• Toxicological Research
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• 제16권1호
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• pp.73-76
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• 2000

Acute oral, intramuscluar, and intravenous toxicity studies of recombinant human interferon $\alpha$2$\alpha$(rhIFN $\alpha$2$\alpha$) were performed in Sprague-Dawley (SD) rats. SD rats were administered with doses of 31.25, 62.5, 125, 250 and 500 MIU/kg, respectively, and clinical signs, mortality and body weight changes were observed for 2 weeks. In all animals administered with rhIFN $\alpha$2$\alpha$, there was neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical signs and autopsy findings. Therefore, $LD_{50}$ of rhIFN $\alpha$2$\alpha$ was considered to be higher than 500 MIU/kg in SD rats.

• Biomolecules & Therapeutics
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• 제2권3호
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• pp.270-280
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• 1994

This study was conducted to evaluate the repeated dose toxicity of DA-3030, a recombinant human granulocyte colony stimulating factor(rhG-CSF), in rats. DA-3030 was administered intravenously once a day for 4 weeks to 20 males and 20 females per group at doses of 0(control), 115 and 1150 $\mu\textrm{g}$/kg, and to 15 males and 15 females per group at doses of 1.15 and 11.5$\mu\textrm{g}$/kg. After the administration period, 5 males and 5 females per group in the 0,115 and 1150 $\mu\textrm{g}$/kg groups were placed on withdrawal for 2 weeks. Through-out the study, all the rats survived. The administration of DA-3030 induced, a marked increase in the number of peripheral neutrophils, elevation of serum alkaline phosphatase activity, and splenomegaly in the rats of both sexes receiving 115 or 1150 $\mu\textrm{g}$/kg. Histopathologic examination revealed extramedullary granulopoiesis in spleen and liver, and increase in the number of activated macrophages in spleen in rats of both sexes in 115 and 115 $\mu\textrm{g}$/kg groups, and increased M/E ratio in 11.5, 115 and 1150$\mu\textrm{g}$/kg groups. Most of the changes produced by DA-3030 were thought to be attributable to exaggerated pharmacological effect of the drug, and subsided or disappeared after the recovery period. Under the present condition, no effect dose of DA-3030 is estimated at 1.15 $\mu\textrm{g}$/kg/day.

• Journal of Environmental Health Sciences
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• 제39권2호
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• pp.130-137
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• 2013

Objectives: The OECD QSAR Application Toolbox was developed by the Organisation for Economic Cooperation and Development (OECD) to facilitate the practical use of QSAR approaches in regulatory contexts as well as to reduce the need for additional animal testing. In this study, human health and the ecotoxicity of chemicals were predicted by applying the OECD QSAR Application Toolbox and the results were compared with experimental data in order to evaluate the applicability of this program. Methods: Read-across, trend analysis, and QSAR of OECD QSAR Application Toolbox were used for the prediction of toxicity. Results: The toxicity prediction was conducted on 6,354 chemicals for which toxicity data have been produced on the six endpoints of skin sensitization, skin irritation, eye irritation, mutagenicity, and acute toxicities of fish and Daphnia. From the total of 6,354, we obtained prediction results for 1,621 chemicals (25.5%). Conclusions: The predicted properties of mutagenicity, skin sensitization, and acute aquatic toxicities were reasonably good when compared with experimental data, but other endpoints were not due to the limitation of applicable chemical groups.

• Restorative Dentistry and Endodontics
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• 제14권1호
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• pp.7-24
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• 1989

The purpose of the study was to evaluate the cytotoxic effects of polycarboxylate cements and zinc phosphate cements in vitro. Human fibroblasts were cultured in ${\alpha}$-MEM, and each cement was manually mixed and filled in glass ring cylinder (8${\times}$8mm in diameter, in height.) Cement filled cylinders were placed in the center of the dish (35mm in diameter) containing 3ml of ${\alpha}$-MEM. Millipore filters to simulate dentinal barrier were also placed between the cylinder and the dish, then stored in 5% $CO_2$ containing chamber for 1 and 2 weeks at the temperature of $36.6^{\circ}C$. The results of the experiments were analyzed by counting the cells in the period of one week and two weeks respectively, and were assessed by calculating the cell multiplication rate and the relative growth rate. The experimental groups and the control group were compared. The results of the study were summarized as follows. 1. Durelone brand of the polycarboxylate cements showed marked cytotoxicity after one week, but after two weeks the toxicity decreased remarkably. Poly-F brand exhibited moderate cytotoxicity after one week, but after two weeks the toxicity slightly decreased. HY-BOND brand was weakly cytotoxic after one week, but after two weeks the toxicity became significant. 2. The cytotoxicity of the zinc phosphate cements was negligible after one week, but after two weeks Lee Smith brand revealed considerable cytotoxicity. 3. In general, the zinc phosphate cements were less cytotoxic than the polycarboxylate cements.

