TOXICITY OF EBROTIDINE ON REPRODUCTION - TOXICITY ON FERTILITY AND GENERAL REPRODUCTIVE-PERFORMANCE, EMBRYO-FETAL TOXICITY AND PERI-NATAL AND POSTNATAL TOXICITY

Reproduction toxicity studies of ebrotidine ethyl]amino]methylene]-4-b romo-benzenesulfonamide, CAS 100981-43-9, FI-3542) are presented in th is paper. Rats dosed with 50, 200 and 500 mg/kg p.o. of ebrotidine wer e used for the fertility and peri- and postnatal toxicity studies, and rabbits dosed with 25, 100 and 250 mg/kg and rats dosed with 50, 200 and 500 mg/kg of ebrotidine were used for the embryotoxicity study. Th e fertility study was designed in accordance with a 2-generation study protocol. The results showed that ebrotidine did not interfere with m ale and female gametogenesis, fertility, organogenesis, postnatal deve lopment and lactation in F-0 or F-1 animals. Only general or non-speci fic effects were attributed to treatment, such as a lower weight gain in parents or fetuses in rats, or a somewhat slower bone calcification in rats, which was shown to be recoverable and had no peri- or postna tal repercussions. Neither did the fertility study reveal a possible l onger duration of gestation nor did the peri- and postnatal study show a lower weight of the F-1 offspring. There was only an increase in ra bbit embryonic mortality, probably related to some cases of abortion a t the high dose. No potential antiandrogenic effect on the reproductiv e function has been found. Among the different doses used in both anim al species, the maximum toxic effect-free dose was that of 25 mg/kg.