Toxicity Testing -- Copyright -- PREFACE -- ACKNOWLEDGMENTS -- Contents -- EXECUTIVE SUMMARY -- SELECT UNIVERSE OF SUBSTANCES -- CHARACTERIZING TOXICITY-TESTING NEEDS -- QUANTITY AND NATURE OF TESTING -- QUALITY OF TESTING -- TOXICITY-TESTING NEEDS -- HEALTH-HAZARD ASSESSMENT -- INTERPRETATION OF PHYSICOCHEMICAL AND EXPOSURE DATA -- APPROACHES TO PRIORITY-SETTING -- INTRODUCTION -- THE NATIONAL TOXICOLOGY PROGRAM -- THE STUDY -- REFERENCES -- PART 1 TOXICITY-TESTING NEEDS IN THE SELECT UNIVERSE -- Contents -- 1 Introduction -- 2 Sample Selection -- THE UNIVERSE AND THE SAMPLING FRAME -- Pesticides and Inert Ingredients of Pesticide Formulations -- Cosmetic Ingredients -- Drugs and Excipients in Drug Formulations -- Food Additives -- Chemicals in Commerce -- CONSIDERATIONS IN DEVELOPING THE SAMPLING STRATEGY -- SAMPLING STRATEGY -- Sample Size -- Sampling Plan -- SCREENING THE SAMPLE FOR MINIMAL TOXICITY INFORMATION -- 3 Operating Policies for Identification, Acquisition, and Organization of Data -- RESTRICTED-ACCESS OR CONFIDENTIAL INFORMATION -- INFORMATION ON TOXICITY IN HUMANS -- CHEMICAL AND PHYSICAL CHARACTERISTICS, MANUFACTURING PROCESSES, PRODUCTION VOLUMES, INTENDED USES AND… -- CHEMICAL REVIEW ARTICLES -- ARTICLES IN FOREIGN LANGUAGES -- SUBSTANCES STRUCTURALLY SIMILAR TO THOSE IN THE SAMPLE -- 4 Data Evaluation -- THE DOSSIER CONCEPT -- GENERAL PRINCIPLES FOR EVALUATION OF TOXICITY-TESTING PROTOCOLS -- CONSIDERATION OF EXPOSURE -- PURITY OF SELECTED SUBSTANCES -- GUIDELINES FOR ASSESSING THE QUALITY OF INDIVIDUAL STUDIES -- Basic Criteria for Scientific Methods -- Selection of Reference Protocols -- Reference Protocol Guidelines for Neurobehavioral-Toxicity Tests -- Reference Protocol Guidelines for Genetic-Toxicity Tests -- PROCEDURES FOR EVALUATION OF THE DATA BASE -- Initial Considerations -- Adequacy Ratings.

Measures of Adequacy for Tests Not Meeting the Reference Protocol Guidelines -- Dossier Review Process -- LIMITATIONS OF THE DATA GATHERING PROCESS -- INTERPRETATION OF DATA ON TESTING QUALITY -- CHARACTERIZING THE SAMPLE AND OPTIONS FOR DRAWING INFERENCES TO THE SELECT UNIVERSE -- Construction of Tables for Analysis -- Statistical Analysis of Data -- Estimates Based on the Sample Alone -- Estimates Based on the Subsample Alone -- Estimates Based on Both the Sample and the Subsample -- MACHINE-READABLE FILES -- 5 Results -- QUANTITY AND NATURE OF TESTING -- Sample of 675 Substances -- Subsample of 100 Substances -- QUALITY OF TESTING -- TESTING NEEDS -- HEALTH-HAZARD ASSESSMENT -- INTERPRETATION AND ANALYSIS OF PHYSICOCHEMICAL AND EXPOSURE DATA -- 6 Summary and Conclusions -- REFERENCES -- Appendix A Sample of 675 Substances and Subsample of 100 Substances from the ''Select Universe'' -- Appendix B Testing for Various Situations of Chemical Use and General Exposure to Direct and Indirect and Indirect Food… -- Appendix C Testing for Various Situations of Chemical Use and General Exposure to Oral or Parenteral Drugs or Color… -- Appendix D Testing for Various Situations of Chemical Use and General Exposure to Inhalation and Veterinary Drugs (Legend… -- Appendix E Testing for Various Situations of Chemical Use and General Exposure to Cosmetics and Dermal, Vaginal-Rectal… -- Appendix F Testing for Various Situations of Chemical Use and General Exposure to Pesticides (Legend of symbols and… -- Appendix G Testing for Various Situations of Chemical Use and General Exposure to Other Marketable Chemicals (Legend of… -- Appendix H Reference Protocols for Toxicity Testing -- REFERENCES -- Appendix I Reference Protocol Guidelines for Neurobehavioral-Toxicity Tests -- PRINCIPLES AND DESCRIPTION OF TESTING FOR NEUROBEHAVIORAL EFFECTS.

