Depleted Uranium

Properties, Uses, and Health Consequences

C. Miller Alexandra

• Publisher: CRC Press
• Year: 2006
• ISBN:
  9781000611601
• Edition: 1
• Topic: Medizin
• Subtopic: Toxikologie

A compilation of published scientific information, including human, animal, cellular, and theoretical studies, Depleted Uranium: Properties, Uses and Health Consequences provides the most current and comprehensive collection of information on depleted uranium health hazards. The editor and her international panel of contributors are clinical and ba

1	Depleted Uranium Biological Effects: Introduction and Early In Vitro and In Vivo Studies David E. McClain and Alexandra C. Miller

CONTENTS

Introduction

Background

Uranium Toxicity and Health Effects: Compiled Reports

Research Approaches: In Vitro Studies

Research Approaches in In Vivo Studies

Cancer in Laboratory Animals

Leukemia in Animals

Uranium Genotoxicity

Nephrotoxicity

Uranium and Bone

Uranium Neurological Effects

Uranium Reproductive/Developmental Effects

Epidemiological Studies

Summary and Conclusions of Depleted Uranium Health Effects

Heavy Metal Alternatives

References

INTRODUCTION

The use of depleted uranium in armor-penetrating munitions remains a source of controversy because of the numerous unanswered questions about its long-term health effects. Although there are no conclusive epidemiological data correlating depleted uranium exposure to specific health effects, studies using cultured cells and laboratory rodents continue to suggest the possibility of leukemogenic, genetic, reproductive, and neurological effects from chronic exposure. Until issues of concern are resolved with further research, the use of depleted uranium by the military will continue to be controversial.

Advances in metallurgy and weapons design in the past several decades have led to new munitions whose effectiveness has provided tactical advantages on the battlefield and, consequently, saved lives of personnel. However, decisions to deploy these munitions have sometimes outpaced our knowledge of how they impact the health of those exposed to them.

Depleted uranium (DU) kinetic energy penetrators are perhaps the best-known example of these advanced munitions, primarily because of their outstanding, well-publicized performance against enemy armor in the 1991 Persian Gulf War. DU munitions were again used in the NATO military actions in Bosnia-Herzegovina (1995) and Kosovo (1999) and, more recently, coalition actions in Iraq.

DU munitions were used only by coalition forces during the 1991 Gulf War, but their use led to DU fragment injuries among coalition forces as a result of friendly fire incidents. Other personnel were exposed via inhalation/ingestion after working around vehicles struck by DU munitions. Such exposures were not considered especially dangerous at the time, because numerous epidemiological studies of uranium miners and millers working with natural uranium had shown few concrete health effects from exposure, and DU has 40% less radioactivity than natural uranium. However, the exposure of wounded personnel to uranium as embedded fragments had no medical precedent, so the earlier studies dealing primarily with inhalation or ingestion exposures in miners were of uncertain utility. As a result, questions were soon raised as to whether it was wise to leave in place fragments possessing the unique radiological and toxicological properties of DU, especially when considering that exposures might extend as long as the 40–50 years remaining in a person’s life span. As these treatment questions were being addressed, a growing public concern about the long-term health and environmental impact of using a radioactive metal like DU on the battlefield fueled forceful national and international efforts to ban the use of DU in munitions.

This chapter aims to summarize the current status of knowledge about the potential health effects of DU based on cellular and animal studies. Studies have been conducted using cultured cells and animal models and have attempted to answer questions relating to toxicity, carcinogenicity, and involvement of radioactivity.

BACKGROUND

Uranium was discovered in the mineral pitchblende in 1789 by the German chemist Martin Heinrich Klaproth. Uranium does not exist in pure metallic form in nature because it is quickly oxidized in air. It occurs most commonly as U₃O₈, uranium oxide, in ores such as pitchblende. Refined uranium metal used in reactors is in the form of UO₂, uranium dioxide.

A sample of uranium was used by the French physicist Henri Becquerel in his discovery of the concept of radioactivity in 1896. Natural uranium has three predominant natural isotopes: ²³⁴U, ²³⁵U, and ²³⁸U, all of which are radioactive; other uranium isotopes can be produced artificially in a reactor. The half lives of the natural isotopes are 2.44 × 10⁵ years for ²³⁴U, 7.10 × 10⁸ years for ²³⁵U, and 4.5 × 10⁹ years for ²³⁸U, and their composition in natural uranium by mass is 0.005% ²³⁴U, 0.711% ²³⁵U, and 99.284% ²³⁸U. Considering the isotope half lives and their mass percentages, it can be calculated that 48.9% of the radioactivity of natural uranium is derived from the isotope ²³⁴U, 2.2% from ²³⁵U, and 48.9% from ²³⁸U (ATSDR 1999). Thus, ²³⁴U contributes as much to the radioactivity of natural uranium as does ²³⁸U, despite the fact it is 20,000 times less abundant. Natural uranium has a low specific radioactivity of about 0.68 µCi/g or 1.8 × 10⁷ Bq, which means natural uranium is considered only a weakly radioactive element. A comparison of depleted uranium to natural uranium is shown in Table 1.1. This chart quite simply shows that DU has an approximately 50% lower specific activity than natural uranium. This chart also shows that DU has a different radioisotope decay chain than natural uranium, making DU very different from natural uranium.

