The effect of natural biomolecules on yttrium oxide nanoparticles from a Daphnia magna survival rate perspective.

The attention to rare earth oxide nanoparticles (NPs), including yttrium oxide (Y2O3), has increased in many fields due to their unique structural characteristics and functional properties. The aim of our study was to investigate the mechanisms by which bio-corona formation on Y2O3 NPs affects their environmental fate and toxicity. The Y2O3 NPs induced toxicity to freshwater filter feeder Daphnia magna at particle concentrations of 1 and 10 mg/L, regardless of particle size. Interactions between naturally excreted biomolecules (e.g. protein, lipids, and polysaccharides) derived from D. magna, and the Y2O3 NPs (30-45 nm) resulted in the formation of an eco-corona, which reduced their toxic effects toward D. magna at a particle concentration of 10 mg/L. No effects were observed at lower concentrations or for the other particle sizes investigated. Copper-zinc (Cu-Zn) superoxide dismutase, apolipophorins, and vitellogenin-1 proteins proved to be the most prominent proteins of the adsorbed corona, and possibly a reason for the reduced toxicity of the 30-45 nm Y2O3 NPs toward D. magna.

Chronic exposure to yttrium induced cell apoptosis in the testis by mediating Ca2+/IP3R1/CaMKII signaling.

Introduction: Environmental pollutants, such as rare earth elements, affect human health and particularly induce reproductive system injury. Yttrium (Y), one of the most widely used heavy rare earth elements, has been reported the cytotoxicity. However, the biological effects of Y3+ in the human body are largely unknown. Methods: To further investigate the effects of Y on the reproductive system, in vivo (rat models) and in vitro studies were performed. Histopathological and immunohistochemical examination were conducted, and western blotting assays were performed to detect the protein expression. TUNEL/DAPI staining were used to detect cell apoptosis, and the intracellular calcium concentrations were also determined. Results: Long-term exposure to YCl3 in rats produced significant pathological changes. YCl3 treatment could induce cell apoptosis in vivo and in vitro. In addition, YCl3 enhanced the concentration of cytosolic Ca2+ and up regulated the expression of IP3R1/CaMKII axis in Leydig cells. However, inhibition of IP3R1 and CaMKII with 2-APB and KN93, respectively, could reverse these effects. Conclusion: Long-term exposure to yttrium could induce testicular injury by stimulating cell apoptosis, which might be associated with activation of Ca2+/IP3R1/CaMKII axis in Leydig cells.

Yttrium chloride-induced cytotoxicity and DNA damage response via ROS generation and inhibition of Nrf2/PPARγ pathways in H9c2 cardiomyocytes.

Increasing exploration of rare-earth elements (REEs) has resulted in a high REEs' exposure risk. Owing to their persistence and accumulation of REEs in the environment, their adverse effects have caused widespread concern. However, limited toxicological data are available for the adverse effects of yttrium (Y) and its underlying mechanisms of action. In the present study, H9c2 cardiomyocytes were used in vitro model to investigate the cardiotoxicity of yttrium chloride (YCl3). Results show that YCl3 treatment resulted in reactive oxygen species (ROS) overproduction, decrease in ∆Ψm, and DNA damage. Mechanistically, we detected expression levels of protein in response to cellular DNA damage and antioxidative defense. Results indicated that the phosphorylation of histone H2AX remarkably increased in a dose-dependent manner. At a high YCl3-exposure concentration (120 µM), specific DNA damage sensors ATM/ATR-Chk1/Chk2 were significantly decreased. The protein levels of key antioxidant genes Nrf2/PPARγ/HO-1 were also remarkably inhabited. Additionally, the antioxidant N-acetyl-L-cysteine (NAC) pretreatment promoted the activation of antioxidative defense Nrf2/PPARγ signaling pathways, and prevented the production of cellular ROS, thus protecting the DNA from cleavage. Altogether, our findings suggest that YCl3 can induce DNA damage through causing intracellular ROS overproduction and inhibition of antioxidative defense, leading to cytotoxicity in H9c2 cardiomyocytes.

A CORM loaded nanoplatform for single NIR light-activated bioimaging, gas therapy, and photothermal therapy in vitro.

Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.

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

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.

