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DNA polymerase arrest by adducted trivalent chromium.

Carcinogenic chromium (Cr6+) enters cells via the sulfate transport system and undergoes intracellular reduction to trivalent chromium, which strongly adducts to DNA. In this study, the effect of adducted trivalent chromium on in vitro DNA synthesis was analyzed with a polymerase-arrest assay in which prematurely terminated replication products were separated on a DNA sequencing gel. A synthetic DNA replication template was treated with increasing concentrations of chromium(III) chloride. The two lowest chromium doses used resulted in biologically relevant adduct levels (6 and 21 adducts per 1,000 DNA nucleotides) comparable with those measured in nuclear matrix DNA from cells treated with a 50% cytotoxic dose of sodium chromate in vivo. In vitro replication of the chromium-treated template DNA using the Sequenase version 2.0 T7 DNA polymerase (United States Biochemical Corp., Cleveland, OH) resulted in dose-dependent polymerase arrest beginning at the lowest adduct levels analyzed. The pattern of polymerase arrest remained consistent as chromium adduct levels increased, with the most intense arrest sites occurring 1 base upstream of guanine residues on the template strand. Replication by the DNA polymerase I large (Klenow) fragment as well as by unmodified T7 DNA polymerase also resulted in similar chromium-induced polymerase arrest. Interstrand cross-linking between complementary strands was detected in template DNA containing 62, 111, and 223 chromium adducts per 1,000 DNA nucleotides but not in template containing 6 or 21 adducts per 1,000 DNA nucleotides, in which arrest nevertheless did occur. Low-level, dose-dependent interstrand cross-linking between primer and template DNA, however, was detectable even at the lowest chromium dose analyzed. Since only 9% of chromium adducts resulted in polymerase arrest in this system, we hypothesized that arrest occurred when the enzyme encountered chromium-mediated interstrand DNA-DNA cross-links between either the template and a separate DNA molecule or the template and its complementary strand in the same molecule. These results suggest that the obstruction of DNA replication by chromium-mediated DNA-DNA cross-links is a potential mechanism of chromium-induced genotoxicity in vivo.

Base Sequence↗

Urinary chromium as a biological marker of environmental exposure: what are the limitations?

Public concern has mounted recently about environmental exposures to chromium in soil, tap water, and ambient air. In response, agencies charged with protecting public health have attempted to study exposure by monitoring urinary chromium levels among potentially exposed populations. While urinary biomonitoring of occupationally exposed workers has been successfully used to assess high-level inhalation exposures in the workplace, evaluating low-level environmental exposures has been problematic. Due to these problems, before an extensive biological monitoring study is conducted of those exposed to low levels of environmental chromium, several issues must be resolved. First, exposures to chromium must occur at the same time as sampling, because the biological half-life of chromium in urine is very short (less than 2 days). Second, reduced bioavailability and bioaccessibility via the oral and dermal routes of exposure limit the capacity of urinary monitoring to measure environmental exposures (e.g., systemic dose is too small to be measured). Third, the dose of chromium must be sufficient such that it may be reliably measured above background levels in urine (range of 0.2 to 2 microg/liter) and above the analytical limit of detection (0.2 microg/liter). Fourth, the inter- and intrapersonal variability in background levels of urinary chromium is known to be significant and influenced by food and beverage intake, smoking, and exercise. Thus, the role of each factor must be carefully understood. Finally, it is imperative to have developed a complete understanding of the clinical significance of elevated urinary chromium levels before a study is performed, because higher than background levels, in and of themselves, are not indicative of a significant health concern. The route of exposure, valence of chromium to which people were exposed, exposure time, and duration must all be understood before the biological data can be implemented. We have conducted a total of nine human exposure studies over the past 3 years in an attempt to understand the kinetics of chromium and the impact on urinary, red blood cell (RBC), and plasma biomonitoring programs. The results of these studies are described here and our recommendations are offered for how to design and implement a urinary chromium biomonitoring study. In our view, given some evidence that the dose of hexavalent chromium [Cr(VI)] is sufficient to be measurable above background concentrations of total chromium [Cr(III) and Cr(VI)], duplicated measurements of chromium in plasma and RBCs are, in most cases, a more definitive gauge of environmental exposure than urinary biomonitoring.

Biological Availability↗

The measurement of volatile chromium in biological materials.

