The subacute neurotoxicity of excess pyridoxine HCl and clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in beagle dogs. II. Pathology.

Abstract

The lesions caused by excess oral pyridoxine hydrochloride (150 mg/kg body weight/day) and clioquinol (200 mg/kg body weight/day), given individually and in combination to adult Beagle dogs, were evaluated. The experimental period was 100 to 112 days, except that four dogs in each of the clioquinol and combined-treatment groups were killed early because of severe debilitation or neurologic disease, and one dog given both compounds died on the third day of compound administration. Degenerative neurologic lesions had distribution specific for the compound given. Pyridoxine-treated dogs had lesions limited to tracts and nerves with neuronal bodies of their nerve fibers in the spinal and trigeminal ganglia. Clioquinol-treated dogs had neurologic lesions limited to the central nervous system. The most lesions were in the rostral dorsal funiculus and distal aspects of the optic nerve fibers, but minimal to mild degenerative changes also occurred in distal aspects of the corticospinal and spinocerebellar tracts. Dogs given both pyridoxine hydrochloride and clioquinol had a combination of the lesions in dogs given pyridoxine or clioquinol individually. Several dogs given clioquinol or pyridoxine plus clioquinol had extraneural lesions, including myocardial degeneration and thyroidal alterations.