• Toxicological Research
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• v.33 no.3
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• pp.239-253
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• 2017

Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide ($Nd_2O_3$) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized $Nd_2O_3-containing$ aerosols via a nose-only inhalation system at doses of $0mg/m^3$, $0.5mg/m^3$, $2.5mg/m^3$, and $10mg/m^3$ for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the $2.5mg/m^3$ and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the $0.5mg/m^3$ treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the $0.5mg/m^3$ group, but were exacerbated in the $10mg/m^3$ group. The lowest-observed-adverse-effect concentration of nano-sized $Nd_2O_3$ was determined to be $0.5mg/m^3$, and the target organ was determined to be the lung, under the present experimental conditions in male rats.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.31 no.3
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• pp.185-193
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• 2021

Objectives: Inhalation toxicity testing of chemical substances to identify carcinogenicity requires a long time and considerable cost, so the selection of test candidates is a very important aspect. This study was performed to determine optimal procedures for selecting carcinogenic inhalation toxicity test substances as conducted by the Occupational Safety and Health Research Institute (OSHRI). Methods: At the beginning, a database was constructed containing complex information such as usage amount, hazard, carcinogenicity prediction, and testability in order to select chemicals requiring carcinogenicity testing. Selection of test substances was carried out with priority given to usage, carcinogenicity, and testability. Results: Chemicals used in large quantities in industrial fields and strongly suspected of carcinogenicity were winnowed down to 12 substances, and these substances were scheduled for future testing by OSHRI. Conclusions: For the stable and reliable operation of carcinogenicity tests as conducted by OSHRI, this study standardized the procedures for selecting carcinogenicity test substances and suggested the introduction of various carcinogenicity prediction techniques.

• Journal of Environmental Health Sciences
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• v.44 no.1
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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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• v.20 no.3
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• pp.273-280
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• 2004

The present study was carried out to investigate the potential toxicity of dimethyl disulfide by a 2-week inhalation in F344 rats. The test article, dimethyl disulfide, was exposed by inhalation to male and female rats at dose levels of 0, 33, 100, or 300 ppm/6 hrs/day for 2 weeks. At the end of treatment period, all males and females were sacrificed. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. The mean body weights of the male 300 ppm group and the female 33 ppm or higher dose groups were significantly lower than those of the control group, respectively. The mean food consumption at male 300 ppm and female 100 and 300 ppm were significantly decreased compared with the controls. Some treatment-related serum biochemical changes, including decreased alkaline phosphatase at male 300 ppm and female 100 and 300 ppm, reduced total bilirubin at male 300 ppm, and decreased alanine aminotransferase at female 300 ppm, were observed in a dose-dependent manner, but these findings were considered to be of no toxicological significance. There were no adverse effects on mortality, clinical signs, hematology, and necropsy findings in any treatment group. Based on these results, it was concluded that the 2-week repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at the dose of male 300 ppm and suppressed or reduced body weight gain and decreased food consumption at the dose of female 33 ppm or higher. In the present experimental conditions, the no-observed-adverse-effect level (NOAEL) was considered to be 100 ppm/6 hrs/day for male rats and below 33 ppm/6 hrs/day for female rats.

• Journal of Environmental Health Sciences
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• v.44 no.1
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• pp.31-43
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• 2018

Objectives: Effective genetic toxicology and molecular biology research techniques and strategies that are highly correlated with the carcinogenic inhalation toxicity test and related research are required. The aim of this study was to maximize the utilization of chemical substances to prevent workers' occupational diseases. Methods: We surveyed the literature, domestic and international references, and the status of relevant domestic and foreign professional organizations. Expert advisory opinions were reflected, and experts were consulted by participating in domestic and overseas academic conferences. Results: The current status of domestic and international genotoxic toxicity evaluation was examined through various documents from related organizations. Cell models for in vitro lung toxicology were investigated and summarized, and the human resources and performance results of genetic toxicity studies and pilot projects were compared and analyzed by holding an advisory meeting. We examined domestic and international genotoxicity guidelines and investigated new test methods for the development of genotoxicity and carcinogenicity. Ultimately, we described long-term future predictions, including the implementation of our researchers' recommendations and occupational genetic toxicology forecasts for future worker health protection. Conclusions: This research project aims to establish current genetic toxicology and molecular biology research techniques and strategies that can maximize the linkage with the carcinogenic inhalation toxicity test and research in the future. We expanded the study of genetic toxicity and establish a foundation forgenetic toxicity in accordance with research trends in Korea and abroad.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.8 no.2
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• pp.272-288
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• 1998

The purpose of this study was to investigate the acute(4 hrs) and repeated-dose(6 hrs a day, 5 days a week, 8 weeks) toxic effects of 1-bromopropane(1-BP) on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows ; 1. The median lethal concentration($LC_{50}$) was estimated 14,374 ppm(confidence limit 95% ; 13,624~15,596 ppm) in acute inhalation. Abnormal clinical signs related to the 1-BP were not observed with the acute inhalation dose. Gross findings of necropsy revealed no evidence of specific toxicity related to the 1-BP. 2. By sub-acute inhalation the body weights of male and female were significantly reduced(p<0.001) by the dose of 1,800 ppm compared with control group, while the relative weights of liver were significantly increased(p<0.001) in both sexes. However there were no significant variation in food consumption, urine biochemistry, hematology and blood biochemistry for the exposed rats compared with the control rats. Abnormal clinical signs and gross findings of necropsy related to the 1-BP were not shown. No toxicologic lesions were observed by the histopathological test.

