RESUMEN
BACKGROUND: We analyzed what kind of lifestyle modification first-year university students need based on the results of a health-consciousness survey conducted in first-year students immediately after they entered a university. METHODS: This population-based cross-sectional study used a "questionnaire survey on lifestyle and health for promoting health" conducted in Japan in 2015. From among an initial pool of 3,912 students, we excluded 314 due to insufficient data. The remaining 3,598 students (2,206 males and 1,392 females) were divided into four groups according to body mass index (BMI) based on Japan Society for the Study of Obesity "Guidelines for the management of obesity disease 2016": low (18.5 > BMI), less than standard (22.0 > BMI ≥ 18.5), standard or higher (25.0 > BMI ≥ 22.0) and obesity (BMI ≥ 25.0). RESULTS: Females had an ideal body image that was at a lower body weight regardless of their BMI. Males in the low BMI and obesity groups tended to be less aware of health issues. For each level of BMI, and in both males and females, the most frequent report of stress was "sometimes feel". The most frequent method for relieving stress was spending time with friends. Among males, those in the obesity group spent more time with "personal computers, televisions and games, etc." in a sitting position. When students were asked to rank which of their lifestyle habits needed the most improvement, "lack of exercise" was the highest, followed by "irregular schedule" and "dietary habits". In daily living behavior, a significant difference was observed for "exercise" among males, but not females. CONCLUSION: The attitudes of both males and females regarding the importance of physical activity and the necessity of efforts to improve health are presented. Health education for university students based on the attitudes may be useful for the prevention of lifestyle-related diseases for themselves in the future and before they become parents.
RESUMEN
As a result of the growing potential industrial and medical applications of multi-walled carbon nanotubes (MWCNTs), people working in or residing near facilities that manufacture them may be exposed to airborne MWCNTs in the future. Because of concerns regarding their toxicity, quantitative data on the long-term clearance of pristine MWCNTs from the lungs are required. We administered pristine MWCNTs well dispersed in 0.5 mg ml(-1) Triton-X solution to rats at doses of 0.20 or 0.55 mg via intratracheal instillation and investigated clearance over a 12-month observation period. The pristine MWCNTs pulmonary burden was determined 1, 3, 7, 28, 91, 175 and 364 days after instillation using a method involving combustive oxidation and infrared analysis, combined with acid digestion and heat pretreatment. As 0.15- and 0.38-mg MWCNTs were detected 1 day after administration of 0.20 and 0.55 mg MWCNTs, respectively, approximately 30% of administrated MWCNTs may have been cleared by bronchial ciliary motion within 24 h of administration. After that, the pulmonary MWCNT burden did not decrease significantly over time for up to 364 days after instillation, suggesting that MWCNTs were not readily cleared from the lung. Transmission electron microscopy (TEM) showed that alveolar macrophages internalized the MWCNTs and retained in the lung for at least 364 days after instillation. MWCNTs were not detected in the liver or brain within the 364-day study period (<0.04 mg per liver, < 0.006 mg per brain).
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Pulmón/metabolismo , Nanotubos de Carbono/química , Administración por Inhalación , Animales , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Límite de Detección , Hígado/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , Microscopía Electrónica de Transmisión , Ratas , Ratas WistarRESUMEN
This study assessed the health risks via inhalation and derived the occupational exposure limit (OEL) for the carbon nanotube (CNT) group rather than individual CNT material. We devised two methods: the integration of the intratracheal instillation (IT) data with the inhalation (IH) data, and the "biaxial approach." A four-week IH test and IT test were performed in rats exposed to representative materials to obtain the no observed adverse effect level, based on which the OEL was derived. We used the biaxial approach to conduct a relative toxicity assessment of six types of CNTs. An OEL of 0.03 mg/m(3) was selected as the criterion for the CNT group. We proposed that the OEL be limited to 15 years. We adopted adaptive management, in which the values are reviewed whenever new data are obtained. The toxicity level was found to be correlated with the Brunauer-Emmett-Teller (BET)-specific surface area (BET-SSA) of CNT, suggesting the BET-SSA to have potential for use in toxicity estimation. We used the published exposure data and measurement results of dustiness tests to compute the risk in relation to particle size at the workplace and showed that controlling micron-sized respirable particles was of utmost importance. Our genotoxicity studies indicated that CNT did not directly interact with genetic materials. They supported the concept that, even if CNT is genotoxic, it is secondary genotoxicity mediated via a pathway of genotoxic damage resulting from oxidative DNA attack by free radicals generated during CNT-elicited inflammation. Secondary genotoxicity appears to involve a threshold.
