Urinary Chromium Excretion Research Articles

RELATIONSHIP BETWEEN S-INSULIN AND CHROMIUM, MANGANESE, COBALT, AND ZINC EXCRETION IN THE URINE IN HEALTHY KHYBER PAKHTUNKHWA PERSONS

Objective: Clinical research has shown that mineral imbalances, including those involving zinc, cobalt, manganese,and chromium, are crucial for the onset and development of diabetes mellitus. To ascertain the function of these traceelements in pathogenesis and the advancement of type 2 diabetes, this investigation aimed to ascertain if there was alink, if any, between the urine excretion of these minerals and s-insulin levels.Study Design: Cross-sectional study.Place and Duration of study: From January to December 2013, this research was carried out at Khyber MedicalUniversity (KMU), Peshawar, at the Institute of Basic Medical Sciences (IBMS).Materials and Methods: This research comprised 200 healthy people from the seven divisions of Khyber Pakhtunkhwa (Abbottabad, Peshawar, Mardan, Bannu, Dera Ismail Khan, Malakand, and Kohat) with normal fastingblood sugar (FBS), creatinine, cholesterol, HDL, LDL, and TAG values. Anthropometric measures and demographicdata were recorded. Serum creatinine, serum insulin, lipid profile, and fasting blood sugar were measured using a bloodsample. Urine samples were taken early in the morning to measure zinc, cobalt, manganese, and chromium levels.Results: It was discovered that there was a near-to-significant negative connection (r: -0.127, p: 0.073) betweenmanganese and s-insulin and a considerably high negative correlation (r: -0.191, p: 0.007) between chromium ands-insulin. Thus, elevated chromium and manganese excretion in the urine in healthy persons may eventually causeT2DM to proceed if improperly managed.Conclusion: the present study revealed a significant correlation of s-insulin with urinary excretion of chromium only.Keywords: Type II diabetes mellitus, s-insulin, trace elements.

Grain source and chromium supplementation: Effects on health, metabolic status, and glucose-insulin kinetics in Holstein heifer calves

Carbohydrate-rich diets may increase urinary excretion of chromium (Cr) and the need to supplement the diet with Cr to meet animal requirements. The present study was performed to examine the effect of the type of grain (corn vs. barley) and Cr-methionine supplementation on health-related variables, blood levels of metabolites and hormones related to energy metabolism, and insulin sensitivity in Holstein calves. Forty-eight newborn heifers (3 d of age) were assigned randomly to 4 diets in a 2 × 2 factorial arrangement. Experimental diets were either corn-based (CBD) or barley-based (BBD) diets supplemented with 0 or 0.05 mg/kg of metabolic body weight. Chromium was provided in milk before weaning (d 3-73 of age) and in prewarmed water after weaning (d 74-94 of age). There was no interaction between the type of grain and Cr on the health-related variables and blood metabolites and hormones. Type of grain did not affect fecal score, respiration rate, and rectal temperature; however, there were tendencies for higher diarrhea occurrence (odds ratio = 1.69) and lower chance of having pneumonia (odds ratio = 0.49) in calves fed BBD versus CBD despite longer duration of diarrhea (0.54 d) and shorter days with pneumonia (0.63 d) in calves fed BBD. Calves supplemented with Cr had lower fecal score during the preweaning and overall periods and respiration rate throughout the study. Supplemental Cr decreased the duration (0.63 d) and chance of having pneumonia (odds ratio = 2.01). Calves fed BBD had lower blood levels of urea N during the postweaning period, with no changes in other blood variables between CBD and BBD. Tendencies were detected for lower blood levels of β-hydroxybutyric acid during the preweaning and overall periods and higher cortisol in Cr-supplemented calves. Chromium supplementation increased insulin clearance rate and decreased the time to half-maximal concentration and the area under the curve in BBD but not CBD calves. The calves were generally healthy, and the type of grain did not affect the health and blood variables related to energy metabolism. However, Cr supplementation increased fecal consistency, decreased respiration rate and days with pneumonia, and increased insulin sensitivity when added to BBD.