• YAKHAK HOEJI
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• 제42권5호
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• pp.534-539
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• 1998

Effect of recombinant human epidermal growth factor (rhEGF, DWP401) on fetal external, visceral and skeletal malformation during organogenesis was examined. Pregnant Sprauge-Daw ley rats were administered with 0.2, 1 and 5mg/kg/day subcutaneously on gestation day 6 through 16. Dams were sacrified at 20th day of gestation. Materal body weight, food consumption and clinical observation were not changed. Significant dose-dependent increase of relative and absolute liver weight were observed in the treatment group, whereas other organ weights were not changed. Placental weight of 1 and 5mg/kg/day group and number of resorption in 5mg/kg/day treatment group were significantly increased. External and visceral malformation of fetuses were not observed with treatment. However, skeletal variations(increase of asymmetry sternebrae, decrease of dumb-bell and asymmetry sternbrae at 5mg/kg/day, and fused stemebrae at 5mg/kg/day) were observed. These results showed that rhEGF (DWP401) may not have embryo and/or fetal developmental toxicity effect in rats.

• Molecules and Cells
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• 제38권12호
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• pp.1096-1104
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• 2015

Particulate $matter_{2.5}$ ($PM_{2.5}$) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which $PM_{2.5}$ aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous $PM_{2.5}$ solution on lipoprotein metabolism. Collected $PM_{2.5}$ from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. $PM_{2.5}$ extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. $PM_{2.5}$ treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by $PM_{2.5}$ solution in a dose-dependent manner. Further, $PM_{2.5}$ solution caused cellular senescence in human dermal fibroblast cells. Microinjection of $PM_{2.5}$ solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of $PM_{2.5}$ induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins.

• Toxicological Research
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• 제18권1호
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• pp.99-106
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• 2002

The United States Environmental Protection Agency (EPA) characterized the cancer hazard of di(2-ethylhexyl)-phthalate (DEHP) as a B2 group (probable human carcinogen) and proposed "Guide-lines for Carcinogen Risk Assessment". This guidelines proposed alternative methods for analyzing carcinogen dose-response data and for extrapolating the effects of observed at high dose to predict that might occur at lower doses relevant to human exposure. This proposed guidelines state that "If in a particular case, the evidence indicated a threshold, as in the case of carcinogenicity being secondary to another toxicity that has a threshold, the margin of exposure analysis for toxicity is the same as is done for a non-cancer endpoint". DEHP is excellent candidate for reconideration under the new guidelines for carcinogen risk assessment (John Doull et al., 1998). This study is conducted about risk assessment for infant exposure on DEHP in powdered milk wing methodology in EPA's new guideline on carcinogenic risk assessment. Estimated cancer risk of DEHP in powdered milk and cow milk is 2.83$\times$$10^5$ (using cancer potency: 1.4$\times$$10^2$/ (mg/kg/day)) as mean and MOE is 12075 (using selected NOEL 20 mg/kg/day) as mean. mg/kg/day) as mean.

• Toxicological Research
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• 제18권1호
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• pp.65-71
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• 2002

A benchmark dose (BMD) approach has been evaluated us a replacement for the traditional NOAEL methodology currently being wed to assess the noncancer effects of toxicants. The endocrine disrupt-ing effect of endosulfan which showed decrement of sperm count and testicular testosterone level in animals, was currently reported. The amount of endosulfan used as pesticide in the country has been continuously increased. The aim of this study was to suggest the permissible intake level (PIL), corresponding to Accept-able Daily Intake (ADI), based on endocrine disrupting effect wing BMD. Various animal data were collected by consideration of critical effect showing endocrine disruption and an animal data for reproductive toxicity was selected. The Power model from BMD software for induction of $BMD_10$ having meaning which is the dose at the 95% lower confidence limit on a 10% response was used due to that the form of selected dose-response animal data was continuous data. The $BMD_10$ was estimated to be 0.393 mg/kg/day based on reproductive toxicity showing decrement of sperm count. The permissible intake level (PIL) was calculated by dividing the $BMD_10$ by the uncertainty factors of 100 with consideration of from animal to human and human variability. The PIL as 0.004 mg/kg/day was compared with traditional ADI as 0.006 mg/kg/day based on the incidence of marked progressive glomerulonephrosis and blood vessel aneurysm in males.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.189-195
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• 2017

This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion.

• The Journal of Internal Korean Medicine
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• 제35권3호
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• pp.244-261
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• 2014

Objectives: This experiments were performed to determine the effects of the Jehasuogamibang (製何首烏加味方: JHGB) on antioxidationactivity and hyperlipidemia induced by a hypercholesterolemic diet in mice. Methods: After treatment with JHGB expert safety in cytotoxicity and toxicity of Human fibroblast cells and liver and kidney, effect on Reactive Oxygen Species, serum total cholesterol, LDL-cholesterol, triglyceride, glucose, HDL-cholesterol, lipid peroxid of liver tissue, significantly increased SOD and catalase. Results: 1. JHGB showed safety in cytotoxicity and toxicity of human fibroblast cells and liver and kidney. 2. JHGB showed significant inhibitory effect on reactive oxygen species. 3. JHGB significantly decreased serum total cholesterol, LDL-cholesterol, triglyceride, and glucose, and significantly increased serum HDL-cholesterol. 4. JHGB significantly decreased lipid peroxide of liver tissue and significantly increased SOD and catalase. Conclusions: These results suggest that Jehasuogamibang is effective in antioxidationactivity and dietary hyperlipidemia-induced mice.