N-hexane neurotoxicity: a mechanism involving pyrrole adduct formation in axonal cytoskeletal protein.

Details

• Personal Author:
  DeCaprio AP
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Hexanes Nervous System Occupational Health Safety Solvents Toxicology
• Keywords:
  NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Neurotoxicity; Pyrroles; Hexanes; Organic-solvents; Pathogenesis; Toxicology; Nerve-damage
• ISSN:
  0161-813X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  199-210
• Volume:
  8
• Issue:
  1
• NIOSHTIC Number:
  nn:00167062
• Citation:
  Neurotoxicology 1987 Jan; 8(1):199-210
• Contact Point Address:
  Biochem and Genetic Toxicology New York State Dept of Health Empire State Plaza Albany, N Y 12201
• CAS Registry Number:
  1H-Pyrrole (CAS RN 109-97-7) ; Hexane (CAS RN 110-54-3)
• Federal Fiscal Year:
  1987
• NORA Priority Area:
  Neurotoxic Disorders ; Neurotoxic Effects
• Performing Organization:
  New York State Dept of Health, New York, New York
• Peer Reviewed:
  True
• Start Date:
  19840501
• Source Full Name:
  Neurotoxicology
• End Date:
  19871031
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/247588/cdc_247588_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]