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Biomedical subjects

B J Greenspan

Publications and source records attributed to B J Greenspan.

9 recordsLinked to original sources

Characterization of a microprocessor-controlled tubular multiple metered dose inhaler aerosol generator for inhalation exposures of pharmaceuticals.

A microprocessor-controlled tubular multiple metered dose inhaler (MDI) aerosol generator was constructed for the delivery of pharmaceutical aerosols to inhalation chambers. The MDIs were mounted in four cassettes containing one to four MDIs on a stepped end plate. The MDIs in each cassette were pneumatically activated at intervals that were controlled by the microprocessor. The cassettes permitted easy replacement of each set of MDIs with a fresh set of MDIs whenever necessary. Aerosol concentration was controlled by varying the number of active MDIs in each cassette and the frequency of activations per minute of each row. Aerosol from the MDIs flowed along the long axis of the tube, which provided a path length sufficient to diminish impaction losses. Using a light-scattering device to monitor the aerosol concentration, the pulsatile output from the MDIs in the cassettes was demonstrated to be adequately damped out provided that the dilution/mixing/aging chamber exceeded 3 ft in length. The tube diameter selected was the minimum compatible with mounting the required number of MDIs so that the linear velocity of the aerosol was adequate to efficiently transport the aerosol out of the dilution chamber. Aerosol concentration and particle size data were recorded for a nose-only rodent exposure chamber. Reproducible aerosol concentrations ranging from 0.03 to 0.6 mg/L were generated. Particle sizes ranged from 2- to 3-microm mass median aerodynamic diameter. Thus, the aerosol generated was within the size range suitable for inhalation exposures.

Aerosols↗

Effects of aerosol exposures to cadmium chloride on the clearance of titanium dioxide from the lungs of rats.

This study deals with the hypothesis that the lymphatic uptake of particles from the lung parenchyma increases when phagocytosis by pulmonary macrophages is inhibited. Cadmium chloride was chosen as the toxicant to inhibit phagocytosis and was administered as an aerosol to rats at concentrations of 1.5 mg Cd/m3 (mass median aerodynamic diameter = 0.4 micron, sigma g = 1.4) and 5.0 mg Cd/m3 (MMAD = 0.4 micron, sigma g = 1.6), each for 30 min. Control animals were exposed to a saline aerosol. Lung clearance and lymphatic uptake were assayed after exposing the cadmium-exposed rats to titanium dioxide (TiO2) dust at concentrations of 12-15 mg/m3 (MMAD = 1.0 micron, sigma g = 2.3) for 6 h. Preexposure to 5 mg Cd/m3 decreased the initial deposition of TiO2 by 40% compared to a saline preexposure. Although the overall clearance of TiO2 from the lungs was not different in the cadmium-exposed animals, the lymph node burden was 2.7 times higher in the CdCl2-exposed animals than in the controls. Exposures to 1.5 mg Cd/m3 had no effect on lung clearance or lymphatic uptake of TiO2. When TiO2 exposure preceded a 5.0 mg Cd/m3 exposure, the results were similar; i.e., more TiO2 was found in the lymph nodes of the animals. This study supports the concept that lymphatic uptake of dust particles increases when phagocytosis by alveolar macrophages is decreased.

Aerosols↗

Acute inhalation toxicopathology of lithium combustion aerosols in rats.

Male and female F344/Lov rats were exposed to aerosols produced by burning lithium metal under conditions designed to stimulate a fire in the containment building of a fusion reactor. Lithium combustion aerosols were generated by sweeping lithium vapor into air atmospheres with controlled CO2 and H2O concentrations. Chemical analyses of the aerosols produced indicated a dependence of the chemical form of carbon dioxide concentrations and relative humidity. Under conditions of low CO2 concentration and low relative humidity (less than 25%), the aerosol was predominantly lithium monoxide with some lithium hydroxide and about 12% lithium carbonate. Under conditions of high relative humidity (greater than 75%), the aerosol was primarily lithium hydroxide with about 23% lithium carbonate. Although these two aerosols might be expected to have different acute toxicities based on their differing alkalinities, the 14-day LC50 values (with 95% confidence limits) determined after 4-hr exposures were 940 (730-1200) mg/m3 for the lithium oxide and hydroxide mixture and 960 (830-1200) mg/m3 for the lithium hydroxide aerosols. Histopathologic lesions were observed in the nasal turbinates, larynx, and occasionally in the lungs with both aerosols. The most prominent lesions were necrotizing laryngitis and ulcerative rhinitis. Pulmonary lesions represented a secondary extension of the upper respiratory tract lesions rather than a primary manifestation of lithium toxicity. The similarities in the LC50 values and also in the histopathologic lesions observed suggest that any Li2O in the aerosol reacted rapidly with water vapor in the respiratory tract to form LiOH prior to deposition.

Aerosols↗

Inhalation toxicity of lithium combustion aerosols in rats.

