In vivo risk evaluation of carbon-coated iron carbide nanoparticles based on short- and long-term exposure scenarios.

BACKGROUND: While carbon-encapsulated iron carbide nanoparticles exhibit strong magnetic properties appealing for biomedical applications, potential side effects of such materials remain comparatively poorly understood. Here, we assess the effects of iron-based nanoparticles in an in vivo long-term study in mice with observation windows between 1 week and 1 year. MATERIALS & METHODS: Functionalized (PEG or IgG) carbon-encapsulated platinum-spiked iron carbide nanoparticles were injected intravenously in mice (single or repeated dose administration). RESULTS: One week after administration, magnetic nanoparticles were predominantly localized in organs of the reticuloendothelial system, particularly the lung and liver. After 1 year, particles were still present in these organs, however, without any evident tissue alterations, such as inflammation, fibrosis, necrosis or carcinogenesis. Importantly, reticuloendothelial system organs presented with normal function. CONCLUSION: This long-term exposure study shows high in vivo compatibility of intravenously applied carbon-encapsulated iron nanoparticles suggesting continuing investigations on such materials for biomedical applications.

Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.

Iron oxide nanoparticles have been extensively used as T2 contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r2 relaxivity. Recent studies show that Fe5C2 nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T2 contrast agent. To this end, we improve the synthetic and surface modification methods of Fe5C2 nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe5C2 nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r2 relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe5C2 nanoparticles showed comparable r2, the casein coating led to an r2 enhancement by more than 2 fold. In particular, casein coated 22 nm Fe5C2 nanoparticle show a striking r2 of 973 mM(-1)s(-1), which is one of the highest among all of the T2 contrast agents reported to date. Small animal studies confirmed the advantage of Fe5C2 nanoparticles over iron oxide nanoparticles in inducing hypointensities on T2-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe5C2 nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles.

Effects of SiC nanoparticles orally administered in a rat model: biodistribution, toxicity and elemental composition changes in feces and organs.

BACKGROUND: Silicon carbide (SiC) presents noteworthy properties as a material such as high hardness, thermal stability, and photoluminescent properties as a nanocrystal. However, there are very few studies in regard to the toxicological potential of SiC NPs. OBJECTIVES: To study the toxicity and biodistribution of silicon carbide (SiC) nanoparticles in an in vivo rat model after acute (24h) and subacute (28days) oral administrations. The acute doses were 0.5, 5, 50, 300 and 600mg·kg(-1), while the subacute doses were 0.5 and 50mg·kg(-1). RESULTS: SiC biodistribution and elemental composition of feces and organs (liver, kidneys, and spleen) have been studied by Particle-Induced X-ray Emission (PIXE). SiC and other elements in feces excretion increased by the end of the subacute assessment. SiC did not accumulate in organs but some elemental composition modifications were observed after the acute assessment. Histopathological sections from organs (stomach, intestines, liver, and kidneys) indicate the absence of damage at all applied doses, in both assessments. A decrease in the concentration of urea in blood was found in the 50mg·kg(-1) group from the subacute assessment. No alterations in the urine parameters (sodium, potassium, osmolarity) were found. CONCLUSION: This is the first study that assesses the toxicity, biodistribution, and composition changes in feces and organs of SiC nanoparticles in an in vivo rat model. SiC was excreted mostly in feces and low traces were retrieved in urine, indicating that SiC can cross the intestinal barrier. No sign of toxicity was however found after oral administration.

Development of a PIXE analysis method for the determination of the biopersistence of SiC and TiC nanoparticles in rat lungs.

With the advent of nanoparticles produced in high quantities and employed in products or processes, the need to evaluate their potential toxicological effects is necessary. For this purpose, biopersistence studies are needed to assess the possible effects of nanoparticles in parallel with a proper characterization. The insoluble character of many nanomaterials makes traditional chemical analytical methods unapplicable for the ex-vivo measurements of their concentration in organs. Ion beam-based techniques such as Particle-Induced X-ray Emission (PIXE) can solve this difficulty. We illustrate that by the measurement of biopersistence of SiC and TiC nanoparticles instilled in rats lungs and investigated over a 60-day time span. The results can be obtained within minutes and the limits of detection are within ppm levels.

Pulmonary effects and biopersistence of deposited silicon carbide whisker after 1-year inhalation in rats.

Silicon carbide whisker (SiCW) is a durable asbestos substitute. To clarify the biopersistence, the changes of geometrical configurations of deposited whiskers, and potential carcinogenicity and fibrogenicity, 42 Wistar male rats were exposed to SiCW for 6 h/day, 5 days/wk for 1 yr by inhalation. The mass median aerodynamic diameter (geometric standard deviation, GSD), the geometric mean fiber diameter (GSD), and the geometric mean fiber length (GSD) were 2.4 microm (2.4), 0.5 microm (1.5) and 2.8 microm (2.3), respectively. The daily average exposure concentrations were 2.6 +/- 0.4 mg/m3 (98 +/- 19 fibers/ml) and the rats were sacrificed at 6 days and 3, 6, and 12 mo after the exposure. The SiCW amount deposited in each rat lung at 6 days after the exposure, determined by an x-ray diffraction method, was 5.3 +/- 1.4 mg. The biological half-time (BHT) was 16 mo calculated from the deposited SiCW at 6 days and 3, 6, and 12 mo. The BHT was more prolonged than normal physiological clearance. The diameter of SiCW in the lung at each sacrificed time during 12 mo of clearance after the inhalation did not change. However, as for the length of SiCW in the lung, longer SiCW tended to be retained in the lung as the clearance time increased, especially after 6 mo. The histopathological examination revealed bronchoalveolar hyperplasia (BAH) in 2 rats at 1 yr after the exposure and severe fibrotic changes around aggregated SiCW.