Chromium is an essential trace element in mammals since dietary chromium deficiency results in glucose intolerance due to decreased sensitivity to insulin. In humans, both adults and children with glucose intolerance have been improved by treatment with chromium. Furthermore, chromium deficiency has been implicated as a causative factor in hypercholesterolemia and atherosclerosis. However, little is known of the metabolism of chromium in humans, primarily because of analytical difficulties. The biologically active form of chromium is the "glucose tolerance factor" (GTF) which is a co-ordination complex of trivalent chromium with nicotinic acid and certain amino acids. At physiological pH, ionic chromium as a simple inorganic salt is insoluble in water, but trivalent chromium forms stable complexes with ascorbic acid, amino acids and other substances present in blood and tissue. Chromium is present in serum, bound to protein and also as dialysable or ultrafiltrable chromium (free chromium). The free chromium includes G.T.F. and other coordination complexes and represents the metabolically active form of the element; the ratio free/protein bound chromium in serum varies within the individual according to the diet and the metabolic state.

Animals↗

Reaction of chromium (VI) with hydrogen peroxide in the presence of glutathione: reactive intermediates and resulting DNA damage.

The reaction of chromium(VI) with hydrogen peroxide was studied in the presence of glutathione. In vitro, reaction of chromium(VI) with hydrogen peroxide alone led to production of hydroxyl radical as the significant reactive intermediate, while reaction of chromium(VI) with glutathione led to formation of two chromium(V)-glutathione complexes and the glutathione thiyl radical. Incubation of chromium(VI) with glutathione prior to addition of hydrogen peroxide led to formation of peroxochromium(V) species and a dramatic increase in hydroxyl radical production over that detected in the reaction of chromium(VI) with hydrogen peroxide alone. In contrast, addition of chromium(VI) to a preincubated mixture of glutathione and hydrogen peroxide led to a decrease in hydroxyl radical production over that obtained in the reaction of chromium(VI) with hydrogen peroxide. When pBR322 DNA was added to the above reactions, the extent of chromium(VI)-induced DNA strand breakage correlated with the relative amount of hydroxyl radical formed. Reaction of chromium(VI) with calf thymus DNA in the presence of a preincubated mixture of glutathione and hydrogen peroxide led to detection of the 8-hydroxydeoxyguanosine adduct, whose formation correlated with that of hydroxyl radical production. No significant chromium-DNA adduct formation was detected. The results suggest that, in the cellular metabolism of chromium(VI), preformed chromium(V)-glutathione complexes may react with hydrogen peroxide in a Fenton-type manner to produce hydroxyl radical as the DNA-damaging agent. However, if glutathione reacts with hydrogen peroxide prior to exposure to chromium(VI), the amount of hydroxyl radical generated may not be sufficient to cause significant DNA damage.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2'-Deoxyguanosine↗

Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men.

The effects of 8 wk of daily chromium supplementation (3.3-3.5 mumol as chromium chloride or chromium picolinate) or placebo (0.1 mumol Cr) and weight training were examined in 36 men in a double-blind design. Strength, mesomorphy, fat-free mass, and muscle mass increased with resistance training independently of chromium supplementation (P < 0.0001). Protein, magnesium, zinc, copper, and iron intakes equalled or exceeded the recommended dietary allowance (RDA) or estimated safe and adequate daily dietary intake (ESADDI) during training and did not change significantly from pretraining intakes (P > 0.05). Chromium supplementation increased the serum chromium concentration and urinary chromium excretion without a difference as a result of the chemical form of chromium (P < 0.05). Resistance training was associated with a significant decrease (P < 0.05) in serum ferritin, total-iron-binding capacity, transferrin saturation, the ratio of enzymatic to immunoreactive ceruloplasmin, and plasma copper, independently of chromium supplementation. However, transferrin saturation was decreased more with chromium picolinate supplementation (24%) than with chromium chloride or placebo (10-13%). Compared with pretraining values, urinary magnesium excretion increased (P < 0.05) and urinary zinc output tended to decrease during the first 4 wk of resistance training and then returned to baseline values for the final 4 wk, which suggests an adaptation in mineral excretion in response to weight training. These findings suggest that routine chromium supplementation has no beneficial effects on body- composition change or strength gain in men. Whether chromium supplementation of individuals with diminished chromium nutriture facilitates propitious changes in body structure and function remains to be determined.

Absorptiometry, Photon↗

Self reported health of people in an area contaminated by chromium waste: interview study.

