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Issues in Risk Assessment (1993)
Commission on Life Sciences (CLS)

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. "EXTRAPOLATION ACROSS SCALES." Issues in Risk Assessment. Washington, DC: The National Academies Press, 1993.

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Issues in Risk Assessment

4
Key Scientific Problems Limiting Application of Ecological Risk Assessment

EXTRAPOLATION ACROSS SCALES

The most common scientific limitation exemplified in the case studies is the problem of extrapolating across scales of space, time, and ecological organization. For the most part, scientific data related to a specific stressor are limited to what can be obtained in a controlled laboratory setting or in a limited field study. Observations of environmental contamination and ecological effects of tributyltin were limited to a few marinas. Testing of pesticides even in the best of circumstances is limited to small field plots and carefully controlled applications. Table 4-1 shows, for all the case studies, the scales at which the data used in the assessments were collected and the scales of interest in decision-making. In most cases, the scales of interest in decision-making are substantially larger in space and of longer duration than could be accommodated in any practical assessment effort. Some form of extrapolation, either with explicit mathematical models or with judgment-based decision rules, is necessary to make the risk assessments useful for decision-making. The PCB study discussed by Di Toro (Appendix E) clearly illustrated the value of explicit models for estimating recovery times in response to hypothetical management actions. In the pesticide registration process described by Kendall (Appendix E), extrapolation is based primarily on qualitative evaluation of test data and information on expected use patterns. Kendall argued that models of ecological effects of pesticides are needed to reduce uncertainty and to account for effects

