• Journal of the Korean Society of Tobacco Science
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• v.36 no.1
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• pp.20-25
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• 2014

As part of a balanced testing battery, subchronic inhalation studies on rats are performed to ensure that proposed cigarette modifications do not increase the toxicity of smoke and to demonstrate any instances where a modification may actually contribute to harm reduction. For subchronic inhalation studies with aerosols, the OECD suggests an exposure regimen of 6 hours/day (OECD Guideline 413, 1981), but alternative regimens have also been published: 1 hour/day and $2{\times}1$ hour/day. The aim of this study was to validate a rodent nose-only exposure system for the assessment of inhalation toxicity of cigarette smoke. In this study, cigarette smoke exposure system is consisted of cigarette smoke generator, smoke concentration adjusting system, and 20-port nose-only exposure system. Male SD rats were exposed for 35 days ($2{\times}1$ hour/day) to 3R4F Reference cigarette smoke and analysed major monitoring items of OECD Gudeline 413. WTPM, was measured in the test atmosphere, respiratory function (Buxco Biosystems) during exposure, postexposure urinary exposure biomarkers and alveolar neutrophiles in BAL fluid (Day 35) were evaluated. Validation demonstrated steady WTPM ($257{\pm}20ug/L$, $502{\pm}27ug/L$) and spatial uniformity (<10%). Nose port temperature ($22{\sim}26^{\circ}C$ and RH (45~75%) were acceptable over 35 days. Reductions in respiratory rate and minute volume and increase in the neutrophiles in BALF and the urinary exposure biomarkers were observed cigarette smoke dose dependently. This validation and 35-day inhalation study has shown that the rodent nose-only exposure system may be useful in the inhalation toxicity assessment of cigarette smoke.

• Journal of the Korean Applied Science and Technology
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• v.29 no.1
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• pp.129-140
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• 2012

Smoke toxicity is the test for the toxicity evaluation of smoke and hazardous gas, caused by combustion of building materials and finishing materials. Smoke toxicity can be evaluated by the mean incapacitation time of mice. This test result can be influenced by the health status of mice and test condition. In acute inhalation toxicity test of hazardous gas, no typical clinical findings and histopathologic abnormalities were observed. Tracheitis and bronchitis as well as acute lung inflammation around terminal bronchiole in some mouse of the highest dose group. Through this study, we established the method for inhalation toxicity test of hazardous gas as well as the SOP of inhalation toxicity test. However, in the future studies, the concentration control methods for inhalation technologies on hazardous gas will be needed to improve continuously and also further studies on other gas inhalation toxicity will be needed to conduct.

• Particle and aerosol research
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• v.12 no.1
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• pp.1-9
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• 2016

In this work, we evaluated the characteristics of flow field and uniformity of the nose-only exposure chambers for the inhalation toxicity test. Computational fluid dynamics (CFD) modeling was carried out to demonstrate uniformity of the nose-only exposure chambers. Because it is very important in the inhalation toxicity experiments that test materials are distributed uniformly to each holder of the chamber. The test was done with these 3 types of chamber with different form to develop inhalation toxicity evaluation system, easy-to-operate system among exposure chamber used for evaluating inhalation toxicity of environmental chemical mixtures. Through CFD interpretation, nose-only exposure chamber was made with the selection of the optimal conditions. For its evaluation, one type of fragrance was selected and measured particle size distribution of each port. The gene becoming luminous to green fluorescence was combined with GPT-SPE, a type of tGFP vector, to be inhaled to the mouse. Based on this, luminous intensity was checked. As a result, total particle number concentration of each port had average value of $3.17{\times}10^6{\sharp}/cm^3$ and range of the highest and lowest concentration value was approximately ${\pm}4.8%$. Autopsy of lung tissues of mouse showed that it had clearly better delivery of gene compared to the control group.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.17 no.3
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• pp.181-191
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• 2007

With the 2-Butanethiol, which is an unidentified inhalation toxic material, acute inhalation toxicity was tested with SD rats. The $LC_{50}$ was evaluated to be 2,500 ppm (9.22 mg/L) or higher which falls under the criteria of acute toxicity Category 3 (500<$LC_{50}$<2,500 ppm) in the Industrial Safety and Health Act. In the subchronical inhalation toxicity test by 0, 25, 100, and 400 ppm, 6 hours a day, 5 days a week, for 13 weeks repeated exposure, though no death or particular clinical presentation was observed, in the female 25 and 400 ppm group, including weight change, and in each concentration group including 400 ppm, change of feed rate, eye stimulation, motility change in male group, and lesions in blood and blood biochemical were observed. In the internal organs weight, 25, 100, and 400 ppm groups in male and 400 ppm group in female showed significant (p<0.05) changes in kidney, liver, thymus, and lung. In the pathological tissue test, severe cortical tubular hyaline droplets were observed in the male 400 ppm group, and all male rats of 400 ppm group and 2 female individuals showed tubular degeneration/regeneration accompanied with pigmentation, showing that the target organs of inhalation exposure of 2-Butanethiol are spleen, kidney, nasal cavity, and adrenal. Through the tests, the NOEL of 2-Butanethiol was evaluated to be 25 ppm (0.092 mg/L) or less for both male and female.

