Ninth Interim Report of the Subcommittee on Acute Exposure Guideline Levels

Subcommittee on Acute Exposure Guideline Levels

Committee on Toxicology

Board on Environmental Studies and Toxicology

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
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Ninth Interim Report of the Subcommittee on Acute Exposure Guideline Levels Subcommittee on Acute Exposure Guideline Levels Committee on Toxicology Board on Environmental Studies and Toxicology Division on Earth and Life Studies NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu

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NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, D.C. 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 Contract Nos. DAMD 17–89-C-9086 and DAMD 17–99-C-9049 between the National Academy of Sciences and US. Army. 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. 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 2003 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 Medicine 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 chairman and vice chairman, respectively, of the National Research Council. www.national-academies.org

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SUBCOMMITTEE ON ACUTE EXPOSURE GUIDELINE LEVELS DANIELKREWSKI(Chair), University of Ottawa, Ontario, Canada EDWARDC.BISHOP, Parsons Corporation, Fairfax, Virginia JAMESV.BRUCKNER, University of Georgia, Athens, Georgia JOHNDOULL, University of Kansas Medical Center, Kansas City, Kansas DAVIDP.KELLY, Dupont Company, Newark, Delaware KANNANKRISHNAN, University of Montréal, Montréal, Canada STEPHENU.LESTER, Center for Health, Environment, and Justice, Falls Church, Virginia JUDITHMACGREGOR, Toxicology Consulting Services, Arnold, Maryland PATRICIAM.MCGINNIS, Syracuse Research Corporation, Ft. Washington, Pennsylvania FRANZOESCH, University of Mainz, Mainz, Germany RICHARDB.SCHLESINGER, Pace University, New York, New York CALVINC.WILLHITE, State of California, Berkeley, California FREDERIKA.DEWOLFF, Leiden University Medical Center, Leiden, Netherlands Staff KULBIRS.BAKSHI, Project Director KELLYCLARK, Editor AIDAC.NEEL, Senior Project Assistant Sponsor U.S. DEPARTMENT OFDEFENSE

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COMMITTEE ON TOXICOLOGY BAILUSWALKER, JR.(Chair), Howard University Medical Center and American Public Health Association, Washington, D.C. MELVINE.ANDERSEN, Colorado State University, Fort Collins, Colorado EDWARDC.BISHOP, Parsons Corporation, Fairfax, Virginia GARYP.CARLSON, Purdue University, West Lafayette, Indiana JANICEE.CHAMBERS, Mississippi State University, Mississippi State, Mississippi LEONARDCHIAZZE, JR., Georgetown University, Washington, D.C. JUDITHA.GRAHAM, American Chemistry Council, Arlington, Virginia SIDNEYGREEN, Howard University, Washington, D.C. MERYLKAROL, University of Pittsburgh, Pittsburgh, Pennsylvania STEPHENU.LESTER, Center for Health Environment and Justice, Falls Church, Virginia DAVIDH.MOORE, Battelle Memorial Institute, Bel Air, Maryland CALVINC.WILLHITE, State of California, Berkeley, California GERALDN.WOGAN, Massachusetts Institute of Technology, Cambridge, Massachusetts Staff KULBIRS.BAKSHI, Program Director SUSANN.J.MARTEL, Senior Staff Officer ELLENMANTUS, Senior Staff Officer KELLYCLARK, Editor AIDANEEL, Senior Project Assistant TAMARADAWSON, Project Assistant

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BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1 Members GORDONORIANS(Chair), University of Washington, Seattle JOHNDOULL(Vice Chair), University of Kansas Medical Center, Kansas City DAVIDALLEN, University of Texas, Austin THOMASBURKE, Johns Hopkins University, Baltimore, Maryland JUDITHC.CHOW, Desert Research Institute, Reno, Nevada CHRISTOPHERB.FIELD, Carnegie Institute of Washington, Stanford, California WILLIAMH.GLAZE, University of North Carolina, Chapel Hill SHERRIW.GOODMAN, Center for Naval Analyses, Alexandria, Virginia DANIELS.GREENBAUM, Health Effects Institute, Cambridge, Massachusetts ROGENEHENDERSON, Lovelace Respiratory Research Institute, Albuquerque, New Mexico CAROLHENRY, American Chemistry Council, Arlington, Virginia ROBERTHUGGETT, Michigan State University, East Lansing BARRYL.JOHNSON, Emory University, Atlanta, Georgia JAMESH.JOHNSON, Howard University, Washington, D.C. JAMESA.MACMAHON, Utah State University, Logan PATRICKV.O’BRIEN, Chevron Research and Technology, Richmond, California DOROTHYE.PATTON, International Life Sciences Institute, Washington, D.C. ANNPOWERS, Pace University School of Law, White Plains, New York LOUISEM.RYAN, Harvard University, Boston, Massachusetts JONATHANM.SAMET, Johns Hopkins University, Baltimore, Maryland KIRKSMITH, University of California, Berkeley LISASPEER, Natural Resources Defense Council, New York, New York G.DAVIDTILMAN, University of Minnesota, St. Paul LAURENA.ZEISE, California Environmental Protection Agency, Oakland Senior Staff JAMESJ.REISA, Director DAVIDJ.POLICANSKY, Associate Director and Senior Program Director for Applied Ecology RAYMONDA.WASSEL, Senior Program Director for Environmental Sciences and Engineering KULBIRBAKSHI, Program Director for Toxicology ROBERTAM.WEDGE, Program Director for Risk Analysis EILEENABT, Senior Staff Officer K.JOHNHOLMES, Senior Staff Officer ELLENMANTUS, Senior Staff Officer SUSANN.J.MARTEL, Senior Staff Officer SUZANNEVANDRUNICK, Senior Staff Officer RUTHE.CROSSGROVE, Managing Editor 1   This study was planned, overseen, and supported by the Board on Environmental Studies and Toxicology.

