• 한국환경보건학회지
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• 제49권3호
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• pp.169-177
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• 2023

Background: The Korea Centers for Disease Control and Prevention (KCDC) has identified cases of people suspected of suffering lung disease potentially caused by chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) used in humidifier disinfectants (HDs). The Korean Ministry of Environment (MoE) epidemiological investigation and toxicity test study found that HDs caused health damage such as asthma and lung disease. Objectives: The main purposes of this study were to classify the HD exposure rating and to analyze the exposure characteristics that affect exposure to CMIT/MIT HDs. Methods: The exposure characteristics and socio-demographic characteristics of victim participants using CMIT/MIT HDs were investigated through questionnaires. An inhalation no observed adverse effect level (NOAEL) for CMIT/MIT was produced based on inhalation toxicity values. Exposure ratings (class 1~class 2) were cross-tabulated with clinical ratings (acceptable~unacceptable). A correlation analysis was conducted with the main exposure characteristics that affect the exposure concentration of CMIT/MIT HDs. Results: The concentration in indoor air of CMIT/MIT was 8.75±25.40 ㎍/m³, and the exposure concentration was 2.30±6.29 ㎍/m³. The CMIT/MIT exposure rating of 67 participants with high exposures of not more than MOE 100 were evaluated as 14.5%, while the damage participants who matched the clinical rating made up 4.5%. The exposure concentration of CMIT/MIT showed a positive correlation with the daily usage amount and usage frequency, and a negative correlation with volume of the indoor environment. Conclusions: A new exposure rating could be suggested and calculated based on the MOE, and the factors affecting the exposure concentration could be identified.

• 한국입자에어로졸학회지
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• 제9권4호
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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.

• 한국식품위생안전성학회:학술대회논문집
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• 한국식품위생안전성학회 2002년도 춘계학술발표대회 및 심포지움
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• pp.216-216
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• 2002

Generally, tobacco smoking has noxious effects such as DNA damage, lung cancer induction, coronary artery disease. Nowadays, as concerns on health and longevity increases, a huge variety of products that aim to assist to quit smoking or reduce addictive symptoms such as nicotine patches are developed and manufactured with safely evaluation, but the safety of the most recent products of interest which do not contain tobacco and nicotine, and shape cigarettes is not evaluated and guaranteed relatively. In this study, we used H-menthol(nicotine free-tobacco fine) which are widely consumed through the world to evaluate the single and repeated dose inhalation toxicity and genotoxicity of H menthol (Nicotine free-tobacco free) herbal cigarettes provided by Cigastop Ltd. in ICR mice.

• 한국산업보건학회지
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• 제24권2호
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• pp.146-151
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• 2014

Objectives: Chrysotile is mineralogically distinct from amphiboles, displaying a notably different chemical structure. The thin sheets that form chrysotile fiber lead to the ability of the lung/macrophage system to decompose the chrysotile fibers. This study was performed in order to compare the physicochemical characteristics of Korean asbestos with those of Canadian amphiboles. Materials: An acid solubility test for each test substance was done to compare pH 4.5 and pH 1.2 distilled water. Asbestos fibers which had been placed in acid solutions for five days, five weeks and weeks were analyzed with a transmission electron microscope equipped with an energy dispersive X-ray spectrometer (TEM-EDS). Results: The composition element (Mg) of Korean chrysotile, Korean anthophyllite and Canadian amosite significantly decreased from 5 days and also decreased significantly after 5 weeks and 10 weeks. Only the composition (Mg) of Canadian crocidolite did not change under any conditions. From 5 days, the Mg of Korean chrysotile, Korean anthophyllite and Canadian amosite were significantly lower than before the acid treatment, but there were no changes over time or by the pH of the acid solutions. Particularly after 10 weeks, the composition (Mg) of Korean chrysotile in the pH 1.2 acid solution showed a rapid reduction of 15.86%. Conclusions: Korean chrysotile was very weak in an acid environment, beginning to show significant changes after 5 days. The Mg component rapidly decreased after 10 weeks in the pH 1.2 acid solution.

