Toxic effects of chromium and its compounds.

Chromium was discovered in 1797 by Vauquelin. Numerous industrial applications raised chromium to a very important economic element. At the same time, with the development of its uses, the adverse effects of chromium compounds in human health were being defined. Trivalent chromium is an essential trace element in humans and in animals. Chromium as pure metal has no adverse effect. Little toxic effect is attributed to trivalent chromium when present in very large quantities. Both acute and chronic toxicity of chromium are mainly caused by hexavalent compounds. The most important toxic effects, after contact, inhalation, or ingestion of hexavalent chromium compounds are the following: dermatitis, allergic and eczematous skin reactions, skin and mucous membrane ulcerations, perforation of the nasal septum, allergic asthmatic reactions, bronchial carcinomas, gastro-enteritis, hepatocellular deficiency, and renal oligo anuric deficiency. Prevention of occupational risks, biological monitoring of workers, and treatment of poisoning are also reported.

Cobalt determination in serum and urine by electrothermal atomic absorption spectrometry.

Cobalt determinations in biological fluids are of great interest in biological or toxicological research programs. Cobalturia is often chosen as an indicator for a biological monitoring program in occupational exposure to cobalt dusts. The method described here derives from the IUPAC reference method for nickel determination. It enables cobaltemia and cobalturia to be measured in small samples (1 mL). The mean usual values for cobalt in biological fluids are very low (2.7 nmol L-1 for serum and 6.7 nmol L-1 for urine), and therefore, thus require an analytical procedure with preconcentration and extraction. The sample is mineralized by wet acid digestion. After digestion, inorganic cobalt is extracted in form of ammonium pyrrolidine dithiocarbamate complex into isobutyl methyl ketone and measured in the organic layer by electrothermal atomic absorption spectrometry. The analytical parameters are described in detail. The extraction output is about 99%. The detection limits are 1.93 and 1.89 nmol L-1 for serum and urine, respectively. Sensitivity (expressed as the concentration that gives a 0.044 absorbance) is 3.4 nmol L-1 for serum and 3.3 nmol L-1 for urine. Within-run precision ranged between 3.9 and 2.5% (coefficients of variation) for serum and 4.2 and 1.1% for urine, at 87 and 136 nmol L-1 levels, respectively. Between-run precision ranged between 4.3 and 3.3% (coefficients of variation) for serum and 4.2 and 2.3% for urine, at 87 and 136 nmol L-1 levels, respectively. At very low concentration, 5.7 nmol L-1 for serum and 2.5 nmol L-1 for urine, the between-run precision is, respectively, 19.5 and 28%. Linearity is effective between 0 and 272 nmol L-1. Interferences and matrix effects are negligible for urine, serum, or plasma samples without hemoglobin. The method is easily applicable for routine determinations.

The French interlaboratory quality assessment programme for copper, zinc and selenium in blood serum.

The group for quality assurance for trace elements of the Société Française de Biologie Clinique (SFBC) has operated an interlaboratory quality assessment programme for copper, zinc and selenium determinations in blood serum since 1988. The primary objective is to enable participants to maintain or improve the accuracy of their analytical performances by comparing their results with other laboratories, every two months, on the basis of three quality criteria: comparison to the mean value, recovery of added copper, zinc and selenium, between-run reproducibility for identical samples. A further aim of this scheme is to evaluate interlaboratory transferability of the results. The procedure for individual and overall evaluation is reported. For each participant a performance score is calculated for each quality criteria, and a global score is attributed. The analytical performances of the participants were considered "good", "acceptable" or "inadequate" according to their global scores. Some of the results observed in this scheme are interpreted on the basis of differences between the notions of quality control and total quality assurance.

[Interlaboratory serum copper-zinc comparisons. Analytical performance during the first year]. / Comparaisons interlaboratoires cuivre-zinc sériques. Evolution de la performance analytique pour la première année.

In 1988 the Trace Elements Commission of the French Society for Clinical Biology operated an interlaboratory comparison program for copper and zinc determination in serum. The main objective is to enable participants to maintain or improve the accuracy of their analytical performance by comparing their results periodically, on the basis of three criteria: comparison of the results with the mean value, accuracy (recovery of copper and zinc additions), between-run reproducibility for identical samples. The statistical methods for evaluation are reported in detail. After one year, the results show a regular improvement in their homogeneity, especially for copper, indicating that the participants have taken into account their results to improve their analytical performance. The recovery of the copper and zinc additions shown a considerable improvement of their homogeneity. The coefficients of variation improved from 30 to 21 p. cent for copper and from 29 to 15 p. cent for zinc. The between-run reproducibility for identical samples was also evaluated. A performance score for each participant was calculated for each evaluation criteria, and a global score was attributed. The procedure for individual and global evaluation was reported in detail. The best scores were obtained for accuracy and the worst for the comparison with the mean value. The participants were considered "good", "acceptable" or "inadequate" in view of their global scores. The global performance was compared to other international interlaboratory comparison programs for copper and zinc in serum.

