• 제목/요약/키워드: Probability of toxicity

검색결과 24건 처리시간 0.028초

다이옥신의 인체 독성에 영향을 미치는 물리화학적 인자에 대한 이론적 접근 (Theoretical Approach for Physicochemical Factors Affecting Human Toxicity of Dioxins)

  • 황인철;박형석
    • Environmental Analysis Health and Toxicology
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    • 제14권1_2호
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    • pp.65-73
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    • 1999
  • Dioxins refer to a family of chemicals comprising 75 polychlorinated dibenzo-p-dioxin (PCDD) and 135 polychlorinated dibenzo-p-furan (PCDF) congeners, which may cause skin disorder, human immune system disruption, birth defects, severe hormonal imbalance, and cancer. The effects of exposure of dioxin-like compounds such as PCBs are mediated by binding to the aryl hydrocarbon receptor (AHR), which is a ligand-activated transcription factor. To grasp physicochemical factors affecting human toxicity of dioxins, six geometrical and topological indices, eleven thermodynamic variables, and quantum mechanical descriptors including ESP (electrostatic potential) were analyzed using QSAR and semi-empirical AM1 method. Planar dioxins with high lipophilicity and large surface tension show the probability that negative electrostatic potential in the lateral oxygen may make hydrogen bonding with DNA bases to be a carcinogen.

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제 1상 임상시험의 SM, CRM, ATD에서 결정된 MTD의 정확성과 안전성 비교 (Precision and Safety Comparison for SM, CRM and ATD in Phase I Clinical Trials)

  • 김동욱;길순경
    • Communications for Statistical Applications and Methods
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    • 제16권1호
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    • pp.51-65
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    • 2009
  • 제 1상 임상시험은 사람을 대상으로 처음 실시되므로 약물 투여의 안전성과 정확성이 신중히 고려되어야 한다. 따라서 제 1상 임상시험에서는 적은 수의 피험자를 통해 최대허용용량(maximum tolerated dose)을 정확하게 찾아야 한다. 제 1상 임상시험에서 최대허용용량을 결정하는 방법에는 표준방법(standard method), 연속재평가방법(continual reassessment method) 그리고 가속적정계획(accelerated titration designs) 방법이 있다. 본 연구에서는 동일한 모형에서 세 방법을 동시에 고려하여 최대허용용량의 안전성과 정확성을 살펴보았다. 또한 세 방법에 대해 최대허용용량에서 기대독성확률을 구하여 비교하였다. 그리고 ATD와 CRM의 단점을 보완한 수정된 ATD와 수정된 CRM을 포함하여 여러 방법들을 동일한 모형에서 동시에 그 성능을 비교하였다.

국내 잔류농약 residue definition과 관련된 식이노출의 과소평가 (Underestimation of Dietary Exposure to Pesticide Residues in Relation to Residue Definition in South Korea)

  • 이미경
    • 한국식품위생안전성학회지
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    • 제35권5호
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    • pp.452-458
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    • 2020
  • 본 연구는 식물성 식품에 대한 잔류농약의 국내와 코덱스의 residue definition 비교를 통해 국내에서 식이노출 과소평가의 가능성이 있는 농약성분을 파악하고 더 나아가 식이노출 과소평가가 위해성 평가에 미치는 영향에 대해 우선적으로 검토가 필요한 농약성분을 알아내고자 하였다. 연구결과, 국내와 코덱스의 residue definition 정보로부터 식이노출 과소평가의 가능성이 있는 44종의 농약성분이 파악되었다. 이들 성분 중 농약성분의 ADI값, 국내 MRL 정보 및 대사물질의 독성학적 정보에 근거하여 다음의 24종 농약성분이 식이노출 과소평가가 위해성 평가에 미치는 영향에 대해 우선적으로 검토가 필요한 것으로 나타났다: acibensolar-S-methyl, chlorfenapyr, chlorothalonil, cyantraniliprole, cyclaniliprole, cyflumetofen, dithiocarbamates, fenamidone, fenpyroximate, fluazifop-P-butyl, fluopicolide, flupyradifuron, fluxapyroxad, glyphosate, hexythiazox, isoprothiolane, isopyrazam, myclobutanil, penthiopyrad, propiconazole, spinetoram, spiromesifen, spirotetramat, trifloxystrobin. 더 나아가 chlorfenapyr, chlorothalonil, dithiocarbamates, fenamidone은 대사물질의 독성이 더 커서 특히 우선적으로 검토가 요구되는 것으로 판단된다. 본 연구는 식품 중 잔류농약에 대한 국내 위해성 평가방법의 개선을 위해 활용될 수 있을 것으로 기대된다.

