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This takes into consideration only the alpha emissions, but the decay process of DU with its daughter isotopes or decay products, thorium and protactinium adds beta and gamma emissions onto the already existing alpha emissions of U DU has a radioactive half-life measured in billions of years. DU is a dense metal; its density is 1. It reacts with most non-metallic elements; it has pyrophoric properties and may spontaneously ignite at room temperature in air, oxygen and water. These unique properties make it appealing for use in many civilian and military applications.
DU is used as X-ray radiation shielding in hospitals, as counter weights for rudders and flaps in commercial aircrafts, in keels of sailing yachts and as ballast in both military and non-military airplanes. DU is used by the military for the production of distinctly powerful projectiles e.
As a projectile, a DU penetrator ignites on impact under high temperature; it has a low melting point. Further, DU sharpens as it melts making it easier to pierce heavy armor. As the projectile pierces, it leaves behind its jacket dispersing DU dust into the environment during impact. The quantity of aerosol production is directly proportional to the hardness of the armor. They usually remain windborne for an extended time. There is empirical documentation that DU aerosols can travel up to 26 miles and theoretical documentation that they can travel further [ 5 ].
Once deposited on the ground the aerosols settle as partially oxidized DU dust. Potential contamination of ground water is another possibility — weathering could mobilize the metal into additional media. U decays primarily by alpha emission. Alpha particles rapidly lose their kinetic energy and have little penetrating power. In the decay process beta and gamma particles are emitted which are more penetrating. Alpha radiation is only hazardous when internalized in the body, but once deposited in living tissue it releases its energy in a concentrated area causing greater damage than beta or gamma radiation.
A Geiger counter measurement by a correspondent in the recent Iraq war show that radiation emitting from a DU bullet fragment registered nearly — times the normal background radiation level. A three-foot long DU fragment from a 12 mm tank shell registered radiation times the background level. A DU tank found by the U. S Army radiological team emitted — millirads of radiation per hour compared to the safety limit of millirads per year.
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A pile of jet-black dust registered a count of emissions in one minute, a level more than times the average background level [ 6 ]. The U. DU weapons were also used in the —5 war in Bosnia, the war in Kosovo, the U.
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Trends toward increased use of DU by industry and, more recently, in warfare suggest that there are large and growing numbers of exposed people worldwide, both at production sites and in areas where DU weapons are deployed. While there is no clear basis for estimating the number of people who have been breathing and ingesting food and water in areas contaminated with aerosolized DU particles, the ever-expanding exposure of humans and the environment to DU particles, several micrometer and smaller, mobile and inhalable, necessitates a sense of urgency to better understand this hazard.
In sum, DU bullets are made of almost pure U and DU bullets and projectiles produce largely insoluble ceramic aerosols upon impact. These aerosols, largely respirable, may be a source of toxicity for those exposed.
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Our specific concern here is whether or not such exposure results in teratogenic outcomes. We present, however, some analysis of the toxicity of natural and non-aerosolized uranium, because the teratogenicty of soluble, natural uranium supports the plausibility of DU being a teratogen, provided it can reach the reproductive organs. DU can enter the body as uranium metal and as uranium oxides from the oxidized DU formed after impact with hard targets and fires. Inhalation of aerosols, ingestion and exposure through contaminated wounds or embedded fragments are all pathways of internal exposure but inhalation is the main route of human exposure both in combat and non-combat situations.
Thereupon, live tissue immediately adjacent to or exposed to these imbedded particles experience infrequent but high LET alpha irradiation along with the potential for chemical toxicity. Because the micro-particles of DU are much larger than individual solubilized molecules, they can create "hot spots" of localized alpha radiation.
For this to be relevant to teratogenicty, however, the particles, rather than their dissolution products, would have to reach the reproductive tissue, a phenomenon for which we are unaware of supporting evidence. Having said this, we hasten to add that the pathways by which radiation exerts its deleterious effects on living beings are by no means fully elucidated. While discussion is beyond the scope of this paper, the "second event" theory [ 72 ], and the "bystander effect" exhibited by low level radiation [ 73 , 74 ] are, newly, the basis for serious re-consideration of certain propositions previously much more widely held as true.
The rate of oxide dissolution will vary depending on crystal structure as well as particle surface area [ 9 ]. Uranyl compounds exhibit variable solubility at different pH values, exhibiting lower solubility at circum-neutral pH and greater solubility under acidic conditions below pH 5 [ 10 ]. A study of the dissolution properties of DU under circumstances simulating its inclusion in internal human lung secretions, demonstrated a shortest possible dissolution half-life of slightly less than 4 years [ 11 ]. To date studies of military personnel exposed to DU munitions in the Gulf War have documented the "isotopic signature" of DU in the urine of personnel 8—9 years subsequent to exposure by inhalation [ 12 ] and 7 years after exposure among those with embedded fragments [ 13 ].
