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Pulmonary deposition, clearance and effects of inhaled soluble and insoluble cadmium compounds.

The factors affecting the deposition of inhaled cadmium particles in different regions of the respiratory tract are discussed. The retention kinetics of inhaled cadmium compounds is determined by the various clearance processes. It is necessary to differentiate clearly between in vitro (water) solubility and in vivo (lung) solubility. Thus both cadmium oxide and cadmium sulfide particles are rather insoluble in water but the former are readily solubilized in the lung while the latter are cleared mainly by mechanical transport via alveolar macrophages. The pulmonary retention half-times of inhaled cadmium compounds are longer by approximately a factor of ten in primates than in rats. Acute pulmonary inflammatory effects of inhaled cadmium compounds are related to their in vivo solubility, and an approximately 10-fold higher dose of cadmium sulfide as compared with the chloride or oxide must be administered to the lung to elicit the same inflammatory response. Differences in biological effects may also exist with respect to the chronic effects of inhaled cadmium compounds, e.g., the pulmonary carcinogenic potency of inhaled cadmium sulfide may be less than that of other cadmium compounds.

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

[Behavioral effects in mice exposed to the prolonged action of cadmium compound and zinc compound].

The aim of the present paper was to determine the effect of cadmium and zinc on the central nervous system in the experimental animals. The animals were given intraperitoneally the solution of cadmium and zinc chloride for 30 days. The behaviour of the mice was being observed in the test of the coordination of movements, the cognitive activity, the spontaneous motility, the motility in the straight rod test and the effect of the examined compounds on the temperature of the animal body was examined. Together with the dose and exposure time increase the cumulative action of cadmium compound was showed, resulting in the inhibiting effect on the central nervous system. The competitive action of zinc compound in relation to the toxic action of cadmium compound was revealed after the administration of the minimal doses.

Animals

Investigation on the carcinogenic effects of various cadmium compounds after inhalation exposure in hamsters and mice.

The inhalation of cadmium chloride aerosols induced lung carcinomas in rats (3). Subsequently, CdCl2 was classified as probably carcinogenic in humans (2). Thus the Cd compounds CdCl2, CdSO4, CdS and CdO were investigated for their carcinogenic potencies in the lungs of hamsters and mice. The same experiment was conducted by GLASER et al. with rats (1).

Administration, Inhalation

[Nephrotoxic action of platinum, chromium and cadmium compounds on marine bony fishes].

Intra-abdominal injections of platinum, chromium and cadmium salts to Myoxocephalus scorpius produce nephrotoxic effect which includes the disturbances in magnesium secretion. Basic ultrastructural changes in the nephron cells of the fish after the injection of nephrotoxic substances are similar to those in mammals. Cis-platinum induces significant damage in the terminal part of the proximal tubules. One day after the injection of chromium compounds, total damage of the proximal tubule is observed, whereas cadmium salt affects cells within the whole nephron. After 5 days of administration of cadmium and chromium salts, partial recovery was found with respect to both functional and ultrastructural properties of nephron cells. Administration of nephrotoxic substances which selectively injure different parts of the nephron enabled to perform more exact differentiation of the nephron elements in marine teleosts.

Animals

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

Effects of mucosal metallothionein in small intestine on tissue distribution of cadmium after oral administration of cadmium compounds.

The effect of mucosal metallothionein (MT) preinduced by zinc (Zn) on tissue distribution of cadmium (Cd) after administration of Cd with several chelating agents was studied in rats. After Cd-cysteine (Cd-Cys) was incubated with intestinal Zn-MT in vitro, all the Cd dissociated from Cys and exchanged the Zn bound to MT. However, dissociation of Cd bound to EDTA (Cd-EDTA) was not observed in the incubation mixture containing intestinal Zn-MT. The concentration of Cd in intestinal mucosa reached a maximum 16 hr after oral administration of Cd-Cys. The Cd level in the intestine was higher than that in the liver and kidney and was similar to that occurring after oral administration of CdCl2. The amount of Cd distributed to the liver and kidney after Cd-EDTA administration was about 30% of the level after CdCl2 administration. Even at 15 mg Cd/kg Cd-EDTA, the Cd level in the intestinal mucosa reached a plateau after 2-4 hr, as it did in the liver and kidney. When Cd-Cys was administered po to control or to Zn-pretreated rats, it was found that Zn pretreatment increased the concentration of Cd in the kidney, as was the case after oral administration of CdCl2. This effect of Zn pretreatment was not observed after oral administration of Cd-EDTA. When Cd-MT was injected into the duodenum, the intestinal absorption of Cd was 60% of that after CdCl2 administration. After the duodenal administration of Cd-MT, at all doses, the concentration of Cd in the kidney was higher than that in the liver. These results suggest that mucosal MT in the small intestine might trap Cd absorbed from the intestinal lumen and transport it to the kidney.

