Chapter IV.

Epidemiological and Population Studies I:
Exposure to Uranium, Depleted Uranium
and Low-Level Ionizing Radiation

(Return to: Top; Table of Contents; Author Index)

Summary:

Epidemiological and population studies provide conclusions based on statistical evaluation of data rather than on reproducible experimental results. It is therefore incumbent on the reader to evaluate the parameters defining a study and the statistical methodology used to arrive at given conclusions.

For example, generally speaking, the larger the population studied (sample size), the better. But it is essential that the individual members of the population share a commonality with respect to whatever alleged causitive factor is being scrutinized if the purpose of the study is to determine whether or not a cause/effect relationship exists. It is also important that the control population be as closely identical as possible to the population under study except in that single causitive factor. Obviously, studies in which multiple factors might compete or interfere with the alleged causitive factor are less reliable and may in some cases be of little value.

Suppose, for example, that 40 individuals living within a five-mile radius of a nuclear facility appear to have a cancer rate that is 25% higher than average (say 10 cancers as opposed to 8). By extending the radius under study to 10 miles, the sample size might be increased ten-fold, to 400, and the results may now show no statistically significant increase in cancer rate. But the fallacy with this study is that the additional 360 individuals are not experiencing the same exposure rates as the 40 living closest to the plant. A more appropriate way to increase the sample size would be to include 10 different nuclear plants and keep the five-mile radius parameter. Now you have 400 people in the sample, all of whom live within the presumably high exposure area. If the cancer rate in this population is not significantly higher than the general population (the control), one might conclude with greater reliability that living near nuclear plants entails no increase in cancer risk.

Because data can be so easily manipulated in population studies that rely on statistical results, it should come as no surprise that conclusions reported in the studies in this and the following two chapters vary so widely, with authors even arriving at directly opposing results. Only a careful analysis of the details presented in the full paper will reveal any flaws in the methodology or conclusions, and this challenge is left to the reader.

In this chapter, several reports on Iraqi civilians following the 1991 Gulf war claim an increase in cancers and congenital defects and point to exposure to depleted uranium as a causitive factor. Other studies of veterans and NGO workers from the Balkan conflict showed no increased levels of urinary uranium. A study of a population living in an area in India with high background radiation found no increased cancer risk while another similar study in China showed increased cancer mortality. And one study determined that civilian exposure to DU remains following a military conflict created sufficient risk that cleanup efforts should be undertaken to minimize that risk.

Details:

In 1998, Birchard (1) reported in Lancet the results of Bill Griffin’s studies on the increasing cases of childhood leukemia, adult cancers and congenital malformations in Iraq between 1989 and 1993, suggesting that the use of DU weapons in 1991 were a causitive factor. Kido (2) and Ishikawa (3) report on the radiation effects of Thorotrast, a drug containing radioactive thorium-232. Benign and malignant lung tumors were shown by Collier (4) to result from inhalation exposure of radon by rats.

Nair (5) reports on a study of 100,000 residents in India exposed to high levels of background radiation and showing no increased cancer risk. On the other hand, Bolviken (6) reports on a study in China where increased mortality from nasopharyngeal carcinoma was observed in a region with high background concentrations of uranium and radon. McDiarmid (7) published an article supporting her take on DU and public health in 2001, following years of study into the small contingent of US troops who had been exposed to DU fragments from “friendly fire”. (See Chapter V for other articles by McDiarmid specifically related to Gulf War veterans.)

Pranjik (8) in 2002 published a review (in Croatian) dealing with the toxicological effects of DU and concluded that more research needed to be done, particularly epidemiological studies of veterans and civilians exposed to DU through military use. Meddings (9) reported findings based on urinary analysis of International Red Cross and Red Crescent workers in Kosovo that suggest these NGO workers did not have body burdens of uranium above those expected from background exposure. Ough (10) studied 103 Canadian veterans who might have been exposed to DU in the 1991 Gulf War and in Kosovo and reported no increased incidence of urinary uranium and only natural uranium in hair samples. Labar (15) reports no significant increases in haematological malignancies resulting from the war in Croatian areas known to have been under heavy DU bombardment. Gustavssen (17) reports no increase in haematolymphatic malignancies in over 9000 Swedish personnel who served in the Balkans in the 1990’s. May (19) studied 46 veterans of the Balkan war to establish suitable biomarkers for DU exposure using blood and urine specimens. Obralic (20) studied the observable increase in cancer incidence in Sarajevo residents between 1998 and 2002 and discovered no discernable difference between this increase and that occurring in other areas of southern Europe. Similarly, Milacic (21) and Ibrulj (22) studied residents in areas exposed to DU munitions and found increased chromosomal aberrations present in blood samples. Milacic’s study included as a control a cohort of in individuals occupationally exposed to X-rays and reported the controls’ chromosomal aberrations exceeded that of the residents. Papathanasiou (23) attempted to study changes in cervical cancer incidence in towns bordering the former Yugoslavian states but found the sample size to be insufficient to make any correlations.