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Nanotubos de Carbono/efectos adversos , Medición de Riesgo , Animales , Humanos , Exposición por Inhalación , Nivel sin Efectos Adversos Observados , Exposición Profesional , Ratas , Ratas WistarRESUMEN
The objective of the present study is to evaluate the cost and effectiveness of decontamination strategies in the special decontamination areas in Fukushima in regard to external radiation dose. A geographical information system (GIS) was used to relate the predicted external dose in the affected areas to the number of potential inhabitants and the land use in the areas. A comprehensive review of the costs of various decontamination methods was conducted as part of the analysis. The results indicate that aerial decontamination in the special decontamination areas in Fukushima would be effective for reducing the air dose rate to the target level in a short period of time in some but not all of the areas. In a standard scenario, analysis of cost and effectiveness suggests that decontamination costs for agricultural areas account for approximately 80% of the total decontamination cost, of which approximately 60% is associated with storage. In addition, the costs of decontamination per person per unit area are estimated to vary greatly. Appropriate selection of decontamination methods may significantly decrease decontamination costs, allowing more meaningful decontamination in terms of the limited budget. Our analysis can help in examining the prioritization of decontamination areas from the viewpoints of cost and effectiveness in reducing the external dose. Decontamination strategies should be determined according to air dose rates and future land-use plans.
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Descontaminación/economía , Descontaminación/métodos , Contaminación Ambiental , Accidente Nuclear de Fukushima , Dosis de Radiación , Agricultura , Contaminación Radiactiva del Aire , Análisis Costo-Beneficio , Ecosistema , Geografía Médica , Humanos , Densidad de Población , Factores de TiempoRESUMEN
Multi-walled carbon nanotubes (MWCNTs) are interesting new materials, but there is some concern about their harmfulness due to their fibrous nature. To determine the difference in the biological effects of MWCMTs by fiber length, we prepared two MWCNT samples from one bulk sample. One consisted of cut up short fibers (Short; average length=0.94 µm) and the other was just dispersed (Long; average length=3.4 µm). The samples were administered to male Wistar rats by intratracheal instillation at doses of 0.2 mg and 1 mg/animal (Short) and 0.2 mg and 0.6 mg/animal (Long). The animals were sacrificed at time points from 3 d to 12 months after administration. Bronchoalveolar lavage fluid (BALF) was taken from the lungs and pathological specimens were prepared. The concentrations of phospholipids, total protein and surfactant protein D (SP-D) in the pulmonary surfactant of the BALF were determined, the surface tension of BALF was measured, and the inflammation score was determined by the point-counting method to assess pulmonary tissue inflammation. The present study suggests that inflammatory response in the lung was slightly higher for long MWCNTs than for short MWCNTs when compared at the same mass dose. The correlation between pulmonary surfactant components and BALF surface tension was also evaluated. The Spearman's rank correlation coefficients obtained for the phospholipid, total protein and SP-D concentrations were -0.068 (p=0.605), -0.360 (p=0.005) and -0.673 (p=0.000), respectively. Surface tension, measured by a simple method, should be reflected in the change of a surfactant protein, such as SP-D.
