Dime bomb toxcity

Dense Inert Metal Explosives DIME-related intoxications What should be threated?

Frederic Baud Expert Toxicologist at OCP

« Le chariot du passé ne nous conduit nulle part » Tolstoï Journées Médico-chirurgicales MSF Paris-December 2015

DIME-related intoxications Summary 1. Elements and alloys used in ammunitions 2. What are DIMEs? What are the DIME-induced injuries 3. Release of elements and alloys from intracorporeal localization 4. Injuries induced by the release/local effects of intracoporeal elements and alloys: –

Non carcinogenic

–

Carcinogenic

5. Conclusion

Chemicals elements and alloys used in military ammunitions 1 1. Lead remained for a while the metal the most widely used in ammunitions 2. As early as the 1950s, the U.S. military had used tungsten carbide in armor-piercing munitions.

3. Depleted uranium (DU) was once the metal of choice for U.S. military kinetic-energy munitions.

DU saw its first widespread combat use in the First Persian Gulf War. 4. Today, the composition of weapons-grade tungsten alloy varies. DIME belongs to this later class of ammunitions.

5. White Phosphorus should be ever kept in mind as it has been commonly used in many conflicts owing to its ability to immediately and long-lasting ignition in contact with oxygen

Adapted from Bardack et al. Environmental Research and Public Health 2014

Metals used in military ammunitions 2 What is Dense Inert Metal Explosive?

• DIME weapons consist of a carbon fiber casing filled with a mixture of explosive and very dense microshrapnel, consisting of very small particles (1–2 mm) or powder of a mix of heavy metals.

• To date, tungsten alloy (heavy metal tungsten alloy, or HMTA) composed of tungsten and other metals such as cobalt and nickel or iron has been the preferred materials for the dense microshrapnel or powder.

• Two common HMTA are: • rWNiCo: tungsten (91–93%), nickel (3–5%) and cobalt (2–4%) • rWNiFe: tungsten (91–93%), nickel (3–5%) and iron (2–4%)

Comparison of injuries caused by DIME vs Conventional explosives

Cutaneous damages caused by DIME

• FB did not find any body imaging (Xray, CT scan) performed in DIME-induced injuries • Imaging in Gunshots: well documented. Hollerman et al AJR 1990 •

Splinters and Shrapnel must result in avoiding MRI. Safety of MR Imaging was documented only for air gun pellets Oliver & Kabala. Clin Radiol 1997

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Lead poisonings resulting from ammunitions There are a few but consistent reports of systemic lead toxicity induced or associated by lead ammunition: single case reports • Bullet lodged in a left knee 14 years ago, presenting with polyneuropathy suggesting lead poisoning confirmed by high plasma lead levels (129 μg.dL-1).De Lima Rev Bras Anestesiol 2012 • Air gun pellet remaining in the maxillary sinus for 50 years: a relevant risk factor for the patient? Finding a squamous cell carcinoma: lead associated or causal factor? Khünel et al Int. J. Oral Maxillofac. Surg. 2010 • Systemic and recurrent lead Poisoning by Intradiscal Firearm Bullet Cristante et al Spine 2010 • A14-year-old female with lead toxicity who presented with an 18-month course of lead toxicity 2 years after sustaining a gunshot wound to the right leg. Coon et al. Pediatrics 2006 • One case series: 15 patients with retained missiles and 15 injured without retained missiles. Patients with extra-articular retained

missiles (EARMs) have significantly elevated blood lead levels compared with matched controls. The occurrence of a bony fracture within the past 30 days is associated with a higher lead level. In 96% of patients with EARMs, elevated lead levels were not clinically significant and did not change patient management. Nguyen J Trauma Injury, Infection, and Critical Care 2005

Lead poisonings resulting from ammunitions Change in Blood Lead Concentration up to 1 Year after a Gunshot Wound with a Retained Bullet • In mixed-model analyses, blood lead levels increased with time post-injury (p < 0.0005) up to 3 months, with number of retained fragments (p < 0.0005), and with increasing age (p < 0.0005).

• Increased blood lead concentration as a function of fragmentation was approximately 30% higher among subjects who had suffered bone fracture in the torso (p < 0.0005).

• Subjects with bullets or fragments lodged near bone (p < 0.0005) or near joints (p = 0.032) had higher blood lead levels.

• Logistic models correctly predicted a blood lead elevation of ≥20 μg/dl in 81% and 85% of subjects at 3 and 6 months postinjury, respectively. The prevalence of elevated blood lead was 11.8% at 3 months and 2.6% at 12 months.

