흰쥐에서 HELIKITTM의 급성 및 아급성 경구독성시험

Acute and Subacute Oral Toxicity of HELIKITTM in Rats

Acute and subacute oral toxicity of HELIKITTM (13C-urea) were carried out in Sprague-Dawley rats of both sex. The toxicity of HELIKITTM was compared with urea (12C-urea which is used for control). In acute toxicity studies, we daily examined number of deaths, clinical signs, body weights and pathological examination for 14 days after single oral administration of HELIKIT or urea (12C-urea) at a dose of 5000mg/kg. The subacute oral toxicity was investigated in Sprague-Dawley rats treated with HELIKITTM at a dose of 40, 200 and 1,000mg/kg/day or 12C-urea at a dose of 1,000mg/kg/day for 4 weeks. In acute toxicity studies, HELIKITTM and urea did not show any toxic effect in rats and oral LD50 value was over 5,000mg/kg in rats. In subacute toxicity studies, no death occurred and no drug-related changes were found in clinical observations: body weight, food consumption, opthalmoscopy, auditory test, urinalysis, hematology, blood chemistry, gross pathological examination or organ weight between HELIKITTM, urea and control groups. In histopathological examinations, the slight thickening of mucosa of the limiting ridge in the stomach was noted in the animals treated with HELIKITTM at a dose of 1,000mg/kg/day and also the changes in urea group at a dose of 1,000mg/kg/day was found, but all of these changes in the stomach regressed after withdrawal of the test article for 2 weeks and reversibility of the effect was revealed. These results indicate that the non toxic dose level of HELIKITTM was 1,000mg/kg/day in the 4 weeks-repeated dose study, suggesting that the substitution of 13C for carbon in urea molecule has no effect on the toxicity of urea and changes in stomach are reversible.