• Journal of Preventive Medicine and Public Health
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• v.19 no.1 s.19
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• pp.123-129
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• 1986

Fetal weight data from 84 litters of Sprague-Dawley rats were statistically analyzed for the effect of position in the uterine horn on fetal weight. The standard score obtained from the mean weight and standard deviation of all fetuses in a uterine horn were studied for position effect. In control group, the heaviest fetus occupied the middle position with a progressive decrease in weights toward the ovarian and cervical ends of the horn. But the effect related to position for the fetal weight was not statistically significant. In contrast, rats acutely or chronically exposed to carbon monoxide showed statistically significant positional differences of fetal weight within the uterine horns. The findings that the intrauterine position effect on fetal weight which is not signicant in control group may act one of confounders at the situation of transplacental toxicological studios.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.22 no.4
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• pp.316-328
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• 2012

Objectives: This study was designed to provide the information regarding chemicals classification and health hazard by evaluating the toxicological effect through repeated inhalation exposure of methyl acrylate(MA) in Sprague-Dawley(SD) rat for 13 weeks. Methods: According to the notification with Ministry of Labor(No. 2009-68) and OECD Test Guideline 413, the rats were exposed to MA at concentration of 0, 56, 168, 280 ppm via whole body inhalation for 6 hours per day, 5 days per week, for 13 weeks. All animals were observed for mortality, morbidity and the change of body weight and food consumption were determined during the exposure period. Necropsy finding, organ weight, hematology, clinical biochemistry and histopathological examination following exposure were also performed. Results: There were no death and abnormal clinical signs relate to exposure MA. However, At 160 ppm and 280 ppm exposure groups, body weight and food consumption showed statistically significant decrease and histopathological changes in lung, trachea, nasal cavity, larynx were observed. Conclusions: MA was mainly affected respiratory tract. It is consequently provided to be classified as category 2(0.2 mg/L/6h < category 2 ${\leq}$ 1.0 mg/L/6h) for specific target organ toxicity following repeated exposure according to Standard for Classification and Labeling of Chemical Substance and Material Safety Data Sheet. The NOAEL(no observable adverse effect level) of MA was also determined to be lower than 56 ppm.

• The Journal of Internal Korean Medicine
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• v.36 no.2
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• pp.189-199
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• 2015

Objectives: The marker substances of cultivated wild ginseng pharmacopuncture that may not be detected during the process of steaming remain controversial. We developed a combined cultivated wild ginseng pharmacopuncture that contains all the marker substances. The aim of this experiment was to investigate the marker substances and test the toxicity of the combined cultivated wild ginseng pharmacopuncture. Methods: The marker substances were detected using HPLC. Intravenous injection toxicity studies were conducted at Medvill, an authorized institution for non-clinical studies, under the regulations of Good Laboratory Practice. We observed survival rates, abnormal behaviors, weight changes, gross findings in autopsy, blood biochemical properties, and histological abnormalities of organs such as the liver and kidney. Results: HPLC data showed that ginsenosides Rg1, Rb1, and Rg3 were detected at concentrations of 19.29, 47.64, and 3.02 μ g /ml, respectively. Administration of combined cultivated wild ginseng pharmacopuncture resulted in no dead animals or significant toxicological changes. Conclusions: The combined cultivated wild ginseng pharmacopuncture contains all the marker substances and is a relatively safe treatment medium. Further studies should be conducted to confirm the present findings.

• Toxicological Research
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• v.13 no.4
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• pp.435-447
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• 1997

l-Muscone is synthesized for use as substitutive material of musk which is the active ingredient of woohwangchungsimwon. The objective of this investigation was to evaluate the acute and subacute toxicity of l-muscone in rats. In oral acute toxicity test, SPF Sprague-Dawley male and female rats were gayaged with l-muscone of two doses(0, 5.0 g/kg). No dead animal and abnormal autopsy findings were found in control and treated group. Body weights were slightly decreased in both sexes of rats treated with 5.0 g/kg. Therefore, oral $LD_{50}$ of l-muscone was consider to be higher than 5.0 g/kg in male and female rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with dosages of 0, 1,000, 1,316, 1,732, 2,279 and 3.000 mg/kg. Decreased body weights and motor activities were observed at high dose group. Intraperitoneal $LD_{50}$ of l-muscone were 1,920 mg/kg in male and female rats. In the subacute study, l-muscone was administrated orally to both sexes of rats for 4 weeks as several doses(0, 10, 100 and 1,000 mg/kg). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysist and other findings. Above data suggest that no observed adverse effect level of l-muscone in rats might be over 1,000 mg/kg/day in this study.

