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Lipoperoxidation products and thiol antioxidants in chromium exposed workers.

Hexavalent chromium is an established carcinogenic agent, which is not directly reactive with DNA. Its genotoxicity involves a reduction step, producing reactive oxygen species and radicals, and also lower valence forms which form stable complexes with intracellular macromolecules. The trivalent form of chromium may directly react with the genetic material and has also been shown to generate oxidative damage in vitro. To further evaluate the importance of in vivo oxidative DNA damage in the toxicity of each valence form, we conducted a comparative study on hexavalent and trivalent chromium-exposed workers (manual metal arc stainless steel welders and leather tanning workers), focusing on the total oxidative status by quantifying the level of lipoperoxidation products in urine. Thiol antioxidants are important in response to oxidative stress, and therefore, the concentration of glutathione and cysteine in peripheral blood lymphocytes was also determined. Chromium exposure was evaluated by quantifying total chromium in plasma and urine. Both groups had a significant increase in lipid peroxidation products expressed as malondialdehyde (MDA) in urine (tanners 1.42 +/- 0.61 micromol/g creatinine, welders 1.67 +/- 1.13 micromol/g creatinine versus controls 0.81 +/- 0.26 micromol/g creatinine, P < 0.005 in both cases) but only welders had a significant decrease in glutathione concentration in lymphocytes. There was a positive correlation between chromium in plasma and urinary MDA in welders, but not in tanners. This work is part of a larger study of which major results have been published previously including cytogenetics and DNA-protein cross-links in workers exposed to the two different forms of chromium. These results are compared with the results of oxidative damage from this study.

Antioxidants↗

Penetration of chromium in intact human skin in vivo.

Graphite furnace atomic absorption spectroscopy was modified to permit analysis of solid material, thereby fully utilizing the high sensitivity of the method. Tangential sections of biopsies from skin tested epicutaneously with K2Cr2O7 were analyzed for the content of chromium 5, 24, and 72 hr after application of the test substance in various concentrations, either in petrolatum or in water. The concentration of chromium as a rule showed 2 maxima, one at the dermal-epidermal junction and the other in upper mid-dermis. The content of chromium was of the same order of magnitude at all 3 times after application. This indicates that a steady state is reached already after 5 hr and that penetration is continuing at 72 hr. The chromium content in normal skin was 0.4-2 ppm. K2Cr2O7 in petrolatum penetrated to a greater extent than in water. The relative penetration of chromium was lower for 0.5% concentration than for 0.05%. A complex of chromium and glycine was found to penetrate into the skin but to a lower extent than K2Cr2O7. It also elicited a positive epicutaneous test reaction in 1 out of 2 individuals hypersensitive to chromium.

Biopsy↗

Hexavalent chromium and lung cancer in the chromate industry: a quantitative risk assessment.

The purpose of this investigation was to estimate excess lifetime risk of lung cancer death resulting from occupational exposure to hexavalent-chromium-containing dusts and mists. The mortality experience in a previously studied cohort of 2,357 chromate chemical production workers with 122 lung cancer deaths was analyzed with Poisson regression methods. Extensive records of air samples evaluated for water-soluble total hexavalent chromium were available for the entire employment history of this cohort. Six different models of exposure-response for hexavalent chromium were evaluated by comparing deviances and inspection of cubic splines. Smoking (pack-years) imputed from cigarette use at hire was included in the model. Lifetime risks of lung cancer death from exposure to hexavalent chromium (assuming up to 45 years of exposure) were estimated using an actuarial calculation that accounts for competing causes of death. A linear relative rate model gave a good and readily interpretable fit to the data. The estimated rate ratio for 1 mg/m3-yr of cumulative exposure to hexavalent chromium (as CrO3), with a lag of five years, was RR=2.44 (95% CI=1.54-3.83). The excess lifetime risk of lung cancer death from exposure to hexavalent chromium at the current OSHA permissible exposure limit (PEL) (0.10 mg/m3) was estimated to be 255 per 1,000 (95% CI: 109-416). This estimate is comparable to previous estimates by U.S. EPA, California EPA, and OSHA using different occupational data. Our analysis predicts that current occupational standards for hexavalent chromium permit a lifetime excess risk of dying of lung cancer that exceeds 1 in 10, which is consistent with previous risk assessments.

