Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants Volume 5 Committee on Spacecraft Exposure Guidelines Committee on Toxicology Board on Environmental Studies and Toxicology Division on Earth and Life Studies

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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 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. Library of Congress Catalog Card Number 95-73151 International Standard Book Number-13: 978-0-309-12844-5 International Standard Book Number-10: 0-309-12844-7 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.

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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

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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

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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

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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

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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

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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

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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), Volume 3 (2008) 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) x

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Preface The National Aeronautics and Space Administration (NASA) is aware of the potential toxicologic hazards to crew that might be associated with pro- longed spacecraft missions. Despite major engineering advances in controlling the atmosphere within spacecraft, some contamination of the air appears inevi- table. NASA has measured numerous airborne contaminants during space mis- sions. As the missions increase in duration and complexity, ensuring the health and well-being of astronauts traveling and working in this unique environment becomes increasingly difficult. As part of its efforts to promote safe conditions aboard spacecraft, NASA requested the National Research Council (NRC) to develop guidelines for establishing spacecraft maximum allowable concentra- tions (SMACs) for contaminants and to review SMACs for various spacecraft contaminants to determine whether NASA’s recommended exposure limits are consistent with the guidelines recommended by the committee. In response to this request, the NRC first developed criteria and methods for preparing SMACs for airborne contaminants, published in its 1992 report Guidelines for Develop- ing Spacecraft Maximum Allowable Concentrations for Space Station Contami- nants. Since then, the NRC’s Committee on Spacecraft Exposure Guidelines has been reviewing NASA’s documentation of chemical-specific SMACs. This re- port is the fifth volume in the series Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants. The first volume was published in 1994, the second and third in 1996, and the fourth in 2000. This report presents SMACs for acrolein, C3 to C8 aliphatic saturated aldehydes, C2 to C9 alkanes, ammonia, benzene, carbon dioxide, carbon monoxide, 1,2-dichloroethane, di- methylhydrazine, ethanol, formaldehyde, limonene, methanol, methylene di- chloride, n-butanol, propylene glycol, toluene, trimethylsilanol, and xylenes. The committee’s review of the SMAC 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 SMAC 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 SMACs were scientifi- xi

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xii Preface cally justified and consistent with the 1992 NRC guideline report. Once these determinations are made for a SMAC 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: 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 David Dankovic, National Institute for Occupational Safety and Health 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 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. 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 Samuel Kacew, University of Ottawa David P. Kelly, DuPont George M. Rusch, Honeywell, Inc. Robert Snyder, Rutgers, The State University of New Jersey

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xiii Preface 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, Noreen Khan-Mayberry, and Torin McCoy (NASA) and Hector Garcia, Shannon Langford, Chiu Wing Lam, and Raghupathy Ramanathan (Wyle Laboratories) for preparing and revising the SMAC 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 Kaufman, University of North Carolina; Kenneth Rosenman, Michigan State University; Kenneth Thummel, University of Washington; Joyce Tsuji, Exponent Environmental Group; Ro- chelle 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

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Contents INTRODUCTION............................................................................................................3 APPENDIX 1 ACROLEIN ........................................................................................................13 2 C3-C8 ALIPHATIC SATURATED ALDEHYDES .......................................34 3 AMMONIA .........................................................................................................48 4 BENZENE...........................................................................................................62 5 n-BUTANOL ......................................................................................................73 6 C2-C9 ALKANES ..............................................................................................85 7 CARBON DIOXIDE ........................................................................................112 8 CARBON MONOXIDE...................................................................................125 9 1,2- DICHLORETHANE.................................................................................144 10 DIMETHYLHYDRAZINE .............................................................................162 11 ETHANOL........................................................................................................190 12 FORMALDEHYDE .........................................................................................206 13 LIMONENE......................................................................................................250 14 METHANOL ....................................................................................................275 15 METHYLENE CHLORIDE ...........................................................................289 16 PROPYLENE GLYCOL .................................................................................314 17 TOLUENE ........................................................................................................329 18 TRIMETHYLSILANOL .................................................................................348 19 XYLENES.........................................................................................................356 xv

