The first edition of this book arose out of my perception that there is a large amount of toxicology lore that is widely accepted as fact and used in toxicological reports, but is not supported by easily accessible references. I also felt that there was a need for a practical, user-friendly introductory text for those coming to toxicology from related fields or professions, and who need some insight into how toxicity studies and investigations are carried out. I thought that the book should be informative but readable and should also act as a gateway to the subject, indicating where further information can be found, including the use of websites for literature searches and other areas, such as regulations and guidelines.
The book is set out as a guide on how to evaluate toxicity and then how to handle and use the data that are generated. After an introduction to the concepts of toxicology, the book takes the reader through the processes of toxicity testing and interpretation before looking at the concepts of hazard prediction and risk assessment and management. Two final chapters look at the evaluation of different chemical classes and at the future of toxicity testing and risk assessment. The audience for this book includes, new graduates starting careers in toxicology, those coming to the subject from different fields, and specialists in particular areas of toxicology who need some background on the other areas.
It is inevitable that as soon as a book hits the shelves (or screens), it will go out-of-date and the pressures of wanting to be up-to-date must be balanced against those to finish the manuscript on time. Suffice it to say that I was aware that the first edition lacked some areas that needed to be addressed, such as safety pharmacology, and would certainly need to be updated if ever a second edition became necessary. Accordingly, this new edition includes two entirely new chapters, one on safety pharmacology and one on the evaluation of different chemical classes. The chapter on alternatives has been completely rewritten and all the others have been reviewed and revised to a greater or lesser extent. The glossary has been expanded slightly and the index has been improved.
I acknowledge that there was some bias toward pharmaceuticals in the first edition in the treatment of the various subject areas. As I am largely a pharmaceutical toxicologist, this bias is still present to some extent; but I have attempted to write the book such that toxicologists in all areas of chemical evaluation may benefit from it. The basic principles of toxicology are common to all areas, whether you are evaluating pharmaceuticals or industrial chemicals. The main differences are in the regulatory guidelines addressed and in the philosophy required in each area; these differences are addressed in the new chapter on different chemical classes.
Throughout the book, words like “may,” “could,” and “however” appear frequently; this is tacit recognition that there are few certainties in life beyond the single gold standard that wherever a statement is made there will be someone to disagree with it. As with any walk of life, if a situation is seen as black and white, it simply means that the intervening shades of grey have not been discovered or are not understood. This is particularly true for any aspect or judgment or interpretation; differing opinions between toxicologists, especially toxicological pathologists, can be extremely frustrating for anyone needing a definitive answer to a question of safety. Getting a decision wrong in toxicology can be associated with far reaching adverse effects and with consequent litigation or (politically far worse) loss of votes. For this reason, toxicologists (especially those in regulatory agencies) tend to be conservative in their opinions; this is not necessarily a bad thing. However, conservatism is made more likely by poor, incomplete, or poorly understood data or results, which may lead to imposition of inappropriately restrictive exposure limits.
As I said in the preface to the first edition, the vastness of the subject means that this book cannot hope to be detailed or complete, for reasons of brevity and time. In view of this, the intention is to provide a basis of knowledge—a series of pointers—which can be expanded through use of the bibliography and references given. There are many different ways of achieving an objective in toxicological study and evaluation, and this book cannot pretend to address them all or to be absolutely definitive in any one area. Toxicologists are known for their differences in opinions and I am (still) just another opinionated toxicologist.
Toxicology is a dynamic subject with unique relevance to the public and, as a result, places heavy responsibility on the people who practice it, those who register or accredit toxicologists, and those who regulate or manage it. The future of toxicology is assured; the means of its future investigation is changing and it behoves us to think about what we are doing or what we are asking toxicologists to do (or, more importantly, not to do). As toxicologists, we should do nothing without thought, without considering the impact of our actions on the animals we use, on the public, or a host of other stakeholders. In many ways, if I cause the reader to think more about toxicology and its importance and impact on this world, I will have achieved one of my unwritten objectives.
