Pathology for Toxicologists

Non-pathologists, such as toxicologists and study personnel, can find it difficult to understand the data they receive from pathologists. Toxicological pathologists write long, detailed and highly technical reports. Study personnel are under daily pressure to decide whether lesions described in pathology reports are treatment-related and thus important to the pharmaceutical company or whether the lesions are background changes and thus of little significance.

Written by experienced toxicological pathologists, Pathology for Toxicologists: Principles and Practices of Laboratory Animal Pathology for Study Personnel serves to bridge the gap in the understanding of pathology data, enabling non-pathologists to more easily comprehend pathology reports, better integrate pathology data into final study reports and ask pathologists relevant questions about the test compound.

This succinct, fully referenced, full colour book is suitable for toxicologists at all stages of their training or career who want to know more about the pathology encountered in laboratory animals used in safety studies. Key features include important chapters on spontaneous and target organ lesions in rats, mice, non-human primates, mini pigs, rabbits and beagle dogs as well as information on general pathology, macroscopic target organ lesions, ancillary pathology techniques, haematology, biochemistry and adversity.

Pathology for Toxicologists: Principles and Practices of Laboratory Animal Pathology for Study Personnel includes:

• Colour diagrams explaining how lesions are caused by either external compounds or spontaneously

• The anatomic variations and background lesions of laboratory animals

• Advice on sampling tissues, necropsy, ancillary pathology techniques and recording data

• A chapter on the haematology and biochemistry of laboratory animals

• Full colour photographs of common macroscopic lesions encountered in laboratory animals

• A comprehensive glossary

Auteur

About the Editor

Elizabeth McInnes edited the successful "Background Lesions in Laboratory Animals, A Color Atlas" (2011) and has published widely on various aspects of toxicological pathology. She qualified as a veterinary surgeon in South Africa in 1988 and completed a PhD at Imperial College, London in 1996. She was awarded Fellowships of the Royal College of Pathologists in 1997 and of the International Academy of Toxicologic Pathology in 2011. She currently runs her own toxicological pathology consultancy business.

Contenu

List of Contributors xi

Preface xiii

1 An Introduction to Pathology Techniques 1
Elizabeth McInnes

1.1 Animal Considerations 2

1.2 Necropsy 2

1.3 Lung Inflation with Fixative 5

1.4 Fixation 5

1.5 Making Glass Slides 6

1.5.1 Trimming 6

1.5.2 Tissue Processing 9

1.5.3 Embedding 9

1.5.4 Microtoming 9

1.5.5 Staining 9

1.5.6 Quality Control 11

1.6 Special Histochemical Stains 12

1.7 Decalcification 13

1.8 Immunohistochemistry 13

1.9 Tissue Crossreactivity Studies 15

1.10 Electron Microscopy 15

1.11 In Situ Hybridisation 16

1.12 Laser Capture Microscopy 16

1.13 Confocal Microscopy 16

1.14 Image Analysis 17

1.15 Digital Imaging 17

1.16 Spermatocyte Analysis 17

1.17 Good Laboratory Practice 17

1.18 Inhalation Studies 18

1.19 Continuous?]Infusion Studies 18

1.20 Carcinogenicity 19

1.21 Biologicals 19

1.22 The Pathology Report 20

1.23 Conclusion 20

References 20

2 Recording Pathology Data 23
Cheryl L. Scudamore

2.1 What is a Pathology Finding? 24

2.2 Standardisation of Pathology Findings 24

2.2.1 Semiquantitative Analysis 24

2.2.2 Nomenclature/Controlled Terminology 26

2.2.3 Ontological Approach 28

2.3 'Inconsistencies' in Pathology Recording 28

2.3.1 Diagnostic Drift 28

2.3.2 Thresholds 28

2.3.3 Lumping versus Splitting 29

2.4 Blind Review 30

2.5 Historical Control Data: Pros and Cons 30

2.6 The Use of Peer Review in Pathology 32

References 32

3 General Pathology and the Terminology of Basic Pathology 35
Elizabeth McInnes

3.1 Cellular Responses to Insults 35

3.2 Inflammation 41

3.3 Circulatory Disturbances 46

3.4 Disorders of Tissue Growth 52

3.5 Tissue Repair and Healing 53

3.6 Neoplasia 54

3.7 Immune System 55

References 57

4 Common Spontaneous and Background Lesions in Laboratory Animals 59
Elizabeth McInnes

4.1 Rats 62

4.2 Mice 63

4.3 Dogs 66

4.4 Minipigs 66

4.5 Non?]Human Primates 67

4.6 Rabbits 67

4.7 Experimental Procedures 67

4.8 Causes of Death in Rats and Mice 67

4.9 Conclusion 68

References 69

5 Target Organ Pathology 72
Elizabeth McInnes

5.1 Skin 72

5.2 Eye 76

5.3 Gastrointestinal Tract 78

5.4 Liver 83

5.5 Respiratory System 85

5.6 Urinary System 89

5.7 Lymphoreticular System 94

5.8 Musculoskeletal System 95

5.9 Cardiovascular System 97

5.10 Endocrine System 99

5.11 Reproductive System 102

5.12 Central and Peripheral Nervous System 104

5.13 Ear 106

References 106

6 Clinical Pathology 112
Barbara von Beust

6.1 Clinical Pathology in Study Phases and Good Laboratory Practice 112

6.1.1 Preanalytic Phase: Study Plan 113

6.1.2 Analytic Phase: Data Generation 114

6.1.3 Postanalytic Phase: Data Interpretation and Reporting 114

6.1.4 Good Laboratory Practice 114

6.2 What is Measured in Clinical Pathology? 115

6.2.1 Interference by Haemolysis, Lipaemia and Icterus 116

6.3 Haematology 117

6.3.1 Manual and Automated Techniques in Haematology 118

6.3.2 Haematocrit and Red Blood Cell Mass 119

6.3.3 Blood Cells 120

6.3.4 The Standard Haematology Profile 124 ...