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Biomedical subjects

R O McClellan

Publications and source records attributed to R O McClellan.

At least 73 records · Page 4Linked to original sources

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.

Aerosols↗

A comparison of genotoxicity of automotive exhaust particles from laboratory and environmental sources.

This research (1) ranked the genotoxicity of methylene chloride extracts of laboratory and environmentally collected particles and (2) evaluated the role of collection location and sample composition on genotoxic potency. Samples of exhaust from a spark-ignition automobile, light-duty diesel automobile, and a heavy-duty diesel engine operated in a laboratory on a dynamometer were studied, as well as samples taken in a highway tunnel and outside the same tunnel. The tunnel samples were collected 30 m inside or 56 m outside the exit portal at times when between 70%-95% of the traffic consisted of diesel trucks. In the Ames Salmonella mutagenicity assay, each extract produced a dose-dependent increase in mutagenicity in strain TA-98 without addition of liver S-9 fraction. Extracts from two tunnel samples collected 1 yr apart, and extracts of particles collected outside the tunnel had similar mutagenic activity. The order of mutagenic activity per microgram of extract in TA-98 without S-9 from the lowest to the highest was environmental sample less than or equal to tunnel less than heavy-duty diesel less than light-duty diesel less than spark ignition. Addition of S-9 or testing in Salmonella strains resistant to the mutagenicity of nitroaromatic compounds (TA-98 NR and TA-98 1,8-DNP6) decreased the mutagenic response. With cell killing, sister chromatid exchanges, and mutations as endpoints in Chinese hamster ovary cells (CHO), the order of potency was tunnel less than light-duty less than spark-ignition samples. All three extracts induced a similar amount of mitotic delay per microgram with or without S-9. Enhanced chromosome aberration frequency was detected only in cells exposed to extracts from spark-ignition exhaust. The data indicated that genotoxic activity was detected in each particle extract, that the potency ranking was similar using different genetic endpoints, and that the magnitude of the genotoxic potency was similar.

Air Pollutants↗

Distribution, retention, and fate of 2-aminoanthracene in rats after inhalation.

The distribution, retention, and fate of 2[3H]aminoanthracene (2-AA) were determined in male Fischer-344 rats after inhalation exposure (70 micrograms/liter; activity mass median diameter = 2.1 micron) for 30 min. Radioactivity was found in the turbinates, trachea, lungs, liver, kidneys, and gastrointestinal tract 20 min after exposure. Lower quantities of radioactivity were found in fat, brain, testes, and muscle. Inhaled 2-AA was excreted predominantly in feces (80%). The remaining 2-AA was excreted in urine. Organic soluble radioactivity was released from urinary conjugates after treatment of urine with acid and with beta-glucuronidase. This result suggests that glucuronides of both ring- and N-hydroxy-2-AA were excreted. The remaining radioactivity was water soluble and accounted for approximately one-half of the total urinary radioactivity. The organic soluble radioactivity found after hydrolysis indicated that inhaled 2-AA is extensively metabolized by rats after inhalation and excreted as conjugated metabolites. Eighty-three percent of orally administered material was absorbed into the body from the GI tract; thus, material cleared by mucociliary action after inhalation would contribute to total body burden. 2-AA, a nitrogen substituted polycyclic aromatic hydrocarbon (PAH), was very similar to other PAHs in its rapid distribution throughout the body and in its route of excretion after inhalation.

Administration, Oral↗

Chemical and biological properties of diesel exhaust particles collected during selected segments of a simulated driving cycle.

Particle emissions, percentage of organic extractable materials, and mutagenicities of extracts from a diesel engine operating on a test stand have been determined for the full Federal Test Procedure driving cycle and several individual segments thereof. Particle samples were collected using a computer controlled high volume sampler. Extracts of the exhaust particles were screened for the potent mutagens nitropyrene/nitrofluoranthenes by mass spectrometry/mass spectrometry (MS/MS). Results indicate that a long acceleration from 0-55 mph produced approximately seven times more particles per second than the full cycle. Also, the 0- to 55-mph acceleration and a subsequent 55-mph cruise produced significantly higher amounts of mutagens than other segments or the full FTP cycle. A direct correlation of both NOx levels and temperature with mutagenicity was noted (r = 0.89 and r = 0.89). The specific activities of the extracts showed decreases or remained unchanged when assayed in TA-98 NR or TA-98 1,8 DNP6, nitroreductase deficient strains of TA-98. Three extracts were found to have high levels of nitropyrenes/nitrofluoranthenes, and two of the three had high specific activities in TA-98.

