• 한국환경성돌연변이발암원학회지
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• 제22권2호
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• pp.97-105
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• 2002

Nowadays a huge variety of products that aim to assist to quit smoking or reduce addictive symptoms are developed and manufactured with safety evaluation, but the safety of the most recent products of interest which do not contain tobacco and nicotine, and shape cigarettes is not evaluated and guaranteed relatively. This study was carried out to evaluate the single and repeated dose inhalation toxicity and genotoxicity of H menthol (Nicotine free-tobacco free) herbal cigarettes provided by Cigastop Ltd. in ICR mice. In this study, doses which we determined to expose to mice were 40 cigarettes for 6 hours a day to mice in single dose and 20 (high dose), 10 (middle dose) and 5 cigarettes (low dose) a day for 28 days in repeated dose inhalation toxicity, in vivo chromosome aberration test and micronucleus test. The particulate substances from H menthol herbal cigarettes also were gathered and used in the Salmonella typhimurium/microsome assay (Salmonella test; Ames test). We could find neither significant changes between control and treatment groups nor dose-response effects of test material at all except serum Ca level of female middle dose treatment group in repeated dose inhalation toxicity test. In conclusion, H menthol herbal cigarettes, when applied clinically intended dose we used, might not show any toxic and/or mutagenic effect.

• Environmental Analysis Health and Toxicology
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• 제16권4호
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• pp.211-221
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• 2001

The purpose of this study was to investigate the acute (4 hours) and repeated-dose (6 hours a day, 5 days a week, 4 weeks) toxic effects of 1-hexene on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows; 1. The median lethal concentration(LC$_{50}$) was estimated 52,694 ppm (confidence limit 95％; 49,494~55,447 ppm) in acute inhalation. Abnormal clinical signs related to the 1-Hexene were not observed with the acute inhalation dose. Cross findings of necropsy revealed on evidence of specific toxicity related to the 1-hexene. II. By repeated inhalation exposure the body weight of male were more or less reduced by the dose of 2,500 ppm and 5,000 ppm compared with control group. However there were no significant variation 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-hexene were not shown. In conclusion when we exposed 1-hexene to SD rats for 4 weeks, 5 days per week, 6 hours per day, the Lowest observed effect level (LOEL) was over 2,500 ppm and Non observed effect level (NOEL) was below 500 ppm.

• Journal of Radiation Protection and Research
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• 제40권4호
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• pp.216-222
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• 2015

천연방사성물질을 취급하는 산업시설의 종사자들은 공정에서 발생하는 공기 중 입자의 흡입에 의해 만성적인 내부피폭을 받을 수 있다. 방사성 물질을 함유한 공기 중 입자 흡입에 의한 내부피폭은 입자의 크기, 모양, 밀도, 흡수형태에 따라 달라진다. 본 연구에서는 공기 중 부유 입자의 물리화학적 특성에 따른 피폭방사선량 민감도를 평가하였다. 흡입에 의한 내부피폭선량 평가는 국제방사선방호위원회 66 인체호흡기모델을 이용하였다. 일반적으로 입자의 크기가 감소할수록 예탁유효선량은 증가하는 경향을 보였으며, 입자 크기 $0.01{\mu}m$와 $100{\mu}m$ 에서의 피폭방사선량은 $^{238}U$ 의 경우 약 100 배, $^{230}Th$ 의 경우 약 50 배 차이를 보였다. 모양인자가 작을수록 피폭방사선량은 높게 나타났으며, 모양인자가 1 일 때 피폭방사선량은 모양인자가 2 일 때 보다 18% 높았다. 입자의 밀도가 증가할수록 피폭방사선량은 높게 나타났으며, 입자 밀도가 $11g{\cdot}cm^{-3}$ 인 경우 피폭방사선량은 밀도가 $0.7g{\cdot}cm^{-3}$ 인 경우에 비해 60% 높게 나타났다. $^{238}U$ 의 경우 피폭방사선량은 흡수형태 S, M, F 순으로 높게 나타났으며, 흡수형태 S 의 경우 F 에 비해 피폭방사선량이 약 9 배 높게 나타났다. $^{230}Th$ 의 경우 피폭방사선량은 흡수형태 F, M, S 순으로 높게 나타났으며, 흡수형태 F 의 경우 S 에 비해 피폭방사선량이 약 16 배 높게 나타났다. 민감도 평가에서 나타난 것처럼 입자의 물리화학적 특성을 고려하지 않고 피폭방사선량을 평가하는 경우 평가값은 실제값에 비해 수십 혹은 수백 배 이상 왜곡 될 수 있다. 천연방사성물질을 취급하는 작업장에서 종사자의 정확한 피폭방사선량 평가를 위해서는 취급하는 물질, 작업환경 등을 고려하고 입자의 물리화학적 특성값을 실측하여 실시하는 것이 바람직하다.

