Table Of ContentH A N D B O O K OF
Second Edition
Library of Congress Cataloging-in-Publication Data
Handbook of toxicology / Michael J. Derelanko, Mannfred A. Hollinger, editors.—2nd ed.
p. cm.
Updated and expanded ed. of: CRC handbook of toxicology. c1995.
Includes bibliographical references and index.
ISBN 0-8493-0370-2 (alk. paper)
1. Toxicology—Handbooks, manuals, etc. I. Derelanko, Michael J. II. Hollinger,
Mannfred A. III. Derelanko, Michael J. CRC handbook of toxicology.
RA1215 .C73 2001
615.9—dc21 2001025086
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Preface to the First Edition
Toxicologists working in the laboratory or office rely on a large information base to design, conduct,
and interpret toxicology studies and to perform risk assessments. Diverse information such as
normal hematology and clinical chemistry values, reproductive indices, physiological parameters,
animal housing requirements, toxicity classifications, and regulatory requirements accumulated
during the toxicologist’s career are generally scattered in file cabinets and on office shelves.
Although practicing toxicologists usually can locate information related to their own areas of
expertise with minimal effort, obtaining reference information in less familiar areas of toxicology
may require considerably more effort, possibly involving a trip to the library or a phone call to a
colleague. A single basic reference source of toxicological information has not been previously
available. We have attempted to fill this void with this publication.
Our goal was to produce a reference book containing practical reference information useful to
practicing toxicologists in the chemical and pharmaceutical industries, contract laboratories, regu-
latory agencies, and academia. Contributors were asked to compile reference material for their own
areas of expertise which would be of value to both experts and students. The task seemed easier
in concept than it proved to be in reality. It quickly became evident that limits had to be placed on
the amount and detail of information included to allow for publication in a reasonable time frame.
Although information for most areas of toxicology is presented, coverage of some areas is clearly
missing. We encourage and welcome constructive comments on improving the information provided
as well as suggestions for additional material which could be included in possible future editions
of this handbook.
We have designed the handbook to allow basic reference information to be located quickly.
Each chapter begins with an outline of its contents. Where possible, text was purposely kept to a
minimum. This book is intended only to be a basic reference source. The user requiring more
detailed discussion should consult the sources cited. Much of the information provided has been
previously published elsewhere. The editors and contributors cannot attest to the accuracy and
completeness of such and, therefore, cannot assume any liability of any kind resulting from the
use or reliance on the information presented in this handbook. Mention of vendors, trade names,
or commercial products does not constitute endorsement or recommendation for use.
Preface to the Second Edition
It has been approximately 10 years since we began compiling information for the first edition of
the CRC Handbook of Toxicology. In reviewing the material contained in the first edition it was
apparent that information such as values for physiological parameters, substance toxicity, and
information related to fundamental toxicology principles and practices remain virtually timeless.
On the other hand, information on such topics as regulatory requirements and guidelines, contract
laboratories, and contact information such as phone numbers and addresses clearly needed updating.
Moreover, although information for most areas of toxicology was included in the first edition,
coverage of some toxicology specialties was clearly missing.
In this respect, the CRC Handbook of Toxicology, Second Edition has been extensively updated
and expanded. Nearly all of the original chapters from the first edition have been updated, with
several receiving extensive revision. Additionally, coverage of inhalation toxicology, neurotoxicol-
ogy, and histopathology has been expanded. Several new regulatory chapters dealing with pesticides,
medical devices, consumer products, and worldwide notification of new chemicals have been added.
Areas of toxicology missing from the first edition such as ecotoxicology and in vitro toxicology
are now covered. Also included is a new chapter providing an extensive overview of the toxicology
of metals.
Since the publication of the first edition, environmental and endocrine toxicology and children’s
health have become major issues that will clearly impact the field of toxicology in the future. To
provide some basic information on these topics, two chapters on basic male and female endocri-
nology and toxicology have been included and tables have been added to the risk assessment chapter
that provide information on differences in physiological and biochemical parameters between
children and adults. When the first edition went to print, the Internet was in its infancy but has
now become an important information-gathering tool for toxicologists. In the second edition, the
authors were asked where possible to reference Web sites they consider sources of valuable
information for their fields of expertise.
The CRC Handbook of Toxicology contains a considerable amount of reference information.
However, because of the size of the handbook and the number of tables and figures it contains,
some users of the first edition reported it was not always easy to identify and locate specific
information quickly. As a search aid for the second edition, headings have been added at the top
of each page identifying the chapter topics. Also we included pages at the end of some of the
chapters to provide additional information closely related to the subject matter of the chapter.