Page
259
Front Matter (R1-R18)
Executive Summary (1-2)
USE OF THE MAXIMUM TOLERATED DOSE IN ANIMAL BIOASSAYS FOR CARCINOGENICITY (3-8)
THE TWO-STAGE MODEL OF CARCINOGENESIS (9-9)
A PARADIGM FOR ECOLOGIC RISK ASSESSMENT (10-12)
Issues In Risk Assessment Use Of Maximum Tolerated Dose in Animal Bioassays for Carcinogenicity (13-14)
BACKGROUND (15-17)
SCOPE OF REPORT (18-20)
DEFINITIONS AND BACKGROUND (21-23)
CORRELATIONS (24-32)
RELATIONSHIP BETWEEN TOXICITY AND CARCINOGENICITY OBSERVED AT MTD (33-42)
QUALITATIVE INFORMATION (43-48)
QUANTITATIVE INFORMATION (49-52)
OPTION 1 (53-53)
OPTION 2 (54-54)
OPTION 3 (55-56)
Option 4A (57-58)
Option 4B (59-60)
5 Conclusions and Recommendations (61-66)
REFERENCES (67-78)
BACKGROUND (79-79)
DEFINING AND DETERMINING THE MTD (80-90)
Appendix B Organizing Subcommittee (91-92)
Appendix C Federal Liaison Group (93-94)
Appendix D Workshop Program (95-96)
Appendix E Workshop Attendees (97-110)
1. INTRODUCTION (111-112)
2.1 Measures of Carcinogenic Potency (113-115)
2.2 Carcinogenic Potency Database (CPDB) (116-116)
2.3 Variation in Carcinogen Potency (117-118)
2.4 Classification of Carcinogens (119-120)
3.1 Empirical Correlations (121-124)
3.2 Range of Possible TD50 Values (125-125)
3.3 Analytical Correlations (126-127)
3.4 Model Dependency (128-129)
3.5 Genotoxic vs. Nongenotoxic Carcinogens (130-130)
4.1 Predictions Based on the MDT (131-131)
4.2 Predictions Based on Mutagenicity and Acute Toxicity (132-134)
5.1 Correlation Between Upper Bounds On the Low Dose Slope and MTD (135-135)
5.2 Correlation Between q1* and the TD50 (136-138)
5.3. Preliminary Estimate of Risk (139-139)
6. INTERSPECIES EXTRAPOLATION (140-140)
6.1 Extrapolation from Rats to Mice (141-143)
6.2 Extrapolation from Rodents to Humans (144-145)
7. CONCLUSIONS (146-148)
8. ACKNOWLEDGEMENTS (149-149)
9. REFERENCES (150-159)
ANNEX A: MAXIMUM LIKELIHOOD METHODS FOR FITTING THE WEIBULL MODEL (160-161)
ANNEX B. SHRINKAGE ESTIMATORS OF THE DISTRIBUTION OF CARCINOGENIC POTENCY (162-163)
ANNEX C: ADJUSTMENT OF POTENCY VALUES FOR LESS THAN LIFETIME EXPOSURE (164-165)
ANNEX D: CORRELATION BETWEEN TD50 AND MTD (166-168)
ANNEX E: CORRELATION BETWEEN TD50S FOR RATS AND MICE (169-172)
Appendix G Informal Search for ''Supercarcinogens" (173-174)
CRITERIA AND CANDIDATE CHEMICALS (175-176)
DATA (177-180)
RESULTS (181-181)
DISCUSSION (182-184)
Issues in Risk Assessment The Two-Stage Model Of Carcinogenesis (185-186)
INTRODUCTION (187-187)
BIOLOGIC CONSIDERATIONS (188-189)
THE TWO-STAGE MODEL (190-195)
APPLICATIONS OF THE TWO-STAGE MODEL TO ANIMAL DATA (196-211)
Data Needs (212-212)
Criteria for Adoption (213-213)
Prospects (214-214)
CONCLUSIONS AND RECOMMENDATIONS (215-216)
REFERENCES (217-222)
BIOLOGICAL FACTORS IN TWO-STAGE MODELS (223-225)
TWO-STAGE MODEL OF CLONAL EXPANSION (226-227)
APPLICATION OF THE TWO-STAGE MODEL TO ANIMAL DATA (228-232)
Appendix B Workshop Program (233-234)
Appendix C Workshop Federal Liaison Group (235-236)
TOPIC GROUP MEMBERS (237-238)
Appendix E Workshop Organizing Task Group (239-240)
Isuees In Risk Assessment A Paradigm for Ecological Risk Assessment (241-242)
1 Introduction (243-246)
2 Scope of Ecological Risk Assessment (247-248)
COMPONENTS OF THE 1983 FRAMEWORK (249-250)
CONSISTENCY OF CASE STUDIES WITH THE 1983 FRAMEWORK (251-253)
INTEGRATION OF ECOLOGICAL RISK INTO THE 1983 FRAMEWORK (254-254)
DEFINITION OF FRAMEWORK COMPONENTS FOR ECOLOGICAL RISK ASSESSMENT (255-258)
EXTRAPOLATION ACROSS SCALES (259-260)
QUANTIFICATION OF UNCERTAINTY (261-261)
VALIDATION OF PREDICTIVE TOOLS (262-262)
VALUATION (263-264)
5 Conclusions (265-266)
6 Recommendations (267-268)
REFERENCES (269-272)
Appendix A Workshop Participants (273-278)
Appendix B Workshop Organizing Subcommittee and Federal Liaison Group (279-280)
Appendix C Workshop Introduction (281-282)
TERRY F. YOSIE BUILDING ECOLOGICAL RISK ASSESSMENT AS A POLICY TOOL (283-285)
D. WARNER NORTH: RELATIONSHIP OF WORKSHOP TO NRC'S 1983 RED BOOK REPORT (286-288)
MICHAEL SLIMAK: U.S. ENVIRONMENTAL PROTECTION AGENCY ACTIVITIES IN ECOLOGICAL RISK ASSESSMENT (289-292)
CASE STUDY 1: TRIBUTYLTIN RISK MANAGEMENT IN THE UNITED STATES (293-293)
Discussion (294-294)
CASE STUDY 2: ECOLOGICAL RISK ASSESSMENT FOR TERRESTRIAL WILDLIFE EXPOSED TO AGRICULTURAL CHEMICALS (295-296)
CASE STUDY 3A: MODELS OF TOXIC CHEMICALS IN THE GREAT LAKES: STRUCTURE, APPLICATIONS, AND UNCERTAINTY ANALYSIS (297-298)
CASE STUDY 3B: ECOLOGICAL RISK ASSESSMENT OF TCDD AND TCDF (299-299)
Discussion (300-300)
CASE STUDY 4: RISK ASSESSMENT METHODS IN ANIMAL POPULATIONS: THE NORTHERN SPOTTED OWL AS AN EXAMPLE (301-301)
Discussion (302-302)
CASE STUDY 5: ECOLOGICAL BENEFITS AND RISKS ASSOCIATED WITH THE INTRODUCTION OF EXOTIC SPECIES FOR BIOLOGICAL CONTROL OF A... (303-303)
Discussion (304-304)
CASE STUDY 1: UNCERTAINTY AND RISK IN AN EXPLOITED ECOSYSTEM: A CASE STUDY OF GEORGES BANK (305-306)
Discussion (307-308)
Generic Issues (309-309)
Analysis of Case Studies (310-310)
DOSE-RESPONSE ASSESSMENT (311-311)
Selection of End Points (312-312)
Consideration of Nonlinearities And Discontinuities (313-313)
Understanding the Stressor (314-314)
Additions to the 1983 Paradigm Needed for Ecological Risk Assessment (315-315)
Modeling Needs for Stress-Response Relationships (316-316)
Methods of Measuring Stressors for Ecological Exposure Assessment (317-317)
Definition of Risk Characterization (318-318)
Components of Risk Characterization (319-319)
Organization and Presentation (320-320)
Differences from and Similarities To the 1983 Report (321-321)
Application to the Case Studies (322-323)
Agricultural Chemicals (324-324)
Northern Spotted Owl (325-325)
General Discussion: Models and Risk Assessment (326-326)
Uncertainties Identified In the Case Studies (327-327)
Implications of Uncertainty for Ecological Risk Assessment (328-328)
VALUATION (329-330)
Risk Assessment Has Many Uses (331-332)
Different Risk Assessment Methods Are Suited to Different Risk Assessment Needs (333-333)
Risk Assessors and Risk Managers Need to Communicate (334-334)
Credibility is Crucial (335-336)
Appendix G Contemplations on Ecological Risk Assessment (337-342)
Appendix H Workshop Summary (343-346)
Appendix I References for Appendixes (347-350)
Appendix J Workshop Program (351-356)

