• Environmental Analysis Health and Toxicology
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• v.20 no.2 s.49
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• pp.109-121
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• 2005

A chemical ranking and scoring (CRS-Korea) system was developed and proposed to use as the first step to prioritize the toxic chemicals for the purpose of monitoring and detailed risk assessment that might follow as necessary. The CRS-Korea system takes a basic concept of risk assessment (both human health risk and ecological risk) in that risk score is determined by the product of toxicity score and exposure score. Included in the toxicity category are acute toxicity, chronic/sub -chronic toxicity, carcinogenicity, and other toxicity. The exposure category consists of quantity released to the environment, bioconcentration, and persistence. A consistent scheme and a comprehensive chemical data base are offered in the CRS-Korea system to calculate a score for the each component in the two categories by using specific physicochemical, fate, and toxic properties and the quantity of the chemical used. The toxicity score is obtained by adding up all the individual scores for the components in the toxicity category. The exposure score is determined by multiplication of the score of the quantity released with the sum of persistent score and bioconcentration score. Equal weight is given to the toxicity score and the exposure score. As the CRS-Korea system was applied to identify 50 national priority chemicals, it was found that significant data gap exists on toxicity and fate properties and that the uncertainty associated with estimating the quantify released to the environment is notably high. The proposed CRS system is only a screening tool in the first step toward the priority setting and should be used with expert judgement and other considerations necessary.

• Toxicological Research
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• v.23 no.4
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• pp.391-403
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• 2007

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

• Molecules and Cells
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• v.42 no.6
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• pp.480-494
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• 2019

Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (${\beta}23$) expression model to screen potential lead compounds inhibiting ${\beta}23$-induced toxicity. High-throughput screening identified several natural compounds as nuclear ${\beta}23$ inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic ${\beta}23$ aggregates and protects SH-SY5Y cells from toxicity induced by ${\beta}23$ expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and ${\alpha}$-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and ${\alpha}$-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited ${\alpha}$-synuclein aggregation but also disaggregated preformed ${\alpha}$-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off ${\beta}23$ cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates.

• Journal of Environmental Analysis, Health and Toxicology
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• v.21 no.4
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• pp.243-251
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• 2018

Pharmaceuticals in wastewater effluents have been recognized as emerging pollutants threatening freshwater organisms. To extend understanding for bioaccumulation and toxicity in those organisms, information on biotransformation products (or metabolites) and their metabolic pathway are crucial. The aim of the present study is to identify and elucidate metabolites of pharmaceuticals formed in exposed organisms using suspect and nontarget screening approach using LC-HRMS. As the target pharmaceuticals, carbamazepine, ketoprofen, metoprolol, propranolol, and verapamil were selected whereas Daphnia magna and Gammarus pulex were used as test organisms. After 24h exposure, metabolites formed in the organisms were identified using LC-HRMS. The structures of metabolites were elucidated via analysis of MS/MS fragment pattern and the comparison with fragment database. As the results, a total of 10 metabolites were identified for 5 parent compounds (C253/C356 for carbamazepine, K211 for ketoprofen, M256 for metoprolol, P218/P276/P306 for propranolol, V196/V291/V441 for verapamil). Among them, the presence of C253 and V291 was confirmed using standard materials. Most of the identified metabolites were formed through oxidative reactions such as hydroxylation, N-demethylation, and dealkylation. Cysteine conjugation (phase II reaction) metabolite (C356) for carbamazepine was found in daphnia. The metabolic pathway of verapamil showed similar metabolic pathways and metabolic pathways for both species. Although the toxicological information on the identified metabolites could not be confirmed, the molecular structure information of the proposed metabolites can be used for future evaluation and prediction of toxicity.

