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[Effects of chromium compounds on the respiratory system. Part 4. Long-term inhalation of chromic acid mist in electroplating to ICR female mice].

In order to determine the effect on the respiratory system of long-term inhalation of chromic acid in electroplating, histopathological examination was performed on mice (ICR, female, n = 50) exposed to chromic acid mist for 12 months (30 min/d, 2 d/wk), by using the authors' miniaturized chromium electroplating system. After 12 months' exposure, the mice were kept for 6 months without exposure. In the upper respiratory tract, round perforations were found in the nasal septum in 6 mice that were sacrificed or died after 10 months' exposure. The perforations were located near the point of the septum, the thinnest part of the nasal septum, and were of pin-hole sige. On the epithelium of the trachea and bronchus, loss of cilia, proliferation of goblet cells or basal cells, and squamous metaplasia were observed in almost all of the exposed mice. These changes appeared to be more advanced in mice exposed for a longer period. In the lung, development of benign adenoma was observed in one mouse in the 6- to 9-months' exposure group, in three in the 10- to 14-months' exposure group and in one in the group examined after 15 to 18 months. Furthermore, adenocarcinomas were found in two mice, one of which died at 17 months and the other was sacrificed 18 months after initiation of exposure. In conclusion, the finding that adenomas and adenocarcinomas were observed in mice exposed to chromic acid mist suggests the need to give careful attention to the possibility of respiratory cancers in chromium electroplating workers.

Adenocarcinoma↗

Incidence and localization of sister chromatid exchanges induced by nickel and chromium compounds.

Carcinogenic nickel compounds enhanced the incidence of sister chromatid exchanges (SCEs) in a concentration-dependent fashion in intact Chinese hamster ovary cells. There was a preferential induction of these exchanges in the heterochromatic regions of the chromosomes. CaCrO4 also caused a dose-dependent induction of SCEs. However, in contrast to NiCl2, the exchanges induced by CaCrO4 were not localized in any particular chromosomal region. The total incidence of exchanges was higher with CaCrO4 than with NiCl2. CaCrO4, crystalline NiS and NiCl2 enhanced the incidence of SCEs at concentrations below the threshold of DNA damage as detected by the technique of alkaline elution. Additionally, following treatment time intervals of 24-48 h, there was an increase in SCEs at concentrations of NiCl2 or CaCrO4 that produced little disruption of cell cycle progression. These results are consistent with the hypothesis that potently carcinogenic nickel compounds which are not very mutagenic exert selective effects on genetically inactive heterochromatin, while potently mutagenic and carcinogenic chromate do not appear to produce a similar predominance of SCEs in heterochromatic regions.

Cell Cycle↗

Recent advances in biological monitoring of hexavalent chromium compounds.

Intratracheal instillation of 51CrCl3 in anaesthetized rabbits resulted in partial absorption. In blood, the absorbed material was entirely confined to the plasma compartment. By contrast, after similar application of Na251CrO4 the bulk of blood radioactivity was present in red blood cells (RBC). It is suggested that Cr (VI) may enter the body not reduced via the lung and may be deposited in RBC for the cell's lifetime (approximately 110 d). Since inhalation of Cr (VI)-containing aerosols or particles is the main occupational exposure route for man, it is concluded that the chromium content of RBC could be used as a selective biological indicator for exposures to (carcinogenic) hexavalent chromium. The new theoretical concept was confirmed in a pilot study with workers of a dye pigment plant. Elevated chromium content of whole blood evoked by exposure to chromate particles correlated strongly with increased chromium values in RBC (correlation coefficient: 0.86).

Animals↗

Analysis of residual amino acid--DNA crosslinks induced in intact cells by nickel and chromium compounds.

Chinese hamster ovary cells were incubated with radioactive amino acids, the DNA was isolated by standard proteinase K/phenol/chloroform extraction and residual amino acids complexed to the DNA were examined as an index of metal induced DNA-protein crosslinks. Using this method, both chromate and nickel caused residual histidine and cysteine to be complexed with the DNA isolated from metal-treated cells. In the case of chromate, a number of amino acids were studied and Tyr, Thr and Cys were found to be complexed to DNA at a level (above the untreated control) that was statistically significant. Stability studies indicated that some of the chromate-induced DNA-protein complexes were mediated by direct participation of chromium(III), whereas others that were resistant to dissociation by EDTA and mercaptoethanol did not seem to involve direct chromium(III) participation. A significant portion of the cysteine complexed to DNA by chromate was believed to involve glutathione since treatment of cells with cycloheximide did not decrease chromate-induced cysteine-DNA crosslinks. In the case of nickel, most of the stable DNA-protein crosslinks did not involve direct metal participation and were probably oxidatively mediated by Ni(II)/Ni(III) redox cycling. These findings present new methodology for analysis of DNA-protein crosslinks by examination of residual amino acids associated with the DNA. This method should be highly sensitive and will yield important information about the mechanism of metal-induced DNA-protein crosslinks.

