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Hypoglycemic potency of novel trivalent chromium in hyperglycemic insulin-deficient rats.

Two sources of chromium III, "chromium 454" and "chromium picolinate," were tested in insulin-deficient Streptozocin-treated diabetic rats. This model was selected in order to evaluate the possibility of any hypoglycemic potency of chromium in a relative absence of blood insulin concentration. Three weeks of the treatment with CRC454 and CrP resulted in a 38% and 11% reduction of blood glucose levels, respectively. Body weight gains were equally improved by both treatments. Blood levels of CK, ALT and AST were significantly reduced by CRC454 and CrP. These results might suggest that any hypoglycemic effect of trivalent chromium under insulin-deficient conditions could be largely dependent upon the type of chromium agent and associated characteristics such as solubility and bioavalibility. In contrast, improvement of body weight gains and blood levels of CK, AST and ALT seems to be less dependent on the type of chromium compound under these experimental conditions. In conclusion, CRC454 showed significant reduction of hyperglycemia under insulin-deficient conditions.

Alanine Transaminase↗

[Perforation of the nasal septum of occupational origin].

Perforations of nasal septum as typical effects of exposure to certain hazards are a particular health problem among the diseases of upper respiratory tract mucous membranes (entry 10 on the list of occupational diseases). To obtain more data on etiopathogenetic factors and correlations between the clinical picture and exposure duration, the documentation of the patients in whom perforation was diagnosed during 1972-1979 was analysed epidemiologically. The examinations covered 185 workers of various industrial branches-salina, chemical plants, leather plants, tanneries, electroplating plants-who developed nasal septum perforation due to local effects of working environment irritants. In the test group the nasal septum was defected mostly in those exposed to chromium compounds (46.5%) and in salina workers (44.3%). In the remaining 9.2% of subjects the septum perforation resulted from exposure to arsenic, nickel, silicone compounds, cadmium, fluorine, soda and ammonia. The clinical course of the disease was presented as classified by industrial branch, occupational exposure, age and length of employment. In addition, procedures of diagnostics, certification and prevention were considered.

Abscess↗

Clastogenicity and mutagenicity of hexavalent chromium in lacZ transgenic mice.

The clastogenic and mutagenic effects of the hexavalent chromium compound K2CrO4 in lacZ transgenic mice (Muta Mouse) were investigated. Male Muta mice were administered an intraperitoneal dose of 40 mg/kg of K2CrO4 once on each of 2 consecutive days. The K2CrO4 induced a significant increase in the peripheral blood micronucleated reticulocyte count. Also, K2CrO4 induced a statistically significant increase in mutant frequency in the liver but not in the bone marrow on day 7 after the second treatment. The reason for the failure to increase the mutant frequency in the bone marrow may have been the rapid cell turnover rate there. The mutation induced by K2CrO4 in the bone marrow may have occurred in more differentiated cells than stem cells, and the rapid proliferative activity may have caused a rapid decrease in mutated cells by day 7. Further study with a sampling point earlier than day 7 is needed. The results obtained in the present study indicate that K2CrO4 has clastogenic and mutagenic potential in vivo.

Animals↗

[So-called Monday leukergy in polishers of chromium-tanned leather].

The authors carried out preliminary leukergy examinations on Mondays and Fridays in 18 polishers exposed to chromium compounds at concentration of 0.1 mg in 1.0 m3 of air. On Mondays leukergy (X*-SD) was significantly higher and amounted to 27.3 +/- 11.4%. On Fridays leukergy amounted to 18.4 +/- 11.4% and it was not statistically different from that in the control group.

Adhesiveness↗

Mortality study among workers producing ferroalloys and stainless steel in France.

