• Title/Summary/Keyword: Inhalation toxicology

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Development of a nanoparticle multi-generator for assessment of inhalation hazard

  • Lee, Sung-Bae;Han, Jeong-Hee;Kim, Tae-Hyun;Cha, Hyo-Geun;Lim, Cheal-Hong
    • Analytical Science and Technology
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    • v.34 no.2
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    • pp.87-98
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    • 2021
  • In this study, we developed the nanoparticle multi-generator by 3D printer fusion deposition modeling (FDM) method that can reliably generate and deliver nanoparticles at a constant concentration for inhalation risk assessment. A white ABS filament was used as the test material, and SMPS was used for concentration analysis such as particle size and particle distribution. In the case of particle size, the particle size was divided by 100 nm or less and 100 to 1,000 nm, and the number of particles concentration, mass concentration, median diameter of particles, geometric average particle diameter, etc were measured. The occurrence conditions were the extruder temperature, the extruding speed of the nozzle, and the air flow rate, and experiments were conducted according to the change of conditions including the manufacturer's standard conditions. In addition, the utility of inhalation risk assessment was reviewed through a stability maintenance experiment for 6 h. As a result of the experiment, the size of the nanoparticles increased as the discharger temperature increased, as the discharge speed of the nozzle increased, and as the air flow rate decreased. Also, a constant pattern was shown according to the conditions. Even when particles were generated for a long time (6 h), the concentration was kept constant without significant deviation. The distribution of the particles was approximately 80 % for particles of 60 nm to 260 nm, 1.7 % for 1 ㎛ or larger, 0.908 mg/㎥ for the mass concentration, 111 nm for MMAD and 2.10 for GSD. Most of the ABS particles were circular with a size of less than 10 nm, and these circular particles were aggregated to form a cluster of grape with a size of several tens to several hundred nm.

Evaluating the Influence of Side Stream Cigarette Smoke at an Early Stage of Non-Alcoholic Steatohepatitis Progression in Mice

  • Kim, Jong Won;Yun, Hyejin;Choi, Seong-Jin;Lee, Sang-Hyub;Park, Surim;Lim, Chae Woong;Lee, Kyuhong;Kim, Bumseok
    • Toxicological Research
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    • v.33 no.1
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    • pp.31-41
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    • 2017
  • Side stream cigarette smoke (SSCS) is known to be as harmful and hazardous to human health as is active smoking. In this study, we investigated the relationship between the exposure to SSCS and its stimulatory and subacute effects on the progression of non-alcoholic steatohepatitis (NASH). A methionine and choline-deficient plus high fat (MCDHF) diet was administered to C57BL/6 mice for 6 weeks. During the first three weeks of MCDHF diet feeding, each diet group was exposed to SSCS (0, 20, $40{\mu}g/L$) or fresh air for 2 hrs per day and 5 days per week. Additional experiments were performed by increasing the concentration (0, 30, $60{\mu}g/L$) and exposure time (6 hours per day) of SSCS. According to histopathologic analysis and serum levels of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), there were no differences in hepatic fat deposition, fibrosis, apoptosis or liver damage in MCDHF-fed mice based on SSCS exposure. There were also no differences in the expression of inflammation-, oxidative stress- or fibrosis-related genes between MCDHF-fed mice with or without SSCS exposure. Therefore, it is concluded that SSCS with current exposure amounts does not have additive detrimental effects on the early stage of NASH.

Gene Expression Analysis of Lung Injury in Rats Induced by Exposure to MMA-SS Welding Fume for 30 Days

  • Oh, Jung-Hwa;Park, Han-Jin;Heo, Sun-Hee;Yang, Mi-Jin;Yang, Young-Su;Song, Chang-Woo;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.3 no.4
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    • pp.306-313
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    • 2007
  • The welding fume has been implicated as a causal agent in respiratory disease such as pneumoconiosis. The molecular mechanism by which welding fume induces toxicity in the lung is still unknown, but studies have focused on histological structure and indirect approach measuring the pulmonary damage markers. In the present study, gene expression profiles were analyzed in the lung of rats exposed by manual metal-arc stainless-steel (MMA-SS) welding fume for 30 days using Affymetrix GeneChip$^{(R)}$. Totally, 379 genes were identified as being either up- or down-regulated over 2-fold changes (P<0.01) in the lung of low- or high-dose group and were analyzed by using hierarchical clustering. We focused on genes involved in immune/inflammation responses were differentially regulated during lung injury induced by welding fume exposure. The information of these deregulated genes may contribute in elucidation of the inflammation mechanism during lung injury such as lung fibrosis.

