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An assessment of the tumorigenic properties of a Hudson County soil sample heavily contaminated with hexavalent chromium.

During much of this century, Hudson County, New Jersey, was a major center for the processing of chromium ore. Some of the residue from this processing was used in landfills and in construction materials throughout the county and, in some cases, in highly populated areas. Given that it is widely accepted that exposure to hexavalent chromium compounds poses a risk for the development of respiratory-tract cancer, concerns were raised that individuals who worked or resided in chromium-contaminated areas might be at increased risk for the development of respiratory cancer. To address these concerns, we evaluated a Hudson County soil sample-heavily contaminated with chromium ore residue (Cr(+6) concentration at 5 895 mg/kg)-with respect to its carcinogenic potential to the respiratory tract of Sprague-Dawley rats. Groups of animals were given repeated intratracheal exposures to one of four materials: (1) Hudson County chromium-contaminated soil (CCS), (2) CCS augmented with calcium chromate (CaCrO4), (3) CaCrO4 alone, or (4) control soil. Nominal total doses of Cr(+6) for each respective group were 324 microg/kg, 7,975 microg/kg, 8,700 microg/kg, and 0.02 microg/kg. Incidences of malignant tumors and nephritis were not elevated in any group. Four primary lung tumors appeared in animals that received CCS + CaCrO4, and one primary lung tumor appeared in the group treated with CaCrO4 alone. These incidences were not significant statistically, but the rare spontaneous occurrence of these tumors in Sprague-Dawley rats suggested that they were treatment related. No primary lung tumors appeared in the control or CCS-treated groups.

Animals↗

Observation of steady state in blood and urine following human ingestion of hexavalent chromium in drinking water.

The uptake and elimination of Cr(VI) in a male volunteer who ingested 2 L/d of water containing 2 mg/L for 17 consecutive days was measured. Total chromium was measured in urine, plasma, and red blood cells (RBCs) for 4 d prior to and 2 wk after dosing (34 d total). The estimated bioavailability (2%) and the plasma elimination half-life (36 h) were consistent with our previous studies of Cr(VI) ingestion in humans. Steady-state chromium concentrations in urine and blood were achieved after 7 d of Cr(VI) ingestion. Both plasma and red blood cell (RBC) chromium concentrations returned rapidly to background levels within a few days after cessation of dosing. Since the concentration of chromium in the RBC should not decrease quickly if the chromium had entered the RBC as Cr(VI), these data support our prior work suggesting that concentrations of 10 mg Cr(VI)/L or less in drinking water of exposed humans appears to be completely reduced to Cr(III) prior to systemic distribution. Clinical chemistry data indicate that no toxicity occurred.

Administration, Oral↗

Nutritional factors influencing the glucose/insulin system: chromium.

Chromium (Cr) improves the glucose/insulin system in subjects with hypoglycemia, hyperglycemia, diabetes and hyperlipemia with no detectable effects on control subjects. Chromium improves insulin binding, insulin receptor number, insulin internalization, beta cell sensitivity and insulin receptor enzymes with overall increases in insulin sensitivity. There have been several studies involving Cr supplementation of subjects with NIDDM and/or lipemia and most have reported beneficial effects of Cr on the glucose/insulin system. In a recent study, Chinese subjects with NIDDM were divided into three groups of 60 subjects and supplemented with placebo, 100 or 500 micrograms of Cr as chromium picolinate 2 times per day for 4 months. Improvements in the glucose/insulin system were highly significant in the subjects receiving 500 micrograms twice per day with less or no significant improvements in the subjects receiving 100 micrograms twice per day after 2 and 4 months. In summary, Cr is involved in the control of the glucose/insulin system and the amount, and likely form of chromium, are critical when evaluating the role of chromium in this system.

Animals↗

Comments on article "Toxicity and carcinogenicity of chromium compounds in humans" by Costa and Klein.

The recent article by Costa and Klein (2006) contains several inaccuracies about the federal drinking water standard for chromium. The federal drinking water standard for chromium is 100 ppb, not 50 ppb as stated by Costa and Klein, and it is based on non-carcinogenic effects, not a one in one million cancer risk level. The question of whether or not hexavalent chromium is carcinogenic via the oral route is the focus of much current interest and has major implications for regulation of chromium in drinking water and soil. The chronic drinking water study of hexavalent chromium currently being conducted by the National Toxicology Program will provide further information that will be useful in addressing this question.

Administration, Oral↗

Chromium effects on chondrocytic differentiation in vitro.

