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PubMed1999

Aerosol reduction during air polishing.

OBJECTIVES: Concern has been expressed about the obvious aerosol cloud that is generated during air polishing of teeth. These concerns have included infection control, potential systemic effects, and environmental surface contamination associated with the particles of sodium bicarbonate powder, water, and patient-generated material. This in vitro study evaluated an aerosol reduction device designed for use during air polishing. METHOD AND MATERIALS: Eight artificial teeth on a Dentoform model were polished with and without the aerosol reduction device. The polishing was performed within a plastic enclosure that had a grid on the sides. The water supply for the air polisher contained a 1% fluorescein solution. The aerosol contamination was determined by counting the number of squares that showed fluorescent spots under an ultraviolet light. RESULTS: The mean contamination without the aerosol reduction device was 175.59 cm2. The mean contamination with the aerosol reduction device was 4.37 cm2, a greater than 97% reduction in aerosol contamination. CONCLUSION: The aerosol reduction device significantly decreased the contamination produced during air polishing.

Aerosols↗
PubMed2002

Beta-agonist aerosol distribution in respiratory syncytial virus bronchiolitis in infants.

UNLABELLED: Bronchodilator aerosols are frequently administered to infants with bronchiolitis but with little success. The efficacy of aerosol treatments depends mainly on adequate targeting of the aerosol particles to the inflamed airways. This study evaluated the lower respiratory tract distribution characteristics of nebulized bronchodilators in infants with acute bronchiolitis. METHODS: Twelve infants (mean age +/- SD, 8 mo +/- 4 mo) who were admitted for acute respiratory syncytial virus bronchiolitis were treated with (99m)Tc-albuterol aerosol. Gamma-scintigraphy was used to assess total body and lung deposition as well as pulmonary distribution of the medication. RESULTS: Of the total 6-min nebulized dose (i.e., drug aerosol dose leaving the nebulizer [not the nebulizer charge]), 1.5% +/- 0.7% reached the right lung, with only approximately one third of that (0.6%) penetrating to the peripheral lung zone. There was 7.8% +/- 4.9% deposition in the upper respiratory and gastrointestinal tracts and 10%-12% remained on the face. No correlation was found between any of the deposition indices and the clinical response data or any of the demographic parameters (e.g., height, weight, body surface area, or clinical score). CONCLUSION: Poor total aerosol deposition in infants may be related as much to their small conducting airways as to the disease state. There is considerable room for improvement in aerosol delivery in this age group, with greater emphasis on targeting narrowed peripheral airways with superfine aerosols.

Acute Disease↗
PubMed2002

Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: randomized trials in Mexican schoolchildren.

OBJECTIVE: To compare antibody responses and side-effects of aerosolized and injected measles vaccines after revaccination of children enrolling in elementary schools. METHODS: Vaccines for measles (Edmonston-Zagreb) or measles-rubella (Edmonston-Zagreb with RA27/3) were given by aerosol or injection to four groups of children. An additional group received Schwarz measles vaccine by injection. These five groups received vaccines in usual standard titre doses. A sixth group received only 1000 plaque-forming units of Edmonston-Zagreb vaccine by aerosol. The groups were randomized by school. Concentrations of neutralizing antibodies were determined in blood specimens taken at baseline and four months after vaccination from randomized subgroups (n = 28-31) of children in each group. FINDINGS: After baseline antibody titres were controlled for, the frequencies of fourfold or greater increases in neutralizing antibodies did not differ significantly between the three groups that received vaccine by aerosol (range 52%-64%), but they were significantly higher than those for the three groups that received injected vaccine (range 4%-23%). Mean increases in titres and post-vaccination geometric mean titres paralleled these findings. Fewer side-effects were noted after aerosol than injection administration of vaccine. CONCLUSION: Immunogenicity of measles vaccine when administered by aerosol is superior to that when the vaccine is given by injection. This advantage persists with aerosolized doses less than or equal to one-fifth of usual injected doses. The efficacy and cost-effectiveness of measles vaccination by aerosol should be further evaluated in mass campaigns.

Aerosols↗
PubMed2004

Characterization of the generation of radiolabeled monodisperse albuterol particles using the spinning-top aerosol generator.

