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

• Toxicological Research
• /
• v.21 no.3
• /
• pp.187-193
• /
• 2005

The rodent Hershberger assay is considered as a potential short term in vivo screening method for the detection of androgenic or anti-androgenic compounds. The objective of this study was to evaluate the anti-androgenic activities of di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and butylbenzyl phthalate (BBP). A 10-day Hershberger assay was performed using immature Sprague-Dawley male rats castrated at 6 weeks of age. Tastosterone propionate (TP, 0.4 mg/kg/day) was administered s.c. to castrated male rats and followed by flutamide (1, 5, 10, or 20 mg/kg/day) treatment for 10 days by oral gavage. Similarly, DEHP, DBP, or BBP were also administered by oral gavage at 250, 500, or 1000 mg/kg/day after TP (0.4 mg/kg/day) administration. As expected, flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1 mg/kg/day and above, and Cowper's glands and glans penis at 5 mg/kg/day and above. DEHP significantly (p<0.05) decreased the seminal vesicles, ventral prostate, LABC and Cowper's glands weights at 1000 mg/kg/day. BBP at 1000 mg/kg/day significantly inhibited TP-induced re-growth of the LABC in the immature castrated male rats, whereas ventral prostate, seminal vesicles, and Cowper's glands weights were unaffected. In contrast to DEHP, DBP did not affect accessory sex organ weights at any concentration. Body weights, combined adrenal glands, and kidney weights were not affected, but liver weights were significantly increased at high dosages in the DEHP, DBP, and BBP treatment groups. Our observations strongly suggest that DEHP acts as an androgen antagonist at the high dose (i.e., 1000 mg/kg/day).

• Biomolecules & Therapeutics
• /
• v.4 no.2
• /
• pp.127-137
• /
• 1996

This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 mg/kg/day, 6 days/week for 26 weeks. At 0.6 mg/kg, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 mg/kg, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 7.6 mg/kg. At 0.0375, 0.15 and 0.6 mg/kg, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 mg/kg were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 mg/kg, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 mg/kg, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy, Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various Iymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 mg/kg. At 0.15 mg/kg, testis was a target organ, while at 0.6 mg/kg hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 mg/kg the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.42 no.2
• /
• pp.119-126
• /
• 2016

Skin is the largest organ that protects the body from the external environmental factors such as smog, cigarette smoke, UV. Protective skin barrier is composed with keratinizational keratinocytes and intercellular lipids such as ceramides, cholesterols and fatty acids combined by the lamellar liquid crystal structure. In this research, we confirmed that the Jeju wild ginseng (JWG) extracts dose-dependently increased the expression of serine-palmitoyltransferase (SPT) protein which is associated with ceramide biosynthesis. In addition, emulsion containing 5% JWG extract was applied on skin of human volunteers for 2 weeks and then significantly reduced transepidermal water loss (TEWL) compared to that of control group. As a results, JWG extract increased the biosynthesis of ceramides that is the key components of the skin lipid through enhancing expression of SPT. In addition, JWG extract reduced TEWL resulting in improvement of skin barrier function. In this context, we suggest that JWG extract could be used as a skin barrier enhancer and moisturing agents in cosmetic fileds.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.30 no.3
• /
• pp.1-19
• /
• 2017

Objectives: The object of this study is to observe the possible ameliorating effects of Nokyongdaebo-tang (NYDBT) on the experimental subacute hemorrhagic anemia (SHA) in rats. Methods: In the present study, SHA in rats was induced by exsanguinations from orbital plexus, and ameliorating effects of NYDBT was observed based on the changes of body and hematopoietic organ (spleen, liver and femur) weights, red blood cell (RBC) related hematological values, smear cytology, histopathological changes and immunohistochemistrical analysis of hematopoietic stem cells in the femur bone marrow, liver and spleen. In addition, the gastrointestinal motility and the surface mucosa thicknesses of remnant fecal pellets in the colon lumen, mucosa thicknesses and the mucous producing cell numbers in the colonic mucosa were analyzed to observe the digestive disorders, especially on the constipation, the major discomfort problems in iron supplement. Results: SHA related abnormal anemic signs were markedly and dose-dependently inhibited by oral administration of NYDBT 500, 250 and 125 mg/kg in a condition of this experiment. In addition, no meaningful changes on the gastrointestinal motilities and mucous component on the colon and remnant feces were noticed in all three different dosages of NYDBT treated rats as compared with intact vehicle and SHA control rats in this study. Conclusions: It, therefore, is expected that NYDBT will be promising as a novel alternative hematopoietic and therapeutic agent for anemia.

