A Comprehensive Guide to Toxicology in Preclinical Drug Development is a resource for toxicologists in industry and regulatory settings, as well as directors working in contract resource organizations, who need a thorough understanding of the drug development process. Incorporating real-life case studies and examples, the book is a practical guide that outlines day-to-day activities and experiences in preclinical toxicology. This multi-contributed reference provides a detailed picture of the complex and highly interrelated activities of preclinical toxicology in both small molecules and biologics. The book discusses discovery toxicology and the international guidelines for safety evaluation, and presents traditional and nontraditional toxicology models. Chapters cover development of vaccines, oncology drugs, botanic drugs, monoclonal antibodies, and more, as well as study development and personnel, the role of imaging in preclinical evaluation, and supporting materials for IND applications. By incorporating the latest research in this area and featuring practical scenarios, this reference is a complete and actionable guide to all aspects of preclinical drug testing. - Chapters written by world-renowned contributors who are experts in their fields - Includes the latest research in preclinical drug testing and international guidelines - Covers preclinical toxicology in small molecules and biologics in one single source

The only up-to-date compilation of renal methods available, this book is the definitive resource for any renal researcher eager to stay ahead. Methods in Renal Toxicology presents a vast array of methods for the study of renal cellular and tubular structure, function, and biochemistry under physiological, toxicological, and pathological conditions. It provides detailed descriptions in easy-to-understand language of methods designed to enhance your research efforts. Methods in Renal Toxicology puts you on the cutting edge with valuable chapters detailing molecular methods and transgene and gene targeting - the most recent approaches to the study of renal toxicology. Overall, the book's topics range from non-invasive assessments of renal function in the whole animal and clinical settings to cellular and molecular approaches. Specifically, the book delves into measurements of clearance and urinary markers, histopathology, and methods to assess renal carcinogenesis, mutagenesis, oxidative stress, mitochondria injury, cellular repair, and drug metabolism and transport. A variety of in vitro methods are also described, including the isolated perfused kidney, micropuncture, microperfusion, microdissection, renal slices, isolated perfused tubules, suspensions of tubules and isolated cells, and primary cell cultures and cell lines. Methods in Renal Toxicology is a must-have resource for all renal investigators. Nowhere else can you find concise descriptions of traditional and up-to-the-minute renal toxicology methods in such a practical, well-written single-volume guide.

Leading investigators review the highlights of current fibrosis research and the experimental methodologies used uncover the mechanisms that drive it. In their discussion of research methodologies utilizing cultured cells to model various aspects of the fibrotic response in vitro, the authors describe the isolation, characterization, and propagation of mesenchymal cells, and highlight the similarities and differences between methods that are appropriate for different types of fibroblasts. Approaches for studying collagen gene regulation and TGF-b production are also discussed, along with experimental methodologies utilizing animal models to study the pathogenesis of fibrosis. The protocols follow the successful Methods in Molecular MedicineTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

Toxicity Assessment Alternatives: Methods, Issues, Opportunities contains a broad array of critical surveys, contributed by active and respected investigators, describing their research and offering updates on toxicity assessment alternatives, directions determined by current and future grant programs, opportunities for mechanistically based test methods to detect endocrine disruptor activity, the use of alternatives in the Department of Defense hazard assessment initiatives, and the issues and opportunities for validation and regulatory acceptance. Several of these advances make use oftransgenic models that reduce the time and cost of carcinogenicity testing. Others use tissue cultures for the assessment of endocrine disrupting chemicals. Cultures of human epidermal keratinocytes are applicable as models for sulfur mustard lesions, and in vitro protein denaturation is used as a chemical test for assessing the ocular and dermal irritation potential of cosmetic prod ucts. Molecular modeling is applied to explaining chemical toxicity. Commercially developed assay systems have undergone extensive evaluation by their manufacturers. Some of these await external valida tion, and others await acceptance by North American and European regulatory agencies. Toxicity Assessment Alternatives: Methods, Issues, Opportunities provides information from members of the scientific and regulatory communities on what has been achieved and what has been accepted in alternatives to animal testing.

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.

Comprehensive Toxicology - the first comprehensive reference work in toxicology, is an in-depth, state-of-the-art review of toxicology of unrivalled quality. It is designed to encompass investigation from a molecular level to the intact organism. Presented in a 13-volume printed form.