抗悪性腫瘍薬VP 16-213 の毒性研究 (第2報) : ラットにおける1箇月間反復経口投与による亜急性毒性

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VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to Crj: CD (Sprague-Dawley) rats of both sexes at dose levels of 3, 10, 30 and 100 mg/kg/day for one month with the object of examining its subacute toxicity and the reversibility of toxic effects. The summarized results obtained are as follows: 1. VP 30 mg/kg suppressed body weight increase and feed intake, and brought soft stool. VP 100 mg/kg decreased body weight and feed intake, and induced diarrhea, depilation and so forth. Furthermore, half of the animals at this dose level died showing systemic debility and emaciation. 2. VP 30 and 100 mg/kg predominantly decreased red blood cell count as well as white blood cell count accompanied with lowered lymphocyte fraction. 3. VP 10 mg/kg and higher lowered total serum protein content and serum alkaline phosphatade activity, and elevated A/G ratio. 4. VP 10 mg/kg and higher caused thymic atrophy and a decrease in testicular weight ; 30 and 100 mg/kg brought suppression of spermatogenesis ; and 100 mg/kg predominantly induced appearance of giant cells in epididymis, hypoplasia of bone marrow, ileocecitis, and atrophy of prostate, seminal vesicle and splenic germinalcenters. 5. Above-described changes excluding exacerbation of the findings on testis and epididymis were shown to be generally reversible. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against rats of both sexes.
日本トキシコロジー学会の論文
1986-04-25

抗悪性腫瘍薬VP 16-213 の毒性研究 (第2報) : ラットにおける1箇月間反復経口投与による亜急性毒性

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