Cannabis adulterated with the synthetic cannabinoid receptor agonist MDMB-4en-PINACA and the role of European drug checking services.

BACKGROUND: European drug checking services exchange information on drug trends within the Trans European Drug Information (TEDI) network, allowing monitoring and coordination of responses. Starting in Spring 2020, several services detected the synthetic cannabinoid receptor agonist MDMB-4en-PINACA in adulterated low-THC cannabis products. METHODS: Cannabis products suspected of adulteration were analyzed for the presence of MDMB-4en-PINACA by 9 services in 8 countries within the TEDI network. If available, phytocannabinoid analysis was also performed. RESULTS: 1142 samples sold as cannabis in herbal, resin and e-liquid form were analyzed, of which 270 were found to contain MDMB-4en-PINACA. All cannabis samples contained low THC (<1%), except the e-liquids which contained no phytocannabinoids. Three serious health incidents requiring hospitalization after use of an adulterated cannabis sample were reported. CONCLUSION: Adulteration of cannabis with synthetic cannabinoid receptor agonists is a new phenomenon that carries risk for people who use it. Given that cannabis consumers are not a usual target group for drug checking services, services and associated harm reduction interventions could be reconfigured to include them.

Embedded fragments from U.S. military personnel--chemical analysis and potential health implications.

BACKGROUND: The majority of modern war wounds are characterized by high-energy blast injuries containing a wide range of retained foreign materials of a metallic or composite nature. Health effects of retained fragments range from local or systemic toxicities to foreign body reactions or malignancies, and dependent on the chemical composition and corrosiveness of the fragments in vivo. Information obtained by chemical analysis of excised fragments can be used to guide clinical decisions regarding the need for fragment removal, to develop therapeutic interventions, and to better anticipate future medical problems from retained fragment related injuries. In response to this need, a new U.S Department of Defense (DoD) directive has been issued requiring characterization of all removed fragments to provide a database of fragment types occurring in combat injuries. OBJECTIVES: The objective of this study is to determine the chemical composition of retained embedded fragments removed from injured military personnel, and to relate results to histological findings in tissue adjacent to fragment material. METHODS: We describe an approach for the chemical analysis and characterization of retained fragments and adjacent tissues, and include case examples describing fragments containing depleted uranium (DU), tungsten (W), lead (Pb), and non-metal foreign bodies composed of natural and composite materials. Fragments obtained from four patients with penetrating blast wounds to the limbs were studied employing a wide range of chemical and microscopy techniques. Available adjacent tissues from three of the cases were histologically, microscopically, and chemically examined. The physical and compositional properties of the removed foreign material surfaces were examined with energy dispersive x-ray fluorescence spectrometry (EDXRF), scanning electron microscopy (SEM), laser ablation inductively-coupled plasma mass-spectrometry (LA-ICP-MS), and confocal laser Raman microspectroscopy (CLRM). Quantitative chemical analysis of both fragments and available tissues was conducted employing ICP-MS. RESULTS: Over 800 fragments have been characterized and included as part of the Joint Pathology Center Embedded Fragment Registry. Most fragments were obtained from penetrating wounds sustained to the extremities, particularly soft tissue injuries. The majority of the fragments were primarily composed of a single metal such as iron, copper, or aluminum with traces of antimony, titanium, uranium, and lead. One case demonstrated tungsten in both the fragment and the connected tissue, together with lead. Capsular tissue and fragments from a case from the 1991 Kuwait conflict showed evidence of uranium that was further characterized by uranium isotopic ratios analysis to contain depleted uranium. CONCLUSIONS: The present study provides a systematic approach for obtaining a full chemical characterization of retained embedded fragments. Given the vast number of combat casualties with retained fragments, it is expected that fragment analysis will have significant implications for the optimal short and long-term care of wounded service members.

Assessment of geographical variation in the respiratory toxicity of desert dust particles.

The health consequences of sand particle inhalation are incompletely understood. This project evaluated the respiratory toxicity of sand particles collected at military bases near Fort Irwin USA, in Iraq (Camp Victory, Taji and Talil), and Khost Afghanistan. Our primary focus was on assessing the role of soluble metals in the respiratory toxicity of the sand particles using in vitro and in vivo methods. Replicating rat type II alveolar cell cultures (RLE-6TN) were exposed to sand extracts or vehicle control in serum-free media for ≤24 h. Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and assessment of lactate dehydrogenase leakage. The relative in vitro cytotoxicity of the sand extracts was Taji ≈ Talil > Afghanistan > Camp Victory ≈ Fort Irwin. We also assessed extracts of Camp Victory, Afghanistan, and Taji sand for acute and delayed pulmonary toxicity in rats following intratracheal administration. Assessments included biochemical analysis of bronchoalveolar lavage fluid (BALF) and lung histopathology. The in vitro cytotoxicity assay results were partially predictive of in vivo responses. The more cytotoxic Taji sand extract induced an acute irritant response in rats following intratracheal administration. Rats given the less cytotoxic Camp Victory sand extract had minimal biochemical or cytological BALF changes whereas rats given either the Afghanistan or Taji sand extracts demonstrated BALF changes that were suggestive of mild lung inflammation. Unexpectedly, we observed similar lung pathology in all extract-exposed rats. The results of our study can be used to prioritize future particle inhalation studies or guide epidemiological study design.

Tissue distribution of tungsten in mice following oral exposure to sodium tungstate.