Abu-Qare (11) reviews the overriding health concerns resulting from exposure to DU. Giannardi (12) determined that civilian exposure to soil contaminated with DU could, over time, provide a substantial health risk, particularly to children, and that every effort should be made to clean up after its use. Shawky (13) reported in 2003 on a statistical evaluation of causes of mortality in Middle Eastern countries as compared with the rest of the world. Sumanovic-Glanuzima (14) reported no statistically significant increase in birth abnormalities or mortalities in the Mostar hospital of Bosnia-Herzegovina from before hostilities and after hostilities in which DU had been used.

Chen (16) modeled the kidney uptake and burden levels resulting from ingestion and inhalation of DU. Tirmarche (18) surveyed available epidemiological literature for affects resulting from uranium exposure and, excepting the radon/uranium miner correlation, found a woeful lack of systematic studies needed to clearly delineate the effects of uranium exposure.

Durakovic (24) tested urine samples from eight ailing Afghani residents from the Jalalabad region for DU and discovered considerably elevated levels of natural, not depleted, uranium, perhaps explaining their illnesses, but creating an anomaly regarding the source of their uranium exposure.

(Return to: Top; Table of Contents; Author Index)

1. Does Iraq's depleted uranium pose a health risk? by K. Birchard. Lancet Vol. 351, Feb. 28, 1998 (pp. 657).

Reports that Bill Griffin, an Irish petrochemical engineer, compiled a literature review and sent it to the UN Commissioner for Human Rights hypothesizing that the current health and environmental problems in Iraq may be linked to DU weapons use in the 1991 conflict. The report notes that the death rate per 1000 Iraqi children under 5 yrs rose from 2.3 in 1989 to 16.6 in 1993. Cases of lymphoblastic leukemia more than quadrupled.  In men, lung, bladder, bronchus, skin and stomach cancers show the greatest increase. In women, the greatest increases are in breast and bladder cancer, and non-Hodgkin lymphoma.  Congenital malformations have also increased, as have diseases of the immune system.

[Birchard199802Lv351n9103p657]. (PMID: 9500343 [PubMed - indexed for MEDLINE])

2. Cancer mortality of Thorotrast patients in Japan: the second series updated 1998, by C Kido, et al., Radiation Research Vol. 152, 1999 (pp. S81-S83).

[Kido199900RRv152nxpS81].

3. Revised organ partition of thorium-232 in Thorotrast patients, by Y Ishikawa, et al., Radiation Research Vol. 152, 1999 (pp. S102-S106).

[Ishikawa199900RRv152nxpS102].

4. Effects of continuous inhalation exposure of rats to radon and its progeny at various levels of dose and dose rate: Interim results, by CG Collier, et al., Radiation Res Vol. 152, 1999 (pp. S141-S144). 

Shows that exposure to radon and radon progeny causes elevated incidences of both benign and malignant lung tumors.  The study was not yet complete at time of publication.

[Collier1999xxRRv152nxpS141].

5. Population study in the high natural background radiation area in Kerala, India, by MK Nair, et al., Radiation Res. Vol. 152, 1999 (pp. S145-S148). 

High radiation level due mostly to Th.  Of total 400,000 population, 100,000 lived in high radiation areas. Preliminary analysis shows no significant increase in cancer for high exposure group.

[Nair1999xxRRv152nxpS145].

6. Relationships between nasopharyngeal carcinoma and radioactive elements in soils in China, by B Bølviken, Medical Hypotheses Vol. 55, 2000 (pp. 513-516). 

Epidemiological and geochemical maps of China indicate association between high mortality from nasopharyngeal carcinoma (NPC) and low Mg in soil, but high levels of U and Th are also present in regions with high NPC.  The author suggests radioactivity from radon and daughter nuclides may be a contributing factor, but neglects the possibility that U or Th chemical toxicity may play a role.

[Bolviken2000xxMHv55nxp513].

7. Depleted uranium and public health, by MA McDiarmid. BMJ (Clin. Res. Ed.) Vol. 322(7279), Jan. 20, 2001 (pp. 123-124).

[McDiarmid200101BMJv322n7279p123].

8. Internal contamination with depleted uranium and health disorders [Article in Croatian], by N Pranjic, et al., Zavod za Medicinu rada, Medicinski fakultet Univerziteta u Tuzli. Med Arh. Vol. 56(1), 2002 (pp. 39-42).