These findings confirm ongoing bioavailability of soluble uranyl ions which, as the dissolution product of internal DU particles, migrate from the initial point of entry into the human body and are eventually, at least partially, excreted in urine. The health effects related to internal exposure may result from either chemical or radiological toxicity.
Solubility determines the kind of toxicity exerted by uranium. The soluble forms of uranium are more associated with toxic chemical effects while insoluble forms are associated with radiological effects. Soluble chemical forms are absorbed within days while insoluble forms generally takes months to years to be absorbed [ 2 ]. DU is organotropic and has long-term retention in its target organs, to wit the kidney and the skeletal tissue. The biological retention capability of DU in bones enhances the particulate radiation to the target organs. Though the mechanism of action of DU oxides are not clear, biodistribution studies detail DU accumulation in the bone, kidney, reproductive system, brain and lung with verified nephrotoxic, genotoxic, mutagenic and carcinogenic properties, as well as reproductive and teratogenic alterations [ 14 ].
However the subject of inquiry from the vantage of teratogenicity is the potential for DU exposure of egg and embryo and of sperm and cells involved in spermatogenesis. New information on how radiation affects cells, as noted in the first paragraph of this section, may contribute to elucidation of how reproductive tissue could be damaged indirectly. With a few exceptions, it is only since the late s that uranium's reproductive toxicity has been studied using animal models.
With at least 6 published studies on topic, Domingo et al. From their maternal animal exposure studies the members of Domingo's group concluded that it was chemical toxicity, not radiation that resulted in teratogenicity [ 15 , 18 — 22 ]. Two studies of orally dosed male rats that were conducted decades earlier demonstrated substantial degeneration of testes and impact on germ cells; another more recent study provided some similar evidence [ 21 , 23 , 24 ]. Very recent research suggests that uranium mimics estrogen in mice [ 25 ].
These studies, using a rat model, have demonstrated that DU pellets embedded in male rats led to elevated uranium concentrations in the testes, and that pellets embedded in females led to detectable uranium in the placenta and to "very low levels" of its accumulation in the fetus, though there was no "overt" teratology. There is preliminary evidence of delayed reproductive impact of embedded DU among female rats; the probability of decreased litter size increased in proportion to time since embedding.
In their human studies, McDiarmid et al. A Chinese study of reproductive toxicity of enriched uranium noted damage to genetic material, dominant lethality and skeletal abnormalities in fetal rats. Chromosome aberrations in spermatogonia, DNA alterations in spermatocytes and strand breakage in sperm were specifically notified [ 29 ]. In sum, aerosolized DU is a vehicle for internal delivery of a DNA-tropic substance that is both a heavy metal and an alpha particle emitter. Chromosomal instabilities have also been documented in humans. In Zaire et al reported finding increased frequency of sister chromatid exchanges in cells of uranium miners [ 30 ].
In Schroder et al. Mutagenicity of uranium was also observed in residents living near uranium mines. Au et al. They found that residents living near the uranium mining and milling sites had higher frequencies than controls of aberrant cells, chromosome deletions and chromosomal aberrations. Consideration of evidence regarding the teratogenicity of heavy metals other than uranium is also relevant for estimation of the hazard that DU poses. First, elegant studies of other heavy metals suggest study designs that may be emulated; second, observed associations can inform and contribute to the choice of outcomes for DU studies since various heavy metals may have similar modes of action.
Accumulated knowledge of heavy metal teratology is quite extensive; animal teratogenesis by a variety of heavy metals, and human teratogenesis by, at minimum, lead and mercury, are long established [ 34 ]. A study of human anencephaly vis a vis parental and in utero ambient exposure to lead, mercury and vanadium is exemplary. Levels of these three substances were measured in the brain, kidney, liver, and lung of 20 anencephalic and 20 control fetuses, all of which were conceived in an area of Venezuela where these heavy metals were are?
In sum, the researchers stated that " [m]ercury and Pb were significantly increased p less than 0. Vanadium was detected exclusively at brain level, being significantly higher in controls p less than 0. Investigation of DU teratogenicity in exposed populations is constrained by the rigor with which such populations can be accurately identified [ 36 ]. Parental exposure to a possible teratogen can be established on, at least, two different levels. Especially when exposure is from the ambient environment rather than from individual activity e.
There have been no studies of DU's teratogenicity with concomitant biomarker documentation of individual DU exposure. The first report that assessed, and supported, the feasibility of use of biomarkers for measurement of DU and other environmental chemical exposures during military deployment has recently been reported [ 37 ]. On the ecological level, being at-risk for exposure requires documentation of i the presence of the suspected teratogen in the ambient environment and ii the location of the allegedly exposed at the time s of peak exposure.
