1. Radiation Dose Limits for Adult Subjects Henry D. Royal, M.D. Associate Director Division of Nuclear Medicine Mallinckrodt Institute of Radiology Professor of Radiology Washington University School of Medicine St. Louis, MO FDA Meeting 11/16/04

2. Past and Present Experiences IAEA International Chernobyl Project Several NAS Committees Presidential Advisory Committee on Human Radiation Experiments Immediate Past President, SNM Veterans Advisory Committee for Environmental Hazards Board of Directors, NCRP US Delegate to UNSCEAR

3. Overview Current Regulations Limitations of Current Regulations Communicating Risks Answers to Questions Other Comments

4. Whole Body, Active Blood-forming Organs, Lens Of The Eye, And Gonads: Rem Single dose3 Annual and total dose commitment 5 Other Organs: Rem Single dose5 Annual and total dose commitment 15

5. Limitations Linked to Occupational Exposure Whole Body Dose No Adjustment for Age No Adjustment for Life Expectancy

6. Linked to Occupational Exposure Rationale Unclear Since Subjects Will Not Directly Benefit From RDRC Studies, Risk Should be Minimal Unfortunately, Minimal Risk is Ambiguously Defined

7. Whole Body Dose Should Be Replaced By ED Dose is a Surrogate for Risk Dose Limits Should Be Modified To Adjust For Age And Life Expectancy

8. Consumer Products Age Cancers per 10 4 Person-Gy Females BEIR V 1990

9. Cancer Rate Age (Years) 020406080 Exposure Latent Period Baseline Cancer Rate

10. Communicating Risks The Magnitude of a Risk Depends on Framing Common Approach: Radiation Increases the Risk of a Fatal Cancer by 4%-5% per Sievert (100 rems)

11. For a 5 Rem ED Participation In this Research Study Will Increase Your Chances of Getting Cancer (Dying) by 2/1000 Communicating Risks

12. What’s Wrong With This Approach? Very Difficult For Most People to Think in Terms of Numerical Risks Does Not Distinguish Between Immediate Deaths and Delayed Deaths Does Not Account for Age or Life Expectancy

13. An Alternative Approach Days of Life Lost 2/1000 Times 15 Years = 10.95 Days

14. Cologne et al: Lancet 2000; 356:303-07 >

15. Loss of Life < 1 Gy – 2 Months >1 Gy – 2.6 Years 60% Cancer 30% Other 10% Leukemia Cologne et al: Lancet 2000; 356:303-07

16. Alcoholic Poor Social Status Grade School Drop-Out Cancer 20% Overweight High Risk Job Orpahned PovertySmoking - Male Heart Disease Motor Vehicle Accidents 1,000 2,000 3,000 4,000 Cohen: Health Physics 61:317-335, 1991 5,000 6,000 Loss of Life Expentancy ( Days) Catalog of Risks

17. Suicide Drinking Water Fire, Burns AlcoholMurder Energy Conservation Motor Vehicle Accidents Loss of Life Expentancy ( Days) 50 100 150 200 Catalog of Risks Cohen: Health Physics 61:317-335, 1991 Air PollutionSmall CarsAIDS Radon Pesticides Poison Natural Hazards Bicycles Spouse Smoking Drowning Radiation Worker 250 300

18. An Alternative Approach Variations in Background Radiation ±100 mrem X 70 Years = 7 rem Not Possible to Measure the Risk Directly “…the possibility that there may be no risks from exposures comparable to external natural background radiation can not be ruled out.” BEIR V 1990 Page 181

19. Unintended Consequences Some Populations Will Not Benefit From Medical Research Increased Collective Dose to Obtain the Same Information Opportunity Costs

20. Answers to Questions Current Dose Limits (5 Rem Annual Dose) Are Appropriate Should Adjust for Age and Life Expectancy So That Dose is A Better Surrogate For Risk

21. Other Comments Get Rid of Organ Doses Accounted for in ED Should be Limited Out of Concern for Deterministic Effects Only Keep Regulations Are Simple Avoid Unintended Consequences