UNLABELLED: Inhaled radiolabeled aerosols provide invaluable information about in vivo drug deposition. Here, we report our methodology for radiolabeling and imaging monodisperse pharmacologic aerosols in order to study basic aerosol science concepts of drug delivery within the human airways. METHODS: We used a spinning-top aerosol generator to produce (99m)Tc-labeled monodisperse albuterol sulfate aerosols of 1.5-, 3-, and 6- micro m mass median aerodynamic diameter. RESULTS: In vitro Andersen cascade validation data showed that technetium and albuterol were coassociated on each impactor stage for all 3 aerosols, and the radiolabeling process itself did not affect their particle size distributions. Good-quality gamma-camera scintigraphic images of lung and extrathoracic deposition were obtained within an asthmatic patient. CONCLUSION: We have successfully radiolabeled and imaged monodisperse albuterol aerosols within the human lungs. This novel technique provides an important tool to relate fundamental concepts of aerosol particle behavior, in vivo deposition, and therapeutic clinical response.

Administration, Inhalation↗
PubMed1991

In vitro inhalation behaviour and therapeutical response of salbutamol particles administered from two metered dose aerosols.

In this study the particle size, as well as the in vitro deposition and the immediate bronchodilating effect on asthmatic patients, of two salbutamol inhalation aerosol preparations (Ventoline, Glaxo, UK, and salbutamol inhalation aerosol, Orion Pharmaceutica, Finland) were compared. The in vitro deposition study was performed using the modified Sierra Andersen cascade impactor. The bronchodilating effect of inhaled aerosol doses were monitored by measuring peak expiratory flow (PEF) values. In the clinical study, the pulse and blood pressure of the patients, as well as the side effects, were also recorded. Due to the anatomy and physiology of human lungs, the accepted optimum size for inhaled drug particles is under 5 microns, and preferably under 2 microns. Over 95% of the drug particles in both aerosol preparations were under 5 microns. 30% of the salbutamol particles in the Ventoline inhalation aerosol were under 2 microns, whereas in Orion salbutamol aerosol 14% of the drug particles were under 2 microns. Respectively 23% of Ventoline and 19% of the Orion salbutamol preparation penetrated into the therapeutically most significant imitated alveolar stages of the modified cascade impactor. Both salbutamol aerosols showed a clear clinical efficacy in the bronchodilating test. In addition, no significant differences existed in the bronchodilating effect of these inhalation aerosols. In conclusion, although there seemed to be a slight difference in the particle size distribution and in the in vitro inhalation behaviour, this variation did not have any effect on the clinical response.

Adult↗
PubMed1990

[Pulmonary clearance of 99mTc-HMPAO aerosol].

The clearance rate of inhaled aerosols of a lipophilic substance, 99mTc-HMPAO (Hexamethyl propylene amine oxime) was studied and compared to that of hydrophilic substances in 6 normal volunteers and 18 patients with lung diseases. The subject in sitting position inhaled a single deep breath of 99mTc-HMPAO aerosols, and held his breath about 30 sec. Then he continued to breath aerosols again for about 3 min. Radioactivity rapidly falls down during breath holding, to about 60% of the peak value (fast phase), with T 1/2 of 3.75 +/- 2.22 sec in 6 normal volunteers. This rapid phase was not appeared in hydrophilic aerosols with 99mTc-DTPA and 99mTc-pertechnetate and in lipophilic aerosol with 123I-IMP aerosol. The clearance of residual activity of 99mTc-HMPAO was slow with T 1/2 of 17.4 +/- 4.0 min. The T 1/2 of 99mTc-DTPA, 99mTc-pertechnetate and 123I-IMP were 50.2 +/- 20.9 min, 11.4 +/- 4.3, and 62.5 +/- 20.8 min respectively. 99mTc-HMPAO may cross transcellularly using the whole alveolar surface. The clearance of aerosols in the fast phase is rapid and depend on the regional perfusion. On the other hand, hydrophilic aerosol pass by an intercellular pathway and the clearance will be diffusion limited. As conclusion, inhalation study of 99mTc-HMPAO might be a new method to evaluate perfusion following ventilation study.

Administration, Inhalation↗
PubMed1982

Problems patients have using pressurized aerosol inhalers.

The use of pressurized aerosol inhalers was assessed in a total of 1173 out-patients attending hospital during a three month period. One hundred and thirty-five patients already being treated with drugs by inhalation were found to have a poor inhaler technique, even though most had received instruction on how to use a pressurized aerosol and were considered to be able to use one of these devices correctly. Eighty patients who had not used an inhaler before were found to be unable to use a pressurized aerosol efficiently after reading an instruction pamphlet or having the correct use of an aerosol demonstrated to them. Fifty-one percent of patients studied were observed to have difficulty in co-ordinating aerosol release with inspiration. In 24% the release of aerosol into the mouth caused a halt of inspiration and in a further 12% the aerosol was actuated into the mouth, but inspiration was achieved through the nose with no air being drawn in through the mouth. Twelve percent of patients already being treated with inhalers actuated the aerosol on two or more occasions during one inspiration.

