VA Radiation & Physical Exposure Service
Depleted Uranium (DU) and Toxic Embedded
FragmentsMelissa A. McDiarmid, MD, MPH
Joanna Gaitens, PhD, MSN/MPH
Katherine S. Squibb, PhD
VA Maryland Health Care System
University of Maryland
Baltimore, USA
DisclaimerDisclaimer
The views expressed in this presentation are those of the author and do not necessarily represent the position of the Department of Veterans Affairs or the United States Government
I have no known conflicts of interest other than that I work for the Department of Veterans Affairs
Topics we will cover: Environmental exposures of concern to
Veterans: Depleted Uranium (DU), Toxic Embedded Fragments
The potential toxicity of DU and retained embedded fragments
Programs available through the VA for Veterans with concerns about these exposures
How Veterans enroll in these programs
What is Depleted Uranium?
By-product of uranium enrichment process through which 235U is extracted from natural uranium for use as nuclear fuel
Leftover is “depleted” with 235U/238U isotopic ratio = 0.245%
Isotopic Comparison of Natural and
Depleted Uranium
Radioactivity
Natural Uranium
Depleted Uranium
Isotope Ci/g Concentration
of isotopes Concentration
of isotopes
234U 6200.0 0.0058% 0.001%
235U 2.2 0.72% 0.2%
238U 0.33 99.28% 99.8%
Relative Radioactivity
1 0.6
*
Chemical vs Radiological Toxicity
Chemical toxicityU234 = U235 = U238
Radiological toxicitySpecific activity: U234 >>> U235 > U238
so Natural U > DU
Primary decay = alpha particles and gamma rays
Military Uses of DU
Tank armor for increased resistance to enemy projectiles
Munitions to increase penetrating power
Used in battle for first
time in Gulf War
Gulf War and OEF/OIF Exposures to DU
Friendly-fire incidents exposed US soldiers to: DU shrapnel Aerosolized DU oxides
Inhalation, ingestion, wound contamination
Burning of munitions storage facility Decontamination of military equipment
DU Embedded Fragment
Potential Toxicity of DU
Systemic effects due to release of U ions to circulation and uptake by organs Specific target organs of U
Kidney Bone
Primarily chemical toxicity of U
Local effects on tissue surrounding DU embedded fragments May be combination of chemical toxicity and
radioactivity of U
Mission of the DU Follow-Up Program
Since 1993:
To provide clinical surveillance for the ‘friendly fire’ DU-exposed GWI Veterans
Since 1998:
To provide biologic monitoring by mail for DU for all GWI and OIF Veterans
The next several slides will cover:
Depleted Uranium Follow-Up Program Purpose Surveillance protocol Findings
Depleted Uranium Mail-In Surveillance Program Purpose Findings
Purpose of DU Friendly Fire Victim Surveillance
Determine health effects, if any, in DU exposed populations (GWI, OEF, OIF)
Develop methods to measure DU exposure in this novel exposure mode (embedded fragments)
Examine surgical and medical management of embedded fragments– still an issue!
Surveillance Protocol during Biennial Inpatient Evaluation
Complete history (medical, social, family, reproductive, occupational exposure, partner)
Extensive laboratory studies (hematology, serum chemistry, neuroendocrine, urinalysis, urine, semen and blood uranium, renal markers, semen analysis)
Chromosomal analysis (mutations, chromosomal aberrations)
Neurocognitive testing Focus group/risk communication
Summary of Surveillance through 2009
Gulf War OIFYear DU-exposed Non-exposed DU-exposed Total
1993-4 33 33
1997 29 38 67
1999 21 + 29 new 50
2001 31 + 8 new 39
2003 32 32
2005 30 + 4 new 3 37
2007
2009
32 + 3 new
36 + 2 new
2 (1 new)
2
37
40
79 unique cases have been evaluated from Gulf War 4 Unique cases have been evaluated from OIF
Mean Urine Uranium Levels through 2007
for the 2009 Cohort
0.001
0.01
0.1
1
10
100
Samples Ranked from Low to High (n=36)
Uri
ne
Ura
niu
m (
μg
U/g
cre
atin
ine)
No shrapnel; No DU (n=19)
Shrapnel; No DU (n=2)
No shrapnel; DU (n=2)
Shrapnel; DU (n=13)
Thun 1975 = 65.1 µg/L
Occupational Decision Level = 0.8 µg/L
Dietary Limit = 0.365 g/L
DU Cut point = 0.1 µg/g creatinine
NHANES 95th% = 0.043 µg/g creatinine
Clinical Findings
No clinically significant differences detected between low and high uranium exposure groups Hematology Neuroendocrine Chemistries Neurocognitive
To provide urine uranium surveillance by mail for any Veteran requesting testing
Second Activity of DU Program:
Purpose of the DU Urine Biomonitoring Program
Determine urine uranium concentrations in Veterans from GWI and forward
Passively survey for exposure scenarios linked to DU exposure other than friendly fire
Provide assistance to Veterans’ primary care providers in interpreting results and answering Veterans questions
Summary of Mail-in Activity through May 31, 2010
Sampling kits requestedN > 4597
1682 > 2915
Samples tested as of 5/31/10
N = 3136
GWI OIFTOTAL
Total uraniumonly 476
Total uranium& DU 813
Total uranium& DU 1847
Positive for DUN = 4*
31
*All friendly fire
Toxic Embedded Fragment Surveillance Center (TEFSC)
and Registry
Background Traumatic injuries via contact with
improvised explosive devices (IEDs) are a major concern in Iraq, and increasingly in Afghanistan More than 40,000 soldiers with traumatic injuries
may have retained embedded fragments.
