Le. Larsen et al., NEURAL TOLERABILITY OF IODIXANOL IN MICE AND DOGS AFTER SINGLE AND REPEATED INTRACISTERNAL ADMINISTRATION, Acta radiologica, 36, 1995, pp. 238-243
The neural tolerability of iodixanol has been assessed in studies in m
ice and dogs. The animals received up to 4 injections in the cisterna
cerebellomedullaris while under light anesthesia. Iotrolan was include
d as a reference substance in 1 study. The observations comprised asse
ssment of clinical behavior, cerebrospinal fluid analysis, hematology,
clinical chemistry and/or macroscopic and microscopic examination at
necropsy. In addition, the repeated-dose dog study, urinalysis and oph
thalmoscopy were performed, electrocardiograms obtained, and respirato
ry rate, blood pressure and rectal temperature measured. Clinical sign
s and minor pathological changes caused by the injection procedures we
re seen in all studies in some animals treated with iodixanol as well
as in control animals. Single (2.0 g I/kg) and repeated (0.960 g I/kg)
intracisternal administration of iodixanol to mice caused no signific
ant toxicological effects. Two dogs treated with a high dose of iodixa
nol (0.256 g I/kg; 0.8 ml/kg) had pathological changes (meningeal infl
ammation and/or necrosis) that were more severe than those observed in
control dogs. Single and repeated intracisternal administration of 0.
128 g I/kg (0.4 ml/kg) of iodixanol to dogs, however, caused no signif
icant toxicological effects. Apart from the findings in the 2 dogs, th
e neurological and neuropathological changes elicited by iodixanol wer
e similar to those induced by control or reference substances. The res
ults from these intracisternal toxicity studies in mice and dogs indic
ate a significant margin of safety regarding the use of iodixanol in c
linical intra-thecal indications.