Aerosols↗
PubMed1997

Detection of impaired intrapulmonary convective mixing by aerosol bolus dispersion in patients with emphysema.

The broadening of an inhaled aerosol bolus (aerosol bolus dispersion) during respiration provides a noninvasive, nonradioactive, and easy to perform technique which is a measure of the extent of convective gas mixing processes in the lung and symmetry of ventilation during the breathing cycle. In this study, this technique was evaluated for the ability to detect ventilation inhomogeneities in pulmonary emphysema (PE). An aerosol bolus undergoes changes in shape between its inspiration and expiration. In comparison with the inhaled bolus, the exhaled bolus is more spread because of convective mixing and may have a shift in the location of the mode caused by asymmetries of filling and emptying of lung units. We hypothesized that in PE these changes differ from healthy subjects and are related to lung health. Twenty nine patients with PE inhaled 25 ml boluses containing 0.9 micron monodisperse aerosol particles into volumetric lung depths of 200, 400, 600, and 800 cm3. The control group were 79 healthy subjects. As each bolus was expired, we measured bolus dispersion (volumetric width at one-half aerosol concentration peak height) and mode shift. In patients with PE exhaled boluses were significantly broader than those exhaled by normal subjects at all volumetric lung depths. At a lung depth of 800 cm3, patients showed a bolus dispersion that was 52% greater than that of healthy subjects (p < 0.0001) and they exhaled the bolus mode earlier (p < 0.0001). Aerosol bolus parameters were not influenced by anthropometric data. Pulmonary function parameters indicating obstruction showed a weak negative correlation with aerosol bolus parameters (R2 < 0.4). The bolus parameters appeared to be supplemental to conventional lung function tests and significantly indicated marked ventilation asymmetry and altered convective gas transport in pulmonary emphysema. The results support the use of the aerosol bolus dispersion test in assessing peripheral parenchymal lung injury.

Administration, Inhalation↗
PubMed1989

Temporal and spatial variations of the Vienna aerosol.

For several intensive sampling periods the mass concentration, light extinction, light scattering and light absorption coefficients, and the mass size distribution of the aerosol have been determined at up to eleven location in the non-industrial town of Vienna. Obviously, large variations of the measured values have been found. The following factors influenced the aerosol markedly: wind speed, wind direction, increased aerosol production such as by space heating or traffic and resuspension. Most of the variations in aerosol were found to be caused by these factors. A comparison of the mass concentration and light absorption of the aerosol upwind and downwind of Vienna permitted the estimation of locally produced aerosols: about 50% of the mass of the aerosol and 75% of the light-absorbing aerosol appears to be produced locally.

Air↗
PubMed2004

Characterization of aerosols from biomass burning--a case study from Mizoram (Northeast), India.

Physical and optical properties of biomass burning aerosols in Northeastern region, India analyzed based on measurements made during February 2002. Large spatial extent of Northeastern Region moist tropical to moist sub-tropical forests in India have high frequency of burning in annual dry seasons. Characterization of resultant trace gases and aerosols from biomass burning is important for the atmospheric radiative process. Aerosol optical depth (AOD) observed to be high during burning period compared to pre- and post-burning days. Peak period of biomass burning is highly correlated with measured AOD and total columnar water vapor. Size distribution of aerosols showed bimodal size distribution during burning day and unimodal size distribution during pre- and post-burning days. Size distribution retrievals from biomass burning aerosols show dominance of accumulation mode particles. Weighted mean radius is high (0.22 microm) during burning period. Columnar content of aerosols observed to be high during burning period in addition to the drastic reduction of visibility. During the burning day Anderson sampler measurements showed dominance of accumulation mode particles. The diurnal averaged values of surface shortwave aerosol radiative forcing af biomass burning aerosols varies from -59 to -87 Wm(-2) on different days. Measured and modeled solar irradiances are also discussed in the paper.

Air Pollutants↗
PubMed2006

The heterogeneous kinetics of HOBr and HOCl on acidified sea salt and model aerosol at 40-90% relative humidity and ambient temperature.

