• Title/Summary/Keyword: Inhalation Toxicology

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A Case of Organophosphate Insecticide Intoxication by Repetitive Parenteral Exposure, Complicated with Intermediate Syndrome and Acute Pancreatitis (반복적인 비경구노출에 의한 유기인계 중독: 중간형증후군과 급성췌장염 1례)

  • Oh, Se-Hyun;Kang, Hui-Dong;Lee, Boo-Soo
    • Journal of The Korean Society of Clinical Toxicology
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    • v.4 no.2
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    • pp.161-165
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    • 2006
  • Organophosphate insecticides, commonly used in agriculture, are a gradually increasing cause of accidental and suicidal poisoning. Intoxication can occur by ingestion, inhalation or dermal contact. Exposure to organophosphorus agents causes a sequentially triphasic illness consisting of the cholinergic phase, the intermediate syndrome, and organophosphate-induced delayed polyneuropathy. Acute pancreatitis as a rare complication of organophosphate intoxication has also been infrequently observed. We report a case of intoxication with organophosphate (phos-phamidon) by parenteral exposure (inhalation and/or dermal contact). A 34-year-old male patient was transferred to our Emergency Medical Center and was intubated due to a progressive respiratory failure. He presented with meiotic pupils, cranial nerve palsies, weak respiration, and proximal limb motor weaknesses without sensory changes. He had been employed in filling syringes with phosphamidon during the previous month. Because the patient's history and symptoms suggested organophosphate intoxication with intermediate syndrome, he was mechanically ventilated for 18 days with continuous infusion of atropine and pralidoxime (total amounts of 159 mg and 216 g, respectively). During his admission, hyperamylasemia and hyperli-pasemia were detected, and his abdominal CT scan showed a finding compatible with acute pancreatitis. He was administered a conservative treatment with NPO and nasogastric drainage. The patient was discharged and showed neither gastrointestinal nor neurologic sequelae upon follow up at one week and three months.

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Inhallation of e-Cigarette Cartridge Solution Aggravates Allergen-induced Airway Inflammation and Hyper-responsiveness in Mice

  • Lim, Heung Bin;Kim, Seung Hyung
    • Toxicological Research
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    • v.30 no.1
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    • pp.13-18
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    • 2014
  • Electronic cigarettes (e-cigarettes) are becoming increasingly popular worldwide and their cellular effects warrant further evaluation. In this study, we investigated the effects of an e-cigarette cartridge solution on allergen related asthmatic airway inflammation (AI) and airway hyperresponsiveness (AHR), when it is delivered by intratracheal route in mice. Asthmatic AI and AHR were induced by systemic sensitization to ovalbumin (OVA) followed by intratracheal, intraperitoneal, and aerosol allergen challenges in BALB/c mice. The cartridge solution of e-cigarette (containing 16 mg/ml nicotine) was diluted 50 times and $100{\mu}l$ of the diluted solution was intratracheally instilled to OVA-sensitized (OVA-S) mice two times a week for 10 weeks. Long-term e-cigarette inhalation elicited no remarkable changes in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase enzymes in serum, however, increased infiltration of inflammatory cells including eosinophils, into airways from blood, aggravated the asthmatic AI and AHR, and stimulated the production of cytokines such as interleukin (IL)-4, IL-5 and IL-13, and OVA-specific IgE production. Our data suggest that the inhalation of e-cigarette solutions can function as an important factor to exacerbate the allergy-induced asthma symptoms. Further studies are needed to address the effects of e-cigarette solutions on human health.

