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Monolayer cell culture techniques for neuronal and glial cells and fibroblasts were used for the investigation of the direct toxicity of x-ray contrast media. The effect of various concentrations of sodium diatrizoate, methylglucamine salts of diatrizoate, iothalamate, iodamide, metrizamide, iocarmate, ioserate, and ioglycamate were studied. The intravenous biliary contrast medium--ioglycamate--was most toxic to all cell types. All the contrast media studied were somewhat toxic to neurons in the concentration of 50 mmol/l and showed variable glial toxicity. In equiosmolar concentrations the contrast media studied showed toxicity on neurons in the following order: iothalamate, diatrizoate, iodamide, ioserate, iocarmate, ioglycamate. Fresh metrizamide solution in equimolar concentrations showed the least toxic effects on neurons but interfered considerably with the growth and survival of glial cells. Metrizamide solution proved to be highly toxic to neurons when refrigerated for two weeks. Methylgucamine iocarmate produced a peculiar swelling of fibroblasts.

In order to clarify whether adverse reactions to radiographic contrast media may be allergic in nature, it is essential to show that contrast media can act as haptens and induce antibody formation in vivo. Experiments in Hooded Lister rats have been carried out using techniques specifically designed to produce favourable conditions for the production of antibodies. No evidence of any antibody formation was found in any of the experiments. These experiments suggest that radiographic contrast media in their native form do not act as haptens, contrary to previously published data, and it therefore seems unlikely that the majority of adverse reactions to radiographic contrast media are allergic in nature.

The effect of small concentrations of diatrizoate, ioglycamate, and iopanoate salts on cultured sympathetic ganglia was studied. Biliary contrast media in clinical blood concentrations caused severe degeneration of cultured neurons, but similar concentrations of diatrizoate caused no effect. This technique may be used to measure the direct neurotoxicity or general cytotoxicity of contrast media.

Some adverse clinical effects of intravascular radiologic contrast agents have been attributed to their interference with the normal hemostatic processes. This study compares the effects of the low osmolality agents with those of the conventional agents by in vitro studies of platelet function, fibrin formation, and fibrinolytic activation. In various degrees, all the contrast agents studied inhibit platelet aggregation and fibrin formation but show virtually no direct activation of fibrinolysis. The new low osmolality agents generally show lesser inhibitory effects on the hemostatic mechanisms. Some clinical implications are discussed.