Table Of Contenthandbook of
HUMAN
TOXICOLOGY
edited by
J.
Edward Massaro, Ph.D.
National Health and Environmental Effects
Research Laboratory
Research Triangle Park, North Carolina
Boca Raton London New York
CRC Press is an imprint of the
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ISBN 13: 978-0-8493-4493-0 (hbk)
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Library of Congress Card Number 97-721
Library of Congress Cataloging-in-Publication Data
Handbook of human toxicology/ edited by Edward J. Massaro.
p. cm.
Includes bibliographical references and index.
ISBN 0-8493-4493-X
I. Toxicology. I. Massaro, Edward J.
[DNLM: I. Poisoning. 2. Poisons. QV 600 H2345 1997]
RA121 l.H286 1997
615.9--dc21
DNLM/DLC
for Library of Congress 97-721
CIP
Cover design: Dawn Boyd
P
reface
Toxicology is a vast and growing polymorphic field, and the sheer quantity and variety
of toxicological and toxicology-related information that has been and currently is being
generated preclude comprehensive coverage of the field in any single volume. Our goal,
therefore, was to develop a compendium of toxicologic information on selected topics that,
if successful, would be supplemented with additional volumes to increase the scope of coverage
of the field. Even within the areas selected for inclusion within this volume, it was possible
to cover only a limited number of topics. Furthermore, aspects of the individual topics
included within each section of this volume could not be covered completely, and some were
not covered at all.
Modern toxicology is an experimental science — it has to be. As in any scientific field in
which nonphenomenological information is of primary importance, understanding toxicologic
effects requires carefully controlled experimental investigation. Furthermore, meaningful
analysis of the mechanisms through which toxicants operate requires accurate data from
experimental manipulation of model systems. Because one biologic system may not respond
to toxic insult precisely like another, comparative data are a necessity. If the differences, as
well as the similarities, among diverse systems can be understood and appreciated, it may be
possible to reliably extrapolate data obtained from one system to another. Although the search
for methods that would allow reliable extrapolation of in vivo animal data and/or in vitro
data to the human condition continues, no methods, except those relating the most funda
mental toxicologic effects, are yet of acceptable reliability. It may not be possible to develop
useful extrapolation methodology from the state of current knowledge, vast though it may
be. Major impediments include identifying and locating important information. Just what is
out there? Useful handbooks can aid in alleviating such problems. Our ultimate goal is the
development of useful handbooks. Your input is solicited and will be appreciated.
T E
he ditor
Edward J. Massaro, Ph. D., is a cell physiologist/biochemist/experimental pathologist
and an established international authority on mechanisms of cytotoxicology of drugs, toxi
cants, and teratogens. He is Senior Research Scientist, Developmental Biology Branch,
National Health and Environmental Effects Research Laboratory (NHEERL), Research
Triangle Park, NC; Research Professor of Biophysical Sciences, State University of New York
at Buffalo (SUNYAB) School of Medicine and Biomedical Sciences; and Adjunct Professor
of Toxicology at Duke University, Durham, NC, and The University of North Carolina-
Chapel Hill. Dr. Massaro has served as the Director of the Inhalation Toxicology Division
of NHEERL; Director of the Center for Air Environment Studies; Professor of Cytotoxicoloy,
Department of Veterinary Science, and Senior Research Associate, Institute for the Study of
Human Development, at The Pennsylvania State University. Dr. Massaro also has served as
the Director of Toxicology and Chemical Carcinogenesis at the Mason Research Institute,
Worcester, MA, and as Professor of Biochemistry at SUNYAB.
Dr. Massaro was graduated from Rutgers University in 1955 with an A.B. degree in
biology and chemistry. He obtained his M.A. degree in biochemistry and cell physiology
from the University of Texas-Austin in 1958 and his Ph.D. degree in anatomy, biochemistry,
and physiology from the University of Texas-Austin and the University of Texas Medical
Branch-Galveston in 1962. Dr. Massaro held both USPHS pre- and postdoctoral fellowships.
Dr. Massaro is a member of the American Association for the Advancement of Science,
American Association for Cancer Research, American Chemical Society, American Society for
Biological and Molecular Chemistry, American Society for Cell Biology, American Society for
Investigative Pathology, American Society for Pharmacology and Experimental Therapeutics,
Biophysical Society, International Association of Bioinorganic Scientists, International Society
for the Study of Xenobiotics, International Society for Trace Element Research in Humans,
International Union of Pharmacology — Section on Toxicology, Metals Specialty Section of
the Society of Toxicology, New York Academy of Sciences, Sigma Xi, Society of Toxicology,
Teratology Society, and The Johns Hopkins Medical and Surgical Association.
Dr. Massaro’s research accomplishments have been recognized both nationally and inter
nationally. He was elected a Fellow of the American Association for the Advancement of
Science in 1986, was the recipient of the Achievement Award of the international journal,
Neurotoxicology, in 1989, and received the Scientific and Technological Achievement Award
of the U.S. Environmental Protection Agency in 1992.