OBJECTIVES: To compare the self reported health of a group of individuals living in an area contaminated by chromium (chromium group) with a group living in an uncontaminated area (control group), and to assess the effects of perception of risk from exposure to chromium on health. DESIGN: Cross sectional study using the SF-36 validated quality of life questionnaire. Further questions were added to examine the relations between perceptions about living on or near land contaminated with chromium and the effects on self reported health. SETTING: An area contaminated with chromium (Cambuslang, Carmyle, and Rutherglen) and a control area (Barrmulloch and Pollok). PARTICIPANTS: Residents of an area containing chromium landfill and residents of an uncontaminated control area. MAIN OUTCOME MEASURES: Scores on SF-36. RESULTS: Little difference was found in health scores between the two groups, and only for general health was there a significantly higher score in the chromium group. Health scores for the chromium group were significantly worse across all dimensions for those who believed that chromium adversely affected health. Most of the chromium group (68%) would prefer money to be spent on improving amenities rather than on chromium remediation. CONCLUSIONS: Similar self reported health among residents of the chromium and control groups indicates that there is no evidence of harm to health from exposure to chromium in this setting. Noticeably lower scores in participants who believed chromium to be harmful to health point to the potential importance of perception and possible anxiety. Given the overall greater desire for better amenities rather than remedial action, policy makers and planners should discuss with residents how best to spend resources before instigating expensive cleaning up programmes.

Adolescent↗

Oral bioavailability of chromium from a specific site.

Analysis of soil from a specific site in New Jersey indicated a low level of sodium and chromium present as a calcium compound. Chromium was then administered orally to young, mature male rats at a level of 240 micrograms/kg for 14 days as chromium-contaminated soil, as CaCrO4, and as an equimolar mixture of the soil and calcium salts for 14 days. The rats were sacrificed 24 hr after the last dosing, and tissues were taken immediately for chromium analysis. Blood, muscle, and liver contained the highest levels of chromium in these animals, although kidney contained the highest concentration per gram of tissue. The total amount of chromium in the tissues was less than 2% of the administered chromium. In a study of the excretion of chromium, the animals were dosed orally for 8 days (with CaCrO4 or contaminated soil, each at the level of 240 mumole Cr/kg), and the chromium in feces and urine was determined on days 1, 2, 7, and 8. After cessation of dosing for 27 days, the same rats were dosed for 2 days at the same level, and chromium in urine and feces was determined for the 2 days. The animals administered the chromium in soil had higher levels of chromium in both urine and feces on all days compared to the group fed the CaCrO4. The total recovery of chromium in any of the 2-day periods was less than 50% of the chromium administered during that period.

Administration, Oral↗

[Chromium content in foods and dietary intake estimation in the Northwest of Mexico].

Chromium is an indispensable nutrient for the carbohydrates and lipids metabolism. In this study the chromium content in the twenty main foods of the diet from Northwestern Mexico was determined, as well as the daily mean intake which was estimated based on the food intake basket of this region. Chromium content was analyzed by atomic absorption spectrophotometry using the graphite furnace technique and previous digestion of foods in microwave oven. The chromium mean intake was estimated considering the chromium daily mean intake for person per day and the chromium content of the foods analyzed in this study. The range chromium content in the foods analyzed was between 0.0004 and 0.1641 microgram/g dry weight. White cheese showed the highest chromium content followed by pasta soup, wheat tortilla, bread and meat. The main foods chromium contributors in the diet were: wheat tortilla (20%), white cheese (11%), corn tortilla (11%), pasta soup (10%), milk (10%), meat (9%) and white bread (8%). The daily chromium intake was 30.43 +/- 1.6 micrograms/d. Chromium values obtained in the food analyzed are considered low. Moreover, chromium intake obtained from the diet is not enough to meet the safety and adequate daily chromium intake. Therefore, the population from the Northwestern Mexico has a suboptimal dietary chromium intake.

Chromium↗

[Effects of chromium compounds on the respiratory system. 2. Difference between water-soluble hexavalent and trivalent compounds].

