Search

Canada has recently invested in the large-scale exploitation of scandium oxide. However, there are no studies available to date to understand its toxicokinetics in the animal or human body, which is necessary to assess exposure and health risks. The aim of this research was to investigate the toxicokinetics of absorbed scandium oxide (Sc 2 O 3) using the rat as an experimental model. Male Sprague-Dawley rats were injected intravenously with 0.3 or 1 mg Sc 2 O 3 /kg body weight (bw). Blood and excreta (urine and feces) were collected sequentially during a 21-day period, and main organs (liver, spleen, lungs, kidneys, brain) were withdrawn at sacrifice on day 21. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for the measurement of Sc element in the different samples. The mean residence time (MRT IV) calculated from the blood profile was 19.7 ± 5.9 h and 43.4 ± 24.6 h at the lower and higher doses, respectively. Highest tissue levels of Sc were found in the lungs and liver; respective lung values of 10.6 ± 6.2% and 3.4 ± 2.3% of the Sc dose were observed at the time of sacrifice while liver levels represented 8.9 ± 6.4% and 4.6 ± 1.1%. Elimination of Sc from the body was not complete after 21 days. Cumulative fecal excretion over the 21-day collection period represented 12.3 ± 1.3% and 5.9 ± 1.0% of the lower and higher Sc doses, respectively, and showed a significant effect of the dose on the excretion; only a small fraction of the Sc dose was recovered in urine (0.025 ± 0.016% and 0.011 ± 0.004% in total, respectively). In addition to an effect of the dose on the toxicokinetics, results highlight the importance of the lung as a site of accumulation and retention of Sc 2 O 3 , which raises the question of the risks of effects related to respiratory exposure in workers. The results also question the relevance of urine as a matrix for biological exposure monitoring. A more in-depth inhalation toxicokinetic study would be necessary. • Intravenously injected scandium oxide accumulates in lungs and liver mainly. • Excretion occurs mainly in feces and little is found in urine. • The dose impacts the toxicokinetics of scandium oxide. • Higher scandium oxide dose resulted in lower cumulative excretion rates. • Lung retention raises the question of risks related to respiratory exposure. [ABSTRACT FROM AUTHOR]

• Toxicokinetics of cerium, praseodymium, neodymium and yttrium were similar. • Kinetics of rare-earth elements (REEs) was influenced by the dose. • Excretion of REEs in urine and feces decreased with increasing doses. • Fraction of REE dose remaining in rat tissues at necropsy increased with dose. • Shift in kinetics at high dose may result from higher retention in lysosomes. 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 (PrCl 3), cerium chloride (CeCl 3), neodymium chloride (NdCl 3) and yttrium chloride (YCl 3) 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 (MRT IV) 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. [ABSTRACT FROM AUTHOR]

This study focused on the generation of aerosols of titanium dioxide (TiO 2 ) nanoparticles (NPs) and their disposition kinetics in rats. Male Sprague-Dawley rats were exposed by inhalation to 15 mg/m 3 of anatase TiO 2 NPs (∼20 nm) during 6 h. Rats were sacrificed at different time points over 14 days following the onset of inhalation. Ti levels were quantified by ICP-MS in blood, tissues, and excreta. Oxidative damages were also monitored (MDA). Highest tissue levels of Ti were found in lungs; peak values were reached only at 48 h followed by a progressive decrease over 14 days, suggesting a persistence of NPs at the site-of-entry. Levels reached in blood, lymph nodes and other internal organs (including liver, kidney, spleen) were circa one order of magnitude lower than in lungs, but the profiles were indicative of a certain translocation to the systemic circulation. Large amounts were recovered in feces compared to urine, suggesting that inhaled NPs were eliminated mainly by mucociliary clearance and ingested. TiO 2 NPs also appeared to be partly transferred to olfactory bulbs and brain. MDA levels indicative of oxidative damage were significantly increased in lungs and blood at 24 h but this was not clearly reflected at later times. Translocation and clearance rates of inhaled NPs under different realistic exposure conditions should be further documented. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • The dose impacts the toxicokinetics of oxide forms of rare earth elements (REEs). • Higher REE dose resulted in lower cumulative excretion rates. • Initial elimination of REE oxides from blood was faster than the chloride form. • Slower cumulative urinary and fecal excretion were determined for REE oxides. • Fractions of REE doses recovered in spleen and lungs were higher for REE oxides. [ABSTRACT FROM AUTHOR]