• Korean Journal of Food Science and Technology
• /
• v.50 no.6
• /
• pp.629-635
• /
• 2018

In this study, the safety aspect of Maesil-cheongs with reduced amygdalin levels was investigated in terms of toxicokinetics and repeated oral toxicity. Plasma or UVC treatment was utilized to obtain Maesil-cheongs with reduced amygdalin levels. The toxicokinetic study demonstrated that the oral absorption of amygdalin decreased remarkably after a single-dose oral administration of both plasma- and UVC-treated Maesil-cheongs. The fourteen-day repeated oral toxicity study revealed that plasma- or UVC-treated Maesil-cheongs did not cause changes in body weight, food intake, water consumption, and absolute and relative organ weights. No significant effects on hematological and serum biochemical parameters were found. Histopathological examination showed no abnormality or toxicological change. These findings suggest that plasma- and UVC-treated Maesil-cheongs have no toxicity potential, and these processes will be useful to obtain products with safe, reduced amygdalin levels.

• Journal of Life Science
• /
• v.32 no.1
• /
• pp.36-43
• /
• 2022

Mucosal immunity is a well-designed defense system that builds precise and dynamic relationships against pathogens, and the gastrointestinal tract is the most important organ with this system, acting as a guardian at the forefront of its activity. Salmonella spp. cause food poisoning, entering the body orally and mainly invading the Peyer's patches of the small intestine. Although Salmonella strains share similar mechanisms for inducing innate immunity, different serotypes may have different effects on the intestinal mucosa due to host specificities and pathogenicity. In this study, we evaluated the effects of Salmonella enteritidis infections in mouse intestine and observed significantly reduced dose-dependent survival rates in a challenge test. Flow cytometry data showed no significant differences in intestinal immune cell populations, although histology indicated increased mucin production and decreased goblet cell counts in the Salmonella-treated groups. Furthermore, Claudin expression was significantly decreased in the samples with Salmonella. To investigate the relationship between S. enteritidis infection and inflammatory response, dextran sodium sulfate (DSS) was administered after infection and the results indicate lower survival rate after DSS treatment. In conclusion, we were able to identify the optimal concentration of S. enteritidis to modulate the intestinal mucosal immunity of mice and inflammatory response.

• Korean Journal of Radiology
• /
• v.23 no.9
• /
• pp.911-920
• /
• 2022

Objective: ⁶⁸Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of ⁶⁸Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of ⁶⁸Ga-NGUL in healthy volunteers and the lesion detection rate of ⁶⁸Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering ⁶⁸Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by ⁶⁸Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, ⁶⁸Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either ⁶⁸Ga-NGUL PET/CT or conventional imaging. Among them, ⁶⁸Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion: ⁶⁸Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, ⁶⁸Ga-NGUL is a valuable option for prostate cancer imaging.

• The Korean Journal of Pesticide Science
• /
• v.17 no.4
• /
• pp.350-358
• /
• 2013

Both 13-week and 1-year studies in dog were required for pesticide registration in domestic pesticide control authority. It is raising issue up whether to request 1-year dog study of pesticides using non-food crop. So at this investigation, relevant toxicity test to establish acceptable daily intake (ADI), target organs, difference of no-observed adverse-effect levels (NOAELs) in 13-week and 1-year of 166 active ingredients are analyzed. The data were evaluated to determine if the 13-week dog study and the long term studies in two rodent species (mice and rats) without 1-year dog study were sufficient for the identification of NOAELs and lowest observed adverse effect levels (LOAELs) for the derivation of ADI. Toxicity end points and dose response data from 13 week and 1-year studies were compared. The analysis showed that 68 ADIs of the 166 pesticides were established from dog studies. Major target organs of dog studies were liver in 49 cases, body weight change in 21 cases, cholinesterase inhibition in 16 cases, and alteration in hematology in 14 cases. Similarity of target organ in 13-week and 1-year was 73%. 22 of 40 pesticides had similar critical effects regardless of duration and had NOAELs within a difference of 1.5-fold of each other. For the remaining 18 pesticides, 14 items had lower NOAELs in the 1-year study than 13-week study primarily due to dose selection and spacing. In only 10% of the cases were additional toxic effects identified in the 1-year study that were not observed in the 13-week study.

• Tuberculosis and Respiratory Diseases
• /
• v.61 no.4
• /
• pp.366-373
• /
• 2006

Background: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. Methods: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. Results: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. Conclusion: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.