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PubMed1991

[Chromium: physiologic role and implications in human pathology].

Reported values for total body stores of chromium vary between 0.4 mg and 6 mg. Chromium stores may be higher in neonates than in adults, relative to body size, whereas tissular chromium may be depleted in the elderly. The recommended daily allowance for chromium is 50 to 200 micrograms/day but actual needs are poorly known. Digestive absorption is better for organic chromium, which is part of the "glucose tolerance factor" (GTF), than for inorganic chromium. Furthermore, chromium (VI) is better absorbed than chromium (III). In the body, chromium (VI) is rapidly reduced to chromium (III) by a number of metabolic pathways. Absorbed chromium binds to proteins, mainly to transferrin which exhibits a high affinity for chromium (III). Most absorbed chromium is eliminated through the kidneys. Renal excretion occurs according to a two or more-compartment model. Current methods used to assay chromium, i.e., atomic absorption spectrometry using a graphite furnace or neutron activation, are sufficiently sensitive and specific to evaluate chromium levels in blood, urine or hair. However, none of these levels accurately reflects chromium body stores. Chromium is part of the GTF molecule. This factor has no effect per se but may facilitate binding of insulin to insulin receptors and amplify the effects of insulin on carbohydrate and lipid metabolism. Chromium deficiency may play a role in a development of some forms of adult diabetes mellitus and of arteriosclerosis. Partial chromium deficiencies seem to be common, especially in individuals with high intakes of refined foods. Acute chromium poisoning is usually due to an excess of chromium (VI) and is sometimes seen in the chromium industry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Role of valence state and solubility of chromium compounds on induction of cytotoxicity, mutagenesis, and anchorage independence in diploid human fibroblasts.

We previously showed that carcinogenic nickel, arsenic, and chromium(VI) compounds induced anchorage independence (AI) in diploid human fibroblastic cells (HFC) derived from foreskins (K. A. Biedermann and J. R. Landolph, Cancer Res., 47: 3815-3823, 1987). To elucidate the role of the valence state of chromium and solubility of chromium compounds in inducing AI, we studied the ability of soluble and insoluble hexavalent [chromium(VI)] and trivalent [chromium(III)] chromium compounds to induce mutation and AI in HFC. Chromium(VI) compounds (PbCrO4, CaCrO4, Na2CrO4, and CrO3) were 1000-fold more cytotoxic to HFC (average 50% lethal dose 0.5 microM) than chromium(III) compounds (CrCl3, Cr2O3, Cr2S3; average 50% lethal dose 500 microM). However, equal concentrations (0.1-10.0 microM) of soluble or insoluble chromium compounds in either +6 or +3 valence states induced similar increases in frequencies of AI in HFC (100-200/10(5]. Chromium(VI)- and chromium(III)-induced AI was a stable phenotype. All soluble chromium(VI) and insoluble chromium(III) compounds studied induced mutation to 6-thioguanine resistance at cytotoxic concentrations in HFC. Insoluble PbCr(VI)O4 and a soluble form of Cr(III)Cl3 were inactive in this assay. Mutation induction by chromium(III) compounds only occurred at cytotoxic concentrations (100-1000 microM) 1000-fold greater than those concentrations of chromium(VI) compounds (0.25-1 microM) which were cytotoxic, mutagenic, and induced AI. Soluble hexavalent Na2(51)CrO4 was taken up facilely by cells at concentrations that induced cytotoxicity, mutation, and AI. At concentrations of 0.25-1.0 microM, which induced AI but were not cytotoxic or mutagenic, or concentrations of 1-1000 microM, which were cytotoxic and mutagenic, soluble trivalent 51CrCl3 was not taken up by cells. An insoluble form of CrCl3 was not taken up intracellularly but did avidly associate with cells over the concentration range 1 to 100 microM which induced AI, cytotoxicity, and mutagenicity. Therefore, both chromium(VI) and chromium(III) compounds induced genotoxic effects in human fibroblasts. Cellular uptake, cytotoxicity, mutagenicity, and AI induced by soluble chromium(VI) compounds all occurred at the low concentrations of 0.2 to 1.0 microM; hence mutagenicity and induction of AI may be coupled for soluble chromium(VI) compounds but not for insoluble PbCrO4, which induced AI but was not mutagenic. Cytotoxicity and mutagenicity of insoluble chromium(III) occurred at concentrations of 10-100 microM, but induction of AI occurred at concentrations of 0.1-10 microM, indicating that inductions of mutagenicity and AI were not coupled for chromium(III) compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Adhesion↗
PubMed2001

Oral bioaccessibility of trivalent and hexavalent chromium in soil by simulated gastric fluid.