A tissue culture study was conducted on the effects of chromium on chondrocytic differentiation. Mesenchymal cells from stage 22-24 chick limb buds were dispersed and cultured as micromasses, where they differentiated into chondrocytes. Addition of chromium(VI) to the cultures indicated that the production of proteoglycans (as detected by Alcian blue staining) was more sensitive to chromium's effects than was cell proliferation. Whereas Alcian blue nodule formation was inhibited by 1 microM Cr(VI), cell proliferation (as detected by cell counts) was not. Chromium (VI) was added to cultures at daily intervals, and these studies indicated that the interval of d 1-2 was the most sensitive period. ADP-ribose transferase activity in these cultures was measured; the pattern of enzyme activity in control cultures was high 1 and 24 h after the start of culture, decreased abruptly between 24 and 48 h, and then decreased more gradually. In the presence of Cr(VI), elevated ADP-ribose transferase levels were maintained throughout the culture period. We suggest that, in presence of 1.0 microM chromium(VI) or higher concentrations, the balance of events favors nucleolytic action rather than repair of damage.

Alcian Blue↗

Designing a biological monitoring program to assess community exposure to chromium: conclusions of an expert panel.

The possible benefits of biological monitoring of large groups of people potentially exposed to environmental contaminants has become an area of much interest in recent years. Because chromite-ore processing residue has been found in some soils in northern New Jersey, urinary chromium monitoring of people in the community was evaluated as a potentially useful tool. In an attempt to identify those who could be exposed and to quantify the magnitude of exposure to the chromium in these soils, the New Jersey Department of Health (NJDOH) initiated a public health screening project. In 1992, the NJDOH proposed to evaluate over 4000 people who lived or worked near these sites. Volunteers were administered a questionnaire and were given a limited physical examination, and a single spot urine sample was collected. Because of the difficulties in using urinary chromium to assess low-level exposure and the potential implications of any regulatory decisions that could be based on the results of this project, a panel of experts was convened to evaluate the protocol. The panel consisted of five scientists and physicians with expertise in toxicology, dermatology, epidemiology, biological monitoring, and analytical chemistry. Like a World Health Organization group, the panel concluded that although urine biomonitoring can be useful in evaluating high levels of exposure to chromium, it is not reliable for assessing low-level exposure similar to that which may have occurred in northern New Jersey. The panel also noted that when urinary biomonitoring is to be used to assess the public's possible exposure, a large number of precautions must be taken to ensure the accuracy and usefulness of the results. The single most important recommendation was to collect a second, and perhaps a third, spot urine (or 24-h urine) sample before concluding that a person may be routinely overexposed. These suggestions are applicable to designing a biomonitoring program for nearly any environmental contaminant to which a community may be exposed. A review of scientific literature associated with biological monitoring of chromium is provided.

Absorption↗

Chromium yeast affects growth performance and plasma traits but not carcass characteristics of growing-finishing pigs depending on the glycemic index.

Forty Swiss Large White pigs (barrows with 31.7 kg initial to 103.7 kg final BW) were equally and randomly assigned to one of four treatments (H0, H200, L0, L200) involving a combination of chromium supplementation (0 or 200 micrograms/kg) and glycemic index (high GI (H) or low GI (L)). Growth performance, energy and protein digestibility, carcass composition, and some plasma traits were investigated. The data indicated, that the substitution of dietary carbohydrates with fat and crude fibre (low GI) resulted in lower growth performance due to impaired energy digestibility. Moreover, the strong stimulation of insulin secretion due to the high and rapid availability of carbohydrates of the diets H0 and H200 caused increased carcass fat deposition. Chromium supplementation also affected plasma insulin and glucagon concentrations. Depending on glycemic index, chromium affected the growth performance. Daily gain was reduced in pigs of the L200 treatment compared to the L0 group. This finding indicated that the energy availability expressed as GI is one of several nutritional factors, which determine the efficacy of dietary chromium. We could not corroborate evidences that dietary chromium modifies the chemical composition of the whole carcass, but depending on GI, chemical composition of the longissimus muscle was affected.

Animal Feed↗

The effect of parity and time between pregnancies on maternal hair chromium concentration.

Values for hair chromium concentration of nulliparous women and parous women who had just given birth to a child were determined by atomic absorption spectrophotometry. Mean values for hair chromium concentration of nulliparous and parous subjects were 309 +/- 23 and 117 +/- 10 ppb, respectively. The difference was highly significant (P less than 0.001). No further significant decrease in hair chromium was observed in women who had borne more than one child. Hair chromium concentration increased significantly with the amount of time between pregnancies, especially when at least 4 years had passed since the end of the last pregnancy (P less than 0.001). These data suggest a state of suboptimal chromium nutrition during pregnancy.

