• Title/Summary/Keyword: Drug safety data

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Establishment of Acceptable Daily Intakes (ADIs) and Risk Assessment for Ephedrine, Menichlopholan, Anacolin, and Etisazole Hydrochloride

  • Min Ji Kim;Ji Young Kim;Jang Duck Choi;Guiim Moon
    • Korean Journal of Environmental Agriculture
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    • v.41 no.4
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    • pp.261-275
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    • 2022
  • BACKGROUND: Prior to implementing a positive list system (PLS), there is a need to establish acceptable daily intake (ADI) and maximum residue limit (MRL) for veterinary drugs that have been approved a few decades ago in South Korea. On top of that, chronic dietary exposure assessment of veterinary drug residues should be performed to determine whether the use of these veterinary drugs would cause health concerns or not. METHODS AND RESULTS: To establish the ADI, the relevant toxicological data were collected from evaluation reports issued by international organizations. A slightly modified global estimate of chronic dietary exposure (GECDE) model was employed in the exposure assessment owing to the limited residual data. Therefore, only the ADI of ephedrine was established due to insufficient data for the other veterinary drugs. Thus, instead of ADI, the threshold of toxicological concern (TTC) value was used for the other drugs. Lastly, the hazard index (HI) was calculated, except for etizazole hydrochloride, due to the potential of mutagenicity. CONCLUSION(S): The HI values of ephedrine, menichlopholan, and anacolin were found to be as high as 6.4%, suggesting that chronic dietary exposure to the residues from these uses was unlikely to be a public health concern. Further research for exposure assessment of veterinary drug residues should be performed using up-todate Korean national health and nutrition examination survey (KNHANES) food consumption data. In addition, all relevant available data sources should be utilized for identifying the potentials of toxicity.

Application and Validation of an Optimal Analytical Method using QuEChERS for the determination of Tolpyralate in Agricultural Products (QuEChERS법을 활용한 농산물 중 제초제 Tolpyralate의 최적 분석법 선발 및 검증)

  • Lee, Han Sol;Park, Ji-Su;Lee, Su Jung;Shin, Hye-Sun;Kim, Ji-Young;Yun, Sang Soon;Jung, Yong-hyun;Oh, Jae-Ho
    • Korean Journal of Environmental Agriculture
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    • v.39 no.3
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    • pp.246-252
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    • 2020
  • BACKGROUND: Pesticides are broadly used to control weeds and pests, and the residues remaining in crops are managed in accordance with the MRLs (maximum residue limits). Therefore, an analytical method is required to quantify the residues, and we conducted a series of analyses to select and validate the quick and simple analytical method for tolpyralate in five agricultural products using QuEChERS (quick, easy, cheap, effective, rugged and safe) method and LC-MS/MS (liquid chromatography-tandem mass spectrometry). METHODS AND RESULTS: The agricultural samples were extracted with acetonitrile followed by addition of anhydrous magnesium sulfate, sodium chloride, disodium hydrogencitrate sesquihydrate and trisodium citrate dihydrate. After shaking and centrifugation, purification was performed with d-SPE (dispersive-solid phase extraction) sorbents. To validate the optimized method, its selectivity, linearity, LOD (limit of detection), LOQ (limit of quantitation), accuracy, repeatability, and reproducibility from the inter-laboratory analyses were considered. LOQ of the analytical method was 0.01 mg/kg at five agricultural products and the linearity of matrix-matched calibration were good at seven concentration levels, from 0.0025 to 0.25 mg/L (R2≥0.9980). Mean recoveries at three spiking levels (n=5) were in the range of 85.2~112.4% with associated relative standard deviation values less than 6.2%, and the coefficient of variation between the two laboratories was also below 13%. All optimized results were validated according to the criteria ranges requested in the Codex Alimentarius Commission (CAC) and Ministry of Food and Drug Safety (MFDS) guidelines. CONCLUSION: In conclusion, we suggest that the selected and validated method could serve as a basic data for detecting tolpyralate residue in imported and domestic agricultural products.