Transference and transformation of chromium compounds, known as occupational carcinogens, in the lung of rats were studied by determining blood chromium levels after a single mist inhalation or an intravenous injection of water-soluble chromic acid (hexavalent) and chromium chloride (trivalent). Conclusion drawn from this study are as follows: Transference of chromium from the lung to the blood stream is ended quickly after the inhalation of chromic acid mist. Alveolar permeability of hexavalent chromic acid is much higher than that of trivalent chromium chloride. The greater part of the transferred chromium in the blood after the inhalation of chromic acid mist is not transformed to any other form; therefore, it seems to be present as the hexavalent form. The hexavalent chromic acid in the blood diffused to the liver, kidneys and the spleen, but the trivalent chromium chloride distributed only in the blood. The hexavalent chromic acid in the blood decreased more slowly than the trivalent chromium chloride. The biological half-time of the chromic acid in the blood was about 60 hours, whereas that of the chromium chloride was only about 2 hours. These results suggest that the water-soluble hexavalent chromium compounds may be apparently different from the trivalent chromium compounds in the transference from the lung and following distribution in the body. These differences might be caused by the high permeability through the cell membrane in hexavalent chromium compounds and the high possibility of binding with proteins in trivalent chromium compounds.

Aerosols↗

Is chromium an important element in HIV-positive patients with metabolic abnormalities? An hypothesis generating pilot study.

BACKGROUND: Chromium plays a role in insulin sensitivity. OBJECTIVES: To compare chromium measurements in HIV-positive patients with or without (N) antiretroviral therapy (ART) to that of healthy controls (HC) and, to determine if there is any association between chromium levels and abnormalities in body composition, glucose and lipid metabolism. DESIGN: A cross-sectional study in 91 HIV patients (75 HIV-ART, 16 HIV-N) and 13 HC. Chromium was assessed in the diet, plasma, toenails, and urine. Fasting blood glycemia and lipids, lipodystrophy score and body fat were also determined. RESULTS: Dietary intake of chromium was similar in the 3 groups. Plasma and toenail Cr were lower in HIV compared to HC, but urinary chromium was similar. However, when the HIV-positive patients on ART were compared to those who were naïve to therapies, urinary excretion of chromium was higher in HIV-ART. In addition, urinary excretion of chromium significantly and positively correlated with lipodystrophy score and negatively with various parameters of metabolic syndrome. CONCLUSION: Despite a similar dietary intake, chromium levels were lower in HIV-positive patients and urinary chromium excretion correlated with some metabolic parameters. Low chromium levels may be due to increased chromium losses. These results support further studies on chromium in HIV patients.

Adult↗

Biomonitoring of chromium(VI) deposited in pulmonary tissues: pilot studies of a magnetic resonance imaging technique in a post-mortem rodent model.

The biomonitoring of individuals exposed to chromium(VI) by inhalation is often based on determinations of chromium in body fluids such as blood, plasma or urine, or on assessments of DNA damage in non-lung surrogate tissues such as peripheral blood lymphocytes. These techniques are of some use as biomarkers of internal exposure or biological effect, mainly in the case of soluble chromium(VI) compounds, but they provide at best only indirect information about chromium(VI) concentrations in the main target organ of interest - the lung. An urgent need exists for a non-invasive technique to permit the visualization and quantification of chromium(VI) in the lung of exposed humans. This study details the development of a lung imaging technique based on the detection of paramagnetic chromium using magnetic resonance imaging (MRI). The intracellular reductive conversion of chromium(VI) is a crucial bioactivation step in its carcinogenicity, and the MRI method described here relies on the conversion of non-paramagnetic (MRI 'silent') chromium(VI) to detectable paramagnetic species such as chromium(III). Initial studies with chromium(III) revealed that a range of 2.5-5 microg chromium(III) instilled in rat lung is considered to be the lower limit of detection of this method. It was possible to demonstrate the presence of 30 microg chromium(VI) in our post-mortem rat model. The ultimate objective of this work is to determine whether this technique has applicability to the biomonitoring of chromium(VI) inhalation exposures that result in internalized lung doses in human subjects.

Animals↗

Reduction of hexavalent chromium collected on PVC filters.

Chromium exists at various valences, including elemental, trivalent, and hexavalent chromium, and undergoes reduction-oxidation reactions in the environment. Since hexavalent chromium is known as a human carcinogen, it is most important to evaluate the oxidation-reduction characteristics of the hexavalent chromium species. Although hexavalent chromium can be reduced to trivalent state, the detailed information on this in workplace environments is limited. The purpose of this study was to investigate hexavalent chromium reduction in time in various conditions. A pilot chrome plating operation was prepared and operated in a laboratory for this study. There was evidence that the hexavalent chromium was reduced by time after mist generation. The percentage ratio (with 95% confidence intervals in parentheses) of hexavalent chromium to total chromium was almost 100% (99.1 approximately 102.3) immediately after mist generation, and was reduced to 87.4% (84.8 approximately 89.9) at 1 hour and 81.0% (78.3 approximately 83.5) at 2 hours, respectively. Another test indicated that hexavalent chromium collected on PVC filters was also reduced by time after sampling. Hexavalent chromium was reduced to 90.8% (88.2 approximately 93.3) at 2 hours after sampling. It also was found that hexavalent chromium was reduced during storage in air. It is recommended that air samples of hexavalent chromium be protected against reduction during storage.