Currendy, Dr. Massaro is editor of the journal, Cell Biochemistry and Biophysics, and the
muldvolume series, Methods in Toxicology. He served as editor (with J.A. Crapo and D.E.
Gardner) of Toxicology of the Lung, is a member of the editorial board of the Modern Nutrition
series, and is a member of the editorial advisory board of the series, Current Topics in Toxicology
and Biological Effects of Heavy Metals. Dr. Massaro has been a member of the editorial board
of the journal, Biological Trace Element Research, for many years and served as associate editor
of the journal, Neurotoxicology, and on the editorial boards of the journals Neurotoxicology,
Environmental Research, Environmental Health Perspectives, Toxicology, Toxicology and Envi
ronmental Health, Toxicology and Applied Pharmacology, Toxicology and Industrial Health,
Drug and Chemical Toxicology, Environmental Pathology and Toxicology, Environmental
Science and Health, Gerontology, and Copeia. Dr. Massaro has served as a reviewer for Chemical
Research in Toxicology since its inception and Teratology, Toxicology, Applied Pharmacology,
and the American Journal of Physiology for many years.
Dr. Massaro has published extensively in the field of metals toxicology. In addition, he
has presented numerous papers at national and international meetings and has been actively
involved in national, state, and local health (human and veterinary), educational, environ
mental, and scientific affairs.
C
ontributors
Yasunobu Aoki, Ph.D. Mitchell D. Cohen, Ph.D.
Research Scientist Research Assistant Professor
Environmental Chemistry Division Nelson Institute of Environmental Medicine
National Institute for Environmental Studies New York University School of Medicine
Ibaraki, Japan TuxedOy New York
Cheng-Long Bai, Ph.D. Christine F. Colie, M.D.
Senior Toxicologist Assistant Professor
Therapeutic Goods Administration Department of Obstetrics and Gynecology
Commonwealth Department of Health Georgetown University Medical Center
and Family Services Washington D. C.
Woden, ACT
Stephanie D. Collier, M.S.
Australia
Doctoral Student
John B. Barnett, Ph.D. Department of Biological Sciences
Professor and Chair Mississippi State University
Microbiology and Immunology Department Mississippi State, Mississippi
West Virginia University
Alan R. Dahl, Ph.D.
Morgantown, West Virginia
Scientist
Leila M. Barraj, D.Sc. ITRI
Lovelace Research Institute
Senior Statistician
Albuquerquey New Mexico
TAS', Inc.
Washington, D.C.
Robert Devlin, Ph.D.
David A. Beckman, Ph.D. Chief Clinical Research Branch
Human Studies Division
Associate Professor
National Health and Environmental Effects Research
Department of Pediatrics
Laboratory
Thomas Jefferson University
US. Environmental Protection Agency
and duPont Hospital for Children
Research Triangle Parky North Carolina
Wilmington, Delaware
Judith S. Douglass, M.S., R.D.
Abdellaziz Ben-Jebria, Ph.D.
Senior Nutritionist
Associate Professor
TAS, Inc.
Department of Chemical Engineering
Washington, D.C.
Penn State University
University Park, Pennsylvania M. Duane Enger, Ph.D.
Professor and Chair
Robert L. Brent, M.D., Ph.D., D.Sc. (Hon)
Department of Zoology and Genetics
Distinguished Professor Iowa State University
Department of Pediatrics Ames, Iowa
Thomas Jefferson University
and duPont Hospital for Children Lynda B. Fawcett, Ph.D.
Wilmington, Delaware Instructor
Department of Pediatrics
Edward J. Carson
Thomas Jefferson University
Southern College of Optometry and duPont Hospital for Children
Memphisу Tennessee Wilmington, Delaware
Kathryn H. Fleming, Ph.D. Hiroshi Imai, Ph.D.
Senior Nutritionist Laboratory Chief
TAS, Inc. Laboratory of Reproductive Biotechnology
Washington, D.C. National Institute of Animal Industry
Ibaraki, Japan
Lawrence J. Folinsbee, Ph.D.
Chief, Environmental Media Assessment Group Y. James Kang, Ph.D., D.V.M.
National Center for Environmental Assessment Associate Professor
U.S. Environmental Protection Agency Departments of Medicine, and Pharmacology
Research Triangle Park, North Carolina and Toxicology
University of Louisville
Susan Groziak, Ph.D., R.D. Louisville, Kentucky
Manager, Nutrition Research and Scientific Publications
Department of Nutrition Research Howard R. Kehrl, M.D.
National Dairy Council Medical Officer
Rosemont, Illinois Human Studies Division
National Health and Environmental Effects
Helen G. Haggerty, Ph.D. Research Laboratory
Senior Research Investigator U.S. Environmental Protection Agency
Department of Biologies Evaluation Research Triangle Park, North Carolina
Bristol-Myers Squibb
Syracuse, New Tork Deborah Keil, Ph.D.
