Principles of Toxicology Testing

The evolution of toxicology testing finds its impetus in the continuing growth of the chemical and pharmaceutical industries, as well as the awareness of public health initiatives, needs, and responses that demand faster, more accurate, more economical methods for screening potential toxicity. Concurrent advances in biotechnology enable viable in vitro systems to compliment traditional animal toxicology testing methods. Today, both methods are often employed together in toxicological analysis, derivation of toxicity mechanisms, and pre-clinical drug development. Principles of Toxicology Testing juxtaposes the principles of animal toxicology testing with in vitro alternative methods to highlight the importance of each for interpretation of the significance and relevance of the other. Divided into three parts, the book emphasizes the universal applications of the field as a science rather than the particular steps of laboratory technique. The first part introduces the fundamentals of the toxicology, toxicokinetics, and human risk assessment. The second part details toxicology testing in animals and describes acute, subchronic, and chronic studies as well as testing for mutagenicity and carcinogenicity. Focusing on study design and determination of classical indicators, it covers short and long term methodologies including dermal, ocular, and reproductive. Presenting the advantages and disadvantages of each method, part three introduces in vitro alternative testing such as cell cultures, cellular methods for acute systemic toxicity, as well as target organ and local toxicity. The author also considers contemporary issues such as chemical exposure, high throughput screening, and the efforts of US and E.U. regulatory agencies to standardize and validate in vitro techniques. By bringing traditional and alternative testing methods into a single volume, Principles of Toxicology Testing challenges you to interpret the significance of toxicology testing results and construct a logical approach toward the ultimate purpose of testing.

Table of Contents:
Basic Concepts in Toxicology Testing Introduction to Principles of Toxicology Types of Toxicology Common Terms and Nomenclature Applications of Toxicology Classification of Toxic Agents Sources of Toxins Effects of Chemicals Toxicological Effects Biochemical Properties Exposure Chemical Interactions Dose-Response Relationship Toxicokinetics Absorption Distribution Biotransformation Elimination Risk Assessment and Regulatory Toxicology Risk Assessment Regulatory Toxicology Descriptive Animal Toxicology Tests Correlation with Human Exposure Animal Welfare and U.S. Animal Welfare Act Chemicals Species Differentiation Methodologies Toxicology Testing In Vivo Acute Toxicology Testing Objectives of Acute Toxicology Tests LD50 and Acute Toxicology Tests Organization of Studies Range-Finding Tests Classical LD50 Other Considerations with LD50 Determinations Applications of LD50 Studies Subchronic and Chronic Toxicology Testing Types or Subchronic and Chronic Toxicity Tests Experimental Design Acute Dermal and Ocular Toxicology Testing Acute Dermal Toxicity Tests Acute Ocular Toxicity Tests Toxicology Testing for Fertility and Reproduction History and Development of Teratogenicity Testing Brief Description of Maternal-Fetal Physiology Mechanisms of Developmental Toxicity Teratogenicity Embryotoxicity Male Reproductive Toxicology Female Reproductive Toxicology Carcinogenicity and Mutagenicity Testing in Vivo Introduction and Definitions Multistage Carcinogenesis Carcinogenic and Genotoxic Agents Carcinogenicity Testing in Vivo Bioassay Protocols for in Vivo Carcinogenicity Testing Mutagenicity Testing in Vivo Toxicology Testing In Vitro Introduction to In Vitro Toxicology Testing History of in Vitro Methods In Vitro Systems History of Cell Culture Cell Culture Methodology Cell Culture Laboratory Cultured Cells Culture Requirements Procedures Cell Culture Methods for Acute Toxicology Testing Acute Target Organ Toxicity Testing Acute Local Toxicology Testing Toxicokinetic Studies in Vitro Metabolic Studies in Cell Culture Mutagenicity Testing in Vitro Bacterial Cell Systems Mammalian Cell Systems Development of Short-Term Test Strategies Reproductive and Teratogenicity Studies In Vitro Alternative Methods for Embryotoxicity Testing Validation of Alternative Methods for Reproductive and Teratogenicity Studies High Throughput Screening and Microarray Analysis High Throughput Screening in Preclinical Drug Testing Microarray Systems Experimental Design and Statistics Establishing Experimental Plan Experimental Design Hypothesis Testing and Statistical Applications Standardization and Validation of Alternative Methods Introduction Validation Process Current Validation Programs Applications of Alternative Models for Toxicology Testing Introduction Significance of Alternative Models for Animal Toxicology Testing Extrapolation to Human Toxicity Use of Alternative Methods for Human and Animal Toxicology Index