• Toxicological Research
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• 제14권3호
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• pp.427-433
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• 1998

The acute and genetic toxicity of DK1002 was subjected in this study. DK1002 which is a morphine-like new drug candidate synthesized by Dong-Kook Pharmaceutical Co. Ltd. is now under developing as a analgesics that have better drug efficacy and least addictive property. In acute toxicity study, the 50% lethal doses ($LD_{50}$) of DK1002 were determined as>2000mg/kg (p.o.), 237.0mg/kg(i.p.), 57.5mg/kg(i.v.), and 1266.9mg/kg (s.c.). And also, to study the genotoxicity of DK1002, we performed bacterial reversion assay with Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and in vitro chromosomal aberration assay with Chinese hamster lung cells in the presence and absence of S-9 metabolic activation system. In vivo micronucleus assay using mouse bone marrow cells was also performed. From these results, DK1002 was revealed nonmutagenic potential in S. typhimurium TA98, TA100, TA1535, and TA537 both in the absence and presecne of metablic activation system. No clastogenicity of DK1002 was observed in chromosomal aberration assay in vitro as well as in micronucleus assay in vivo.

• 한국응용곤충학회지
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• 제10권1호
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• pp.13-22
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• 1971

이 실험은 이화명나방 월동 유충에 대한 유기인 살출제의 in vitro에 있어서의 ChE저해력과 약제의 화학 구조와의 관계, in vivo에 있어서의 국소 시용법에 의한, 살충제의 독성과 화학 子조와의 관계, 특히 ChE 저해력과 살충력(독성)과의 관계를 비교 연구할 목적으로 실험하였으며 그 결과를 다음과 같이 요약할 수 있다. 1, Phosphate compounds는 thiophosphate compounds보다 in vitro에 있어서의 ChE 저해력은 강하다고 할 수 있으나 in vivo에 있어서의 독성은 비례적으로 반드시 강하다고 할 수 없다. 2. Alcoxy 즉 diethoxy는 dimethoxy보다 ChE 저해력과 독성이 비례적으로 반드시 강하다고 할 수 없다. 3. $(RO)_2PO(S)X$ 부분에 있어서 이 X부분이 달라짐에 따르는 ChE 저해력과 살충력에 대해서는 약제에 따라서 각각 다르게 나타나므로 언급할 수 없다. 4. ChE 저력이 강한 약제는 살충력도 비례적으로 강하다고 할 수 없다. 그러나 화학 구조상 안정성이고 실용 농약인 Ethylparathion, Malathion, Let aycid, EPN, Sumithion 및 Diazinon 등에서 고찰할 때 반드시 비례적인 것은 아니나 어느 정도의 파행 관계가 있지 않은가 추찰된다.

• Entomological Research
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• 제48권6호
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• pp.533-539
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• 2018

The RNA interference (RNAi) has been considered as an important genetic tool and applied to develop a new living modified (LM) crop trait which is an improvement of nutrient quality or pest management. The RNAi of DvSnf7 has been used for resistance to LM maize and the Western Corn Rootworm which is a major agricultural pest for the US Corn Belt. Most of the environmental risk assessments (ERA) of double strand RNA (dsRNA) have been performed using in vitro transcript products, and not in vivo expressed product. A large amount of dsRNA was required for the acute toxicity assay of water fleas. Therefore development of massive dsRNA purification techniques is critical. Daphnia, a freshwater microcrustacean, is a model organism for studying cellular and molecular mechanism involved in life history traits and ecotoxicology. In this study, we established the massive dsRNA purification method using Escherichia coli and implemented acute toxicity assays to Daphnia magna. As a result, the present RNase A and DNase I, dsRNA was efficiently purified without any special techniques or equipment. Even though purified dsRNA existed during the acute toxicity test, lethality or abnormal behavior were not observed in D. magna. These results indicated that GFP and DvSnf7 dsRNA were not significantly affected to D. magna due to their lack of sequence matching in its genome. The purification method of dsRNA and the acute toxicity assay of water fleas using purified dsRNA would be suitable for the toxicological studies of LMOs to aquatic non-target organisms.

• Journal of Applied Biological Chemistry
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• 제58권2호
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• pp.113-116
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• 2015

Silver materials may be toxic in humans because they can enter the body and accumulate, typically in the lungs. We hypothesized that the cytotoxicity of naive silver materials is affected by their size and shape. Our in vitro assays revealed that the overall toxicity was in the following order: submicro-particles>wires>micro-particles. These results contrast with previous studies, which showed that silver wires are the most toxic among the three tested materials, possibly due to differences in cell lines. Evaluations of in vivo pulmonary toxicity revealed eryptosis in the cavity lining of the lung sections. The observed eryptosis was consistent with the in vitro results. Our results indicate that silver materialinduced cytotoxicity must be measured and compared using various methods.

• Toxicological Research
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• 제35권4호
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• pp.343-351
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• 2019

Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of inhouse candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.

