Online monitoring of epithelial barrier kinetics and cell detachment during cisplatin-induced toxicity of renal proximal tubule cells.

Real-time and non-invasive assessment of tissue health is crucial for maximizing the potential of microphysiological systems (MPS) for drug-induced nephrotoxicity screening. Although impedance has been widely considered as a measure of the barrier function, it has not been incorporated to detect cell detachment in MPS with top and bottom microfluidic channels separated by a porous membrane. During cell delamination from the porous membrane, the resistance between both channels decreases, while capacitance increases, allowing the detection of such detachment. Previously reported concepts have solely attributed the decrease in the resistance to the distortion of the barrier function, ignoring the resistance and capacitance changes due to cell detachment. Here, we report a two-channel MPS with integrated indium tin oxide (ITO) electrodes capable of measuring impedance in real time. The trans-epithelial electrical resistance (TEER) and tissue reactance (capacitance) were extracted from the impedance profiles. We attributed the anomalous initial increase observed in TEER, upon cisplatin administration, to the distortion of tight junctions. Cell detachment was captured by sudden jumps in capacitance. TEER profiles illuminated the effects of cisplatin and cimetidine treatments in a dose-dependent and polarity-dependent manner. The correspondence between TEER and barrier function was validated for a continuous tissue using the capacitance profiles. These results demonstrate that capacitance can be used as a real-time and non-invasive indicator of confluence and will support the accuracy of the drug-induced cytotoxicity assessed by TEER profiles in the two-channel MPS for the barrier function of a cell monolayer.

Comparative Acute Toxicity and Oxidative Stress Responses in Three Aquatic Species Exposed to Stannic Oxide Nanoparticles and Stannic Chloride.

We experimentally investigated the toxicity of stannic oxide nanoparticles (SnO2 NPs) to three freshwater species including Scenedesmus obliquus, Daphnia magna, and Danio rerio. To evaluate effect, toxicological impacts were compared to that of stannic chloride (SnCl4). Based on the actual concentration of Sn, SnO2 NPs suspensions inhibited growth of S. obliquus in a dose-dependent manner, demonstrating a median effect concentration of 2.28 ± 0.53 mg/L. However, SnO2 NP suspensions were found to exhibit limited acute toxicity in D. magna and D. rerio. Moreover, the toxicity of the SnO2 NP suspension was lower than SnCl4 for all three trophic aquatic organisms. Comparison of component-specific contribution to overall toxicity indicated that, in SnO2 NP suspensions, particulate Sn more significantly contributed to toxicity than dissolved Sn-ions. Furthermore, we found that the toxic mechanism of the SnO2 NP suspension involved the induction of oxidative stress by increasing intracellular ROS accumulation.

The Pneumotoxic Effect and Indium Ion Release Induced by Indium Tin Oxide Nanoparticles.

With the increasing industrial production and the broaden applications of indium tin oxide (ITO) materials, frequent exposure has posed great concerns for people, especially the workers in the indium related manufacturing plants. The exposed-workers have been reported to adverse effect and even die from the ITO-induced pulmonary disorders called "indium lung." In addition to the epidemiologic studies, the increasing animal studies also demonstrated the lung injuries induced by the acute or chronic respiratory exposure of ITO nanoparticles (ITO NPs). They could enter into the cells owing to the small particle size and induce oxidative stress, inflammatory responses, cytotoxicity or even genotoxicity. The indium ions released from the ITO particles via lysosomal acidification considered as the actual entity responsible for the toxicity of ITO NPs. To date, no effective therapies are available against ITO-induced pulmonary diseases, which calls for the full explorations of the pathological factors. Our present mini-review summarizes the current reports on ITO nanoparticles-induced pneumotoxic effect with focus on the indium ion release, which could help warrant the health risks of ITO and other ITO-based materials.

New interplay between interstitial and alveolar macrophages explains pulmonary alveolar proteinosis (PAP) induced by indium tin oxide particles.