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Líquido del Lavado Bronquioalveolar/química , Pulmón/efectos de los fármacos , Nanotubos de Carbono/toxicidad , Administración por Inhalación , Animales , Líquido del Lavado Bronquioalveolar/citología , Recuento de Leucocitos , Pulmón/metabolismo , Pulmón/patología , Masculino , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Fosfolípidos/metabolismo , Neumonía/metabolismo , Neumonía/patología , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Ratas , Ratas WistarRESUMEN
Despite the enormous cost of radiation decontamination, there has been almost no quantitative discussion on how much it would reduce the long-term external radiation exposure in the Evacuation Zone and Planned Evacuation Zone (restricted zone) in Fukushima. The aim of this study is to assess the effectiveness of decontamination and return options and to identify important parameters for estimating the long-term cumulated effective dose (CED) during 15, 30 and 70 year period using data on land-use, population and decontamination in the restricted zone (about 1100 km(2)) in Fukushima. Decontamination of the land is assumed to have a certain efficacy in terms of the reduction of CED. The EeCC (external exposure conversion coefficient) is the parameter having the greatest effect on the percentage of area having CED during the 30 years above 100 m Sv after decontamination, ranging from 13% (EeCC=0.2) to 55% (EeCC=0.6). Therefore, we recommend a detailed investigation of the EeCC in Japan.
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Descontaminación , Accidente Nuclear de Fukushima , Sistemas de Información Geográfica , Dosis de Radiación , Monitoreo de Radiación , Contaminantes Radiactivos/análisis , Humanos , Japón , Plantas de Energía NuclearRESUMEN
Inhalation studies and intratracheal instillation studies using laboratory animals are commonly conducted for pulmonary toxicity tests of nanomaterials. In our study, male Wister rats were exposed to nickel oxide (NiO) particles including a nano-scale, even for aerosols and suspensions, in a 4-week inhalation and intratracheal instillation. Using polymorphonuclear neutrophils (PMNs) in bronchoalveolar lavage fluid as a biomarker of inflammation, we attempted to quantify the relationship between responses to inhalation and intratracheal instillation of the nanoparticles, based on surface area doses. Four kinds of NiO suspension samples with different specific surface areas were singly injected via the tracheas of the rats. The relationship between the instilled doses and PMN production was examined 3 days and 1 month after the instillation. In parallel, 4-week inhalation studies, using two of the suspensions, were conducted for aerosols generated by a pressurized nebulizer. NiO samples induced PMN responses 3 days after instillation according to the surface area doses, but not the mass doses, as has been reported in many studies. When the same NiO samples were tested in a 4-week inhalation and intratracheal instillation, the amount of pulmonary deposition of the sample after the 4-week inhalation, and an intratracheally instilled dose about ten-times higher, induced similar PMN responses 3 days after termination of inhalation and instillation. Using the relationship between these responses to 4-week inhalation and intratracheal instillation, it may be possible to estimate what aerosol concentrations of other nanomaterials might cause the same responses of PMN production as intratracheal instillation tests.
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Líquido del Lavado Bronquioalveolar , Nanopartículas/administración & dosificación , Neutrófilos/efectos de los fármacos , Níquel/administración & dosificación , Neumonía/inducido químicamente , Animales , Líquido del Lavado Bronquioalveolar/citología , Relación Dosis-Respuesta a Droga , Exposición por Inhalación , Instilación de Medicamentos , Recuento de Leucocitos , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/ultraestructura , Masculino , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Nanopartículas/química , Nanopartículas/toxicidad , Neutrófilos/ultraestructura , Níquel/química , Níquel/toxicidad , Tamaño de la Partícula , Neumonía/patología , Ratas , Ratas Wistar , Propiedades de Superficie , Pruebas de Toxicidad Subaguda , Tráquea/efectos de los fármacosRESUMEN
The genotoxicity of single-walled carbon nanotubes (SWCNTs) was determined using a battery of genotoxicity assays, comprising a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test and a mammalian erythrocytes micronucleus test. SWCNTs had no mutagenicity in S. typhimurium TA98, TA100, TA1535 or TA1537, or in E. coli WP2uvrA, in the absence or presence of metabolic activation. SWCNTs did not increase the number of structural or numerical chromosomal aberrations after short-term or continuous exposure. In the micronucleus test using CD-1 mice, SWCNTs did not affect the proportion of immature erythrocytes, the total proportion of erythrocytes or the number of micronuclei in immature erythrocytes. SWCNTs appear not to pose a genotoxic risk.
