Characterization of toxicological effects of complex nano-sized metal particles using in vitro human cell and whole blood model systems.

Metal oxide fumes form at high temperatures, for instance, during welding or firing ammunition. Inhalation exposure to high levels of airborne metal oxide particles can cause metal fume fever, cardiovascular effects, and lung damage in humans, but the associated underlying pathological mechanisms are still not fully understood. Using human alveolar epithelial cells, vascular endothelial cells, and whole blood model systems, we aimed to elucidate the short-term effects of well-characterized metal particles emitted while firing pistol ammunition. Human lung epithelial cells exposed to gunshot smoke particles (0.1-50 µg/ml) produced reactive oxygen species (ROS) and pro-inflammatory cytokines (interleukin 8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF)) that activate and recruit immune cells. Particles comprising high copper (Cu) and zinc (Zn) content activated human endothelial cells via a non-ROS-mediated mechanism that triggered immune activation (IL-8, GM-CSF), leukocyte adhesion to the endothelium (soluble intercellular adhesion molecule 1 (sICAM-1)), and secretion of regulators of the acute-phase protein synthesis (interleukin 6 (IL-6)). In human whole blood, metal oxides in gunshot smoke demonstrated intrinsic properties that activated platelets (release of soluble cluster of differentiation 40 ligand (sCD40L), platelet-derived growth factor B-chain homodimer(PDGF-BB), and vascular endothelial growth factor A (VEGF-A)) and blood coagulation and induced concomitant release of pro-inflammatory cytokines from blood leukocytes that further orchestrate thrombogenesis. The model systems applied provide useful tools for health risk assessment of particle exposures, but more studies are needed to further elucidate the mechanisms of metal fume fever and to evaluate the potential risk of long-term cardiovascular diseases.

Comparing acute toxicity of gunshot particles, from firing conventional and lead-free ammunition, in pulmonary epithelial cell cultures.

Numerous studies demonstrated that the use of lead (Pb)-containing ammunition is associated with mainly chronic health problems and also is a burden on the environment and wildlife. Recently, a number of reports showed evidence of undesirable acute health effects related to the use of newly developed Pb-free small-caliber ammunition. In this study, particles from leaded and Pb-free ammunition were collected in liquid collection medium, in a highly controlled chamber, while firing a pistol (9 mm) or a rifle (7.62 × 51 mm). The emitted particles were typically smaller than 4 µm, with the great majority in even smaller size ranges, as shown by gravimetrical analysis and a multistage impactor. Chemical analysis revealed significant differences in content and concentration of several metals in the particles. After administration of the liquids to alveolar and bronchial in vitro cell systems, particles were taken up by the cells; the Pb-free particles displayed higher cytotoxicity (EC50 = 2 µg/cm(2)) than particles from Pb ammunition. High correlation factors (>0.9) were found between cell death and content of copper and zinc. Particles from both Pb-containing and Pb-free ammunition were able to induce oxidative stress and the proinflammatory marker interleukin (IL)-8 in both in vitro systems. These results support previous findings that indicate an association between gunshot emissions and metal fume fever. This study demonstrates the usefulness of combining chemical data with biological in vitro responses in assessing acute toxicological effects from emissions from firing both Pb and Pb-free ammunition.

Broad exposure screening of air pollutants in the occupational environment of Swedish soldiers deployed in Afghanistan.

The main objective of this study was to perform an initial characterization of Swedish soldiers' exposure to air pollutants in Afghanistan and screen for potential health hazards. Stationary monitoring was performed in two military camps, International Security Assistance Force Headquarters in Kabul and Camp Northern Lights in Mazar-e Sharif, at both outdoor and indoor locations. A broad screening including particulate matter (PM10 and PM2.5), polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs, n-alkanes, nitrogen dioxide (NO2), sulfur dioxide, toxic metals, and volatile organic compounds (VOCs) was performed over 2 weeks in the autumn of 2009. The results were compared to current air quality guidelines. Particulate matter was identified as the main potential health hazard since military exposure guidelines for marginal effects were exceeded outdoors. In addition, especially in Kabul, levels of particle-bound PAHs and oxy-PAHs were high, whereas levels of toxic metals were generally low. Among gaseous pollutants, elevated NO2 levels in Kabul supported combustion as a major contributor to the poor air quality. VOC levels were generally low, but levels of some pollutants exceeded current guidelines. Because of elevated concentrations of particles with a high content of toxic organics, further monitoring and characterization of the occupational environment are warranted.

Distribution, chemical speciation, and mobility of lead and antimony originating from small arms ammunition in a coarse-grained unsaturated surface sand.

This study quantified the heavy metal contamination caused by firing 500 high-velocity 7.62-mm jacketed Swedish military rounds. Contamination of solid and aqueous phases was studied, with Pb and Sb being the two contaminants of primary interest. The distribution of the Pb and Sb were measured in terms of depth of penetration in sand and grain size distribution of the bullet particles. The Pb- and Sb-contaminated sand was then used as a source material in two bench-scale unsaturated lysimeters to measure the transport of Pb and Sb through two coarse-grained sands, which were taken from the berms on two Swedish military small arms ranges. The lysimeters were subjected to an infiltration cycle that reproduced spring snowmelt, which is the most significant infiltration event of the year in northern climates. The levels of mobile Pb and Sb were monitored in the effluent from the lysimeters. Extended X-ray absorption fine-structure spectroscopy analysis was performed on the contaminated sands to determine Pb speciation before and after leaching. Ninety-three percent of the mass of bullets was found in the top 30 cm of sand. Lead oxide was the predominant species of Pb before and after leaching. Transport of Pb was small, with aqueous concentrations remaining stable at <2 microg L(-1). Antimony was far more mobile, with solute breakthrough occurring between 5 and 14 d and concentrations rising to over 125 microg L(-1) within 1 month.