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xvi Contents FIGURES, AND TABLES FIGURES 3-1 BMDS graphic representation of results for data on eye irritation, 54 6-1 Concentration-response slopes for decreases in respiratory rate after exposures to n-heptane, n-octane, and n-nonane, 96 8-1 Prediction of CO uptake and COHb saturation using CFK equation, 126 8-2 CO and COHb concentrations and toxic health effects observed on spacestation, 133 11-1 Ethanol concentrations (mg/L) measured in U.S. Lab Condensate (USL) and Russian Service Module (SM) condensate on ISS, 192 11-2 Breath acetaldehyde concentrations (ng/mL) in Asian (left) and Caucasian (right) volunteers, 200 12-1 Formaldehyde concentration measured in the ISS atmosphere, 211 13-1 Major Pathways for d-Limonene Metabolism, 254 18-1 Structures of compounds tested by Kim et al. (2006), 351 TABLES 1-1 SMACs for Acrolein, 1996, 15 1-2 SMACs for Acrolein, 2008, 22 1-3 Estimates of BMC and BMCL for 13-wk Exposures in Rats, Reported by Feron et al. (1978) with 180- and 1,000-d ACs, 26 1-4 Summation of Benchmark Dose Analysis Results, 28 1-5 Selected Inhalation Exposure Levels for Acrolein from Various Agencies, 30 2-1 Physical Properties of C3 to C8 Straight-Chain Aliphatic Aldehydes, 35 2-2 SMACs for C3 to C8 Aliphatic Saturated Aldehydes from James (2000), 36 2-3 Acceptable Concentrations for Identified Toxicological End Points, 2000, 38 2-4 Selected Odor Characteristics of C3 to C8 Aliphatic Saturated Aldehydes, 39 2-5 SMACs for C3 to C8 Aliphatic Saturated Aldehydes, 2008, 41 2-6 Incidence of Effects in the Most Sensitive End Point in Each Sex of Rats and Mice (10 Animals per Dose Group) and Estimates of BMC10 and BMCL10 for 13-wk Exposures, 43 2-7 Incidence of Effects and Estimates of BMC5 and BMCL5 for 2-y Exposures, 44 2-8 Selected Inhalation Exposure Levels for Selected C3 to C8 Aliphatic Saturated Aldehydes, 45 3-1 SMACs for Ammonia Vapors, 1994, 50 3-2 Human and Pig Responses to Ammonia Vapors, 53 3-3 VAS Severity Score Averages for Exposures of 3 to 178 min, 54 3-4 Results from BMD Analysis of Sundblad et al. 2004 Data, 54 3-5 SMACs for Ammonia Vapors, 2008, 55 3-6 Time-Averaged Scores for Each Subject and Measured Effect, 56 3-7 Air Standards for Ammonia Set by Other Organizations, 58 3-8 ACs for Ammonia, 59 4-1 Benzene End Points and Acceptable Concentrations, 1996, 65 4-2 Exposure Limits Set by Other Organizations, 69 5-1 SMACs Set in Volume 3 for n-Butanol, 75

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xvii Contents 5-2 Comparison of Blood Parameters in Male Rats after 3 Months of Exposure to n-Butanol or n-BA, 77 5-3 ACs for n-Butanol Toxicity and Proposed SMACs, 82 6-1 Physical and Chemical Properties of C2-C9 n-Alkanes, 87 6-2 Toxicity Summary for C5-C9 Saturated Alkanes (Excluding n-Hexane), 92 6-3 Predicted RD0, RD10, and RD50 Values for C7-C11 Alkanes from Sensory Irritation Investigations, 97 6-4 Exposure Limits Set by Other Organizations, 101 6-5 Spacecraft Maximum Allowable Concentrations C2-C9 Alkanes (ppm), 101 6-6 Acceptable Concentrations, 102 7-1 Applicability of a Benchmark Dose Modeling Approach, 118 7-2 Comparison of Exposure Standards, 120 7-3 End Points and Acceptable Concentrations (Wong 1996), 123 8-1 COHb Effect Level (2% to 24%), 128 8-2 Other Organizations’ Recommendations for CO Exposure, 131 8-3 Calculated COHb and Recorded CO Aboard Mir Spacestation Post- Fire Event, 134 8-4 Spacecraft Maximum Allowable Concentrations, 135 9-1 Tumors Found in NCI Bioassay of EDC, 148 9-2 A Summary of Exposure Standards or Recommended Levels by Other Organizations for EDC Vapors, 150 9-3 Air Concentration and Specified Carcinogenic Risk Levels, 151 9-4 Summary of 1,000-d ACs for Vapors to EDC by Inhalation, 156 9-5 A Summary of SMACs for EDC for Various Durations, 159 10-1 Physical and Chemical Properties of UDMH, 163 10-2 LC50 Values for UDMH (95% Confidence Interval), 167 10-3 Incidence of Cancers in Female Mice Exposed 6 Months to DMNA- Contaminated UDMH, 172 10-4 Inhalation Toxicity Summary, 177 10-5 Exposure Limits Set by Other Organizations, 181 10-6 Spacecraft Maximum Allowable Concentrations, 181 10-7 End Point and Acceptable Concentrations, 182 11-1 Acceptable Concentrations for Ethanol End Points in Volume 3, 193 11-2 Toxicity Summary (For New Studies or Those Not Reviewed in Volume 3 SMAC Document), 194 11-3 Updated Acceptable Concentrations for Ethanol, 203 12-1 Occupational Exposure Limits and Other Established Limits for Formaldehyde, 207 12-2 Shuttle Orbiter Data on Formaldehyde Concentrations (ppm) in Spacecraft Air, 210 12-3 Current Acceptable Concentrations and SMACs for Formaldehyde, 213 12-4 Summary of Critical Toxicologic Studies on Formaldehyde Inhalation, 214 12-5 ACs for Sensory Irritation in the 1994 SMAC Document, 226 12-6 Results of Benchmark Dose Risk Analysis Conducted by Schlosser et al. (2003) and Comparison with EPA (1987) Risk Estimate Used as Basis for Existing SMAC, 234 12-7 Time-Weighted, Site-Averaged Unit-Length Labeling Index Data from Schlosser et al. (2003), Derived from Original Work of Monticello et al. (1996), 239 12-8 Acceptable Concentrations, 242

