Lee, Somin;Ahn, Kyu Sup;Ryu, Hyeon Yeol;Kim, Hye Jin;Lee, Jin Kyu;Cho, Myung-Haing;Ahn, Mi Young;Song, Kyung Seuk
International Journal of Industrial Entomology and Biomaterials
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제32권1호
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pp.12-25
/
2016
Recently, research investment in the improvement of food safety as a food source and specializing of nutritional source of edible insects is being actively conducted. Cricket especially has been attracting considerable interest in entomophagy; however, research on the safety assessment of cricket is limited. This study investigated the effects of cricket ethanol extract when orally administrated in Sprague-Dawley rats. Here, we performed a 4 wk repeated oral dose toxicity test in Sprague-Dawley rats following the Organization for Economic Cooperation and Development test guidelines 407 under Good Laboratory Practice regulation. Rats were randomly allocated 4 groups: vehicle control, 250, 500, 1,000 mg/kg test groups and administrated based on body weight for 28 d. The animals were observed for mortalities and clinical signs, body weight changes, food and water consumption. At the end of treatment period, blood and urine were collected and analyzed. Subsequently, the animals were sacrificed and subjected to gross pathological examination and organ weight measurement. The organs were preserved for histopathological examination. The results showed that there were no systemic toxicological effects related with the cricket ethanol extract in the 4 wk oral repeated dose toxicity study. It is considered that NOAEL of cricket ethanol extract is greater than 1,000 mg/kg/d and there was no target organ detected.
Objectives : This study aimed to evaluate the single oral dose toxicity and four weeks repeated dose determination of Gamisasangja-tang (GST) in male and female Sprague-Dawley rats. Methods : In the single oral toxicity study, rats were orally administered a single dose of 0 and 5,000 mg/kg GST. There were 5 rats in each group. After single administration, mortality, clinical signs, body weight changes and gross pathological finding were observed for 14 days. In the 4-weeks repeated oral dose determination study, rats were orally administered a single dose of 0, 1,250, 2,500 or 5,000 mg/kg GST. There were 5 rats in each group. Mortality, clinical signs, body weight changes, food consumption and gross pathological finding were observed for 28 days. Organ weight, clinical chemistry and hematology were tested after 28 days. Results : There was no mortality in either of the two studies. There were also no significant differences in clinical sign, body weight, organ weights, hematological or serum chemical parameters between the GST and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of GST is over 5,000 mg/kg, so this finding would be expected to provide scientific evidence for the safety of GST.
Objectives: HMCO5 is an extract obtained from 8 different herbal mixtures. We undertook a safety evaluation of HMCO5 for a dose range finding (DRF) toxicity test in specific pathogen free (SPF) Sprague-Dawley (SD) male and female rats. Methods: The male and female rats were divided into 4 groups, respectively; G(0), treated with distilled water: G(1), treated with 222 mg/kg HMC05: G(2), treated with 667 mg/kg HMC05, and G(3), treated with 2,000 mg/kg HMC05; HMC05 was administered orally for 4 weeks. The safety evaluation examined clinical signs, mortality, body weight, food consumption, water consumption, ophthalmic findings, urinalysis, hematological values, absolute & relative organ weights, and necropsy findings during the tests. Results: There were no changes in clinical signs, mortality, body weight, food consumption, water consumption, and ophthalmic findings examined during the test periods. In serum biochemical values, triglyceride was increased in male group G(3) and Na$^+$ decreased significantly in male groups G(2), G(3) and G(4). In male group G(4), spleen weight decreased relatively and increases of absolute & relative left ovary weights were found. In addition, an adhesion of liver to diaphragm was found in male group G(2). However, we could not find any dose-interrelationships in these changes. Conclusions: These results indicate that HMC05 extract did not show any toxicity in the DRF toxicity study. Therefore, it suggests that establishment of 1,000, 333 and 111 mg/kg dosages are moderate in a repeated dose 26-week oral toxicity study of HMC05.
