• Toxicological Research
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• 제11권1호
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• pp.91-101
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• 1995

A perinatal and postnatal study of KTC-1, a new semisyntheitic rifamycin antituberculous drug, was conducted in Sprague-Dawley rats. Dosages of KTC-1 0, 12, 27.6, and 63.5 mg/kg/day were administered to dams orally by gavage from day 17 of gestation to day 21 of lactation. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. At 63.5 mg/kg/day, weakness, dark-red discharge around eyes, a loss in body weight, and a decrease in food and water consumption were observed in dams. An increase in the weight of adrenal gland and spleen, and a decrease in the weight of kidney and heart were also found. An increase in neonatal deaths during the lactation period, a loss in body weight, a delay in physical development, a decrease in traction ability, an increase in the number of errors and the time required for the multiple T-maze trial were found in F1 offspring. In addition, an increase in the incidence of visceral variations and retarded ossification were observed in F1 4 day old rats. An increase in the incience of skeletal anomalies was seen in F2 fetuses. There were no sings of maternal toxicity or embryotoxicity at 12 and 27.6 mg/kg/day. From the results mentioned above, it can be concluded that the no-effect dose levels(NOELs)for dams, F1 offspring, and F2 fetuses are 27.6 mg/kg/day.

• Toxicological Research
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• 제14권3호
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• pp.401-409
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• 1998

Group of 40 male and 40 female ICR mice was given daily per oral treatment with the combination of enalapril plus Ginkgo biloba extract (EGb 761), 3+9mg/kg/day(low dosage group), 10+30mg/kg/day (middle dosage group), 30+90mg/kg/day (high dosage group) for 3 months in drinking water according to Established Regulation of Korean National Institute of Safety Research (1994. 4.14). Appearance, behavior, mortality, and food consumption of mouse of treated groups were not affected during the experimental periods. No significant the combination of enalapril plus Ginkgo biloba extract (EGb 761)-related changes were found in urinalysis, hematology, serum chemistry, and organ weight, Lung edema were observed and the weight of lung were increased in low dosage treated group of the male mice, which be associated with enalapril treatment, but these changes were not found in middle and high dosage group. Our results suggest that to toxic changes were found in rat treated orally with the combination of enalapril plus Ginko biloba extract (EGb 761) for 3 months.

• Toxicological Research
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• 제29권3호
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• pp.211-215
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• 2013

The trace toxic metal copper was assayed using mercury immobilized on a carbon nanotube electrode (MCW), with a graphite counter and a reference electrode. In this study, a macro-scale convection motor was interfaced with a MCW three-electrode system, in which a handmade MCW was optimized using cyclic- and square-wave stripping voltammetry. An analytical electrolyte for tap water was used instead of an expensive acid or base ionic solution. Under these conditions, optimum parameters were 0.09 V amplitude, 40 Hz frequency, 0.01 V incremental potential, and a 60-s accumulation time. A diagnostic working curve was obtained from 50.0 to 350 ${\mu}g/L$. At a constant Cu(II) concentration of 10.0 ${\mu}g/L$, the statistical relative standard deviation was 1.78% (RSD, n = 15), the analytical accumulation time was only 60 s, and the analytical detection limit approached 4.6 ${\mu}g/L$ (signal/noise = 3). The results were applied to non-treated drinking water. The content of the analyzed copper using 9.0 and 4.0 ${\mu}g/L$ standards were 8.68 ${\mu}g/L$ and 3.96 ${\mu}g/L$; statistical values $R^2$ = 0.9987 and $R^2$ = 0.9534, respectively. This method is applicable to biological diagnostics or food surveys.

• Toxicological Research
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• 제29권3호
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• pp.203-209
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• 2013

A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of ${\varepsilon}$-acetamidocaproic acid (AACA), the primary metabolite of zinc acexamate (ZAC), in rat plasma by using normetanephrine as an internal standard. Sample preparation involved protein precipitation using methanol. Separation was achieved on a Gemini-NX $C_{18}$ column ($150mm{\times}2.0mm$, i.d., 3 ${\mu}m$ particle size) using a mixture of 0.1% formic acid-water : acetonitrile (80 : 20, v/v) as the mobile phase at a flow rate of 200 ${\mu}l/min$. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of AACA were linear over the concentration range of 20~5000 ng/ml in rat plasma. The coefficient of variation and relative error at four QC levels were ranged from 1.0% to 5.8% and from -8.4% to 6.6%, respectively. The present method was successfully applied for estimating the pharmacokinetic parameters of AACA following intravenous or oral administration of ZAC to rats.

• Toxicological Research
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• 제21권1호
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• pp.51-55
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• 2005

To investigate the acute toxicity of adventitious roots extract derived from wild ginseng, it was orally administered to beagle dogs with a single dose. In acute toxicity test, three groups (9 beagle dogs of male) were administered with different dosages of adventitious roots extract (prepared by Biopia Corp.) 500 mg/kg (G2), 1,000 mg/kg (G3), 2,000 mg/kg (G4) and one group (G1, 2 beagle dogs of male) were received by only capsule without the extract according to the Regulation on Korea Food and Drug Administration (1999. 12. 22). There were vomitus for a time and mucous stool at the day, and anorexia and mucous stool at the first day in the group of 2,000 mg/kg administration. There were mucous stool in one and anorexia for a while in two beagle dogs at the first day in the 1,000 mg/kg administration. But no death or abnormal clinical sign was observed through the study period. Therefore, the adventitious roots extract derived from wild ginseng is considered not to have the acute toxicity in the beagle dogs. These results suggest that LD/sub 50/ value of the test substance was considered to be more than 2,000 mg/kg in the beagle dogs.

