• Title/Summary/Keyword: toxicity evaluation

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Applicability of QSAR Models for Acute Aquatic Toxicity under the Act on Registration, Evaluation, etc. of Chemicals in the Republic of Korea (화평법에 따른 급성 수생독성 예측을 위한 QSAR 모델의 활용 가능성 연구)

  • Kang, Dongjin;Jang, Seok-Won;Lee, Si-Won;Lee, Jae-Hyun;Lee, Sang Hee;Kim, Pilje;Chung, Hyen-Mi;Seong, Chang-Ho
    • Journal of Environmental Health Sciences
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    • v.48 no.3
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    • pp.159-166
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    • 2022
  • Background: A quantitative structure-activity relationship (QSAR) model was adopted in the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH, EU) regulations as well as the Act on Registration, Evaluation, etc. of Chemicals (AREC, Republic of Korea). It has been previously used in the registration of chemicals. Objectives: In this study, we investigated the correlation between the predicted data provided by three prediction programs using a QSAR model and actual experimental results (acute fish, daphnia magna toxicity). Through this approach, we aimed to effectively conjecture on the performance and determine the most applicable programs when designating toxic substances through the AREC. Methods: Chemicals that had been registered and evaluated in the Toxic Chemicals Control Act (TCCA, Republic of Korea) were selected for this study. Two prediction programs developed and operated by the U.S. EPA - the Ecological Structure-Activity Relationship (ECOSAR) and Toxicity Estimation Software Tool (T.E.S.T.) models - were utilized along with the TOPKAT (Toxicity Prediction by Komputer Assisted Technology) commercial program. The applicability of these three programs was evaluated according to three parameters: accuracy, sensitivity, and specificity. Results: The prediction analysis on fish and daphnia magna in the three programs showed that the TOPKAT program had better sensitivity than the others. Conclusions: Although the predictive performance of the TOPKAT program when using a single predictive program was found to perform well in toxic substance designation, using a single program involves many restrictions. It is necessary to validate the reliability of predictions by utilizing multiple methods when applying the prediction program to the regulation of chemicals.

Acute and repeated dose 26-week oral toxicity study of 20(S)-ginsenoside Rg3 in Kunming mice and Sprague-Dawley rats

  • Li, Chunmei;Wang, Zhezhe;Li, Guisheng;Wang, Zhenhua;Yang, Jianrong;Li, Yanshen;Wang, Hongtao;Jin, Haizhu;Qiao, Junhua;Wang, Hongbo;Tian, Jingwei;Lee, Albert W.;Gao, Yonglin
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.222-228
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    • 2020
  • Background: 20(S)-ginsenoside-Rg3 (C42H72O13), a natural triterpenoid saponin, is extracted from red ginseng. The increasing use of 20(S)-ginsenoside Rg3 has raised product safety concerns. Methods: In acute toxicity, 20(S)-ginsenoside Rg3 was singly and orally administrated to Kunming mice and Sprague-Dawley (SD) rats at the maximum doses of 1600 mg/kg and 800 mg/kg, respectively. In the 26-week toxicity study, we used repeated oral administration of 20(S)-ginsenoside Rg3 in SD rats over 26 weeks at doses of 0, 20, 60, or 180 mg/kg. Moreover, a 4-week recovery period was scheduled to observe the persistence, delayed occurrence, and reversibility of toxic effects. Results: The result of acute toxicity shows that oral administration of 20(S)-ginsenoside Rg3 to mice and rats did not induce mortality or toxicity up to 1600 and 800 mg/kg, respectively. During a 26-week administration period and a 4-week withdrawal period (recovery period), there were no significant differences in clinical signs, body weight, food consumption, urinalysis parameters, biochemical and hematological values, or histopathological findings. Conclusion: The mean oral lethal dose (LD50) of 20(S)-ginsenoside Rg3, in acute toxicity, is above 1600 mg/kg and 800 mg/kg in mice and rats, respectively. In a repeated-dose 26-week oral toxicity study, the no-observed-adverse-effect level for female and male SD rats was 180 mg/kg.

