• Toxicological Research
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• v.31 no.1
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• pp.77-88
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• 2015

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

• Imaging Science in Dentistry
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• v.48 no.2
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• pp.103-109
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• 2018

Purpose: To analyze cone-beam computed tomography (CBCT) use, indications, and exposure parameters in San $Jos{\acute{e}}$, Costa Rica. Materials and Methods: A cross-sectional study was performed. All CBCT examinations over a period of 6 months at 2 radiological centers in San $Jos{\acute{e}}$, Costa Rica were evaluated. The examinations were performed with Veraview EPOC X550 and Veraviewepocs 3D R100 equipment. The patients' age and sex, clinical indication for CBCT, region of interest (ROI), repeat examinations, specialty of the referring dentist, field-of-view (FOV), tube voltage (kV), tube current (mA), and radiation dose (${\mu}Gy$) were evaluated. Patients were classified by age as children (${\leq}12years$), adolescents(13-18 years), and adults(${\geq}19years$). Results: The mean age of the 526 patients was 49.4 years. The main indications were implant dentistry and dental trauma. The most frequent ROIs were posterior, while anterior ROIs were much less common. The highest percentage of repeat examinations was in children. Fifty-six percent of the referring dentists were specialists. The most commonly used FOV was small. The mean tube voltage and current were 79.8 kV and 7.4 mA for Veraview EPOC X550 and 89.9 kV and 6 mA for Veraviewepocs 3D R100, respectively. The mean doses for children, adolescents, and adults were $6.9{\mu}Gy$, $8.4{\mu}Gy$, and $7.8{\mu}Gy$, respectively. Conclusion: Although CBCT was most commonly used in adults for implant dentistry, most repeat examinations were in children, and the highest mean dose was in adolescents. Additional dose optimization efforts should be made by introducing low-dose protocols for children and adolescents.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.111-121
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• 2010

In order to investigate the preliminary repeat oral dose toxicity and to determine the highest dosage for further 4-week repeated dose toxicity test, Low Molecular Weight Fucoidan (LMF) has been showed various pharmacological effects, was orally administered to female and male rats, once a day for 14 days at dose levels of 2,000, 1,000, 500 and 0 (vehicle control) mg/kg (body weights) in a volume of 10 ml/kg. The mortality and changes on the body weights, clinical signs, hematology, serum biochemistry and gross observations were monitored with organ weight and histopathology of principle organs. As the results of 14-day repeated oral treatment of LMF, no LMF treatment related mortalities were detected up to 2,000 mg/kg in both male and female rats, respectively. In addition, no noticeable changes on the body weight and clinical signs were detected except for significant decreases on the body weights and gains restricted to male 2,000 mg/kg treated groups as compared with male vehicle control. No meaningful changes on the organ weights, hematological, serum biochemistrical, gross and histopathological findings were observed. Therefore the highest dosage in the 4-week repeated dose toxicity test is suggested as 2,000 mg/kg in both female and male rats, respectively.

• Toxicological Research
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• v.23 no.1
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• pp.65-72
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• 2007

This study was conducted to obtain information of the oral dose acute toxicity of PGB-2, a novel polyglucosamine polymer produced from Citrobacter sp. BL-4 (a new strain) in male and female mice. Mortality, body weight changes, clinical signs were monitored during 14 days after single oral dose of test article at dose levels of 2000, 1000, 500, 250 and 125 ml/kg. Gross lesions, organ weight and histopathology of principal organs were examined after necropsy. As the results, we could not find any mortalities, clinical signs, changes in the body weight and gross findings except for white foci in the liver. In addition, no PGB-2-treatment related abnormal changes on the organ weight and histopathology of principle organs were detected except for atypical signs of liver. White liver foci were confirmed as focal infiltration of inflammatory cells. The results suggest that the PGB-2 is relatively safe in mice but the possibility of hepatotoxicity could not be excluded. The $LD_{50}$ and approximate LD in mice after single oral dose of PGB-2 were considered over 2000 mg/kg, respectively. In future, the potential hepatotoxicity of PGB-2 should be evaluated through the repeat dose toxicity test prior to develop as a new agent.

• Herbal Formula Science
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• v.16 no.1
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• pp.147-168
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• 2008