The skin penetration rate of methidathion in vitro and pharmacokinetics of methidathion in vivo were studied with male Sprague-Dawley rats by dermal treatment. The in vitro skin penetration rates for Sprague-Dawley rats of methidathion technical (50 mg, 100 ${mu}ell$) and emulsifable concentrate (EC,40mg, 100${mu}ell$) were determined as 18.4 $\mu\textrm{g}$/c $m^2$/h (RSD : 6.5) and 18.5 $\mu\textrm{g}$/c $m^2$/h (RSD : 3.2), respectively. Dose-related systemic exposure (AUC) was observed in rats after dermal treatment. The corresponding AUC, $T_{max}$, $C_{max}$, and $T_{1}$2/ of methidathion in plasma were 1.5$\mu\textrm{g}$.hr/ml, 6 h, 0.10 $\mu\textrm{g}$/ml, and 16 h, for 116mg/kg doses, 3.2 $\mu\textrm{g}$. hr/ml, 8 h, 0.12 $\mu\textrm{g}$/ml, and 23 h, for 232 mg/kg doses and 10 $\mu\textrm{g}$. hr/ml, 12 h, 0.32 $\mu\textrm{g}$/ml, and 20 h, for 1,160 mg/kg doses respectively. The urinary excretion of methidathion, estimated wing an equation derived from the in vitro skin penetration study was 0.24~0.35% of the absorbed dose. The concentration of methidathion in kidney was higher than that in liver. Dose-dependent absorption and excretion of methidathion without saturation was observed under in vivo experimental condition.n.n.
Park, Sang-Jin;Lim, Kwang-Hyun;Noh, Jeong-Ho;Jeong, Eun Ju;Kim, Yong-Soon;Han, Byung-Cheol;Lee, Seung-Ho;Moon, Kyoung-Sik
Toxicological Research
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제29권4호
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pp.285-292
/
2013
Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energygiving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day.
This study was carried out to investigate the testicular toxicity of environmental toxicant, 2-bromopropane(2-BP) recently caused occupational intoxication in Korea by light microscopy and electron microscopy. To evaluate the effect on spermatogenesis and find target germ cell 10 weeks old male Sprague-Dawley rats were treated with 5g/10m ℓ/kg/day of 2-bromopropane for 3 consecutive days orally and observed on day 1 or day 7 after treatment. 2-BP induced depletion of spermatogonia and early spermatocytes on stages I-IX or extensive degeneration of germ cells on the other stages on day 1. But extensive degeneration of germ cells without stage specificity was observed and round spermatid formed multinucleated giant cells in the lumen of seminiferous tubules on day 7. Electron microscopically Sertoli cells showed irregular shape of nucleus and cytoplasmic vauolation. And spermatocyte showed a extensive heterochromatin and cytoplasmic vacuolation. But there was no histopathological changes in the interstial cells. On the base of the results the target germ cell was spermatogonia in the early of the study but Srtoli cells also effected by high-dosed 2-BP in the late of the study.
Peripheral ameloblastic odontoma is a rare variant of odontogenic tumor occurring in the extraosseous region. The present report describes a spontaneous tumor in male Sprague-Dawley (SD) rats. The clinically confirmed nodule in the right mandibular region was first observed when the rat was 42 weeks and remained until the terminal sacrifice date when the animal was 48 weeks of age. At necropsy, a well demarcated nodule, approximately $2.5{\times}2.0{\times}2.0cm$, protruded from the ventral area of the right mandible. The nodule was not attached to mandibular bone and was not continuous with the normal teeth. Histopathologically, the tumor was characterized by the simultaneous occurrence of an ameloblastomatous component and composite odontoma-like elements within the same tumor. The epithelial portion formed islands or cords resembling the follicle or plexiform pattern typical of ameloblastoma and was surrounded by mesenchymal tissue. Formation of eosinophilic and basophilic hard tissue matrix (dentin and enamel) resembling odontoma was observed in the center of the tumor. Mitotic figures were rare, and areas of cystic degeneration were present. Immunohistochemically, the epithelial component was positive for cytokeratin AE1/AE3 (CK AE1/AE3), and the mesenchymal component and odontoblast-like cells were positive for vimentin, in the same manner as in normal teeth. On the basis of these findings, the tumor was diagnosed as a peripheral ameloblastic odontoma in an extraosseous mandibular region in a SD rat. In the present study, we report the uncommon spontaneous peripheral ameloblastic odontoma in the SD rat. We also discuss here the morphological characteristics, origin, histochemical, and immunohistochemical features for the diagnosis of this tumor.