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Daño del ADN/efectos de los fármacos , Mutágenos/farmacocinética , Mutágenos/toxicidad , Nanotubos de Carbono/toxicidad , Animales , Biotransformación/genética , Línea Celular , Aberraciones Cromosómicas/efectos de los fármacos , Cricetinae , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Ratones , Pruebas de Micronúcleos/métodos , Pruebas de Mutagenicidad/métodos , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genéticaRESUMEN
The genotoxicity of multi-walled carbon nanotubes (MWCNTs) was evaluated in vivo with comet assays using the lung cells of rats given MWCNTs. The MWCNTs were intratracheally instilled as a single dose at 0.2 or 1.0 mg kg(-1) or a repeated dose at 0.04 or 0.2 mg kg(-1) , once a week for 5 weeks, to male rats. The rats were sacrificed 3 or 24 h after the single instillation and were sacrificed 3 h after the last instillation in the repeated instillation groups. Histopathological examinations of the lungs revealed that MWCNTs caused inflammatory changes including the infiltration of macrophages and neutrophils after a single instillation and repeated instillation at both doses. In comet assays using rat lung cells, no changes in % Tail DNA were found in any group given MWCNTs. These findings indicate that MWCNTs do not have the potential to cause DNA damage in comet assays using the lung cells of rats given MWCNTs at doses causing inflammatory responses.
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Ensayo Cometa/métodos , Pulmón/efectos de los fármacos , Nanotubos de Carbono/química , Tráquea/efectos de los fármacos , Animales , Daño del ADN/efectos de los fármacos , Pulmón/citología , Masculino , Ratas , Ratas Sprague-Dawley , Tráquea/citologíaRESUMEN
CONTEXT: Widespread production and use of nanomaterials have caused the release of increasing amounts of nanomaterials into the environment. The introduction of novel materials into industry requires safety evaluations as well as an understanding of the impact of the nanomaterials on human health, because the unique properties and size of nanomaterials may also result in unique health risks. Skin and eyes have the highest risk of exposure to nanomaterials, because deposition to the superficial organs has the potential to be a major route of exposure during the manufacturing, use, and disposal of nanomaterials. However, information on the dermal and eye irritation and sensitization of fullerene C(60) nanoparticles is still lacking. OBJECTIVES: This study was performed to examine the potential irritating and sensitizing effects of fullerenes on the skin and eyes. METHODS: The dermal and eye irritation study was performed using rabbits according to the Organisation for Economic Co-operation and Development (OECD) Guidelines 404 and 405, respectively. The skin sensitization study was carried out in accordance to the OECD Guideline 406 using guinea pigs. The concentrations of the fullerenes in the test substances were the maximum allowable for administration. Fullerenes were applied at 50 mg in dermal irritation, 40 mg in skin sensitization, and 100 mg in eye irritation studies. RESULTS: No dermal responses, including erythema/eschar or edema, were found in rabbits treated with fullerenes. No rabbits exhibited corneal opacity, abnormality of the iris, or chemosis eye at any time point after the application of fullerenes. Fullerenes caused conjunctival redness and blood vessel hyperemia at 1 h, but not at 24 h. No erythema or edema was observed after the challenge with fullerenes in the fullerene-treated guinea pigs. CONCLUSION: Reversible minimal potential for acute irritation of the eyes was induced by fullerenes, but neither irritation nor sensitization was caused on the skin. Although the present study provided initial information on the acute irritation and acute sensitization of highly purified C(60) fullerenes, information on the toxicological effects of fullerenes and their derivatives is still limited. Further information is needed to clarify the potential for toxicity given the complex nature of fullerenes and their derivatives.
