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Biomedical subjects

W Dalbey

Publications and source records attributed to W Dalbey.

10 recordsLinked to original sources

Short-term exposures of rats to airborne hydrogen fluoride.

A series of acute inhalation exposures was performed with airborne hydrogen fluoride (HF) to establish the concentration response for nonlethal effects in the rat. Exposures were either 2 or 10 min long; concentrations ranged from 135 to 8621 ppm. Three additional exposures (20 to 48 ppm) were performed for 60 min. A mouth-breathing (MB) model with a tracheal cannula was used in most of the exposures to maximize delivery of the HF to the lower respiratory tract. Endpoints on the day after exposure included hematology, serum chemistry, bronchoalveolar lavage, pulmonary function, organ weights, and histopathology. Nasal resistance was measured in nose-breathing (NB) groups. Effects of exposure were generally limited to the respiratory tract and included alveolitis, bronchial lesions, altered parameters of pulmonary function and bronchoalveolar lavage, and mucosal necrosis, inflammation, and fibrinopurulent exudate in airways. Observed changes were concentration related and appeared more pronounced in major airways near the point of entry (trachea in MB animals and nose in NB animals). One group of MB animals exposed for 10 min to 1454 ppm was evaluated at 3 and 14 wk after exposure; the acute effects had resolved by those times. The effects of 2-min exposures were consistently more severe than those from 10-min exposures to the same product of concentration x time. Exposures of MB animals for 60 min to 20 or 48 ppm HF did not result in observable adverse effects, although quasistatic pressure-volume curves were shifted upward slightly after 48 ppm. These data provide an integrated picture of the concentration-related effects of short nonlethal exposures to HF.

Administration, Inhalation↗

Acute effects of 10-minute exposure to hydrogen fluoride in rats and derivation of a short-term exposure limit for humans.

A series of acute inhalation exposures of female rats was conducted with hydrogen fluoride (HF) to establish a concentration-response curve for nonlethal exposures. Durations of 2 and 10 min were used to simulate possible short-term exposures. Concentrations of HF ranged from 593 to 8621 ppm for 2-min exposures and from 135 to 1764 ppm for 10-min exposures. Additional exposures were performed for 60 min at 20 and 48 ppm HF for comparison to existing Emergency Response Planning Guidelines. Animals were evaluated on the day after exposure for changes in parameters of bronchoalveolar lavage, pulmonary function, hematology, serum chemistry, body weight, organ weights, and histopathology. Most exposures were performed with orally cannulated animals to bypass absorption of HF in the nose and achieve maximum delivery of HF to the lower airways. One of the primary uses of the resulting data was to estimate a concentration to which most people could be exposed for 10 min without severe of irreversible health effects. This level was 130 ppm. It was predicted that irritation would occur at this concentration, but the effects on t he respiratory tract would not be "serious" and would be expected to be reversible. The results of this experiment and the subsequent analysis of the data provide an important aid in he planning of responses to an accidental release of HF.

Animals↗

Subchronic and developmental toxicity studies of vaporized diisopropyl ether in rats.

Two inhalation studies were performed with a vaporized sample of commercial-grade diisopropyl ether (DIPE). In the subchronic study, Sprague-Dawley rats (14/sex) were exposed to 0 (both untreated and sham-exposed controls), 480, 3300, or 7100 ppm DIPE for 6 h/d, 5 d/wk, for approximately 90 d. DIPE itself accounted for 91-95% of the vapors, with the remainder being a mixture of 27-29 compounds. Exposure to DIPE did not adversely affect clinical signs, body weight, serum chemistry, hematology, or the number of sperm or spermatids. Exposure of males to 7100 ppm resulted in hypertrophy of liver cells associated with increased liver weight and in increased kidney weight with an increased incidence of hyaline droplets in proximal tubules of the kidney. Females had increased weight of both liver and kidney, although kidney increased only in relation to sham-exposed controls and no morphological changes were observed in either organ. At 3300 ppm, weights of liver and kidney were again increased in males; the liver weights were increased in females only compared to sham-exposed controls and not untreated controls. No abnormalities were observed morphologically. No changes were observed with 480 ppm. In the developmental toxicity study, pregnant Sprague-Dawley rats (22/group) were exposed to 0 (both untreated and sham-exposed controls), 430, 3095, or 6745 ppm for 6 h/d on gestation d 6-15. Animals were sacrificed on gestation d 20. With 6745 ppm, dams had a slight reduction in body weight gain and a significant decrease in food consumption. A concentration-related increase in the incidence of rudimentary 14th ribs was observed, but its significance was uncertain. There was no apparent toxicity, either maternal or fetal, at the lowest exposure concentration. Both studies indicated a low order of toxicity for DIPE.

