Social pressure to minimize the use of animal testing, the ever-increasing concern on animal welfare, and the need for more human-relevant and more predictive toxicity tests are some of the drivers for new approaches to chemical screening. This book focuses on The Adverse Outcome Pathway, an analytical construct that describes a sequential chain of causally linked events at different levels of biological organization that lead to an adverse health or ecotoxicological effect. While past efforts have focused on toxicological pathway-based vision for human and ecological health assessment relying on in vitro systems and predictive models, The Adverse Outcome Pathway framework provides a simplified and structured way to organize toxicological information. Within the book, a systems biology approach supplies the tools to infer, link, and quantify the molecular initiating events and the key events and key event relationships leading to adverse outcomes. The advancement of these tools is crucial for the successful implementation of AOPs for regulatory purposes.

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.

Much of organic chemistry is based on the ability of suitably structured chemicals to bind together through the formation of covalent bonds. Biochemistry is replete with exam ples of enzymatically catalyzed reactions in which normal body constituents can be linked through covalent bonds during the process of intermediary metabolism. The finding that xenobiotic chemicals that enter the body from the environment, are metabolized to highly reactive species, and then covalently react with cellular macromolecules to induce toxic and carcinogenic effects was an observation that spawned the research featured in the Fifth International Symposium on Biological Reactive Intermediates (BRI V). The group of investigators that became fascinated with this process and its signifi cance in terms of human health began their discussions in Turku, Finland (J 975), and continued them at Guildford, England (1980), College Park, Maryland (1985), Tucson, Arizona (1990), and Munich, Germany (1995). Among the results were a series of reports listed below, as well as the book for which this serves as the Preface. • Jollow, DJ., Kocsis, J.J., Snyder, R. and Vainio, H. (eds), Biological Reactive Intermediates: Formation, Toxicity and Inactivation, Plenum Press, NY, 1975. • Snyder, R., Park, D.V., Kocsis, J.J., Jollow, D.V., Gibson, G.G. and Witmer, C.M. (eds), Biological Reactive Intermediates II: Chemical Mechanisms and Biological Effects, Plenum Press, N.Y., 1982.

This up-to-date, comprehensive toxicology handbook is devoted to the effects of environmental pollution on fish. Fish species represent nearly half of all vertebrates and have become important sentinels for environmental contamination and model organisms for understanding adverse outcomes from exposures. This new edition is written by recognized experts, and it highlights the significant research progress in fish toxicology that has resulted from rapid technological developments in analytical, biochemical, and genomic sciences. The book: Discusses fundamental topics such as toxicokinetics in fishes, processes governing biotransformation within these organisms, and reactive oxygen species and oxidative stress. Explains key target organ systems for chemical impacts in fish, such as the nervous and immune systems, and how fishes can develop resistance to chemical toxicity. Covers multi-transgenerational effects on fishes, epigenetics, proteomics and metabolomics, and adverse outcome pathways. Replacing the case studies in the first edition, this update delves into the impacts of microplastics, pharmaceuticals, and oil spills in dedicated final chapters. With nearly 200 illustrations and tables, this comprehensive reference work presents concepts in a way that is useful for both novices to and experts in the field of fish toxicology.

Principles of Toxicology concisely and efficiently presents the scientific basis for toxicology as it applies to the workplace and the environment, covering diverse chemical hazards encountered in modern workplaces and natural environments and providing a practical understanding of these hazards for those concerned with protecting the health of humans and ecosystems. The work presents not only theory, but also practical information regarding chemical hazards to give the student and new professional a working knowledge of the practice of toxicology and the ability to solve problems in environmental and industrial settings. Case histories and examples from industrial and environmental exposures to chemicals are included to demonstrate the application of toxicological principles. To allow for seamless reader comprehension and further exploration of covered topics, the work is supplemented with numerous illustrations to clarify and summarize key points, as well as annotated bibliographies. In the 4th edition, all chapters and references have been updated to account for the latest scientific thinking, and new color figures have been added. New topics covered in 4th Edition of Principles of Toxicology include: Regulatory toxicology, including the key regulatory framework in which much of the field of toxicology operates Alternative methods in toxicology, including cutting-edge approaches to developing new information on the toxicity of drugs and chemicals The dilemma of selecting safe exposure limits, guiding readers through practical considerations and pitfalls in developing and using safe exposure limits Ecological risk assessment, with detailed discussion of methods and considerations when evaluating the effects of contaminants on plants and animals. Providing information on the principles of toxicology and the application of those principles to solve problems in environmental and industrial settings, Principles of Toxicology serves as an excellent textbook resource for advanced undergraduate, graduate, and professional students in a range of environmental and health fields. It is also valuable to health professionals who need toxicological information and assistance beyond what is found in an introductory text to general toxicology.

Risk assessment has become a dominant public policy tool for making choices, based on limited resources, to protect public health and the environment. It has been instrumental to the mission of the U.S. Environmental Protection Agency (EPA) as well as other federal agencies in evaluating public health concerns, informing regulatory and technological decisions, prioritizing research needs and funding, and in developing approaches for cost-benefit analysis. However, risk assessment is at a crossroads. Despite advances in the field, risk assessment faces a number of significant challenges including lengthy delays in making complex decisions; lack of data leading to significant uncertainty in risk assessments; and many chemicals in the marketplace that have not been evaluated and emerging agents requiring assessment. Science and Decisions makes practical scientific and technical recommendations to address these challenges. This book is a complement to the widely used 1983 National Academies book, Risk Assessment in the Federal Government (also known as the Red Book). The earlier book established a framework for the concepts and conduct of risk assessment that has been adopted by numerous expert committees, regulatory agencies, and public health institutions. The new book embeds these concepts within a broader framework for risk-based decision-making. Together, these are essential references for those working in the regulatory and public health fields.

Toxicodynamics in Drug Research, Volume 2: Public Health and Toxicology Issues examines the implications of public health issues and the impact of pharmaceuticals, chemical and food toxicants, dietary phytochemicals, and medical treatments on human health. Volume 2: Public Health and Toxicology Issues in Drug Research: Toxicity and Toxicodynamics covers topics on pharmacokinetics and toxicokinetics such as population pharmacokinetics/toxicokinetics, the design of toxicokinetic studies, and the use of toxicokinetic data in preclinical safety assessments. The book investigates the health effect caused by the bioaccumulation of pharmaceutical and personal care products and the impact of drug-induced toxicity on different systems of the body. It discusses the mechanistic pathways of food toxicants and illustrates the molecular mechanisms of the chemopreventive role of dietary phytochemicals. It also delves into the toxic effects of medical treatments and materials. Ethical, legal, societal, and professional issues in toxicology round off the coverage providing a valuable resource to interested in learning more about the health impact and public health issues related to the toxicity of pharmaceuticals, dietary supplements, personal care products, and medical treatments. Discusses the impact of pharmaceuticals, food, and chemical toxicants on human health Examines the toxic effects of medical treatments, clinical administrations, and materials Explores public health issues around drug safety and toxicology