The effect of sodium salicylate on the rat embryo in culture: an in vitro model for the morphological assessment of teratogenicity.

The optimum teratogenic dose of subcutaneously administered sodium salicylate was determined in vivo at 9.5 days of gestation. Fetuses from rats injected with this dose at 9.5 days were examined at 11.5 days and its propensities for producing resorption as well as deformities noted. Next, maternal serum levels 3-3.5 hours and 18.5 hours after salicylate injection were determined. Having established the feasibility of determining an effect due to salicylate at 11.5 days, after injection at 9.5 days, the following experiments were performed in vitro in animals cultured between 9.5 and 11.5 days by the method of New et al. (1976a): (1) Sodium salicylate was added to the culture serum, at levels equivalent to those obtained 3-3.5 hours after maternal injection of the optimum teratogenic dose, for 24 of the 48 hours culture period. (2) Rats were cultured for the first 24 hours of the 48 hours culture period in serum taken from rats injected 3.5 hours previously with the optimum teratogenic dose. (3) Rats were cultured for 24 out of 48 hours in serum from animals which had been injected with the optimum teratogenic dose 18.5 hours before bleeding. (4) Rats were cultured for 24 out of 48 hours in serum containing salicylate added to make up levels normally associated with (3). (5) A control culture was performed. The experiment indicates great similarity between the results obtained from animals cultured in serum with salicylate added and results from culture in serum of salicylate treated rats. It appears therefore that sodium salicylate - acting directly on the feto-placental unit - is the active teratogen rather than any of its metabolites.