Do essential elements (P and Fe) have mitigation roles in the toxicity of individual and binary mixture of yttrium and cerium to Triticum aestivum?

Essential elements can affect the bioavailability, uptake, and toxicity of metals. However, hardly any research has focused on the roles of essential elements on the toxicity of rare earth metals. Here we examined how P and Fe modified the individual and binary toxicity of Y and Ce to Triticum aestivum, respectively. Standard root elongation tests were used to quantify the toxicity of both single and binary mixtures at three levels of P addition (1, 5, and 10 µM) and Fe addition (0.1, 1, and 5 mM). Our results showed that both P and Fe can alleviate individual toxicity of Y or Ce irrespective of the dose indicators as suggested by the enhanced EC50 values. Both P and Fe might mitigate Y/Ce toxicity by limiting Y/Ce uptake into roots and improving nutritional status of wheats, whereas P can also decrease free Y/Ce ion activities in the exposure media. As for the mixture toxicity of Y and Ce, only improved P, but not Fe can exhibit approximately additive mixture toxicity, which can be adequately predicted by the simple Concentration Addition model. Our results suggested the important roles of P and Fe in assessing Y and Ce toxicity accurately.

Critical Aspects on the Chemical Stability of NaYF4-Based Upconverting Nanoparticles for Biomedical Applications.

This review summarizes essential information about the chemical stability of NaYF4-based upconverting nanoparticles (UCNPs) in aqueous solutions, a crucial aspect for achieving high quality standards for biomedical materials. We present an in-depth analysis of the major experimental evidence and proposed mechanisms that provide a theoretical framework for understanding UCNPs degradation, destabilization, and dissolution under different conditions such as media composition, temperature, particle size, and the synthetic methods employed. The ion release and disintegration of the UCNP crystal structure may trigger cytotoxic events within living organisms and impact on their optical properties, precluding their safe use in biological environments. Also, we present a summary of the characterization techniques' toolbox employed for monitoring and detecting these degradation processes. Closing the existing "information gap" that links UCNP physicochemical properties, such as solubility and chemical stability, with the biological response of living organisms or tissues, is vital for using these nanoparticles as biological tracer probes, theranostic vehicles, or for clinical purposes. The understanding of chemical phenomena at the nanoparticle solid-liquid interface is mandatory to complete the molecular picture of nanosized objects, orienting in a rational manner the efforts of research and development in the early stages of these functional materials.

Study on cytotoxicity, cellular uptake and elimination of rare-earth-doped upconversion nanoparticles in human hepatocellular carcinoma cells.

The growing use of rare-earth doped upconversion nanoparticles (UCNPs) has caused increasing concern about their biosafety. Here, to understand the toxicity of UCNPs and their mechanism in HepG2 cells, we systematically study the cytotoxicity, uptake and elimination behaviors of three types of UCNPs combined multiple cytotoxicity evaluation means with inductively coupled plasma mass spectrometry (ICP-MS) detection. Sodium yttrium fluoride, doped with 18% (molar ratio) ytterbium and 2% erbium (NaYF4: Yb3+, Er3+) was selected as the model UCNPs with two sizes (35 and 55 nm), and the poly(acrylic acid) and polyethylenimine were selected as the representatives of negative and positive surface coating of UCNPs, respectively. UCNPs were found to induce cytotoxicity in time- and dose-dependent manners, which might be mediated by reactive oxygen species generation and oxidative stress. Apoptosis, inflammation, and metabolic process were enhanced after cells exposed to 200 mg/L UCNPs for 48 h. Increase in the protein levels of cleaved caspased-9, cleaved caspase-3 and Bax and decrease in the anti-apoptotic protein, Bcl-2 suggested that the mitochondria mediated pathway was involved in UCNP-induced apoptosis. With the aid of ICP-MS, it demonstrated that the cytotoxicity was associated with internalized amount of UCNPs, which largely relied on their surface properties rather than size in the tested range. By comparing UCNPs with Y3+ ions, it demonstrated that NPs properties played a nonnegligible role in the cytotoxicity of UCNPs. These findings provide new insights for fundamental understanding of cytotoxicity of UCNPs and may contribute to more rational use of these materials in the future.

Reversible Ratiometric Probe Combined with the Time-Gated Method for Accurate In Vivo Gastrointestinal pH Sensing.

