Toxicokinetics of praseodymium and cerium administered as chloride salts in Sprague-Dawley rats: impacts of the dose and of co-exposure with additional rare earth elements.

We conducted a rat exposure study to assess the impacts of dose and co-exposure with other rare earth elements (REEs) on the toxicokinetics of praseodymium (Pr) and cerium (Ce). We first determined the kinetic profiles of elemental Pr and Ce in blood, urine and feces along with tissue levels at sacrifice on the seventh day following intravenous injection of PrCl3 or CeCl3 at 0.3 or 1 mg/kg bw (of the chloride salts) in adult male Sprague-Dawley rats (n = 5 per group). In blood, Pr and Ce half-lives for the initial phase (t1/2α) increased with increasing doses, while their half-lives for the terminal phase (t1/2ß) were similar at both doses. In urine, a minor excretion route, no significant effect of the dose on the cumulative excretion was apparent. In feces, a major excretion route, the fraction of the Pr dose recovered was significantly lower at the 1 mg/kg bw dose compared to the 0.3 mg/kg bw dose, while no significant dose effect was apparent for Ce. In the liver and spleen, which are the main sites of REEs accumulation, there was a significant effect of the dose only for Ce retention in the spleen (i.e., increased retention of Ce in spleen at higher dose). Results were compared with those of a previous toxicokinetic study with a similar design but an exposure to a quaternary mixture of CeCl3, PrCl3, NdCl3 and YCl3, each administered at 0.3 mg/kg bw or 1 mg/kg bw. A mixture effect was apparent for the initial elimination phase (t1/2α) of Pr and Ce from blood and for the fecal excretion of Ce at the 1 mg/kg bw. In urine and liver, there was no evident overall mixture effect; in the spleen, there was a higher retention of Pr and Ce in rats exposed to the mixture at the 0.3 mg/kg bw, but not at the 1 mg/kg bw dose. Overall, this study showed that the dose and mixture exposure are two important factors to consider as determinants of the toxicokinetics of REEs.

Prenatal exposure of rare earth elements cerium and ytterbium and neonatal thyroid stimulating hormone levels: Findings from a birth cohort study.

BACKGROUND: Prior studies have suggested exposure to heavy metals and endocrine disrupting chemicals could disturb the homeostasis of thyroid stimulating hormone (TSH), but no epidemiology study concerning the influence of rare earth elements (REE) exposure during pregnancy on neonatal TSH levels. The present study aimed to investigate the relationships between prenatal REE exposure and neonatal TSH levels. METHODS: A total of 7367 pregnant women were recruited from Wuhan Children's Hospital between September 2012 and October 2014 in Wuhan, China. Urinary concentrations of cerium (Ce), and ytterbium (Yb) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Immunofluorescence assay was used to detect neonatal TSH levels. The associations between REE exposure and neonatal TSH levels were evaluated using multivariate linear regression models. RESULTS: The geometric means of maternal urinary Ce and Yb concentrations were 0.060 µg/g creatinine and 0.025 µg/g creatinine, respectively. The results showed that per doubling of maternal urinary Ce and Yb were associated with 4.07% (95% CI: -5.80%, -2.31%), 5.13% (95% CI: -6.93%, -3.30%) decreased neonatal TSH levels respectively in the adjusted model. Sex stratified analysis demonstrated that the decreased neonatal TSH levels were observed both in male infants and female infants, and the decrease was greater in male infants in urinary Ce. There were no significant interactions between maternal urinary Ce, Yb and infant sex (Ce: P for interaction = 0.173, Yb: P for interaction = 0.967). CONCLUSIONS: Our findings demonstrated that increased maternal urinary Ce and Yb were associated with decreased neonatal TSH levels. Further researches from different populations are warranted to verify the association and to explore the mechanisms.

Investigation of rare earth elements in urine and drinking water of children in mining area.

To compare the contents of rare earth elements in urine and drinking water of children in the mining and control areas and evaluate the health risk of children in the mining area.Urine and drinking water of 128 children in the mining area and 125 children in the control area were collected from June to July 2015. The contents of rare earth elements were determined using inductively coupled plasma mass spectrometry.The detection rates of rare earth elements, including yttrium (Y), lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), and samarium (Sm), in the urine of children in the exposed group were all 100%, except for samarium (98%); the rates in the control group were 85.7%, 100%, 100%, 98%, 98%, and 59.2%, respectively, and the remaining elements were not detectable. The concentrations of Y, La, Ce, Pr, Nd, and Sm in the urine of children in the exposed group were significantly higher than that in the control group (P < .01). In addition, the composition ratio of lanthanum was higher than that in the control group. The detection rates of lanthanum and Ce in the drinking water of children in the exposed group were 1.44% and 0.72%, respectively. The others were not detectable; the rates in the control group were all 0%.The pollution caused by the presence of Y, La, Ce, Pr, Nd, and Sm in the mining area might affect the health of children in the area, but drinking water might not be the cause.

