CHRONIC TOXICITY OF EBROTIDINE IN RATS AND DOGS

The results obtained in the chronic toxicity studies of ebrotidine eth yl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-35 42) by oral route in rats and in Beagle dogs are reported. Rats were a dministered for 6 months and dogs for 12 months. The doses were 50, 20 0 and 500 mg/kg in rats and 50, 200 and WO mg/kg in dogs. The dose of 400 mg/kg was reduced to 350 mg/kg after 3 months of treatment, due to its toxicity. The effects probably related to the administration of e brotidine were as follows: three dogs from the high dose group died af ter 3, 4.5 and 8 months of treatment (in rat there was no mortality); occult blood in faeces; lower weight gain in the high dose group (in r ats only females were affected); lower food consumption in rats from t he high dose group (and also females from the middle dose group); redu ction of erythrocyte count and packed cell volume, only in rats and at the end of the study; alkaline phosphatases increment in rats and dog s; proteinemia decrease in rats; and a tendency to decrease in the tes ticular weight, which was not statistically significant (p > 0.05). Th e only histopathological changes observed were moderate erosions or ul cerations in the intestinal mucosa of some dogs from the high dose gro up. These effects coincide with those published for other competitive H-2-receptor inhibitors. The maximum toxic effect-free level was 50 mg /kg for both rats and dogs, which provides a wide safety margin with r espect to the therapeutic dose.