Advances in Molecular Toxicology, Volume Thirteen, features the latest advances in the subspecialties of the broad area of molecular toxicology. This series details the study of the molecular basis of toxicology by which a vast array of agents encountered in the human environment, and produced by the human body, manifest themselves as toxins. The work not only documents these examples, but also covers the complex web of chemical and biological events that give rise to toxin-induced symptoms and disease. The new technologies that are being harnessed to analyze and understand these events are also reviewed by leading experts in the field.

This book tells the story of Agent Orange, its usage and the policies that surround it. Agent Orange contains a contaminant known as TCDD. It was the most widely used defoliant from 1965 - 1970 and became one of three major tactical herbicides used in Vietnam. More than 45 major health studies were conducted with Vietnam veterans from the United States, Australia, New Zealand, and Korea seeking a relationship between veterans' health and TCDD. Allegations of birth defects in the families of Vietnam veterans and the Vietnamese represented a case study in propaganda and deliberate misinformation by the government of Vietnam. The Policies of the US Government implemented by Congress and the Department of Veterans Affairs (DVA) identified 17 recognized associated presumptive diseases that failed the tests of "cause and effect" and common sense. This book tells the story of Agent Orange, its usage, the health studies and those policies from a diverse range of perspectives, delving into science, statistics, history, policy and ethics. It is of interest to scholars engaged in history, political and social philosophy and ethics.

This first, complete reference on standardized methods for laboratory analysis is tailor-made for clinical toxicologists, containing all relevant data and protocols for routine and specialized laboratory analysis. All the procedures described conform to standards stipulated by the International Standards Organisation (ISO) and academic societies, such as the IUPAC and ICC.

Neatly divided into two volumes, the first chapters deal with requirements for toxicological analyses, quality assessment, the evaluation of analytical results, forensic aspects, clinical chemistry and therapeutic drug monitoring, while the majority of chapters contain detailed protocols for the analysis of all classes of toxicants.

A handy desktop reference for the practitioner.

The evaluation of potential mutagenic activity is a critical step in the assessment of the safety of both new and pre-existing chemical types. In Genetic Toxicology: Principles and Methods, expert contributors help to satisfy the demand for education in this tremendously important area of study. The volume covers three basic areas: the scientific basis of the discipline, the methodologies of the main test assays, and the application of the methods, all aimed primarily at scientists in the safety departments of the industries working with both natural and synthetic chemicals. Written in the highly successful Methods in Molecular Biology (TM) 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. Intuitive and cutting-edge, Genetic Toxicology: Principles and Methods provides crucial support to both laboratory workers in providing quality information on the appropriate application of techniques and to study directors in their assay selection and protocol design in this vital field.

This unique book bridges the gap between toxicology and chemistry at a level understandable by a wide spectrum of readers with various interests and a broad range of backgrounds in chemistry, biochemistry, and toxicology. The third edition has been thoroughly updated and expanded to reflect recent advances in important areas of research, including toxicogenetics and toxic effects on various body systems. Toxicological Chemistry and Biochemistry, Third Edition begins by outlining the basic concepts of general chemistry, organic chemistry, and biochemistry needed to understand the topics in the book. The author then presents an overview of environmental chemistry so that you can understand the remainder of the material covered within that framework. He also discusses biodegradation, bioaccumulation, and biochemical processes that occur in water and soil.

The new chapter on toxic effects considers toxicities to the endocrine and reproductive systems, and the section on xenobiotics analysis deals with the determination of toxicants and their metabolites in blood and other biological materials. The chapter on the genetic aspects of toxicology discusses the ways in which chemical damage to DNA can cause mutations, cancer, and other toxic effects on specific body systems, and it considers the role of genetics in determining individual susceptibilities to various toxicants.

Toxicological Chemistry and Biochemistry, Third Edition retains the basic information and structure that made the first two editions popular with students and industry professionals, while enhancing the usefulness of the book and modernizing it in important areas. Review questions and supplementary references at the end of each chapter round out the third edition of this bestselling work.