Chromium is found in soil from natural sources and anthropogenic activities. The ingestion of soil contaminated with chromium especially by children can have toxic consequences. Therefore, it is important to quantify the oral bioaccessibility of chromium in chromium in contaminated soil. In this study, chromium-51 as chromic (III) chloride and sodium chromate (VI), was mixed with an Atsion sandy soil and a Keyport clay soil and stored for 4 mo at either 21-25 degrees C or 2-4 degrees C. Utilizing simulated gastric conditions, the oral bioaccessibility of chromium in soil was determined. When the effects of soil on the bioaccessibility of chromium were compared, the data revealed the the bioaccessibility of chromium (III) from the clay soil was significantly lower than from the sandy at 21-25 degrees C. However, at 2-4 degrees C, more chromium (III) was extracted by synthetic gastric fluid from the clay soil than from the sandy soil. Temperature was also a factor as evidenced by the higher bioaccessibility of chromium (IV) in the sandy soil at 2-4 degrees C and of both chromium species in the clay soil at the same temperature. Reduction of the soluble chromium (VI) chemical to the nonsoluble chromium (III) compound in the acidic soils by naturally occurring organic matter in soil would explain the lower bioaccessibilty of chromium (VI) at 21-25 degrees C. At 2-4 degrees C, the data indicate that the rate of chromium (VI) reduction to chromium (III) was slowed. Although the results of this study are limited to one low concentration of chromium (III) and chromium (VI) and indicate that the bioaccessibility of chromium in soil can range between 18% and 72%, the data also suggest that there may be a potential health hazard from oral exposure to chromium in heavily contaminated sites. Therefore, more extensive research should be conducted to determine if thes findings can be extended to environmentally relevant concentrations.

Aluminum Silicates↗
PubMed1991

Distribution of chromium within cells of the blood.

Although a number of investigators have examined the uptake of chromium in red blood cells (RBC) or whole blood, little is known about chromium uptake in white blood cells (WBC). Radiolabeled chromium (51Cr) was used to determine chromium uptake and distribution. Isolated RBC and enriched WBC populations were exposed in vitro to potassium chromate (Cr+6) and uptake was determined over a 2-hr time period. Exposure of either rat or human blood cells to 50 microM K2CrO4 for 2 hr resulted in greater accumulation of chromium within WBC than RBC. Uptake by rat WBC was significantly greater than that of human; whereas, uptake by human RBC was greater than that of the rat. Exposure of human whole blood to 50 microM K2CrO4, prior to isolation of WBC, also resulted in an increased uptake of chromium by WBC. Fisher 344 rats were exposed either orally or intravenously to a single dose of K2CrO4 and the distribution of chromium within blood cells was determined 1 hr, 24 hr, or 7 days following exposure. Regardless of the route or time following exposure, WBC chromium levels were consistently greater than those of RBC. However, the absolute levels of chromium did change with time. A comparison of chromium distribution 24 hr following a single oral exposure (1 ppm Cr+6) to the distribution 7 days following exposure demonstrated a reduction in chromium levels for RBC (10-fold) and for WBC (approximately 2.5-fold). In contrast, intravenous administration of chromate resulted in no significant decrease in RBC chromium levels when compared 1 hr, 24 hr, and 7 days following exposure. Although no difference in WBC chromium content was observed at 1 and 24 hr after exposure, an approximate 1.7-fold decrease in chromium content was detected at Day 7 for WBC. Intravenous administration of chromic chloride (Cr+3) resulted in a low level of chromium associated with RBC following 1 hr, and chromium was undetected in the WBC. These data demonstrate that WBC accumulate hexavalent chromium following both in vitro and in vivo exposure. In addition, white blood cells accumulate chromium to a greater extent than red blood cells. Since WBC accumulate chromium, their use as a target for the development of biomarkers of chromium exposure may be warranted.

Animals↗
PubMed2000

Threshold mechanisms and site specificity in chromium(VI) carcinogenesis.

