Subchronic delayed neurotoxicity evaluation of jet engine lubricants containing phosphorus additives.
Synthetic polyol-based lubricating oils containing 3% of either commercial tricresyl phosphate (TCP), triphenylphosphorothionate (TPPT), or butylated triphenyl phosphate (BTP) additive were evaluated for neurotoxicity in the adult hen using clinical, biochemical, and neuropathological endpoints. Groups of 17-20 hens 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 control hens was included which received 7.5 mg/kg of one isomer of TCP (tri-ortho-cresyl phosphate, TOCP) on the same regimen, with an additional oral dose of 500 mg/kg given 12 days before 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 saline controls after 6 weeks of treatment. After 13 weeks of dosing, NTE was inhibited 23 to 34% in brains of lubricant-treated hens. Clinical assessments of walking ability did not indicate any differences between the negative control group and lubricant-treated hens. Moreover, neuropathological examination revealed no alterations indicative of organophosphorus-induced delayed neuropathy (OPIDN). In hens treated with the positive control, significant inhibition of NTE was observed in brain and spinal cord at both 6 and 13 weeks of dosing; this group also demonstrated clinical impairment and pathological lesions indicative of OPIDN. In conclusion, the results of the present study indicated that synthetic polyol-based lubricating oils containing up to 3% TCP, TPPT, or BTP had low neurotoxic potential and should not pose a hazard under realistic conditions of exposure.
Daughtrey
W
W
Exxon Biomedical Sciences, Inc., East Millstone, New Jersey 08875-2350, USA.
Biles
R
R
Jortner
B
B
Ehrich
M
M
D000110:Acetylcholinesterase / Q000378:metabolism; D000401:Aircraft; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002490:Central Nervous System / Q000187:drug effects*; D002645:Chickens; D004950:Esterases / Q000378:metabolism; D008153:Lubrication; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology; D014317:Tritolyl Phosphates / Q000633:toxicity*
D014317:Tritolyl Phosphates; D004950:Esterases; D000110:Acetylcholinesterase