: 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.

: The USAMBRDL has an interest in the potential inhalation toxicity of yellow dye (SY) and a yellow/green dye mixture (SY/SG) used in colored smoke munitions. Rats were exposed by inhalation to aerosols of SY or SY/SG generated in a respirable particle size range for 6 hr/day, 5 days/week for 4 weeks. Nominal exposure concentrations selected for both dye exposures were 0, 10, 50, and 250 mg/cum. Animals exposed to the highest concentration of SY (230mg/cum) showed only a slight decrease in weight gain (8 percent) and mild respiratory function changes, with no observable histopathological lesions. Exposure to the lower concentrations of SY dye elicited no observed response. Animals exposed to the highest level of SY/SG dye (210 mg/cum) displayed signs of pulmonary inflammation with histopathological evidence of mild Type II pulmonary epithelial cell hyperplasia and proliferation of foamy alveolar macrophages. Some of the animals exposed to the medium concentration of SY/SG dye mixture (49 mg/cum) showed similar signs. Thus, the lowest toxic exposure concentration of SY dye is > or = 230 mg/cum and that of SY/SG dye is > or = 50 mg/cum under the exposure regime used. Originator supplied keywords include: Solvent Yellow; Solvent Green; 2-(2'-quinolyl)-1,3-indandione, 1,4-di-p-toluidinoanthraquinone.

Canine α 1 -antitrypsin (A 1 AT) was isolated from plasma using gel filtration, affinity, and ion-exchange chromatography. Total protein of the plasma sample was decreased by 99% whereas the antitrypsin activity per milligram of protein was increased 17-fold. Although the antitrypsin activity of the isolated A 1 AT was heat stable after heating at 56 and 80°C for 30 min, the elastase inhibitory activity was only heat stable after heating at 56°C and was lost after heating at 80°C. These data further support the hypothesis that trypsin and elastase bind to two different sites on A 1 AT. Canine A 1 AT had molecular weights of approximately 110,000 after filtration by Sephadex G-100 Superfine and 57,000 following sodium dodecyl sulfate electrophoresis. An in vitro macrophage migration assay was used to assess the effects of A 1 AT on the migration of pulmonary alveolar macrophages (PAM). At a concentration of 200 μg protein/ml, the A 1 AT preparation significantly inhibited PAM migration. Furthermore, heating this concentration of A 1 AT at 56 or 80°C for 30 min did not destroy its ability to inhibit PAM migration. Since A 1 AT has been shown to be present in alveolar lavage fluid and associated with PAM, an increase in the amount of A 1 AT during pulmonary inflammation may influence the number of PAM present in the lung.

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