Toxicity Testing in the 21st Century

Author: National Research Council

Publisher: National Academies Press

ISBN: 9780309109925

Category: Nature

Page: 217

View: 652

Advances in molecular biology and toxicology are paving the way for major improvements in the evaluation of the hazards posed by the large number of chemicals found at low levels in the environment. The National Research Council was asked by the U.S. Environmental Protection Agency to review the state of the science and create a far-reaching vision for the future of toxicity testing. The book finds that developing, improving, and validating new laboratory tools based on recent scientific advances could significantly improve our ability to understand the hazards and risks posed by chemicals. This new knowledge would lead to much more informed environmental regulations and dramatically reduce the need for animal testing because the new tests would be based on human cells and cell components. Substantial scientific efforts and resources will be required to leverage these new technologies to realize the vision, but the result will be a more efficient, informative and less costly system for assessing the hazards posed by industrial chemicals and pesticides.
Toxicity Testing in the 21st Century

Author: National Research Council

Publisher: National Academies Press

ISBN: 9780309151733

Category: Nature

Page: 217

View: 115

Advances in molecular biology and toxicology are paving the way for major improvements in the evaluation of the hazards posed by the large number of chemicals found at low levels in the environment. The National Research Council was asked by the U.S. Environmental Protection Agency to review the state of the science and create a far-reaching vision for the future of toxicity testing. The book finds that developing, improving, and validating new laboratory tools based on recent scientific advances could significantly improve our ability to understand the hazards and risks posed by chemicals. This new knowledge would lead to much more informed environmental regulations and dramatically reduce the need for animal testing because the new tests would be based on human cells and cell components. Substantial scientific efforts and resources will be required to leverage these new technologies to realize the vision, but the result will be a more efficient, informative and less costly system for assessing the hazards posed by industrial chemicals and pesticides.
Using 21st Century Science to Improve Risk-Related Evaluations

Author: National Academies of Sciences, Engineering, and Medicine

Publisher: National Academies Press

ISBN: 9780309453486

Category: Nature

Page: 201

View: 776

Over the last decade, several large-scale United States and international programs have been initiated to incorporate advances in molecular and cellular biology, -omics technologies, analytical methods, bioinformatics, and computational tools and methods into the field of toxicology. Similar efforts are being pursued in the field of exposure science with the goals of obtaining more accurate and complete exposure data on individuals and populations for thousands of chemicals over the lifespan; predicting exposures from use data and chemical-property information; and translating exposures between test systems and humans. Using 21st Century Science to Improve Risk-Related Evaluations makes recommendations for integrating new scientific approaches into risk-based evaluations. This study considers the scientific advances that have occurred following the publication of the NRC reports Toxicity Testing in the 21st Century: A Vision and a Strategy and Exposure Science in the 21st Century: A Vision and a Strategy. Given the various ongoing lines of investigation and new data streams that have emerged, this publication proposes how best to integrate and use the emerging results in evaluating chemical risk. Using 21st Century Science to Improve Risk-Related Evaluations considers whether a new paradigm is needed for data validation, how to integrate the divergent data streams, how uncertainty might need to be characterized, and how best to communicate the new approaches so that they are understandable to various stakeholders.
Reducing, Refining and Replacing the Use of Animals in Toxicity Testing

Author: Dave Allen

Publisher: Royal Society of Chemistry

ISBN: 9781849737920

Category: Science

Page: 362

View: 747

Toxicity testing is used to assess the safety or hazards presented by substances such as industrial chemicals, consumer products, and pharmaceuticals. At present, many methods involve laboratory animals. Alternative procedures, some involving human cell-based technologies, are now being developed which reduce, refine, or replace animal usage and minimize the pain and distress caused. These new tests must protect public health and the environment at least as well as currently accepted methods. This book describes the ever-expanding "toolbox" of methods available to assess toxicity. Such techniques often result from our growing understanding of the biochemical and cellular pathways that mediate toxicity mechanisms. This permits evaluations of information generated from several sources to generate a "weight of evidence". By combining in silico, in vitro, and ex vivo methods with technologies that rely on biochemical- and cell-based in vitro assays, toxicologists are developing mechanistically based alternatives to live animal experimentation. This text also explores the complexities associated with adequate validation, and the assessment of test reliability and relevance. It provides an essential reference source for postgraduates, academics and industrialists working in this rapidly changing area.
High-Throughput Screening Methods in Toxicity Testing

