Chemical speciation of trivalent actinides and lanthanides in biological fluids: the dominant in vitro binding form of curium(III) and europium(III) in human urine.

Radionuclides represent a serious health risk to humans in the case of incorporation. To elucidate the potential of time-resolved laser-induced fluorescence spectroscopy (TRLFS) to determine the dominant radionuclide species in natural biofluids, we investigated the in vitro speciation of curium(III) in human urine samples. Because in speciation studies trivalent lanthanides are often used as analogues for trivalent actinides, we also probed the suitability of this theory by investigating the speciation of europium(III) in human urine. Comparison with reference spectra of both heavy metals in model urine and of their complexes with single organic and inorganic urine constituents then allowed for the determination of the dominant species. Furthermore, the chemical composition of all urine samples was analyzed, and the parameters affecting the speciation of the metals were determined. The pH was found to be the most important parameter because for both, the actinide and the lanthanide, two analogue species were identified in dependence on the pH. In samples with slightly acidic pH a curium(III) and europium(III) citrate complex dominates, respectively, whereas in samples with near-neutral pH a higher complex with phosphate and calcium as the main ligands and the additional participation of citrate and/or carbonate is formed in each case. Comparison with thermodynamic modeling yields some discrepancies, especially at higher pH, which is due to a lack of data for the complex formation of the higher species for both heavy metals. Nevertheless, TRLFS has proven to be a suitable method for the direct determination of the dominant heavy metal species in untreated natural human urine samples.

Curium(III) citrate speciation in biological systems: a europium(III) assisted spectroscopic and quantum chemical study.

Citrate complexes are the dominant binding form of trivalent actinides and lanthanides in human urine at pH < 6. Hence, an accurate prediction of the speciation of these elements in the presence of citrate is crucial for the understanding of their impact on the metabolism of the human organism and the corresponding health risks. We studied the complexation of Cm(III) and Eu(III), as representatives of trivalent actinides and lanthanides, respectively, in aqueous citrate solution over a wide pH range using time-resolved laser-induced fluorescence spectroscopy. Four distinct citrate complexes were identified and their stability constants were determined, which are MHCit(0), M(HCitH)HCit(2-), M(HCit)(2)(3-), and M(Cit)(2)(5-) (M = Cm, Eu). Additionally, there were also indications for the formation of MCit(-) complexes. Structural details on the EuHCit(0) and EuCit(-) complexes were obtained with FT-IR spectroscopy in combination with density functional theory calculations. IR spectroscopic evidence for the deprotonation of the hydroxyl group of the citrate ion in the EuCit(-) complex is presented, which also revealed that the complexation of the Eu(3+) ion takes place not only through the carboxylate groups, like in EuHCit(0), but additionally via the hydroxylate group. In both EuHCit(0) and EuCit(-) the carboxylate binding mode is mono-dentate. Under a very low metal : citrate ratio that is typical for human body fluids, the Cm(III) and Eu(III) speciation was found to be strongly pH-dependent. The Cm(III) and Eu(III) citrate complexes dominant in human urine at pH < 6 were identified to be Cm(HCitH)HCit(2-) and a mixture of Eu(HCitH)HCit(2-) and EuHCit(0). The results specify our previous in vitro study using natural human urine samples (Heller et al., Chem. Res. Toxicol., 2011, 24, 193-203).

Urinary monitoring of exposure to yttrium, scandium, and europium in male Wistar rats.

On the assumption that rare earth elements (REEs) are nontoxic, they are being utilized as replacements of toxic heavy metals in novel technological applications. However, REEs are not entirely innocuous, and their impact on health is still uncertain. In the past decade, our laboratory has studied the urinary excretion of REEs in male Wistar rats given chlorides of europium, scandium, and yttrium solutions by one-shot intraperitoneal injection or oral dose. The present paper describes three experiments for the suitability and appropriateness of a method to use urine for biological monitoring of exposure to these REEs. The concentrations of REEs were determined in cumulative urine samples taken at 0-24 h by inductively coupled plasma atomic emission spectroscopy, showing that the urinary excretion of REEs is <2 %. Rare earth elements form colloidal conjugates in the bloodstream, which make high REEs accumulation in the reticuloendothelial system and glomeruli and low urinary excretion. The high sensitivity of inductively coupled plasma-argon emission spectrometry analytical methods, with detection limits of <2 µg/L, makes urine a comprehensive assessment tool that reflects REE exposure. The analytical method and animal experimental model described in this study will be of great importance and encourage further discussion for future studies.

Distribution, elimination, and renal effects of single oral doses of europium in rats.

Single doses of europium (III) chloride hexahydrate were orally administered to several groups of rats. Cumulative urine samples were taken at 0-24 h, and blood samples were drawn after 24-h administration. The europium concentration was determined in these samples by inductively coupled plasma atomic emission spectroscopy. The volume, creatinine, ß-2-microglobulin, and N-acetyl-ß-D-glucosaminidase were measured in the urine samples to evaluate possible europium-induced renal effects. The blood samples showed low europium distribution, with an average of 77.5 µg/L for all groups. Although the urinary concentration and excretion showed dose-dependent increases, the percentage of europium excreted showed a dose-dependent decrease, with an average of 0.31% in all groups. The administration of europium resulted in a significant decrease of creatinine and a significant increase of urinary volume, N-acetyl-ß-D-glucosaminidase, and ß-2-microglobulin. Rare earth elements, including europium, are believed to form colloidal conjugates that deposit in the reticuloendothelial system and glomeruli. This specific reaction may contribute to low europium bioavailability and renal function disturbances. Despite low bioavailability, the high performance of the analytical method for determination of europium makes the blood and urine sampling suitable tools for monitoring of exposure to this element. The results presented in this study will be of great importance in future studies on the health impacts of rare earth elements.

Distribution and excretion of lanthanides: comparison between europium salts and complexes.

Europium (152,154Eu) was intravenously injected into rats as: (i) the chloride salt at pH 7.4, (ii) the chloride salt at pH 3, (iii) the albumin complex and (iv) the DTPA complex, and tissue uptake was determined 24 h later. For the chlorides, the target organ for uptake was liver (about 60% of dose) whilst europium complexes were rapidly excreted in urine and were predominantly taken up into the kidney (about 0.5% of dose) and bone. Liver uptake of EuCl3, pH 7.4, corresponded to that of a colloidal material with most 152Eu present in the non-hepatocyte population; however, EuCl3, pH 3, was handled in a different manner, with significant uptake by hepatocytes. The differing tissue distributions of EuCl3 and Eu-albumin suggest that plasma albumin does not readily bind injected EuCl3. Renal uptake of europium, although a relatively low proportion of the injected dose, was associated with many subcellular fractions, including lysosomes, suggesting significant intracellular uptake and thus possible retention.