This experiment was carried out to study the toxic effect of solublized methylcellulose (MC). Sprague-Dawley rats were dosed with 1%(w/v) MC in 0.9% saline by gavage at a dose of 10ml/kg b.w/day or by intravenous injection at a dose of 5ml/kg b.w/day for 28 days. Clinical signs were observed once a day. Body weights, water and food consumptions were measured and urinalysis was performed several times during the experiment. Rats were sacrificed on days 3, 7, 15 and 28 for hematology, blood chemistry, organ weights and histopathology. The relative weight of the spleen and foamy cells of the spleen were increased in the gavage group. Body weight gain, food consumptions, the values of RBC, Hb, MCH, Hct, serum proteins, glucose, bilirubin, AST, and ALP were decreased in I.V. treatment group. On the other hand, water consumptions, the values of serum cholesterol, creatinine, and BUN were increased. Microscopic findings were granulomas, distended sinusoids, and hypertrophy of Kupffer cells with vacuoles in the liver. Spleen exhibited granuloma, increased extramedullary hematopoiesis, and congestion. Kidney exhibited foamy cells in the glomeruli, distension of the tubules. The findings appeared more severe when the treatment was extended. In conclusion, MC solution is not a safe vehicle for intravenous administration because of the toxic effects on the liver, kidney and spleen. In addition, a long-term and large dosage of oral administration of MC appears to be unsafe also and needs to be investigated further.
Objectives: This study was carried out to analyze the single dose toxicity of Mecasin(Gami-Jakyak Gamcho buja Decoction) pharmacopuncture in muscle of Sprague-Dawley rats. Methods: All experiments were performed at the Medvill, an institution acknowledged to conduct non-clinical studies, under the Good Laboratory Practice (GLP) regulations. Sprague-Dawley rats were chosen in this pilot study. The reason Sprague-Dawley rats were chosen is that they have been widely used in safety test in the field of medicine, so the results can be easily compared with many other databases. Doses of Mecasin pharmacopuncture, 0, 500, 1,000, and 2,000mg/kg, were registered to the experimental groups, and a dose of normal saline solution, 10 ml/kg, was registered to the control group. Mecasin pharmacopuncture and normal saline were injected into the thigh of the rats by disposable syringes at intervals of six hours twice a day. This study was performed under the approval of the Institutional Animal Ethic Committee. Results: There is no death or abnormality in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To inspect abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The above outcomes suggest that treatment with Mecasin pharmacopuncture is relatively safe. Further evaluations and studies on this subject are needed to prove more concrete evidence.
The purpose of this study was to determine the effects of Puerariae flos herb-acupuncture on hippocampal neural cell proliferation. Sprague-Dawley rats were randomly assigned into 4 groups; control group, control with herb-acupuncture group, alcohol group, alcohol with herb-acupuncture group group. Control groups were received with NaCl, while alcohol intoxication groups were injected intraperitoneally with alcohol (2 g/㎏) twice per day for 3 days. Herb-acupuncture groups were injected on Zhongwan (CV 12) for 5 consecutive days. Bromo-deoxyuridine (BrdU) was injected into all animal per day for 5 days. For the detection of BrdU-positive cells in dentate gyrus of hippocampus, immunohistochemistry was performed. In alcohol group, a significant decrease in BrdU-positive cells was observed compared to control group. In alcohol with herb-acupuncture group, BruU-positive cells increased significantly compared to alcohol group. In conclusion, the present results revealed that new cell proliferation is enhanced in the dentate gyros of young Sprague-Dawley rats through Puerariae flos herb-acpuncuture in an acute alcoholic intoxication condition.
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