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Chronic chromium exposure-induced changes in testicular histoarchitecture are associated with oxidative stress: study in a non-human primate (Macaca radiata Geoffroy).

BACKGROUND: Reproductive toxicity of chromium is in dispute despite positive findings in rodents. Recently we reported epididymal toxicity of hexavalent chromium (CrVI) in bonnet monkeys and in this paper we report its testicular toxicity. METHODS: Adult monkeys (Macaca radiata) were given drinking water containing CrVI (100, 200, 400 p.p.m.) for 6 months and testes were removed for ultrastructural and biochemical analyses. RESULTS: CrVI treatment disrupted spermatogenesis, leading to accumulation of prematurely released spermatocytes, spermatids and uni- and multinucleate giant cells in the lumen of seminiferous tubules. Transmission electron microscopy revealed granulation of chromatin and vacuolation between acrosomal cap and manchette microtubules of elongated spermatids and in the Golgi area of round spermatids. Pachytene spermatocytes had fragmented chromatin and swollen mitochondria with collapsed cristae. Spermatocytes and spermatogonia in the basal compartment were unaffected. Macrophages containing phagocytosed sperm and dense inclusions in Sertoli cells were seen. Specific activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase and concentrations of the non-enzymatic antioxidants glutathione, vitamins A, C and E decreased, while concentrations of H(2)O(2) and hydroxyl radicals increased in the testis of chromium-treated monkeys. Withdrawal of chromium treatment for 6 months normalized spermatogenesis and the status of pro- and antioxidants in the testis. CONCLUSIONS: CrVI disrupts spermatogenesis by inducing free radical toxicity, and supplementation of antioxidant vitamins may be beneficial to the affected subjects.

Animals↗

Effects of pyridinium chlorochromate adulterant (urine luck) on testing for drugs of abuse and a method for quantitative detection of chromium (VI) in urine.

Pyridinium chlorochromate (PCC) as an adulterant is popular for concealing drug-positive results. When 11-nor-delta9-THC-9-carboxylic acid (THC-acid) in urine was treated with 2 mmol/L of PCC (Cr6+ 104 microg/mL), 58-100% of the THC-acid was lost. The loss increased with decreasing pH and increasing reaction time (0-3 days). Free codeine and free morphine remained unaffected by PCC at pH within the physiological range of the urine (pH 5-7). At lower pH, the loss of free morphine varied from 0 to 100%. Amphetamine, methamphetamine, benzoylecgonine, and PCP remained unaffected by PCC when exposed to the oxidant for three days in urine pH of 3-7. Chromium (VI) from PCC in a urine solution was detected by a color reaction with 1,5-diphenylcarbazide (DPC). When the reagent was added to the urine, an immediate red-violet color appeared. The chromium-DPC complex showed a characteristic absorption peak at wavelength 544 nm with a shoulder at wavelength 575 nm. The ratio of absorption was used to identify the chromium compound. The concentration of chromium (VI) was determined by measuring absorption at wavelength 544 nm and was linear over 0.5-20 microg/mL. The limit of detection of the procedure was 0.37 microg/mL.

Anti-Infective Agents↗

Interactions of trace metals in mouse and rat tissues; zinc, chromium, copper, and manganese with 13 other elements.

Tissues of rats and mice fed a nonessential metal in drinking water for life were analyzed for the essential metals chromium, copper, manganese and zinc. The study involved 505 rats and 843 mice. Livers, lungs, hearts, kidneys and spleens were pooled in groups according to age at death, averaging 5 for rats and 8 for mice, in order to provide adequate sample weight. Copper was significantly higher in livers of rats fed tin, germanium, niobium and zirconium than in controls. Similarly, niobium was associated with deposition of manganese in heart and zinc deposition in liver. Chromium levels were depressed in heart, kidney and spleen by germanium. In mice the greatest effects occurred when indium and rhodium were fed, all four essential trace metals exhibiting raised levels principally in kidney but also in heart and spleen. Chromium levels were raised in all organs but heart when hexavalent chromium was fed. From these data it is apparent that the ingestion of a nonessential metal can enhance the retention of an essential trace metal, perhaps thus avoiding toxicity from the nonessential one.

