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Pregnant female rats were given orally M73101 (0,100,250 and 600 mg/kg) or aspirin (225 mg/kg) on gestational days 7 to 17. About two-thirds of treated females in each group were sacrificed at day 21 of pregnancy and their fetuses were examined for abnormalities. The remaining females were allowed to deliver spontaneously in order to observe postnatal development of their offspring. The results were summarized as follows: 1. No significant effects of M73101 on number of the corpora lutea, litter size, fetal mortality, fetal weight or sex ratio were observed, but aspirin exhibited the intrauterine deaths and growth retardation in fetuses. 2. No external, internal or skeletal malformations attributable to M73101 were seen in fetuses, although aspirin caused malformations of various organ systems. 3. No apparent effects of M73101 on F1 generation were observed on postnatal development including emotionality, learning ability and reproductive performance. There were no adverse influences of M73101 on postnatal development of F2 generation. Aspirin, however, showed adverse effects on postnatal survival, growth, emotionality and mating performance of F1 generation.

journal of toxicological sciences

REPRODUCTION STUDY OF 4-ETHOXY-2-METHYL-5-MORPHOLINO-3(2H)-PYRIDAZINONE (M73101) IN RATS (II). ADMINISTRATION OF M73101 DURING THE PERIOD OF MAJOR ORGANOGENESIS