Effects of work schedule and period of exposure on changes in urinary chromium and nickel excretion among rotating shift workers in a stainless-steel plant

ABSTRACTWe investigated the association between the period of exposure and changes in urinary excretion of chromium and nickel among rotating shift workers in a stainless-steel plant. The study participants were composed of two groups: the workers who were occupationally exposed to metals (“exposed group”) and those who were not occupationally exposed to metals (“unexposed group”). The exposed and unexposed groups consisted of 56 and 40 male rotating shift workers, respectively. Urine samples were collected immediately before and immediately after the day shift, evening shift, and night shift. Urinary chromium and nickel were measured using inductively coupled plasma mass spectrometry. To correct for variations in urine dilution, urinary metal concentrations were expressed as a ratio to urinary creatinine concentration. In the exposed group, post-shift urinary excretion of chromium was significantly higher than pre-shift excretion. However, although urinary chromium excretion clearly increased after the day and night shift [63% (p < .0001) and 87% (p < .0001), respectively], urinary chromium excretion after the evening shift was only slightly higher than that measured before the evening shift (8%, p = .028). Similar patterns were found for urinary nickel excretion (p = .0001, 0.20, and 0.18 for the day, evening, and night shifts, respectively). Non-uniform urinary excretion of metals between the day shift, evening shift, and night shift were observed in the exposed group; specifically, urinary metal excretion increased only slightly during the evening shift. In the unexposed group, no significant increase or decrease was found in median urinary chromium or nickel excretion (p= .63–0.87). Work shift-specific permissible exposure level would be necessary.

Grain source and chromium supplementation: effects on feed intake, meal and rumination patterns, and growth performance in Holstein dairy calves

Carbohydrate-rich diets may increase urinary excretion of chromium (Cr) and increase its requirements. This study was conducted to investigate the effect of grain type (barley v. corn) and Cr supplementation on feed intake, feeding behavior and weight gain in dairy calves. Forty-eight neonatal Holstein female calves were assigned randomly to four experimental diets in a 2×2 factorial arrangement. Experimental diets were either barley-based diet (BBD) or corn-based diet (CBD) supplemented with (+Cr) or without (−Cr) Cr as Cr-methionine (0.05 mg/kg of BW0.75). Chromium was provided in milk (from days 3 to 73 of life) during the pre-weaning period and then in pre-warmed water (from day 74 until day 94 of life) after weaning. Meal length tended to increase in calves fed the BBD v. CBD during the pre-weaning period. During the post-weaning period, meal size, inter-meal interval, and eating rate increased concurrently but meal frequency and eating time decreased in the BBD v. CBD. During the pre-weaning period, feed efficiency, BW at weaning, and heart girth increased and non-nutritive oral behaviors tended to decrease with Cr supplementation. Due to increased meal frequency, the starter feed intake but not eating time increased by Cr supplementation during the post-weaning period. Supplementing Cr increased starter feed intake, final BW, average daily gain and heart girth during the overall period. Rumination time increased in BBD+Cr calves due to increases in the frequency and duration of rumination, or decreased rumination bout interval. Overall, the type of grain had no effect on feed intake and growth performance; however, Cr supplementation decreased non-nutritive oral behaviors and increased starter feed intake via increasing the meal frequency and thereby improved growth performance.

Urinary Chromium Excretion in Response to an Insulin Challenge Is Not a Biomarker for Chromium Status

Over 50 years ago, chromium (Cr) was proposed to be an essential trace element; however, recent studies indicate that this status should be removed as the effects of Cr supplementation appear to be pharmacological rather than nutritional. The pharmacological basis for Cr's effects can explain the inability of investigators to discover a biomarker for Cr status. One potential biomarker has not been examined to date. Cr is known to be mobilized in the body in response to insulin (or insulin release in response to a glucose challenge), resulting in an increase in urinary Cr excretion. The magnitude of increase in urinary Cr loss as a function of dietary Cr intake was tested as a potential biomarker for Cr. Zucker lean rats housed in carefully controlled metal-free conditions were provided a series of purified diets containing variable Cr contents (from 16 μg/kg diet to 2,000 μg/kg) for 23 weeks. The 16 μg/kg diet contained less Cr than any diet examined to date. Urine samples were collected before and after insulin and glucose challenges (0, 2, 6, and 12 h postinjection). Urinary Cr levels were analyzed by the standard method of addition using graphite furnace atomic absorption. The rate of urinary Cr loss after a glucose or insulin challenge was found to not be dependent on the Cr content of the rats' diets. Blood iron levels of the rats were also measured to determine if the addition of Cr to the diet altered iron status. The Cr content of the diet was found to have no affect on blood iron levels. Overall, the study demonstrated that insulin-stimulated urinary Cr excretion cannot be used as a biomarker for Cr status.

