Semen Uranium Concentrations in Depleted Uranium Exposed Gulf War Veterans: Correlations with Other Body Fluid Matrices.

Environmental metal exposure, as well as dietary metals, may adversely affect semen quality even as others play an essential role in normal spermatogenesis and fertility. Measures of seminal fluid metals have therefore been of high interest in the last several decades but have shown inconsistent results in correlations with some semen quality parameters. As well, environmental metal measures across various body fluid matrices have not been consistently correlated contrary to what one might hypothesize based on a systemic body burden of metal. This may be due to the body fluid matrices assessed and to other differences in laboratory methods and sample preparation. Measures of uranium, a potentially toxic metal in humans, have not previously been reported in the semen of environmentally metal-exposed populations. We report here uranium seminal fluid results and the high correlation of uranium concentrations across several body fluid matrices in a cohort of military veterans exposed to depleted uranium in combat events during the Iraqi Gulf War. These results inform the risk communication conversation for exposed populations and broaden the public health assessments from various exposure scenarios.

The U.S. Department of Veterans' Affairs depleted uranium exposed cohort at 25 Years: Longitudinal surveillance results.

BACKGROUND: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. METHODS: During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. RESULTS: On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature. CONCLUSIONS: At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.

Significance of dermatologic findings in a cohort of depleted uranium-exposed veterans of Iraqi conflicts.

BACKGROUND: Depleted uranium (DU)-containing weapons have been used in military operations since 1991. There is interest in following veterans who were occupationally exposed to DU by either inhalation or retention of fragments. A cohort of DU-exposed Gulf War I veterans has been followed longitudinally at the Baltimore Veterans Administration Medical Center since 1993. OBJECTIVE: The aim was to monitor chronic dermatological findings associated with occupational DU exposure in the 2013 cohort. METHODS: Thirty-five veterans were evaluated. This study was reviewed and approved by the institutional review board and the Baltimore Veterans Administration Medical Center research service. Depleted uranium exposure was measured using creatinine-adjusted urine uranium concentrations (micrograms of uranium per gram of creatinine [µgU/gCrea]). Detailed medical histories, physical examinations, and exposure histories were performed. RESULTS: Using a cutoff level of 0.1 µgU/gCrea, 11 veterans were placed in the high-uranium exposure group, whereas 23 veterans were placed in the low-uranium exposure group. Retained fragments were documented in 91% of the high-exposure group versus that in 13% of the low-exposure group (P < 0.001), and fragment-related scarring was significantly increased in the high-exposure group (P = 0.002). Other dermatological findings such as dermatitis were also assessed. CONCLUSIONS: Fragment retainment and related scarring was significantly increased in veterans exposed to high levels of DU. Continuous monitoring of this cohort will yield interesting dermatological findings related to DU exposure.

Mutagenicity monitoring following battlefield exposures: Longitudinal study of HPRT mutations in Gulf War I veterans exposed to depleted uranium.

A total of 70 military Veterans have been monitored for HPRT T-cell mutations in five separate studies at 2-year intervals over an 8-year period. Systemic depleted uranium (DU) levels were measured at the time of each study by determining urinary uranium (uU) excretion. Each HPRT study included 30-40 Veterans, several with retained DU-containing shrapnel. Forty-nine Veterans were evaluated in multiple studies, including 14 who were in all five studies. This permitted a characterization of the HPRT mutation assay over time to assess the effects of age, smoking and non-selected cloning efficiencies, as well as the inter- and intra-individual variability across time points. Molecular analyses identified the HPRT mutation and T-cell receptor (TCR) gene rearrangement in 1,377 mutant isolates. An unexpected finding was that in vivo clones of HPRT mutant T-cells were present in some Veterans, and could persist over several years of the study. The calculated HPRT mutant frequencies (MFs) were repeatedly elevated in replicate studies in three outlier Veterans with elevated urinary uranium excretion levels. However, these three outlier Veterans also harbored large and persistent in vivo HPRT mutant T-cell clones, each of which was represented by a single founder mutation. Correction for in vivo clonality allowed calculation of HPRT T-cell mutation frequencies (MutFs). Despite earlier reports of DU associated increases in HPRT MFs in some Veterans, the results presented here demonstrate that HPRT mutations are not increased by systemic DU exposure. Additional battlefield exposures were also evaluated for associations with HPRT mutations and none were found.

