Three studies were conducted to provide information on the biological fate, distribution of radiation doses among tissues, and implications for potential health consequences of an inhalation exposure to mixed-oxide nuclear fuel materials. In each study, Fischer-344 rats, beagle dogs, and cynomolgus monkeys inhaled one of three aerosols: 750{degrees}C calcined mixed oxides of UO{sub 2} and PuO{sub 2}, 1750{degrees}C sintered (U,Pu)O{sub 2}, or 850{degrees}C calcined {open_quotes}pure{close_quotes} PuO{sub 2}. These materials were collected from glove-box enclosures immediately after industrial processing of mixed-oxide fuel materials. Lung retention, tissue distribution, and mode of excretion of {sup 238-240}Pu, {sup 241}Am, and uranium (when present) were quantified by radiochemical analysis of tissue and excreta samples from animals sacrificed at selected times to 6.5 yr after inhalation exposure.

Rats were exposed by chronic inhalation to diesel exhaust or oil shale dust, alone and in combination to examine pathophysiologic interactions between the dusts. The three agents all accumulated progressively in lungs and caused similar pneumoconiotic responses. The effects of combined exposures tended to be greater than additive. The magnitude of effects was more closely correlated to particle lung burden than to exposure concentration. This suggests that effects of prolonged human exposures to combined dust atmospheres may be estimated better on the basis of predicted lung burden than exposure concentration. 14 refs., 2 figs., 2 tabs.

Inhalation studies conducted on nickel subsulfide (Ni3S2 have shown this compound to be highly toxic to the respiratory tract of rats and mice exposed for 12 d. To assess the subchronic inhalation toxicity of Ni3S2, groups of F344/N rats and B6C3F1 mice were exposed to 0, 0.11, 0.22, 0.44, 0.88, and 7.8 mg Ni/m3 (as Ni3S2), 6 h/d, 5 d/wk, for 13 wk. Concentrations of Ni in lungs of rats and mice exposed for 73 wk were similar, but the incidence and severity of the toxic effects of Ni3S2 exposure were greater among rats than mice. Exposure resulted in depressed weight gain and increased lung weights. Inhalation of Ni3S2 did not affect motility, viability or morphology of sperm in males, nor did it alter the estrous cycle length of females. Major histopathological lesions related to nickel exposure occurred in the nose, lung, and lung-associated lymph nodes of both species. The major findings were focal chronic inflammation of the lung, atrophy of the olfactory epithelium, and hyperplasia of the bronchial and mediastinal lymph nodes. In addition, focal interstitial fibrosis developed in lungs of mice exposed to 0.88 and 7.8 mg Ni/m3. The lowest exposure concentrations resulting in respiratory tract lesions were 0.44 mg Ni/m3 for mice and 0.11 mg Ni/m3 for rats. Results indicate that subchronic inhalation exposure of rats and mice to Ni3S2 concentrations below the current threshold limit value VLVI for nickel produces significant lesions in the respiratory tract.

In spite of stringent standards for occupational exposure of workers to airborne beryllium, new cases of chronic beryllium disease continue to occur. Many of these cases are among workers involved in the machining of beryllium metal. Although the exposure history of most individuals recently diagnosed as having chronic beryllium disease included exposures above the current occupational standard (2 μg/m3), there are limited data on the source of beryllium aerosols and on the inhalation toxicology of beryllium metal. Similar information is lacking on the source terms and toxicology of beryllium metal alloys. Although no cases of chronic beryllium disease have been diagnosed among machinists working exclusively with beryllium alloys, it is not clear whether this results from a lower probability for inhalation exposures above the occupational limits or from an intrinsically lower toxicity of beryllium in dilute alloys. The work reported here was undertaken to better define the potential aerosol source term for occupational exposures to beryllium metal and beryllium alloys during two common operations: sawing and milling. Standard machining methods were used to saw and mill billets of beryllium metal, beryllium–nickel alloy, and beryllium–copper alloy. Particle size distributions and aerosol concentrations were measured to evaluate material typical of that which might be accidently inhaled by workers conducting these operations. All particles were irregular in shape and had projected area diameters extending down to the micrometer range. Concentrations of airborne beryllium in the general workplace remained less than 2 μg/m3 because of engineering controls, but peak concentrations in the ventilation shrouds exceeded 7 mg/m3 during the milling of beryllium metal. The rate of total aerosol production was highest when using beryllium metal and was more than a factor of 10 lower when using nickel and copper alloys. This difference probably resulted from the more brittle nature of beryllium metal and its response to mechanical disruption. Taking into account the mass fraction of beryllium in the alloys (approximately 2%), the airborne beryllium production rate for the alloys was more than a factor of 500 lower than for the metal. These results indicate that the potential for accidental exposure to beryllium from machining of metal is significantly greater than from machining of alloys.