• Toxicological Research
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• 제26권3호
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• pp.233-236
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• 2010

The analytical in vivo chromium ion was searched for using a voltammetric hollow-fiber dialysis sensor via square wave stripping voltammetry (SW), cyclic voltammetry (CV), and chronoamperometry. Under optimum parameters, the analytical results indicated linear working ranges of 50~400 mg/l CV and $10{\sim}80\;{\mu}g/l$ SW within a 30-sec accumulation time. The analytical detection limit (S/N) was $6.0\;{\mu}g/l$. The developed method can be applied to in vivo tissues and in ex vivo toxicity assay, as well as to other materials that require chromium analysis.

• 약학회지
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• 제45권6호
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• pp.739-745
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• 2001

Of all pesticides, carbamates are known to be most common, since alternatives such as organophosphates have long lifetime and are extremely toxic to produce a delayed neurotoxic effect. Although a number of studies about toxicity of carbofuran, a most widely used carbamate, have been reported, its cardiovascular toxicity has not yet been studied. In the present study, we investigated its cardiovascular toxic effect in anesthetized rat in vivo and in isolated Langendorff rat heart, In anesthetized rat model, carbofuran (10 mg/kg) significantly reduced heart rate, and transiently increased blood pressure. In isolated rat heart, carbofuran (10${\mu}{\textrm}{m}$) caused a significant depression in the left ventricular developed pressure (LVDP), indicating contractile dysfunction by carbofuran. Carbofuran (10${\mu}{\textrm}{m}$) also decreased coronary flow rate (CFR) in isolated heart, indicating carbofuran-induced coronary dysfunction. These results suggest that carbofuran can cause cardiac dysfunction in rat in vivo and vitro.

• Environmental Analysis Health and Toxicology
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• 제10권3_4호
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• pp.29-40
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• 1995

To investigate and evaluate the scavenging and antioxidative effects of various ftavonoids on paraquat induced pulmonary toxicity, in vivo and vitro tests of eight flavonoids(catechin, epicatechin, flayone, chrysin, apigenin, quercetin, morin and biochanin A) were carried out. In vitro test, inhibitory and antioxidative effects of lipoxygenase dependent lipidperoxidation, NADPH dependent cytochrome p-450 reductase to liver and lung microsome and superoxide anion production in rat peritoneal exudated macrophage were studied. In vivo test, biochemical parameters and cell population in bronchoalveolar lavage fluid(BALF) in mouse and rats after administration of paraquat and flavonoids were tested. The results are summerized as follows; 1. All flavonoids tested inhibited on NADPH dependent cytochrome p-450 reductase in liver and lung microsome. 2. All flavonoids tested showed the inhibitory effects on the superoxide anion production in rat peritoneal exudated macropharge. 3. Lactate dehydrogenase, acid phosphatase and total protein in BALF of mouse which increased by the administration of paraquat, decreased significantly by catechin, chrysin, morin and biochanin A. 4. Numbers of alveolar macropharge and PMN in BALF of rats which increased by the administration of paraquat decreased by all the tested flavonoids. Therefore, all flavonoids tested showed the useful compounds for scavenger and antioxidant on paraquat induced pulmonary toxicity.

• Korean Journal of Acupuncture
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• 제36권1호
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• pp.74-80
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• 2019

Objectives : TA, a polyherbal extract, typically is used for pharmacopuncture therapy on patients with traffic accident-related injuries and musculoskeletal diseases. This study was performed to evaluate the safety of the TA extract, using a micronucleus test. Methods : The dose range and sampling time were first established. An in vivo micronucleus test was then performed to determine the induction of micronuclei in mouse bone marrow cells after a single intramuscular administration of TA to 7-week-old ICR mice (0.2 ml/animal, at 24 hours post-dosing). Results : The incidence of micro-nucleated polychromatic erythrocytes (PCEs) in PCEs in the TA group was similar to that in the negative-control group, while that in the positive-control group was significantly greater. The positive- and negative-control groups did not differ in the ratio of PCEs to total erythrocytes. Conclusions : Our toxicity study indicates that the TA extract does not induce micronucleus formation in mouse bone marrow cells.

• Archives of Pharmacal Research
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• 제14권1호
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• pp.73-77
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• 1991

The effects of pyridoxine (PN) on rifampicin (RMF) toxicity were investigated by both in vivo and in vitro methods. RMF (30 mg/kg) was injected intraperitoneally and PN(150 mg/kg) was administered orally to rats for 10 consecutive days. After treatment, clinical chemistry and hematologic profiles were measured. RMF and PN plus RMF did not show any adverse effects at this in vivo experimental condition. Thymidine incorporations of mice bone marrow cells were examined in vitro. RMF showed a decrease in thymidine uptake in a dose-dependent manner, but PN showed a reversal of the thymidine uptake suppression caused by RMF (p<0.01). On the other hand, PN showed a decrease in thymidine uptake at a high concentration level.