Ten years have elapsed since the International Agency for Research on Cancer (IARC) evaluated the carcinogenicity of chromium and chromium compounds. Further studies performed during the last decade have provided further epidemiological, experimental and mechanistic data which support the IARC conclusions. A wealth of results indicate that, at variance with chromium(0) and chromium(III), chromium(VI) can induce a variety of genetic and related effects in vitro. The lack of carcinogenicity of chromium(0) and chromium(III) compounds in experimental animals is well established, and only a minority of animal carcinogenicity data with chromium(VI) compounds were positive (30 out of 70, i.e. 42.9%). Moreover, most positive studies used administration routes which do not mimic any human exposure and by-pass physiological defense mechanisms. Typically, positive results were only obtained at implantation sites and at the highest dose tested. Exposure to chromium(VI) has been known for more than a century to be associated with induction of cancer in humans. Carcinogenicity requires massive exposures, as is only encountered in well defined occupational settings, and is site specific, being specifically targeted to the lung and, in some cases, to the sinonasal cavity. Increased death rates for cancers at other sites, which were occasionally reported in some epidemiological studies, were almost invariably not statistically significant, and inconsistent (being counterbalanced by other studies which apparently showed decreased rates for the same cancers). As we recently quantified in human body compartments, chromium(VI) can be reduced in body fluids and non-target cells, which results in its detoxification, due to the poor ability of chromium(III) to cross cell membranes. In target cells, chromium(VI) tends to be metabolized by a network of mechanisms leading to generation of reduced chromium species and reactive oxygen species, which will result either in activation or in detoxification depending on the site of the intracellular reduction and its proximity to DNA. When introduced by the oral route, chromium(VI) is efficiently detoxified upon reduction by saliva and gastric juice, and sequestration by intestinal bacteria. If some chromium(VI) is absorbed by the intestine, it is massively reduced in the blood of the portal system and then in the liver. These mechanisms explain the lack of genotoxicity, carcinogenicity, and induction of other long-term health effects of chromium (VI) by the oral route. Within the respiratory tract, chromium(VI) is reduced in the epithelial-lining fluid, pulmonary alveolar macrophages, bronchial tree and peripheral lung parenchyma cells. Hence, lung cancer can only be induced when chromium(VI) doses overwhelm these defense mechanisms. The efficient uptake and reduction of chromium(VI) in red blood cells explains its lack of carcinogenicity at a distance from the portal of entry into the body. All experimental and epidemiological data, and the underlying mechanisms, point to the occurrence of thresholds in chromium(VI) carcinogenesis.

Administration, Inhalation↗
PubMed1989

Molecular basis of hexavalent chromium carcinogenicity: effect on gene expression.

The carcinogenicity of chromium(VI) compounds is explained in terms of the "uptake-reduction" model. According to this model, chromium (VI) enters cells as the anionic tetrahedral species chromate, CrO4(2-), using normal cellular anion transport systems, such as the sulfate transport system. Redox-active enzymes and small molecules reduce chromium (VI) intracellularly and produce "reactive intermediates" capable of damaging cellular constituents. DNA is presumed to be a critical target within the cell; however, chromium (VI) itself is unreactive toward DNA under physiological conditions in vitro. Thus, the ability of chromium(VI) to damage DNA depends on the presence of cellular components capable of producing putative DNA-damaging agents, such as chromium(VI) thioester, chromium(V), chromium(IV), chromium(III), thiyl radical and hydroxyl radical, upon reaction with the chromium(VI). The exact nature of the DNA damage will be strongly dependent on the reactive intermediates produced by cellular components and systems active in chromium(VI) metabolism. The chromium(VI)-induced DNA damage disrupts the normal functioning of DNA in critical cellular processes, including transcription and replication. The effect of chromium(VI)-induced DNA damage on the function of DNA as a template for transcription has been examined in chick embryo liver in vivo. Chromium(VI) induced DNA-protein and DNA interstrand cross-links and suppressed the induction of 5-aminolevulinic acid synthase and cytochrome P-450 mRNA by porphyrinogenic drugs. In contrast, chromium(VI) increased the basal steady-state mRNA levels of these two inducible genes, but had no effect on the steady-state mRNA levels of the constitutive genes, beta-actin, conalbumin and albumin. Nuclear "run-off" transcription experiments showed that the effect of chromium(VI) on the steady-state levels of basal and drug-inducible 5-aminolevulinic acid synthase mRNA was principally the result of changes in the transcription rate of the 5-aminolevulinic acid synthase gene. Chromium(VI)-induced changes in gene expression correlated with the presence of DNA interstrand and DNA-protein cross-links, suggesting that chromium(VI)-induced DNA lesions lead to changes in expression of the targeted genes.

