The assessment of peripheral neurotoxicity in dogs: comparative studies with acrylamide and clioquinol

Abstract

Monomeric acrylamide was given to beagles in daily oral doses of 15 mg/kg for 22 days and at 5 mg/kg for 60 days. The animals of the high dose group developed neurological signs consistent with peripheral neuropathy. Electrophysiological measurements on the saphenous nerve revealed abnormal nervous function at the end of the treatment period. Conduction velocity was affected to the greatest extent, followed by absolute refractory period and chronaxy. At 30 days upon cessation of treatment conduction velocity and chronaxy were restored to normal but absolute refractory period remained pathological. At that time the first morphological changes of peripheral nerves were detected. Administration of the 5-mg/kg dose resulted in some disability of gait, lengthening of the absolute refractory period and, in half of the animals, in discrete morphological changes. By contrast, after the oral administration of clioquinol up to 200 mg-kg per day for a one-year period there were no signs of functional nor structural alterations of the nervous system. The beagle dog is considered to be a species well suited to reveal neurotoxicity.