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 acety lcholinesterase (AChE) in the blood and central nervous system (CNS) o f swine 6, 12, 24 and 48 h after a single oral dose of 800 mg tri-o-cr esyl phosphate (TOCP)/kg. At all evaluated intervals, inhibition of NT E activity in leukocytes and the CNS was 88% or higher, with only slig ht differences in NTE inhibition apparent among the various tissues ex amined. This extreme inhibition of NTE activity precluded correlation between inhibition of NTE in peripheral leukocytes and the CNS. Howeve r, the similarity in NTE response in leukocytes and the CNS following TOCP administration indicates the potential for leukocyte NTE as a bio chemical marker for organophosphorus ester-induced delayed neurotoxici ty (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 tissu e examined. in general, plasma AChE activity was more severely depress ed in all animals and responded more rapidly to TOCP administration. H owever, erythrocyte AChE more accurately reflected the enzyme's activi ty in the CNS and the clinical response to TOCP. Based on the data pro vided by this study, a threshold inhibition of erythrocyte AChE betwee n 59 and 74% is required for production of acute cholinergic signs.