ISSUES IN RISK ASSESSMENT -- Copyright -- Preface -- Contents -- Executive Summary -- USE OF THE MAXIMUM TOLERATED DOSE IN ANIMAL BIOASSAYS FOR CARCINOGENICITY -- THE TWO-STAGE MODEL OF CARCINOGENESIS -- A PARADIGM FOR ECOLOGIC RISK ASSESSMENT -- Issues In Risk Assessment Use Of Maximum Tolerated Dose in Animal Bioassays for Carcinogenicity -- 1 Introduction -- BACKGROUND -- SCOPE OF REPORT -- 2 Correlations Between Carcinogenic Potency and Other Measures of Toxicity -- DEFINITIONS AND BACKGROUND -- CORRELATIONS -- RELATIONSHIP BETWEEN TOXICITY AND CARCINOGENICITY OBSERVED AT MTD -- 3 Advantages and Disadvantages of Bioassays that Use the MTD -- QUALITATIVE INFORMATION -- QUANTITATIVE INFORMATION -- 4 Options Considered -- OPTION 1 -- OPTION 2 -- OPTION 3 -- OPTION 4 -- Option 4A -- Option 4B -- 5 Conclusions and Recommendations -- REFERENCES -- Appendix A Workshop Summary Maximum Tolerated Dose: Implications For Risk Assessment -- INTRODUTION -- BACKGROUND -- DEFINING AND DETERMINING THE MTD -- Appendix B Organizing Subcommittee -- Appendix C Federal Liaison Group -- Appendix D Workshop Program -- Appendix E Workshop Attendees -- Appendix F Correlation Between Carcinogenic Potency and the Maximum Tolerated Dose: Implications for Risk Assessment -- 1. INTRODUCTION -- 2. CARCINOGENIC POTENCY -- 2.1 Measures of Carcinogenic Potency -- 2.2 Carcinogenic Potency Database (CPDB) -- 2.3 Variation in Carcinogen Potency -- 2.4 Classification of Carcinogens -- 3. CORRELATION BETWEEN TD50 AND THE MTD -- 3.1 Empirical Correlations -- 3.2 Range of Possible TD50 Values -- 3.3 Analytical Correlations -- 3.4 Model Dependency -- 3.5 Genotoxic vs. Nongenotoxic Carcinogens -- 4. PREDICTION OF THE TD50 -- 4.1 Predictions Based on the MDT -- 4.2 Predictions Based on Mutagenicity and Acute Toxicity -- 5. LOW DOSE RISK ASSESSMENT.

5.1 Correlation Between Upper Bounds On the Low Dose Slope and MTD -- 5.2 Correlation Between q1* and the TD50 -- 5.3. Preliminary Estimate of Risk -- 6. INTERSPECIES EXTRAPOLATION -- 6.1 Extrapolation from Rats to Mice -- 6.2 Extrapolation from Rodents to Humans -- 7. CONCLUSIONS -- 8. ACKNOWLEDGEMENTS -- 9. REFERENCES -- ANNEX A: MAXIMUM LIKELIHOOD METHODS FOR FITTING THE WEIBULL MODEL -- ANNEX B. SHRINKAGE ESTIMATORS OF THE DISTRIBUTION OF CARCINOGENIC POTENCY -- ANNEX C: ADJUSTMENT OF POTENCY VALUES FOR LESS THAN LIFETIME EXPOSURE -- ANNEX D: CORRELATION BETWEEN TD50 AND MTD -- ANNEX E: CORRELATION BETWEEN TD50S FOR RATS AND MICE -- Appendix G Informal Search for ''Supercarcinogens" -- CRITERIA AND CANDIDATE CHEMICALS -- DATA -- RESULTS -- DISCUSSION -- Issues in Risk Assessment The Two-Stage Model Of Carcinogenesis -- The Two-Stage Model of Carcinogenesis -- INTRODUCTION -- BIOLOGIC CONSIDERATIONS -- THE TWO-STAGE MODEL -- APPLICATIONS OF THE TWO-STAGE MODEL TO ANIMAL DATA -- DISCUSSION -- Data Needs -- Criteria for Adoption -- Prospects -- CONCLUSIONS AND RECOMMENDATIONS -- REFERENCES -- Appendix A Workshop Summary -- TWO-STAGE MODEL OF CARCINOGENESIS -- BIOLOGICAL FACTORS IN TWO-STAGE MODELS -- TWO-STAGE MODEL OF CLONAL EXPANSION -- APPLICATION OF THE TWO-STAGE MODEL TO ANIMAL DATA -- Appendix B Workshop Program -- Appendix C Workshop Federal Liaison Group -- Appendix D Workshop Attendees -- TOPIC GROUP MEMBERS -- Appendix E Workshop Organizing Task Group -- Isuees In Risk Assessment A Paradigm for Ecological Risk Assessment -- 1 Introduction -- 2 Scope of Ecological Risk Assessment -- 3 Revision of 1983 Framework To Incorporate Ecological Risk Assessment -- COMPONENTS OF THE 1983 FRAMEWORK -- CONSISTENCY OF CASE STUDIES WITH THE 1983 FRAMEWORK -- INTEGRATION OF ECOLOGICAL RISK INTO THE 1983 FRAMEWORK.