• 대한약침학회지
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• 제12권4호
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• pp.5-32
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• 2009

Objectives: This study was performed to analyse single dose toxicity of pure melittin(Sweet Bee Venom-Sweet BV) extracted from the bee venom by utilizing protein isolation method of gel filtration. Methods: All experiments were conducted at Biotoxtech, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Six weeks old female Sprague-Dawley rats were chosen for the pilot study and determined 30㎎/㎏ which is 4285 times higher than the clinical application dosage as the high dosage, followed by 15 and 7.5㎎/㎏ as mid and lose dosage, respectively. Equal amount of excipient to the Sweet BV experiment groups was administered as the control group. Results: 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all groups, and higher occurrence in the higher dosage groups. Hyperemia and movement disorder diminished with elapsed time. 3. For the weight measurement, male groups showed larger reduction in weight in accordance with higher dosage. Female groups didn't s how significant changes. 4. To verify abnormalities of organs and tissues, cerebellum, cerebrum, liver, lung, kidney, and spinal nerves were removed and conducted histological observation with H-E staining. No abnormalities were detected in any of organs and tissues. 5. One female rat in the 30㎎/㎏ group had amputated toe near the administered area and histopathological finding was hemorrhage with inflammation. This is presumed as a secondary infection after the administration of Sweet BV. Conclusion: Above findings suggest Sweet BV is relatively s safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5727-5731
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• 2015

Background: There is a long standing interest in natural compounds especially those with a high polyphenolic content and high scavenging activity for hazardous free radicals. Cornus mas (CM) fruit is well known for its antioxidant activities; however, its toxicity against human cancers needs to be addressed. Here, we investigated selective anticancer effects of CM on different human cancer cells. Materials and Methods: A hydro-alcoholic extract of CM (HECM) was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was assessed with respectto DPPH radical scavenging. MTT assays were used to evaluate the cytotoxicity of different doses of CM (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer) and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.05) or very significant (P<0.001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, HECM reduced the cell viability to values below 26%, even at the lowest doses. In all cases, $IC_{50}$ was obtained at doses below $5{\mu}g/ml$. The mean growth inhibition was 81.8%, 81.9%, 81.6% and 79.3% in SKOV3, MCF-7, PC-3 and A549 cells, respectively. Conclusions: Altogether, to our best knowledge, this is a first study that evaluated toxicity of a HECM with high antioxidant activity in different human cancer cells in vitro. Our results indicated that a hydro-alcoholic extract of CM possesses high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important and relevant than a maximally tolerated one.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.71-71
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• 1993

Carboxylesterase is widely distributed in the tissues of vertebrates, insects, plants and mycobacteria. Among various tissues of animals and humans, the highest esterase activity with various substrates is found in the liver. Kidney has moderate carboxylesterase activity in the proximal tubules. Considerable esterase activity is also found in the small intestine epithet elial cells and serum of mammals. Besides these tissues, carboxylesterase has been found in the lung, testis, adipose tissue, nasal mucosa and even in the central nervous system. Hepatic microsomal carboxylesterase catalyzes the hydrolysis of a wide variety of endogenous and exogenous compounds such as carboxylester, thioester and aromatic amide. Since carboxylesterases are important for metabolic activation of prodrugs and detoxification of xenobiotics, differences in substrate specificity and immunological properties of this enzyme are important in connection with choosing a suitable laboratory animal for the evaluation of biotransformation and toxicity of drugs. On the other hand, liver, kidney, intestine and serum were found to contain multiple forms of carboxylesterases in animal species and humans. In fact, we have purified more than fifteen isoforms of carboxylesterases from microsomes of liver, kidney and intestinal mucosa of nine animal species and humans. and characteristics of these isoforms were compared each other in terms of their physical and immunochemical properties. On the other hand, we have reported that hepatic microsomal carboxylesterases are induced by many exogenous compounds such as phenobarbital, polycyclic aromatic hydrocarbons, Aroclor 1254, aminopyrine and clofibrate. Later, we showed that some isoforms of hepatic carboxylesterase were induced by glucocorticoids such as dexamethasone and 16 ${\alpha}$-carbonitrile, but other isoforms were rather inhibited by these compounds. These findings indicate that involvement of carboxylesterases in the metabolism and toxicity of drugs should be explained by the isoforms involved. Since 1991, we have carried out detailed research investigating the types of carboxylesterases involved in the metabolic activation of CPT-11, a derivative of camptothecin, to the active metabolite, SN-38. The results obtained strongly suggest that some isoforms of carboxylesterase of liver microsomes and intestinal mucosal membrane are exclusively involved in CPT-11 metabolism. In this symposium, the properties of carboxylesterase isoforms purified from liver, kidney and intestine of animal species and humans are outlined. In addition, metabolism of CPT-11, a novel antitumor agent, by carboxylesterases in relation to the effectiveness will also be discussed.

