SWCNT 및 MWCNT의 기관내 점적주입 후 폐 계면활성제의 분석

이병우(Byeongwoo Lee),서정관(Jungkwan Seo),심일섭(Ilseob Shim),엄익춘(Igchun Eom),김필제(Plije Kim) 한국환경보건학회 2017 한국환경보건학회지 Vol.43 No.4

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.

국내산 백석면과 안소필라이트의 물리화학적 특성과 호흡기계 내 변화 연구

정용현 ( Yong Hyun Chung ),한정희 ( Jeong Hee Han ),강민구 ( Min Gu Kang ),김종규 ( Jong Kyu Kim ),양정선 ( Jeong Sun Yang ) 한국산업위생학회 2012 한국산업보건학회지 Vol.22 No.3

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 × 106 fibers/mg, average size 0.08 um × 4.39 um, anthophyllite ; 5,182 × 106 fibers/mg, average size 0.95 um × 7.29 um) 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 cannot be found in the bronchoalveolar lavage fluid.

Induction of Inflammatory Responses in Mice Treated with Cerium Oxide Nanoparticles by Intratracheal Instillation

Park, Eun-Jung,Cho, Wan-Seob,Jeong, Jayoung,Yi, Jong-heop,Choi, Kyunghee,Kim, Younghun,Park, Kwangsik The Pharmaceutical Society of Japan 2010 Journal of Health Science Vol.56 No.4

<P>Cerium oxide nanoparticles have a high thermodynamic affinity for oxygen and sulfur, which makes them useful in applications such as catalysts, solar cells, and gas sensors. In this study, we investigated the effects of intratracheal instillation of cerium oxide nanoparticles on the inflammatory responses in mice. The number of neutrophils in bronchoaveolar lavage (BAL) fluids was significantly elevated on day 1 after instillation. Inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor (TNF)-α, and IL-6, were also increased in BAL fluid and the cytokine increase initiated the differentiation of naive T cells, followed by the induction of Th1-type cytokines [IL-12 and interferon (IFN)-γ] and Th2-type cytokines (IL-4, IL-5, and IL-10). The secretion of Th1-type cytokines was more dominant than that of Th2-type cytokines. The inflammatory responses were maintained for 28 days by a positive feedback stimulation of IFN-γ and IL-10. In the lung, the expression of inflammatory genes was increased in a time-dependent manner, and granuloma formation appeared on day 14 after instillation. This suggests that intratracheal instillation of cerium oxide nanoparticles causes a delayed-type hypersensitivity reaction and lung fibrosis in mice.</P>

수컷랫드(Sprague-Dawley)에서글리옥살(glyoxal)의단회기도내투여에따른급성독성시험

김현영,김기천,김인현,김민석,김성환,이규홍 한국산업보건학회 2019 한국산업보건학회지 Vol.29 No.4

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.

Intratracheal Instillation of Platinum Nanoparticles May Induce Inflammatory Responses in Mice

Park, Eun-Jung,Kim, He-Ro,Kim, Young-Hun,Park, Kwang-Sik 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.5

Platinum nanoparticles (PNPs) are potentially useful for sensing, catalysis, and other applications in the biological and medical sciences. However, toxicity data on the PNPs are very limited. In this study, we prepared PNPs using $K_2PtCl_6$, (21 nm in phosphate buffered saline) and tested inflammatory responses in mice after a single intratracheal instillation. The concentrations of pro-inflammatory cytokines (IL-1, TNF-${\alpha}$, and IL-6), TH0 cytokine (IL-2), TH1-type cytokine (IL-12), and TH2-type cytokines (IL-4 and IL-5) were increased in broncho-alveolar lavage fluid by PNPs. It was found that the induciton of TH2-type cytokines were higher than TH1-type cytokine on day 28 after instillation. TGF-${\beta}$ was also significantly increased in broncho-alveolar lavage fluid during the experimental period. IgE level in serum was increased with the increase of B cells distribution. Intracellular level of glutathione (GSH) was diminished by treatment of PNPs. When the distribution of T cell subtype ($CD4^+/CD8^+$) was analyzed, the ratio was decreased. Gene expression of matrix metalloproteinases was found to be significantly increased on day 1. By histopathological examination, cell infiltration of macrophages and neutrophils was observed in lung tissue during the experimental period. Based on these findings, it is suggested that the exposure to PNPs may induce inflammatory responses in mice.

Histopathological changes in the lungs of rats instilled with Korean chrysotile

Jeong Hee Han,Yong Hyun Chung,Cheol Hong Lim 환경독성보건학회 2021 환경독성보건학회지 Vol.36 No.3

To evaluate the pulmonary toxicity of Korean chrysotile (KC), 1 or 2 mg of KC (low- and high-concentration groups, respectively) was instilled in the lungs of Sprague-Dawley rats by a single intratracheal instillation. The lungs were examined using a light microscope at several time points (5 days, 5 weeks, and 10 weeks). Up to 10 weeks after KC instillation, differences were observed in the pathological reactions and ultimately in lung recovery between the two groups. At 5 days after KC instillation, lung weight increased and severe bronchiolitis obliterans developed in proportion to the KC concentration administered. From 5 to 10 weeks after KC administration, the lung weight of the low-concentration group increased and bronchiolitis obliterans worsened. In the high-concentration group, the lung weight and the severity of bronchiolitis obliterans at 10 weeks after administration of KC declined compared to those at 5 weeks. In conclusion, the effects of KC on lung tissue were initially found to be more influenced by the amount of fiber, but over time, the effects were influenced by the residual fibrous material in the lung tissue and its biodurability.