Mutagenicity Tests↗

Respiratory tract clearance of 14C-labeled diesel exhaust compounds associated with diesel particles or as a particle-free extract.

Radiolabeled diesel exhaust particles or dichloromethane extracts of these particles were intratracheally instilled (10 mg) into Fischer-344 rats and the clearance of 14C radioactivity was measured. Approximately 88% of the 14C radioactivity associated with the particles was soluble in dichloromethane. The clearance of 14C radioactivity from lungs occurred in two phases. The initial, more rapid phase of lung clearance of both particle-associated 14C radioactivity (Particle 14C) and extract-associated 14C radioactivity (Extract 14C) was very similar (t 1/2 approximately equal to 3 hr). However, the second phase of lung clearance of the remaining Particle 14C was much slower (t 1/2 approximately equal to 25 days) than the second phase of lung clearance of the Extract 14C (t 1/2 approximately equal to 2.9 days). Tracheal clearance rates of 14C radioactivity from both instillation studies were both rapid and similar (t 1/2 approximately equal to 10-12 hr). These results indicate that diesel engine exhaust particles reduce the lung clearance rate of the organic compounds associated with these particles. These studies also point to the possibility that the rate limiting step in the lung clearance of organic compounds associated with inhaled diesel exhaust particles may be the rate at which they dissociate from these particles in vivo. This is because the long-term clearance rate of the particle-associated organic compounds was shown here to be much slower than that of the same organic compounds in a particle-free form but not as slow as the lung clearance rate reported for diesel exhaust core particles (T.L. Chan, P.S. Lee, W.E. Hering, J. Appl. Toxicol. 1, 77-82 (1981].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biokinetics of inhaled 239PuO2 in the beagle dog: effect of aerosol particle size.

This study was designed to measure the effect of aerosol particle size on the deposition, retention, excretion and translocation of 239Pu inhaled as the dioxide by Beagle dogs. To address these questions, young adult male and female Beagle dogs received single brief inhalation exposures to one of three monodisperse aerosols of 239PuO2 having sizes of 0.72, 1.4 or 2.8 microns activity median aerodynamic diameter (AMAD). Periodic collections of urine and faeces were made for each dog until sacrifice at times ranging from 4 hours to 2 years after exposure. The results indicate long term retention of a substantial percentage of the initial pulmonary burden (IPB), and that the retention was affected by particle size. The percentage of the initial pulmonary lung burden retained in the long term component and its effective half time (TE) were 90 per cent with TE = 680 days for the 0.72 micron AMAD aerosol, 68 per cent with TE = 1400 days for the 1.4 microns AMAD aerosol and 82 per cent with TE = 1800 days for the 2.8 microns AMAD aerosol. The major route of elimination of 239Pu from lung was via the faeces, but significant amounts were also translocated to thoracic lymph nodes (approximately 15 per cent IPB by 2 years). Small amounts were translocated to liver (0.2 per cent IPB) and skeleton (0.1 per cent IPB) by 2 years after exposure. The average alpha-radiation dose to the lung was projected to be twice as large for the 2.8 microns AMAD group as for the 0.72 micron AMAD group at 10 years after exposure.

Aerosols↗

Dog pulmonary macrophage metabolism of free and particle-associated [14C]benzo[a]pyrene.

Pulmonary macrophages (PM) are involved in the clearance of inhaled particulate matter from the lung. PM also are capable of metabolizing xenobiotics such as benzo[a]pyrene (BaP). The objective of this investigation was to measure the ability of PM isolated from dogs to metabolize BaP coated onto diesel exhaust particles and to compare this metabolism with that of BaP in solution. PM were isolated from male beagle dogs and incubated with 1 microM [14C]BaP (solution or diesel particle coated) for select times up to 48 h. After incubation of PM with [14C]BaP, both the cells and the media were individually analyzed for [14C]BaP metabolites by high-performance liquid chromatography. Total quantities of [14C]BaP metabolites in both the media (125 pmol/10(6) cells) and cells (45 pmol/10(6) cells) increased with incubation time for up to 48 h. BaP-9,10-diol and BaP-7,8-diol were the major metabolites in organic extracts from the culture media, whereas BaP-7,8-diol and BaP-4,5-diol were the major metabolites in extracts of cells. Small quantities of BaP phenols and BaP quinones were detected in both the cells and media. Total quantities of BaP metabolites (20-30 pmol/10(6) cells) were not significantly different when PM were incubated for 24 h with either [14C]BaP in solution or [14C]BaP coated on diesel particles. The data suggest that particles retained in lungs are capable of being acted upon by PM metabolizing enzymes and that the ensuing metabolism may play an important role in the metabolic fate of organic material inhaled on particulate matter.

