Feline nervous system response to chronic intoxication with commercial grades of methyl n-butyl ketone, methyl isobutyl ketone, and methyl ethyl ketone

Peter S. Spencer, Herbert H. Schaumburg

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Twenty-eight 2-3 kg cats received sc injections twice daily, 5 days a week for up to 8.5 months, of the following commericial solvents: (1) methyl n-butyl ketone (MBK, 99.66% purity), (2) methyl ethyl ketone (MEK, 99.98% purity), (3) methyl isobutyl ketone (MiBK, 98.79% purity), (4) 9:1 mixtures of MEK MBK, or (5) MEK MiBK, respectively. Four control cats similarly received an equivalent volume of saline. Tissues removed at biopsy, or after systemic perfusion with fixatives, were examined by light and electron microscopy. The following tissues were studied: pacinian corpuscles, plantar nerves, and interosseous muscles taken by biopsy from hindfect of cats in groups 1-5 after 40 and 135 days of intoxication; posterior tibial nerves and pacinian corpuscles of cats in group 2 taken by biopsy after 8.5 months; hindlimb spinal roots and ganglia, nerves, and muscles, plus multiple levels of the spinal cord and medulla oblongata of group 1 animals sampled after perfusion following 2, 4, or 6 months of intoxication. Symmetrical, distal weakness developed progressively after 8 weeks of MBK treatment, first in the hindlimbs and later in all limbs. Nerve fiber pathological changes, characterized by multifocally swollen axons filled with neurofilaments, secondary changes of myelin sheaths and overt fiber breakdown, were seen concurrently in sampled areas of the peripheral and central nervous systems of MBK-treated animals with and without neurological signs. Degeneration first affected the distal parts of nerve tracts, spreading proximally at later stages. This spatial-temporal distribution of disease, a characteristic of several experimental toxic neuropathies, is designated central-peripheral distal axonopathy. In animals intoxicated with a mixture of MEK and MBK, subclinical pathological changes were seen in tibial nerves supplying calf muscles but not in pacinian corpuscles located in the hindfeet. These data indicate that MBK is neurotoxic to cats. Cats treated with MEK alone, MiBK alone, or 9:1 mixtures of these compounds, failed to develop detectable nervous system damage.

Original languageEnglish (US)
Pages (from-to)301-311
Number of pages11
JournalToxicology and Applied Pharmacology
Volume37
Issue number2
DOIs
StatePublished - Aug 1976

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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