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Suggested Citation:"Front Matter." National Research Council. 2008. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 3. Washington, DC: The National Academies Press. doi: 10.17226/12527.
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SPACECRAFT WATER EXPOSURE GUIDELINES FOR SELECTED CONTAMINANTS VOLUME 3 Committee on Spacecraft Exposure Guidelines Committee on Toxicology Board on Environmental Studies and Toxicology Division on Earth and Life Studies

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 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 Grant No. NNX07AP75G 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 author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project. International Standard Book Number-13: 978-0-309-12838-4 International Standard Book Number-10: 0-309-12838-2 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 2008 by the National Academy of Sciences. All rights reserved. Printed in the United States of America.

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. Ralph J. Cicerone 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. Charles M. Vest 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. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

COMMITTEE ON SPACECRAFT EXPOSURE GUIDELINES Members GAROLD S. YOST (Chair), University of Utah, Salt Lake City A. JOHN BAILER, Miami University, Oxford, OH DAROL E. DODD, The Hamner Institute for Health Sciences, Research Triangle Park, NC KEVIN E. DRISCOLL, Procter and Gamble Pharmaceuticals, Mason, OH DAVID W. GAYLOR, Gaylor and Associates, Eureka Springs, AR JACK R. HARKEMA, Michigan State University, East Lansing DAVID G. KAUFMAN, University of North Carolina, Chapel Hill KENNETH ROSENMAN, Michigan State University, East Lansing KENNETH E. THUMMEL, University of Washington, Seattle JOYCE TSUJI, Exponent Environmental Group, Inc., Bellevue, WA ROCHELLE TYL, RTI International, Research Triangle Park, NC JUDITH T. ZELIKOFF, New York University School of Medicine, Tuxedo Staff EILEEN N. ABT, Project Director JENNIFER SAUNDERS, Project Director (up to December 2007) RUTH E. CROSSGROVE, Senior Editor HEIDI MURRAY-SMITH, Research Associate TAMARA DAWSON, Program Associate PANOLA GOLSON, Senior Program Assistant Sponsor NATIONAL AERONAUTICS AND SPACE ADMINISTRATION v

COMMITTEE ON TOXICOLOGY Members WILLIAM E. HALPERIN (Chair), New Jersey Medical School, Newark LAWRENCE S. BETTS, Eastern Virginia Medical School, Norfolk EDWARD C. BISHOP, HDR Engineering, Inc., Omaha, NE JAMES V. BRUCKNER, University of Georgia, Athens GARY P. CARLSON, Purdue University, West Lafayette, IN MARION EHRICH, Virginia Tech, Blacksburg SIDNEY GREEN, Howard University, Washington, DC MERYL KAROL, University of Pittsburgh, Pittsburgh, PA JAMES MCDOUGAL, Wright State University School of Medicine, Dayton, OH ROGER MCINTOSH, Science Applications International Corporation, Baltimore, MD GERALD WOGAN, Massachusetts Institute of Technology, Cambridge Staff SUSAN N.J. MARTEL, Senior Program Officer for Toxicology EILEEN N. ABT, Senior Program Officer for Risk Analysis ELLEN K. MANTUS, Senior Program Officer MIRSADA KARALIC-LONCAREVIC, Manager of the Technical Information Center RADIAH A. ROSE, Editorial Projects Manager TAMARA DAWSON, Senior Program Assistant vi

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1 Members JONATHAN M. SAMET (Chair), University of Southern California, Los Angeles RAMON ALVAREZ, Environmental Defense Fund, Austin, TX JOHN M. BALBUS, Environmental Defense Fund, Washington, DC DALLAS BURTRAW, Resources for the Future, Washington, DC JAMES S. BUS, Dow Chemical Company, Midland, MI RUTH DEFRIES, Columbia University, New York, NY COSTEL D. DENSON, University of Delaware, Newark E. DONALD ELLIOTT, Willkie, Farr & Gallagher LLP, Washington, DC MARY R. ENGLISH, University of Tennessee, Knoxville J. PAUL GILMAN, Covanta Energy Corporation, Fairfield, NJ JUDITH A. GRAHAM (Retired), Pittsboro, NC WILLIAM M. LEWIS, JR., University of Colorado, Boulder JUDITH L. MEYER, University of Georgia, Athens DENNIS D. MURPHY, University of Nevada, Reno DANNY D. REIBLE, University of Texas, Austin JOSEPH V. RODRICKS, ENVIRON International Corporation, Arlington, VA ARMISTEAD G. RUSSELL, Georgia Institute of Technology, Atlanta ROBERT F. SAWYER, University of California, Berkeley KIMBERLY M. THOMPSON, Harvard School of Public Health, Boston, MA MARK J. UTELL, University of Rochester Medical Center, Rochester, NY Senior Staff JAMES J. REISA, Director DAVID J. POLICANSKY, Scholar RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies EILEEN N. ABT, Senior Program Officer for Risk Analysis SUSAN N.J. MARTEL, Senior Program Officer for Toxicology KULBIR BAKSHI, Senior Program Officer ELLEN K. MANTUS, Senior Program Officer RUTH E. CROSSGROVE, Senior Editor 1 This study was planned, overseen, and supported by the Board on Environmental Studies and Toxicology. vii

OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY Estimating Mortality Risk Reduction and Economic Benefits from Controlling Ozone Air Pollution (2008) Respiratory Diseases Research at NIOSH (2008) Evaluating Research Efficiency in the U.S. Environmental Protection Agency (2008) Hydrology, Ecology, and Fishes of the Klamath River Basin (2008) Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007) Models in Environmental Regulatory Decision Making (2007) Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007) Sediment Dredging at Superfund Megasites: Assessing the Effectiveness (2007) Environmental Impacts of Wind-Energy Projects (2007) Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget (2007) Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006) New Source Review for Stationary Sources of Air Pollution (2006) Human Biomonitoring for Environmental Chemicals (2006) Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment (2006) Fluoride in Drinking Water: A Scientific Review of EPA’s Standards (2006) State and Federal Standards for Mobile-Source Emissions (2006) Superfund and Mining Megasites—Lessons from the Coeur d’Alene River Basin (2005) Health Implications of Perchlorate Ingestion (2005) Air Quality Management in the United States (2004) Endangered and Threatened Species of the Platte River (2004) Atlantic Salmon in Maine (2004) Endangered and Threatened Fishes in the Klamath River Basin (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 (six volumes, 2000-2008) 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 (2000) Hormonally Active Agents in the Environment (1999) Research Priorities for Airborne Particulate Matter (four volumes, 1998-2004) The National Research Council’s Committee on Toxicology: The First 50 Years (1997) Carcinogens and Anticarcinogens in the Human Diet (1996) viii

Upstream: Salmon and Society in the Pacific Northwest (1996) Science and the Endangered Species Act (1995) Wetlands: Characteristics and Boundaries (1995) Biologic Markers (five volumes, 1989-1995) 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 ordered from the National Academies Press (800) 624-6242 or (202) 334-3313 www.nap.edu ix

OTHER REPORTS OF THE COMMITTEE ON TOXICOLOGY Review of Toxicologic and Radiologic Risks to Military Personnel from Exposures to Depleted Uranium (2008) Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, Volume 1 (2007), Volume 2 (2008) Review of the Department of Defense Research Program on Low-Level Exposures to Chemical Warfare Agents (2005) Review of the Army's Technical Guides on Assessing and Managing Chemical Hazards to Deployed Personnel (2004) Spacecraft Water Exposure Guidelines for Selected Contaminants, Volume 1 (2004), Volume 2 (2007) Toxicologic Assessment of Jet-Propulsion Fuel 8 (2003) Review of Submarine Escape Action Levels for Selected Chemicals (2002) 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), Volume 4 (2004), Volume 5 (2007), Volume 6 (2008), Volume 7 (2008) 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), Volume 5 (2008) x

Preface The National Aeronautics and Space Administration (NASA) maintains an active interest in the environmental conditions associated with living and work- ing in spacecraft and identifying hazards that might adversely affect the health and well-being of crew members. Despite major engineering advances in con- trolling the spacecraft environment, some water and air contamination is inevi- table. Several hundred chemical species are likely to be found in the closed envi- ronment of the spacecraft, and as the frequency, complexity, and duration of human space flight increase, identifying and understanding significant health hazards will become more complicated and more critical for the success of the missions. NASA asked the National Research Council (NRC) Committee on Toxi- cology to develop guidelines, similar to those developed by the NRC in 1992 for airborne substances, for setting exposure guidance levels for spacecraft water contaminants. In 2000, the NRC report Methods for Developing Spacecraft Wa- ter Exposure Guidelines was published, and NASA now uses those methods to develop 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 NRC guidelines, NASA requested that the NRC committee independently review the draft SWEG documents. In its evaluations, the com- mittee reviews the documents as many times as necessary until it is satisfied that the SWEGs are scientifically justified. This report is the third volume in the se- ries, Spacecraft Water Exposure Guidelines for Selected Contaminants. Space- craft Water Exposure Guidelines Volume 1, published in 2004, used the NASA guidelines to establish exposure concentrations for chloroform, dichloro- methane, di-n-butyl phthalate, di(2-ethylhexyl)phthalate, 2-mercaptobenzothia- zole, nickel, phenol, N-phenyl-beta-naphthylamine, and silver. Volume 2, pub- lished in 2007, presented SWEGs for acetone, alkylamines, ammonia, barium, cadmium, caprolactam, formaldehyde, formate, manganese, total organic car- bon, and zinc. This report presents SWEGs for antimony, benzene, ethylene glycol, methanol, methyl ethyl ketone, and propylene glycol. xi