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Ojo/efectos de los fármacos , Fulerenos/toxicidad , Irritantes/toxicidad , Piel/efectos de los fármacos , Animales , Seguridad de Productos para el Consumidor , Cobayas , Masculino , Conejos , Pruebas CutáneasRESUMEN
The genotoxicity of single-wall carbon nanotubes (SWCNTs) was evaluated in vivo using the comet assay after intratracheal instillation in rats. The SWCNTs were instilled at a dosage of 0.2 or 1.0mg/kg body weight (single instillation group) and 0.04 or 0.2mg/kg body weight once a week for 5weeks (repeated instillation group). As a negative control, 1% Tween 80 was instilled in a similar manner. As a positive control, ethyl methanesulfonate (EMS) at 500mg/kg was administered once orally 3h prior to dissection. Histopathologically, inflammation in the lung was observed for all the SWCNTs in both single and repeated groups. In the comet assay, there was no increase in% tail DNA in any of the SWCNT-treated groups. In the EMS-treated groups, there was a significant increase in% tail DNA compared with the negative control group. The present study indicated that a single intratracheal instillation of SWCNTs (1.0mg/kg) or repeated intratracheal instillation (0.2mg/kg) once a week for five weeks induced a clear inflammatory response (hemorrhage in the alveolus, infiltration of alveolar macrophages and neutrophiles), but no DNA damage, in the lungs in rats. Under the conditions of the test, SWCNTs were not genotoxic in the comet assay following intratracheal instillation in rats.
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Mutágenos/toxicidad , Nanotubos de Carbono/toxicidad , Animales , Ensayo Cometa , Daño del ADN , Exposición por Inhalación/efectos adversos , Intubación Intratraqueal/efectos adversos , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Mutágenos/administración & dosificación , Mutágenos/clasificación , Nanotubos de Carbono/clasificación , Neumonía/inducido químicamente , Neumonía/patología , Ratas , Ratas EndogámicasRESUMEN
The genotoxic potential of two products of multi-walled carbon nanotubes (coded as N-MWCNTs, diameter of 44 nm/BET surface area of 69 m²/g and MWNT-7, diameter of 70 nm/BET surface area of 23 m²/g) was evaluated using a battery of genotoxicity assays, comprising a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and a mammalian erythrocytes micronucleus test. Neither type exerted mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, and TA1537, or in Escherichia coli WP2uvrA, in the absence or presence of metabolic activation. The products of MWCNTs did not increase the number of structural chromosomal aberrations either, regardless of metabolic activation, though they increased the number of numerical chromosomal aberrations, one slightly and the other distinctly, in the absence of metabolic activation. In ICR mice, the two products did not affect the proportion of immature erythrocytes, the total proportion of erythrocytes, or the number of micronuclei in immature erythrocytes.
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Aberraciones Cromosómicas/inducido químicamente , Mutágenos/toxicidad , Nanotubos de Carbono/toxicidad , Animales , Línea Celular , Cricetinae , Cricetulus , Relación Dosis-Respuesta a Droga , Eritrocitos/efectos de los fármacos , Eritrocitos/ultraestructura , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Micronúcleos con Defecto Cromosómico/inducido químicamente , Microscopía Electrónica de Rastreo , Pruebas de Mutagenicidad/métodos , Mutágenos/química , Mutación , Nanotubos de Carbono/química , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Espectrofotometría Atómica , Propiedades de SuperficieRESUMEN
The genotoxicity of fullerene C(60) nanoparticles was evaluated in vivo with comet assays using the lung cells of rats given C(60) nanoparticles. The C(60) nanoparticles were intratracheally instilled as a single dose at 0.5 or 2.5mg/kg or repeated dose at 0.1 or 0.5mg/kg, once a week for 5 weeks, to male rats. The lungs were obtained 3 or 24h after a single instillation and 3h after repeated instillation. Inflammatory responses were observed in the lungs obtained 24h after a single instillation at 2.5mg/kg and repeated instillation at 0.5mg/kg. Histopathological examinations revealed that C(60) nanoparticles caused slight changes including hemorrhages in alveoli and the cellular infiltration of macrophages and neutrophils in alveoli. In comet assays using rat lung cells, no increase in % Tail DNA was found in any group given C(60) nanoparticles. These findings indicate that C(60) nanoparticles had no potential for DNA damage in comet assays using the lungs cells of rats given C(60) even at doses causing inflammation.