Author: Pablo Steinberg

Publisher: John Wiley & Sons

ISBN: 9781118538241

Category: Science

Page: 570

View: 560

Explores the benefits and limitations of the latesthigh-throughput screening methods With its expert coverage of high-throughput in vitroscreening methods for toxicity testing, this book makes it possiblefor researchers to accelerate and streamline the evaluation andrisk assessment of chemicals and drugs for toxicity. Moreover, itenables them to comply with the latest standards set forth by theU.S. National Research Council's "Toxicity Testing in the 21stCentury: A Vision and Strategy" and the E.U.'s REACH legislation.Readers will discover a variety of state-of-the-science,high-throughput screening methods presented by a group of leadingauthorities in toxicology and toxicity testing. High-Throughput Screening Methods in Toxicity Testing isdivided into five parts: General aspects, including predicting the toxicity potential ofchemicals and drugs via high-throughput bioactivity profiling Assessing different cytotoxicity endpoints Assessing DNA damage and carcinogenesis Assessing reproductive toxicity, cardiotoxicity, andhaematotoxicity Assessing drug metabolism and receptor-related toxicity Each chapter describes method principles and includes detailedinformation about data generation, data analysis, and applicationsin risk assessment. The authors not only enumerate the advantagesof each high-throughput method over comparable conventionalmethods, but also point out the high-throughput method'slimitations and potential pitfalls. In addition, the authorsdescribe current research efforts to make high-throughput toxicityscreening even more cost effective and streamlined. Throughout the book, readers will find plenty of figures andillustrations to help them understand and perform the latesthigh-throughput toxicity screening methods. This book is ideal for toxicologists and other researchers whoneed to implement high-throughput screening methods for toxicitytesting in their laboratories as well as for researchers who needto evaluate the data generated by these methods.
The History of Alternative Test Methods in Toxicology

Author:

Publisher: Academic Press

ISBN: 9780128136980

Category: Medical

Page: 352

View: 756

The History of Alternative Test Methods in Toxicology uses a chronological approach to demonstrate how the use of alternative methods has evolved from their conception as adjuncts to traditional animal toxicity tests to replacements for them. This volume in the History of Toxicology and Environmental Health series explores the history of alternative test development, validation, and use, with an emphasis on humanity and good science, in line with the Three Rs (Replacement,Reduction, Refinement) concept expounded by William Russell and Rex Burch in 1959 in their now classic volume, The Principles of Humane Experimental Technique. The book describes the historical development of technologies that have influenced the application of alternatives in toxicology and safety testing. These range from single cell monocultures to sophisticated, miniaturised and microfluidic organism-on-a-chip devices, and also include molecular modelling, chemoinformatics and QSAR analysis, and the use of stem cells, tissue engineering and hollow fibre bioreactors. This has been facilitated by the wider availability of human tissues, advances in tissue culture, analytical and diagnostic methods, increases in computational processing, capabilities, and a greater understanding of cell biology and molecular mechanisms of toxicity. These technological developments have enhanced the range and information content of the toxicity endpoints detected, and therefore the relevance of test systems and data interpretation, while new techniques for non-invasive diagnostic imaging and high resolution detection methods have permitted an increased role for human studies. Several key examples of how these technologies are being harnessed to meet 21st century safety assessment challenges are provided, including their deployment in integrated testing schemes in conjunction with kinetic modelling, and in specialized areas, such as inhalation toxicity studies. The History of Alternative Test Methods in Toxicology uses a chronological approach to demonstrate how the use of alternative methods has evolved from their conception as adjuncts to traditional animal toxicity tests to replacements for them. This volume in the History of Toxicology and Environmental Health series explores the history of alternative test development, validation, and use, with an emphasis on humanity and good science, in line with the Three Rs (Replacement, Reduction, Refinement) concept expounded by William Russell and Rex Burch in 1959 in their now-classic volume, The Principles of Humane Experimental Technique. The book describes the historical development of technologies that have influenced the application of alternatives in toxicology and safety testing. These range from single cell monocultures to sophisticated miniaturised and microfluidic organism-on-a-chip devices, and also include molecular modelling, chemoinformatics and QSAR analysis, and the use of stem cells, tissue engineering and hollow fibre bioreactors. This has been facilitated by the wider availability of human tissues, advances in tissue culture, analytical and diagnostic methods, increases in computational processing capabilities, and a greater understanding of cell biology and molecular mechanisms of toxicity. These technological developments have enhanced the range and information content of the toxicity endpoints detected, and therefore the relevance of test systems and data interpretation, while new techniques for non-invasive diagnostic imaging and high resolution detection methods have permitted an increased role for human studies. Several key examples of how these technologies are being harnessed to meet 21st century safety assessment challenges are provided, including their deployment in integrated testing schemes in conjunction with kinetic modelling, and in specialised areas, such as inhalation toxicity studies.
Principles of Toxicology Testing