Fluorescence sensing has the advantages of being real time, noninvasive, and convenient and having a low impact on the original environment for in vivo detection. Here, a reversible time-gated ratiometric in vivo detection method that could eliminate the interferences from probe amount, photon scattering, and absorption is proposed. Correspondingly, the composite probe must be able to reversibly respond to changes in the microenvironment and emit two luminescence signals at the same working wavelength but different lifetimes. Benefitting from the reversible detection mechanism, the probes could be used to monitor a dynamic biological process and the ratio signal value could be determined only by the concentration of analytes, independent of the probe concentration. Furthermore, benefitting from the same working wavelength, the read-out errors from photon absorption and scattering could be minimized. This method is very suitable for in vivo detection in which the probe distribution and depth are unknown and variable. As a typical model, different pH values in the gastrointestinal area and pH changes caused by drugs and fasting are successfully monitored.

Dispersion stability and biocompatibility of four ligand-exchanged NaYF4: Yb, Er upconversion nanoparticles.

Surface modification to obtain high dispersion stability and biocompatibility is a key factor for bio-application of upconversion nanoparticles (UCNPs). A systematic study of UCNPs modified with four hydrophilic molecules separately, comparing their dispersion stability in biological buffers and cellular biocompatibility is reported here. The results show that carboxyl-functionalized UCNPs (modified by 3,4-dihydrocinnamic acid (DHCA) or poly(monoacryloxyethyl phosphate (MAEP)) with negative surface charge have superior even-distribution in biological buffers compared to amino-functionalized UCNPs (modified by (aminomethyl)phosphonic (AMPA) or (3-Aminopropyl)triethoxysilane (APTES)) with positive surface charge. Subsequent investigation of cellular interactions revealed high levels of non-targeted cellular uptake of the particles modified with either of the three small molecules (AMPA, APTES, DHCA) and high levels of cytotoxicity when used at high concentrations. The particles were seen to be trapped as particle-aggregates within the cellular cytoplasm, leading to reduced cell viability and cell proliferation, along with dysregulation of the cell cycle as assessed by DNA content measurements. The dramatically reduced proportion of cells in G1 phase and the slightly increased proportion in G2 phase indicates inhibition of M phase, and the appearance of sub-G1 phase reflects cell necrosis. In contrast, MAEP-modified UCNPs are bio-friendly with increased dispersion stability in biological buffers, are non-cytotoxic, with negligible levels of non-specific cellular uptake and no effect on the cell cycle at both low and high concentrations. MAEP-modified UCNPs were further functionalized with streptavidin for intracellular microtubule imaging, and showed clear cytoskeletal structures via their upconversion luminescence. STATEMENT OF SIGNIFICANCE: Upconversion nanoparticles (UCNP) are an exciting potential nanomaterial for bio-applications. Their anti-Stokes luminescence makes them especially attractive to be used as imaging probes and thermal therapeutic reagents. Surface modification is the key to achieving stable and compatible hydrophilic-UCNPs. However, the lack of criteria to assess molecular ligands used for ligand exchange of nanoparticles has hampered the development of surface modification, and further limits UCNP's bio-application. Herein, we report a systematic comparative study of modified-UCNPs with four distinct hydrophilic molecules, assessing each particles' colloidal stability in biological buffers and their cellular biocompatibility. The protocol established here can serve as a potential guide for the surface modification of UCNPs in bio-applications.

Model-based rationalization of mixture toxicity and accumulation in Triticum aestivum upon concurrent exposure to yttrium, lanthanum, and cerium.

Rare earth elements (REEs) often co-exist in the environment, but predicting their 'cocktail effects' is still challenging, especially for high-order mixtures with more than two components. Here, we systematically investigated the toxicity and accumulation of yttrium, lanthanum, and cerium mixtures in Triticum aestivum following a standardized bioassay. Toxic effects of mixtures were predicted using the reference model of Concentration Addition (CA), Ternary model, and Ternary-Plus model. Interactions between the REEs in binary and ternary mixtures were determined based on external and internal concentrations, and their magnitude estimated from the parameters deviated from CA. Strong antagonistic interactions were found in the ternary mixtures even though there were no significant interactions in the binary mixtures. Predictive ability increased when using the CA model, Ternary model, and Ternary-Plus model, with R2= 0.78, 0.80, and 0.87 based on external exposure concentrations, and R2= 0.72, 0.73, and 0.79, respectively based on internal concentrations. The bioavailability-based model WHAM-FTOX explained more than 88 % and 85 % of the toxicity of binary and ternary REE treatments, respectively. Our result showed that the Ternary-Plus model and WHAM-FTOX model are promising tools to account for the interaction of REEs in mixtures and could be used for their risk assessment.

