• Journal of Pharmacopuncture
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• v.16 no.4
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• pp.22-29
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• 2013

Objectives: This study was performed to analyze the toxicity of the test substance, anti-inflammatory pharmacopuncture (AIP), when used as a single intramuscular-dose in 6-week-old, male and female Sprague-Dawley rats and to find the lethal dose. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices. Twenty (20) female and 20 male Spague-Dawley rats were divided into 4 groups of five 5 female and 5 male animals per group. The rats in the three experimental groups received single intramuscular injections with 0.1-$m{\ell}$, 0.5-$m{\ell}$ and 1.0-$m{\ell}$/animal doses of AIP, Groups 2, 3, and 4, respectively, and the control group, Group 1, received a single intramuscular injection with a 1.0-$m{\ell}$ dose of normal saline. Clinical signs were observed and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematology, clinical chemistry, histopathological tests and necropsy were performed on the injected parts. Results: No deaths occurred in any of the groups. Also, histopathological tests showed that AIP had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusions: As a result of single intramuscular-dose tests of the test substance AIP in 4 groups of rats, the lethal dose for both males and females exceeded $1.0m{\ell}$/animal. Therefore, AIP is a relatively safe pharmacopuncture that can be used for treatment, but further studies should be performed.

• Analytical Science and Technology
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• v.34 no.6
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• pp.275-283
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• 2021

This study presents the development of cell-based microfluidic chips for the performance of acute eye irritation tests due to chemicals and examined some of their applications. Microfluidic chips were fabricated by photolithography and soft lithography, and they had three compartments with different areas for cell culture. Rabbit corneal epithelial cells were used for the eye irritation test. The death of cells cultured inside the chip was monitored at regular time intervals after treatment with an aqueous solution of chemicals, and the cell death rate constants were calculated based on the viability curve. The performance of the microfluidic chip was verified by examining the effects of cell-cell junctions, cell-substrate adhesion, and initial cell numbers compared to cell death rates. Eye irritation tests were performed at various concentrations of an aqueous solution of sodium dodecyl sulfate (SDS), a standard substance for the eye irritant test. The cells were exposed to the SDS aqueous solution for 300 s, and the resulting eye irritation was assessed by cell viability. Finally, the equation for calculating the toxicity score (TS) was derived based on the weighting factor for each compartment in the chip. The cell-based microfluidic chip developed in this study may be used for eye irritation tests from chemicals used in cosmetics and pharmaceuticals.

• The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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• v.13 no.2
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• pp.112-120
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• 2008

A series of experiments were conducted to establish a marine ecotoxicological standard method using marine primary producers, Skeletonema costatum, Heterosigma akashiwo, Prorocentrum micans, Isochrysis galbana, Tetraselmis suecica as candidate test species. Marine diatom, S. costatum was selected as standard test species in terms of the ecological roles and international uses as test species. Test methods and test acceptability criteria are as follows; $72{\sim}96$ hr population growth inhibition $EC_{50}$ as endpoint. Static non-renewal method, and population growth rates over 0.04/hr in control as test acceptability criterium. S. costatum is widely distributed in the world ocean and used for standard species of marine toxicity test method by ISO (International Standardization Organization). Possible salinity ranges for this test method are $20{\sim}35\;psu$, and reproducibility and interlaboratory test results were consistent through the calibration tests. Sensitivity of the test method was comparable or better than other toxicity tests such as rotifer neonate mortality, bioluminescent bacterial inhibition, seaweed sporulation and sea urchin fertilization tests.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Journal of Environmental Health Sciences
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• v.43 no.4
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• pp.247-256
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• 2017

Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

• Journal of Environmental Health Sciences
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• v.39 no.4
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• pp.369-375
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• 2013