IEDs are packed with heterogeneous material that may lead to local and systemic adverse health effects.
VHA directed to address the issue of embedded fragments
Presidential Task Force Recommendation P-7 directed the VHA to establish a registry and medical surveillance program for Veterans with embedded fragments
Health concerns related to embedded fragments
Local effects Risk of the development of tumors at the
fragment sites
Systemic effects Risk of target organ effects arising from
chemicals released from fragments
Fate of DU Metal Fragments in Rat Muscle In Situ
Correlation of radiographic appearance with histologic appearance. (A) Thick fibrotic capsule with shards of corroded DU in lumen; (B) thick cellular capsule lined by squamous metaplasia, particles, and shards of corroded DU in wall and lumen; (C) particles and shards of disintegrated DU fragment scattered throughout a soft tissue sarcoma (Hahn et al, 2002).
1995 film 2001 filmChange in DU fragment appearance over time; suggests oxidation in situ and removal is warranted.
Embedded DU Fragment in 1991 Gulf War Veteran
New Alloy Used in Munitions: W/Ni/Co
Metastatic tumors caused by implanted tungsten alloy (W/Ni/Co) fragments in rats Rhabdomyosarcomas
rapidly metastasize to lung Survival time is
significantly reduced
Kalinich et al. Env. Hlth Perspec.113: 729-734, 2005
Evidence supports development of Toxic Embedded Fragment
Surveillance Center (TEFSC) Local Effects
Evidence from DU Program and medical device and fragment literature
New studies of metal implanted animals with new tungsten alloy (W, Co, Ni) demonstrating rapid carcinogenesis
Systemic Effects Known renal, reproductive and neurological
effects of metals (e.g. Pb, Cd, Ni, Mn, Cu)
The next several slides will cover:
Toxic Embedded Fragment Surveillance Center Mission Specific functions of TEFSC
VA’s Embedded Fragment Registry Purpose of the registry Eligibility criteria Screening process for identifying eligible
veterans Data captured in the registry
VA Toxic Embedded Fragment Surveillance Center
Established at Baltimore VA Medical Center
Mission: To provide care and active medical surveillance for Veterans with retained embedded fragments
Functions of TEFSC
Fragment Characterization
Biomonitoring & Medical Surveillance
Registry Development
Case Consultation
Chemical analysis of removed fragments Surface chemistry Total fragment composition
Analysis of tissue surrounding fragments Chemical analysis of tissue Characterization of tissue morphology
Histology- proliferative cells, neoplastic cells
Analyzing fragment composition is an essential
function of TEFSC
Summary of Composition of Fragments from
Military Personnel 2006-2008 (AFIP data)*407 fragments analyzed
1 radioactive
44 Organic materials 10 plastic & polymers 1 fabric and 1 wood26 Stones
336 non-radioactive alloys (steel & brass)
and non-alloyed metals
DU with traces ofAl, Cr, Cu, Ti, Zn
Fe, Cu, Al, Ni, Pb, Zn with traces of other elements
including Cr, Mn, Sn, Sb, Ti, W
*Division of Biophysical Toxicology, Armed Forces Institute of PathologyCenteno JA, et al. (2009)
70 Non-Metals337 Metals
Fragment data informs biomonitoring and medical
surveillance protocol
Fragment composition data helps: Identify a list of toxicants to include in
biomonitoring panels Identify outcomes of concern and means of
surveillance Identify potential biomarkers of early effect
Fragment Analysis Process
1. TEFSC sends fragment collection kit to requesting VA
2. VA obtains fragment from Veteran and mails completed kit to TEFSC
4. TEFSC sends result letters to Veteran and VA Provider
3. Fragment is analyzed
Biological Specimens also provide insight into exposure
Toxicants of interest Metals: Al, As, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb,
U, W, Zn Plastics/polymer components: Isocyanate,
Acrylics, Diethylhexylphthalates Others: Based on fragment analysis data
Biological Specimens Urine, blood, other body fluids when indicated
Biological Monitoring Process