• Journal of Microbiology and Biotechnology
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• v.30 no.6
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• pp.920-925
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• 2020

In India, nanotechnology has been used in therapeutic applications for several millennia. One example of a traditional nanomedicine is Rajath Bhasma (also called calcined silver ash), which is used as an antimicrobial and for the treatment of various ailments and conditions such as memory loss, eye diseases, and dehydration. In this study, we aimed to characterize the physical composition and morphology of Rajath Bhasma and its suitability for use as a non-toxic antimicrobial agent. First, Rajath Bhasma was physically characterized via i) Fourier-transform infrared spectroscopy to analyze the surface functional groups, ii) scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy to observe the morphology and elemental composition, and iii) X-ray diffraction to determine the crystalline phases. Thereafter, functional characterization was performed through toxicity screening using zebrafish embryos and through antimicrobial activity assessment against gram-positive (Staphylococcus epidermidis) and gram-negative (Escherichia coli) bacteria. Rajath Bhasma was found to harbor alkene, hydroxyl, aldehyde, and amide functional groups originating from biological components on its surface. The main component of Rajath Bhasma is silver, with particle size of 170-210 nm, and existing in the form of spherical aggregates with pure crystalline silver structures. Furthermore, Rajath Bhasma did not exert toxic effects on zebrafish embryos at concentrations below 5 ㎍/ml and exhibited effective antimicrobial activity against both gram-positive and gram-negative bacteria. The present results indicate that Rajath Bhasma is a potentially effective antimicrobial agent without toxicity when used at concentrations below 5 ㎍/ml.

• Fisheries and Aquatic Sciences
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• v.15 no.3
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• pp.241-250
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• 2012

Polycyclic aromatic hydrocarbons (PAHs), butyltins (BTs), nonylphenol (NP), and fecal sterols concentrations in sediments were investigated from Gunsan coast of Korea to evaluate organic pollution from anthropogenic activities. Sediment toxicity was also examined by bacterial bioluminescence toxicity test (Vibrio fischeri). The concentrations of 16 PAHs in sediments ranged from 67.9 to 425 ng/g dry wt; BTs ranged from 2.79 to 14.1 ng Sn/g dry wt; NP ranged from 20.7 to 2171 ng/g dry wt; and coprostanol, a fecal sterol, ranged from 7.60 to 245 ng/g dry wt. Effective concentration 50% ($EC_{50}$) of sediments ranged from 0.38 to 23.8 mg/mL. Most of the chemicals were present at levels lower than or comparable to the previously reported values from Korea. However, NP levels in the present study were in the high range of levels reported from the Korean coast, and 40% of the measured samples exceeded screening and ecotoxicological values of NP suggested by the Netherlands and Canada. This suggests that an ongoing source of NP is a serious concern in the Gunsan coast. High levels of contaminants were found in the proximity of potential sources, such as the outfall of a wastewater treatment plant for NP, an anthracite-fired power plant for PAHs, and ports for BTs, fecal sterols, and sediment toxicity. This indicates that Gunsan coast has various potential sources of marine sediment contaminants.

• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.97-106
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• 1997

This study was carried out to investigate the testicular toxicity of environmental toxicant, 2-bromopropane(2-BP) recently caused occupational intoxication in Korea by light microscopy and electron microscopy. To evaluate the effect on spermatogenesis and find target germ cell 10 weeks old male Sprague-Dawley rats were treated with 5g/10m ℓ/kg/day of 2-bromopropane for 3 consecutive days orally and observed on day 1 or day 7 after treatment. 2-BP induced depletion of spermatogonia and early spermatocytes on stages I-IX or extensive degeneration of germ cells on the other stages on day 1. But extensive degeneration of germ cells without stage specificity was observed and round spermatid formed multinucleated giant cells in the lumen of seminiferous tubules on day 7. Electron microscopically Sertoli cells showed irregular shape of nucleus and cytoplasmic vauolation. And spermatocyte showed a extensive heterochromatin and cytoplasmic vacuolation. But there was no histopathological changes in the interstial cells. On the base of the results the target germ cell was spermatogonia in the early of the study but Srtoli cells also effected by high-dosed 2-BP in the late of the study.

