1. Slide 1 The Fifth Decade of U.S. Actinide Worker Follow-up Anthony C. James, PhD, CRadP Director, Research Professor U.S. Transuranium & Uranium Registries College of Pharmacy Richland, WA 99354-4959, USA tjames@tricity.wsu.edu www,ustur.wsu.edu Columbia Chapter Health Physics Society (CCHPS) Symposium Russia’s Hanford: Health Studies at Mayak Battelle Auditorium, Richland, Friday, April 17 th, 2009 “Learning from Plutonium and Uranium Workers”

2. Slide 2 USTUR: Learning from Plutonium and Uranium Workers The USAEC Vision

3. Slide 3 USTUR: Learning from Plutonium and Uranium Workers The US Transuranium Registry (USTR)

4. Slide 4 USTUR: Learning from Plutonium and Uranium Workers The U.S. Transuranium & Uranium Registries – 2009

5. Slide 5 USTUR: Learning from Plutonium and Uranium Workers USTUR’s Voluntary Tissue Donors To date, 327 previous workers with actinides (plutonium, americium and/or uranium) have voluntarily donated their tissues for scientific research – including 36 whole-body donors – from various weapons or other sites (not just Hanford). These donors, and a further 93 living Registrants with documented accidental exposures to actinide elements, voluntarily released their employment, occupational exposure histories and medical records. Each individual donor’s autopsy examination results, together with USTUR’s subsequent measurements of the actinide contents of tissues and major organs provide a unique collection of scientific data which encompasses all types of accidental exposure to actinides over the history of U.S. nuclear materials production and handling. The privacy of each donor is rigorously protected – and USTUR’s research protocols must be approved annually by WSU’s independent Institutional Review Board (IRB).

6. Slide 6 USTUR: Learning from Plutonium and Uranium Workers The Registries: Historical Profile of Partial-body Donations (“Routine” Autopsy Cases)

7. Slide 7 USTUR: Learning from Plutonium and Uranium Workers Major USTR Landmark: 1st Whole Body Donation (1979) Donor (radiochemist) worked with unsealed 241 Am source in his doctoral research (1952-54) First indication of intake was detection of 241 Am in urine sample (1958 routine surveillance program) – No chelation therapy Contemporary estimate of intake 0.23 – 1.1 μCi (~ 8 – 40 kBq!)

8. Slide 8 USTUR: Learning from Plutonium and Uranium Workers USTUR: Historical Profile of Whole-body Donations

9. Slide 9 USTUR: Learning from Plutonium and Uranium Workers Year of Intake for USTUR Whole-body Donors

10. Slide 10 Self-selected for relatively “high” (recorded) intakes of transuranium elements – primarily 239 Pu/ 238 Pu/ 241 Am. Additional exposure to external radiation (  /n). In majority of cases, there is also additional exposure to industrial toxic materials - Beryllium (Be), asbestos, toxic chemicals, organic solvents, benzene/toluene. Any pathological findings are SUMMED effects of “natural” disease incidence (including “normal” incidence of malignant cancer in matched, non-exposed population) and ALL occupational exposure factors. Some self-selection for existing cancer (Rocky Flats Plant). Exposure Characteristics of USTUR Registrants USTUR: Learning from Plutonium and Uranium Workers

11. Slide 11 USTUR: Learning from Plutonium and Uranium Workers FY2008 Whole-Body Donations January: 87-y-old 239 Pu-contaminated puncture wound(s) (Hanford – 1960s). March: 95-y-old 239 PuO 2 acute inhalation (Rocky Flats – 1965 Pu fire – high intake). March: 72-y-old 241 AmO 2 chronic inhalation (U.S. Radium Corporation – 1960s – very high intake – heavily chelated). September: 83-y-old U 3 O 8 -fume acute inhalation (Hanford – 1948 – up to 300 μg-U/d in urine).