산삼, 우황, 웅담, 사향의 연구 동향 분석 및 비만 치료제로써의 응용 가능성 탐색 연구 (The Analysis of Study Trends of Wild ginseng, Bovis Calculus, Ursi Fel, Moschus and The Study on Applied Possibility as Obesity medications)

  • 김민우;송윤경;임형호
    • 한방비만학회지
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    • 제11권2호
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    • pp.41-68
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    • 2011
  • Objectives: After organizing segmentations related to obesity from classics and each studies, we would like to examine the value of wild ginseng, bovis calculus, ursi fel and moschus as a obesity medicine. Methods: We found out 4 drugs which are wild ginseng, bovis calculus, ursi fel and moschus from the classics, such as "Shin-Nong-Bon-Cho-Kyung", "Myoung-Eui-Byul-Lok", "Bon-Cho-Gang-Mok", "Bon-Cho-Jong-Shin", "Bon-Cho-Bi-Yo", "Bon-Cho-Gu-Jin" and "Deuk-Bae-Bon-Cho", we searched websites such as RISS, Korean traditional knowledge portal, the society of Korean medicine for obesity research, Korean pharmacopuncture institute, the Korean academy of oriental rehabilitation medicine and Korean acupuncture & moxibustion society as well. Results: 1. We couldn't find the contents related to the efficacy of improving obesity through wild ginseng, bovis calculus, ursi fel and moschus from the classics. 2. Wild ginseng had a study dealing with the efficacy of anticancer, obesity, toxicity, immunity, sulfation, diabetes, plasma proteins, depression, hypertension, endometriosis and hair loss. Especially among 6 studies related to obesity, apart from the study that treated extract of wild ginseng directly to the cell or oral administration to the animals, also have studies that had an efficacy of improving obesity through injecting pharmacopuncture to acupuncture point and vein, etc. 3. Bovis calculus had a study about efficacy related to arthritis, liver, inflammation of cornea, obesity, anticancer, immunity, antacid, heart, lumbar pain, hypertension, toxicity, a digestive organ and sasang constitution, especially in case of obesity, had each studies about oral administration of complex prescription and about cell unit experiment of pharmacopuncture. 4. Ursi fel had a study about efficacy related to liver, arthritis, inflammation of cornea, immunity, obesity, anticancer, antacid, lumbar pain, digestive organ, toxicity, cell protection, skin ailment, etc. Especially in case of obesity, had each studies about oral administration of animal experiment and about cell unit experiment of pharmacopuncture. 5. Moschus had a study about efficacy related to liver, the central nervous system, arthritis, inflammation of cornea, immunity, obesity, anticancer, hypertension, heart, lumbar pain, etc. Especially in case of obesity, had one study about oral administration of complex prescription. Conclusion: Through the result of probability as a obesity medicine of wild ginseng, bovis calculus, ursi fel and moschus, we could identify the possibility of each drug as a obesity medicine. Also in the future, it is considered that studies about one or complex prescription and pharmacopuncture as a obesity medicine will be needed.

석유화학단지 주변 주거지역 다환방향족탄화수소(PAHs)의 농도와 Monte-Carlo 모의실험을 통한 위해성평가 (Seasonal Concentration of Polycyclic Aromatic Hydrocarbons (PAHs) in Residential Areas Around Petrochemical Complexes and Risk Assessment Using Monte-Carlo Simulation)

  • 박동윤;최영태;양원호;최길용;이채관
    • 한국환경보건학회지
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    • 제47권4호
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    • pp.366-377
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    • 2021
  • Background: Polycyclic aromatic hydrocarbons (PAHs) are generated in petrochemical complexes, can spread to residential areas and affect the health of residents. Although harmful PAHs are mainly present in particle phase, gas phase PAHs can generate stronger toxic substances through photochemical reaction. Therefore, the risk assessment for PAHs around the petrochemical complex should consider both particle and gas phase concentrations. Objectives: This study aimed to investigate the concentration characteristics of particle and gas phase PAHs by season in residential areas around petrochemical complexes, and to assess the risk of PAHs. Methods: Samples were collected for 7 days by seasons in 2014~2015 using a high volume air sampler. Particle and gas phase PAHs were sampled using quartz filter and polyurethane foam, respectively, analyzed by GC-MS. Chronic toxicity and probabilistic risk assessment were performed on 14 PAHs. For chronic toxicity risk assessment, inhalation unit risk was used. Monte-Carlo simulation was performed for probabilistic risk assessment using the mean and standard deviation of measured PAHs. Results: The concentration of particle total PAHs was highest in autumn. The gas phase concentration was highest in autumn. The average gas phase distribution ratio of low molecular weight PAHs composed of 2~3 benzene rings was 85%. The average of the medium molecular weight composed of 4 benzene rings was 53%, and the average of the high molecular weight composed of 5 or more benzene rings was 9%. In the chronic toxicity risk assessment, 7 of the 14 PAHs exceeded the excess carcinogenic risk of 1.00×10-6. In the Monte-Carlo simulation, Benzo[a]pyrene had the highest probability of exceeding 1.00×10-6, which was 100%. Conclusions: The concentration of PAHs in the residential area around the petrochemical complex exceeded the standard, and the excess carcinogenic risk was evaluated to be high. Therefore, it is necessary to manage the air environment around the petrochemical complex.