Adult↗

Transverse strength, ductility, and qualitative elemental analysis of cobalt-chromium alloy after various durations of induction melting.

PURPOSE: The aim of this study was to compare the transverse strength and ductility of bars cast from cobalt-chromium alloy that had been melted for various lengths of time (n = 5 per group). To determine its elemental composition, the cobalt-chromium alloy was also analyzed qualitatively. MATERIALS AND METHODS: Transverse strength and ductility of the cobalt-chromium bars was measured by a three-point loading test. Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) were used to determine the composition of the samples compared with unmelted cobalt-chromium alloy. RESULTS: The transverse strengths of the test bars cast from the cobalt-chromium alloy, which had been induction-melted for various lengths of time, did not differ significantly (p = .056); but the ductility of the test bars was affected by the duration of induction melting of the alloy (p < .001). According to the SEM/EDS analysis, the amount of silicon in the cobalt-chromium alloy decreased with lengthening duration of induction melting of the alloy. CONCLUSIONS: This study supports the previous finding that good resistance to deflection fatigue is correlated with increased ductility of cobalt-chromium alloy and vice versa.

Analysis of Variance↗

Addition of ferrous sulfate to cement and risk of chromium dermatitis among construction workers.

Lowering the water-soluble chromium content of cement to < 2 ppm has been suggested to diminish the risk of allergic hand dermatitis caused by chromium among construction workers. The prevalence of chromium dermatitis was determined for a representative sample of 913 house construction workers and 707 concrete element prefabrication workers, with a questionnaire and clinical examination, before the use of cement with such a low content of water-soluble chromium was started on Finnish construction sites in 1987. The prevalence of allergic contact dermatitis caused by water-soluble chromium, diagnoses confirmed with patch tests among the workers with hand dermatitis, was 9/117 (7.7%). 4 of them were new 4/105 (4%) and 5 had been diagnosed earlier. In 1987, the prevalence of work-related hand dermatitis (allergic and irritant together) was 6.8% among the construction workers and 8.9% among the concrete element prefabrication workers. The Finnish Register of Occupational Diseases was checked for reports of chromium dermatitis and other forms of hand dermatitis from 1978 to 1992. The results indicated that, after 1987, the occurrence of allergic contact dermatitis caused by chromium decreased to less than 1/3 the previous level, whereas the occurrence of irritant contact dermatitis remained stable throughout the observation period. Regardless of some potential confounders, the addition of ferrous sulfate to cement during the production process may have reduced the number of cases of allergic contact dermatitis among construction and concrete element prefabrication workers. Our results agree with the results of Danish studies and Swedish observations.

Adolescent↗

Neurologic symptoms due to possible chromium deficiency in long-term parenteral nutrition that closely mimic metronidazole-induced syndromes.

BACKGROUND: We previously described a patient on home parenteral nutrition (HPN) who developed glucose intolerance and neuropathy that only responded to an infusion of chromium. A patient on HPN who had neuropathy and glucose intolerance was studied. He was also on metronidazole, which could have caused the neuropathy, but the symptoms and signs persisted. METHODS: Baseline clinical examination, nerve conduction studies, serum vitamin and trace element levels, and glucose tolerance were measured. Then, 250 micrograms of trivalent chromium as the chloride salt was infused daily for 2 weeks. The above studies were repeated. RESULTS: The patient at baseline had peripheral neuropathy of the axonal type and was glucose intolerant. Serum chromium was raised in this patient above the reference range. Despite raised serum levels, the infusion of chromium resulted in clinical remission that was marked 4 days after starting the infusion. Normalization of nerve conduction also occurred within 3 weeks of the initial study. CONCLUSIONS: Neuropathy and glucose intolerance may occur despite increased serum chromium levels and respond to chromium infusion. The previous use of drugs such as metronidazole should not exclude chromium as a potential treatment for neuropathy in HPN patients.

Adult↗

Effects of dietary chromium and zinc on egg production, egg quality, and some blood metabolites of laying hens reared under low ambient temperature.