DETERMINATION OF ADEQUACY OF NEUROBEHAVIORAL-TOXICITY TESTING -- REFERENCES -- Appendix J Reference Protocol Guidelines for Genetic-Toxicity Tests -- REFERENCE -- Appendix K Conceptual Issues Concerning the Interpretation of Results of Studies of Reproductive and Developmental Toxicity -- Appendix L Major Components of A Dossier -- SYNOPSIS -- Appendix M Procedures, Rationale, and Results of Data Identification and Acquisition -- TYPES OF DATA COLLECTED -- SOURCES OF DATA -- ACCESS TO DATA -- AUTOMATED STORAGE AND RETRIEVAL DATA BASES -- OTHER SOURCES -- NRC TOXICOLOGY INFORMATION CENTER (TIC) -- GOVERNMENT AGENCY FILES -- MANUFACTURERS, COMMERCIAL USERS, AND TRADE ORGANIZATIONS -- AVAILABILITY AND ROLE OF INFORMATION OTHER THAN TOXICITY DATA -- REFERENCES -- PART 2 SETTING PRIORITIES FOR TOXICITY TESTING -- 1 Introduction -- 2 Decision of the Priority-Setting System -- GOAL OF PRIORITY-SETTING -- CHEMICALS CONSIDERED -- STRUCTURE OF THE SYSTEM -- ANALYSIS OF INFORMATION -- Estimating Exposure -- Estimating Toxic Effects -- ASSESSMENT AND DECISION-MAKING -- DESIGN FACTORS -- Describing the Priority-Setting System -- Accuracy of Stages or Tests -- Measuring Performance -- Cost -- 3 Briefly Following a Chemical Through an Illustrative System -- STAGE 1 -- STAGE 2 -- STAGE 3 -- STAGE 4 -- 4 Detailed Description of the Operation of an Illustrative System -- INTRODUCTION -- ELEMENTS OF DESIGN -- Goal -- Universe -- Assessment -- Structure -- Rules for Selection -- Design Parameters -- STAGE 1 -- Exposure Data Elements -- Toxicity Data Elements -- Selection Rules -- STAGE 2 -- Exposure Data Elements -- Toxicity Data Elements -- Selection Rules -- STAGE 3 -- Exposure Data Elements -- Toxicity Data Elements -- Selection Rules -- STAGE 4 -- 5 Future Development, Implementation, and Refinement of the System -- DEVELOPMENT -- IMPLEMENTATION.

FURTHER REFINEMENT -- EVALUATION -- POSSIBLE NEW DATA ELEMENTS -- The Use of Surveys and Epidemiologic Information -- Developing Very-Low-Cost (VLC) Tests -- Random Sampling -- 6 Conclusions and Recommendations -- REFERENCES -- Appendix A Review of Selected Priority-Setting Systems -- NATIONAL TOXICOLOGY PROGRAM -- Chemical Nomination -- Evaluation of Nominated Chemicals -- Public Comment -- Peer Review -- Chemical Selection -- SEQUENTIAL TESTING FOR CHEMICAL RISK ASSESSMENT (ASTILL ET AL., 1981) -- A RANKING ALGORITHM FOR EEC WATER POLLUTANTS (BROWN ET AL., 1980) -- ESTIMATION OF TOXIC HAZARD--A DECISION TREE APPROACH (CRAMER ET AL.,1978) -- AN AUTOMATIC PROCEDURE FOR ASSESSING POSSIBLE CARCINOGENIC ACTIVITY OF CHEMICALS PRIOR TO TESTING (DEHN AND HELMES, 1974) -- TOXICOLOGICAL PRINCIPLES FOR THE SAFETY OF DIRECT FOOD ADDITIVES AND COLOR ADDITIVES USED IN FOOD (U.S.DEPARTMENT OF HEALTH -- RANKING OF ENVIRONMENTAL CONTAMINANTS FOR BIOASSAY PRIORITY (GORI, 1977) -- PRIORITY-SETTING OF TOXIC SUBSTANCES FOR GUIDING MONITORING PROGRAMS (KORNREICH ET AL., 1979) -- RANKING CHEMICALS FOR TESTING: A PRIORITY-SETTING EXERCISE UNDER THE TOXIC SUBSTANCES CONTROL ACT (NISBET, 1979) -- CHEMICAL SCORING SYSTEM DEVELOPMENT (ROSS AND LU, 1980) -- SELECTING PRIORITIES FROM LARGE SETS OF ALTERNATIVES: THE CASE OF TOXIC SUBSTANCES REGULATION (WILHELM, 1981) -- REFERENCES -- Appendix B Mathematical Modeling of the Priority-Setting Process and Resulting Decision Rules -- THE FORMAL MODEL -- Measuring Performance -- Budget Cost -- Minimizing Misclassification Cost -- The Pilot Model -- Comparison with Weinstein's Model -- RULES FOR CHOOSING CHEMICALS GENERATED BY THE MODEL -- SELECTION RULES FOR AN ILLUSTRATIVE PRIORITY-SETTING SYSTEM FOR CANCER -- REFERENCES -- Appendix C Expert Judgment and the Treatment of Uncertainty -- PROBABILITY JUDGMENTS.

USE OF PROBABILITIES IN DECISION-MAKING -- ELICITATION OF PROBABILITY JUDGMENTS -- QUALITY OF PROBABILITY JUDGMENTS -- IMPROVING THE QUALITY OF PROBABILITY JUDGMENTS -- REFERENCES -- Appendix D The Analysis of Structure-Activity Relationships in Selecting Potentially Toxic Compounds for Testing -- NONADDITIVITY -- CHEMICAL CLASSES RELATED TO HEALTH EFFECTS IN HUMANS -- REFERENCES -- Appendix E Costs of Misclassification -- Appendix F Differences Between Part 1 and Part 2.