Adult↗

Influence of exercise training on tissue chromium concentrations in the rat.

This study reports on the effects of exercise training on the chromium concentrations in the heart, liver, kidney, and gastrocnemius muscle of normal Sprague-Dawley rats. A pair-fed (to the trained rats' intake) and a preexperimental group were also studied in order to control food intake and to ascertain any age-related influence on tissue chromium levels, respectively. Four groups of animals were examined: exercise-trained, pair-fed, preexperimental, and sedentary control. Chromium determination was performed by flameless atomic absorption spectrophotometry. The results from this study show that exercise training increases while pair-feeding and normal aging both decrease chromium levels in tissues. It is suggested that the male Sprague-Dawley rat adapts to exercise training by enhancing tissue levels of chromium or by simply maintaining the high levels of the element found at a younger age.

Aging↗

The trace element chromium--a role in glucose homeostasis.

To better define the normal metabolism of the trace element chromium, we studied its diurnal variation and its response to an oral glucose challenge in nine healthy volunteers. Plasma and urine chromium concentrations were measured by electrothermal atomic-absorption spectroscopy and plasma insulin by radioimmunoassay. A significant inverse relationship was found between plasma chromium and plasma insulin concentrations both over a 24-h period (P less than 0.001) and after a 75-g glucose load (P less than 0.01). This interesting observation, suggesting the removal of chromium from the plasma compartment after meals (confirmed by glucose tolerance test), is not explained simply by increased urinary loss but might be explained by transient changes in uptake or binding of chromium by insulin-sensitive tissues.

Adult↗

Measurement of DNA-protein cross-links in human leukocytes following acute ingestion of chromium in drinking water.

Increased DNA-protein cross-linking (DPX) in circulating leukocytes has been proposed as a potential biomarker for exposure and genotoxic damage caused by inhalation of certain reactive chemicals, such as hexavalent chromium [Cr(VI)]. This study was designed to determine whether ingestion of a single dose of potassium dichromate alone [Cr(VI)] or potassium dichromate fully reduced to Cr(III) with orange juice (prior to ingestion) causes an increase in DPX of circulating leukocytes in humans. Four adult male volunteers ingested a bolus dose of 5000 micro chromium in a 0.51 volume of water (10 p.p.m.), and blood samples were collected at 0, 60, 120, 180 and 240 min afterwards for analysis of DPX formation in circulating leukocytes. Results were compared to each person's own background concentration of DPX in leukocytes. Blood and urine samples were also collected for up to 2 weeks following the dose to examine the pattern of uptake and excretion of chromium. The results showed that there was no significant change in DPX observed following either Cr(VI) or Cr(III) ingestion, even though blood and urine chromium measurements indicated systemic uptake of a substantial fraction of the ingested chromium. Since Cr(III) does not possess DPX-inducing properties while Cr(VI) does, these results suggest that the Cr(VI) was reduced to Cr(III) intragastrically prior to absorption or that the amount of Cr(VI) absorbed into the blood was insufficient to produce DPX. These results are consistent with prior research that indicated that DPX would not occur following exposure to Cr(VI) except at very high doses.

Administration, Oral↗

Alterations of rat adipose tissue metabolism associated with dietary chromium supplementation.

Net free fatty acid release from adipose tissue taken from male rats fed a stock diet unsupplemented with chromium was significantly greater than that from adipose tissue taken from chromium-supplemented rats. This enhanced net lipolysis was unaccompanied by any evidence of a compensatory increase in reesterification. Specifically, the glycerokinase-catalyzed direct phosphorylation of glycerol, which might have provided an alternate supply of alpha-glycerophosphate for reesterification in the absence of glycolytic production of alpha-glycerophosphate, was significantly reduced. These animals also showed an abnormal glucose tolerance response. In contrast, male rats fed a purified diet unsupplemented with chromium appeared to be marginally chromium-deficient as judged by a glucose tolerance test but did not show any alterations in adipose tissue metabolism attributable to the adequacy of chromium nutriture.

Adipose Tissue↗

Maternal and fetal insulin-like growth factor system and embryonic survival during pregnancy in rats: interaction between dietary chromium and diabetes.

