Practical Toxicology: Evaluation, Prediction, and Risk, Third Edition, 3rd Edition (Hardback) book cover

Practical Toxicology

Evaluation, Prediction, and Risk, Third Edition, 3rd Edition

By David Woolley, Adam Woolley

CRC Press

528 pages | 15 B/W Illus.

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Description

Practical Toxicology: Evaluation, Prediction, and Risk, Third Edition shows how to conduct a program of safety evaluation and testing and then to interpret and apply the resulting data and information in the real world, beginning with the basic concepts in toxicology and progressing to the interpretation of the resulting data. Revised and updated chapters on risk assessment guide the reader to setting the foundations necessary for submission to regulatory authorities. In addition, a new chapter in the book reviews the errors in toxicology, mistakes, misuse, mismanagement, and misunderstanding with a view to avoiding these in the future.

New Chapters in the Third Edition:

  • Toxicology in silico
  • Errors in Toxicology
  • Safety Assessment of Extractables and Leachables.

This new edition follows a practical sequence from introducing the basics of toxicology (including the vital concept of normality in controls) to describing a test program and then interpreting the data and translating that to risk assessment that can be used in a number of real world situations where safety and secure risk assessment are essential. Although written primarily from the perspective of pharmaceutical development, the test designs and toxicological problems encountered in that field are entirely relevant to those with other classes of chemicals, the only difference being the regulatory context. Toxicology is an international discipline and the book has been written to take into account some of the differences in regulatory nuance between the main regions of the world.

Completely revised and written in an easily accessible style, the text address several audiences—from students and post-graduates coming to the subject for the first time to established professionals who find themselves needing to learn about toxicology, toxicity testing, interpretation of the results, and risk assessment. It is intended primarily as a textbook, with case studies and information on where to go to ask questions, but can also be used as a practical reference book. It covers all the basics of toxicology and the main aspects of safety evaluation testing and risk assessment while reviewing critically the current state of the discipline. It also provides a foundation for those seeking registration or certification.

Table of Contents

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

General Objectives Of Toxicological Study

Biology And Outcome Of Toxic Reactions

Cellular Basis And Consequences Of Toxic Change

Expression Of Toxicity

Target Organ Expression Of Toxicity

Ethics Of Toxicological Assessment

The Three Rs: Reduce, Refine, And Replace

References 

Normality: Definition and Maintenance

Introduction

What Is Normality?

Normality As A Range

Experimental Normality

Control Groups As Normality

Establishing And Maintaining Normality In Experimental Groups

Baseline Data And Historical Controls

Summary

References

Determination of Toxicity: The Basic Principles

Introduction

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

Summary

References

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

Target Organ Toxicity

Functional Toxicity Testing

Pharmacology And Safety Pharmacology In Vitro

Metabolism

Kinetics

Toxicity Testing

Carcinogenicity

Reproductive Toxicity

Sensitization

Irritation And Corrosion

Phototoxicity

Ecotoxicology

Pitfalls In In Vitro Toxicology

Omics

Future Utility

Summary

Toxicology in silico

Introduction

(Q)SAR Methodologies

Model validity

Regulations, QSARs And Experts

Case Study: ICH M7

Choosing A (Q)SAR

Commercial vs non-commercial

Pitfalls In In Silico Toxicology

Summary

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

Central Nervous System—Modified Irwin Screen

Cardiovascular System

Respiratory System

Gastrointestinal (Gi) Tract

Renal Function

Pitfalls Of Safety Pharmacology Studies

Summary

References

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 and developmental toxicology

Study designs for reproductive toxicology

Pitfalls in reproductive toxicology

Summary

Determination: Genotoxicity and Carcinogenicity

Genotoxicity

General Principles in Genotoxicity

Test Battery and Study Design

Test Systems and Tests

Pitfalls in Genotoxicity

Genotoxicity Testing In Vitro—Sensitivity and Specificity

Carcinogenicity

General Principles In Carcinogenicity

Test Systems for Carcinogenicity

Study Design and Methods of Assessment

Choice of Dose Levels

Parameters Measured

Other Systems for Carcinogenicity Assessment

Pitfalls In Carcinogenicity Studies

Overview of the Future of Carcinogenicity Assessment

Summary

Determination: Dermal Toxicity—Sensitization, Irritation, and Corrosion

Introduction

General principles of dermal toxicology

Factors in dermal toxicity

Test systems

Study design and parameters measured

Dermal Irritation and Corrosion

Ocular Irritation

Irritation by Other Routes

Sensitization

Allergic Sensitization in Guinea Pigs

Allergic Sensitization in Mice (Local Lymph Node Assay)

