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Comparison of Nerve Excitability Testing, Nerve Conduction Velocity, and Behavioral Observations for Acrylamide Induced Peripheral Neuropathy
Freeborn, D., G. Jung, Kathy Mcdaniel, V. Moser, AND D. Herr. Comparison of Nerve Excitability Testing, Nerve Conduction Velocity, and Behavioral Observations for Acrylamide Induced Peripheral Neuropathy. Society of Toxicology Meeting, New Orleans, LA, March 13 - 17, 2016.
This abstract will be presented at the Society of Toxicology Meeting March 13-17, 2016, New Orleans, LA
Nerve excitability (NE) testing is a sensitive method to test for peripheral neurotoxicity in humans,and may be more sensitive than compound nerve action potential (CNAP) or nerve conduction velocity (NCV).We used acrylamide to compare the NE and CNAP/NCV methods. Behavioral tests known to be sensitive to acrylamide-induced neurotoxicity were included. Male Long-Evans rats aged 10-11weeks were given acrylam ide in their drinking water at 0, 1.5, 2.5 or 3.0 mM for 6 weeks .These concentrations resulted in an average exposure of 0, 10.3, 14 .7, and 14.4 mg/kg/day of acrylamide. NE testing occurred during the 5th week, and CNAP/NCV testing was during the 5th week of treatment. Only 5 animals in the 3.0 mM group were tested due to pronounced neuromuscular and respiratory toxicity, and were not included in statistical analysis. Behavioral testing occurred weekly during treatment, prior to electrophysiology testing,and included open-field evaluations and measures of forelimb/hindlimb grip strength and landing foot splay. Both 1.5 and 2.5 mM treatments altered measures of neuromuscular and sensory function, including increased splay,lower hindlimb grip strength and rearing,and impaired gait and righting reflex.These changes worsened over the 6 weeks of exposure. NE tests indicated decreased nerve excitability, possibly coupled with increases in K+ channel activation in sciatic motor nerves and tail mixed nerves. These changes were observed at the 2.5 mM treatment concentration. Tail motor nerves and CNAPs/NCV in tail mixed nerves were not altered significantly. Results indicate that for acrylamide-induced peripheral neurotoxicity, NE testing detected changes in physiological function,which differed between types of nerves,and was more sensitive than traditional CNAP/NCV methods. Behavioral changes were consistent with previous studies. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.