Constructive comments on how future editions of the CRC Handbook of Toxicology can be improved
are welcome.
The number of chapters in the second edition has increased from the original 22 to 33 with
over 200 new tables and figures added. It is said, “A picture is worth a thousand words.” Thus, as
in the first edition, text has been kept to a minimum where possible and practical reference
information is provided in tables and figures that are useful to practicing toxicologists in the
chemical and pharmaceutical industries, contract laboratories, regulatory agencies, and academia.
As before, much of the information provided has been previously published elsewhere. Although
considerable effort was made to obtain the information from reliable sources, the editors and
contributors cannot attest to its accuracy and completeness and, therefore, cannot assume any
liability of any kind resulting from the use or reliance on the information provided in this handbook.
Mention of vendors, trade names, or commercial products does not constitute an endorsement or
recommendation for use.
Michael J. Derelanko
Mannfred A. Hollinger
Editors
Michael J. Derelanko, Ph.D., D.A.B.T., F.A.T.S., is Corporate Manager of Toxicology and Risk
Assessment at Honeywell International Inc., in Morristown, New Jersey. Dr. Derelanko received a
B.S. degree from Saint Peter’s College in 1973. He was a National Institutes of Health predoctoral
trainee in the Albert S. Gordon Laboratory of Experimental Hematology at New York University,
receiving M.S. and Ph.D. degrees. He received the 1976 New York University Gladys Mateyko
Award for Excellence in Biology. Following a two-year postdoctoral fellowship in gastrointestinal
pharmacology at Schering-Plough Corporation, he began his career in industrial toxicology in 1980
as a research toxicologist in the laboratories of Allied Chemical Corporation.
Dr. Derelanko is a Diplomate of the American Board of Toxicology and a Fellow of the
Academy of Toxicological Sciences. He is a member of the Society of Toxicology, the Society for
Experimental Biology and Medicine, and the honorary research society Sigma Xi. He has served
on the content advisory committee of the New Jersey Liberty Science Center, has chaired or been
a member of industrial and government toxicology advisory committees, is actively involved with
the Chemical Industry Institute of Toxicology, and serves on the speaker’s bureau of the New Jersey
Association for Biomedical Research.
Dr. Derelanko has authored numerous papers in experimental hematology, gastrointestinal
pharmacology, and toxicology. He has been actively involved in educating the public about toxi-
cology, particularly at the middle school level. He has delivered invited lectures on this subject at
national meetings. Dr. Derelanko’s current research interests involve understanding the toxicity of
aliphatic oximes. He is coeditor along with Dr. Mannfred A. Hollinger of the first edition of the
CRC Handbook of Toxicology and author of CRC’s Toxicologist’s Pocket Handbook.
Mannfred A. Hollinger, Ph.D., is a Professor in the Department of Medical Pharmacology and
Toxicology, School of Medicine, University of California, Davis. Dr. Hollinger is former editor of
Current Topics in Pulmonary Pharmacology and Toxicology, Focus on Pulmonary Pharmacology
and Toxicology, and Yearbook of Pharmacology, and assistant editor of The Journal of Pharma-
cology and Experimental Therapeutics. Dr. Hollinger serves on the editorial advisory board of The
Journal of Pharmacology and Experimental Therapeutics, Research Communications in Chemical
Pathology and Pharmacology, and The Journal of The American College of Toxicology. Dr.
Hollinger is at present series editor of Pharmacology and Toxicology: Basic and Clinical Aspects
for CRC Press. He is a member of the American Society of Pharmacology and Experimental
Therapeutics and the Society of Toxicology.
Born in Chicago, he obtained his B.S. degree from North Park College in 1961 and his M.S.
(1965) and Ph.D. (1967) degrees from Loyola University, Chicago. He was employed by Baxter
Laboratories from 1961 to 1963. From 1967 to 1969, Dr. Hollinger was a postdoctoral research
fellow in the Department of Pharmacology, Stanford University Medical School. Since coming to
Davis in 1969, Dr. Hollinger has participated in several team-taught courses to undergraduate,
graduate, and medical students.
While at Davis, Dr. Hollinger has published numerous research papers as well as a monograph
on respiratory pharmacology and toxicology. He continues to serve as a referee for many of the
principal pharmacology and toxicology journals. Dr. Hollinger was the recipient of a Burroughs-
Wellcome Visiting Scientist Fellowship to Southampton, England in 1986 as well as a National
Institutes of Health Fogarty Senior International Fellowship to Heidelberg, Germany in 1988. His
current research interests deal with pulmonary fibrosis.
