Peripheral Nervous System Toxicity

Exposure to n-hexane, methyl n-butyl ketone, and other six-carbon aliphatic hydrocarbons is associated with the development of a characteristic peripheral polyneuropathy caused by demyelinization and retrograde axonal degeneration. 12 Onset of symptoms may be delayed for months to years after initial exposure. Toxicity is attributed to a metabolite, 2,5-hexanedione, produced by the cytochrome P-450-mediated biotransformation of the parent compounds. This neurotoxic metabolite is thought to inhibit glutaraldehyde-3-phosphate dehydrogenase, which supplies energy for axonal transport. Long, distal nerves seem to be most vulnerable, characteristically producing foot and wrist drop with numbness and paresthesias. The electromyelogram typically shows a decrease in nerve conduction velocity.

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