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Ddn~ng Water and Health Volume ~ SAFE DOMING CODER CO~IbEE Board on Tot and Environmen1~1 HeaRb Herds Assembly of Lid Sciences Nabona1 Research CouncH NATIONAL ACADEMY PRESS Non, D.C. 1980

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The National Research Council was established 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 of advising the federal government. The Council operates in accordance with general policies determined by the Academy under the authority of its Congressional charter of 1863, which establishes the Academy as a private, non-profit, self-governing membership corporation. The Council has become the principal operating agency of both the Academy of Sciences and the National Academy of Engineering in the conduct of their services to the government, the public, and the scientific and engineering communities. It is administered jointly by both Academies and the Institute of Medicine. The Academy of Engineenog and the Institute of Medicine were established in 1964 and 1970, respectively, under the charter of the Academy of Sciences. 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 Engineenng, and the Institute of Medicine The members of the Committee responsible for the report were chosen for their competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. At the request of and funded by the U.S Environmental Protection Agency Contract No. 68-01-3169 Library of Congress Catalog Card Number: 77-89284 International Standard Book Number: 0-309-02932-5 A bailable from NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, D.C. 20418 ~ irst Printing, SeptemDcr 1980 Second Printing. NIay 1985 Third Printing, November 1986 Fourth Printing, March 1988 Printed in the United States of America

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- - - List of Participants SAFE DRINKING WATER COMMITTEE JOHN DOULL, University of Kansas Medical Center, Kansas City, Chairman I. CARRELL MORRIS, Haward University, Cambridge, Massachusetts, Vice Chairman JOSEPH F. BO=ELLECA, Medical College of Virginia, Richmond RIC~RD S. ENGELB=CHT, University of Illinois, Urbana DAVID G. HOEL, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina CORNELIUS W. KRUSE, Johns Hopkins University, Baltimore EDWIN H. LENNE=E, California Department of Health, Berkeley SHELDON D. MUCH, University of Texas Medical School of Houston PAUL M. NEWBE~E, Massachusetts Institute of Technology, Cambridge MALCOLM C. PIKE, University of Southern California, Los Waggles MARVIN A. SC~ElDER~N, National Cancer Institute, Bethesda, Ma~- land RONALD C. SHANK, University of California, Irvine IRWIN H. SUFFET, Drexel University, Philadelphia SHELDON WOLFF, University of California, San Francisco . . .

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iv List of Participants NA`NRC Staff RILEY D. HOUSEW~GHT, Project Director ROBERT ]. GOLDEN, Assistant Project Director ROY WIDDUS, Sta~O~cer FRANCES M. PETER, Editor Subcommittee on Epidemiology MARVIN A. SCHNElDER~N, National Cancer Institute, Bethesda, M - land, Chairman EDWARD C. HAMMOND, American Cancer Society, Inc., New York IAN T. T. HIGGINS, University of Michigan, An Arbor GEORGE B. HUTCHISON, Harvard School of Public Health, Boston ABRAHAM M. LILIE~ELD, Johns Hopkins University, Baltimore MALCOLM C. PIKE, University of Southern California School of Medicine, Los Angeles ARTHUR H. WOLFF, University of Illinois at the Medical Center, Chicago Subcommittee on Nutrition - PAUL M. NEWBE~E, Massachusetts Institute of Technolo~, ~mbridge, Chairman RENATE D. KIMBROUGH, Center for Disease Control, Atlanta ORVILLE A. LEVANDER, Agriculture Research Center, Beltsville, Maryland BOYD L. O'DELL, University of Missouri, Columbia DAPHNE A. ROE, Cornell University, Ithaca, New York RONALD C. SHANK, University of California, Irvine Subcommittee on Risk Assessment DAVID G. HOEL, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, Chairmar' DAVID ~LROD, New York State Department of Health, Albany CHARLES C. BROWN, National Cancer Institute, Bethesda, Maryland ROBERT L. DEDRICK, National Institutes of Health, Bethesda, Maryland CARROL S. ~L, Camegie-Mellon University, Pittsburgh SHELDON WOLFF, University of California, San Francisco