In this review we used the published data on depleted uranium (experimental and epidemiological) from the current literature. Depleted uranium is a toxic heavy metal that in high dose may cause poisoning and health effects as those caused by lead, mercury, and chromium. It is slightly radioactive. The aim of this review was to select, to arrange, to present references of scientific papers, and to summarise the data in order to give a comprehensive image of the results of toxicological studies on depleted uranium that have been done on animals (including carcinogenic activity). We have also used epidemiological posted study results related to occupational and environmental exposure to depleted uranium. The toxicity of uranium has been studied extensively. The results of the studies indicated primarily its chemical toxicity, particularly renal effects, but depleted uranium is not radiological hazard. Uranium is not metal determined to be carcinogenic (the International Agency of Research on Cancer). The military use of depleted uranium will give additional insight into the toxicology of depleted uranium. The present controversy over the radiological and chemical toxicity of depleted uranium used in the Gulf War requests further experimental and clinical investigations of its effects on the biosphere and human beings.

[Pranjic2002xxMAv56n1p39]. ( PMID: 11917690 [PubMed - indexed for MEDLINE]).

9. Depleted uranium in Kosovo: an assessment of potential exposure for aid workers, by DR Meddings, et al., Unit of the Chief Medical Officer, International Committee of the Red Cross, Geneva, Switzerland. dmeddings@icrc.org. Health Phys. Vol. 82(4), Apr. 2002 (pp. 467-472).

BACKGROUND: During the Kosovo conflict approximately 11 tons of depleted uranium munitions were used against armored targets, predominantly in the west. Potential exposure to uranium amongst employees of the International Red Cross and Red Crescent Movement in western Kosovo was assessed. METHODS: Individuals (n = 31) who had resided at least 3 mo in western Kosovo provided 24-h urine collections and completed an administered questionnaire. Specimens were analyzed for creatinine concentration, and uranium concentration was determined using inductively coupled mass spectrometry. FINDINGS: Subjects ranged in age from 22 to 45 y, and 77% were male. Mean duration of residency was 11 mo, and 14 individuals were in western Kosovo throughout the hostilities. Almost three quarters of subjects reported seeing destroyed tanks or vehicles, predominantly while passing by within a vehicle. Two individuals spent time within 50 m of a destroyed tank or vehicle while outside of a vehicle. Urinary uranium concentrations ranged from 3.5 to 26.9 ng of uranium per liter of urine (median 8.9 ng L(-)). Creatinine normalized values ranged from 2.9 to 21.1 ng of uranium per gram of creatinine (median 7.4 ng g(-1) creatinine). These results fall toward the lower end of urinary uranium determinations made amongst non-exposed populations drawn from a literature review. INTERPRETATION: These results do not indicate an increased exposure to uranium amongst adults living and working in western Kosovo who do not spend time in proximity to destroyed vehicles. Environmental sampling and replication of these results amongst a sample including children and individuals reporting intensive exposure to destroyed vehicles would further develop the exposure assessment.

[Meddings200204HPv82n4p467]. (PMID: 11906135 [PubMed - indexed for MEDLINE]).

10. An examination of uranium levels in Canadian forces personnel who served in the Gulf War and Kosovo, by EA Ough, et al., Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, ON. ough-e@rmc.ca. Health Phys. Vol. 82(4), Apr. 2002 (pp. 527-532).

A uranium bioassay program was conducted involving 103 active and retired Canadian Forces personnel. The total uranium concentrations in each of two 24-h urine collections were analyzed separately at independent commercial laboratories by inductively coupled plasma mass spectrometry (ICP-MS) and by instrumental neutron activation analysis (INAA). The mean and median concentrations were determined to be 4.5 ng L(-1) and 2.8 ng L(-1), respectively, from ICP-MS and 17 ng L(-1) and 15 ng L(-1), respectively, from INAA. The total uranium concentrations were sufficiently low so that isotopic (238U:235U ratio) assays could not be performed directly from urine samples. Isotopic assays were performed on hair samples from 19 of the veterans participating in the testing. The isotopic hair assays were scattered around the natural 238U:235U ratio of 137.8, ranging from 122 +/- 21 to 145 +/- 16 (1sigma). Due to concern expressed in the media over possible depleted uranium exposure and long-term retention in bone, a single bone sample (vertebrate bone marrow) from a deceased member of the Canadian Forces was also analyzed for total uranium content and isotopic ratio by ICP-MS. The sample was shown to have 16.0 +/- 0.3 microg kg(-1) uranium by dry weight and a 238U:238U isotopic ratio of 138 +/- 4, consistent with natural uranium.

[Ough200204HPv82n4p527]. (PMID: 11908516 [PubMed - indexed for MEDLINE]).

11. Depleted uranium--the growing concern, by AW Abu-Qare, et al., Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. J Appl Toxicol. Vol. 22(3), May-June 2002 (pp. 149-152).