12. Slide 12 USTUR: Learning from Plutonium and Uranium Workers USTUR Web Site – Case Narrative for Registrant 0846

13. Slide 13 USTUR: Learning from Plutonium and Uranium Workers USTUR Web Site – Narrative File Downloads for Registrant 0846

14. Slide 14 USTUR: Learning from Plutonium and Uranium Workers 241 Am External Counts (PNNL) – With and Without Lungs

15. Slide 15 USTUR: Learning from Plutonium and Uranium Workers Case 0846: External 241 Am Counts Pre- and Post-Autopsy USTUR/PNNL “In Vivo” Radiobioassay and Research Facility (IVRRF) Collaboration

16. Slide 16 USTUR: Learning from Plutonium and Uranium Workers Comparison of External 241 Am Counting with Actual Tissue Contents Case 0720: Rocky Flats PuO 2 Inhalation Case 0269: Hanford Pu(NO 3 ) 4 Inhalation Lynch et al. (submitted to Radiat. Prot. Dosim.)

17. Slide 17 USTUR: Learning from Plutonium and Uranium Workers Web Publication of Tissue Analysis Results

18. Slide 18 USTUR: Learning from Plutonium and Uranium Workers USTUR Pathology Database – Now on the Web (April 6 th, 2009)!

19. Slide 19 USTUR: Learning from Plutonium and Uranium Workers USTUR Downloadable Pathology Database

20. Slide 20 USTUR: Learning from Plutonium and Uranium Workers Keyword Search for “Mesothelioma” New case – not yet ICD-coded

21. Slide 21 USTUR: Learning from Plutonium and Uranium Workers Pathology Database – Case Report

22. Slide 22 Malignant Neoplasms as Primary Cause of Death in USTUR Registrants (with Exposure Co-Factors): 4. ICD-10 Codes C43.6 – C63.9 USTUR: Learning from Plutonium and Uranium Workers Case No.SourceICD-10SiteFractionSmokerBeAsbestosToxic_ChemSolventsBenzene/TolueneSEER 1975-2005 0158AC43.6Skin (Melanoma) ------ 0041DC43.9Skin (Melanoma)3.6%------1.3% 0102DC43.9Skin (Melanoma) YNYYN- 0245AC43.9Skin (Melanoma) YNYYN- 0084DC45.0MesotheliomaN----- 0256DC45.0MesotheliomaYYYYY- 0648AC45.0Mesothelioma5.4%NYYYY-- 1040DC45.0Mesothelioma-N-YY- 0677AC45.7MesotheliomaN--Y-- 0013DC45.9MesotheliomaNNNYNN 0020DC50.9Breast0.9%Y------ 0079DC55Uterus0.9%YNNNNN- 0022DC61ProstateYN-YN- 0058DC61Prostate------ 0189DC61ProstateY----- 0253DC61Prostate6.3%------12.8% 0269AC61ProstateYNNNNN 0425AC61ProstateNY---- 0778AC61ProstateYYYYYY 1030AC63.9Penis0.9%YNN-NN0.0% All NeoplasmsCount =111/31735.0% SEER: Surveillance, Epidemiology & End Results - http://seer.cancer.gov /http://seer.cancer.gov /

23. Slide 23 Malignant Neoplasms as Primary Cause of Death in USTUR Registrants (with Exposure Co-Factors): 2. ICD-10 Codes C22 – C25.9 USTUR: Learning from Plutonium and Uranium Workers Case No. SourceICD-10SiteFractionSmokerBeAsbestosToxic_ChemSolvents Benzene/ Toluene SEER 1975-2005 0262DC22.0LiverNY---- 0306AC22.1LiverYNNNYN 0147DC22.9Liver5.4%YNNNNN1.9% 0371AC22.9LiverYN-YY- 0446AC22.9LiverYYYNYY 1054DC22.9Liver------ 0054DC24.1Gallbladder0.9%------0.3% 0099DC25.0Pancreas----- 0104AC25.0PancreasYNNNNN 0461AC25.2Pancreas4.5%YNNNNN4.9% 0341AC25.9PancreasNYNNNN 0846DC25.9PancreasNY--NY All NeoplasmsCount =111/31735.0% SEER: Surveillance, Epidemiology & End Results - http://seer.cancer.gov/http://seer.cancer.gov/

