• Toxicological Research
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• 제35권4호
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• pp.343-351
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• 2019

Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of inhouse candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.

• Toxicological Research
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• 제34권1호
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• pp.49-53
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• 2018

Cyclohexanone ($C_6H_{10}O$, CAS No. 108-94-1) is a colorless oily liquid obtained through the oxidation of cyclohexane or dehydrogenation of phenol. It is used in the manufacture of adhesives, sealant chemicals, agricultural chemicals, paint and coating additives, solvent, electrical and electronic products, paints and coatings, photographic supplies, film, photochemicals, and as an intermediate in nylon production. Owing to the lack of information on repeated inhalation toxicity of cyclohexaone, in this study, we aimed to characterize the subacute inhalation toxicity. B6C3F1 mice were exposed to 0, 50, 150, and 250 ppm of cyclohexanone for 6 hr/day, 5 days/week for 4 weeks via whole-body inhalation in accordance with the OECD Test Guideline 412 (subacute inhalation toxicity: 28-day study). Mortality, clinical signs, body weights, food consumption, hematology, serum biochemistry, organ weights, as well as gross and histopathological findings were evaluated between the control and exposure groups. No mortality or remarkable clinical signs were observed during the study. No adverse effects on body weight, food consumption, hematology, serum biochemistry, and organ weights, gross or histopathological lesions were observed in any male or female mice in any of the exposure groups, although some statistically significant changes were observed in organ weights. We concluded that no observable adverse effect level (NOAEL) is above 250 ppm in mice exposed to cyclohexanone for 6 hr/day for 5 days/week.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.270-274
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• 1993

The acute toxicity of a recombinant granulocyte-macrophage colony stimulating factor (code name: LBD-005) was evaluated in both sexes of ICR mice, 5~6 weeks old, by the oral, subcutaneous and intravenous routes of administration. Based on the results of the acute toxicity study, LBD-005 was not considered to induce any toxic effect on the mice in mortalities, clinical findings, body weights and gross findings. It is suggested that $LD_50$ values in mice would be >48 mg/kg in the oral route and >24 mg/kg in the subcutaneous or intravenous route.

• 한국환경보건학회지
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• 제49권2호
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• pp.89-98
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• 2023

Background: Organophosphorus flame retardants (OPFRs) are a group of chemical substances used in building materials and plastic products to suppress or mitigate the combustion of materials. Although OPFRs are generally used in mixed form, information on their mixture toxicity is quite scarce. Objectives: This study aims to elucidate the toxicity and determine the types of interaction (e.g., synergistic, additive, and antagonistic effect) of OPFRs mixtures. Methods: Nine organophosphorus flame retardants, including TEHP (tris(2-ethylhexyl) phosphate) and TDCPP (tris(1,3-dichloro-2-propyl) phosphate), were selected based on indoor dust measurement data in South Korea. Nine OPFRs were exposed to the luminescent bacteria Aliivibrio fischeri for 30 minutes and the human hepatocyte cell line HepG2 for 48 hours. Chemicals with significant toxicity were only used for mixture toxicity tests in HepG2. In addition, the observed EC_x values were compared with the predicted toxicity values in the CA (concentration addition) prediction model, and the MDR (model deviation ratio) was calculated to determine the type of interaction. Results: Only four chemicals showed significant toxicity in the luminescent bacteria assays. However, EC₅₀ values were derived for seven out of nine OPFRs in the HepG2 assays. In the HepG2 assays, the highest to lowest EC₅₀ were in the order of the molecular weight of the target chemicals. In the further mixture tests, most binary mixtures show additive interactions except for the two combinations that have TPhP (triphenyl phosphate), i.e., TPhP and TDCPP, and TPhP and TBOEP (tris(2-butoxyethyl) phosphate). Conclusions: Our data shows OPFR mixtures usually have additivity; however, more research is needed to find out the reason for the synergistic effect of TPhP. Also, the mixture experimental dataset can be used as a training and validation set for developing the mixture toxicity prediction model as a further step.