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Ensayo Cometa/métodos , Fulerenos/toxicidad , Pulmón/efectos de los fármacos , Nanopartículas/toxicidad , Animales , Ensayo Cometa/normas , Daño del ADN/efectos de los fármacos , Daño del ADN/fisiología , Fulerenos/administración & dosificación , Inyecciones Espinales , Pulmón/citología , Pulmón/fisiología , Masculino , Pruebas de Mutagenicidad/métodos , Pruebas de Mutagenicidad/normas , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Ratas , Ratas Sprague-DawleyRESUMEN
Multi-walled carbon nanotubes (MWCNTs), dispersed in suspensions consisting mainly of individual tubes, were used for intratracheal instillation and inhalation studies. Rats intratracheally received a dose of 0.2 mg, or 1 mg of MWCNTs and were sacrificed from 3 days to 6 months. MWCNTs induced a pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups, and presence of small granulomatous lesion and persistent neutrophil infiltration in the high-dose groups. In the inhalation study, rats were exposed to 0.37 mg/m(3) aerosols of well-dispersed MWCNTs (>70% of MWCNTs were individual fibers) for 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inhalation exposures delivered less amounts of MWCNTs into the lungs, and therefore less pulmonary inflammation responses was observed, as compared to intratracheal instillation. The results of our study show that well-dispersed MWCNT can produce pulmonary lesions, including inflammation.
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Pulmón/efectos de los fármacos , Nanotubos de Carbono/toxicidad , Administración por Inhalación , Fosfatasa Alcalina/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocinas CXC/análisis , Quimiocinas CXC/metabolismo , Pulmón/química , Pulmón/patología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/patología , Masculino , Nanotubos de Carbono/química , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Estadísticas no Paramétricas , Pruebas de ToxicidadRESUMEN
Single-wall carbon nanotubes (SWCNTs) were well-dispersed by ultrasonication to conduct an inhalation study. SWCNTs were generated using a pressurised nebuliser with liquid suspension of SWCNTs. Wistar rats were exposed to the well-dispersed SWCNT (diameter of bundle: 0.2 µm; length of bundle: 0.7 µm) for 4 weeks. The low and high mass concentrations of SWCNTs were 0.03 ± 0.003 and 0.13 ± 0.03 mg/m(3), respectively. The rats were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. There were no increases of total cell or neutrophil counts in the bronchoalveolar lavage fluid (BALF), or the concentration of cytokine-induced neutrophil chemoattractant in the lungs or BALF in both the high and low concentration-exposed groups. Pulmonary infiltration of neutrophils was not observed in either exposed group throughout the observation period. Well-dispersed SWCNT did not induce neutrophil inflammation in the lung under the conditions in the present study.
