• The Journal of Internal Korean Medicine
• /
• v.39 no.4
• /
• pp.676-685
• /
• 2018

Objectives: The aim of this study was to estimate the single oral toxicity of Peucedani Radix (PR) ethanol extracts. PR is one of the important herbs for removal of phlegm, the viscous turbid pathological product that can accumulate in the body and cause a variety of diseases. However, research on the pharmacologic toxicity of PR is lacking. Methods: In this study, PR was orally administered to 5-week-old male ICR mice at an oral dose of 2,000, 3,000, or 5,000 mg/kg. After a single-dose administration, the mortality and behavioral changes were observed daily and body weights were measured every two days. After 14 days, the organ weight, organ index, macroscopy, hematological analysis, and serum biochemistry analysis were determined. Results: No mortality, body weight changes, abnormal behavioral changes, or anatomical signs of toxicity were found. The organ weight, organ index, hematological analysis, and serum biochemistry analysis were also within the normal ranges. Conclusions: These results suggest that the 50% lethal dose of PR is more than 5,000 mg/kg. This could indicate that PR is a safe drug without acute toxicity and side effects.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.23 no.1
• /
• pp.1-10
• /
• 2013

Objectives: The present study investigated the potential subacute toxicity of 1,4-dichlorobutane (1,4-DCB) by a 2-week repeated oral dose in male Sprague-Dawley rats. Materials and Methods: The test chemical was administered once daily by gavage to male rats at dose levels of 0, 74, 222, 667, and 2000 mg/kg/day for 2 weeks. All rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food and water consumption, urinalysis, hematology, serum biochemistry, gross findings, and organ weights were examined. Results: At 2000 mg/kg/day, treatment-related clinical signs, as evidenced by hypothermia, decreased locomotor activity, piloerection, lying on side, and prone position were observed. All the rats were found dead on test day 2. At 667 mg/kg/day, polyuria, suppressed body weight gain, food consumption, and spleen and thymus weights, and increased adrenal gland and liver weights were observed.Hematological and serum biochemical investigations revealed increases in the alanine aminotransferase, alkaline phosphataseand total bilirubinand decreases in the serum $Na^+$ level, white blood cell count and lymphocyte ratio. There were no treatment-related adverse effects in the 74 and 222 mg/kg/day groups. Conclusions: In the present experimental conditions, target organs were determined to be spleen, thymus,and liver. The no-observed-adverse-effect level was considered to be 222 mg/kg/day in male rats.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.24 no.6
• /
• pp.1034-1041
• /
• 2010

The oriental medicine Jangwonhwan, which is a boiled extract of 12 medicinal herbs/mushroom, has been prescribed for patients with cognitive dysfunction and it is originally from the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified recipe of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushroom, was shown to reduce ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease. The toxicity of LMK02 was investigated in SD rats by oral repeated adminstration for 4 weeks and we tried to determine test does for 13 weeks repeated study. Quality control of tablet form of LMK02 was established by estimating indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02 was investigated in 6 weeks old specific pathogen free (SPF) Sprageu-Dawley rats by oral administration. Each test group were consist of 5 male and 5 female and they received doses of 500, 1,000 and 2,000 mg/kg/day of test substance for 4 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 control group. Urinalysis : We observed increase of PRO(p<0.01), SG(p<0.01) in female rats of 1,000 mg/kg/day and 2,000 mg/kg/day(p<0.01). Also, we observed increase of pH and KET in female rats of 1,000 mg/kg/day(p<0.05) and of 2,000 mg/kg/day(p<0.01). WBC in female rats in 1,000 mg/kg/day and 2,000 mg/kg/day were on increase. Hematological test : We observed increase of MCV in male rats of 250 mg/kg/day. (p<0.05) Serum biochemistry test : We found increase of CHO in female rats of 2,000 mg/kg/day(p<0.05). During the experimental period, there were no animals dead or moribund. There were no treatment related changes of general symptom, food and water consumption, organ weight and autopsy According to the results of 4-week repeated dose range finding study, the highest dose was established as 1000 mg/kg for 13-week repeated dose toxicity study and we determined to put 2 more groups by common ratio two.

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

• Korean Journal of Agricultural Science
• /
• v.48 no.4
• /
• pp.1003-1013
• /
• 2021

Thioredoxin (TRX) protein is an antioxidant responsible for reducing other proteins by exchanging cysteine thiol-disulfide and is also known for its anti-allergic and anti-aging properties. On the other hand, epidermal growth factor (EGF) is an important material used in the cosmetics industry and an essential protein necessary for dermal wound healing facilitated by the proliferation and migration of keratinocytes. EGF also assists in the formation of granulation tissues and stimulates the motility of fibroblasts. Hence, genetically modified soybeans were developed to overexpress these industrially important proteins for mass production. A single-dose oral-toxicity-based study was conducted to evaluate the potential toxic effects of TRX and EGF proteins, as safety assessments are necessary for the commercial use of seed-specific protein-expressing transgenic soybeans. To achieve this rationale, TRX and EGF proteins were mass purified from recombinant E. coli. The single-dose oral-toxicity tests of the TRX and EGF proteins were carried out in six-week old male and female Institute of Cancer Research (ICR) mice. The initial evaluation of the single-dose TRF and EGF treatments was based on monitoring the toxicity signatures and mortality rates among the mice, and the resultant mortality rates did not show any specific clinical symptoms related to the proteins. Furthermore, no significant differences were observed in the weights between the treatment and control groups of male and female ICR mice. After 14 days of treatment, no differences were observed in the autopsy reports between the various treatment and control groups. These results suggest that the minimum lethal dose of TRX and EGF proteins is higher than the allowed 2,000 mg·kg^-1 limit.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.28 no.6
• /
• pp.413-420
• /
• 2002

