Methods In Toxicology

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.

This fully updated book explores all-new and revised protocols involving the use of in silico models, particularly with regard to pharmaceuticals. Divided into five sections, the volume covers the modeling of pharmaceuticals in the body, toxicity data for modeling purposes, in silico models for multiple endpoints, a number of platforms for evaluating pharmaceuticals, as well as an exploration of challenges, both scientific and sociological. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and implementation advice necessary for successful results. Authoritative and comprehensive, In Silico Methods for Predicting Drug Toxicity, Second Edition aims to guide the reader through the correct procedures needed to harness in silico models, a field which now touches a wide variety of research specialties.

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 --

This book focuses on an important aspect of the methods in laboratory animal inhalation toxicology. It is targeted to students in toxicology programs and scientists contemplating performing inhalation studies.

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.

Exposure to toxic chemicalsâ€"in the workplace and at homeâ€"is increasing every day. Human behavior can be affected by such exposure and can give important clues that a person or population is in danger. If we can understand the mechanisms of these changes, we can develop better ways of testing for toxic chemical exposure and, most important, better prevention programs. This volume explores the emerging field of neurobehavioral toxicology and the potential of behavior studies as a noninvasive and economical means for risk assessment and monitoring. Pioneers in this field explore its promise for detecting environmental toxins, protecting us from exposure, and treating those who are exposed.

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.

This detailed volume examines the complex study of the assessment of in situ bioavailability and toxicity of organic chemicals in aquatic systems with a toolbox of reliable techniques. Beginning with a section on approaches for chemical analytical and bioanalytical techniques in bioavailability research, the book continues with methods to monitor effects in situ and conduct bioassays to assess the effects of complex environmental samples. It concludes with descriptions of various computational models. Written for the Methods in Pharmacology and Toxicology series, chapters feature the kind of expert implementation advice that leads to greater success in the field. Authoritative and versatile, In Situ Bioavailability and Toxicity of Organic Chemicals in Aquatic Systems serves as an ideal guide to aid in tackling the challenge of analyzing and understanding chemical pollution in aquatic systems.

This book contains selected papers from a workshop on modern statistical methods in toxicology held during the EUROTOX '90 conference in Leipzig. The papers deal with the biostatistical evaluation of the commonly used toxicological assays, i.e. mutagenicity, long-term carcinogenicity, embryotoxicity and chronic toxicity assays. The biological background is considered in detail, and most of the related statistical approaches described. In five overview papers, the present state of the art of the related topics is given, while in several contributed papers new approaches are discussed. The most important features are: - A new view on the per-litter analysis problem in em- bryotoxicity assays. - A highly sophisticated treatment of the so-called muta-tox problem in mutagenicity assays. - A detailed discussion of the multiplicity problem based on the closed testing procedure. This volume provides readers with an overview of modern biostatistical methods for several toxicological assays and is in part intended for direct, practical use.

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.