Mutagenicity monitoring following battlefield exposures: Molecular analysis of HPRT mutations in Gulf War I veterans exposed to depleted uranium.

Molecular studies that involved cDNA and genomic DNA sequencing as well as multiplex PCR of the HPRT gene were performed to determine the molecular mutational spectrum for 1,377 HPRT mutant isolates obtained from 61 Veterans of the 1991 Gulf War, most of whom were exposed to depleted uranium (DU). Mutant colonies were isolated from one to four times from each Veteran (in 2003, 2005, 2007, and/or 2009). The relative frequencies of the various types of mutations (point mutations, deletions, insertions, etc.) were compared between high versus low DU exposed groups, (based on their urine U concentration levels), with HPRT mutant frequency (as determined in the companion paper) and with a database of historic controls. The mutational spectrum includes all classes of gene mutations with no significant differences observed in Veterans related to their DU exposures.

Biologic monitoring and surveillance results for the department of veterans affairs' depleted uranium cohort: Lessons learned from sustained exposure over two decades.

BACKGROUND: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly fire incidents have been monitored in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. METHODS: An in-patient clinical surveillance protocol was performed on 35 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. RESULTS: Although urine U concentrations continue to be elevated in this group, illustrating on-going in situ mobilization of U from embedded fragments, no consistent U-related health effects have been observed. CONCLUSIONS: Now more than 20 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As tissue concentrations continue to accrue with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.

Detection of a wide variety of human and veterinary fluoroquinolone antibiotics in municipal wastewater and wastewater-impacted surface water.

As annual sales of antibiotics continue to rise, the mass of these specially-designed compounds entering municipal wastewater treatment systems has also increased. Of primary concern here is that antibiotics can inhibit growth of specific microorganisms in biological processes of wastewater treatment plants (WWTPs) or in downstream ecosystems. Growth inhibition studies with Escherichia coli demonstrated that solutions containing 1-10 µg/L of fluoroquinolones can inhibit microbial growth. Wastewater samples were collected on a monthly basis from various treatment stages of a 30 million gallon per day WWTP in Maryland, USA. Samples were analyzed for the presence of 11 fluoroquinolone antibiotics. At least one fluoroquinolone was detected in every sample. Ofloxacin and ciprofloxacin exhibited detection frequencies of 100% and 98%, respectively, across all sampling sites. Concentrations of fluoroquinolones in raw wastewater were as high as 1900 ng/L for ciprofloxacin and 600 ng/L for ofloxacin. Difloxacin, enrofloxacin, fleroxacin, moxifloxacin, norfloxacin, and orbifloxacin were also detected at appreciable concentrations of 9-170 ng/L. The total mass concentration of fluoroquinolones in raw wastewater was in the range that inhibited E. coli growth, suggesting that concerns over antibiotic presence in wastewater and wastewater-impacted surface water are valid. The average removal efficiency of fluoroquinolones during wastewater treatment was approximately 65%; furthermore, the removal efficiency for fluoroquinolones was found to be negatively correlated to biochemical oxygen demand removal and positively correlated to phosphorus removal.

Long-term exposure to depleted uranium in Gulf-War veterans does not induce chromosome aberrations in peripheral blood lymphocytes.

Depleted uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic, and long-term exposure may cause adverse health effects. This study evaluates genotoxic effects of exposure to DU by measuring chromosome damage in peripheral blood lymphocytes with fluorescence in situ hybridization whole-chromosome painting. Study participants are Gulf War-I Veterans with embedded DU fragments and/or inhalation exposure due to involvement in friendly-fire incidents; they are enrolled in a long-term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 39 to 62 years. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use, against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. Translocation frequencies in these Veterans were all well within the normal range of published values for healthy control subjects from around the world. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans.

