• Toxicological Research
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• v.19 no.3
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• pp.211-215
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• 2003

This study was carried out to investigate the acute oral toxicity of a crude extract derived from fruiting body of Phellinus gilvus (PGE) using male and female SD rats. Groups consisted of five male and female rats were treated with a single dose of the test substance intragastrically at 0, 500, 1,000, 2,000, and 5,000 mg/kgaj, respectively. Clinical signs, body weight change, and food and water consumption change were observed for 14 days after administration. No mortality or abnormal clinical signs in animals were shown during the observation period at the dose used in this study. Also there was no difference in net body weight gain, water and food consumption or gross pathological findings at terminal sacrifice among the groups of rat treated with different doses of the test substance. The results suggested that acute oral toxicity of PGE in rats is very low at the conditions employed in this study and $LD_{50}$ of PGE was estimated to be over 5,000 mg/$\textrm{m}{\ell}$ in both sexes of rats.

• The Journal of Internal Korean Medicine
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• v.35 no.3
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• pp.223-243
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• 2014

Objectives: To provide information on the safety of GST (GamiSasangja-tang; CnidiiFructus, Sophora Root, Angelica Gigas Root, Clematidis Radix, Stemonae Radix, Spirodelae Herba), we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of GST in Sprague-Dawley rats. Methods: Female and male rats were treated with GST at oral doses of 1,250, 2,500, and 5000 mg/kg. The GST was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. The rats were then monitored for 4 extra weeks to determine recovery time after the study period. Results: We found no mortality or abnormalities among clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights or histological markers in any of the rats tested. Conclusions: The no-observed adverse effects level (NOAEL) is considered as over 5000 mg/kg for male and female rats.

• Journal of Oriental Neuropsychiatry
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• v.23 no.3
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• pp.143-160
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• 2012

Objectives : To provide information on the safety of ACM, we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of ACM in Sprague-Dawley rats. Methods : Female and male rats were treated with ACM with oral doses of 800, 2000, and 5000 mg/kg. The ACM was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. Moreover, the rats were monitored for 4 extra weeks to determine recovery time after the study period. Results : We found no mortality and no abnormalities in clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers in any of the rats tested. Conclusions : The no-observed adverse effects level (NOAEL) was considered as over 5000 mg/kg for male and female rats.

• Preventive Nutrition and Food Science
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• v.11 no.2
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• pp.115-119
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• 2006

The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

• The Korea Journal of Herbology
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• v.32 no.4
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• pp.33-38
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• 2017

Objectives : Termitomyces albuminosus (Berk.) Heim is one of the famous wild edible mushrooms in the southern part of China. It is known that Termitomyces albuminosus, like Aconitum koreanum used in Korean traditional medicine, contains a kind of cerebroside, termitomycesphin, causing a pharmacologic effect on the neuron system. The pharmacologic effect of Termitomyces albuminosus can be used to possibly replace Aconitum koreanum. However, It needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was conducted to obtain acute information of the toxicity of dried-Termitomyces albuminosus powder and to secure its safety in clinical applications. Methods : In order to calculate approximate lethal dose(ALD), test substance was orally administered to male and female SD-rat at dose levels of 5,000 and 0 (vehicle control) mg/kg (body weight). Based on the result of this toxicity, also the estimation of safety classification was calculated using the HED-based (human equivalent dose) MOS (margin of safety). Results : There were no mortalities, test substances treatment-related clinical signs, no changes in the body or organ weights, and no gross or histopathological findings at 14 days after treatment with test substance. Thus, the approximate lethal dose of dried-Termitomyces albuminosus powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the limit dose, 5000 mg/kg, it was estimated that dried-Termitomyces albuminosus powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.

• The Korea Journal of Herbology
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• v.33 no.4
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• pp.53-58
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• 2018

Objectives : Kaempferia parviflora Rhizome is black ginger indigenous to Laos and Thailand. It has been used as a folk medicine to improve blood flow and promote vitality and longevity with good health and well being. For these reasons, Kaempferia parviflora Rhizome has been focused on developing it as a food or food supplement. In addition, Kaempferia parviflora Rhizome could be under consideration of new prescription based on its characteristic compounds, polymethoxyflavonoids. However, it needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was carried out to identity acute information of the toxicity of Kaempferia parviflora Rhizome powder and to make sure of its safety in clinical applications. Methods : Test substance was orally administered to male and female SD-rat at dose levels of 5000 mg/kg to estimate approximate lethal dose(ALD). Based on the acute information of the toxicity, the safety classification was estimated using the HED(human equivalent dose)-based MOS(margin of safety). Results : At 14 days after treatment with test substance. there were no of test substance related with mortalities and clinical signs. In addition, no changes in the body or organ weights and no gross or histopathological findings were observed. Thus, the ALD of Kaempferia parviflora Rhizome powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the single oral toxicity test using the highest and limit dose, 5,000 mg/kg and the decision guideline for safety classification based on HED-based MOS, it was estimated that Kaempferia parviflora Rhizome powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.

