Repeated Exposure of 3,4-Dichloro-1-butene Leads to Decreased Grip Strength and Alters Peripheral Nerve Function and Somatosensory Evoked Potentials in Adult Male Long-Evans Rats
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3,4-Dichloro-1-butene (DCB) is used in manufacturing rubber and cosmetics. An analysis using Hard-Soft Acid-Base (HSAB) concepts predicted that DCB will react with cellular proteins and potentially cause neurotoxicity after repeated exposure. Adult male Long-Evans rats were treated with DCB via oral gavage (corn oil vehicle) using concentrations of 0, 100, 175, or 225 mg/kg/day for 8 weeks. Behavioral observations (open field activity, foot splay, grip strength) were conducted weekly. Peripheral nerve function was evaluated in vivo with nerve excitability testing, consisting of compound muscle action potential (CMAP) or nerve action potential recordings by stimulating the tail (motor and mixed) nerves and sciatic (motor) nerve. Compound nerve action potentials (CNAP) and nerve conduction velocity (NCV; tail nerves) were assessed in vivo, along with somatosensory function by recording evoked potentials (SEPs) over the cortex and cerebellum. Animals treated with DCB had a dose-related suppression in weight-gain compared to controls throughout the study. Behavioral tests indicated a reduction in forelimb and hindlimb grip strength in the high-dose group. At all doses, nerve excitability data showed an effect on tail mixed nerve action potentials, suggesting alterations to nerve fibers that were consistent with neuronal depolarization (altered Na+ conduction) and possible K+ channel activity. In the high-dose group, CNAP recordings showed an increase in amplitude and NCV, possibly due to a loss of small nerve fibers. A reduction in latency was seen in the SEP cerebellum recordings, suggesting faster conduction and/or less inhibitory input. These changes further support the possibility that small afferent nerve fibers were altered. DCB treatment was associated with the development of an additional peak (N1-P1) at the front of the somatosensory cortical response, changes which could be related to effects at the cortical level or possibly a splitting of the afferent volley. Overall, this data indicates that treatment with DCB over this dose range and duration influences peripheral nerve and somatosensory function. Future studies should include histopathology to assess nerve fiber degeneration. This is an abstract of a proposed presentation and does not necessarily reflect US EPA policy.