N-acetyl cysteine protects against chlorine-induced tissue damage in an ex vivo model.

High-level concentrations of chlorine (Cl2) can cause life-threatening lung injuries and the objective in this study was to understand the pathogenesis of short-term sequelae of Cl2-induced lung injury and to evaluate whether pre-treatment with the antioxidant N-acetyl cysteine (NAC) could counteract these injuries using Cl2-exposed precision-cut lung slices (PCLS). The lungs of Sprague-Dawley rats were filled with agarose solution and cut into 250 µm-thick slices that were exposed to Cl2 (20-600 ppm) and incubated for 30 min. The tissue slices were pre-treated with NAC (5-25 mM) before exposure to Cl2. Toxicological responses were analyzed after 5 h by measurement of LDH, WST-1 and inflammatory mediators (IL-1ß, IL-6 and CINC-1) in medium or lung tissue homogenate. Exposure to Cl2 induced a concentration-dependent cytotoxicity (LDH/WST-1) and IL-1ß release in medium. Similar cytokine response was detected in tissue homogenate. Contraction of larger airways was measured using electric-field-stimulation method, 200 ppm and control slices had similar contraction level (39 ± 5%) but in the 400 ppm Cl2 group, the evoked contraction was smaller (7 ± 3%) possibly due to tissue damage. NAC-treatment improved cell viability and reduced tissue damage and the contraction was similar to control levels (50 ± 11%) in the NAC treated Cl2-exposed slices. In conclusion, Cl2 induced a concentration-dependent lung tissue damage that was effectively prevented with pre-treatment with NAC. There is a great need to improve the medical treatment of acute lung injury and this PCLS method offers a way to identify and to test new concepts of treatment of Cl2-induced lung injuries.

Development of air sampling strategies for monitoring common air pollutants in a mission area at Camp Victoria in Kosovo--stationary vs. personal monitoring.

It can be problematic to collect representative samples in the occupational environment of deployed soldiers using personal samplers. In this study, several air sampling strategies were examined to identify the most efficient method for collecting air samples that were representative of the soldiers' exposure profiles at the Swedish KFOR Camp Victoria outside Pristina, Kosovo. Stationary monitoring was performed during two 5-day sampling campaigns, one in summer and one in winter. The acquired data were related to measurements obtained by personal monitoring of three and four subgroups, respectively. Patrolling soldiers, mechanics, and indoor workers were selected to represent groups with different exposure profiles, and the particles, metals associated with particles, nitrogen dioxide, sulfur dioxide, polycyclic aromatic hydrocarbons, aldehydes, and volatile organic compounds that they were exposed to were measured. Generally, low concentrations of the analytes were found in both sampling periods, but the variability was greater in the winter campaign. Samples collected by stationary samplers captured most of the variation in the personnel's exposure, according to principal component analysis (PCA). However, the results also indicate that personal exposure to most potential pollutants would be underestimated if a single outdoor station was used to monitor them. Nevertheless, combined data from stations located outdoors and in relevant microenvironments (workshop, office, and guard station) provided substantially better representation. Thus, it may be possible to obtain monitoring data without using personal samplers in these inherently problematic situations.

Field evaluation and calibration of a small axial passive air sampler for gaseous and particle bound polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs.

Polycyclic aromatic hydrocarbons (PAHs) and their oxygenated analogues (OPAHs) are ubiquitous air pollutants known to cause adverse health effects. PAH air levels are commonly monitored by active sampling but passive sampling has become popular because of its lower cost and simplicity, which facilitate long-term sampling and increased spatial coverage. However, passive samplers are less suitable for short-term sampling and are in general less accurate than active samplers because they require reliable sampling rate (Rs) measurements for individual analytes under diverse environmental conditions. In this study a small passive sampler designed to sample both particle-bound and gaseous compounds was evaluated and calibrated for PAHs and OPAHs in a traffic environment by co-deployment with active samplers for two weeks. Despite the relatively low average air concentrations of PM10 (20 µg/m(3)), PM2.5 (5 µg/m(3)), total PAHs (4.2 ng/m(3)), and OPAHs (2.3 ng/m(3)) at the site, detectable quantities (on average 24 times above blank values) of the full range of PAHs and OPAHs were captured, with low variability (average RSD of 16%). This was accomplished by using a Tenax(®) TA-modified glass fiber substrate that is compatible with highly sensitive thermal desorption GC-MS analysis, which made it possible to achieve detection limits per sample in the pg range. Experiments with inverted samplers revealed that the relative contribution of gravitational settling to the sampling of particles carrying PAHs and OPAHs was around 3.5 times larger than other deposition mechanisms. Average Rs values for individual OPAHs and PAHs were 0.046 ± 0.03 m(3)/day and 0.12 ± 0.07 m(3)/day, respectively, with no appreciable difference between the values for particle-associated and gaseous compounds. Furthermore, the Rs values were competitive with other currently used passive samplers if normalized for substrate area. Overall, the new sampler's performance, simplicity and ability to generate relatively time-resolved data make it a promising candidate for diverse SVOC monitoring studies.