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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board ofthe National Research Council, whose members are drawn from the councils ofthe 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. NAG 9-1451 between the National Academy of Sciences and the National Aeronautics and Space Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authoress and do not necessarily reflect the view of the organizations or agencies that provided support for this project. International Standard Book Number 0-309-09166-7 (Book) International Standard Book Number 0-309-53074-1 (PDF) Library of Congress Control Number 2004102556 Additional copies of this report are available from: The National Academies Press 500 Fifth Street, NW Box 285 Washington, DC 20055 800-624-6242 202-334-3313 (in the Washington metropolitan area) http://www.nap.edu Copyright 2004 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medirine 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. Wm. 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. Harvey V. Fineberg 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. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council w~N.national-academies.org

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SUBCOMMITTEE ON SPACECRAFT EXPOSURE GUTDET,TNES GAROT,D S. YOST (Chair), University of Utah, Salt Lake City DONAT,D E. GARDNER (Chair from September 1999 to July 2002), Consultant, Raleigh, NC GARY P. CART,SON, Purdue University, West Lafayette, IN DAROT, E. DODD, ManTech Environmental Technology, Inc., Dayton, OH KEVIN E. DRTSCOT,T,, Procter and Gamble Pharmaceuticals, Mason, OH ET,ATNE M. FAUSTMAN, University of Washington, Seattle CHART,ES E. FETGT,EY, University of South Carolina, Columbia WTT,T,TAM E. HAT,PERTN, University of Medicine and Dentistry of New Jersey, Newark RAT,PH L. KODET,T,, National Center for Toxicological Research, Jefferson, AR KENNETH E. THUMMET,, University of Washington, Seattle JOYCE TSUIT, Exponent Environmental Group, Inc., Bellevue, WA ROBERT SNYDER (member from September 1999 to November 2001), Environmental and Occupational Health Sciences Institute, Piscataway, NJ BERNARD M. WAGNER (member from September 1999 to July 2001), Consultant, Short Hills, NJ BERNARD WEISS, University of Rochester, Rochester, NY JUDITH T. ZET,TKOFF, New York University School of Medicine, Tuxedo Staff SUSAN N.J. MARTET,, Project Director KET,T,Y CT,ART`, Editor TAMARA DAWSON, Project Assistant Sponsor NATTONAT, AERONAUTICS AND SPACE ADMTNTSTRATTON v

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COMMITTEE ON TOXICOLOGY BAILUS WALKER JR. (Chair), Howard University Medical Center and American Public Health Association, Washington, DC MELVIN E. ANDERSON, CIIT-Centers for Health Research, Research Triangle Park, NC EDWARD C. BISHOP, Parsons Corporation, Fairfax, VA GARY P. CARLSON, Purdue University, West Lafayette, IN JANICE E. CHAMBERS, Mississippi State University, Mississippi State LEONARD CHIAZZE JR., Georgetown University, Washington, DC JUDITH A. GRAHAM, American Chemistry Council, Arlington, VA SIDNEY GREEN, Howard University, Washington, DC MERYL KAROL, University of Pittsburgh, Pittsburgh, PA STEPHEN U. LESTER, Center for Health Environment and Justice, Falls Church, VA DAVID H. MOORE, Battelle Memorial Institute, Bet Air, MD CALVIN C. WILEHITE, Department of Toxic Substances, State of California, Berkeley GERALD WOGAN, Massachusetts Institute of Technology, Cambridge Staff KULBIR S. BAKSHI, Program Director ROBERTA M. WEDGE, Program Director for Risk Analysis SUSAN N.J. MARTEL, Senior Staff Officer ELLEN K. MANTUS, Senior Staff Officer KELLY CLARK, Assistant Editor AIDA NEEL, Senior Project Assistant TAMARA DAWSON, Project Assistant Vl

