• Toxicological Research
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• v.30 no.3
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• pp.205-210
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• 2014

Didecyldimethylammonium chloride (DDAC) is used for various purposes, such as a fungicide for coolants, an antiseptic for wood, and disinfectant for cleaning. Despite the increasing likelihood of DDAC inhalation, available data on its toxicity from inhalation are scarce. Therefore, this study was aimed at confirming the toxicity of DDAC after inhalation exposure for 2 wk. Male Sprague-Dawley rats were exposed to approximately $0.15mg/m^3$, $0.6mg/m^3$, and $3.6mg/m^3$ DDAC aerosols in whole-body exposure chambers. After DDAC exposure for 2 wk, effects of DDAC on body weight, blood, bronchoalveolar lavage (BAL), and the lungs were verified. The mass median aerodynamic diameter of DDAC aerosols was $1.86{\mu}m$ and the geometric standard deviation was 2.75. The concentrations of DDAC aerosols for the low, medium, and high groups were $0.15{\pm}0.15mg/m^3$, $0.58{\pm}0.40mg/m^3$, and $3.63{\pm}1.56mg/m^3$, respectively. Body weight gain was significantly influenced by DDAC exposure. In the high group, a body weight decrease of 2.6 g was observed, whereas a 25.8 g increase was observed in the normal control group after the first 3 days. The low and medium groups showed 23.3 g and 20.4 g increases, respectively, after the first 3 days. Decreases in body weight were recovered during the next 4 days. In contrast, no changes were noted in hematological and blood biochemistry parameters after DDAC exposure. Furthermore, only mild effects were observed on bronchoalveolar cell differentiation counts and cell damage parameters in the BAL fluids of the medium and high groups. Although inflammatory cell infiltration and interstitial pneumonia were partially observed, fibrosis was not found in the lungs of the medium and high groups. In conclusion, body weight gain and the lungs were mainly affected by DDAC exposure. The no-observed-adverse-effect level (NOAEL) for DDAC was determined as $0.15mg/m^3$.

• Toxicological Research
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• v.27 no.1
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• pp.19-23
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• 2011

It has been proposed that acute phase response can be a mechanism by which inhaled particles exert adverse effects on the cardiovascular system. Although some of the human acute phase proteins have been widely studied as biomarkers of systemic inflammation or cardiovascular diseases, there are only a few studies that investigated the role of serum amyloid P (SAP), a major acute phase protein in mice. In this study, we investigated the changes in SAP, following inhalation exposure to nickel hydroxide nanoparticles (nano-NH). We conducted 1) acute (4 h) exposure to nano-NH at 100, 500, and $1000\;{\mu}g/m^3$ and 2) sub-acute (4h/d for 3d) exposure at $1000\;{\mu}g/m^3$, then measured serum SAP protein levels along with hepatic Sap mRNA levels. The results show that inhaled nano-NH can induce systemic acute phase response indicated by increased serum SAP levels and hepatic Sap mRNA levels. To the best of our knowledge, this is the first study showing induction of SAP in response to repeated particle exposure, and the results suggest that SAP can be used as a biomarker for systemic inflammation induced by inhaled particles.

• Toxicological Research
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• v.14 no.4
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• pp.495-500
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• 1998

The effect of acute toluene exposure on behaviour and monoamine concentrations in the various brain regions were investigated in the rat. Toluene was adminstered via inhalation to rats at concentrations of 0, 1000, 10000, 40000 ppm for 20 min. During exposure to toluene, spontaneous locomotor activity was counted. After exposure, animals were sacrificed instantly and brains were separated. Regional concentratons of brain monoamines (norepinephrine, NE; dopamine, DA; 5- hydroxytryptamine, 5-HT) and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; homovanillic acid, HVA; 5-hydroxyindole-3-acetic acid, 5-HIAA) were determined. The changes in locomotor activity during toluene exposure depended on the toluene concentration. At 1000 ppm concentration, spontaneous locomotor activity increased initially and thereafter decreased. At higher concentrations (10000 ppm and 40000 ppm), spontaneous locomotor activity decreased and eventually ceased. A regional analysis of VA, NE, 5-HT, VOPAC, HVA, and 5-HIAA indicated a significant decrease in VA concentrations in cerebellum and striatum while NE and 5-HT concentrations were significantly increased in the cerebellum and cortex. 5-HIAA concentrations were significantly increased in all brain regions. DOPAC concentrations were significantly increased in cerebellum and cortex while decreased in striatum. These results especially indicated that metabolic conversion of DA to HVA in striatum was highly increased by toluene inhalation. However, It remains to elucidate between behavioural responses and monoamine changes.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.25.1-25.9
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• 2016

