• Environmental Analysis Health and Toxicology
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• 제26권
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• pp.6.1-6.8
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• 2011

Objectives: The present study investigated the potential adverse effects of multi-wall carbon nanotubes (MWCNTs) on pregnant dams and embryonic development following maternal exposure in rats. Methods: MWCNTs were orally administered to pregnant rats from gestational day (GD) 6 through 19 at dose levels of 0, 8, 40, 200, and 1000 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, oxidant-antioxidant status, gross findings, organ weights, and Caesarean section findings were examined. Results: All animals survived to the end of the study. A decrease in thymus weight was observed in the highest dose group. However, maternal body weight, food consumption, serum biochemical parameters, and oxidant-antioxidant balance in the kidneys were not affected by treatment with MWCNTs. No treatment-related differences in gestational index, embryo-fetal mortality, or fetal and placental weights were observed between treated and control groups. Conclusions: The results show that 14-day repeated oral dosing of MWCNTs during pregnancy induces minimal maternal toxicity at 1000 mg/kg/day in rats. Under these experimental conditions, the no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1000 mg/kg/day for embryonic development.

• 대한약침학회지
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• 제19권3호
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• pp.231-238
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• 2016

Objectives: This study used repeated intravenous injections of Saeng Maek San (SMS) injection in Sprague-Dawley (SD) rats to assess the toxicity and the stability of SMS. Methods: Six-week-old male and female SD rats reared by Orient bio Inc were chosen for this pilot study. They were randomly split into four groups: Group 1 (G1), the control group (0.3 mL of normal saline solution/day/animal), and Groups 2, 3 and 4 (G2, G3 and G4), the experimental groups (0.1, 0.2 and 0.3 mL/day/animal of SMS), respectively. Each animal received an intravenous injection of SMS once a day for four weeks. Clinical signs, body weight changes, and food consumption were monitored during the observation period, and urinalysis and hematology were conducted after four weeks of SMS or saline administration. Results: No deaths occurred in any of the four groups during the observation period. Compared to the control group, male and female rats in groups 3 and 4 (0.2 and 0.3 mL/animal/day) showed hemoglobinuria, but the low-dosage group (G2, 0.1 mL/animal/day) showed no significant changes in the clinical signs test. No significant changes due to SMS were observed in the experimental groups regarding body weight changes, food consumption urinalysis, or hematology. Conclusion: During this study, no mortalities were observed in any of the experimental groups and no hemoglobinuria was observed in the low dosage group (0.1 mL/animal/day) while it was intermittently observed in groups 3 and 4 (0.2 and 0.3 mL/animal/day). Thus, we suggest that the no-observed adverse-effect level (NOAEL) is 0.1 mL/animal/day in male and female SD rats.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.354-363
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• 1996

This study was conducted to investigate the repeated dose toxicity of DA-9601, an antiulcer agent of Artemisia app. extract, in rats. DA-9601 was administered orally once a day for 4 weeks to 10 males and 10 females per group at doses of 0(vehicle control), 125, 500 or 2000 mg/kg/day. Throughout the study, no treatment-related deaths and clinical signs were observed. In female rats receiving 125 mg/kg of DA-9601, water consumption increased slightly on day 4, 11 and 25. Hematological examination showed a decrease of MCV and an increase of PLT in male rats at the doses of 500 and 2000 mg/kg groups. Blood biochemistry revealed slight decreases of cholesterol, BUN and Na in male rats and decreases of total bilirubin and creatinine and slight increases of globulin and Cl in female rats. The organ weights at the end of 4 weeks showed slight changes in some organs of treated groups. But, all these changes were not considered to be of toxicological importance, because they did not show dose-response relationship and relevance to gross and microscopic findings. Histopathologically, abnormal treatment-related changes were not observed in any organ and target organs were not detected. On the basis of these results, the NOAEL(no-observed-adverse-effect level) of DA-9601 was estimated to be more than 2000 mg/kg/day under the conditions tested.

• Biomolecules & Therapeutics
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• 제6권2호
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• pp.171-181
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• 1998

DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.

• 동의생리병리학회지
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• 제26권1호
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• pp.47-52
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• 2012

The aim of this study was to investigate the acute toxicity and safety of fermented Soshiho-tang extract using male and female ICR mice. Mice were treated with fermented Soshiho-tang extract once orally at 1250, 2500 or 5000 mg/kg and observed for two weeks. At the doses used, no mortality or abnormal clinical signs in animals were shown during at the observation period. In addition, no differences were found between control and treated groups in body weight, hematology and biochemical analysis, and other findings. Above data strongly suggest that no observed adverse effect level of fermented Soshiho-tang extract might be over 5000 mg/kg/day in this study.

