• Safety and Health at Work
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• 제1권2호
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• pp.192-200
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• 2010

Objectives: We have investigated the toxic effects of the inhalation of subchronic and acute levels of n-octane. Methods: The rats were exposed to n-octane of 0, 2.34, 11.68 and 23.36 mg/L (n = 5 rats/group/gender) in an acute inhalation test (Organization for Economic Co-operation and Development (OECD) TG 403), or to 0, 0.93, 2.62 and 7.48 mg/L (n = 10 rats/group/gender) for a subchronic inhalation test (OECE TG 413), to establish a national chemical management system consistent with the Globally Harmonized Classification System (GHS). Results: Acutely-exposed rats became lethargic but recovered following discontinuation of inhalation. Other clinical symptoms such as change of body weight and autopsy finds were absent. The LC50 for the acute inhalation toxicity of n-octane was determined to exceed 23.36 mg/L and the GHS category was 'not grouping'. Subchronically-treated rats displayed no significant clinical and histopathological differences from untreated controls; also, target organs were affected hematologically, biochemically and pathologically. Therefore, the no observable adverse effect level was indicated as exceeding 7.48 mg/L and the GHS category was 'not grouping' for the specific target organ toxicity upon repeated exposure. Conclusion: However, n-octane exposure should be controlled to be below the American Conference of Industrial Hygienists recommendation (300 ppm) to prevent inhalation-related adverse health effects of workers.

• Toxicological Research
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• 제31권4호
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• pp.393-402
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• 2015

This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats.

• 한국환경보건학회지
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• 제43권1호
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• pp.23-41
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• 2017

Objectives: In this study, we seek to perform a priority selection for test substances for chronic inhalation toxicity studies, including acute and subchronic inhalation toxicity studies, which are to be performed after the construction of a chronic/carcinogenicity inhalation toxicity study facility and enactment of pertinent legislation. Methods: Through this study, qualitative and quantitative priority evaluation of test substances according to acute, subchronic and chronic categories were respectively performed and priorities were suggested by expert group review, redundancy and other methods. Meanwhile, a draft on test substance selection criteria, procedures and methods referring to the National Toxicology Program (NTP) system was proposed. Results: This study selected priorities for candidate substances for chronic inhalation toxicity studies to be conducted from 2016. Conclusions: In the future, by assessing in advance the toxicological effects of chemicals to which workers can be potentially exposed in the workplace via long-term inhalation, expected health disturbances among workers will be reduced and it is anticipated that occupational disease induced by chemicals will be effectively prevented.

• 한국연초학회지
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• 제36권1호
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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.

• Safety and Health at Work
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• 제3권3호
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• pp.224-234
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• 2012

Objectives: This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. Methods: This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. Results: During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. Conclusion: The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS).

• Environmental Analysis Health and Toxicology
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• 제25권2호
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• pp.131-143
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• 2010

We performed the tests of acute and subchronic inhalation toxicity of methyl formate, which has limited toxicological data in spite of its widespread use and enhanced hazard consequent on its high volatility. The median lethal concentration ($LC_{50}$) was evaluated to be above 5,000ppm(12.27 mg/L). In the test with subchronic inhalation, there are no deaths, but with reduction of body weight, food intake, organ weight by exposure to 400 (0.98 mg/L) and 1,600 (3.92 mg/L) ppm, dose-dependently. There were statistical differences in some hematological and blood biochemical parameters as compared to control (e.g. neutrophile and lymphocyte in the 1,600 ppm group, calcium and A/G in 1,600 ppm group). Methyl formate under the exposure of 1,600 ppm showed the respiratory findings with nasal, it was confirmed that the chemical has respiratory hazard with 1,600 ppm inhalation exposure, induces nasal epithelial atrophy, olfactory cell degeneration/regeneration and the contraction of olfactory cells, etc. According to the notification with Ministry of Labor (No. 2009-68) for classification, labeling and MSDS of chemicals, it is suggested for methyl formate to be classified as category 4 in acute (10.0$4\leq20.0$ mg/L), category 2 (0.2$\leq$1.0 mg/L/6h, 90 days) in specific target organ-repeated exposure.

• 한국산업보건학회지
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• 제24권2호
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• pp.169-181
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• 2014

Objectives: The purpose of this study was to obtain information regarding classification and health hazards that may result from a 13-week inhalation exposure to 2-methylpentane by Sprague-Dawley rats. Materials: The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 413. The rats were divided into four groups(ten male and ten female rats in each group) and exposed to 0 ppm, 290 ppm, 1,160 ppm, 4,640 ppm 2-Methylpentane in each exposure chamber for six hours per day, five days per week, for 13 weeks. Results: No death or particular clinical presentation including weight change and change of feed rate was observed. The relationships between dose, gender and response were also not significantly changed in urinalysis, hematologic examination, or biochemical examination of blood(except for total cholesterol being up, total protein being up, and chloride ion being down in males), and blood coagulation time. For the relative weight measurement of organs, in the male group the weight change of both kidney and liver were increased in proportion to dose. In histopathological examination, nephropathy in the kidney(cystic change of renal tubules, regenerative tubule, inflammatory cell infiltration and necrosis in the interstitial tissue) was increased in a dose-dependent manner in the male group(290 ppm, 1,160 ppm, 4,640 ppm). However, other organs were not affected by the test substance. Conclusions: 2-methylpentane was estimated as a chemical causing nephropathy in the male group. NOAEL(No Observable Adverse Effect Level) in the female group is more than 4,640 ppm, while inthe male group it is less than 290 ppm.

• Toxicological Research
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• 제33권1호
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• pp.15-23
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• 2017

Acanthopanax divaricatus (Siebold & Zucc.) Seem. var. albeofructus (ADA), a traditional medical herb, has been used to treat arthritis and muscular injury, to strengthen muscle and bone, and to get vital energy. However, information regarding its toxicity is limited. ADA was administered by oral gavage to groups of rats at doses of 0 (control), 1,000, 1,500, 2,000, 2,500, and 3,000 mg/kg five times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, organ weights, necropsy, histopathological finding, vaginal cytology, and sperm morphology were compared between control and ADA-treated groups. Salivation was intermittently observed in both sexes receiving 2,500 and 3,000 mg/kg directly after dosing. Absolute liver weights increased in females receiving 2,000, 2,500, and 3,000 mg/kg ADA (P < 0.05, P < 0.01, and P < 0.01, respectively) and so did the relative liver weights (P < 0.001). Salivation and increased liver weight were ADA-related changes but not considered to be adverse effects. Salivation was intermittent and transient, and the liver weight increase was minor and not accompanied by other changes such as hepatic morphological or functional alterations. The no-observed-adverse-effect-level was determined to be at least 3,000 mg/kg in both sexes of rats.

• 한국산업보건학회지
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• 제17권3호
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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.

• Toxicological Research
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• 제31권2호
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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.