Animals↗

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.

Aerosols↗

Generation and characterization of radiolabeled diesel exhaust.

To evaluate the potential health risks associated with increased use of diesel engines, information is needed on the biological fate of inhaled diesel exhaust components. Appropriately radiolabeled exhaust produced by burning radiolabeled fuel could be used to gain this information. The purpose of this study was to characterize different radiolabeled diesel exhausts with respect to their potential use in studies of the biological fate of exhaust carbon particles and particle-associated organic compounds (particle extracts). A single-cylinder diesel engine was used to burn diesel fuel containing trace amounts of 14C-labeled hexadecane, dotriacontane, benzene, phenanthrene or benzo(a)pyrene. Greater than 98% of the 14C in all additives was converted to volatile materials upon combustion. The remainder was distributed in varying amounts between the carbon particles and particle extracts. Aromatic additives labeled carbon particles more efficiently than aliphatic additives. Column chromatography of the particle extracts showed that, in most cases, the majority of the radioactivity eluted in fractions identical to the specific fuel additive employed, suggesting that a large amount of the particle-associated organic compounds consisted of uncombusted fuel constituents. Applying an electrical load to the engine-electrical generator increased carbon particle radioactivity, but had variable effects on the amount of radioactivity in the particle extracts. 67Ga-tetramethylheptanedione was also studied as a fuel additive to label carbon particles. 67Ga was incorporated into the exhaust particles and lung deposition of particles in rats was found to be approximately 10%. However, the 67Ga-radiolabel was found to separate from the particles in vivo, making it an unsuitable radiolabel for studying the long-term lung retention of diesel exhaust carbonaceous particles.

Animals↗

Inhalation of 1-nitropyrene associated with ultrafine insoluble particles or as a pure aerosol: a comparison of deposition and biological fate.

A large number of the environmental particulate pollutants in the atmosphere, including diesel engine exhaust, have a complex mixture of organic compounds associated with them. Organic solvent extracts of many of these particulate pollutants have been shown to contain mutagenic activity which does not require metabolic activation in the Ames bioassay. Much of this direct-acting mutagenic activity has been attributed to nitroaromatic compounds present in these extracts. In the studies reported here, the direct-acting mutagen, [3H]nitropyrene (3H-NP), was used as a model nitroaromatic compound. Rats were exposed to this radiolabeled compound by nose-only inhalation either as a coating (approximately 6% by mass) on relatively inert, ultrafine 67Ga2O3 particles or as a homogeneous ultrafine aerosol. The tissue deposition, retention, and biological fate of each aerosol were investigated and compared. Respiratory tract clearance of 3H radioactivity from each exposure was very rapid with no apparent differences seen in the lung retention of this inhaled compound between each exposure over the course of these studies. Higher 3H-radioactivity levels were seen in stomach and large intestines of rats exposed to the 67Ga2O3-associated 3H-NP than in the same tissues from rats exposed to the pure 3H-NP aerosol. Rats exposed to the 3H-NP-67Ga2O3 aerosol excreted the majority of the deposited 3H radioactivity in the feces (75 +/- 18%), whereas pure 3H-NP exposed animals excreted a major portion of the radiolabeled in the urine (76 +/- 18%). It appeared that the major portion of the pure 3H-NP aerosol was cleared from the respiratory tract by direct absorption into blood, while the 67Ga2O3-associated 3H-NP was cleared by both blood absorption and mucociliary clearance followed by ingestion and fecal excretion. These differences in the deposition and biological fate between the particle-associated NP and the pure NP aerosol may have important implications in terms of the metabolic fate of inhaled nitroaromatic compounds and the health risks associated with human exposures to particulate environmental pollutants that contain this class of compounds.

Aerosols↗

Retention of monodisperse or polydisperse aluminosilicate particles inhaled by dogs, rats, and mice.

This study compared long-term retention of 134Cs-labeled fused aluminosilicate particles inhaled by three animal species. Dogs, rats, and mice were briefly exposed to 0.7-, 1.5-, or 2.8-micron activity median aerodynamic diameter (AMAD) monodisperse particles or a polydisperse aerosol with 1.5 to 2.0 micron AMAD and geometric standard deviation of 1.5 to 2.0. Tissues and excreta were collected for up to 850 days after exposure to determine retention and clearance patterns of the inhaled particles. Simulation models were developed for each animal species and aerosol. Solubilization was the dominant factor in long-term lung clearance for most of the particles inhaled by dogs; mechanical clearance was dominant in rats and mice. After accounting for solubility, physical clearance from the lung to the gastrointestinal tract and to lung-associated lymph nodes (LALNs) was independent of particle size within the size range investigated. Rats and mice demonstrated a rapid clearance from the pulmonary region, with most of the mechanically cleared particles going to the gastrointestinal tract; significant translocation to the LALNs occurred for only a few days. The dogs cleared deposited particles at a slower rate, with most of the long-term clearance going to LALNs. A small portion of the initial deposit was retained in the upper respiratory tract of all three species. Results from the data for dogs were used to make long-term predictions for chronic inhalation of particles by humans.

