Development Of An In Vitro Neurotoxicity Assay

Scientists agree that exposure to toxic agents in the environment can cause neurological and psychiatric illnesses ranging from headaches and depression to syndromes resembling parkinsonism. It can even result in death at high exposure levels. The emergence of subclinical neurotoxicity-the concept that long-term impairments can escape clinical detection-makes the need for risk assessment even more critical. This volume paves the way toward definitive solutions, presenting the current consensus on risk assessment and environmental toxicants and offering specific recommendations. The book covers: The biologic basis of neurotoxicity. Progress in the application of biologic markers. Reviews of a wide range of in vitro and in vivo testing techniques. The use of surveillance and epidemiology to identify neurotoxic hazards that escape premarket screening. Research needs. This volume will be an important resource for policymakers, health specialists, researchers, and students.

In recent years, the need to develop acceptable alternatives to conventional animal testing for neurotoxicity and developmental neurotoxicity has been increasingly recognized, and much effort is being directed toward the development of alternative models, utilizing mostly mammalian cells in culture but also non-mammalian model systems. In Vitro Neurotoxicology: Methods and Protocols presents a series of cellular, biochemical, and molecular methodological protocols in the area of in vitro neurotoxicology, with an emphasis on mammalian cell culture systems. Opening with a section on methodologies for preparing several cellular systems of variable complexity, amenable for in vitro neurotoxicological studies, the thorough volume continues with coverage of methods to measure cellular death and major mechanisms, methods for assessing mechanisms of nervous system cell toxicity related to impairment of cell signaling, while a final section illustrates additional methods for assessing important nervous system processes such as cell proliferation, neuritogenesis, and synaptogenesis. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, In Vitro Neurotoxicology: Methods and Protocols serves researchers with an interest in assessing or characterizing the potential neurotoxicity of environmental contaminants, drugs, or other chemicals.

Well-respected leaders in the field of in vitro neurotoxicology take a fresh look at their own and other's work, critically and comparatively analyzing it across experimental systems and toxicants, and synthesizing essential principles for in vitro neurotoxicity testing. Neurotoxicants of significance to human health are emphasized, especially those for which metabolism and dose-responses are well well studied both in vivo and in vitro: lead, mercury, organophosphorous insecticides, polychlorinated biphenyls and dioxin, ethanol, and endogenous proteins. The goal is to set out new concepts and research directions that will hasten significant improvement in the methods and systems for in vitro neurotoxicity 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.

Book deals with alternatives to in vivo animal testing. Contents - the place of in vitro methods in biomedical research; serum-free monolayer cultures of fetal chick brain and retina, immunoassays of developmental markers, mathematical data analysis, and establishment of optimal culture conditions; serum-free aggregate cultures of fetal rat brain and liver cells, methodology and some practical applications in neurotoxicology; a tiered system for in vitro neurotoxicity testing, a place for neural cell line and organotypic cultures; cellular neuronal development in vitro, neurobiological and neurotoxicological studies in cultured model systems; electron microscopic analysis of cultured cells; use of organotypic slice cultures in neurobiological research.

Handbook of Developmental Neurotoxicology, Second Edition, provides a comprehensive view of the fundamental aspects of neurodevelopment, the pathways and agents that affect them, relevant clinical syndromes, and risk assessment procedures for developmental neurotoxicants. The editors and chapter authors are internationally recognized experts whose collaboration heralds a remarkable advance in the field, bridging developmental neuroscience with the principles of neurotoxicology. The book features eight new chapters with newly recruited authors, making it an essential text for students and professionals in toxicology, neurotoxicology, developmental biology, pharmacology, and neuroscience. Presents a comprehensive, up-to-date resource on developmental neurotoxicology with updated chapters from the first edition Contains new chapters that focus on subjects recent to the field Includes well-illustrated material, with diagrams, charts, and tables Contains compelling case studies and chapters written by world experts

A developmental neurotoxicity study will provide information on the effects of repeated exposure to a substance during in utero and early postnatal development. The test substance is administered daily, generally orally, to mated females (rats are ...