• Toxicological Research
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• v.19 no.4
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• pp.267-275
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• 2003

The purpose of our study was to evaluate the toxicity of the thimerosal in embryos and neonates. Thimerosal (also known as mercurothiolate) is a mercury-containing compound used in trace amounts to prevent bacteria and other organisms from contaminating vaccines, especially in opened multi-dose vials. The toxicity of mercury is well known and those most at risk occurrs in unborn babies and newborn babies. Test methods included in vitro whole embryo culture (WEC) system and in vivo test of neonatal toxicity in Wistar rats. Ethylmercury and methylmercury were used as positive controls for the evaluating of toxic effects of mercury. In WEC assay, treated concentrations of thimerosal, ethylmercury and methylmercury were up to 0.01, 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2.5 and 5 $\mu\textrm{g}$/$\textrm{m}{\ell}$, respectively. All compounds didn't show any morphological abnormalities, but showed retardation of growth and development in dose dependent manner (> 0.5 $\mu\textrm{g}$/$\textrm{m}{\ell}$). These data indicated that thimerosal showed developmental toxicity in vitro. In vivo neonatal toxicity, Wistar rats were administered subcutaneously with thimerosal, ethyl mercury, or methylmercury (5, 25, 50, 250, and 500 $\mu\textrm{g}$/kg) during from postnatal day (PND) 4 to 25. Significant effects of these compounds on relative organ weights and organ morphology were not observed in this experiment. However, accumulation of mercury was detected in the kidney and testis when treated with thimerosal, ethylmercury, or methylmercury. These results suggest that thimerosal may be a harmful compound to embryo and neonate, but used concentration of thimerosal in these experiments is much higher than that of clinical application. Further investigation is needed on the safety of vaccine components, i.e. a thimerosal using in vitro and in vivo tests in the future.

• Toxicological Research
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• v.19 no.4
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• pp.277-283
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• 2003

Polychlorinated biphenyls (PCBs) has been widely used as plasticizer, insulator, lubricant, paint and ink. The persistence of PCBs in the environment and their bioaccumulation in living organism make a raise concerns regarding their toxic effects in immune system and subsequent effects on human health. However little has been known about effect of PCB, an endocrine disrupter, on splenocytes. In this study, for identifying the effect on the organs and immune cell of mice by the concentration and time of commercial PCB mixture (Aroclor 1254), each 3 mice were tested at the concentration of 3, 30, 300, 1,000 mg/kg respectively, and their organ's weight were measured in 4, 7, 14 days, respectively. Also according to concentration and time, PCB was evaluated for the effects on splenocyte viability and lipopolysaccaride (LPS) and concanavaline A (Con A)-induced splenocyte proliferation on mice spleen. In liver and lung, there were significantly defferent by concentration and time of PCB (p < 0.0001). In respect of concentration of PCB, no significant effects on mice's liver by Aroclor 1254 concentration below than 300 mg/kg were observed except at the concentration of 1,000 mg/kg doses (p < 0.0001). But there was not significant different change in mice spleen by concentration and time of PCB (p=0.2206) and the mode of weight change of spleen was different to of liver and of lung. Viabilities of splenocytes were decreased following treatment with high concentration of PCB. Also, LPS and Con A-induced cell proliferations were decreased by Aroclor 1254 at 1,000 mg/kg. These data suggest that Aroclor 1254 is the immunotoxic compound that may have an effect on mouse immune system.

