Target Organ Toxicology Series – serie

Carcinogens, like chemicals with other toxic hazards, often produce adverse effects only in specific organs or tissues. The factors determining whether a chemical induces cancer in an organ range from simple toxicokinetics to complex phenomena such as expression or lack of expression of specific genes.; This volume examines the site-specific factors involved in carcinogenesis in the liver, gastrointestinal tract, kidney, urinary bladder, respiratory system, skin, nervous system, male reproductive system, and haematopoietic system. For each organ, the book provides current information on chemicals causally associated with cancer, mechanisms of carcinogenesis, and pathophysiology of induced tumours, and identifies the processes determining susceptibility in the organ. Full consideration is also given to the procedures used in animal carcinogenesis studies and the extrapolation of the results to humans.

Toxicology of the Gastrointestinal Tract focuses on the specifics of the mechanisms and adverse effects of xenobiotic agents and pharmaceuticals on the structure and function of the GI tract. The book focuses on a number of specific areas of intestinal research. Beginning with the well-recognized and major functions of nutrient absorption and its role as a protective barrier, the text elaborates on the expanding body of knowledge that relates to the intestines as a major metabolic and immunologic organ involved in the synthesis and degradation of both natural and foreign substances. It includes an overview of the function and dysfunction of the human absorptive process and the effects of microbial flora on these processes, as well as specific classes of toxicants that target the GI tract. The international panel of contributors presents a critical appraisal of the interactions of chemicals and drugs with the gastrointestinal system and the experimental methods and regions of research on which to focus future efforts.Providing a complete and multidisciplinary overview of the gastrointestinal system both in health and as it is involved in the toxicity of exogenous agents, Toxicology of the Gastrointestinal Tract brings together the current and growing knowledge of this critical organ system in a single volume.

The most up-to-date treatment of inhalation toxicology available, Toxicology of the Lung, Fourth Edition examines the subject from a target-organ perspective. Completely revised and updated, the book includes contributions from an entirely new set of authors, each of them a leading international authority in their respective specialties. As with the previous editions, it presents the latest advances in our knowledge of how the lung responds to airborne contaminants. It discusses the assessment of nanomaterials, pulmonary administration of new therapeutics, health effects of inhaled particulate matter from diesel exhaust, and respiratory genomics.The new edition provides insight into current thinking about the critical need for understanding the kinetics and dynamic interactions associated with toxic effects. It explores the appropriateness of recent advances made across disciplines and addresses human clinical testing and emerging technology for using animal and in vitro models to detect adverse effects. The book examines how airborne substances can alter the physiological, biochemical, and morphological functioning of biological systems and covers the latest modeling approaches for predicting deposition and fate of inhaled particles.Illustrating on-going research efforts for delineating the association between airborne substances and systemic effects, the book provides authoritative reviews of selected areas. The editor makes the information accessible to readers who do not have a background in pulmonary physiology without sacrificing the scientific rigor required by those who do. These features make this the ultimate resource on how pollutants affect allergies, infection, and other lung diseases.

The gastrointestinal tract is the most important of the three major routes of entry (and clearance) of xenobiotics and biologic entities into the bodies of mammals. As such, it is also the major route for administration of pharmaceuticals to humans. Gastrointestinal Toxicology, Second Edition describes the mechanism for entry and clearance of xenobiotics, as well as the barriers, immunologic and metabolic issues, and functions present in the GI tract.Appearing in this volume are also considerations of the microbiome and its actions and influence on the function of the GI tract and on the toxicity and pharmacodynamics of ingested substances (including nutrients, toxins, and therapeutics). These fifteen chapters written by experienced experts in the field address methods to evaluate GI function; specifics of GI function and toxicity assessment in canines and minipigs; classes of compounds with their toxicity; species differences; and the toxicity (and promise) of nanoparticles. Those needing to understand the structure, function, and methods of studying the GI tract will find this volume a singular source of reference.

Highlighting latest advances in genetics and biochemistry, the completely revised Third Edition reviews the field from basic science, clinical, epidemiological, and regulatory perspectives. Contributions from top opinion leaders in the field bring together developments in molecular embryology and cell biology as they apply to problems in developmental toxicology. It covers testing of pharmaceutical and environmental agents and interpretation of developmental toxicology data, highlighting mathematical and statistical techniques, as well as the effects of toxic exposure on the functional development of various organs.The relationship between maternal and developmental toxicology is examined, in addition to current techniques for studying chemical disposition, metabolism, and placental transfer. Close attention is given to the regulatory aspects of testing and risk assessment. Pre- and postconceptional clinical care and genetic factors in clinical developmental toxicology are also discussed.Key topics include: the roles of apoptosis and signal transduction pathways in normal and abnormal developmentthe role of epigenetic changes in developmentthe role of nutrition and individual susceptibilitythe utility of bioinformaticsglobal and targeted gene expression changes