Mercury is one of the most frequently used heavy metal in dental clinic. Mercury poisoning rises up when someone is exposed to mercury chronically. In 1818, Amalgam was used for dental restorative procedure, and after then study about mercury toxicity has begun. Clinical signs of mercury toxicity in oral & maxillofacial area were increases of salivation, metallic taste, swelling and pain of tongue, redness and ulceration of oral mucosa, and increased mobility and loss of teeth. After we injected mercury($HgCl_{2}$) into intraperitoneum of rat, studied about histopathological changes of submandibular gland cell. Experimental group was divided into two groups by amount of mercury. (Group 1 was 0.5mg/Kg of mercury injection, group 2 was 1.0mg/Kg of mercury injection.) 1. After 3days of intraperitoneal injection, black granules were observed at macrophage cell in both group. In group 2, author found hyperchromatism of nucleus, and vacuolization of cellular matrix and nucleus of acinar cell. 2. After 1week of intraperitoneal injection, author found severe vacuolization of nucleus and cellular matrix, and irregular granules around nuclear membrane at mucous cell and serous cell in both group. Vacuolization of nucleus and cellular matrix was seen at duct cell in group 2. 3. After 2weeks of intraperitoneal injection, author could found severe vacuolization of cellular matrix, and sometimes nucleus was positioned in central area of cellular matrix at mucous and serous cell in both group. Vacuolization of nucleus and cellular matrix was found at vascular endothelial cell in group 2. 4. After 4weeks of intraperitoneal injection, destruction and distortion of gland cells were distinct. Vacuolization and destruction of nucleus and cellular matrix was found at duct cell in group 2. After intraperitoneal injection of mercury, we found equanimity of mercury and destruction of cellular matrix at serous cell, mucous cell, and duct cell of submandibular gland. So, we thought that metallic taste of mercury poisoning patient would be due to excretion of saliva containing mercury.

• Biomolecules & Therapeutics
• /
• v.5 no.2
• /
• pp.133-149
• /
• 1997

4-week repeated dose toxicity of DA-5018, a new capsaicin analogue analgesic agent, was examined in 5D rats at dosage levels of 0,0.4,2, 10 and 50 mg/kg/day. DA-5018 was administered orally to 17 males and 17 females per group at doses of 0, 10 and 50 mg/kg and to 12 males and 12 females per group at doses of 0.4 and 2 mg/kg. After the administration period, 5 males and 5 females at the 0, 10 and 50 mg/kg were placed on withdrawal for 2 weeks. Treatment-related clinical signs were observed at 10 and 50 mg/kg. Clinical signs observed immediately after the administration of DA-5018 were grooming, sedation or depression, lacrimation, atacia, reddening of extremities and ears, ventral or lateral recumvincy, respiratory distress, cyanosis and convulsion. Delayed-type clinical signs including focal scabbing and depilation around nose were also observed 1 or 2 weeks after the start of administration of DA-5018. Only at the 50 mg/kg group, corneal opacities, reduced body weight gain (male) and death (male 6/17, female 3/17) were noted. In blood biochemical analysis, serum levels of glucose and triglyceride decreased at 10 and 50 mg/kg. In hematological examination, there were increases in the number of red blood cell, hemoglobin content and percent of hematocrit at 10 and 50 mg/kg. Pulmonary enlargement and hemorrhagic spot, focal scabbing and depilation around nose and corneal opacities were seen at the necropsy of the animals died during the dosing of DA-5018 50 mg/kg. Focal scabbing and depilation around nose were observed in the animals terminally necropsied at doses of 10 and 50 mg/kg. Histopathological examination revealed pulmonary hemorrhage, focal necrosis in the scabbed area, corneal necrosis, fibrosis and neovasculization in the stroma. At 0.4 and 2 mg/kg, there were no significant toxic changes attributable to the administration of DA-5018. In conclusion, target organs following to 4-week repeated dose of DA-5018 in the rat were determined to be lung, skin and eyes. Definite toxic dose and no-observed-adverse-effect-level (NOAEL) were estimated to be 50 and 2 mg/kg/day, respectively.

• Toxicological Research
• /
• v.29 no.4
• /
• 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.

• Toxicological Research
• /
• v.23 no.4
• /
• pp.363-371
• /
• 2007

Isaria sinelairii (IS) was orally administered at doses of 0, 0.04, 0.2, and 1 g/kg/day over a 13-week period. There were no observed clinical signs or deaths related to treatment in all the groups tested. Therefore, the approximate lethal oral dose of I. sinclairii was considered to be higher than 1 g/kg in rats. Throughout the administration periods, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis) or gross pathology were detected. Minor changes were found in hematological parameters for the 0.04 g/kg/day and 0.2 g/kg/day IS treated groups (triglyceride reductions of $20.1{\sim}46.6%$ and platelet increases), but all changes were within physiological range. Microscopic examination failed to identify any treatment-related histopathologic changes in the organs of the IS-treated rats other than nuclear enlargement (cellular atypia) of the tubular regions in the medulla of the kidney in the high dose group. From these results, one can conclude that the no-observed effect level (NOAEL) of I. sinclairii is less than 0.04 g/kg/day in rats.

• Toxicological Research
• /
• v.22 no.2
• /
• pp.135-144
• /
• 2006

This study was performed to evaluate repeated-dose toxicities of STB-HO-BM in Sprague-Dawley rats. STB-HO-BM was administered orally to rats at dose levels of 0, 100, 300 and 1,000 mg/kg/day for 13 weeks. In recent study, there were no dose related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with STB-HO-BM. Gross and histopathological findings revealed no evidence of specific toxicity related to STB-HO-BM. These results suggest that the oral no observed adverse effect level (NOAEL) of STB-HO-BM may be over 1,000 mg/kg in rats.