A mortality study was carried out among the workers of a plant that had produced ferrochromium and stainless steel, and was still producing stainless steel, in order to determine whether exposure to chromium compounds, to nickel compounds, and to polycyclic aromatic hydrocarbons (PAH) could result in a risk of lung cancer for the exposed workers. The cohort comprised 2269 men whose vital status were recorded between 1 January 1952 and 31 December 1982. The smoking habits of 67% of the cohort members were known from medical records. The observed numbers of deaths were compared with the expected ones based on national rates with adjustment for age, sex, and calendar time. A low mortality, achieving statistical significance, was found from all causes (observed = 137, standardised mortality ratio (SMR) = 0.82) and from benign respiratory diseases (observed = one, SMR = 0.15). With regard to mortality from lung cancer, a non-significant excess appeared in the whole cohort (observed = 12, SMR = 1.40). Among the exposed workers, however, a significant lung cancer excess was found (observed = 11, SMR = 2.04) that contrasted with a low SMR (0.32) in the non-exposed group. This excess is unlikely to be explained by smoking, as the tobacco consumption of these two groups was similar. No trend was observed for mortality from lung cancer either according to time since first exposure, or according to duration of exposure. A nested case-control study clearly suggested that this excess of deaths from lung cancer was attributable to former PAH exposures in the ferrochromium production workshops rather than to exposures in the stainless steel manufacturing areas.

Case-Control Studies↗

[Use of colored samples in the detection of occupational exposure to allergic effects of chromium and nickel compounds].

By using a coloured sample with diphenylcarbazide, chromium content in raw materials and industrial intermediate products was determined. At the same time chromium content was determined quantitatively by atomic absorption. The method was said to be simple and easy to be done in any industrial physician's conditions. The sample's sensitivity was said to be 1:100 000. Results of the determinations indicated that protective leather gloves contained considerable content of chromium, and chromium-free machine oils and lubricants were polluted with chromium's minute quantities as the oils and lubrications were being used. It was stated that coloured samples aiming at the detection of chromium, cobalt and nickel should be routinely used in preventive activity of industrial physicians.

Chromium↗

Mortality from lung cancer and cardiovascular diseases among stainless-steel producing workers.

The mortality pattern of workers involved in the production of stainless steel (SS) was studied from 1968 to 1984 in order to investigate a possible risk of lung cancer in relation to exposure to chromium compounds, polycyclic aromatic hydrocarbons, and silica. The role of heat exposure in mortality from cardiovascular diseases also was examined. The cohort was comprised of 4,227 workers. Complete individual job histories were provided by the company (UGINE SA). The smoking habits of 24 percent of the cohort members were known from the interview of workers still active during the data collection. The observed numbers of deaths were compared with the expected ones based on national rates with adjustment for age, sex, and calendar time (standardized mortality ratio, SMR). No significant excesses of lung cancer were observed among workers employed in the manufacture of ferroalloys (SMR = 0.68) and in the melting and casting of SS (SMR = 1.04), whereas a significant excess appeared among SS foundry workers (SMR = 2.29). This excess was higher and remained significant among workers with more than 30 years since first employment in the foundry area (SMR = 3.34). Among subjects exposed to heat, no excess was observed for all cardiovascular diseases or for ischemic heart diseases.

Cardiovascular Diseases↗

[Reduction of chromium (VI) by reference bacterial strains].

Collection bacterial strains were found to be capable of chromium (VI) reduction although they had not been in contact with chromium compounds before. Strains capable of nitrate respiration could use bichromate ions as a terminal electron acceptor in the absence of competing acceptors. Cr(VI) was reduced to Cr(III) when bichromate was added to the cultural broth whose redox potential reached -140 mV.

Bacteria↗

Layered and pillared metal carboxyethylphosphonate hybrid compounds.

