Book Review: The Illustrated Dictionary of Toxicologic Pathology and Safety Science

The work of the toxicologic pathologist is intimately embedded in all aspects of toxicology. Pathology issues pertaining to the development of drugs or other xenobiotics are inherently complex in nature, particularly when they result in submissions to regulatory agencies. To be effective, all scientists involved in compound development need to quickly become familiar with histopathological and toxicological frameworks in order to ensure timeline-considerate progression along the regulatory process. Therefore, being current on histopathological terminology as it applies to toxicological principals in drug or compound development and able to broadly apply these terms are essential to any scientist working in nonclinical safety. In this regard, the Illustrated Dictionary of Toxicologic Pathology and Safety Science (IDTP), edited by Sahota, Spaet, Bentley, and Wojcinski, is particularly timely, as both scientific fields—compound developmental toxicology and toxicologic pathology—are rapidly changing to accommodate the scientific demands of the 21st century. Overall, the IDTP highlights a vital point, namely, that both disciplines must communicate clearly to be understood and thereby work effectively together.

Prior to reviewing this book, with an almost 30-year career in toxicologic pathology, I had concluded that textbook information pertaining to toxicology and toxicologic pathology could only be presented in so many ways. But with the publication of the IDTP by CRC Press in 2019, Sahota proved this notion wrong. He recruited outstanding names in the field to be his coeditors and over 70 subject matter experts to author respective sections of the book. On top of this, he assembled an advisory group of 6 globally renowned experts in the field of toxicologic pathology to create a book that is unusual, interesting, intriguing, creative, and brave in many ways.

The book, priced at approximately $230, measures 11.5 × 8.5 × 1.5 inches, and weighs about 0.5 pounds, which translates to a quite sizable but manageable format, where the book can still be held comfortably in 1 hand while turning the pages. Contributing to my delight in reviewing this book is the fact that the 671 pages are printed on nonglossy paper which reduces light reflection and is, therefore, much easier on the eye. As this book is as much an atlas as it is a dictionary, containing over 800 images, one could argue that glossy paper would be a must to achieve optimal image quality. The generously sized images (most are reading column width of 3.5 × 2.2 inches or larger) are, however, of superb color balance and crispness throughout the text. One drawback of the images is, though, that about half of them do not contain arrows or intraimage labels to point the viewer to the actual change depicted in the image. This is not an issue for the pathologist reader but defeats, in most cases, the point of the illustration for any nonpathologist. The IDTP is also available in pdf version as one continuous file, which makes key word searching effortless.

The content of the book is divided into general introductory information in the Preface, Acknowledgments, Editors, Contributors and the Advisory Group section and the book’s main sections consisting of

The Illustrated Dictionary section (pp. 1-392) with 3 appendices:

Appendix 1 (pp. 393-427) presents an Overview of Drug Development, Nonclinical Safety & Toxicologic Pathology and Important/Special Topics.

Appendix 2 (pp. 429-583) is entitled Diagnostic Criteria of Proliferative Lesions in Rodents (Rats and Mouse) and selected Non-Rodent Laboratory Species.

Appendix 3 consists of a Mini-Atlas of Organ system Anatomy and Histology

The book also contains a Further Reading by Organ System section (pp. 619-625), a Figure Acknowledgements section (pp. 627-646), and an Index section (pp. 647-671).

As the title of the IDTP indicates, the main Dictionary section (about 3/4) of the book is written in an alphabetic dictionary format with illustrating images of selected rodent and nonrodent terms. Pretty much every page contains at least 1 image, table, or diagram but often more. In the Preface, the editors mention that the Dictionary section entails about 70% of toxicologic pathology terms and about 30% of nonpathology terms. When randomly picking a page number, for example, page 173 under the letter I, one finds the terms IARC, iatrogenic, IC50, ICH, ICSH, idiosyncratic drug reaction, immature, and immune-mediated hemolytic anemia. While acknowledging the herculean task the editors and authors of the IDTP engaged in, the scientific rigor of this book would improve even more if the inclusion and exclusion criteria that determined the terms selected for the Dictionary section were disclosed to the reader. Without this information, the reader is literally surprised by what terms they find under the respective alphabetic letters, as obviously not all possible terms can be included in a book of manageable size.