Abnormalities, Drug-Induced↗

Four-week inhalation exposures of rats to aerosols of three lubricant base oils.

Sprague-Dawley rats were exposed to aerosols of one of three base stocks used to formulate lubricating oils. These stocks were a solvent-refined oil (SRO), a hydrotreated and acid-washed white oil (WTO) and a severely hydrotreated and hydrocracked oil (HBO). Exposures were for 6 h per day, 5 days per week for ca. 4 weeks. There were four groups of rats for each study (10 per sex per group). Aerosol concentrations were ca. 0, 50, 210 and 1000 mg m-3 for each material; the mass median aerodynamic diameter was ca. 1 microns. Following the last exposure, all animals were sacrificed and necropsied. Samples were taken for serum chemistry, hematology, sperm morphology, weights of seven organs and histopathology on at least nine organs. Body weights and clinical signs were not affected by exposures. The only treatment-related changes were in the lung and associated lymph nodes. Both the wet weight of the lung and the dry/wet weight ratio increased in a concentration-related manner. Associated with the increased weight were accumulations of foamy alveolar macrophages, particularly in alveoli close to alveolar ducts. Mild infiltration by neutrophils was observed with WTO and SRO; thickened alveolar walls were noted with the highest concentration of HBO. These mild responses to exposures at very high concentrations indicate a low degree of toxicity for these aerosols.

Administration, Inhalation↗

Role of exposure parameters in toxicity of aerosolized diesel fuel in the rat.

Sprague-Dawley rats were exposed to aerosolized diesel fuel (ADF) to determine the potential health effects in military troops during exposure to this visual obscurrant. Acute range finding studies were performed to estimate exposure conditions at which minimal (less than 1%) mortality would occur. This information was used in the design of a repeated exposure study to test the relative significance of the frequency of exposures, the duration of exposure, and aerosol concentration in any toxicity which might occur. Animals were exposed once or three times per week for a total of nine times to concentrations ranging from 1.3 mg ADFl-1 to 6 mg ADFl-1 and exposure durations of 2 or 6 h. Body weight and food consumption were recorded at weekly intervals during the exposure period and in animals that were retained for 2 weeks after the last exposure. Animals were used for a variety of endpoints, including neurotoxicological tests, pulmonary function tests, hematology, clinical chemistry, organ weights, and histopathology, either within 2 days of the last exposure or after the 2-week recovery period. Animals exposed to ADF showed an initial depression in body weight followed by a slower rate of growth than the sham exposed controls. No exposure related changes were observed in any of the neurotoxicology assays. The lung was the primary site of toxicity. Focal accumulations of pulmonary free cells were observed histologically, with thickening and hypercellularity of nearby alveolar walls. The number of lavaged pulmonary free cells increased similarly. Both pulmonary wet and dry weights increased. Lung volumes were altered by exposure, including increased FRC and decreased TLC. Carbon monoxide diffusing capacity was decreased. Histologic abnormalities were not observed in any other organs. Of the exposure parameters tested, the frequency of exposure appeared to be the most significant in relation to degree of toxicity.

Aerosols↗

Metabolism of environmental pollutants by the isolated perfused lung.

An isolated perfused rabbit lung system was developed for the study of pulmonary metabolism of foreign compounds. The main features of the system include the use of autologous whole blood, constant pressure perfusion, subatmospheric ventilation, and measurement of a variety of physiological and biochemical parameters. Pulmonary metabolism of benzo(a)pyrene has been investigated with this system. In addition to the 3-hydroxy metabolite, three dihydrodiols and an unidentified polar metabolite were also found. The polar metabolite accounted for approximately 50% of all metabolites found in the five compartments of the perfusion system. Pretreatment with 3-methylcholanthrene increased total metabolism of benzo(a)pyrene and shifted the pattern of metabolites. The perfusion system for the rabbit has been extensively modified for use with rats and guinea pigs. These smaller animals are currently being used to investigate pulmonary metabolism of trichloroethylene.

Animals↗