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BOARD ON ENVTRONMENTAL STUDIES AND TOXTCOLOGY! Members JONATHAN M. SAMET (Chair9, Johns Hopkins University, Baltimore, MD DAVID AEEEN, University of Texas, Austin THOMAS BURKE, Johns Hopkins University, Baltimore, MD JUDITH C. CHOW, Desert Research Institute, Reno, NV COSTEL D. BENSON, University of Delaware, Newark E. DONALD ELLIOTT, Yale Law School, New Haven, CT CHRISTOPHER B. FIEED, Carnegie Institute of Washington, Stanford, CA WILLIAM H. GLAZE, Oregon Health and Science University, Beaverton SHERR} W. GOODMAN, Center for Naval Analyses, Alexandria, VA DANIEE S. GREENBAUM, Health Effects Institute, Cambridge, MA ROGENE HENDERSON, Lovelace Respiratory Research Institute, Albuquerque, NM CAROL HENRY, American Chemistry Council, Arlington, VA ROBERT HUGGETT, Michigan State University, East Lansing BARRY L. JOHNSON Emory University, Atlanta, GA JAMES H. JOHNSON, Howard University, Washington, DC JUDITH L. MEYER, University of Georgia, Athens PATRICK Y. O'BRIEN, ChevronTexaco Energy Technology Co., Richmond, CA DOROTHY E. PATTON, International Life Sciences Institute, Washington, DC STEWARD T.A. PICKETT, Institute of Ecosystem Studies, Millbrook, NY ARMISTEAD G. RUSSELL, Georgia Institute of Technology, Atlanta LOUISE M. RYAN, Harvard University, Boston, MA KIRK SMITH, University of California, Berkeley LISA SPEER, Natural Resources Defense Council, New York, NY G. DAVID TIEMAN, University of Minnesota, St. Paul CHRIS G. WHIPPLE, Environ Incorporated, Emeryville, CA LAUREN A. ZEISE, California Environmental Protection Agency, Oakland Senior Staff JAMES J. REISA, Director DAVID J. POEICANSKY, Associate Director RAYMOND A. WASSEL, Senior Program Director for Environmental Sciences and ~ . . ~ engineering KUEBIR BAKSHI, Program Director for Toxicology ROBERTA M. WEDGE, Program Director for Risk Analysis K. JOHN HOLMES, Senior Staff Officer SUSAN N.J. MARTEE, Senior Staff Officer SUZANNE VAN DRUNICK, Senior Staff Officer EIEEEN N. ABT, Senior Staff Officer EEEEN K. MANTUS, Senior Staff Officer RUTH E. CROSSGROVE, Managing Editor This study was planned, overseen, and supported by the Board on Environmental Studies and Toxicology. . . v''

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OTHER REPORTS OF THE BOARD ON ENVTRONMENTAL STUDIES AND TOXTCOLOGY Air Quality Management in the United States (2004) Endangered and Threatened Fishes in the Klamath River Basin: Causes of Decline and Strategies for Recovery (2004) Cumulative Environmental Effects of Alaska North Slope Oil and Gas Development (2003) Estimating the Public Health Benefits of Proposed Air Pollution Regulations (2002) Biosolids Applied to Land: Advancing Standards and Practices (2002) The Airliner Cabin Environment and Health of Passengers and Crew (2002) Arsenic in Drinking Water: 2001 Update (2001 ~ Evaluating Vehicle Emissions Inspection and Maintenance Programs (2001) Compensating for Wetland Losses Under the Clean Water Act (2001) A Risk-Management Strategy for PCB-Contaminated Sediments (2001) Acute Exposure Guideline Levels for Selected Airborne Chemicals (3 volumes, 2000-2003) Toxicological Effects of Methylmercury (2000) Strengthening Science at the U.S. Environmental Protection Agency (2000) Scientific Frontiers in Developmental Toxicology and Risk Assessment (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 (4 volumes, 1998-2003) Arsenic in Drinking Water (1999) The National Research Council's Committee on Toxicology: The First 50 Years (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 volumes, 1989- 1995) Review of EPA's Environmental Monitoring and Assessment Program (3 volumes, 1994-1995) Science and Judgment in Risk Assessment (1994) Pesticides in the Diets of Infants and Children (1993) Dolphins and the Tuna Industry (1992) Science and the National Parks (1992) Human Exposure Assessment for Airborne Pollutants (1991) Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991) Decline of the Sea Turtles (1990) Copies of these reports may be orderedirom the National Academies Press (800) 624-6242 or (202) 334-3313 www.nap.edu . . . v'''

