• Title/Summary/Keyword: Drug safety assessment

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An Artificial Neural Network-Based Drug Proarrhythmia Assessment Using Electrophysiological Characteristics of Cardiomyocytes (심근 세포의 전기생리학적 특징을 이용한 인공 신경망 기반 약물의 심장독성 평가)

  • Yoo, Yedam;Jeong, Da Un;Marcellinus, Aroli;Lim, Ki Moo
    • Journal of Biomedical Engineering Research
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    • v.42 no.6
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    • pp.287-294
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    • 2021
  • Cardiotoxicity assessment of all drugs has been performed according to the ICH guidelines since 2005. Non-clinical evaluation S7B has focused on the hERG assay, which has a low specificity problem. The comprehensive in vitro proarrhythmia assay (CiPA) project was initiated to correct this problem, which presented a model for classifying the Torsade de pointes (TdP)-induced risk of drugs as biomarkers calculated through an in silico ventricular model. In this study, we propose a TdP-induced risk group classifier of artificial neural network (ANN)-based. The model was trained with 12 drugs and tested with 16 drugs. The ANN model was performed according to nine features, seven features, five features as an individual ANN model input, and the model with the highest performance was selected and compared with the classification performance of the qNet input logistic regression model. When the five features model was used, the results were AUC 0.93 in the high-risk group, AUC 0.73 in the intermediate-risk group, and 0.92 in the low-risk group. The model's performance using qNet was lower than the ANN model in the high-risk group by 17.6% and in the low-risk group by 29.5%. This study was able to express performance in the three risk groups, and it is a model that solved the problem of low specificity, which is the problem of hERG assay.

Monitoring of Heavy Metals in Vegetables in Korea (국내 유통 중인 채소류의 중금속 모니터링)

  • Go, Myoung Jin;Lee, Jin Ha;Park, Eun Heui;Park, Sang Wook;Kim, In Kyung;Ji, Young Ae
    • Journal of Food Hygiene and Safety
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    • v.27 no.4
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    • pp.456-460
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    • 2012
  • This study was carried out as a survey on the level of lead (Pb), cadmium (Cd), arsenic (As) and mercury (Hg) in 5 items of agricultural products (lettuce, pumpkin, head lettuce, cabbage and crown daisy) for which safety guidelines are not yet established in Korea. The 407 samples were collected from local markets in 9 regional places and the levels of metals were measured by ICP-MS and mercury analyzer. The average levels of Pb, Cd, As and Hg were 0.026, 0.018, 0.008 and 0.003 mg/kg for lettuce, 0.002, 0.001, 0.001 and 0.0006 mg/kg for pumpkin, 0.002, 0.005, 0.001 and 0.0005 mg/kg for head lettuce, 0.001, 0.002, 0.0002 and 0.0006 mg/kg for cabbage and 0.022, 0.014, 0.006 and 0.004 mg/kg for crown daisy. For risk assessment, the daily dietary exposures of Pb, Cd and Hg by intake of these agricultural products were calculated and compared with PTWI (provisional tolerable weekly intake) established by JECFA. The daily dietary exposure of heavy metals by intake of these agricultural products were 0.13, 0.56 and 0.09% of PTWI, respectively. These monitoring results will be utilized as fundamental data for the establishment of Korean standards of Pb, Cd, As and Hg in 5 items of agricultural products and valuable source for DB construction for science-based safety control of heavy metals in foods including agricultural products.

Monitoring and Exposure Assessment of Pesticide Residues in Domestic Agricultural Products (국내 유통 다소비 농산물의 잔류농약 모니터링 및 노출평가)

  • Kang, Namsuk;Kim, Seongcheol;Kang, Yoonjung;Kim, Dohyeong;Jang, Jinwook;Won, Sera;Hyun, Jaehee;Kim, Dongeon;Jeong, Il-Yong;Rhee, Gyuseek;Shin, Yeongmin;Joung, Dong Yun;Kim, Sang Yub;Park, Juyoung;Kwon, Kisung;Ji, Youngae
    • The Korean Journal of Pesticide Science
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    • v.19 no.1
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    • pp.32-40
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    • 2015
  • This study was implemented to evaluate food safety on residual pesticides in agricultural products of Korea and to use as a data base for the establishment of food policy. A total of 196 pesticide upon these products were analyzed using multi class pesticide multiresidue methods of Korean Food Code, and 232 samples of 15 agricultural products collected from 9 regions were supplied for this study. In the results, 64 kinds of pesticides were detected in 53 samples, chlorpyrifos and procymidone of them were shown a high frequency of detection in the analyzed pesticides. Among them, two samples (chlorpyrifos in perilla leaves and picoxystrobin in peach) were detected over Maximum Residue Limits (MRLs). The levels of the detected pesticide residues were within safe levels. Also, the intake assessment for pesticide residues including chlorpyrifos at multi pesticide residue monitoring were carried out. The result showed that the ratio of EDI (estimated daily intake) to ADI (acceptable daily intake) was 0.001~0.902% which means that the detected pesticide residues were in a safe range so that residual pesticides in the agricultural products in Korea are properly controlled.