The HOBr and HOCl uptake coefficient gamma on H(2)SO(4)-acidified submicron salt aerosol of known size distribution was measured in an atmospheric pressure laminar flow reactor. The interaction time of the trace gas with the aerosol was in the range 15 to 90 s and led to gamma values in the range 10(-4) to 10(-2). The acidity of the aerosol is essential in order to enable heterogeneous reactions of HOBr on NaCl, recrystallized sea salt (RSS) and natural sea salt (NSS) aerosols. Specifically, HOCl only reacts on acidified NSS aerosol with a gamma ranging from 0.4 x 10(-3) to 1.8 x 10(-3) at a relative humidity (rh) at 40 and 85%, respectively. Uptake experiments of HOBr on aqueous H(2)SO(4) as well as on H(2)SO(4)-acidified NaCl, RSS or NSS aerosol were performed for rh ranging from 40 to 93%. The gamma value of HOBr on acidified NSS reaches a maximum gamma = 1.9 x 10(-2) at rh = 76 +/- 1% and significantly decreases with increasing rh in contrast to acidified NaCl and RSS aerosols whose gamma values remain high at gamma = (1.0 +/- 0.2) x 10(-2) at rh >/= 80%. An explanation based on the formation of an organic coating on NSS aerosol with increasing rh is proposed.

Journal Article↗
PubMed1983

Comparison of local anesthetics as bronchodilator aerosols.

Lidocaine aerosols have been ineffective at preventing airway constriction provoked by non-reflex stimuli. To determine if there were any advantages to using more potent amide-type local anesthetics or local anesthetics from other chemical classes, the authors compared the protection afforded by pretreatment with aerosols of lidocaine, bupivacaine, hexylcaine, and procaine against a subsequent prolonged challenge (5 min) with 10% citric acid aerosols in barbiturate-anesthetized Basenji-Greyhound dogs. The local anesthetics were administered as aerosols (4% solutions) for 10 min immediately preceding the citric acid challenge. In control experiments, that employed pretreatment with aerosols of isotonic saline rather than local anesthetics, the citric acid challenge aerosol increased pulmonary resistance by an average of 3.3 +/- 0.8 (+/- SE) cmH2O X 1(-1) X s during the first 15-min postchallenge, and reduced dynamic compliance by one-third during this time. None of the local anesthetics prevented citric-acid-induced changes in pulmonary mechanics. The average increases in pulmonary resistance (0-15 min postchallenge) elicited by citric acid aerosols in dogs pretreated with lidocaine, hexylcaine, bupivacaine, and procaine were 2.1 +/- 0.6, 2.1 +/- 0.6, 3.2 +/- 1.3, and 3.3 +/- 1.0 cmH2O X 1(-1) X s, respectively. The authors concluded that local anesthetic aerosols have little or no effect against other than reflex bronchoconstriction, and none of those tested were more effective than lidocaine.

Anesthetics, Local↗
PubMed2002

Regional lung functional impairment in acute airway obstruction and pulmonary embolic dog models assessed with gadolinium-based aerosol ventilation and perfusion magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-based aerosol ventilation and perfusion magnetic resonance (MR) images were used to define regional functional impairment in acute airway obstruction (AO) and pulmonary embolic (PE) dog models. METHODS: The aerosol study was performed in 10 anesthetized normal dogs in a supine position during 20-minute spontaneous inhalation of an aerosol of 100- or 200-mmol-Gd/L Gd-DTPA solute produced by an ultrasonic nebulizer in an open-circuit delivery system, combined with a dynamic perfusion study after a 3-second intravenous bolus injection of a 0.1 mmol/kg dose of Gd-DTPA. These MR studies were also performed in the same 10 dogs approximately 30 minutes after obstructing the segmental (n = 6) or lobar (n = 4) bronchus with a balloon catheter, and in another six dogs after segmental (n = 6) and lobar (n = 4) pulmonary arterial embolization with enbucrilate. Regional lung enhancement was assessed on time-signal intensity (SI)-curves and ventilation- and perfusion-weighted images produced by a subtraction technique. RESULTS: The normal lungs were gradually and gravity-dependently enhanced with time after Gd-DTPA aerosol inhalation regardless of the respiratory SI changes, except for three animals with the fastest breathing rate. The averaged maximal relative lung SI increase against the baseline in the successful animals was significantly greater in the slowly and deeply breathing animals than in the fast and shallow breathing animals, regardless of the difference in Gd-concentration (100 mmol Gd/L: 153.3% +/- 69.7% vs. 54.2% +/- 23%; P < 0.001; and 200 mmol Gd/L: 189.7% +/- 68.0% vs. 75.6% +/- 42.2%; P < 0.0001, respectively). There was an additional enhancement of 382% +/- 101 in the ventral lung and 722% +/- 160 in the dorsal lung on the pulmonary arterial phase perfusion image even in the slowly and deeply breathing animals who inhaled 200-mmol-Gd/L aerosol, and the enhancement effect was significantly greater compared with that with the aerosol (P < 0.0001). The ventilation- and perfusion-weighted images clearly defined the regionally matched perfusion-ventilation deficits in all the AO models, and the regionally mismatched perfusion-ventilation in all the PE models. CONCLUSION: Gd-based aerosol can provide efficient lung enhancement in spontaneously and adequately breathing animals, using a relatively noninvasive aerosol delivery system. The combined use of Gd-based perfusion MR imaging may be acceptable for defining regionally impaired function associated with acute AO and PE.

