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Chromium compounds, besides being occupational carcinogens, can also induce allergic contact dermatitis (ACD) and other immunomodulatory effects. In this study we investigate cell viability, uptake and intracellular distribution of chromium in human primary dendritic cells (DCs), either immature (iDCs) or driven to differentiate by a specific maturation stimulus (LPS) (mature DCs, mDCs), when exposed for 48 h to concentrations of soluble radiolabelled Na251CrO4 ranging from 5 to 0.5 microM. The modulation of the expression of membrane markers (CD80, CD86, MHC class II) correlated with the immunological functions of DCs was also measured. After 48 h of exposure the mean IC50 values in 4 donors were 36 and 31 microM in iDCs and mDC respectively, as detected by propidium iodide incorporation. Cellular uptake of chromium was nearly linear with increasing doses. At 48 h post-exposure chromium was accumulated preferentially in the nuclear and cytosolic fractions (44.1 to 66% and 13.1 to 31% of total cellular chromium, respectively). Although a high inter-individual variability was observed, an increase in the expression of CD86 and, to a lower extent, CD80 and MHC class II membrane markers was found in mDCs of single donors. These results highlight the relevance of searching for the biodistribution of trace metals in primary cells of the immune system. Moreover, they suggest that DCs differentiation markers can help in measuring the immunotoxicity of metal compounds with sensitisation potential.

Objectives: The paper describes the results of a polycentric study for the assessment of reference values of urinary chromium (U-Cr) in the Italian population., Method: A total of 890 subjects (58.3% males and 41.7% females) were selected on the basis of standardized criteria in eight different areas of Italy. Urinary chromium was determined on morning spot samples collected using standardized procedures. The U-Cr was determined independently by three laboratories using an Electrothermic atomization-Atomic Absorption Spectrometry (ETA-AAS) method with a detection limit of 0.05 microgram/l, adopting-for the statistical analysis-the median value of the results of the three laboratories. The between-laboratories within-subjects standard deviation was 0.049 microgram/l. Due to the high proportion (approx, 28%) of undetectable chromium levels, the geometric mean (GM) and geometric standard deviation (GSD) were estimated using a procedure of linear interpolation. The analysis of the effects of some variables (sex, age, center, residence, smoking and drinking habits) on the U-Cr values, was also performed, by multiple regression analysis after logarithmic transformation, using GM and SD., Results: The reference value of U-Cr was of 0.08 microgram/l as an estimated GM, whereas the expected distribution ranged from not detectable (nd) (95% CI = nd-0.06) to 0.24 microgram/l (95th percentile; 95% CI = 0.20-0.31). Among the variables studied, only geographical area and sex significantly influenced the U-Cr levels. In subjects selected in the provinces of Bari and Venice values of U-Cr were significantly lower than those determined in subjects residing in other areas., Conclusions: From our investigation the reference values for U-Cr were lower than those obtained in previous investigations. In addition it confirms a further reduction in U-Cr levels following the previous decline reported in the 1970s and 1980s. In over 20 years U-Cr values in the general population dropped from values greater than 1 microgram/l to values between 0.5 and 0.2 microgram/l. The reasons of this progressive decline cannot be attributed in our opinion to a reduced intake of the metal, but mainly to the improvement in analytical instrumentation and methods. A further decrease may be ascribed to a more accurate definition of the reference groups and to a better control of pre-analytical factors. Considering that the reference values for U-Cr are much lower than those determined some decades ago, toxicological studies in order to verify the significance of biological limit values currently suggested for chromium seem to be necessary.