Animals↗
PubMed1994

Base-specific arrest of in vitro DNA replication by carcinogenic chromium: relationship to DNA interstrand crosslinking.

We have previously shown that trivalent chromium can bind to purified DNA and form lesions capable of obstructing DNA replication in vitro. Trivalent chromium is not, however, carcinogenic to humans. Rather, it is the end product of the intracellular reduction of hexavalent chromium, which is carcinogenic. The process of chromium reduction yields several reactive intermediates which may also interact with DNA, perhaps producing different lesions than those generated when trivalent chromium binds DNA. The present study was undertaken to determine whether the treatment of DNA with hexavalent chromium in the presence of ascorbate (the intracellular reductant responsible for most in vivo chromium reduction), would also generate DNA lesions capable of obstructing replication. Using increasing chromium concentrations and a constant ascorbate:chromium ratio of 0.5:1 to generate biologically relevant adduct levels, a DNA polymerase arrest assay revealed that polymerase arresting lesions were formed and were indistinguishable from those generated by trivalent chromium, in that the most prominent arrests sites were one base upstream of guanine residues on the template strand. Measurement of the amount of chromium bound to template DNA in relation to the number of arrests demonstrated that only a subset (18.5%) of the chromium adducts were capable of causing polymerase arrest. Arrest assays performed with increasing ratios of ascorbate to chromium showed that high ratios (> or = 5:1) resulted in decreased polymerase arrests. DNA interstrand crosslinks in the arrest assay template were detected by renaturing agarose gel electrophoresis, and were shown to decrease markedly with increasing ascorbate to chromium ratios, whereas chromium binding levels remained unchanged. These results strongly implicate DNA interstrand crosslinks as the polymerase arresting lesion. The present study confirms and extends our previous study with trivalent chromium, and suggests that while the initial chemical nature of the DNA lesions formed by either trivalent chromium or reductive intermediates of hexavalent chromium may differ, their effect on DNA replication is the same.

Ascorbic Acid↗
PubMed1997

Intermediates produced in the reaction of chromium(VI) with dehydroascorbate cause single-strand breaks in plasmid DNA.

Ascorbate (vitamin C) is a biological reductant of the human carcinogen chromium(VI). The product of this reaction is presumed to be dehydroascorbate. However, we have found that chromium(VI) can also react with dehydroascorbate. This reaction was monitored by UV/ visible and electron paramagnetic resonance (EPR) spectroscopies. In sodium acetate buffer at pH 3.8, the reaction of chromium(VI) and excess dehydroascorbate produced chromium(V) and chromium(IV) intermediates. At high reaction concentration, the chromium(V) intermediate formed an EPR silent dimer, which dissociated upon dilution to lower concentration. UV/ visible experiments at pH 3.8 demonstrated that manganese(II) catalyzed the disproportionation of chromium(IV) to chromium(V) and chromium(III). The ability of the reaction intermediates to induce strand breaks in pBR322 DNA was determined at pH 3.8 and pH 5.8. At pH 3.8, chromium(IV) appeared to be the major species responsible for induction of strand breaks because the time course for formation of strand breaks did not parallel that of chromium(V), and strand breaks were decreased in the presence of the chromium(IV) scavenger manganese(II). At pH 5.8, fewer strand breaks were observed; however, the time course for their formation followed that of chromium(V). There has been much effort devoted to identification of the intermediate responsible for the induction of strand breaks during reactions of chromium(VI) with biological reductants. The current results suggest that it is not a single type of species that universally produces the DNA strand breaks observed in different chromium(VI) systems and that the reactivity of intermediates will depend on the chosen experimental conditions. Understanding this variability in chromium(VI) reactions may help to resolve the conflicting results from in vitro studies that are aimed at deciphering mechanisms of chromium(VI)-induced cancers.

Chromium↗
PubMedDate not supplied

[Contribution of the incidence of urban sewage spreading to dietary chromium].