Recently, several studies have reported on the health and environmental consequences of the use of depleted uranium. Depleted uranium is a heavy metal that is also radioactive. It is commonly used in missiles as a counterweight because of its very high density (1.6 times more than lead). Immediate health risks associated with exposure to depleted uranium include kidney and respiratory problems, with conditions such as kidney stones, chronic cough and severe dermatitis. Long-term risks include lung and bone cancer. Several published reports implicated exposure to depleted uranium in kidney damage, mutagenicity, cancer, inhibition of bone, neurological deficits, significant decrease in the pregnancy rate in mice and adverse effects on the reproductive and central nervous systems. Acute poisoning with depleted uranium elicited renal failure that could lead to death. The environmental consequences of its residue will be felt for thousands of years. It is inhaled and passed through the skin and eyes, transferred through the placenta into the fetus, distributed into tissues and eliminated in urine. The use of depleted uranium during the Gulf and Kosovo Wars and the crash of a Boeing airplane carrying depleted uranium in Amsterdam in 1992 were implicated in a health concern related to exposure to depleted uranium. Copyright 2002 John Wiley & Sons, Ltd.

[AbuQare200205JATv22n3p149]. (PMID: 12015793 [PubMed - indexed for MEDLINE]).

12. Military use of depleted uranium: assessment of prolonged population exposure, by C Giannardi, et.al., Fisica Ambientale, Dipartimento di Firenze ARPAT. Journal of Environmental Radioactivity Vol.64(2,3), 2003 (pp. 227-236).

This work is an exposure assessment for a population living in an area contaminated by the use of depleted uranium (DU) weapons. RESRAD 5.91 code was used to evaluate the average effective dose at depths of 1, 10, 20 cm of contaminated soil in a residential farming scenario. Critical pathways and groups are identified in soil inhalation and ingestion; critical group is identified in children playing with the soil. From the available information on DU release at targeted sites, both critical and average exposure can produce toxicological hazards. The annual dose limit for the population can be exceeded within a few years from DU deposition for soil inhalation. As a result, clean up at targeted sites must be planned on the basis of measured concentration, when available, while special measures must be adopted anyway to reduce unaware exposures.

[Giannardi200302JERv64n2p227]. (PMID: 12500807 [PubMed - indexed for MEDLINE]).

13. Causes of death in the Eastern Mediterranean Region during the years 1998-2000, by S Shawky, PO Box 115, Jeddah 21411, Kingdom of Saudi Arabia. Tel. +966 (2) 6318318. Fax. +966 (2) 6323142. E-mail: shshawky@hotmail.com. Saudi Med J. Vol. 24(4), Apr. 2003 (pp. 380-387).

OBJECTIVE: This paper aims to consider the available mortality data as an insight to epitomize the mortality pattern and the main leading causes of death specific to the Easter Mediterranean Region (EMR) in order to set priorities for future research in the region. METHODS: Data was taken from the last 3 World Health Organization (WHO) mortality statistics. Crude mortality rates were compared between the 6 WHO regions for the years 1998, 1999 and 2000. Proportional mortality and standardized proportional mortality ratios were calculated for the causes of death and types of malignant neoplasm deaths and compared between the EMR and the other regions of the world. Spearman coefficient rank-order correlation was calculated to detect significant correlation between the ranking of the main causes of death in EMR and the 3 basic demographic, socio-economic and health care indicators in the 6 regions of the world. RESULTS: The results of this study showed that approximately 9 per 1,000 of the world's population die annually. Africa and Europe have the highest mortality rates. The main causes of death worldwide are cardiovascular diseases, infectious or parasitic diseases, malignant neoplasm, infectious respiratory diseases and other respiratory diseases. In EMR, approximately 8 per 1,000 die annually. The causes of death in EMR can be classified into 3 categories. 1) Non-prominent in EMR as compared to other regions of the world. 2) Prominent in EMR and significantly correlated to the basic indicators. 3) Prominent in EMR but not related to the basic indicators. These include deaths due to wars, congenital anomalies, perinatal conditions, genitourinary diseases, endocrine disorders, road traffic accidents, cancer bladder, lymphoma leukemia CONCLUSION: The results of this study emerged the need for extensive epidemiological studies to investigate thoroughly the main causes of death influencing mortality in EMR, specially that they coincide with the health consequences of depleted uranium. Also, most of these health conditions were previously described among the United States and European veterans who served in the Gulf War.

[Shawky200304SMJv24n4p380]. (PMID: 12754539 [PubMed - in process]).

14. Incidence of major congenital malformations in a region of Bosnia and Herzegovina allegedly polluted with depleted uranium, by D Sumanovic-Glamuzina , et al., Department of Pediatrics, Mostar University Hospital, Mostar, Bosnia and Herzegovina. dara.glamuzina@tel.net.ba. Croat Med J. Vol. 44(5), Oct. 2003 (pp. 579-584).

