• Journal of Environmental Health Sciences
• /
• v.48 no.2
• /
• pp.106-115
• /
• 2022

Background: Current research suggests that humans are exposed to microplastics through consumption of foods and beverages, the airway route, and a variety of other means. Objectives: We evaluated oxidative stress and inflammation from polyethylene microplastics (PE-MPs) in the neonatal liver through intragastric administration or intratracheal instillation in pregnant mice. Methods: PE-MPs were administered from gestational day 9 to postnatal day 7. The intragastric administration group (0.01 mg/mouse/day or 0.1 mg/mouse/day) and intratracheal instillation group (6 ㎍/mouse/day or 60 ㎍/mouse/day) of PE-MPs were administered. After sacrifice, the oxidative stress and inflammation of the neonatal livers were measured. Results: As a result of the oxidative stress caused by PE-MPs in the neonatal livers, glutathione peroxidase decreased in a concentration-dependent manner in the intragastric administration group compared to the control group and intratracheal instillation decreased in high concentration PE-MPs. The catalase level increased at high concentrations of intragastric administration and intratracheal instillation. To confirm the level of inflammation caused by PE-MPs, monocyte chemoattractant protein-1 and tumor necrosis factoralpha were increased compared to the control group except for intratracheal intilation-high concentration PEMPs. The C-reactive protein level was decreased by intragastric administration compared to the control group and intratracheal instillation was increased compared to the control group. Conclusions: Despite the difficulty in comparing the toxic intensity between intragastric administration and intratracheal instillation of PE-MPs, our study revealed that oxidative stress and inflammation were induced in the neonatal liver. However, it is necessary to evaluate the toxic effects of microplastics on various organs as well. Overall, the present study indicates that the evaluation of toxic effects of long-term microplastic exposure, potential of microplastic toxicity on next-generation offspring and toxicity mechanism in human should be considered for further investigations.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.29 no.4
• /
• pp.508-516
• /
• 2019

Objectives: The present study was performed to obtain acute toxicity information on glyoxal in male rats after intratracheal instillation. Methods: In order to calculate the LD₅₀ of glyoxal using Probit analysis with SAS, the test article was one intratracheal instillation to male Sprague-Dawley rats at dose levels of 0, 225, 451 or 902 mg/kg. During the test period, mortality, clinical signs, and body and organ weights were examined. At the end of the 14-day observation period, all animals were sacrificed and complete gross postmortem and histopathological examinations were performed. Results: Four animals of the 902 mg/kg group died within one week after the administration of glyoxal. All treatment group in a dose dependent manner, decreased body weight was found during the study period. The absolute and relative lung weight, and histopathological changes (bronchiolar-alveolar hyperplasia, chronic inflammation) of lung exhibited an increased in glyoxal treated groups in a dose dependent manner. However, there were no changes on the organ weights and histopathological changes of any other organ except lung. Conclusions: The results obtained in the present study suggest that the LD₅₀ in male Sprague-Dawley rats after a single intratracheal instillation of glyoxal was considered to be 866.9 mg/kg and the lung was found to be the target organ for glyoxal.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.31 no.4
• /
• pp.473-483
• /
• 2021

Objectives: The present study aimed to evaluate the potential toxicity of 2-butoxyethanol after intratracheal instillation in male rats. Methods: In order to calculate median lethal dose (LD₅₀) of 2-butoxyethanol using Probit analysis with SAS program, the 2-butoxyethanol was administered with dose levels of 0, 101.64, 203.28 and 406.56 mg/kg by once intratracheal instillation to male rats. During the test period, clinical signs, mortality, body weights, organ weights, hematology, and serum biochemistry were examined. At the end of 14 days observation period, all animals were sacrificed and gross finding and histopathological examination were performed. Results: All animals of 406.56 mg/kg group died within 2 weeks after the administration of 2-butoxyethanol. Treatment-related clinical signs, gross observation and histopathological changes (mucous cell hyperplasia, alveolar macrophage aggregation, and hemorrhage) of lung exhibited an increased in 2-butoxyethanol treated groups in a dose dependent manner. However, there were no changes in the organ weights, hematology and serum biochemistry, and histopathology of any other organ except lung. Conclusions: On the basis of the results, it was concluded that a single intratracheal instillation of 2-butoxyethanol in male Sprague-Dawley rats resulted in some adverse effects on mortality, clinical sign, and histopathology in the lung. In the experimental conditions, the LD₅₀ of 2-butoxyethanol was considered to be 287.2 mg/kg and lung was founded to be the target organ of 2-butoxyethanol.