The sewage sludges contain fertilizing matters that justify their use in agriculture. Simultaneously, they hold minerals that are directly proportional to the nature and intensity of industrial activity. The more abundant are chromium, lead, zinc; cadmium and mercury are also found. The concentration in chromium varies from 0.2 to 20.0 g/kg of dry matter. Its assimilation by the rootlet and, later, its intestinal absorption, are essentially dependent on its chemical state; the hexavalent forms have a high biodisponibility and are more toxic than the trivalent compounds. In vegetals, the assimilated chromium is stopped in the root, associated to iron hydrates; a small fraction reaches the leaves and a weaker part comes up to the grain. (Table I). If the concentration of chromium--mainly hexavalent salts--is very important in soil, the mechanism of regulation in the rootlet becomes inefficacious and chromium diffuses in the whole plant (Table II). The development of spraying of sludges and composts will increase the quantity and efficiency of chromium in vegetals, because of various factors: the wastes of many industries: chromium plating plants, tanneries, painting and dyeing industries throw out hexavalent chromium; if the sewage sludges are purified by an irradiation treatment, it will tend to oxidize the whole chromium in hexavalent forms; at last, the presence of sewage sludges in the arable soil favours the assimilation of chromium by inhibiting that of iron (Figure 1). Then, in absence of iron hydrates that regularize the diffusion of chromium in the plant, this latter tends to overrun more easily the aerial tissues and organs of vegetals. On the whole, the spraying of sewage sludges supplies the soil with chromium that will easily be assimilated by the plant, considering that it will be mainly at an hexavalent state. Compared with other trace elements held in the sludges, chromium is assimilated by the plant in a clearly more important proportion (Table III). That is why the consequences of spraying concern more particularly chromium than other elements, even if they are toxic. The intensification of spraying will contribute to increase the chromium intake that varies from 100 to 200 micrograms/day and whose 60% are provided by foods of vegetal origin. The consequences of a more important intake will be dependent on chemical state of chromium. If the hexavalent salts are predominant, an increase of intake will provoke a high intestinal absorption, a raising of chromium rate in liver, kidney, spleen, bone, etc. This situation will eventually be responsible for a chronic intoxication.(ABSTRACT TRUNCATED AT 400 WORDS)

Agrochemicals↗
PubMedDate not supplied

Mechanism of chromium(VI) carcinogenesis. Reactive intermediates and effect on gene expression.

Since chromium(VI) is unreactive toward DNA under physiological conditions in vitro, the ability of carcinogenic chromium(VI) compounds to damage DNA depends on the presence of cellular redox components that reduce chromium(VI) to reactive species capable of interacting with DNA. We have examined the role of glutathione and hydrogen peroxide in chromium(VI)-induced DNA damage in vitro. Upon reaction with chromium(VI), glutathione produced chromium(V) and glutathione thiyl radical reactive intermediates, whereas hydrogen peroxide produced chromium(V) and hydroxyl radical. Reaction of DNA with chromium(VI) in the presence of glutathione resulted in binding of chromium and glutathione to DNA with little or no DNA strand breakage. Reaction of DNA with chromium(VI) in the presence of hydrogen peroxide produced the 8-hydroxydeoxyguanosine adduct and extensive DNA strand breakage in the absence of significant Cr-DNA adduct formation. These results suggest that the nature of chromium(VI)-induced DNA damage will be strongly dependent on reactive intermediates such as chromium(V), glutathione thiyl radical, and hydroxyl radical, produced by cellular components active in chromium(VI) metabolism. In order to assess the ability of chromium(VI)-induced DNA damage to affect the normal template function of DNA, we investigated the effects of chromium(VI) on steady-state mRNA levels of various genes in chick embryo liver in vivo, and compared the effects to the levels of DNA damage observed. Chromium(VI) induced DNA-protein and DNA interstrand cross-links in chick embryo liver in vivo and suppressed the induction of 5-aminolevulinic acid synthase and cytochrome P-450 mRNA expression by porphyrinogenic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

The interaction of chromium with nucleic acids.

