• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.148-148
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• 2003

The cynomolgus monkey(Macaca fascicularis) is used widely in efficacy and safety assessment of new drugs. The ranges of physiological variables are important end points in the toxicological study. Both the basic physiological variables such as body weight, body temperature, blood pressure, urine pH and blood variables such as biochemical and hematological variables were determined in nineteen male and sixteen female monkey prior to treatment.(omitted)

• Toxicological Research
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• 제30권4호
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• pp.291-296
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• 2014

Saururus chinensis has been reported to contain compounds such as lignans, alkaloids, diterpenes, flavonoids, tannins, steroids, and lipids. Fermentation is commonly used to break down certain undesirable compounds, to induce effective microbial conversion, and to improve the potential nutraceutical values. Previous studies have reported that the fermentation process could modify naturally occurring constituents, including isoflavons, saponins, phytosterols, and phenols, and could enhance biological activities, specifically antioxidant and antimicrobial properties. The probiotic strains used for fermentation exert beneficial effects and are safe. In this study, the antioxidative effects of the Bacillus subtilis fermentation of Saururus chinensis were investigated in a rat model with Triton WR-1339-induced hyperlipidemia by comparing the measured antioxidative biological parameters of fermented Saururus chinensis extract to those of nonfermented Saururus chinensis extract. Fermentation played a more excellent role than nonfermentation in ultimately protecting the body from oxidative stress in the liver of the experimental rats with Triton WR-1339-induced hyperlipidemia.

• Toxicological Research
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• 제23권4호
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• pp.405-413
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• 2007

This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

• Toxicological Research
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• 제32권4호
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• pp.301-309
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• 2016

Due to undesirable hazardous interactions with biological systems, this investigation was undertaken to evaluate the effect of chronic exposure to silver on certain biochemical and some oxidative stress parameters with histopathological examination of brain, as well as the possible protective role of selenium and/or vitamin E as nutritional supplements. Thirty six male rats were divided into six groups of six each: the first group used as a control group. Group II given both vitamin E (400 mg/kg) of diet and selenium (Se) (1 mg/L) in their drinking water. Group III given silver as silver nitrate ($AgNO_3$) (20 mg/L). Group IV given vitamin E and $AgNO_3$. Group V given both $AgNO_3$ and selenium. Group VI given $AgNO_3$, vitamin E and Se. The animals were in the same exposure conditions for 3 months. According to the results which have been obtained; there was an increase in serum lactate dehydrogenase (LDH), lipase activities and cholesterol level, a decrease in serum total protein, calcium and alkaline phosphatase (ALP) activity in Ag-intoxicated rats. Moreover, the findings showed that $Ag^+$ ions affected antioxidant defense system by decreasing superoxide dismutase (SOD) activity and increasing vitamin E concentration with a high level of malondialdehyde (MDA) in brain tissue. The histological examination also exhibited some nervous tissue alterations including hemorrhage and cytoplasm vacuolization. However, the co-administration of selenium and/or vitamin E ameliorated the biochemical parameters and restored the histological alterations. In conclusion, this study indicated that silver could cause harmful effects in animal body and these effects can be more toxic in high concentrations or prolonged time exposure to this metal. However, selenium and vitamin E act as powerful antioxidants which may exercise adverse effect against the toxicity of this metal.

• Toxicological Research
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• 제19권3호
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• pp.205-210
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• 2003

The aim of this study was to estimate the influence of 37 bp insertion/deletion (I/O) poly-morphism of the low density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) gene on anthropometrical or biochemical parameters in korean general population. To determine the frequency of the genotype, we analyzed 244 samples of Korean origin. The frequency of the I allele was 0.55 in men and 0.56 in women, which were significantly higher than the frequency (0.26) that was reported in Czech population of Caucasian origin. In addition, the I allele of this polymorphism was significantly associated with higher value of body mass index (BMI) in our subjects by ANOVA test (P<0.05), and this association was maintained after controlling for age and gender by ANCOVA test (P<0.05). Thus, our results suggest that the I/O polymorphism of the LRPAP1 gene may be useful as a genetic marker for obesity in Korean general population.

• Toxicological Research
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• 제13권1_2호
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• pp.71-78
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• 1997

The mutational effects of pentachlorophenol (PCP) on the hypoxanthine phosphoribosyl transf erase (hprt) locus in human T-cell were analysed by T-cell clonal assay in vitro. Cells were exposed for 24 hours at primary culture to 0~100 ppm (W/V) PCP in dimethyl sulfoxide. Treated cells were allowed at the same time to stimulate by phytohemagglutinin (PHA) and T-cell growth factor (TCGF) and then seeded in medium containing 6-thioguanine to select for hprt-negative routants. We have also defined the optimal condition for the determination of mutant frequency. The parameters investigated include survival counting, first and second subculture for clonal efficiency plating and mutant plating. Under the optimal conditions, mutant frequencies of high dose-treated cells were significantly higher than those of non-treated or low dose cells. The results indicated a clear dose-effect relationship and showed that mutant frequency in 50 ppm PCP treated cell was 4.31$\times$$10^{-5}$ (background, 8.32$\times$$10^{-6}$). Above data strongly suggest that hprt mutation assay can be used as a biomarker for the environmental risk assessment.

• Toxicological Research
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• 제6권1호
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• pp.21-28
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• 1990

This study was undertaken to evaluate the immune responses to sheep red blood cell (SRBC) and potential anti-tumor effect of Bacillus Calmette-Guerin (BCG) in the mice bearing rumor induced by DMBA. The frequencies of tumor appearances were 62% in DMBA-treated mice and 14% in DMBA and BCG-treated group, respectively. Cellular immune response such as delayed-type hypersensitivity (DTH) to SRBCs, natural killer (NK) cell activity and antigen-binding cell (ABC) assay were decreased apparently in the tumor bearing mice compared to the normal controls. Humoral immune responses such as hemagglutinin (HA) and hemolysin (HE) were noted to be reduced in the tumor bearing mice, but the spleen index increased in tumor bearing mice. All the immunological parameters in the DMBA and BCG-group appeared to be higher than those of only DMBA-treated group. These results indicated that DMBA-induced tumor suppressed host immune responses. Also, they imply the idea that BCG enhanced the immune responses of tumor-bearing host and antitumor effects.

• 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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• 제3권1호
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• pp.45-53
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• 1987

A teratogenicity study was carried out on Sprague-Dawley rats which have been given the intravenously or intraperitonealy injections of rHuIFN-${\alpha}$A, an available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the off springs was observed. No changes were observed in all aspects of parameters between the treated and the control dams. The incidence of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. The rHuIFN-${\alpha}A$ caused no effects on parturition, lactation, and postnatal growth.