Subchronic Neurotoxicity of Oil Formulations Containing Either Tricresyl Phosphate or Tri-Orthocresyl Phosphate

Abstract

This study was conducted to determine the threshold concentration of tricresyl phosphate (TCP) in aviation engine oil able to cause delayed peripheral neuropathy in adult hens after repeated exposure. The study also evaluated the predictive value of endpoints usually used to measure acute peripheral neurotoxicity (neurotoxic esterase [NTE] inhibition, ataxia, and histopathologic changes), as measures of neurotoxicity in a subchronic study. Animals that received oil containing 3% TCP showed significant neurotoxicity that could not be accounted for by the small amount of TOCP present. Oil containing 1% TCP was without neurotoxic activity. There was an excellent correlation between percentage inhibition of NTE and development of neuropathy. An association was also seen for ataxia and neuropathology. Further study is needed to determine the phosphate ester isomers responsible for the significant neurotoxic potency demonstrated by the aviation engine oil containing 3% TCP. © 1993, American College of Toxicology. All rights reserved.