Native and denatured calf thymus DNA, and homopolyribonucleotides were compared with respect to chromium and protein binding after an in vitro incubation with rat liver microsomes, NADPH, and chromium (VI) or chromium (III). A significant amount of chromium bound to DNA when chromium (VI) was incubated with the native or the denatured form of DNA in the presence of microsomes and NADPH. For both native and denatured DNA the amount of protein bound to DNA increased with the amount of chromium bound to DNA. Denatured DNA had much higher amounts of chromium and protein bound than native DNA. There was no interaction between chromium(VI) and either form of DNA in the absence of the complete microsomal reducing system. The binding of chromium(III) to native or denatured DNA was small and relatively unaffected by the presence of microsomes and NADPH. The binding of chromium and protein to polyriboadenylic acid (poly(A], polyribocytidylic acid (poly(C], polyriboguanylic acid (poly(G] and polyribouridylic acid (poly(U] was determined after incubation with chromium(VI) in the presence of microsomes and NADPH. The magnitude of chromium and protein binding to the ribopolymers was found to be poly(G) much greater than poly(A) approximately equal to poly(C) approximately equal to poly(U). These results suggest that the metabolism of chromium(VI) is necessary in order for chromium to interact significantly with nucleic acids. The metabolically-produced chromium preferentially binds to the base guanine and results in DNA-protein cross-links. These findings are discussed with respect to the proposed scheme for the carcinogenicity of chromium(VI).

Animals↗
PubMed2000

Lung cancer among workers in chromium chemical production.

BACKGROUND: An elevated risk of lung cancer among workers in chromate production facilities has previously been reported. This excess risk is believed to be the result of exposure to hexavalent chromium. There have been mixed reports about whether trivalent chromium exposure is also associated with an excess lung cancer risk. Previous studies of measured hexavalent chromium exposure and lung cancer risk have not examined cigarette smoking as a risk factor. METHODS: A cohort of 2,357 workers first employed between 1950 and 1974 at a chromate production plant was identified. Vital status of the workers was followed until December 31, 1992. Work histories of cohort members were compiled from the beginning of employment through 1985, the year the plant closed. Annual average exposure estimates, based on historical exposure measurements, were made for each job title in the plant for the years 1950-1985. These exposure estimates were used to calculate the cumulative hexavalent chromium exposure of each member of the study population. Following closure of the plant, settled dust samples were collected and analyzed for hexavalent and trivalent chromium. The trivalent/hexavalent concentration ratios in each plant area were combined with historic air-sampling data to estimate cumulative trivalent chromium exposure for each individual in the study cohort. Smoking status (yes/no) as of the beginning of employment and clinical signs of potential chromium irritation were identified from company records. RESULTS: Cumulative hexavalent chromium exposure showed a strong dose-response relationship for lung cancer. Clinical signs of irritation, cumulative trivalent chromium exposure, and duration of work were not found to be associated with a risk of lung cancer when included in a proportional hazards model with cumulative hexavalent chromium exposure and smoking. Age-specific data on cumulative hexavalent chromium exposure, observed and expected numbers of lung cancer cases, and person-years of observation are provided. CONCLUSIONS: Cumulative hexavalent chromium exposure was associated with an increased lung cancer risk; cumulative trivalent chromium exposure was not. The excess risk of lung cancer associated with cumulative hexavalent chromium exposure was not confounded by smoking status. The current study offers the best quantitative evidence to date of the relationship between hexavalent chromium exposure and lung cancer. Am. J. Ind. Med. 38:115-126, 2000. Published 2000 Wiley-Liss, Inc.

Chemical Industry↗
PubMed1992

Excessive chromium intake in children receiving total parenteral nutrition.