24. Slide 24 Malignant Neoplasms as Primary Cause of Death in USTUR Registrants (with Exposure Co-Factors): 3. ICD-10 Codes C34.1 – C41.4 USTUR: Learning from Plutonium and Uranium Workers Case No.SourceICD-10SiteFractionSmokerBeAsbestosToxic_ChemSolventsBenzene/TolueneSEER 1975-2005 0240AC34.1Lung YNNYYN 0255AC34.1Lung YNYYYN 0005AC34.9Lung Y----- 0008AC34.9Lung YNNNNN 0011DC34.9Lung Y----- 0038DC34.9Lung Y----- 0063AC34.9Lung NNNNNN 0064AC34.9Lung YNNYNN 0081DC34.9Lung Y----- 0083DC34.9Lung ------ 0091DC34.9Lung ------ 0100AC34.9Lung YNNNNN 0103DC34.9Lung ------ 0149AC34.9Lung YNNN-- 0161DC34.9Lung Y----- 0185DC34.9Lung ------ 0187DC34.9Lung Y----- 0188DC34.9Lung ------ 0197DC34.9Lung YN-YY- 0203DC34.9Lung31.5%------32.1% 0205AC34.9Lung ------ 0213NC34.9Lung YNNNNN 0226DC34.9Lung YNYYN- 0232AC34.9Lung ------ 0247AC34.9Lung NNYYN- 0252DC34.9Lung YN-YY- 0334AC34.9Lung YYYYYN 0375AC34.9Lung Y----- 0669AC34.9Lung YNNNNN 0720AC34.9Lung YYNNNN 0727AC34.9Lung YY-YY- 0779DC34.9Lung Y---N- 0841AC34.9Lung YNY-Y- 1036AC34.9Lung Y--Y-- 1065AC34.9Lung Y-Y-YY 1059AC40.2Bone1.8%------0.2% 0769AC41.4Bone------

25. Slide 25 USTUR: Learning from Plutonium and Uranium Workers Summary of Preliminary Findings on USTUR Registrants (Through 2008) No significant association found between [preliminary/rough estimates of ] tissue-weighted equivalent dose received and malignant cancer as a primary (or secondary) cause of death (α = 0.05). Statistically significant associations found between cause of death due to any type of cancer and exposure to: - benzene or toluene (odds ratio = 5.71; 95% CI: 1.04 to 31.34) - smoking habit (odds ratio = 5.41; 95% CI: 1.42 to 20.67) - rate of cigarette smoking (odds ratio = 2.70; 95% CI: 1.37 to 5.30). Lung cancer deaths found to be related to exposure to: - chlorinated solvents (odds ratio = 10.85; 95% CI: 1.02 to 115.16) - duration of exposure to these materials (odds ratio = 1.12; 95% CI: 1.01 to 1.24). Source: Fallahian,N. A. “Study of the Association Between Exposure to Transuranic Radionuclides and Cancer Death,” PhD Dissertation, Idaho State University, 2008

26. Slide 26 USTUR: Learning from Plutonium and Uranium Workers USTUR Data Enable Accurate Reconstructions of Tissue Doses Actually Received by Individuals – Example of USTUR Case 0262 Worked as engineer at Hanford (1951-82). Died 1990 – at age 71 y. Cause of death: - hepatocellular carcinoma (ICD-10 Code C22.0) - with metastases in diaphragm, lungs and liver. At autopsy: - all major soft tissue organs harvested, including axillary lymph node (for radiochemistry and NHRTR sample storage); - Skin of both hands saved for histology/autoradiography; - Bones from half skeleton dissected out – for radiochemistry; - Contents of 238 Pu, 239+240 Pu, 241 Am measured for all tissues/organs.

