Toxicokinetics of rare earth element oxides administered intravenously to rats

Rare earth elements (REEs) are increasingly used in a wide range of applications. However, their toxicokinetic behaviors in animals and humans are not yet fully documented, hindering health risk assessments. We used a rat experimental model to provide novel data on the toxicokinetics of the insoluble oxide forms of praseodymium (Pr), neodymium (Nd), cerium (Ce) and yttrium (Y) administered intravenously. Detailed blood, urinary and fecal time courses were documented through serial sampling over 21 days in male Sprague-Dawley rats exposed to a mixture of these REE oxides administered at two different doses (0.3 or 1 mg kg^-1 bw of each REE oxide commercially sold as bulk μm-sized particles). Tissue REE levels at the time of sacrifice were also measured. Significant effects of the dose on REE time courses in blood and on cumulative urinary and fecal excretion rates were observed for all four REE oxides assessed, as lower cumulative excretion rates were noted at the higher REE dose. In the liver, the main accumulation organ, the fraction of the administered REE dose remaining in the tissue at necropsy was similar at both doses. Toxicokinetic data for the REE oxides were compared to similar data for their chloride salts (also administered intravenously in a mixture, at 0.3 and 1 mg kg^-1 bw of each REE chloride) obtained from a previous study. Compared to their chloride counterparts, faster elimination of REE oxides from the blood was observed in the first hours post-dosing. Furthermore, higher mean residence time (MRT) values as well as slower cumulative urinary and fecal excretion were determined for the REE oxides. Also, while liver REE retention was similar for both REE forms, the fractions of the administered REEs recovered in the spleen and lungs were noticeably higher for the REE oxides, at both dose levels. This study highlights the importance of both the dose and form of the administered REEs on their toxicokinetic profiles. Results indicate that chronic exposure and increased doses of REEs may favor bioaccumulation in the body, in particular for insoluble oxide forms of REEs, which are eliminated more slowly from the body.