Objectives: This study was conducted to identify factors determining the toxicity of manufactured silver nano-particles (AgNPs) on aquatic organisms. Methods: For this purpose, we prepared several AgNPs with varied characteristics, including hydrodynamic size (nano-$^{ABC}Ag^{Cit}\;vs$-sized-$^{ABC}Ag^{Cit}$), impurities ($^{ABC}Ag$ stock vs $^{ABC}Ag$), and citrate capping ($^{ABC}Ag^{Cit}$), using a commercially available manufactured AgNP ($^{ABC}Ag$ stock). Acute tests were conducted using larval zebrafish (Danio rerioI). In addition, in order to determine the ecotoxicological potentials of various capping agents, toxicity tests were conducted with microbes, waterfleas, and fish for eight different capping agents that are used for NPs. Results: The toxicity of AgNPs in terms of 96 h fish $LC_{50}$ increased in the following order: $^{ABC}Ag$ stock < $^{ABC}Ag=^{ABC}Ag^{Cit}=nano-^{ABC}Ag^{Cit}$ < ${\mu}$-sized-$^{ABC}Ag^{Cit}$ < $AgNO_3$. After removing impurities by dialysis, 96 h $LC_{50}$ value decreased significantly from $126.6{\mu}g/L$ (95% confidence intervals [CI]: 107.0-146.2) ($^{ABC}Ag$ stock) to $78.6{\mu}g/L$ (CI: 72.7-84.8) ($^{ABC}Ag$). For ${\mu}$-sized-$^{ABC}Ag^{Cit}$ (ranging between 3.9 and 40.6 nm) and $^{ABC}Ag^{Cit}$ (40.6 nm and $9.1{\mu}m$), the 96 h $LC_{50}$ of the former ($43.9{\mu}g/L$, CI: 36.0-51.7) was approximately two-fold lower than that of the latter ($87.0{\mu}g/L$, CI: 73.5-100.3). Conclusions: In this study, we found that for acute lethality, the contribution of impurities and particle size was significant, but that of citrate was negligible.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.127-133
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• 2015

Objectives : Previous studies have shown that the amount of melittin, the main active ingredient in bee venom pharmacopuncture, tends to decrease substantially with time during pharmacopuncture manufacture. This study aimed to assess whether the stability of bee venom pharmacopuncture improved with pharmacopuncture additives. Methods : Components were measured using high performance liquid chromatography. Acute toxicity and antigenicity tests by subcutaneous and venous routes were conducted at Korea Pharmaceutical Test & Research Institute and mortality, adverse reactions, and body weight changes were assessed. Results : Stability tests using additives revealed that bee venom without additives was most stable. Bee venom pharmacopuncture without additives was further tested for toxicity in subcutaneous and venous administration in mice and no changes pertaining to toxicity were found over the testing period. Conclusions : Bee venom pharmacopuncture without additives was found to be most stable, and further, it did not show toxicity or antigenicity in subcutaneous and venous administration in mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.8
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• pp.960-964
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• 2007

This study was performed to examine the toxicity of Psoralea corylifolia L. by the single-dose oral toxicity tests in rat and bacterial reverse mutation assay. In single-dose oral toxicity tests, 5 mL ethanol extract of P. corylifolia L. were directly injected into 10 rats (5 males and 5 females) at a dosage of 2 g/kg. Death practice was not detected during breeding periods (14 days), and $LD_{50}$ was calculated over 2 g/kg. No difference were observed with control group in the growth rate and histological observations. In bacterial reverse mutation assay, his(-) Salmonella Typhimurium TA98, TA100, TA1535, TA1537 and trp(-) Escherichia coli WP2uvrA (pKM101) were used for assessing the toxicity of ethanol extracts of P. corylifolia L.. No significant difference in formation of the colonies and no dose-dependent increase was observed regardless of the addition of S9 mix. The results showed that ethanol extracts of P. corylifolia L. did not have single-dose oral toxicity and mutagenic toxicity.

• Toxicological Research
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• v.33 no.2
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• pp.107-118
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• 2017

Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2001.05a
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• pp.42-43
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• 2001

Ecotoxicology is a research area for adverse effect of chemicals to ecosystem. While toxicology is directly related to human health, relation between ecotoxicology and human health is indirect. In this connection, public awareness of environmental effect has been rather behind that for health effects. Historically the first concern in ecotoxicology was adverse effect of pollution on organisms in waters receiving industrial wastewater. (omitted)