• Radiation Oncology Journal
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• v.25 no.2
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• pp.109-117
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• 2007

[ $\underline{Purpose}$ ]: To evaluate the incidences and potential predictive factors for symptomatic radiation pneumonitis (SRP) and radiographic pulmonary toxicity (RPT) following adjuvant radiotherapy (RT) for patients with breast cancer. A particular focus was made to correlate RPT with the dose volume histogram (DVH) parameters based on three-dimensional RT planning (3D-RTP) data. $\underline{Materials\;and\;Methods}$: From September 2003 through February 2006, 171 patients with breast cancer were treated with adjuvant RT following breast surgery. A radiation dose of 50.4 Gy was delivered with tangential photon fields on the whole breast or chest wall. A single anterior oblique photon field for supraclavicular (SCL) nodes was added if indicated. Serial follow-up chest radiographs were reviewed by a chest radiologist. Radiation Therapy Oncology Group (RTOG) toxicity criteria were used for grading SRP and a modified World Health Organization (WHO) grading system was used to evaluate RPT. The overall percentage of the ipsilateral lung volume that received ${\geq}15\;Gy\;(V_{15}),\;20\;Gy\;(V_{20})$, and $30\;Gy\;(V_{30})$ and the mean lung dose (MLD) were calculated. We divided the ipsilateral lung into two territories, and defined separate DVH parameters, i.e., $V_{15\;TNGT},\;V_{20\;TNGT},\;V_{30\;TNGT},\;MLD_{TNGT}$, and $V_{15\;SCL},\;V_{20\;SCL},\;V_{30SCL},\;MLD_{SCL}$ to assess the relationship between these parameters and RPT. $\underline{Results}$: Four patients (2.1%) developed SRP (three with grade 3 and one with grade 2, respectively). There was no significant association of SRP with clinical parameters such as, age, pre-existing lung disease, smoking, chemotherapy, hormonal therapy and regional RT. When 137 patients treated with 3D-RTP were evaluated, 13.9% developed RPT in the tangent (TNGT) territory and 49.2% of 59 patients with regional RT developed RPT in the SCL territory. Regional RT (p<0.001) and age (p=0.039) was significantly correlated with RPT. All DVH parameters except for $V_{15\;TNGT}$ showed a significant correlation with RPT (p<0.05). $MLD_{TNGT}$ was a better predictor for RPT for the TNGT territory than $V_{15\;SCL}$ for the SCL territory. $\underline{Conclusion}$: The incidence of SRP was acceptable with the RT technique that was used. Age and regional RT were significant factors to predict RPT. The DVH parameter was good predictor for RPT for the SCL territory while $MLD_{TNGT}$ was a better predictor for RPT for the TNGT territory.

• 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.

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.213-224
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• 2016

Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

• Toxicological Research
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• v.22 no.3
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• pp.237-244
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• 2006

Two kinds of sepiolite, a $500^{\circ}C$ heat-treated sepiolite, and a $700^{\circ}C$ heat-treated sepiolite were analyzed for their physicochemical properties. After these sepiolites were instilled into rat lungs, the effects of the substances on lung pathological changes were evaluated. The lungs instilled with sepiolite increased their weight compared with the unexposed control. The pathological examination further showed increased legions of granuloma with early fibrosis. The heat treated sepiolites, however, did not show any toxicological differences from the untreated sepiolites. Thus chronic experiments are needed to evaluate the durability of mineral fibers, which is an essential experiment for evaluating biopersistence of fibers in lungs.

• Environmental Analysis Health and Toxicology
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• v.19 no.1
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• pp.93-100
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• 2004

Pretilachlor [2-chloro-N -(2, 6-diethylphenyl)-N-(2-propoxyethyl) acetamide, $C_{17}$H$_{26}$ClNo$_2$, M.W.=311.9, CAS No.51218-49-6]는 제초제의 일종으로 본 연구에서는 박테리아 복귀 돌연변이 시험과 포유동물 세포를 이용한 염색체 이상 시험 및 마우스를 이용한 in vivo소핵 시험을 수행하여 pretilachlor의 유전독성을 평가하였다. 박테리아 복귀 돌연변이 시험에서 pretilachlor는 Salmonella typhimurium TA98, TA 100, TA1535, TA1537 균주의 대사 활성계 존재 및 부재시 313-5,000$\mu\textrm{g}$/plate의 범위에서 농도 의존적인 돌연변이 율의 증가를 관찰할 수 없었다. 또한 포유동물 세포인 Chinese hamster lung (CHL) fibroblast를 이용한 염색체 이상 시험에서 pretilachlor는 대사 활성계 존재 및 부재시 1.56-6.24$\mu\textrm{g}$/mL의 농도에서 clastogenicity를 보이지 않았고, 137.5-550.1 mg/kg의 pretilachlor를 복강 주사한 마우스의 골수세포를 이용한 in vivo소핵 시험의 결과에서도 통계적으로 유의한 소핵 유발능을 관찰할 수 없었다었다

