Front Cover -- A Comprehensive Guide to Toxicology in Preclinical Drug Development -- Copyright -- Dedication -- Contents -- Foreword -- Contributors -- Chapter 1 - Introduction -- Chapter 2 - ADME in Drug Discovery -- INTRODUCTION -- ADME -- USE OF PRECLINICAL ADME DATA -- TWO EVOLVING TECHNOLOGIES IMPACTING ADME IN DRUG DISCOVERY -- References -- Chapter 3 - Pharmacokinetics and Toxicokinetics -- INTRODUCTION -- DRUG ADMINISTRATION AND DELIVERY -- INTRAVENOUS ADMINISTRATION -- ABSORPTION AFTER EXTRAVASCULAR DOSING -- CALCULATION OF EXPOSURE-BASED SAFETY MARGINS -- PRACTICAL CONSIDERATIONS -- CONCLUSIONS -- References -- Chapter 4 - Development of Preclinical Formulations for Toxicology Studies -- INTRODUCTION -- ANIMAL SPECIES, SAMPLING VOLUMES AND SAMPLING SITES -- DOSING ROUTE -- DOSING VOLUME -- FORMULATION DEVELOPMENT -- PHYSICO-CHEMICAL PROPERTY CHARACTERIZATION -- SOLUBILITY ENHANCEMENT -- SPECIAL DOSAGE FORMS -- DECISION TREE -- IN VITRO EVALUATION OF THE PERFORMANCE OF A TOXICOLOGICAL STUDY -- CASE STUDY -- CONCLUDING REMARKS -- References -- Chapter 5 - Acute, Sub-Acute, Sub-Chronic and Chronic General Toxicity Testing for Preclinical Drug Development -- INTRODUCTION -- REGULATORY CONSIDERATIONS FOR CONDUCTING PRECLINICAL TOXICOLOGY STUDIES -- GENERAL CONSIDERATIONS FOR THE CONDUCT OF PRECLINICAL TOXICOLOGY STUDIES -- STUDY TYPES USED IN THE ASSESSMENT OF GENERAL TOXICOLOGY -- SPECIAL CONSIDERATIONS FOR BIOPHARMACEUTICAL SAFETY EVALUATIONS -- COMMON PROTOCOL COMPONENTS OF GENERAL TOXICITY ASSESSMENTS IN GLP STUDIES -- FINAL THOUGHTS -- References -- Chapter 6 - Contemporary Practices in Core Safety Pharmacology Assessments -- BACKGROUND AND OVERVIEW -- SAFETY PHARMACOLOGY AS A REGULATORY SCIENCE -- TEMPORAL APPLICATION OF CURRENT EXPERIMENTAL PARADIGMS -- CARDIOVASCULAR SYSTEM AND MODELS OF SAFETY ASSESSMENT.

CARDIAC ION CHANNELS AND THE HERG ASSAY -- IN VIVO CARDIOVASCULAR SAFETY STUDY -- RESPIRATORY SYSTEM AND MODELS OF SAFETY ASSESSMENT -- CENTRAL NERVOUS SYSTEM AND MODELS OF SAFETY ASSESSMENT -- APPROACHES TO TIER I CNS SAFETY EVALUATION -- EVALUATING CNS SAFETY -- References -- Chapter 7 - Genetic Toxicology Testing -- INTRODUCTION -- THE CONCEPT OF THRESHOLDS -- GENETIC TOXICITY TESTING TO SUPPORT CLINICAL TRIALS -- THE SENSITIVITY AND SPECIFICITY OF IN VITRO ASSAYS -- IN VIVO CORE TESTS -- OTHER IN VIVO TESTS FOR GENOTOXICITY -- ADDITIONAL TESTS INDICATING GENOTOXICITY -- GENETOX TESTING STRATEGY: DISCOVERY THROUGH DEVELOPMENT -- CONCLUDING REMARKS AND FUTURE DIRECTIONS -- References -- Chapter 8 - Clinical Pathology -- INTRODUCTION -- CORE CLINICAL PATHOLOGY TESTING -- HEMATOLOGY -- CYTOLOGICAL EVALUATION OF BONE MARROW -- EMERGING BIOMARKERS AND APPLICATION WITHIN THE CLINICAL PATHOLOGY LABORATORY -- CLINICAL PATHOLOGY INDICATORS OF TARGET ORGAN TOXICITY -- INTERPRETATION OF CLINICAL PATHOLOGY DATA IN PRECLINICAL SAFETY STUDIES -- References -- Chapter 9 - Best Practice in Toxicological Pathology -- INTRODUCTION -- HISTOPATHOLOGY PROCESSES AND PROCEDURES -- HISTOPATHOLOGICAL EXAMINATION -- INTERPRETATION OF PATHOLOGY DATA AND PATHOLOGY REPORT -- ADVERSE AND NON-ADVERSE FINDINGS -- SPONTANEOUS AND INDUCED HISTOPATHOLOGICAL LESIONS IN PRECLINICAL STUDIES -- RISK ASSESSMENT -- References -- Suggested Further Reading for Comprehensive Toxicological Pathology -- Chapter 10 - Molecular Pathology: Applications in Nonclinical Drug Development -- INTRODUCTION -- IMMUNOHISTOCHEMISTRY -- BIOMARKERS: BEST PRACTICES FOR PATHOLOGY EVALUATION -- DIGITAL PATHOLOGY IMAGING -- TOXICOGENOMICS -- MICRORNAS -- CONCLUSION -- References -- Chapter 11 - Infusion Toxicology and Techniques -- INTRODUCTION -- PRECLINICAL INFUSION MODELS -- REGULATORY GUIDELINES.

