• Toxicological Research
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• v.22 no.3
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• pp.267-273
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• 2006

Tungtungmadic acid(3-caffeoyl, 4-dihydrocaffeoyl quinic acid: CDCQ) is a new chlorogenic acid derivative isolated from the Salicornia herbacea. The suppressive effects of CDCQ on the progress of acute carbon tetrachloride($CCl_4$)-induced hepatic fibrosis were investigated in mice. CDCQ significantly suppressed $CCl_4$-induced hepatic necrosis and inflammation, as determined by serum enzymatic activities of alanine and aspartate aminotransferase and serum TNF-$\alpha$ levels in a dose-dependent manner. In addition, increased hepatic lipid peroxidation and fibrosis after acute $CCl_4$ treatment were suppressed by the administration of CDCQ. CDCQ also significantly prevented the elevation of hepatic hydroxyproline and collagen content and ${\alpha}$-smooth muscle actin(${\alpha}$-SMA) expression in the liver of $CCl_4$-intoxicated mice. These results suggest that the suppressive effects of CDCQ against the acute $CCl_4$-induced hepatic fibrosis possibly related to its ability to block both hepatic inflammation and the activation of hepatic stellate cells.

• Toxicological Research
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• v.25 no.4
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• pp.237-242
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• 2009

This study was carried out to investigate the irritation of the prodigiosin isolated from Zooshikella rubidus on the skin and eyes in New Zealand white rabbits. The tests were performed on the basis of Korea Food and Drug Administration (KFDA) guidelines. Prodigiosin induced severe eye irritation at high concentration (0.5 g/site/ml) but there was no eye irritation at low concentration (0.3 mg/sitel ml). The primary irritation index was calculated from higher concentration (0.5 g/site/ml) to lower concentration (0.3 mg/site/ml). There were found non-irritation or induced mild irritation at lower concentration of prodigiosin application. On the basis of this study, it could be concluded that the prodigiosin may be non-irritant to mild irritant of usual application at lower concentration (0.3 mg/site) resulting it is safe and useful in dyeing technology of fabrics.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.125-132
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• 2002

To evaluate the modifying effect of Kwao Kreu, Pueraria mirifica (PM) well-known as a rejuvenating folk medicine from Thailand, peri- and post-natal studies were carried out in rats. PM extract was administered to pregnant Sprague Dawley (SD) rats by oral gavage from gestation 6 (GD 6) to postnatal day 21 (PND 21). The amount of administered in this study was 0.042, 0.42 and 4.2 mg/kg/day, respectively. There were no treatment related changes of dams in deaths, clinical signs, and parturition. Treatment related changes in body weight, food consumption and lactation of dams were not observed. F1 fetuses in external abnormality, physical development, reflex/sensory functions and behavioral development were not found. No adults and F1 fetuses in organ weight was found with the exception of vagina and uterus of F1 fetuses. The results showed that PM extract, up to 4.2 mg, had no adverse effects on the peri- and post-natal development of rats. Therefore, PM extract has no adverse effects on peri- and post-natal development of rats.

• Toxicological Research
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• v.18 no.2
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• pp.195-203
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• 2002

This study was performed to evaluate single and repeated-dose toxicities oj a new cophalosporin antibiotic agent IDC-7l81 in Sprague-Dawley rats. IDC-7181 was injected intravenously to rats at dose levels of 0, 3.2, 16, 80, 400 and 2,000 mg/kg/day for single-dose toxicity study and at dose levels of 0, 10, 50 and 250 mg/kg/day for 4-week repeated-dose toxicity study. In both studies, there were no dose-related changes in mortality clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with IDC-7l8l. Gross and histopathological findings revealed no evidence of specific toxicity related to IDC-7181. These results suggest that the intravenous maximum tolerated dose value of IDC-7181 may be over 250 mg/kg and $LD_{50}$ value may be over 2,000 mg/kg in rats.

• Toxicological Research
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• v.18 no.3
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• pp.285-292
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• 2002

The repeated toxicity of Gleditschia-saponin produced and provided by S.S. Bio-Tech Bench Co. was evaluated in Sprague-Dawley rats. Gleditschia-saponin was administered to rats by oral route at dose levels of high (180 mg/kg/day), medium (90 mg/kg/day) and low (45 mg/kg/day) once a day for 14 days. Saline was administered to another group of rats as control. Each group was consisted of 5 male and female rats. There were no dose-related changes in clinical findings, food and water consumption, organ weights, urine analysis, biochemical examination and hematological findings in all groups of animals treated with Gleditschia.- saponin, except body weights. Body weighs in male and female rats were increased significantly (p < 0.05) from day 4 to 14 in low, middle and high dose groups than control group. Body weight in high dose group was increased higher than control or low, middle dose groups on day 14. Gross and histopathological findings revealed no evidence of specific toxicity to Gleditschia.-saponin. Therefore, it was concluded that Gleditschia-saponin had no toxic or side effects in Sprague-Dawley rats in an repeated oral toxicity tests.

