Three groups of Sprague-Dawley CD rats (males and females) were initially a
dministered p.o. with ebrotidine, a novel H-2-receptor antagonist, mixed wi
th the diet, at 50, 200, and 500 mg/kg/d, respectively. Two concurrent cont
rol groups of animals were used. After 13 months, initial 200 mg/kg was low
ered to 150 mg/kg, and a new group was administered with 300 mg/kg, due to
the body weight reduction observed in the top dose group. After 24 months,
survivors were killed and necropsied, and a histopathological study was per
formed. The frequencies of the different tumour types that were found were
not raised due to the treatment. Lower frequencies of some types of pituita
ry and mammary gland tumours, in the groups treated with the higher doses,
were the only statistically significant changes. Among the non-neoplastic e
ffects, a lower body weight increment and food consumption (500 and 300 mg/
kg, both sexes), lower survival (500 mg/kg, males), presence of lipoid pneu
monia (500 mg/kg, only in males, and 300 mg/kg, both sexes), and lithiasis
in urinary system (500 mg/kg) were observed. No changes in gastric mucosa (
the maim target organ) were attributable to ebrotidine. Regarding the non-n
eoplastic effects, 150 mg/kg was the no observed adverse effect level. Acco
rding to the previous results of the carcinogenicity study in mice, conjoin
tly with those of the study in rats reported here, there is no evidence of
carcinogenic risk either in males or in females in these species. (C) 1998
Wiley-Liss, Inc.