This experiment was conducted to evaluate the effects of chromium (chromium picolinate, CrPic) and zinc (ZnSO4 x H2O) on egg production, egg quality, and serum insulin, corticosterone, glucose, cholesterol, and total protein concentrations of laying hens reared under a low ambient temperature (6.8 degrees C). One hundred twenty laying hens (Hy-Line; 32 wk old) were divided into 4 groups, 30 hens per group. The laying hens were fed the control diet (T1) or the control diet supplemented with either 400 microg of Cr/kg of diet (T2), 30 mg of Zn/kg of diet (T3), or 400 microg of Cr plus 30 mg of Zn/kg of diet (T4). Although the dry matter intake (DMI) was similar (p > 0.05) for all treatment groups, supplemental chromium and zinc either individually or together increased live-weight change, egg production, and improved feed efficiency (p < 0.05). However, no significant differences were observed between T4 and T2 or T3. Compared to T1, supplemental chromium and zinc increased egg weight, eggshell weight, eggshell thickness, egg specific gravity, and Haugh unit (p < 0.05) in T2, T3, and T4 groups, among which there was no significant difference. Serum insulin concentration increased (p < 0.05) and corticosterone concentration decreased (p < 0.05) with dietary chromium and zinc supplementation. Serum glucose and choles- terol concentrations decreased (p < 0.05) and protein concentrations increased (p < 0.001) with dietary chromium and zinc supplementation in all treatment groups. The results of this study indicated that either supplemental dietary chromium or zinc increased plasma insulin and decreased corticosterone concentrations and that had a positive effect on performance of laying hens under low ambient temperature.

Animals↗

Absorption of inorganic, trivalent and hexavalent chromium following oral and intrajejunal doses in rats.

The intestinal absorption of trivalent and hexavalent chromium (Cr) given orally (experiment I) or infused in the intestine (experiment II) was investigated in rats. The nonabsorbable form of chromium (51Cr2O3) and water-soluble and more absorbable Na2(51)CrO4 (the hexavalent form of Cr) were compared. Total retention of chromium given orally ranged around 15 percent of the dose, regardless of the chromium compounds applied. The absorption rate of chromic oxide, which is considered a nonabsorbable compound, was 14.4 as a percentage of chromium intake. This result indicates that some loss of chromium has to be taken into account in metabolic trials made by the indicator method. In isolated rat intestine, from the injected Cr 2.5% of chromic oxide and 43.2% of sodium chromate were absorbed during an hour (experiment II). The absorbed chromium was transferred to the liver where the liver tissue retained 10.9% of chromic oxide and 51.1% of sodium chromate. Radioactivity of v. cava caudalis following intestinal injection of Na2CrO4 was thirtyfold greater than after Cr2O3 dosing. This phenomenon can be explained by the lower blood clearance of chromate. Different absorption rate of chromate depending on the route of administration could be due to the fact that the hexavalent form given orally was reduced to Cr3+ in the acidic environment of the stomach. When Na2CrO4 was infused directly in the intestine of rats, such reduction could not occur. This means that the acidic gastric juice might play a role in inhibiting the intestinal absorption of Na2CrO4 when this compound is given orally.

Administration, Oral↗

Effects of aerobic exercise and training on the trace minerals chromium, zinc and copper.

Aerobic exercise and training lead to numerous changes and/or adaptations in the normal physiological functioning of the body. The trace minerals chromium, zinc, and copper are directly involved in maintaining and regulating many of these physiological processes, especially those involved in normal carbohydrate, fat and protein metabolism and the ultimate formation of usable energy. Therefore, it is important to establish whether exercise and training alter the functions of these trace elements, and to determine the overall effects of exercise on nutritional status and physical performance. Exercise results in a marked mobilisation of chromium into circulation, while zinc and copper levels have been shown to either remain stable or increase. Exercise also results in large increases in excretion of chromium, zinc and copper. Urinary chromium excretion has been shown to increase on an exercise day compared with a rest day, while increased zinc losses occur in urine and sweat and increased copper losses occur in urine, and faeces. When exercise-enhanced trace mineral losses are coupled with dietary intakes below the recommended levels, which are commonplace for both sedentary and exercising individuals, the nutritional status and overall health of exercising individuals may be suboptimal. Individuals who train intensively may be at special risk due to repeated increased losses. Trained athletes have lower resting urinary chromium losses, larger increases in urinary chromium losses due to exercise, lower resting serum zinc levels, and possible alterations in copper nutriture compared with sedentary controls. These changes suggest an altered metabolism and/or nutritional status of the trace minerals chromium, zinc, and copper in trained individuals and those who exercise strenuously.