27. Slide 27 USTUR: Learning from Plutonium and Uranium Workers Measured and “Modeled” Excretion of 239 Pu in Urine for Case 0262 Source: James, A.C., et al. “USTUR Whole Body Case 0262: 33-y Follow-up of PuO 2 in a Skin Wound and Associated Axillary Node.” Radiat. Prot. Dosim. 127: 114-119 (2007)

28. Slide 28 USTUR: Learning from Plutonium and Uranium Workers Measured and “Modeled” 239 Pu Content of Tissues (At Autopsy) for Case 0262 Source: James, A.C., et al. “USTUR Whole Body Case 0262: 33-y Follow-up of PuO 2 in a Skin Wound and Associated Axillary Node.” Radiat. Prot. Dosim. 127: 114-119 (2007)

29. Slide 29 USTUR: Learning from Plutonium and Uranium Workers NIOSH-IREP (EEOICPA) “Probability of Causation” Calculations for Case 0262 Liver Cancer Legal Standard EEOICPA Standard

30. Slide 30 USTUR: Learning from Plutonium and Uranium Workers Distribution of Equivalent Dose Rate to Liver (Measured at Death) for USTUR Registrants

31. Slide 31 USTUR: Learning from Plutonium and Uranium Workers Application of USTUR 40-y Follow-up of U.S. Actinide Workers to Ensure Safe DOE/EM Site Clean-up Tony, Welcome home and thank you for keeping me well-informed regarding your activities. I wanted to let you know that [DOE is actively concerned with the] potential for [worker] radiological exposures in combination with silica, asbestos, and beryllium in the course of the D and D activities spurred by the 6 billion in stimulus funding. We have drafted a memo specifying continued compliance with DOE's health and safety requirements ………………………………. I will take every opportunity to suggest that USTUR is helping us understand more clearly the lessons of the past and supporting the development of hazard controls which may offset the exposures associated with the anticipated increase in activity by EM in particular. Thank you again, Mike April 16 th, 2009 Message to USTUR from Dr. Michael Ardaiz, DOE’s Chief Medical Officer

32. Slide 32 USTUR: Learning from Plutonium and Uranium Workers Test Tissues – USTUR Case 0817 Malignant neoplasm of the esophagus Primary inhalation exposure at Rocky Flats (PuO 2 ) Also UO 2 and asbestos 37-y (self-reported) exposure to Be 239 Pu concentration in tissues (Bq/kg wet) Lung: 38.0 ± 0.1 Femur (shaft): 2.2 ± 0.2 Digested sample aliquots Lung: ~ 25 g in 40 mL acid solution Femur ~13 g in 75 mL acid solution

33. Slide 33 USTUR: Learning from Plutonium and Uranium Workers Dr. Michael Ketterer, Dept. of Chemistry, Northern Arizona University (NAU)

34. Slide 34 USTUR: Learning from Plutonium and Uranium Workers Dr. Philip Doble, University of Technology Sydney (UTS), Australia “Metallomics”: Laser Ablation - Inductively Coupled Plasma - Mass Spectrometry (LA-ICP-MS) – Elemental Scanning of Tissue Sections, e.g., 31 P + in Lymph Node from Case 0846

35. Slide 35 USTUR: Learning from Plutonium and Uranium Workers Dr. Philip Doble, University of Technology Sydney (UTS), Australia Positive LA-ICP-MS Scan for 9 Be + in Thoracic Lymph Node from Case 0846 (1960s U.S. Radium Corp. chronic 241 AmO 2 inhalation – self-reported beryllium work)

36. Slide 36 USTUR: Learning from Plutonium and Uranium Workers In Summary: U.S. Pu Workers c.f., MAYAK USTUR provides individual life-time follow-up of “at risk” – i.e., known actinide-exposed – U.S. workers. With relatively few exceptions, USTUR’s “at risk” cohort of Pu workers were exposed well below the contemporary “dose limits” – i.e., at levels that are RELEVANT to occupational exposure in a REGULATED workplace (and HIGHER than MIGHT conceivably be received by a member of the U.S. public). To find the health outcomes (effects on tissues) – OR LACK THEREOF – AND LONGEVITY at these (relevant) levels of exposure we need to work with a well-characterized “at risk” cohort, i.e., USTUR Registrants. Health outcomes that “jump out” of USTUR study are INDUSTRIAL RELATED – NOT Pu-related!!

37. Slide 37 CCHPS MAYAK Symposium, Apr 17 th, 2009 - James Disclaimer: “This presentation was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, expressed or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof.”