An outbreak of occupational asthma due to chromium and cobalt

Five metal turners employed by an aerospace manufacturer presented to the Birmingham Chest Clinic occupational lung disease unit. Four cases of occupational asthma (OA) due to chromium salt (3) and cobalt (1) were diagnosed by serial peak-expiratory flow measurements and specific inhalation challenge testing. To measure the extent of the outbreak and to provide epidemiological data to ascertain the aetiology. Participants answered a detailed, self-administered questionnaire, designed to detect occupational lung disease. Urine chromium and cobalt excretion, spirometry and exhaled nitric oxide measurements were taken. Those with possible, probable or definite non-OA or OA, after questionnaire, were invited to undertake two-hourly peak flow measurements and received specialist follow-up. A total of 62 workers (95% of workforce) participated. Sixty-one per cent of employees were working in higher metalworking fluid (MWF) exposure areas. Ninety per cent of workers had urinary chromium excretion indicating occupational exposure. Sixty-six per cent of workers reported active respiratory symptoms, although there were no significant differences between exposure groups. Two further workers with probable OA were identified and had significantly higher urinary chromium and cobalt concentration than asymptomatic controls. Eighteen cases of occupational rhinitis (OR) were identified, with significantly raised urinary chromium concentration compared with asymptomatic controls. Chromium salt and cobalt can be responsible for OA and OR in workers exposed to MWF aerosols. Onset of symptoms in those with positive specific challenges followed change in MWF brand. Workers with OA had increased urinary concentrations of chromium and cobalt, and those with OR had increased urinary concentrations of chromium.

Toxic effects of chromium on tannery workers at Sialkot (Pakistan)

Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. Results revealed that all the workers were male with average age of 33 years and 15 (13%) had skin rashes, 14 (12%) had chronic bronchitis, 10 (8%) had gastritis and 4 (3%) conjunctivitis. The tannery workers had significantly raised median (interquartile range) of BCr 569 (377-726) nmol/L as compared to 318 (245-397) nmol/L in the control (p < 0.001). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. The urinary chromium excretion was significantly high in workers 131 (46-312) nmol/L as compared to 13 (3-26) nmol/L in controls (p < 0.01). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes.

Is Chromium an Essential Trace Element in Human Nutrition?

It has been recognized that chromium is an essential trace element associated with carbohydrate metabolism, and chromium deficiency causes an impaired glucose tolerance. Recently, however, Vincent et al. have reported that chromium is not an essential trace element. In the present report, the author evaluated the nutritional essentiality of chromium by reviewing several previous reports. In almost all previous reports, the chromium concentration in the animal feed used was higher than 0.1 μg/g, and it is difficult to consider that the experimental animals were in a low-chromium state. In addition, the amount of chromium administered to the animals for the improvement of glucose tolerance was at a pharmacological level, and corresponded to a level that far exceeded the human daily chromium intake (20 to 80 μg/day). On the other hand, recent research has clearly shown that feeding with a severely low-chromium diet (0.016 μg/g) does not impair glucose tolerance. The amount of chromium absorbed in humans estimated from chromium intake (20 to 80 μg/day), chromium absorption rate (1%), and urinary chromium excretion (<1 μg/day) is less than 1 μg/day, which is much lower than those of other essential trace elements. In addition, because there is an inconsistency between the chromium concentration in food and chromium intake, chromium intake seems to be dependent on chromium contamination during food processing and cooking. It is concluded that there is a high possibility that chromium is not an essential trace element.

