• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.46-55
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• 1998

Any compound which disrupts the integrity of psychological aspects of performance, in particular, cognitive ability and psychomotor function analogous to the psychological behaviors of routine life, is known to be behaviorally toxic. A significant level of behavioral toxicity will interfere with patient safety and quality of life, and also may be counter-therapeutic by exacerbating the condition that the drug was prescribed for. Now, behavioral toxicity of psychotropic drugs has become one of the main growth areas of psychopharmacological research. Evaluation of the potential of drug-induced behavioral toxicity is important not only to the experimental researcher involved in human psychopharmacology, but also to the clinical practitioner treating psychiatric patients. This article attempts to describe behavioral toxicity of the three classes of psychotropic drugs - benzodiazepines, antidepressants and neuroleptics. After a brief discussion of some methodological issues arising in the investigation of behavioral toxicity, each of these drug classes is reviewed in the context of practical importance rather than purely scientific concern. The last session summarizes some suggestions for future studies on drug-induced behavioral toxicity.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.171-181
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• 1998

DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.

• Food Science of Animal Resources
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• v.23 no.2
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• pp.137-144
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• 2003

This study was carried out to investigate safety evaluation of IGEs separated and refined from bovine milk and commercial recombinant human IGFs. In order to evaluate toxicity of these samples, acute toxicity test and short term toxicity test were investigated with IGF-I separated and refined from colostrum and commercial recombinant human IGF-I from R&D systems company. for acute toxicity test, we selected recombinant human IGF-I from R&D systems company and establish one control group and three dose-level groups(0, 10, 20 and 50 $\mu\textrm{g}$ per rat). We have intravenously injected tail of rats with selected sample once. After 20 days, pathological cellular tissue analyses were investigated with liver, kidney and spleen of 12 rats in all test groups. However, Morbid tissue and abnormal statistical results were not discovered in all cellular tissues. For short term toxicity test, we selected IGF-I separated and refined from colostrum and establish one control group and three dose-level groups(0, 5, 10 and 15 $\mu\textrm{g}$/day per rat). Rats were orally injected with selected sample once a day during two weeks. After short term toxicity test period, Pathological cellular tissue analyses were investigate with liver, kidney and spleen of 12 rats in all test groups. However, Morbid tissue and abnormal statistical results were not discovered in all cellular tissues. These results suggest that IGF-I treated groups show no significant toxicological findings with changes of body weight, food consumption, water consumption, and pathological findings compared with control groups.

• Environmental and Resource Economics Review
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• v.15 no.4
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• pp.643-672
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• 2006

This study has assessed the industrial human toxicity index by means of toxic substances emissions in South Korean industry. The data used in analysis are the 146 kinds of the toxic chemicals emissions and final demands, total outputs in the input-output table. As a results, human carcinogenic index was $11.86198{\times}10^3$ for overall industries, and $0.26360{\times}10^3$ for average. The industries of higher human toxicity index can be ranked as follows: Mother vehicles and parts (7.85033) > Pig iron and crude steel(4.57409) > Primary iron and steel products(4.36668) > Other transportation equipments and parts(3.43293) > Inorganic basic chemical products(2.64379), etc. Such result can be considered as the priority order of regulation based on industrial characteristics, when the demand and industrial policies should be carried out for the deduction fof toxic substances.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.89-94
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• 1998

CJ50001 is a recombinant human granulocyte colony-stimulating facto, (rHuG-CSF) that stimulates the formation of neutrophils from bone marrow stem cells. It was produced in E. colt and purified through refolding and several processes. We produced CS970125(300) using purified C150001 and additives in order to test the stability of CJ50001. When CS970125(300) was stored at 50'S for more than 1 week, high molecular weight proteins were formed and those proteins were detected by non-reducing SDS-PAGE, gel filtration HPLC, and Western blot. Those proteins showed single band at the same position of CJ50001 in reducing SDS-PAGE. These data indicated that those high molecular weight proteins were the multimers of C150001. In biological assays, iu viro and in viro, the multimers did not have biological activity and inhibitory action to that of CJ 50001. The mutimers did not induce toxicity in mice and rats in acute toxicity test. These results suggest that if Cs970125(300) containing CJ50001 is stored at 5$0^{\circ}C$, CJ50001 will be the multimers that do not have biological activity and inhibitory effect to CJ50001 and do not induce acute toxicity.