Contributors
Mohamed B. Abou-Donia, Ph.D. Michael J. Derelanko, Ph.D., D.A.B.T.,
Professor of Pharmacology and Neurobiology F.A.T.S.
Department of Pharmacology and Cancer Corporate Manager of Toxicology and Risk
Biology Assessment
Duke University Medical Center Honeywell International Inc.
Durham, North Carolina Morristown, New Jersey
Patrick J. Devine, Ph.D.
Aqel W. Abu-Qare, Ph.D.
Research Associate
Research Associate
Department of Physiology
Department of Pharmacology and Cancer
The University of Arizona
Biology
Tucson, Arizona
Duke University Medical Center
Durham, North Carolina
Jill Dolgin, Pharm.D.
Drug Information Product Manager
Carol S. Auletta, D.A.B.T., R.A.C., M.B.A.
Product Information Department
Senior Director
SmithKline Beecham
Toxicology
Philadelphia, Pennsylvania
Huntingdon Life Sciences
Princeton Research Center
Brendan J. Dunn, M.S.
East Millstone, New Jersey
Manager, Toxicology and Risk Assessment
Honeywell International Inc.
William H. Baker, D.V.M., Dipl., A.C.V.P. Morristown, New Jersey
Associate Director of Pathology
Springborn Laboratories, Inc. Donald J. Ecobichon, Ph.D.
Spencerville, Ohio Queen’s University
Department of Pharmacology and Toxicology
Kingston, Ontario, Canada
Kimberly L. Bonnette, M.S., LATG
Manager of Acute Toxicology
Eman M. Elmasry, Ph.D.
Springborn Laboratories, Inc.
Associate Professor
Spencerville, Ohio
Faculty of Pharmacy
Zagazig University
G. Allen Burton, Jr., Ph.D.
Zagazig, Egypt
Brage Golding Distinguished Professor of
Research and Director
Henry C. Fogle, B.S., M.S.
Institute for Environmental Quality
Manager, International Regulatory Affairs
Wright State University
Honeywell International Inc.
Dayton, Ohio
Hopewell, Virginia
Rodger D. Curren, Ph.D. Ramadevi Gudi, Ph.D.
President Study Director, Cytogenetics Studies
Institute for In Vitro Sciences, Inc. BioReliance Corp.
Gaithersburg, Maryland Rockville, Maryland
John W. Harbell, Ph.D. Robert V. House, Ph.D.
Vice President and Chief Scientific Officer Staff Scientist
Institute for In Vitro Sciences, Inc. Covance Laboratories, Inc.
Gaithersburg, Maryland Madison, Wisconsin
Patricia B. Hoyer, Ph.D.
Jane E. Harris, Ph.D.
Professor
Director of Toxicology
Department of Physiology
BASF Corp.
The University of Arizona
Princeton, New Jersey
Tucson, Arizona
Steven J. Hermansky, Pharm.D., Ph.D., David Jacobson-Kram, Ph.D., D.A.B.T.
D.A.B.T. Vice President
Associate Director Toxicology and Laboratory Animal Health
Product Safety and Toxicology BioReliance Corp.
Schering-Plough HealthCare Products Rockville, Maryland
Memphis, Tennessee
Daniel R. Lavoie, M.S.
Aquatic Toxicologist
Kimiko Hirayama, Ph.D.
Institute for Environmental Quality
Professor
Wright State University
Kumamoto University College of Medical
Dayton, Ohio
Science
Kumamoto, Japan
Barry S. Levine, D.Sc., D.A.B.T.
Director
Richard M. Hoar, Ph.D. Toxicology Research Laboratory
Consultant in Developmental Toxicology Associate Professor of Pharmacology
Williamstown, Massachusetts Department of Pharmacology
University of Illinois
Chicago, Illinois
David J. Hoffman, Ph.D.
Ecotoxicologist
Karen M. MacKenzie, Ph.D., D.A.B.T.
Patuxent Wildlife Research Center
Consultant
U.S. Geological Survey
Anderson, South Carolina
Laurel, Maryland
and Adjunct Professor
Rosemary C. Mandella, Ph.D., D.A.B.T.
University of Maryland
Associate Director of Toxicology
Huntingdon Life Sciences
Gary M. Hoffman, B.A., D.A.B.T. Princeton Research Center
Study Director and Director of Inhalation East Millstone, New Jersey
Toxicology
Huntingdon Life Sciences Dennis J. Naas, B.S.
Princeton Research Center President, Owner
East Millstone, New Jersey AccuTox Consulting Services, Ltd.
