Chair in Toxicological Risk Assessment and Management, and Public Health Research Center (CReSP), Department of Environmental and Occupational Health, University of Montreal, Roger-Gaudry Building, U436, Main Station, P.O. Box 6128, Montreal, QC, H3C 3J7, Canada.
Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, K1A 0K9, Canada.
Arch Toxicol. 2023 Dec;97(12):3061-3074. doi: 10.1007/s00204-023-03598-x. Epub 2023 Sep 7.
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 PrCl or CeCl 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 (t1/2) increased with increasing doses, while their half-lives for the terminal phase (t1/2) 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 CeCl, PrCl, NdCl and YCl, each administered at 0.3 mg/kg bw or 1 mg/kg bw. A mixture effect was apparent for the initial elimination phase (t1/2) 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.
我们进行了一项大鼠暴露研究，以评估剂量和与其他稀土元素（REEs）共同暴露对镨（Pr）和铈（Ce）的毒代动力学的影响。我们首先确定了静脉注射 PrCl 或 CeCl 后第 7 天，雄性 Sprague-Dawley 大鼠（每组 5 只）的血液、尿液和粪便中的元素 Pr 和 Ce 的动力学特征，以及组织水平。在血液中，初始阶段（t1/2）的 Pr 和 Ce 半衰期随着剂量的增加而增加，而终末阶段（t1/2）的半衰期在两种剂量下相似。在尿液中，作为一种次要的排泄途径，剂量对累积排泄量没有明显影响。在粪便中，作为一种主要的排泄途径，1 mg/kg bw 剂量回收的 Pr 剂量分数明显低于 0.3 mg/kg bw 剂量，而 Ce 则没有明显的剂量效应。在肝脏和脾脏中，这是 REEs 蓄积的主要部位，只有 Ce 在脾脏中的蓄积受到剂量的显著影响（即，高剂量时脾脏中 Ce 的蓄积增加）。结果与之前的毒代动力学研究进行了比较，该研究采用了类似的设计，但暴露于 CeCl、PrCl、NdCl 和 YCl 的四元混合物中，每个剂量为 0.3 mg/kg bw 或 1 mg/kg bw。Pr 和 Ce 从血液中的初始消除阶段（t1/2）和 Ce 在粪便中的排泄在 1 mg/kg bw 时表现出明显的混合物效应。在尿液和肝脏中，没有明显的总体混合物效应；在脾脏中，暴露于混合物的大鼠在 0.3 mg/kg bw 时 Pr 和 Ce 的保留率较高，但在 1 mg/kg bw 时则不然。总体而言，这项研究表明，剂量和混合物暴露是考虑 REEs 毒代动力学的两个重要因素。