• Toxicological Research
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• 제27권4호
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• pp.231-240
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• 2011

Gryllus bimaculatus (Gb) was orally administered at doses of 0, 0.04, 0.2, 1 and 5 g/kg bw/day for 13 consecutive weeks. There were no observed clinical signs or deaths related to treatment in all the groups tested. Therefore, the approximate lethal oral dose of G. bimaculatus was considered to be higher than 5 g/kg in rats. Throughout the administration period, 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 5 g/kg Gb-treated group (triglyceride reduction of 35.8%), but all changes were within normal physiological ranges. Microscopic examination did not identify any treatment-related histopathologic changes in the organs of Gb-treated rats in the high dose group. From these results, one can conclude that the no-observed adverse effect level (NOAEL) of G. bimaculatus is higher than 5 g/kg bw/day in rats.

• Toxicological Research
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• 제35권1호
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• pp.65-74
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• 2019

Tetrahydrocurcumin (THC) is a major metabolite of curcumin, which is obtained from Curcuma longa. THC has various benefits and overcomes the bioavailability issue of curcumin. To establish it as a pharmacologically active molecule, its safety profile has to be determined. Thus, the present study aimed to determine the preclinical safety profile of THC in a 90-day subchronic and reproductive/developmental toxicity study in Wistar rats. THC at oral doses of 100, 200, and 400 mg/kg was administered daily for 90 days. Rats in the recovery group were kept for 14 days after treatment termination. The animals were observed for treatment-related morbidity, mortality, and changes in clinical signs, clinical pathology, and histopathology. In the reproductive/developmental toxicity study, THC at 100, 200, and 400 mg/kg was administered orally to rats and the reproductive/developmental parameters in adult male and female rats and pups were observed. THC at up to 400 mg/kg/day of did not have any significant effect on all parameters in male and female rats in both toxicity studies. Thus, 400 mg/kg/day can be considered as the no-observed-adverse-effect-level of THC in rats.

• Toxicological Research
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• 제20권3호
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• pp.263-272
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• 2004

This study was to investigate single and repeated-dose toxicities of DFA IV, a new candidate of nutraceutical which has preventive effect on anemia and osteoporosis. In single-dose oral toxicity study, the test article were administered once by gavage to rats at dose level of 0, 2,000 and 5,000 mg/kg. No dead animal, abnormal sign and abnormal necropsy finding was found in control and treated groups. Thus the approximate lethal dose of DFA IV was considered to be higher than 5,000 mg/kg in rats. In four week repeated dose oral toxicity study, the test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg. No abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, hematological findings, necropsy findings, organ weights and histopathological findings. In urinalysis, specific gravity was increased in 2,000 mg/kg groups of male rats. In serum biochemical analysis, creatine phosphokinase was increased in all treatment groups of male rats. These increases in urine specific gravity and serum creatine phosphokinase activity were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, four week repeated oral dose of DFA IV to rats did not cause apparent toxicological change at the dose of 500, 1,000 or 2000 mg/kg body weight. Thus it is suggested that no-observed-adverse-effect level (NOAEL) of DFA IV in rats would be 2,000 mg/kg/day body weight.

• 한국약용작물학회지
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• 제27권3호
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• pp.173-185
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• 2019

Background: Galgeun-tang used in traditional Korean medicine, is a mixture of the medicinal plants Cinnamomi Ramulus, Ephedrae Herba and Puerariae Radix, and has been prescribed for the treatment of various ailments, including fever. Although the use of traditional medicinal herbs to treat diseases has recently increased, their safety and toxicity profiles incompletely elucidated. Thus, we evaluated Galgeun-tang's toxicity in male and female Sprague-Dawley rats. Methods and Results: Galgeun-tang (1,000, 2,000 and 4,000 mg/kg) was orally administered to rats for 13 weeks, and then, they were maintained for 4 weeks without administration (recovery period). Their clinical signs, and hematological and urinary properties, were monitored. The results showed that Galgeun-tang administeration slightly increased serum creatinine, urea nitrogen and, aspartate aminotransferase levels. Additionally, 2,000 and 4,000 mg/kg Galgeun-tang significantly increased urinary bilirubn and protein levels of male and female rats, which were restored during the recovery period. Conclusions: The no-observed-adverse-effect level of orally administered Galgeun-tang was 4,000 mg/kg in both female and male rats, and no target organs were identified. In addition, 400 mg/kg was found to be the no-observed-effect level for toxicity under the study conditions.

• Toxicological Research
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• 제19권3호
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• pp.227-234
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• 2003

2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones (CFCs) which have a great potential to destroy the ozone layer and to warm the earth's environment. The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 17 in ICR mice. The test chemical was administered subcutaneously to pregnant mice at dose levels of 0, 313, 625 or 1,250 mg/kg/day. All dams were subjected to caesarean section on GD 18 and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1,250 mg/kg group, maternal toxicity included an increase in the incidence of abnormal clinical signs and a decrease in the maternal body weight, body weight gain, and corrected body weight. Developmental toxicity included a decrease in the fetal body weight, a reduction in the placental weight, an increase in the fetal skeletal variation and ossification delay. There were no adverse effects on either pregnant dams or embryo-fetal development in the 313 and 625 mg/kg groups. These results suggest that a 12-day subcutaneous dose of 2-BP is embryotoxic at a maternally toxic dose (i.e., 1,250 mg/kg/day) in ICR mice. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 625 mg/kg/day for dams and embryo-fetuses, respectively.