CHOOSING THE APPROPRIATE INFUSION MODEL -- INFUSION BEST PRACTICES -- INFUSION TECHNIQUES -- EQUIPMENT -- BACKGROUND DATA - RESULTANT PATHOLOGIES -- CONCLUDING REMARKS -- References -- Chapter 12 - The Preparation of a Preclinical Dossier to Support an Investigational New Drug (IND) Application and First-in ... -- INTRODUCTION -- THE DRUG DEVELOPMENT PIPELINE -- PRESENTATION OF THE NONCLINICAL PACKAGE -- ESTABLISHING THE CLINICAL SAFETY OF A NEW DRUG CANDIDATE -- SUMMARY AND CONCLUSIONS -- References -- Chapter 13 - Developmental and Reproductive Toxicology -- OVERVIEW AND HISTORY OF REPRODUCTIVE TESTING GUIDELINES -- STUDY DESIGNS -- EVALUATING FERTILITY AND REPRODUCTION -- EMBRYO-FETAL DEVELOPMENT -- PRE- AND POST-NATAL DEVELOPMENT STUDIES -- TOXICOKINETICS -- DEVELOPMENTAL TOXICITY TESTING OF BIOPHARMACEUTICALS IN RODENTS AND RABBITS -- REPRODUCTIVE AND DEVELOPMENTAL ASSESSMENTS IN NON-HUMAN PRIMATES -- ALTERNATIVE METHODS USED IN REPRODUCTIVE AND DEVELOPMENTAL TOXICITY TESTING -- CONCLUDING REMARKS AND FUTURE DIRECTIONS -- References -- Chapter 14 - Immunotoxicology Assessment in Drug Development -- HISTORY AND CURRENT REGULATORY FRAMEWORK FOR IMMUNOTOXICOLOGY TESTING -- DEVELOPMENTAL IMMUNOTOXICOLOGY -- EVALUATION OF HUMORAL IMMUNITY -- EVALUATION OF INNATE IMMUNITY -- EVALUATION OF CELL-MEDIATED IMMUNITY -- INTERPRETATION OF IMMUNOTOXICOLOGY DATA -- CONCLUDING REMARKS AND FUTURE DIRECTIONS -- References -- Chapter 15 - Juvenile Toxicity Testing to Support Clinical Trials in the Pediatric Population -- INTRODUCTION -- APPROACHES TO STUDY DESIGNS -- GENERAL DESIGN CONSIDERATIONS -- DATA INTERPRETATION -- VALUE OF JUVENILE TOXICITY STUDIES -- CASE STUDY #1 - NEONATAL SWINE MODEL FOR INFANT FORMULA TESTING -- CASE STUDY #2 INFLUENCE OF PERINATAL METABOLISM AND STAGE OF ORGAN DEVELOPMENT IN RATS -- References.