Acute Disease↗
PubMed1998

In situ measurements of organics, meteoritic material, mercury, and other elements in aerosols at 5 to 19 kilometers

In situ measurements of the chemical composition of individual aerosol particles at altitudes between 5 and 19 kilometers reveal that upper tropospheric aerosols often contained more organic material than sulfate. Although stratospheric aerosols primarily consisted of sulfuric acid and water, many also contained meteoritic material. Just above the tropopause, small amounts of mercury were found in over half of the aerosol particles that were analyzed. Overall, there was tremendous variety in aerosol composition. One measure of this diversity is that at least 45 elements were detected in aerosol particles. These results have wide implications for the complexity of aerosol sources and chemistry. They also offer possibilities for understanding the transport of atmospheric aerosols.

Journal Article↗
PubMed1987

Effect of particle size of bronchodilator aerosols on lung distribution and pulmonary function in patients with chronic asthma.

The particle size of bronchodilator aerosols may be important in determining the site of deposition in the lung and their therapeutic effect. The distribution of aerosols (labelled with technetium-99m diethylene triamine pentacetic acid) of two different particle sizes has been studied by gamma camera imaging. The particles had mass median aerodynamic diameters (geometric standard deviations) of 1.4 (1.4) and 5.5 (2.3) micron, and they were administered from a jet nebuliser to eight patients with chronic severe stable asthma. There was no significant difference in peripheral lung deposition with the two aerosols in any patient. The bronchodilator effect of the two aerosols was determined from cumulative dose-response studies. To avoid large doses that might mask possible differences in effect due to aerosol size, small, precisely determined incremental amounts of salbutamol (25-250 micrograms total lung dose) were used. The two doses were given via a nebuliser on separate occasions and the bronchodilator response was measured from FEV1, forced vital capacity, and peak expiratory flow 30 minutes after each dose. Bronchodilatation was similar with the two aerosols at each dose of salbutamol. There was therefore no difference in distribution within the lung or any difference in bronchodilator effect between an aerosol of small (1.4 micron) particle size and an aerosol of 5.5 microns in patients with severe but stable asthma.

Albuterol↗
PubMed2005

Suitability of caspofungin for aerosol delivery: physicochemical profiling and nebulizer choice.

BACKGROUND: Aerosolized antifungal therapy is a promising route of drug delivery for pulmonary aspergillosis due to attainment of high localized concentrations. Caspofungin, a new antifungal agent with proven efficacy against invasive aspergillosis, has ideal potential for aerosolization. STUDY OBJECTIVE: To examine in vitro the suitability of caspofungin for aerosol administration by characterizing factors that influence efficacy and airway tolerance of aerosol delivery: physicochemical properties, aerodynamics of drug particles, and efficiency of nebulizing systems. DESIGN: Physicochemical characteristics of caspofungin solutions (10 mg/mL and 30 mg/mL) were analyzed: osmolality, pH, viscosity, and surface tension. A time-of-flight aerosol spectrometer API Aerosizer was used to determine aerosol particle size and distribution. Drug output was quantified by high-performance liquid chromatography assay. Nebulizer efficiency was measured by drug output and respirable fraction (percentage of aerosolized particles with a 1 to 5 mum aerodynamic diameter) and compared among three jet nebulizer/compressor systems: device 1, Micromist (Hudson RCI; Temecula, CA)/Pulmo-Aide (model 5650D; DeVilbiss; Somerset, PA); device 2, Sidestream MS 2400/Envoy model IRC 1192 (Invacare; Elyria, OH); and device 3, Pari LC Star/Proneb Ultra (Pari Respiratory Equipment; Midlothian, VA). MEASUREMENTS AND RESULTS: Caspofungin requires 0.9% NaCl rather than sterile water as the diluent and addition of 0.3N NaOH buffer to adjust acidity of solutions (pH 6.17 to 6.26) in order to achieve optimal physicochemical properties for airway tolerability (osmolality, 150 to 550 milliosmol per kilogram; chloride ion, 31 to 300 mmol/L; and pH 7.4). The drug output rate increased with higher concentrations of drug solution: device 1, 4.0 mg/min vs 12.5 mg/min; device 2, 5.4 mg/min vs 14.7 mg/min; and device 3, 2.3 mg/min vs 12 mg/min, respectively. The percentage of particles within the respirable range varies depending on device and concentration of drug solutions (10 mg/mL vs 30 mg/mL): device 1, 85% vs 38%; device 2, 44% vs 57%; and device 3, 83% vs 93%, respectively. CONCLUSION: Caspofungin solution with adjustments appears to have physicochemical and aerodynamic characteristics suitable for aerosolization when used with either the Pari LC Star/Proneb Ultra or Micromist/Pulmo-Aide devices. Further in vivo testing is warranted.