Chromium (Cr) depletion may exacerbate hyperglycemia and negative outcomes of pregnancy in the streptozotocin (STZ) diabetic pregnant rat model through the regulation of the insulin-like growth factor (IGF) system. To test this hypothesis, 40 female rats, all fed a low Cr diet (i.e., 70 microgram Cr/kg diet ) from 21 d of age, were randomly assigned one of four treatments, applied on Day 1 of pregnancy, in a 2 x 2 factorial design: 1) very low Cr diet (40 microgram Cr/kg diet) + citrate buffer injection, 2) very low Cr diet + STZ injection (30 mg STZ/kg body wt in citrate buffer), 3) adequate Cr diet (2 mg Cr [from added CrK(SO4)2]/kg diet) + citrate buffer injectionand 4) adequate Cr diet + STZ injection. Blood and tissues were collected on Day 20 of pregnancy. Chromium depletion increased (P < 0.05) urinary hydroxyproline excretion, 22-kDa IGF binding protein (IGFBP) concentration and litter size but decreased (P < 0. 05) placental wt, percentage of protein per fetus, and fetal IGF-I and -II concentrations. Chromium had no effect (P > 0.10) on maternal hormones, 32-kDa IGFBP, glucose, or placental and fetal hydroxyproline concentrations. Diabetes decreased (P < 0.05) maternal wt gain, embryonic survival, litter size, mean pup wt and maternal insulin concentrations, increased (P < 0.05) maternal blood glucose, IGF-I concentrations and maternal hydroxyproline excretion but did not affect fetal concentrations of hormones, IGFBP, glucose or hydroxyproline. Interaction between chromium and diabetes tended (P < 0.10) to affect maternal IGF-II concentrations, but had no effect on other maternal or fetal variables. In conclusion, maternal chromium depletion did not exacerbate hyperglycemia or pregnancy outcome in STZ-induced diabetic rats, but may negatively affect fetal protein content by decreasing fetal IGF-II concentrations. Diabetes may negatively affect fetal growth through its effect on maternal glucose, insulin and IGF-I.

Animals↗

Nasal cell micronuclei, cytology and clinical symptoms in stainless steel production workers exposed to chromium.

The objective of the present study was to determine whether workers in stainless steel production with low exposure to various forms of chromium show an increase in micronucleated nasal cells or an excess of nasal symptoms or disease. Altogether, 48 workers employed in a stainless steel production chain were studied, 29 of them in the steel melting shop with exposure to hexavalent chromium (Cr(6+)), 14 in the sintering and crushing departments of the ferrochromium plant with exposure to trivalent chromium (Cr(3+)) and five in the mine with exposure to chromite ore (Cr(3+)). Thirty-nine workers from the cold rolling mill, with very low exposure to chromium, served as referents. All the subjects were never smokers with a minimum of 14 years employment in the same department. There were no significant differences between the exposure groups and the referents regarding the mean frequency of centromere-negative or centromere-positive micronuclei (studied by pancentromeric fluorescence in situ hybridization), nasal diseases and symptoms or mucociliary clearance of the nasal cavity. No statistically significant differences in the incidence of cell atypia or inflammatory cells were detected between the exposed workers and the reference group, except for an increase in lymphocytes among the chromite ore workers. Anterior rhinoscopy indicated slight inflammatory changes in nasal mucosa and secretion more often in the Cr(6+) and Cr(3+) groups than in the referents, the Cr(6+)-exposed workers showing more livid or oedemic epithelium. In conclusion, the stainless steel production workers, with low exposure to dusts or fumes containing hexavalent or trivalent chromium, did not show clinical changes in the nasal mucosa or an increase in nasal cell micronuclei or symptoms of nasal diseases, except for slight changes in the nasal epithelium and secretion.

Adult↗

Apoptosis and P53 induction in human lung fibroblasts exposed to chromium (VI): effect of ascorbate and tocopherol.