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xviii Contents 13-1 Metabolites in Urine, 255 13-2 Incidence of Kidney Lesions, Including Cancer, in Male Rats Dosed Orally with d-Limonene for 2 Years, 256 13-3 Inhalation Toxicity of d-Limonene, 257 13-4 Oral Toxicity of d-Limonene in Rodents, 257 13-5 Oral Toxicity of d-Limonene (Non-NTP Studies), 259 13-6 Limonene Occupational Exposure Limits Set, Recommended, or Proposed by Other Organizations, 267 13-7 Spacecraft Maximum Allowable Concentrations for Limonene, 267 13-8 Acceptable Concentrations and Proposed SMACs for Limonene, 268 14-1 Methanol Concentrations in Foods and Beverages, 276 14-2 Background Blood Methanol and Formate Concentrations in Humans, 276 14-3 Toxicity Summary, 278 14-4 Air Standards for Methanol Vapors Set by Other Organizations, 283 14-5 SMACs for Methanol Vapors, 283 14-6 Acceptable Concentrations for Methanol (ppm), 285 15-1 Summary of Previously Published SMACS for DCM (Wong 1996), 293 15-2 Summary of Rodent Carcinogenicity Bioassays for Exposure to DCM by Inhalation, 294 15-3 Exposure Limits Recommended or Set by Other Organizations, 297 15-4 Summary of Noncancer Effects of Chronic Inhalation Exposures to DCM, 299 15-5 Incidence of Hepatic Vacuolization in Rats from DCM Inhalation, 301 15-6 Summary of BMC and BMCL for Hepatic Vacuolization for Various Models, 301 15-7 Non-neoplastic Changes in Female F344/N Rats Exposed to DCM for 2 y, 302 15-8 DCM and Renal Tubular Degeneration (NTP 1986): Summary of Results from the BMD Method, 304 15-9 Summary of 1,000-d ACs, 307 15-10 Summary of Spacecraft Maximum Allowable Concentration, 309 15-11 Acceptable Concentrations for Cancer Risk of 1 in 10,000, 309 16-1 Physical and Chemical Properties of Propylene Glycol, 315 16-2 Toxicity Studies of Propylene Glycol (Inhalation Exposures), 319 16-3 Spacecraft Maximum Allowable Concentrations for PG, 321 16-4 Summary of Acceptable Concentrations and SMACs for Various Durations, 326 17-1 Spacecraft Maximum Allowable Concentrations for Toluene, 331 17-2 Summary of Dose-Response Data for Ototoxicity, 333 17-3 Toxicity Summary, 336 17-4 Air Standards for Toluene Vapors Set by Other Organizations, 340 17-5 2008 Spacecraft Maximum Allowable Concentration for Toluene Vapors, 340 17-6 Acceptable Concentrations for Toluene, 340 18-1 Previously Set SMACs for TMS, 349 18-2 Lipophilicity (Octanol-Water Partition Coefficient) of Three Compounds Compared with Their Antimicrobial Activity in Two Strains of Bacteria, 351 18-3 Comparison of TEELs for TMS and t-Butanol, 353 18-4 Previous and Revised SMACs for TMS, 354 19-1 A Summary of SMACs for Xylene, 360

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xix Contents 19-2 Toxicity Summary of Studies Included in This Document, 366 19-3 Exposure Limits Set or Recommended by Other Organizations, 370 19-4 ATSDR Inhalation Minimal Risk Levels, 370 19-5 Summary of SMACs for Xylene for Various Durations of Exposure, 373 19-6 A Summary of Updated and New ACs and SMACs for Various Durations, 382

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