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OCR for page 259
Issues in Risk Assessment 4 Key Scientific Problems Limiting Application of Ecological Risk Assessment EXTRAPOLATION ACROSS SCALES The most common scientific limitation exemplified in the case studies is the problem of extrapolating across scales of space, time, and ecological organization. For the most part, scientific data related to a specific stressor are limited to what can be obtained in a controlled laboratory setting or in a limited field study. Observations of environmental contamination and ecological effects of tributyltin were limited to a few marinas. Testing of pesticides even in the best of circumstances is limited to small field plots and carefully controlled applications. Table 4-1 shows, for all the case studies, the scales at which the data used in the assessments were collected and the scales of interest in decision-making. In most cases, the scales of interest in decision-making are substantially larger in space and of longer duration than could be accommodated in any practical assessment effort. Some form of extrapolation, either with explicit mathematical models or with judgment-based decision rules, is necessary to make the risk assessments useful for decision-making. The PCB study discussed by Di Toro (Appendix E) clearly illustrated the value of explicit models for estimating recovery times in response to hypothetical management actions. In the pesticide registration process described by Kendall (Appendix E), extrapolation is based primarily on qualitative evaluation of test data and information on expected use patterns. Kendall argued that models of ecological effects of pesticides are needed to reduce uncertainty and to account for effects

OCR for page 260
Issues in Risk Assessment TABLE 4-1 Scales of Observation and Management in Case Studies Evaluated by the Committee Case Study Observational Scale Management Scale Spatial Temporal Spatial Temporal Tributyltin < 1m3 < 1 yr Chesapeake Bay > 5 yr ~ 1 ha (laboratory) < 5 yr (field) Agricultural chemicals ~ 1 ha < 1 yr (field test) Agricultural region > 5 yr PCB and TCDD < 1 L ~ 1-month (laboratory) Lakes or rivers > 10 yr Spotted owl ~ 300 km2 < 6 yr Pacific northwest > 100 yr Species introduction < 100 m2 ~ 1 yr (greenhouse) Agricultural region >> 1 yr Georges Bank ~ 104 km2 last 30 yr ~ 104 km2 next 5 yr