• Toxicological Research
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• v.18 no.2
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• pp.139-147
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• 2002

Hantaan (HTNV) and Puumala (PUUV) viruses cause hemorrhagic fever with renal syndrome in human. In the present study, the repeated dose toxicity of the HTNV-PUUV combination vaccine was evaluated in Sprague-Dawley rats. Animals were injected subcutaneously for 28 days with dosages of 0, 0.017, 0.17 and 1.7 dose/kg body weight per day, respectively. No any significant changes of body weight, food and water consumptions were shown. There were no death and clinical findings during the experimental period. In both male and female rats, there were not significant changes in hematological and serum biochemical analysis, urinalysis, and ophthalmoscopic and histopathological examination. These results indicate that the HTNV-PUUV combination vaccine may have no toxic effects and no observed adverse effect level (NOAEL) may be over 1.7 dose/kg/day at subcutaneous route in rats.

• Toxicological Research
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• v.18 no.2
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• pp.167-174
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• 2002

Historical control data have been shown to be valuable in the proper interpretation and validation of reproductive toxicology studies. The present data were compiled from rat fertility and early embryonic development studies conducted at Korea Institute of Toxicology during the 1994∼2001 period. These data were assembled in order to provide background information for the general and reproductive data collected in 11 fertility and early embryonic development studies using Sprague-Dawley rats obtain-ing from the Breeding Facility, Korea Institute of Toxicology, Korea. A total of 274 males and 274 females were used in these studies during the eight-year period. Parameters of fertility and early embryonic development included clinical sign, body weights, food consumption, organ weights, estrus cycle, copulation index, precoital time, fertility index, pregnancy index, sperm parameters, and early embryonic development parameters. Most of the values were comparable to the previous historical control data reported by other investigators. These data can be wed not only as a historical data base for the meaningful interpretation of data from reproductive and developmental toxicity studies, but also as a contribution to biological characterization of Sprague-Dawley rats.

• Toxicological Research
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• v.19 no.1
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• pp.51-66
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• 2003

This study was performed to evaluate single and repeated-dose toxicities of Bee Venom Extracts (F1, F3) in Spraque-Dawley. F1 was injected subcutaneously to rat at dose levels of 0, 0.0002, 0.002, 0.02 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. F3 was injected subcutaneously to rat at dose level of 0, 0.003, 0.03, 0.3 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. In both studies, there were no dose related changes in mortality, clinical sign, body weight change, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with Bee Venom (F1, F3). Gross and histopathological findings revealed no evidence of specific toxicity related to Bee Venom (F1, F3). These results suggest that the subcutaneous NOEL (No Observed Effect Level) of Bee Venom (F1, F3) may be over F1 -0.02 mg/kg, F3-0.3 mg/kg.

• Toxicological Research
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• v.13 no.3
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• pp.265-274
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• 1997

Uhwangchungsimwon(UC) is widely used as a herbal medicine on various circulatory disorders in Korea. The objective of this investigation was to characterize the acute, subacute hepatotoxic potency of orally administered UC in rats. In the acute and short-term studies, male rats of 150~170g were gavaged with 0, 7.5 g/kg once daily for up to 1, 5, 10 consecutive days. No differences in body weight, serum enzyme activities, absolute and relative liver weight and histopathological examination on liver between control and UC-fed groups were found. In the subacute study, UC was administered orally to both sexes of rats for 30 days(0, 1.875, 3.75 or 7.5 g/kg/day). There were no-doserelated hepatotoxic signs of general symptoms, body weight gain, water consumption and serum biochemical analysis. Slight decreases of food consumption observed at 3.75 and 7.5 g/kg groups of both sexes were due to be full of UC fed. Gross necropsy and histopathology revealed no evidence of hepatotoxicity related to UC. Our data indicate that hepatotoxicity was not caused by administration of UC up to 7.5 g/kg/dayfor 30 days in rats.

• Toxicological Research
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• v.13 no.4
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• pp.449-460
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• 1997

Single and 4 weeks oral administration of l-muscone, a major active ingredient of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dosage of 2,000 mg/kg and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of l-muscone, 0.2 mg/kg/day(low dosage group), 2 mg/kg/day(middle dosage group), or 20 mg/kg/day(high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korean Food and Drug Administration(1996.4.16). $LD_{50}$ value for beagle dogs was more than 2,000 mg/kg on oral route for both male and females. In animals administered with l-muscone, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, eye examination, hematology, serum chemistry, organ weight and other findings. No histolopathological lesions were observed in both control and treatment groups. Above data strongly suggest that l-muscone in beagle dogs is considered to be safe.