• Advances in Traditional Medicine
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• v.5 no.4
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• pp.283-293
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• 2005

Our previous study showed that a novel synthetic shikonin derivative, 6-(1-hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) induced apoptosis. In the present study, we investigated its anti-metastatic activities as compared with shikonin because DMNQ S-52 was synthesized for overcoming weak points of shikonin such as high toxicity, low solubility and deleterious effects. DMNQ S-52 showed the weaker cytotoxicity $(IC_{50};\;12.3{\pm}1.6\;{\mu}M)$ against Lewis lung carcinoma (LLC) cells than that of shikonin $(IC_{50};\;4.2{\pm}1.1\;{\mu}M)$. DMNQ S-52, at non-toxic concentrations $(less\;than\;10\;{\mu}M)$, significantly inhibited the invasion and migration of LLC cells. DMNQ S-52 also significantly inhibited the production of MMP-9, MTl-MMP and uPAR. Moreover, daily i.p. administration of DMNQ S-52 at dose of 5 mg/kg in mice resulted in a potent inhibition of the primary tumor size of LLC in the lung as well as the metastasis of lymph nodes. These findings suggest that the DMNQ S-52 has therapeutic potential to inhibit metastasis via inhibition of MMP family and uPA/plasminogen system.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.45-54
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• 2017

Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultra-performance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites. The unconfirmed metabolite $M_{un}$ differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar in vivo metabolism to DTX-IN. Conversely, DTX-LP showed significantly diminished excretion in rabbit feces or urine, approximately halving the cumulative excretion rates compared to DTX-IN. Liposomal delivery of DTX did not alter the in vitro or in vivo drug metabolism. Delayed excretion of pulmonary-targeting DTX-LP may greatly enhance the therapeutic efficacy and reduce the systemic toxicity in the chemotherapy of non-small cell lung cancer. The identification of $M_{un}$ may further suggest an alternative species-specific metabolic pathway.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 1997.12a
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• pp.102-102
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• 1997

• Toxicological Research
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• v.35 no.3
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• pp.225-232
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• 2019

Thymus vulgaris L. is widely used as an ingredient in cooking and in herbal medicine. However, there is little information about its toxicity. The present study was performed to evaluate the acute and repeated 28-day oral dose toxicity of thyme essential oil in rats. For the acute toxicity test, two groups of three rats were used. The rats received a single dose of essential oil: 300 or 2,000 mg/kg of body weight (bw). The rats were observed individually during the first four hours, and then daily until day 14. For the toxicity test with repeated doses, four groups of 10 rats were used. Doses of 100, 250, and 500 mg/kg/day were tested for 28 days. At the end of the experiment, blood was collected and the animals were sacrificed. Histopathological examination showed that in the lungs of rats given the 2,000 mg/kg bw dose, polymorph nuclear infiltrates, hemosiderin macrophages, and interstitial space thickening were present. In the repeated dose study, all rats survived the 28-day treatment period and apparently showed no signs of toxicity. The hematological and biochemical parameters were not altered. The histopathological study of the organs showed severe changes in the lung, with the dose of 500 mg/kg/day; in the other organs, no alterations were observed or the changes were slight. The body weight was only altered in male rats given the 500 mg/kg dose. The relative weight of the organs did not show any significant changes. Our studies revealed that the essential oil of Thymus vulgaris has moderate oral toxicity according to the results of the acute test, whereas the results of the 28-day oral toxicity test suggest that the no-observed-adverse effect level (NOAEL) is greater than 250 mg/kg/day.

• Journal of Korean Traditional Oncology
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• v.17 no.1
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• pp.39-43
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• 2012

Objective : This study reports one case of a patient diagnosed with squamous cell carcinoma of the lung cancer with bone metastasis. Methods : A 56-year old male patient was diagnosed as squamous cell lung cancer in 1997 and received chemotherapy. The chemotherapy stopped after one cycle because of toxicity and the lung abscess. After four months from the diagnosis, rib metastasis was found and received the radiation therapy for two weeks. After the treatment, adverse effects such as nausea and anorexia appeared. The patient visited K. Korean Medicine Hospital and started the treatment with the allergen removed Rhus verniciflua stokes (aRVS) since December, 1997. Results and Conclusion : During treatment, the patient's quality of life had improved, and he had survived for 14 years after the administration of aRVS. This case suggests that aRVS can be an alternative treatment for the advanced NSCLC patients with bone metastasis.