• Nuclear Engineering and Technology
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• v.55 no.4
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• pp.1460-1467
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• 2023

A robust approach was conducted to determining the absolute oral bioavailable (f_ab) fractions of ²³⁸U and ²³²Th in rats exposed to contaminated soil along with their hematotoxicity and nephrotoxicity. The soil sample is the International Atomic Energy Agency-312 (IAEA-312) certified reference material, whereas blood, bones, and kidneys of in vivo female Sprague-Dawley (SD) rats estimate ²³⁸U- and ²³²Th-f_ab fractions post-exposure. We predict the bioavailable concentration (C_ab) and f_ab values of ²³⁸U and ²³²Th after acute soil ingestion. The blood ²³⁸U (0.750%) and ²³²Th (0.028%) reach their maximum f_ab values after 48 h. The ²³⁸U (f_ab: 0.169-0.652%) accumulates mostly in the kidney, whereas the ²³²Th (f_ab: 0.004-0.021%) accumulates primarily in the bone. Additionally, ²³⁸U is more bioavailable than ²³²Th. Post 48 h acute ingestion demonstrates noticeable histopathological and hematological alterations, implying that intake of ²³⁸U in co-contaminated soil can lead to erythrocytes and proximal tubules damage, whereas, ²³²Th intake can harm erythrocytes. Our study provides new directions for future research into the health implications of acute oral exposures to ²³⁸U and ²³²Th in co-contaminated soils. The findings offer significant insight into the utilization of in vivo SD rat testing to estimate ²³⁸U and ²³²Th bioavailability and toxicity in exposure assessment.

• Journal of Pharmacopuncture
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• v.18 no.4
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• pp.45-50
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• 2015

Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively.

• Journal of Oriental Neuropsychiatry
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• v.23 no.2
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• pp.99-120
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• 2012

Objectives : The oriental medicine Jangwonhwan, a boiled extract of 12 medicinal herbs/mushrooms, has been prescribed to patients with cognitive dysfunction, as originally described in the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified formula of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushrooms, was shown to reduce the ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model for Alzheimer's disease. The toxicity of LMK02-Jangwonhwan was investigated in SD rats, by a daily oral administration for 13 weeks and NOAEL(No observed adverse effect dose), a definite toxic dose and target organ, as well. Methods : Quality control of the tablet form of LMK02-Jangwonhwan was established by estimating the indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02-Jangwonhwan was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats by oral administration. Each test group consisted of 10 male and 10 female rats. The groups received doses of 500, 1,000 or 2,000 mg/kg/day of test substance for 13 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of the control group. Results : The 13-week repeated oral treatment doses didn't result in any specific symptoms or death. There were no significant changes in the rat's weight and food consumption. Further, ophthalmic examination, urinalysis, hematological, serum biochemistry test and organ weight revealed no significant differences. Conclusions : The no-observed-adverse-effect level(NOAEL) of LMK02 for male and female Sprague-Dawley rats was determined as 2,000mg/kg/day and the target organ wasn't confirmed. Because no significant adverse effects were observed, the target organ could not be determined.

• Toxicological Research
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• v.26 no.3
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• pp.209-216
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• 2010

Limb bud (LB) and central nerve system (CNS) cells were prepared from 12.5 day old pregnant female Crj:CD (SD) rats and treated with olaquindox and vitamin A. Cytotoxicity and inhibition on differentiation were measured in each cell. Three doses of olaquindox (4, 21 and 100 mgkg), and 0.2 and 75 mg/kg of vitamin A were administered to pregnant rat for 11 days from $6^{th}$ to $16^{th}$ of pregnancy. $IC_{50}$ values of olaquindox for proliferation and differentiation in CNS cell were 22.74 and $28.32\;{\mu}g/ml$ and 79.34 and $23.29\;{\mu}g/ml$ in LB cell and those values of vitamin A were 8.13 and $5.94\;{\mu}g/ml$ in CNS cell and 0.81 and $0.05\;{\mu}g/ml$ in LB cell, respectively. Mean body weights of pregnant rats were decreased at high dose of olaquindox (110 mg/kg) but relative ovary weight, number of corpus lutea, and number of implantation were not changed. Resorption and dead fetus were increased at high dose of olaquindox, and relative ovary weight, the number of corpus lutea and implantation, and sex ratio of male to female were not significantly changed in all dose of olaquindox. Mean fetal and placenta weights were significantly (p < 0.01) decreased in rats of high group. Seven fetuses out of 103 showed external anomaly like bent tail, and 10 out of 114 fetuses showed visceral anomalies at high group. The ossification of sternebrae and metacarpals were significantly (p < 0.01) increased by low and middle dose of olaquindox but it was significantly (p < 0.01) prohibited by high dose of olaquindox. In rats treated with vitamin A, the resorption and dead fetus were increased by high dose. Mean fetal weights were significantly (p < 0.01) increased by low dose but significantly (p < 0.01) decreased by high dose. Thirty four fetuses out of 52 showed external anomaly; bent tail (1), cranioarchschisis (14), exencephaly (14), dome shaped head (22), anophthalmia (15), brcahynathia (10) and others (19). Forty five fetuses out of 52 showed soft tissue anomaly; cleft palate (42/52) and anophthalmia (22/52) by high dose of vitamin A. Sixty one fetuses out of 61 (85.2%) showed skull anomaly; defect of frontal, partial and occipital bone (21/61), defect of palatine bone (52/61) and others (50/61). In summary, we support that vitamin A is strong teratogen based on our micromass and in vivo data, and olaquindox has a weak teratogenic potential in LB cell but not in CNS cell. We provide the in vivo evidence that a high dose of olaquindox could have weak embryotoxic potential in rats.