xii Preface The committee’s review of the SWEG documents involved both oral and written presentations to the committee by the authors of the documents. The committee examined the draft documents and provided comments and recom- mendations for how they could be improved in a series of interim reports. The authors revised the draft SWEG documents based on the advice in the interim reports and presented them for re-examination by the committee as many times as necessary until the committee was satisfied that the SWEGs were scientifi- cally justified and consistent with the 2000 NRC guideline report. Once these determinations are made for a SWEG document, it is ready to be published as an appendix in a volume like this one. The committee’s interim reports were reviewed in draft form by individu- als chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC's Report Review Committee. The pur- pose 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, evidence, and responsiveness to the study charge. The review comments and draft manu- scripts remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of one or more of the interim reports listed above: Michael Aschner, Vanderbilt University Medical Center Lawrence S. Betts, Eastern Virginia Medical School H. Tim Borges, Oak Ridge National Laboratory Barbara G. Callahan, University Research Engineers and Associates Janice E. Chambers, Mississippi State University Rakesh Dixit, MedImmune, Inc. Donald E. Gardner, Inhalation Toxicology Associates, Inc. Robert A. Goyer, Chapel Hill, North Carolina Sidney Green, Howard University Rogene Henderson, Lovelace Respiratory Research Institute Samuel Kacew, University of Ottawa Florence K. Kinoshita, Hercules Incorporated Gary Krieger, NewFields Loren D. Koller, Loren Koller & Associates, LLC John L. O’Donoghue, University of Rochester, School of Medicine and Dentistry George M. Rusch, Honeywell, Inc. 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 interim report or this volume before their release.

Preface xiii The review of each interim report was overseen by a review coordinator, and we thank the following individuals for serving in this capacity for one or more of the interim reports listed above: James V. Bruckner, University of Georgia Sidney Green, Howard University Rogene Henderson, Lovelace Respiratory Research Institute Samuel Kacew, University of Ottawa David P. Kelly, DuPont George M. Rusch, Honeywell, Inc. Robert Snyder, Rutgers, The State University of New Jersey Mary E. Vore, University of Kentucky Appointed by the National Research Council, the coordinators were re- sponsible for making certain that an independent examination of these reports 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. Special thanks are extended to John James and Noreen Khan-Mayberry (NASA) and Hector Garcia and Raghupathy Ramanathan (Wyle Laboratories) for preparing and revising the SWEG documents. We also thank members of the committee who contributed to the development of this document, including A. John Bailer, Miami University; Darol Dodd, the Hamner Institute for Health Sciences; Kevin Driscoll, Procter and Gamble Pharmaceuticals; David Gaylor, Gaylor and Associates; Jack Harkema, Michigan State University; David Kauf- man, University of North Carolina; Kenneth Rosenman, Michigan State Univer- sity; Kenneth Thummel, University of Washington; Joyce Tsuji, Exponent Envi- ronmental Group; Rochelle Tyl, RTI International; and Judith Zelikoff, New York University School of Medicine. We are grateful for the assistance of the NRC staff in supporting this pro- ject and preparing the report. James J. Reisa, director of the Board on Environ- mental Studies and Toxicology, contributed to this effort. We especially wish to recognize the contributions of Eileen Abt, program director; Jennifer Saunders, project director (through December 2007); Heidi Murray-Smith, research asso- ciate; Ruth Crossgrove, senior editor; Mirsada Karalic-Loncarevic, manager of the Technical Information Center; Radiah Rose, editorial projects manager; Tamara Dawson, program associate; and Panola Golson, senior program assis- tant. Garold S. Yost, Ph.D., Chair, Committee on Spacecraft Exposure Guidelines