Occupational exposure to indium tin oxide (ITO) particles has been associated with the development of severe lung diseases, including pulmonary alveolar proteinosis (PAP). The mechanisms of this lung toxicity remain unknown. Here, we reveal the respective roles of resident alveolar (Siglec-Fhigh AM) and recruited interstitial (Siglec-Flow IM) macrophages contributing in concert to the development of PAP. In mice treated with ITO particles, PAP is specifically associated with IL-1α (not GM-CSF) deficiency and Siglec-Fhigh AM (not Siglec-Flow IM) depletion. Mechanistically, ITO particles are preferentially phagocytosed and dissolved to soluble In3+ by Siglec-Flow IM. In contrast, Siglec-Fhigh AM weakly phagocytose or dissolve ITO particles, but are sensitive to released In3+ through the expression of the transferrin receptor-1 (TfR1). Blocking pulmonary Siglec-Flow IM recruitment in CCR2-deficient mice reduces ITO particle dissolution, In3+ release, Siglec-Fhigh AM depletion, and PAP formation. Restoration of IL-1-related Siglec-Fhigh AM also prevented ITO-induced PAP. We identified a new mechanism of secondary PAP development according to which metal ions released from inhaled particles by phagocytic IM disturb IL-1α-dependent AM self-maintenance and, in turn, alveolar clearance.

Evaluating the cytotoxicity of tin dioxide nanofibers.

Tin dioxide nanofibers (SnDNFs) are small fibers that have many applications. Tin dioxide nanofibers can be used in cosmetics, solar cells, toxic gas release sensors, and air pollution control. To date there have been few studies on the cytotoxicity of SnDNFs. The goal of this research is to determine if electrospun SnDNFs are toxic in a lung cancer cell line (A549). Considering the nano-scale size of the fibers, they can easily be inhaled and enter the pulmonary system and cause toxic effects in the lung. Occupational exposure to SnDNFs has been linked to pulmonary disease, making the A549 cell line important in this study. Nanofiber toxicity can vary based upon the characteristics of the fibers. Smaller nanofibers have been shown to have more toxic effects than their larger counterparts. The synthesized SnDNFs were characterized using SEM, Raman spectroscopy, and powder X-ray diffractometer (PXRD). SEM images showed the fibers to be 200-300 nm in diameter. Raman spectroscopy and PXRD indicated that the fibers were in the rutile phase. After quantifying the SnDNFs, the fibers were introduced to A549 cells at concentrations ranging from 0.02-500 µg mL-1 and incubated at 37°C. These cells were quantified with the MTT assay to measure cell proliferation (IC50 = 0.02 mg mL-1), while lactate dehydrogenase (LDH) leakage was used to determine cytotoxicity, and apoptosis assays to assess the mechanism of cell death. Increasing concentration of SnDNF generated a consequential decrease in cell proliferation and viability. The percent cytotoxicity of SnDNF was not significantly changed at the various concentrations and time frames. In order to gain additional insight about the mechanism of cytotoxicity of SnDNFs, genes with links to inflammation and apoptosis were evaluated and found to be over-expressed in treated cells. At the concentrations of SnDNF examined, SnDNF was mildly toxic to the A549 cells.

Comparison of the toxicity of sintered and unsintered indium-tin oxide particles in murine macrophage and epidermal cells.

Indium-tin oxide (ITO) is used to produce flat panel displays and several other technology products. Composed of 90% indium oxide (In2O3) and 10% tin oxide (SnO2) by weight, ITO is synthesized under conditions of high heat via a process known as sintering. Indium lung disease, a recently recognized occupational illness, is characterized by pulmonary alveolar proteinosis, fibrosis, and emphysema. Murine macrophage (RAW 264.7) and epidermal (JB6) cells stably transfected with AP-1 to study tumor promoting potential, were used to differentiate between the toxicological profiles of sintered ITO (SITO) and unsintered mixture (UITO). We hypothesized that sintering would play a key role in free radical generation and cytotoxicity. Exposure of cells to both UITO and SITO caused a time and dose dependent decrease of the viability of cells. Intracellular ROS generation was inversely related to the dose of both UITO and SITO, a direct reflection of the decreased number of viable RAW 264.7 and JB6/AP-1 cells observed at higher concentrations. Electron spin resonance showed significantly increased hydroxyl radical (OH) generation in cells exposed to UITO compared to SITO. This is different from LDH release, which showed that SITO caused significantly increased damage to the cell membrane compared to UITO. Lastly, the JB6/AP-1 cell line did not show activation of the AP-1 pathway. Our results highlight both the differences in the mechanisms of cytotoxicity and the consistent adverse effects associated with UITO and SITO exposure.