Various expert bodies have recommended that the daily parental intake of chromium in children receiving total parenteral nutrition (TPN) should be 0.20 micrograms/kg. To test whether this recommendation is appropriate, we assessed chromium intake, serum chromium concentrations, and renal function in 15 children receiving TPN. The median duration of TPN use was 9.5 (range 1.3-14) years. The children's glomerular filtration rate (GFR), measured by plasma clearance of indium-111-DTPA was lower than that of non-TPN controls (70 [SD 17] vs 110 [10] ml/min per 1.73 m2). The daily chromium intake averaged 0.15 (0.09) micrograms/kg daily but the serum chromium concentration was 20 (4 to 42) times higher than that of the controls (2.1 [1.2] vs 0.10 [0.03] micrograms/l; p less than 0.0001). GFR was significantly inversely correlated with serum chromium concentration (r = -0.60, p less than 0.02), daily chromium intake (r = -0.69, p less than 0.01), cumulative parenteral chromium intake (r = -0.72, p less than 0.01), and TPN duration (r = -0.52, p less than 0.05). We discontinued chromium supplementation of TPN solutions and reassessed the children a year later. Contaminating chromium concentrations were 1.0-1.8 micrograms/l in TPN solutions and 0.9 micrograms/l in fat emulsions. Drinking water contained 4.3-5.7 micrograms/l. Thus, the chromium intake without supplementation was only 0.05 (0.01) micrograms/kg daily. The mean serum chromium concentration fell to 0.50 (0.30) micrograms/l but was still significantly higher than that in the controls (p less than 0.01). The GFR did not change significantly (65 [14] ml/min per 1.73 m2). No patient has shown signs of chromium deficiency. Although our patients were receiving less than the recommended chromium intake during supplementation, their high serum concentrations suggested excessive intake. The recommended parenteral chromium intake for children should be lowered.

Adolescent↗
PubMed1994

Use of molecular epidemiological techniques in a pilot study on workers exposed to chromium.

OBJECTIVES: Molecular epidemiological techniques, capable of detecting damage to DNA, were used to see if such damage occurred in the lymphocytes of a group of workers exposed to chromium. The two aims of this pilot study were to see if these new techniques might make useful biological monitoring tools for workers exposed to chromium and also, to help assess whether the current occupational exposure limit for chromium (VI) was sufficiently protective in this specific working situation. METHODS: Volunteer groups of 10 workers exposed to chromium and 10 non-exposed workers provided urine and blood samples towards the end of the working week. Chromium concentrations were measured in whole blood, plasma, lymphocytes, and urine. Lymphocytes were used to examine two forms of DNA damage in the two groups; these were the level of DNA strand breakage and, the production of 8-hydroxydeoxyguanosine. RESULTS: Chromium concentration in whole blood, plasma, and urine of workers exposed to chromium was significantly raised (P < 0.01) compared with non-exposed controls, but in isolated lymphocytes, there was only a modest but significant (P < 0.05) increase in chromium in the group exposed to chromium. There was no difference in the levels of DNA strand breaks or 8-hydroxydeoxyguanosine between the groups. Air monitoring for chromium was not undertaken but current levels for the group exposed to chromium were reported to be around 0.01 mg/m3, which is 20% of the current United Kingdom occupational exposure limit. CONCLUSIONS: We were unable to detect any damage in lymphocytic DNA due to exposure to chromium. This may have been due to the low chromium exposure (< 20% of the United Kingdom occupational exposure limit), the ability of plasma to detoxify chromium (VI) to chromium (III) before it reached the lymphocytes, or perhaps the insensitivity of the molecular techniques used. It is now important to test these and other such techniques on groups exposed to levels closer to the United Kingdom occupational exposure limit.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Possible adverse effect of chromium in occupational exposure of tannery workers.

Our aim was to investigate the adverse effects of occupational exposure to trivalent chromium. We measured chromium and iron levels in serum and urine and hemoglobin levels in tannery workers and unexposed persons. We studied three groups of subjects. Group 1 included 15 non-smoking male tannery workers highly exposed to chromium from tanning and retanning departments. Group 2 included 14 non-smoking male tannery workers with moderate chromium exposure from dying, drying and finishing departments. Group 3 included 11 healthy, non-smoking male subjects without direct chromium exposure. Higher serum chromium levels were observed in groups 1 and 2 with respect to group 3 (mean values respectively: 0.43; 0.25 and 0.13 microg x l(-1)). Urine chromium levels in group 1 were higher than those in controls (mean values: 1.78 and 1.35 microg x l(-1)). In group 1 an inverse association was found between serum chromium and urine iron (-0.524), urine chromium and hemoglobin (-0.594) and between the urine chromium to iron ratio and hemoglobin (-0.693, p<0.05). The results suggest a chromium adverse effect on iron metabolism, possibly associated with excessive body chromium accumulation. In conclusion, chromium urine test could be recommended for diagnosis of chromium adverse effect on iron metabolism. Further studies are needed to quantify the relationship between urine chromium and hemoglobin metabolism.

Adult↗
PubMed2001

Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene.