Assistant Professor
Jack R. Harkema, Ph.D., D.V.M. Department of Medical Laboratory Sciences
Department of Pathology Medical University of South Carolina
Michigan State University Charleston, South Carolina
East Lansing, Michigan
Chong S. Kim, Ph.D.
James T. Heimbach, Ph.D. Senior Research Scientist
Chief Operating Officer Human Studies Division
TAS, Inc. National Health and Environmental Effects
Washington, D.C. Research Laboratory
U.S. Environmental Protection Agency
Kimiko Hirayama, Ph.D Research Triangle Park, North Carolina
Professor
Jane Q. Koenig, Ph.D.
College of Medical Science
Kumamoto University Professor
Kumamoto, Japan Department of Environmental Health
University of Washington
Robert V. House, Ph.D. Seattle, Washington
Senior Immunologist
Shinji Koizumi, Ph.D.
Life Sciences Department
ITT Research Institute Senior Researcher
Chicago, Illinois Department of Experimental Toxicology
National Institute of Industrial Health
Claude L. Hughes, Jr., M.D., Ph.D. Kawasaki, Japan
Associate Professor of Comparative Medicine
Rebecca Liebes, Ph.D.
and Obstetrics and Gynecology
Comparative Medicine Clinical Research Center Graduate Fellow
Bowman Gray School of Medicine Department of Human Nutrition and Food Management
Wake Forest University Ohio State University
Winston-Salem, North Carolina Columbus, OH
Dallas M. Hyde, Ph.D. Daniel L. Luchtel, Ph.D.
Department of Anatomy, Physiology, and Cell Biology Professor
School of Veterinary Medicine Department of Environmental Health
University of California University of Washington
Davis, California Seattle, Washington
Andrew Т. Mariassy, Ph.D. Kent E. Pinkerton, Ph.D.
Department of Anatomy Department of Anatomy, Physiology, and Cell Biology
Nova Southeastern University School of Veterinary Medicine
Coral Gables·, Florida University of California
Davis, California
Edward J. Massaro, Ph.D.
Charles G. Plopper, Ph.D.
Senior Research Scientist
Developmental Biology Branch Department of Anatomy, Physiology, and Cell Biology
National Health and Environmental Effects School of Veterinary Medicine
Research Laboratory University of California
Research Triangle Park, North Carolina Davis, California
Richard Mattes, Ph.D. James D. Prah, Ph.D.
Member Research Psychologist
Monell Chemical Senses Center Human Studies Division
Philadelphia, Pennsylvania National Center for Environmental Assessment
U.S. Environmental Protection Agency
John T. McBride, M.D. Research Triangle Park, North Carolina
Department of Pediatrics
Stephen B. Pruett, Ph.D.
University of Rochester Medical Center
Professor
Rochester, New York
Department of Biological Sciences
Mississippi State University
Denis M. Medeiros, Ph.D.
Mississippi State, Mississippi
Professor of Human Nutrition,
and Associate Dean for Research Daniel J. Raiten, Ph.D.
Department of Human Nutrition and
Senior Staff Scientist
Food Management
Life Sciences Research Office
The Ohio State University
Federation of American Sciences for Experimental Biology
Columbus, Ohio
Bethesda, Maryland
Robert R. Mercer, Ph.D.
Krystyna M. Rankin, Ph.D.
Department of Medicine
Postdoctoral Fellow
Duke University Medical Center
Monell Chemical Senses Center
Durham, North Carolina
Philadelphia, Pennsylvania
Gregory D. Miller, Ph.D., F.A.C.N.
Kathleen E. Rodgers, Ph.D.
Vice President, Nutrition Research
Associate Professor
and Technology Transfer
Livingston Research Center
National Dairy Council
School of Medicine
Rosemont, Illinois
University of Southern California
Los Angeles, California
Daniel L. Morgan, Ph.D.
Head, Respiratory Toxicology James L. Schardein, M.S., A.T.S.
Laboratory of Toxicology Senior Vice President, Director of Research
National Institute of Environmental Health Sciences Will Research Laboratories
Research Triangle Park, North Carolina Ashland, Ohio
Kevin T. Morgan, B.V.Sc., Ph.D. Richard B. Schlesinger, Ph.D.
Department of Experimental Pathology Professor
and Toxicology Department of Environmental Medicine
Chemical Industry Institute of Toxicology New York University Medical Center
Research Triangle Park, North Carolina Tuxedo, New York
Iyabo O. Obasanjo, D.V.M., Ph.D. Steven Schrader, Ph.D.
Fellow Chief, Functional Toxicology Section
Comparative Medicine Clinical Research Center Robert A. Taft Laboratory
Bowman Gray School of Medicine Centers for Disease Control
Wake Forest University National Institute for Occupational Safety and Health
Winston-Salem, North Carolina Cincinnati, Ohio