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OTHER REPORTS OF THE COMMITTEE ON TOXTCOLOGY Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals (2001) Evaluating Chemical and Other Agent Exposures for Reproductive and Developmental Toxicity (2001) Acute Exposure Guideline Levels for Selected Airborne Contaminants, Volume 1 (2000), Volume 2 (2002), Volume 3 (2003) Review of the US Navy's Human Health Risk Assessment of the Naval Air Facility at Atsugi, Japan (2000) 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) Re-Evaluation of Drinking-Water Guidelines for Diisopropyl Methylphosphonate (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) 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) IX

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Preface The National Aeronautics and Space Administration (NASA) maintains an active interest in the environmental conditions associated with living and working in spacecraft and identifying hazards that might adversely affect the health and well-being of crew members. Despite major engineering advances in controlling the spacecraft environment, some water and air contamination appears to be inevitable. Several hundred chemical species are likely to be found in the closed environment ofthe spacecraft, and as the frequency, complexity, and duration of human space flight increase, identi- fying and understanding significant health hazards will become more com- plicated and more critical for the success of the missions. NASA asked the National Research Council (NRC) Committee on Toxicology to develop guidelines, similar to those developed by the NRC in 1992 for airborne substances, for examining the likelihood of adverse effects from water contaminants on the health and performance of space- craft crews. In 2000, the NRC report Methods for Deve1/toping Spacecraft Water Exposure Guicle1/tines was published, and NASA now uses those methods for developing spacecraft water exposure guidelines (SWEGs) for individual water contaminants. NASA is responsible for selecting the water contaminants for which SWEGs will be established. To ensure that the SWEGs are developed in accordance with the NRC guidelines, NASA requested that the NRC subcommittee independently review the draft SWEG documents. In its evaluations, the subcommittee reviews the docu- ments as many times as necessary until it is satisfied that the SWEGs are scientifically justified. This report is the first volume in the series Space- craft Water Exposure Guidelines for Selected Contaminants. It presents the Xl

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. . x!! Preface SWEGs that have been established for chloroform, dichioromethane, di-n- buty! phthalate, di(2-ethy~hexyI) phthalate, 2-mercaptobenzothiazole, nickel, phenol, N-phenyI-beta-naphthylamine, and silver. This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with proce- dures approved by the NRC's Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evi- dence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity ofthe delibera- tive process. We wish to thank the following individuals for their review of this report: Joseph F. Borzelleca, Virginia Commonwealth University; Roy DeHart, Vanderbilt University; David Gaylor, Gaylor & Associates; F. William Sunderman Jr., University of Connecticut; Mark Utell, University of Rochester School of Medicine. 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 George M. Rusch, Honeywell Corporation. Appointed by the NRC, he was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review com- ments were carefully considered. Responsibility for the final content ofthis report rests entirely with the authoring committee and the institution. Special thanks are extended to John James (NASA); Raghupathy Ramanathan, Hector Garcia, and Chiu-Wing Lam (all from Wyle Laborato- ries); and Jean Hampton (University of Texas) for preparing and revising the SWEG documents. We are grateful for the assistance of the NRC staff in supporting this project and preparing the report. Staff members who contributed to this effort are James J. Reisa, director of the Board on Environmental Studies and Toxicology; Kulbir Bakshi, program director for the Committee on Toxicology; and Kelly Clark, editor. We especially wish to recognize the contributions of project director Susan Martel end project assistants Tamara Dawson and Jessica Brock (through March 2002~. Finally, we would like to thank all the members ofthe subcommittee for their dedicated efforts throughout the development ofthis report. Inpartic- ular, we would like to recognize the longstanding contributions and leader- ship of Donald Gardner, who chaired the subcommittee from September

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Preface . . . x''' 1999 to July 2002, and who also chaired the previous Subcommittee on Spacecraft Maximum Allowable Concentrations for almost a decade. Garold S. Yost, Ph.D. Chair, Subcommittee on Spacecraft Water Exposure Guidelines Bailus Walker Jr., Ph.D., M.P.H. Chair, Committee on Toxicology

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Contents Introduction Appendixes. Spacecraft Water Exposure Guidelines 2 3 Di-n-butyl Phthalate 88 4 Di(2-ethylhexyl) Phthalate 121 2-Mercaptobenzothiazole 169 Chloroform ll Dichloromethane 5 6 Nickel ~v_ 7 Phenol 248 ~ N-Phenyl-beta-naphthylamine. 9 Silver........................................ ....290 ..... 324

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Spacecraft Water Exposure Guidelines for Selected Contaminants Volume ~

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