• Toxicological Research
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• v.18 no.1
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• pp.13-22
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• 2002

In Korea, 2,320 tonnes of acetanilide were mostly wed as intermediates for synthesis in phar-maceuticals or additives in synthesizing hydrogen peroxide, varnishes, polymers and rubber. Only small amount of 120 kg were wed as a stabilizer for hydrogen peroxide solution for hair colouring agents in 1998. Readily available environmental or human exposure data do not exist in Korea at the present time. However, potential human exposures from drinking water, food, ambient water and in work places are expected to be negligible because this chemical is produced in the closed system in only one company in Korea and the processing factory is equipped with local ventilation and air filtering system. Acetanilide could be distributed mainly to water based on EQC model. This substance is readily biodegradable and its bioaccumulation is low. Acute toxicity of acetanilide is low since the L $D_{50}$ of oral exposure in rats is 1,959 mg/kg bw. The chemical is not irritating to skin, but slightly irritating to the eyes of rabbits. horn repeated dose toxicity, the adverse effects in rats were red pulp hyperplasia of spleen, bone marrow hyperplasia of femur and decreased hemoglobin, hematocrit and mean corpuscular hemoglobin concentration. The LOAEL for repeated dose toxicity in rats was 22 mg/kg/day for both sexes. Acetanilide is not considered to be genotoxic. In a reproductive/developmental toxicity study, no treatment-related changes in precoital time and rate of copulation, impregnation, pregnancy were shown in all treated groups. The NOAELs for reproduction and developmental toxicity (off-spring toxicity) are considered to be 200 mg/kg bw/day and 67 mg/kg bw/day, respectively. Ecotoxicity data has been generated in a limited number of aquatic species of algae (72 hr- $E_{b}$ $C_{50}$; 13.5 mg/l), daphnid (48hr-E $C_{50}$ > 100 mg/l) and fish (Oryzias latipes, 96hr-L $C_{50}$; 100 mg/l). Form the acute toxicity values, the predicted no effect concentration (PNEC) of 0.135 mg/1 was derived win an assessment factor of 100. On the basis of these data, acetanilide was suggested as currently of low priority for further post-SIDS work in OECD.in OECD.D.

• Toxicological Research
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• v.19 no.2
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• pp.123-131
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• 2003

This study was carried out to assess the combined repeated dose, reproduction and developmental toxicities of benzoyl peroxide for OECD SIDS (Screening Information Data Set) program. Male and female Sprague-Dawley rats were exposed to benzoyl peroxide at dose levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for males and for 41-51 days for females. No deaths were found in all animals including control group during exposure period. No hematological effects attributable to benzoyl peroxide were observed in all treated groups. Significant decrease in the weight of testes and epididymis were observed in males at 1,000 mg/kg/day. In females at 1,000 mg/kg/day, slight histopathological effects in uterus such as epithelial vacuolation or hyperplasia were observed. No treatment-related changes in precoital time and rate of copulation, fertility and gestation period were noted in all treated groups. There was no evidence of teratogenic effect of benzoyl peroxide, but body weight of pups at 1,000 mg/kg/day was significantly decreased. NOAEL for combined repeated dose and reproduction/developmental toxicity was 500 mg/kg/day.

• Advances in Traditional Medicine
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• v.6 no.1
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• pp.21-26
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• 2006

The ethanolic extract of Fleurya interrupta Gaud, (Urticaceae) was tested for its possible neuropharmacological effects on experimental animals, For the primary neuropharmacological screening of this plant, the ethanolic extract of its aerial parts was subjected to preliminary evaluation for acute toxicity, antinociceptive activity and central nervous system (CNS) activities. At the doses of 125 and 250 mg/kg, the extract significantly (P < 0.01 and P < 0. 001) and dose-dependently increased the frequency of acetic acid induced writhing in mice. In the pentobarbitone induced sleeping time test, the extract at the above dose levels, significantly and dose-dependently decreased the pentobarbitone induced sleeping time (P < 0.001) and increased the time for onset of sleep (P < 0.001) in mice. In the open field and hole cross tests, test animals showed an increase in their movement in the both tests from the 2nd observation period (30 min) and persisted throughout the entire experimental period (240 min). These results of the extract may attribute a stimulating action on the CNS. On the basis of these findings, it can be assumed that the extract exerts its stimulating effect on the CNS in mice by interfering with the cortical function or increasing the effect of some CNS stimulating neurotransmitters.