A series of carboxyethylphosphonate hybrid materials has been prepared: Mn(II)(O3PCH2CH2COOH) *H2O (1), Mn(III)(OH)(O3PCH2CH2COOH)*H2O (2), Al3(III)(OH)3(O3PCH2CH2CO2)2 *3H2O (3) and Cr2(III)(OH)3(O3PCH2CH2CO2) *3H2O (4). Compounds 1 and 2 were synthesized from Mn(III)(CH3COO)3 *2H2O under hydrothermal, or refluxing treatments, respectively. The crystal structures of the manganese-bearing solids have been solved ab initio from laboratory X-ray powder diffraction data and refined by the Rietveld method. 1 crystallises in a orthorhombic cell and 2 in monoclinic symmetry. Both solids have inorganic 2D layered structures with the acid carboxylic groups pointing towards the interlayer space, and the layers linked only through hydrogen bonds. The inorganic layers of these compounds are formed by manganese atoms in distorted octahedral environments linked together by the phosphonate groups. The crystal structure of 3 has been solved ab initio from synchrotron X-ray powder diffraction data. This solid shows a pillared structure with the phosphonate and carboxylate groups cross-linking the inorganic layers. These layers contain chains of aluminium octahedra running parallel to each other. 4 is amorphous and the IR-UV-VIS spectra suggest a framework with Cr(III) cations in octahedral environments. Thermal, spectroscopic and magnetic data for manganese and chromium compounds as well as the structural details of these solids are discussed.

Journal Article↗

Chromium VI-induced apoptosis in a human bronchial epithelial cell line (BEAS-2B) and a lymphoblastic leukemia cell line (MOLT-4).

Hexavalent chromium compounds are well-documented human carcinogens. In vitro experiments show Cr (VI) induces cell death by apoptosis by activating p53 protein. The aim of this study was to evaluate Cr (VI)-induced apoptosis in a human bronchial epithelial cell line (BEAS-2B) and in a lymphoblastic leukemia cell line (MOLT-4). Cr (VI) caused a dose- and time-dependent increase in the apoptosis rate in both cell lines. Western blotting showed increased p53 protein expression in MOLT-4 cells, but not in BEAS-2B cells, after exposure to 0.5 and 3 muM hexavalent chromium for 12 hours and 4 hours, respectively. Apoptotic cell death induced by Cr (VI) was not decreased by pretreatment with caspase-3, -8, and -9 inhibitors. These preliminary results provide evidence of Cr (VI)-induced apoptosis, which deserves further investigation in occupationally exposed workers.

Apoptosis↗

Pathways of Cr (III) and Cr (VI) in the rat after intratracheal administration.

51Cr-labelled Cr3+ and CrO2-4 solutions were administered intratracheally to male rats in doses of 0.1 and 10 micrograms of Cr per rat to evidentiate metabolic differences especially in the lung and in the mechanisms of excretion. Twenty four hours after administration the highest 51Cr amount was present in the lungs for both valency states, being in the Cr (III)-treated group, however, about two times higher. In all other tissues tested the values in the Cr (VI)-treated animals were much higher. Intracellularly, in the Cr (III)-treated group more than 40% of the total lung homogenate was found in the nuclear fraction and only 10% in the cytosol. In the Cr (VI)-treated group 25% was present in the nuclei and more than 50% in the cytosol. Gel filtration 24 h after intratracheal injection showed that in both cytosols chromium was eluted in three peaks including a low-molecular-weight component. Quantitatively, however, the ratios between the 51Cr associated with the three peaks were significantly different between the Cr (III)- and the Cr (VI)-treated animals. This suggests that binding of chromium to low-molecular-weight components should be involved in the passage of this element from the lung to the other tissues. Excretion studies for 7 days showed that after this time the Cr (III)-treated animals excreted about 4% of the dose via urine and more than 36% via faeces, whereas in the Cr (VI)-treated rats the 51Cr was eliminated nearly equally between urine and faeces.

Animals↗

Effects of chromium(VI) and chromium(III) on energy charge and oxygen consumption in rat thymocytes.