Some forms of hexavalent chromium [Cr(VI)] are known to cause damage to respiratory tract tissue, and are thought to be human lung carcinogens. Because Cr(VI) is mutagenic and carcinogenic at doses that evoke cell toxicity, the objective of these experiments was to examine the effect of Cr(VI) on the growth, survival, and mode of cell death in normal human lung fibroblasts (HLF cells). DNA adduct formation was monitored as a marker for bioavailability of genotoxic chromium. We also examined the modulation of these endpoints by vitamins C and E. Long-term Cr(VI) exposures were employed, which decreased clonogenic cell survival by 25% to 95% in a dose-dependent manner. The predominant cellular response to Cr(VI) was growth arrest. We found that Cr(VI) caused up to 20% of HLF cells to undergo apoptosis, and documented apoptotic morphology and the phagocytosis of apoptotic bodies by neighboring cells. P53 levels increased 4- to 6-fold in chromium-treated cells. In contrast with previous studies using CHO cells, the present study using HLFs found that pretreatment with either vitamin C or E did not exhibit a significant effect on Cr-induced apoptosis or clonogenic survival. In addition, pretreatment with vitamin C did not affect the p53 induction observed after chromium treatment. Neither vitamin had any effect on Cr-DNA adduct formation. These data indicate that although pretreatment with vitamin C or E alters the spectrum of cellular and/or genetic lesions induced by chromium(VI), neither vitamin altered the initiation or progression of apoptosis in diploid human lung cells.

Antioxidants↗

Quantifying the stress induced by distress in patients with lumbar disc herniation in terms of natural killer cell activity measurements: chromium release assay versus multiparameter flow cytometric assay.

STUDY DESIGN: A comparative study was conducted. OBJECTIVES: To attempt quantification of the stress in patients with lumbar disc herniation by measuring natural killer cell activity, and to evaluate the assay methodology. SUMMARY OF BACKGROUND DATA: Stressful events may have adverse effects on health. Distress in the patient with lumbar disc herniation also may be a stressful event. Previous findings have shown the activity of natural killer cells to be impaired in medical student volunteers and after bereavement or other stressful life events. However, the stress in patients with spinal disorders has not been evaluated. The standard assay for natural killer cell activity has been the chromium release assay. However, this assay requires the use of radioactive chromium. Flow cytometric assay is a nonradioactive method that analyzes the activated natural killer lymphocyte subsets: CD45+, CD56+, CD69+. METHODS: Peripheral blood lymphocytes were obtained from 20 patients with lumbar disc herniation (mean age, 30.8 years) and 20 healthy individuals (mean age, 38.9 years). Both chromium release assay and flow cytometric assay were performed for each patient. RESULTS: The mean natural killer cell activity in the patients (8.0% +/- 4.3%) was significantly lower than in the 20 healthy adult volunteers (12.6% +/- 4.5%). The mean natural killer cell activity in the healthy volunteers was 12.6% +/- 4.5% for the chromium release assay and 11.0% +/- 4.1% for the flow cytometric assay. The correlation (r = 0.77) of natural killer cell activity between the two methods was high. CONCLUSIONS: Natural killer cell activity in the patients with lumbar disc herniation was significantly lower than in healthy individuals, and the stress induced by pain and other distress may be present in patients with lumbar disc herniation. For measuring natural killer cell activity, flow cytometric assay is a reproducible assay, and it may be a viable alternative to the standard chromium release assay.

Adult↗

Occupational asthma caused by chromium.

We report four cases of occupational asthma caused by chromium salts, three of whom showed dual and one isolated early asthmatic responses on specific chromium bronchoprovocation test (BPT). All of them were ex-smokers. Two showed positive skin-prick tests to 10 mg/ml of Cr2(SO4)3, but negative results on patch testing. The remaining two showed positive results on patch testing with Cr2(SO4)3. Three had airway hyperresponsiveness to methacholine on initial examination. Although initial methacholine airway challenge testing showed a negative result in the remaining patient, airway hyperresponsiveness developed transiently 24 h after an isolated immediate asthmatic reaction induced by chromium. Three patients were reassessed after complete avoidance of chromium. Two subjects showed marked improvement of their symptoms with significant increases of PC20 methacholine. We conclude that chromium induces occupational asthma in exposed workers. Further investigations are needed to clarify the pathogenetic mechanism.

Adult↗

Detergents and bleaches are sources of chromium contact dermatitis in Israel.

Total chromium levels were determined in 38 detergents and 12 bleaches on the market in Israel (45 locally produced, 5 imported). The samples were analyzed by Zeeman-corrected graphite furnace atomic absorption spectrophotometry. Chromium levels were higher than 5 ppm in 28 (56%) of the 50 products, from 1 to 5 ppm in 16 (32%), and lower than 1 ppm in only 6 (12%). Among the 5 imported products, only 1 had a chromium level below 1 ppm and the other 4 (1 from Germany, 3 from the USA) had high levels. Since a most 90% of the detergents and bleaches examined contained chromium levels higher than 1 ppm, it is concluded that these consumer products may be the cause of the high incidence of chromium sensitivity in Israel.

Anti-Infective Agents, Local↗