Seasonal Changes in the Microbial Communities on Lettuce (Lactuca sativa L.) in Chungcheong-do, South Korea

  • Woojung Lee;Min-Hee Kim;Juyeon Park;You Jin Kim;Eiseul Kim;Eun Jeong Heo;Seung Hwan Kim;Gyungcheon Kim;Hakdong Shin;Soon Han Kim;Hae-Yeong Kim
    • Journal of Microbiology and Biotechnology
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    • v.33 no.2
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    • pp.219-227
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    • 2023
  • Lettuce is one of the most consumed vegetables worldwide. However, it has potential risks associated with pathogenic bacterial contamination because it is usually consumed raw. In this study, we investigated the changes in the bacterial community on lettuce (Lactuca sativa L.) in Chungcheong-do, South Korea, and the prevalence of foodborne pathogens on lettuce in different seasons using 16S rRNA gene-based sequencing. Our data revealed that the Shannon diversity index showed the same tendency in term of the number of OTUs, with the index being greatest for summer samples in comparison to other seasons. Moreover, the microbial communities were significantly different between the four seasons. The relative abundance of Actinobacteriota varied according to the season. Family Micrococcaceae was most dominant in all samples except summer, and Rhizobiaceae was predominant in the microbiome of the summer sample. At the genus level, the relative abundance of Bacillus was greatest in spring samples, whereas Pseudomonas was greatest in winter samples. Potential pathogens, such as Staphylococcus and Clostridium, were detected with low relative abundance in all lettuce samples. We also performed metagenome shotgun sequencing analysis on the selected summer and winter samples, which were expected to be contaminated with foodborne pathogens, to support 16S rRNA gene-based sequencing dataset. Moreover, we could detect seasonal biomarkers and microbial association networks of microbiota on lettuce samples. Our results suggest that seasonal characteristics of lettuce microbial communities, which include diverse potential pathogens, can be used as basic data for food safety management to predict and prevent future outbreaks.

Sample Size Estimation for Risk Assessment and Monitoring Based on Heavy Metal Monitoring Data from Food Items (위해평가 및 모니터링 수행을 위한 표본크기 추정연구: 식품 중 중금속 모니터링 데이터를 중심으로)

  • Kang, Hui Seung;Ko, Ahra;Jeong, Da-Hyun;Ha, Mira;Hwang, Myung-Sil;Hong, Jin-Hwan;Hwang, In Gyun;Yoon, Hae-Jung
    • Journal of Food Hygiene and Safety
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    • v.30 no.2
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    • pp.127-131
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    • 2015
  • This study aimed to calculate the required sample size to monitor food items during risk assessment studies. Based on a data set from a previous study (2,400 data points for heavy metal assessment from 17 food items), the required sample size was estimated by using a single equation with the standard deviation value, error range, and 95%-99% confidence intervals. The required sample size was calculated with each of the heavy metals for the assessment. The results showed that cadmium, lead, and mercury of required sample sizes for further monitoring were range of 7-90, 7-1, 062, and 11-238, respectively. We found that the required sample size varied depending on the standard deviation of the previous monitoring data. This study provides a basic method to determine the minimum sample size required in food monitoring to devise practical sampling strategies.

Rapid determination and quantification of hair-growth compounds in adulterated products by ultra HPLC coupled to quadrupole-orbitrap MS

  • Lee, Ji Hyun;Park, Han Na;Kang, Gihaeng;Kim, Nam Sook;Park, Seongsoo;Lee, Jongkook;Kang, Hoil
    • Analytical Science and Technology
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    • v.32 no.2
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    • pp.56-64
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    • 2019
  • Recently, a number of adulterated products, which are advertised as hair-growth enhancer have been emerged among those who suffer hair loss disease. For continuous control of illegal products, in this study, a rapid and sensitive method for simultaneous screening of 12 compounds that enhance hair-growth was established to protect public health by ultrahigh-performance liquid chromatography coupled to quadrupole-orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS). Fragmentation pathways of them were proposed based on $MS^2$ spectral data obtained using the established method. In this analysis, the LODs and LOQs ranged from 0.05 to 50 ng/mL and from 0.17 to 167 ng/mL, respectively. The square of the linear correlation coefficient ($R^2$) was determined as more than 0.995. The intra- and inter-assay accuracies were respective 88-112 % and 88-115 %. Their precision values were measured within 5 % (intra-day) and 10 % (inter-day). Mean recoveries of target compounds in adulterated products ranged from 84 to 115%. The relative standard deviation of stability was less than 12 % at $4^{\circ}C$ for 48 h. The method was employed to screen 14 dietary supplements advertised to be effective for the treatment of hair loss. Some of the products (~21 %) were proven to contain synthetic drugs that promote hair growth such as triaminodil, minoxidil, and finasteride.

