Toxicity studies of VP 16-213 (I)--Acute toxicity in mice, rats and rabbits

Abstract

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was examined for its oral, subcutaneous or intravenous acute toxicity using Slc : ICR mice, Crj : CD (Sprague-Dawley) rats and JW-NIBS rabbits of both sexes. The summarized results obtained are as follows: A mode of manifestation of toxic effects was classified into immediate-type symptoms predominantly caused by the carrier and delayed-type symptoms predominantly caused by VP regardless of animal species and routes of administration, excluding the case of intravenous dosing to rabbits. Referring to the delayed-type toxic signs, depilation, diarrhea and suppression of body weight increase were observed for mice and rats regardless of administration routes, and diarrhea was noted in rabbits by oral route. Necropsy of three species of animals and histopathology on rabbits revealed thymic and splenic atrophy in mice and rats as well as thymic atrophy and inflammatory changes of intestine in rabbits dying by oral administration. The drug-related cause of death for mice and rats seemed to be due to the cytocidal action of VP as an oncostatic drug, but the cause of death for rabbits by oral administration was considered to be somewhat different from that for mice and rats. LD50 values (mg/kg) were as follows, showing oral toxicity in rabbits being rather potent as compared with that in mice or rats: (table; see text).