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

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

Anthony C. James, PhD, CRadPDirector, Research Professor

U.S. Transuranium & Uranium Registries

College of Pharmacy

Richland, WA 99354-4959, USA

[email protected]

www,ustur.wsu.edu

Columbia Chapter Health Physics Society (CCHPS) Symposium

Russia’s Hanford: Health Studies at MayakBattelle Auditorium, Richland, Friday, April 17th, 2009

“Learning from Plutonium and Uranium Workers”

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USTUR: Learning from Plutonium and Uranium Workers

The USAEC Vision

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The US Transuranium Registry (USTR)

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The U.S. Transuranium & Uranium Registries – 2009

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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).

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The Registries: Historical Profile of Partial-body Donations(“Routine” Autopsy Cases)

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Major USTR Landmark: 1st Whole Body Donation (1979)

• 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!)

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USTUR: Historical Profile of Whole-body Donations

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Year of Intake for USTUR Whole-body Donors

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• 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).

Exposure Characteristics of USTUR Registrants


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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).

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USTUR Web Site – Case Narrative for Registrant 0846

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USTUR Web Site – Narrative File Downloads for Registrant 0846

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241Am External Counts (PNNL) – With and Without Lungs

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Case 0846: External 241Am Counts Pre- and Post-Autopsy

USTUR/PNNL “In Vivo” Radiobioassay and Research

Facility (IVRRF) Collaboration

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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.)

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Web Publication of Tissue Analysis Results

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USTUR Pathology Database – Now on the Web (April 6th, 2009)!

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USTUR Downloadable Pathology Database

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Keyword Search for “Mesothelioma”

New case – not yet ICD-coded

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Pathology Database – Case Report

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Malignant Neoplasms as Primary Cause of Death in USTUR Registrants(with Exposure Co-Factors): 4. ICD-10 Codes C43.6 – C63.9


Case No. Source ICD-10 Site Fraction Smoker Be Asbestos Toxic_Chem Solvents Benzene/Toluene SEER 1975-20050158 A C43.6 Skin (Melanoma) - - - - - -

0041 D C43.9 Skin (Melanoma) 3.6% - - - - - - 1.3%

0102 D C43.9 Skin (Melanoma) Y N Y Y N -

0245 A C43.9 Skin (Melanoma) Y N Y Y N -

0084 D C45.0 Mesothelioma N - - - - -

0256 D C45.0 Mesothelioma Y Y Y Y Y -

0648 A C45.0 Mesothelioma 5.4% N Y Y Y Y - -

1040 D C45.0 Mesothelioma - N - Y Y -

0677 A C45.7 Mesothelioma N - - Y - -

0013 D C45.9 Mesothelioma N N N Y N N

0020 D C50.9 Breast 0.9% Y - - - - - -

0079 D C55 Uterus 0.9% Y N N N N N -

0022 D C61 Prostate Y N - Y N -

0058 D C61 Prostate - - - - - -

0189 D C61 Prostate Y - - - - -

0253 D C61 Prostate 6.3% - - - - - - 12.8%

0269 A C61 Prostate Y N N N N N

0425 A C61 Prostate N Y - - - -

0778 A C61 Prostate Y Y Y Y Y Y

1030 A C63.9 Penis 0.9% Y N N - N N 0.0%

All Neoplasms Count = 111/317 35.0%

•SEER: Surveillance, Epidemiology & End Results - http://seer.cancer.gov/

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Malignant Neoplasms as Primary Cause of Death in USTUR Registrants(with Exposure Co-Factors): 2. ICD-10 Codes C22 – C25.9


Case No. Source ICD-10 Site Fraction Smoker Be Asbestos Toxic_Chem Solvents Benzene/

