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.
This second edition volume expands on the previous edition by exploring the latest advancements in high throughput screening (HTS) in toxicity studies by using in vitro, ex vivo, and in vivo models. This volume also covers the application of artificial intelligence (AI) and data science to curate, manage, and use HTS data. 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, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, High Throughput Screening Assays in Modern Toxicology, Second Edition is a valuable resource for scientists pursuing chemical toxicology research. This book will aid scientists and researchers in translating new HTS techniques into standardized chemical toxicology assessment tools that can refine, reduce, and replace animal testing. .
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.
Author: Committee on Predictive-Toxicology Approaches for Military Assessments of Acute Exposures
The US Department of Defense (DOD) is faced with an overwhelming task in evaluating chemicals that could potentially pose a threat to its deployed personnel. There are over 84,000 registered chemicals, and testing them with traditional toxicity-testing methods is not feasible in terms of time or money. In recent years, there has been a concerted effort to develop new approaches to toxicity testing that incorporate advances in systems biology, toxicogenomics, bioinformatics, and computational toxicology. Given the advances, DOD asked the National Research Council to determine how DOD could use modern approaches for predicting chemical toxicity in its efforts to prevent debilitating, acute exposures to deployed personnel. This report provides an overall conceptual approach that DOD could use to develop a predictive toxicology system. "Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense" reviews the current state of computational and high-throughput approaches for predicting acute toxicity and suggests methods for integrating data and predictions. This report concludes with lessons learned from current high-throughput screening programs and suggests some initial steps for DOD investment.
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 book focuses on various aspects and properties of high-throughput screening (HTS), which is of great importance in the development of novel drugs to treat communicable and non-communicable diseases. Chapters in this volume discuss HTS methodologies, resources, and technologies and highlight the significance of HTS in personalized and precision medicine.
Hayes' Principles and Methods of Toxicology has long been established as a reliable reference to the concepts, methodologies, and assessments integral to toxicology. The new sixth edition has been revised and updated while maintaining the same high standards that have made this volume a benchmark resource in the field. With new authors and new chap
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.
Serving as a practical handbook about ADMET for drug therapy, this book presents effective technologies, methods, applications, data interpretation, and decision-making tactics for pharmaceutical and preclinical scientists. Chapters cover case studies and in vivo, in vitro, and computational tools for drug discovery and development, with new translational approaches to clinical drug investigations in various human populations. Illustrates ADME properties, from bedside to bench and bench to bedside, for the design of safe and effective medicine in human populations Provides examples that demonstrate the integration of in vitro, in vivo, and in silico data to address human PKPD and TKTD and help determine the proper therapeutic dosage Presents successful tools for evaluating drugs and covers current translational ADMET with regulatory guidelines Offers a hands-on manual for researchers and scientists to design and execute in vitro, in silico, preclinical, and clinical studies Includes discussion of IND / NDA filing and drug labeling to support drug registration and approval
This new fifth edition of Information Resources in Toxicology offers a consolidated entry portal for the study, research, and practice of toxicology. Both volumes represents a unique, wide-ranging, curated, international, annotated bibliography, and directory of major resources in toxicology and allied fields such as environmental and occupational health, chemical safety, and risk assessment. The editors and authors are among the leaders of the profession sharing their cumulative wisdom in toxicology’s subdisciplines. This edition keeps pace with the digital world in directing and linking readers to relevant websites and other online tools. Due to the increasing size of the hardcopy publication, the current edition has been divided into two volumes to make it easier to handle and consult. Volume 1: Background, Resources, and Tools, arranged in 5 parts, begins with chapters on the science of toxicology, its history, and informatics framework in Part 1. Part 2 continues with chapters organized by more specific subject such as cancer, clinical toxicology, genetic toxicology, etc. The categorization of chapters by resource format, for example, journals and newsletters, technical reports, organizations constitutes Part 3. Part 4 further considers toxicology’s presence via the Internet, databases, and software tools. Among the miscellaneous topics in the concluding Part 5 are laws and regulations, professional education, grants and funding, and patents. Volume 2: The Global Arena offers contributed chapters focusing on the toxicology contributions of over 40 countries, followed by a glossary of toxicological terms and an appendix of popular quotations related to the field. The book, offered in both print and electronic formats, is carefully structured, indexed, and cross-referenced to enable users to easily find answers to their questions or serendipitously locate useful knowledge they were not originally aware they needed. Among the many timely topics receiving increased emphasis are disaster preparedness, nanotechnology, -omics, risk assessment, societal implications such as ethics and the precautionary principle, climate change, and children’s environmental health. Introductory chapters provide a backdrop to the science of toxicology, its history, the origin and status of toxicoinformatics, and starting points for identifying resources. Offers an extensive array of chapters organized by subject, each highlighting resources such as journals, databases,organizations, and review articles. Includes chapters with an emphasis on format such as government reports, general interest publications, blogs, and audiovisuals. Explores recent internet trends, web-based databases, and software tools in a section on the online environment. Concludes with a miscellany of special topics such as laws and regulations, chemical hazard communication resources, careers and professional education, K-12 resources, funding, poison control centers, and patents. Paired with Volume Two, which focuses on global resources, this set offers the most comprehensive compendium of print, digital, and organizational resources in the toxicological sciences with over 120 chapters contributions by experts and leaders in the field.
This book provides comprehensive information on the alternative (non-animal) dermal toxicity test methods currently available for industrial, regulatory, and academic use and also explores potential future developments. It encompasses all areas of dermal toxicity, including skin irritation, skin corrosion, skin sensitization, UV-induced effects, and skin genotoxicity. An individual chapter is devoted to each test method, with coverage of the scientific basis, validation status and regulatory acceptance, applications and limitations, available protocols, and potential role within testing strategies. In addition, perspectives from the test developer are presented, for example regarding critical steps in the protocol. The closing section addresses areas that may be of relevance for the future of dermal toxicity safety testing, including the validation and regulatory acceptance of integrated testing strategies, novel complex skin models, and high-throughput screening techniques.
Food toxicology studies how natural or synthetic poisons and toxicants in diverse food products cause harmful, detrimental, or adverse side effects in living organisms. Food toxicology is an important consideration as food supply chain is becoming more multinational in origin, and any contamination or toxic manifestation may cause serious, wide-spread adverse health effects. Food Toxicology covers various aspects of food safety and toxicology, including the study of the nature, properties, effects, and detection of toxic substances in food and their disease manifestations in humans. It will also include other aspects of consumer product safety. The first two chapters discuss the measurement of toxicants and toxicity and the importance of dose-response in food toxicology. Additional chapters discuss the aspects of food associated carcinogenesis and food-derived chemical carcinogenesis, food allergy, pathogens associated with fruits and vegetables, and the detrimental effects of radionuclides exposure. The chapters also cover the most important heavy metal contaminants, namely mercury, lead and vanadium, and Fluoride toxicity, which is extensively discussed in its own chapter. Toxicologists, scientists, researchers in food toxicology, nutritionists, and public health care professionals will find valuable information in this book on all possible intricate areas of food toxicology.