• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.108-113
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• 1994

Toxicity study of recombinant hepatitis B vaccine (LBD-008), a newly developed drug for acute and chronic hepatitis, was investigated in mice and guinea pigs. 1. Mice showed no production of antibodies against LBD-008 inoculated with aluminum hydroxide gel (Alum) as an adjuvant, judged by the heterologous anaphylaxis (PCA) test using rats. On the other hand, antibodies against ovalbumin (OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-008 only and of LBD-008 with complete Freund's adjuvant (CFA) as an adjuvant did not produce positive reactions in any of homologous active systemic anaphylaxis (ASA). On the other hand, the inoculation of ovalbumin with complete Freund's adjuvant (CFA) produced positive reaction in both of PCA and ASA. 3. These findings suggested that LBD-008 has no antigenic potential in mice or guinea pigs.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.11.1-11.6
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• 2016

Objectives A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. Methods Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor ("Survey on the work environment") and by the Ministry of Environment ("Survey on the circulation amount of chemicals"). Risk was determined according to exposure in workplaces and chemical hazard. Results In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be $0.990mg/m^3$, as compared to the threshold exposure level of $5mg/m^3$. The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. Conclusions DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the occupational exposure limit. Therefore, we suggest management of working environments, with exposure levels below $5mg/m^3$ and all workers utilizing local exhaust ventilation and respiratory protection when handling DEHP.

• Journal of Environmental Health Sciences
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• v.44 no.2
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• pp.153-159
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• 2018

Objectives: This study was carried out to determine $LD_{50}$ of benzo[a]pyrene to decide the possibility to designate them as toxic substance on the Act on the Registration and Evaluation, etc. of Chemical Substances, and to suggest that they should be managed in what level on the Chemical Control Act. Methods: Based on the result of a preliminary study, 300 mg/kg was set as the middle dose. A highest dose of 2,000 mg/kg and a lowest dose of 50 mg/kg were selected based on the OECD TG 423. Benzo[a]pyrene was orally administered once to female and male SD rats at dose levels of 50, 300, 2,000 mg/kg (body weight). All animals were monitored daily for clinical signs and mortality over 14 days. Also testicular spermatid count, motility and etc. were examined as well. Results: Under the condition of this experiment, $LD_{50}$ of benzo[a]pyrene was assumed to be >2,000 mg/kg. In the lesion according to autopsy, there were no specific symptoms in the control and experimental groups. At 2,000 mg/kg, a decrease in the sperm motility was observed. Benzo[a]pyrene should be designated to be toxic substance as the material assumed to be reproduction-toxicity on the Act on the Registration and Evaluation, etc. of Chemicals. Therefore we should abide by legal procedures determined by Chemicals Control Act in treating it. Conclusion: Considering the significant result that sperm motility in the experimental group was inferior to that in the reference group, we suggest that benzo[a]pyrene be designated as a toxic substance.

• Toxicological Research
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• v.34 no.4
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• pp.343-354
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• 2018

Aluminum oxide nanoparticles ($Al_2O_3$ NPs) are among the most widely used nanomaterials; however, relatively little information about their risk identification and assessment is available. In the present study, we aimed to investigate the potential toxicity of $Al_2O_3$ NPs following repeated inhalation exposure in male Sprague-Dawley rats. Rats were exposed to $Al_2O_3$ NPs for 28 days (5 days/week) at doses of 0, 0.2, 1, and $5mg/m^3$ using a nose-only inhalation system. During the experimental period, we evaluated the clinical signs, body weight change, hematological and serum biochemical parameters, necropsy findings, organ weight, and histopathology findings. Additionally, we analyzed the bronchoalveolar lavage fluid (BALF), including differential leukocyte counts, and aluminum contents in the major organs and blood. Aluminum contents were the highest in lung tissues and showed a dose-dependent relationship in the exposure group. Histopathology showed alveolar macrophage accumulation in the lungs of rats in the $5mg/m^3$ group during exposure and recovery. These changes tended to increase at the end of the recovery period. In the BALF analysis, total cell and neutrophil counts and lactate dehydrogenase, tumor necrosis factor-${\alpha}$, and interleukin-6 levels significantly increased in the 1 and $5mg/m^3$ groups during exposure. Under the present experimental conditions, we suggested that the no-observed-adverse-effect level of $Al_2O_3$ NPs in male rats was $1mg/m^3$, and the target organ was the lung.

• Journal of Aquaculture
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• v.11 no.2
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• pp.223-230
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• 1998

This study was carried out for the purpose of developing environmental friendly and effective chemical treatment method for the disease control in the land-based flounder culture which is industrially popular in the coastal area in Korean. The chemicals such as flounder, Paralichthys olivaceus and their effects on the fish based on the 24hr-$LC_{50}$, $LT_{50}$, 24-hour survival rate at each experimental concentration, recovery rate of the survived individual from chemical treatment, and the histological change of the gill after chemical treatment were investigated and analyzed. The 24hr-$LC_{50}$ was 321.65 ppm for formalin, 419.62 ppm for chlorine dioxide, and 395.97 ppm for hydrogen peroxide, respectively. The $LT_{50}$ was 15-hour for formalin, 17-hour for chlorine dioxide and 24-hour for hydrogen peroxide, respectively. Fishes exposed to the experimental concentration of three chemicals were quickly susceptible in the order of formalin, chlorine dioxide and hydrogen peroxide with a trend of shorter half lethal time at higher concentration. Initial survival rate of the flounder soon after chemical treatment was the highest in the hydrogen peroxide treatment compared with the other two chemicals. The histological damage by the hydrogen peroxide treatment was negligible compared with the other two chemicals. Accordingly, hydrogen peroxide treatment showed the lowest toxicity compared with the other two chemicals to the experimental fishes.