• Toxicological Research
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• 제21권1호
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• pp.63-70
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• 2005

Gami-Honghwa-Tang (KH-19), a herbal prescription for reducing the side effect of radiotherapy, is composed of eight crude herbs such as Rehmanniae Radix Preparata, Angelicae Gigantis Radix, Cnidii Rhizoma, Paeoniae Radix, Corni Fructus, Moutan Cortex Radicis, Lycii Fructus, Carthami Flos, and Glycyrrhizae Radix. In this study, marker substances in KH-19 were analyzed by high performance liquid chromatography-diode array detector (HPLC-DAD) and safety evaluation of standardized KH-19 was evaluated by good laboratory practices (GLP) guideline of Korea Food and Drug Administration. HPLC-DAD was employed to determine the quantities and the qualities of several marker substances such as 5-hydroxymethyl-2-furaldehyde (5-HMF), paeonol, loganin, paeoniflorin, glycyrrhizin, and decursin in the KH-19. In acute oral toxicity study on rat, transient inhibition of body weight was shown, but change in general symptom was not detected. No dead animal was observed up to 5,000 mg/kg in both male and female animals. In acute oral toxicity study on Beagle dog, transient vomiting, diarrhea, anorexia, and body weight reduction were observed, However, no dead animal was observed up to 2,000 mg/kg in both male and female animals.

• 한국환경성돌연변이발암원학회지
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• 제23권1호
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• pp.35-40
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• 2003

Polycyclic aromatic hydrocarbons (PAH) are frequently detected in food, water, soil, and sediment and are widespread environmental pollutants formed by the incomplete combustion of fossil fuels, woods and other organic matter. PAHs are considered to be probable human carcinogens. The mechanism of action of PAHs has been studied extensively, however it is not clear how PAHs turn on CYP1A1 in human breast cancer. Our laboratory have been studied the effect of PAHs in the human breast cancer cell MCF7. In this study, we examined the ZR-75-1 human breast cancer cells as a new system to evaluate bioactivity of PAHs. ZR-75-1 human breast cancer cell line responses to estrogen and progesteron. We have been able to estbilish long term culture system of this cells then used for the study to observe the effect of PAHs. We demonstrate that PAHs induced the CYP1A1 promoter and 7-ethoxyresolufin O-deethylase (EROD) activity in a concentration-dependant manner. RT-PCR analysis indicated that PAHs significantly up-regulate the level of CYP1A1 mRNA. Some of PAHs showed stronger stimulatory effect on CYP1 gene expression than TCDD. Apparently, ZR-75-1 cells have Aryl hydrocarbon receptors, therefore it would be good experimental tool to study the cross-talk between PAHs and steroid actions.

• 한국환경성돌연변이발암원학회지
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• 제18권1호
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• pp.32-36
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• 1998

It is previously reported that 6-paradol can induce prolonged analgesia in experimental animals. In order to investigate the mutagenicity of 6-paradol, Ames Samonella/microsome plate assay was carried out with Salmonella typhimurium strains, TA 98, TA 100, TA 1535 and TA 1538, 6-Paradol was nonmutagenic in Salmonella typhimurium with and without rat liver microsomal activation. The rec assay with Bacillus substilis strains H 17 $rec^+$ and M 45 $rec^+$ was carried out ot test 6-paradol and other compounds (1-3 mg/disc) for DNA damaging activity, 6-Paradol was also nonmutagenic in DNA damaging activity. The relative size of the inhibition zone for 6-paradol was smaller than that of capsaicin. We have also determined the pathological effects of this compound on the various tissues of rats after administrating(i.p.) with increasing doses of 4, 8, 12, 16 mg/kg at 2 hour intervals and found no significant changes in terms of histology.

• 한국환경성돌연변이발암원학회지
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• 제18권1호
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• pp.43-46
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• 1998

굴(Oester)껍질에 은 이온을 도입해 개발한 수질 정화제 Ag-Os의 복귀 돌연변이원성을 관찰하기 위하여, Salmonella typhymurium TA 1535, TA 1537, TA 98, TA 100 이용하였고, DAN-손상여부를 관찰하기 위하여 Bacillus Subtils H-17($Rec^+$)와 H-45($Rec^-$)을 이용하였다. Ag-Os에 의한 복귀 돌연변이는 관찰되지 않았고, 이는 S9을 첨가시에도 같은 현상을 나타내었다. Rec-assay에 의한 DNA 손상도 관찰되지 않은 결과로 미루어, 수질 정화제 Ag-Os는 본 시험 조건에서 변이원성을 보이지 않음을 확인하였다.

• BMB Reports
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• 제34권1호
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• pp.90-94
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• 2001

The mutagenic activity of chitosan oligosaccharide and its antimutagenic effect against 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were investigated using the Salmonella/Ames test. No mutagenic activity was found in the Salmonella typhimurium strains TA 98 and TA 100, either with or without S9 activation. In contrast, chitosan oligosaccharide showed an inhibitory effect on the mutagenic activity of the cooked food mutagen, MeIQx, in the presence of S9. The influence of chitosan oligosaccharide on the genotoxicity of MeIQx was examined using a host-mediated assay in mice. The oligosaccharide was administered for 14 consecutive days (intragastric application at doses of 0.1 or 0.5 g/kg body wt) to mice. S. typhimurium TA 98 was given intravenously before an oral dose of MeIQx (4.5 mg/kg body wt.). The number of $his^+$ revertants were determined from the Ever of mice. The intragastric application of oligosaccharide led to a 47% reduction in the number of mutants induced by MeIQx (p<0.05). These results suggested that chitosan oligosaccharide had antimutagenic properties against MeIQx in vitro and in vivo.