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Pyrimethamine Teratogenesis by Short Term Administration in Goettingen Miniature Pig
Authors:Yuzuru YAMAMOTO  Masatoshi OHNISHI  Ei-ichi KOKUE  Toyoaki HAYAMA  Hiroaki AOYAMA  Masahiro KANEDA  Shoji TERAMOTO
Affiliation:Laboratory of Veterinary Pharmacology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183,;**Department of Toxicology, Institute of Environmental Toxicology, Kodaira, Tokyo 187, Japan
Abstract:Pyrimethamine was mixed with mashed feed and given to pregnant sows of Goettingen miniature pig through a part of the period of organogenesis. A high incidence of the major malformations such as cleft palate, club foot and micrognathia was observed in 13 out of 24 newborns from 5 pregnants which a teratogenic dose (3.6 mg/kg of body weight/day) from day 11 to day 22 of gestation, the first half of the organogenetic period. Only one cleft palate was observed among the 23 newborns from 4 pregnants administered the same dose through the second half of the period. Among the 51 newborns from 10 pregnants which the same dose through the first or second quarter, only 4 newborns showed external major malformations. However, 19 out of 38 live newborns without external major malformations in these groups died within 2 days after birth. Clinical symptoms of these neonatally dead young were similar to splayleg, a naturally occurring functional anomaly in pigs. No internal malformation was revealed by the autopsy of these dead newborns.
Keywords:pyrimethamine    splayleg    Goettingen miniature pig    pyrimethamine teratogenesis
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