Contents INTRODUCTION.............................................................................................. 3 APPENDIX 1 ANTIMONY.............................................................................................. 13 2 BENZENE ................................................................................................. 45 3 ETHYLENE GLYCOL ............................................................................ 86 4 METHANOL........................................................................................... 126 5 METHYL ETHYL KETONE................................................................ 147 6 PROPYLENE GLYCOL........................................................................ 165 FIGURES AND TABLES FIGURES 1-1 BMD model curves for changes in red blood cells due to ingestion of antimony, 36 2-1 Metabolic fate of benzene, 49 2-2 Urinary metabolites of benzene, 50 3-1 Metabolic pathways showing oxidation of EG, 89 3-2 Curve for 90-d renal tubular degeneration, 124 3-3 Curve for 90-d tubular crystal formation, 124 3-4 Curve for 90-d subacute inflammation, 125 4-1 Calculated 24-h blood methanol kinetics for a 70-kg person ingesting water containing methanol at 40 mg/L, 142 xv

xvi Contents 4-2 Calculated multiday blood methanol kinetics for a 70-kg person ingesting water containing methanol at 40 mg/L, 143 5-1 Proposed pathways for metabolism of MEK in guinea pigs, 150 TABLES 1-1 Physical and Chemical Properties of Antimony and Two Soluble Antimony Compounds, 14 1-2 Oral Toxicity Summary, 27 1-3 Spacecraft Water Exposure Guidelines (SWEGs) for Soluble Antimony (Salts) in Humans, 30 1-4 Current Regulatory and Guideline Levels from Other Organizations for Oral Ingestion of Antimony, 31 1-5 Summary of BMDs for Hematologic Effects of Antimony, 37 1-6 Summary of Acceptable Concentrations and Spacecraft Water Exposure Guidelines for Antimony, 40 2-1 Physical and Chemical Properties of Benzene, 45 2-2 Benzene Water Regulations and Guidelines Set by Other Organizations, 69 2-3 Spacecraft Water Exposure Guidelines for Benzene, 70 2-4 End Points and Acceptable Concentrations for Benzene, 70 3-1 Physical and Chemical Properties of Ethylene Glycol, 86 3-2 Summary of Toxic Effects, 93 3-3 Water Quality Limits Set by Other Organizations, 106 3-4 Spacecraft Water Exposure Guidelines for Ethylene Glycol, 108 3-5 Kidney Lesions in Male Rats Exposed for 10 d to EG in Their Drinking Water, 113 3-6 Log-Logistic Model of Kidney Lesions Found in Rats Drinking EG- Contaminated Water for 10 d, 113 3-7 Lesions Found in Male Rats Ingesting EG-Contaminated Water for 90 d, 115 3-8 BMD Analysis for Lesions Seen in Rats Ingesting EG-Contaminated Water for 90 d, 115 3-9 Acceptable Concentrations of EG in Drinking Water to Prevent Adverse Effects, 117 4-1 Physical and Chemical Properties of Methanol, 126 4-2 Methanol Concentrations in Foods and Beverages, 127 4-3 Background Blood Methanol and Formate Concentrations in Humans, 128 4-4 Toxicity Summary, 131 4-5 Drinking Water Standards for Methanol Set by Other Organizations, 137 4-6 Air Standards for Methanol Vapors Set by Other Organizations, 138 4-7 Spacecraft Water Exposure Guidelines for Methanol, 139 4-8 Acceptable Concentrations for Methanol, 141

Contents xvii 5-1 Physical and Chemical Properties of MEK, 148 5-2 Toxicity Summary, 156 5-3 Exposure Limits for MEK Vapors Set by Other Organizations, 158 5-4 Acceptable Concentrations for MEK, 159 5-5 Spacecraft Water Exposure Guidelines for MEK, 160 6-1 Physical and Chemical Properties of Propylene Glycol, 166 6-2 Toxicity Summary of PG Administered by Oral Route, 169 6-3 LD50 of PG Administered by Oral Route, 174 6-4 SWEGs for PG, 181 6-5 Summary of ACs and SWEGs for PG, 185

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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 is inevitable. Several hundred chemical species are likely to be found in the closed environment of the spacecraft, and as the frequency, complexity, and duration of human space flight increase, identifying and understanding significant health hazards will become more complicated and more critical for the success of the missions.

To protect space crews from contaminants in potable and hygiene water, NASA requested that the National Research Council NRC provide guidance on how to develop water exposure guidelines and subsequently review NASA's development of the exposure guidelines for specific chemicals. This book presents spacecraft water exposure guidelines (SWEGs) for antimony, benzene, ethylene glycol, methanol, methyl ethyl ketone, and propylene glycol.

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