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Mark D Hoover

Publications and source records attributed to Mark D Hoover.

13 recordsLinked to original sources

A theoretical framework for evaluating analytical digestion methods for poorly soluble particulate beryllium.

Complete digestion of all chemical forms and sizes of particulate analytes in environmental samples is usually necessary to obtain accurate results with atomic spectroscopy. In the current study, we investigate the physicochemical properties of beryllium particles likely to be encountered in samples collected from different occupational environments and present a hypothesis that a dissolution theory can be used as a conceptual framework to guide development of strategies for digestion procedures. For monodisperse single-chemical constituent primary particles, such as those encountered when handling some types of beryllium oxide (BeO) powder, theory predicts that a digestion procedure is sufficient when it completely dissolves all primary particles, independent of cluster size. For polydisperse single-chemical constituent particles, such as those encountered during the handling of some types of beryllium metal powder, theory predicts that a digestion procedure is sufficient only when it completely dissolves the largest particle in the sample. For samples with unknown or multi-chemical constituent particles and with particles having undefined sizes, e.g., fume emissions from a copper-beryllium alloy furnace operation or dust from a beryl ore crushing operation, a surface area-limited and single-constituent-dependent dissolution theory may not predict complete dissolution, thereby requiring non-routine robust treatment procedures with post-digestion filtration, followed by examination of residual particulate material. Additionally, for beryllium, and likely other poorly soluble materials, particulate reference materials of various chemical forms and size distributions are needed to better evaluate and harmonize analytical digestion procedures. Figure Generation of aerosol particles during machining of beryllium oxide.

Aerosols↗

Exposure pathway assessment at a copper-beryllium alloy facility.

Controlling beryllium inhalation exposures to comply with regulatory levels (2 micro g m(-3) of air) does not appear to prevent beryllium sensitization and chronic beryllium disease (CBD). Additionally, it has proven difficult to establish a clear inhalation exposure-response relationship for beryllium sensitization and CBD. Thus, skin may be an important route of exposure that leads to beryllium sensitization. A 2000 survey had identified prevalence of sensitization (7%) and CBD (4%) in a beryllium alloy facility. An improved particulate migration control program, including dermal protection in production areas, was completed in 2002 at the facility. The purpose of this study was to evaluate levels of beryllium in workplace air, on work surfaces, on cotton gloves worn by employees over nitrile gloves, and on necks and faces of employees subsequent to implementation of the program. Over a 6 day period, we collected general area air samples (n = 10), wipes from routinely handled work surfaces (n = 252), thin cotton glove samples (n = 113) worn by employees, and neck wipes (n = 109) and face wipes (n = 109) from the same employees. In production, production support and office areas geometric mean (GM) levels of beryllium were 0.95, 0.59 and 0.05 micro g per 100 cm(2) on work surfaces; 42.8, 73.8 and 0.07 micro g per sample on cotton gloves; 0.07, 0.09 and 0.003 micro g on necks; and 0.07, 0.12 and 0.003 micro g on faces, respectively. Correlations were strong between beryllium in air and on work surfaces (r = 0.79), and between beryllium on cotton gloves and on work surfaces (0.86), necks (0.87) and faces (0.86). This study demonstrates that, even with the implementation of control measures to reduce skin contact with beryllium as part of a comprehensive workplace protection program, measurable levels of beryllium continue to reach the skin of workers in production and production support areas. Based on our current understanding of the multiple exposure pathways that may lead to sensitization, we support prudent control practices such as use of protective gloves to minimize skin exposure to beryllium salts and fine particles.

Air Pollutants, Occupational↗

Differences in dissolution behavior in a phagolysosomal simulant fluid for single-constituent and multi-constituent materials associated with beryllium sensitization and chronic beryllium disease.

Particle dissolution within macrophage phagolysosomes is hypothesized to be an important source of dissolved beryllium for input to the cell-mediated immune reaction associated with development of beryllium sensitization and chronic beryllium disease (CBD). To better understand the dissolution of beryllium materials associated with elevated prevalence of sensitization and CBD, single-constituent (beryllium oxide (BeO) particles sampled from a screener operation, finished product BeO powder, finish product beryllium metal powder) and multi-constituent (particles sampled from an arc furnace during processing of copper-beryllium alloy) aerosol materials were studied. Dissolution rates were measured using phagolysosomal simulant fluid (PSF) in a static dissolution technique and then normalized to measured values of specific surface area to calculate a chemical dissolution rate constant (k) for each material. Values of k, in g/(cm2 day), for screener BeO particles (1.3 +/- 1.9 x 10(-8)) and for BeO powder (1.1 +/- 0.5 x 10(-8)) were similar (p = 0.45). The value of k observed for beryllium metal powder (1.1 +/- 1.4 x 10(-7)) was significantly greater than observed for the BeO materials (p < 0.0003). For arc furnace particles, k (1.6 +/- 0.6 x 10(-7)) was significantly greater than observed for the BeO materials (p < 0.00001), despite the fact that the chemical form of beryllium in the aerosol was BeO. These results suggest that dissolution of beryllium differs among physicochemical forms of beryllium and direct measurement of dissolution is needed for multi-constituent aerosol. Additional studies of the dissolution behavior of beryllium materials in a variety of mixture configurations will aid in developing exposure-response models to improve understanding of the risk of beryllium sensitization and CBD.