• Environmental Analysis Health and Toxicology
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• v.17 no.1
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• pp.81-93
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• 2002

There were no specific effects for test materials on Sprague-Dawiey (S.D.) rats in clinical symptoms, amounts of food intakes, weight changes, laboratory findings, and pathology after whole body 1, 1-Dichloro-1-fluoroethane (used as coolant, metal cleaner and solvents) exposure (0, 1,500, 3,000, and 6,000 ppm) for 13 weeks (6 hour/day, 5 days/week). However, the loss of capillary vessels in eyeball (pupil) was observed in a female rat among 6,000 ppm group. Though there was a tendency for MCHC (Mean Corpuscular Hemoglobin Concentration) in rat to be decreased (p<0.05), it was not regarded as abnormal because the values were within normal limits. In asthma-stimulation related evaluations. there was also a tendency for inflammatory cell counts in bronchoalveolar lavages to be increased. But it had no statistical significance, and also no dependency on sex and the exposed concentration . Based on this result, the non observed effect level (NOEL) induced by 1, 1-Dichloro-1-fluoroethane inhalation was evaluated in groups with 3,000 ppm below (S.D. Rats, 13 weeks). Finally, it was concluded that the short term exposal of 1, 1-Dichloro-1-fluoroethane is not considered as a asthma stimulant by inhalation despite of some study limitations such as test animals use and short-term exposure.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1784-1794
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• 2004

To study the effects between Cd inhalation toxicity and methanol extract of Radix Achyranthis Bidentatae, 4 rat groups were exposed to Cd aerosol by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cd concentration in air was 0.98㎎/㎥ and mass median diameter(MMD) was 1.78㎛. 3 different dose intraperitoneal injections of methanol extract of Radix Achyranthis Bidentatae to 3 inhalation exposure groups applied 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 Ⅲ(p<0.05). The highest lung weight was from inhalation exposure group Ⅲ and the highest liver and kidney weight were from inhalation exposure group Ⅱ(p<0.05). The lowest Cd content in lung was 22.77㎍/g from inhalation exposure group Ⅲ(p<0.05). The highest Cd concentration in blood was 11.71㎍/㎗ from inhalation exposure group Ⅰ(p<0.05). Cd concentrations of 14.87㎍/g in liver and 17.91㎍/g in kidney were the highest from inhalation exposure group Ⅰ(p<0.05). The lowest Cd concentration in liver and kidney were 5.71㎍/g and 3.17㎍/g from the control(p<0.05). For weekly Cd concentration in urine, the highest value was 0.48㎍/㎖ from inhalation exposure group Ⅲ of the 3rd week and inhalation exposure group Ⅰ, Ⅱ of the 4th week. For weekly Cd concentration in feces, the highest value was 0.32㎍/g from inhalation exposure group Ⅰ, Ⅱ, Ⅲ. The highest metallothionein concentration in lung was 89.02㎍/g from inhalation exposure group Ⅲ(p<0.05). The highest metallothionein concentrations in liver and kidney were 265.47㎍/g and 214.21㎍/g from inhalation exposure group Ⅲ, respectively(p<0.05). The highest Hct, Hb, and WBC values were from inhalation exposure group Ⅱ and the highest RBC value was from inhalation exposure group Ⅲ(p<0.05). Mostly damaged part in liver tissue was hepatic lobule and the degrees of damage were lessened by the intraperitoneal injection of methanol extract of Radix Achyranthis Bidentatae. Proximal, distal convoluted tubules and glomerulus in kidney tissue were mostly damaged part. Degeneration and swelling were partially observed but the degrees of kidney tissue damage were lessened more or less by the intraperitoneal injection of methanol extract of Radix Achyranthis Bidentatae.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.24 no.2
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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.

• Journal of the Korean Institute of Gas
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• v.21 no.1
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• pp.6-17
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• 2017

Objectives : The purpose of this study was to obtain information regarding Globally Harmonized System(GHS) classification and health hazards that may result from a 4 weeks inhalation exposure of 3-Methylpentane in Sprague-Dawley rats. Methods : The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 412(Subacute Inhalation Toxicity). The Rats were divided into 4 groups(5 male and 5 female rats in each group) and exposed to 0 ppm, 284 ppm, 1,135 ppm, 4,540 ppm 3-Methylpentane in each exposure chamber for 6 h/day, 5 days/week, for 4 weeks. After two weeks, the test animals were autopsied and carried out blood test and biochemical tests and histopathological examination. We used PRISTIMA (Toxicology data management system) to confirm the system and to have confidence of the raw data. Results : No death and particular clinical presentation including weight change and change of feed rate was observed. Relationship between dose, gender and response was also not significantly changed in hematologic examination, biochemical examination of blood and blood coagulation time. The histopathologic lesions caused by the test substance did not appear. Conclusions : NOAEL(No Observable Adverse Effect Level) of 3-Methylpentane is more than 4,540 ppm in male group and female group and the Ministry of Employment and Labor Guidance Announcement No. 2013-37(criteria for the classification marks and Safety of Chemicals) Specific target organ toxicity(repeated exposure) was determined with a substance that is not the separator material.