Animals↗

Distribution of cobalt chromium wear and corrosion products and biologic reactions.

Replacement hip arthroplasty with the use of ultrahigh molecular weight polyethylene for the cup articulating with a metal head has provided a low friction arthroplasty with years of success. However, the search for improved materials and designs for articulating surfaces continues. The use of metallic heads articulating with metallic cups is now being reconsidered for total hip replacements. Success will be enhanced if wear and corrosion of the articulating surfaces can be kept below that of the metal on ultrahigh molecular weight polyethylene couple. Concern has been raised about the release, and biologic fate, of metal species from corrosion and wear. Titanium alloys have been shown to have limitations as an articulating surface showing significant wear, and the alloy per se should not be considered for wear couples in total hip replacements. The cobalt chromium alloys are known to have reasonable wear and corrosion properties and continue to be evaluated. The issue of cobalt chromium wear and corrosion products and how this relates to the biologic performance of total hip replacement devices is reviewed. Under the condition of wear as currently experienced at the articulating surfaces of cobalt chromium alloys and ultrahigh molecular weight polyethylene, the amount of metallic products transferred to the tissues is sufficiently low to be well tolerated by the biologic system. Nickel and cobalt ions arc, rapidly transported from the implant site and eliminated in the urine. Chromium is stored in the tissue and eliminated more slowly. The issue of host hypersensitivity to these elements remains of concern. All 3 elements, in ionic form, are known to cause contact dermatitis. Untoward biologic reactions, including hypersensitivity, should be minimized if wear and corrosion phenomena are minimized.

Alloys↗

Urinary excretion of chromium following ingestion of chromite-ore processing residues in humans: implications for biomonitoring.

Biomonitoring programs for urinary chromium (Cr) typically attempt to evaluate occupational exposure via the inhalation route. This study investigated whether Cr can be detected in the urine of people following the ingestion of soils that contain relatively high concentrations of chromium in chromite ore processing residue (COPR). To evaluate the reasonableness of using urinary monitoring to assess environmental exposure, six volunteers ingested 400 mg of soil/day (low-dose group), two others ingested 2.0 g of soil/day (high-dose group) for 3 consecutive days, and one person ingested a placebo on each of 3 days. The soil and COPR mixture contained concentrations of total chromium (Cr) and hexavalent chromium [Cr(VI)] of 103 +/- 20 and 9.3 +/- 3.8 mg/kg, respectively. Therefore, the low-dose group ingested 41 micrograms Cr/day [including 3.7 micrograms Cr(VI)] and the high-dose group ingested 206 micrograms Cr/day [including 18.6 micrograms Cr(VI)] on each of 3 consecutive days. All urine samples were collected and analyzed individually for total Cr on the day prior to dosing, during the 3 days of dosing, and up to the first void 48 h after the last dose. No significant increases in urinary Cr excretion were found when background excretion data were compared with data following each of the 3 days of dosing or in daily mean urine concentrations of the high- vs the low-dose groups. It appears that Cr present in a soil and COPR mixture at Cr doses up to 200 micrograms/day is not sufficiently bioavailable for biomonitoring of urine to be informative.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of chromium on the immune system.

Chromium is a naturally occurring heavy metal found commonly in the environment in trivalent, Cr(III), and hexavalent, Cr(VI), forms. Cr(VI) compounds have been declared as a potent occupational carcinogen among workers in chrome plating, stainless steel, and pigment industries. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that together with oxidative stress oxidative tissue damage and a cascade of cellular events including modulation of apoptosis regulatory gene p53, contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. On the other hand, chromium is an essential nutrient required to promote the action of insulin in body tissues so that the body can use sugars, proteins and fats. Chromium is of significant importance in altering the immune response by immunostimulatory or immunosuppressive processes as shown by its effects on T and B lymphocytes, macrophages, cytokine production and the immune response that may induce hypersensitivity reactions. This review gives an overview of the effects of chromium on the immune system of the body.

