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This work concentrates on cellular and molecular toxicity of selected well-known drugs or chemicals on the cardiovascular system. The primary objective is to provide a better understanding of the mechanisms by which xenobiotics are toxic to mammalian tissues and cells. The use of in vitro cellular and tissue systems provides attractive experimental models to assess toxic manifestations of xenobiotics. This work addresses the most recent findings on the cellular and molecular mechanisms of toxicity of several important cardiotoxic agents: doxorubicin, ethanol, cocaine, and the catecholamines. It presents an overview of vascular toxins and their biochemical effects. Included is a summary of in vitro cardiovascular techniques for assessing toxicity of xenobiotics. This publication is important for those in toxicology, tissue culture, pharmacology, in vitro toxicology, developmental biology and related areas.
This work concentrates on cellular and molecular toxicity of selected well-known drugs or chemicals on the cardiovascular system. The primary objective is to provide a better understanding of the mechanisms by which xenobiotics are toxic to mammalian tissues and cells. The use of in vitro cellular and tissue systems provides attractive experimental models to assess toxic manifestations of xenobiotics. This work addresses the most recent findings on the cellular and molecular mechanisms of toxicity of several important cardiotoxic agents: doxorubicin, ethanol, cocaine, and the catecholamines. It presents an overview of vascular toxins and their biochemical effects. Included is a summary of in vitro cardiovascular techniques for assessing toxicity of xenobiotics. This publication is important for those in toxicology, tissue culture, pharmacology, in vitro toxicology, developmental biology and related areas.
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.
Written as an advanced text for toxicology students, this book is much more than an introduction and provides in-depth information describing the underlying mechanisms through which toxicants produce their adverse responses. • Links traditional toxicology to modern molecular techniques, important for teaching to graduate courses and professional studies • Uses a didactic approach with basic biological or theoretical background for the methodology presented • Brings together and comprehensively covers a range of dynamic aspects in biochemical and molecular toxicology • Guides student and professional toxicologists in comprehending a broad range of issues, compiled and authored by a diverse group of experts • “A good introductory textbook covering the biochemical toxicology of organic substances and the relevant methodology in some detail.... It offers good value for money and can be recommended as a textbook for appropriate courses” – BTS Newsletter review of the 4th edition
Cell culture techniques allow a variety of molecular and cell biological questions to be addressed, offering physiological conditions whilst avoiding the use of laboratory animals. In addition to basic techniques, a wide range of specialised practical protocols covering the following areas are included: cell proliferation and death, in-vitro models for cell differentiation, in-vitro models for toxicology and pharmacology, industrial application of animal cell culture, genetic manipulation and analysis of human and animal cells in culture.
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.
Cell Culture Methods for in vitro Toxicology introduces the reader to a range of techniques involved in the use of in vitro cell culture in toxicological studies. It deals with major cell types studied in the field of toxicology and will be useful for anyone wishing to start work with animal cell cultures or to refresh their knowledge relating to in vitro cell models. Fundamental chapters deal with the general biology of cytotoxicity and cell immortalisation these are key issues for in vitro systems addressing the `3Rs' principle. Up-to-date overviews deal with the use of cells from liver, brain and intestine. In addition, biochemical analysis of cell responses, biotransformation pathways in cells and recombinant approaches to the early detection of cell stress are also covered in detail. Prominent features of in vitro technologies also include regulation, biosafety and standardisation. Dedicated chapters deal with these issues in a practical way in order to lead the reader to the right source of information. This book provides an up-to-date, informative and practical review of cell culture methods for in vitro toxicology. It will be of equal benefit to students and experienced toxicologists with little experience of in vitro cell culture.
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.
Animal Experimentation: Working Towards a Paradigm Change critically appraises current animal use in science and discusses ways in which we can contribute to a paradigm change towards human-biology based approaches.
This work concentrates on cellular and molecular toxicity of selected well-known drugs or chemicals on the cardiovascular system. The primary objective is to provide a better understanding of the mechanisms by which xenobiotics are toxic to mammalian tissues and cells. The use of in vitro cellular and tissue systems provides attractive experimental models to assess toxic manifestations of xenobiotics. This work addresses the most recent findings on the cellular and molecular mechanisms of toxicity of several important cardiotoxic agents: doxorubicin, ethanol, cocaine, and the catecholamines. It presents an overview of vascular toxins and their biochemical effects. Included is a summary of in vitro cardiovascular techniques for assessing toxicity of xenobiotics. This publication is important for those in toxicology, tissue culture, pharmacology, in vitro toxicology, developmental biology and related areas.