Joseph L. McQuirter, Stephen J. Rothenberg, Gracie A. Dinkins, Vladislav Kondrashov, Mario Manalo, and Andrew C. Todd. American Journal of Epidemiology2004

Lead poisonings resulting from ammunitions Change in Blood Lead Concentration up to 1 Year after a Gunshot Wound with a Retained Bullet

Joseph L. McQuirter, Stephen J. Rothenberg, Gracie A. Dinkins, Vladislav Kondrashov, Mario Manalo, and Andrew C. Todd. American Journal of Epidemiology2004

Lead poisonings resulting from ammunitions

Lead poisonings resulting from ammunitions

Factors resulting in lead poisonings • Enfants. Wiley et al. Pediatrics 1992; Lyons & Filston. J Pediatr Surg 1994 • Un projectile près ou dans une articulation ou une séreuse. Jensen et al Skeletal radiol 1990; Farber et al. AJR 1994; Peh et al. AJR 1995

• Au contact du LCR • Plus la surface de plomb en contact avec les fuides est grande plus l’intoxication est rapide et massive • Facteur d’ostéolyse: immobilisation forcée notamment en cas d d’arthrite • Etats hypermétaboliques: fièvre, alcoolisme, sarcoïdose, Paget, certains cancers, hyperthyroïdie (Cagin et coll Ann Med Intern 1978; 89: 509), Kerizian-Sousse P. MD Thesis. Paris 2004

Release of other metals in exposure not related to explosives Titanium exposure from spinal arthrodesis Serum Titanium levels after instrumented spinal arthrodesis.

Richardson et al Spine 2008 Meng et al Spine 2010

Aluminium-induced encephalopathy

Conclusions Release of metals from metals set within the body • There is a consistent body of knowledge supporting the assumption that intracorporeal elements and heavy metal alloys may slowly release elements.

• As fas as we know, all elements may result in some release • However, significant release, as assessed by blood levels, is a a rare event in comparison with the number of individuals living with intracorporeal elements or alloys: far less than 5% of exposed individuals.

• Case series highighted a number of factors increasing the likelihood of release

From a surgical point of view (proposed by FB) Except for: white phosphorus radio-active materials Surgical removal of foreign bodies, by itself, is never a vital surgical emergency Relative emergency: intra-articular foreign body; intracardiac? (Pollak & Bohnert Forensic Sci Int 1999)

Injuries and sequellae resulting from retained foreign bodies Non-carcinogenic diseases

Systemic toxicity related to metal hip prostheses.

Bradberry et al. Clin Toxicol (Phila). 2014; 52(8):837-47 One in eight of all total hip replacements requires revision within 10 years, 60% because of wear-related complications.

The bearing surfaces may be made of cobalt/chromium, stainless steel, ceramic, or polyethylene.

Friction between bearing surfaces and corrosion of non-moving parts can result in increased local and systemic metal concentrations.

Systemic toxicity related to metal hip prostheses.

Bradberry et al. Clin Toxicol (Phila). 2014; 52(8):837-47 Systemic toxicity • Ten of these eighteen patients had undergone revision from a ceramic-containing bearing to one containing a metal component.

• The other eight had metal-on-metal prostheses.

• Systemic toxicity was first manifest months and often several years after placement of the metal-containing joint.

Systemic toxicity related to metal hip prostheses.

Bradberry et al. Clin Toxicol (Phila). 2014; 52(8):837-47 Systemic toxicity • The reported systemic features fell into three main categories: • Neuro-ocular toxicity (14 patients). Neurotoxicity was manifest as peripheral neuropathy (8 cases), sensorineural hearing loss (7) and cognitive decline (5); ocular toxicity presented as visual impairment (6). All these neurological features, except cognitive decline, have been associated with cobalt poisoning previously.

• Cardiotoxicity (11 patients) • Thyroid toxicity (9 patients).

Systemic toxicity related to metal hip prostheses.

Bradberry et al. Clin Toxicol (Phila). 2014; 52(8):837-47 Bradberry et al propose the following criteria for assessing the likelihood that clinical features are related to cobalt toxicity: 1. Clinical effects consistent with the known neurological, cardiac, or thyroidal effects of cobalt, and for which any other explanation is less likely, 2. Increased blood cobalt concentrations (substantially higher than those in patients with wellfunctioning prostheses) several months after hip replacement, 3. After new hip replacement, a fall in the blood cobalt concentration, usually accompanied by signs of improvement in features.