- The Author -
Contents
1. Introduction to Toxicology: The Necessity of Measurement
1. Introduction to Toxicology: The Necessity of Measurement
- Introduction
- The Beginnings of Toxicological Measurement
- Toxicology and Toxicity Defined
- It is Natural So It Must be Safe - Everyday Toxicological Conundrums
- Natural Medicines and Poisons
- General Objectives of Toxicological Study
- Nature and Outcome of Toxic Reactions
- Cellular Basis and Consequences of Toxic Change
- Expression of Toxicity
- Target Organ Expression of Toxicity
- The Necessity for Toxicological Assessment
- Ethics of Toxicological Assessment
- The Three Rs: Reduce, Refine, and Replace
2. Normality: Definition and Maintenance
- Introduction
- What is Normality?
- Normality as a Range
- Experimental Normality
- Protocol Design and Procedure as Sources of Abnormality
- Control Groups as Normality
- Establishing and Maintaining Normality in Experimental Groups
- Baseline Data and Historical Controls
3. Determination of Toxicity: The Basic Principles
- Circumstances of Toxicity Testing
- Effects Sought in Toxicity Studies
- Basic Principles of Toxicological Investigation
- Toxicokinetic Design
- Regulatory Framework and Influences
- Regulation of Study Conduct - Good Laboratory Practice
4. Determination of Toxicity: In Vitro and Alternatives
- Introduction
- Rationale for In Vitro Toxicology
- How and When to Use In Vitro or Alternative Techniques
- Considerations in Screening Program Design
- Areas of Use of In Vitro Toxicology
- Considerations in the Development of In Vitro Tests
- Validation of In Vitro Methods
- Test Systems and Endpoints
- Toxicity in Silico
- Computer Prediction Systems
- Target Organ Toxicity
- Functional Toxicity Testing
- Pharmacology and Safety Pharmacology In Vitro
- Metabolism
- Kinetics
- Toxicity Testing
- Carcinogenicity
- Reproductive Toxicity
- Irritation and Corrosion
- Phototoxicity
- Ecotoxicology
- Pitfalls in In Vitro Toxicology
- Future Utility
- Overview
5. Safety Pharmacology
- Introduction
- General Principles
- Tests to be Conducted
- What to Test?
- Design
- Test Systems for Safety Pharmacology
- Safety Pharmacology in Toxicity Studies
- Tests and Their Conduct
- Pitfalls of Safety Pharmacology Studies
- Overview
6. Determination: General and Reproductive Toxicology
- General Toxicology
- Test Systems for General Toxicology
- Study Designs in General Toxicology
- Examinations for Specific Toxicities
- Pitfalls in General Toxicology
- Reproductive Toxicology
- Study Designs for Reproductive Toxicology
- Pitfalls in Reproductive Toxicology
7. Determination: Genotoxicity and Carcinogenicity
- Genotoxicity
- Carcinogenicity
- Pitfalls in Carcinogenicity Studies
8. Determination: Dermal Toxicity - Sensitization, Irritation, and Corrosion
- Introduction
- General Principles of Dermal Toxicology
- Factors in Dermal Toxicity
- Test Systems
- Study Design and Parameters Measured
- Sensitization
- Pitfalls in Irritation and Sensitization
9. Determination: Environmental Toxicology and Ecotoxicology
- Introduction
- Relevance of Environmental Assessment to Chemical Development
- General Principles of Environmental Toxicology and Ecotoxicology
- Pollution, Routes of Entry, and Environmental ADME
- Factors in Testing for Environmental Effect
- Test Systems and Study Types for Ecotoxicology
- Environmental Assessment of Agrochemicals
- Environmental Assessment of Pharmaceuticals
- Pitfalls in Environmental Toxicology
10. Interpretation: Basic Principles
- Introduction
- Steps in Interpretation
- Use of Background Data in Interpretation
- Statistics and Significance in Toxicology
- Assessing Exposure
- The Reality of Difference - The Interpretation of Small Differences
- The Reproducibility of Difference
- Overview of Interpretation
11. Interpretation: Different Data Types
