Biokinetics and dosimetry of inhaled Cm aerosols in beagles: effect of aerosol chemical form.

This study was designed to provide tissue distribution data of 244Cm that was inhaled by beagle dogs. Two chemical forms that were presumed to bracket the solubility of pure Cm compounds in vivo were used: 244Cm2O3 (oxide) and 244Cm(NO3)3 (nitrate). Adult dogs of both sexes received a single brief pernasal exposure to either a monodisperse aerosol of 244Cm2O3 (1.4 micron activity median aerodynamic diameter, AMAD, and 1.16 geometric standard deviation, sigma g) or a polydisperse aerosol of 244Cm(NO3)3 (1.1 micron AMAD, 1.74 sigma g). The resulting initial pulmonary burdens (IPB) were 1.5 and 1.7 kBq kg-1 body mass for the oxide and nitrate groups, respectively. The tissue distribution data obtained from the dogs that were serially sacrificed from 4 h to 2 y after exposure showed that both chemical forms were very soluble in vivo. For the oxide group, 78% IPB was cleared from the lung with a T 1/2 of 7.6 d, whereas for the nitrate group, 42% IPB cleared with a T 1/2 of 0.6 d. The lung retention for each group was described by three-component exponential functions. Most of the Cm that cleared the lung was redeposited in the liver (37% IPB) and skeleton (27% IPB), with lesser amounts in the muscle, fat and connective tissue (3.5% IPB) and kidney (approximately 2% IPB). The only significant difference noted in the biokinetics of Cm for the two exposure groups was a more rapid translocation of Cm from the lung to liver and bone during the first 10-20 d after exposure to the nitrate compared to the oxide chemical form. Extrapolation of these data to obtain estimates of committed dose equivalents for man indicate substantial agreement with the limits for occupational exposure specified by ICRP 30 (1979).

Deposition and retention of inhaled aggregate 67Ga2O3 particles in beagle dogs, Fischer-344 rats, and CD-1 mice.

Deposition and retention of inhaled 67Ga2O3 aerosols were measured in ten beagle dogs to provide reasonable estimates for human deposition and in Fischer-344 rats and CD-1 mice to estimate lung burdens in small animals frequently used in toxicological evaluations. Aggregated particles of 67Ga2O3, 0.1 micron mass median diameter (MMD), were produced using heat treatment of 67Ga tetramethylheptanedione. Whole-body counting and gamma camera imaging were used to measure deposition. Pulmonary deposition in dogs was measured as 25% of the inhaled particles for the 0.1 micron particles. Tracheobronchial and nasopharyngeal deposition were much lower, 7% and 7% respectively. Pulmonary deposition of 0.1 micron (MMD) particles was calculated as 10% and 11% of inhaled particles in Fischer-344 rats and 15 and 20% in mice for two separate nose-only exposures of each species.

Biokinetics of inhaled 244Cm oxide in the rat: effect of heat treatment at 1150 degrees C.

A study was conducted in rats to determine solubility and subsequent metabolism of an inhaled aerosol of curium treated at high temperatures. Young adult Fischer-344 rats received a single inhalation exposure to one of three monodisperse aerosols of 244Cm2O3 (0.70, 1.3, or 2.6 micron activity median aerodynamic diameter) heat-treated at 1150 degrees C. Animals were maintained individually in metabolism cages for excreta collection and serially sacrificed in groups of two male and two female rats from 2 to 33 days after inhalation exposure. Additionally an injection study with curium citrate was done to define the systemic behavior of Cm in this rat model. The in vivo solubility was inversely related to the aerosol particle size. The relationship of the results of this study to results from other experimental inhalation studies with curium oxide aerosols is discussed, as is the relevance to bioassay interpretation and risk assessment in man.

Lung retention and metabolic fate of inhaled benzo(a)pyrene associated with diesel exhaust particles.

Polycyclic aromatic hydrocarbons (PAHs) are a class of compounds considered to have human carcinogenic potential and have been found associated with many respirable, environmental particle pollutants. The effect of these ultrafine, insoluble, carrier particles on the lung retention and metabolic fate of inhaled PAHs was investigated with a radiolabeled model PAH, [3H]benzo(a)pyrene (3H-BaP). Fischer-344 rats were exposed (30 min) by nose-only inhalation to 3H-BaP adsorbed (approximately 0.1% by mass) onto diesel engine exhaust particles. These aerosols were generated in a dynamic aerosol generation system by vapor condensation methods. The total mass concentration of these aerosols was 4-6 micrograms/liter of air with a mass median diameter of 0.14 micron. Lung clearance of the inhaled particle-associated 3H radioactivity occurred in two phases. The initially rapid clearance of this inhaled radiolabel had a half-time of less than 1 hr. The second, long-term component of lung clearance had a half-time of 18 +/- 2 days and represented 50 +/- 2% of the 3H radioactivity that had initially deposited in lungs. In contrast, previous inhalation studies with a pure 3H-BaP aerosol showed that greater than 99% of the 3H radioactivity deposited in lungs was cleared within 2 hr after exposure (Sun et al., Toxicol. Appl. Pharmacol. 65, 231-244, 1982). By HPLC analysis, the majority of diesel soot-associated 3H radioactivity retained in lungs was BaP (65-76%) with smaller amounts of BaP-phenol (13-17%) and BaP-quinone (5-18%) metabolites also being detected. No other metabolites of BaP were detected in lungs of exposed rats. Tissue distribution and excretion patterns of 3H radioactivity were qualitatively similar to previous inhalation studies with 3H-BaP coated Ga2O3 aerosols (Sun et al., 1982). These findings suggest that inhaled PAHs may be retained in lungs for a greater period of time when these compounds are associated with diesel engine exhaust particles. In addition, these compounds retained in lungs can be metabolized in lungs. These results may have significant implications for the health risks that may be involved with human exposure to particle-associated organic pollutants.