The Combustion Gases Toxicity Evaluation of Plastics Material by Colorimetric Gas Detector Tubes (가스검지관법에 의한 플라스틱재료의 연소가스 독성평가)

  • 박영근;김동일;현성호
    • Fire Science and Engineering
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    • v.16 no.4
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    • pp.77-84
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    • 2002
  • In this paper, we had analyzed comsbustion gases using a GASTEC colorimetric gas detector tube according to the method of NES 713 in order to combustion gases toxicity evaluation for beads polystyrene foam, extruded polystyrene foam, rigid polyurethane foam, flexible polyurethane foam, flexible polyvinyl chloride pipe, vinyl floor cover, polyethyelene foam(flame retardant untreated) and polyethyelene foam (flame retardant treated) of plastics material. As results of gas analyses by using this method, comsbustion gases producted from small specimens of plastics material had reached fatal to man at 30 minutes exposure time that had possesed toxicity index of more than 1. Toxicity indexes of each specimen were estimated range of 4.3∼179.2, flexible polyvinyl chloride showed the hightest toxicity index at 179.2, and beads polystyrene foams showed the lowest toxicity index at 4.3.

Toxicity and Antitumor Activities of Korean Medicinal Plants (I) (한국산 생약의 독성 및 항암 작용 (제1보))

  • Chang, Il-Moo;Chi, Hyung-Joon
    • Korean Journal of Pharmacognosy
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    • v.12 no.3
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    • pp.125-130
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    • 1981
  • Thirty species of Korean medicinal plants which have been frequently used in Oriental herb prescriptions were evaluated on their acute toxicity and potential antitumor activities against P-388 lymphocytic leukemia. The criteria for toxicity evaluation of measuring weight loss, toxicity day survivors and computing log cell kill indicated that 11 species possessed acute toxicity according to the doses administered. No significant antitumor activities were observed while the root of Angelica gigas Nakai (Umbelliferae) exhibited only 24% increased life span.

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Toxicity Evaluation of Endocrine Disrupting Chemicals Using Human HepG2 Cell Line, Lumbricus rubellus and Saccharomyces cerevisiae (HepG2 인간 세포주, Lumbricus rubellus 및 Saccharomyces cerevisiae를 이용한 내분비교란물질의 독성평가)

  • Sohn, Ho-Yong;Kim, Hong-Ju;Kum, Eun-Joo;Cho, Min-Seop;Lee, Jung-Bok;Kim, Jong-Sik;Kwon, Gi-Seok
    • Journal of Life Science
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    • v.16 no.6
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    • pp.919-924
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    • 2006
  • Toxicity evaluation systems for various chemicals and their metabolites have been developed during last decades. In this study, the acute toxicity of endocrine disrupting chemicals, such as endosulfan, bisphenol A, vinclozolin, and 3,5-dichloroaniline, was evaluated using HepG2 cell line, Lumbricus rubellus and Saccharomyces cerevisiae, respectively. The extents of toxicity of the chemicals in different bioassay systems varied substantially, such as endosulfan>3,5-dichloroaniline> bisphenol A in HepG2 cell line system, endosulfan>bisphenol A>3,5-dichloro aniline in L. rubellus system, and 3,5-dichloroaniline>endosulfan>bisphenol A in S. cerevisiae system. Meanwhile, no cytotoxicity was observed by treatment of vinclozolin in the evaluation systems. Our results suggest that earthworm and yeast are useful to evaluate acute toxicity of endocrine disrupting chemicals, and direct comparison of toxicity data from different bioassay systems is unattainable. Based on our results, we propose that the bioassay system with earthworm or yeast, a rapid, simple and economic system, could be applied as pre-test for the toxicity evaluation using human cell line or animals.

The Design and Fabrication of μCCA-μGI Device for Toxicity Evaluation of Acetaminophen (아세트아미노펜 독성평가를 위한 μCCA-μGI 디바이스의 개발)

  • Chang Jung-Yun;Shuler Michael L.
    • Journal of Pharmaceutical Investigation
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    • v.36 no.4
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    • pp.263-269
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    • 2006
  • Deficiencies in the early ADMET(absorption, distribution, metabolism, elimination and toxicity) information on drug candidate extract a significant economic penalty on pharmaceutical firms. Microscale cell culture analogue-microscale gastrointestinal(${\mu}CCA-{\mu}GI$) device using Caco 2, L2 and HEp G2/C3A cells, which mimic metabolic process after absorption occurring in humans was used to investigate the toxicity of the model chemical, acetaminophen(AAP). The toxicity of acetaminophen determined after induction of CYP 1A1/2 in Caco 2 cells was not significant. In a coculture system, although no significant reduction in viability of HEp G2/C3A and L2 cells was found, approximately 5 fold increase in the CYP 1A1/2 activity was observed. These results appear to be related to organ-organ interaction. The oral administration of a drug requires addition of the absorption process through small intestine to the current ${\mu}CCA$ device. Therefore, a perfusion coculture system was employed for the evaluation of the absolution across the small intestine and resulting toxicity in the liver and lung. This system give comprehensive and physiologic information on oral uptake and resulting toxicity as in the body. The current ${\mu}CCA$ device can be used to demonstrate the toxic effect due to organ to organ interaction after oral administration,