Air Pollutants↗

Effects of the single or repeated inhalation exposure of Syrian hamsters to aerosols of 239PuO2.

Male Syrian hamsters were scheduled to be exposed by inhalation approximately every 60 days for 1 year (7 exposures) to aerosols of 239PuO2 beginning at 84 days of age. Other hamsters were exposed once when 84 or 320 days of age. Plutonium-239 deposited in the lungs by the repeated inhalation exposures was cleared from the lungs at a rate similar to that following a single inhalation exposure. The incidence of radiation pneumonitis, bronchiolar epithelial hyperplasia, and alveolar squamous metaplasia were the only lesions that were related to radiation dose. Only two primary lung tumours were found among the hamsters exposed to 239PuO2. No primary lung tumours were found in the control hamsters. It was concluded that the incidence of lung tumours was not increased by the protraction of the alpha radiation dose to the lungs from repeated inhalation exposure.

Aerosols↗

Cytotoxicity and mutagenicity of vapor-phase pollutants in rat lung epithelial cells and Chinese hamster ovary cells grown on collagen gels.

Lung epithelial cell (cell line designated LEC) and Chinese hamster ovary (CHO) cells were grown on hydrated collagen gels and exposed directly to toxic vapor-phase pollutants. The cells were exposed to graded concentrations of phenol, formaldehyde, a volatile fraction of process stream material from an experimental coal gasifier and the nonparticulate, vapor phase of diesel engine exhaust. During exposures, the cells were maintained at an air/collagen interface by removing the medium overlying the hydrated collagen gel. Morphological changes indicative of cell retraction were found in LEC cell cultures exposed to phenol, formaldehyde, or diesel exhaust. Damage following exposure to the toxicants was quantitated in LEC and CHO cells by Trypan blue dye exclusion, a measure of plasma membrane integrity. Clone-forming ability was also used to measure cell survival in CHO cells. When measured by Trypan blue dye exclusion, phenol (EC50 = 2.1 mg/l) caused membrane damage to LEC cells but not CHO cells, while formaldehyde (EC50 = 31 and 42 micrograms/l for LEC and CHO, respectively) and diesel exhaust (EC50 = 11 and 29% of tailpipe exhaust in LEC and CHO cells, respectively) caused damage to both cell types. No cytotoxicity was observed in LEC or CHO cells exposed to the fraction from the coal gasifier. Essentially no mutagenic activity was associated with the exposure of CHO cells to formaldehyde or the vapor phase of diesel exhaust. Mutagenic activity was found in CHO cells exposed to ethylene oxide, the positive control. The results of this study indicate that mammalian cells grown on collagen gels can readily be exposed to vapors of chemicals and chemical mixtures. The cell exposure system may be generally useful in the analysis of toxic damage to mammalian cells resulting from gaseous or vapor-phase pollutants.

Air Pollutants↗

Dose-response relationships for bone cancers from plutonium in dogs and people.

The risk of bone cancers developing from internally deposited plutonium must be estimated from studies in laboratory animals because no plutonium-induced cancers have been observed in people. Studies of the effects of 226Ra and 239Pu injected into beagle dogs at the University of Utah and 238PuO2 inhaled by beagle dogs at the Inhalation Toxicology Research Institute provide a key link to understanding the longterm effects of inhaled alpha-emitting radionuclides in people. Injected radium and plutonium are rapidly deposited in bone whereas plutonium deposited in lung by inhalation is translocated to bone more slowly, depending on its chemical form. The development of bone cancers is a late occurring effect seen after either injection of plutonium or radium or inhalation of plutonium. The incidence of bone cancers from alpha radiation to the skeletons of dogs was compared to bone cancer incidences in radium dial painters to estimate bone cancer risk from inhaled plutonium in people. A risk factor of 1200 bone cancers/10(6) rad to skeleton (average dose) was estimated.

Age Factors↗

Role of inhalation studies with animals in defining human health risks for vehicle and power plant emissions.

