Anthony C. James, PhD, CRadP USTUR Director, Research Professor College of Pharmacy

1. EURADOS WG7 Meeting Forschungszentrum Karlsruhe GmbH, Institut für Strahlenforschung (ISF) Monday, April 6th, 2009 Examples of Critical U.S. Transuranium & Uranium Registries (USTUR) Cases Involving Chelation Therapy Anthony C. James, PhD, CRadP USTUR Director, Research Professor College of Pharmacy Richland, WA 99354-4959, USA tjames@tricity.wsu.edu www.ustur.wsu.edu “Learning from Plutonium and Uranium Workers”

2. Explosion of ion-exchange column containing ~ 100 g 241Am Chemical operator injured – acid burns, superficial cuts (face and upper body) From 1 to 5 Ci (~ 40 – 200 GBq!) deposited on injured worker and his clothing Major USTR Landmark: 1976 Hanford 241Am Incident USTUR: Learning from Plutonium and Uranium Workers

3. USTUR Whole-body Case # 0269[James et al., 2007 (Montpellier, 2006)]

4. USTUR Case #0269 – Decorporation Treatments • Within a day of the accident, patient treated with i.v. Ca-EDTA: • 1 g per injection – per day. • Injection regimen  1-week-on, 1-week-off. • Continued for following 6 months. • Oral administration of Ca-EDTA – and various other “experimental” chelating agents – attempted over following years. • Intravenous Ca-DTPA: • 869 d – 0.2 g  2 • 870 d – 0.4 g  2 • 871 d – 0.6 g  2 • 872 → 952 d – 0.8 g  2 per day – intermittently. • 954 → 963 d – 1.0 g  2 per day – intermittently. • 1031 → 1642 d – 1.0 g  1 per day – intermittently.

5. USTUR Whole-body Case # 0269 – 239/240Pu-in-Urine Data

6. USTUR Whole-body Case # 0269 – 239/240Pu-in-Feces Data

7. USTUR Whole-body Case # 0269 – All 239/240Pu Bioassay Data

8. USTUR Whole-body Case # 0269 – Biokinetic Modeling

9. USTUR Whole-body Case # 0269 – Modeling Method

10. USTUR Whole-body Case # 0269 – Modeling Hypotheses

11. USTUR Whole-body Case # 0269 – Modeling Method

12. USTUR Whole-body Case # 0269 – Modeling Results

13. USTUR Whole-body Case # 0269 – Modeling Results

14. USTUR Whole-body Case # 0269 – Modeling Results

15. Case 0269: Summary of Tissue Radiochemistry Results

16. USTUR Whole-body Case # 0269 – EDTA Modeling Results EDTA Flush Build-up Time Constant (Tissues) = 145 EDTA Excretion Build-up Time Constant (Urine) = 240 EDTA Excretion Enhancement Factor (to Urinary Path) = 5.100 EDTA Excretion Enhancement Factor (to Bladder) = 14.900 EDTA Tissue Uptake Factor = 1.000 EDTA Liver Clearance Factor = 1.370 EDTA Marrow Clearance Factor = 1.370 EDTA ST0 Clearance Factor = 1.370 EDTA ST1 Clearance Factor = 1.370 EDTA ST2 Clearance Factor = 1.370 EDTA Bone Surface Clearance Factor = 1.370

17. USTUR Whole-body Case # 0269 – DTPA Modeling Results DTPA Excretion Enhancement Factor (to Urinary Path) = 1.000 DTPA Urinary Path Flush Factor (to Bladder) = 1.000 DTPA Excretion Enhancement Factor (to Bladder) = 15.500 DTPA Tissue Uptake Factor = 0.000 DTPA Liver 2 Clearance Factor = 1.000 DTPA Liver 1 to Liver 2 Clearance Factor = 0.056 DTPA Liver 1 Fecal Factor = 0.500 DTPA Marrow Clearance Factor = 18.000 DTPA ST0 Clearance Factor = 1.440 DTPA ST1 Clearance Factor = 1.440 DTPA ST2 Clearance Factor = 1.440 DTPA Bone Surface Clearance Factor = 6.660

18. Autoradiographic Visualization of Bone Growth/Chelation Dynamics in the Weanling Rat • From James and Taylor, 1971 • Key • i.v. injection of citrate-buffered (monomeric) 239Pu(NO3)4 – 5 µCi/kg • 21 d untreated • DTPA at 7 d • DTPA at 30 min • From [b] - untreated • From [c] – DTPA 7 d • 1 d untreated

19. USTUR Whole-body Case # 0269 – Modeling Results

20. USTUR Whole-body Case # 0269 – Modeling Results

21. Web Publication of Tissue Analysis Results USTUR: Learning from Plutonium and Uranium Workers

22. SF/ICP-MS: Determination of 241Pu • 241Pu • T1/2 = 14.1 y, b-emitter • not detectable by a-spectrometry • 241Pu was detected in: • 269.003 (liver) • 269.031 (femur, PE) • 269.052 (humerus, PE) • 720.001 (lung) • 720.004 (liver) ICP-MS in USTUR Program

23. SF/ICP-MS (at NAU) vsa-spectrometry ICP-MS in USTUR Program

24. The Mound Glove Box Explosion (1968)

25. Original Publication of Mound 238Pu Cases

26. DTPA-enhanced Urinary 238Pu Excretion (Employee ‘C’)

27. 238Pu Excretion in Feces (3 Employees)

