Toxicity of inhaled 144CeCl3 in beagle dogs. 3. LF-41.
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Biomedical subjects
Publications and source records attributed to R O McClellan.
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Selenium compounds released into urban atmospheres as a result of fossil fuel combustion may pose an inhalation hazard to people. Two chemical forms of selenium produced during coal combustion and present in combustion effluent are selenious acid. H2SeO3, and elemental selenium, Se. In an attempt to determine the toxicity of selenium compounds relative to other trace elements, the cytotoxicity of H2SeO3 and Se to rabbit alveolar macrophages in vitro was investigated. Macrophages were obtained by lung lavage and exposed in tissue culture after 20 h. Neither selenious acid nor elemental selenium caused cell lysis at concentrations which decreased total cell viability. Selenious acid was an order of magnitude more toxic then elemental selenium. Elemental selenium was similar in toxicity to environmental contaminants such as CdCl2 and V2O5. These in vitro cytotoxicity data can be used to predict the risk posed to people inhaling selenium compounds at levels found in urban atmospheres.
Mutagenicity of extracts of particles collected from the exhaust of six different European and American diesel cars was evaluated in Salmonella strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98. The extracts demonstrated direct, dose-related mutagenicity in all strains except TA 1535, with the potencies varying from 6-17 revertants/micrograms in TA 100, the most sensitive strain. Addition of Aroclor 1254 induced rat liver homogenate fractions decreased the direct response in TA 100 and increased the response in four of the six extracts in TA 98. Differences in the extractable organic fraction of the particles and the particulate emission rates for the six cars had a greater influence on the amount of mutagenicity emitted (revertants per mile) than the actual mutagenic potency of the organics. The ranking of the cars by revertants/mile was different than ranking by revertants/micrograms extractable organics. The response of two of the six extracts in a nitroreductase deficient strain of Salmonella (TA 100 FR1) were significantly lower than the response in TA 100, suggesting that reduction of nitroaromatics by bacterial enzymes may be influential in the direct response. Results of testing triplicate samples collected in three different cars demonstrated good repeatability in sampling and bioassay procedures.
General Motors and Volkswagen diesel passenger cars (1980 and 1981 model year) were operated on a climate controlled chassis dynomometer and the particulate portion of the exhaust was collected on high volume filters. Dichloromethane extracts of the exhaust particles (soot) collected while the cars were operated under simulated highway, urban and congested urban driving cycles were assayed for mutagenicity in Salmonella strains TA-98 and TA-100. Driving pattern did not significantly influence the mutagenic potency of the exhaust particle extracts or estimates of the amount of mutagenicity emitted from the exhaust despite large differences in particle emission rates and extractable fraction of the particles. Mutagenicity of extracts of exhaust particles collected while the vehicles were operated at test chamber temperatures of 25, 50, 75 and 100 degrees F were also very similar. The results suggest that driving pattern and environmental temperature do not significantly alter the emission of genotoxic combustion products from the exhaust.
Determinations were made of respiratory tract deposition and gastrointestinal tract burdens following whole body inhalation exposures, typical of those used in many chronic exposures; these were compared to values obtained in nose-only exposures. Fischer-344 rats were exposed in large volume chambers, in a whole body mode, to 0.1 micron volume median diameter (VMD) 67Ga2O3 particles 5 hrs/day. Deposition per unit of exposure time and retention were essentially identical following either 1 or 3 day exposures. The lung deposition of particles was 2.8 units/hr for males and 2.2 units/hr for females if the exposure concentration was expressed as 1 unit/L. These values represent a deposition of approximately 15% of the inhaled particles, similar to values obtained for nose-only exposures. Aerosol deposition per kgm body weight was 24% higher in females than males. Passage of material into the gastrointestinal tract was 1.6-fold greater for these whole body exposures as compared to nose-only exposures to the same aerosol mainly resulting from extra material ingested by grooming of the pelt. Approximately 60% of the pelt burden was calculated to be ingested following whole body exposures.
The influence of diesel fuel composition on mutagenicity of exhaust particle associated organic compounds has been investigated using nine fuels varying in aromatic content and distillation properties. The tests were conducted with Oldsmobile Delta-88 and Peugot 504 diesel cars operated according to the EPA Federal Test Procedure. The particulate exhaust from each test was collected on a filter, extracted in dichloromethane and the resulting extract evaluated for mutagenicity in Salmonella strain TA-100. Mutagenicity of extracts of particles collected from the Oldsmobile were highest in the higher aromatic content fuels (greater than 30%) but similar for intermediate (20%) and low (13%) aromatic content fuels. No influence of aromaticity on mutagenicity was observed in samples collected from the Peugeot under the same conditions. Thus, fuel aromatic content may enhance the production of mutagenic combustion products at higher concentrations, but may be dependent upon engine type. A good correlation was observed between mutagenicity of the particle extracts and the initial boiling point of the fuel (r = 0.89). Gas chromatography/mass spectrometric analysis of the aromatic fraction of the fuels showed that the fuel producing the most mutagenic combustion products was highest in phenanthrene type compounds.
The particulate exhaust of diesel engines consists of 0.1--0.2 micrometers mass median diameter particles composed of a carbonaceous core and adsorbed organic compounds. A technique was needed to determine accumulated lung burdens of particles in animals exposed to diesel exhaust as a determinant of dose. A method was developed for determining lung burdens of diesel soot particles in rats at 1 day, and at 1, 5, 15, 33 and 52 weeks after cessation of a subchronic exposure to diluted diesel exhaust. Lung tissue was dissolved in tetramethylammonium hydroxide and the diesel soot separated by centrifugation. The soot was suspended in water by sonication and the light absorption of samples was compared to standard suspensions of diesel soot. Recovery from lungs spiked with 50-1000 micrograms of soot was 89 +/- 5%. Rats exposed over a period of 18 weeks to diluted diesel exhaust at average net diesel particles concentrations of 150, 940 and 4100 micrograms/m3 had lung burdens of 35, 220 and 1890 micrograms/g lung, respectively, one day after the last exposure. The long-term clearance rates of soot had estimated half-times of 87 +/- 28, 99 +/- 4 days, for the low and medium exposure groups, respectively. The clearance half-time for the high level exposure group of 165 +/- 8 days was significantly longer (P less than 0.0001) than those of the other two groups.
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