Deferoxamine pretreatment prevents Cr(VI)-induced nephrotoxicity and oxidant stress: Role of Cr(VI) chelation

Deferoxamine (DFO) is a recognized iron chelator which has been shown to exert nephroprotection in models of toxic nephropathies. In the present work the potential protective effects of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress were evaluated. Rats were injected with a single injection (15mg/kg, s.c.) of potassium dichromate (K2Cr2O7). DFO was given as a single i.p. injection 30min before K2Cr2O7 administration at three different doses (100, 200 and 400mg/kg). It was found that DFO pretreatment attenuated, in a dose-dependent way, K2Cr2O7-induced renal dysfunction and structural alterations evaluated by serum creatinine, blood urea nitrogen, creatinine clearance, proteinuria, plasma glutathione peroxidase activity, urinary excretion of N-acetyl-β-d-glucosaminidase and histological analyses. Furthermore, DFO prevented the K2Cr2O7-induced renal oxidant stress and the decrease in the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and catalase. Finally it was found that DFO, at 400mg/kg, decreases renal Cr(VI) content which prompted us to evaluate the potential Cr(VI) chelating properties of this compound. Indeed was found in an in vitro assay that DFO was an effective Cr(VI) chelator with an IC50 of 800μg. In additional groups of rats was found that DFO posttreatment was ineffective to attenuate K2Cr2O7-induced nephrotoxicity and renal oxidant stress. Furthermore, DFO was unable to modify urinary excretion of total chromium. The nephroprotective effect of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress may be explained, at least partially, by the ability of DFO to chelate Cr(VI) and to attenuate renal Cr(VI) content. However, it cannot be excluded that the ability of DFO to chelate iron may also be involved in the protection observed in our study.

Increased insulin resistance is associated with increased urinary excretion of chromium in non-diabetic, normotensive Saudi adults

The role of trivalent chromium in improving glucose tolerance is well documented. Increased urinary chromium has been reported in type 2 diabetes mellitus, but it was not clear whether this had preceded diabetes mellitus, or was caused by it. Aim was to investigate the relationship between urinary chromium and the degree of insulin resistance in non-diabetic normotensive Saudi adults. 357 healthy adults aged 18–50 years were recruited randomly in a cross-sectional study design. Anthropometric and demographic information were taken. Insulin, glucose and free fatty acids were measured in fasting blood samples. Fasting urinary chromium and creatinine were also determined. Using modified QUICKI, subjects were labeled as high insulin resistant, or low insulin resistant. High insulin resistant subjects were matched for age and sex to low insulin resistant subjects. High insulin resistant subjects had higher mean BMI (p<0.001), mean waist circumference (p<0.01), and median urinary chromium (p<0.001) compared to low insulin resistant subgroup. Higher urinary chromium in high insulin resistant subgroup indicates a renal lesion leading to chromium deficiency and possibly diabetes mellitus eventually. Chromium supplementation might help to protect against the development of diabetes mellitus in this group of high insulin resistant non-diabetic Saudi individuals.

Tissue accumulation and urinary excretion of chromium in rats fed diets containing graded levels of chromium chloride or chromium picolinate

To attempt a risk assessment of the excess intake of trivalent chromium (Cr), tissue Cr accumulation and urinary Cr excretion were examined in weanling rats fed experimental diets containing graded levels of Cr chloride (CrCl3) or Cr picolinate (CrPic). Thirty-six male weanling 4-weeks-old Wistar rats were divided into six groups and fed a casein-based semi-purified diet (Cr content: <0.02 microg/g) supplemented with 1, 10, or 100 microg Cr/g as CrCl3 or CrPic for 28 days. Among the experimental groups, no significant difference was observed in body weight; however, supplementation of 100 microg Cr/g to the diets caused a significant low liver weight irrespective of the chemical species of Cr. Activities of serum aspartate aminotransferase and alanine aminotransferase were significantly elevated in rats given CrPic at 100 microg Cr/g. In the liver, kidney and femur, Cr accumulation increased with elevation of the dietary Cr level. No influence of the difference in the chemical species of supplemented Cr was observed in the liver and kidney, but CrCl3 caused significantly higher Cr accumulation than CrPic in the femur of rats given 100 microg Cr/g. Daily urinary Cr excretion elevated with the increase of the dietary Cr level. Rats given CrPic showed significantly higher daily urinary Cr excretion than those given CrCl3, particularly at a dietary Cr level of 100 microg/g. The rate of urinary Cr excretion in rats given CrPic was constant, irrespective of the dietary Cr level, but that of rats given CrCl3 fell with the increase of the dietary Cr level. These results indicate that the lowest adverse effect level of dietary Cr is less than 100 microg/g, irrespective of the chemical species of Cr.