4. When judged by these criteria, the systemic features in 10 of the reported cases are likely to be related to cobalt exposure from a metal-containing hip prosthesis

The diagnosis of heavy metal poisoning for intracorporeal foreign bodies The definitive diagnosis of heavy metal-induced poisoning requires to fill out a number of criteria, including: • A past history suggestive of exposure • Taking into account for any possible occupational, medicine-related, and household exposures • Any evidence of presence/exposure provided by body imaging • Signs and symptoms suggestive of the suspected heavy metal(s) • When available: increased levels of biomarkers of exposure • Assessment of the internal dose using either the blood and/or urine metal concentrations The French Consensus on the diagnosis of metal or metalloid poisoning and misuse of chelation. Toxicol Analyt Clin 2015

Experimental Toxicology in non-carcinogenic diseases Depleted Uranium • Renal dysfunction induced by long-term exposure to depleted uranium in rats (360 days in rats) Zhu et al Arch Toxicol 2009 • Evaluation of the Effect of Implanted Depleted Uranium (DU) on Adult Rat Behavior and Toxicological Endpoints: No behavioural effects but the concentration of uranium in urine directly correlated with the number of implanted DU pellets, indicating that DU was migrating into the body from the implanted pellets

(150 days).

Arfsten et al J Toxicol Environ Health 2014

Injuries and sequellae resulting from retained foreign bodies Carcinogenic diseases

Experimental Toxicology 1 An experimental study showed that a military-grade composition of tungsten, nickel, and cobalt induced a highly-aggressive, metastatic rhabdomyosarcoma when implanted into the leg muscle of laboratory rats to simulate a shrapnel wound.

• Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats Kalinich et al Environ Health Persp 2005 Miller et al. Carcinogenesis 2001 Miller et al. Environ Health Persp 1998

• Implanted Depleted Uranium Fragments Cause Soft Tissue Sarcomas in the Muscles of Rats Hahn et al Environ Health Persp 2002

Experimental Toxicology 3

Foreign-body-induced carcinogenesis • Réactions tissulaires aux corps étrangers Betz et Smollar. Acta Chir Belg 1971

• Beyond foreign-body-induced carcinogenesis: Impact of reactive oxygen species derived from inflammatory cells in tumorigenic conversion and tumor progression.

Okada Int. J. Cancer: 2007; 121, 2364–2372

Evaluation of the carcinogenic risks to humans associated with surgical implants and other foreign bodies Ă? a report of an IARC Monographs Programme Meeting

A meeting was held within the International Agency for Research on Cancer (IARC) Programme on the Evaluation of Carcinogenic Risks to Humans of surgical implants and other foreign bodies.

Evaluations resulted in a classification of Group 2B (possibly carcinogenic to humans) for: (1) polymeric implants prepared as thin smooth films [with the exception of poly(glycolic acid)]; (2) metallic implants prepared as thin smooth films; and (3) implanted foreign bodies consisting of metallic cobalt, metallic nickel and a particular alloy powder consisting of 66Âą67% nickel, 13Âą16% chromium and 7% iron.

Group 3 (not classifiable as to their carcinogenicity to humans) were made for: (1) organic polymeric materials as a group; (2) orthopaedic implants of complex composition and cardiac pacemakers; (3) silicone breast implants; (4) dental materials; and (5) ceramic implants.

McGregor et al. Eur J Cancer 2000

Conclusion

• There is no valuable information about the Short-term effects as well as the Long-term effects of DIME explosives. Therefore, we cannot provide any definitive conclusion.

• However, the cumulative experience resulting from long-term follow-up of foreign bodies, including splinters of grenade, gunshot as well as medical use of metal alloys in orthopedic surgery suggests: • Release of elemental metals from the foreign bodies may occur • This is a extremely rare adverse event of any implanted heavy metal, however. Local effects as well as systemic effects may result in: • Direct systemic toxicity • Carcinogenesis

The respective part of non-specific local inflammation and mutagenic, carcinogenic effect is a pending question of major relevancy in the carcinogenic process If suspected adverse effect, measurement of urine and/or blood heavy metal is an easy-toperform evidence of likelihood of toxicity and hazard

The last but not the least Great Thanks to the Paris Poison Control Centre, and more especially to Dr Antoine Villa Dr Jérôme Langrand For helping me in the bibliography and refining the presentation Thanks for your attention