Abstract
The CRC Press publication of the textbook Toxicologic Pathology: Nonclinical Safety Assessment (TP:NCSA), edited by Sahota, Hardisty, Popp, and Gopinath, filled a critical gap within the professional field when it was published in 2013. Toxicologic pathologists go through an extended “on-the-job” learning phase in industry, academia, or regulatory settings, as most residencies in anatomic/clinical pathology focus on diagnostic skills and provide little or no exposure to concepts pertaining to toxicologic pathology, drug development, and nonclinical safety assessment. As pointed out in chapters 2 and 4 of TP:NCSA, the skill set and knowledge base of a toxicologic pathologist is significantly different from that of a diagnostic pathologist and has to be developed over many years, through mentorship by experienced toxicologic pathologists, reading of a broad variety of slides from safety studies conducted in several species, and the in-depth study of the pertinent literature. The on-the-job information concerning drug development provided to pathologists starting out in the industry or academia may, therefore, vary greatly depending on the professional environment. The editors of the TP:NCSA have identified and set out to mitigate this source of variability among pathologists. They compiled a manageable, compactly sized book that provides in 21 chapters, on precisely 1,000 pages, the crucial knowledge foundation on which every pathologist, who begins working in the nonclinical safety environment, can build a career.
All four editors (Sahota, Popp, Hardisty, and Gopinath) are seasoned, renowned experts in the field of toxicologic pathology, looking back on impressive professional careers in industry and academia, with proliferative publication records and long-standing contributions to the profession in leadership functions for several influential organizations.
According to information in the book’s preface, the editors carefully considered the list of the 53 contributing authors for the book. Although the writing style varies notably between some chapters, the care that was taken to select the authors is well reflected in the quality of writing with regard to clarity and succinctness of the material presented. Most authors are globally recognized subject matter experts on the respective topic of their chapters (e.g., Principles of Clinical Pathology—Robert Hall [chapter 6]; Urinary System—Ken Frazier and John Seely [chapter 12]; and Nervous System—Mark Butt, Robert Sills, and Alys Bradley [chapter 20]). As such, these authors not only bring substantial referenceable knowledge to the chapters, but also and more importantly communicate an overarching intrinsic understanding of the subject matter that is uniquely theirs. This is what takes the book out of the “textbook category for beginning toxicologic pathologists” and places it right beside well-established reference texts such as Greaves’s Histopathology of Preclinical Toxicity Studies (Academic Press (AP), 3rd ed., 2007) and Haschek’s et al. Toxicologic Pathology (AP, 3rd ed., 2013). Overall, TP:NCSA carves a nice niche for itself with regard to both format and content in comparison with these “beloved giants.”
Compared to Greaves, TP:NCSA provides greater ease of orientation and predicts what the chapter will cover due to a “Contents” list preceding each chapter and subdivisions of the text by subheadings.
Compared to Haschek’s 3-volume set, the hard copy version of TP:NCSA is “sleek,” moving with ease from the office shelf to the microscope table and back; it also makes a perfect travel companion by fitting in any carry-on bag. The notable concession made for a manageable format of TP:NCSA is a small print font size, which makes the text more difficult to read compared to the other two reference textbooks. This is particularly noticeable with the glossy paper of the hard cover book version and less of an issue with the PDF version of TP:NCSA.
The 21 chapters of TP:NCSA are divided into two sections, I and II. Section I contains the first 8 chapters and is entitled “Concepts in Drug Development.” In this section of the book, a well-thought-out didactic approach unfolds in front of the reader's eyes, as one is presented from chapter to chapter (ranging from “Overview of Drug Development” to “Introduction to Toxicologic Pathology” to “Spontaneous Lesions in Control Animals Used in Toxicity Studies”) with reasons why preclinical safety assessments are conducted and what tools best aid these assessments. This section provides the needed orientation, context, and rationale for being effective as a toxicologic pathologist.
Section II of TP:NCSA, entitled “Organ Systems,” is comprised of the remaining 13 chapters. It addresses individual organs within the larger context of their functional units in classic pathology textbook manner. For example, in the Gastrointestinal Tract chapter (chapter 9) under subheading 9.3: “Functional Anatomy,” anatomic sites ranging from the “Oral Cavity” to “Small and Large Intestines” are discussed, but also addressed under this subheading are topics such as Biotransformation, Enterohepatic Circulation, Bacteria, Lymphoid Tissue, and the Enteric Nervous System. Most chapters of section II are exquisitely referenced with citations following almost every major statement and an extensive reference list following each chapter (e.g., Cardiovascular and Endocrine System both with reference lists of 19 and 15 pages, respectively). Furthermore, the organ-specific chapters have high-quality figures of H&E micrographic illustrations and/or tables in which key points are summarized.
As a regulatory review pathologist, I very much enjoyed the introductory chapters “Overview of Drug Development” (chapter 1) and “Nonclinical Safety Evaluation of Drugs” (chapter 2). The section on “Reporting Pathology Data for the Regulatory Scientist and Clinician” in chapter 2 is particularly relevant. Although there is some redundancy among topics addressed in the first section (especially in chapters 1, 2, and 4, e.g., length of nonclinical safety studies and phases of clinical trials), as they are presented from different angles in each chapter, repetition becomes a good thing helping the reader reiterate a fact or concept and committing it to memory. Chapter 7 provides a superb summary of the applications of toxicogenomics in drug development and how these techniques may affect the toxicologic pathologist. Of particular value to regulatory reviewers are the data tables in chapter 8, listing spontaneous lesions in Wistar rats, CD1 mice, beagle dogs, and cynomolgous monkeys for various study durations.
Encompassing both sections I and II of the book is the 30-page index, which is quite comprehensive, but some key words such as “Peer Review” did not make it as an index entry although mentioned in several chapters. Here, the PDF version superbly complements the book version, as it allows searching the text for keywords.
However, if one must choose, I still prefer the book version. The PDF version is divided into individual PDF files by chapter, which makes keyword searches more cumbersome because each PDF must be searched individually. Overall, editors and authors have produced a highly valuable reference contribution to the professional field of toxicologic pathology by marrying two conceptional sections into one book. In my opinion, this book will be essential to the veterinary toxicologic pathologist starting out in the profession as well as to the seasoned toxicologic pathologist working for years in compound development. The book is also very useful to toxicologists, pharmacologists, and regulatory reviewers who seek greater comprehensive understanding of pathology issues in nonclinical safety assessment.
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