Dustiness of fine and nanoscale powders.

Dustiness may be defined as the propensity of a powder to form airborne dust by a prescribed mechanical stimulus; dustiness testing is typically intended to replicate mechanisms of dust generation encountered in workplaces. A novel dustiness testing device, developed for pharmaceutical application, was evaluated in the dustiness investigation of 27 fine and nanoscale powders. The device efficiently dispersed small (mg) quantities of a wide variety of fine and nanoscale powders, into a small sampling chamber. Measurements consisted of gravimetrically determined total and respirable dustiness. The following materials were studied: single and multiwalled carbon nanotubes, carbon nanofibers, and carbon blacks; fumed oxides of titanium, aluminum, silicon, and cerium; metallic nanoparticles (nickel, cobalt, manganese, and silver) silicon carbide, Arizona road dust; nanoclays; and lithium titanate. Both the total and respirable dustiness spanned two orders of magnitude (0.3-37.9% and 0.1-31.8% of the predispersed test powders, respectively). For many powders, a significant respirable dustiness was observed. For most powders studied, the respirable dustiness accounted for approximately one-third of the total dustiness. It is believed that this relationship holds for many fine and nanoscale test powders (i.e. those primarily selected for this study), but may not hold for coarse powders. Neither total nor respirable dustiness was found to be correlated with BET surface area, therefore dustiness is not determined by primary particle size. For a subset of test powders, aerodynamic particle size distributions by number were measured (with an electrical low-pressure impactor and an aerodynamic particle sizer). Particle size modes ranged from approximately 300 nm to several micrometers, but no modes below 100 nm, were observed. It is therefore unlikely that these materials would exhibit a substantial sub-100 nm particle contribution in a workplace.

Comparison of air sampling methods for aerosolized spores of B. anthracis Sterne.

Bacillus anthracis Sterne spores were aerosolized within a chamber at concentrations ranging from 1 x 10³ to 1.7 x 104 spores per cubic meter of air (particles (p)/m³) to compare three different sampling methods: Andersen samplers, gelatin filters, and polytetrafluoroethylene (PTFE) membrane filters. Three samples of each type were collected during each of 19 chamber runs. Chamber concentration was determined by an aerodynamic particle sizer (APS) for the size range of 1.114-1.596 µm. Runs were categorized (low, medium, and high) based on tertiles of the APS estimated air concentrations. Measured air concentrations and recovery efficiency [ratio of the measured (colony forming units (CFU)/m³) to the APS estimated (particles/m³) air concentrations] for the sampling methods were compared using mixed-effects regression models. Limits of detection for each method were estimated based on estimated recovery efficiencies. Mean APS estimated air concentrations were 1600 particles/m³, 4100 particles/m³, and 9100 particles/m³ at the low, medium, and high tertiles, respectively; coefficient of variation (CV) ranged from 25 to 40%. Statistically significant differences were not observed among the three sampling methods. At the high and medium tertiles, estimated correlations of measured air concentration (CFU/m³) among samples collected from the same run of the same type were high (0.73 to 0.93). Among samples collected from the same run but of different types, correlations were moderate to high (0.45 to 0.85); however, correlations were somewhat lower at the low tertile (-0.31 to 0.75). Estimated mean recovery efficiencies ranged from 0.22 to 0.25 CFU/particle with total CVs of approximately 84 to 97%. Estimated detection limits ranged from 35 to 39 particles/m³. These results will enable investigators to conduct environmental sampling, quantify contamination levels, and conduct risk assessments of B. anthracis.

Recovery efficiency and limit of detection of aerosolized Bacillus anthracis Sterne from environmental surface samples.

After the 2001 anthrax incidents, surface sampling techniques for biological agents were found to be inadequately validated, especially at low surface loadings. We aerosolized Bacillus anthracis Sterne spores within a chamber to achieve very low surface loading (ca. 3, 30, and 200 CFU per 100 cm(2)). Steel and carpet coupons seeded in the chamber were sampled with swab (103 cm(2)) or wipe or vacuum (929 cm(2)) surface sampling methods and analyzed at three laboratories. Agar settle plates (60 cm(2)) were the reference for determining recovery efficiency (RE). The minimum estimated surface concentrations to achieve a 95% response rate based on probit regression were 190, 15, and 44 CFU/100 cm(2) for sampling steel surfaces and 40, 9.2, and 28 CFU/100 cm(2) for sampling carpet surfaces with swab, wipe, and vacuum methods, respectively; however, these results should be cautiously interpreted because of high observed variability. Mean REs at the highest surface loading were 5.0%, 18%, and 3.7% on steel and 12%, 23%, and 4.7% on carpet for the swab, wipe, and vacuum methods, respectively. Precision (coefficient of variation) was poor at the lower surface concentrations but improved with increasing surface concentration. The best precision was obtained with wipe samples on carpet, achieving 38% at the highest surface concentration. The wipe sampling method detected B. anthracis at lower estimated surface concentrations and had higher RE and better precision than the other methods. These results may guide investigators to more meaningfully conduct environmental sampling, quantify contamination levels, and conduct risk assessment for humans.

Aerosolization of single-walled carbon nanotubes for an inhalation study.

