• Journal of Korean Medicine for Obesity Research
• /
• v.18 no.1
• /
• pp.36-49
• /
• 2018

Objectives: The study is aimed at evaluating the possible toxicity in 90-day repeated oral administration of modified Samjung-hwan (mSJH) in Sprague-Dawley (SD) rats. This study was conducted to detect the no-observed adverse effect level (NOAEL). Methods: Modified SJH extract was administered orally in male and female SD rats at dose of 0, 1,000, 2,000, 4,000 mg/kg. Each group consisted of 10 rats of each gender. The modified SJH extract was given once a day for 90 days. We monitored the changes of mortalities, clinical signs, body weight changes, food consumption, ophthalmologic findings, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histological markers of all animals treated with modified SJH extract during the study period. Results: There were no toxicologically significant changes in mortalities, clinical signs, body weight gains, food consumption, ophthalmologic findings, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histological markers in any of rats tested. Conclusions: The NOAEL of the modified SJH extract in male rats and no observed effect level (NOEL) in female rats are considered 4,000 mg/kg.

• Toxicological Research
• /
• v.19 no.3
• /
• pp.173-180
• /
• 2003

The present study was conducted to investigate the single and 2-week repeated dose toxicity of red ginseng acidic polysaccharide (RGAP) in Sprague-Dawley rats. The test article was administered orally to rats at dose levels of 0, and 2000 mg/kg/day for single dose toxicity study and at dose levels of 0, 250, 500, and 1000 mg/kg/day for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated RGAP. Based on these results, it was concluded that the 2-week repeated oral dose of RGAP may have no toxic effect in rats at a dose level of 1000 mg/kg/day. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 1000 mg/kg/day for both sexes.

• Toxicological Research
• /
• v.20 no.2
• /
• pp.123-129
• /
• 2004

The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.

• Biomolecules & Therapeutics
• /
• v.2 no.2
• /
• pp.161-172
• /
• 1994

This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

• Toxicological Research
• /
• v.31 no.4
• /
• pp.393-402
• /
• 2015

This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats.

• Biomolecules & Therapeutics
• /
• v.6 no.3
• /
• pp.317-327
• /
• 1998

The subchronic toxicity study of rHuEPO, a newly developed recombinant erythropoietin, was investigated for 13 weeks in Beagle dogs intravenously treated with doses of 100, 500 and 2,500 lU/kg/day. There were no significant changes in body weight, food intake, physical and opthalmic examination, urine analysis, etc. Any toxic response was not observed except for enlarged spleen and extramedullary hematopoiesis. These results indicate that the no-observed adverse effect level (NOAEL) of rHuEPO is 100 lU/kg in Beagle dogs.

• Toxicological Research
• /
• v.35 no.4
• /
• pp.371-387
• /
• 2019

Although the dried root of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae) is a popular medicinal plant in East Asia, there has been no systemic toxicological evaluation of a water extract of Saposhnikoviae Radix (SRE). In this experiment, an oral acute and 13-week subchronic toxicological evaluations of SRE (500-5,000 mg/kg body weight) were performed in both sexes of Crl:CD(SD) rats. Based on the results from mortality, clinical signs, effects on body weight and organ weight, clinical biochemistry, hematology, urinalysis, and histopathology, significant acute, 4-week repeated dose range finding (DRF) and 13-week subchronic toxicity of SRE was not observed in either sex of rats; thus, the no observed adverse effect level (NOAEL) was 5,000 mg (kg/day). To identify anti-hyperuricemia potential of SRE, the suppressive effect of SRE was determined in mice challenged with potassium oxonate (PO; 250 mg/kg) via intraperitoneal injection for 8 days (each group; n = 7). SRE supplementation suppressed the uric acid level in urine through significant xanthine oxidase (XO) inhibitory activity. Kidney dysfunctions were observed in PO-challenged mice as evidenced by an increase in serum creatinine level. Whereas, SRE supplementation suppressed it in a dose-dependent manner. Collectively, SRE was safe up to 5,000 mg (kg/day) based on NOAEL found from acute and 13-week subchronic toxicological evaluations. SRE had anti-hyperuricemia effect and lowered the excessive level of uric acid, a potential factor for gout and kidney failure.

• Korean Journal of Plant Resources
• /
• v.28 no.4
• /
• pp.371-381
• /
• 2015

The object of this study was to obtain single oral dose toxicity of Arisaema Rhizome (Arisaema amurense f. serratum (Nakai) Kitag) aqueous extracts. Arisaema Rhizome (Chunnamsong in Korean) is one of the most important folk remedy plants used in Asia. In the study, a 28-day rat oral gavage study has been conducted with the extracts from Arisaema Rhizome at dose of 1,250, 2,500 and 5,000 ㎎/㎏/day. The following endpoints were evaluated: clinical observations, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Based on the analysis of these endpoints, it was estimated that NOEL (no observed effect level) for male rats and NOAEL (no observed adverse effect level) for female rats are 5000 ㎎/㎏/day of the water-extracts from Arisaema Rhizome.

• Journal of Applied Biological Chemistry
• /
• v.65 no.4
• /
• pp.397-403
• /
• 2022

Smilax sieboldii is one of the Smilax species. A number of Smilax plants have long been used in traditional medicine in the tropics and subtropics worldwide. Repeated dose oral toxicity test is an essential experiment for toxicity evaluation before efficacy evaluation. The purpose of this study is to evaluate toxicity and the no-observed adverse effect level (NOAEL) using oral administration of Smilax sieboldii extract (SSE) in male and female ICR mice for 4 weeks. SSE was orally administered daily for 4 weeks at a dose of 500, 1000, and 2000 mg/kg/day (MPK). There were no significant differences in mortalities, clinical signs, body weight changes, food intake, hematological analysis, serum clinical chemistry test and relative organ weights in all animals administrated with SSE. The results obtained in this study suggest that SSE did not show any toxic effect in ICR mice and the NOAEL of SSE was regarded as over 2000 MPK.

• Journal of Applied Biological Chemistry
• /
• v.62 no.2
• /
• pp.123-127
• /
• 2019

Medicinal herb in Asian countries has been traditionally used for a long time. However, the safety and adverse effect of medicinal herb have not been established yet. The aim of this study is to evaluate toxicity in the oral administration of Clausena excavata (C. excavata) in male ICR mice for 3 weeks and the noobserved adverse effect level (NOAEL). C. excavata has been used as a medicinal herb for the treatment of dermatopathy, malaria, abdominal pain, dysentery, and enteritis. C. excavata was orally administered daily for 21 days at a dose of 100, 250, 500, 1000, and 2000 mg/kg/day (MPK). There were no significant differences in mortalities, clinical signs, body weight changes, hematological, and serum biochemistry examination in all animals administrated with C. excavate. Consequently, these findings indicated that C. excavata did not affect the toxic effect in ICR mice and the NOAEL of C. excavata was considered as more than 2000 MPK.