• 한국산업보건학회지
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• 제28권2호
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• pp.175-189
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• 2018

Objectives: In this study, we analyze statistics on industrial accidents caused by chemical skin contact and provide skin toxicity hazard information on the related domestic system and circulation volumes. Methods and Results: We analyzed occupational fatalities and skin diseases caused by chemical leaks and contact from 2007 to 2016(10 years) and surveyed data on occupational skin diseases using the 2014 work environment survey data. The NIOSH Skin Notation Profiles for 57 chemical substances, which are provided to prevent occupational skin diseases, were searched and hazard information on skin contact with chemical substances was classified. In order to identify skin toxicity information among domestically distributed and legally regulated substances and to investigate skin-toxic substances, MSDS basic data on 19,740 chemical substances provided on the homepage of Korea Occupational Safety & Health Agency were searched. Acute toxicity(dermal) category 1-4 substances totaled 1,020, and the number of chemical substances classified as category 1 and 2 substances were 135 and 137, respectively. In the chemical substances prescribed by the Ministry of Employment and Labor, 173 substances were classified into acute toxicity(dermal) categories 1-4, 58 of which correspond to category 1 or 2. Conclusions: Within the present range of industrial accidents, the proportion of skin diseases due to contact with chemicals is not high. However, there is always a risk of occupational skin diseases due to increasing chemicals and due to the use of new chemicals. It is hoped that this information will be used by workplace safety and health officials and health and safety experts to prevent acute toxity(dermal) due to chemical skin contact.

• 한국환경보건학회지
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• 제44권1호
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• pp.44-54
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• 2018

Objectives: To protect individuals working at the site as well as the surrounding general population from a chemical accident, several emergency exposure guidance levels have been used to set a level of concern for certain chemicals. However, a level of concern has not been established for many substances that are frequently used or produced in large quantities in Korean workplaces. In the present study, we investigated the guidance levels for protecting populations from chemical exposure and the estimation of level of concern using acute inhalation and oral toxicity data. Methods: The number of chemicals to which emergency exposure guidance levels (e.g., ERPG-2, AEGL-2, PAC-2, and IDLH) can be applied were determined among 822 hazardous chemicals according to the 'Technical Guidelines for the Selection of Accident Scenarios (revised December 2016)'. The ERPG and AEGL values were compared across all three tiers for the 31 substances that appeared on both lists. We examined the degree of difference between the emergency exposure guidance levels and the estimates of level of concern calculated from acute inhalation or acute oral toxicity data. Results: Among the 822 hazardous chemicals, emergency exposure guidance levels can be applied to 359 substances, suggesting that the estimates of level of concern should be calculated using acute toxicity data for 56.3% of the hazardous chemicals. When comparing the concordance rates of ERPG and AEGL for 31 substances, the difference between the two criteria was generally small. However, about 40% of the substances have values diverging by more than three-fold in at least one tier. Such discrepancies may cause interpretation and communication problems in risk management. The emergency exposure guidance levels were similar to the estimates of level of concern calculated using acute inhalation toxicity data, but the differences were significant when using acute oral toxicity data. These results indicate that the level of concern derived from acute oral toxicity data may be insufficient to protect the population in some cases. Conclusion: Our study suggests that the development of standardized guidance values for emergency chemical exposure in the Korean population should be encouraged. It is also necessary to analyze acute toxicity data and fill the information gaps for substances that are important in Korean workplace situations.