Single-walled carbon nanotubes (SWCNT) are being produced in increasing quantities because of high interest in applications resulting from their unique properties. Because of potential respiratory exposures during production and handling, inhalation studies are needed to determine potential toxicity. A generation system was designed to produce respirable aerosol at 5 mg/m(3) for a 1-wk animal (mouse) exposure. The starting material used in these experiments was as-produced powder from the high pressure carbon monoxide method that was sieved to number 6 mesh (< 2.3 mm). An acoustic feeder system was developed that handled the SWCNT powder without causing compaction of the material. The feed rate was adjustable, allowing output concentrations as high as 25 mg/m(3). The powder particles were reduced in size using a mill that produced high shear forces, tearing the agglomerates apart. The resulting aerosol was size-separated using a settling chamber and two cyclones to produce a respirable aerosol. The mass output efficiency of the entire system for producing a respirable aerosol from bulk material was estimated to be about 10%.

Pulmonary toxicity of Expancel microspheres in the rat.

Expancel microspheres are thermoplastic microspheres enclosing hydrocarbon. These microspheres expand when heated, producing many applications. Because they have unknown biological persistence and toxicity, we investigated the toxicity of two unexpanded (11.1 and 15.4 micro m mean diameter) and two expanded (3.1 and 5.5 micro m mass median aerodynamic diameter) Expancel microspheres in intratracheally-instilled, male, Sprague-Dawley rats. Pulmonary histopathology was evaluated at 28 days postexposure. Bronchoalveolar lavage fluid was evaluated at days 1, 7, 14, and 28 days postexposure. Crystalline silica was the positive control. By histopathology, both unexpanded and expanded microspheres caused granulomatous bronchopneumonia characterized by macrophages and giants cells, suggesting a persistent foreign body response. Expanded, but not unexpanded microspheres, also caused eosinophilic bronchitis and bronchiolitis, mucous metaplasia of airways and organized granulomatous inflammation with associated fibrosis and frequent airway obstruction. In contrast, alveolar macrophage activation, polymorphonuclear leukocytes, LDH and albumin in bronchoalveolar laveage fluid were initially elevated but returned to near control levels at 28 days, and did not reflect the persistent granulomatous bronchopneumonia caused by Expancel microspheres. These findings emphasize the importance of histopathology for evaluating pulmonary toxicity, suggest that Expancel microspheres are a potential occupational hazard, and indicate a need for additional studies on their potential pulmonary toxicity. [Supplementary materials are available for this article. Go to the publisher's online edition of Toxicology Pathology for the following free supplemental resources: motion within unexpected microspheres in H&E-stained lung (supplementary Figure 1); broncholar epithelium 28 days following exposure to 551 DE 20 microspheres (supplementary Figure 2); membrane ruffling and some instances of phagocytosis within the microspheres (supplementary Figure 3)]

Do vitreous fibers break in the lung?

In order to determine whether breakage of long vitreous fibers in the lung could be responsible for removing significant numbers of these fibers, an intratracheal instillation study was done with a preparation consisting of mostly long fibers of two different types. Following instillation of both fibers, laboratory rats were sacrificed at 6 times up to 14 days. The NK (conventional borosilicate glass) fiber preparation had about 20% short fibers (length < or = 15 microm) initially, and fibers recovered from the lungs remained at that proportion for the entire 14 days. But the HT (a new rock or stone wool) fiber preparation, which had about 5% short fibers initially, jumped to about 50% short fibers at 2 days and remained at that proportion for the rest of the study. The appearance of many short HT fibers where there were few initially is conclusive evidence that these long fibers break, and it explains their rapid removal from the lung. Since the HT fibers dissolve rapidly at acid pH, but slowly at the near neutral pH of the extracellular lung fluid, it is likely that acid attack by phagocytic cells is causing the long fibers to dissolve and break. The long NK fibers dissolve rapidly at neutral pH but slowly at acid pH and thus appear to clear by more or less uniform dissolution without apparent breakage. The long fibers of these two kinds are removed rapidly at about the same rate, but by a different mechanism.

Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material.

Carbon nanotubes represent a relatively recently discovered allotrope of carbon that exhibits unique properties. While commercial interest in the material is leading to the development of mass production and handling facilities, little is known of the risk associated with exposure. In a two-part study, preliminary investigations have been carried out into the potential exposure routes and toxicity of single-walled carbon nanotube material (SWCNT)--a specific form of the allotrope. The material is characterized by bundles of fibrous carbon molecules that may be a few nanometers in diameter, but micrometers in length. The two production processes investigated use-transition metal catalysts, leading to the inclusion of nanometer-scale metallic particles within unrefined SWCNT material. A laboratory-based study was undertaken to evaluate the physical nature of the aerosol formed from SWCNT during mechanical agitation. This was complemented by a field study in which airborne and dermal exposure to SWCNT was investigated while handling unrefined material. Although laboratory studies indicated that with sufficient agitation, unrefined SWCNT material can release fine particles into the air, concentrations generated while handling material in the field were very low. Estimates of the airborne concentration of nanotube material generated during handling suggest that concentrations were lower than 53 microg/m(3) in all cases. Glove deposits of SWCNT during handling were estimated at between 0.2 mg and 6 mg per hand.