DEFINITION OF FRAMEWORK COMPONENTS FOR ECOLOGICAL RISK ASSESSMENT -- 4 Key Scientific Problems Limiting Application of Ecological Risk Assessment -- EXTRAPOLATION ACROSS SCALES -- QUANTIFICATION OF UNCERTAINTY -- VALIDATION OF PREDICTIVE TOOLS -- VALUATION -- 5 Conclusions -- 6 Recommendations -- REFERENCES -- Appendix A Workshop Participants -- Appendix B Workshop Organizing Subcommittee and Federal Liaison Group -- Appendix C Workshop Introduction -- Appendix D Opening Plenary Presentations -- TERRY F. YOSIE BUILDING ECOLOGICAL RISK ASSESSMENT AS A POLICY TOOL -- D. WARNER NORTH: RELATIONSHIP OF WORKSHOP TO NRC'S 1983 RED BOOK REPORT -- MICHAEL SLIMAK: U.S. ENVIRONMENTAL PROTECTION AGENCY ACTIVITIES IN ECOLOGICAL RISK ASSESSMENT -- Appendix E Case Studies and Commentaries -- CASE STUDY 1: TRIBUTYLTIN RISK MANAGEMENT IN THE UNITED STATES -- Discussion -- CASE STUDY 2: ECOLOGICAL RISK ASSESSMENT FOR TERRESTRIAL WILDLIFE EXPOSED TO AGRICULTURAL CHEMICALS -- Discussion -- CASE STUDY 3A: MODELS OF TOXIC CHEMICALS IN THE GREAT LAKES: STRUCTURE, APPLICATIONS, AND UNCERTAINTY ANALYSIS -- CASE STUDY 3B: ECOLOGICAL RISK ASSESSMENT OF TCDD AND TCDF -- Discussion -- CASE STUDY 4: RISK ASSESSMENT METHODS IN ANIMAL POPULATIONS: THE NORTHERN SPOTTED OWL AS AN EXAMPLE -- Discussion -- CASE STUDY 5: ECOLOGICAL BENEFITS AND RISKS ASSOCIATED WITH THE INTRODUCTION OF EXOTIC SPECIES FOR BIOLOGICAL CONTROL OF A... -- Discussion -- CASE STUDY 1: UNCERTAINTY AND RISK IN AN EXPLOITED ECOSYSTEM: A CASE STUDY OF GEORGES BANK -- Discussion -- Appendix F Breakout Sessions -- HAZARD IDENTIFICATION -- Generic Issues -- Analysis of Case Studies -- DOSE-RESPONSE ASSESSMENT -- Aspects of An Adequate Stress-Response Analysis for Ecological Risk Assessment -- Selection of End Points -- Consideration of Nonlinearities And Discontinuities -- Expression of Uncertainty.

Understanding the Stressor -- Understanding the Response -- Other Considerations -- Additions to the 1983 Paradigm Needed for Ecological Risk Assessment -- Application of Stress-Response Analysis In Case Studies -- Modeling Needs for Stress-Response Relationships -- EXPOSURE ASSESSMENT -- Methods of Measuring Stressors for Ecological Exposure Assessment -- Test of the Definition -- RISK CHARACTERIZATION -- Definition of Risk Characterization -- Components of Risk Characterization -- Organization and Presentation -- Differences from and Similarities To the 1983 Report -- Application to the Case Studies -- MODELING -- Use of Models in the Case Studies -- Tributyltin -- Agricultural Chemicals -- Polychlorinated Biphenyls and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin -- Species Introductions -- Northern Spotted Owl -- Georges Bank Fishery -- General Discussion: Models and Risk Assessment -- UNCERTAINTY -- Uncertainties Identified In the Case Studies -- Implications of Uncertainty for Ecological Risk Assessment -- Recommendations for Dealing With Uncertainty -- VALUATION -- RISK ASSESSMENT AND THE REGULATORY PROCESS -- Risk Assessment Has Many Uses -- Different Risk Assessment Methods Are Suited to Different Risk Assessment Needs -- Risk Assessors and Risk Managers Need to Communicate -- Credibility is Crucial -- Appendix G Contemplations on Ecological Risk Assessment -- Appendix H Workshop Summary -- Appendix I References for Appendixes -- Appendix J Workshop Program.