Pulmonary health effects in Gulf War I service members exposed to depleted uranium.

OBJECTIVE: In a population of Gulf War I veterans who sustained inhalational exposure to depleted uranium during friendly fire incidents in 1991, we evaluated whether those with high body burdens of uranium were more likely to have pulmonary health abnormalities than those with low body burdens. METHODS: We compared self-reported respiratory symptoms, mean pulmonary function values, and prevalence of low-dose chest computed tomography abnormalities between high and low urine uranium groups. RESULTS: We found no significant differences in respiratory symptoms, abnormal pulmonary function values, or prevalence of chest computed tomography abnormalities between high and low urine uranium groups. Overall, the cohort's pulmonary function values fell within the expected clinical range. CONCLUSIONS: Our results support previous estimates that the depleted uranium levels inhaled during the 1991 friendly fire incidents likely do not cause long-term adverse pulmonary health effects.

The Gulf War depleted uranium cohort at 20 years: bioassay results and novel approaches to fragment surveillance.

During the 1991 GulfWar, U.S. service members were exposed to depleted uranium (DU) through friendly-fire incidents involving DU munitions and vehicles protected by DU armor. Routes of exposure to DU involved inhalation of soluble and insoluble DU oxide particles, wound contamination, and retained embedded DU metal fragments that continue to oxidize in situ and release DU to the systemic circulation. A biennial health surveillance program established for this group of Veterans by the U.S. Department of Veterans Affairs has shown continuously elevated urine DU concentrations in the subset of veterans with embedded fragments for over 20 years. While the 2011 assessment was comprehensive, few clinically significant U-related health effects were observed. This report is focused on health outcomes associated with two primary target organs of concern for long term effects of this combat-related exposure to DU. Renal biomarkers showed minimal DU-related effects on proximal tubule function and cytotoxicity, but significant biomarker results were observed when urine concentrations of multiple metals also found in fragments were examined together. Pulmonary tests and questionnaire results indicate that pulmonary function after 20 y remains within the clinical normal range. Imaging of DU embedded fragment-associated tissue for signs of inflammatory or proliferative reactions possibly associated with foreign body transformation or with local alpha emissions from DU was also conducted using PET-CT and ultrasound. These imaging tools may be helpful in guiding decisions regarding removal of fragments.

Uranium quantification in semen by inductively coupled plasma mass spectrometry.

In this study we report uranium analysis for human semen samples. Uranium quantification was performed by inductively coupled plasma mass spectrometry. No additives, such as chymotrypsin or bovine serum albumin, were used for semen liquefaction, as they showed significant uranium content. For method validation we spiked 2g aliquots of pooled control semen at three different levels of uranium: low at 5 pg/g, medium at 50 pg/g, and high at 1000 pg/g. The detection limit was determined to be 0.8 pg/g uranium in human semen. The data reproduced within 1.4-7% RSD and spike recoveries were 97-100%. The uranium level of the unspiked, pooled control semen was 2.9 pg/g of semen (n=10). In addition six semen samples from a cohort of Veterans exposed to depleted uranium (DU) in the 1991 Gulf War were analyzed with no knowledge of their exposure history. Uranium levels in the Veterans' semen samples ranged from undetectable (<0.8 pg/g) to 3350 pg/g. This wide concentration range for uranium in semen is consistent with known differences in current DU body burdens in these individuals, some of whom have retained embedded DU fragments.

Surveillance for long-term health effects associated with depleted uranium exposure and retained embedded fragments in US veterans.

OBJECTIVE: To ensure that all veterans with retained embedded fragments are properly monitored for potential health effects of embedded materials. METHODS: Urine biomonitoring and health surveillance programs were developed to gather information about health risks associated with chemicals released from embedded fragments. RESULTS: Elevated systemic exposure to depleted uranium (DU) that continues to occur in veterans with DU fragments remains a concern, although no clinically significant DU-related health effects have been observed to date. Other metals and local tissue reactions to embedded fragments are also of concern. CONCLUSIONS: Knowledge gained from these programs will help to develop guidelines for surgical removal of tissue-embedded fragments.

