Acute Toxicology Testing Perspectives and Horizons

INTRODUCTION. OLDEST AND MOST COMMON TESTS. QUESTIONS OF RELEVANCE AND SENSITIVITY. DEFINING TEST OBJECTIVES. USE OF SCREENS IN TOXICOLOGICAL RESEARCH: THEORY AND PRACTICE. INNOVATIONS AND ALTERNATIVES: RATIONALE. ACUTE TOXICOLOGY PROGRAM: STUDY DESIGN AND DEVELOPMENT. THE HAZARD/TOXICITY PROFILE. TIER TESTING. BATTERIES. TEST SELECTION AND DESIGN. TESTS FOR DERMAL IRRITATION AND CORROSION. HISTORY AND OVERVIEW. DERMAL IRRITATION. Primary Dermal Irritation (PDI) in Rabbits. Design Alternatives and Innovations. In Vitro Alternatives. DERMAL CORROSIVITY. DESIGN ALTERNATIVES AND INNOVATIONS. PERCUTANEOUS ABSORPTION. OCULAR IRRITATION TESTING. HISTORY OF OCULAR IRRITATION TESTING. ACUTE EYE IRRITATION TESTS IN RABBITS. Adequacy and Limitations of Current In Vivo Methods. PRESCREENS AND IN VIVO ALTERNATIVES. OVERVIEW OF IN VIVO ALTERNATIVES. DERMAL SENSITIZATION. MECHANISMS. OBJECTIVES AND GENERAL FEATURES OF TESTS. HISTORY. BUEHLER TEST. GUINEA PIG MAXIMIZATION TEST (GPMT). GUINEA PIG SPLIT ADJUVANT TEST. MOUSE EAR SWELLING TEST (MEST). TEST SYSTEM MANIPULATION. PRACTICAL PROBLEMS AND SOLUTIONS. POTENCY PREDICTIONS. IN VITRO ALTERNATIVES. PHOTOSENSITIZATION/PHOTOTOXICITY. THEORY, MECHANISMS AND HISTORY. FACTORS INFLUENCING PHOTOTOXICITY/PHOTOSENSITIZATION. PREDICTIVE IN VIVO TESTS FOR PHOTOTOXICITY. PREDICTIVE IN VIVO TESTS FOR PHOTOSENSITIZATION. IN VITRO TEST SYSTEMS. LETHALITY TESTING. HISTORICAL PERSPECTIVE. PROTOCOL DESIGNS. Classical Designs. Dose Probe Designs. Up-and-Down Method. Pyramiding Studies. Limit Tests. Fixed Dose Procedure. Quality Control Screens. USING LETHALITY DATA IN SAFETY ASSESSMENT-THE MLD. ALTERNATIVES TO LETHALITY TESTING. SAFETY CONSIDERATIONS FOR THE ADMINISTRATION OF AGENTS BY THE PARENTERAL ROUTES. PARENTERAL ROUTES AND RATES. Intravenous. Subcutaneous. Intramuscular. Considerations of Bolus vs. Infusion. TEST SYSTEMS. Irritation (IV, IM & SC). Pyrogenicity. Blood Compatibility. IN VITRO ALTERNATIVES. ACUTE SYSTEMIC TOXICITY TESTS. INTRODUCTION. SCREENS. ACUTE SYSTEMIC TOXICITY CHARACTERIZATION. TESTING WITH NONRODENT SPECIES. ACUTE MECHANISTIC STUDIES. ROUTES, FORMULATIONS AND VEHICLES. MECHANISMS OF ABSORPTION AND DISTRIBUTION OF MAJOR AND MINOR ROUTES. COMPARISONS AND CONTRASTS. GAVAGING TECHNIQUE. VEHICLES AND FORMULATION OF MATERIALS. DOSING CALCULATIONS. CONSIDERATIONS SPECIFIC TO ANIMAL TEST MODELS. COMMON MODEL SPECIES AND THEIR CHARACTERISTICS. CROSS SPECIES EXTRAPOLATION. MODEL SELECTION. LIMITATIONS OF MODELS. SUSCEPTIBILITY FACTORS. SPECIES PECULIARITIES. STRAIN DIFFERENCES. ANIMAL CARE, HUSBANDRY & WELFARE. STATISTICAL ANALYSIS FOR ACUTE TOXICOLOGY. BASIC CONCEPTS. SIGNIFICANCE AND ERROR. FUNCTIONS OF STATISTICS. EXPERIMENTAL DESIGN. RANDOMIZATION & TRANSFORMS. TESTING FOR SIGNIFICANCE. REGRESSION AND MODELING. APPLICATIONS IN TOXICOLOGY. SPECIAL CASE OF SCREENING. ACUTE INHALATION. GENERAL PRINCIPLES. BASICS OF RESPIRATORY PHYSIOLOGY. MECHANICS OF EXPOSURE. INHALATION DOSIMETRY OF COMMON SPECIES. COMMON TEST DESIGNS. PROBLEMS AND ISSUES. USE OF AVAILABLE INFORMATION SOURCES. CONSIDERATIONS IN ADOPTING NEW TEST SYSTEMS. VALIDATION OF ALTERNATIVE AND NEW TESTS. SAR MODELS. SAFETY FACTORS, POTENCY PREDICTORS AND PROTECTING SOCIETY. MIXTURES. SPECIAL CASES: Military Agents. Combustion Toxicology. Medical Devices. Polymers-Special Issues. APPENDICES. REGULATORY ACRONYMS. MOVING AVERAGE TABLES. VEHICLES. DEFINITION OF TERMS AND LEXICON OF CLINICAL OBSERVATIONS. INDEX. 1988, ISBN 0-936923-0607.

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Biography

Shayne C. Gad, Christopher P. Chengelis