Objectives After the initial investigations by the Korea Centers for Disease Control in 2011, over 1000 suspicious cases of humidifier disinfectant (HD) victims were subsequently reported by 2015, and numbers are still increasing dramatically in 2016 in the midst of the prosecutors' office investigation. This study attempts to summarize the current understandings of the related health effects of HD based upon a systemic review of published epidemiologic studies and toxicology investigations. Methods Published studies of HDs were searched through PubMed and TOXLINE under the search words 'humidifier disinfectant,' and related reports were identified from the references and published report list of regulatory agencies including the Korean National Institute of Environmental Research, US Environmental Protection Agency, and EU European Chemicals Agency. Results Case reports and epidemiologic studies have reported the clinical features of severe forms of HD lung damage, together with epidemiologic findings of seasonal occurrence and demographic variations, including the heightened susceptibility of young children. Toxicological studies have reported inhalation toxicities together with positive findings of in vitro genotoxicity studies. Conclusions This study examined unsolved issues based on cases of upper respiratory diseases and diseases of other organs, including cancers, among suspected victims of HDs. These issues should be clarified in future research for the management and prevention of health effects from HDs and chemicals of other related household products.

• Toxicological Research
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• v.14 no.3
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• pp.329-332
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• 1998

Ingredients and concentrations of organic solvents in 7 kinds of adhesive sold on the domestic market were qualitatively and quantitatively analysed. Vapor concentrations were also analysed to estimate inhalation concentratins when adhesives were abused to get high. Acetone, methyl ethyl ketone, methyl cyclopenatane, cyclohexane and toluene were identified to be used in domstic adhesives as solvents. When organic solvents of adhesives were vaporized in the vial at the room temprature for 30 mins, concentrations of organic solvents in air were in the range of 5,000~140,000ppm. Among these solvents, toluene, known to have strong hallucination effect, showed 5,000~35,000 ppm. The putative concentration of toluene in case of glue sniffing was estimated to be about 5,000ppm in consideration of glue sniffing circumstances. Toluene was found in all adhesives in this study, even adhesives which toluene was not described in label.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.518-524
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• 2003

Ultrasonic nebulizer with the application of new engineering methodology and the design of electronic circuit was made for lead inhalation toxicology study and 2730ppm lead nebulizing solution was used to generate lead aerosol. After modification of source and inlet temperatures, the results of particle size analysis for lead aerosol were as following. The highest particle counting for source temperature 20℃ was 39933.66 in inlet temperature 100℃ and particle diameter 0.75tLm. The highest particle counting for source temperature 50℃ was 39992.71 in inlet temperature 250℃ and particle diameter 0.75μm. The highest particle counting for source temperature 70℃ was 37569.55 in inlet temperature 50℃ and particle diameter 0.75μm. The ranges of geometric mean diameter(GMD) were 0.754-0.784μm for source temperature 2℃, 0.758-0.852μm for source temperature 50℃, and 0.869-1.060μm for source temperature 70℃. The smallest GMD was 0.754μm in source temperature 20℃ and inlet temperature 20℃, and the largest GMD was 1.060μm in source temperature 70℃ and inlet temperature 250℃. The ranges of geometric standard deviation(GSD) were 1.730-1.782 for source temperature 20℃, 1.734-1.894 for source temperature 50℃, and 1.921-2.148 for source temperature 70℃. The lowest GSD was 1.730 in source temperature 20℃ and inlet temperature 20℃, and the highest GSD was 2.148 in source temperature 70℃ and inlet temperature 250℃. Lead aerosol generated in this study was polydisperse. The ranges of mass median diameter(MMD) were 1.856-2.133μm for source temperature 20℃, 1.877-2.894μm for source temperature 50℃, and 3.120-6.109μm for source temperature 70℃. The smallest MMD was 1.856μm in source temperature 20℃ and inlet temperature 20℃, and the largest MMD was 6.109μm in source temperature 70℃ and inlet temperature 250℃. Slight increases for GMD, GSD, and MMD values were observed with same source temperature and increase of inlet temperature. MMD for inhalation toxicology testing in EPA guidance is less than 4μm. In this study, source temperature 20℃ and 50℃ with inlet temperature from 20℃ to 250℃ were conformed to the EPA guidance, but inlet temperature 20℃ and 50℃ for source temperature 70℃ were conformed EPA guidance. MMD for inhalation toxicology testing in OECD and EU is less than 3μm. In this study, source temperature 20℃ and 50℃ with inlet temperature from 20℃ to 250℃ were conformed to the EPA guidance, but none for source temperature 70℃.

