Organophosphorus compounds which, after acute administration, inhibit neurotoxic esterase (NTE) by > or = 65% and undergo a subsequent 'aging' reaction, produce a delayed neuropathy characterized by degeneration of large and long nerve fibers. The present studies examine in detail the NTE-inhibiting properties of triphenyl phosphite (TPP), a plasticizer which produces ataxia and degeneration of the spinal cord in animals. A neurotoxic dosing regimen (1184 mg/kg/week, sc, for 2 weeks) inhibited both brain and spinal cord NTE (< or = 40%) only marginally 4 and 48 hr postdosing. By contrast, TPP was shown in vitro to be a potent inhibitor of rat brain NTE relative to Mipafox or diisopropyl phosphorofluoridate. Preincubation of 10 micromolar TPP in buffer (37 deg C) resulted in a time-dependent loss of TPP's ability to inhibit NTE. In summary, TPP is a powerful NTE inhibitor in vitro, but only a marginal NTE inhibitor after in vivo administration. These results raise questions as to the causal events mediating TPP-induced neuropathy in the rat. (Copyright (c) 1987 Academic Press, Inc.)