• 약학회지
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• 제58권1호
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• pp.62-70
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• 2014

A 28-day repeated-dose oral toxicity test was performed to determine the no-observed-effect level (NOEL) and establish an optimum dose of the highly toxic Aconiti Ciliare Tuber (ACT) used as a folk remedy. Repeated oral doses of 1,250, 2,500, and 5,000 mg/kg/day of the hot water extract of ACT were administered to five male and five female Sprague-Dawley rats in each group for 4 weeks. The indicators for toxicity included results of examination of common symptoms and changes in weight and feed intake, eye test, urinalysis, hematological and serum biochemical analyses, and post-mortem weight measurement of organs, and visual inspections. All animals survived at the end of the experiment; in addition, we observed no specific test substance-mediated symptoms. We observed no test substance-mediated changes in body weight and feed intake. We observed statistically significant changes in male OB and pH levels (p<0.05). Further, the biochemical test showed statistically significant changes in the IP value of male rats and $CL^-$valueoffemalerats (p<0.05). However, all changes were within historical data. The post-mortem examinations showed no test substance-mediated changes. Moreover, statistically significant changes under the test conditions were confirmed to have been caused by factors other than the test substance. Thus, the maximum NOEL of ACT extract in rats was estimated to be 5,000 mg/kg/day.

• 한국안전학회지
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• 제37권2호
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• pp.10-17
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• 2022

Currently, in Korea, lower and upper tier qualifying quantities of the 97 substances requiring preparation for accidents have been designated. The information on the submission of chemical accident prevention management plan varies depending on whether the handling volume is above or below the lower or upper qualifying quantity. Because the criteria of the lower and upper qualifying quantities of substance requiring preparation for accidents are not stipulated in the Chemical Substances Control Act, this study attempted to establish a criterion through significance verification. In addition, the study investigated whether these qualifying quantities are related to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), toxic concentration endpoint, and National Fire Protection Association (NFPA). Finally, by comparing the risk categorization of the GHS, endpoint, and NFPA, it was evaluated whether the circulation-volume-based risk categorization of the substance requiring preparation for accidents that are in the top 13 is appropriate. The qualifying quantities of benzene, toluene, and sulfuric acid needed to be adjusted upward, while those of methyl alcohol and ammonia were adjusted downward from the current qualifying quantities. It is required to establish a quantified criterion that fully reflects the domestic situations in Korea and various indicators such as toxicity, physicochemical properties, and circulation volume for the qualified criterion of hazardous chemical substances. The study is expected to be helpful in establishing an efficient system by systematizing the criterion for qualifying quantity.

• 대한임상독성학회지
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• 제10권1호
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• pp.8-14
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• 2012

Purpose: The Tox-Info system is a poisonous substance information database developed by the Korean National Institute of Food and Drug Safety Evaluation. The aim of this study was to estimate the coverage effectiveness of the Tox-Info system by comparing the toxic substances included in the database with the distribution of the toxic substances implicated in the cases of intoxicated patients presenting to emergency departments. The secondary aim of the study was to propose any additional substances that should be added to the database. Methods: We retrospectively reviewed the medical records of patients suffering with toxic exposure who had visited any of 12 selected emergency departments in Korea from January 2010 to December 2011. The identified toxic substances were classified into groups including prescription drugs, agricultural chemicals, household products, animals or plants, herbal drugs, and others. We calculated the coverage rate of the Tox-Info database relative to the number of intoxication cases and the type of toxic substances involved. Results: A total of 5,840 intoxicated patient records were collected. Their mean age was $46.6{\pm}20.5$ years and 56.2% were female. Of the total intoxication cases, 87.8% of the identified toxic substances were included in the Tox-Info database, while only 41.6% of all of the types of identified toxic substances were included. Broken down by category, 122 prescription drugs, 15 agricultural chemicals, 12 household products, 14 animals or plants and 2 herbal drugs involved in poisoning cases were not included in the Tox-info database. Conclusion: This study demonstrated the clinical usefulness of the Tox-Info system. While 87.8% of the substances involved in the cases were included in the Tox-Info database, the database should be continuously updated in order to include even the most uncommon toxic substances.

