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Biomedical subjects

U Glaser

Publications and source records attributed to U Glaser.

10 recordsLinked to original sources

Ultrastructural observations in hamster and rat lungs after chronic inhalation of cadmium compounds.

Long-term inhalation of CdCl2 at concentrations as low as 12.6 micrograms Cd/m3 causes development of lung tumors in rats (4). No information, however, was available on the chronic carcinogenicity of CdO, CdS and CdSO4 which are especially relevant to the occupational area. In the present joint study of the Fh-ITA and the Fh-IUCT, rats and hamsters were exposed to CdCl2, CdSO4, CdO and CdS in a chronic inhalation carcinogenicity set-up (2, 3). The goal of the ultrastructural investigation was to compare inflammatory reactions and fibrotic lesions, as well as epithelial alterations occurring in the species under study. The present communication focusses especially on observations obtained from male and female hamsters and rats chronically exposed to CdO. In addition, we report preliminary results from a short-term inhalation study with CdO.

Administration, Inhalation↗

Carcinogenicity of sodium dichromate and chromium (VI/III) oxide aerosols inhaled by male Wistar rats.

In inhalation chambers, male Wistar rats of the strain TNO-W74 were continuously exposed to submicron aerosols of sodium dichromate and to a pyrolyzed Cr(VI)/Cr(III) (3:2) oxide mixture. The sodium dichromate (Na2Cr2O7) aerosol had the chromium concentrations of 25, 50 and 100 micrograms/m3, the chromium oxide mixture (Cr5O12) had the chromium concentration of 100 micrograms/m3. After 18 months of inhalation the rats were held under conventional conditions for a further year. The experimental groups consisted of 20 rats and the control group of 40 rats. More than 90% of the rats in each group reached 2 years. At the end of the study the mortality rates amounted to 35%, 45% and 25% in the 3 sodium dichromate aerosol groups, respectively, and 50% in the chromium oxide mixture aerosol group, which was not significantly different from that of the controls (42.5%), living under the same conditions in filtered fresh air. In all sodium dichromate exposed groups significant effects were neither found clinically nor from hematology and clinical chemistry compared to the controls. In the chromium oxide mixture group, however, there was a number of significant findings. Elevated white and red blood cell counts and serum cholesterol as well as decreased serum total immunoglobulin levels at different stages of the study were observed together with few local lung effects determined histopathologically in this group. We assume that these effects are mainly due to the increased chromium lung burden of the rats. At the end of the study the lung chromium retention was about 10 times higher for the rats exposed to chromium oxide versus sodium dichromate at an aerosol Cr-concentration of 100 micrograms/m3, while the kidney chromium retention was measured to be nearly equal in both groups. Three primary lung tumors (2 adenomas and 1 adenocarcinoma) and 1 malign tumor of the pharynx were found at the highest Cr-concentration (100 micrograms/m3) of the sodium dichromate aerosol, 1 primary adenoma of the lung was in the chromium oxide mixture group exposed also to a Cr-concentration of 100 micrograms/m3. No primary lung tumors were observed in the other experimental and control groups. These results indicate a weak carcinogenicity at 100 micrograms/m3 for the rats continuously exposed to submicron Na2Cr2O7 and Cr5O12 aerosols. Thus, there may be a small carcinogenic risk from occupational relevant chromium air levels. However, results have to be confirmed with larger animal populations.

Administration, Inhalation↗

Bioavailability indicators of inhaled cadmium compounds.

In a thirty-day inhalation study male Wistar rats were continuously exposed to submicron aerosols of three different cadmium compounds. The cadmium chloride (CdCl2) and cadmium oxide (CdO) aerosol concentrations were 0.1 mg/m3 Cd. Because of its lower solubility the cadmium sulfide (CdS) level was 1 mg/m3 Cd. For CdCl2 and CdO, most of the cadmium was found in the lung cytosolic compartment, but for CdS only 30% of the cadmium was retrieved from the lung cytosols. This was observed both at the end of the inhalation and also after an additional 2-month period in fresh air. The cadmium contents of the lung homogenates, cytosols, and the lung cytosolic metallothionein were found to be twice as much for exposure to CdO than for exposure to CdCl2. For exposure to CdS at cadmium concentrations 10 times higher the same cadmium levels were found as for CdO. These results are confirmed by results from alveolar lavage analysis indicating that in the lung-inhaled CdO is even more available to lung tissue than the very soluble CdCl2, and CdO has an availability 10 times as much as CdS. This study proved that lung compartmental cadmium and metallothionein contents as well as lung lavage analysis can describe the bioavailability of inhaled cadmium.

Aerosols↗

Low level chromium (VI) inhalation effects on alveolar macrophages and immune functions in Wistar rats.

In inhalation chambers, 5-week-old male Wistar rats of the strain TNO-W-74 were continuously exposed to submicron aerosols of sodium dichromate in concentrations from 25 (low level) to 200 micrograms/m3 Cr (high level). Subacute exposure (28 days) to 25 and 50 micrograms/m3 Cr resulted in "activated" alveolar macrophages with stimulated phagocytic activities, and significantly elevated antibody responses to injected SRBC's. After subchronic (90 days) low level exposure there was a more pronounced effect on activation of the alveolar macrophages, with increased phagocytic activities. However, at high Cr (VI) exposure level (200 microgram/m3), inhibited phagocytic function of the alveolar macrophages was seen. In rats which were exposed to this chromium aerosol concentration for 42 days, the lung clearance of inert iron oxide was reduced significantly. The humoral immune system was still stimulated at subchronic low chromium aerosol concentrations of 100 micrograms/m3, but significantly depressed at 200 micrograms/m3 Cr. These results show that respiratory defence and immunologic functions were stimulated or inhibited depending on dose and time of chromium (VI) inhalation.

Aerosols↗

[The effect of organophosphates on heart ATPase in the rat].

The effect of organophosphate intoxication with diisopropylfluorophosphate (DFP), paraoxon and parathion on the activity of some ATPases of rat hearts was examined. Biochemical and histochemical methods were employed to determine the activities of the transport ATPase, of the myofibres and mitochondrial ATPases using different doses and antidote application. The organophosphates studied here had an inhibitory effect on the activities of enzymes. Biochemical measurements showed that the ATPase activities are dependent upon the duration of poisoning, the dose of poison and the applied organophosphates. DFP caused the highest restriction in activity of the examined ATPases. The Ca2+-stimulated ATPase was more sensitive than the Na+/K+-ATPase to the application of organophosphates. The antidote therapy determined the grade of influence on activity. Combined treatments of organophosphate poisoning with atropine and obidoxime chloride in the high doses of 7.5 mg/kg and 12.5 mg/kg body weight i.m. proved to be the most effective against the organophosphate intoxication. Antidote combination of small doses and also single application of atropine or obidoxime chloride might cause a stimulation of activity of the Na+/K+-ATPase and a significant decline of the Ca2+-ATPase.

Adenosine Triphosphatases↗