Automotive vehicles and power plants using fossil fuels emit a complex array of gases and particulate material. The physical and chemical characteristics of these emissions vary markedly between sources and comprise only a portion of the contributors to air pollution exposure of people. Further, it is well recognized that a single form of self-inflicted air pollution, cigarette smoking, is the dominant cause of air pollution-induced disease. These factors minimize our potential for developing an adequate understanding of the health effects of vehicle and power plant emissions by studying only people. The alternative is to use the human data to the extent feasible and complement it with information gained in studies with macromolecules, organelles, cells, tissues and whole animals. Within this context, this paper reviews the use of inhalation studies with animals for defining human health risks of airborne materials, especially particulate materials. The major areas covered are: the fate of inhaled materials, the pathogenesis of disease induced by inhaled materials and long-term animal studies to identify late-occurring effects. Emphasis is placed on the utility of studies in whole animals as integrative models in which the multiple processes such as xenobiotic metabolism, cell injury, repair, transformation and promotion under the influence of many host factors interact in a manner that may not be directly observed in isolated cells or tissues.

Air Pollutants↗

The induction of liver tumors by 239Pu citrate or 239PuO2 particles in the Chinese hamster.

The influence of radiation dose distribution on the frequency of 239Pu-induced liver tumors was evaluated in the Chinese hamster. Different concentrations of 239Pu citrate 239PuO2 particles of known sizes were injected intravenously via the jugular vein. About 60% of the injected 239Pu citrate was deposited in the liver and 40% in the bone. The 239Pu citrate was rather uniformly distributed throughout the liver parenchyma. Injected plutonium oxide particles were taken up by the reticuloendothelial system with 90% of the body burden deposited in the liver. The 239PuO2 particles were localized in the Kupffer cells and produced nonuniform dose distributions that were dependent on particle size. There was an activity- and dose-dependent increase in the incidence of total liver parenchymal cell tumors following injection with either plutonium particles or citrate. For animals that received 14.0-, 2.7-, 0.3-, and 0.04-Gy dose to liver from 239Pu citrate the cumulative tumor incidence was 39, 32, 5, and 0%, respectively. Animals that were injected with the 0.24 micron 239PuO2 particles had doses of 42.0, 7.2, and 0.8 Gy to the liver and tumor incidences of 34, 26, and 5%, respectively. Plutonium citrate also produced hemangiosarcomas of the liver and tumors in bone and bone marrow. The latent period for liver tumor appearance in animals exposed to 239Pu citrate or 239PuO2 particles increased as the injected activity decreased. For animals injected with a similar total activity (7.4 Bq/g), the lifetime cumulative liver tumor incidence was similar for animals exposed to either 239Pu citrate (32%) or 239PuO2 (26%). There was little effect of particle size on liver tumor incidence. These data indicate that, in Chinese hamster liver, local radiation dose distribution is less important in altering tumor incidence than injected activity or average dose. However, the more uniform irradiation from 239Pu citrate administration was more effective in cancer production than the nonuniform irradiation from 239PuO2 particles.

Alpha Particles↗

Influence of radiation dose patterns on lung tumor incidence in dogs that inhaled beta emitters: a preliminary report.

Different radiation dose patterns to the lung from inhaled beta-emitting radionuclides may influence the frequency and kind of biological effects. To determine the magnitude of this influence, groups of Beagle dogs were exposed to aerosols of 90Y, 91Y, 144Ce, or 90Sr in relatively insoluble particles and observed for their life spans. Different dose patterns were achieved by using these radionuclides having similar beta emissions and chemical form but having physical half-lives ranging from 2.6 days to 28 years. The range of initial lung burdens of radionuclides studied resulted in a range of biological effects from early deaths at the highest radiation doses to no discernible effects at the lowest doses. The effective half-lives of the four radionuclides in the lung ranged from 2.5 to 600 days. Within 1.5 years after exposure, some dogs died with radiation pneumonitis and pulmonary fibrosis. Between 1.5 and 10 years after exposure, 42 pulmonary carcinomas and 28 pulmonary sarcomas were observed in 163 dogs that died. Protracted irradiation of the lung from 90Sr or 144Ce resulted in a relatively high radiation dose and produced more total lung tumors but fewer lung tumors per rad than less protracted irradiation from 90Y or 91Y. At 10 years after inhalation exposure, the difference in risk per rad among the different dose patterns was a factor of 4 to 8, indicating that the different radiation dose patterns from inhaled beta emitters do influence lung tumor risk factors, at least at high (greater than 20,000 rad) doses to lung.

Aerosols↗