• Environmental Analysis Health and Toxicology
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• v.6 no.3_4
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• pp.123-132
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• 1991

Acute poisoning with organic solvents and other volatile compounds now usually follows deliberate inhalation (volatile substance abuse) or ingestion of these compounds. The effect of butane gas inhalation was analyzed for serum, liver, brain, lung and muscle. And the observations are revealed on rat cholinesterase activity, lactatedehydrogenase activity and electrophoretic pattern of lactatedehydrogenase isozyme. The results are as follows: 1. The rat cholinesterase activity on serum, liver and muscle show the decreased by increasing of inhalation time of butane gas in particular the lung cholinesterase activity was greatly affected. 2. Butane gas inhalation brought out the lactatedehydrogenase activity increased of the serum and the tissues and had an important effect especially in both the liver and muscle 1actatedehydrogenase activities. 3. Each tissue was found to have a characteristic distribution of lactatedehy-drogenase isozymes on celluloseacetate electrophoresis and the development of inhalation time is shown the disappearance and diffusion of band. The toxicity of butane gas inhalation was most prominence in the liver and lung toxicity was occurred also.

• Toxicological Research
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• v.33 no.1
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• pp.7-14
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• 2017

Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were $0.63{\mu}m$, $0.81{\mu}m$, and $1.65{\mu}m$, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low ($0.11{\pm}0.06mg/m^3$), the middle ($0.36{\pm}0.20mg/m^3$) and the high ($1.41{\pm}0.71mg/m^3$) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high ($1.41{\pm}0.71mg/m^3$) male group and 15% lower in the high ($1.41{\pm}0.71mg/m^3$) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle ($0.36{\pm}0.20mg/m^3$) and the high ($1.41{\pm}0.71mg/m^3$) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle ($0.36{\pm}0.20mg/m^3$) and the high ($1.41{\pm}0.71mg/m^3$) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is $0.11mg/m^3$.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.474-483
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• 2004

To know the effects between Cd inhalation toxicity and extract of Radix Achyranthis Bidentatae, 4 rat groups were exposed to Cd aerosol in air using whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cd concentration in air was 1.03㎎/㎥ and mass median diameter(MMD) was 1.69㎛. 3 different dose intraperitoneal injections of extract of Radix Achyranthis Bidentatae to 3 inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were from inhalation exposure group I and the highest lung and liver weight were also from inhalation exposure group I. The highest kidney weight was from inhalation exposure group III. The lowest Cd content in lung was 33.49㎍/g from inhalation exposure group I. The lowest Cd concentration in blood was 9.36㎍/㎗ from inhalation exposure control. Cd concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. The lowest Cd concentration in liver was 21.08㎍/g from inhalation exposure group III and The lowest Cd concentration in kidney was 15.78㎍/g from inhalation exposure group II. For weekly Cd concentration in urine, the value of the fourth week from inhalation exposure group III was the highest. For weekly Cd concentration in feces, the value of the first week from inhalation exposure group III was the highest. The highest metallothionein concentration in lung was 53.42 ㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 188.18㎍/g from inhalation exposure group III. The highest metallothionein concentration in kidney was 143.92㎍/g from inhalation exposure group III. The highest Hct, Hb, and WBC values were from inhalation exposure group II and the highest RBC value was from inhalation exposure group III.

• 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.

• Environmental Analysis Health and Toxicology
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• v.21 no.2 s.53
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• pp.173-184
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• 2006

From the harmfulness expectation test conducted through a toxicity anticipation program, methylcyclohexane turned out to be harmful and simulative, but no carcinogenicity was anticipated. In a four-hour acute inhalation toxicity test, the result showed that lethal concentration ($LC_{50}$) was 3,750 ppm (15,054 mg/L), which was identified as a harmful substance on the basis of the harmful substance classification standard $2 of the Industrial safety and health law. methylcyclohexane fell under the category $4(2,500 substance from the GHS standard acute toxicity harmfulness classification. Also, from subchronic inhalation toxicity test that included 6 hours a day, five days a week, and for 13 weeks, we could observe weight, activity, long term weight, blood and blood biochemical influence from the exposure of test substance. No-observed effect level (NOEL) was determined below $100{\sim}400ppm$ inboth male and female. This material falls under the Category 2 ($50{\sim}250ppm/6hours/90days$) in the GHS (Globally Harmonized System) standard trace long-term whole body toxicity repeated exposure, and can be classified as a harmful substance in accordance with the Industrial Safety and Health Law harmful substance standard $NOEL{\leq}0.5mg/L/6hr/90day$ (rat).

• Toxicological Research
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• v.16 no.4
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• pp.302-309
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• 2000

The purpose of this study is to investigate toxic effects of iso-butylalcohol (iBA) in Sprague-Dawley (SD) rats under the exposure of 6 hours a day, 5 days a week for 13 weeks by inhalation, and to evaluate the occupational safety of iBA in comparison with the permissible exposure level (PEL) stipulated by the Occupational Safety and Health Administration (OSHA). iBA did not induce any abnormal changes from the aspects of clinical signs, feed consumption, ophthalmic test, urinalysis, hematology and blood chemistry during and at the terminal of the inhalation toxicity tests. We did not find any abnormal findings in the gross and microscopic observations due to the inhalation of iBA. There was no alteration in relative organ weights by the inhalation of iBA. No observed adverse effect level (NOAEL) of iBA was considered to be more than 3,000 ppm in rats under the inhalation of 6 hours a day, 5 days a week for 13 weeks. Fifty ppm of iBA, the PEL regulated by OSHA, is too conservative for working places. As iBA showed no abnormal observations in all the experimental parameters at any concentration under this experimental condition, we suggest that 150 ppm is safe enough for the PEL of iBA in the working areas, even taking into onsideration that OSHA lowered the PEL to 50 ppm for fear of the probable risk of its skin irritation.