FETAL TOXICITY OF AMINOGUANIDINE IN MICE AND RATS

Abstract

t has been reported that aminoguanidine (AG) sulfate injected into hen's eggs at the earlier incubation stages induced retardation of development of body and liver, aplasia of gallbladder and enlarged spleen in high frequency without high mortality. The present study deals with the influence of AG against rodent animals and their fetuses. AG sulfate showed low lethality at the intraperitoneal administration against young mice and rats. When the maximum tolerated dose of AG sulfate (750 mg/kg in mice and 500 mg/kg in rats) was intraperitoneally injected into pregnant mice and rats on day 0 to 6 or day 7 to 13 of gestation, the incidence of resorption was comparatively high in the day 7 to 13 group of both species, but severe abnormalities as observed in the chick embryos and other external abnormalities were not induced in rodent fetuses. ¹⁴C-AG hydrochloride intraperitoneally injected to pregnant mice on day 12 was widely distributed in the maternal body and fetuses within 1 hr and rapidly excreted. Furthermore, AG might be hardly metabolized in mice, while a metabolite clearly appeared in chick embryos. Therefore, the lower toxicity of AG on rodent animals as compared with chick embryos may be due to the fact that the agent is not metabolized and rapidly excreted from maternal body and fetuses.