Measures of genotoxicity in Gulf war I veterans exposed to depleted uranium.

Exposure to depleted uranium (DU), an alpha-emitting heavy metal, has prompted the inclusion of markers of genotoxicity in the long-term medical surveillance of a cohort of DU-exposed Gulf War veterans followed since 1994. Using urine U (uU) concentration as the measure of U body burden, the cohort has been stratified into low-u (<0.10 µg U/g creatinine) and high-u groups (≥ 0.10 µg U/g creatinine). Surveillance outcomes for this cohort have historically included markers of mutagenicity and clastogenicity, with past results showing generally nonsignificant differences between low- vs. high-U groups. However, mean hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutant frequencies (MFs) have been almost 50% higher in the high-U group. We report here results of a more comprehensive protocol performed in a 2009 evaluation of a subgroup (N = 35) of this cohort. Four biomarkers of genotoxicity [micronuclei (MN), chromosome aberrations, and MFs of HPRT and PIGA] were examined. There were no statistically significant differences in any outcome measure when results were compared between the low- vs. high-U groups. However, modeling of the HPRT MF results suggests a possible threshold effect for MFs occurring in the highest U exposed cohort members. Mutational spectral analysis of HPRT mutations is underway to clarify a potential clonal vs. a threshold uU effect to explain this observation. This study provides a comprehensive evaluation of a human population chronically exposed to DU and demonstrates a relatively weak genotoxic effect of the DU exposure. These results may explain the lack of clear epidemiologic evidence for U carcinogenicity in humans. Environ. Mol. Mutagen., 2011. © 2011 Wiley-Liss, Inc.

Patch testing with uranyl acetate in veterans exposed to depleted uranium during the 1991 Gulf war and the Iraqi conflict.

BACKGROUND: The Depleted Uranium Follow-Up Program is a clinical surveillance program run by the Baltimore Veterans Affairs Medical Center since 1993 for veterans of the Gulf and Iraqi wars who were exposed to depleted uranium (DU) as a result of "friendly-fire" incidents. OBJECTIVES AND METHODS: In 2009, 40 veterans from this cohort were screened for skin reactivity to metals by patch-testing with extended metal series and uranyl acetate (0.25%, 2.5%, and 25%). A control arm comprised 46 patients without any known occupational exposures to DU who were seen at the University of Maryland Dermatology Clinic for evaluation of allergic contact dermatitis. RESULTS: Excluding irritant reactions, no patch-test reactions to uranyl acetate were observed in the participants. Irritant reactions to DU were more common in the clinic cohort, likely reflective of the demographic differences between the two arms of the study. Biologic monitoring of urine uranium concentrations in the DU program participants with 24-hour urine samples showed evidence of percutaneous uranium absorption from the skin patches. CONCLUSION: We conclude that dermatitis observed in a subset of the veterans was unrelated to their military DU exposure. Our data suggest that future studies of skin testing with uranyl acetate should utilize 0.25%, the least irritating concentration.

Biological monitoring for depleted uranium exposure in U.S. Veterans.