• 디지털융복합연구
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• 제12권8호
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• pp.101-112
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• 2014

본 연구에서는 한국의 제품 안전관리를 위한 시나리오 기반의 리스크 평가기법을 개발, 제시한다. 이를 위해 먼저 한국의 제품 안전관리를 위한 관련 규제정책을 살펴보고, 이 법의 시행을 위해 필요한 제품 리스크 평가기법을 일반상해의 경우와 유해물질의 경우로 구분하여 제시한다. 본 연구에서 제시되는 리스크 평가기법의 특징은 다음과 같다. (i) 제품의 사용 시 발생할 수 있는 부상 시나리오에 기반을 둔 방법이다. (ii) 시나리오 발생 확률과 인체에 미치는 부상 심각도를 바탕으로 리스크를 평가한다. (iii) 유해물질 함유 제품의 경우 유해물질의 인체에의 위해성 여부를 확인한 후 부상 심각도를 고려해서 리스크를 평가한다. 부상 시나리오의 확률을 결정하기 위하여 본 연구에서는 시나리오를 몇 가지 구성 요인으로 분해하고 이들 각각의 요인 확률을 추정하여 전체 시나리오의 확률을 결정한다. 본 연구에서 제시된 기법을 통하여 리스크 평가를 수행한 결과를 제시하고 이를 제품 안전관리를 위한 품목 분류에 활용할 수 있음을 보인다.

• 한국환경보건학회지
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• 제48권3호
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• pp.183-194
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• 2022

Background: No study has examined the regulatory factors associated with fatal health problems due to the use of humidified disinfectants (HD) in South Korea. Objectives: This study aimed to identify and discuss the deficiencies and limitations found in the Toxic Chemical Control Acts (TCCA) that failed to prevent the health risk of chemicals in HD products. Methods: The South Korean TCCA was reviewed focusing on acts in operation from 1994 through the end of 2011, the period when HD was allowed in manufacturing and marketing. Results: The TCCA was the act intended to regulate the toxicity of chemicals in HD products. We found the TCCA to lack three key legal clauses which would have been essential to controlling the health risk of HD. First, there was the exemption of toxic and hazard testing for existing chemicals, including chloromethylisothiazolinone (CMIT), methylisothiazolinone (MIT), and benzalkonium chloride (BKC). Secondly, there were no articles requiring industry to provide animal inhalation test result for polymers such as polyhexamethylene guanidine (PHMG) and Oligo(2-)ethoxyethoxyethyl guanidine chloride (PGH). Finally, there was a lack of articles on examining the risk of products as well as on addressing changes in the usage of products. These articles were found to be generally provided in the US Toxic Substance Chemical Act (TSCA) and the EU Registration, Evaluation and Authorization of Chemicals (REACH). Conclusions: In conclusion, the Ministry of Environment of South Korea had not updated key articles for regulating hazardous chemicals, causing large-scale health problems due to HD which had been fundamentally addressed in chemical-related acts in other countries.

• 한국안전학회지
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• 제35권6호
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• pp.15-24
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• 2020