Author: Frank A Barile

Publisher: CRC Press

ISBN: 9781842145296

Category: Medical

Page: 362

View: 715

Nationally, toxicology programs have evolved from a traditional exploration of the chemistry and applied toxicity of chemicals and drugs to a more comprehensive study of toxicology and toxicology testing as independent entities. Consequently, the second edition of Principles of Toxicology Testing starts with basic toxicological principles, includin
Validation of Alternative Methods for Toxicity Testing

Author: Chantra Eskes

Publisher: Springer

ISBN: 9783319338262

Category: Medical

Page: 407

View: 420

This book provides information on best practices and new thinking regarding the validation of alternative methods for toxicity testing. It covers the validation of experimental and computational methods and integrated approaches to testing and assessment. Validation strategies are discussed for methods employing the latest technologies such as tissue-on-a-chip systems, stem cells and transcriptomics, and for methods derived from pathway-based concepts in toxicology. Validation of Alternative Methods for Toxicity Testing is divided into two sections, in the first, practical insights are given on the state-of-the-art and on approaches that have resulted in successfully validated and accepted alternative methods. The second section focuses on the evolution of validation principles and practice that are necessary to ensure fit-for-purpose validation that has the greatest impact on international regulatory acceptance of alternative methods. In this context validation needs to keep pace with the considerable scientific advancements being made in toxicology, the availability of sophisticated tools and techniques that can be applied in a variety of ways, and the increasing societal and regulatory demands for better safety assessment. This book will be a useful resource for scientists in the field of toxicology, both from industry and academia, developing new test methods, strategies or techniques, as well as Governmental and regulatory authorities interested in understanding the principles and practicalities of validation of alternative methods for toxicity testing.
Mammalian Toxicology

Author: Mohamed Abou-Donia

Publisher: John Wiley & Sons

ISBN: 9781119940418

Category: Medical

Page: 716

View: 335

Mammalian Toxicology surveys chemical agents and examines how such chemicals impact on human health, emphasizing the importance in minimizing environmental exposure to chemical and physical hazards in our homes, communities and workplaces through such media as contaminated water, soil and air. Starting with the basic principles on a wide range of toxic agents, this textbook describes how they enter the body, their mechanisms of action once inside, and strategies for diagnosis, prevention and treatment. Topics covered include: General principles of toxicology: pharmacological and toxicological principles underpinning the study of toxicology, risk assessments and mechanisms of cell death Disposition: routes of chemical exposures, entry into the body and various tissues, storage, metabolic biotransformation and elimination, with examples from various toxicants. Toxic agents: the occurrences, disposition in the body, health effects, toxic mechanisms, antidotes and treatments of a range of agents including pesticides, metals, solvents, gases, nanomaterials, food components and additives, pharmaceuticals, drugs of abuse, natural toxins, endocrine disruptors, radiation, and warfare weapons. Toxic effects: including neurotoxicity, developmental toxicity, immunotoxicity, teratogenecity, male and female reproductive toxicity, mutagenecity, carcinogenicity, pulmonary toxicity, cardiovascular toxicity, hepatotoxicity, gastrointestinal toxicity and cardiovascular toxicity Toxicology and society: epidemiological studies of chemical-induced diseases in human populations, and a vision for toxicology in the 21st century. Mammalian Toxicology is an essential primer for students of toxicology, biochemistry, biology, medicine and chemistry. It is also appropriate for professional toxicologists in research or regulatory affairs, and anyone who needs to understand the adverse effects of toxic agents on the human body.
Practical Toxicology

Author: David Woolley

Publisher: CRC Press

ISBN: 9781498709309

Category: Medical

Page: 528

View: 288

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.