Elizabeth McInnes - Pathology for Toxicologists: Principles and Practices of Laboratory Animal Pathology for Study Personnel

This edition first published 2017 2017 John Wiley & Sons Ltd

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1. Elizabeth McInnes
2. Cerberus Sciences
   Thebarton, SA
   Australia

1. Natasha Neef
2. Vertex Pharmaceuticals
   Boston, MA
   USA

1. Cheryl L. Scudamore
2. MRC Harwell, Harwell Science and Innovation Campus
   Oxfordshire
   UK

1. Bhanu Singh
2. Discovery Sciences
   Janssen Research & Development
   Spring House, PA
   USA

1. Barbara von Beust
2. Independent consultant
   Winterthur
   Switzerland

Seemingly minor differences in opinion between the study pathologist and the study director or vice president of safety assessment (positions often filled by toxicologists) can escalate to cause real problems with the development of a test article in the pharmaceutical and agrochemical industries. Pathology is an imprecise science that relies on the observation of subtle variations in patterns of cellular arrangement and the tinctorial affinity of certain cells for staining procedures. Non-pathologists, such as toxicologists, can find it difficult to understand the data they receive from pathologists, partly due to the subjectivity of the discipline and the variations between pathologists, and partly due to the terminology that pathologists use.

There is a lack of pathological texts aimed at study personnel. This book has been written for toxicologists at all stages of their training or career who want to know more about the pathology encountered in laboratory animals, including study directors, study monitors, undergraduate and postgraduate toxicology students, toxicology report reviewers and research scientists employed in the pharmaceutical industry. The aim is to help study personnel bridge the gap in the understanding of pathology data. The book will enable them to understand the pathology reports they receive and the common pathologies encountered, so that they can more easily integrate pathology data into their final study report and ask pathologists relevant questions where there are gaps in understanding.

We have attempted to make the book user-friendly and easy to understand. Important lesions in rats, mice, non-human primates, mini pigs and beagle dogs, the most common laboratory animals used in the industry, are discussed. The compound-induced pathology in all the major organ systems is covered, as are clinical pathology, adversity and the limitations of pathology. There is also a glossary, which should help all non-pathologists understand the language of toxicological pathology. The aim is to demystify such terms as chronic focal hepatic hypertrophy with Ito cell tumor.

This book is intended to give study personnel an insight into the uncertainties encountered by the pathologist when reading studies and to provide them with explanations for why pathologists cannot always make up their minds. We trust it will improve communication and understanding between pathologists, toxicologists and study directors, so that a more succinct and helpful toxicologist report can be written.

Elizabeth McInnes

Elizabeth McInnes

Cerberus Sciences, Thebarton, SA, Australia

• Understand the role of study personnel in necropsies.
• Understand the various steps involved in producing glass slides from harvested tissues.
• Understand the ancillary techniques used in toxicological pathology.
• Discover what carcinogenicity, inhalation and crossreactivity studies entail.

This book is aimed at all study personnel including study monitors, study directors and toxicologists who are exposed to pathology reports, necropsies, peer review, haematology and biochemistry results and adversity on a regular basis. The secret to an informative, relevant and useful pathology report is an open and collegial relationship between the study director and the study pathologist (Keane, 2014). This chapter aims to describe the various stages of the pathological process (e.g. necropsy, fixation of tissues, cutting of slides) in order to demonstrate where crucial errors which can cause problems at a later stage, may arise. In addition, it includes a brief overview of ancillary techniques that pathologists sometimes use (e.g. electron microscopy). Finally, it discusses carcinogenicity studies, digital pathology, biological drugs and crossreactivity studies, and their impact on study personnel. Throughout the chapter, the client is referred to as the sponsor of a particular pharmaceutical study.

Pathology is the study of disease, particularly the structural and functional changes in tissues and organs. Toxicological pathology is concerned predominantly with cell and tissue injury in animals treated with introduced chemical compounds or biological drugs. Studies are regulated by international bodies such as the Organisation for Economic Co-operation and Development (OECD), the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Animal testing to determine the safety of pharmaceuticals, medical devices and food/colour additives is required by the FDA before it will give approval to begin clinical trials in humans. Pathology data may be quantitative (haematology, chemistry data, organ weights) or qualitative (microscopic diagnoses), and the toxicological pathology report is divided into macroscopic and microscopic findings. Study personnel are ultimately responsible for the study report, including the pathology report and data. Thus, study personnel need to understand what the pathology report means and how it has been generated. This chapter aims to help the study director understand the processes involved in a study, from harvesting tissues from the animal to generating glass slides to producing a pathology report.