[Quality assurance or quality control. Lessons from an intercomparison circuit]. / Assurance qualité ou contrôle qualité. Les enseignements d'un circuit d'intercomparaison.

This article deals with the evaluation of the three year results of the French interlaboratory control for serum copper and zinc analysis. We pointed out some results interpreted on the basis of the existence of differences between the notions of quality control and total quality assurance. The main finding was a surprising change in the annual range in the final results of the laboratories. All 'good' laboratories in the first year showed a significant fall in their individual performance the second year. We can interpret that as a falling off of vigilance in relation with the self satisfaction after the publication of the first results. We concluded that good laboratory practices must be accompanied by a quality program not limited to an analytical control.

[Levels of manganese in biological media: value, samplings, physiopathological variations. Bibliographic review]. / Dosage du manganèse dans les milieux biologiques: intérêt, prélèvements, variations physiopathologiques. Revue bibliographique.

The great diversity of methods for manganese analysis in biological materials (serum, plasma, whole blood, urine, spinal fluid and hair) reveals the difficulty in measuring extremely small quantities of this element. An examination of these methods demonstrate that the most used one is flameless atomic absorption spectrometry. This review offers a comparison of the different instrument settings. Authors' recommendations for the collecting of samples are reported in detail. A description of the preliminary steps, the handling of the specimen samples, the preparation of the standards, procedures used, analytical criteria and perturbations is also included. Normal values and their physiological and pathological variations are also described.

[Interlaboratory tests: completion of a method of aluminum assay in serum by electrothermal atomic absorption spectrometry]. / Essais interlaboratoires: mise au point d'une méthode de dosage de l'aluminium dans le sérum par spectrométrie d'absorption atomique électrothermique.

After carrying out a prior analysis of published literature, the members of the SFBC trace-elements study group present an interlaboratory trial on the measurement of aluminum in serum using electrothermal atomic absorption spectrometry. The means of measurement chosen, following methods reliability criteria, was the use of a standard addition calibration of the samples diluted 1/5 in nitric acid 0.02 mol.l-1. Standard addition calibration was performed on two serums and gives acceptable results. Measurements are preferably carried out in 'tantalised' graphite tubes or pyrolytic tubes with platforms. However, when using graphite tubes, their quality must be checked because measurements can be seriously affected by poor quality tubes.

Role of solubilized chromium in the induction of morphological transformation of Syrian hamster embryo (SHE) cells by particulate chromium(VI) compounds.

Chromium(VI) compounds--Ca, Sr, Zn and Pb chromates--were studied for cytotoxicity and morphological transformation in Syrian hamster embryo (SHE) cells in relation to their solubilization in cell culture conditions and intracellular Cr concentration. Ca, Sr and Zn chromates were completely solubilized after 1 day of incubation in cell cultures; for Pb chromate, 20-36% Cr was solubilized only after 7 days. In two parallel transformation assays, the SHE cells were treated with suspensions or with corresponding supernatants (containing only solubilized Cr) of these compounds. A statistically significant relationship was observed between the Cr treatment concentration and the amount of Cr per cell, irrespective of the compound (except suspensions of Pb chromate). The cytotoxicity was due to extracellular solubilized chromium because treatments with either supernatants or suspensions of Ca, Sr and Zn chromates gave the same LC50 of 0.31 +/- 0.01 microgram Cr/ml. A clear dose-response relationship was observed for the induction of morphological transformation for each compound, either previously solubilized or in suspension. The expression of the transformation frequencies as a function of the Cr concentration/cell revealed that (i) the transformation frequency is dependent on the Cr concentration/cell irrespective of the Cr compound Ca, Sr or Zn chromate, (ii) the transformation frequency induced by solubilized Pb chromate is higher than that induced by the other compounds at the same concentration of Cr/cell. A double treatment with solutions of Cr and Pb at corresponding concentrations induced the same transformation frequency as the solubilized Pb chromate. The results show that the solubilization of particulate Cr(VI) compounds is a critical step for their cytotoxic and transforming activities; the intracellular soluble Cr is the sole causative agent of the transforming activity of Ca, Sr and Zn chromates, while Pb appears to act synergistically with Cr in inducing the transformation by Pb chromate.