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List of Participants v Subcommittee on Toxicology SHELDON D. MU~HY, University of Texas Medical School at Houston, Chairman JOSEPH F. BO=ELLECA, Medical College of Virginia, Richmond JAMES V. BRUCKNER, University of Texas Medical School at Houston DONALD R. BUHLER, Oregon State University, Corvallis HANS P. DROBECK, Sterling-Winthrop Research Institute, Rensselaer, New York NAMES E. GIBSON, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina MARGARET HITCHCOCK, Yale University Medical School, New H even, Connecticut JOHN C. LOPER, University of Cincinnati College of Medicine ROBERT E. MENZER, University of Maryland, College Park ROBERT I. ROBERTS, University of Iowa College of Medicine, Iowa City RUDY I. RICHARDSON, University of Michigan School of Public Health, Ann Arbor CRAIG SCHNELL, Purdue University, West Lafayette, Indiana Consultant FORREST H. NIELSEN, U.S. Department of Agriculture, Grand Forks, North Dakota EPA Project Officer JOSEPH COTR~O, Once of Water Supply, U.S. Environmental Protection Agency, Washington, D.C. EPA Liaison Representative WILLIAM MARCUS' Office of Water Supply, U.S. Environmental Protec- tion Agency? Washington, D.C.

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Contents PREFACE I EXECUTIVE SONY I I EPIDEMIOLOGICAL STUDIES Cancer Frequency and Certain Organic Constituents of Drinking Water, 5 Water Hardness and Cardiovascular Disease, 21 III PROBLEMS OF RISK ESTIMATION 1X 5 25 IV TOXICITY OF SELECTED DRINKING WATER CONT~INANTS 67 V THE CONTRIBUTING OF DRIP KING WATER TO MINERAL NUTRITION IN HUMANS APPEND IX 1977 AMENDMENT TO SAFE DRINKING WATER ACT INDEX . . V11 265 405 407

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Preface In 1975 the National Academy of Sciences-National Research Council initiated a series of studies to meet the congressional mandate of the Safe Drinking Water Act (PL 93-523~. Results of these studies were published in Drinking Water and Health (National Academy of Sciences, 1977~. Amendments to the act in 1977 called for revisions of the studies "reflecting new information which has become available since the most recent previous report [and which] shall be reported to the Congress each two years thereafter" (see Appendix). Results of studies completed by the Safe Drinking Water Committee since 1977 are contained in this book and a companion volume entitled Drinking Cater and Health, Volume 2. This book provides an evaluation of several epidemiological studies relating to drinking water, elaboration of previous studies of risk estimation (National Academy of Sciences 1977), a toxicok~gica1 assessment of selected drinking water contami- nants' and an exarr~ination of the contribution of drinking water to the mineral nutrition in humans. Drinking Water and Health, Volume 2, contains an assessment of processes and chemicals for the disinfection of drinking water ider~tification of the by-products resulting from their use, and an evaluatior~ of granular activated carbon for removal of organic and other contaminants from drinking water. The general approach to the study, the considerations that enter into evaluation of health effects, and the reasons for the selection of subjects are discussed in the following paragraphs. The findings of the study are IX