Aerosols↗

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 microm) 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 x 10(-8)g/(cm2 . day). In contrast, the BeO chemical dissolution rate constant in cell-free media was < 8.1 x 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.

Animals↗

Characterization of physicochemical properties of beryllium aerosols associated with prevalence of chronic beryllium disease.

Little is known about the physicochemical properties of beryllium aerosols associated with increased risk of beryllium sensitization and chronic beryllium disease (CBD). Such information is needed to evaluate whether airborne mass of beryllium is the appropriate metric of exposure or alternatively to provide a scientific basis for using information on particle size, surface area, and chemistry to support an improved exposure limit based on bioavailability through the inhalation and dermal routes of exposure. Thus, we used a suite of analytical techniques to characterize aerodynamically size-fractionated beryllium particles and powders that have been associated in epidemiological studies with higher prevalence of CBD. Aerosol particles were sampled from the ventilation systems of production lines for powders of beryllium metal and beryllium oxide and for ingots of copper-beryllium alloy. End product powders from the metal and oxide production lines were also collected. Particles released during production of beryllium metal were found to be complex, having heterogeneous composition, including reactive species such as fluorine. Powders from beryllium metal production were of high purity with only a minor component of beryllium oxide. Both particles and powders from oxide production were high-purity oxide. Particles released during production of copper-beryllium alloy were heterogeneous, being predominantly copper oxides. Thus, all particles and powders contain at least some beryllium in the form of beryllium oxide. These data justify efforts to thoroughly characterize beryllium aerosol properties when performing exposure assessments. The data also suggest that differences in particle chemical composition, size, number, and surface area may influence bioavailability of beryllium and contribute to risk of CBD. However, a scientific basis does not yet exist to replace mass as the current metric of exposure.

Aerosols↗

Characterization of plutonium aerosol collected during an accident.

This study determined the plutonium particle size distribution and dissolution rate of PuO2 aerosol collected during the 16 March 2000 release of an undetermined amount of PuO2 in a room within a plutonium facility at Los Alamos National Laboratory. The facility has been in operation since 1978 to support the development, fabrication, and testing of Pu heat sources for the U.S. Department of Energy. Several workers were in the room at the time of the release and in vivo study of five of the workers began the day after the exposure event. Four of the subjects subsequently received chelation therapy. Over 30 fixed air filter samplers (FASs) and four continuous air monitors (CAMs) were operating in the room during the radiological release. One 47-mm-diameter glass fiber FAS filter and one 25-cm-diameter mixed cellulose ester CAM filter containing Pu aerosol from the incident were examined in the study described here. Total alpha radioactivity on the filters was determined by gross alpha counting. Isotopic identification of the Pu was made by alpha spectrometry. Film autoradiography was used to characterize the spatial distribution of alpha-emitting particles on the filters. Track-etch autoradiography was used to estimate the distribution of alpha radioactivity in individual plutonium particles on the filters for particle size measurement. The glass fiber filter was then cut into six sections. Particles from two sections were resuspended in alcohol, dispersed as an aerosol using a Lovelace nebulizer, and characterized by aerodynamic diameter using a Lovelace Multi-jet cascade impactor. The measured activity median aerodynamic diameter from the cascade impactor was 4.8 mum with a geometric standard deviation of 1.5. That agreed with the size distribution obtained from the alpha track detection technique. The remaining four filter sections were used in an in vitro dissolution study with synthetic serum ultrafiltrate. The retention of undissolved Pu was consistent with a biphasic exponential function. The majority of the Pu dissolved with a half-time of 900 d. The information on particle size distribution and solubility from this study was useful in assigning a radiation dose to the exposed workers, supporting the decision to administer chelation therapy, and providing a model for characterizing accident-associated aerosols in the future.

Aerosols↗

Efficacy of a technique for exposing the mouse lung to particles aspirated from the pharynx.

Recent studies have demonstrated that the mouse lung can be exposed to soluble antigens by aspiration of these antigens from the pharynx. This simple technique avoids the trauma associated with intratracheal instillation. In this study, the pharyngeal aspiration technique was validated for exposing the mouse lung to respirable particles. Using respirable fluorescent amine-modified polystyrene latex beads and beryllium oxide particles, we investigated the localization of aspirated particles within the lung and the relationship between the amount of material placed in the pharynx and the amount deposited in the lung. For exposure, mice were anesthetized with isoflurane in a bell jar, placed on a slant board, and the tongue was gently held in full extension while a 50-microl suspension of particles was pipetted onto the base of the tongue. Tongue restraint was maintained until at least two breaths were completed. Less than a minute after exposure, all mice awoke from anesthesia without visible sequela. There were no significant differences in particle distribution between the left and right side of the lung (p=.16). Particles were widely disseminated in a peribronchiolar pattern within the alveolar region. There was a linear and significant correlation (r2=.99) between the amount administered and the amount deposited in the lung. In beryllium-exposed mice, measurable lung beryllium was 77.5 to 88.2% of the administered beryllium. These findings demonstrate that following aspiration of pharyngeal deposited particles, exposures to the deep lung are repeatable, technically simple, and highly correlated to the administered dose.