Development and Performance Evaluation of Aerosol Generator of MWCNTs for Inhalation Toxicology (흡입 독성 평가를 위한 다중벽 탄소나노튜브의 에어로졸 발생장치 개발 및 성능 평가)

  • Lee, Gun-Ho;Jeon, Ki Soo;Yu, Il Je;Ahn, Kang-Ho
    • Particle and aerosol research
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    • v.9 no.4
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    • pp.231-238
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    • 2013
  • Carbon nanotubes (CNTs) are one of the nanomaterials that were discovered by Iijima in 1991 for the first time. CNTs have long cylindrical and axi-symmetric structures. CNTs are made by rolling graphene sheets. Because of their large length-to-diameter ratio, they are called nanotubes. CNTs are categorized as single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs) based on the shell structures. CNTs are broadly used in various fields, such as scanning probe microscopy, ultra fine nano balance and medicine, due to their extraordinary thermal conductivity, electrical and mechanical properties. Because long, straight CNTs have the same shape as asbestos, which cause cancer in cells lining the lung, there have been many studies on the effects of MWCNTs on human health that have been conducted. Stable atomization of CNTs is very important for the estimation of inhalation toxicity. In the present study, electro-static assisted axial atomizer (EAAA), which is the instrument that uses MWCNTs and aerosolizes them by transforming the single fiber shape using ultrasonic dispersion and electric field, was invented. EAAA consists of a ultrasonic bath for dispersion of MWCNTs and a particle generator for atomizing single fibers. The performance evaluation was conducted in order to assess the possibilities of 6-hour straight atomization with stability, which is the suggested exposure time in a day for the estimation of inhalation toxicity.

Model Algorithms for Estimates of Inhalation Exposure and Comparison between Exposure Estimates from Each Model (흡입 노출 모델 알고리즘의 구성과 시나리오 노출량 비교)

  • Park, Jihoon;Yoon, Chungsik
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.29 no.3
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    • pp.358-367
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    • 2019
  • Objectives: This study aimed to review model algorithms and input parameters applied to some exposure models and to compare the simulated estimates using an exposure scenario from each model. Methods: A total of five exposure models which can estimate inhalation exposure were selected; the Korea Ministry of Environment(KMOE) exposure model, European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment(ECETOC TRA), SprayExpo, and ConsExpo model. Algorithms and input parameters for exposure estimation were reviewed and the exposure scenario was used for comparing the modeled estimates. Results: Algorithms in each model commonly consist of the function combining physicochemical properties, use characteristics, user exposure factors, and environmental factors. The outputs including air concentration ($mg/m^3$) and inhaled dose(mg/kg/day) are estimated applying input parameters with the common factors to the algorithm. In particular, the input parameters needed to estimate are complicated among the models and models need more individual input parameters in addition to common factors. In case of CEM, it can be obtained more detailed exposure estimates separating user's breathing zone(near-field) and those at influencing zone(far-field) by two-box model. The modeled exposure estimates using the exposure scenario were similar between the models; they were ranged from 0.82 to $1.38mg/m^3$ for concentration and from 0.015 to 0.180 mg/kg/day for inhaled dose, respectively. Conclusions: Modeling technique can be used for a useful tool in the process of exposure assessment if the exposure data are scarce, but it is necessary to consider proper input parameters and exposure scenario which can affect the real exposure conditions.

Twenty-Eight-Day Repeated Inhalation Toxicity Study of Nano-Sized Neodymium Oxide in Male Sprague-Dawley Rats

  • Kim, Yong-Soon;Lim, Cheol-Hong;Shin, Seo-Ho;Kim, Jong-Choon
    • Toxicological Research
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    • v.33 no.3
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    • pp.239-253
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    • 2017
  • Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide ($Nd_2O_3$) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized $Nd_2O_3-containing$ aerosols via a nose-only inhalation system at doses of $0mg/m^3$, $0.5mg/m^3$, $2.5mg/m^3$, and $10mg/m^3$ for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the $2.5mg/m^3$ and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the $0.5mg/m^3$ treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the $0.5mg/m^3$ group, but were exacerbated in the $10mg/m^3$ group. The lowest-observed-adverse-effect concentration of nano-sized $Nd_2O_3$ was determined to be $0.5mg/m^3$, and the target organ was determined to be the lung, under the present experimental conditions in male rats.