Basic Principles of the Validation for Good Laboratory Practice Institutes

  • Cho, Kyu-Hyuk;Kim, Jin-Sung;Jeon, Man-Soo;Lee, Kyu-Hong;Chung, Moon-Koo;Song, Chang-Woo
    • Toxicological Research
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    • v.25 no.1
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    • pp.1-8
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    • 2009
  • Validation specifies and coordinates all relevant activities to ensure compliance with good laboratory practices (GLP) according to suitable international standards. This includes validation activities of past, present and future for the best possible actions to ensure the integrity of non-clinical laboratory data. Recently, validation has become increasingly important, not only in good manufacturing practice (GMP) institutions but also in GLP facilities. In accordance with the guideline for GLP regulations, all equipments used to generate, measure, or assess data should undergo validation to ensure that this equipment is of appropriate design and capacity and that it will consistently function as intended. Therefore, the implantation of validation processes is considered to be an essential step in a global institution. This review describes the procedures and documentations required for validation of GLP. It introduces basic elements such as the validation master plan, risk assessment, gap analysis, design qualification, installation qualification, operational qualification, performance qualification, calibration, traceability, and revalidation.

Noninvasive Monitoring of Bleomycin-induced Lung Injury in Rats Using Pulmonary Function Test

  • Yang, Mi-Jin;Yang, Young-Su;Kim, Yong-Bum;Cho, Kyu-Hyuk;Heo, Jeong-Doo;Lee, Kyu-Hong;Song, Chang-Woo
    • Toxicological Research
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    • v.24 no.4
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    • pp.273-280
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    • 2008
  • The single intratracheal instillation (ITI) of bleomycin (BLM) is a widely used method for inducing experimental pulmonary fibrosis in rat model. In the present study, pulmonary function tests (PFTs) of tidal volume ($V_T$), minute volume ($V_M$), and respiratory frequency ($F_R$) have been applied to study their possibility as a tool to monitor the progress of BLM-induced lung injury in rat model. Rats were treated with a single ITI of BLM (2.5 mg/kg) or saline (control). Animals were euthanized at 3, 7, 14, 21, and 28 days post-ITI. Lung toxicity effects were evaluated by inflammatory cell count, lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF), and light microscopic examination of lung injury. The PFT parameters were measured immediately before the animals were sacrificed. BLM treatment induced significant cellular changes in BALF-increase in number of total cells, neutrophils, and lymphocytes along with sustained increase in number of macrophages compared to the controls at days 3, 7, and 14. BALF LDH level was significantly increased compared to that in the controls up to day 14. On day 3, infiltration of neutrophils was observed in the alveolar spaces. These changes developed into marked peribronchiolar and interstitial infiltration by inflammatory cells, and extensive thickening of the interalveolar septa on day 7. At 14, 21, and 28 days, mild peribronchiolar fibrosis was observed along with inflammatory cell infiltration. The results of PFT show significant consistencies compared to the results of other toxicity tests. These data demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days post-ITI of BLM based on the observation of fibrosis at 14, 21, and 28 days. Further, the progress of lung injury can be traced by monitoring the PFT parameters of $F_R$, $V_T$, and $V_M$.

The Effect of Butane gas on Rat Cholinesterase and Lactatedehydrogenase (Butane gas가 흰쥐 혈청과 조직의 Lactatedehydrogenase 및 Cholinesterase에 미치는 영향)

  • 윤수홍;박은주;조수열;최현태
    • Environmental Analysis Health and Toxicology
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    • v.6 no.3_4
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    • pp.123-132
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    • 1991
  • Acute poisoning with organic solvents and other volatile compounds now usually follows deliberate inhalation (volatile substance abuse) or ingestion of these compounds. The effect of butane gas inhalation was analyzed for serum, liver, brain, lung and muscle. And the observations are revealed on rat cholinesterase activity, lactatedehydrogenase activity and electrophoretic pattern of lactatedehydrogenase isozyme. The results are as follows: 1. The rat cholinesterase activity on serum, liver and muscle show the decreased by increasing of inhalation time of butane gas in particular the lung cholinesterase activity was greatly affected. 2. Butane gas inhalation brought out the lactatedehydrogenase activity increased of the serum and the tissues and had an important effect especially in both the liver and muscle 1actatedehydrogenase activities. 3. Each tissue was found to have a characteristic distribution of lactatedehy-drogenase isozymes on celluloseacetate electrophoresis and the development of inhalation time is shown the disappearance and diffusion of band. The toxicity of butane gas inhalation was most prominence in the liver and lung toxicity was occurred also.

