The Fifth Decade of U.S. Actinide Worker Follow-up

1. Columbia Chapter Health Physics Society (CCHPS) Symposium Russia’s Hanford: Health Studies at Mayak Battelle Auditorium, Richland, Friday, April 17th, 2009 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 “Learning from Plutonium and Uranium Workers”

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

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

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

5. USTUR’s Voluntary Tissue Donors • To date, 327 previous workers with actinides (plutonium, americium and/or uranium) have voluntarilydonated 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). USTUR: Learning from Plutonium and Uranium Workers

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

7. 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

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

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

10. Exposure Characteristics of USTUR Registrants • Self-selected for relatively “high” (recorded) intakes of transuranium elements – primarily 239Pu/238Pu/241Am. • 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). USTUR: Learning from Plutonium and Uranium Workers

11. 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

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

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

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

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

16. Comparison of External 241Am Counting with Actual Tissue Contents Case 0720: Rocky Flats PuO2 Inhalation Case 0269: Hanford Pu(NO3 ) 4 Inhalation Lynch et al. (submitted to Radiat. Prot. Dosim.) USTUR: Learning from Plutonium and Uranium Workers

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

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

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

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

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

22. Malignant Neoplasms as Primary Cause of Death in USTUR Registrants (with Exposure Co-Factors): 4. ICD-10 Codes C43.6 – C63.9 • SEER: Surveillance, Epidemiology & End Results - http://seer.cancer.gov/ USTUR: Learning from Plutonium and Uranium Workers

23. Malignant Neoplasms as Primary Cause of Death in USTUR Registrants (with Exposure Co-Factors): 2. ICD-10 Codes C22 – C25.9 • SEER: Surveillance, Epidemiology & End Results - http://seer.cancer.gov/ USTUR: Learning from Plutonium and Uranium Workers

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

25. Summary of Preliminary Findings on USTUR Registrants (Through 2008) • No significant association found between [preliminary/rough estimates of ] tissue-weighted equivalent dose receivedand 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 USTUR: Learning from Plutonium and Uranium Workers

26. 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 238Pu, 239+240Pu, 241Am measured for all tissues/organs. USTUR: Learning from Plutonium and Uranium Workers

27. Measured and “Modeled” Excretion of 239Pu in Urine for Case 0262 Source: James, A.C., et al. “USTUR Whole Body Case 0262: 33-y Follow-up of PuO2 in a Skin Wound and Associated Axillary Node.” Radiat. Prot. Dosim. 127: 114-119 (2007) USTUR: Learning from Plutonium and Uranium Workers

28. Measured and “Modeled” 239Pu Content of Tissues (At Autopsy)for Case 0262 Source: James, A.C., et al. “USTUR Whole Body Case 0262: 33-y Follow-up of PuO2 in a Skin Wound and Associated Axillary Node.” Radiat. Prot. Dosim. 127: 114-119 (2007) USTUR: Learning from Plutonium and Uranium Workers

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

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

31. Application of USTUR 40-y Follow-up of U.S. Actinide Workers to Ensure Safe DOE/EM Site Clean-up Message to USTUR from Dr. Michael Ardaiz, DOE’s Chief Medical Officer 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 16th, 2009 USTUR: Learning from Plutonium and Uranium Workers

32. Test Tissues – USTUR Case 0817 • Malignant neoplasm of the esophagus • Primary inhalation exposure at Rocky Flats (PuO2) • Also UO2 and asbestos • 37-y (self-reported) exposure to Be • 239Pu 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 USTUR: Learning from Plutonium and Uranium Workers

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

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

35. Positive LA-ICP-MS Scan for 9Be+ in Thoracic Lymph Node from Case 0846 (1960s U.S. Radium Corp. chronic 241AmO2 inhalation – self-reported beryllium work) Dr. Philip Doble, University of Technology Sydney (UTS), Australia USTUR: Learning from Plutonium and Uranium Workers

36. 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!! USTUR: Learning from Plutonium and Uranium Workers

37. 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.” Thank you for your attention! www.ustur.wsu.edu CCHPS MAYAK Symposium, Apr 17th, 2009 - James