BACKGROUND: As part of an ongoing medical surveillance program for U.S. veterans exposed to depleted uranium (DU), biological monitoring of urine uranium (U) concentrations is offered to any veteran of the Gulf War and those serving in more recent conflicts (post-Gulf War veterans). OBJECTIVES: Since a previous report of surveillance findings in 2004, an improved methodology for determination of the isotopic ratio of U in urine ((235)U:(238)U) has been developed and allows for more definitive evaluation of DU exposure. This report updates previous findings. METHODS: Veterans provide a 24-hr urine specimen and complete a DU exposure questionnaire. Specimens are sent to the Baltimore Veterans Affairs Medical Center for processing. Uranium concentration and isotopic ratio are measured using ICP-MS at the Armed Forces Institute of Pathology. RESULTS: Between January 2003 and June 2008, we received 1,769 urine specimens for U analysis. The mean urine U measure was 0.009 microg U/g creatinine. Mean urine U concentrations for Gulf War and post-Gulf War veterans were 0.008 and 0.009 microg U/g creatinine, respectively. Only 3 of the 1,700 (0.01%) specimens for which we completed isotopic determination showed evidence of DU. Exposure histories confirmed that these three individuals had been involved in "friendly fire" incidents involving DU munitions or armored vehicles. CONCLUSIONS: No urine U measure with a "depleted" isotopic signature has been detected in U.S. veterans without a history of retained DU embedded fragments from previous injury. These findings suggest that future DU-related health harm is unlikely in veterans without DU fragments.

Depleted uranium exposure and health effects in Gulf War veterans.

Health effects stemming from depleted uranium (DU) exposure in a cohort of Gulf War veterans who were in or on US Army vehicles hit by friendly fire involving DU munitions are being carefully monitored through the Baltimore Veterans Affairs (VA) DU Follow-Up Program initiated in 1993. DU exposure in this cohort has been directly measured using inductively coupled plasma-mass spectrometer (ICP-MS) isotopic analysis for DU in urine specimens. Soldiers with embedded DU fragments continue to excrete elevated concentrations of U in their urine, documenting ongoing systemic exposure to U released from their fragments. Biennial surveillance visits provide a detailed health assessment that includes basic clinical measures and surveillance for early changes in kidney function, an expected target organ for U. Tests also include measurements of genotoxicity and neuroendocrine, neurocognitive and reproductive function. With the exception of the elevated urine U excretion, no clinically significant expected U-related health effects have been identified to date. Subtle changes in renal function and genotoxicity markers in veterans with urine U concentrations greater than 0.1 microg(-1) creatinine, however, indicate the need for continued surveillance of these DU-exposed veterans.

Biological monitoring and surveillance results of Gulf War I veterans exposed to depleted uranium.

OBJECTIVE: To relate medical surveillance outcomes to uranium biomonitoring results in a group of depleted uranium (DU)-exposed, Gulf War I veterans. METHODS: Thirty-two veterans of Gulf War I who were victims of 'friendly fire' involving DU weapons, in whom exposure assessment can accurately be measured, had urine uranium concentrations determined using ICP-MS technology. Clinical laboratory parameters were measured and related to urine uranium concentrations. Data were examined by stratifying the cohort into a low U group, <0.10 mug/g creatinine versus a high U group, >/=0.10 mug/g creatinine and assessing differences between groups. RESULTS: Over a decade after first exposure, soldiers possessing embedded DU fragments continue to excrete elevated concentrations of uranium in urine. No clinically significant uranium related health effects were observed in blood count, blood chemistries including renal markers, neuropsychological measures, and semen quality or genotoxicity measures. Markers of early changes in renal glomerular and tubular function were not statistically different between groups; however, genotoxicity measures continue to show subtle, mixed results. CONCLUSION: Persistent urine uranium elevations continue to be observed more than 12 years since first exposure. Despite this, renal and other clinical abnormalities were not observed, likely due to the 'relatively' low uranium burden in this cohort compared to historical uranium-exposed occupational groups. Continuing surveillance is indicated, however, due to the on-going nature of the exposure. These results are an important finding in light of the on-going controversy regarding health effects observed in soldiers of the Gulf War and other conflicts, whose uranium exposure assessment is unable to be accurately determined.

Prediction of renal concentrations of depleted uranium and radiation dose in Gulf War veterans with embedded shrapnel.