Inorganic As Concentration in Rice Grown Around the Abandoned Mining Areas and its Health Risk Assessment

  • Kim, Hyuck-Soo;Kang, Dae-Won;Kim, Da-In;Lee, Seul;Park, Sang-Won;Yoo, Ji-Hyock;Kim, Won-Il
    • Korean Journal of Soil Science and Fertilizer
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    • v.49 no.5
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    • pp.584-588
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    • 2016
  • The current study was carried out to investigate total and inorganic arsenic (As) concentrations in 112 rice samples (husked rice and polished rice) grown around the abandoned mining areas and to estimate the potential health risk through dietary intake of rice in Korea. Mean concentrations of total As in husked rice and polished rice were 0.23 and $0.13mg\;kg^{-1}$, respectively. Also, average inorganic As concentrations in husked rice and polished rice were 0.09 and $0.05mg\;kg^{-1}$, respectively. These levels are lower than the standard guideline value ($0.2mg\;kg^{-1}$) for inorganic As in polished rice recommended by Korea Ministry of Food and Drug Safety and Codex. For health risk assessment, the average values of cancer risk probability was $5.7{\times}10^{-5}$ which was less than the acceptable cancer risk of $10^{-6}{\sim}10^{-4}$ for regulatory purpose. Also, hazard quotient values were lower than 1.0. Therefore, these results demonstrated that human exposure to inorganic As through dietary intake of rice collected from abandoned mining areas might not cause adverse health effects.

Toxicogenomics and Cell-based Assays for Toxicology

  • Tong, Weida;Fang, Hong;Mendrick, Donna
    • Interdisciplinary Bio Central
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    • v.1 no.3
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    • pp.10.1-10.5
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    • 2009
  • Toxicity is usually investigated using a set of standardized animal-based studies which, unfortunately, fail to detect all compounds that induce human adverse events and do not provide detailed mechanistic information of observed toxicity. As an alternative to conventional toxicology, toxicogenomics takes advantage of currently advanced technologies in genomics, proteomics, metabolomics, and bioinformatics to gain a molecular level understanding of toxicity and to enhance the predictive power of toxicity testing in drug development and risk/safety assessment. In addition, there has been a renewed interest, particularly in various government agencies, to prioritize and/or supplement animal testing with a battery of mechanistically informative in vitro assays. This article provides a brief summary of the issues, challenges and lessons learned in these fields and discuss the ways forward to further advance toxicology using these technologies.

Risk Assessment of Lead and Cadmium through Mushrooms (버섯류 중 납, 카드뮴 위해성 평가)

  • Choi, Hoon;Park, Sung-Kug;Lee, Bum-Noh;Kim, Meehye
    • Korean Journal of Food Science and Technology
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    • v.44 no.6
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    • pp.666-672
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    • 2012
  • The present study was carried out in order to assess the dietary exposure as well as the risk for lead (Pb) and cadmium (Cd) exposure through mushrooms among the Korean population. Various samples (n=536) covering 17 kinds of mushrooms were collected from retail outlets and markets in Korea. The contents of Pb were 0.005 (King oyster)-0.026 (Matsutake) mg/kg in raw mushrooms and 0.014 (Oyster)-16.411 (Manna lichen) mg/kg in dry mushrooms, respectively. The contents of Cd were 0.002 (Enoki)-0.205 (Hericium erinaciium) mg/kg in raw mushrooms and 0.021 (Vegetable worms)-2.650 (Agaricus blazei Muill) mg/kg in dry mushrooms, respectively. The mean dietary exposure of Pb for the general population was $0.053{\mu}g/day$, taking 0.03% of provisional tolerable weekly intake (PTWI). The mean dietary exposure of Cd for the general population was $0.168{\mu}g/day$, corresponding to 0.37% of provisional tolerable monthly intake (PTMI). Therefore, the level of the overall dietary exposure to heavy metals through mushroom for the Korean population was far below the recommended JECFA levels, indicating little possibility of concern.

A 14-Day Repeated Dose Toxicity of Epimedii Herba Aqueous Extract Administered by Oral Gavage in F344 Rats