Antifungal Agents↗
PubMed2006

Prolastin aerosol therapy and sputum taurine in cystic fibrosis.

BACKGROUND: Neutrophil elastase in the cystic fibrosis airways inhibits opsonophagocytosis and induces the expression of interleukin-8, a neutrophil chemoattractant. Prolastin is a therapeutic preparation of alpha-1 proteinase inhibitor (alpha1,-PI), a neutrophil elastase inhibitor. The objective of this study was to determine the effects of Prolastin aerosol therapy on airway inflammation in cystic fibrosis. METHODS: The primary endpoint of this study was sputum taurine, an amino-acid present in high concentrations in neutrophils. Sputum taurine correlates with respiratory exacerbations of cystic fibrosis. Seventeen patients with cystic fibrosis were each assigned to three sequential 10-day periods including first, aerosol therapy of 5 ml saline solution bid; second, aerosol therapy of 250 mg Prolastin bid; third, no aerosol therapy. On days 8, 9 and 10 of each period, early morning sputum was collected for the quantification of alpha1-PI, neutrophil elastase activity, IL-8 and taurine. RESULTS: During Prolastin therapy, a 3-fold increase in sputum alpha1-PI was observed (P = 0.002). Baseline values of sputum alpha1-PI correlated with the values obtained after Prolastin aerosol (R = 0.77, P < 0.01). Sputum neutrophil elastase activity remained unchanged but taurine decreased after Prolastin therapy (during therapy P = 0.052, after therapy P = 0.026). Prolastin aerosol therapy had no adverse effect on pulmonary function. CONCLUSIONS: Aerosol therapy with Prolastin in patients with cystic fibrosis leads to a progressive decrease in sputum taurine. This suggests that even in the absence of sustained elastase inhibition, Prolastin aerosol therapy may have a beneficial effect on airway inflammation in patients with cystic fibrosis.

Administration, Inhalation↗
PubMed1975

New apparatus and method for the toxicological investigation of metered aerosols in rats.

A new apparatus and method for the toxicological investigation of metered aerosols in rats, which is also suitable for tests in other small laboratory animals, is described. It permits: 1. simultaneous treatment of 5 or more animals, 2. administration of metered aerosol doses to individual animals, 3. ventilation of the cages, 4. mechanical tilting of the metered aerosol packs to ensure thorough mixing of the content, and 5. continuous automatic tilting, administration and ventilatied under different ventilation conditions. Blood gases and fluorinated chlorohydrocarbons (abbreviation: fluorocarbons) in the arterial blood were also determined. In tests with spontaneous ventilation of the animal chambers without positive pressure, significant acidosis and hypoxia occurred after 40 puffs of metered aerosol. Where ventilation of the chambers was insufficient, the fluorocarbons led to dose-dependent toxic and lethal effects. The substance and the additives contained in the metered aerosol did not interfere with these effects. After active ventilation with 0.5 atm no symptoms of acidosis or hypoxia were observed. Up to 160 puffs of metered aerosol, no indications of toxic effects were established in the rats. Half-life of the fluorocarbons in the arterial blood after one puff of metered aerosol was 69 to 80 sec for fluorocarbon 11 and 57 to 67 sec for fluorocarbon 12.

Acidosis, Respiratory↗