• 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.

• Toxicological Research
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• v.24 no.3
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• pp.201-206
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• 2008

Exposure to formaldehyde(FA) is closely associated with adverse health effects such as irritation, inflammation, and squamous cell carcinomas of the nasal cavities. Owing to its rapid metabolism and elimination, exposure to FA does not always result in an increased concentration in blood or urine of animals and humans. Therefore, the development of biomarkers for FA exposure is necessary for risk assessment. In the present study, the effects of FA were investigated on the expression of genes involved in the MAPK pathway in vitro and results confirmed in rats exposed to FA by inhalation. Treatment of Hs 680.Tr human tracheal epithelial cells with FA induced gene expression for PDGFA, TNFSF11, SHC1, and HRAS. HRAS expression was also increased in tracheas of rats exposed to FA. In addition, FA exposure induced the expression of RASSF4, a member of the Rasassociation domain family of Ras effectors, in rat tracheas. In conclusion, data showed FA-inducible expression of genes involved in the MAPK pathway occurred and increased expression of HRAS and RASSF4 was noted in rat tracheas subchronically exposed to FA by inhalation. These genes may serve as molecular targets of FA toxicity facilitating the understanding of the toxic mechanism.

• Toxicological Research
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• v.31 no.2
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• pp.203-211
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• 2015

Trichloroacetonitrile is used as an intermediate in insecticides, pesticides, and dyes. In Korea alone, over 10 tons are used annually. Its oral and dermal toxicity is classified as category 3 according to the globally harmonized system of classification and labelling of chemicals, and it is designated a toxic substance by the Ministry of Environment in Korea. There are no available inhalation toxicity data on trichloroacetonitrile. Thus, the present study performed inhalation tests to provide data for hazard and risk assessments. Sprague-Dawley rats were exposed to trichloroacetonitrile at concentrations of 4, 16, or 64 ppm for 6 hour per day 5 days per week for 13 weeks in a repeated study. As a result, salivation, shortness of breath, and wheezing were observed, and their body weights decreased significantly (p < 0.05) in the 16 and 64 ppm groups. All the rats in 64 ppm group were dead or moribund within 4 weeks of the exposure. Some significant changes were observed in blood hematology and serum biochemistry (e.g., prothrombin time, ratio of albumin and globulin, blood urea nitrogen, and triglycerides), but the values were within normal physiological ranges. The major target organs of trichloroacetonitrile were the nasal cavity, trachea, and lungs. The rats exposed to 16 ppm showed moderate histopathological changes in the transitional epithelium and olfactory epithelium of the nasal cavity. Nasal-associated lymphoid tissue (NALT) and respiratory epithelium were also changed. Respiratory lesions were common in the dead rats that had been exposed to the 64 ppm concentration. The dead animals also showed loss of cilia in the trachea, pneumonitis in the lung, and epithelial hyperplasia in the bronchi and bronchioles. In conclusion, the no-observed-adverse-effect level (NOAEL) was estimated to be 4 ppm. The main target organs of trichloroacetonitrile were the nasal cavity, trachea, and lungs.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.242-251
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• 2019

Background: Korean Red Ginseng has been widely used in traditional oriental medicine for a prolonged period, and its pharmacological effects have been extensively investigated. In addition, Angelica gigas and deer antlers were also used as a tonic medicine with Korean Red Ginseng as the oriental herbal therapy. Methods: This study was conducted to evaluate the potential toxicological effect of KGC-HJ3, Korean Red Ginseng with angelica gigas and deer antlers, on reproductive and developmental functions including fertility, early embryonic development, maternal function, and embryo-fetal development. KGC-HJ3 was administered by oral gavage to Sprague-Dawley rats (22 animals per sex per group) at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on fertility and early embryonic development. In addition, KGC-HJ3 was also administered by oral gavage to mating-proven Sprague-Dawley rats (22 females per group) during the major organogenesis period at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on maternal function and embryo-fetal development. Results and conclusion: No test item-related changes in parameters for fertility, early embryonic development, maternal function, and embryo-fetal development were observed during the study period. On the basis of these results, it was concluded that KGC-HJ3 did not have toxicological potential on developmental and reproductive functions. Therefore, no observed adverse effect levels of KGC-HJ3 for fertility, early embryonic development, maternal function, and embryo-fetal development is considered to be at least 2000 mg/kg/day.