• Environmental Analysis Health and Toxicology
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• 제25권3호
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• pp.215-222
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• 2010

The market size of engineered nanoparticles is rapidly increasing due to the fast application of nanotechnologies into different industries and consumer products. The development of new technology and materials has improved human's quality of life, but it also entails the possibility of exposure to new materials. In this study, we compared the distribution in the body by the inflow of silver nanoparticles having another diameter and shape at 1 h or 24 h after injection via the tail vein. And, we compared the cell composition and cytokine concentration in BAL fluid, and histopathological changes. As results, discharge of silver nanoparticles having small diameter and sphere shape was more rapid than that of big diameter or plate shape. It is estimated that the toxicity in liver and lung was proportional to accumulation level. The persistence of inflammation was also longer in mice treated with plate shape. Consequently, we suggest that the first choice of silver nanoparticles having small diameter and sphere shape in applying is desirable.

• 한국산업보건학회지
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• 제29권2호
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• pp.119-140
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• 2019

Objectives: This study was based on the occurrence of a coffee roasting process-related disorder(bronchiolitis obliterans; published by NIOSH in the US) among workers exposed to chemicals called diacetyl in a coffee processing facility. Flavorings added to coffee contain diacetyl and 2,3-pentanedione, all of which are subject to exposure in a number of food manufacturing processes, including coffee roasting, grinding, and packaging. Therefore, this study aims to review the toxicity to workers related to food processing and food additive manufacturing to prevent occupational diseases. Methods: We surveyed the related literature, domestic and international references, and the status of relevant domestic and foreign professional organizations. The present situation of workers was investigated by reviewing literature on the safety and health of workers in the coffee roasting process using domestic and foreign literature and presentations. Expert advisory opinions were reflected, and experts were consulted by participating in domestic and overseas academic conferences. Results: Most of the fragrance materials for coffee were harmful and hazardous substances according to the GHS classification, and research was carried out through a second external consultation. A literature review on the measurement of air pollutant emissions from coffee roasters and the estimation of air pollutant emissions during coffee roasting examined the characteristics of pollutants emitted during coffee roasting. Conclusions: Two chemicals identified as causing bronchiolitis obliterans in the coffee roasting process are believed to explain why the disease is difficult to treat. This information can be used effectively in the future prevention of this disease. Future studies should clearly identify the potential for toxicity of alpha-diketones and the bases of OELs in relation to the occurrence of obstructive bronchiolitis, including measurement of various organic compounds and alpha-diketones from ground coffee, as well as various coffee grinds and coffee bean varieties. In particular, it is necessary to clarify the current understanding of the dose-response relationship between alpha-diketone and lung disease in workers involved in coffee roasting.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.393-402
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• 2019

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with $IC_{50}$ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect $I_{Na}$, $I_{Ks}$ or $I_{K1}$, but decreased $I_{hERG}$ in a dose-dependent manner ($IC_{50}$: $6.53{\mu}M$). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to $3{\mu}M$, but it at $10{\mu}M$ induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.