• Biomolecules & Therapeutics
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• 제3권1호
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• pp.91-96
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• 1995

The effects of toluene inhalation on the contents of amino acid neurotransmitters in rat brain were investigated and blood toluene concentrations inducing changes of behavior and amino acid neurotransmitter contents in rat brain were observed. Male wistar rats were exposed to toluene vapor (single dose : 1700, 5000 and 10000 ppm for 2 hrs, repeated dose : 1700 and 5000 ppm for 2 hrs/day$\times$6 days). Toluene concentrations in blood and the inhalation chamber were assayed by GC with headspace sampler. HPLC method following PITC derivatization was used to measure the amino acid contents in brain tissues such as frontal cortex, caudate, hippocampus, cerebellum and brain stem. Glutamic acid and aspartic acid levels were increased by single inhalation of toluene (5000 ppm) in all the brain areas assayed in this experiment. In caudate and cerebellum, taurine levels were decreased by single inhalation of low dose toluene (1700 ppm), but increased by repeated administration. At high blood toluene concentration, GABA levels were increased in all the brain areas assayed in this experiment and the increasing extents of inhibitory amino acid contents measured in caudate and hippocampus were greater than those of excitatory amino acids. These results suggest that the changes of amino acid neurotransmitter contents in brain by exposure to toluene may modulate toluene-induced behaviors.

• Toxicological Research
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• 제20권3호
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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.

• Toxicological Research
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• 제26권3호
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• pp.217-222
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• 2010

Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary fibrosis as a side effect. However, few investigations have focused on the dose-response effects of bleomycin on pulmonary fibrosis. Therefore, in the present study, we investigated the effects of different doses of bleomycin in male mice. ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The animals were sacrificed at 7 and 24 days postinstillation. The severity of pulmonary fibrosis was evaluated according to inflammatory cell count and lactate dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF), and lung tissues were histologically evaluated after hematoxylin and eosin (H&E), and Masson's trichrome staining. BT groups exhibited changed cellular profiles in BAL fluid compared to the VC group, which had an increased number of total cells, neutrophils, and lymphocytes and a modest increase in the number of macrophages at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose-dependent increase in LDH levels and inflammatory cell counts. However, at 24 days after treatment, collagen deposition, interstitial thickening, and granulomatous lesions were observed in the alveolar spaces in addition to a decrease in inflammatory cells. These results indicate that pulmonary fibrosis induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg. These data will be utilized in experimental animal models and as basic data to evaluate therapeutic candidates through non-invasive monitoring using the pulmonary fibrosis mouse model established in this study.

• 한국산업보건학회지
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• 제8권2호
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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.