OBJECTIVES: To determine the prevalence of major congenital malformations in West Herzegovina, a part of Bosnia and Herzegovina, immediately and five years after 1991-1995 military activities, which allegedly included the use of weapons with depleted uranium. METHODS: The study included all live-born and stillborn neonates and excluded all aborted fetuses in two one-year cohorts (1995 and 2000) of neonates in the Maternity Ward of the Mostar University Hospital. Malformations were recorded according to the recommendations of the EUROCAT protocol. RESULTS: Major malformations were found in 40 (2.16%) out of 1,853 neonates in 1995 (95% confidence interval [CI], 1.49-2.82%) and in 33 (2.26%) out of 1,463 neonates five years later (95% CI, 1.50-3.01%), ie, at comparable prevalence. In both cohorts, anomalies of the musculoskeletal system were the most common, followed by anomalies of the digestive system (in 1995) and the cardiovascular system (in 2000). The prevalence of malformations and the organ systems involved were essentially comparable with those in other populations not affected by military activities. CONCLUSION: Despite alleged environmental pollution in some regions of the former Yugoslavia, which was attributed to military activities and the presence of depleted uranium (the "Balkan syndrome"), there was no significant postwar increase in the prevalence of congenital malformations.

[SumanovicGlamuzina200310CMJv44n5p579]. (PMID: 14515417 [PubMed - in process]).

15. Haematological malignancies in childhood in Croatia: investigating the theories of depleted uranium, chemical plant damage and 'population mixing', by Labar B, et al., Faculty of Medicine, University of Zagreb, Croatia. blabar@iskon.hr . Eur J Epidemiol. Vol. 19 (1), 2004 (pp. 55-60).

Some of potential causes proposed to explain the reported increase of haematological malignancies in childhood during or after the war period in several countries include depleted uranium, chemical pollution and population mixing theory. The aim of this study was to define the population of Croatian children aged 0-14 years who were potentially exposed to each of those risks during the war and to investigate any possible association between the exposure and the incidence of haematological malignancies. The authors analyzed the data reported by the Cancer Registry of Croatia during the pre-war period (1986-1990), war period (1991-1995) and post-war period (1996-1999). In the group of 10 counties potentially exposed to depleted uranium and two counties where chemical war damage occurred, no significant difference in incidence of the studied haematological malignancies was noted in comparison to pre-war period. The incidence of lymphatic leukaemia significantly increased in four counties where population mixing had occurred during the war period, supporting the 'mixing theory'. In those counties, the incidence of Hodgkin's lymphoma decreased during and after the war. In Croatia as a whole, decreases in incidence of myeloid leukaemias during war and non-Hodgkin lymphoma after the war were noted. [Labar2004xxEJEv19n1p55] (PMID: 15012023 [PubMed - indexed for MEDLINE]).

16. Model results of kidney burdens from uranium intakes, by Chen J, et al., Radiation Protection Bureau, Health Canada, 775 Brookfield Road, 6302D1, Ottawa K1A 1C1, Canada. jing_chen@hc-sc.gc.ca . Health Phys. Vol. 86 (1), Jan. 2004 (pp. 3-11).

Uranium is a naturally occurring element, which is both radiologically and chemically toxic. When dealing with intakes of uranium, whether natural or depleted, chemical toxicity to the kidney usually predominates over radiological toxicity. This is especially true for uranium compounds in soluble (inhalation Type F) and moderately soluble (inhalation Type M) forms. To assess chemical toxicity, information on kidney burden per unit intake is required. This study summarizes the kidney burdens per unit intake for common exposures from uranium ingestion and inhalation. ICRP models developed for radiation dosimetry purposes can equally well be used to estimate kidney burdens from uranium intakes. While dosimetric quantities and data are tabulated in ICRP publications, data on uranium burdens in kidney are not explicitly given in these tabulations. In this work, the most recent ICRP models were utilized to generate a compilation of kidney burdens from common intakes. Calculations were made for four age groups from infant to adult. For all age groups, long-term chronic uranium ingestion will result in a kidney burden of 6.6% of daily uranium intake. Comparisons of kidney burdens due to acute ingestion and acute inhalation show that inhaled uranium compounds of Type F and Type M will generally result in higher burdens to kidney compared to the same amount of uranium compounds ingested. [Chen200401HPv86n1p3] (PMID: 14695003 [PubMed - indexed for MEDLINE]).

17. Incidence of cancer among Swedish military and civil personnel involved in UN missions in the Balkans 1989-99, by Gustavsson P, et al., Dept of Occupational and Environmental Health, Stockholm Center for Public Health, Stockholm, Sweden. per.gustavsson@smd.sll.se . Occup Environ Med. Vol. 61 (2), Feb. 2004 (pp. 171-173).