Effect of different exposure compounds on urinary kinetics of aluminium and fluoride in industrially exposed workers.

OBJECTIVE: To conduct a field study to obtain information on the urinary concentrations of aluminium (Al) and fluoride (F-) depending on the different compounds exposed to in the aluminum industry. METHODS: 16 workers from one plant that produced aluminium fluoride (AlF3), and from two plants that produced aluminium electrolytically by two different processes participated in the study for one working week. Pollutants were monitored by eight hour personal sampling every day, and urine samples were collected during the week. Al and F- were analysed in both atmospheric and urine samples by atomic absorption spectrometry and an ion selective electrode. RESULTS: The principal results show different characteristics of kinetic curves of Al and F- excretion in workers with different exposures. Some characteristics of excretory peaks were linked to specific exposures--for instance, after exposure to AlF3 there was one delayed Al peak associated with one delayed F- peak about eight hours after the end of the daily shift, and after mixed exposure to HF and AlF3, two F- peaks were noted, one fast peak at the end of the shift and another delayed peak at 10 hours synchronised with an Al peak. In one of the electrolysis plants, the exposure to Al and F- compounds led to the simultaneous excretion of Al and F- peaks, either as a single peak or two individual ones depending on the type of technology used on site (open or enclosed potlines). The average estimated half life of Al was 7.5 hours, and of F- about nine hours. Quantitative relations between excretion and exposure showed an association between the F- atmospheric limit value of 2.5 mg/m3 with a urinary F- concentration of 6.4 mg/g creatinine at the end of the shift, a peak of 7.4 mg/g creatinine, and 7.4 mg excreted a day. For Al, the exposure to 1.36 mg/m3 during the shift corresponded to a urinary concentration at the end of the shift of 200 microgram/g creatinine. Daily excretion of 200 micrograms corresponded to an exposure to 0.28 mg/m3. CONCLUSION: Particular differences in the behaviour of Al and F- in urine depended upon the original molecular form in the pollutant. These results reinforce the principle that, in biological monitoring, the sampling strategy and the choice of limit value should be dependent on kinetic data that take the exposure compound of the element in question into account.

An international quality-assessment program for measurement of aluminum in human plasma: a progress report.

In view of the increasing interest in measurement of aluminum in plasma of hemodialysis patients and the analytical difficulties, which may lead to false clinical interpretations, we organized an international interlaboratory quality-control program that has operated since 1983. The results obtained after four years (72 participants) demonstrate a lessened discrepancy of the results. This program allowed some laboratories to improve their results and even to solve some of their analytical problems. This surveillance will be continued and extended to include the analysis of dialysis fluids.

Decreased serum ceruloplasmin concentration in aluminum welders exposed to ozone.

During an epidemiological survey on arc welders, serum copper and ceruloplasmin were determined in two groups of workers. One group consisted of aluminum welders who were divided into two groups: 13 welders working inside aluminum tanks (confined atmosphere) and 8 welders engaged in the production of vans for dump trucks (nonconfined atmosphere). The reference group consisted of 26 workers of the same plant who were not exposed to welding fumes. Ozone, the major pollutant in aluminum arc welding, was thought to be the principal factor in the significant decrease (P less than 0.01) of mean ceruloplasmin in confined welders. This decrease in the level of ceruloplasmin was still within the reference values and was not linked to age or to tobacco consumption. We found a linear relationship between ceruloplasmin concentration and the cumulated worktime along the week. This effect could be a sign in the serum of a lung reaction against oxidant activity in this type occupational exposure.

Determination of manganese in biological materials by electrothermal atomic absorption spectrometry: a review.

The great diversity of methods for measuring manganese in biological materials (serum, plasma, whole blood, urine, spinal fluid, and hair) reflects the difficulty in measuring extremely small quantities of this element. Detailed examination of these methods demonstrates that the one most used is flameless atomic absorption spectrometry. In this review we report the different instrument settings for wavelength, slit width, protection gases, graphite furnaces, type of background correction, amounts measured, and thermal programs. We give detailed recommendations by various authors for collecting samples. A thorough description of the preliminary steps and the handling of the specimen samples is also included: direct determination with or without dilution, addition of a matrix modifier or determination after ashing, with or without chelation-extraction steps. The preparation of the standards, procedures used, analytical criteria (accuracy, precision, specificity, detection limit, linearity), problems (interferences, matrix effects), and reference values and their physiological variations are also described. We give a consensus of recommendations concerning the choice of a method.