Characterization of an aerosol sample from the auxiliary building of the Three Mile Island reactor.

Analyses for radioisotopic composition and dissolution characteristics were performed on an aerosol filter sample collected for a week by an air sampler located in the auxiliary building of the Three Mile Island nuclear reactor. The major radioisotopes found on the filter were 89Sr, 90Sr, 134Cs and 137Cs. Greater than 90% of both 89-90Sr and 134-137Cs dissolved within 48 hr in an in vitro test system. Scanning electron microscopic analyses showed the presence of respirable size particles as well as larger particles ranging up to 10 micron in diameter. The major matrix components were Fe, Ca, S, Mg, Al and Si. Although the radionuclides were present in a heterogeneous matrix, they were in a soluble form. This information enables a better evaluation of bioassay data and predictions of dose distribution resulting from an inhalation exposure to this aerosol. Further, the combination of techniques used in this study may be applicable to the characterization of other aerosols of unknown composition.

Retention and dosimetry of 106Ru inhaled along with inert particles by Fischer-344 rats.

This study was done to provide data useful for predicting the deposition, retention and radiation dose patterns for humans who might be exposed to an aerosol containing 106RuO4 and respirable particles. Ruthenium-106 tetroxide was introduced into air containing inert particles. The inert particles were monodisperse. 0.69 micrometer diameter fused aluminosilicate and very small residue particles from nebulized droplets. A complex exposure atmosphere resulted. In addition to condensation of 106RuO4 on pre-existing particles, self-nucleation occurred, presumably resulting from the formation of RuO2. It appears there was a significant amount of 106RuO4 present in the inhalation exposure system. When a group of Fischer-344 rats inhaled this exposure atmosphere, approx. 12% of the initial body burden reached the pulmonary region of the respiratory tract. Of the remaining 88% of the initial burden, 60% was deposited in the upper respiratory tract, 10% in the tracheobronchial region and 18% was external contamination, primarily on the nares and head skin. Most of the initial body burden was cleared via the gastrointestinal system and excreted via feces. Clearance of 106Ru from the pulmonary region had an effective half-time of approx. 30 days and was predominantly by dissolution. Relative radiation doses accumulated to 100 days after inhalation exposure, normalized to a lung dose of 1.0, were nasopharyngeal mucosa, 11; trachea and larynx, 5; lower large intestine, 5; upper large intestine, 2; liver, 0.9; and kidneys, 0.9. Other tissues and organs received lesser relative doses. Comparable results are predicted for man inhaling a similar exposure atmosphere, which could be encountered under certain circumstances in nuclear industry operations.

Generation and characterization of condensation aerosols of benzo[alpha]pyrene.

Condensation aerosols of benzo[a]pyrene (BAP) with particle sizes ranging from 0.1 to 2 micrometers (aerodynamic diameter) were produced and studied. These aerosols were generated in a glove box by direct vaporization of BaP and homogeneous condensation of the vapor. The aerosol concentration ranged from 50 to 700 micrograms/l with aerosol production rates up to 15 mg BaP per minute. The effects of vaporization temperature and flow rate of diluting air on the particle size distribution and aerosol output were studied. The BaP aerosol was produced with relatively constant mass concentration and particle size distribution for more than 5 h. The aerosol was physicochemically and thermally stable. Data on the in vitro dissolution of BaP particles in aqueous solvents and in different dissolution systems suggested that the organic BaP particle does not dissolve in simple aqueous solvents. Proteins, surfactants, or ethyl alcohol enhanced the rate of dissolution of BaP. The rate of dissolution of BaP particles was inversely proportional to particle size.

Generation and characterization of condensation aerosols of vanadium pentoxide and pyrene.

Generation and characterization of submicron aerosols of V2O5 and pyrene, two materials with very different physicochemical properties, were studied. Vaporization-condensation methods were used to generate the aerosols. The effects of various experimental conditions on particle size and aerosol mass concentration were investigated. Also, chemical stability of the aerosols and the source materials with respect to temperature was determined. Experimental results show that there are significant differences in the nature of pyrene and V2O5 aerosols. These methods and experimental conditions can be easily adapted for generation of heterogeneous condensation aerosols of pyrene and V2O5.