The cytotoxic effects of chromium compounds in two oxidation states have been studied in rat thymocytes. endogenous nucleotide levels and oxygen consumption were examined as relevant parameters of the physiological state of the cell. Incubation of rat thymocytes with Cr(VI) produced a marked unbalance of endogenous purine nucleotide pool and a parallel decrease in oxygen consumption. A close correlation between the reduction of oxygen consumption and ATP level in rat thymocytes treated with increasing concentrations of Cr(VI) has been found. In rat thymocytes permeabilized with digitonin and in isolated rat liver mitochondria both Cr(VI) and Cr(III) showed, at different range of concentrations, a marked inhibition of maximal oxygen consumption rate (uncoupled respiration). The effects observed were depending on chromium oxidation state and on different mitochondrial sites of substrate oxidation.

Adenosine Diphosphate↗

Chromium determination by supercritical fluid chromatography with inductively coupled plasma mass spectrometric and flame ionization detection.

Supercritical fluid chromatography (SFC) has been investigated for the separation of a pair of beta-ketonate chromium compounds and a thermally labile organochromium dimer. A limited comparison between flame ionization detection (FID) and inductively coupled plasma mass spectrometric (ICP-MS) detection of these compounds is presented. The beta-ketonate complexes were observed with both detectors, while the thermally labile dimer was not observed with ICP-MS detection. Detection limits for these compounds with ICP-MS were in the range of 0.9 to 3 pg with FID giving values between 10 and 250 pg. Reproducibility of the method is between 1 and 4% relative standard deviation (R.S.D.). The technique provided a linear response over approximately three orders of magnitude. The effect of two mobile phases (nitrous oxide and carbon dioxide) on the detection by each of the detectors are presented in a qualitative manner. Finally, the SFC-ICP interface heating method and the manner in which the restrictor is heated in the FID system are compared and there effect on the chromatography discussed.

Chromatography, High Pressure Liquid↗

A cohort mortality study among gas generator utility workers.

An earlier cohort study tracked the mortality experience through 1988 of male employees at five utility companies in the United States. Workers employed by the Pacific Gas and Electric Company (PG&E) were part of that study, but results for PG&E employees overall or for those involved in gas generator plant operations where hexavalent chromium compounds were used in open and closed systems from the 1950s to early 1980s were not reported. To evaluate risk of lung cancer and other diseases, a cohort of 51,899 PG&E male workers was followed for mortality from 1971 through 1997. Observed numbers of deaths were compared with those expected based on rates in the general California population, with standardized mortality ratios (SMR) and corresponding 95% confidence intervals (CI) calculated for the total cohort and for subsets defined by potential for gas generator plant exposure. A total of 10,591 deaths were observed, a number significantly less than expected (SMR, 0.89; 95% CI, 0.87 to 0.91). No significant excesses of total or specific cancers were observed, with SMR typically near or below 1.0. Lung cancer mortality in the entire cohort was close to expected (SMR, 0.98; 95% CI, 0.92 to 1.05), with no excess detected among persons who worked (SMR, 0.81; 95% CI, 0.35 to 1.60) or trained (SMR, 0.57; 95% CI, 0.12 to 1.67) at gas generator facilities. Furthermore, risk of lung cancer did not increase with increasing duration of employment or time since hire. The study thus provides no evidence that occupational exposures at PG&E facilities resulted in increased risk of lung cancer or any other cause of death. The results indicate that any chromium exposures were of insufficient magnitude to result in increased risk of lung cancer.

Adult↗

Risk of lung cancer among former chromium smelter workers.

