In a chronic study conducted by the National Toxicology Program (NTP), gavage administration of 100 or 200 mg ethyl acrylate (EA)/kg to F344 rats and B6C3F1 mice resulted in a significant dose-dependent increase of squamous cell papillomas and carcinomas in the forestomach (FS), with no increase in the incidence of tumors at any other site. Current studies were designed to investigate the temporal relationship between cell proliferation and carcinogenicity. Work in this laboratory indicated that carcinogenic doses of EA administered by gavage for 3 or 6 months resulted in a sustained increase in FS epithelial cell proliferation (hyperplasia) for as long as exposure to EA continued. However, hyperplasia regressed to background levels and resulted in no neoplastic lesions in 19 and 15 months of recovery, respectively. On the other hand, EA administration to male F344 rats, 5 days/week, for 12 months resulted in development of FS papillomas (2/5) after two months post treatment recovery. Further, rats treated for 12 months and allowed 9 months recovery developed squamous cell carcinomas (3/13) and papillomas (1/13). No significant elevation in liver CP or neoplasia was seen in any of the rats included in this study.