With only ecological-level information regarding exposure, there is a limit to the clarity that can be achieved regarding the biological activity, in a given individual, of the ambient toxin. Exposure to DU aerosols, most often the "by-product" of war, usually occurs along with other possible, probable and known risky exposures.
This poses a particular challenge to inference: distinguishing the role of DU, per se, and requires weighing the evidence as thoughtfully as possible. Indeed, engagement with this challenge is one of the main objectives of this paper. The most important strategy to address this type of challenge is to relate findings in various settings, especially, unusual settings, in which populations received exposure. To the extent that the occurrence of possible risk factors for teratogenesis varies between contexts, the consistency of DU exposure across those contexts increases the probability that it is the or an explanatory factor.
In this article, consideration of DU's reproductive toxicity includes its mutagenic and teratogenic potential, i. Studies that consider paternal DU exposure are, uniformly, included. While animal studies pertaining to a variety of endpoints have been referenced above, the human epidemiological studies considered here are limited to those that focus on physical malformations. Epidemiological-type studies of congenital malformations and uranium though not depleted uranium exposure are included; studies of populations exposed to other heavy metals and to other sources of low-level radiation are not.
But, there is only one study of congenital malformations among residents of a uranium mining area. The several studies of reproductive outcomes among military personnel who served in the Gulf War, though not specifically in areas of Iraq where DU munitions were employed, are included. Findings of studies of all Gulf War veterans are interpreted accordingly — in these studies, Gulf War deployment, though used as an indicator of DU exposure means only substantially increased probability of exposure compared to non-Gulf War populations.
The earliest DU "research" is an instance of preliminary, "shoe leather" epidemiology that was carried out by community activists in the United States [ 38 ]. In a letter addressed to TERA, a community activist enumerated birth defects among infants born in Socorro County between and The writer said she was referencing cases reported in the State of New Mexico's passive birth defects registry, i. The writer also reported two infants with birth defects in that were known to her but not recorded in the registry.
There was nothing remarkable about the 16 other abnormalities she enumerated. All the instances of hydrocephalus occurred between and In another community activist requested and received a count of all hydrocephalic births in New Mexico and in Socorro County for the years — from the State Department of Health.
The registry report documented a total of 19 infants born with hydrocephalus in New Mexico during those 5 years; 3 of them were Socorro County residents. Though there are several reasons why these findings cannot be considered the results of a methodologically rigorous investigation, the data are provocative, are a cause for concern and should be followed up. It would also be most valuable to seek out and aggregate other "shoe leather" findings.
Hydrocephalus is also a component of the congenital malformation syndrome Goldenhar Syndrome. ABDC generates a birth defects registry by solicitation of reports of children with birth defects from parents. With thousands of parents reporting their children's defects and possible risk factors, including Gulf War exposures, the data brought the apparent excess to light.
Goldenhar Syndrome is a variable cluster of eye, ear, face and vertebral malformations, often includes hydrocephalus. The utilization of military hospital births is an additional challenge to detection of association. Only active duty military personnel and their wives deliver at military hospitals.
It is possible that one or more debilitating wartime exposures led both to termination of active duty status and increased risk of siring an affected child; if so, the choice of study population leads to bias against observing an association. From an epidemiological perspective, this study was designed to test a particular hypothesis and, though sample size obviated statistical association, it affirmed a strong likelihood of increased risk.
Shortly after the Gulf War a German physician working in Iraq began to publicize his observations of catastrophic and ongoing ill health and distinctive patterns of abnormality among the Iraqi population. Gunther, the president of the Austrian-based humanitarian and relief organization Yellow Cross International had spent much time in Iraq and has had an appointment as Professor of Infectious Diseases and Epidemiology at the University of Baghdad.
Though he has not published systematic data, he is convinced by his clinical experience that DU munitions are the cause of much of the horrific human toll that he saw. As early as he published a book entitled "Uranium Projectiles: Severely Maimed Soldiers, Deformed Babies, Dying Children" in which he presented his impressions of post Gulf War ill health, both in words and photographs.
A second, tri-lingual German, English, French edition was published in and again the volume is more images than text [ 42 ]. Of 28 photographs of diseased or malformed children in the edition, four pertain to the classical infectious diseases associated with poverty and poor hygiene and two to malnutrition; the captions of the photographs of four malformed children indicate hydrocephalus. There are reports on the internet of papers delivered at international conferences, held in Iraq, on DU. The reports describe work being carried out by a clinical epidemiology research team in one of the three major maternity hospitals in Basra, Iraq [ 43 , 44 ].
Basra, a city of some 1. Since the Basra team has kept a congenital malformations registry; each newborn is assessed before discharge from hospital [ 45 ]. Both internet-published reports references data for the birth cohort as the non-exposed group.
There were between 9, and 13, births included in the registry annually between and At the World Uranium Weapons Conference held in Hamburg, Germany October 16—19, a member of the Basra team reported data for total congenital malformations in Table 1 gives the number and rate of total malformations recorded in the registry by year.