Pulmonary toxicity of indium-tin oxide production facility particles in rats.

Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. Occupational exposures to potentially toxic particles generated during ITO production have increased in recent years as the demand for consumer electronics continues to rise. Previous studies have demonstrated cytotoxicity in vitro and animal models have shown pulmonary inflammation and injury in response to various indium-containing particles. In humans, pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which indium materials or specific processes in the workplace may be the most toxic to workers is unknown. Here we examined the pulmonary toxicity of three different particle samples that represent real-life worker exposures, as they were collected at various production stages throughout an ITO facility. Indium oxide (In2O3), sintered ITO (SITO) and ventilation dust (VD) particles each caused pulmonary inflammation and damage in rats over a time course (1, 7 and 90 days post-intratracheal instillation), but SITO and VD appeared to induce greater toxicity in rat lungs than In2O3 at a dose of 1 mg per rat. Downstream pathological changes such as PAP and fibrosis were observed in response to all three particles 90 days after treatment, with a trend towards greatest severity in animals exposed to VD when comparing animals that received the same dose. These findings may inform workplace exposure reduction efforts and provide a better understanding of the pathogenesis of an emerging occupational health issue.

Determination of mutagenicity and genotoxicity of indium tin oxide nanoparticles using the Ames test and micronucleus assay.

In this study, the mutagenicity and genotoxicity of indium tin oxide (ITO) nanomaterial were assessed using two standard genotoxicity assays, the Salmonella reverse mutation assay (Ames test) and the in vitro micronucleus (MN) assay. Seven different concentrations (12.5, 25, 50, 75, 100, 125, and 150 µg/plate) of this nanomaterial were tested using the Ames test on the TA98 and TA100 strains in the presence and absence of the S9 mixture. At all the concentrations tested, this substance did not significantly increase the number of revertant colonies compared with the control with or without S9 mixture. The genotoxic effects of ITO were investigated in human peripheral lymphocytes treated with 125, 250, 500, and 750 µg/ml concentrations of this substance for 24- and 48-h treatment periods using an MN test. Nuclear division index (NDI) was also calculated in order to determine the cytotoxicity of ITO. It was determined that ITO increased MN frequency in the 750 µg/ml concentration in 24- and 48-h treatments. In addition, ITO dose dependently decreased the NDI significantly for two treatment periods.

Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice.

Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.

Cytotoxicity and characterization of particles collected from an indium-tin oxide production facility.

Occupational exposure to indium compound particles has recently been associated with lung disease among workers in the indium-tin oxide (ITO) industry. Previous studies suggested that excessive alveolar surfactant and reactive oxygen species (ROS) may play a role in the development of pulmonary lesions following exposure to indium compounds. However, toxicity at the cellular level has not been comprehensively evaluated. Thus, the aim of this study was to assess which, if any, compounds encountered during ITO production are toxic to cultured cells and ultimately contribute to the pathogenesis of indium lung disease. The compounds used in this study were collected from eight different processing stages at an ITO production facility. Enhanced dark field imaging showed 5 of the compounds significantly associated with cells within 1 h, suggesting that cellular reactions to the compound particles may be occurring rapidly. To examine the potential cytotoxic effects of these associations, ROS generation, cell viability, and apoptosis were evaluated following exposures in RAW 264.7 mouse monocyte macrophage and BEAS-2B human bronchial epithelial cell lines. Both exhibited reduced viability with exposures, while apoptosis only occurred in RAW 264.7 cells. Our results suggested that excessive ROS production is likely not the predominant mechanism underlying indium-induced lung disease. However, the effects on cell viability reveal that several of the compounds are cytotoxic, and therefore, exposures need to be carefully monitored in the industrial setting.

Inorganic tin compounds do not induce micronuclei in human lymphocytes in the absence of metabolic activation.