Amino Acids↗

[Eye lesion from chromium compounds and its treatment in an experiment].

Experiments on 68 rabbits with degree III burn induced by potassium bichromate were made to study and compare the therapeutic effect of subconjunctival injections of autoplasma with heparin and penicillin and instillations of spermaceti oil. Administration of spermaceti oil for the treatment of burns provides a more remarkable clinical effect, contributing to a milder course of burn process.

Animals↗

Review of genetic effects and mechanisms of action of chromium compounds.

When similar experimental conditions are adopted to test Cr(VI) and Cr(III) genotoxicity, only the former gives positive results, and Cr(III) is scored as genetically inert. Since Cr(III) seems to be the main final genotoxic agent inside the cell, the observed difference in genetic activity of the two oxidation states can be referred to the easy transport of Cr(VI) across the plasma membrane, as opposed to the lack of membrane carriers for Cr(III). If the experimental design is adjusted to Cr(III) properties, Cr(III) appears (mildly) genotoxic. The accepted inactivity of Cr(III) on whole cells is thus questionable and the environmental impact of Cr(III) accumulation is worth reconsidering.

Animals↗

Substituent effects in bis(arene)chromium compounds containing a CN group in the aromatic ring.

The crystal structures of Cr(PhCN)(2) (2), (PhCN)Cr(PhCH(3)) (3) and (PhCN)Cr(PhCF(3)) (4) prepared by means of the Metal Vapor Synthesis (MVS) technique have been determined. Compounds (2), (3) and (4) crystallize as discrete sandwich complexes having intrinsic C(2v)(mm2), C(s)(m) and C(1)(1) symmetries, respectively. The X-ray diffraction study has revealed a synperiplanar conformation for (2) and (3), and a synclinal conformation for (4) with a torsion angle (C(ipso)1-Centroid1-Centroid2-C(ipso)2) of phi = 63.5 degrees . The angles between the ligand planes are 2.2, 3.9 and 1.8 degrees , respectively. The Cr atom is slightly (by 0.04-0.06 A) displaced towards the substituents from the line connecting the centers of the opposite aromatic rings. The Cr-C(ipso) distances are 2.115 (2)-2.137 (2), 2.112 (2) and 2.185 (3) A for CN, CF(3) and CH(3) groups, respectively. The CN groups as well as the H atoms lie out of the C(6) ring planes and are bent towards the Cr atom, but the C atom of the CH(3) group also lying out of the C(6) ring plane is bent away from the Cr atom. The C atom of the CF(3) group is essentially coplanar to the C(6) ring plane. There are no unusual intermolecular contacts in the structures of (2)-(4).

Chromium↗

Sinonasal cancer and occupational exposure to formaldehyde and other substances.

A case-control study of cancer of the nose and paranasal sinuses was conducted in France to determine whether occupational exposure to formaldehyde was associated with an increased risk of sinonasal cancer. Exposures to 14 other substances or groups of substances were also studied (wood dust, leather dust, textile dust, flour dust, sugar dust, coal/coke dust, nickel compounds, chromium compounds, chromium VI, welding fumes, soldering fumes, cutting oils, paints and lacquers, glues and adhesives). Cases (n = 207) and controls (n = 409) were interviewed to obtain detailed information on job history and other potential risk factors for sinonasal cancer. In addition, a questionnaire specially designed for this study was used to help assess exposures to formaldehyde and other substances of interest. The questionnaires were translated into history of occupational exposure by an expert in industrial hygiene, without knowledge of case-control status. Several exposure variables (lifetime average level, duration, cumulative level) were used to describe the risk related to exposure to formaldehyde. Potential confounding factors (occupational and non-occupational) were examined and adjusted for when necessary. No significant association was found between exposure to formaldehyde and squamous-cell carcinomas of the sinonasal cavities. Because of the strong association between exposure to wood dust and nasal adenocarcinoma, it was not possible to assess an independent effect of formaldehyde on this type of cancer. However, among males exposed to medium or high levels of wood dust, the risk of adenocarcinoma associated with formaldehyde was significantly elevated for the highest exposure categories for average level (OR = 5.3, 95% confidence interval = 1.3-22.2), cumulative level (OR = 6.9, 95% CI = 1.7-28.2) and duration of exposure (OR = 6.9, 95% CI = 1.7-27.8). Although a residual confounding effect of wood dust could not be excluded, this study suggests that exposure to both formaldehyde and wood dust may increase the risk of nasal adenocarcinoma, by comparison with the risk due to wood dust alone. This study also indicated an increased risk among males who had been exposed to glues and adhesives, for all histologic types, which was not explained by a confounding effect of paints and lacquers, wood dust or formaldehyde. No other significant association was observed.

