Neurotoxicity of glycidamide, an acrylamide metabolite, following intraperitoneal injections in rats

Acrylamide (2‐propenamide) monomer produces central‐peripheral distal axonopathy in humans and some animal species. Its neurotoxicity is characterized by abnormal sensation, decreased motor strength, and ataxia. Acrylamide forms adducts with glutathione, proteins, and DNA. Recent studies demonstrated that acrylamide is metabolized to its epoxide, glycidamide (2,3‐epoxy‐1‐propanamide). We studied the neurotoxicity potential of glycidamide in male Sprague‐Dawley rats. Animals (groups of 6) were injected ip daily with either aqueous acrylamide or glycidamide at an acrylamide‐equivalent dose of 50 mg/kg (0.70 mmol/kg). Both treatments resulted initially in the rats circling, which was followed by the onset of ataxia at 7–9 d and hindlimb paralysis at 12–14 d. Treated animals showed muscle wasting. At termination, acrylamide‐ and glycidamide‐treated rats weighed 105% and 86% of initial weight, respectively, compared to 145% for controls. Animals were anesthetized and perfused with 10% neutral phosphate‐buffere...