A Study on GHS Classification of 3-Methylpentane by Subacute Inhalation Toxicity (아급성흡입독성시험을 이용한 3-Methylpentane의 GHS 분류·표시)

  • Chung, Yong Hyun;Han, Jeong Hee;Shin, Seo Ho
    • Journal of the Korean Institute of Gas
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    • v.21 no.1
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    • pp.6-17
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    • 2017
  • Objectives : The purpose of this study was to obtain information regarding Globally Harmonized System(GHS) classification and health hazards that may result from a 4 weeks inhalation exposure of 3-Methylpentane in Sprague-Dawley rats. Methods : The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 412(Subacute Inhalation Toxicity). The Rats were divided into 4 groups(5 male and 5 female rats in each group) and exposed to 0 ppm, 284 ppm, 1,135 ppm, 4,540 ppm 3-Methylpentane in each exposure chamber for 6 h/day, 5 days/week, for 4 weeks. After two weeks, the test animals were autopsied and carried out blood test and biochemical tests and histopathological examination. We used PRISTIMA (Toxicology data management system) to confirm the system and to have confidence of the raw data. Results : No death and particular clinical presentation including weight change and change of feed rate was observed. Relationship between dose, gender and response was also not significantly changed in hematologic examination, biochemical examination of blood and blood coagulation time. The histopathologic lesions caused by the test substance did not appear. Conclusions : NOAEL(No Observable Adverse Effect Level) of 3-Methylpentane is more than 4,540 ppm in male group and female group and the Ministry of Employment and Labor Guidance Announcement No. 2013-37(criteria for the classification marks and Safety of Chemicals) Specific target organ toxicity(repeated exposure) was determined with a substance that is not the separator material.

Use of Tumor Necrosis Factor Receptor (TNFR)-Knockout Mice to Probe the Mechanism of Chemically-Induced Asthma

  • Karol, Meryl H.;Matheson, Joanna M.;Lange, Robert W.;Lemus, Ranulfo;Luster, Michael I.
    • Toxicological Research
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    • v.17
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    • pp.305-307
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    • 2001
  • Toluene diisocyanate (TDI) is widely used in the manufacture of polyurethanes and is a recognized cause of occupational asthma. Although extensive investigations have been undertaken, the molecular mechanism(s) of the disease is still unclear. We hypothesized that inflammatory cytokines are required during both the sensitization and elicitation phases of the disease and have utilized TNF-R knock-out (KO) mice to address the hypothesis. Black C57 TNFR knock-out mice were exposed to TDI by sc injection and challenged by inhalation of 100 ppb TDI vapor. Control animals included: wild type C57 animals, sham-exposed animals that were challenged with TDI, and animals that were injected with anti-TNF antibodies prior to sensitization and again prior to challenge. Total IgE was increased in the knock-out animals compared with the wild type sensitized and challenged animals whereas TDI-specific IgG antibodies did not differ significantly in KO and wild type animals. There was less inflammation in the nares and trachea in KO animals compared with the wild type animals exposed to TD1 as well as less goblet cell hyperplasia and epithelial damage. Airway reactivity was assessed in animals treated with anti-TNF$\alpha$ antibody and found to be substantially reduced compared with that in sensitized and challenged animals. These results indicate that TNF$\alpha$ plays a role in the immunologic and physiologic responses and in airways inflammation in this animal model and suggests a role for TNF in occupational asthma due to TDI.

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Initial Risk Assessment of Acetanilide with Respect to Human Health (아세트아닐리드의 초기 인체위해성 평가)

  • Lee, Su-Rae;Park, Seon-Ju;Lee, Mi-Kyung;Nam, U-Kyung;Chung, Sun-Hwa;Seog, Geum-Su;Park, Kwang-Sik;Kim, Kyun;Kim, Yong-Hwa
    • Environmental Analysis Health and Toxicology
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    • v.15 no.1_2
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    • pp.31-37
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    • 2000
  • Acetanilide may be released into the environment through air and wastewater from its production and use sites and exposed to human. Acetanilide is known to produce an analgesic effect and may pose adverse effects on human health by overly exposure. According to the EUSES system, acetanilide showed a high MOS (Margin of safety) value exceeding 6$\times$10$^4$ on a regional exposure, which is safe enough for public health. Whereas the lowest MOS value in dermal exposure was estimated as 3$\times$10$^{-4}$ on a local basis (workplace), the risk could be partly counteracted by taking preventive measures such as using mask and globes and good ventilation in the work places. Acetanilide may pose a potential risk for workers by dust inhalation. For the sake of health protection in the work places, additional data should be accumulated with respect to repeated dose toxicity, reproduction toxicity and developmental toxicity, etc. It is, therefore, recommended that acetanilide should be a candidate for further work to supplement the lacking data until it is proved to be safe in the occupational health aspects.

