EVALUATION OF THE NEUROTOXICITY OF GLYCIDAMIDE, AN EPOXIDE METABOLITEOF ACRYLAMIDE - BEHAVIORAL, NEUROCHEMICAL AND MORPHOLOGICAL-STUDIES

Acrylamide is an important chemical used in;he synthesis of polyacryla mides, which have a wide variety of industrial applications, The princ ipal toxic effect of acrylamide, both in animals and in humans, is neu rotoxicity. Peripheral nervous system effects are most prominent, but central nervous system effects have also been reported, Acrylamide is metabolized to the epoxide glycidamide, whose adducts to hemoglobin an d to DNA have been identified in animals and humans. This metabolite m ay be involved in the reproductive and carcinogenic effects of acrylam ide. In the present study we investigated whether glycidamide would ex ert neurotoxic effects similar to those caused by its parent compound. Male rats were injected i.p. with acrylamide (25 or 50 mg/kg) or glyc idamide (50 or 100 mg/kg) daily for 8 days. Reduced weight gain was ev ident in animals exposed to glycidamide or to the higher dose of acryl amide. Both compounds induced lethargy and ataxia, but the posture of glycidamide-treated rats differed from that of animals treated with ac rylamide. At the high doses, both compounds significantly affected rat s' behavior in the rotarod test; on the other hand, only acrylamide wa s effective in the hindlimb splay test. Acrylamide inhibited activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in sciatic and tib ial nerves, as well as in brain. Glycidamide inhibited GAPDH activity only in brain and activity of creatine kinase in both peripheral and c entral tissues. Acrylamide also caused profound urinary retention and distended bladders, while the effects of glycidamide were minimal. Mor phological abnormalities were seen in sciatic nerves and dorsal root g anglion cells of rats treated with acrylamide (50 mg/kg x 12), but not in rats exposed to glycidamide (100 mg/kg x 11), These results indica te that the toxicities of acrylamide and glycidamide differ and sugges t that acrylamide itself may be primarily responsible for its peripher al neurotoxicity.