• Toxicological Research
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• v.22 no.4
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• pp.315-322
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• 2006

TALP-32 is highly basic protein with a molecular weight of 32 kDa purified from human term placenta. Some basic proteins such as defensins and cecropins are known to induce cell death by increasing membrane permeability and some of them are under development as an anticancer drug especially targeting multi-drug resistant cancers. Therefore, we investigated cytotoxic effect and mechanism of TALP-32 When HeLa cell was incubated with TALP-32, cytotoxicity was increased in time and dose dependent manner. As time goes by, HeLa cells became round and plasma membrane was ruptured. Increase of plasma membrane permeability was determined with LDH release assay. Also in transmission electron microscopy, typical morphology of necrotic cell death, such as cell swelling and intracellular organelle disruption was observed, but DNA fragmentation and caspase activation was not. And necrotic cell death was determined with Annexin V/Pl staining. The cytotoxicity of TALP-32 was minimal and decreased or RBC and Hep3B respectively. These data suggests that TALP-32 induces necrosis on rapidly growing cells but not on slowly growing cells implicating the possibility of its development of anticancer peptide drug.

• Toxicological Research
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• v.28 no.3
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• pp.179-185
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• 2012

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (${\beta}2m$), glutathione S-transferase alpha (GST-${\alpha}$), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

• Toxicological Research
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• v.28 no.3
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• pp.165-172
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• 2012

Raphanus sativus (Cruciferaceae), commonly known as radish is widely available throughout the world. From antiquity it has been used in folk medicine as a natural drug against many toxicants. The present study was designed to evaluate the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE) in vitro and in vivo test. The $IC_{50}$ values of REE in human liver derived HepG2 cells was over 5,000 ${\mu}g/ml$ in tested maximum concentration. The effect of REE to protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay. REE showed their hepatoprotective activities on tacrine-induced cytotoxicity and the $EC_{50}$ value was 1,250 ${\mu}g/ml$. Silymarin, an antihepatotoxic agent used as a positive control exhibited 59.7% hepatoprotective activity at 100 ${\mu}g/ml$. Moreover, we tested the effect of REE on carbon tetrachloride ($CCl_4$)-induced liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of 50 mg/kg were orally administered to $CCl_4$-treated rats. The results showed that REE and silymarin significantly reduced the elevated levels of serum enzyme markers induced by $CCl_4$. The biochemical data were supported by evaluation with liver histopathology. These findings suggest that REE, can significantly diminish hepatic damage by toxic agent such as tacrine or $CCl_4$.

• Toxicological Research
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• v.33 no.3
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• pp.211-218
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• 2017

Cytochrome P450 1B1 (CYP1B1) acts as a hydroxylase for estrogen and activates potential carcinogens. Moreover, its expression in tumor tissues is much higher than that in normal tissues. Despite this association between CYP1B1 and cancer, the detailed molecular mechanism of CYP1B1 on cancer progression in HeLa cells remains unknown. Previous reports indicated that the mRNA expression level of Herc5, an E3 ligase for ISGylation, is promoted by CYP1B1 suppression using specific small interfering RNA, and that ISGylation may be involved in ubiquitination related to ${\beta}-catenin$ degradation. With this background, we investigated the relationships among CYP1B1, Herc5, and ${\beta}-catenin$. RT-PCR and western blot analyses showed that CYP1B1 overexpression induced and CYP1B1 inhibition reduced, respectively, the expression of $Wnt/{\beta}-catenin$ signaling target genes including ${\beta}-catenin$ and cyclin D1. Moreover, HeLa cells were treated with the CYP1B1 inducer $7,12-dimethylbenz[{\alpha}]anthracene$ (DMBA) or the CYP1B1 specific inhibitor, tetramethoxystilbene (TMS) and consequently DMBA increased and TMS decreased ${\beta}-catenin$ and cyclin D1 expression, respectively. To determine the correlation between CYP1B1 expression and ISGylation, the expression of ISG15, a ubiquitin-like protein, was detected following CYP1B1 regulation, which revealed that CYP1B1 may inhibit ISGylation through suppression of ISG15 expression. In addition, the mRNA and protein expression levels of Herc5 were strongly suppressed by CYP1B1. Finally, an immunoprecipitation assay revealed a direct physical interaction between Herc5 and ${\beta}-catenin$ in HeLa cells. In conclusion, these data suggest that CYP1B1 may activate $Wnt/{\beta}-catenin$ signaling through stabilization of ${\beta}-catenin$ protein from Herc5-mediated ISGylation for proteosomal degradation.