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A systematic review of cytogenetic studies conducted in human populations exposed to cadmium compounds.

BACKGROUND: Exposure to cadmium fumes or dusts has been associated with an increased risk of lung cancer and the characterisation of the genotoxic potential of cadmium compounds is, among other possible mechanisms, an important element in the assessment of the carcinogenic hazard of the element. While there is some evidence that in experimental systems, cadmium compounds may exert genotoxic effects, the results of the epidemiological studies having examined cytogenetic endpoints in humans exposed to cadmium appear conflicting. Therefore, a systematic review was undertaken to assess whether a cytogenetic effect of cadmium exposure is supported by the studies with the strongest design. METHODS: The relevant literature was identified through several databases and assessed with a check-list by two reviewers. Causes of heterogeneity between studies were looked for. Results were extracted and the strength of the evidence was evaluated with causality criteria. RESULTS: No studies met the criteria for being considered as very convincing. Several factors were identified that could explain contradictory findings (small sample size, selection bias, insufficient characterisation of exposure, lack of consideration of confounders) but their actual impact could not be conclusively assessed with the published information. Importantly, it should be recognised that the absence of a clear mechanism for the cytogenetic action of cadmium compounds did not allow to select the most appropriate endpoint to be examined. CONCLUSIONS: No clear association between cadmium exposure and cytogenetic endpoint appeared but no definite conclusion can be drawn from the existing studies in humans. Future research efforts should mainly focus on experimental studies to understand how cadmium compounds could produce genotoxic/carcinogenic effects, in order to target the most relevant endpoint to be examined in humans.

Cadmium Compounds↗

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↗

113Cd Shielding Tensors of Monomeric Cadmium Compounds Containing Nitrogen Donor Atoms. 3. CP/MAS Studies on Five-Coordinate Cadmium Complexes Having N(3)X(2) (X = H, N, O, and S) Donor Atoms.

The principal elements of the (113)Cd shielding tensor for a set of five- coordinate compounds having mixed donor atoms coordinating to the cadmium were determined via CP/MAS NMR experiments. The first complex, [HB(3,5-Me(2)pz)(3)]CdBH(4) (where pz = pyrazolyl), has a CdN(3)H(2) inner coordination sphere. The isotropic chemical shift in the solid state is 355.1 ppm, and its chemical shift anisotropy (CSA, Deltasigma) is -596 ppm with an asymmetry parameter (eta) of 0.64. The second complex, [HB(3,5-Me(2)pz)(3)]Cd[H(2)B(pz)(2)], has five nitrogen donor atoms bonded to the cadmium. This N(5) or N(3)N(2) compound was the only material of this study to manifest dipolar splitting of the cadmium resonance from the quadrupolar (14)N. The isotropic chemical shift, CSA, and the value of eta for this material were therefore determined at higher field where the dipolar splitting was less than the linewidth, yielding values of 226.6 ppm, -247 ppm, and 0.32, respectively. A second N(5) material, [HB(3-Phpz)(3)]Cd[H(2)B(3,5-Me(2)pz)(2)], was also investigated and has an isotropic shift of 190.2 ppm, a CSA of 254 ppm, and an eta of 0.86. Also studied was [HB(3-Phpz)(3)]Cd[(Bu(t)CO)(2)CH], which has an CdN(3)O(2) inner core. The isotropic chemical shift of this complex is 173.6 ppm, and the values of Deltasigma and eta were determined to be -258 ppm and 0.38, respectively. The final compound, [HB(3,5-Me(2)pz)(3)]Cd[S(2)CNEt(2)], with N(3)S(2) donor atoms, has an isotropic shift of 275.8 ppm, an eta of 0.51, and a CSA of +375 ppm. Utilizing previous assignments, the most shielded tensor element was determined to be oriented normal to the plane of the tridentate ligand. The shielding tensor information is used to speculate on the coordination geometry of the CdN(3)O(2) inner core complex.

Journal Article↗

Biological assessment of exposure in factories with second degree usage of cadmium compounds.

Biological assessment of occupational exposure to cadmium in five different factories with low-level second degree usage of Cd-compounds has been carried out. In 124 exposed and control male workers the following measurements, were performed: cadmium in blood (CdB) and urine (CdU), B2-microglobulin (B2M), creatinin in urine (Creat), hemoglobin (Hb) and hematocrit (Ht). Analysis of 34 pairs of workers matched according to age, smoking habits, ethnic origin and factory, established a significant difference only in CdU, the geometric means being 0.67 microgram/g Creat in the exposed group and 0.48 microgram/g Creat in the control group. Significant correlation was found between CdU x age and CdB x smoking habits. Multiple regression analysis showed that for each year increase in age CdU increased 3%, for each percent increase of CdB CdU increased 0.28%; for each cigarette smoked per day CdB increased 1.6%. It is concluded that in this type of work the low external cadmium exposure does not express itself in different CdB-levels, but only in different CdU-levels, indicating an increased body burden due to long term low levels occupational cadmium exposure. In biological assessment of exposure to Cd, it is essential to take age and smoking habits fully into account.

Adult↗

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↗