Are Internalized Metals a Long-term Health Hazard for Military Veterans?

Military personnel on today’s battlefields face a plethora of potentially toxic hazards, not the least of which is exposure to heavy metals. Metals can be internalized through various routes, including ingestion and—as the most likely routes for military personnel—inhalation and embedding of fragments. Metal-containing particulates in smoke from destroyed vehicles and open-air burn pits, as well as environmental dust, present a risk for internalizing metals via inhalation. Likewise, wounds containing embedded metal fragments can result in a long-term depot of potentially toxic metals.

The recent conflicts in Iraq and Afghanistan resulted in more than 45000 wounded US personnel. Based on US Department of Defense (DoD) casualty reports, an estimated two-thirds of these wounded personnel may have retained metal fragments.¹ In an attempt to balance the surgical morbidity that can result from extensive fragment removal with the hypothetical health risk of the embedded metal, standard surgical guidelines recommend leaving embedded fragments in place except under certain circumstances. As a result, wounded veterans may carry these fragments for the rest of their lives.

The health risk of embedded fragments was traditionally considered low because they were thought to be inert once in the body. However, case reports on medical issues associated with embedded fragment wounds began appearing in the scientific literature in 1977.^2–7 In most instances, these wounds were incurred during wartime, many years before the adverse health effect manifested, and the embedded fragment was lead, iron, or steel. However, the use of novel materials on the modern battlefield—in military munitions and in improvised explosive devices—presents the possibility of embedded fragment wounds with metals whose toxicologic and carcinogenic properties are not well known. Such was the case with depleted uranium munitions, which were first used extensively for combat during Operation Desert Storm. As a result of several friendly fire incidents, concern was raised about the wisdom of leaving in place fragments with the unique chemical and radiologic properties of depleted uranium. During the past 20 years, patient follow-up at the Baltimore Veterans Affairs Medical Center showed no adverse health effects from these fragments.⁸ Likewise, laboratory animal studies using implanted fragments of depleted uranium showed no adverse health effects,⁹ with the exception of 1 investigation that tested a larger depleted uranium fragment. In this case, sarcoma formation occurred at the fragment implantation site.¹⁰

Concern about the health and environmental effects of depleted uranium led many countries to search for alternatives to it in armor-penetrating munitions, and tungsten-based materials were proposed as substitutes. However, when pellets of a military-grade tungsten/nickel/cobalt composite were implanted into the leg muscle of laboratory rodents, highly aggressive malignant rhabdomyosarcomas developed.^11,12 Conversely, when pellets of a tungsten/nickel/iron composite were tested, no tumors formed.^12,13 These results highlight the uncertainty facing medical providers when dealing with embedded metal fragment injuries. In response to this concern, in 2007 the DoD released Health Affairs Policy Letter 07-029, which directed medical personnel to send all surgically excised fragments for laboratory analysis.¹⁴ The DoD further directed that these laboratory results be entered into the patient’s medical record.

Research with laboratory animals also showed that embedded metal fragments are not static but tend to solubilize; the released metals travel to and deposit in various tissues in the body.¹⁵ Of particular concern is the finding that metals from embedded fragments can solubilize and cross the blood-brain barrier in a dose-dependent and metal-specific manner.¹⁶ This finding suggests that in multitrauma cases, especially those involving traumatic brain injuries, the presence of embedded metal fragments should not be ignored.

Although inhalation is a primary route of exposure for internalized metals, the final deposition of the metals ultimately depends on the size, composition, and solubility of the inhaled particles. Respiratory effects from inhaling particulate matter from desert dust storms or open-air burn pits are one area of concern. Inhalation of desert dust particulates may have played a role in the manifestation of Gulf War syndrome,¹⁷ as well as outbreaks of respiratory ailments of unknown etiology termed “severe acute pneumonitis” among personnel in the recent conflicts in Iraq and Afghanistan.¹⁸ A more thorough investigation of Iraqi desert dust showed that these particles possessed a clay or quartz core surrounded by an inorganic layer of calcium carbonate containing various metals, including—in order of decreasing concentration—aluminum, iron, uranium, nickel, cobalt, copper, lead, chromium, strontium, tin, manganese, zinc, barium, arsenic, and vanadium. Metal concentrations varied, but aluminum and iron appeared in the highest concentrations, with aluminum sometimes reaching levels as high as 10000 ppm.¹⁹ A recent study of metal levels in lung biopsies from US military personnel deployed to Iraq and Afghanistan showed substantially higher levels in the samples from personnel who had constrictive bronchiolitis as compared with controls or those who had autoimmune bronchiolitis. Metals found at substantially higher levels included aluminum, cadmium, silicon, and vanadium.²⁰

Although the respiratory system is the primary site of damage resulting from inhalation of metal-associated particulates, evidence suggests that inhalation of these particulates also results in long-term immunologic, cardiovascular, and neurologic problems. For example, when samples of Iraqi desert dust were administered intratracheally to laboratory mice, lung inflammation and fibrosis developed, and regulatory T cells from the spleen and thymus were depleted.²¹ In addition, inhalation of fine particulate matter (PM_2.5) containing cadmium, lead, strontium, tin, vanadium, and zinc substantially increased blood pressure among study participants,²² and long-term exposure to metal-containing particulate matter was proposed as a factor in chronic hypertension.²³ Particulate matter containing vanadium or nickel induced extensive injury to myocardial mitochondria when administered intratracheally to laboratory rats.²⁴ Inhalation of metal-containing particulate matter was also shown to increase metal content in the brains of laboratory animals^25–27 and humans.²⁸ Many metals enter the brain through the olfactory neurons,^29,30 whereas other metals use alternate means of crossing the blood-brain barrier.³¹ Disruption of the blood-brain barrier was shown to enhance the entry of certain metals into the brain,³² suggesting that heavy metals and the integrity of the blood-brain barrier play an important role in the onset of neurologic diseases.^33,34

From laboratory animal studies and human health reports, it is clear that internalized metals—from both inhalation and embedded fragments—can lead to the development of cardiovascular, immunologic, and neurologic ailments. However, a lack of information on the long-term health effects of internalized metals, alone and in combination with polytrauma, can result in veterans suffering from these types of injuries and not receiving appropriate medical care. Several areas deserve further investigation:

• information on the biokinetics of internalized military-relevant metals and metal mixtures,

• effects of internalized metals on long-term cardiovascular and neurologic health, and

• consequences of internalized metals on recovery from polytraumatic injury.

More important is the prompt identification and tracking of people with embedded metal fragments. Identification and tracking include following the guidelines in the DoD Health Affairs Policy Letter 07-029, which states that all surgically excised fragments should be sent for laboratory analysis and that all laboratory results should be included in the patient’s health record.¹⁴ This information is critical in identifying veterans with internalized metals so that they can be referred to the US Department of Veterans Affairs Toxic Embedded Fragment Center for long-term health surveillance. The information obtained from further research and proper tracking of wounded service members will enable medical personnel to provide the proper care that our veterans deserve.