A Collaborative Study to Establish the Second Korean National Reference Standard for Snake Venom

  • Han, Kiwon;Jung, Kikyung;Oh, Hokyung;Song, Hojin;Park, Sangmi;Kim, Ji-Hye;Min, Garam;Lee, Byung-Hwa;Nam, Hyun-sik;Kim, Yang Jin;Ato, Manabu;Jeong, Jayoung;Ahn, Chiyoung
    • Toxicological Research
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    • v.34 no.3
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    • pp.191-197
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    • 2018
  • In 2015, a candidate for the second national reference standard (NRS) of Gloydius snake venom was produced to replace the first NRS of Gloydius snake venom. In the present study, the potencies of the candidate were determined by a collaborative study, and the qualification of the candidate was estimated. The potencies of the candidate were determined by measuring the murine lethal titers and lapine hemorrhagic titers of venom against the regional working reference standard (RWRS) for antivenom using the methods described in the previous report for the first NRS of Gloydius snake venom. Three Korean facilities contributed data from a total of 30 independent assays. Subsequently, two foreign national control research laboratories contributed to this collaborative study. The results were calculated using the Reed-Muench method for lethality and determined using a mixed-effects model for hemorrhage. The general common potencies of the lethal and hemorrhagic titers were obtained from the results of the 30 tests performed at three Korean facilities. The results are expressed in micrograms for 1 test dose (TD) with a 95% confidence interval as follows: a lethal titer of $90.13{\mu}g/TD$ (95% confidence interval = $87.39{\sim}92.86{\mu}g$) and a hemorrhagic titer of $10.80{\mu}g/TD$ (95% confidence interval = $10.46{\sim}11.14{\mu}g$). In addition, the candidate preparation showed good quality evaluation according to the results of the quality estimation of the candidate and is judged to be suitable to serve as the Korean NRS for snake venom. In conclusion, the second NRS of Gloydius snake venom was established in this study and will be used for national quality control, including a national lot release test of Korean antivenom products.

Identification of Pitfalls Related to the Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Liquid Chromatography-Time of Flight Mass Spectrometry (액체크로마토그래프-질량분석기를 이용한 정성 및 정량 오류의 확인)

  • Kwon, Jin-Wook;Cho, Yoon-Jae;Rhee, Gyu-Seek
    • Korean Journal of Environmental Agriculture
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    • v.34 no.3
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    • pp.230-237
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    • 2015
  • BACKGROUND: To identify the sources of inaccuracy in LC/MS/MS methods used in the routine quantitation of small molecules are described and discussed. METHODS AND RESULTS: Various UPLC coupled to triple quadrupole mass spectrometer and time of flight (TOF) were used to identify the potential sources of inaccuracy and inducing the pitfalls of qualification and quntitation during the veterinary drug residue analysis. Some of stable isotope labelled veterinary drugs, which were used as internal standards, presented "cross-talk", regardless of manufactures of mass spectrometer and types of spectrometer. Group of sulfonamides also presented inaccuracy qualification and quantitation due to the multi-residue analytical method with the same fragment ions at the close retention times. CONCLUSION: The phenomena of "cross-talk" occurring between subsequently monitored transition from stable isotope labelled and isotope non-labelled authentic chemical were identified. To prevent errors and achieve more accurate data during the analysis of small molecules by LC/MS/MS SRM method, Followings should be taken care of and kept checking; purity and concentration of stable isotope as an internal standard, prevention of carry-over during the separation in column, minimizing the ion suppression by matrix effect, identification of retention time, precursor ion and product ion, and full knowledge of data processing including smoothing and peak integration.