With the development of the chemical industry, the chemical accident is increasing every year, thereby increasing the risk of accidents caused by chemicals. The Ministry of Environment provides the criteria for determining shelter-in-place or outdoor evacuation by material, duration of accident, and distance from the toxic substance leak. However, it is hard to say that the criteria for determining the transition point are not clear. Transition point mean the time that evacuation method is switched from shelter-in-place to outdoor evacuation. So, the purpose of this study was to calculate appropriate transition point by comparing the cumulative toxic load. Namdong-gu in Incheon Metropolitan City was finally selected as the target area, considering the current status of the population of Incheon Metropolitan City in 2016 and the statistical survey of chemicals in 2016. The target materials were HCl, HF, and NH₃. Modeling was simulated by ALOHA and performed assuming that the entire amount would be leaked for 10 min. Residents' evacuation scenarios were assumed to be shelter-in-place, immediate outdoor evacuation, and outdoor evacuation at an appropriate time after shelter-in-place. Based on the above method, the appropriate transition point from residents located in A(800 m away), B(1,200 m away), C(1,400 m away) and D(2,200 m away) was identified. In HCl, appropriate transition point was after 15 min, after 16 min, after 17 min, after 20 min in order by A, B, C and D. In HF, appropriate transition point was before 1 min or after 16 min, before 4 min or after 19 min, before 5 min or after 20 min, before 14 min or after 26 min in order by A, B, C and D. In NH₃, appropriate transition point at A was before 4 min or after 16. Others are not in chemical cloud. This study confirmed the transition point to minimize the cumulative toxic load can be obtained by quantitative method. Through this, it might be possible to select evacuation method quantitatively that cumulative toxic load are minimal. In addition, if the shelter-in-place is maintained without transition to outdoor evacuation, the cumulative toxic load will increase more than outdoor evacuation. Therefore, it was confirmed that actions to reduce the concentration of chemicals in the room were necessary, such as conducting ventilation after the chemical cloud passed through the site.

• Natural Product Sciences
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• 제5권2호
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• pp.107-111
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• 1999

To investigate less toxic antiviral agents from Basidiomycetes, EA, the water soluble substance, was isolated from the carpophores of Elfvingia applanata (pers.) Karst. Anti-varicella zoster virus (Oka strain; anti-VZV/Oka) activity of EA was examined in MRC-5 cells by plaque reduction assay in vitro. And the combined antiviral effects of EA with nucleoside anti-VZV agents, acyclovir and vidarabine, were examined on the multiplication of VZV/Oka. EA exhibited a concentration-dependent reduction in the plaque formation of VZV/Oka with a 50% effective concentration $(EC_{50})$ of $464.14\;{\mu}g/ml$. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combination of EA with acyclovir showed more potent synergism with CI values of $0.18{\sim}0.62$ for $50{\sim}90%$ effective levels than that of EA with vidarabine with CI values of $0.67{\sim}1.04$.

• 생약학회지
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• 제30권1호
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• pp.25-33
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• 1999

In order to find less toxic antiviral agents from basidiomycetes, EA, the water soluble substance, was prepared from the carpophores of Elfvingia applanata (Pers.) Karst. EA was examined for antiviral activity against five strains of pathogenic viruses such as encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV) Indiana and New Jersey strains, influenza A virus (Flu A), and varicella zoster virus (VZV) in vitro. Antiviral activity was evaluated by plaque reduction assay. Among five strains of viruses tested, EA exhibited the most potent antiviral activity against VSV Indiana strain with 50% effective concentration $(EC_{50})$ of 0.104 mg/ml in Vero cells, and its selectivity index (SI) was 36.5. EA was also examined for the virucidal activity, antiviral activity in preincubation on VSV Indiana strain in order to examine possible mode of antiviral activity. Preincubation of Vero cells with EA did not confer protection against VSV, however, prolonged exposure of cells to EA inhibited the replication of virus dose-dependently. In virucidal activity, the titer of infectious virus did not decrease significantly.

• 생약학회지
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• 제30권3호
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• pp.244-249
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• 1999

In order to find less toxic antiviral agents from Basidiomycetes, EA, the water soluble substance, was prepared from the carpophores of Elfvingia applanata(Pers.) Karst. Antiviral activity of EA against vesicular stomatitis virus [Indiana serotype, VSV(IND)] was examined in Vero cells using plaque reduction assay in vitro. And the combined antiviral effects of EA with interferon (IFN) alpha or gamma were examined on the multiplication of VSV(IND). EA caused a concentration-dependent reduction in the plaque formation of VSV(IND) with 50% effective concentration $(EC_{50})$ of $104.02\;{\mu}g/ml$. The results of combination assay were evaluated by the combination index (CI) that was analysed by the multiple drug effect analysis. All cases of the combination of EA with IFN alpha or IFN gamma showed potent synergism with CI values of $0.38{\sim}0.52$ for $50{\sim}90%$ effective levels.

• Toxicological Research
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• 제31권4호
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• pp.403-414
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• 2015

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.