Depleted uranium toxicity

Background

• Uranium is an alpha-emitting, radioactive heavy metal that occurs naturally in nearly all rocks and soil. Natural uranium is made up of the three naturally occurring isotopes of uranium namely ²³⁴U, ²³⁵U, and ²³⁸U. Naturally occurring uranium deposits are over 99% ²³⁸U. You eat, drink, and breather natural uranium on a daily basis.
• Health hazards of natural uranium have been studied extensively since 1940s. Health impact of Depleted Uranium (DU) has been studied since the early 1970s.
• Enrichment is the industrial process by which natural uranium is separated into enriched uranium which has an increased percentage of ²³⁵U and depleted uranium which has a decreased percentage of ²³⁵U.
  • DU is a byproduct of the enrichment process.
  • DU has 40% less radioactivity than natural uranium. It has a specific activity of 0.33 microCi/g.
  • DU has the same chemical properties as naturally occurring uranium, it simply has different ratio of isotopes of ²³⁴U, ²³⁵U, and ²³⁸U.
  • DU health effects will be the same as for natural uranium because the toxicity is primarily due to the chemical toxicity rather than radiotoxicity.
• United States Armed Forces have used depleted uranium in the manufacture of ammunition, armor, and aircraft.
  • DU's high density, self-sharpening quality and pyrophoricity make it a good choice for projectile munitions.
  • DU's density makes it a good armor choice.
  • DU's density also makes it a good choice for counterbalance weights used in aircraft and on helicopter rotors.

'	Natural Uranium	Depleted Uranium
Isotope	Concentration of isotope	Concentration of isotope
234U	0.0058%	0.0010%
235U	0.72%	0.20%
238U	99.28%	99.80%
Relative Radioactivity	1.0	0.6

Routes of exposure

• Inhalation - minor route of exposure for general population. Major route for occupational population. On average in US individual daily intake of uranium is 0.007 micrograms by inhalation.
• Oral - predominant route of exposure for general population through ingestion of food and drinking water. Average daily intake of uranium in US is 1.9 micrograms by ingestion.
• Dermal - unlikely route of exposure for general population. Potential route of exposure for military service members.

Toxicokinetics

• DU is poorly absorbed following inhalation, oral, or dermal exposure route.
  • Amount absorbed heavily dependent on the solubility of the compound.
  • <0.1-6% of uranium is absorbed following oral exposure.
• 67% of uranium in blood is filtered in the kidneys and leaves body in urine within 24 hours. Remainder is distributed to tissues primarily bone, liver, and kidney.
• Retention half-time for uranium in bone is 70-200 days.
• Retention in body skeleton (66%), liver (16%), kidneys (8%), other tissues (10%)

Radiation Toxicity

• Alpha emitter thus not serious external radiation hazard. Alpha radiation has poor penetrating ability. Direct contact with bare DU for 250 hours is necessary to exceed annual occupational exposure limits.
• Internal exposure via inhalation, ingestion, wound contamination or retained fragments warrants some concern.
• Chronic exposure by inhalation is potential radiologic hazard to the lung and thoracic lymph nodes.
• Genotoxicity, mutagenicity and reproductive effects are being studied.

Chemical Toxicity

• Kidney dysfunction main chemically-induced effect of uranium
• Can develop tubulopathy or renal tubular acidosis

Clinical Features

• Exposure normally does not cause symptoms, as small amounts are quickly passed
• If significantly large exposure, can cause renal damage due to heavy metal properties

Differential Diagnosis

• Alpha radiation exposure
• Heavy metal toxicity

Evaluation

• Patients who feel they have been exposed to high levels of DU should be evaluated

History

• Circumstances : date, time, route of exposure, amount
• Evidence of wound or embedded fragments?
• Prolonged skin contact i.e. through keeping of a souvenir?

Workup

• UA
• CBC
• BMP for renal function
• CXR if significant inhalation exposure
• Tests for uranium exposure if close proximity/large exposure or any abnormalities:
  • Beta-2 microglobulin 24h urine to evaluate for tubulopathy
  • Urine uranium level; if elevated, check 24h excreted DU level to include isotope-specific ratios

Management

• Remove patient from exposure
• Externally decontaminate if residue present on patient
• Base further treatment on symptoms observed
• Renal tubulopathy treatment:
  • Needs to be initiated early, prior to fixation of uranium in the skeleton
  • Sodium bicarbonate to alkalinize urine
  • Consider heavy metal chelation therapy
  • Monitor renal function

Disposition

• Most cases of exposure have no permanent effect
• Likelihood to develop any health effects is low
• If exposure is via inhalation and significant amounts of insoluble uranium compounds deposited in lungs than patient will need long-term surveillance/follow-up

References

1. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Uranium (Update), February 2013.
2. McDiarmid, M.A. (2001). Depleted uranium and public health. BMJ, 322(7279), 123-124.
3. U.S. Army Environmental Policy Institute (AEPI). (June 1995). Health and Environmental Consequences of Depleted Uranium Use in the U.S. Army: Technical Report.
4. Department of Defense. (August 4, 1998). Health Effects of Depleted Uranium - Fact Sheet.
5. U.S. Army Environmental Policy Institute, (AEPI). (June 1994). Health and Environmental Consequences of Depleted Uranium Use by the U.S. Army, Summary Report to Congress.
6. World Health Organization (WHO), Guidance On Exposure to DU- For Medical Officers and Programme Administrators, 2001.
7. World Health Organization (WHO), Depleted Uranium: Sources, Exposure and Health Effects, 2001.
8. World Health Organization (WHO), Depleted Uranium Fact Sheet, revised January 2003.