Mobilization of uranium (U) from embedded depleted uranium (DU) metal fragments in Gulf War veterans presents a unique exposure scenario for this radioactive and nephrotoxic metal. In a cohort of exposed veterans, urine U concentrations measured every two years since 1993 persistently range from 10 to over 500 times normal levels, indicating that embedded DU fragments give rise to chronic, systemic exposure to U. Health effects of this exposure are not fully known, but clinical surveillance of these soldiers continues in light of animal studies showing that U released from implanted DU pellets results in tissue accumulation of U. The biokinetic model for uranium recommended by the International Commission on Radiological Protection was used to predict kidney U concentrations and tissue radiation doses in veterans with DU shrapnel based on their urine U excretion. Results suggest that kidney U concentrations in some individuals reached their peak within six years after the war, while in others, concentrations continue to increase and are approaching 1 ppm after 10 y. These results are consistent with urine biomarker tests of renal proximal tubular cell function and cytotoxicity which have shown elevated mean urinary protein excretion indicative of functional effects in veterans with high urine U concentrations (> or =0.10 microg g(-1) creatinine). Predicted lifetime effective radiation dose from DU released to the blood for the highest exposed individual in this cohort was substantially less than the National Council on Radiation Protection (NCRP) limit for occupational exposure. These results provide further support for current health protection guidelines for DU, which are based on the metal's chemical rather than its radiological toxicity. In light of the potential for continued accumulation of U in the kidney to concentrations approaching the traditional guidance level of 3 ppm U, these results indicate the need for continued surveillance of this population for evidence of developing renal dysfunction.

Uranium analysis in urine by inductively coupled plasma dynamic reaction cell mass spectrometry.

Urine uranium concentrations are the best biological indicator for identifying exposure to depleted uranium (DU). Internal exposure to DU causes an increased amount of urine uranium and a decreased ratio of 235U/238U in urine samples, resulting in measurements that vary between 0.00725 and 0.002 (i.e., natural and depleted uranium's 235U/238U ratios, respectively). A method based on inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS) was utilized to identify DU in urine by measuring the quantity of total U and the 235U/238U ratio. The quantitative analysis was achieved using 233U as an internal standard. The analysis was performed both with and without the reaction gas oxygen. The reaction gas converted ionized 235U+ and 238U+ into 235UO2+ (m/z = 267) and 238UO2+ (m/z = 270). This conversion was determined to be over 90% efficient. A polyatomic interference at m/z 234.8 was successfully removed from the 235U signal under either DRC operating conditions (with or without oxygen as a reaction gas). The method was validated with 15 urine samples of known uranium compositions. The method detection limit for quantification was determined to be 0.1 pg U mL(-1) urine and an average coefficient of variation (CV) of 1-2% within the sample measurements. The method detection limit for determining 235U/238U ratio was 3.0 pg U mL(-1) urine. An additional 21 patient samples were analyzed with no information about medical history. The measured 235U/238U ratio within the urine samples correctly identified the presence or absence of internal DU exposure in all 21 patients.

Biologic monitoring for urinary uranium in gulf war I veterans.

Biologic monitoring for total uranium in urine of Gulf War I veterans concerned about past exposure to depleted uranium (DU) has been offered by the Departments of Veterans Affairs and Defense since the late 1990's. DU, a component of U.S. munitions and tank armor, was first used during that conflict. Two hundred and twenty-seven veterans submitted samples for analysis from January 2000 through December 2002, which included a 24-h urine sample for determination of total urinary uranium concentration and completed questionnaires describing their wartime exposure experiences. Thirty questionnaire items characterizing DU exposure opportunities were collapsed into 19 exposure categories. Urine uranium (U) results were stratified into low and high uranium groups with 0.05 microg U g creatinine as the cut point. Exposure scenarios in the high and low uranium groups were similar in frequency and type with only the presence of retained shrapnel being predictive of a high urine uranium value, as found in the first phase of this surveillance of 169 veterans performed prior to 2000. Twenty-two veterans exhibited U levels in the high range. Isotopic analysis, available for 21 of these 22, revealed that all but three of these samples contained natural and not depleted uranium. These three participants had retained DU shrapnel as a result of their past injuries. Thus, even with an enlarged cohort, elevated urine uranium values in the absence of retained DU fragments are unlikely. The utility of isotopic analysis to more fully characterize uranium biomonitoring results is also demonstrated.