Chromium↗

The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent.

The element chromium apparently has a role in maintaining proper carbohydrate and lipid metabolism in mammals. As this role probably involves potentiation of insulin signalling, chromium dietary supplementation has been postulated to potentially have effects on body composition, including reducing fat mass and increasing lean body mass. Because the supplement is absorbed better than dietary chromium, most studies have focused on the use of chromium picolinate [Cr(pic)(3)]. Cr(pic)(3) has been amazingly popular with the general public, especially with athletes who may have exercise-induced increased urinary chromium loss; however, its effectiveness in manifesting body composition changes has been an area of intense debate in the last decade. Additionally, claims have appeared that the supplement might give rise to deleterious effects. However, over a decade of human studies with Cr(pic)(3) indicate that the supplement has not demonstrated effects on the body composition of healthy individuals, even when taken in combination with an exercise training programme. Recent cell culture and in vivo rat studies have indicated that Cr(pic)(3) probably generates oxidative damage of DNA and lipids and is mutagenic, although the significance of these results on humans taking the supplement for prolonged periods of time is unknown and should be a focus for future investigations. Given that in vitro studies suggest that other forms of chromium used as nutritional supplements, such as chromium chloride, are unlikely to be susceptible to generating this type of oxidative damage, the use of these compounds, rather than Cr(pic)(3), would appear warranted. Potential neurological effects (both beneficial and deleterious) from Cr(pic)(3) supplementation require further study.

Animals↗

Beneficial effect of chromium-rich yeast on glucose tolerance and blood lipids in elderly subjects.

Twenty-four volunteers, mean age 78, including eight mildly non-insulin-dependent diabetics, were randomly allocated to one of two groups and were fed (daily for 8 wk) 9 g of either chromium-rich brewers' yeast (experimental) or chromium-poor torula yeast (control). Before and after yeast supplementation, the serum glucose and insulin response to 100 g oral glucose was measured at 30 min intervals for 2 h. Fasting serum cholesterol, total lipids, and triglycerides were also determined. In the total experimental group (normals + diabetics) and in both the diabetic and nondiabetic experimental subgroups, glucose tolerance improved significantly and insulin output decreased after supplementation. Cholesterol and total lipids fell significantly after supplementation in the total experimental group. The cholesterol decrease was particularly marked in hypercholesterolemic subjects (cholesterol > 300 mg/dl). In the control group, no significant change in glucose tolerance, insulin, triglycerides, or total lipids was found. Cholesterol was significantly lowered in the nondiabetic but not in the diabetic group. Thus, chromium-rich brewers' yeast improved glucose tolerance and total lipids in elderly subjects, while chromium-poor torula yeast did not. An improvement in insulin sensitivity also occurred with brewers' yeast supplementation. This supports the thesis that elderly people may have a low level of chromium and that an effective source for chromium repletion, such as brewers' yeast, may improve their carbohydrate tolerance and total lipids. The improvement in serum cholesterol in some control subjects, as well as in the total experimental group, also suggests the presence of a hypocholesterolemic factor other than chromium in both brewers' and torula yeast.

Aged↗

Chromium in the prevention and control of diabetes.

Chromium is an essential nutrient involved in the metabolism of glucose, insulin and blood lipids. Suboptimal dietary intake of chromium is associated with increased risk factors associated with diabetes and cardiovascular diseases. Within the past five years, chromium has been shown to improve glucose and related variables in subjects with glucose intolerance and type 1, type 2, gestational and steroid-induced diabetes. Severe neuropathy and glucose intolerance of a patient on total parenteral nutrition, who was receiving currently recommended levels of chromium, were reversed by additional supplemental chromium. Chromium increases insulin binding to cells, insulin receptor number and activates insulin receptor kinase leading to increased insulin sensitivity. Additional studies are urgently needed to elucidate the mechanism of action of chromium and its role in the prevention and control of diabetes.

Animals↗

Chromium-induced membrane damage: protective role of ascorbic acid.

Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80-100 g body weight). It has been observed that the intoxication with chromium (i.p.) at the dose of 0.8 mg/100 g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospholipid of both liver and kidney. The alkaline phosphatase, total ATPase and Na(+)-K(+)-ATPase activities were significantly decreased in both liver and kidney after chromium treatment, except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid (i.p. at the dose of 0.5 mg/100 g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

Adenosine Triphosphatases↗

[Effects of chromium and fish oil on insulin resistance and leptin resistance in obese developing rats].