Behavioral Toxicity of Psychotropic Drugs (향정신성약물의 행동학적 독성)

  • Yoon, Jin-Sang
    • Korean Journal of Biological Psychiatry
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    • v.5 no.1
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    • pp.46-55
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    • 1998
  • Any compound which disrupts the integrity of psychological aspects of performance, in particular, cognitive ability and psychomotor function analogous to the psychological behaviors of routine life, is known to be behaviorally toxic. A significant level of behavioral toxicity will interfere with patient safety and quality of life, and also may be counter-therapeutic by exacerbating the condition that the drug was prescribed for. Now, behavioral toxicity of psychotropic drugs has become one of the main growth areas of psychopharmacological research. Evaluation of the potential of drug-induced behavioral toxicity is important not only to the experimental researcher involved in human psychopharmacology, but also to the clinical practitioner treating psychiatric patients. This article attempts to describe behavioral toxicity of the three classes of psychotropic drugs - benzodiazepines, antidepressants and neuroleptics. After a brief discussion of some methodological issues arising in the investigation of behavioral toxicity, each of these drug classes is reviewed in the context of practical importance rather than purely scientific concern. The last session summarizes some suggestions for future studies on drug-induced behavioral toxicity.

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Simple and Rapid Evaluation System for Endosulfan Toxicity and Selection of Endosulfan Detoxifying Microorganism Based on Lumbricus rubellus (Lumbricus rubellus를 이용한 endosulfan의 간편, 신속 독성 평가 및 endosulfan 분해 미생물의 선별)

  • Sohn Ho-Yong;Kim Hong-Ju;Kum Eun-Joo;Lee Jung-Bok;Kwon Gi-Seok
    • Journal of Life Science
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    • v.16 no.1
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    • pp.108-113
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    • 2006
  • To compensate the problems of chemical assay in detoxification of recalcitrant and a practical approach in selection of bioremediation bacteria, a simple and rapid toxicity evaluation system was constructed based on Lumbricus rubellus. Long term-culture and specific equipment are not necessary, and semi-quantitative analysis of toxicity at sub-lethal concentration is possible by measuring of dose-dependent increased yellowish secreted compounds. When the toxicity of endosulfan, its metabolites and structurally related chemicals were measured for 24 h, the results were coincided with previous reports. Toxicity was found in endosulfan, endosulfan sulfate, aldrin, and dieldrin, respectively. Rapid and economic selection of endosulfan-detoxifying bacteria was possible using our system. Klebsiella pneumoniae KE-1, K. oxytoca KE-8 and Pseudomonas sp. KS-2P, reported endosulfan degrading bacteria, ameliorated the endosulfan toxicity, whereas E. coli, B. subtilis and other bacteria failed to protect the toxicity of endosulfan in L. rubellus. Our results suggest that the constructed system is useful to selection of microorganism as well as toxicity evaluation against toxic recalcitrants.

Principles and Methods for the Reproductive-toxicological Evaluation of New Drug Candidates (의약후보물질의 생식독성평가 원칙 및 방법)

  • 정문구;김종춘
    • Toxicological Research
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    • v.16 no.3
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    • pp.229-238
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    • 2000
  • The purpose of reproductive toxicity studies is to evaluate all effects resulting from paternal or maternal exposure that interfere with conception, development, birth, and maturation of offspring. In 1966, the US Food and Drug Administration (US FDA) published guidelines for a three-segment study for drug testing to examine adverse effects on fertility and pregnancy. Three segments were proposed: Segment I, Study of Fertility and General Reproductive Performance, to provide information on breeding, fertility, nidation, parturition, neonatal effects and lactation: Segment II, Teratological study, to provide information on embryo toxicity and teratogenicity: and Segment III. perinatal and Postnatal Study, to provide information on late fetal development, labour and delivery, neonatal viability, and growth and lactation. The classic guideline is still used to this day with only monor modification throughout the world. In the present review, the principles and methods of reproductive toxicity studies are discussed with special attention given to scientific issues.

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