slide 1 examples of critical u.s. transuranium & uranium registries (ustur) cases involving...

Examples of Critical U.S. Transuranium & Uranium Registries (USTUR) Cases Involving Chelation Therapy

Anthony C. James, PhD, CRadPUSTUR Director, Research Professor

College of Pharmacy

Richland, WA 99354-4959, USA

[email protected]

www.ustur.wsu.edu

EURADOS WG7 MeetingForschungszentrum Karlsruhe GmbH,

Institut für Strahlenforschung (ISF)Monday, April 6th, 2009

“Learning from Plutonium and Uranium Workers”

USTUR: Learning from Plutonium and Uranium Workers

Major USTR Landmark: 1976 Hanford 241Am Incident

• 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

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

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.

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

0.1 1 10 100 1,000 10,000 100,000

T im e since inha la tion , d

0.1

1

10

100

1,000

10,000U

rin

ary

exc

retio

n r

ate

, d

pm

/d

KeyU ntreated

i.v. C a-ED TA

O ral C a-ED TA

Zr-C itrate

i.v. C a-D TPA

Approx. 8X untreated

Approx. 50X untreated

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

1 10 100 1,000 10,000 100,000

T im e since inhalation, d

0.01

0.1

1

10

100

1,000

10,000

100,000

1,000,000F

eca

l exc

retio

n r

ate

, d

pm

/d

KeyU ntreated

i.v. C a-ED TA

i.v. C a-D TPA

Zr-c itra te

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

USTUR Whole-body Case # 0269 – Biokinetic Modeling

USTUR Whole-body Case # 0269 – Modeling Method

USTUR Whole-body Case # 0269 – Modeling Hypotheses

USTUR Whole-body Case # 0269 – Modeling Method

USTUR Whole-body Case # 0269 – Modeling Results

Case 0269: Summary of Tissue Radiochemistry Results

Tissue Measured Tissue Content, kBq

Whole Body 2.280

Lungs 0.0267

Lymph Nodes 0.00019

Liver 0.937

Skeleton 1.178

Muscle, Skin, etc. 0.141

Kidneys 0.00169

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

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

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

a. 21 d untreated

b. DTPA at 7 d

c. DTPA at 30 min

d. From [b] - untreated

e. From [c] – DTPA 7 d

f. 1 d untreated

USTUR Whole-body Case # 0269 – Modeling Results


Web Publication of Tissue Analysis Results

SF/ICP-MS: Determination of 241Pu

241Pu • T1/2 = 14.1 y, -emitter• not detectable by -spectrometry241Pu 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

SF/ICP-MS (at NAU) vs -spectrometry


The Mound Glove Box Explosion (1968)

Original Publication of Mound 238Pu Cases

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

238Pu Excretion in Feces (3 Employees)

Case #0682 - 238Pu Skeletal Contents


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 Web Site – Case Narrative for Registrant 0846


USTUR Web Site – File Downloads for Registrant 0846


Case #0846 Urine Data – First Year


Case #0846 Urine Data – Second Year


Case #0846 Urine Data – Years 2-3


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


External Counts Pre- and Post-Autopsy


NHRTR – FY2008: THEMIS Bar-coded Sample Inventory Chain of Custody/Database System


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).

• 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.

Radiochemistry: Tissue Sample Actinide Separation and Measurement

HPA/CRCE Seminar – ACJ – April 2nd, 2009

Radiochemistry

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

Description USTUR 150-220-310 TEVA-TRU-DGA

Separation techniqueExtraction

chromatography + anion exchange (gravity fed)

Extraction chromatography

(vacuum-assisted)

Sample loading 3 times once

Number of samples in batch 18 24

Reagents used 345 mL/sample 110 mL/sample

Time for Pu/Am separation 5+ days 1 day

Benefits & Limitations of ICP-MS

•Rapid analysis (10 min vs 42 hr for -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


New Frontier: Laser Ablation ICP-MS

LA-ICP-MS in USTUR Program

Phillip Doble, Ph.D., Senior Lecturer, Department of Chemistry & Forensic Science, University of Technology, Sydney, Australia

Application of LA-ICP-MS to USTUR/NHRTR

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?


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!)


Voxel Modeling of DOE 241Am Phantom (USTUR Case #0102)

George Tabatadze M.S. (UNLV Medical Physics) - ISU Ph.D. Project


Voxel Modeling of DOE 241Am Phantom (USTUR Case #0102)

George Tabatadze M.S. (ISU Graduate Student)


Potential ‘Phantom’ Resource? - Whole Limbs from Case #0846

th International Congress of the International

Radiation Protection Association (IRPA)Buenos Aires, Argentina

October 8th- 24th, 2008

Uncertainty in Internal Doses: Using Bayes to TransferInformation from One Worker to Another

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

James, A.C.,1 Birchall, A.2 and Puncher, M.2

1United States Transuranium and Uranium Registries, 1854 Terminal Drive, Richland, WA 99354, USA2 Health Protection Agency-Radiation Protection Division, Chilton, Oxon OX11 0RQ, UK


USTUR Organization – FY2009 (Planned)


In Conclusion: USTUR and EURADOS WG7

• USDOE/WSU’s USTUR/NHRTR are unique resources of data and tissue materials voluntarily donated by hundreds of individual workers

- the measured actinide contents of tissues and major organs at autopsy 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.

• USTUR cases include lifetime follow-up of extensively chelated individuals with comprehensive medical and bioassay records.

• USTUR is working hard to refine and organize these (privacy-protected) data – and make them readily available for research study by collaborating scientists – in the U.S. and internationally.

• USTUR and DOE welcome the opportunity to work closely with EURADOS WG7 to ensure that the Registries’ data and materials resources are utilized most effectively to reduce uncertainty in the assessment, management and potential ‘treatment’ of accidental (or malevolent) exposures to actinides.

RAP/HSEP Joint Committee Meeting, Jan 8th, 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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