Pathology of 6-aminonicotinamide toxicosis in the rabbit.

Daily doses of 6-aminonicotinamide (3-5 mg/kg) given by ip injection produced ataxia of the hind limbs progressing to an ascending paresis/paralysis, anorexia, diarrhoea and death in male and female New Zealand White and Dutch Belted rabbits. At autopsy, caecal and gastric distention were seen and the apex of the gall bladder had necrotic foci. Light microscopic lesions included atrophy and necrosis of the white lobe of Harder's gland and atrophy of seminiferous tubules with cellular necrosis, vacuolation and the presence of multinucleated giant cells. Cytoplasmic vacuolation was observed in epithelial cells from many tissues, usually in the basal portion of the cells. Vacuolation of the epithelium of the sacculus rotundus and vermiform appendix was found within the same time frame as histiocytic hyperplasia in these organs. Spongiosis and gliosis were seen in certain parts of the central nervous system. Ultrastructural alterations in the gall bladder epithelium consisted of distention of intercellular space, mild distention of perinuclear space and coalescing, intracytoplasmic, membrane-bound vacuoles, a few of which contained membranous debris. Some alterations of 6-aminonicotinamide toxicosis were prevented by simultaneous administration of nicotinamide with 6-aminonicotinamide.