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PREFACE Extremely hazardous substances (EHSs)1 can be released accidentally as a result of chemical spills, industrial explosions, fires, or accidents involving railroad cars or trucks transporting EHSs, or intentionally through terrorist activities. Workers and people in communities surrounding industrial facilities where EHSs are manufactured, used, or stored and in communities along the nation’s railways and highways are potentially at risk of being exposed to airborne EHSs during accidental and intentional releases. Pursuant to the Superfund Amendments and Reauthorization Act of 1986, the U.S. Environmental Protection Agency (EPA) has identified approximately 400 EHSs on the basis of acute lethality data in rodents. The National Advisory Committee (NAC) on Acute Exposure Guideline Levels for Hazardous Substances has developed acute exposure guideline levels (AEGLs) for approximately 80 EHSs to date. In 1998, EPA and the U.S. Department of Defense (DOD) requested that the National Research Council (NRC) independently review the AEGLs developed by the NAC. In response to that request, the NRC organized within its Committee on Toxicology the Subcommittee on Acute Exposure Guideline Levels. The NAC’s Standing Operating Procedures for Developing AEGLs for Airborne Chemicals was reviewed by the subcommittee and published in May 2001. That report provides step-by-step guidance for the derivation of AEGLs for hazardous chemicals. In December 2000, the subcommittee’s first report, Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 1, was published by the NRC; volumes 2 and 3 in that series were published in 2002 and 2003, respectively. The subcommittee meets two to three times each calendar year. At those meetings, the subcommittee hears presentations from the NAC staff and its contractor—the Oak Ridge National Laboratory—on draft AEGL documents. At some meetings, the subcommittee also hears presentations from NAC’s collaborators from foreign countries, such as Germany. The subcommittee provides its comments and recommendations on those documents to NAC in its interim reports, and the NAC uses those comments to make revisions. The revised reports are presented by the NAC to the subcommittee at subsequent meetings until the subcommittee concurs with the final draft documents. The revised reports are then published as appendixes in the subcommittee’s reports. The present report represents the subcommittee’s ninth interim report. It summarizes the subcommittee’s conclusions and recommendations for improving NAC’s AEGL documents for 13 chemicals: Methanol, acrylic acid, crotonaldehyde, hydrogen sulfide, phenol, cyclohexylamine, ethylenediamine, HFE-7100, carbon monoxide, ethylenimine, propylenimine, allylamine, and chlorine dioxide. 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. 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 1   As defined pursuant to the Superfund Amendments and Reauthorization Act of 1986.

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possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: David Gaylor of Gaylor & Associates and Nancy Kerkvliet of Oregon State University. 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: Judith A.Graham of the American Chemistry Council. Appointed by the National Research Council, she was responsible for making certain that an independent examination of this report 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. The subcommittee gratefully acknowledges the valuable assistance provided by the following persons: Ernest Falke and Paul Tobin (both from EPA); Cheryl Bast, Po Yung Lu, Sylvia Milanez, Sylvia Talmage, Claudia Troxel, Annetta Watson, and Robert Young (all from Oak Ridge National Laboratory). Aida Neel was the project assistant and Kelly Clark was the editor. We are grateful to James J.Reisa, director of the Board on Environmental Studies and Toxicology, for his helpful guidance. The subcommittee particularly acknowledges Kulbir Bakshi, project director for the subcommittee, for bringing the report to completion. Finally, we would like to thank all members of the subcommittee for their expertise and dedicated effort throughout the development of this report. Daniel Krewski, Chair Subcommittee on Acute Exposure Guideline Levels Bailus Walker, Chair Committee on Toxicology