All isotopes of uranium, natural or manmade, decay by emission of alpha particles of various energies, a process by which the uranium is transformed into another element that is also radioactive. The decay series continues until reaching a nonradioactive isotope of lead. Alpha particles have very low penetrating power but deposit large amounts of energy during penetration. Thus, alpha particles represent little hazard when on the surface of the skin but are potentially a significant hazard if inhaled or ingested, whereby they come in close contact with sensitive tissues (Hartmann et al., 2000). Beta and gamma radiation are also emitted during certain transformations, but those radiation levels are lower. Workers exposed to natural uranium could receive radiation exposures to all of the isotopes in the transformation series.

The use of uranium as nuclear fuel or in nuclear weapons requires enrichment of the fissionable isotope ²³⁵U. The enrichment process concentrates ²³⁵U in the metal to specific activities required to sustain nuclear reactions. The by-product of enrichment is uranium with reduced levels of the ²³⁵U isotope, or “depleted” uranium. The Nuclear Regulatory Commission considers the specific activity of DU to be no more than 0.36 µCi/g, but more aggressive enrichment processes can drive this value slightly lower (~0.33 µCi/g) (ATSDR 1999). This means DU has roughly 50% of the radioactivity of natural uranium. Even though DU has less specific radioactivity than natural uranium, it retains all of its chemical properties. The large-scale production of enriched uranium for nuclear weapons and fuel over the decades has resulted in an abundance of cheap DU, a factor that has played a role in its use in a wide variety of applications (e.g., radiation shielding, compact counterweights, armor, kinetic energy weapons). The properties of DU that make it useful as an armor-penetrating munition are its density (1.68 times that of lead) and the ability to engineer into it a molecular structure that facilitates entry into a hardened target by “shedding” outer layers of the metal during penetration.

TABLE 1.1
Comparison of the Relative Contribution of Uranium Isotopes^a (Natural and Depleted)

Isotope	Specific Activity (Ci/g)μ	DU SA by Wt% (Ci/g)μ	Natural Uranium SA by Wt% (Ci/g)μ
^238U	0.333	0.332	0.331
^236U (not naturally occurring)	63.6	0.0001	0
^235U	2.2	0.0044	0.051
^234U	6200	0.093	0.310
Total		0.4295	0.692
^a Contribution of the daughter products is not included.

URANIUM TOXICITY AND HEALTH EFFECTS: COMPILED REPORTS

Toxicology studies of natural uranium partially relevant to understanding DU health effects are numerous, beginning with the first reported observations of uranium-induced kidney abnormalities in the mid-1800s (see Hodge 1973b). Most of our detailed knowledge of uranium toxicity is derived from studies in the 1940s and early 1950s as the Manhattan Project, and the need for enriched uranium for reactors led to a requirement to understand better the occupational hazards presented to uranium workers. Much of that original work is described in the classic multivolume monographs of Voeglen and Hodge (Voeglen 1949, 1953) and in Hodge et al. (Hodge et al. 1973a), which are often together considered the definitive compilations of toxicology and pharmacokinetic data for uranium in animals and humans. It is important to keep in mind, however, that these studies are about natural uranium.

Additional biological information about uranium has accumulated since then that has reinforced our understanding of both uranium and DU health effects. The Agency for Toxic Substances and Disease Registry (ATSDR) has produced a very thorough reference that summarizes what is known and not known about the toxic effects of natural uranium exposure (ATSDR 1999). The controversy surrounding the use of DU during and after the 1991 Gulf War led to a number of other excellent literature reviews of uranium and DU health effects (Institute of Medicine 2000; The Royal Society 2001, 2002). These literature searches were not able, however, to answer many questions as DU studies had not been completed and the significant differences between natural uranium and DU in terms of total radioactivity and decay chain, continue to make it difficult to make claims about the potential hazards of DU exposure. Additionally, DU exposure conditions, chronic, wounding, etc., are considerably different than that for natural uranium (intermittent, inhalation). Therefore, it is important to keep in mind that these reports are about natural uranium which is considerably different from DU. Secondly, the type of exposure to natural uranium (intermittent, short term) considered in these reports is considerably different from the type of exposure to DU (chronic) that could occur following wounding by DU shrapnel.

RESEARCH APPROACHES: IN VITRO STUDIES

The earliest studies on DU effects involved using cellular model systems and were conducted in the mid-1990s at the U.S Armed Forces Radiobiology Research Institute. A strategic research approach involving the progression from cellular studies to animal model and finally to human epidemiology considerations was the approach used by Dr. Miller and colleagues (Figure 1.1). This research group used an immortalized human cell line to study neoplastic transformation, genomic instability, genotoxicity, and radiation-induced damage. The neoplastic transformation model approach was used to evaluate carcinogenic potential of DU (Figure 1.2). In this approach, human cells are exposed to the test material and then plated for colony formation. An evaluation of the colony morphology is used to define the state of transformation of the exposed cells. These were the first studies to demonstrate that DU could transform human cells into the malignant phenotype. Miller et al. (1998b) observed transformation of human osteoblast (HOS) cells to a tumorigenic phenotype after exposure to uranyl chloride, a soluble DU compound. DU-treated cells also demonstrated anchorage-independent growth, increased levels of the k-ras oncogene, and decreased levels of Rb tumor suppressor protein. The latter changes are associated with the malignant phenotype in other heavy metal treated cells. A comparison to insoluble DU (uranium dioxide), and other nonradioac...