Heavy metal tungsten alloys have replaced lead and depleted uranium in many munitions applications, due to public perception of these elements as environmentally unsafe. Tungsten materials left in the environment may become bioaccessible as tungstate, which might lead to population exposure through water and soil contamination. Although tungsten had been considered a relatively inert and toxicologically safe material, recent research findings have raised concerns about possible deleterious health effects after acute and chronic exposure to this metal. This investigation describes tissue distribution of tungsten in mice following oral exposure to sodium tungstate. Twenty-four 6-9 weeks-old C57BL/6 laboratory mice were exposed to different oral doses of sodium tungstate (0, 62.5, 125, and 200 mg/kg/d) for 28 days, and after one day, six organs were harvested for trace element analysis with inductively coupled plasma mass spectrometry (ICP-MS). Kidney, liver, colon, bone, brain, and spleen were analyzed by sector-field high-resolution ICP-MS. The results showed increasing tungsten levels in all organs with increased dose of exposure, with the highest concentration found in the bones and the lowest concentration found in brain tissue. Gender differences were noticed only in the spleen (higher concentration of tungsten in female animals), and increasing tungsten levels in this organ were correlated with increased iron levels, something that was not observed for any other organ or either of the two other metals analyzed (nickel and cobalt). These findings confirmed most of what has been published on tungsten tissue distribution; they also showed that the brain is relatively protected from oral exposure. Further studies are necessary to clarify the findings in splenic tissue, focusing on possible immunological effects of tungsten exposure.

Study of inorganic particles, fibers, and asbestos bodies by variable pressure scanning electron microscopy with annexed energy dispersive spectroscopy and micro-Raman spectroscopy in thin sections of lung and pleural plaque.

In a previous work it has been demonstrated that micro-Raman spectroscopy is a technique able to recognize crystalline phases on untreated samples. In that case, inorganic particles and uncoated fibers from bronchoalveolar lavage (BAL) of a patient affected by pneumoconiosis were identified and characterized. In this work the technique is applied to asbestos bodies, that is, to coated fibers, and on crystallizations and fibrous phases observed in the plural plaque from patients affected by mesothelioma. From the Raman analysis the abundant fibrous material observed in the pleural area is talc, whereas rounded grains in the pleural tissue show the Raman spectrum of apatite, a calcium phosphate mineral particular to bones. In the pulmonary tissue many asbestos bodies, consisting of the incorporated fibers coated by iron-rich proteins, were observed. Under the 632.8 nm laser beam of the spectrometer, photo-crystallization of hematite in the iron-rich material forming the asbestos bodies can be proposed by the changes in the Raman spectra acquired during subsequent acquisitions. Nevertheless, the identification of the mineral phase constituting the incorporated fiber was possible by analyzing the Raman spectra; the results were confirmed by variable pressure scanning electron microscopy with annexed energy dispersive spectroscopy (VP-SEM-EDS) analyses.

Asbestos health hazard: a spectroscopic study of synthetic geoinspired Fe-doped chrysotile.

The chrysotile fibres toxicity appears correlated to the redox activity of iron present in the chrysotile structure. In fact the generation of reactive oxygen species and other radicals appears catalyzed by iron ions and closely related to Fe ions organization in specific crystallographic sites having a capability to activate free radical generation. The Fe substitution to Mg and/or Si in the chrysotile structure appears important for asbestos health hazard investigation. Infrared and Raman spectroscopic analyses have been utilized to investigate Mg and/or Si ions replacement by Fe ions in chrysotile structure as a function of the Fe doping extent. Geoinspired synthetic chrysotile at different Fe doping extents has been obtained as unique phase by hydrothermal reaction in the presence or not of metallic Fe in the synthetic environment. The results highlight that Fe can replace both Mg and Si, differently modifying the chrysotile structure as a function of the Fe doping extent and the Fe doping process. The contemporary iron substitution into the octahedral and tetrahedral sheets reveals an appreciable increase of the dehydroxylation temperature which occurs at higher temperature than for iron-free sample. The results highlight the role of Fe substitution in the asbestos structure influencing the health hazard of biological systems.

Environmental exposure to asbestos and other inorganic fibres using animal lung model.

Professional exposure to asbestos fibres is widely recognized as very dangerous to human health and for this reason many countries have banned their commercial uses. People, nevertheless, continue to be exposed to low dose of asbestos from natural and anthropogenic sources still in loco, for which the potential hazard is unknown. The aim of this research is to assess environmental exposure in an area with outcropping serpentinite rocks, which bear asbestos mineralizations, using sentinel animals which are a non-experimental animal model. We studied the burden of inorganic fibres in cattle lungs which come from two areas in Italy's Western Alps bearing serpentinitic outcrops: Susa Valley with a heavy anthropization and Lanzo Valleys, with a minor human impact. The identification and quantification of inorganic fibres were performed by Scanning Electron Microscope (SEM) and Energy Dispersive Spectrometer (EDS). In comparison to humans, studies of animals have some advantages, such as no occupational exposure or history of smoking and, in the case of cattle, a sedentary life restricted to one region. Results spotlight that over than 35% of inorganic fibres found both in Susa and Lanzo valleys, belong to asbestos mineralogical species (asbestos tremolite/actinolite, chrysotile s.s., asbestos grunerite, crocidolite). We also observed a higher concentration of artificial fibrous products in Susa samples showing a correlation with the level of anthropization. These results confirm that sentinel animals are an excellent model to assess breathable environmental background because it is possible to eliminate some variables, such as unknown occupational exposure.