TolueneSEER

1975-2005

0262 D C22.0 Liver N Y - - - -

0306 A C22.1 Liver Y N N N Y N

0147 D C22.9 Liver 5.4% Y N N N N N 1.9%

0371 A C22.9 Liver Y N - Y Y -

0446 A C22.9 Liver Y Y Y N Y Y

1054 D C22.9 Liver - - - - - -

0054 D C24.1 Gallbladder 0.9% - - - - - - 0.3%

0099 D C25.0 Pancreas - - - - -

0104 A C25.0 Pancreas Y N N N N N

0461 A C25.2 Pancreas 4.5% Y N N N N N 4.9%

0341 A C25.9 Pancreas N Y N N N N

0846 D C25.9 Pancreas N Y - - N Y

All Neoplasms Count = 111/317 35.0%

•SEER: Surveillance, Epidemiology & End Results - http://seer.cancer.gov/

Slide 24Malignant Neoplasms as Primary Cause of Death in USTUR Registrants(with Exposure Co-Factors): 3. ICD-10 Codes C34.1 – C41.4


Case No. Source ICD-10 Site Fraction Smoker Be Asbestos Toxic_Chem Solvents Benzene/Toluene SEER 1975-20050240 A C34.1 Lung Y N N Y Y N 0255 A C34.1 Lung Y N Y Y Y N 0005 A C34.9 Lung Y - - - - - 0008 A C34.9 Lung Y N N N N N 0011 D C34.9 Lung Y - - - - - 0038 D C34.9 Lung Y - - - - - 0063 A C34.9 Lung N N N N N N 0064 A C34.9 Lung Y N N Y N N 0081 D C34.9 Lung Y - - - - - 0083 D C34.9 Lung - - - - - - 0091 D C34.9 Lung - - - - - - 0100 A C34.9 Lung Y N N N N N 0103 D C34.9 Lung - - - - - - 0149 A C34.9 Lung Y N N N - - 0161 D C34.9 Lung Y - - - - - 0185 D C34.9 Lung - - - - - - 0187 D C34.9 Lung Y - - - - - 0188 D C34.9 Lung - - - - - - 0197 D C34.9 Lung Y N - Y Y - 0203 D C34.9 Lung 31.5% - - - - - - 32.1%0205 A C34.9 Lung - - - - - - 0213 N C34.9 Lung Y N N N N N 0226 D C34.9 Lung Y N Y Y N - 0232 A C34.9 Lung - - - - - - 0247 A C34.9 Lung N N Y Y N - 0252 D C34.9 Lung Y N - Y Y - 0334 A C34.9 Lung Y Y Y Y Y N 0375 A C34.9 Lung Y - - - - - 0669 A C34.9 Lung Y N N N N N 0720 A C34.9 Lung Y Y N N N N 0727 A C34.9 Lung Y Y - Y Y - 0779 D C34.9 Lung Y - - - N - 0841 A C34.9 Lung Y N Y - Y - 1036 A C34.9 Lung Y - - Y - - 1065 A C34.9 Lung Y - Y - Y Y 1059 A C40.2 Bone 1.8% - - - - - - 0.2%0769 A C41.4 Bone - - - - - -

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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

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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.

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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)

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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)

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NIOSH-IREP (EEOICPA) “Probability of Causation” Calculations for Case 0262 Liver Cancer

Legal Standard

EEOICPA Standard

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Distribution of Equivalent Dose Rate to Liver (Measured at Death) for USTUR Registrants

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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 16th, 2009

Message to USTUR from Dr. Michael Ardaiz, DOE’s Chief Medical Officer

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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 ± 0.1Femur (shaft): 2.2 ± 0.2

• Digested sample aliquots Lung: ~ 25 g in 40 mL acid solution Femur ~13 g in 75 mL acid solution

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Dr. Michael Ketterer, Dept. of Chemistry, Northern Arizona University (NAU)

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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., 31P+ in Lymph Node from Case 0846

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Dr. Philip Doble, University of Technology Sydney (UTS), Australia

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)

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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!!

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CCHPS MAYAK Symposium, Apr 17th, 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.”

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