Casarett & Doull's Essentials of Toxicology 4th Edition

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liable for any indirect, incidental, special, punitive, consequential or similar damages that result
from the use of or inability to use the work, even if any of them has been advised of the
possibility of such damages. This limitation of liability shall apply to any claim or cause
whatsoever whether such claim or cause arises in contract, tort or otherwise.
Contents

Contributors
Preface

UNIT 1
GENERAL PRINCIPLES OF TOXICOLOGY
1. The Evolving Journey of Toxicology: A Historical Glimpse
Philip Wexler and Antoinette N. Hayes
2. Principles of Toxicology
Lauren M. Aleksunes and David L. Eaton
3. Mechanisms of Toxicity
Lois D. Lehman-McKeeman
4. Risk Assessment
Elaine M. Faustman

UNIT 2
DISPOSITION OF TOXICANTS
5. Absorption, Distribution, and Excretion of Toxicants
Angela L. Slitt
6. Biotransformation of Xenobiotics
Andrew Parkinson, Brian W. Ogilvie, David B. Buckley, Faraz Kazmi, and Oliver Parkinson
7. Toxicokinetics
Kannan Krishnan

UNIT 3
NON-ORGAN-DIRECTED TOXICITY
8. Chemical Carcinogenesis
James E. Klaunig and Zemin Wang
9. Genetic Toxicology
Joanna Klapacz and B. Bhaskar Gollapudi
10. Developmental Toxicology
John M. Rogers

UNIT 4
TARGET ORGAN TOXICITY
11. Toxic Responses of the Blood
Martyn T. Smith and Cliona M. McHale
12. Toxic Responses of the Immune System
Barbara L.F. Kaplan, Courtney E.W. Sulentic, Helen G. Haggerty, Michael P. Holsapple,
and Norbert E. Kaminski
13. Toxic Responses of the Liver
Robert A. Roth, Hartmut Jaeschke, and James P. Luyendyk
14. Toxic Responses of the Kidney
Rick G. Schnellmann
15. Toxic Responses of the Respiratory System
George D. Leikauf
16. Toxic Responses of the Nervous System
Virginia C. Moser, Michael Aschner, Jason R. Richardson, Aaron B. Bowman, and Rudy J.
Richardson
17. Toxic Responses of the Cornea, Retina, and Central Visual System
Donald A. Fox and William K. Boyes
18. Toxic Responses of the Heart and Vascular System
Matthew J. Campen
19. Toxic Responses of the Skin
Donald V. Belsito
20. Toxic Responses of the Endocrine System
Patricia B. Hoyer and Jodi A. Flaws
21. Toxic Responses of the Reproductive System
Paul M.D. Foster and L. Earl Gray Jr.

UNIT 5
TOXIC AGENTS
22. Toxic Effects of Pesticides
Lucio G. Costa
23. Toxic Effects of Metals
Alexander C. Ufelle and Aaron Barchowsky
24. Toxic Effects of Solvents and Vapors
James V. Bruckner, S. Satheesh Anand, and D. Alan Warren
25. Toxic Effects of Radiation and Radioactive Materials
David G. Hoel
26. Toxic Effects of Plants and Animals
John B. Watkins, III
27. Food Toxicology: Fundamental and Regulatory Aspects
Supratim Choudhuri
28. Toxic Effects of Calories
Martin J.J. Ronis, Kartik Shankar, and Thomas M. Badger
29. Nanoparticle Toxicology
David B. Warheit, Günter Oberdörster, Agnes B. Kane, Scott C. Brown, Rebecca D. Klaper,
and Robert H. Hurt

UNIT 6
ENVIRONMENTAL TOXICOLOGY
30. Ecotoxicology
Richard T. Di Giulio and Michael C. Newman
31. Air Pollution
Daniel L. Costa and Terry Gordon

UNIT 7
APPLICATIONS OF TOXICOLOGY
32. Analytical and Forensic Toxicology
Bruce A. Goldberger, Dayong Lee, and Diana G. Wilkins
33. Clinical Toxicology
Louis R. Cantilena Jr.
34. Occupational Toxicology
Peter S. Thorne
Answers to Chapter Questions
Index
Contributors

Lauren M. Aleksunes, PharmD, PhD, DABT

Associate Professor
Department of Pharmacology and Toxicology
Rutgers University
Piscataway, New Jersey
Chapter 2

S. Satheesh Anand, PhD, DABT

Manager, Safety Assessment
Life Science Research
Battelle
West Jefferson, Ohio
Chapter 24

Michael Aschner, PhD

Professor
Department of Molecular Pharmacology
Albert Einstein College of Medicine
Bronx, New York
Chapter 16