Contents:
1. Bacterial and Plant Toxins - General Mode of Action A.E. Frankel and P.D. Hall 2. Diphtheria Toxin-Structure, Function and its Therapeutic Use R.C. Ratts and J.C. VanderSpek 3. Ricin A-Structure, Function and its Clinical Applications M. Colmbatti 4. Pathways of Delivering Toxins into the Cytosol of Target Cells M. Lord, P.J. Day, M.E. Jackson, S.R. Owens, J.C. Simpson, D.C. Smith and L.M. Roberts 5. Engineering Immunotoxins for Improving their Therapeutic Activity Y. Reiter, G. Denkberg and C. Cohen 6. Ligand-receptor Interactions Studied with Chimeric Proteins H. Lorberboum-Galski 7. Chimeric Proteins: a Novel Approach for Eliminating Specific Cell Populations for Targeted Human Therapy A. Ben-Yehudah, R. Belostotsky, R. Aqeilan, Y. Azar, I. Steinberger, A. Fishman, A. Nechushtan, S. Yarkoni and H. Lorberboum-Gaski 8. Chimeric Neurotoxins - a Molecular Neurosurgery Approach P. Lazarovici 9. Targeted Immunotherapy of Autoimmune Diseases by Chimeric Toxins B.A. Holder and J.G. Krueger 10. Immunotoxins for Targeted Cancer Therapy R.J. Kreitman 11. Molecular Targeting of Brain Tumors with Cytotoxins W. Debinski 12. Toxins in the Development of Vaccines C.T. Hsu, C.Y. Ting and J. Hwang

Antisense technology may result in dramatic changes in the therapy of many diseases and may provide tools to dissect pharmacological processes and to confirm the roles of various genes. In this volume, progress in the understanding of antisense technology and its use in creating new drugs is discussed. Potential caveats, pitfalls and limitations of the technology are also presented. In the next few years the pace at which new molecular targets will be identified will increase exponentially as the sequencing of the human genome and of other genomes proceeds.

Series Information:
Hagley Perspectives on Business and Culture

Considerable investment has been made by both pharmaceutical and biotechnology companies in pharmaceutical products of biotechnology. However, because relatively few of these products have been marketed, lack of relevant experience means that uncertainty still surrounds the most appropriate strategy for their safety evaluation. The 13th CMR International Workshop, held in February 1997, provided the opportunity for regulatory authority and industry experts from Europe, Japan and the USA to share their experiences of designing safety evaluation programmes for specific product classes: colony stimulating factors, growth factors, hormones, interferons, interleukins, monoclonal antibodies for therapeutic use, and gene therapy products. Participants worked together to recommend those studies that should be considered for such safety evaluation, and those that may be unnecessary. These recommendations subsequently made a valuable contribution to the ICH guideline Safety Studies for Biotechnological Products', which was finalised at ICH 4 in Brussels in July 1997. The Workshop proceedings not only describe the recommendations but also provide the reader with an appreciation of the science behind safety evaluation strategies used by experts, the influence of different regulatory systems on these strategies, and the type of data required by both toxicologists and clinicians before they have sufficient confidence to administer pharmaceutical products of biotechnology to humans.

This book focuses on the principles, methods, and interpretation involved in establishing the safety, risk, and hazard assessment of small molecules. It presents the regulatory requirements for risk and hazard identification as per the guidelines of the Organization for Economic Cooperation and Development (OECD), Paris, and the International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use ICH and Schedule 'Y', India. It serves as reference material for undergraduate and postgraduate pharmacy degree students as well as senior researchers to learn about the principles, methods, and interpretations of systemic dosage (acute and repeated dose) and genotoxicity (in vitro and in vivo), special toxicological investigations such as reproductive and developmental toxicology, carcinogenicity, and toxicokinetics using animal models or in vitro methods, as applicable. This book is the first of its kind in providing information on the principles and methods of implementation of Good Laboratory Practice based on the guidelines of OECD. It includes detailed chapters about the regulatory requirements and guidelines in pharmaceutical products and agrochemicals. It also describes the infrastructure needed for preclinical studies, including in vivo and in vitro facilities.

