THE RAT AS A MODEL TO EVALUATE THE GASTRIC IRRITATION POTENTIAL OF ALKALINE PRODUCTS

Animal models historically used to assess the acute gastric irritation potential of accidental ingestion of consumer products include the do g, pig, rabbit, and cat. In looking at alternative methods that are of shorter duration and more cost-effective, the rat is being evaluated as a potential model. Acute gastric irritation is known to increase as the reserve alkalinity of the formulation increases. In initial exper iments to assess the rat as a potential model, animals were dosed via oral gavage with 1 of 4 formulations ranging in reserve alkalinity fro m 4.0 to 10.8. Necropsies were performed at 15 and 60 min after dosing . Macroscopic and microscopic evaluations of the stomach revealed morp hological differences in the various treatment groups that distinguish granular formulations having either a low (R.A. = 4.0), moderate (R.A . = 7.1), or higher (R.A. = 10.8) reserve alkalinity. Additionally, it was observed that the acute gastric changes in rats dosed with a liqu id formulation having a low (R.A. = 4.2) reserve alkalinity were simil ar to those in rats dosed with a granular formulation having a moderat e reserve alkalinity (R.A. = 7.1). This suggests that other factors su ch as types of ingredients, pH, and physical form influence the extent of acute gastric irritation and demonstrates that an evaluation of on ly reserve alkalinity is not sufficient to ensure the safety of these products. This preliminary work supports the rat as a potential model to assess the acute gastric irritation potential of alkaline formulati ons or substances.