Administration, Oral

Acute inhalation study in the rat of comparative uptake, distribution and excretion for different cadmium containing materials.

Single 2-hr inhalation exposures were conducted at levels of approximately 100 mg/m3 (based on cadmium content) with the use of two cadmium pigments (cadmium red and cadmium yellow), a dust of cadmium carbonate, and a cadmium fume. An air exposed control group also was included. The rate of elimination of cadmium in the urine and feces, and the cadmium levels in selected tissues were measured at several intervals following the exposure. In addition, observations of the animals for clinical signs of toxicity and mortality and measurements of organ weights and body weight were performed. There was no mortality in the control, cadmium red or cadmium yellow exposed groups. In the cadmium carbonate exposed group, 3 out of 52 rats died, and in the cadmium fume exposed group, 25 out of 52 rats died. Cadmium blood levels indicated that cadmium from the cadmium carbonate and fume was absorbed to a greater degree than cadmium from the red and yellow pigments. The major route of elimination of cadmium following exposure to the two pigments was via the feces, with 80% being cleared within 24 hr. Elimination was slower following exposure to the carbonate. The levels of cadmium in the liver and kidneys were much higher following exposure to the carbonate than following exposure to the red and yellow pigments. It appeared that these cadmium compounds were not equivalent with respect to toxicity, absorption, distribution or excretion. Exposure to the two insoluble compounds, cadmium red and cadmium yellow, did not produce mortality and resulted in rapid elimination in the feces with lower tissue levels of cadmium than observed following exposure to the cadmium carbonate.

Animals

The search for chelate antagonists for chronic cadmium intoxication.

Cadmium is unique among the metals because of its combination of toxicity in low dosages, long biological half-life (of about 30 years in humans), its low rate of excretion from the body and the fact that it is stored predominantly in the soft tissues (liver and kidney). There has been an increase in exposure to cadmium because its presence in fertilizers and sewage sludge and also its increased industrial use in Cd-Ni batteries. Although there are a number of reports on occupational and environmental exposures to cadmium compounds, treatment of cadmium poisoning has been difficult because there is neither a safe practical means of evaluating bioavailable body burden nor is there a recommended therapeutic chelating agent for chronic cadmium intoxication. In this review, the various factors affecting the chelation of cadmium such as its binding to intracellular metallothionein, the structural requirements of compounds for effective removal of cadmium, the excretion pattern of cadmium after its mobilization from intracellular stores and the recent developments in the design and synthesis of new compounds for cadmium chelation are discussed. The importance of protecting sensitive organs such as kidney and brain during cadmium chelation is addressed. The progress made during the last decade on the synthesis of new compounds, especially derivatives of dithiocarbamates, is remarkable. Some of these compounds provide promise for development of a useful and safe therapeutic chelating agent which can be used for the assessment of cadmium body burden and for preventive removal of cadmium as well as for use in overt cadmium poisoning in humans.

Animals

[Health effects of occupational exposure to cadmium and its compounds and proposed preventive measures].

The paper presents effects of cadmium compounds upon human organism. Special attention was paid to disturbances resulting from chronic occupational exposure to those compounds. In addition, the description of toxic effects was supplemented with suggestions to carry on pre-employment and periodic examinations that would enable undertaking appropriate preventive measures for the population occupationally exposed to cadmium compounds.

Cadmium