1. TEFSC sends kit is sent to requesting VA
2. Veteran provides 24-hour urine sample and completes questionnaire
3. VA mails completed kit to Baltimore VA
5. TEFSC sends result letters to Veteran and VA Provider
4. Specimen and questionnaire are analyzed
Surveillance protocol involves periodic follow-up to identify
potential health outcomes Perform baseline urinalysis
based on chemical composition of removed fragment(s)
Perform periodic follow up urinalysis to identify specific biomarkers of exposure and effects
based on baseline results
Conduct periodic radiologic surveillance of embedded fragment location and shape
Consider target organ surveillance for toxicants of concern
Purpose of the VA Embedded Fragment Registry
To track, monitor and provide appropriate medical care and follow up for Veterans with embedded fragments resulting from injuries sustained during their tour of duty Identify Veterans who served in Iraq and Afghanistan
and who have embedded fragments Identify health concerns associated with embedded
fragments Develop medical and surgical management guidelines
for Veterans with embedded fragments
Any Veteran who served in Operation Enduring Freedom or
Operation Iraqi Freedom who has or likely has a retained fragment as
the result of an injury received while serving in the area of conflict
are eligible for inclusion into the registry.
Individuals with embedded fragments are identified by
both the VA and the DoD
The VA has created a process to screen Veterans for embedded fragments at their local VA facility
DoD is creating their own “Embedded Metal Fragment Registry”
The DoD and VA are collaborating to ensure that all Veterans who have embedded fragments are identified
and receive appropriate follow-up care.
The VA Screening process for Veterans with fragments uses the
“Clinical Reminder” system
Screening Questions Do you have or suspect you have a retained
fragment as the result of an injury received while serving in the area of conflict?- Were you injured by a bullet? - Were you injured as a result of a blast or explosion?
- Were you in or on a vehicle at the time of the blast or explosion? - Was the blast or explosion caused by: IED, RPG, land mine, grenade, enemy fire, friendly fire, don’t know, or other?
- Did you have shrapnel, fragments or bullets removed during surgery?
- If yes, were they sent to the lab for analysis? - Do you have retained shrapnel, fragments or bullets in your body?
- If yes, have they been documented by radiograph?
Screening information is automatically captured in the
VA’s Embedded Fragment Registry
Then TEFSC determines if the following services are needed: Fragment analysis Biological monitoring Clinical Consultation
The VA’s registry will also identify if the individual is in DoD’s registry AND if the individual had a
fragment removed and analyzed by DoD.
The Embedded Fragment Registry will capture “basic”
data Screening Details
Answers to screening question Local VA contact person
Referral Status Demographic Information Healthcare Information
Contact information for Primary Care Provider VA facility where Veteran receives care
…and Exposure/Health Details Injury and exposure information
Developed standardized exposure questionnaire
Biomonitoring data Tests ordered, analyses methods, results,
interpretation of results, tracking information
Fragment analysis data Analyses methods, results, interpretation of results,
tracking information
Health outcomes Results of specific clinical tests ICD-9 codes
Much of the registry data will come from existing data sources
Data Registry Sources
Screening data
Patient’s electronic medical record
Demographic information
Healthcare information
Health outcome data
Biomonitoring Data Baltimore VA Lab system
Fragment Data DoD electronic files
The registry will help the
VA and the DoD
refine how cases are identified
and
provide appropriate medical care for individuals with embedded fragments.
Conclusion
Toxic Embedded Fragment Surveillance Center
andDepleted Uranium Program
1-800-815-7533