• Toxicological Research
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• v.17
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• pp.25-35
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• 2001

In 1990, Tolerable Daily Intake (TDI) of 10 pg TCDD/kg/day for dioxins based on carcinogenicity and reproductive toxicity was determined by WHO/EURO, that resulted in the establishment of TDIs in other countries. In Japan, Ministry of Health and Welfare and Environment Agency, respectively established the TDI of 10 pg TCDD/kg/day and Health Risk Assessment Index of 5 pg TCDD/kg/day in 1996. Accumulation of new scientific data, especially by molecular toxicology since 1990, resulted in the reevaluation of TDI by WHO-ECEH and IPCS in May, 1998. At this meeting, it was stressed that \circled1 toxic effects of dioxin is mediated through Ah-receptor in both animals and humans, \circled2 use of ebody burdeni concept is better than the use of traditional NOAEL/UF approach, \circled3 inclusion of coplanar PCBs in the TDI by the use of new WHO-TEF. LOAELs (0.16~200 ng TCDD/kg/day) obtained from reproductive toxicity and immunotoxicity in rats, and neurobehavioral toxicity and induction of endometriosis in rhesus monkeys are calculated to be the body burden of 10~50 ng TCDD/kg that is 14~37 pg TEQ/kg/day as human daily intake. Finally TDI of 1~4 pg TEQ/kg/day was established by applying the UF of 10. In Japan, reproductive toxicity and immunotoxicity in rats were used to obtain LOAELs (100~200 ng TCDD/kg/day). Finally TDI of 4 pg TEQ/kg/day was established in June 1999 by applying the UF of 10 to human daily intake of 43.6 pg TEQ/kg/day which corresponds to the body burden of 86 ng TCDD/kg.

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.59-69
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• 2002

Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. YHB216 is a new rHu-EPO developed by Yuhan Research Institute. In this study, we investigated the single dose and 4-week repeated dose toxicity of YHB216 in Beagle dogs. In the single dose toxicity study, YHB216 was administered intravenously at single dose levels of 0 and 25,000 IU/kg to dogs (2 dogs/sex/group). There were no treament-related changes in survivals, clinical signs, body weight gain, hematological values, blood chemical values, and necropsy finding during experimental period. In the repeated dose toxicity study, YHB216 was administered intravenously to dogs for 4 weeks at the dose levels of 0, 100, 500, and 2,500IU／kg (3 dogs/sex／group). There were no toxicologically significant changes in clinical signs, body weights, food and water consumptions, ophthalmoscopy, urinalysis and blood chemistry. There were increased values of red blood cell, hemoglobin, and hematocrit at all treated groups. Spleen revealed increased weight and extramedullary hematopoiesis at 500 IU/kg or more. These changes are all considered to be Pharmacology-related effects and were recovered after 4-week recovery period. From these results, it is concluded that LD50 value was above 25,000 IU/kg in the single dose toxicity study of YHB216 in dogs and the no observed adverse effect level (NOAEL) was 100 IU/kg day in the repeated dose toxicity study of YHB216 in dogs.

• BMB Reports
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• v.50 no.11
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• pp.535-536
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• 2017

A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by first searching for candidate human disease genes that confer toxicity in yeast, and second, identifying modulators of toxicity. This study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for example. In the subsequent proof-of-concept study focused on ALS, similar functional relationships between a specific kinase and ALS-associated genes were observed in mammalian cells and zebrafish, supporting findings in human-yeast genetic interaction screens. Results of combined analyses highlighted MAP2K5 kinase as a potential therapeutic target in ALS.

• Journal of Korean Neurosurgical Society
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• v.67 no.4
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• pp.418-430
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• 2024

Objective : Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods : This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 µM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results : A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 µM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 µM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion : The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.

• Toxicological Research
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• v.18 no.1
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.