Acute toxic and teratogenic effects of cyclic imides in rodents

Four structurally different cyclic imides or related derivatives (o-(N-phthalimido)acetophenone (1), 2,3-dihydrophthalazine-1,4-dione (2), N-(4-methylphenyl)diphenamide (3), and 4,6-dihydro-5H-dibenz[c,e]azepine (4) were examined for acute toxicity in mice at multiple doses, for long term toxicity at a single dose in rats, and for deleterious effects on fertility and pup development in rodents. No deleterious effects were observed when mice were administered agents at 20, 50, and 100 mg/kg/day for seven days. All other measured characteristics and values were normal for the four compounds. The principle effect of the compounds was to reduce the percent pregnancies in treated mice compared to the controls. Compound 2 afforded the greatest reduction of pregnancy (54%) at 100 mg/kg/day. Compounds 3 and 4 caused a minor reduction in pregnancy (12-20%). The compounds did not appear to cause measureable teratogenic effects; pups of treated rodents thrived and survived as well as controls. There were no effects on murine male fertility when compounds were administered at 20, 50, and 100 mg/kg/day for six weeks.