Ethyl acrylate-induced gastric toxicity. I. Effect of single and repetitive dosing

Ethyl acrylate (EtAc) is widely used in the production of polymers and copolymers for use in the preparation of latex paints, textiles, paper coatings, and specialty plastics. EtAc caused squamous cell carcinomas and papillomas in the forestomach (nonglandular portion of the stomach) of both sexes of F344 rats and B6C3F1 mice when administered chronically by gavage. The current studies were undertaken to investigate and characterize the nature of the acute gastric toxicity caused by EtAc. Gavage administration of a single dose of 100, 200, or 400 mg/kg EtAc (in corn oil) to F344 male rats caused dose-and time-dependent mucosal and submucosal edema and vacuolization of the tunica muscularis in the forestomach and mild submucosal edema in the glandular stomach. Equivalent sc or ip doses did not produce similar gastric lesions. Treatment of rats with two or four consecutive oral daily doses (200 mg/kg each) of EtAc caused mucosal edema associated with vesicle formation, mucosal hyperplasia, submucosal edema and inflammation, and vacuolization of the tunica muscularis of the forestomach. Submucosal edema and inflammation were also observed in the glandular stomach and mucosal erosions or ulcers were observed in both portions of the stomach after repeated oral exposure to EtAc. The absence of systemic toxicity plus the dependency of gastric lesions on the gavage route of administration suggest that the EtAc-induced gastric lesions may be a consequence of localized hemodynamic changes, specifically those characteristic of a classical immediate inflammatory response to an injurious agent at the site of administration.