  • Han, Hyoung-Yun;Yang, Young-Su;Kim, Soo Nam;Han, Su-Cheol;Han, Kang-Hyun;Lee, Jong-Hwa;Jeong, Ja Young;Roh, Hang-Sik;Seok, Ji Hyeon;Kim, Jeong-Ah;Min, Byung-Sun
    • Natural Product Sciences
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    • v.21 no.1
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    • pp.34-41
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    • 2015
  • The objective of this study is to characterize a toxicity of Epimedii Herba (EH) in F344 rats and to find a dose levels for the 13 weeks toxicity study. EH is well known as medicinal herb in many Asian countries for traditional medicines of antibacterial and antiviral effects, estrogenic and antiestrogenic effects, and for treatment of osteoporosis, hypotensives, fatigue, kidney disorders, and related complications. However, the indispensable and basic information of toxicological evaluation of EH extract is insufficient to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and MFDS guideline in this study. The extract of EH was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed of 5 male and female rats. In this study, there were no treatment of EH-related adverse changes in clinical observations, mortality, body weights, food consumption, urinalysis, gross finding at necropsy, and organ weight examination. Total red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, total cholesterol, and phospholipid were decreased in males and females at 5000 mg/kg/day compared to the control animals. Mean corpuscular volume and reticulocyte counts were increased in males and females at 5000 mg/kg/day compared to control animals. Therefore, we recommend that dose level of 5000 mg/kg/day is a highest treatment group in 13-week EH extract exposure study for further toxicity assessment.

Occupational Exposure to Antineoplastic Drugs: Identification of Job Categories Potentially Exposed throughout the Hospital Medication System

  • Hon, Chun-Yip;Teschke, Kay;Chua, Prescillia;Venners, Scott;Nakashima, Lynne
    • Safety and Health at Work
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    • v.2 no.3
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    • pp.273-281
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    • 2011
  • Objectives: Studies examining healthcare workers' exposure to antineoplastic drugs have focused on the drug preparation or drug administration areas. However, such an approach has probably underestimated the overall exposure risk as the drugs need to be delivered to the facility, transported internally and then disposed. The objective of this study is to determine whether drug contamination occurs throughout a facility and, simultaneously, to identify those job categories that are potentially exposed. Methods: This was a multi-site study based in Vancouver, British Columbia. Interviews were conducted to determine the departments where the drugs travel. Subsequent site observations were performed to ascertain those surfaces which frequently came into contact with antineoplastic drugs and to determine the job categories which are likely to contact these surfaces. Wipe samples were collected to quantify surface contamination. Results: Surface contamination was found in all six stages of the hospital medication system. Job categories consistently found to be at risk of exposure were nurses, pharmacists, pharmacy technicians, and pharmacy receivers. Up to 11 job categories per site may be at risk of exposure at some point during the hospital medication system. Conclusion: We found drug contamination on select surfaces at every stage of the medication system, which indicates the existence of an exposure potential throughout the facility. Our results suggest that a broader range of workers are potentially exposed than has been previously examined. These results will allow us to develop a more inclusive exposure assessment encompassing all healthcare workers that are at risk throughout the hospital medication system.

In Silico Approach for Predicting Neurotoxicity (In silico 기법을 이용한 신경독성 예측)

  • Lee, So-yeon;Yoo, Sun-yong
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2022.05a
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    • pp.270-272
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    • 2022
  • Safety is one of the factors that prevent clinical drugs from being distributed on the market. In the case of neurotoxicity, which is the main cause of safety problems caused by drug side effects, risk assessment of drugs and compounds is required in advance. Currently, experiments for testing drug safety are based on animal experimetns, which have the disadvantage of being time-consuming and expensive. Therefore in order to solve the above problem, a neurotoxic prediction model through an in silico experiment was suggested. In this study, the category of neurotoxicity was expanded using a unified medical language system and various related compound data were obtained based on an integrated database. The SMILES (Simplified Molecular Input Line Entry System) of the obtained compounds were converted into fingerprints and it is used as input of machine learning. The model finally predicts the presence or absence of neurotoxicity. The experiment proposed in this study can reduce the time and cost required for the in vivo experiment. Furthermore, it is expected to shorten the research period for new drug development and reduce the burden of suspension of development.

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Risk Assessment of Mercury through Food Intake for Korean Population (식품 중 수은 위해평가)

  • Choi, Hoon;Park, Sung-Kug;Kim, Mee-Hye
    • Korean Journal of Food Science and Technology
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    • v.44 no.1
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    • pp.106-113
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    • 2012
  • The present study was conducted to assess the dietary exposure to mercury and the associated risks for Koreans resulting from their food intake. The probabilistic approach in the Monte Carlo simulation was used to estimate dietary exposures. Based on several reports regarding heavy metals published by KFDA in the 2000s, 178 types of representative foods were selected and data were collected on the occurrence of mercury. The contents of mercury in foods ranged: agricultural products 0.1 (fruits)-45.4 ${\mu}g/kg$ (mushrooms), 3.7 ${\mu}g/kg$ (meat), and 9.3 (Echinodermata, chordata)-194.9 ${\mu}g/kg$ (fish). Others categories investigated were alcoholic beverages (0.7 ${\mu}g/kg$) and processed food (4.4 ${\mu}g/kg$). The mean and 95th percentile for exposure to dietary mercury were 4.29 and 12.48 ${\mu}g/day$, corresponding to 13.6% and 39.7% of PTWI (Provisional Tolerable Weekly Intake), respectively. Therefore, overall level of mercury exposure for Koreans through food intake is below levels recommended by JECFA, indicating the least possibility of risk, and is less than or similar to levels reported in other countries.