No prominent toxicity of polyethylene microplastics observed in neonatal mice following intratracheal instillation to dams during gestational and neonatal period

Han YoungHoon,Song YoungMin,Kim Geun Woo,Ha ChangSu,Lee JiSun,Kim MinHee,Son HyeYoung,Lee GiYong,Gautam Ravi,Heo Yong 한국독성학회 2021 Toxicological Research Vol.37 No.4

Microplastics (MPs) have been recently recognized as a global environmental threat and its exposure as a risk factor to human health. Health effects through MPs exposure have been recently reported, especially through oral route of exposure. Since MPs could be exposed to humans through routes other than oral, this study was designed to evaluate whether MPs exposed through the inhalation route could be delivered to fetal mice and exhibit systemic toxicity. Polyethylene (PE) with 10–45 μm diameter were administered at 0 (distilled water, vehicle control), 6 (low administration), and 60 (high administration) μg/ mouse/day to 3 pregnant dams per group from gestational day 9 to postnatal day (PND) 7 through intratracheal instillation. Dams and neonates were sacrificed at PND 7 and blood was collected. Various neonatal organs including brain, lung, heart, stomach, intestine, kidneys, and ovaries were collected for histopathological observation and weight measurement. No influence of PE-MPs administration was observed on the number of offsprings born, but the body and organs’ weight were heavier overall in the high administration group of dams and neonates than the other groups with statistical significance achieved in the heart and spleen weight. Level of serum acetylcholinesterase and glutathione peroxidase activity was decreased in the high administration group of dams and neonates compared with the other groups. Lung was the organ with highest number of PE-MPs present in the both administration groups of dams, and PE-MPs were also detected in liver and intestine of the high administration dams. Whereas, PND7 neonates showed accountable numbers of PE-MPs only in kidneys of the high administration group. Overall, the present study indicates that PE-MPs instilled intratracheally could be delivered to neonates from dams. Even though adverse effects from PE-MPs exposure during pregnant and lactational period are less prominent on both dam and neonate, potential of second-generation toxicity could be considered for further investigation.

Sublethal pulmonary toxicity screening of silica nanoparticles in rats after direct intratracheal instillation

Han Hyoung-Yun 한국독성학회 2022 Toxicological Research Vol.38 No.4

The present aimed to characterize the toxicity of silica nanoparticles in Sprague Dawley rats and determine the dose levels for a repeated-dose toxicity study. Silica nanoparticles ( SiO2, 20 nm and 50 nm) were administered as a single intratracheal instillation of standardized SiO2 20 nm (low dose, 200 μg/mL; high dose, 400 μg/mL) and 50 nm (low dose, 200 μg/mL; high dose, 400 μg/mL). Each group consisted of five male rats. We documented the mortality rate, clinical signs, body weight, bronchoalveolar lavage fluid analysis, hematological values, serum chemistry values, organ weight, gross findings at necropsy, and histopathological assessments. Rats treated with 200 μg/mL and 400 μg/mL SiO2 50 nm exhibited a decreased mean corpuscular volume, while those treated with 400 μg/mL of SiO2 50 nm showed increases in absolute monocyte and absolute lymphocyte count as well as prothrombin time. In addition, rats treated with 400 μg/mL SiO2 20 nm and 50 nm presented reduced creatinine, alanine aminotransferase, and sodium levels. Therefore, a single intratracheal instillation of SiO2 20 nm and 50 nm elicited no toxicity up to a dose of 400 μg/mL, and the approximate lethal dose of this test substance exceeded 400 μg/mL in male Sprague Dawley rats under the present experimental conditions.

수컷 랫드(Sprague-Dawley)에서 2-부톡시에탄올(2-butoxyethanol)의 단회 기도내 투여에 따른 급성 독성시험

김현영 ( Hyeon-young Kim ),김인현 ( In-hyeon Kim ),김민석 ( Min-seok Kim ),김성환 ( Sung-hwan Kim ),이규홍 ( Kyuhong Lee ) 한국산업보건학회 2021 한국산업보건학회지 Vol.31 No.4

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.

Acute toxicity of benzalkonium chloride in Balb/c mice following intratracheal instillation and oral administration

Handule Lee,Kwangsik Park 환경독성보건학회 2019 환경독성보건학회지 Vol.34 No.3

Benzalkonium chloride is a cationic surfactant widely used as a disinfectant, preservative, and sanitizer in many public places as well as domestically. The purpose of this study is to compare the acute toxicity of lethal doses (LDx) and the target organs after intratracheal instillation and oral ingestion by mice, which is a preliminary test prior to the repeated dose toxicity test. When Balb/c mice were treated with a single dose of benzalkonium chloride via oral administration, LD50 was 241.7 ㎎/㎏. However, it was comparatively decreased to 8.5 ㎎/㎏ following intratracheal treatment, which suggests that lung may be the main target of toxicity. Although the histopathology showed inflammatory responses in the lung after intratracheal instillation, it still did not confirm that the inflammatory responses were the key factors inducing death in the treated animal. Acute and fatal mechanisms such as bronchoconstriction or neurotoxicity associated with benzalkonium chloride exposure should be further investigated.