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Oxidative DNA damage and its repair enzyme expression induced by welding fume inhalation.

  • Kim, Soo-Jin;Paik, Sang-Gi;Yu, Il-Je;Oky Maeng;Hyun, Jin-Suk;Sung, Jae-Hyuk;Han, Jeong-Hee;Maeng, Seung-Hee
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.126-126
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    • 2003
  • Welding fume (WF) induces pulmonary disease including pneumoconiosis. To investigate whether reactive oxygen species-induced oxidative DNA damage occurs during welding fume exposure and the upregulation of DNA repair mechanisms is accompanied, SPF SD rats were exposed to welding fumes with the concentrations of 65.6${\pm}$2.9 mg/㎥(low dose) and 116.8${\pm}$3.9 mg/㎥ (high dose) of total suspended particulate for 2 hrs per day in an inhalation chamber for a total of 2hrs, 15 or 30 days.(omitted)

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Study on Inhalation Toxicity of 1-Hexene in SD Rats (SD Rats를 이용 1-hexene의 흡입독성 연구)

  • 김현영;임철홍;정용현;이권섭;이성배;이준연;한정희;전윤석;이용묵
    • Environmental Analysis Health and Toxicology
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    • v.16 no.4
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    • pp.211-221
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    • 2001
  • The purpose of this study was to investigate the acute (4 hours) and repeated-dose (6 hours a day, 5 days a week, 4 weeks) toxic effects of 1-hexene on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows; 1. The median lethal concentration(LC$_{50}$) was estimated 52,694 ppm (confidence limit 95%; 49,494~55,447 ppm) in acute inhalation. Abnormal clinical signs related to the 1-Hexene were not observed with the acute inhalation dose. Cross findings of necropsy revealed on evidence of specific toxicity related to the 1-hexene. II. By repeated inhalation exposure the body weight of male were more or less reduced by the dose of 2,500 ppm and 5,000 ppm compared with control group. However there were no significant variation hematology and blood biochemistry for the exposed rats compared with the control rats. Abnormal clinical signs and gross findings of necropsy related to the 1-hexene were not shown. In conclusion when we exposed 1-hexene to SD rats for 4 weeks, 5 days per week, 6 hours per day, the Lowest observed effect level (LOEL) was over 2,500 ppm and Non observed effect level (NOEL) was below 500 ppm.

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Inhalation toxicity assesment of C.I.No. Reactive Red 195 in Rats (아조계 반응성염료 C.I.No. Reactive Red 195의 흡입독성평가)

  • Chung, Yong Hyun;Han, Jeong Hee;Song, Kyung Seuk;Kim, Hyeon Yeong;Lee, Sung Bae;Yu, Il Je
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.11 no.3
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    • pp.198-205
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    • 2001
  • Many reactive dyes have been used in occupational settings without knowing their toxicity and health hazard information. To investigate the toxicity of reactive dye, C.I.No. Reactive Red 195 was exposed to male and female Sprague Dawley rats by inhalation for 28 days. The rats were exposed C.I.No. Reactive Red 195 for 6 hrs per day and 5days per week. The concentrations for the inhalation exposure were 0, 10, 40 and $160mg/m^3$. After 4 weeks of exposure, rats were examined for exposure related changes through pathology, blood biochemistry and hematology. There were no dose related changes including clinical signs, body weight and relative organ weight changes, hematological and biochemical and histopathological findings. The results indicate that no observed adverse effect level (NOAEL) of 28 days inhalatrion toxicity test for C.I.No. Reactive Red 195 was $160mg/m^3$.

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Formaldehyde 가스 흡입에 의한 마우스의 급성독성 및 소핵 유발성에 관한 연구

  • Kim, Choong-Yong;Kim, Kyun;Shim, Jeom-Soon;Kim, Yong-Hwa;Roh, Jung-Koo
    • Toxicological Research
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    • v.7 no.1
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    • pp.61-71
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    • 1991
  • The acute and genetic effect of formaldehyde on mice through inhalation route was studied. The Riley's chamber with one stack of cage was used for the exposure and the micronucleus test was performed under unprecedently maximum exposure concentration. LC50's of formaldehyde in mice by whole body exposure for 4 hours were 105.5 ppm with 95% confidence interval of 72.6 ppm and 143.2 ppm for male, and 159.2 ppm with 95% confidence interval of 116.5 ppm and 272.7 ppm for female. Cinicial symptoms by acute exposure were salivation, lacrimation, and abnormal respiration.

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