Adenocarcinoma↗

Occupational risk factors for renal cell carcinoma in Montreal.

BACKGROUND: Little is known about the role of workplace exposures on the risk of renal cell cancer. METHODS: A population-based case-control study was undertaken in Montreal to assess the association between hundreds of occupational circumstances and several cancer sites, including the kidney. A total of 142 male patients with pathologically confirmed renal cell carcinoma, 1900 controls with cancer at other sites and 533 population-based controls were interviewed. Detailed job histories and relevant data on potential confounders were obtained. A group of chemists-hygienists evaluated each job reported and translated them into a history of occupational exposures using a checklist of 294 substances. Multivariate logistic regression models using either population, cancer controls, or a pool of both groups were used to estimate odds ratios. RESULTS: There were some indications of excess risks among printers, nursery workers (gardening), aircraft mechanics, farmers, and horticulturists, as well as in the following industries: printing-related services, defense services, wholesale trade, and retail trade. Notwithstanding the low precision of many of the odds ratio estimates, the following workplace exposures showed some evidence of excess risk: chromium compounds, chromium (VI) compounds, inorganic acid solutions, styrene-butadiene rubber, ozone, hydrogen sulphide, ultraviolet radiation, hair dust, felt dust, jet fuel engine emissions, jet fuel, aviation gasoline, phosphoric acid and inks. CONCLUSIONS: For most of these associations there exist no, or very little, previous data. Some associations provide suggestive evidence for further studies.

Adult↗

Binding of chromium to chromatin and DNA from liver and kidney of rats treated with sodium dichromate and chromium(III) chloride in vivo.

The in vivo binding of chromium to whole chromatin, polynucleosomes, DNA, and cytoplasmic RNA-protein fraction from liver and kidney was examined after treatment of rats with sodium dichromate and chromium(III) chloride. Significant amounts of chromium were bound to DNA and the nonhistone proteins of chromatin and to cytoplasmic RNA-protein fraction. The binding of chromium to the nuclear and cytoplasmic nucleic acid fractions varied considerably, depending on the tissue and the oxidation state of the chromium administered. The level of chromium bound to whole chromatin was greater in the liver than in the kidney after treatment with either chromium compound. Chromium entered the liver and kidney tissues at a slower rate after chromium(III) treatment than after chromium(VI) treatment. At early times after chromium(VI) treatment, more chromium was bound to the liver and kidney chromatin and DNA than after chromium(III) treatment. A much smaller proportion of the chromium bound to chromatin was associated with the DNA after treatment with chromium(III) than after treatment with chromium(VI). However, 40 hr after injection, there was no significant difference in the level of chromium on the DNA from both the liver and kidney of chromium(VI)- and chromium(III)-treated animals. No DNA damage was detected in either liver or kidney nuclei after chromium(III) treatment, using the technique of alkaline elution. A possible correlation between chromium binding to chromatin and DNA damage is discussed.

Animals↗

Mutagenicity of a series of hexacoordinate chromium (III) compounds.

17 chromium(III) compounds have been tested for DNA-damaging capabilities using an E. coli differential repair assay and for mutagenicity in strains of Salmonella typhimurium. 4 of these compounds were active in both assays. Another 4 compounds were positive only in the repair assay and 9 were devoid of activity in both assays. Most of the doubly active complexes contain aromatic amine ligands like 2,2'-bipyridine and 1,10-phenanthroline. Closely related complexes of ligands derived from saturated amines are much less active. It appears that chromium(III) in the proper ligand environment can have considerable genetic toxicity and could represent one of the several possible ultimate species in a mechanism for chromium mutagenesis and carcinogenesis.

Chromium↗

Oxidation of inactive trivalent chromium to the mutagenic hexavalent form.