Offering a basis for further research into the interactions of hosts and pathogens, this work gathers up-to-date findings, and details basic structures, functions and immunology. It provides descriptions of a variety of experimental endotoxin neutralizing agents, as well as a guide to clinical research initiatives and the latest treatments.

The Sapporo International Symposium on "Recent Advances in Nitric Oxide Research" was held in Sapporo, Japan, in 1997, following the Fifth International Meeting on the Biology of Nitric Oxide in Kyoto, Japan, organized by Dr. Salvador Moncada, Dr. Noboru Toda, and Dr. Hiroshi Maeda. The field of nitric oxide research continues to expand rapidly, and our understanding of the physiological and pathophysiological roles of NO has increased greatly. The Kyoto Meeting was stimulating and informative, providing impetus for the Sapporo Symposium, which I had the great honor to organize. To communicate the information from these events, Dr. Ichiro Sakuma and I decided to publish this book. The contents of its chapters were contributed by the participants who were active at the Sapporo symposium and cover the majority of the presentations made during that symposium. Dr. Csaba Szabo of Children's Hospital Medical Center in Cincinnati (U. S. A. ) reviews the roles of peroxynitrite and poly(ADP-ribose)synthetase in shock, inflammation, and reperfusion injury, and Dr. David A. Geller and his colleagues of the University of Pittsburgh (U. S. A. ) review the regulation and function of NO in the liver. As contributions from the Hokkaido University School of Medicine (Sapporo), Dr. Hiroko Togashi and colleagues present their data on transient cerebral ischemia and NO production, Dr.

Cell Culture Methods for in vitro Toxicology introduces the reader to a range of techniques involved in the use of in vitro cell culture in toxicological studies. It deals with major cell types studied in the field of toxicology and will be useful for anyone wishing to start work with animal cell cultures or to refresh their knowledge relating to in vitro cell models. Fundamental chapters deal with the general biology of cytotoxicity and cell immortalisation these are key issues for in vitro systems addressing the 3Rs' principle. Up-to-date overviews deal with the use of cells from liver, brain and intestine. In addition, biochemical analysis of cell responses, biotransformation pathways in cells and recombinant approaches to the early detection of cell stress are also covered in detail. Prominent features of in vitro technologies also include regulation, biosafety and standardisation. Dedicated chapters deal with these issues in a practical way in order to lead the reader to the right source of information. This book provides an up-to-date, informative and practical review of cell culture methods for in vitro toxicology. It will be of equal benefit to students and experienced toxicologists with little experience of in vitro cell culture.

Structure-Activity Relationships in Environmental Science is the first book of its kind that brings together information from a variety of sources into one document. It provides a comprehensive overview of the entire field of quantitative structure-activity relationships (QSARs) as well as being a reference for SAR experts. The book comprises three parts. Part One covers the theoretical background of structure-activity studies and Part Two deals with the practical applications of such methods in the environmental sciences. Part Three critically discusses SAR models with respect to their reliability and their aptness in environmental hazard and risk assessment. Recommendations are made as to which model to use and the case is presented for using QSARs in hazard assessment. The use of QSARs is becoming increasingly important since there is little experimental data available on environmentally relevant chemicals. Structure-Activity Relationships in Environmental Sciences will thus serve as an invaluable guide to both postgraduate and research scientists as well as professional ecologists.