Thomas M. Badger, PhD

Professor Emeritus
Department of Pediatrics
University of Arkansas for Medical Sciences
Little Rock, Arkansas
Chapter 28

Aaron Barchowsky, PhD

Professor
Department of Environmental and Occupational Health
Graduate School of Public Health
University of Pittsburgh
Pittsburgh, Pennsylvania
Chapter 23
Donald V. Belsito, MD
Leonard C. Harber Professor
Department of Dermatology
Columbia University Medical Center
New York, New York
Chapter 19

Aaron B. Bowman, PhD

Associate Professor
Department of Pediatrics
Vanderbilt University Medical Center
Nashville, Tennessee
Chapter 16

William K. Boyes, PhD

Environmental Health Scientist
Toxicity Assessment Division/Neurotoxicology Branch
U.S. Environmental Protection Agency
Research Triangle Park, North Carolina
Chapter 17

Scott C. Brown, PhD

Principal Scientist
The Chemours Company
Wilmington, Delaware
Chapter 29

James V. Bruckner, PhD

Professor Emeritus
Department of Pharmaceutical and Biomedical Sciences
College of Pharmacy
University of Georgia
Athens, Georgia
Chapter 24

David B. Buckley, PhD, DABT

Director, DMPK
Roivant Sciences, Inc
Durham, North Carolina
Chapter 6

Matthew J. Campen, PhD, MSPH

Regent’s Professor
Department of Pharmaceutical Sciences
 College of Pharmacy
University of New Mexico
Albuquerque, New Mexico
Chapter 18

Louis R. Cantilena, Jr., MD, PhD1

Professor of Medicine and Pharmacology
Director, Division of Clinical Pharmacology and Medical Toxicology
Uniformed Services University
Bethesda, Maryland
Chapter 33

Supratim Choudhuri, PhD

Toxicologist
Division of Biotechnology and GRAS Notice Review, Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
U.S. Food and Drug Administration
College Park, Maryland
Chapter 27

Daniel L. Costa, ScD, DABT

Office of Research and Development (Emeritus)
U.S. Environmental Protection Agency
Adjunct Professor
Chapel Hill, University of North Carolina
Chapter 31

Lucio G. Costa, PhD, ATS

Department of Environmental and Occupational Health Sciences
University of Washington
Seattle, Washington
Chapter 22

Richard T. Di Giulio, PhD

Sally Kleberg Professor of Environmental Toxicology
Nicholas School of the Environment
Duke University
Durham, North Carolina
Chapter 30

David L. Eaton, PhD, DABT, ATS, NASEM

Dean and Vice Provost
University of Washington
Seattle, Washington
 Chapter 2

Elaine M. Faustman, PhD, DABT

Professor and Director
Institute for Risk Analysis and Risk Communication
Department of Environmental and Occupational Health Sciences
University of Washington
Seattle, Washington
Chapter 4

Jodi A. Flaws, PhD

Professor
Department of Comparative Biosciences
University of Illinois
Urbana, Illinois
Chapter 20

Paul M.D. Foster, PhD, ATS

Senior Scientist; Chief, Toxicology Branch
Division of the National Toxicology Program (NTP), retired
National Institute of Environmental Health Sciences (NIEHS)
Fuquay-Varina, North Carolina
Chapter 21

Donald A. Fox, PhD, ATS, ARVO Fellow

Toxicology and Pharmacology Expert
Robson Forensic
Austin, Texas
Chapter 17

Bruce A. Goldberger, PhD, F-ABFT

Chief, Director and Professor
Departments of Pathology, Immunology, and Laboratory Medicine
College of Medicine, University of Florida
Gainesville, Florida
Chapter 32

B. Bhaskar Gollapudi, PhD

Senior Managing Scientist
Health Sciences Center
Exponent, Inc.
Alexandria, Virginia
Chapter 9

Terry Gordon, PhD

 Professor
Department of Environmental Medicine
New York University School of Medicine
New York, New York
Chapter 31

L. Earl Gray, Jr., PhD

Research Biologist
Office of Research and Development
National Health and Environment Effects Research Laboratory
Reproductive Toxicology Branch
Environmental Protection Agency
Durham, North Carolina
Chapter 21

Helen G. Haggerty, PhD

Distinguished Research Fellow
Immuno and Molecular Toxicology
Drug Safety Evaluation
Bristol-Myers Squibb
New Brunswick, New Jersey
Chapter 12

Antoinette N. Hayes, MS, DABT

Lead Associate Scientist
Nonclinical Drug Safety and Bioanalytical
Alnylam Pharmaceuticals
Cambridge, Massachusetts
Chapter 1