Animals↗

Chromium, nickel and cobalt contents of some Australian cements.

The total chromium, nickel and cobalt concentrations of 8 Australian Portland cements ranged from 49 to 99 micrograms/g, 5 to 54 micrograms/g and < or = 1 to 13 micrograms/g, respectively. The water-soluble chromate concentrations of the cements ranged from 0.2 to 8.1 micrograms/g, and the sodium sulphate-extractable chromates from 1.4 to 9.7 micrograms/g. Results for water-soluble nickel (< or = 0.2 microgram/g) and cobalt (< or = 0.05 microgram/g) indicate that the metals are present only as water-insoluble compounds. The significance of the various data is considered from a dermatological point of view. Cement extracts for the analysis of water-soluble hexavalent chromium (chromates) are stable for at least 12 days. The optimum extraction time for hexavalent chromium in cement appears to be 1 h. Almost 100% reduction of hexavalent chromium is possible after 1 h using 100x the stoichiometric value of iron (II) sulphate. The chromates can become gradually insolubilized when the solution from the water added is in direct contact with the cement, i.e., over a period of > 60 min to 7 days, even without the addition of iron (II) sulphate.

Chromium↗

Chromium content in human skin after in vitro application of ordinary cement and ferrous-sulphate-reduced cement.

The amount of chromium found in human skin after in vitro application of cement suspensions on full-thickness human skin in diffusion cells was investigated. Cement suspensions made from ordinary Portland cement or Portland cement with the chromate reduced with added ferrous sulphate were used. The cement suspensions were either applied on the skin surface under occlusion for 48 h or applied repeatedly every 24 h for 96 h. No statistically significant difference in chromium content of skin layers between skin exposed to ordinary Portland cement, skin exposed to cement with added ferrous sulphate and unexposed skin was observed, despite a more permeable skin barrier at the alkaline pH of the cement suspensions, i.e., pH 12.5. Increased chromium levels in epidermis and dermis were seen when ordinary Portland cement was applied as a suspension with added sodium sulphate (20%) on the skin surface for 96 h. The content of water-soluble chromium in ordinary Portland cement may vary due to the alkali sulphate content of the cement.

Cementation↗

Contribution to chromium and nickel enrichment during cooking of foods in stainless steel utensils.

Nickel ingestion can cause exacerbation of dermatitis in patients who are already nickel-sensitive; Chromium (Cr VI) is the 2nd allergen, after nickel. However, stainless steel is widely used in home cookware. In this study, we determined nickel and chromium levels by atomic absorption spectrometry in 11 habitual menus cooked in different grades of stainless steel utensils. We noted a great difference in nickel and chromium intake depending on the menu, and a significant difference between the glass and stainless steel saucepans, but this was very low compared with the levels of nickel and chromium contained in the menus; mean intakes of these elements were under the tolerable daily intake (TDI) recommended by the World Health Organization. Hence, there is no advantage for nickel-sensitive patients in switching to materials other than stainless steel, provided that this is of good quality.

Allergens↗

Daily chromium intake by infants in Belgium.

The chromium content of human breast milk, infant formulae, cow's milk and beikost was measured by graphite furnace atomic absorption spectrometry following different digestion steps. No significant variation in chromium concentration during lactation was found. The mean concentration was 0.18 ng/ml. The daily chromium intake for Belgian infants of 3 months of age using different types of food was estimated. Exclusively breast fed infants consumed 0.1 microgram/day, while for infants fed cow's milk the intake was five times higher. The exclusive use of commercial infant formulas resulted in an intake of 2 up to 10 micrograms chromium a day.

Adult↗

Ground water flow in a desert basin: challenges of simulating transport of dissolved chromium.