Leukaemia cases among European UN soldiers in the Balkans have been related hypothetically to exposure to depleted uranium. This study was performed to investigate the risk of cancer among Swedish personnel (8750 men and 438 women) involved in UN missions in the Balkans 1989-99. The overall incidence of cancer was slightly higher than expected; 34 cancers were observed and 28.1 were expected based on national cancer rates. Among military men, there were eight cases of testicular cancer versus 4.6 expected. There was one case of chronic myeloid leukaemia, and no cases of acute leukaemia. The overall risk of cancer was increased in a subgroup of 648 men taking part in convoy operations, based on only five cancers at four different sites. The study gives no support for the hypothesis that UN service in the Balkans could lead to haematolymphatic malignancies after short latency. However, no exposure assessment was performed, and future follow up is necessary for evaluation of long term risks. [Gustavsson200402OEMv61n2p171] (PMID: 14739385 [PubMed - indexed for MEDLINE]).

18. Uranium exposure and cancer risk: a review of epidemiological studies, (in French) by Tirmarche M, et al. , Service de Radiobiologie et d'Epidemiologie, Direction de la Radioprotection de l'Homme, Institut de Radioprotection et de Surete Nucleaire (IRSN), Fontenay-aux-Roses. margot.tirmarche@irsn.fr . Rev Epidemiol Sante Publique. Vol. 52 (1), Feb. 2004 (pp. 81-90).

OBJECTIVE: At the end of 2000, certain diseases including leukemia were reported among soldiers who participated in the Balkan and in the Gulf wars. Depleted uranium used during these conflicts was considered as a possible cause. Its radiotoxicity is close to that of natural uranium. This paper reviews the epidemiological knowledge of uranium, the means of exposure and the associated risk of cancer. METHODS: The only available epidemiological data concerns nuclear workers exposed to uranium. A review of the international literature is proposed by distinguishing between uranium miners and other workers of the nuclear industry. French studies are described in details. RESULTS: In ionizing radiation epidemiology, contamination by uranium is often cited as a risk factor, but the dose-effect relationship is rarely studied. Retrospective assessment of individual exposure is generally insufficient. Moreover, it is difficult to distinguish between uranium radiotoxicity, its chemical toxicity and the radiotoxicity of its progeny. A causal relation between lung cancer and radon exposure, a gas derived from the decay of uranium, has been demonstrated in epidemiological studies of miners. Among other nuclear workers exposed to uranium, there is a mortality deficit from all causes (healthy worker effect). No cancer site appears systematically in excess compared to the national population; very few studies describe a dose-response relationship. CONCLUSION: Only studies with a precise reconstruction of doses and sufficient numbers of workers will allow a better assessment of risks associated with uranium exposure at levels encountered in industry or during conflicts using depleted uranium weapons. [Tirmarche200402RESPv52n1p81] (PMID: 15107695 [PubMed - indexed for MEDLINE]).

19. Military deployment human exposure assessment: urine total and isotopic uranium sampling results, by May LM, et al., Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Room A1044, Bethesda, MD 20814-4799, USA. J Toxicol Environ Health A. Vol. 67 (8-10), April 2004 (pp. 697-714).

Currently the Department of Defense (DoD) does not use exposure biomarkers to measure service members' exposure to environmental chemicals. Blood and urine exposure biomarkers for volatile organic compounds (VOC), selected heavy metals, depleted uranium (DU), and chemical warfare agents are currently available but have not been field tested or validated by the DoD in military deployments as a tool to document exposures. The Military Deployment Human Exposure Assessment Study, a prospective cohort of 46 soldiers deployed to Bosnia, was designed to field test blood and urine exposure biomarkers as a mechanism to document exposures to these chemicals during military deployments. Blood and urine were collected before, during, and after deployment. Standard questionnaire, environmental, and occupational monitoring data collection methods were conducted for comparison to the exposure biomarker results. This article compares and reports the pre-, during, and postdeployment urine total and isotopic uranium measurements and compares them to perceived exposures captured on questionnaire, to environmental data collected by the United Nations Environmental Program in Bosnia, and to standard U.S. urine uranium reference levels (CDC, 2003). Additionally, the questionnaire and environmental and occupational measurements are reported. The results of the study indicate that exposure biomarkers may be a valuable tool to the DoD in exposure and risk assessment with regard to environmental and occupational exposures to uranium. [May200404JTEHAv67n8to10p697] (PMID: 15192863 [PubMed - indexed for MEDLINE]).

20. The number of malignant neoplasm in Sarajevo region during the period 1998-2002, by Obralic N, et al., Clinical Center University Sarajevo. Med Arh. Vol. 58 (5), 2004 (pp. 275-278).