Biokinetic measurements and modelling of urinary excretion of cerium citrate in humans.

Tracer kinetics in healthy human volunteers was studied applying stable isotopes of cerium citrate to obtain biokinetic human data for the urinary excretion of cerium. These data were then used to compare and validate the biokinetic model for lanthanides (cerium) proposed by Taylor and Leggett (Radiat Prot Dosim 105:193-198, 2003), which is substantially improved and more realistic than the biokinetic model currently recommended by the International Commission on Radiological Protection (ICRP Publication 67, 1993); both models are primarily based on animal data. In the present study, 16 adults were investigated and two cerium tracers were simultaneously administered, both intravenously and/or orally. The cerium concentrations in urine were determined by inductively coupled plasma mass spectrometry. Ingested cerium citrate was poorly absorbed, and its low excretion was similar to the prediction of the biokinetic model of Taylor and Leggett. In contrast, after injection of cerium citrate its urinary excretion was rapidly increased, and the model underestimated the experimental results. These results suggest that urinary excretion of cerium may be dependent on the administered chemical form of cerium (speciation).

Assessment the Exposure Level of Rare Earth Elements in Workers Producing Cerium, Lanthanum Oxide Ultrafine and Nanoparticles.

In order to assess occupational exposure level of 15 rare earth elements (REEs) and identify the associated influence, we used inductively coupled plasma mass spectrometry (ICP-MS) based on closed-vessel microwave-assisted wet digestion procedure to determinate the concentration of Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu in urinary samples obtained from workers producing ultrafine and nanoparticles containing cerium and lanthanum oxide. The results suggest that La and Ce were the primary component, together accounting for 97 % of total REEs in workers. The urinary levels of La, and Ce among the workers (6.36, 15.32 µg.g-1 creatinine, respectively) were significantly enriched compared to those levels measured in the control subjects (1.52, 4.04 µg.g-1 creatinine, respectively) (p < 0.05). This study simultaneously identified the associated individual factors, the results indicate that the concentrations in over 5 years group (11.64 ± 10.93 for La, 27.83 ± 24.38 for Ce) were significantly elevated compared to 1-5 years group (2.58 ± 1.51 for La, 6.87 ± 3.90 for Ce) (p < 0.05). Compared the urinary levels of La and Ce at the separation and packaging locations (9.10 ± 9.51 for La, 22.29 ± 21.01 for Ce) with the other locations (2.85 ± 0.98 for La, 6.37 ± 2.12 for Ce), the results show urinary concentrations were significantly higher in workers at separation and packaging locations (p < 0.01). Inter-individual variation in levels of La and Ce in urine is the result of multi-factorial comprehensive action. Further researches should focus on the multiple factors contributing to the REEs levels of the occupationally exposed workers.

Direct Quantification of Rare Earth Elements Concentrations in Urine of Workers Manufacturing Cerium, Lanthanum Oxide Ultrafine and Nanoparticles by a Developed and Validated ICP-MS.

Rare earth elements (REEs) have undergone a steady spread in several industrial, agriculture and medical applications. With the aim of exploring a sensitive and reliable indicator of estimating exposure level to REEs, a simple, accurate and specific ICP-MS method for simultaneous direct quantification of 15 REEs ((89)Y, (139)La, (140)Ce, (141)Pr, (146)Nd, (147)Sm, (153)Eu, (157)Gd, (159)Tb, (163)Dy, (165)Ho, (166)Er, (169)Tm, (172)Yb and (175)Lu) in human urine has been developed and validated. The method showed good linearity for all REEs in human urine in the concentrations ranging from 0.001-1.000 µg ∙ L(-1) with r² > 0.997. The limits of detection and quantification for this method were in the range of 0.009-0.010 µg ∙ L(-1) and 0.029-0.037 µg ∙ L(-1), the recoveries on spiked samples of the 15 REEs ranged from 93.3% to 103.0% and the relative percentage differences were less than 6.2% in duplicate samples, and the intra- and inter-day variations of the analysis were less than 1.28% and less than 0.85% for all REEs, respectively. The developed method was successfully applied to the determination of 15 REEs in 31 urine samples obtained from the control subjects and the workers engaged in work with manufacturing of ultrafine and nanoparticles containing cerium and lanthanum oxide. The results suggested that only the urinary levels of La (1.234 ± 0.626 µg ∙ L(-1)), Ce (1.492 ± 0.995 µg ∙ L(-1)), Nd (0.014 ± 0.009 µg ∙ L(-1)) and Gd (0.023 ± 0.010 µg ∙ L(-1)) among the exposed workers were significantly higher (p < 0.05) than the levels measured in the control subjects. From these, La and Ce were the primary components, and accounted for 88% of the total REEs. Lanthanum comprised 27% of the total REEs while Ce made up the majority of REE content at 61%. The remaining elements only made up 1% each, with the exception of Dy which was not detected. Comparison with the previously published data, the levels of urinary La and Ce in workers and the control subjects show a higher trend than previous reports.