The Truth of Toxicity Caused by Yttrium Oxide Nanoparticles to Yeast Cells.

Yttrium oxide (Y2O3) nanoparticles have widespread applications; however, toxicity due to these nanoparticles has also been reported. In this study, we evaluated the in vitro toxicity of Y2O3 nanoparticles according to the technical specifications published by the International Standard Organization (ISO/TS 19337:2016). We used Saccharomyces cerevisiae as a model microorganism represented the environment. We carried out catch ball analysis of yttrium oxide and yttrium ion toxicities. The result showed that Y2O3 nanoparticles (20 mg/5 ml) and YCl3 (5 mg/5 ml) treatment caused oxidative stress in yeast cells. Based on transcriptome analysis, fluorescent spectroscopy, and solubility analysis of Y2O3 nanoparticles, we conclude that the toxicity is due to yttrium ions derived from the nanoparticles. The ions induce oxidative stress and cause protein denaturation, which in turn induces proteasome formation to eliminate denatured proteins. Yttrium nanoparticles induce oxidative stress, which has associated with heavy metal ions. Thus, the use of yttrium nanoparticles or yttrium ions must be controlled like heavy metals.

Ecotoxicity of rare earths in the marine mussel Mytilus galloprovincialis and a preliminary approach to assess environmental risk.

The increasing use of rare earth elements (REEs) in diverse technological applications has augmented the demand and exploitation of these worldwide, leading to a higher input of REEs + Yttrium (Y) in the marine environment. The present study investigated the ecotoxicity of Lanthanum (La) and Y to Mytilus galloprovincialis developing embryos and juveniles. This was achieved by quantifying the embryogenesis success after 48 h, and survival of juveniles after 96 h of exposure to different concentrations of La and Y. Results show that both La and Y are more toxic to developing embryos and larvae than to juveniles of M. galloprovincialis. Predicted no-effect concentration (PNEC) values were also derived for the embryo development as a preliminary approach to assess the environmental risk for these compounds to marine organisms. Results revealed that La is more toxic than Y. The high sensitivity of the early developmental stages to these compounds highlight the relevance of including these stages when evaluating the toxicity of chemicals where little information is available. Although older life stages may be more tolerant to toxicants, the population survival will be compromised if new recruits are not viable, with implications to the whole ecosystem health and functioning of the impacted area. Information on the ecotoxicity of chemicals with expanded technological use and that may be released during deep-sea mining activities is urgent in order to help estimate environmental impacts.

Comparative study of toxicological assessment of yttrium oxide nano- and microparticles in Wistar rats after 28 days of repeated oral administration.

Despite their enormous advantages, nanoparticles (NPs) have elicited disquiet over their safety. Among the numerous NPs, yttrium oxide (Y2O3) NPs are utilised in many applications. However, knowledge about their toxicity is limited, and it is imperative to investigate their potential adverse effects. Therefore, this study explored the effect of 28 days of repeated oral exposure of Wistar rats to 30, 120 and 480 mg/kg body weight (bw) per day of Y2O3 NPs and microparticles (MPs). Before initiation of the study, characterisation of the particles by transmission electron microscopy, dynamic light scattering, Brunauer-Emmett-Teller and laser Doppler velocimetry was undertaken. Genotoxicity was evaluated using the comet and micronucleus (MN) assays. Biochemical markers aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase and lactate dehydrogenase in serum, liver and kidney were determined. Bioaccumulation of the particles was analysed by inductively coupled plasma optical emission spectrometry. The results of the comet and MN assays showed significant differences between the control and groups treated with 120 and 480 mg/kg bw/day Y2O3 NPs. Significant biochemical alterations were also observed at 120 and 480 mg/kg bw/day. Haematological and histopathological changes were documented. Yttrium (Y) biodistribution was detected in liver, kidney, blood, intestine, lungs, spleen, heart and brain in a dose- and the organ-dependent manner in both the particles. Further, the highest levels of Y were found in the liver and the lowest in the brain of the treated rats. More of the Y from NPs was excreted in the urine than in the faeces. Furthermore, NP-treated rats exhibited much higher absorption and tissue accumulation. These interpretations furnish rudimentary data of the apparent genotoxicity of NPs and MPs of Y2O3 as well as the biodistribution of Y. A no-observed adverse effect level of 30 mg/kg bw/day was found after oral exposure of rats to Y2O3 NPs.