Aerosols↗

[Effects of cultural conditions on hexavalent chromium uptake and the cytotoxicity thereof in KB cell culture].

To reveal the effects of cultural conditions on the cytotoxicity of hexavalent chromium, the uptake of sodium chromate (Na2CrO4) by KB cells and the colony-forming efficiency of the cells were examined under various cultural conditions. The results were summarized as follows: 1) The chromium uptake by the cells after a certain period of incubation with hexavalent chromium was inhibited with the decrease of the temperature (3 degrees, 20 degrees, 37 degrees C), increase of the serum concentration (0, 10, 20, 30%) and increase of pH (6.8-8.2) of the medium. In particular, low temperatures inhibited the chromium uptake by the cells remarkably. However, in relation to the serum addition, no marked effect was found. 2) The chromium uptake by the cells increased with the volume of the medium containing an identical concentration of chromium (2 ppm) and then reached saturation when it was about 0.23 microgram per 10(6) cells. On the other hand, the chromium uptake positively correlated with the concentration of chromium and the total chromium in the medium. 3) The difference of chromium uptake by the cells in different culture media was more marked at acidic pH than that at alkaline pH. However, there was no effect of calcium chloride and glucose concentrations on the uptake of chromium. The chromium uptake by the cells in Ca-Mg-free phosphate-buffered solution (PBS(-] was higher than that in other culture media. Consequently, the above results suggested that the chromium uptake by the KB cells might be affected by the various cultural conditions, especially by temperature, pH and medium volume.

Cations↗

Evidence for chromium acting as an essential trace element in insulin-dependent glucose uptake in cultured mouse myotubes.

Previous work from this and other laboratories has suggested that the trace element chromium plays some role in glucose homeostasis. In this study, we sought to characterise an in vitro cell culture model in which the effects of chromium on insulin-dependent glucose uptake could be studied. Mouse C2C12 myoblasts were differentiated to form myotubes in culture in chromium-replete or chromium-poor media. Chromium levels in standard media were 0.56 +/- 0.01 micrograms/l (mean +/- S.E.M.) compared with 0.09 +/- 0.01 micrograms/l in chromium-poor media. In chromium-poor media, insulin-stimulated uptake of radiolabelled glucose was reduced by almost 50% compared with that found in chromium-replete media. This decreased response could be restored by the addition of physiologically relevant (0.3 micrograms/l) concentrations of inorganic chromium (P < 0.001). The sensitivity of these cells to insulin was reduced dramatically by a reduction in the chromium content of the medium and was again increased (P < 0.001) by chromium addition. The concentrations of chromium required to restore the sensitivity to insulin were of the same order as those found physiologically; much higher concentrations of chromium could also stimulate glucose uptake in the absence of insulin but such concentrations were supra-physiological.

Animals↗

[Chromium as an essential element].

Chromium was known for many years to be an element causing allergic reactions and having neurotoxic and carcinogenic effects. These effects can be observed especially in the case of hexavalent chromium. Only a little more than four decades ago trivalent chromium has been known as an essential element with relation to glycide and lipid metabolism. And only during several last years this chromium function has been revealed on a molecular level. After absorption in the gastrointestinal tract, chromium is most likely transported to cells bound to the plasma protein transferrin. Insulin initiates chromium transport into the cells where it is bound to the oligopeptide apochromodulin. This oligopeptide combined with four chromium(III) atoms forms chromodulin, which is important for amplifying the insulin signalling effect. After binding to insulin-activated receptor, chromodulin increases tyrosine kinase activity by one order. This enzyme forms a part of intracellular portion of insulin receptor. Chromium supplementation in people with chromium deficiency can improve glucose tolerance and some lipid metabolism parameters. The supplementation is indicated in persons with impaired glucose tolerance both in preclinical and manifested stadium of type 2 diabetes mellitus where increased lost of chromium in urine was documented. In these patients, chromium deficiency can participate in insulin resistance and hyperlipidaemia. Chromium is usually applied in the form of organic compounds: yeast extract or chromium(III) picolinate. Cr(III) picolinate can be reduced to compounds of Cr(II) in the cells which can then produce free hydroxyl radical in the so called Fenton reaction.

