Ronald C. Scripsick

Surface area of respirable beryllium metal, oxide, and copper alloy aerosols and implications for assessment of exposure risk of chronic beryllium disease

The continued occurrence of chronic beryllium disease (CBD) suggests the current occupational exposure limit of 2 microg beryllium per cubic meter of air does not adequately protect workers. This study examined the morphology and measured the particle surface area of aerodynamically size-separated powders and process-sampled particles of beryllium metal, beryllium oxide, and copper-beryllium alloy. The beryllium metal powder consisted of compact particles, whereas the beryllium oxide powder and particles were clusters of smaller primary particles. Specific surface area (SSA) results for all samples (N=30) varied by a factor of 37, from 0.56 +/- 0.07 m(2)/g (for the 0.4-0.7 microm size fraction of the process-sampled reduction furnace particles) to 20.8 +/- 0.4 m(2)/g (for the </=0.4 microm size fraction of the metal powder). Large relative differences in SSA were observed as a function of particle size for the powder of beryllium metal, from 4.0 +/- 0.01 m(2)/g (for the particle size fraction >6 microm) to 20.8 +/- 0.44 m(2)/g (for the particle size fraction </=0.4 microm). In contrast, little relative difference in SSA (<25%) was observed as a function of particle size for the beryllium oxide powder and particles collected from the screening operation. The SSA of beryllium metal powder decreases with increasing particle size, as expected for compact particles, and the SSA of the beryllium oxide powders and particles remains constant as a function of particle size, which might be expected for clustered particles. These associations illustrate how process-related factors can influence the morphology and SSA of beryllium materials. To avoid errors in predicting bioavailability of beryllium and the associated risks for CBD, the mechanisms of particle formation should be understood and the SSA of beryllium particles should be measured directly.

BIOAVAILABILITY OF BERYLLIUM OXIDE PARTICLES: AN IN VITRO STUDY IN THE MURINE J774A.1 MACROPHAGE CELL LINE MODEL

Beryllium metal and its oxide and alloys are materials of industrial significance with recognized adverse effects on worker health. Currently, the degree of risk associated with exposure to these materials in the workplace is assessed through measurement of beryllium aerosol mass concentration. Compliance with the current mass-based occupational exposure limit has proven ineffective at eliminating the occurrence of chronic beryllium disease (CBD). The rationale for this research was to examine the mechanism of beryllium bioavailability, which may be pertinent to risk. The authors tested the hypothesis in vitro that dissolution of particles engulfed by macrophages is greater than dissolution in cellular medium alone. Physicochemical changes were evaluated in vitro for well-characterized high-purity beryllium oxide (BeO) particles in cell-free media alone and engulfed by and retained within murine J774A.1 monocyte-macrophage cells. The BeO particles were from a commercially available powder and consisted of diffuse clusters (aerodynamic diameter range 1.5 to 2.5 μm) of 200-nm diameter primary particles. Following incubation for 124 to 144 hours, particles were recovered and recharacterized. Recovered particles were similar in morphology, chemical composition, and size relative to the original material, confirming the relatively insoluble nature of the BeO particles. Measurable levels of dissolved beryllium, representing 0.3% to 4.8% of the estimated total beryllium mass added, were measured in the recovered intracellular fluid. Dissolved beryllium was not detected in the extracellular media. The BeO chemical dissolution rate constant in the J774A.1 cells was 2.1 ± 1.7 × 10−8 g/(cm2 ⋅ day). In contrast, the BeO chemical dissolution rate constant in cell-free media was < 8.1 × 10−9 g/(cm2 ⋅ day). In vivo, beryllium dissolved by macrophages may be released in the pulmonary alveolar environment, in the lymphatic system after transport of beryllium by macrophages, or in the alveolar interstitium after migration and dissolution of beryllium particles in tissue. These findings demonstrate a mechanism of bioavailability for beryllium, are consistent with previously observed results in canine alveolar macrophages, and provide insights into additional research needs to understand and prevent beryllium sensitization and CBD.

Physicochemical characteristics of aerosol particles generated during the milling of beryllium silicate ores: implications for risk assessment.