Midland, Michigan
Mannfred A. Hollinger, Ph.D.
Professor Rajesh K. Naz, Ph.D.
Department of Medical Pharmacology and Director
Toxicology Division of Research
School of Medicine Department of Obstetrics and Gynecology
University of California Medical College of Ohio
Davis, California Toledo, Ohio
Paul E. Newton, Ph.D., D.A.B.T. Joseph C. Siglin, Ph.D., D.A.B.T.
Senior Study Director and Director of Director of Research
Inhalation Toxicology Springborn Laboratories, Inc.
MPI Research, Inc. Spencerville, Ohio
Mattawan, Michigan
Suresh C. Sikka, Ph.D., H.C.L.D.
John C. Peckham, D.V.M., M.S., Ph.D.
Associate Professor and Urology Research
Veterinary Pathologist
Director
Experimental Pathology Laboratories, Inc.
Tulane University Health Sciences Center
Research Triangle Park, North Carolina
New Orleans, Louisiana
William J. Powers, Jr., Ph.D., D.A.B.T.
Vice President
Peter T. Thomas, Ph.D.
Global Preclinical Development
Director
Johnson & Johnson
Toxicology
Raritan, New Jersey
Covance Laboratories, Inc.
Madison, Wisconsin
Barnett A. Rattner, Ph.D.
Ecotoxicologist
Patuxent Wildlife Research Center Valentine O. Wagner III, M.S.
U.S. Geological Survey Study Director
Laurel, Maryland Bacterial Mutagenesis Studies
and Adjunct Professor BioReliance Corp.
University of Maryland Rockville, Maryland
Dawn D. Rodabaugh, B.S.
Christopher W. Wilson, B.S.
Assistant Toxicologist–Study Director
Assistant Toxicologist–Study Director
Springborn Laboratories, Inc.
Springborn Laboratories, Inc.
Spencerville, Ohio
Spencerville, Ohio
Richard H. C. San, Ph.D.
Scientific Director
Akira Yasutake, Ph.D.
Genetic Toxicology
Chief in Biochemistry Section
BioReliance Corp.
National Institute for Minamata Disease
Rockville, Maryland
Kumamoto, Japan
Gene E. Schulze, Ph.D., D.A.B.T.
Associate Director Robert R. Young, M.S.
Department of Toxicology Director
Bristol-Myers Squibb Pharmaceutical Research Toxicology Operations
Institute BioReliance Corp.
Syracuse, New York Rockville, Maryland
Acknowledgments
The editors and contributors thank the following individuals who helped with the preparation of
the CRC Handbook of Toxicology, Second Edition by providing information, advice, constructive
criticism, technical expertise, or secretarial skills: Dr. Bjorn Thorsrud, Dr. David Serota, Dr. David
Dolan, Dr. George Rusch, Dr. Leigh Ann Naas, Dr. Hans Certa, Dr. George Dearlove, Dr. Gregory
Kearns, Dr. Jill Merrill, Gary Roy, Donald Surprenant, Rita Levy, Renee Bolduc, Bob Nellis, Christy
Calhoun, Michelle Delaurier, Ronald Brzozowski, Elise Larsen, Daniel Murray, Greg Mun, and
Regina Carbon Tihan.
As the second edition of the handbook contains a significant amount of information from the
first edition, the editors again acknowledge the following individuals for their help in the publication
of the earlier handbook: Dr. David Serota, Dr. Kurt Weingand, Dr. Walter Loeb, Dr. George Rusch,
Dr. Rosemary Mandella, Dr. C. Anita Bigger, Dr. Donald Putman, Renee Brown, Rita Levy, Cynthia
Nofziger, Cathy Beck, Cindy Moore, Doris Bridgeman, Isabelle Baker, Antoinette Keesey, David
Keesey, Robin Larkin, Donna Blaszcak, Diane Blansett, Ellen Whiting, Sharon Harris, Farrell
Merriman, Gary Roy, Joseph Townsend, Pam Errico, Elizabeth Regan, Kristin Ballard, Kim Cayz,
Michael Mercieca, Jane Clark, Hans Raabe, Betsy Schadly, Skip Wagner, Robert Young, Bernette
Cockrell, Christine Holzer, Trina Rode, Carol Winiarski, Dolores Yili, Georgene Rutledge, Rusty
Rush, Deborah Douds, Todd Merriman, and Gregory Kowalski.
The editors extend a special thanks to the authors and publishers who graciously allowed the
reprinting of many of the tables and figures in the handbook.