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Exposición por Inhalación/análisis , Pulmón/efectos de los fármacos , Macrófagos Alveolares/efectos de los fármacos , Nanotubos de Carbono/toxicidad , Administración por Inhalación , Fosfatasa Alcalina/metabolismo , Animales , Líquido del Lavado Bronquioalveolar , Quimiocina CXCL1/metabolismo , Hemo-Oxigenasa 1/metabolismo , Histocitoquímica , Pulmón/química , Pulmón/metabolismo , Macrófagos Alveolares/química , Macrófagos Alveolares/metabolismo , Masculino , Microscopía Electrónica , Tamaño de la Partícula , Fagocitosis , Ratas , Ratas Wistar , Estadísticas no ParamétricasRESUMEN
Titanium dioxide (TiO2) is widely used as a white pigment in paints, plastics, inks, paper, creams, cosmetics, drugs and foods. In the present study, the genotoxicity of anatase TiO2 nanoparticles was evaluated in vivo using the comet assay after a single or repeated intratracheal instillation in rats. The nanoparticles were instilled intratracheally at a dosage of 1.0 or 5.0 mg/kg body weight (single instillation group) and 0.2 or 1.0 mg/kg body weight once a week for 5 weeks (repeated instillation group) into male Sprague-Dawley rats. A positive control, ethyl methanesulfonate (EMS) at 500 mg/kg, was administered orally 3 h prior to dissection. Histopathologically, macrophages and neutrophils were detected in the alveolus of the lung in the 1.0 and 5.0 mg/kg TiO2 groups. In the comet assay, there was no increase in % tail DNA in any of the TiO2 groups. In the EMS group, there was a significant increase in % tail DNA compared with the negative control group. TiO2 nanoparticles in the anatase crystal phase are not genotoxic following intratracheal instillation in rats.
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Nanopartículas/toxicidad , Neumonía/inducido químicamente , Titanio/toxicidad , Administración por Inhalación , Animales , Ensayo Cometa , Masculino , Neumonía/patología , Ratas , Ratas Sprague-Dawley , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad SubagudaRESUMEN
It is important to conduct a risk assessment that includes hazard assessment and exposure assessment for the safe production and handling of newly developed nanomaterials. We conducted an inhalation study of a multi-wall carbon nanotube (MWCNT) as a hazard assessment. Male Wistar rats were exposed to well-dispersed MWCNT for 4 weeks by whole body inhalation. The exposure concentration in the chamber was 0.37 ± 0.18 mg/m³. About 70% of the MWCNTs in the chamber were single fiber. The geometric mean diameter (geometric standard deviation, GSD) and geometric mean length (GSD) of the aerosolized MWCNTs in the chamber were 63 nm (1.5) and 1.1 µm (2.7), respectively. The amounts of MWCNT deposited in the rat lungs were determined by the X-ray diffraction method and elemental carbon analysis. The average deposited amounts at 3 days after the inhalation were 68 µg/lung by the X-ray diffraction method and 76 µg/lung by elemental carbon analysis. The calculated deposition fractions were 18% and 20% in each analysis. The amount of retained MWCNT in the lungs until 3 months after the inhalation decreased exponentially and the calculated biological half times of MWCNT were 51 days and 54 days, respectively. The clearance was not delayed, but a slight increase in lung weight at 3 days after the inhalation was observed.
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Pulmón/metabolismo , Nanotubos de Carbono , Administración por Inhalación , Animales , Pulmón/patología , Masculino , Ratas , Ratas Wistar , Distribución Tisular , Pruebas de Toxicidad Subaguda , Difracción de Rayos XRESUMEN
The present study was conducted to assess the pulmonary and systemic responses in rats after intratracheal instillation of highly pure, well-dispersed, and well-characterized SWCNTs. Exposure to SWCNTs up to 2 mg/kg did not produce mortality, changes in clinical signs, or body weights during the observation period. Dose-dependent changes were observed in the lung weight, BALF inflammatory cells, and biochemical parameters such as LDH value, protein content, IL-1ß and IL-6 activity, and histopathology. In the 0.04 mg/kg SWCNT-exposed group, almost no changes were observed during the observation period. In the 0.2 mg/kg SWCNT-exposed group, pulmonary inflammatory responses were observed after instillation. In the 1 mg/kg and 2 mg/kg SWCNT-exposed group, acute lung inflammation and subsequent granuloma accompanied by increased lung weights were observed. Furthermore, the histopathological findings in the lungs of rats exposed to SWCNTs showed inflammatory responses related with the vital reaction to the foreign substance that was instilled intratracheally, and there were no fibrosis, atypical lesion, or tumor-related findings even at the highest dose (2 mg/kg) of SWCNT-exposed groups up to 6 months after instillation. For all groups, histopathological changes due to the instillation exposure of SWCNTs were observed only in the lungs and lung-associated lymph nodes and not in the other tissues examined (i.e. the liver, kidney, spleen, and cerebrum).