• Toxicological Research
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• 제30권1호
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• pp.55-63
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• 2014

Objectives: The use of indium compounds, especially those of small size, for the production of semiconductors, liquid-crystal panels, etc., has increased recently. However, the role of particle size or the chemical composition of indium compounds in their toxicity and distribution in the body has not been sufficiently investigated. Therefore, the aim of this study was to examine the effects of particle size and the chemical composition of indium compounds on their toxicity and distribution. Methods: Male Sprague-Dawley rats were exposed to two different-sized indium oxides (average particle sizes under 4,000 nm [IO_4000] and 100 nm [IO_100]) and one nano-sized indium-tin oxide (ITO; average particle size less than 50 nm) by inhalation for 6 hr daily, 5 days per week, for 4 weeks at approximately $1mg/m^3$ of indium by mass concentration. Results: We observed differences in lung weights and histopathological findings, differential cell counts, and cell damage indicators in the bronchoalveolar lavage fluid between the normal control group and IO- or ITO-exposed groups. However, only ITO affected respiratory functions in exposed rats. Overall, the toxicity of ITO was much higher than that of IOs; the toxicity of IO_4000 was higher than that of IO_100. A 4-week recovery period was not sufficient to alleviate the toxic effects of IO and ITO exposure. Inhaled indium was mainly deposited in the lungs. ITO in the lungs was removed more slowly than IOs; IO_4000 was removed faster than IO_100. IOs were not distributed to other organs (i.e., the brain, liver, and spleen), whereas ITO was. Concentrations of indium in the blood and organ tissues were higher at 4 weeks after exposure. Conclusions: The effect of particle size on the toxicity of indium compounds was not clear, whereas chemical composition clearly affected toxicity; ITO showed much higher toxicity than that of IO.

• Toxicological Research
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• 제8권1호
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• pp.41-48
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• 1992

The actue toxicity of a recombinant granulocyte macrophage colony-stimulating factor (code name: LBD-005) was evaluated in both sexes of Sprague-Dawley rats, 4 weeks old, by the oral, subcutaneous and intravenous routes of administration. LBD-005 in the acute toxicity study in the rats was not considerde to induce any toxicological effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that $LD_{50}$ values in rats would be >48 mg/kg in the oral route and >12 mg/kg in the subcutaneous or intravenous route.

• Biotechnology and Bioprocess Engineering:BBE
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• 제11권3호
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• pp.187-198
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• 2006

The aromatic hydrocarbons (AHs), which include benzene, polycyclic aromatic hydrocarbons, and dioxin, are important chemical and environmental contaminants in industry that usually cause various diseases. Over the years, numerous studies have described and evaluated the adverse health effects induced by AHs. Currently, "Omics" technologies, transcriptomics and proteomics, have been applied in AH toxicity studies. Proteomics has been used to identify molecular mechanisms and biomarkers associated with global chemical toxicity. It could enhance our ability to characterize chemical-induced toxicities and to identify noninvasive biomarkers. The proteomic approach (e.g. 2-dimensional electrophoresis [2-DE]), can be used to observe changes in protein expression during chemical exposure with high sensitivity and specificity. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and electrospray ionization-quadrupole (ESI-Q)-TOF MS/MS are recognized as the most important protein identification tools. This review describes proteomic technologies and their application in the proteomic analysis of AH toxicity.

• Bulletin of the Korean Chemical Society
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• 제33권10호
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• pp.3265-3268
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• 2012

Nanoparticles (NPs) are increasingly used in consumer products, which have aroused many concerns and debates regarding their fate in biological systems from a point of their safety/toxicity. Although a number of studies on the biological effects of NPs have been published, these are often complicated by the possible toxicity of conventional NPs, caused by contamination with chemical precursors or additives during their synthesis and/or purification procedures. To explicitly understand the toxicity basis of NPs, it is necessary to directly address a main problem related to their intrinsic/inherent toxicity and/or incompatibility with biological objects. The present study is designed to take advantage of a novel laser-assisted method called laser ablation to generate Ag, Au, Co, and Cu NPs in biocompatible aqueous solution, and to evaluate the toxicity of the resulting ultra-pure NPs. Our results show that the ultra-pure NPs with nascent surfaces possess moderate cytotoxicity to human cells in a cell-dependent manner.