|
Single and 4 weeks intravenous administration of water-soluble DDB derivative(DDB-S), hepatitis therapeutics, to beagle dogs of both sews were performed to investigate both acute and subacute toxicity. Beagle dogs in acute toxicity experiment were administered intravenously with single dosage of 200㎎/㎏ and body weights and clinical signs were observed for 7 days. In subacute toxicity test, groups of 9 male and 9 female dogs were given daily different dosages of DDB-S, 2.6㎎/㎏/day (low dosage group), 6.0㎎/㎏/day (middle dosage group) and 10㎎/㎏/day (high dosage group) for 4 week by intravenous route according to the Regulation of Korean Food and Drug Administration(1996. 4. 16). Single administration of DDB-S caused severe salivation and vomiting, however, the dogs recovered health within a short time and no animals died of the test compound. Autopsy of animals revealed no abnormal gross findings. Therefore, LDP value of DDB-S for Beagle dogs was more than 200㎎/㎏ on intravenous route for both male and female. In subacute toxicity test, no animals were died after intravenous administration of DDB-S. Some animals showed severe salivation and vomiting, especially on high dosage group, however, the dogs recovered the health after 2 days. Statistically significant changes were observed in body weight, drinking water and food intake in middle and high dosage groups, however, these changes were not dose-dependent. Significant changes in hematological and biochemical parameters were also observed in some animals, but, the alteration had no relationship with dosage. In addition, no differences were found between control and treated groups in urinalysis, relative and absolute organ weight etc. No histopathological lesions were observed in both control and treated animals. Above data suggest that no toxic dose level of DDB-S in beagle dogs isconsidered to be 10㎎/㎏/day.
|