Neurotoxicity of Synthetic Cannabinoids JWH-081 and JWH-210

  • Cha, Hye Jin;Seong, Yeon-Hee;Song, Min-Ji;Jeong, Ho-Sang;Shin, Jisoon;Yun, Jaesuk;Han, Kyoungmoon;Kim, Young-Hoon;Kang, Hoil;Kim, Hyoung Soo
    • Biomolecules & Therapeutics
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    • v.23 no.6
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    • pp.597-603
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    • 2015
  • Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

Monitoring and Risk Assessment of Pesticide Residues for Circulated Agricultural Commodities in Korea-2013 (국내 유통 농산물의 잔류농약 모니터링 및 위해평가-2013년)

  • Kim, Jae-Young;Lee, Sang-Mok;Lee, Han-Jin;Chang, Moon-Ik;Kang, Nam-Sook;Kim, Nam-Sun;Kim, Heejung;Cho, Yoon-Jae;Jeong, Jiyoon;Kim, Mee Kyung;Rhee, Gyu-Seek
    • Journal of Applied Biological Chemistry
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    • v.57 no.3
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    • pp.235-242
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    • 2014
  • The purpose of this study is the establishment of scientific processes for making food safety policies. Thus, we investigated pesticide residue level of the agricultural commodities from market, and performed risk assessment. Fifteen agricultural items are chosen based on the frequency of Korean consumption. The samples were collected from 9 cities where populations are more than one million. Total 283 active ingredients were monitoring ( total sample number =232). Single-analysis of target pesticides was for three kinds of possible growth regulators and the multicomponent analysis was for 280 kinds of pesticides, a total of 283 species were selected to perform the pesticide residues. Before monitoring the analytes, the improvements of the analytical methods were done by method validations under the CODEX analytical method development guidelines and can produce metrics that represent the international standards applied in accordance with the guidelines. In addition to residual pesticides detected during monitoring we compare the ADI to EDI values using detected result and dietary consumption data which is extracted from annual market basket survey. The 163 samples were non-detected in the total 232 samples so it means that every agricultural commodity will residual pesticides-free in 70.3%. The detected residual pesticides showed for a total of 69 cases (29.7%). Two of samples violate Korean MRL (0.9%). The ratio of EDI compared to ADI resulted in only from 0.00087 to 0.902%. In result, we can assume that all detected residual pesticides are very safe level and current policies of Korean pesticides control may be working.

The Development for guideline of raw matrials on technical document of Medical Device (의료기기 허가.기술문서 원자재 작성 가이드라인 개발)

  • Park, Ki-Jung;Ryu, Gyu-Ha;Lee, Sung-Hee;Lee, Chang-Hyung;Jung, Jin-Baek;Lee, Jae-Keun;Hur, Chan-Hoi;Kim, Hyung-Bum;Choi, Min-Yong;Kim, Yong-Woo;Hwang, Sang-Yeon;Jung, Jae-Hoon;Koo, Ja-Jung;Hong, Hye-Kyung;Lim, Kyung-Taek;Kang, Se-Ku;Kwak, Young-Ji
    • Journal of Biomedical Engineering Research
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    • v.31 no.6
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    • pp.434-437
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    • 2010
  • For approval of medical devices manufactured or imported, submission of technical documents as well as the application form is required. The manufacturer (or importer) should properly identify the raw materials the applied product is made of and the manufacturing processes the product undergoes before it is shipped in the application form. In the technical documents, scientific data to evaluate the efficacy, safety, and quality of the applied product that has been described in the application form should be provided. Therefore, identifying the raw materials that were used for the parts of the applied product and describing the physical and chemical characteristics of the raw materials are quite important and essential in ensuring the efficacy, safety, and quality of the applied product. To describe the physical and chemical characteristics of the raw materials correctively, the applicant is required to have broad knowledge in the scientific fields such as chemical, polymer, metal, and ceramic science and engineering. But most of the applicant are not experts in these fields, so that the description in the application form often includes wrong and improper descriptions. Thus, we developed a guideline which explains the raw materials for medical devices, show the their examples. The purpose of this description guideline is to help the applicant properly completing the "Raw materials or constituents and their volumes" part in the application form.