Highlighting latest advances in genetics and biochemistry, the completely revised Third Edition reviews the field from basic science, clinical, epidemiological, and regulatory perspectives. Contributions from top opinion leaders in the field bring together developments in molecular embryology and cell biology as they apply to problems in developmental toxicology. It covers testing of pharmaceutical and environmental agents and interpretation of developmental toxicology data, highlighting mathematical and statistical techniques, as well as the effects of toxic exposure on the functional development of various organs.The relationship between maternal and developmental toxicology is examined, in addition to current techniques for studying chemical disposition, metabolism, and placental transfer. Close attention is given to the regulatory aspects of testing and risk assessment. Pre- and postconceptional clinical care and genetic factors in clinical developmental toxicology are also discussed.Key topics include: the roles of apoptosis and signal transduction pathways in normal and abnormal developmentthe role of epigenetic changes in developmentthe role of nutrition and individual susceptibilitythe utility of bioinformaticsglobal and targeted gene expression changes

This new edition presents an integrated approach to neurotoxicology, the study of organisms’ responses to changes in their environment and how interruption of the flow of information by chemical exposure causes a wide range of effects – from learning deficits, sensory disturbances in the extremities, and muscle weakness to seizures and signs similar to neurodegenerative disorders such as Parkinson’s or Alzheimer’s disease.  It is an essential resource for understanding the sites and mechanisms of neurotoxicity, for formulating testable hypotheses about the effects of neurotoxicants, and for improving the risk assessment process.

Despite being regarded as the most common toxicological target in the endocrine system, the adrenal gland has often been neglected in regulatory testing. Adrenal Toxicology addresses the increased interest in adrenocortical toxicology and the need for a resource that makes techniques available to examine adrenal endocrine disruption. Examining current techniques and the latest advancements, Adrenal Toxicology reviews the endocrinology, pharmacology, pathology and toxicology of the adrenal gland. This text provides information on the range of drugs and chemicals that affect adrenocortical function and suggests standardized approaches for in vivo and in vitro assessment. This volume also presents recent developments in the molecular mechanisms of toxicity to the adrenal cortex and medulla, and considers environmental adrenal endocrine disruption in sentinel species.Adrenal Toxicology: reflects the major developments made over the past decadefocuses on the latest research techniques, including their uses and limitationsprovides an integrated strategy for adrenal toxicology evaluationidentifies knowledge and data gaps, providing impetus for regulatory consideration

This key volume of the Target Organ Toxicology Series provides a fresh and modern approach to the subject of skin toxicology from the perspective of how the skin forms a barrier that protects the body from the external environment and how chemicals and drugs interact with the barrier properties of the skin. Any defects or perturbations to this barrier may result in damage to the skin or may alter absorption.With contributions from over 40 international experts in the field of skin biology, the book presents the central role of the skin barrier to health and disease reviewing; The skin’s anatomy and physiology, with focus on the stratum corneum as a barrier to foreign substances.Dermal absorption, cutaneous metabolism, and epidermal transporters.Altered barriers, racial skin types, aged skin, photoaged skin, cosmetics and skin sensitization. Modern approaches to drug delivery across the skin barrier, including liposomes, microneedle technology, active and passive transdermal delivery. Examples and case studies of chemical toxicity after topical exposures ranging from arsenic, metal working fluids, bromine, jet fuel, sulfur mustard and including the emerging area of nanomaterial penetration. Toxicology of the Skin is essential reading for drug delivery pharmacologist, formulation scientists, dermatologists, toxicologists, molecular biologists, engineers, surgeons, students and anyone interested in skin irritation and skin absorption.

With contributions by international experts in academia, chemical manufacturing, government research laboratories, regulatory agencies, and private consulting, this guide explores the potentially damaging influence of environmental agents on the endocrine system. It examines endocrine toxicology’s increased importance in environmental safety issues due to legislative directives established over the past ten years.Covering all principal areas of EPA concern, Endocrine Toxicology, Third Edition provides: putative endocrine disruptors and mechanisms of endocrine toxicity the history and status of the regulatory processmechanisms of toxic effects in various hormonal systemscomparisons of the endocrine responses in humans, livestock, and wildlifetesting methods in mammalian, fish, avian, and amphibian modelsvaluable insight into the approaches of various personnel in the field, including: government officials who make and oversee policy; scientists in charge of development and validation of testing methods; basic researchers who identify toxic mechanisms; and manufacturers responsible for environmentally benign product certification

This text presents a range of topics from the molecular events surrounding hormone actions to epidemiologic studies of the effects of environmental and occupational chemicals on reproductive organs. The endocrine systems covered include the adrenal cortex, thyroid and parathyroid, gonads, and the endocrine pancreas. Of particular importance are the chapters covering the general characteristics of the estrogen receptors and the androgen receptors. The book also describes some of the underlying toxic mechanisms involving pancreatic B cells and metal-induced changes in male sex accessory glands.

Many of the toxic effects elicited by xenobiotics can be explained at the molecular level by their interaction with receptors or by disruption or interference with receptor-mediated signal transduction pathways. This volume describes molecular approaches and reviews of current research. It provides reviews of numerous research areas which are directly related to the analysis of the molecular mechanism by which xenobiotics modulate signal transduction and gene expression.