Phytotoxicity of individual and binary mixtures of rare earth elements (Y, La, and Ce) in relation to bioavailability.

Rare earth elements (REEs) are typically present as mixtures in the environment, but a quantitative understanding of mixture toxicity and interactions of REEs is still lacking. Here, we examined the toxicity to wheat (Triticum aestivum L.) of Y, La, and Ce when applied individually and in combination. Both concentration addition (CA) and independent action (IA) reference models were used for mixture toxicity analysis because the toxicity mechanisms of REEs remain obscure. Upon single exposure, the EC50s of Y, La, and Ce, expressed as dissolved concentrations, were 1.73 ±â€¯0.24 µM, 2.59 ±â€¯0.23 µM, and 1.50 ±â€¯0.22 µM, respectively. The toxicity measured with relative root elongation followed La < Y ≈ Ce, irrespective of the dose descriptors. The use of CA and IA provided similar estimates of REE mixture interactions and toxicity. When expressed as dissolved metal concentrations, nearly additive effects were observed in Y-La and La-Ce mixtures, while antagonistic interactions were seen in Y-Ce mixtures. When expressed as free metal activities, antagonistic interactions were found for all three binary mixtures. This can be explained by a competitive effect of REEs ions for binding to the active sites of plant roots. The application of a more elaborate MIXTOX model in conjunction with the free ion activities, which incorporates the non-additive interactions and bioavailability-modifying factors, well predicted the mixture toxicity (with >92% of toxicity variations explained). Our results highlighted the importance of considering mixture interactions and subsequent bioavailability in assessing the joint toxicity of REEs.

Y2O3 Nanoparticles Caused Bone Tissue Damage by Breaking the Intracellular Phosphate Balance in Bone Marrow Stromal Cells.

Y2O3 nanoparticles (NPs) have become great promising products for numerous applications in nanoscience especially for biomedical application, therefore increasing the probability of human exposure and gaining wide attention in biosecurity. It is well known that rare earth (RE) materials are deposited in the bone and excreted very slowly. Nevertheless, the effect of Y2O3-based NPs on bone metabolism has not been exactly known yet. In the present study, the effects of Y2O3 NPs on bone marrow stromal cells (BMSCs) and bone metabolism in mice after intravenous injection were studied. The results demonstrated that Y2O3 NPs could be taken up into BMSCs and localized in acidifying intracellular lysosomes and underwent dissolution and transformation from Y2O3 to YPO4, which could lead to a break in the intracellular phosphate balance and induce lysosomal- and mitochondrial-dependent apoptosis pathways. Furthermore, after being administered to mice, a higher concentration of yttrium occurred in bone, which caused the apoptosis of bone cells and induced the destruction of bone structure. However, the formation of a YPO4 coating on the surface of Y2O3 NPs by pretreatment of Y2O3 NPs in lysosome-simulated body fluid could observably decrease the toxicity in vivo and in vitro. This study may be useful for practical application of Y2O3 NPs in the biomedical field.

Optical Control of Metal Ion Probes in Cells and Zebrafish Using Highly Selective DNAzymes Conjugated to Upconversion Nanoparticles.

