Issues in risk assessment / Committee on Risk Assessment Methodology, Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council.

Format:

Book

Author/Creator:

National Research Council (U.S.). Committee on Risk Assessment Methodology.

Contributor:

National Research Council (U.S.). Board on Environmental Studies and Toxicology.

Language:

English

Subjects (All):

Health risk assessment.

Carcinogenicity testing.

Ecology.

Risk assessment.

Environmental health.

Physical Description:

1 online resource (374 p.)

Edition:

1st ed.

Place of Publication:

Washington, DC : National Academy Press, 1993.

Language Note:

English

Summary:

The scientific basis, inference assumptions, regulatory uses, and research needs in risk assessment are considered in this two-part volume. The first part, Use of Maximum Tolerated Dose in Animal Bioassays for Carcinogenicity, focuses on whether the maximum tolerated dose should continue to be used in carcinogenesis bioassays. The committee considers several options for modifying current bioassay procedures. The second part, Two-Stage Models of Carcinogenesis, stems from efforts to identify improved means of cancer risk assessment that have resulted in the development of a mathematical dose-response model based on a paradigm for the biologic phenomena thought to be associated with carcinogenesis.

Contents:

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

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

Data Needs

Criteria for Adoption

Prospects

CONCLUSIONS AND RECOMMENDATIONS

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

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

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

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

CASE STUDY 4: RISK ASSESSMENT METHODS IN ANIMAL POPULATIONS: THE NORTHERN SPOTTED OWL AS AN EXAMPLE

CASE STUDY 5: ECOLOGICAL BENEFITS AND RISKS ASSOCIATED WITH THE INTRODUCTION OF EXOTIC SPECIES FOR BIOLOGICAL CONTROL OF A...

CASE STUDY 1: UNCERTAINTY AND RISK IN AN EXPLOITED ECOSYSTEM: A CASE STUDY OF GEORGES BANK

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

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.

Notes:

Bibliographic Level Mode of Issuance: Monograph

Includes bibliographical references.

ISBN:

9786610211586

9781280211584

128021158X

9780309584906

0309584906

9780585025476

0585025479

OCLC:

42329150