Asunto(s)
Pulmón/efectos de los fármacos , Nanotubos de Carbono/toxicidad , Administración por Inhalación , Animales , Líquido del Lavado Bronquioalveolar , Citocinas/inmunología , L-Lactato Deshidrogenasa/metabolismo , Recuento de Leucocitos , Pulmón/inmunología , Pulmón/patología , Pulmón/ultraestructura , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Masculino , Microscopía Electrónica de Transmisión , Nanotubos de Carbono/análisis , Nanotubos de Carbono/ultraestructura , Tamaño de los Órganos/efectos de los fármacos , RatasRESUMEN
The present paper summarizes the results of our studies on dermal and eye irritation and skin sensitization due to carbon nanotubes (CNTs), whose potential applications and uses are wide and varied, including CNT-enhanced plastics, electromagnetic interference/radio-frequency (EMI/RFI) shielding, antistatic material, flexible fibers and advanced polymers, medical and health applications, and scanning probe microscopy. Skin and eyes have the highest risk of exposure to nanomaterials, because deposition of nanomaterials to the surficial organs has the potential to be a major route of exposure during the manufacturing, use, and disposal of nanomaterials. Two products composed of single-walled carbon nanotubes (SWCNTs) and two products composed of multi-walled carbon nanotubes (MWCNTs) were tested regarding acute dermal and acute eye irritation using rabbits, and skin sensitization using guinea pigs. The concentrations of the CNTs in the substances were the maximum allowable for administration. The two products of SWCNTs and one of the products of MWCNTs were not irritants to the skin or eyes. The other product of MWCNTs caused very slight erythema at 24h, but not at 72h, after patch removal in the dermal irritation experiments and conjunctival redness and blood vessel hyperemia at 1h, but not at 24h, in eye irritation experiments. These findings showed that one product of MWCNTs was a very weak acute irritant to the skin and eyes. No products of SWCNTs and MWCNTs exhibited skin-sensitization effects. Our knowledge of the toxicological effects of CNTs is still limited. Further information is needed to clarify the potential for irritation and sensitization given the complex nature of CNTs.
Asunto(s)
Ojo/efectos de los fármacos , Irritantes/toxicidad , Nanotubos de Carbono/toxicidad , Piel/efectos de los fármacos , Animales , Dermatitis Alérgica por Contacto , Cobayas , Masculino , Conejos , Pruebas de Irritación de la PielRESUMEN
The genotoxic potential of a high purity sample of single-wall carbon nanotubes (SWCNTs) was evaluated using a battery of in vitro and in vivo genotoxicity assays. These comprised a bacterial reverse mutation test (Ames test), an in vitro chromosomal aberration test, and an in vivo mouse bone marrow micronucleus test. The SWCNTs exerted no genotoxicity in Salmonella typhimurium TA97, TA98, TA100, and TA1535, or in Escherichia coli WP2 uvrA/pKM101, whether in the absence or presence of metabolic activation and at concentrations of 12.5-500 µg/plate. In the chromosomal aberration test, at 300-1000 µg/mL, the SWCNTs did not increase the number of structural or numerical chromosomal aberrations, whether the test was conducted with or without metabolic activation. In the in vivo bone marrow micronucleus test, doses of 60 mg/kg and 200mg/kg SWCNTs did not affect the proportions of immature and total erythrocytes, nor did it increase the number of micronuclei in the immature erythrocytes of mice. The results of these studies show that the high purity and well-dispersed sample of SWCNTs are not genotoxic under the conditions of the in vitro bacterial reverse mutation assay, chromosomal aberration assay, or in vivo bone marrow micronucleus test, and thus appear not to pose a genotoxic risk to human health in vivo.