Spatial and temporal distributions of metal ions in vitro and in vivo are crucial in our understanding of the roles of metal ions in biological systems, and yet there is a very limited number of methods to probe metal ions with high space and time resolution, especially in vivo. To overcome this limitation, we report a Zn2+-specific near-infrared (NIR) DNAzyme nanoprobe for real-time metal ion tracking with spatiotemporal control in early embryos and larvae of zebrafish. By conjugating photocaged DNAzymes onto lanthanide-doped upconversion nanoparticles (UCNPs), we have achieved upconversion of a deep tissue penetrating NIR 980 nm light into 365 nm emission. The UV photon then efficiently photodecages a substrate strand containing a nitrobenzyl group at the 2'-OH of adenosine ribonucleotide, allowing enzymatic cleavage by a complementary DNA strand containing a Zn2+-selective DNAzyme. The product containing a visible FAM fluorophore that is initially quenched by BHQ1 and Dabcyl quenchers is released after cleavage, resulting in higher fluorescent signals. The DNAzyme-UCNP probe enables Zn2+ sensing by exciting in the NIR biological imaging window in both living cells and zebrafish embryos and detecting in the visible region. In this study, we introduce a platform that can be used to understand the Zn2+ distribution with spatiotemporal control, thereby giving insights into the dynamical Zn2+ ion distribution in intracellular and in vivo models.

Facile surface functionalization of upconversion nanoparticles with phosphoryl pillar[5]arenes for controlled cargo release and cell imaging.

Upon surface functionalization and stabilization of ß-NaYF4:Yb/Er upconversion nanoparticles (UCNPs) with phosphoryl pillar[5]arenes (PP5) via a facile ligand exchange method, we constructed a new hybrid material (PP5-UCNPs) with good water dispersibility especially in a physiological environment and superior capability of controlled cargo release and cell imaging.

Response of the freshwater mussel, Dreissena polymorpha to sub-lethal concentrations of samarium and yttrium after chronic exposure.

Samarium (Sm) and yttrium (Y) are commonly used rare earth elements (REEs) but there is a scarcity of information concerning their biological effects in non-target aquatic organisms. The purpose of this study was to determine the bioavailability of those REEs and their toxicity on Dreissena polymorpha after exposure to increasing concentration of Sm and Y for 28 days at 15 °C. At the end of the exposure period, the gene expression of superoxide dismutase (SOD), catalase (CAT), metallothionein (MT), glutathione-S-transferase (GST), cytochrome c oxidase 1 (CO1) and cyclin D (Cyc D) were analysed. In addition, we examined lipid peroxidation (LPO), DNA strand breaks (DSB), GST and prostaglandin cyclooxygenase (COX) activities. Results showed a concentration dependent increase in the level of the REEs accumulated in the soft tissue of mussels. Both REEs decreased CAT but did not significantly modulated SOD and MT expressions. Furthermore, Sm3+ up-regulated GST, CO1 and Cyc D, while Y3+ increased and decreased GST and CO1 transcripts levels, respectively. Biomarker activities showed no oxidative damage as evidenced by LPO, while COX activity was decreased and DNA strand breaks levels were changed suggesting that Sm and Y exhibit anti-inflammatory and genotoxic effects. Factorial analysis revealed that the major impacted biomarkers by Sm were LPO, CAT, CO1 and COX, while GST gene expression, COX, Cyc D and CAT as the major biomarkers affected by Y. We conclude that these REEs display different mode of action but further investigations are required in order to define the exact mechanism involved in their toxicity.

Subchronic toxicity study of yttrium nitrate by 90-day repeated oral exposure in rats.

Concerns regarding the adverse effects of long-term exposure to low levels of rare earth elements (REEs) from foods on human health have arisen in recent years. Nevertheless, no official acceptable daily intake (ADI) has yet been proposed for either total REEs or individual REE. In accordance with the Organization for Economic Co-operation and Development (OECD) testing guideline, the present study was undertaken to evaluate the subchronic toxicity of yttrium, a representative heavy REE with higher contaminated level in foods in China, to achieve a no observed adverse effect level (NOAEL) which is a critical basis for the establishment of an ADI. Yttrium nitrate was orally administered to rats at doses of 0, 10, 30 and 90 mg/kg/day for 90 days followed by a recovery period of 4 weeks. The following toxicity indices were measured: mortality, clinical signs, daily food consumption and weekly body weight; urinalysis, hematology, blood coagulation, clinical biochemistry and histopathology at the end of administration and recovery periods. No toxicologically significant changes were found in any yttrium-treated group as compared to the concurrent control group. Under the present experimental condition, the NOAEL in rats was thus set at 90 mg/kg for yttrium nitrate, i.e. 29.1 mg/kg for yttrium.