Subchronic Delayed Neurotoxicity Evaluation of Jet Engine Lubricants Containing Phosphorus Additives

Synthetic polyol-based lubricating oils containing 3% of eithercommercial tricresyl phosphate (TCP), triphenylphosphorothionate(TPPT), or butylated triphenyl phosphate (BTP) additive wereevaluated for neurotoxicity in the adult hen using clinical,biochemical, and neuropathological endpoints. Groups of 17–20hens were administered the oils by oral gavage at a "limit dose"of 1 g/kg, 5 days a week for 13 weeks. A group of positive controlhens was included which received 7.5 mg/kg of one isomer ofTCP (tri-ortho-cresyl phosphate, TOCP) on the same regimen,with an additional oral dose of 500 mg/kg given 12 days beforethe end of the experiment. A negative control group receivedsaline. Neurotoxic esterase (NTE) activity in brain and spinalcord of hens dosed with the lubricating oils was not significantlydifferent from saline controls after 6 weeks of treatment. After13 weeks of dosing, NTE was inhibited 23 to 34% in brains oflubricant-treated hens. Clinical assessments of walking abilitydid not indicate any differences between the negative controlgroup and lubricant-treated hens. Moreover, neuropathologicalexamination revealed no alterations indicative of organophosphorus-induceddelayed neuropathy (OPIDN). in hens treated with the positivecontrol, significant inhibition of NTE was observed in brainand spinal cord at both 6 and 13 weeks of dosing; this groupalso demonstrated clinical impairment and pathological lesionsindicative of OPIDN. In conclusion, the results of the presentstudy indicated that synthetic polyol-based lubricating oilscontaining up to 3% TCP, TPPT, or BTP had low neurotoxic potentialand should not pose a hazard under realistic conditions of exposure.