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.