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A - Medical results

BackgroundThis study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years.MethodsPhase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo.ResultsDMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation.ConclusionOverall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals.

Effect of Hyperglycemia on the Urinary Chromium Excretion in the Streptozotocin-Induced Mice

Effect of Hyperglycemia on the Urinary Chromium Excretion in the Streptozotocin-Induced Mice

The effect of high and low glycemic index diets on urinary chromium in healthy individuals: a cross-over study.

Insufficient dietary intake of chromium as an essential nutrient leads to signs and symptoms that are similar to those observed for diabetes and cardiovascular diseases. We postulate that in healthy individuals, urinary chromium excretion following a high glycemic index diet is higher than after a low glycemic index diet. A sequential randomized controlled cross-over study was carried out at the Metabolic Unit of Nutrition Department of King's College London. Sixteen healthy individuals aged 18 - 60 years were recruited from 26 volunteers. A low or high glycemic index diet (as the main meals/day) was given to the volunteers over six days. Fasting blood glucose and insulin changes were determined and 24-hr urine samples were collected to measure chromium excretion before intervention and every second day within each treatment with a one wash-out period using Dynamic Reaction Cell Inductively Coupled Plasma Mass Spectrometer. During the six-day diet study, there were no significant differences in 24-hr urinary chromium losses between the two groups following the low glycemic index (0.58+/-0.08 microg/24 hr) and high glycemic index diets (0.48+/-0.06 microg/24 hr). However, during day six there was a trend towards greater loss of chromium after the high glycemic index diet (0.73+/-0.1 microg/24 hr) in comparison with the low glycemic index diet (0.54+/-0.07 microg/24 hr). Evidence that urinary chromium loses following the high glycemic index diets have not been clearly demonstrated in normal subjects. These results suggest that chromium excretion may need to be observed for longer than six days to address this question.

Metal ion levels in a triathlete with a metal-on-metal resurfacing arthroplasty of the hip

A prospective study of serum and urinary ion levels was undertaken in a triathlete who had undergone a metal-on-metal resurfacing arthroplasty of the hip four years previously. The one month study period included the final two weeks of training, the day of the triathlon, and the two weeks immediately post-race. Serum cobalt and chromium levels did not vary significantly throughout this period, including levels recorded on the day after the 11-hour triathlon. Urinary excretion of chromium increased immediately after the race and had returned to pre-race levels six days later. The clinical implications are discussed.

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.

Exposure and inhalation risk assessment in an aluminium cast-house

To date the exposure, absorption and respiratory health effects of cast-house workers have not been described since most studies performed in the aluminium industry are focused on exposure and health effects of potroom personnel. In the present study, we assessed the external exposure and the absorbed dose of metals in personnel from the aluminium cast house. This was combined with an evaluation of respiratory complaints and the lung function of the personnel. 30 workers from an aluminium casting plant participated and 17 individuals of the packaging and distribution departments were selected as controls. The exposure was assessed by the quantification of total inhalable fume with metal fraction and by the determination of urinary aluminium, chromium, beryllium, manganese and lead concentration. Carbon monoxide (CO), carbon dioxide (CO2), aldehydes and polyaromatic hydrocarbons and man-made mineral fibres concentration were assessed as well. In order to evaluate their respiratory status each participant filled out a questionnaire and their lung function was tested by forced spirometry. Total inhalable fume exposure was maximum 4.37 mg m(-3). Exposure to the combustion gases, man-made mineral fibres and metal fume was well below the exposure limits. Beryllium could not be detected in the urine. The values of aluminium, manganese and lead in the urine were all under the respective reference value. One individual had a urinary chromium excretion above the ACGIH defined biological exposure index (BEI) of 30 microg g(-1) creatinine. There was no significant difference in any of the categories of the respiratory questionnaire and in the results of the spirometry between cast house personnel and referents (Chi-square, all p > 0.05). Exposure in cast houses seem to be acceptable under these conditions. However, peak exposure to fumes cannot be excluded and the potential risk of chromium and beryllium exposure due to the recycling of aluminium requires further attention.

A physiologically based model for the ingestion of chromium(III) and chromium(VI) by humans.