Abstract The purposes of this study were to determine whether the gas-phase composition of lithium combustion aerosols can 1) significantly alter the chemical composition of lithium combustion aerosols and 2) significantly change their particle size distribution. The gas composition of the respiratory tract was of special interest. Chain-aggregate lithium combustion aerosols were generated in dry, CO2-free air prior to reaction with 0, 0.10, 0.50, 1.0, 1.75, or 5.0 percent CO2 in air at 52 percent relative humidity and 38°C, to simulate interactions of lithium combustion aerosols with CO2 and H2O in the atmosphere and in the respiratory tract. Aerosols were analyzed at ∼ 1 3-sec intervals during the first 12 sec and at 1 102 and 150 sec after mixing. There was no conversion of aerosols to Li2CO3 in CO2-free air, but there was conversion within 3 sec after mixing of aerosols with the differently CO2-enriched atmospheres. The extent of conversion to Li2CO3 depended on the molar CO2/LiOH ratio in the range from 0 (0.0% CO2) to 17 (1.0% CO2), but was 77 percent at higher molar ratios. Results showed that the respiratory tract contains sufficient CO2 in the gas phase to alter the composition of lithium combustion aerosols, if inhaled. Changes in particle size distribution during the reaction were not sufficient to affect deposition patterns in the respiratory tract. Incomplete conversion to Li2CO3 indicates that the reaction rate was not controlled solely by gas phase CO2 and H2O diffusion. Eidson, A.F.; Allen, M.D.; Lykos, A.N.J.: Lithium Combustion Aerosol Reactions in Air Containing Carbon Dioxide and Water Vapor. Appl. Ind. Hyg. 3:197–202; 1988.

: Male and female F344/N rats were exposed nose-only to a respirable powder of copper-zinc alloy. No rats died as a result of the exposures. Body weights were reduced relative to sham-exposed rats for rats exposed to 240 and 480 mg. hr Cu-Zn/cu.m week. All of the additional observed biological responses to inhaled Cu-Zn were restricted to the respiratory tract. Lung weights were increased due to an inflammatory response for rats exposed to 120 mg. hr Cu-Zn/ cu.m or more per week. Exposure to 240 mg. hr Cu-zn/cu.m per week caused restrictive pulmonary functional disorder, as evidenced by a reduced lung capacity, reduced quasistatic compliance, reduced carbon monoxide diffusing capacity, and increased percent forced vital capacity exhaled in 0.1 second. Exposure-related responses in lavage fluid indicators of lung damage included increased beta-glucuronidase, increased lactate dehydrogenase, and increases in inflammatory cells, total protein, and collagen. Histological lesions produced by Cu-Zn were atrophy of the nasal olfactory epithelium and hyperplasia of goblet cells in the respiratory epithelium, focal necrotizing alveolitis, alveolar macrophage hyperplasia, and goblet cell hyperplasia of bronchial and bronchiolar epithelium. The inhaled Cu-Zn alloy caused exposure-related inflammatory and cytotoxic responses in the respiratory tract, but the inhaled Cu-Zn cleared rapidly and the responses largely resolved after cessation of exposures.

Beryllium metal has special nuclear and structural properties that make it useful for applications in fission and fusion reactor designs. Unfortunately, concerns for its toxicity have made designers wary of using beryllium metal. The work being reported here was undertaken to characterize the aerosols produced by two very common operations performed during preparation or modification of components for use in reactor systems: sawing and milling of beryllium metal. The study also covered beryllium metal alloys to allow comparison. Information from this study is to enable better assessments of the risk of using beryllium metal in reactor designs.

