NEUROTOXICITY OF NONIONIC X-RAY CONTRAST-MEDIA AFTER INTRACISTERNAL ADMINISTRATION IN RATS

The neurotoxicity of an X-ray contrast medium appears inversely relate d to the hydrophilicity of the agent. To further test this hypothesis, four non-ionic X-ray contrast agents, differing in hydrophilicity, (i oversol, iopromide, iohexol and iopamidol) were injected into the cist ernal magna of ether-anesthetized rats. Iopromide demonstrated an acut e median lethal dose of 122 mg I/kg. Other signs of toxicity included convulsions, apnea, dyspnea and hypoactivity. In contrast, ioversol, i ohexol and iopamidol caused no deaths when administered intracisternal ly, up to a dose of 1000 mg I/kg. Animals treated with these nonionic agents displayed signs of convulsions, apnea, dyspnea, chewing and hyp oactivity. Iopromide possesses a hydrophilicity (e.g., water to octano l partition coefficient) approximately 8.5 times smaller than ioversol , 4.6 times smaller than iohexol and 2.3 times smaller than iopamidol. These data support the hypothesis that tri-iodinated X-ray contrast m aterials with smaller degrees of hydrophilicity produce greater toxici ty to the central nervous system.