Bioconcentration of persistent organic pollutants in four species of marine phytoplankton.

The uptake of polychlorinated biphenyls (PCBs) was studied in four species of marine algae. A novel experimental system to establish and maintain constant dissolved concentrations of PCBs was employed. Headspace sampling was used to verify that the freely dissolved concentrations remained constant with time. The headspace analysis also allowed sorption to dissolved organic carbon (DOC) to be quantified for all but the most lipophilic PCB congeners. Equilibration with the dissolved phase was rapid for three of the four algae species (<1 d for the majority of congeners). Organic carbon-normalized algae/water partition coefficients (KAlgW) were similar for three of the four species, but were lower by a factor of 10 to 20 for Phaeodactylum tricornutum. The KAlgW values of the first three species were similar to the octanol/water partition coefficient (Kow) for those PCB congeners for which DOC sorption could be quantified. These KAlgW values also agreed well with organic carbon-normalized bioconcentration factors for PCBs in suspended particulate matter (BCF(SPM)) sampled in Baltic Sea surface water during the summer.

Chemical and biological evaluation of technetium (I) tricarbonyl complexes with EHIDA and DPD. 99m (I) complexes of EHIDA and DPD.

BACKGROUND: 99mTc-phosphate and 99mTc-IDA complexes, made by the addition of 99mTcO4- to the kits, have been applied to bone and gallbladder imaging respectively, for many years. In this paper, an effort to label DPD and EHIDA with [99mTc(CO)3(H2O)3]+ was carried out. MATERIAL AND METHODS: DPD and EHIDA were synthesised and prepared in kit form in INS "Vinca". A carbonyl labelling agent Isolink (Mallinckrodt Medical B.V.) and a carbonyl precursor (NCRS Demokritos) were applied. The samples of each compound were added to a vial containing 99mTc-carbonyl precursor, in which original pH (10/11) was neutralised to a pH of around 5.5 or 7.5, the same one as the pH of the investigated compounds. After heating, the reaction products were analysed by HPLC equipped with UV and g-detector, with TEAP 0.05 M, methanol and water as solvent. The biological evaluation of 99m99mTc(I)-coordinated compounds, as well as 99mTc-DPD and 99mTc-EHIDA complexes, involved a bio distribution examination on Wistar rats. RESULTS: The results have shown that hydrophilic organometallic [99mTc(CO)3(H2O)3]+ precursor facilitates the formation of Tc (I) complexes with these ligands, based on the tricarbonyltechnetium (I) core. The changes in structure of DPD and EHIDA labelled molecules influenced biological behaviour: 99Tc(CO)3 -DPD did not accumulate in bone (< 1% of the complex was found in the femur), while 99Tc(CO)3-EHIDA has shown slower billiary excretion and faster filtration through the kidneys. DISCUSSION: The results of the labelling of DPD and EHIDA with [99mTc(CO)3(H2O)3]+ and their chemical and biological behaviour, in comparison with the same one for 99mTc-DPD and 99mTc-EHIDA, confirmed that different oxidation states of technetium make the formation of a variety of complexes with quite different behaviour possible.

Synthesis, radioiodination, and biodistribution of some nido- and closo-monocarbon carborane derivatives.

Iodination and radioiodination reactions of several anionic nido- and closo-monocarbon carboranes were conducted. Iodinations occurred more rapidly with nido-carboranes than with closo-carboranes. The most rapid iodination and radioiodination reactions occurred with unsubstituted carboranes. C-amino and C-ammonium derivatives did not iodinate under the conditions studied. Both nido- and closo-carboranes with C-NH-acetyl and C-NH-succinyl substituents iodinated, but the nido-carboranes iodinated under milder reaction conditions. Biodistributions of nido-1-succinylamido-[(131)I]carborane and closo-1-succinylamido-[(125)I]carborane were similar in mice, but blood clearance of the nido- compound was slower.

Carbon disulfide at a Chinese viscose factory external and internal exposure assessment.

This article presents the results of carbon disulfide exposure measurements in a Chinese viscose rayon factory. The objectives of the study were to identify the external exposure levels at a large factory and to investigate the 2-thiothiazolidine-4-carboxylic acid (TTCA) concentrations in the urine of the subjects who were exposed to carbon disulfide in the working place atmosphere. The metabolism of carbon disulfide in the exposed subjects was also studied in order to demonstrate the best points in time for the internal exposure sampling. The measurement of the amount of personal exposure to carbon disulfide in the air of the workplace was performed by GC-FPD; the presence of TTCA in the workers urine was analyzed by use of a modified HPLC method. The kinetics of TTCA excretion was studied by analyses at different time-points both during and after exposure to carbon disulfide in the subjects. A total of 155 personal samples were obtained. The carbon disulfide concentration in the staple viscose hall was 13.72 +/- 1.12 mg m-3 in terms of the geometric mean +/- geometric standard deviation, and was 20.05 +/- 1.33 mg m-3 in the filament spinning hall. The TTCA values in the subjects who worked in the staple spinning hall were 1.18 +/- 0.43 mg g-1 creatinine and 1.07 +/- 0.38 mg g-1 creatinine for subjects working in the filament spinning hall. The best time for TTCA sampling is at the end of the working shift, the TTCA excretion was stable for a period of 4-12 h after exposure of the subjects to the carbon disulfide. It might be that the Chinese have different anthropometric characteristics; a sampling bias may therefore appear among different races.