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.
In Vitro Methods in Pharmaceutical Research provides a comprehensive guide to laboratory techniques for evaluating in vitro organ toxicity using cellular models. Step-by-step practical tips on how to perform and interpret assays for drug metabolism and toxicity assessment are provided, along with a comparison of different techniques available. It is a welcome addition to the literature at a time when interest is growing in cellular in vitro models for toxicology and pharmacology studies. - Meets the continuing demand for information in this field - Compares In Vitro techniques with other methods - Describes cell-culture methods used to investigate toxicity in cells derived from different organs - Includes contributions by leading experts in the field
Toxicology has made tremendous strides in the sophistication of the models used to identify and understand the mechanisms of agents that can harm or kill humand and other higher organisms. Non-animals or in vitro models started to gain significant use in the 1960s. As a result of the increased concern over animal welfare, economic factors, and the need for greater sensitivity and understanding of mechanisms, interest in in vitro^n models has risen. This volume demonstrates that there now exists a broad range of in vitro models for use in either identifying or understanding most forms of toxicity. The availability of in vitro models spans both the full range of endpoints (irritation, sensitization, lethality, mutagenicity, and devlopmental toxicity) and the full spectrum of target organ systems (skin, eye, heart, liver, kidney, nervous system, etc.). Chapters are devoted to each of these speciality areas from a perspective of presenting the principal models and their uses and limitations. Chapters that overview the principles involved in the general selection and use of models, and that address the issues of safety concerns and regulatory acceptance of these methods are also included.
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.
The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysâ€"an effort requiring funding, interagency coordination, and data management strategies.
In Vitro Toxicology Systems brings together important issues and considerations needed in order to develop a workable, reliable, integrated testing strategy for the replacement of animals in toxicity testing regimes. This thorough volume includes sections on in vitro models for systemic organ toxicity, neurotoxicity, sensory organs, immunotoxicity and reproductive toxicity and addresses how stem cells may be used going forward. The book also tackles difficult areas of toxicology such as carcinogenicity and nanotoxicology, with additional chapters dedicated to kinetics, metabolism, and in vitro in vivo extrapolation. The book also addresses biological processes such as stress response pathways and mechanistic biomarkers and how these can be uncovered and measured using high content approaches. Reliable and authoritative, In Vitro Toxicology Systems will be of benefit not only to students, scientists and regulators working in the field of chemical safety assessment but also to a wider scientific audience.
This book summarizes early pioneering achievements in the field of human neural stem cell (hNSC) research and combines them with the latest advances in stem cell technology, including reprogramming and gene editing. The powerful potential of hNSC to generate and repair the developing and adult CNS has been confirmed by numerous experimental in vitro and in vivo studies. The book presents methods for hNSC derivation and discusses the mechanisms underlying NSC in vitro fate decisions and their in vivo therapeutic mode of action. The long-standing dogma that the human central nervous system (CNS) lacks the ability to regenerate was refuted at the end of the 20th century, when evidence of the presence of neurogenic zones in the adult human brain was found. These neurogenic zones are home to human neural stem cells (hNSCs), which are capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. NSCs isolated from human CNS have a number of clinical advantages, especially the innate potential to differentiate into functional neural cells. Nevertheless, their full clinical exploitation has been hindered by limited access to the tissue and low expansion potential. The search for an alternative to CNS sources of autologous, therapeutically competent hNSCs was the driving force for the many studies proving the in vitro plasticity of different somatic stem cells to generate NSCs and their functional progeny. Now the era of induced pluripotent stem cells has opened entirely new opportunities to achieve research and therapeutic goals with the aid of hNSCs.
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.
In Vitro Toxicology details the protocols and methods of in vitro testing, highlighting the usefulness of models, methods and the cost-effectiveness and reproducibility of such methodologies. The current approaches and strategies required to develop an easy, reliable, validated and high throughput system for use in alternative animal models to circumvent in vivo testing are discussed in detail. The book also includes chapters on the principles involved in the general selection and use of models that address safety concerns, regulatory acceptance and the current understandings and strategies for the identification of biomarkers in toxicity testing. Furthermore, principles involved in the general selection and use of models that address the issues of safety concerns and regulatory acceptance of these models are discussed, making the book beneficial to students, scientists, and regulators working in toxicology, as well as those in the field of chemicals and the safety assessment of novel materials. - Discusses new techniques and protocols in a clear and concise manner - includes examinations of nanotoxicity, genotoxicity and carcinogenicity - Explains practical laboratory methods and the theories behind in vitro testing
This volume presents 30 state-of-the-art protocols and reviews to set up and apply primary hepatocyte cultures for research and screening purposes. The first part of the book focuses on the use of these particular liver-based in vitro models to study the different aspects of the hepatocyte life cycle, including cell growth, differentiation and cell death. The second part of the book is targeted towards the demonstration of the applicability of primary hepatocyte cultures, or liver-based in vitro models derived thereof, for functionality and toxicity testing. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Protocols In In-Vitro Hepatocyte Research is intended for basic and applied researchers in the area of pharmacology and toxicology, both in academic and industrial settings.