The genotoxic evaluation (in vitro analysis) of a series of eight inorganic tin(II) and tin(IV) compounds [tin(II) acetate, tin(II) chloride, tin(II) ethylhexanoate, tin(II) oxalate, tin(II) oxide, tin(IV) acetate, tin(IV) chloride and tin(IV) oxide], for the detection of micronuclei in human blood lymphocytes, was performed in the absence of metabolic activation by the cytokinesis-block micronucleus assay. Human lymphocytes were treated for over one cell cycle (31 hours), with concentrations ranging from 1 to 75 µM (1, 5, 10, 20, 50 and 75 µM), of tin(II) and tin(IV) salts dissolved in dimethyl sulfoxide. The above-listed concentrations cover the values that have been detected in humans with no occupational exposure to tin compounds. The experimental results show the absence of genotoxicity for all inorganic compounds tested in the specific concentrations and experimental conditions. Cytotoxic effects of tin(II) and tin(IV) compounds were evaluated by the determination of cytokinesis block proliferation index and cytotoxicity percentage. Our observations on the cytotoxicity pattern of the tested tin(II) and tin(IV) compounds indicate that they are cytotoxic in several tested concentrations to human lymphocytes treated in vitro. The observed differences in cytotoxicity of each tested compound might reflect differences in their chemical structure.

Safety assessment of Tin(IV) oxide as used in cosmetics.

Tin(IV) oxide functions as an abrasive, bulking, and opacifying agent in cosmetic products and is used at concentrations up to 0.4% in rinse-off products and up to 1.3% in leave-on products. The Cosmetic Ingredient Review Expert Panel (Panel) noted that tin(IV) oxide is a water-insoluble inorganic metal compound and should not be percutaneously absorbed; therefore, systemic exposure is not likely. Studies of dermal application of tin(IV) oxide were considered to determine toxicity at the site of application. The Panel concluded that tin(IV) oxide is safe in the present practices of use and concentration.

Influence of pH and temperature on the activity of SnO2-bound α-amylase: a genotoxicity assessment of SnO2 nanoparticles.

Immobilization of biologically important molecules on a myriad of nanosized materials has attracted great attention due to their small size, biocompatibility, higher surface-to-volume ratio, and lower toxicity. These properties make nanoparticles (NPs) a superior matrix over bulk material for the immobilization of enzymes and proteins. In the present study, Bacillus amyloliquefaciens α-amylase was immobilized on SnO2 nanoparticles by a simple adsorption mechanism. Nanoparticle-adsorbed enzyme retained 90% of the original enzyme activity. Thermal stability of nanosupport was investigated by thermogravimetric and differential thermal analysis. Scanning electron microscopic studies showed that NPs have porous structure for the high-yield immobilization of α-amylase. The genotoxicity of SnO2-NPs was analyzed by pUC(19) plasmid nicking and comet assay and revealed that no remarkable DNA damage occurred in lymphocytes. The pH-optima was found to be the same for both free and SnO2-NPs bound enzyme, while the temperature-optimum for NPs-adsorbed α-amylase was 5°C higher than its free counterpart. Immobilized enzyme retained more than 70% enzyme activity even after its eight repeated uses.

Subchronic toxicity study of indium-tin oxide nanoparticles following intratracheal administration into the lungs of rats.

OBJECTIVES: We aimed to analyze the subchronic toxicity and tissue distribution of indium after the intratracheal administration of indium-tin oxide nanoparticles (ITO NPs) to the lungs of rats. METHODS: Male Wistar rats were administered a single intratracheal dose of 10 or 20 mg In/kg body weight (BW) of ITO NPs. The control rats received only an intratracheal dose of distilled water. A subset of rats was periodically euthanized throughout the study from 1 to 20 weeks after administration. Indium concentrations in the serum, lungs, mediastinal lymph nodes, kidneys, liver, and spleen as well as pathological changes in the lungs and kidneys were determined. Additionally, the distribution of ionic indium and indium NPs in the kidneys was analyzed using laser ablation-inductively coupled plasma mass spectrometry. RESULTS: Indium concentrations in the lungs of the 2 ITO NP groups gradually decreased over the 20-week observation period. Conversely, the indium concentrations in the mediastinal lymph nodes of the 2 ITO groups increased and were several hundred times higher than those in the kidneys, spleen, and liver. Pulmonary and renal toxicities were observed histopathologically in both the ITO groups. Both indium NPs and ionic indium were detected in the kidneys, and their distributions were similar to the strong indium signals detected at the sites of inflammatory cell infiltration and tubular epithelial cells. CONCLUSIONS: Our results demonstrate that intratracheal administration of 10 or 20 mg In/kg BW of ITO NPs in male rats produces pulmonary and renal toxicities.