Hexavalent chromium is a known carcinogen. Previous epidemiologic studies in the 1950s of United States workers from seven facilities producing chromium compounds from chromite ore have reported a markedly increased risk for dying from lung cancer. As part of a high risk notification project of workers from four of these facilities, a mortality study was performed. The cohort was assembled in 1990-1991 from the Social Security records of four former chromate producing facilities in northern New Jersey. The study subjects were known to have worked at these facilities some time between 1937 and 1971. Proportionate mortality and proportionate cancer mortality ratios (PCMR) were calculated. The overall risk for lung cancer was a PCMR of 1.51 (confidence limits [CL] 1.29-1.74) for white men and 1.34 (CL 1.00-1.75) for black men. These risks increased with increasing duration of employment and latency since time of first employment. The PCMR for greater than 20 years duration of work and more than 20 years since first exposure was 1.94 (CL 1.15-3.06) for white men and 3.08 (CL 1.13-6.71) for black men. The risk for lung cancer for white men remains elevated more than 20 years after exposure has ceased (PCMR, 1.29; CL 1.03-1.60). The PCMR for nasal cavity/sinus cancer was also found to be a significantly increased, 5.18 (CL 2.37-11.30). A cluster of bladder cancer was seen among black workers from one facility, (PCMR, 3.30; CL 1.42-6.51). Despite the cessation of exposure, former chromium workers remain at significantly increased risk of lung cancer. Although there have been case reports of nasal cavity/ sinus cancer in association with chromium exposure, this is the first epidemiologic study to report a significant increase in these cancers. Limitations in this study include lack of exposure data and lack of information on smoking habits. The lack of increase in other smoking-related diseases besides lung cancer indicates that the increase in lung cancer cannot be attributed to cigarette smoking. The ongoing elevated risk of lung cancer after cessation of exposure emphasizes the need for developing early detection texts for lung cancer.

Chromium↗

Induction of spindle inhibition and abnormal mitotic figures by Cr(II), Cr(III) and Cr(VI) ions.

A differential staining technique for chromosomes and spindles was used to compare the effects of chromium compounds of different oxidation states with either no, or very low (Cr(II) and Cr(III) or high (Cr(VI) carcinogenic properties. Neither CrCl2, nor CrCl3 (except at 10(-4) M) had any effect on spindle formation and/or chromosome segregation after exposure up to 10(-7) and 10(-5) M, respectively. None of them significantly influenced the mitotic index. In contrast, the Cr(VI) products (Na2CrO4 and CaCrO4) induced a dose-dependent increase of aberrant division patterns up to 10(-4) and 10(-5) M, respectively. Moreover, with CaCrO4, a high frequency of cells with dislocated metaphase chromosomes or malformed spindles with clustered chromosomes were observed. Since these cell types are potential sources of aneuploid daughter cells, they represent a potential risk for cancer induction. These experiments clearly demonstrate that the differential staining methods allows discrimination between spindle modifiers which induce lethal toxicity and those which may lead to possible tumour induction.

Carcinogens↗

XRCC1 protects against particulate chromate-induced chromosome damage and cytotoxicity in Chinese hamster ovary cells.

Water-insoluble hexavalent chromium compounds are well-established human lung carcinogens. Lead chromate, a model insoluble Cr(VI) compound, induces DNA damage, chromosome aberrations, and dose-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between lead chromate-induced DNA damage and chromosome aberrations is unknown. Our study focus was on examining the role of XRCC1 in lead chromate-induced cytotoxicity and structural chromosomal aberrations in CHO cells. Three different cell lines were used: AA8 (parental), EM9 (XRCC1 mutant), and H9T3 (EM9 complemented with human XRCC1 gene). Cytotoxicity was significantly higher in EM9 cells when compared to AA8 and H9T3 cells, indicating that XRCC1 is important for protecting cells from lead chromate particles-induced cell death. The frequency of damaged metaphase cells was not affected by XRCC1 deficiency. However, the total amount of Cr(VI)-induced chromosome damage was exacerbated by XRCC1 deficiency, and the spectrum of damage changed dramatically. Chromatid and isochromatid lesions were the most prominent aberrations induced in all cell lines. XRCC1 was essential to reduce the formation of chromatid lesions but not for isochromatid lesions. In addition, XRCC1 deficiency resulted in a dramatic increase in the number of chromatid exchanges, indicating that XRCC1 is involved in protection from lead chromate-induced chromosome instability.

Animals↗