Micropollutants가 연안 생물에 미치는 독성효과에 관한 연구 -1. 어류에 미치는 독성- (Toxic Effect of Micropollutants on Coastal Organisms -I. Toxicity on Some Marine Fishes-)

  • 최문술;목묘직수
    • 한국수산과학회지
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    • 제27권5호
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    • pp.529-534
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    • 1994
  • 해역에 오염을 일으킬 것으로 예상되는 Micropollutants로서 크롬, 구리, 아연, 수은, 카드뮴 및 LAS를 택하여 서해안의 대표적인 유용 어종인 조피볼락, 넙치 및 숭어에 대한 급성독성실험을 행한 결과 다음과 같은 결론을 얻었다. 1. 각종 중금속이나 LAS에 대한 넙치, 숭어, 조피볼락의 내성은 일정한 경향이 없었으나 기수성 어류인 숭어가 대체로 약하였고 독성물질 중 수은과 LAS의 독성이 특히 강하였다. 2. 크롬의 어종별 96hr-LC50은 8.4mg/l, 숭어1.14mg/l, 조피볼락 26.65mg/l으로 조피볼락이 타어종에 비해 내성이 훨씬 강하였다. 3. 구리의 어종별 96hr-LC50은 넙치 16.1mg/l, 숭어 2.32mg/l, 조피볼락 0.18mg/l으로 조피볼락의 내성이 타어종에 비해 매우 낮았으며 특히 조피볼락의 MATC는 $0.053{\sim}0.0053mg/l$으로 서해 연안역의 $92{\sim}93$년도 농도가 $0.003{\sim}0.012mg/l$인 점으로 보아 구리 오염에 주의할 필요가 있음을 알 수 있었다. 4. 아연의 어종별 96hr-LC50은 넙치 5.2mg/l, 숭어 13.75mg/l, 조피볼락 6.95mg/l으로 나타났다. 5. 수은의 어종별 96hr-LC50은 넙치 0.28mg/l, 숭어 0.1mg/l, 조피볼락 0.01mg/l으로 조피볼락이 타어종에 비해 내성 낮았으며, 특히 조피볼락의 MATC는 $0.0007{\sim}0.007mg/l$으로 $92{\sim}93$년도의 서해 연안역의 수은 농도가 $0.001{\sim}0.005mg/l$인 점을 고려하여 볼 때 수은 오염에 주의할 필요가 있음을 알 수 있었다. 6. 카드뮴의 어종별 96hr-LC50은 넙치 28.4mg/l, 숭어 2.55mg/l, 조피볼락 28.7mg/l으로 나타났다. 7. LAS의 96hr-LC50은 0.79mg/l이었고, 숭어에 대한 96hr-LC50은 0.06mg/l, 조피볼락 1.08mg/l으로 기수성 어류인 숭어의 내성이 매우 낮은 점이 특이하였다.

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Clinical Pharmacology of Mycophenolic Acid as Immunosuppressant in Organ Transplaantation

  • Kang, Ju-Seop;Lee, Joo-Won;Jhee, Ok-Hwa;Om, Ae-Son;Lee, Min-Ho;Shaw, Leslie M.
    • Biomolecules & Therapeutics
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    • 제13권2호
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    • pp.65-77
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    • 2005
  • Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

냉동보존된 생쥐배아를 이용한 정도관리에 관한 연구 (Studies on Quality Control by Frozen-Thaw 2-Cell Mouse Embryos)