• A physiological-based toxicokinetic model was developed for rare earth elements. • Model parameters were derived from the literature and novel toxicokinetic data. • Biomonitoring equivalents (BEs) are proposed. • BEs are based on urinary levels corresponding to critical dose levels. • The model and BEs provide rapid screening tools of populations for risk assessment. Toxicokinetic models are useful tools to better understand the fate of contaminants in the human body and to establish biological guidance values to interpret biomonitoring data in human populations. This research aimed to develop a biologically-based toxicokinetic model for four rare earth elements (REEs), cerium (Ce), praseodymium (Pr), neodymium (Nd) and yttrium (Y), and to establish biomonitoring equivalents (BE) serving as biological guidance values. The model was constructed using physiological data taken from the literature as well as new experimental kinetic data. These new data indicated that REEs readily disappeared from blood and accumulated mostly in the liver; excretion occurred mainly through feces although a small fraction was eliminated in urine. To properly reproduce the observed kinetics, the model was represented as 19 compartments, which include main tissues and their components (such as retention by macrophages) supplied by blood, as well as routes of excretion. The transfer coefficients between compartments were determined numerically by adjustments to experimental data. Simulations gave good fits to available experimental kinetic data and confirmed that the same model structure is applicable to the four elements. BEs of 0.3 µg/L of Pr and Nd were derived from the provisional RfD of 0.5 mg/kg bw/day established by the U.S. EPA. These BEs can be updated according to new reference dose values (RfD). Overall, the model can contribute to a better understanding of the significance of biological measurements and to the inference of exposure levels; it can also be used for the modeling of other REEs. The BEs will further allow rapid screening of different populations using biological measurements in order to guide risk assessments. [ABSTRACT FROM AUTHOR]

The toxicity and kinetics of nanoparticles (NPs) have been related to their physical and chemical properties. To better understand their fate and reactivity in the body, intrinsic properties of NPs (size, shape, surface area, particle number) and mobility properties (agglomeration) need to be evaluated. A systematic study of the toxicokinetics of inhaled silver (Ag) NPs and the evolution of malondialdehyde (MDA) marker of oxidative stress over time was performed by testing the effect of the particle number as metric and using the rat as an experimental model. Aerosols of Ag NPs with lower- and higher-total particle numbers but with the same mass concentration (15 mg/m3) and initial particle size (20 nm) were generated with a nose-only inhalation unit, and exposure conditions (including size distribution) were monitored. Rats were placed in the inhalation unit for six consecutive hours (some rats sacrificed at 3 h) and the time courses of elemental Ag in lungs, blood, extrapulmonary tissues and excreta were determined over a 14-day period. Microscopy characterization showed that Ag NPs used for aerosol generation had two kinds of shape: spherical shape or elongated (like a rugby ball). Monitoring of size distribution of (agglomerated) particles in the aerosol revealed that the median aerodynamic diameter was slightly greater for the lower-count (92 nm; 1.6 × 105 p/cm3) compared to the higher-count of particles (81 nm; 3.5 × 105 p/cm3). Higher peak levels of Ag element were observed in lungs (2–5 times higher at all times), blood (2–3 times higher) and GI tract (2–3 times higher) of rats exposed to the aerosol with lower-total particle number. However, some similarities in the kinetics were observed between the two conditions, such as the relative tissue distribution, time-to-peak levels (Tmax) and excretion profiles. In both conditions, only a fraction of the inhaled dose was quantitated in the lungs, and the observed lung time-course showed that Ag continued to reach the lungs several hours after the end of the inhalation period. Following inhalation, Ag NPs were excreted mainly in feces and a minor fraction was recovered in urine. For Ag NPs, some particle characteristics were documented earlier to have an impact their toxicity. However, in our study, there was no difference in malondialdehyde (MDA) levels in blood and lungs between the two exposure conditions tested. Further investigations are needed to confirm if the biodistribution pattern of Ag NPs and oxidative stress is conditioned by the particle number. • We assessed the impact of the particle count as an exposure metric on the toxicokinetics of inhaled silver nanoparticles. • Peak levels of silver were higher in lungs, blood and GI tract of rats exposed to lower-total particle number aerosol. • Relative tissue distribution, time-to-peak levels (Tmax) and excretion were similar between the two conditions. • Malondialdehyde levels in blood and lungs were similar between the two exposure conditions. [ABSTRACT FROM AUTHOR]