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x Preface summarized at the end of each chapter and briefly in the Executive Summary. Economic considerations are not a part of this study. The epidemiology chapter provides a critical assessment of the most recent studies on cancer frequency and organic constituents of drinking water. It points out deficiencies in the evidence and the probabilities of false associations' and discusses the potential for further research on this subject. Little new information was found on the subject of water hardness and cardiovascular disease beyond the recent study on the relationship of trace elements to cardiovascular disease (National Academy ofSciences, 1979~. Reliable and direct information on the toxicity to humans of most chemicals is very difficult to obtain. Usually, it must be based on accidental or occupational exposures which, by their very nature, are uncontrolled. The value and limitations of using acute exposure of subprimate animal species for assessment of risk from accidental spills and discharges are examined. Data from chronic exposure of animals are used to determine acceptable daily intakes (ADI) and risk estimates. The appropriateness of using one or the other of these expressions and the use of safety factors or a particular model for carcinogenic risk estimation are analyzed. Some important quantitative aspects of inter- species toxicology are summarized. The health effects resulting from chemical, particulate, and radioactive contaminants in drinking water were evaluated in Drinking Water and Health (National Academy of Sciences, 1977~. Radioactive contaminants are not considered in this study. Asbestos, one of the particulates examined in the first study, will be reevaluated when the several- studies now underway are completed. The number of volatile organic com- pounds identified in drinking water has increased from 300 at the time of the first study to over 700 at present. Limitations on time, manpower, and scientific information have permitted an in-depth evaluation of only a few of these compounds that have recently been found in drinking water. The evaluation process for each chemical consisted of reviews of both acute and chronic toxicity and, when the data were judged to be adequate, a suggested no-adverse-response level (SNARL) for 24-hr, 7- day, and chronic exposure. Risk estimates were calculated for those chemicals suspected of being carcinogens (National Academy of Sciences, 19771. Special attention was given to a list of compounds prepared by the Subcommittee on Chemistry of Disinfectants and Products of the Safe

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Preface xi Drinking Water Committee. This list consists of compounds that are formed as a result of chlorination or other methods of disinfecting water. Several other compounds were reviewed because of their involvement in potential spill situations or because sufficient new data had become available to justify a reevaluation of several chemicals examined in the first study. Previous studies by the Safe Drinking Water Committee have had as their principal concern the identification and toxicological evaluation of substances found in drinking water. Quantitation of these adverse consequences forms the scientific base for establishment of standards. The last chapter of this volume is a departure from these previous studies. It is a review of the contribution of drinking water to mineral nutrition in humans. It focuses on both the benefits and the adverse effects of selected elements in drinking water, in cases in which symptoms of both deficiency and toxicity are known to occur. Quantita- tive differences between flee amount of an element required for adequate nutrition and the smallest amount exhibiting toxicological symptoms are examined. The differences in water intake between young and adult humans were investigated. Infants (7 kg) consume approximately one-third as much water on the average as an adult, but their body weight is only approximately one-tenth of adult weight and their food intake is obviously lower. For this reason the water intake of an infant may contribute a significant quantity of a given element (National Academy of Sciences, 19741. Variations in water intake among adults are considered in Drinking Water and Health (National Academy of Sciences, 1977~. Requirements for nutrients are discussed in terms of recommended dietary allowances (RDA~s) (National Academy of Sciences, 1974) or those intakes that have been judged adequate and safe (National Academy of Sciences 1980) not minimal intakes necessary for survival. It is a pleasure to express' on behalf of the committee and the subcommittees a special note of thanks to the stab: Dr. Riley D. Housewright, Dr. Robert J. Golden, Dr. Roy Widdus, and Ms. Frances M. Peter whose informed and tireless efforts aided the committee in planning, conducting, and editing the study. We are grateful to Mr. David Goff. Ms. Virginia White, and Ms. Edna Paulson who assisted in an extensive search of the scientific literature. We also acknowledge the assistance of members of the stab of the Environmental Protection Agency, especially Dr. Joseph Cotruvo and Dr. William Marcus.

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xii Preface Organization of the meetings and preparation of the manuscripts were made easier by the dedicated secretarial services of Mrs. Delores Banks, Ms. Helen Harvin, and Ms. Merle Morgan. JOHN DOULL, Chairman Safe Drinking Water Committee REFERENCES National Academy of Sciences. 1974. Recommended Dietary Allowances, 8th revised ed. Food and Nutrition Board, National Academy of Sciences, Washington, D.C. 124 pp. National Academy of Sciences. 1977. Drinking Water and Health. Safe Drinking Water Committee National Academy of Sciences, Washington, D.C. 939 pp. National Academy of Sciences. 1979. Geochemistry of Water in Relation to Cardiovascu- lar Disease. Panel on the Geochemistry of Water in Relation to Cardiovascular Disease, National Academy of Sciences, Washington, D.C. 98 pp. National Academy of Sciences. 1980. Recommended Dietary Allowances, 9th rev. cd. Food and Nutrition Board, National Academy of Sciences, Washington, D.C. 185 pp.