• Korean Journal of Environmental Agriculture
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• v.4 no.2
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• pp.118-125
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• 1985

To establish an evaluation system of aquatic toxicity of chemicals at no-effect level, flow through and early life stage toxicity test were performed on a freshwater fish, the medaka (Oryzias latipes). The characteristics of medaka as a bioassay organism for the chronic toxicity test were discussed. Maximum acceptable toxicant concentration(MATC) of butachlor for the madaka in soft water was estimated using survival, growth, and reproduction as indicators of toxic effects. During a 3-month period, the fry of medaka were exposed to butachor concentrations ranging from 0.16 to 0.0l mg/liter and the DO concentration, temperature, and pH in the exposure chamber were measured to check the test condition. The highest concentration showed slight decrease of growth rate in medaka and reduced hatchability of spawning egg. Survival, growth, and reproductive success of adults in butachlor concentration of 0.04 and 0.01 mg/liter were not different from those of the control. The MATC was estimated to be between 0.04 and 0.16 mg/liter for medaka.

• Journal of the Korean Chemical Society
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• v.37 no.1
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• pp.154-161
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• 1993

Four kinds of new phosphinate derivatives with a pendant monoazacrown ether were synthesized and their biological activities were tested. These biologically active phosphinates were synthesized in relatively good yields (61∼72%) by one step reactions of phenylphosphinate with aldehyde and monoazacrown ether. Toxicity of these compounds was tested by intraperitoneal injection of the compounds to male mouse and revealed $LD_{50}$ value of 65∼90 mg/kg, which showed enhanced toxicity by attachment of a pendant azacrown ether to a simple phenylphosphinate structure. Although the ring size effect of the pendant crown ethers, (monoaza-15-crown-5 and monoazo-18-crown-6), beening negligible, the identity of the ester functional group in the phosphinate structure exerted sizable influence on toxicity. Thus, phosphinate derivative with octyl or propyl ester group showed somewhat higher toxicity than that with ethyl ester group.

• Journal of Environmental Health Sciences
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• v.45 no.5
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• pp.457-464
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• 2019

Objectives: Quantitative structure-activity relationship (QSAR) is one of the effective alternatives to animal testing, but its credibility in terms of toxicity prediction has been questionable. Thus, this work aims to evaluate its predictive capacity and find ways of improving its credibility. Methods: Using $TOPKAT^{(R)}$, OECD toolbox, and $Derek^{(R)}$, all of which have been applied world-wide in the research, industrial, and regulatory fields, an analysis of prediction credibility markers including accuracy (A), sensitivity (S), specificity (SP), false negative (FN), and false positive (FP) was conducted. Results: The multi-application of QSARs elevated the precision credibility relative to individual applications of QSARs. Moreover, we found that the type of chemical structure affects the credibility of markers significantly. Conclusions: The credibility of individual QSAR is insufficient for both the prediction of chemical toxicity and regulation of hazardous chemicals. Thus, to increase the credibility, multi-QSAR application, and compensation of the prediction deviation by chemical structure are required.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.263-269
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• 2006

Deficiencies in the early ADMET(absorption, distribution, metabolism, elimination and toxicity) information on drug candidate extract a significant economic penalty on pharmaceutical firms. Microscale cell culture analogue-microscale gastrointestinal(${\mu}CCA-{\mu}GI$) device using Caco 2, L2 and HEp G2/C3A cells, which mimic metabolic process after absorption occurring in humans was used to investigate the toxicity of the model chemical, acetaminophen(AAP). The toxicity of acetaminophen determined after induction of CYP 1A1/2 in Caco 2 cells was not significant. In a coculture system, although no significant reduction in viability of HEp G2/C3A and L2 cells was found, approximately 5 fold increase in the CYP 1A1/2 activity was observed. These results appear to be related to organ-organ interaction. The oral administration of a drug requires addition of the absorption process through small intestine to the current ${\mu}CCA$ device. Therefore, a perfusion coculture system was employed for the evaluation of the absolution across the small intestine and resulting toxicity in the liver and lung. This system give comprehensive and physiologic information on oral uptake and resulting toxicity as in the body. The current ${\mu}CCA$ device can be used to demonstrate the toxic effect due to organ to organ interaction after oral administration,

• The Korean Journal of Pesticide Science
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• v.15 no.4
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• pp.383-388
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• 2011

We investigated methiozolin acute toxicity using with Sprague-Dawley rats. The results of acute oral toxicity using rats showed $LD_{50}$ value of over 2,000 mg/kg bw for methiozolin. The calculate acute dermal $LD_{50}$ value of methiozolin was over 4,000 mg/kg. The skin irritation test showed moderately irritation and weak response of eye irritation test was observed in this experimental condition. According to these results, We concluded that methiozolin was Category IV in GHS chemical classification for acute toxicity. Future, we need more chronic toxicity test for safety.