Use of and occupational exposure to indium in the United States.

Indium use has increased greatly in the past decade in parallel with the growth of flat-panel displays, touchscreens, optoelectronic devices, and photovoltaic cells. Much of this growth has been in the use of indium tin oxide (ITO). This increased use has resulted in more frequent and intense exposure of workers to indium. Starting with case reports and followed by epidemiological studies, exposure to ITO has been linked to serious and sometimes fatal lung disease in workers. Much of this research was conducted in facilities that process sintered ITO, including manufacture, grinding, and indium reclamation from waste material. Little has been known about indium exposure to workers in downstream applications. In 2009-2011, the National Institute for Occupational Safety and Health (NIOSH) contacted 89 potential indium-using companies; 65 (73%) responded, and 43 of the 65 responders used an indium material. Our objective was to identify current workplace applications of indium materials, tasks with potential indium exposure, and exposure controls being used. Air sampling for indium was either conducted by NIOSH or companies provided their data for a total of 63 air samples (41 personal, 22 area) across 10 companies. Indium exposure exceeded the NIOSH recommended exposure limit (REL) of 0.1 mg/m(3) for certain methods of resurfacing ITO sputter targets, cleaning sputter chamber interiors, and in manufacturing some inorganic indium compounds. Indium air concentrations were low in sputter target bonding with indium solder, backside thinning and polishing of fabricated indium phosphide-based semiconductor devices, metal alloy production, and in making indium-based solder pastes. Exposure controls such as containment, local exhaust ventilation (LEV), and tool-mounted LEV can be effective at reducing exposure. In conclusion, occupational hygienists should be aware that the manufacture and use of indium materials can result in indium air concentrations that exceed the NIOSH REL. Given recent findings of adverse health effects in workers, research is needed to determine if the current REL sufficiently protects workers against indium-related diseases.

Corneal manifestations in chemical injury with stannous chloride.

Chemical injuries are potentially devastating ocular accidents that can lead to permanent damage to the ocular surface and visual loss. The majority of serious chemical injuries occur in factory workers who are exposed to hazardous chemicals in their day-to-day life. The ocular effects of commonly encountered acids and alkalis are well documented in the literature. Here we report briefly on the corneal and other ocular effects of stannous chloride, which is sparsely reported in the currently available literature.

Nose-to-brain translocation and nervous system injury in response to indium tin oxide nanoparticles of long-term low-dose exposures.

Indium tin oxide (ITO) is a semiconductor nanomaterial with broad application in liquid crystal displays, solar cells, and electrochemical immune sensors. It is worth noting that, with the gradual increase in worker exposure opportunities, the exposure risk in occupational production cannot be ignored. At present, the toxicity of ITO mainly focuses on respiratory toxicity. ITO inhaled through the upper respiratory tract can cause pathological changes such as interstitial pneumonia and pulmonary fibrosis. Still, extrapulmonary toxicity after nanoscale ITO nanoparticle (ITO NPs) exposure, such as long-term effects on the central nervous system, should also be of concern. Therefore, we set up exposure dose experiments (0 mg·kg-1, 3.6 mg·kg-1, and 36 mg·kg-1) based on occupational exposure limits to treat C57BL/6 mice via nasal drops for 15 weeks. Moreover, we conducted a preliminary assessment of the neurotoxicity of ITO NPs (20-30 nm) in vivo. The results indicated that ITO NPs can cause diffuse inflammatory infiltrates in brain tissue, increased glial cell responsiveness, abnormal neuronal cell lineage transition, neuronal migration disorders, and neuronal apoptosis related to the oxidative stress induced by ITO NPs exposure. Hence, our findings provide useful information for the fuller risk assessment of ITO NPs after occupational exposure.

