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Toxicity Testing in the 21st Century

Toxicity Testing in the 21st Century
Author: National Research Council
Publisher: National Academies Press
Total Pages: 217
Release: 2007-10-05
Genre: Nature
ISBN: 0309109922

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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.


Pesticides in the Diets of Infants and Children

Pesticides in the Diets of Infants and Children
Author: National Research Council
Publisher: National Academies Press
Total Pages: 402
Release: 1993-02-01
Genre: Science
ISBN: 0309048753

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Many of the pesticides applied to food crops in this country are present in foods and may pose risks to human health. Current regulations are intended to protect the health of the general population by controlling pesticide use. This book explores whether the present regulatory approaches adequately protect infants and children, who may differ from adults in susceptibility and in dietary exposures to pesticide residues. The committee focuses on four major areas: Susceptibility: Are children more susceptible or less susceptible than adults to the effects of dietary exposure to pesticides? Exposure: What foods do infants and children eat, and which pesticides and how much of them are present in those foods? Is the current information on consumption and residues adequate to estimate exposure? Toxicity: Are toxicity tests in laboratory animals adequate to predict toxicity in human infants and children? Do the extent and type of toxicity of some chemicals vary by species and by age? Assessing risk: How is dietary exposure to pesticide residues associated with response? How can laboratory data on lifetime exposures of animals be used to derive meaningful estimates of risk to children? Does risk accumulate more rapidly during the early years of life? This book will be of interest to policymakers, administrators of research in the public and private sectors, toxicologists, pediatricians and other health professionals, and the pesticide industry.


Toxicity Testing for Assessment of Environmental Agents

Toxicity Testing for Assessment of Environmental Agents
Author: National Research Council
Publisher: National Academies Press
Total Pages: 270
Release: 2006-04-07
Genre: Nature
ISBN: 0309164869

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Toxicity testing in laboratory animals provides much of the information used by the Environmental Protection Agency (EPA) to assess the hazards and risks associated with exposure to environmental agents that might harm public health or the environment. The data are used to establish maximum acceptable concentrations of environmental agents in drinking water, set permissible limits of exposure of workers, define labeling requirements, establish tolerances for pesticides residues on food, and set other kinds of limits on the basis of risk assessment. Because the number of regulations that require toxicity testing is growing, EPA called for a comprehensive review of established and emerging toxicity-testing methods and strategies. This interim report reviews current toxicity-testing methods and strategies and near-term improvements in toxicity-testing approaches proposed by EPA and others. It identifies several recurring themes and questions in the various reports reviewed. The final report will present a long-range vision and strategic plan to advance the practices of toxicity testing and human health assessment of environmental contaminants.


Acute Toxicology Testing

Acute Toxicology Testing
Author: Shayne C. Gad
Publisher: Academic Press
Total Pages: 561
Release: 1997-10-27
Genre: Medical
ISBN: 008052592X

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Acute toxicology testing provides the first line of defense against potentially dangerous chemicals. This book is a complete and practical guide to conducting and interpreting all regulatory required and commonly used acute toxicity tests. It presents detailed protocols for all of the common test designs and reviews their development and objectives. Acute Toxicology Testing, Second Edition will interest not only workers in the pharmaceutical industry, but also researchers and students in toxicology and public health. Key Features * Over 100 tables summarizing and interpreting results * Complete coverage of all major test designs and their limitations and advantages * Current status of alternative test designs and models


Validation of Alternative Methods for Toxicity Testing

Validation of Alternative Methods for Toxicity Testing
Author: Chantra Eskes
Publisher: Springer
Total Pages: 418
Release: 2016-09-26
Genre: Medical
ISBN: 3319338269

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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.


The History of Alternative Test Methods in Toxicology

The History of Alternative Test Methods in Toxicology
Author:
Publisher: Academic Press
Total Pages: 352
Release: 2018-10-20
Genre: Medical
ISBN: 0128136987

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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.