Chromium (VI) is a widely used industrial chemical, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome, and wood treatment. On the contrary, chromium (III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate, are used as micronutrients and nutritional supplements, and have been demonstrated to exhibit a significant number of health benefits in rodents and humans. However, the cause for the hexavalent chromium to induce cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that chromium (VI) induces an oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following chromium (VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. In this paper, we have demonstrated concentration- and time-dependent effects of sodium dichromate (chromium (VI) or Cr (VI)) on enhanced production of superoxide anion and hydroxyl radicals, changes in intracellular oxidized states as determined by laser scanning confocal microscopy, DNA fragmentation and apoptotic cell death (by flow cytometry) in human peripheral blood mononuclear cells. These results were compared with the concentration-dependent effects of chromium (VI) on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Chromium (VI)-induced enhanced production of ROS, as well as oxidative tissue and DNA damage were observed in these cells. More pronounced effect was observed on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Furthermore, we have assessed the effect of a single oral LD50 dose of chromium (VI) on female C57BL/6Ntac and p53-deficient C57BL/6TSG p53 mice on enhanced production of superoxide anion, lipid peroxidation and DNA fragmentation in the hepatic and brain tissues. Chromium (VI)-induced more pronounced oxidative damage in p53 deficient mice. This in vivo study highlighted that apoptotic regulatory protein p53 may play a major role in chromium (VI)-induced oxidative stress and toxicity. Taken together, oxidative stress and oxidative tissue damage, and a cascade of cellular events including modulation of apoptotic regulatory gene p53 are involved in chromium (VI)-induced toxicity and carcinogenesis.

Animals↗
PubMed1999

Chromium.

Chromium occurs primarily in the trivalent state (III), which is the most stable form, or in the hexavalent state (VI), which is a strong oxidizing agent. Elemental chromium (0) does not occur naturally on earth. Trivalent chromium (III) is an essential trace metal necessary for the formation of glucose tolerance factor and for the metabolism of insulin. Commercial applications of chromium compounds include tanning (III), corrosion inhibition, plating, glassware-cleaning solutions, wood preservatives (VI), manufacture of safety matches, metal finishing (VI), and the production of pigments (III, VI). Hexavalent chromium (VI) contaminated local soil when chromium waste slag was part of the fill material present in residential, public, and industrial areas. In some urban areas, about two-thirds of the chromium in air results from the emission of hexavalent chromium from fossil fuel combustion and steel production. The remaining chromium in air is the trivalent form. The residence time of chromium in air is < 10 days, depending on the particle size. Trivalent compounds generally have low toxicity and the gastrointestinal tract poorly absorbs these compounds. Hexavalent chromium is a skin and mucous membrane irritant and some of these hexavalent compounds are strong corrosive agents. Hexavalent chromium compounds also produce an allergic contact dermatitis characterized by eczema. Sensitivity to trivalent compounds is much less frequent, but some workers may react to high concentrations of these compounds. Hexavalent chromium is recognized by the International Agency for Research on Cancer and by the US Toxicology Program as a pulmonary carcinogen. The increased risk of lung cancer occurs primarily in workers exposed to hexavalent chromium dust during the refining of chromite ore and the production of chromate pigments. Although individual studies suggest the possibility of an excess incidence of cancer at sites outside the lung, the results from these studies are inconsistent.

Animals↗
PubMed1992

Permeation of chromium salts through human skin in vitro.

Chromium permeation studies were performed on full thickness human skin in diffusion cells. All samples were analysed for the total chromium content by graphite furnace Zeeman-corrected atomic absorption spectrometry. Some samples were analysed by an ion chromatographic method permitting the simultaneous determination of Cr(VI) and Cr(III) as well. The amounts of chromium found in all skin layers were significantly higher when potassium dichromate was applied to the skin compared with chromium chloride or chromium nitrate. Chromium could only be detected in the recipient phase after application of the dichromate solution. Chromium skin levels increased with increasing concentrations of applied chromium salts up to 0.034 M Cr. The amount of chromium in recipient phase and skin layers increased with increasing pH when the applied solution contained potassium dichromate. This was ascribed to a decreased skin barrier function of the skin. The amount of chromium found in all skin layers after application of chromium chloride decreased with increasing pH due to lower solubility of the salt. The % of chromium found in the recipient phase as chromium(VI) increased with increasing total chromium concentration indicating a limited reduction ability of the skin in vitro.

Chlorides↗