Inhalation of beryllium dusts generated during milling of ores and cutting of beryl-containing gemstones is associated with development of beryllium sensitization and low prevalence of chronic beryllium disease (CBD). Inhalation of beryllium aerosols generated during primary beryllium production and machining of the metal, alloys, and ceramics are associated with sensitization and high rates of CBD, despite similar airborne beryllium mass concentrations among these industries. Understanding the physicochemical properties of exposure aerosols may help to understand the differential immunopathologic mechanisms of sensitization and CBD and lead to more biologically relevant exposure standards. Properties of aerosols generated during the industrial milling of bertrandite and beryl ores were evaluated. Airborne beryllium mass concentrations among work areas ranged from 0.001 μg/m3 (beryl ore grinding) to 2.1 μg/m3 (beryl ore crushing). Respirable mass fractions of airborne beryllium-containing particles were < 20% in low-energy input operation areas (ore crushing, hydroxide product drumming) and > 80% in high-energy input areas (beryl melting, beryl grinding). Particle specific surface area decreased with processing from feedstock ores to drumming final product beryllium hydroxide. Among work areas, beryllium was identified in three crystalline forms: beryl, poorly crystalline beryllium oxide, and beryllium hydroxide. In comparison to aerosols generated by high-CBD risk primary production processes, aerosol particles encountered during milling had similar mass concentrations, generally lower number concentrations and surface area, and contained no identifiable highly crystalline beryllium oxide. One possible explanation for the apparent low prevalence of CBD among workers exposed to beryllium mineral dusts may be that characteristics of the exposure material do not contribute to the development of lung burdens sufficient for progression from sensitization to CBD. In comparison to high-CBD risk exposures where the chemical nature of aerosol particles may confer higher bioavailability, respirable ore dusts likely confer considerably less. While finished product beryllium hydroxide particles may confer bioavailability similar to that of high-CBD risk aerosols, physical exposure factors (i.e., large particle sizes) may limit development of alveolar lung burdens.

Specific surface area determinations of U and Pu oxide particles

Abstract Important factors that can influence the dissolution rate of a particle deposited in the lung include chemical composition of the particle, crystalline structure, and amount of surface interacting with body fluids. Specific surface area determinations were made on samples of mixed uranium and plutonium oxides from industrial facilities and on samples of depleted uranium oxide, using a 85Kr adsorption technique. Samples of respirable particles collected on filters during aerosolization of these materials for animal exposures, as well as the starting materials, were examined. Specific surface areas ranged from 3 to 40 m2 g−1. Results were used to determine shape factors used in a simulation model of the retention, distribution, and excretion of particles deposited in the lungs of animals during an inhalation exposure. For two aerosol samples, the specific surface area increased with each overnight heat treatment; this suggests that heat transformed the samples. Measurements made before and after a 30-day dissolution study of uranium oxides in lung serum simulant demonstrated a decrease in specific surface area (∼50%). This suggests that particle size or surface roughness changes as dissolution proceeds.

Differences in estimates of size distribution of beryllium powder materials using phase contrast microscopy, scanning electron microscopy, and liquid suspension counter techniques

Accurate characterization of the physicochemical properties of aerosols generated for inhalation toxicology studies is essential for obtaining meaningful results. Great emphasis must also be placed on characterizing particle properties of materials as administered in inhalation studies. Thus, research is needed to identify a suite of techniques capable of characterizing the multiple particle properties (i.e., size, mass, surface area, number) of a material that may influence toxicity. The purpose of this study was to characterize the morphology and investigate the size distribution of a model toxicant, beryllium. Beryllium metal, oxides, and alloy particles were aerodynamically size-separated using an aerosol cyclone, imaged dry using scanning electron microscopy (SEM), then characterized using phase contrast microscopy (PCM), a liquid suspension particle counter (LPC), and computer-controlled SEM (CCSEM). Beryllium metal powder was compact with smaller sub-micrometer size particles attached to the surface of larger particles, whereas the beryllium oxides and alloy particles were clusters of primary particles. As expected, the geometric mean (GM) diameter of metal powder determined using PCM decreased with aerodynamic size, but when suspended in liquid for LPC or CCSEM analysis, the GM diameter decreased by a factor of two (p < 0.001). This observation suggested that the smaller submicrometer size particles attached to the surface of larger particles and/or particle agglomerates detach in liquid, thereby shifting the particle size distribution downward. The GM diameters of the oxide materials were similar regardless of sizing technique, but observed differences were generally significant (p < 0.001). For oxides, aerodynamic cluster size will dictate deposition in the lung, but primary particle size may influence biological activity. The GM diameter of alloy particles determined using PCM became smaller with decreasing aerodynamic size fraction; however, when suspended in liquid for CCSEM and LPC analyses, GM particle size decreased by a factor of two (p < 0.001) suggesting that alloy particles detach in liquid. Detachment of particles in liquid could have significance for the expected versus actual size (and number) distribution of aerosol delivered to an exposure subject. Thus, a suite of complimentary analytical techniques may be necessary for estimating size distribution. Consideration should be given to thoroughly understanding the influence of any liquid vehicle which may alter the expected aerosol size distribution.

In-place filter testing geometry effects on test result uncertainty : Single stage systems

In-place filter testing is a widely accepted practice for assuring performance of high-efficiency particulate air (HEPA) filter systems. American Society of Mechanical Engineers (ASME) standards address aspects of uncertainty in in-place filter test results through limits on spatial variation of test aerosol concentration and flow velocity. This article augments the standards by developing an approximate expression for test result uncertainty. The expression uses concentration, flow velocity, and penetration heterogeneities as indices of spatial variation. The uncertainty expression is used to evaluate testing of a hypothetical HEPA filter system meeting requirements of the standards and of an operating field HEPA filter system. At a performance acceptance limit of 5×10−4 penetration, uncertainty in tests on the standard system is just over the inferred ASME system acceptance limit of 6.7%. Uncertainty for field system tests is more than twice the limit. The uncertainty expression is used to determine lim...