remain confidential to protect the integrity of the deliberative process. The committee wishes to thank the following individuals, who are neither officials nor employees of the NRC, for their participation in the review of this report: John L. Emmerson, Eli Lilly (retired) Portland, Oregon; Diane W. Cox, University of Alberta; Henry A. Anderson, Wisconsin Division of Public Health; Dennis Thiele, University of Michigan; Richard Stevens, University of Connecticut; George Becking, Phoenix OHC; George Cherian, University of Western Ontario; Vincent Piccirillo, NPC, Incorporated; Joseph Rodricks, The Life Sciences Consultancy. The individuals listed above have provided many constructive comments and suggestions. It must be emphasized, however, that responsibility for the final content of this report rests entirely with the authoring committee and the NRC. The committee gratefully acknowledges the following individuals for providing background information and for making presentations to the committee: Edward Ohanian, Joyce Donohue, and James Taft, all of EPA; Debbie Reed, of the office of Senator J. Robert Kerrey (Nebraska); and Allison Yates and Paula Trumbo, of the NRC Food and Nutrition Board. The committee also acknowledges Scott Baker, of the International Copper Association; Ken Poirier, of Toxicology Excellence for Risk Assessment; and Magdalena Araya, of the University of Chile, for information on the international tri-site acute copper study. We are grateful for the assistance of the NRC staff in preparing the report. Staff members who contributed to this effort are Carol A. Maczka, senior program director for toxicology and risk assessment; Michelle Catlin, postdoctoral research associate; Ruth E. Crossgrove, editor; Judy Estep, senior project assistant; Laura Holliday, senior project assistant; and Mirsada Karalic-Loncarevic, information specialist. Finally, I would like to thank all the members of the committee for their dedicated efforts throughout the development of this report. Richard J. Bull, Ph.D. Chairman Committee on Copper in Drinking Water

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Copper in Drinking Water Contents     EXECUTIVE SUMMARY   1 1   INTRODUCTION   9     Chemical and Physical Properties   11     Sources of Copper in Drinking Water   12     Committee's Approach to Its Charge   12     Structure of the Report   13     References   14 2   PHYSIOLOGICAL ROLE OF COPPER   16     Essentiality   16     Biochemistry and Physiology   17     Factors Affecting Bioavailability   21     Conclusions   26     Recommendations   26     References   27 3   HEALTH EFFECTS OF COPPER DEFICIENCIES   33     Teratogenesis of Copper Deficiency   33     Health Effects of Copper Deficiencies in Adults   42     Conclusions   43     References   45

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Copper in Drinking Water 4   DISORDERS OF COPPER HOMEOSTASIS   51     Menkes Disease   51     Occipital Horn Syndrome   53     Wilson Disease   55     Genetic Characteristics of Wilson and Menkes Diseases   56     Heterozygotes for Wilson Disease   58     Aceruloplasminemia   62     Tyrolean Infantile Cirrhosis   64     Indian Childhood Cirrhosis   64     Idiopathic Copper Toxicosis   65     Other Genetic Disorders   65     Disease-Induced Changes in Copper Homeostasis   66     Conclusions   67     Recommendations   68     References   69 5   HEALTH EFFECTS OF EXCESS COPPER   78     Acute Toxicity   78     Chronic Toxicity   87     Animal Studies   95     Conclusions   111     Recommendations   112     References   113 6   RISK CHARACTERIZATION   127     Copper Deficiency   127     Copper Toxicity from Single or Short-Term Exposure   130     Copper Toxicity from Chronic Exposure   132     Chronic Copper Exposure through Tap Water   138     Dietary Contribution and Total Copper Intake   139     Conclusions   141     Recommendations   144     References   145

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Copper in Drinking Water Copper in Drinking Water

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