In order to study the effects of chromium and fish oil on insulin resistance and leptin resistance in obese rats, 50 rats were divided randomly into five groups: basal diet group was fed on normal diet, other four groups were fed on high fat diet. In addition to high fat diet, chromium group fed chromium (3 mg/kg BW), fish oil group fish oil(5 ml/kg BW) and chromium + fish oil group fed chromium(3 mg/kg BW) plus fish oil(5 ml/kg BW). Blood samples were collected in the following five weeks from tail each week to determine blood sugar, insulin and leptin. The results showed that blood sugar, insulin and leptin in fish oil group and chromium group were lower than those in high fat diet control group. Chromium and fish oil improved the insulin resistance and leptin resistance.

Animals↗

[Study on the blood glucose and lipid of soybean milk rich in chromium to diabetic rats].

UNLABELLED: To reveal the effects of soybean milk with chromium fortification on the blood glucose and lipid of diabetic rat dealt with alloxan. The alloxan diabetic rats were divided into three groups and were fed continuously with the soybean milk without chromium fortification [Cr 0.25 microgram/(d.kg BW)], and with low chromium [Cr 30 micrograms/(d.kg BW)] and high chromium fortification [Cr 300 micrograms/(d.kg BW)] respectively for four weeks. The blood samples from all experimental rats tail vine were obtained each week. Blood glucose, total cholesterol, triglyceride, very low-density lipoprotein, high-density lipoprotein and insulin were tested. RESULTS: The concentrations of blood glucose, total cholesterol, triglyceride, very low-density lipoprotein and insulin were lowered significantly, and high-density lipoprotein was elevated significantly in the rats fed by soybean milk with high chromium fortification during the experimental period. The effect of improving blood glucose concentration in the group of soybean milk with high chromium fortification is significantly better than that in other groups. CONCLUSION: The present investigation indicates that soybean milk with chromium fortification can improve glucose and lipid metabolism of diabetic rat, and has a potential use in the diabetes mellitus prevention and control.

Alloxan↗

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↗

[Experiment study on the estrogen-like effect of compounds of mercury, chromium and manganese].

OBJECTIVE: In order to study estrogen-like effect of compounds of Mercury, Chromium and Manganese. METHODS: Mercury Chloride, Manganese Sulfate, Chromium Chloride and Chromium trioxide were selected to perform proliferation assay of MCF-7 human breast cancer cells and binding assay of estrogen receptor for rat uterine. RESULTS: Mercury Chloride could stimulate the proliferation of MCF-7 cell, the maximal increase of MCF-7 cells was measured by Mercury Chloride at 10(-7) mol/L. The effect was blocked completely by a pure antigestrogen ICI182, 780; but Mercury Chloride could not bind to ER by competing with E2. Chromium Chloride, Chromium Trioxide and Manganese Sulfate were not able to stimulate the proliferation of MCF-7 cell and bind to ER through competing against 3H-E2 in vitro. CONCLUSION: Mercury Chloride exhibited the estrogenicity through binding and activating ER; Chromium Chloride, Chromium trioxide and Manganese Sulfate did not show any estrogenicity.

Animals↗

Killing of chromium-damaged cells by mismatch repair and its relevance to carcinogenesis.

Hexavalent chromium compounds are widespread environmental contaminants that are well recognized as human carcinogens and potent respiratory toxicants. Intracellular metabolism of chromium(VI) leads to the production of numerous chromium-DNA adducts that are primarily formed at the phosphate groups. The mechanism of toxicity of these DNA modifications in human cells has been uncertain for a long time because chromium and other phosphate-based adducts did not block DNA replication with purified polymerases. Our recent studies identified mismatch repair proteins as activators of toxic responses to chromium-DNA damage, which resolved an apparent discrepancy in genotoxic activity of chromium adducts in cells and in vitro. The discovered mechanism of toxicity provided the basis for a novel model of chromium carcinogenesis based on the selection of resistant clones that lack mismatch repair and progress to cancer due to high levels of spontaneous mutagenesis.

Base Pair Mismatch↗