Studies of the acute inhalation toxicity of lithium combustion aerosols were undertaken to aid in evaluating the health hazards associated with the proposed use of lithium metal in fusion reactors. A system was developed to generate lithium combustion aerosols by sweeping vapor from molten lithium metal into a controlled air atmosphere. Male and female F344/Lov rats, 9-12 wk of age, were exposed once for 4 h to concentrations of 2600, 2300, 1400, or 620 mg/m3 of aerosol (MMAD = 0.69 micrometer, sigma g = 1.45) that was approximately 80% lithium carbonate and 20% lithium hydroxide to determine the acute toxic effects. Fourteen-day LC50 values (with 95% confidence limits) of 1700 (1300-2000) mg/m3 for the male rats and 2000 (1700-2400) mg/m3 for the female rate were calculated. Clinical signs of anorexia, dehydration, respiratory difficulty, and perioral and perinasal encrustation were observed. Body weights were decreased the first day after exposure in relation to the exposure concentration. In animals observed for an additional 2 wk, body weights, organ weights, and clinical signs began to return to preexposure values. Histopathologic examination of the respiratory tracts from the animals revealed ulcerative or necrotic laryngitis, focal to segmental ulcerative rhinitis often accompanied by areas of squamous metaplasia, and, in some cases, a suppurative bronchopneumonia or aspiration pneumonia, probably secondary to the laryngeal lesions. The results of these studies indicate the moderate acute toxicity of lithium carbonate aerosols and will aid in the risk analysis of accidental releases of lithium combustion aerosols.

Aerosols↗

Generation of Li combustion aerosols for animal inhalation studies.

A system was developed for generating Li aerosols to determine the potential health hazards of postulated accidents associated with the use of Li as a fusion reactor blanket or coolant. The aerosol was generated by sweeping Ar through a stainless steel chamber filled with Li metal that was heated inductively to temperatures up to 1300 degrees C. Argon carried the Li vapor into a burning chamber where it was mixed with air. The reaction of Li vapor with air formed an intense white flame that produced typical branched-chain condensation aerosol particles. This system generated well-controlled concentrations up to 2500 mg/m3 for periods of 4 h. The mass median aeordynamic diameter of the aerosol was approximately 0.66 micron with a geometric standard deviation of 1.5. Aerosols could be generated that were greater than 96% Li2O and LiOH, LiOH.H2O, or Li2CO3 by controlling the CO2 and H2O concentrations in the supply air. The system is currently being used to investigate the acute toxicity of Li combustion aerosols in laboratory animals.

Accidents↗

The effects of in vitro and aerosol exposures to cadmium on phagocytosis by rat pulmonary macrophages.

Aerosol exposures of rats were performed to assess the in vivo effects of cadmium on the phagocytosis of latex particles by pulmonary macrophages. An in vitro assay for particle uptake was devised which allowed quantification of phagocytosis by adhering and nonadhering macrophages. In vitro exposure to CdCl2 caused dose-dependent decreases in viability (trypan blue exclusion), percentage cells with particles, total number of particles phagocytized, and the ability of the macrophages to adhere to a siliconized glass surface. In vivo effects were studied following 30-min aerosol exposures to 1.5 mg/m3 Cd (MMAD = 0.35 micron, sigma g = 1.45) or 5.0 mg/m3 Cd (MMAD = 0.45 micron, sigma g = 1.60) as CdCl2. Phagocytic activity in the in vitro test system was increased immediately and at Day 1 in the low exposure group. However, following exposure to 5.0 mg/m3 Cd, phagocytic activity was depressed until 8 days postexposure. The results show that cadmium is capable of modifying the phagocytic ability of macrophages in vivo as well as in vitro. Determinations of the total number of particles phagocytized were found to be more sensitive than percentage cells phagocytizing in detecting the effects of cadmium exposure.

Aerosols↗

Response of primate joint afferent neurons to mechanical stimulation of knee joint.

1. One hundred thirty-eight knee joint afferents from posterior articular nerve (PAN), in primates, were recorded in dorsal root filaments. Responses of afferents were studied in relation to both passive manipulations of the knee and active contractions of quadriceps, semimembranosus, and gastrocnemius muscles. 2. When the knee was passively rotated, most neurons discharged only when extreme angular displacements were achieved. Response of neurons responding to passive extensions was linearly related to the torque applied to the knee. With maintained extensions, discharge in extension neurons adapted slowly. Some of the time constants of adaptation were similar to those for simultaneously recorded torque relaxation. 3. Contractions of quadriceps, semimembranosus, or gastrocnemius muscles could activate many neurons in the absence of changes in joint angle. For quadriceps-activated neurons, rather high torques (mean = 2,450 g with cm) were required. 4. The results support the hypothesis that joint afferents function as capsullar stretch receptors, responding to those mechanical events which result in loading of the capsule.

Adaptation, Physiological↗