Comparison of subchronic neurotoxicity of 2-hydroxyethyl acrylate and acrylamide in rats

Abstract

The comparative neurotoxicity of subchronic exposure to 2-hydroxyethyl acrylate (HEA) and acrylamide (ACR) was evaluated using a functional observational battery (FOB) and neuropathology. Three dose levels of each compound (HEA: 3, 20, 60 mg/kg; ACR: 1, 4, 12 mg/kg) were administered intraperitoneally to male and female Long-Evans rats ( n = 10/sex/dose level), 5 days/week for 13 weeks. Two vehicle control groups were also included. The FOB, which includes home-cage and open-field observations and interactive tests of sensory, neuromuscular, and autonomic function, was administered before dosing, at monthly intervals, and on the day after the last dose. Subsets of rats ( n = 6/sex/dose level) were then perfused and tissues from the brain, spinal cord, and peripheral nerve were prepared for light microscopic evaluation. There were clear differences between the effects of HEA and ACR. ACR produced time- and dose-related changes in FOB measures of muscle tone and equilibrium, and produced axonal degeneration in peripheral nerves and within long tracts of the spinal cord. HEA exposure was also associated with changes in muscular function on FOB testing, but the magnitude of the effects was not as great as with ACR and not dose related. In addition, no neuropathological changes were detected after HEA exposure. Thus, the effects of HEA did not resemble those of ACR. The FOB data were summarized in domains of neurobehavioral functions. Using a composite score analysis, ACR was shown to produce prominent effects in the neuromuscular domain whereas HEA was largely without effect. When the data are analyzed in this manner, the neurotoxic potential of HEA appears to be minimal.