Pitfalls in irritation and sensitization

Summary

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

Ecotoxicology In Vitro

Invertebrates

Mesocosms and Field Tests and Studies

Environmental assessment of agrochemicals

Environmental assessment of pharmaceuticals

Pitfalls in environmental toxicology

Summary

References

Interpretation: Basic Principles

Introduction

The Interpretation Challenge

The Scope of Interpretation

Interpretation as a Dynamic Process

Steps In Interpretation

Study Design

Controls and Expectation

Use of Background Data in Interpretation

Statistics and Significance in Toxicology

Statistical Process

Data Treatment and Transformation

Assessing Exposure

Integration of Exposure Information

Toxicokinetics

The Reality of Difference—the interpretation of small differences

The Reproducibility of Difference

Summary

Interpretation: Different Data Types

Individual Data Sets

Safety Pharmacology

General Toxicology

Toxicokinetics

Clinical Pathology

Morphological Pathology

The Cell

Subcellular Organelles

Composition Of The Cytoplasm Or Cell Contents

Plasma Membrane Changes

Hypertrophy And Atrophy

Hyperplasia And Metaplasia

Changes To Whole Tissues Or Organs

Inflammation

Changes In Blood Supply

Repair And Reversibility

Neoplasia

Overview Of Interpretation In General Toxicology

Reproductive Toxicology

Genotoxicity

Carcinogenicity

Environmental Toxicology And Ecotoxicology

Epidemiology And Occupational Toxicology

Epidemiology

Occupational Toxicology

Case Study: Ciprofibrate

Summary

References

Prediction of Hazard

Introduction

Principles of prediction

Steps in the prediction process

Prediction from minimal databases

Pediction for individuals

Summary

Background to Risk Due to Toxicity

Introduction

Overview of risk analysis

Levels of risk and factors that affect risk

Risk perception

Acceptability and tolerability of risk

Comparative risk

Synthetic versus natural

Risk expression and quantification

Summary

References

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

Pbpk Models And Scaling

Models For Rodent Bioassay Data

Target Population, Dose, And Exposure

Prediction Of Exposure

Measurement Of Exposure

Process And Factors In Risk Assessment

Physical Form And Formulation

Route Of Exposure

Bioavailability

Dose Response

Safety Evaluation And Human Data

Purpose And Target Population

Setting Safety Factors And Margins

Hazard Weighting And Safety Factors

Safety Factor Rationale

Exposure Limits

Dose Level Selection For Starting Risk Assessment

Noel And Noael

The Benchmark Dose

Setting Exposure Limits

Use Of The Therapeutic Dose For Setting Wels/Oels For Pharmaceuticals

Thresholds Of Toxicological Concern

Summary

References

Safety Assessment of Extractables, Leachables and Impurities

Introduction

Definitions

Regulatory background

Toxicological assessment

Risk assessment

impurities in practice

Summary

References

Risk Assessment and Management in the Workplace

Introduction

Factors In Workplace Risk Assessment

Workplace Risk Assessment

Workplace Exposure Assessment

Risk Management In The Workplace

Summary

Risk Assessment: Carcinogenicity, the Environment, Evolution, and Overview of Risk Assessment

Introduction

Risk Assessment And Carcinogenicity

Risk Assessment And The Environment

International Management Of Environmental Risks

The Evolution Of Risk Assessment

Summary

Evaluation of Specific Classes of Chemical

Introduction

Regulatory Influences

The Basic Toxicity Test Package

Human Pharmaceuticals

Veterinary Pharmaceuticals

Medical Devices

Agrochemicals/Plant Protection Products

Biocides

Cosmetics

General And Industrial Chemicals—Reach

Tobacco Products

Summary

References

Errors in toxicology

Introduction

Errors through the ages

A brief history of early regulations

Modern mistakes and mismanagement

Clinical trials with new medicinal products

Contamination

Misunderstanding

The public and toxicology

Summary

References

The Future of Toxicity Testing and Risk Assessment

Introduction

Challenges For Toxicology

Evolution Of Toxicity Testing

Development Of New Test Methods And Models

The Future Of Toxicity Testing

A New Paradigm For Safety Evaluation

What Will The Future Of Testing Look Like?

Challenges For Risk Assessment And Management

Evolution Of Risk Assessment

Summary

References

About the Originator

Author

Subject Categories

BISAC Subject Codes/Headings:
MED071000
MEDICAL / Pharmacology
MED096000
MEDICAL / Toxicology
SCI026000
SCIENCE / Environmental Science