28. Case #0682 - 238Pu Skeletal Contents

29. FY2008 Whole-Body Donations • January: 87-y-old 239Pu-contaminated puncture wound(s) (Hanford – 1960s). • March: 95-y-old 239PuO2 acute inhalation (Rocky Flats – 1965 Pu fire – high intake). • March: 72-y-old 241AmO2 chronic inhalation (U.S. Radium Corporation – 1960s – very high intake – heavily chelated). • September: 83-y-old U3O8-fume acute inhalation (Hanford – 1948 – up to 300 μg-U/d in urine). USTUR: Learning from Plutonium and Uranium Workers

30. USTUR Web Site – Case Narrative for Registrant 0846 USTUR: Learning from Plutonium and Uranium Workers

31. USTUR Web Site – Case Narrative for Registrant 0846 USTUR: Learning from Plutonium and Uranium Workers

32. USTUR Web Site – File Downloads for Registrant 0846 USTUR: Learning from Plutonium and Uranium Workers

33. Case #0846 Urine Data – First Year USTUR: Learning from Plutonium and Uranium Workers

34. Case #0846 Urine Data – Second Year USTUR: Learning from Plutonium and Uranium Workers

35. Case #0846 Urine Data – Years 2-3 USTUR: Learning from Plutonium and Uranium Workers

36. Post Mortem 241Am External Counts (PNNL) – With and Without Lungs USTUR: Learning from Plutonium and Uranium Workers

37. External Counts Pre- and Post-Autopsy USTUR: Learning from Plutonium and Uranium Workers

38. NHRTR – FY2008: THEMIS Bar-coded Sample Inventory Chain of Custody/Database System USTUR: Learning from Plutonium and Uranium Workers

39. The Management Information System (THEMIS) • Assigns a unique barcode to each individual sample. • Records a sample’s mass or volume. • Tracks the sample’s current location as it is moved within the NHRTR facility (e.g., from one freezer to another). • Tracks the sample’s location (e.g., as it is ‘shipped’ for radiochemical analysis). USTUR: Learning from Plutonium and Uranium Workers

40. Radiochemistry: Tissue Sample Actinide Separation and Measurement • USTR & USUR (pre-1992) • Analyses carried out primarily by Los Alamos (LASL/LANL). • USTUR (1992-2006) • Analyses carried out by Washington State University (WSU) • Nuclear Radiation Center (NRC), Pullman, WA. • USTUR (2006-2008) • Limited analyses carried out in temporary (leased) laboratory at Columbia Basin College, Pasco, WA (no tissue digestion facilities). • Tried “full-service” commercial laboratories. • New separations procedures and ICP-MS. • USTUR (2009+) • New (leased) “in-house” radiochemistry facilities. HPA/CRCE Seminar – ACJ – April 2nd, 2009

41. Comparison of Analytical Performance: USTUR-150-220-310 vs. TEVA-TRU-DGA Radiochemistry

42. Benefits & Limitations of ICP-MS • Rapid analysis (10 min vs 42 hr for a-spectrometry) • Low detection limits • High precision (1-3 %) • 240Pu/239Pu isotopic ratio measurement • 236U and 241Pu detection • Limited for 241Am and 238Pu determination c.f. AS ICP-MS in USTUR Program

43. New Frontier: Laser Ablation ICP-MS Phillip Doble, Ph.D., Senior Lecturer, Department of Chemistry & Forensic Science, University of Technology, Sydney, Australia LA-ICP-MS in USTUR Program

44. LA-ICP-MS: Potential Applications to USTUR/NHRTR • Spatial distribution of actinides, 226Ra and major matrix elements (Ca, Mg, Sr, P) in autopsy samples • Actinide and 226Ra concentration measurements • Others? Application of LA-ICP-MS to USTUR/NHRTR

45. Donor (radiochemist) worked with unsealed 241Am source in his doctoral research (1952-54) First indication of intake was detection of 241Am in urine sample (1958 routine surveillance program) – No chelation therapy Contemporary estimate of intake 0.23 – 1.1 μCi (~ 8 – 40 kBq!) Major USTR Landmark: 1st Whole Body Donation (1979) USTUR: Learning from Plutonium and Uranium Workers

46. Voxel Modeling of DOE 241Am Phantom (USTUR Case #0102) George Tabatadze M.S. (UNLV Medical Physics) - ISU Ph.D. Project USTUR: Learning from Plutonium and Uranium Workers

47. Voxel Modeling of DOE 241Am Phantom (USTUR Case #0102) George Tabatadze M.S. (ISU Graduate Student) USTUR: Learning from Plutonium and Uranium Workers

48. Voxel Modeling of DOE 241Am Phantom (USTUR Case #0102) George Tabatadze M.S. (ISU Graduate Student) USTUR: Learning from Plutonium and Uranium Workers

49. Potential ‘Phantom’ Resource? - Whole Limbs from Case #0846 USTUR: Learning from Plutonium and Uranium Workers

50. 12th International Congress of the International Radiation Protection Association (IRPA) Buenos Aires, Argentina October 8th- 24th, 2008 Uncertainty in Internal Doses: Using Bayes to Transfer Information from One Worker to Another James, A.C.,1 Birchall, A.2 and Puncher, M.2 1United States Transuranium and Uranium Registries, 1854 Terminal Drive, Richland, WA 99354, USA 2 Health Protection Agency-Radiation Protection Division, Chilton, Oxon OX11 0RQ, UK • Scenario • Comprehensive bioassay follow-up of a worker who accidentally inhaled 241AmO2 yields knowledge of the lung absorption behavior of this material. • Can this knowledge be applied rigorously to improve dose estimates for another worker inhaling same material (with relatively sparse bioassay data and unknown time of intake)? • Demonstrate use of the Weighted Likelihood Monte Carlo Sampling (WeLMoS) method (Puncher and Birchall, 2008) to derive posterior probability distributions of doses for the second worker. 5-month aqueous suspension