• Journal of Environmental Health Sciences
• /
• v.43 no.4
• /
• pp.273-279
• /
• 2017

Objectives: Carbon nanotubes (CNTs) are next-generation industrial nanoparticles which possess excellent mechanical strength along with good thermal conductivity and electric properties. Given these characteristics, carbon nanotubes are being widely applied in various fields, including research and development. However, concerns have been raised over hazardous properties due to their similar fiber shape to asbestos. Recent studies have shown that CNTs pose potential hazards which may cause fibrosis and/or lung inflammation similarly to asbestos. Methods: After intratracheal instillation of SWCNTs and MWCNTs to rats, pulmonary surfactant (PS) of the SWCNTs and MWCNTs was measured and analyzed using bronchoalveolar lavage fluid collected from the lung. After a single intratracheal instillation of SWCNTs and MWCNTs, phospholipid predominantly showed a significant increase compared to the control group, while proteins exhibited a significant increase both three days and one week after instillation. Results: As a result of surface tension, MWCNTs showed a significant decrease three days after treatment compared to the control group. In the case of the total cell number three days after instillation, MWCNTs revealed a temporarily significant increase when compared to the control group. For PMN number, when compared to the control group, SWCNTs displayed a significant increase throughout the observation period, while MWCNTs showed a significant increase three days and three months after treatment. Conclusions: After exposure to CNTs, the total cell number and PNT number, which indicate inflammatory response, were significantly increased. Therefore, this study suggests fiber-shaped CNTs may have a harmful effect on the lungs.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.24 no.3
• /
• pp.336-344
• /
• 2014

Objectives: This study was performed to assay the effect of neodymium oxide on the generation of reactive oxygen species and DNA oxidative damage by intratracheal instillation. Methods: Two groups of rats were exposed to neodymium oxide($Nd_2O_3$) via intratracheal instillation with doses of 0.5 mg and 2.0 mg, respectively. At two days and at 12 weeks after exposure, the contents of neodymium oxide in the lung, liver, kidney, heart and brain, leukocyte, olive tail moment, ROS, RNS, lactate dehydrogenase, albumin, cytokine and MDA from BALF were measured. Results: Neodymium oxide contents in the liver, kidney, heart, and brain were detected at less than $1{\mu}g/g$ tissue concentration. However, in the lungs at four weeks the highest amount were detected and then found to be drastically reduced at 12 weeks. ROS and RNS in bronchoalveolar lavage increased in concentration dependently at two days, four weeks and 12 weeks after neodymium oxide instillation. However, ROS and RNS decreased with the passage of time. At two days the total number of WBC in BALF in the high concentration group was significantly increased, and at four weeks the total number of WBC were significantly increased in the low and high concentration groups(p<0.01). At two days after exposure, the LDH of the low and high concentration groups was significantly increased. At 12 weeks, only the LDH of the high concentration group was significantly increased compared to in the control group(p<0.01). As a result of Comet assay, after two days, damage to the DNA of the low and high concentration groups was observed. Conclusions: Intratracheal instillation of neodymium oxide induces the generation of ROS and DNA damage in rats.

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2004.05a
• /
• pp.101-101
• /
• 2004

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.24 no.3
• /
• pp.321-329
• /
• 2014

Objectives: This study was performed to produce data on the pulmonary toxicity of neodymium oxide($Nd_2O_3$) by intratracheal instillation. Methods: Two groups of rats were exposed to neodymium oxide by intratracheal instillation with doses of 0.5 mg and 2.0 mg, respectively. At two days, four weeks and 12 weeks after exposure, body weight change, organ weight change and histopathological change were observed. At 12 weeks after exposure, lung function change was measured. Results: The body weight of rats in the high concentration group decreased after 12 weeks by 4-5% compared with the control group. At four weeks and 12 weeks after the administration of neodymium oxide, the absolute weight of the lungs of the high concentration group were significantly increased when compared with the control group(p<0.05). At 12 weeks after the injection of neodymium oxide, breath frequency and respiratory minute volume were increased, but inhalation time and expiratory time were decreased. Bronchiolar epithelial hyperplasia, alveolar type II cell hypertrophy/hyperplasia and foreign body granulomatous inflammation were observed in the high exposure group. Conclusions: Body weight decrease, lung absolute weight and breath frequency increase, and pathological lung change were all observed. We found that pulmonary toxicity of neodymium oxide nanoparticles by intratracheal instillation could be confirmed.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.22 no.3
• /
• pp.224-234
• /
• 2012

