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Effect of the dose on the toxicokinetics of a quaternary mixture of rare earth elements administered to rats. 2021

Malek Jomaa, and Denis Dieme, and Mathieu Desrosiers, and Jonathan Côté, and Hamadi Fetoui, and Guillaume Pelletier, and Andy Nong, and Michèle Bouchard
Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and Public Health Research Center (CReSP), University of Montreal, Roger-Gaudry Building, U424, P.O. Box 6128, Main Station, Montreal, QC, H3C 3J7, Canada.

Large human biomonitoring studies are starting to assess exposure to rare earth elements (REEs). Yet, there is a paucity of data on the toxicokinetics of these substances to help interpret biomonitoring data. The objective of the study was to document the effect of the administered dose on the toxicokinetics of REEs. Male Sprague-Dawley rats were injected intravenously with 0.3, 1 or 10 mg/kg body weight (bw) of praseodynium chloride (PrCl3), cerium chloride (CeCl3), neodymium chloride (NdCl3) and yttrium chloride (YCl3) administered together as a mixture. Serial blood samples were withdrawn up to 72 h following injection, and urine and feces were collected at predefined time intervals up to 7 days post-dosing. The REEs were measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). For a given REE dose, the time courses in blood, urine and feces were similar for all four REEs. However, the REE dose administered significantly impacted their kinetics, as lower cumulative excretion in urine and feces was associated with higher REE doses. The fraction of REE remaining in rat tissues at the terminal necropsy on post-dosing day 7 also increased with the dose administered, most notably in the lungs and spleen at the 10 mg/kg bw dose. The toxicokinetic parameters calculated from the blood concentration-time profiles further showed significant increases in the mean residence time (MRTIV) for all four REEs at the 10 mg/kg bw dose. The shift in the REE kinetics at high dose may be explained by a higher retention in lysosomes, the main organelle responsible for accumulation of these REEs in different tissues.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D008297 Male Males
D008674 Metals, Rare Earth A group of elements that include SCANDIUM; YTTRIUM; and the LANTHANOID SERIES ELEMENTS. Historically, the rare earth metals got their name from the fact that they were never found in their pure elemental form, but as an oxide. In addition, they were very difficult to purify. They are not truly rare and comprise about 25% of the metals in the earth's crust. Rare Earth Metal,Rare Earth Metals,Earth Metal, Rare,Earth Metals, Rare,Metal, Rare Earth
D009354 Neodymium An element of the rare earth family of metals. It has the atomic symbol Nd, atomic number 60, and atomic weight 144.24, and is used in industrial applications.
D011221 Praseodymium An element of the rare earth family of metals. It has the atomic symbol Pr, atomic number 59, and atomic weight 140.91.
D002563 Cerium An element of the rare earth family of metals. It has the atomic symbol Ce, atomic number 58, and atomic weight 140.12. Cerium is a malleable metal used in industrial applications.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D015019 Yttrium An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers.

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