Reproductive and Developmental Effects of Depleted Uranium DU in Rats

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Reproductive and Developmental Effects of
Depleted Uranium (DU) in Rats

• LT Darryl Arfsten, Ph.D.
• MSC, USNR

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Naval Health Research CenterEnvironmental Health
Effects Laboratory

• Mission Develop Occupational Exposure Limits
  (OELs) for Navy-unique situations and chemicals
• Ongoing work
• Halogenated fluorocarbon fire
• suppressants
• Propylene glycol fog/fire fighting drills
• Carbon dioxide/enclosed living spaces
• JP-5, JP-8
• Break-Free CLP on skin

NHRC EHE Lab WPAFB Ohio
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Reproductive Toxicity of Implanted Depleted
Uranium

• Project
• Characterize effects of DU shrapnel on rodent
  reproductive success and health of offspring
• Sponsor
• U.S. Army Medical Research Acquisition Activity
• Requirements
• PRMRP, Defense Appropriations Act 2001
• BAA 99-1, Gulf War Illness Research Military
  Relevant Disease Management

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Depleted Uranium (DU)

• Waste material formed in uranium enrichment
  process
• Uranium depleted of isotopes 234U and 235U
• Emits low-level radiation, 40 less radioactive
  than natural uranium
• Heavy metal, 1.6x the density of lead
• 1 cm319 grams

DU Storage containers
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Applications

• Kinetic energy armor penetrator munitions
• Armor plating (Ex. M1A1)

120 mm APFSDS
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Perceptions
The US military response when asked about the
health effects of DU weapons Ó (Hear no evil,
see no evil, say no evil)
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Reproductive Effects?
Study More birth defects found in Gulf War
babies December 8, 1997 CNN
More birth defects found among Gulf War vets'
children THE ASSOCIATED PRESS Wednesday, June 4,
2003
Iraqi cancers, birth defects blamed on U.S.
depleted uranium By LARRY JOHNSONSEATTLE
POST-INTELLIGENCER FOREIGN DESK EDITOR
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Inoperable DU Shrapnel McDiarmid et al. 2000,
2001
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Health Hazards Radiological

• DU emits beta, gamma, and alpha particles
• Radiation levels very low (4.05x10-7 Ci/g)
• Cancer from alpha particle emission a concern for
  persons with internal DU fragments

Alpha ray tracks emitted from plutonium present
in ape lung tissue
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Health Hazards Radiological
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Health Hazards Chemical

• Similar to uranium kidney toxicity
• DU is a heavy metal biological effects similar
  to lead?
• Neurotoxic in rats
• Mutagenic in vitro
• Developmental effects in rats?
• Carcinogenic in rats?

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Pellet Implantation

• Surgical implantation simulate soft tissue
  shrapnel injury in leg
• Rats implanted with 4, 8, 12 or 20 DU
  (treated), or
• 4, 8, 12, or 20 Tantalum steel pellets (inert
  controls)
• 1 x 2 mm pellets 20 pellets 0.4 rat BW
• 6 lbs of DU in 154 lbs human!!!

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Treatment Groups
P1 adults 378 F1 offspring 2,457
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Study Design

• 2-Generation Reproductive Toxicity Study in Rats

30-Day F1 Generation
Implanted Adults Male x Female
120-Day F1 Generation
F2 Generation
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Adult Uranium Excretion

• ICP/MS LOD 0.5 µg/mg
• NEL, Las Vegas, NV
• Pooled samples N10 per dose group
• No U found in urine of animals without DU pellets
• No U found in bedding, food, water, nylabones

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Reproduction/Development
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Reproduction/Development
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Neurobehavioral Testing
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Neurobehavioral Testing
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12
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4
8
12
8
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Immune Function of Pups

• 1 male, 1 female randomly selected from each
  litter at PND20
• Immune function evaluated beginning PND 56-90
  (adult stage)
• PC group treated with cyclophosphamide (CPA)
  immune suppressant

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Immune Function Testing
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Immune Function Testing
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Summary

• 30-d DU implantation does not result in overt
  toxicity in implanted adults (6 lbs of DU in 154
  lbs human)
• DU implantation does not appear to adversely
  impact
• P1 reproduction
• F1 pup survival through PND 90 (early adulthood)
• F1 physical development (rib cage morphol eval
  on-going)
• Some evidence of a neurobehavioral effect in F1
  offspring further study and comparison to 120 d
  implantation offspring
• Ongoing F1 after 120 d implantation F2 mating
  

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Acknowledgements
NHRC/EHEL Angie Thitoff Scott Lohrke Eric
Johnson Anne Jung Fred McDougle Shawn
McInturf Robert Carpenter CDR W Jederberg CDR J
Rossi LT E Wilfong HMC B Dean HM1 Lopez HM2
Miller HM2 Fike HM3 Steele ABE3 Nolte AN1 Tyson
CAPT K Still Bruce Briggs AFRL Brenda
Schimmel Tim Bausman Therlo Bailey Amanda
Lear Peggy Parish LTC B Ketzenberger MAJ S
Stutler MAJ G Siegel 88th ABW Mark Mays Chris
Anthony
Wright State University Adam Lenger Joseph
Cunningham, Jr. Mike Varney Keith Grasman Lori
Healey Jen Rutkiewicz Richard L. Salisbury
Jr. University of Cincinnati Chris Allen
Wisconsin Bureau of Environ Hlth Marni
Bekkedal Y-12 National Security Complex Mike
Monnet Hal Clift Paul Turner