The overwhelming majority (97%) of the 1,769 urine specimens submitted by Gulf War and post-Gulf War veterans had urine U levels in the range of those found in the general U.S. population, that is, ≤95th percentile of NHANES results collected between 2001 and 2002 (CDC 2005
). More importantly, only 3 of the 1,700 urine specimens that underwent isotopic analysis had a DU isotopic signature. These three came from individuals reporting embedded fragments from DU friendly fire–related injury.
Only a small percentage of samples (2.2% Gulf War and 1.5% post-Gulf War) had urine U concentrations above the DU surveillance program’s cut-point of 0.05 μg U/g creatinine. The vast majority of these samples were Unat
. The source of exposure for these individuals was most likely drinking water. The concentration of U in drinking water varies across the United States and the world, depending on the composition of the local bedrock. For example, unusually high concentrations of Unat
in drinking water have been found in areas of Finland (Kurttio et al. 2002
), Canada (Zamora et al. 1998
), and the United States (Orloff et al. 2004
). Another potential source of Unat
exposure may be related to residence near a uranium mine or mill.
The findings of this study are generally consistent with those reported previously for surveillance of Gulf War personnel performed between August 1998 and December 1999 (McDiarmid 2001a
) and from January 2000 through December 2002 (McDiarmid 2004a
) (see ). We found no statistical difference in the means of the urine U between the 169 samples received from 1998 through 1999 and the 277 samples received between 2000 and 2002 (the earlier reports of mail-in surveillance results cited above). However, when we compared mean urine U measures for these two cohorts (0.020 and 0.023 μg U/g creatinine) with the mean of the 1,769 samples reported here (0.009 μg U/g creatinine), we observed a statistically significant difference (p
= 0.001). This difference can be explained by the change in the methodology used to measure the urine U concentration value. As noted above, starting in July 2003 samples were analyzed by ICP-MS. This methodology is more sensitive at lower urine U concentrations than is the KPA method formerly used to measure urine U concentrations. For samples collected and analyzed before 2003, we used the detection limit value for the KPA method in the calculation of the creatinine-standardized urine U concentrations for samples with U concentrations at or below the detection limit. This small overestimate of urine U concentrations is likely the basis for the higher group averages calculated for the earlier two cohorts.
As mentioned above, isotopic analysis of the samples examined for this study detected only three individuals who are excreting DU in their urine. Levels of urine U are higher in this group of three compared with the isotopically Unat group (0.037 vs. 0.009 μg U/g creatinine). When we consider the entire surveillance population, dating back to 1998 (n= 2,246), only a total of four individuals have been identified as excreting DU in their urine. Exposure history confirms that these four individuals were injured as a result of friendly fire and have retained embedded fragments.
The results reported here are also consistent with those of another Department of Veterans Affairs–sponsored DU surveillance program, which has been following for 15 years a dynamic cohort of 77 Gulf War veterans with known exposure to DU from documented friendly fire incidents during the 1991 Gulf War. Among this group, only those with retained DU fragments from traumatic injury continue to excrete higher concentrations of U in their urine (McDiarmid et al. 2000, 2001b, 2004b, 2006, 2007, 2009
). Urine U levels in those without retained DU fragments, but who sustained a historically documented inhalation exposure during the friendly fire incidents, are similar to general population levels and are isotopically consistent with Unat
The persistent elevation of urine U observed in those with retained fragments is supported by animal studies in which DU pellets implanted into the animals (Hahn et al. 2002
; Pellmar et al. 1999
) oxidized in situ
, thus serving as a metal depot for ongoing systemic exposure. As the metal ions are released to the circulation, they are filtered by the kidney and excreted in urine, resulting in higher U concentrations.
The data reported here on this expanded surveillance cohort of both Gulf War and more recently deployed soldiers and veterans confirm previous findings that, in the absence of retained DU fragments, it is highly unlikely that an individual will have chronically elevated urine U.
Historically, concern has been raised about the long lag time between exposure during deployment and subsequent biomonitoring performed years later. A transient U elevation from a one-time inhalation exposure could be missed if sampling occurred too long after U exposure, whereas measurements taken at the time of a potential exposure incident may indicate that an exposure to DU has occurred. Estimates reported by the Royal Society of London (2002)
suggest that a DU oxide inhalation dose sufficiently high to cause significant health effects would still be detectable 10 years after exposure, using analytical techniques currently available.
The rate of elimination of an inhaled dose of DU depends on many parameters, including the chemical and physical form of the DU oxide particles inhaled and the exposure dose. Data collected as part of a U.S. Army DU aerosol characterization and risk assessment study, which characterized DU aerosols created by the perforation of an Abrams tank and a Bradley Fighting Vehicle with a large-caliber DU penetrator, indicate that soldiers in friendly fire incidents inhaled DU that was a mixture of soluble and insoluble DU oxides (Parkhurst et al. 2005
). Soluble oxides would have been rapidly absorbed through the lungs and cleared by the kidney. Insoluble oxides would have been phagocytized by lung macrophages and cleared from alveolar areas either through the mucocilliary system to the mouth or by transport to lung-associated lymph nodes.
We also address the concern regarding the lag time between exposure and biomonitoring by including veterans from recent military conflicts in our surveillance program. We achieved a shortened time interval between potential initial exposure and assessment of urine U with this group, because we obtained many of these specimens within several weeks of the veterans’ return from deployment. Closing this gap between potential exposure opportunity and sample collection and the fact that we are still observing normal urine U results gives some reassurance that large numbers of soldiers from previous conflicts likely did not incur urine U elevations that were missed because of the delay in sampling.
Even if participants in the Gulf War conflicts had transient exposure to DU, it is highly unlikely that this would result in significant, subsequent health effects for several reasons. The clearance of U from the body is relatively rapid (nearly two-thirds of an acute dose is cleared through the kidney in 24 hr; Agency for Toxic Substances and Disease Registry 1999
). Acute effects of U on the kidney (the primary target organ for soluble U compounds) do not persist after short exposures, and only under chronic exposure conditions does accumulation of U in the kidney cause long-term effects (Royal Society of London 2002
). In addition, the absence of expected effects is supported by findings from the DU Surveillance Program for friendly fire victims. In 15 years of follow-up, no clinically significant U-related health effects have been observed in the cohort, including those with retained DU fragments (McDiarmid et al. 2000, 2001b, 2004b, 2006, 2007, 2009
), except for subtle changes in renal proximal tubule markers in veterans with retained fragments (McDiarmid et al. 2009
To summarize, the U biomonitoring results obtained over three reporting periods—the present study and two previous reports (McDiarmid et al. 2001a; 2004a
)—have shown that > 95% of the 2,246 total urine specimens collected since 1998 had urine U concentrations similar to those found in the general U.S. population (CDC 2005
), and all but one sample, which has a Unat
isotopic signature, had U concentrations < the occupational decision level (0.8 μg/L) used by the Fernald Environmental Management Project for U-exposed workers (Fernauld Environmental Management Project 1997
). In addition, review of exposure histories confirms previous findings that the presence of a retained DU fragment and history of friendly fire exposure are the best predictors of an elevated urine U concentration.
This indicates that for most veterans who are concerned about exposure to DU as a result of their deployment, urine U concentrations outside the normal range are a rare occurrence and DU isotopic signatures are even more uncommon. No persistent urine U elevations have been detected in potentially exposed veterans without a history of DU-embedded fragments. This further suggests that future DU-related health harm is unlikely.