SUBCHRONIC DELAYED NEUROTOXICITY EVALUATION OF JET ENGINE LUBRICANTS CONTAINING PHOSPHORUS ADDITIVES

Synthetic polyol-based lubricating oils containing 3% of either commer cial tricresyl phosphate (TCP), triphenylphosphorotihionate (TPPT), or butylated triphenyl phosphate (BTP) additive were evaluated for neuro toxicity in the adult hen using clinical, biochemical, and neuropathol ogical endpoints. Groups of 17-20 hens were administered the oils by o ral gavage at a ''limit dose'' of a g/kg, 5 days a week for 13 weeks. A group of positive control hens was included which received 7.5 mg/kg of one isomer of TCP (tri-ortho-cresyl phosphate, TOCP) on the same r egimen, with an additional oral dose of 580 mg/kg given 12 clays befor e the end of the experiment. A negative control group received saline. Neurotoxic esterase (NTE) activity in brain and spinal cord. of hens dosed with the lubricating oils was not significantly different from s aline controls after 6 weeks of treatment. After 13 weeks of dosing, N TE was inhibited 23 to 34% in brains of lubricant-treated hens. Clinic al assessments of walking ability did not indicate any differences bet ween the negative control group and lubricant-treated hens. Moreover, neuropathological examination revealed no alterations indicative of or ganophosphorus-induced delayed neuropathy (OPIDN). In hens treated wit h the positive control, significant inhibition of NTE was observed in brain and spinal cord at both 6 and 13 weeks of dosing; this group als o demonstrated clinical impairment and pathological lesions indicative of OPIDN, In conclusion, the results of the present study indicated t hat synthetic polyol-based lubricating oils containing up to 3% TCP, T PPT, or BTP had low neural oxic potential and should not pose a hazard under realistic conditions of exposure. (C) 1996 Society of Toxicolog y