Due to the specific war and post-war situation in Bosnia and Herzegovina it is possible to notice some differences in the number, type, advancement, biological course, treatment and its outcome. The actual situation which appeared in connection to depleted uranium has additionally raised questions about its influence on human health and about eventual increase in the number of malignant diseases in Bosnia and Herzegovina. In public, we often see that there are claims about enormous increase in the incidence of cancer. In order to achieve a realistic picture of actual condition and to avoid panic and ignorant attitude, correct and constant data of malignant tumors are necessary. THE AIM OF THE STUDY: To collect and analyze data on population with malignant tumors in the region of Sarajevo city, which represents a symbol of difficult times in our country in the recent past. MATERIAL AND METHODS: We have collected and analysed data on, population with malignant tumors which included persons with permanent residence in Sarajevo Canton during 5-year period, from 01.01.1998, until 31.12.2002. Results were compared to regional and world indicators, and were observed in the light of specific local situation. RESULTS: During period of 5 years (1998-2002) 7733 new cases of malignant tumors were registered in Sarajevo Canton; 3940 among men and 3809 among women. Mostly registered tumors were: lung cancer, amelanotic skin tumors, breast cancer, colorectal cancer, cervical and uterine cancer, urinary bladder cancer, prostate cancer and cancer of larynx. CONCLUSIONS: Number of all malignant tumors in the region of Sarajevo Canton correlates to those in South European countries and the one estimated by GLOBCAN 2000. High number was registered in 1998, possibly due to normalization of the health services (diagnostics and treatment of malignant tumors), which didn't exist during the war and early post-war period. After 2000, there is a gradual increase in the number of people with malignant tumors. The most common tumors are lung and breast cancer. Significant differences to estimation and data registrated in other South European counties is high number of laryngeal cancer, urinary bladder cancer, bone and cartilage sarcoma, brain tumors and malignant lymphomas among both genders. Cervical cancer is extremely high up on the list, which correlates with data in developing countries. The incidence of smoking in Bosnia and Herzegovina is extremely high, almost complete, which can influence not only the appearance of lung cancer but also laryngeal and urinary bladder cancer. It is hard to say whether the war and post-war stress, irregular and insufficient nutrition during and after the siege of the city or some other factor have influenced their appearance among exposed population and differences in the observed incidence. [Obralic2004xxMAv58n5p275] (PMID: 15628249 [PubMed - indexed for MEDLINE]).

21. Examination of the health status of populations from depleted-uranium-contaminated regions, by Milacic S, et al., Faculty of Medicine, University of Belgrade, and Institute of Occupational Medicine and Radiological Protection, Serbia and Montenegro. smilacic@afrodita.rcub.ab.ac.yu . Environ Res. Vol. 95 (1), May 2004 (pp. 2-10).

During the NATO air strikes on the Federal Republic of Yugoslavia (Serbia and Montenegro) in 1999, depleted-uranium ammunition was used on 112 locations, mainly Kosovo, in the south of Serbia, and one location in Montenegro. Blood samples of residents from depleted-uranium-contaminated areas were gathered and blood cell and chromosomal aberrations were analyzed. During the last 3 years blood samples from 21 residents of Kosovo (Strpce), from 29 residents from the south of Serbia (the Vranje and Bujanovac regions), and from 19 technical television workers from the site of Pljackovica, in the vicinity of Vranje, were collected. Blood samples from 33 residents of central Serbia and 46 occupational workers exposed to X-rays were used as controls. All subjects studied were without any clinical symptoms of disease. The examinations included general clinical assessment; urine samples for alpha-and gamma-spectrometry analysis; complete blood counts; ratio-percentages of blood cells in stained (Giemsa) capillary smears, individual leukocyte line elements; morphological changes observed under a microscope; the presence of immature forms or blasts; and leukocyte enzyme activity [alkaline phosphatase leukocyte (APL)]. Chromosomal aberrations were evaluated in 200 peripheral blood lymphocytes in mitosis. An increased incidence of rogue cells and chromosomal aberrations was found in the blood of the residents of Vranje and Bujanovac, but this was below the incidence of chromosomal aberrations in individuals occupationally exposed to ionizing irradiation. Blast cells were not found. Blood counts were decreased in only a few samples, while morphological changes of both nuclei and cytoplasm were marked in individuals in south and central Serbia. Enzymatic activity (as measured by the APL score) was decreased in samples with chromosomal aberrations and cyto-morphological changes in subjects from the south of Serbia. The contamination level measured by this examination was low. Because of the presence of depleted uranium (uranium-238) in the soil and in plants, the prevention of consequences necessitates the identification of the initial biological effects on sensitive tissues. Early identification of serious blood cell changes is important for appropriate medical treatment. [Milacic200405ERv95n1p2] (PMID: 15068925 [PubMed - indexed for MEDLINE]).

22. Micronuclei occurrence in population exposed to depleted uranium and control human group in correlation with sex, age and smoking habit, Ibrulj S, et al., Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Bosnia and Herzegovina. Med Arh. Vol. 58 (6), 2004 (pp. 335-338).

