Depleted Uranium (DU) and Toxic Embedded Fragments

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Depleted Uranium (DU) and Toxic Embedded
Fragments

• Melissa A. McDiarmid, MD, MPH
• Joanna Gaitens, PhD, MSN/MPH
• Katherine S. Squibb, PhD
• VA Maryland Health Care System
• University of Maryland
• Baltimore, USA

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Disclaimer

• 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

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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

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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

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Isotopic Comparison of Natural and Depleted
Uranium


Natural

Depleted
Radioactivity

Uranium

Uranium

Concentration

Concentration

Isotope

m
Ci/g

of isotopes

of isotopes

234
U

6200.0

0.0058

0.001


235
U

2.2

0.72

0.2

238
U

0.33

99.28

99.
8

Relative


1

0.6


Radioactivity

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Chemical vs Radiological Toxicity

• Chemical toxicity
• U234 U235 U238
• Radiological toxicity
• Specific activity U234 gtgtgt U235 gt U238
• so Natural U gt DU
• Primary decay alpha particles and gamma rays

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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

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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

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DU Embedded Fragment
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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

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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

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The next several slides will cover

• Depleted Uranium Follow-Up Program
• Purpose
• Surveillance protocol
• Findings
• Depleted Uranium Mail-In Surveillance Program
• Purpose
• Findings

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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!

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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

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Summary of Surveillance through 2009
Gulf War Gulf War OIF
Year 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
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Mean Urine Uranium Levels through 2007 for the
2009 Cohort
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Clinical Findings

• No clinically significant differences detected
  between low and high uranium exposure groups
• Hematology
• Neuroendocrine
• Chemistries
• Neurocognitive

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Second Activity of DU Program
To provide urine uranium surveillance by mail for
any Veteran requesting testing
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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

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Summary of Mail-in Activity through May 31, 2010
TOTAL
GWI
OIF
Sampling kits requested N gt 4597
1682
gt 2915
Total uranium only 476
Samples tested as of 5/31/10 N 3136
Total uranium DU 1847
Total uranium DU 813
Positive for DU N 4
3
1
All friendly fire
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Toxic Embedded Fragment Surveillance Center
(TEFSC) and Registry
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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.

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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

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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

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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).
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Embedded DU Fragment in 1991 Gulf War Veteran
1995 film
2001 film
Change in DU fragment appearance over time
suggests oxidation in situ and removal is
warranted.
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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
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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)

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The next several slides will cover

• Toxic Embedded Fragment Surveillance Center
• Mission
• Specific functions of TEFSC
• VAs Embedded Fragment Registry
• Purpose of the registry
• Eligibility criteria
• Screening process for identifying eligible
  veterans
• Data captured in the registry

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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

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Functions of TEFSC

• Fragment Characterization
• Biomonitoring Medical Surveillance
• Registry Development
• Case Consultation

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Analyzing fragment composition is an essential
function of TEFSC

• 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

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Summary of Composition of Fragments from
Military Personnel 2006-2008 (AFIP data)
407 fragments analyzed
70 Non-Metals
337 Metals
44 Organic materials 10 plastic polymers
1 fabric and 1 wood 26 Stones
336 non-radioactive alloys (steel brass) and
non-alloyed metals
1 radioactive
Fe, Cu, Al, Ni, Pb, Zn with traces of other
elements including Cr, Mn, Sn, Sb, Ti, W
DU with traces of Al, Cr, Cu, Ti, Zn
Division of Biophysical Toxicology, Armed Forces
Institute of Pathology Centeno JA, et al. (2009)
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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

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Fragment Analysis Process
1. TEFSC sends fragment collection kit to
requesting VA
2. VA obtains fragment from Veteran and mails
completed kit to TEFSC
3. Fragment is analyzed
4. TEFSC sends result letters to Veteran and VA
Provider
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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

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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
4. Specimen and questionnaire are analyzed
5. TEFSC sends result letters to Veteran and VA
Provider
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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

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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

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• 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.

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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.
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The VA Screening process for Veterans with
fragments uses the Clinical Reminder system
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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, dont
  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?

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Screening information is automatically captured
in the VAs Embedded Fragment Registry
The VAs registry will also identify if the
individual is in DoDs registry AND if the
individual had a fragment removed and analyzed by
DoD.

• Then TEFSC determines if the following services
  are needed
• Fragment analysis
• Biological monitoring
• Clinical Consultation

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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

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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

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Much of the registry data will come from existing
data sources
Data Registry Sources
Screening data Patients electronic medical record
Demographic information Patients electronic medical record
Healthcare information Patients electronic medical record
Health outcome data Patients electronic medical record
Biomonitoring Data Baltimore VA Lab system
Fragment Data DoD electronic files
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Conclusion

• The registry will help the
• VA and the DoD
• refine how cases are identified
• and
• provide appropriate medical care for individuals
  with embedded fragments.

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Toxic Embedded Fragment Surveillance Center
andDepleted Uranium Program1-800-815-7533