The incidence of food poisoning continues to rise and now there is even greater interest in the subject of microbial food poisoning and food safety, than when the first edition of this popular book was published. As in the first edition of his book, Adrian Eley summarizes information on the principal agents that cause food poisoning and emphasizes their mode of action. Also discussed in chapters written by specially selected expert in the area are epidemilogical features of food poisoning, microbiological control of food production, mycoticoxic fungi and food safety legislation. Each chapter has been comprehensively updated to include any changes in for example laboratory practice, legislation, etc. Also included in this edition is a new chapter on food hygiene. Microbial Food Poisoning, Second Edition, appeals to students studying a wide range of courses, including medical microbiology, food science, and technology, nutrition, general microbiology and environmental health. This book will also be of use to professionals in a range of disciplines including food science, medicine, health sciences and environmental and public health.

This volume offers the most comprehensive presentation available on metal toxicology. It discusses not only metals but also the toxic endpoints, such as neurotoxicity, renal toxicity, and cancer induction. Chapters are written by experts in their respective fields, focusing on carcinogenesis and human exposures and highlighting the major aspects and issues of toxicity in general.

Emerging Nanotechnologies in Immunology aims to deliver a systematic and comprehensive review of data concerning the nature of interaction and nano-related risks between the nanophamaceuticals currently in the pipeline of S&T development for skin, ocular, and nasal drug delivery, including absorption, toxicity, and the ability to distribute after systemic exposure. The scientific development of manufactured nanomaterials for drug delivery is increasing rapidly. One of the most prominent applications is topical drug delivery, where cutaneous, ocular, and nasal exposure becomes even more relevant. These targets are the first barrier that nanoparticles encounter when in contact with the human body. The contributors addresses a representative set of the broad spectrum of nanopharmaceuticals currently being used, including cationic lipid nanoparticles, polymeric PLGA, PLA nanoparticles, biomacromolecules-based nanoparticles, and other scaffolds tissue engineered skin substitutes. Regulation and risk is also covered, since the safety of these nanophamaceuticals still represents a barrier to their wide innovative use.

The volumes that comprise Chemical Sensitivity are the first major scientific books to be published on chemical sensitivity, a growing world-wide health problem. These volumes present clinical experiences in diagnosing and treating chemical sensitivity in over 20,000 patients under controlled conditions.

Biological Effects of Low-Level Exposures, more commonly referred to as BELLE, began as a conference in May 1990. Its members are committed to the enhanced understanding of low-dose responses of all types to human exposures to chemical and physical agents, whether of an expected or paradoxical nature.
The focus of BELLE encompasses dose-response relationships to toxic agents, pharmaceuticals, and natural products over wide dosage ranges in both in vitro systems and in vivo systems, including human populations. While BELLE promotes the scientific understanding of low-level effects, its primary goal is the scientific evaluation of existing literature and ways to improve research and assessment methods.

How to protect against ischemia/reperfusion damage is one of the most urgent problems in medicine. It is known that ischemic damage can be attenuated by improving the oxygen balance of the ischemic heart, but the damage-producing mechanism is not yet fully understood. This book provides the latest information on the pathophysiology of ischemia/reperfusion damage and presents new ideas for more effective methods for protection. In the first two sections, the roles of such factors as various ions and phospholipids that modulate ischemia/reperfusion damage are explored, providing a clear and updated explanation of the mechanisms involved. In the third section, the myocardial and vascular remodeling procedure in hearts that have undergone ischemia/reperfusion is explained in terms of signal transduction, enabling a new understanding of the remodeling process. In the final section, a new approach to protection against ischemia/reperfusion damage is presented.

Covers developments in food safety and foodborne illness, organizing information to provide easy access to many topics, both general and specific. Comprehensive summaries of important advances in food science, compiled from over 550 sources worldwide, are presented.

Numerous reports demonstrate that the reproductive system could be affected by multiple potential toxicological agents. The volume includes different aspects of the development of new approaches to in vitro testing using sperm cells and systems involved on reproduction in mammals. Comparative analysis of in vivo and in vitro methods has been included to take steps towards the further development of and applications of new systems for germline toxicology.