Neurotoxicity of acrylamide and related compounds in rats. Effects on rotarod performance, morphology of nerves and neurotubulin.

Neurotoxic properties of acrylamide and seven related compounds in rats were studied with regard to the effects on rotarod performance, morphology of nerves and neurotubulin. Compounds used in the present study were acrylamide, N-hydroxymethylacrylamide, N-isopropylacrylamide, methacrylamide, N-methylacrylamide, crotonamide, diacetone acrylamide, and N-tert-butylacrylamide. Animals were given chemicals in their drinking water for 90 days. Deficit of rotarod performance was produced by five compounds; acrylamide, N-hydroxymethylacrylamide, N-isopropylacrylamide, methacrylamide, and N-methylacrylamide. Morphological changes in tibial and sural nerves, such as shrinkage and loss of myelinated fibres, myelin retraction, and corrugated myelin sheaths, were observed after treatment with these five compounds. Depression of the [3H]colchicine-binding to neurotubulin (the soluble protein) of sciatic nerves was detected after giving these five compounds. After acrylamide dosing, the depression progressed with time. A significant reduction of the colchicine-binding to neurotubulin was also detected in the spinal cord of both the cervical and the lumbar regions, but neither in the brain nor the cerebellum.