Animals↗

Effects of aerosolized dust in goats on lung clearance of Pasteurella and Mannheimia species.

The objective was to determine whether the inhalation of large quantities of feedyard dust predisposed the animals to pulmonary bacterial proliferation. Two control groups, C1 and C2, did not receive dust treatments, and two principal groups (P1 and P2) received a total of 14 dust treatments each. The C1 and P1 groups of goats each received a transthoracic challenge of live Mannheimia haemolytica (4 x 10(6) colony forming units, CFU) The C2 and P2 groups of goats each received a transthoracic challenge of live Pasteurella multocida (1.0 x 10(6) CFU/goat). The results showed that dusted animals had fever when compared with non-dusted controls. In addition, dusted animals demonstrated a leukocytosis with neutrophilia after the first dust treatment that was not sustainable. Finally, dusted animals demonstrated pulmonary clearance of two potential bacterial pathogens that was not significantly different from that shown by control (not dusted) animals.

Administration, Inhalation↗

Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats.

In this study, we determined the carcinogenicity of depleted uranium (DU) metal fragments containing 0.75% titanium in muscle tissues of rats. The results have important implications for the medical management of Gulf War veterans who were wounded with DU fragments and who retain fragments in their soft tissues. We compared the tissue reactions in rats to the carcinogenicity of a tantalum metal (Ta), as a negative foreign-body control, and to a colloidal suspension of radioactive thorium dioxide ((232)Th), Thorotrast, as a positive radioactive control. DU was surgically implanted in the thigh muscles of male Wistar rats as four squares (2.5 x 2.5 x 1.5 mm or 5.0 x 5.0 x 1.5 mm) or four pellets (2.0 x 1.0 mm diameter) per rat. Ta was similarly implanted as four squares (5.0 x 5.0 x 1.1 mm) per rat. Thorotrast was injected at two sites in the thigh muscles of each rat. Control rats had only a surgical implantation procedure. Each treatment group included 50 rats. A connective tissue capsule formed around the metal implants, but not around the Thorotrast. Radiographs demonstrated corrosion of the DU implants shortly after implantation. At later times, rarifactions in the radiographic profiles correlated with proliferative tissue responses. After lifetime observation, the incidence of soft tissue sarcomas increased significantly around the 5.0 x 5.0 mm squares of DU and the positive control, Thorotrast. A slightly increased incidence occurred in rats implanted with the 2.5 x 2.5 mm DU squares and with 5.0 x 5.0 mm squares of Ta. No tumors were seen in rats with 2.0 x 1.0 mm diameter DU pellets or in the surgical controls. These results indicate that DU fragments of sufficient size cause localized proliferative reactions and soft tissue sarcomas that can be detected with radiography in the muscles of rats.

Animals↗

Effects of aerosolized feedyard dust that contains natural endotoxins on adult sheep.

OBJECTIVE: To determine the clinical, clinicopathologic, and histologic effects of aerosolized feedyard dust that contains natural endotoxins on adult sheep. ANIMALS: Eighteen 3-year-old Saint Croix sheep. PROCEDURE: A prospective randomized controlled study was conducted. There were 2 treatment groups (dust-endotoxin group, n = 9; control group, 9). Aerosolized feedyard dust was provided continuously during a 4-hour period for each application (once in week 1, 3 times in week 2, and 7 times in week 3) to sheep in a semiairtight tent. All sheep were euthanatized and necropsied 8 hours after the treatment group received the last dust treatment. Variables measured before and after each dust treatment were rectal temperature, total WBC count, and concentrations of fibrinogen and haptoglobin. RESULTS: Mean amount of dust administered during each treatment was 451 g/4 h. Filter collection indicated 51 mg of dust/m3 and 7,423 ng of endotoxin. Mean rectal temperature at 8 hours (40.4 C) and mean WBC counts 12 and 24 hours after dust treatment were significantly higher for the treated group than the means of the respective variables for the control group. Similar responses were observed with repeated dust-endotoxin treatments; however, with each subsequent treatment, there was a diminished response. Sheep in the treatment group had generalized alveolar septal thickening and hypercellularity. CONCLUSIONS AND CLINICAL RELEVANCE: Feedyard dust induced a temporary febrile response and leukocytosis in sheep in the treatment group. Exposure to dust that contains endotoxins may be a stressor preceding acute infectious respiratory tract disease of marketed sheep.

Aerosols↗

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.

Aerosols↗