- Individual Data Sets
- Safety Pharmacology
- General Toxicology
- Morphological Pathology
- Reproductive Toxicology
- Genotoxicity
- Carcinogenicity
- Environmental Toxicology and Ecotoxicology
- Case Studies
- The Fundamentals of Interpretation
12. Prediction of Hazard
- Introduction
- Principles of Prediction
- Steps in the Prediction Process
- Factors for Consideration in Prediction
- Prediction from Minimal Databases
- Computer Models for Toxicity Prediction
- Prediction for Individuals
- Prediction Summary
13. Background to Risk Due to Toxicity
- Introduction
- Overview of Risk Analysis
- Levels of Risk and Factors That Affect Risk
- Summary
14. Risk Assessment in Practice and Setting Exposure Limits
- Introduction
- Risk Assessment as a Process
- Data Quality
- Data Selection for Risk Assessment
- Single Effect Versus General Risk Assessment
- Tools and Models in Risk Assessment
- Target Population, Dose, and Exposure
- Process and Factors in Risk Assessment
- Setting Safety Factors and Margins
- Exposure Limits
- Dose Level Selection for Starting Risk Assessment
- Setting Exposure Limits
- Summary
15. Risk Assessment and Management in theWorkplace
- Introduction
- The Historical and Regulatory Background
- Classification and Exposure Limits
- Factors in Workplace Risk Assessment
- Workplace Risk Assessment
- Workplace Exposure Assessment
- Risk Management in the Workplace
- Overview
16. Risk Assessment: Carcinogenicity, The Environment, Evolution, and Overview of Risk Assessment
- Introduction
- Notes on Risk Assessment and Carcinogenicity
- Notes on Risk Assessment and The Environment
- International Management of Environmental Risks
- The Evolution of Risk Assessment
- Overview of Risk Assessment
17. Evaluation of Specific Classes of Chemical
- Regulatory Influences
- The Basic Toxicity Test Package
- Human Pharmaceuticals
- Veterinary Pharmaceuticals
- Medical Devices
- Agrochemicals/Plant Protection Products
- Biocides
- Cosmetics
- General and Industrial Chemicals—Reach
- Overview
18. The Future of Toxicity Testing and Risk Assessment
- Introduction
- Challenges for Toxicology
- Challenge for Risk Assessment and Management
- Influences on Toxicity Testing and Risk Assessment
- Utility of Animal Experiments in Risk Assessment
- Development of New Test Methods and Models
- In Vitro Toxicology and the Future
- Toxicology in Silico
- The Future of Safety Evaluation and Risk Assessment
Appendix: Useful Websites
Bibliography
Select Glossary
Index
About the Author
ADAM WOOLLEY is Director and Consultant Toxicologist, ForthTox Limited, Linlithgow, UK. He received his M.Sc. in Biochemistry from London University, London, UK. Mr. Woolley is a Fellow of the Royal College of Pathologists, London, UK, where he is an examiner in toxicology and is also a board member and Diplomate of the American Board of Toxicology. He is an Honorary Consultant at the School of Pharmacy and Pharmaceutical Sciences at Manchester University, Manchester and is a member of the British Toxicology Society and US Society of Toxicology. With over thirty five years of experience, including eighteen years in contract research and nine years in the pharmaceutical industry, Mr. Woolley is an expert in pharmaceutical development, including proteins and gene therapy agents, agrochemicals, human and veterinary pharmaceuticals, and industrial chemicals. He has conducted numerous toxicity studies, reviewed reports, and data packages, and is the author of the First Edition of Informa Healthcare’s A Guide to Practical Toxicology: Evaluation, Prediction, and Risk.
Product Details
- Hardcover: 472 pages
- Publisher: CRC; 2 edition (July 26, 2008)
- Language: English
- ISBN-10: 1420043145
- ISBN-13: 978-1420043143
- Product Dimensions: 9.1 x 6.2 x 1.1 inches
List Price: $69.95