Toxicologic Biomarkers PDF

Preface

Biomarkers can be broadly defined as indicators of processes, events, or changes in a biological system. This definition implies that biomarkers have the ability to reflect, predict, or take the place of biological endpoints that cannot be easily or directly measured or that take extended periods of time to become apparent.While physiological measurements that can be classified as biomarkers have been performed to some extent for many years, only recently has there been an explosion of interest in the development and application of biomarkers for specific health and disease endpoints. This interest has been driven primarily by the emerging needs of two separate disciplines, i.e., environmental epidemiology and commercial development of new bioactive compounds. In environmental epidemiology, biomarker science has evolved in large part from the recognition that ‘‘classical'' epidemiology may not be able to solve critical questions regarding causation of inherited or environmentally induced disease and that sensitive and valid markers of exposure, effect, and susceptibility are crucial to this process. For product development, interest in biomarkers has accelerated as the direct result of the requirement to more efficiently, rapidly, and economically evaluate and screen new chemical entities. (e.g., pesticides and drugs) intended for the marketplace. In addition, the potential application of biomarkers has recently been expanded to other diverse areas, such as personal injury litigation and chemical/biological warfare defense.

In theory, anything that one can measure in an organism can represent a marker for some biological event or process. Unfortunately, this definition is so expansive that it could easily encompass the majority of topics in biology and medicine and would be impossible to cover in a single text. Consequently, Toxicologic Biomarkers restricts its theme to indicators of adverse effects or outcomes in humans, which is the primary focus of the science of toxicology and which is relevant to many other fields, including pharmacology and epidemiology. Within this theme the book has a broad scope of coverage. Such breadth is important, since these are multidisciplinary fields which impact many basic and applied sciences. In addition to these major topics, the application of toxicologic biomarkers in several important specialized areas is also covered. Despite the often very different rationale for employing biomarkers across various disciplines, general approaches to their development and interpretation share many commonalities. For example, progress in biomarker discovery has been enabled to a great degree by major technical advances in bioanalytical chemistry and molecular genetics. Methods for biomarker quantitation, regardless of their ultimate application, frequently involve similar analytical techniques, such as microarraybased genomics, mass spectrometry, immunoassay, or cytogenetic analysis. Other issues, including validation and appropriate statistical analysis of biomarker data, are cross-cutting and impact the potential use of such data in all areas.

Toxicologic Biomarkers presents a comprehensive view of the theory, development, and practical application of biomarkers in toxicology and related professional and scientific fields. The book consists of a series of stand-alone chapters, each of which addresses the significance of biomarkers to a specific area. In addition, several chapters address relevant issues common to biomarkers in general. This approach allows readers to easily determine which chapter(s) would be of primary interest for their particular purpose. The differing focus and authorship of each chapter also serves to provide a unique perspective on each specific area covered. The intended audience for Toxicologic Biomarkers includes pharmaceutical and chemical product development scientists, regulatory managers, epidemiologists, faculty and students in toxicology, risk assessment, and environmental health, lawyers, physicians and clinical laboratory scientists, and anyone else with either a broad-based interest in or a need for discipline-specific information on biomarkers.