HYTE (Hyeonggaeyeongyotang Extract), a polyherbal formula has been used as folk medicine, 28days repeat oral dose toxicity was tested in SD rats according to KFDA Guideline[2005-60]. Methods : In this study, mortality, clinical signs, body weight and gains, food and water consumption, ophthalmologic observation, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathological observations were conducted during 28days of dosing periods. Results: 1. No HYTE treatment-related mortalities and clinical signs were detected in all dosing levels tested in male and female rats during the whole experimental periods. 2. No HYTE treatment-related changes on body weight, gains and food consumption were detected in all dosing levels tested in male and female rats during the whole experimental periods except for 2000mg/kg-dosing female groups in which significantly increase of body weight, gains, food and water consumption were detected compared to that of vehicle control in some points. 3. No HYTE treatment-related changes on ophthalmologic examination were detected in all dosing levels tested in male and female rats. 4. No HYTE treatment-related changes on urinalysis were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing female groups in which, significantly increase of urine volume and related decrease on the urine specific gravity were detected as secondary effects of increase on the water consumptions not HYTE treatment-related toxicological signs. 5. No HYTE treatment-related changes on hematology were detected in all dosing levels tested in male and female rats except for increases in the total WBC count and lymphocytes of 2000mg/kg-dosing male and female groups with decrease of large unstained cells as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. 6. No HYTE treatment-related changes on serum biochemistry were detected in all dosing levels tested in male and female rats. 7. No HYTE treatment-related changes on gross findings, organ weight and histopathology were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing male and female groups in which, spleen and thymus organ weights, hypertrophy at gross observation and hyperpalsia of lymphoid cells and follicles at histopathological observation in spleen and thymus were detected as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. Conclusions : Based on these results, the NOAEL and MTD of HYTE in SD rats were considered as over 2000mg/kg, respectively at 28days repeat oral dose toxicity test because most of these findings were considered as results of pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs or secondary effects.

• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.482-488
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• 2013

Two piperazine-containing 3,4-dihyroquinazolines (BK10007S/8S) have been synthesized, based on our previous work on the synthesis and antitumoral activity of 3,4-dihyroquinazolines. After evaluating them for T-type calcium channel blocking effect and in vitro anti-cancer effect, they were profiled for acute and repeat dose toxicity (40 mg/kg, 2 weeks) to BALB/c mice. BK10007S/8S were further in vivo evaluated against human pancreatic MIA PaCa-2 carcinoma in $BALB/c^{nu/nu}$ nude mice, which exhibited 54 and 61% tumor growth inhibition through 57-day oral administration of 2 mg/kg of body weight, respectively.

• Korean Chemical Engineering Research
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• v.54 no.6
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• pp.762-766
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• 2016

In this study, natural extract including Phellodendro namurense, Eucommia ulmides Oliv and Prunus padus were tested for antimicrobial activity and safety. Antimicrobial activity was measured by using opportunistic microbes such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. As safety test, cell viability test, single dose oral toxicity test, single dose inhalation toxicity test, repeat dose inhalation toxicity test and eye irritation test were done. From antimicrobial test, natural extract showed execellent antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Escherichia coli. From 5 kinds of safety tests, toxicity was not observed. From experimental results, natural extract including Phellodendro namurense, Eucommia ulmides Oliv and Prunus padus showed superb safety and antimicrobial effect.

• Korean Chemical Engineering Research
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• v.51 no.5
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• pp.536-539
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• 2013

In this study, mixed plant extracts including Phellodendro namurense and Eucommia ulmides Oliv were tested for antimicrobial activity and safety. Antimicrobial activity was measured by disc diffusion method using normal skin flora and opportunistic microbes such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. As safety test, single dose oral toxicity test, single dose inhalation toxicity test and repeat dose inhalation toxicity test were done. From antimicrobial test, plant extracts showed significant antimicrobial activity Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, however, did not indicate any antibacterial effect on Escherichia coli. From 3 kinds of safety tests, toxicity of mixed plant extracts was not observed. From experimental results, mixed plant extracts including Phellodendro namurense and Eucommia ulmides Oliv showed good potential for natural antimicrobial agent.

• Journal of Society of Preventive Korean Medicine
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• v.20 no.2
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• pp.97-109
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• 2016

Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

• Journal of Society of Preventive Korean Medicine
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• v.19 no.1
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• pp.145-159
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• 2015

Objective : In the previous study, co-administration of Gongjindan-gamibang (GJD) with sorafenib increased oral bioavailability of sorafenib through augment the absorption, therefore, the effects of GJD co-administration on the pharmacokinetics of sorafenib were observed after single and 7-day repeated oral co-administration with 3.5 hr-intervals in the present study. Method : After 50 mg/kg of sorafenib treatment, GJD 100 mg/kg was administered with 3.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 7th sorafenib treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : GJD markedly inhibited the absorption of sorafenib, from 1 hr to 24 hrs after end of first 3.5 hr-interval co-administration, the $C_{max}$ (-43.27%), $AUC_{0-t}$ (-56.29%) and $AUC_{0-inf}$ (-66.70%) of sorafenib in co-administered rats were dramatically decreased as compared with sorafenib single treated rats. However, GJD significantly increased the absorption of sorafenib, from 4 hr to 8 hrs after end of last 7th 3.5 hr-interval co-administration, the $AUC_{0-t}$ (34.08%) and $AUC_{0-inf}$ (37.31%) of sorafenib in co-administered rats were dramatically increased as compared with sorafenib single treated rats. Conclusion : Although GJD decreased the oral bioavailability of sorafenib through inhibition of gastrointestinal absorptions after end of first 3.5 hr-interval co-administration, it is observed that GJD increases the oral bioavailability of sorafenib as facilitated the absorption after end of last 7th repeated co-administration. Hence, the co-administration of GJD and sorafenib should be avoided in the combination therapy of sorafenib with GJD on anticancer therapy.