Objectives: To assess the hazard of Korea chrysotile and anthophylite, fibers were analyzed for their physicochemical properties by transmission electron microscope equipped with energy dispersive X-ray spectrometer (TEM-EDS). Methods: To evaluate the biopersistence of 2 domestic asbestos, Sprague-Dawely rats were exposed to 2 mg asbestos by intratracheal instillation. Each asbestos (chrysotile ; $8,814,244{\times}10^6$ fibers/mg, average size $0.08{\mu}m{\times}4.39{\mu}m$, anthophyllite ; $5,182{\times}10^6$ fibers/mg, average size $0.95{\mu}m{\times}7.29{\mu}m$) were evaluated after a single intratracheal instillation. At times from 1 week to 4 weeks after exposure, the numbers of asbestos fivers in the bronchoalveolar lavage fluid and in the lung were calculated. Results: Anthophyllite fivers continuously have retained for 4 weeks but chrysotile fivers were rarely found at 4 weeks after exposure in the bronchoalveolar lavage fluid. Chrysotile fivers at 4 weeks after treatment were not observed but anthophyllite was easily observed in the lung with phase contrast microscopy. According to electron microscopic observation of asbestos in the lung, within 1 week after the administration of chrysotile fivers were decreased rapidly but anthophyllite fivers were very little change for 4 weeks. When chrysotile fivers have been lost Fe in 1 week, there were no significant changes in anthophyllite fivers in the lung. Conclusions: These findings indicate that after a long time exposure to chrysotile, asbestos bodies can not be found in the bronchoalveolar lavage fluid.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.4
• /
• pp.487-499
• /
• 2000

Background : Acute lung injury is an hypoxic respiratory failure resulting from damage to the alveolar-capillary membrane, which can be developed by a variety of systemic inflammatory diseases. In this study the therapeutic effects of intra-tracheal pulmonary surfactant instillation was evaluated in the intratracheal endotoxin induced acute lung injury model of a rat. Methods : Twenty Sprague-Dawley rats were divided into 4 groups, and normal saline (2 ml/kg, for group 1) or LPS (5 mg/kg, for group 2, 3, and 4) was instilled into the trachea respectively. Either normal saline (2 ml/kg, for group 1 & 2, 30 min later) or bovine surfactant (15 mg/kg, 30 min later for group 3, 5 hr later for group 5) was instilled into the trachea. The therapeutic effect of intratracheal surfactant therapy was evaluated with one chamber body plethysmography (respiratory frequency, tidal volume and enhanced pause), ABGA, BAL fluid analysis (cell count with differential, protein concentration) and pathologic examination of the lung. Results : Intratracheal endotoxin instillation increased the respiration rate decreased the tidal volume and int creased the Penh in all group of rats. Intratracheal instillation of surfactant decreased Penh, increased arterial oxygen tension, decreased protein concentration of BAL fluid and decreased lung inflammation at both times of administration (30 minute and 5 hour after endotoxin instillation). Conclusion : Intratracheal instillation of surfactant can be a beneficial therapeutic modality as discovered in the acute lung injury model of rats induced by intratracheal LPS intillation. It deserves to be evaluated for treatment of human acute lung injury.

• Tuberculosis and Respiratory Diseases
• /
• v.38 no.2
• /
• pp.143-154
• /
• 1991

Pneumconiosis is a sort of pulmonary fibrosis consequent to the inhalation of the respirable dusts. Thus, the pathogenesis of silicosis have concentrated largely on the early response of alveolar macrophage and the later fibroblastic stimulation. But the role of the other cells and continuing cell injury in the pathogenesis has not been fully studied. And the chemical factors such as prostaglandin, fibroblast stimulating factor and inhibiting factor and chemotaxin are also participated in the mechanism of pulmonary fibrosis in silicosis. In order to clarify the role of alveolar cells and prostaglandin, we investigated the changes of the cellularities in bronchoalveolar lavage fluid and tissue pathology in the experimental silicosis with the time sequence. The experimental animals were divided into 3 groups; control group received only intratracheal injection of 0.5 ml saline, silica group received the intratracheal instillation of 40 mg silica with the same amount saline, and aspirin group received 450 mg/kg of aspirin after silica instillation. The results were as follows: 1) The total cells of bronchoalveolar lavage fluid in the silica group markedly increased in comparison with the control group, but there was no significant difference between the silica and aspirin groups. 2) The percentages of alveolar macrophages to the total number of cells in the silica group tended to be lower than those in the control group and also lower than those in the aspirin group at the 1st week after silica instillation. 3) The percentages of neutrophils to the total number of cells in the silica group were significantly higher than those in the control group during the entire period and also higher than those in the aspirin group at the 3rd day after silica instillation. 4) In the silica group, the percentages of lymphocytes to the total number of cells were increased 143 progressively with the time course and those were significantly higher than those in the control group from the 3rd week after silica administration. There were marked differences of lymphocyte percentages between the silica and aspirin groups at the 1st week after silica instillation. 5) The inflammatory change was observed in the rat lung at the 1st day after silica instillation. Also the silicotic nodule appeared in the silica group at the 1st week but we could not find out that nodule in the aspirin group at that time. The fibrotic changes in the rat lung tended to be increased progressively with the time course, therefore, the diffuse fibrotic pattern appeared in the whole field at the 20th week after silica instillation. 6) By the electron microscopy, there were gradual increases of phagosomes and vacuoles in the alveolar macrophage in the silica group as compared with the control group. These results suggest that the neutrophils and the lymphocytes have also participated in the pulmonary fibrosis even though the alveolar macrophage has a major role, and prostaglandin mediate the inflammation and pulmanary fibrosis in the experimental silicosis.