Soluble trivalent chromium compounds (chromium potassium sulfate, chromium nitrate, chromium chloride, neochromium and chromium alum) were inactive for Salmonella typhimurium TA100, even at milligram amounts per plate. No effect could be detected either in the absence or in the presence of rat-liver, lung or muscle microsomal fractions, of rat-muscle mitochondria (with or without ATP), of oxidized glutathione (GSSG), or of human serum, plasma or erythrocyte lysates. Conversely, addition of a strongly oxidizing agent (potassium permanganate) resulted in toxic effects in plates incorporating more than 40--80 microgram of compounds and elicited a dose-effect mutagenic response at 10--40 microgram per plate. These effects could be ascribed to oxidation of chromium from the trivalent to the active hexavalent state. Insoluble chromite, as tested in the spot test, was spontaneously mutagenic, owing to contamination of the industrial product with hexavalent chromium. The results obtained may be useful to interpret the findings of carcinogenicity tests and to predict health hazards linked to chromium.

Chromium↗

Assessment of efficacy of quercetin-5'-sulfonic acid sodium salt in the treatment of acute chromium poisoning: experimental studies.

Hexavalent chromium compounds exhibit higher toxicity than its trivalent compounds since chromium ions in the +6 oxidation state easily cross biological membranes. It has recently been proposed that substances reducing chromium ions from the +6 to the less toxic +3 oxidation state can be beneficial in management of acute chromium poisoning. In vitro studies also demonstrated quercetin-5 '-sulfonic acid sodium salt (NaQSA) to reduce chromium ions from the +6 to the +3 oxidation state. The aim of the study was to determine efficacy of NaQSA in treatment of acute poisoning with a hexavalent chromium compound. The experiment was carried out on male and female Wistar rats which were divided into 4 experimental (A,B,C,D) and control (K) groups. All animals received intragastrically a single CrO3 dose equal to its LD50. Thirty minutes after administration of CrO3, NaQSA was administered intragastrically at a dose of 50 mg/kg (group A) and 100 mg/kg (group B). In groups C and D, NaQSA was administered ip 2 h after administration of CrO3 and then twice a day for 4 days at doses of 50 mg/kg (group C) and 100 mg/kg (group D). Only intragastric administration of NaQSA at a dose of 100 mg/kg decreased mortality in acute poisoning with CrO3. In groups B and D, aminotransferase activity was statistically significantly dropping from day 7 of the experiment in comparison with the group K, which indicates lesser damage to the liver in animals treated with NaQSA. Bilirubin concentrations in groups B and D were also much lower than in the group K, but the difference between average bilirubin levels in these groups and the K was not statistically significant. The results of the study suggest the usefulness of NaQSA in the treatment of poisoning with hexavalent chromium compounds.

Acute Disease↗

[Effects of several compounds on the chromium uptake from surrounding medium by HeLa cells (author's transl)].

Radiochromium uptake from surrounding by HeLa cells was examined, the results were as follows: 1) The chromium uptake by the cells after a certain period of incubation in Ca-Mg free phosphate buffered solution (PBS) with radiosodiumchromate (Na251CrO4) was higher than that in serum free Eagle's minimum essential medium with the same concentration of the radiochromate. 2) When the various amount of L-ascorbic acid was added to the above rabiochromate containing PBS, the chromium uptake by the cells decreased with dependence on the concentration of the acid in the surrounding medium. However, when sodiumthiosulfate was added to the medium, no remarkable effect was found. 3) When cells were incubated in the radiochromic chloride(51CrCl3)containing medium with 6.5 microgram/ml of sodium oxalate, sodium acetate or sodium nitrate, the chromium uptake by the cells increased in comparison with the control. Above results suggested that the chromium uptake by the HeLa cells from surrounding medium was affected by several chemicals and the uptake or binding capacity of chromium was closely related to the reported cytotoxicity of the chromium compounds.

Ascorbic Acid↗

Carcinogenicity of trace elements with reference to evaluations made by the International Agency for Research on Cancer.

The monograph program of the International Agency for Research of on Cancer has evaluated many trace elements for their carcinogenicity to humans. Five groups of compounds were considered human carcinogens: arsenic and arsenic compounds, beryllium and beryllium compounds, cadmium and cadmium compounds, hexavalent chromium compounds, and nickel compounds. Antimony trioxide, cobalt and cobalt compounds, lead and inorganic lead compounds, methylmercury compounds, and metallic nickel were considered possibly carcinogenic to humans. Antimony trisulfide, trivalent chromium compounds, metallic chromium, ferric oxide, organolead compounds, metallic mercury, inorganic mercury compounds, selenium and selenium compounds, and titanium dioxide were not classifiable. Trace elements studied to a limited extent include copper, manganese, tin, vanadium, and zinc. Among the problems are the lack of relevant data, the definition of active species, the extrapolation of the results of experimental studies to humans, the methodological problems of epidemiologic studies, and the possible anticarcinogenic activity of some trace elements.

Humans↗