Assessment of the delayed neurotoxicity of tributyl phosphate, tributoxyethyl phosphate, and dibutylphenyl phosphate.
There industrial organophosphorus compounds were tested for their ability to cause organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the adult hen. The compounds tested were tributyl phosphate (TBP), tributoxyethyl phosphate (TBEP), and dibutylphenyl phosphate (DBPP). The acute oral LD50 of TBP and DBPP were estimated to be 1,863 and 1,500 mg/kg, respectively, and the dose equal to the LD50 was used as a test dose. The acute oral LD50 of TBEP was greater than 5,000 mg/kg and 5,000 mg/kg was used as a test dose. An oral dose of 750 mg tri-o-cresyl phosphate (TOCP) was used as a positive control. For the acute delayed neurotoxicity test, hens were given two test doses of the test materials 21 days apart and killed 21 days after the second dose. None of the hens given TBP, TBEP, or DBPP exhibited nerve damage or clinical signs which distinguished them from untreated control animals. A single dose of TOCP resulted in paralysis and a histopathological profile typical of a distal neuropathy. For the assay of the inhibition of esterases, hens were killed 24 hours after a single dose equal to the greater of either the LD50 or 5000 mg/kg. TOCP administration resulted in over 90% inhibition of brain neurotoxic esterase (NTE), but none of the other three compounds inhibited NTE to an extent (greater than 70%) which would be expected to result in OPIDN. Administration of TOCP, TBEP, or DBPP resulted in approximately a 70% decrease in plasma butyrylcholinesterase (BuChE) activity. TBP caused a 2-3 fold increase in BuChE activity. TBEP administration resulted in about 45% inhibition of acetycholinesterase (AChE) in brain. These results indicate that TBP, TBEP, and DBPP are all unlikely to cause OPIDN with any single sublethal dose.
Carrington
C D
CD
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.
Lapadula
D M
DM
Othman
M
M
Farr
C
C
Nair
R S
RS
Johannsen
F
F
Abou-Donia
M B
MB
D000818:Animals; D001921:Brain / Q000187:drug effects; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors; D002645:Chickens; D002800:Cholinesterase Inhibitors; D005260:Female; D007928:Lethal Dose 50; D009422:Nervous System Diseases / Q000139:chemically induced*; D010755:Organophosphates / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010525:Peripheral Nerves / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects; D013997:Time Factors; D014317:Tritolyl Phosphates / Q000633:toxicity
D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D009943:Organophosphorus Compounds; D014317:Tritolyl Phosphates; C025742:dibutyl phenylphosphate; C009524:tributyl phosphate; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; C013320:tris(2-butoxyethyl) phosphate; C025541:tri-o-cresyl phosphate