The effect of a single oral dose of tri-o-cresyl phosphate on neurotoxic esterase and acetylcholinesterase activities in the central nervous system, erythrocytes and plasma.
This study reports the activity of neurotoxic esterase (NTE) and acetylcholinesterase (AChE) in the blood and central nervous system (CNS) of swine 6, 12, 24 and 48 h after a single oral dose of 800 mg tri-o-cresyl phosphate (TOCP)/kg. At all evaluated intervals, inhibition of NTE activity in leukocytes and the CNS was 88% or higher, with only slight differences in NTE inhibition apparent among the various tissues examined. This extreme inhibition of NTE activity precluded correlation between inhibition of NTE in peripheral leukocytes and the CNS. However, the similarity in NTE response in leukocytes and the CNS following TOCP administration indicates the potential for leukocyte NTE as a biochemical marker for organophosphorus ester-induced delayed neurotoxicity (OPIDN) development. As the distribution pattern of NTE in the CNS of swine closely parallels that of man, these results further suggest that swine may prove a useful animal model for the study of OPIDN. The activity of AChE was highly variable based on time of assay and tissue examined. In general, plasma AChE activity was more severely depressed in all animals and responded more rapidly to TOCP administration. However, erythrocyte AChE more accurately reflected the enzyme's activity in the CNS and the clinical response to TOCP. Based on the data provided by this study, a threshold inhibition of erythrocyte AChE between 59 and 74% is required for production of acute cholinergic signs.
Barrett
D S
DS
Comparative Toxicology Laboratories, College of Veterinary Medicine, Kansas State University, Manhattan 66506.
Oehme
F W
FW
D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002490:Central Nervous System / Q000187:drug effects / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D013552:Swine; D013997:Time Factors; D014317:Tritolyl Phosphates / Q000494:pharmacology* / Q000633:toxicity
D002800:Cholinesterase Inhibitors; D014317:Tritolyl Phosphates; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase; C025541:tri-o-cresyl phosphate