Animals↗

Chromium(III) bound to DNA templates promotes increased polymerase processivity and decreased fidelity during replication in vitro.

Carcinogenic chromium [Cr(VI)] compounds are reduced intracellularly to DNA- and protein-reactive chromium(III) species. However, the role of Cr(III) ions in chromium-induced genotoxicity remains unclear. We have investigated the effects of chromium(III) binding on DNA replication and polymerase processivity in vitro. Chromium ions bind slowly and in a dose-dependent manner to DNA. Micromolar concentrations of free chromium inhibit DNA replication, but if the unbound chromium is removed by gel filtration, the rate of DNA replication by polymerase I (Klenow fragment) on the chromium-bound template is increased greater than 6-fold relative to the control. This increase is paralleled by as much as a 4-fold increase in processivity and a 2-fold decrease in replication fidelity. These effects are optimum when very low concentrations of chromium ions are bound to the DNA [3-4 Cr(III) ions per 1000 nucleotide phosphates]. Increased concentrations of chromium lead to the production of DNA-DNA cross-links and inhibition of polymerase activity. These results suggest that low levels of DNA-bound chromium(III) ions may contribute to chromium mutagenesis and carcinogenesis by altering the kinetics and fidelity of DNA replication.

Binding Sites↗

Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism.

Evidence suggests that chromium supplementation may alleviate symptoms associated with diabetes, such as high blood glucose and lipid abnormalities, yet a molecular mechanism remains unclear. Here, we report that trivalent chromium in the chloride (CrCl3) or picolinate (CrPic) salt forms mobilize the glucose transporter, GLUT4, to the plasma membrane in 3T3-L1 adipocytes. Concomitant with an increase in GLUT4 at the plasma membrane, insulin-stimulated glucose transport was enhanced by chromium treatment. In contrast, the chromium-mobilized pool of transporters was not active in the absence of insulin. Microscopic analysis of an exofacially Myc-tagged enhanced green fluorescent protein-GLUT4 construct revealed that the chromium-induced accumulation of GLUT4-containing vesicles occurred adjacent to the inner cell surface membrane. With insulin these transporters physically incorporated into the plasma membrane. Regulation of GLUT4 translocation by chromium did not involve known insulin signaling proteins such as the insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, and Akt. Consistent with a reported effect of chromium on increasing membrane fluidity, we found that chromium treatment decreased plasma membrane cholesterol. Interestingly, cholesterol add-back to the plasma membrane prevented the beneficial effect of chromium on both GLUT4 mobilization and insulin-stimulated glucose transport. Furthermore, chromium action was absent in methyl-beta-cyclodextrin-pretreated cells already displaying reduced plasma membrane cholesterol and increased GLUT4 translocation. Together, these data reveal a novel mechanism by which chromium may enhance GLUT4 trafficking and insulin-stimulated glucose transport. Moreover, these findings at the level of the cell are consistent with in vivo observations of improved glucose tolerance and decreased circulating cholesterol levels after chromium supplementation.

3T3-L1 Cells↗

The toxicology of chromium with respect to its chemical speciation: a review.

The properties of trivalent and hexavalent chromium are reviewed with respect to acute and chronic oral toxicity, dermal toxicity, systemic toxicity, toxicokinetics, cytotoxicity, genotoxicity and carcinogenicity. The hexavalent chromium compounds appear to be 10-100 times more toxic than the trivalent chromium compounds when both are administered by the oral route. Dermal irritancy and allergy are more frequently caused by contact with soluble hexavalent chromium compounds. The cytotoxicity of soluble and insoluble hexavalent chromium compounds to fibroblasts is 100-1000 times greater than that demonstrated by trivalent chromium compounds. In short-term tests, the hexavalent chromium compounds demonstrated genotoxic effects four times more frequently than did the trivalent chromium compounds. Carcinogenicity appears to be associated with the inhalation of the less soluble/insoluble hexavalent chromium compounds. The toxicology of chromium does not reside with the elemental form. It varies greatly among a wide variety of very different chromium compounds. Oxidation state and solubility are particularly important factors in considering the toxicity of chromium with respect to its chemical speciation.

Animals↗