Studies are being conducted with Fischer-344 rats to determine the inhalation toxicology of a respirable power of copper-zinc alloy. Phase I involved standardization of methods, characterization of aerosols, and exposures of rats in whole-body of nose-only systems to air concentrations of 100 mg Cu-Zn/m/sup 3/, or 100 mg titanium dioxide/m/sup 3/. The titanium dioxide was included to determine if effects observed in exposed animals resulted from inhaling the Cu-Zn powder or inhaling a comparable amount of nuisance dust. Sham-exposed and shelf control rats were included. Rats were exposed 2.5 hr/day for 2 or 5 consecutive days, then killed for evaluations. Results include body weights, core temperatures, selected organ weights, hematology, clinical chemistry, and histopathology. Significant findings were 1) all rats were stressed when exposed in whole-body or nose-only exposure systems, 2) except for a greater body weight loss for rats exposed nose-only, indicators of stress were similar for the two types of exposure systems, 3) no consistent differences were seen between sham-exposed and TiO/sub 2/-exposed rats, and 4)adverse effects from exposure to Cu-Zn alloy powder included body weight loss, decreased ability to maintain body temperature (measured in rats exposed nose-only), rhinitis, and an inflammatory response in the lung.

The study was conducted to determine the rate of dissolution of uranium product (yellowcake) obtained from four uranium ore processing mills. Thirty day dissolution experiments were conducted in vitro using two solvents: a simulant of an ultrafiltrate of blood serum (SUF) containing diethylenetriaminepentaacetic acid (DTPA) and 0.1M HCl. Dissolution data are expressed as graphs of the logarithm of the percentage initial U undissolved vs time in hours and fitted to a negative exponential equation. The samples were characterized using x-ray powder diffraction and infrared spectroscopic techniques. All samples were mixtures of (NH/sub 4/)/sub 2/U/sub 2/O/sub 7/ (ammonium diuranate) and ..cap alpha..-U/sub 3/O/sub 8/. The combined results show that (NH/sub 4/)/sub 2/U/sub 2/O/sub 7/ dissolved much more rapidly in either solvent than does ..cap alpha..-U/sub 3/O/sub 8/. Dissolution half times in SUF containing DTPA were: (NH/sub 4/)/sub 2/U/sub 2/O/sub 7/ approx. = 10 hr, ..cap alpha..-U/sub 3/O/sub 8/ approx. = 10/sup 4/ hr. The percentage of total material present as the more soluble (NH/sub 4/)/sub 2/U/sub 2/O/sub 7/ form was shown to vary from 99.4% to 51%. The results indicate that caution must be exercised in the interpretation of bioassay results of workers from different U mills since the highly variablemore » chemical composition of yellowcake may result in widely variable in vivo solubility and excretion.« less

Male and female F344/N rats were exposed nose-only to a respirable powder of copper-zinc alloy. No rats died as a result of the exposures. Body weights were reduced relative to sham-exposed rats for rats exposed to 240 and 480 mg. hr Cu-Zn/cu.m week. All of the additional observed biological responses to inhaled Cu-Zn were restricted to the respiratory tract. Lung weights were increased due to an inflammatory response for rats exposed to 120 mg. hr Cu-Zn/cu.m or more per week. Exposure to 240 mg. hr Cu-zn/cu.m per week caused restrictive pulmonary functional disorder, as evidenced by a reduced lung capacity, reduced quasi-static compliance, reduced carbon monoxide diffusing capacity, and increased percent forced vital capacity exhaled in 0.1 second. Exposure-related responses in lavage-fluid indicators of lung damage included increased beta-glucuronidase, increased lactate dehydrogenase, and increases in inflammatory cells, total protein, and collagen. Histological lesions produced by Cu-Zn were atrophy of the nasal olfactory epithelium and hyperplasia of goblet cells in the respiratory epithelium, focal necrotizing alveolitis, alveolar macrophage hyperplasia, and goblet cell hyperplasia of bronchial and bronchiolar epithelium. The inhaled Cu-Zn alloy caused exposure-related inflammatory and cytotoxic responses in the respiratory tract, but the inhaled Cu-Zn cleared rapidly and the responsesmore » largely resolved after cessation of exposures.« less