A physiologically based model of human chromium kinetics has been developed, based on an existing physiologically based model of human body and bone growth (O'Flaherty, 1993, Toxicol. Appl. Pharmacol. 118, 16-29; 1995a, Toxicol. Appl. Pharmacol. 131, 297-308; 2000, Toxicol. Sci. 55, 171-18) and an existing physiologically based model of chromium kinetics in rats (O'Flaherty, 1996, Toxicol. Appl. Pharmacol. 138, 54-64). Key features of the adapted model, specific to chromium, include differential absorption of Cr(VI) and Cr(III), rapid reduction of Cr(VI) to Cr(III) in all body fluids and tissues, modest incorporation of chromium into bone, and concentration-dependent urinary clearance consistent with parallel renal processes that conserve chromium efficiently at ambient exposure levels. The model does not include a physiologic lung compartment, but it can be used to estimate an upper limit on pulmonary absorption of inhaled chromium. The model was calibrated against blood and urine chromium concentration data from a group of controlled studies in which adult human volunteers drank solutions generally containing up to 10 mg/day of soluble inorganic salts of either Cr(III) (chromic chloride, CrCl(3)) or Cr(VI) (potassium dichromate, K(2)Cr(2)O(7)) (Finley et al., 1997, Toxicol. Appl. Pharmacol. 142, 151-159; Kerger et al., 1996, Toxicol. Appl. Pharmacol. 141, 145-158; Paustenbach et al., 1996, J. Toxicol. Environ. Health 49, 453-461). In one of the studies, in which the chromium was ingested in orange juice, urinary clearance was observed to be more rapid than when inorganic chromium was ingested. Chromium kinetics were shown not to be dependent on the oxidation state of the administered chromium except in respect to the amount absorbed at these ambient and moderate-to-high exposures. The fraction absorbed from administered Cr(VI) compounds was highly variable and was presumably strongly dependent on the degree of reduction in the gastrointestinal tract, that is, on the amount and nature of the stomach contents at the time of Cr(VI) ingestion. The physiologically based model is applicable to both single-dose oral studies and chronic oral exposure, in that it adequately reproduced the time dependence of blood plasma concentrations and rates of urinary chromium excretion in one of the subjects who, in a separate experiment, ingested daily 4 mg of an inorganic Cr(VI) salt in 5 subdivided doses of 0.8 mg each for a total of 17 days. The high degree of variability of fractional absorption of Cr(VI) from the gastrointestinal tract leads to uncertainty in the assignment of a meaningful value to this parameter as applied to single Cr(VI) doses. To model chronic oral chromium exposure at ambient or moderately above-ambient levels, the physiologically based model in its present form should be usable with urinary clearance set to a constant value of 1-2 liters/day and the gastrointestinal absorption rate constants set at 0.25/day for Cr(III) and 2.5/day for Cr(VI). The model code is given in full in the Appendix.

Urinary excretion of trace elements in humans after sodium 2,3-dimercaptopropane-1-sulfonate challenge test.

To evaluate the effects of intravenous sodium 2,3-dimercaptopropane-1-sulfonate (DMPS, Dimaval) on urinary excretion of essential trace elements in subjects who received this chelating agent as a mercury challenge test. Eleven subjects sought medical attention due to concern with the toxicity of mercury released from dental amalgam fillings. The subjects were given DMPS 3 mg/kg intravenously. Spot urine samples were collected 1 hour before and 1 hour after the DMPS dose for laboratory analysis. In addition to mercury, the urinary excretion of copper, zinc, selenium, magnesium, manganese, molybdenum, chromium, cobalt, and aluminum were measured. A significant increase in urinary excretion of mercury (3- to 107-fold) was observed after the DMPS dose. The DMPS treatment led to a 2- to 119-fold increase in copper excretion; 3- to 43.8-fold in selenium excretion; 1.6- to 44-fold in zinc excretion; and 1.75- to 42.7-fold in magnesium excretion. The excretion of manganese, chromium, cobalt, aluminium, and molybdenum remained unchanged. In this study, an intravenous DMPS challenge test produced a significant increase in mercury excretion and also led to an increased excretion of copper, selenium, zinc, and magnesium.

BEHAVIOR OF HEAVY METALS IN HUMAN URINE AND BLOOD FOLLOWING CALCIUM DISODIUM ETHYLENEDIAMINE TETRAACETATE INJECTION: OBSERVATIONS IN METAL WORKERS

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) mug/ dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the ''circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.