Chemotoxic-type effects are determined by dose, the molecular toxicity of each agent and the physiological characteristics of the contrast agents (i.e. osmolality, viscosity, hydrophilicity, affinity to proteins, calcium binding properties and sodium content). Chemotoxic effects of iodine-based contrast media are more likely to occur in patients who are debilitated or medically unstable. High osmolality (osmotoxicity) causes shift of fluids from the intracellular to the extracellular space, leading to cell dehydration and an increase in intracellular fluid viscosity precipitating cellular dysfunction. Low hydrophilicity may reduce the biological tolerance to iodinated contrast media since it is associated with an increase in lipophilicity and higher affinity of the contrast medium molecule to plasma proteins and cell membrane. High hydrophilicity of non-ionic contrast media is produced by hydroxyl (-OH) groups, which are symmetrically distributed, thereby offering a good coverage of the benzene ring and restricting access to lipophilic areas of the iodinated contrast molecule.

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