A large chromium plume that evolved from chromium releases in a valley near the Mojave River was studied to understand the processes controlling fate and migration of chromium in ground water and used as a tracer to study the dynamics of a basin and range ground water system. The valley that was studied is naturally arid with high evapotranspiration such that essentially no precipitation infiltrates to the water table. The dominant natural hydrogeologic processes are recharge to the ground water system from the Mojave River during the infrequent episodes when there is flow in the river, and ground water flow toward a playa lake where the ground water evaporates. Agricultural pumping in the valley from the mid-1930s to the 1970s significantly altered ground water flow conditions by decreasing water levels in the valley by more than 20 m. This pumping declined significantly as a result of dewatering of the aquifer, and water levels have since recovered modestly. The ground water system was modeled using MODFLOW, and chromium transport was simulated using MT3D. Several innovative modifications were made to these modeling programs to simulate important processes in this ground water system. Modifications to MODFLOW include developing a new well package that estimates pumping rates from irrigation wells at each time step based on available drawdown. MT3D was modified to account for mass trapped above the water table when the water table declines beneath nonirrigated areas and to redistribute mass to the system when water levels rise.

Chromium↗

Quest for the molecular mechanism of chromium action and its relationship to diabetes.

Despite forty years of research on the potential role of chromium in carbohydrate and lipid metabolism, significant progress has only recently been made regarding the mode of action of chromium at a molecular level. The oligopeptide low-molecular-weight chromium-binding substance (LMWCr) may function as part of a novel insulin-signaling autoamplification mechanism. The proposed mechanism of action also sheds some light on the potential of chromium-containing compounds as nutritional supplements or in the treatment of adult-onset diabetes and other conditions. The potential relationship between the results of recent studies on diabetic patients and the proposed mode of action of LMWCr are discussed.

Chromium↗

Plasma chromium after glucose administration.

Sharp increases in the concentration of chromium in plasma were found in five subjects with normal glucose utilization after administration of glucose by mouth. This rise was not observed in two diabetics when glucose tolerance was impaired; however, it appeared when glucose tolerance was improved and when trace amounts of trivalent chromium were given as a dietary supple-ment. The source of chromium which became elevated was most likely an internal pool. Possibly there is a relation between chromium and insulin function.

Blood↗

Toxicity and mutagenicity of hexavalent chromium on Salmonella typhimurium.

Four hexavalent and two trivalent chromium compounds were tested for toxicity and mutagenicity by means of the Salmonella typhimurium/mammalian-microsome test. All hexavalent compounds yielded a complete inhibition of bacterial growth at doses of 400 to 800 mug/plate, a significant increase of his(+) revertant colonies at doses ranging from 10 to 200 mug, and no effect at doses of less than 10 mug. The distinctive sensitivity of the four Salmonella strains tested (TA1535, TA1537, TA98, and TA100) suggested that hexavalent chromium directly interacts with bacterial deoxyribonucleic acid by causing both frameshift mutations and basepair substitutions. The latter mutations, which are prevalent, are amplified by an error-prone recombinational repair of the damaged deoxyribonucleic acid. On the average, 1 mumol of hexavalent chromium yielded approximately 500 revertants of the TA100 strain, irrespective of the compound tested (sodium dichromate, calcium chromate, potassium chromate, or chromic acid). The mutagenic potency of the hexavalent metal was not enhanced by adding the microsomal fraction of rat hepatocytes, induced either with sodium barbital or with Aroclor 1254. The two trivalent compounds (chromium potassium sulfate and chromic chloride), with or without the microsomal fraction, were neither toxic nor mutagenic for the bacterial tester strains.

Chromates↗

Characterization of enzymatic reduction of hexavalent chromium by Escherichia coli ATCC 33456.

