Organ-Specific Toxicologic Pathology:an Introduction

Matthew A. Wallig1, Wanda M. Haschek1, Colin G. Rousseaux21University of Illinois at Urbana Champaign, Urbana, IL, USA, 2University of Ottawa, Ottawa, Ontario, Canada

This third volume of Haschek and Rousseaux’sHandbook of Toxicologic Pathology (3rd edition),entitled Systems Toxicologic Pathology, containsorgan-specific toxicologic pathology addressingthe pathology of cells, tissues, and organs withinthe respiratory system, integument, digestivesystem, liver, pancreas, kidney, lower urinarytract, cardiovascular system, bones and joints,eyes, immune system, hematopoietic system,endocrine system, male and female reproductivesystems, and embryo and fetus after exposure toxenobiotics including toxicants and bio-pharmaceutical compounds. In this edition, wehave added new chapters addressing the earand the mammary gland.

The first volume, Practice of ToxicologicPathology, contains a detailed introduction to thefield of toxicologic pathology, including funda-mental concepts, descriptions of basic methodol-ogies used in toxicologic pathology, and coreissues involved in the practice of general toxico-logic pathology. The second volume, SafetyAssessment Including Current and Emerging Issuesin Toxicologic Pathology, includes topics morespecific to the toxicologic pathologist in industry,including the following: drug development(Overview of Drug Development, Chapter 21;Discovery Toxicology and Pathology, Chapter 23);safety and risk assessment (Pathology in Non-Clin-ical Drug Safety Assessment, Chapter 24; Carcinoge-nicity Assessment, Chapter 27; Risk Assessment,Chapter 31), the reporting of data (Preparation ofthe Pathology Report for a Toxicology Study, Chapter28; Interpretation of Clinical Pathology Results inNon-Clinical Toxicology Testing, Chapter 29; Risk

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Communication for Toxicologic Pathologists, Chapter32), and many other related issues. Also coveredin this volume are specific topics orientedaround etiology, such as food and nutritionaltoxicologic pathology (Food and ToxicologicPathology: An Overview, Chapter 35; NutritionalToxicologic Pathology, Chapter 36); phycotoxins(Phycotoxins, Chapter 38), mycotoxins (Myco-toxins, Chapter 39), and poisonous plants (SelectedPoisonous Plants Affecting Animal and HumanHealth, Chapter 40); and physical agents such asbiomedical devices (Biomedical Materials andDevices, Chapter 26), nanoparticles (Nanoparticu-lates, Chapter 43) and radiation (Radiation andOther Physical Agents, Chapter 44).

A brief description of the field of toxicologicpathology is included before describing howbest to approach the information held in thisvolume.

Pathology can be defined as the study ofmolecular, cellular and organ responses of theliving organism when exposed to injurious agentsor deprived of essential substances. Pathologicresponses represent a spectrum of primarychanges ranging from adaptation to cell deathto malignant transformation; secondary changessuch as inflammation, fibrosis and neoplasia;and clinical alterations in tissue fluids such asplasma. In the field of toxicologic pathologythe response of the organism to toxic injury isaffected by many factors, including organreserve capacity. However, when the responseto injurious agents or deprivations is deleteriousto the organism, we recognize these responses asdisease.

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ORGAN-SPECIFIC TOXICOLOGIC PATHOLOGY: AN INTRODUCTION1508

Toxicologic pathology combines the disciplinesof pathology and toxicology and also draws frommany related biomedical fields. The field of toxi-cologic pathology requires knowledge of bothpathology and toxicology, so that integration ofmorphological and functional changes can beevaluated with respect to their biological signifi-cance following exposure to a xenobiotic. This isparticularly true in the assessment of the safety,efficacy, and quality of chemicals for human use.Similarly, the effects of unexpected encounterswith xenobiotics necessitate description of thestructural and functional adverse effects causedby these compounds so as to enable predictionof risk for adverse effects following unintentionalexposure. Understanding the underlying biologyof toxicant-induced disease at the structural,biochemical, and molecular levels is vital for pre-dicting low-dose extrapolations of disease poten-tial. Therefore, a considerable amount of researchhas gone not only into describing and delineatingxenobiotic-induced lesions, but also into devel-oping tissue-specific methods for detectingdisease in affected tissues and organs. This isreflected in the expanded sections in each of thechapters of this volume on tissue-specific evalua-tion of toxicity, including biomarkers, immuno-histochemistry, in vitro techniques, and animalmodels (see below).

Volume III has been designed to enable readyaccess to current information concerning toxico-logic pathology of specific organ systems. Eachchapter has been organized into four mainsections: (1) basic structure/function and cell

III. SYSTEMS TOXICO

biology; (2) evaluation of toxicity; (3) responseto injury; and (4) mechanisms of toxicity. Thisformat ensures that each organ, or system, isaddressed in the same manner, allowing thereader to use this volume in part or whole as heor she wishes. For example, if the reader is inter-ested in studying the mechanisms of toxicity fora number of organ systems, then reading thatparticular section in each of the relevant chaptersshould reveal the desired information. Theupdated chapters in this volume each have anexpanded section on evaluation of toxicity,including tissue-specific biomarkers where rele-vant. Furthermore, important “background”lesions in each system are discussed in order toprovide essential information regarding the chal-lenge of determining true xenobiotic-inducedlesions from non-toxicological lesions unique tothe strain or species of animal. In addition, theinformation in each systems chapter has beenupdated to reflect current concepts – for example,in the digestive system chapter (Digestive Tract,Chapter 56), new information about the impactof microbiota in the intestine and its impact ondisease is presented. Also included arenumerous color images that supplement orreplace the black and white images from thesecond edition. All chapters have been peer-reviewed by one or more knowledgeable editors.As in the previous edition, we have includeda reading list at the end of each chapter, consist-ing of books, reviews and pertinent articles thatsupplement or expand the information pre-sented in the chapter itself.

LOGIC PATHOLOGY