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Hepatic Tissue Changes by the 1,3-Dichloropropanol Inhalation in the Rat (1, 3-Dichloropropanol 흡입에 의한 랫드간의 조직변화에 관한 연구)

  • Kim Sung-Hwa;Park O-Sung;Lee Sung-Bae;Choi Jong-Yun;Kwon Hyo Jung;Son Sek-Woo;Park Il-Kwon;Lee Kyoung-Youl;Son Hwa-Young;Lee Mee-Young;Lee Guen-Jwa;Kim Hyeon-Young;Lee Kang-Yi
    • Toxicological Research
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    • v.21 no.2
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    • pp.141-150
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    • 2005
  • 1,3-Dichloro-2-propanol (1,3-DCP) is known as chloride chemicals and causes severe hepatotoxic agent. The Ito cells and Kupffer's cells of the liver in the 5 old F344 Rats were exposed to 1,3-DCP gas chamber for 6 hours/ a day, 5 days/ a week, and 13 weeks, in the 0, 5, 20, 80 ppm, respectively. After then the body weights, liver weights, and relative liver weight to body weight were measured, and the hepatic tissues were prepared by the routine and Immunostain method, and observed by the LM, and EM. In the results, there were severe body weight decrease (p<0.05) in the 80 ppm of the male and female rats. The relative liver weights to the body weight were increased relate with exposed 1,3-DCP concentration (P<0.001). Inflammatory cells, infiltration was observed at the perivascular area in the 20 ppm exposed group, and bilirubin pigment infiltration, bile duct hyperplasia, inflammation hepatocytic necrosis, fibrosis were observed in the 80 ppm exposure group. In the 80 ppm exposure group, disarrangement of the endothelial cells, erythrocytes and hepatic cell fragment in the Disse space and numerous migration macrophages were observed in the necrotic area by EM observation. In the immunostained hepatic tissues positive stained ED1 cells were extremely increased (P<0.05) in central vein area, but ED2 was weakly positive immunostained in the 80 ppm exposed group. Immunostained desmin was observed in the Ito cell. It was no difference in the low and medium exposed group but it was typical increase in the necrotic area. In conclusion, These results suggest that NOAEL of 1,3-DCP may be 5 ppm in rats and the Immunostained of desmin, ED1 and ED2 positive cells activated in the inflammatory liver were related to the exposure volume and density. The increase of the Ito cells were related to the severe phagocytosis of the Kupffer's cells.

Arsenic Poisoning (비소 중독)

  • Kim Yang Ho;Lee Ji Ho;Sim Chang Sun;Jeong Kyoung Sook
    • Journal of The Korean Society of Clinical Toxicology
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    • v.2 no.2
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    • pp.67-71
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    • 2004
  • Arsenic poisoning has three types of poisoning. First, acute arsenic poisoning is usually caused by oral intake of large amount of arsenic compound with purpose of homicide or suicide. Second, chronic arsenic poisoning is caused by inhalation of arsenic in the occupational setting or by long-term oral intake of arsenic-contaminated well water. Third, arsine poisoning occurs acutely when impurities of arsenic in non-ferrous metal react with acid. Clinical manifestation of acute arsenic poisoning is mainly gastrointestinal symptoms and cardiovascular collapse. Those of chronic poisoning are skin disorder and cancer. Arsine poisoning shows massive intravascular hemolysis and hemoglobinuria with acute renal failure. Exposure evaluation is done by analysis of arsenic in urine, blood, hair and nail. Species analysis of arsenic is very important to evaluate inorganic arsenic acid and mono methyl arsenic acid (MMA) separated from dimethyl arsenic acid (DMA) and trimethyl arsenic acid (TMA) which originate from sea weed and sea food. Treatment with dimercaprol (BAL) is effective in acute arsenic poisoning only.

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