Evaluation of deoxyribonucleic acid toxicity induced by the radiopharmaceutical 99mTechnetium-Methylenediphosphonic acid and by stannous chloride in Wistar rats.

Radiopharmaceuticals are employed in patient diagnostics and disease treatments. Concerning the diagnosis aspect, technetium-99m (99mTc) is utilized to label radiopharmaceuticals for single photon computed emission tomography (SPECT) due to its physical and chemical characteristics. 99mTc fixation on pharmaceuticals depends on a reducing agent, stannous chloride (SnCl(2)) being the most widely-utilized. The genotoxic, clastogenic and anegenic properties of the 99mTc-MDP(methylene diphosphonate used for bone SPECT) and SnCl(2) were evaluated in Wistar rat blood cells using the Comet assay and micronucleus test. The experimental approach was to endovenously administer NaCl 0.9% (negative control), cyclophosphamide 50 mg/kg b.w. (positive control), SnCl(2) 500 μg/mL or 99mTc-MDP to animals and blood samples taken immediately before the injection, 3, and 24 h after (in the Comet assay) and 36 h after, for micronucleus test. The data showed that both SnCl(2) and 99mTc-MDP-induced deoxyribonucleic acid (DNA) strand breaks in rat total blood cells, suggesting genotoxic potential. The 99mTc-MDP was not able to induce a significant DNA strand breaks increase in in vivo assays. Taken together, the data presented here points to the formation of a complex between SnCl(2) in the radiopharmaceutical 99mTc-MDP, responsible for the decrease in cell damage, compared to both isolated chemical agents. These findings are important for the practice of nuclear medicine.

Early life stage and genetic toxicity of stannous chloride on zebrafish embryos and adults: toxic effects of tin on zebrafish.

Humans are exposed to stannous chloride (SnCl(2)), known as tin chloride, present in packaged food, soft drinks, biocides, dentifrices, etc. Health effects in children exposed to tin and tin compounds have not been investigated yet. Therefore, we evaluated the possible teratogenic effects and genotoxic of SnCl(2) in zebrafish (Danio rerio) adults and their embryos. In the embryo-larval study, SnCl(2) showed embryo toxicity and developmental delay after exposure to the various concentrations of 10-250 µM for 120 h. Teratogenic effects including morphological malformations of the embryos and larvae were observed. The embryos exposed to 100 µM displayed tail deformation at 28 hpf and the larvae exposed to 50 µM showed reduced body growth, smaller head and eyes, bent trunk, mild pericardial edema, and smaller caudal fin at 96 hpf. The results of the teratological study show that SnCl(2) induced a significant decrease in the number of living embryos and larvae. Regarding the chromosome analysis, SnCl(2) induced a dose-dependent increase in the micronucleus (MN) frequency in peripheral erythrocytes of adult zebrafish. In blood cells, the 25 µM dose of SnCl(2) caused a nonsignificant increase in the total chromosomal aberrations, but the high doses significantly increased the total number of chromosomal aberrations compared with the control groups. Overall, the results clearly indicate that SnCl(2) is teratogenic and genotoxic to zebrafish.

Cytotoxicity and solubility evaluation of two types of whiskers by cell magnetometry.

OBJECTIVES: We investigated two types of whiskers, an antimony-containing tin-oxide-coated aluminum borate whisker (CABW) and an aluminum borate whisker (ABW), which are asbestos substitutes, in order to evaluate the safety of these fibers. METHODS: The cytotoxicity and solubility of CABW and ABW were evaluated by cell magnetometry, LDH assay and solubility test. RESULTS: ABW was found to be cytotoxic by cell magnetometry and slightly less soluble than CABW. In addition, it was found that the solubility of both fibers was intermediate between that of chrysotile and rock wool, as compared to our previous test results. Regarding the LDH assay, no significant difference was found among the fibers tested. These findings suggested that CABW, the surface of which is coated with antimony-containing tin oxide, had lower cytotoxicity and slightly higher solubility than ABW. CONCLUSIONS: This study was only a short-term cytotoxicity and solubility study. Therefore, further safety assessment should be carried out in long-term experiments to examine the half-life of these fibers and monitor the potential development of lung carcinoma or mesothelioma after intratracheal instillation of these fibers in rats.