Toxicity Testing for Assessment of Environmental Agents

Toxicity Testing for Assessment of Environmental Agents
Author: National Research Council
Publisher: National Academies Press
Total Pages: 271
Release: 2006-05-07
Genre: Nature
ISBN: 0309100925

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Toxicity testing in laboratory animals provides much of the information used by the Environmental Protection Agency (EPA) to assess the hazards and risks associated with exposure to environmental agents that might harm public health or the environment. The data are used to establish maximum acceptable concentrations of environmental agents in drinking water, set permissible limits of exposure of workers, define labeling requirements, establish tolerances for pesticides residues on food, and set other kinds of limits on the basis of risk assessment. Because the number of regulations that require toxicity testing is growing, EPA called for a comprehensive review of established and emerging toxicity-testing methods and strategies. This interim report reviews current toxicity-testing methods and strategies and near-term improvements in toxicity-testing approaches proposed by EPA and others. It identifies several recurring themes and questions in the various reports reviewed. The final report will present a long-range vision and strategic plan to advance the practices of toxicity testing and human health assessment of environmental contaminants.


A Comprehensive Guide to Toxicology in Preclinical Drug Development

A Comprehensive Guide to Toxicology in Preclinical Drug Development
Author: Ali S. Faqi
Publisher: Academic Press
Total Pages: 904
Release: 2012-11-02
Genre: Business & Economics
ISBN: 0123878152

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A Comprehensive Guide to Toxicology in Preclinical Drug Development is designed for toxicologists who need a thorough understanding of the drug development process. This multi-contributed reference will provide a detailed picture of the complex and highly interrelated activities of preclinical toxicology in both small molecules and biologics --


Science and Judgment in Risk Assessment

Science and Judgment in Risk Assessment
Author: National Research Council
Publisher: National Academies Press
Total Pages: 668
Release: 1994-01-01
Genre: Science
ISBN: 030904894X

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The public depends on competent risk assessment from the federal government and the scientific community to grapple with the threat of pollution. When risk reports turn out to be overblownâ€"or when risks are overlookedâ€"public skepticism abounds. This comprehensive and readable book explores how the U.S. Environmental Protection Agency (EPA) can improve its risk assessment practices, with a focus on implementation of the 1990 Clean Air Act Amendments. With a wealth of detailed information, pertinent examples, and revealing analysis, the volume explores the "default option" and other basic concepts. It offers two views of EPA operations: The first examines how EPA currently assesses exposure to hazardous air pollutants, evaluates the toxicity of a substance, and characterizes the risk to the public. The second, more holistic, view explores how EPA can improve in several critical areas of risk assessment by focusing on cross-cutting themes and incorporating more scientific judgment. This comprehensive volume will be important to the EPA and other agencies, risk managers, environmental advocates, scientists, faculty, students, and concerned individuals.


Principles of Toxicology Testing, Second Edition

Principles of Toxicology Testing, Second Edition
Author: Frank A Barile
Publisher: CRC Press
Total Pages: 368
Release: 2013-04-02
Genre: Medical
ISBN: 1842145282

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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, including absorption, distribution, metabolism, and elimination of toxins, including chemicals and drugs. The book then continues with animal (in vivo) and in vitro toxicology testing methods associated with toxicological analysis and preclinical drug development. As in the first edition, the book begins with an introduction into the fundamentals of toxicology (Section I) to prepare readers for the subsequent topics and continues through with a discussion of toxicokinetics and human risk assessment. This introductory material is useful in understanding the applications of toxicology testing. Section II describes the fundamental principles of toxicology testing in animals in greater detail. This section describes acute toxicity studies as well as subchronic and chronic studies performed on animals. Special emphasis is placed on study design and determination of classical indicators for acute and chronic testing, such as the LD50. The book examines other short- and long-term animal toxicity testing methodologies, including dermal, ocular, and reproductive toxicity testing. In addition, mutagenicity and carcinogenicity studies are also discussed in separate chapters. Section III introduces and discusses in vitro alternatives to animal toxicology tests. This section emphasizes cell culture methodology and cellular methods for acute systemic toxicity, target organ toxicity, and local toxicity. The contributors present the advantages and disadvantages of alternative methods. They also describe the use of high-throughput screening and its applications, the concepts of standardization and validation of in vitro techniques (especially large, organized validation efforts currently supported by US and EU regulatory agencies), and the theories supporting the development of in vitro methodologies. This second edition is a must-read for undergraduate and graduate toxicology students. Industrial and academic research centers will also find the text useful for establishing a toxicology testing laboratory.