David G. Hoel, PhD

Distinguished University Professor
Department of Public Health Sciences
Medical University of South Carolina
Charleston, South Carolina
Chapter 25

Michael P. Holsapple, PhD, ATS

Professor
Michigan State University
MPH Toxicology Consulting, LLC
East Lansing, Michigan
Chapter 12
Patricia B. Hoyer, PhD
Professor Emeritus
Department of Physiology
College of Medicine
The University of Arizona
Tucson, Arizona
Chapter 20

Robert H. Hurt, PhD

Professor of Engineering
Brown University
Providence, Rhode Island
Chapter 29

Hartmut Jaeschke, PhD, ATS

Professor and Chair
Department of Pharmacology, Toxicology, and Therapeutics
University of Kansas Medical Center
Kansas City, Kansas
Chapter 13

Norbert E. Kaminski, PhD

Professor, Pharmacology and Toxicology
Director, Institute for Integrative Toxicology
College of Human Medicine
Michigan State University
East Lansing, Michigan
Chapter 12

Agnes B. Kane, MD, PhD

Professor
Department of Pathology and Laboratory Medicine
Brown University
Providence, Rhode Island
Chapter 29

Barbara L.F. Kaplan, PhD

Assistant Professor
Center for Environmental Health Sciences
Department of Basic Sciences
College of Veterinary Medicine
Mississippi State University
Mississippi State, Mississippi
Chapter 12
Faraz Kazmi, PhD
Scientist
Pharmacokinetics, Dynamics and Metabolism
Janssen Research and Development
Spring House, Pennsylvania
Chapter 6

Joanna Klapacz, PhD

Senior Toxicologist
Toxicology and Environmental Research and Consulting
The Dow Chemical Company
Midland, Michigan
Chapter 9

Rebecca D. Klaper, PhD

Professor and Director of the Great Lakes Genomics Center
School of Freshwater Sciences
University of Wisconsin-Milwaukee
Milwaukee, Wisconsin
Chapter 29

James E. Klaunig, PhD

Professor
Department of Environmental Health
Indiana University
Bloomington, Indiana
Chapter 8

Kannan Krishnan, PhD, DABT, FATS, FCAHS

Chief Scientific Officer
Institut de recherche Robert-Sauvé en santé et en sécurité du travail
Montreal, Quebec, Canada
Chapter 7

Dayong Lee, PhD, F-ABFT

Houston Forensic Science Center
Houston, Texas
Chapter 32

Lois D. Lehman-McKeeman, PhD, ATS

Vice President
Pharmaceutical Candidate Optimization
Bristol-Myers Squibb Company
Princeton, New Jersey
 Chapter 3

George D. Leikauf, PhD

Professor
Department of Environmental and Occupational Health
Graduate School of Public Health
University of Pittsburgh
Pittsburgh, Pennsylvania
Chapter 15

James P. Luyendyk, PhD

Associate Professor
Department of Pathobiology and Diagnostic Investigation
Michigan State University
East Lansing, Michigan
Chapter 13

Cliona M. McHale, PhD

Senior Researcher
School of Public Health
University of California, Berkeley
Berkeley, California
Chapter 11

Virginia C. Moser, PhD

Retired
Division of Toxicity Assessment
National Health and Environmental Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park, North Carolina
Chapter 16

Michael C. Newman, PhD

A. Marshall Acuff, Jr. Professor of Marine Science
College of William & Mary
Virginia Institute of Marine Science
Gloucester Point, Virginia
Chapter 30

Günter Oberdörster, PhD

Professor of Toxicology
University of Rochester Medical Center
Rochester, New York
Chapter 29
Brian W. Ogilvie, PhD
Vice President of Scientific Consulting
Sekisui XenoTech, LLC
Kansas City, Kansas
Chapter 6

Andrew Parkinson, PhD

CEO
XPD Consulting
Shawnee, Kansas
Chapter 6

Oliver Parkinson, PhD

Consultant
XPD Consulting
Shawnee, Kansas
Chapter 6

Jason R. Richardson, PhD

Professor
Pharmaceutical Sciences
Northeast Ohio Medical University
Rootstown, Ohio
Chapter 16

Rudy J. Richardson, ScD

Professor of Toxicology
Environmental Health Sciences
University of Michigan
Ann Arbor, Michigan
Chapter 16

John M. Rogers, PhD

Director, Toxicity Assessment Division
National Health and Environmental Effects Research Laboratory
Office of Research and Development
United States Environmental Protection Agency
Research Triangle Park, North Carolina
Chapter 10

Martin J.J. Ronis, PhD

Professor
Department of Pharmacology and Experimental Therapeutics
Louisiana State University Health Sciences Center