• 한국환경과학회지
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• 제7권3호
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• pp.301-310
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• 1998

Recently, bathes have been suspected to an Important source of indoor exposure to volatile organic compounds(VOCs). Two experiments were conducted to evaluate chloroform exposure and corresponding body burden by exposure routes while bathing. Another experiment was conducted to ekamine the chloro- form dose during dermal exposure and the chloroform decay In breath after dermal exposure. The chioroform dose was determined based on exhaled breath analysis. The ekamine breath concentration measured after normal baths (2.8 Vg/$m^3$) was approxidmately 13 tomes higher that measured prior to normal bathes (0.2 ug/$m^3$). Based on the means of the normalized post exposure chloroform breath concentration. the dermal exposure was estimated to contribute to 74% of total chloroform body burden while bathing. The Internal dose from bathing (Inhalation plus dermal) was comparable to the dose ostimated Srom dally water Ingestion. The rusk associated 10 a weekly, 30-min bath was estimated to be 1 x 10.5, while the rusk firom dally Ingestion of tap water was to be $0.5{\times}0^{-5} for 0.151 and 6.5{\times}10^{-5}$ for 2. 0 1. Chloroform breath concentration Increased gradually during the 60 minute dermal exposure. The breath decay after the dermal exposure showed two-phase mechanism, with early raped decay and the second slow decay. The mathematical model was developed to describe the relationship between water and air chloroform concentrations, with $R^2$ : 0.4 and p<0.02.

• Toxicological Research
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• 제26권4호
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• pp.293-300
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• 2010

tert-Butyl acetate (TBAc) is an organic solvent, which is commonly used in architectural coatings and industrial solvents. It has recently been exempted from the definition of a volatile organic compound (VOC) by the Air Resources Board (ARB). Since the use of TBAc as a substitute for other VOCs has increased, thus its potential risk in humans has also increased. However, its inhalation toxicity data in the literature are very limited. Hence, inhalation exposure to TBAc was carried out to investigate its toxic effects in this study. Adult male rats were exposed to TBAc for 4 h for 1 day by using a nose-only inhalation exposure chamber (low dose, $2370\;mg/m^3$ (500 ppm); high dose, $9482\;mg/m^3$ (2000 ppm)). Shamtreated control rats were exposed to clean air in the inhalation chamber for the same period. The animals were killed at 2, 7, and 15 days after exposure. At each time point, body weight measurement, bronchoalveolar lavage fluid (BALF) analysis, histopathological examination, and biochemical assay were performed. No treatment-related abnormal effects were observed in any group according to time course. Based on those findings, the median lethal concentration ($LC_{50}$) of TBAc was over $9482\;mg/m^3$ in this study. According to the MSDS, the 4 h $LC_{50}$ for TBAc for rats is over $2230\;mg/m^3$. We suggested that this value is changed and these findings may be applied in the risk assessment of TBAc which could be beneficial in a sub-acute study.

• Safety and Health at Work
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• 제2권1호
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• pp.34-38
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• 2011

Objectives: The antimicrobial activity of silver nanoparticles has resulted in their widespread use in many consumer products. Yet, despite their many advantages, it is also important to determine whether silver nanoparticles may represent a hazard to the environment and human health. Methods: Thus, to evaluate the genotoxic potential of silver nanoparticles, in vivo genotoxicity testing (OECD 474, in vivo micronuclei test) was conducted after exposing male and female Sprague-Dawley rats to silver nanoparticles by inhalation for 90 days according to OECD test guideline 413 (Subchronic Inhalation Toxicity: 90 Day Study) with a good laboratory practice system. The rats were exposed to silver nanoparticles (18 nm diameter) at concentrations of $0.7\;{\times}\;10^6$ particles/$cm^3$ (low dose), $1.4\;{\times}\;10^6$ particles/$cm^3$ (middle dose), and $2.9\;{\times}\;10^6$ particles/$cm^3$ (high dose) for 6 hr/day in an inhalation chamber for 90 days. The rats were killed 24 hr after the last administration, then the femurs were removed and the bone marrow collected and evaluated for micronucleus induction. Results: There were no statistically significant differences in the micronucleated polychromatic erythrocytes or in the ratio of polychromatic erythrocytes among the total erythrocytes after silver nanoparticle exposure when compared with the control. Conclusion: The present results suggest that exposure to silver nanoparticles by inhalation for 90 days does not induce genetic toxicity in male and female rat bone marrow in vivo.