Observation of micronuclei presents reliable method for evaluation of genotoxicity effects on chromosomal level. One of genotoxins evidenced in the environment as impact of the last conflict in Bosnia and Herzegovina is depleted uranium. This research included an evaluation of genctic load in lymphocytes of individuals from population exposed to depleted uranium and the control group in correlation with sex, age and smoking habit. Results have shown increased micronuclei formation within exposed population and their statistically significant correlation with ages. [Ibrulj2004xxMAv58n6p335] (PMID: 15648227 [PubMed - indexed for MEDLINE]).

23. Effect of depleted uranium weapons used in the Balkan war on the incidence of cervical intraepithelial neoplasia (CIN) and invasive cancer of the cervix in Greece, by Papathanasiou K, et al., Second Department of Obstetrics & Gynaecology, Aristotles University of Thessaloniki, Hippocratio Hospital, Thessaloniki, Greece. Clin Exp Obstet Gynecol. Vol. 32 (1), 2005 (pp. 58-60).

OBJECTIVE: To compare the incidence rates of CIN and invasive cancer of the cervix in two district areas near the borders with the former Yugoslavia and an urban area away from these borders three years before and three years after the bombings in this country. MATERIAL: Two peripheral hospitals (in Kilkis and Serres) which are near the border with the former Yugoslavia and one University hospital (Hippocratio hospital of Thessaloniki) in a rural area away from the borders, where routine Papanicolaou smear tests for screening of CIN and invasive cancer of the cervix are performed in the general female population. METHODS: Hospital records were searched for abnormal smear test results. Incidence rates of CIN and invasive cancer of the cervix three years before (1997-1999) and three years after (2000-2002) the bombings were calculated and compared in the three different settings. The relation between the mean age of the first occurrence of an abnormal smear test was also examined. The results were examined using the chi-square test. RESULTS: The incidence of CIN in the three-year period 1997-1999 was 0.68% and 0.9% for the two district hospitals of Kilkis and Serres, respectively. These figures rose to 1.11% and 1.13% in the three-year period 2000-2002 for the two district hospitals. The incidence of CIN in the three-year period 1997-1999 was 1.06% for the Hippokrateion University Hospital of Thessaloniki and 0.88% for the three-year period 2000-2002. There has been a small but not statistically significant increase in the incidence rates of CIN in the two district areas near the borders with the former Yugoslavia over the last few years (p = 0.355 for Kilkis and p = 0.472 for Serres), compared with the small but statistically significant decrease in the incidence of CIN in the urban area of Thessaloniki (p = 0.0275). The rates of invasive cancer of the cervix diagnosed from the routine smear tests were too small to make any conclusions. CONCLUSION: The increase in the incidence of precancerous lesions of the cervix in areas near the borders with the former Yugoslavia during the last three years may be influenced by environmental factors such as exposure to depleted uranium due to the bombings of 1999. To comfirm this bigger epidemiological studies are needed. [Papathanasiou2005xxCEOGv32n1p58] (PMID: 15864941 [PubMed - in process]).

24. The quantitative analysis of uranium isotopes in the urine of the civilian population of eastern Afghanistan after Operation Enduring Freedom, by Durakovic A., Uranium Medical Research Centre, Washington, DC 20008, USA. Mil Med. Vol. 170 (4), April, 2005 (pp. 277-284).

The purpose of this study was to determine the concentrations and precise isotopic compositions of four uranium isotopes (234U, 235U, 236U, and 238U) in urine specimens from the civilian population of Afghanistan after Allied Forces Operation Enduring Freedom. Eight male civilians from Nangarhar-Jalalabad region who presented with symptoms of fatigue, fever, musculoskeletal and neurological alterations, headaches, and respiratory impairment after inhalation of dust during the bombing raids in June 2002 had urine samples collected under controlled conditions and analyzed in duplicate for 234U, 235U, 236U, and 238U, with multicollector, inductively coupled, plasma ionization mass spectrometry. Control samples with an internal urine standard were analyzed with the same method. The mean concentration of uranium in eight samples was found to be considerably greater (275.04 ng/L; SD, 137.80 ng/L; SE, 48.72 ng/L) than what is regarded as a reference range (1-20 ng/L). The 238U/235U ratio was 137.87 +/- 0.20, which is consistent with that of natural uranium. The 234U/238U ratio for the Afghan samples was 0.000055 +/- 0.000001, also consistent with natural uranium. 236U, which usually forms a component of depleted uranium, was not detected (measured 236U/ 238U ratio, < 10(-7)). Our results demonstrate that contamination in Afghanistan with a source consistent with natural uranium has resulted in total uranium concentrations up to 100 times higher than the normal range for various geographic and environmental areas throughout the world. The cause of our findings is currently being evaluated as a part of our ongoing research.
[Durakovic200504MMv170n4p277] (PMID: 15916293 [PubMed - indexed for MEDLINE]).

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