Following the success of the first edition, this book is designed to provide practical and timely information for toxicologic pathologists working in pharmaceutical drug discovery and development. The majority of the book (Organ Systems) will provide detailed descriptions of histopathological lesions observed in drug development. In addition, it will provide information to assist the pathologist in making determinations of the origin of lesions as well as its relevance to human risk.
Toxicologic Pathology: Nonclinical Safety Assessment, Second Edition includes 2 new concept chapters. The first of the new chapters address approaches for the evaluation of unique therapeutic modalities such as cell therapies, gene therapies, and gene expression knockdown therapies. While these still represent new developing therapeutic approaches, there has been significant experience with the therapeutic modalities in the last 5 years. The second new chapter addresses the nonclinical safety assessment of medical devices, a topic of increasing importance that was not addressed in a unique chapter in the first edition. The other concept chapters have been updated and cover important topics including the overview of drug development; principles of nonclinical safety assessment; an introduction to toxicologic pathology; techniques used in toxicologic pathology, clinical pathology, toxicokinetics, and drug development toxicogenomics; and spontaneous lesions.
The 13 organ system chapters provide the specifics related to pathologic characteristics, differential diagnosis, and interpretation of toxic responses in each organ system. These chapters are specifically important for the bench pathologist but also for the toxicologist who interacts with pathologists and function as study toxicologists and project team representatives in the drug development arena.
Table of Contents:
Preface
Acknowledgments
Editors
Contributors
Section I Concepts in Drug Development
Chapter 1 Overview of Drug Development
James A. Popp and Jeffery A. Engelhardt
Chapter 2 Nonclinical Safety Evaluation of Drugs
Thomas M. Monticello and Jeanine L. Bussiere
Chapter 3 Nonclinical Safety Evaluation of Advanced Therapies
Timothy K. MacLachlan, Kendall S. Frazier, and Mercedes Serabian
Chapter 4 Nonclinical Safety Evaluation of Medical Devices
Kathleen A. Funk, Victoria A. Hampshire, and JoAnn C. L. Schuh
Chapter 5 Pathology and the Pathologist in Pharmaceutical Research and Development
Page R. Bouchard, Christopher J. Clarke, and Dominique Brees
Chapter 6 Routine and Special Techniques in Toxicologic Pathology
Daniel J. Patrick, Matthew L. Renninger, and Peter C. Mann
Chapter 7 Principles of Clinical Pathology
Niraj K. Tripathi and Jacqueline M. Tarrant
Chapter 8 Toxicokinetics and Drug Disposition
David D. Christ
Chapter 9 Toxicogenomics in Toxicologic Pathology
Arun R. Pandiri, David E. Malarkey, and Mark J. Hoenerhoff
Chapter 10 Spontaneous Lesions in Control Animals Used in Toxicity Studies
Robert C. Johnson, Robert H. Spaet, Gitte Jeppesen, Ursula Junker, and Robert Stull
Section II Organ Systems
Chapter 11 Gastrointestinal Tract
Judit E. Markovits, Graham R. Betton, Donald N. McMartin, and Theresa Boulineau
Chapter 12 Liver, Gallbladder, and Exocrine Pancreas
Russell C. Cattley, James A. Popp, and Steven L. Vonderfecht
Chapter 13 Respiratory System
Tom P. McKevitt and David J. Lewis
Chapter 14 Urinary System
Kendall S. Frazier and John Curtis Seely
Chapter 15 Hematopoietic System
Kristin Henson, Tanasa Osborne, and Gregory S. Travlos
Chapter 16 The Lymphoid System
Patrick J. Haley
Chapter 17 Bone, Muscle, and Tooth
John L. Vahle, Joel R. Leininger, Philip H. Long, D. Greg Hall, and Heinrich Ernst
Chapter 18 The Cardiovascular System
Calvert Louden, David Brott, Chidozie J. Amuzie, Bindu Bennet, and Ronnie Chamanza
Chapter 19 Endocrine Glands
Richard A. Peterson, Sundeep Chandra, and Mark J. Hoenerhoff
Chapter 20 Reproductive System and Mammary Gland
Justin D. Vidal, Charles E. Wood, Karyn Colman, Katharine M. Whitney, and Dianne M. Creasy
Chapter 21 Skin
Zbigniew W. Wojcinski, Lydia Andrews-Jones, Daher Ibrahim Aibo, Rie Kikkawa, and Robert Dunstan
Chapter 22 Nervous System
Mark T. Butt, Alys Bradley, and Robert Sills
Chapter 23 Special Senses: Eye and Ear
Kenneth A. Schafer, Oliver C. Turner, and Richard A. Altschuler
Index