Initially reporting on only the — data, the authors observed "an apparent increase in the incidence rate from upwards". Therefore, " [t]o improve statistical efficiency of the data collected and overcome small numbers of cases recorded, the pattern and incidence of congenital malformations are grouped into two periods, to and to Incidence data, by class of malformation were reported for the time periods , —, — and —; the data are redacted and presented in Table 2. In particular, rates have been calculated. Category names and data for all malformation categories are presented below exactly as they were specified in the internet articles.
Malformation categories in which cases were first documented in — are listed only in the Fasy report, which includes data through that later time point. Of particular note, the report of data through does not include hydrocephalus and the report of data through indicates no diagnosed cases of hydrocephalus between and at the study hospital. However, by personal communication one of the Basra researchers confirmed to the authors that there were infants diagnosed with hydrocephalus born during the years — , indeed that hydrocephalus was more commonly diagnosed during the latter part of the 90's than previously [ 45 ].
No information beyond that given in the table is provided regarding the particular cases included in each grouping. Research by Al-Shammosy pertains exclusively to neural tube defects and describes the findings of a study that identified all year births with a neural tube defect NTD at the Diwaniah maternal and children's hospital [ 46 ]. Diwaniah is a city slightly north and east of Basra and, like Basra, is in the area heavily bombarded with DU munitions during the Gulf War.
The overall NTD incidence rate in Diwaniah was 8. Table 3 gives the incidence rates for particular NTDs. Al-Shammosy raises concern about universal maternal exposure to DU while stating, without providing any supportive data, that he investigated other possible risk factors for NTDs but found nothing unusual. During that 8-month period there were 33 cases of NTDs among births, 5. The percent of patients seen whose malformation was anencephaly or hydrocephalus rose from 0.
The abstract does not give any information on parents' residence or fathers' occupation. Sumanovic-Glamuzina et al. Live and stillborns were examined 0 — 3 days postpartum, though a few malformations were noted later. This study is so sorely compromised methodologically that it defies interpretation. For example, the protocol for detecting birth defects was different for the two cohorts. Also, the distinctions between the two-birth cohorts vis a vis exposure is unclear. There are no studies of birth defects among offspring of American or allied veterans of the Gulf War which distinguish veterans by the area of Iraq in which they were stationed.
Thus, all Gulf War veterans' studies, from the point of view of assessing the teratogenic capacity of DU munitions, have a "contaminated" exposed group. The war-exposed group is comprised of individuals whose DU exposure would have ranged on a continuum from none to heavy, and they cannot be sorted further.
The and studies by Araneta et al of birth defects among offspring born to Gulf War veterans have their study populations and comparison criteria rigorously defined [ 49 , 50 ]. In the larger, updated study data from all areas in the United States in which there were active birth defects surveillance systems operating during — were analyzed. Occurrences of individual birth defects aggregated into 48 groupings among offspring of male and female Gulf War veterans and non-deployed veterans were ascertained through the first year of life.
Those data provide the basis for comparisons regarding birth defects among offspring of gender-specific groups of veterans, including deployed veterans conceiving children pre-war vs. Analysis relied on statistical tests to identify significantly different prevalence rates for individual groupings of birth defects among cohorts being compared. An infant with multiple anomalies was usually included in several birth defect groups. There were infants conceived post-war to deployed female veterans and 4, infants conceived post-war to deployed male veterans.
The statistically significant findings are detailed in Table 4.
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Unfortunately, due to design features neither study can contribute to elucidating the nature of the relationship between parental DU exposure and congenital malformations in offspring. Cowan et al. Study offspring of male Gulf War veterans numbered over 30, and of females Gulf War veterans nearly 4, Limiting post-war assessment of reproductive outcomes among wartime military personnel to those remaining on active-duty excludes individuals for whom war-induced debility engenders early termination of service.
It is surely possible that on the population level wartime DU exposure related to termination of service; but if this is the case, the exposed cohort is also depleted of those who are the hypothesized at-risk population. What remains unknown is the extent to which this finding of no association is related to the a priori exclusion, from the pool of potential study parents, of persons who'd left service.
There is one other large cohort study that compared reproductive outcomes among Gulf War veterans and non-Gulf veterans. From an epidemiological perspective, a distinctive feature of the study by Kang et al. Beginning in and using stratified random sampling, Kang et al. There were offspring of male and female Gulf War veterans and of non-Gulf War veterans. Prevalence of any birth defect, to re-iterate, by self-report, was elevated among offspring of Gulf War veterans of both genders.
The authors' classification of the remaining defects was only minimally informative: Data analysis did not separate offspring of exposed fathers and exposed mothers; nor were the sub-categories particularly informative. Skip slideshow About This Journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. Comorbidities in children with intellectual disabilities Snezana R.
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