Blood lymphocyte subsets and serum immunoglobulins were studied in 15 men (mean age: 35 years), not exposed to toxic agents, and in 15 healthy men, exposed to dust containing several compounds (including lead chromate), working in a factory producing plastic materials. Worker blood lead and urine chromium (Cr) levels were significantly higher than controls, while serum Cr concentration was unchanged. In the worker blood, CD4+ helper-inducer (mainly CD4+-CD45RO- "virgin"), CD5--CD19+ B, CD3--CD25+ activated B and CD3--HLA-DR+ activated B and natural killer (NK) lymphocytes were significantly reduced (about 30-50 %). The investigated workers were exposed to hexavalent Cr, as lead chromate, whereas normal population (control group) was mainly exposed to trivalent Cr. In the control group, urinary Cr showed a significant positive correlation with CD16+-56+ NK, CD5+-CD19+ B and HLA-DR+ activated T, B and NK lymphocytes and a negative correlation with serum IgA immunoglobulins; moreover, serum Cr was significantly correlated with all blood lymphocytes and HLA-DR+, CD3--HLA--DR+ and CD3--CD25+ lymphocyte subsets. These data suggest that trivalent Cr may be involved in mechanisms regulating the immune response in humans.

Multielemental analysis, using neutron activation, was carried out on the urine, whole blood, pubic hair and toenails of thirty subjects occupationally exposed to hard metal dusts. A high concentration of Co, W and Cr was observed in all samples analysed. The concentrations determined, when subjected to statistical analysis using pattern recognition techniques (e.g. cluster analysis), indicated a positive correlation, at p = 0.001, for the pair (Co, W) in urine and blood, as well as a possible influence of Cr on this pair.

Rats treated intravenously with 51Cr-labelled sodium chromate, 0.1 or 100 microgram Cr/rat, excreted more 51Cr into bile in a 2-hr period than did the animals given equal amounts of chromium in the trivalent state. Distinct patterns of hepatic intracellular distribution of the radiotracer were also observed. In the Cr-VI rats over 50% of the liver chromium was present in the supernatant fraction whereas in the Cr-III rats almost all the liver radioactivity was localized in the cell organelles. Fractionation of bile on Sephadex G-75 demonstrated binding of chromium to low-molecular weight substances. It is suggested that complexes of chromium with low-molecular weight components of liver cytosol are involved in the passage of this element from the liver to bile. A low cytosolic content of diffusable Cr-complexes associated with the incorporation of a large fraction of liver chromium in cell organelles may be a factor contributing to the low rates of 51Cr biliary excretion in the animals given Cr-III. 24 hr after the injection of 51Cr to bile duct-ligated rats appreciable levels of radiotracer were found in the gastrointestinal tract. The animals given Cr-VI exhibited significantly higher values of chromium content in the gut than those treated with Cr-III.

51Cr-labelled Cr3+ and CrO2-4 solutions were administered intratracheally to male rats in doses of 0.1 and 10 micrograms of Cr per rat to evidentiate metabolic differences especially in the lung and in the mechanisms of excretion. Twenty four hours after administration the highest 51Cr amount was present in the lungs for both valency states, being in the Cr (III)-treated group, however, about two times higher. In all other tissues tested the values in the Cr (VI)-treated animals were much higher. Intracellularly, in the Cr (III)-treated group more than 40% of the total lung homogenate was found in the nuclear fraction and only 10% in the cytosol. In the Cr (VI)-treated group 25% was present in the nuclei and more than 50% in the cytosol. Gel filtration 24 h after intratracheal injection showed that in both cytosols chromium was eluted in three peaks including a low-molecular-weight component. Quantitatively, however, the ratios between the 51Cr associated with the three peaks were significantly different between the Cr (III)- and the Cr (VI)-treated animals. This suggests that binding of chromium to low-molecular-weight components should be involved in the passage of this element from the lung to the other tissues. Excretion studies for 7 days showed that after this time the Cr (III)-treated animals excreted about 4% of the dose via urine and more than 36% via faeces, whereas in the Cr (VI)-treated rats the 51Cr was eliminated nearly equally between urine and faeces.

This study describes investigations on the possible mechanisms involved in the transfer of Cr from the dialysate to the blood during peritoneal dialysis. The ability of Cr(III) compounds to penetrate across a membrane at physiological pH seems rather questionable, as it is well known that Cr(III) tends to form polymeric chains. Therefore, a systematic study was undertaken to describe the pathways involved in this transport. The characteristics during 'in vitro' dialysis were compared to the behaviour of Cr during acute 'in vivo' experiments on anesthetized rabbits. It appeared that lactate, a common substance of the dialysate, plays an extremely important role in the mobility and subsequent transfer of Cr(III) across the peritoneum.