Chromium reduction by Escherichia coli ATCC 33456 quantitatively transferred hexavalent chromium, Cr(VI), to trivalent chromium, Cr(III). The reduced chromium was predominantly present in the external medium. Supernatant fluids of cell extract, obtained by centrifugation at 12,000 and 150,000 x g, showed almost the same Cr(VI) reduction activity, indicating that Cr(VI) reduction by E. coli ATCC 33456 was a largely soluble reductase activity. In studies with respiratory inhibitors, no inhibitory effects on aerobic and anaerobic Cr(VI) reduction were demonstrated by addition of cyanide, azide, and rotenone into both intact cell cultures and supernatant fluids of E. coli ATCC 33456. Although cytochromes b and d were identified in the membrane fraction of cell extracts, Cr(VI) was not reduced by the membrane fraction alone. The cytochrome difference spectra analysis also indicated that these cytochromes of the respiratory chain require the presence of the soluble Cr(VI) reductase to mediate electron transport to Cr(VI). Stimulation of Cr(VI) reduction by an uncoupler, 2,4-dinitrophenol, indicated that the respiratory-chain-linked electron transport to Cr(VI) was limited by the rate of dissipation of the proton motive force.

Aerobiosis↗

Chromium content of lungs of chromate workers with lung cancer.

The chromium content was measured in the lungs of chromate workers, obtained at necropsy in six patients and at surgery in two. The mean chromium content of peripheral lung tissue was 36.7 micrograms per gm wet weight (range 0.50 to 130.2 micrograms) and that of the large airways was 0.51 micrograms per gm wet weight (range 0.22 to 0.99 micrograms). These means values were high compared with those from control lungs of a non-chromate exposed lung cancer patients--respectively 0.21 micrograms per gm in lung tissue and 0.11 micrograms per gm in the large bronchi. The longer the exposure period, the higher was the chromium content in the lungs. The concentration of chromium in the upper lobes was significantly higher than that in the lower lobes, suggesting regional differences either in clearance from or deposition in the lung. Moreover, it was apparent that the metal remained in the lungs long after exposure to chromate had ceased

Aged↗

Hexavalent chromium removal in vitro and from industrial wastes, using chromate-resistant strains of filamentous fungi indigenous to contaminated wastes.

Two chromate-resistant filamentous fungi, strains H13 and Ed8, were selected from seven independent fungal isolates indigenous to Cr(VI)-contaminated soil because of their ability to decrease hexavalent chromium levels in the growth medium. Morphophysiological studies identified strain H13 as a Penicillium sp. isolate and Ed8 as an Aspergillus sp. isolate. When incubated in minimal medium with glucose as a carbon source and in the presence of 50 microg/mL Cr(VI), these strains caused complete disappearance of Cr(VI) in the growth medium after about 72 h of incubation. Total chromium concentration in growth medium was constant during culture growth, and no accumulation of chromium in fungal biomass was observed. Quantitative determinations of oxidized and reduced chromium species during the reduction process revealed stoichiometric conversion of Cr(VI) to Cr(III). A decrease in Cr(VI) levels from industrial wastes was also induced by Ed8 or H13 biomass. These results indicate that chromate-resistant filamentous fungi with Cr(VI)-reducing capability could be useful for the removal of Cr(VI) contamination.

Aspergillus↗

Serum chromium and ageing.

Serum chromium levels were measured in 81 subjects (56 males and 25 females) with a mean age of 54 years (range 22-91 years). The mean serum chromium level in those under the age of 60 years was 1.6 +/- (SE) 0.125 ppb (30.7 +/- 2.4 nmol/l) whereas in those over the age 60 years it was 1.9 +/- 0.195 ppb (36.5 +/- 3.7 nmol/l). There was no evidence of any change in serum chromium levels with increasing age (r = 0.0096; p greater than 0.1) when all the subjects were considered. However, amongst the males a small but definite increase in serum chromium from 1.5 +/- 0.135 ppb (28.8 +/- 2.6 nmol/l to 2.1 +/- 0.25 ppb (40.6 +/- 4.8 nmol/l) was demonstrated.

Adult↗