  • 한선남;김향미;정혜원;오승은;손영수;유한기;안정자;우복희
    • Clinical and Experimental Reproductive Medicine
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    • 제20권2호
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    • pp.165-176
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    • 1993
  • These studies were carried out to investigate the optimal freezing protocol for 2 cell mouse embryos and to find the probability of quality control with 2-cell embryos frozen. The embryos showed the best survival by the protocol composed of a freezing solution with the cryoprotectants(1.5M propanediol + 0.1M sucrose), and a 2-steop thawing method(room temperature, 20 sec-37$^{\circ}C$, 20 sec). The developmental ability of frozen-thaw 2-cell embryos did not differ from that of fresh 2-cell embryos in m-KRB medium with 0.4% bovine serum albumin. But development of frozen-thaw embryos was depended on the supplements of the medium. In the albumin-free medium, the developmental rate(rate of blastocysts) was significantly reduced, compared with that in the medium with 0.4% BSA. Also, when frozen-thaw embryos were cultured in the meduim with human fetal cord serum(HCS), the developmental rate of frozen-thaw embryos was sligtly reduced, compared with that of fresh 2-cell embryos. Finally, frozen-thaw 2-cell mouse embryos were more sensitive to the toxic agent of disposable-plastic syringe. Therefore, toxicity of medium could be effectively detected by frozen-thaw 2-cell mouse embryos.

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Development of the DVH management software for the biologically-guided evaluation of radiotherapy plan

  • Kim, Bo-Kyong;Park, Hee-Chul;Oh, Dong-Ryul;Shin, Eun-Hyuk;Ahn, Yong-Chan;Kim, Jin-Sung;Han, Young-Yih
    • Radiation Oncology Journal
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    • 제30권1호
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    • pp.43-48
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    • 2012
  • Purpose: To develop the dose volume histogram (DVH) management software which guides the evaluation of radiotherapy (RT) plan of a new case according to the biological consequences of the DVHs from the previously treated patients. Materials and Methods: We determined the radiation pneumonitis (RP) as an biological response parameter in order to develop DVH management software. We retrospectively reviewed the medical records of lung cancer patients treated with curative 3-dimensional conformal radiation therapy (3D-CRT). The biological event was defined as RP of the Radiation Therapy Oncology Group (RTOG) grade III or more. Results: The DVH management software consisted of three parts (pre-existing DVH database, graphical tool, and $Pinnacle^3$ script). The pre-existing DVH data were retrieved from 128 patients. RP events were tagged to the specific DVH data through retrospective review of patients' medical records. The graphical tool was developed to present the complication histogram derived from the preexisting database (DVH and RP) and was implemented into the radiation treatment planning (RTP) system, $Pinnacle^3$ v8.0 (Phillips Healthcare). The software was designed for the pre-existing database to be updated easily by tagging the specific DVH data with the new incidence of RP events at the time of patients' follow-up. Conclusion: We developed the DVH management software as an effective tool to incorporate the phenomenological consequences derived from the pre-existing database in the evaluation of a new RT plan. It can be used not only for lung cancer patients but also for the other disease site with different toxicity parameters.

Differential Diagnosis of Acute Liver Failure in Children: A Systematic Review

  • Berardi, Giuliana;Tuckfield, Lynnia;DelVecchio, Michael T.;Aronoff, Stephen
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제23권6호
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    • pp.501-510
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    • 2020
  • Purpose: To develop a probability-based differential diagnosis for pediatric acute liver failure (PALF) based on age and socioeconomic status of the country of origin. Methods: Comprehensive literature search using PubMed, EMBASE, and SCOPUS databases was performed. Children 0-22 years of age who met PALF registry criteria were included. Articles included >10 children, and could not be a case report, review article, or editorial. No language filter was utilized, but an English abstract was required. Etiology of PALF, age of child, and country of origin was extracted from included articles. Results: 32 full text articles were reviewed in detail; 2,982 children were included. The top diagnosis of PALF in developed countries was acetaminophen toxicity (9.24%; 95% CredI 7.99-10.6), whereas in developing countries it was Hepatitis A (28.9%; 95% CredI 26.3-31.7). In developed countries, the leading diagnosis of PALF in children aged <1 year was metabolic disorder (17.2%; 95% CredI 10.3-25.5), whereas in developing countries it was unspecified infection (39.3%; CredI 27.6-51.8). In developed countries, the leading diagnosis in children aged >1 year was Non-A-B-C Hepatitis (8.18%; CredI 5.28-11.7), whereas in developing countries it was Hepatitis A (32.4%; CredI 28.6-36.3). Conclusion: The leading causes of PALF in children aged 0-22 years differ depending on the age and developmental status of their country of origin, suggesting that these factors must be considered in the evaluation of children with PALF.