[Toxicity studies of VP 16-213 (III)--Oral six-month chronic toxicity in rats].
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 1, 3, 10 and 30 mg/kg/day for six months with the object of examining its chronic toxicity and the reversibility of toxic effects. The summarized results obtained are as follows: VP 30 mg/kg suppressed body weight increase and feed intake, and brought transient diarrhea, anemia and depilation. Some animals receiving this dose died showing systemic debility, emaciation and ataxia. VP 3 mg/kg and higher predominantly decreased red blood cell count as well as white blood cell count accompanied with lowered lymphocyte fraction. VP 30 mg/kg lowered total serum protein content and elevated A/G ratio in males, and lowered serum alkaline phosphatase activity in females. VP 10 and 30 mg/kg predominantly induced thymic atrophy, testicular atrophy with suppression of spermatogenesis and tubular atrophy, a decrease in epididymal weight, and splenic erythropoiesis. Above-described changes excluding the findings on testis and epididymis in VP 30 mg/kg group were shown to be generally reversible. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 1 mg/kg/day against rats of both sexes.
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D001854:Bone Marrow Cells; D002452:Cell Count; D004435:Eating / Q000187:drug effects; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006403:Hematologic Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D013997:Time Factors; D014556:Urine
D005047:Etoposide