Authored by Burkhardt et al, Appendix 1 of the IDTP integrates the work of the toxicologic pathologist into the larger context of its application, the drug development and safety assessment arena. The authors succinctly describe and summarize the essence of toxicologic pathology, as it relates to the regulatory process of drug development, touching on the regulatory phases of drug development, the role of the toxicologic pathologist, pathology raw data, and why it is different from other GLP data, peer review, adversity, alternative animal models, regulatory guidance, digital pathology, CROs, vaccines, biologics, and gene therapy products. I recommend this section in and of itself to everyone starting a career in any area of the nonclinical safety sciences, including toxicologic pathologists coming out of graduate training, toxicologists entering into drug development as study directors or GLP principal investigators as well as scientists of regulatory agencies. Even for the more seasoned professional reader from any of these backgrounds, the information entailed in Appendix 1 is well worth one’s time.

The editors of the IDTP were quite creative with the incorporation of Appendix 2, as the idea of utilizing the INHAND nomenclature (https://www.toxpath.org/inhand.asp#pubg) in a text book has, to my knowledge, not been done before and shows great ingenuity. I see this section as advocacy for a better understanding by the nonpathologist of what the toxicological pathologist has to say through use of globally harmonized terminology. This is something regulatory reviewers would like to see more of in regulatory submissions—all toxicological pathologists using agreed upon, harmonized terminology for the same changes, especially in time progressive studies with the same test article. I wonder, though, why this information was not integrated into the Dictionary section, as the approach taken by the editors results in quite a bit of redundant information as well as the need to flip back and forth between the various sections (eg, see Zymbal’s gland hyperplasia p. 392 Dictionary section and p. 573 Appendix 2).

A very succinct but overall informative summary on key anatomical and histological features of the following organ systems is provided in form of a Mini-Atlas in Appendix 3:

Bone, Muscle and Tooth

Cardiovascular system

Endocrine Glands

Gastrointestinal tract

Hematopoietic system

Nervous system

Reproductive system and Mammary gland

Respiratory system

Skin

Special Senses

Urinary System

Several of these sections (e.g. Urinary System) only contain a few representative H&E photos or diagrams with short figure legends but no explanatory text. These sections are in my opinion of limited use, as the nonpathologist would need much more information for a basic understanding of the interactive tissue components that govern these organ systems, while the toxicologic pathologists of the presumed readership of this book are already familiar with normal tissue architecture. The true gems that make Appendix 3 more than worthwhile are those organs system sections that have not only histological photos of the key micro-anatomic contributors but also entail explanatory text that provides structure and orientation as to how the tissue system functions in toto. Particularly useful here are comparisons pertaining to species differences and extrapolations to humans. For example, the Special Senses section (p. 617) points out that although the chinchilla is an uncommon laboratory animal, it is commonly used in otic research because its ear shares an audiogram range and anatomy that is similar to humans. Specifically, because chinchillas have a semi-open eustachian tube, they are a useful model for pediatric otitis media.

The book is unique in many ways pertaining to format and content, as it might pass for the offspring from “the marriage” of the 2 classic toxicologic pathology atlases (by McInnes Background Lesions in Laboratory Animals: A Color Atlas, 2012, ¹ and Gopinath and Mowat’s recently updated Atlas of Toxicological Pathology, 2014 ² ) to 2 familar texts in toxicology and regulator toxicology (by Hodgson, Mailman and Chambers Dictionary of Toxicology, 2015, ³ and Gad’s Regulatory Toxicology, 2019 ⁴ ). Not surprisingly, many of these editors/authors are shown to have contributed in some function to the conception of the IDTP.

In summary, contrary to what one would assume from the book’s title, this isn’t “just” a dictionary illustrating toxicologic pathology findings. In its entirety, this book’s message highlights for the reader the depth to which toxicologic pathology is integrated into the scientific content of drug/compound development and regulatory safety evaluations. This book brings toxicologic pathology to life by literally illustrating its integral embedment into the toxicological safety sciences. This book is, therefore, not only useful to toxicologic pathologists who want to quickly brush up on the definition of a diagnostic term but also invites the entirety of the toxicology profession to understand and utilize toxicologic pathology to achieve greater efficiency in their specific area of drug or compound development and safety assessment.