1. Thyroid dose estimation for epidemiologic studies André Bouville (NCI, retired) and Vladimir Drozdovitch (NCI) Workshop on Radiation and Thyroid Cancer Tokyo, Japan, 22 February 2014 1

2. Outline Background information Principles of dose reconstruction Examples of studies and dose estimates Concluding remarks 2

3. Background information 3

4. Analytic epidemiologic studies Requirement: – Unbiased individual dose estimates for a large number of subjects Examples of studies: – Chernobyl: UA-US and BY-US studies among children – Chernobyl: UA-US in utero study – Fallout: Marshall Islands study 4

5. Exposure Pathways

6. Pasture-cow-milk pathway ( 131 I)

7. Principles of thyroid dose reconstruction in a large environmental study 7

8. Six Principles of Dose Reconstruction 8 ● Perform person-based measurements. ● Administer interviews. ● Conduct environmental measurements. ● Obtain realistic estimates of dose. ● Validate the dose estimates. ● Estimate the uncertainties attached to the dose estimates.

9. Principle #1: person-based measurements 9 ● Objective: perform as many person-based measurements as possible. ● Rationale: dose estimates are much less uncertain when they are based on: person-based measurements, than on environmental radiation measurements, or on data on activities released into the environment.

10. Thyroid dose is propor- tional to area under the curve Thyroid Dose Estimation (multiple measurements) 10

11. Thyroid dose is propor- tional to area under the curve Curve derived from 131 I models plus data from questionnaire Thyroid Dose Estimation (usual case) 11

12. Principle #2: personal interviews 12 ● Objective: identify the conditions of radioiodine intake as early as possible. ● Rationale: - the internal dose estimates are very sensitive to the conditions of radioiodine intake. It is important to clarify if inhalation occurred in a single day or over several days and if ingestion was a significant mode of exposure, - because of memory loss, the personal interviews should be performed soon after the accident.

13. Personal interview

14. Inhalation: residence history (including number of hours spent indoors) during the first two months following the accident Ingestion: consumption rates and origin (market or own garden) of water, milk, and leafy vegetables Countermeasures: sheltering, evacuation, and/or stable iodine administration, if conducted 14 Questions to interviewees (in case of exposure to 131 I)

15. Principle #3: environmental measurements 15 ● Objective: development of a model predicting the variation with time of the intake rate of 131 I. ● Rationale: - environmental measurements ( 131 I in air, water, soil, vegetation, foodstuffs + 137 Cs in air and soil) are the best data that could supplement the person-based measurements, - when environmental measurements are not available, estimates of released activities, combined with models of atmospheric transport, have to be used.

16. 137 Cs deposition map (Chernobyl accident)

17. Principle #4: realistic dose estimation Principle #5: validation of dose estimates Principle #6: estimation of uncertainties 17 ● Objectives: obtain realistic (unbiased) estimates of dose for all subjects of the epidemiologic study; make sure that the estimated doses are reasonably reliable; and quantify the uncertainties ● Rationale: the dose estimates have to be credible and arguments must exist to defend their credibility.

18. Examples of studies and dose estimates 18

19. Chornobyl Accident – 26 April 1986 The most severe accident that ever occurred in the nuclear power industry.

20. NCI Chornobyl thyroid study Cohort study of about 25,000 subjects (13,000 Ukrainians and 12,000 Belarusians) exposed as children. Lived in contaminated areas of Ukraine and Belarus. All subjects had a person-based measurement ( 131 I activity in the thyroid). 20

21. Distribution of thyroid dose estimates 21 Thyroid dose interval (Gy) Number of subjects UkraineBelarus N%N% <0.26,72951.05,40746.1 0.2 – 0.492,82921.42,86724.4 0.5 – 1.992,73520.72,81224.0 2.0 – 9.998386.36125.2 ≥10730.6340.3 All13,20410011,732100 Mean (Gy)0.650.58

22. Distribution of GSD according to dose (Ukrainian cohort) 22 GSD intervalN% Mean thyroid dose (Gy) ≥32171.60.017 2.0 – 2.992942.20.26 1.5 – 1.994,71135.70.68 1.26 – 1.497,98260.50.66

23. In-utero study of thyroid cancer in Ukraine Number of subjects: 2,584, including three groups: Subgroup L1-C: 720 subjects. Their mothers: – lived in a contaminated area in April-June 1986; and – had a person-based measurement ( 131 I activity in thyroid). Subgroup L2-C: 776 subjects. Their mothers: – lived in a contaminated area in April-June 1986; and – did not have a person-based measurement, but a number of women from the same settlement of residence had such a measurement. Subgroup L1-NC: 1088 subjects. Their mothers: – lived in a non-contaminated area in April-June 1986; and – did not have a person-bases measurement, and no other woman from the same settlement of residence had such a measurement. 23

24. Estimation of doses for the 2,584 in-utero subjects 24 Direct thyroid measurements (for 720 MOTHERS) Subjects of contaminated areas 1496 Subjects of “non-contaminated” areas 1088 Individual Questionnaires History of pregnancy Behavior: milk consumption milk consumption leafy vegetablesleafy vegetables relocation Sets of personal information

25. 25 Results of in utero thyroid dose calculation Thyroid dose, mGy Contaminated areas (L1-C + L2-C) “Non-contaminated” areas (L1-NC) Number of persons % % 0-2057738.693485.8 20-5028118.812411.5 50-10021914.6232.1 100-20018612.470.6 200-50015810.6-- 500-1000503.3-- >1000251.7-- Total14961001088100

26. 1946-1958: 66 nuclear tests, ~100 MT 66 nuclear tests, ~100 MT Release of 131 I: Release of 131 I: 150 Chernobyl 1500 Fukushima 1954: BRAVO test 1954: BRAVO test Resulted in high doses in northern atolls and to evacuations. Nuclear weapons testing in the Marshall Islands

27. There are significant differences in estimating internal doses for Marshallese compared to estimating doses to populations exposed to fallout from the Chernobyl or Fukushima accidents: 1)No animal milk products available. 2)Unusual exposure pathways.

28. Bioassay of urine from Rongelap community members collected within 16 to19 days of fallout exposure from the BRAVO test provided the first ever measurements to confirm 131 I from exposure to fallout. Marshall Islands: person-based measurements

29. Estimates of thyroid dose (mGy) to adults MajuroKwajaleinUtrikRongelap Internal dose (short-term) 22 66 740 7,600 Internal dose (long-term) 0.76 1.3 25 14 INTERNAL DOSE (TOTAL) 23 67 760 7,600 EXTERNAL DOSE 9.8 22 140 1,600 29

30. Concluding remarks 30

31. Concluding remarks (1 of 2) All dose reconstructions are different because: – Radioactive releases are different – Environmental conditions are different – Population habits are different, and – Countermeasures are different. However, there are principles of dose reconstruction that apply to all environmental studies. 31

32. Concluding remarks (2 of 2) It is important to obtain realistic estimates of dose because: – they may be used in research projects such as epidemiologic studies or risk assessment, – the affected populations have the right to know the extent to which they were exposed to radiation. Multi-agency cooperation and multi-disciplinary expertise is needed to obtain dose estimates of a high degree of reliability. 32

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