NIOSHTIC-2 Publications Search
N-hexane neurotoxicity: a mechanism involving pyrrole adduct formation in axonal cytoskeletal protein.
Neurotoxicology 1987 Jan; 8(1):199-210
Literature on the neurotoxic effects of n-hexane (110543) was reviewed, and hypotheses for mechanisms linking pyrrole (109977) formation in axonal cytoskeletal protein with nerve degeneration in gamma-diketone neuropathy were presented. Aggregated neurofilament masses caused by a proposed increase in hydrophobic interactions were hypothesized to become lodged at areas of axonal constriction, blocking nutrient transport into the distal axon. Tertiary structure alterations accompanying pyrrole formation at certain critical lysine-epsilon-amine functions in the neurofilament subunit proteins were hypothesized to underlie the neuropathy. A third hypothesis, involving charge neutralization of neurofilament proteins, implicated the loss of positive charge following the pyrrolylation reaction as the critical molecular lesion. The author postulated that the carboxy terminal tail of the neurofilament was the critical target in gamma-diketone neuropathy. This region was postulated to be particularly vulnerable to pyrrolylation due to its unusually high lysine content. It was hypothesized that this pyrrolylation induced structural and physicochemical alterations in the carboxy terminus, leading to cytoskeletal disorganization with subsequent blockade of axonal nutrient flow and ultimate nerve degeneration. Evidence to support this hypothesis was presented. The authors conclude that it is currently unclear whether pyrrolylation is sufficient to induce gamma-diketone neuropathy, or if secondary pyrrole autoxidation is also necessary.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Neurotoxicity; Pyrroles; Hexanes; Organic-solvents; Pathogenesis; Toxicology; Nerve-damage
Biochem and Genetic Toxicology New York State Dept of Health Empire State Plaza Albany, N Y 12201
Issue of Publication
Neurotoxic Disorders; Neurotoxic-effects
New York State Dept of Health, New York, New York
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division