Cytotoxic and neoplastic transforming effects of industrial hexavalent chromium pigments in Syrian hamster embryo cells.

Twenty eight moderately water-soluble to insoluble chromium (VI) compounds, such as zinc and lead chromate, industrial and laboratory synthesized pigments, and the analytical reagents strontium, barium and calcium chromate, were physicochemically characterized and studied for cytotoxicity and morphological transformation in cultured Syrian hamster embryo (SHE) cells. In vivo validation of malignancy of transformed SHE cells was performed. A high physicochemical diversity among the complex chromium pigments was revealed. The solubility of the compounds was greatly increased after incubation in a complete medium and even higher under cell culture conditions. The cytotoxic effects appeared to be due principally to extracellular solubilized chromium because the most solubilized compounds. Zn, Ca and Sr chromates, were equitoxic at about the same Cr concentration treatment and 8-fold more cytotoxic than less soluble compounds such as some Pb chromates and Ba chromate. However, certain physicochemical properties of lead chromate pigments could also influence their cytotoxic activity. All test compounds were, in a dose-dependent manner, efficient in inducing morphological transformation of SHE cells. Many of the Cr pigments, although physicochemically different, were similarly effective in transformation induction. Nevertheless, compounds among Zn and Pb chromates had various transforming potencies. Ba chromate was the least active in inducing transformation. Certain physicochemical properties could mediate the transforming activity but no particular relationship could be established between any one of the physicochemical parameters and the transforming potency. Cloned morphologically-transformed colonies of SHE cells were grown in soft agar medium and showed true neoplastic behaviour by tumour formation in syngeneic animals. These results show that various chromate pigments containing either Zn or Pb, of medium to very low aqueous solubility, induced neoplastic transformation of SHE cells.

Chromosome aberrations in peripheral blood lymphocytes of welders and characterization of their exposure by biological samples analysis.

Chromosomal aberrations in cultured lymphocytes obtained from 55 welders and 55 matched controls were analyzed. Depending on the welding techniques and the nature of the consumables and metals welded, three separate groups of welders were examined. Chromium, nickel, and manganese levels in serum and urine were measured to assess the exposure to welding fumes. A statistically significant increase of chromosomal aberrations was found in one of the three analyzed groups of welders. This group used the semi-automatic metal active gas welding process with cored wire containing nickel for welding mild steel. These welders had significantly higher concentrations of serum and urine manganese and, unlike the other welders, significantly elevated concentrations of nickel, both in serum and urine. However, no significant correlations between nickel or manganese levels and the frequency of chromosomal aberrations were found. There was a significant correlation between the length of welding employment of these welders and the frequency of chromosomal breaks, although there was no significant correlation between age and the frequency of chromosomal aberrations. The other two groups of welders, for which the analyses of biologic fluids proved chromium and manganese exposure, had no statistically significant higher frequency of chromosomal aberrations. One of these groups used the manual metal arc welding process with coated electrodes for welding mainly mild steel and the other group used the tungsten inert gas welding process for welding stainless steel. A significant correlation between the daily amount of cigarettes smoked and the frequency of chromosomal breakages, in controls as in welders, was observed. The present data indicate that certain welding processes may generate fumes that seem to have a clastogenic activity.

Respiratory hazards in hard metal workers: a cross sectional study.

A cross sectional study was conducted on 513 employees at three hard metal plants: 425 exposed workers (351 men, 74 women) and 88 controls (69 men, 19 women). Cough and sputum were more frequent in workers engaged in "soft powder" and presintering workshops compared with controls (12.5% and 16.5% v 3.5%). Spirometric abnormalities were more frequent among women in sintering and finishing workshops compared with control women (56.8% v 23.8%) and abnormalities of carbon monoxide test were more frequent in exposed groups than in controls; this difference was more pronounced in women (31.4% v 5.6%) than in men (18.5% v 13%). No significant correlation was observed between duration of exposure and age adjusted lung function tests. Slight abnormalities of chest radiographs (0/1, 1/1 according to ILO classification) were more frequent in exposed men than controls (12.8% v 1.9%) and mostly in soft powder workers. In subjects with abnormal chest radiographs FVC, FEV1 and carbon monoxide indices (fractional uptake of CO or CO transfer index or both) were lower compared with those with normal chest radiographs. Although relatively mild, the clinical, radiological, and functional abnormalities uncovered call for a regular supervision of workers exposed to hard metal dust.