THE KEY TO SIGHT TESTING

By EMMA TAYLOR

CONTENTS SUMMARY INTRODUCTION HISTORICAL PERSPECTIVE OF REGULATORY TOXICOLOGY, RISK ASSESSMENT, THE COMMITTEE’S FIRST TASK AND KEY POINTS FROM ITS INTERIM REPORT, THE COMMITTEE’S SECOND TASK AND APPROACH, ORGANIZATION OF THE REPORT, REFERENCES, VISION LIMITATIONS OF CURRENT TESTING STRATEGIES, DESIGN CRITERIA FOR A NEW TOXICITY-TESTING PARADIGM, OPTIONS FOR A NEW TOXICITY-TESTING PARADIGM, OVERVIEW OF COMMITTEE’S LONG-RANGE VISION FOR TOXICITY TESTING, COMPONENTS OF THE VISION COMPONENT A: CHEMICAL CHARACTERIZATION, COMPONENT B: TOXICITY TESTING OF COMPOUNDS AND METABOLITES, COMPONENT C: DOSE-RESPONSE AND EXTRAPOLATION MODELING, COMPONENT D: POPULATION-BASED AND HUMAN EXPOSURE DATA, COMPONENT E: RISK CONTEXTS, TOXICITY-TESTING STRATEGIES IN PRACTICE, TOXICITY TESTING AND RISK ASSESSMENT, TOOLS AND TECHNOLOGIES TOOLS AND TECHNOLOGIES FOR CHEMICAL CHARACTERIZATION, MAPPING TOXICITY PATHWAYS, TOOLS AND TECHNOLOGIES FOR DOSE-RESPONSE AND EXTRAPOLATION MODELING, DEVELOPING THE SCIENCE BASE AND ASSAYS TO IMPLEMENT THE VISION SCOPE OF SCIENTIFIC KNOWLEDGE, METHODS, AND ASSAY DEVELOPMENT, STRATEGY FOR KNOWLEDGE AND ASSAY DEVELOPMENT AND VALIDATION, BUILDING A TRANSFORMATIVE RESEARCH PROGRAM, CONCLUDING REMARKS, PREREQUISITES FOR IMPLEMENTING THE VISION IN REGULATORY CONTEXTS INSTITUTIONAL CHANGE TO MEET THE VISION, REGULATORY USE OF NEW METHODS, SUMMARY CHANGE OFTEN INVOLVES A PIVOTAL EVENT THAT BUILDS ON PREVIOUS HISTORY AND OPENS THE DOOR TO A NEW ERA PIVOTAL EVENTS IN SCIENCE INCLUDE THE DISCOVERY OF PENICILLIN, THE ELUCIDATION OF THE DNA DOUBLE HELIX, AND THE DEVELOPMENT OF COMPUTERS ALL WERE MARKED BY INAUSPICIOUS BEGINNINGS FOLLOWED BY UNHERALDED AD- VANCES OVER A PERIOD OF YEARS BUT ULTIMATELY RESULTED IN A PHARMA- COPOEIA OF LIFE-SAVING DRUGS, A MAP OF THE HUMAN GENOME, AND A PERSONAL COMPUTER ON ALMOST EVERY DESK IN TODAY’S WORKPLACE TOXICITY TESTING IS APPROACHING SUCH A SCIENTIFIC PIVOT POINT IT IS POISED TO TAKE ADVANTAGE OF THE REVOLUTIONS IN BIOLOGY AND BIO- TECHNOLOGY ADVANCES IN TOXICOGENOMICS, BIOINFORMATICS, SYSTEMS BIOLOGY, EPIGENETICS, AND COMPUTATIONAL TOXICOLOGY COULD TRANS- FORM TOXICITY TESTING FROM A SYSTEM BASED ON WHOLE-ANIMAL TESTING TO ONE FOUNDED PRIMARILY ON IN VITRO METHODS THAT EVALUATE CHANGES IN BIOLOGIC PROCESSES USING CELLS, CELL LINES, OR CELLULAR COMPONENTS, PREFERABLY OF HUMAN ORIGIN ANTICIPATING THE IMPACT