Toxicologic Pathology A Primer

There has been an enormous growth of interest in the field of toxicologic pathology and particularly on its impact on nonclinical safety assessment in global drug development and in the environment. Toxicologic pathologists play an important role in detecting test article-related adverse effects by characterizing morphologic changes in animal tissues and/or body fluids under prescribed study conditions or less clearly defined conditions in the environment and in the interpretation of these findings relative to human risk. In fact, pathology evaluation is often the single most important decision-making factor in nonclinical safety assessments as 80% of drug candidate attrition has been attributed to pathology findings in toxicity studies. There are currently no primers or basic overviews covering the field of toxicologic pathology, whereas there are at least several basic books that cover the sister field of toxicology.

Toxicologic Pathology: A Primer is a practical, easy-to-use reference designed to contain core information provided by board-certified veterinary pathologists, all experts in the field. The Primer contains the basic, underlying principles of toxicologic pathology at the introductory level; thus it will be valuable to the veterinary pathology student who may be considering a career in the field as well as a companion to the seasoned toxicologic pathologist who wants a succinct refresher. The Primer is arranged as chapters presenting each major organ system preceded by an overview chapter covering the field of toxicologic pathology followed by a ?concept? chapter describing the role of toxicologic pathology in drug development. Photomicrographs and illustrations provide visual context.

The organ system chapters provide histopathologic descriptions of lesions observed in toxicity studies of test articles in drug development and testing of chemicals that may negatively impact the environment. Each organ system chapter provides additional information related to a particular lesion to aid the reader in better understanding its toxicologic significance relative to human risk.

Each organ system chapter contains:

• A brief introduction
• A succinct description of the anatomy and physiology of the system
• Descriptions of the most important pathological lesions
• Differential diagnoses
• Biological consequences, pathogenesis, and/or mechanism of lesion formation
• Associated clinical pathology correlates

Nonclinical safety scientists such as study directors, non-pathology-oriented contributing scientists such as senior toxicology report reviewers, scientific management of Contract Research Organizations (CROs), and students should find the Primer useful in helping them understand the fundamentals of toxicologic pathology.

1. Introduction to Toxicologic Pathology

Robert R. Maronpot and Abraham Nyska

2. Overviews of Drug Development and Nonclinical Safety; Interactions with Toxicologic Pathologist; Regulatory Aspects

Jim Fikes, John Kapeghian and Zbigniew W. Wojcinski

3. Gastrointestinal System

Thomas Nolte and Judit E. Markovits

4. Liver, Gallbladder and Exocrine Pancreas

Russell C. Cattley, James A. Popp, and Steven L. Vonderfecht

5. Respiratory System

Tom McKevitt

6. Urinary System

Kendall S. Frazier and John Curtis Seely

7. Hematopoietic System

Stephan Schmidtbauer and Hans Harleman

8. The Lymphoid System

Steven Laing

9. Bone, Muscle, and Tooth

Matthias Rinke and Christine Ruehl-Fehlert

10. Cardiovascular System

Roger H. Alison and Vasanthi Mowat

11. Endocrine System

Thomas J. Rosol

12. Male Reproductive System

Catherine Picut and Quinci Plumlee

13. Female Reproductive System & Mammary Gland

Daniel G. Rudmann

14. Integumentary System

Maurice Cary, Kelly Diegel and Lars Mecklenburg

15. Nervous System

Ian Taylor, Ingrid D. Pardo and Alok K. Sharma

16. Special Senses

JoAnn J. L. Schuh

Dr. Pritam S Sahota studied for his Veterinary Medicine (BVSc) and Veterinary Pathology (MVSc and PhD) degrees at Punjab Agricultural University in India (1976). He is a Diplomate of the American Board of Toxicology. After completing his PhD, he immigrated to the USA in 1976 and worked for Dawson Research Corporation in Orlando, Florida for 10 years (1976-86) with increasing responsibilities as Toxicologic Pathologist, Senior Toxicologic Pathologist, and Scientific Director. While working briefly for Dynamac Corporation in Research Triangle Park, NC (1986-87), Dr. Sahota conducted retrospective scientific audits on 23 NTP carcinogenicity studies and participated in discussions with the representatives of NTP, FDA and EPA to summarize the results of scientific audits of approximately 200 carcinogenicity studies. In 1987, Dr. Sahota joined Ciba-Geigy Pharmaceuticals in Summit, NJ as Head/Manager of Pathologists and helped establish Pathology Peer Review, Scheduling and Quality Control systems. He continued to work primarily in this position with increasing responsibilities in Ciba-Geigy and then Novartis Pharmaceuticals (resulting from Ciba/Sandoz merger in 1997) up to 2000, when he became Head of Pathology (Director→ Executive Director: 2000-12, East Hanover, NJ). In addition to his pathology responsibilities, Dr. Sahota also served as International Project Team Representative for several marketed drugs including an antihypertensive blockbuster, Diovan, where he successfully defended company position with the FDA and various International Regulatory Authorities. During 2010-12, he successfully led following Global Preclinical Safety initiatives at Novartis: Patient Centricity, Cardiotoxicity, Ocular Toxicity, and evaluation of rodent carcinogenicity potential based on short-term toxicity and genotoxicity studies to minimize delays in regulatory submissions. Dr. Sahota also held an adjunct academic appointment of Assistant Professor in the University of Med