Chapter 16 - Photosafety: Current Methods and Future Direction -- REGULATORY STATUS -- DOSIMETRY -- LIGHT SOURCES -- SPECTRAL ABSORPTION -- REACTIVE OXYGEN SPECIES -- THE IN VITRO 3T3 NEUTRAL RED UPTAKE PHOTOTOXICITY TEST -- IN VITRO PHOTOGENOTOXICITY -- RECONSTRUCTED SKIN EPIDERMIS SYSTEMS -- GENERAL IN VIVO TECHNIQUES -- EVALUATION OF IN VIVO PHOTOTOXIC RESPONSES -- THE MOUSE -- PHOTOCARCINOGENESIS -- THE GUINEA PIG -- THE RAT -- THE RABBIT -- THE PIG -- References -- Chapter 17 - Preclinical Evaluation of Carcinogenicity using the Rodent Two-Year Bioassay -- INTRODUCTION -- THE CHRONIC CARCINOGENICITY BIOASSAY IN STANDARD-BRED RODENTS -- References -- Chapter 18 - Carcinogenicity Evaluations using Genetically Engineered Animals -- INTRODUCTION -- DEVELOPMENT AND VALIDATION OF GENETICALLY ENGINEERED MOUSE MODELS FOR USE IN CARCINOGENICITY TESTING -- DESIGN OF CARCINOGENICITY STUDIES IN GENETICALLY ENGINEERED MICE -- CONCLUSIONS -- References -- Chapter 19 - Current Strategies for Abuse Liability Assessment of New Chemical Entities -- INTRODUCTION -- EXPERIMENTAL PROTOCOLS -- REGULATORY GUIDELINES -- SELF-ADMINISTRATION -- DRUG DISCRIMINATION -- DRUG DEPENDENCE LIABILITY -- IDENTIFICATION OF DISCONTINUATION SYNDROME -- References -- Chapter 20 - Impact of Product Attributes on Preclinical Safety Evaluation -- INTRODUCTION -- SAFETY EVALUATION -- SAFETY PHARMACOLOGY -- DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY -- GENOTOXICITY -- CARCINOGENICITY AND TUMORIGENICITY -- IMMUNOTOXICITY -- DRUG INTERACTION ASSESSMENT -- FIRST-IN-HUMAN DOSE SELECTION -- CONCLUSION -- References -- Chapter 21 - Preclinical Development of Monoclonal Antibodies -- INTRODUCTION -- HISTORY OF ANTIBODY THERAPEUTICS: THE DISCOVERY OF SERUM THERAPY -- ANTIBODY STRUCTURE AND FUNCTION -- NOMENCLATURE OF MONOCLONAL ANTIBODIES -- PRECLINICAL DEVELOPMENT OF MONOCLONAL ANTIBODIES.

NONCLINICAL SAFETY EVALUATION/TOXICOLOGY PLANS TO SUPPORT THE FIRST-IN-HUMAN (FIH) STUDY -- DOSE SELECTION FOR THE FIH STUDY -- REPEAT-DOSE TOXICOLOGY STUDIES BEYOND FIH -- IMMUNOGENICITY OF MONOCLONAL ANTIBODIES -- IMMUNOTOXICITY -- REPRODUCTIVE AND DEVELOPMENTAL TOXICITY EVALUATION -- CARCINOGENICITY -- DRUG INTERACTIONS -- PARTNERSHIP IN MAB DEVELOPMENT -- SUMMARY -- References -- Chapter 22 - Preclinical Development of Non-Oncogenic Drugs (Small and Large Molecules) -- INTRODUCTION -- PRECLINICAL DEVELOPMENT OF SMALL MOLECULES -- PHARMACOKINETICS AND TOXICOKINETICS -- TOXICITY STUDIES -- SAFETY EVALUATION OF IMPURITIES AND DEGRADANTS IN NEW DRUG PRODUCTS -- CONSIDERATIONS FOR THE CONDUCT OF JUVENILE ANIMAL TOXICITY STUDIES -- SPECIAL TOXICOLOGY STUDIES -- PRECLINICAL DEVELOPMENT OF BIOTECHNOLOGY-DERIVED PHARMACEUTICALS (LARGE MOLECULES) -- PRECLINICAL SAFETY TESTING OF BIOTECHNOLOGY-DERIVED PHARMACEUTICALS -- References -- Chapter 23 - Preclinical Development of Oncology Drugs -- INTRODUCTION -- CYTOTOXIC VS. TARGETED DRUGS -- PHARMACOLOGY EVALUATION -- TRANSLATIONAL MEDICINE -- PHARMACOKINETIC AND PHARMACODYNAMIC MODELING -- TOXICOLOGY EVALUATION -- DRUG METABOLISM AND PHARMACOKINETICS (DMPK) -- OTHER CONSIDERATIONS: CHANGES IN ROUTE OR FORMULATION -- References -- Chapter 24 - Safety Evaluation of Ocular Drugs -- INTRODUCTION -- STRUCTURE AND FUNCTION OF THE EYE -- PHARMACOKINETICS AND DRUG DISPOSITION IN THE EYE -- REGULATORY CONSIDERATIONS IN OCULAR SAFETY ASSESSMENT -- PRACTICAL CONSIDERATIONS IN ASSESSING OCULAR SAFETY -- TECHNIQUES FOR IN-LIFE OCULAR EVALUATION -- HISTOPATHOLOGY -- EXAMPLES OF ADVERSE EFFECTS IN THE EYE -- INTEGRATED ASSESSMENT OF OCULAR SAFETY -- References -- Chapter 25 - Preclinical Toxicology of Vaccines1 -- INTRODUCTION TO VACCINES/ADJUVANTS FOR THE PREVENTION OF INFECTIOUS DISEASES -- SPECIAL TOPICS.

TOXICITIES ASSOCIATED WITH VACCINES.