In a chronic study conducted by the National Toxicology Program (NTP), gavage administration of 100 or 200 mg ethyl acrylate/kg to F344 rats and B6C3F1 mice resulted in a significant dose-dependent increase of squamous cell papillomas aid carcinomas in the forestomach (FS), with no increase in the incidence of tumors at any other site. Current studies were designed to investigate the relationship between cell proliferation and carcinogenicity and the effect of age on this relationship. Stop-studies in which 100 or 200 mg EA/kg was administered to 3 or 13 month old rats daily, 5 days/week, for 3, 6, or 12 months was initiated to investigate the progression of this lesion. Rats sacrificed at the end of the treatment regimens had severe epithelial hyperplasia of the FS associated with increased cell proliferation as detected by increased bromodeoxyuridine incorporation into DNA of FS epithelial cells. Old rats were more sensitive than the 3 month old rats. Forestomach hyperplasia induced by EA included upward and downward cell proliferation. However, forestomachs of young or old rats treated for 3 or 6 months and sacrificed 8 weeks after the last EA dose exhibited a significant decline in the incidence and severity of these lesions. Histopathologic evaluation of forestomachs of EA-treated rats (3 month) which were allowed a 19 month recovery (with no exposure to EA) showed further decline in the incidence and severity of mucosal cell hyperplasia and cell proliferation. Reversibility of forestomach lesions from rats treated for 6 or 12 months are currently in progress.
