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 the Workplace

• 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

• Adam Woolley, ForthTox Limited, Linlithgow, UK
  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, U.K., 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.