Neuropathy or Neurotoxic Target Esterase

Of several avian species sensitive to OPIDP, the adult hen has been accepted as a suitable species for evaluating the potential hazards from organophosphorus esters (Johnson 1974 Johnson and Richardson 1983 Seifert and Wilson 1994 Glynn 

Other species, including rats, rabbits, guinea pigs, and hamsters, do not exhibit consistent delayed neurotoxic responses to the neuropathic organophosphorus compounds (e.g., tri-ortho cresyl phosphate). 

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A third enzyme may have limited potential as a measure of exposure. Neurotoxic esterase, also known as neuropathy target esterase (NTE), is inhibited by certain organophosphate esters. When brain NTE is inhibited above 70% for acute or possibly as low as 50% for repeated exposures, there is a consensus that delayed neuropathy is likely. NTE also is found in lymphocytes and platelets (Lotti et al. 1984). The... 

Some OP compounds induce delayed neurotoxic effects ("delayed neuropathy") after acute poisoning. This delayed neurotoxic action is independent of cholinesterase inhibition but related to phosphorylation of a specific esterasic enzyme in the nervous tissue, called "neurotoxic esterase" or "neuropathy target esterase" (NTE) (Johnson, 1982). NTE is present in the nervous tissue, liver lymphocytes, platelets, and other tissues, but its physiological function is unknown. There is a rather large inter-individual variation of lymphocyte and platelet NTE activity (Table 2). 

DEF is a relatively weak inhibitor of acetylcholinesterase. The compound is hydrolyzed to a large extent in the intestine to -butyl mercaptan, which is responsible for the late acute effects of DEF. The putative molecular target in neural tissue for initiation of delayed neuropathy is neurotoxic esterase or neuropathy target esterase (NTE). 

The esterase got the names neurotoxic esterase or neuropathy target esterase, and the ester phenyl valerate (PV) was found to be a good substrate for this esterase. However, PV is also hydrolyzed by other esterases because paraoxon, which does not give symptoms of delayed neurotoxicity, inhibited the PV activity as much as 80%. The NTE is defined as the hydrolytic activity against PV that is not inhibited by paraoxon but by mipafox. About 3% of the activity is not inhibited by mipafox plus paraoxon. Thus, the part of PV activity due to neurotoxic esterase should be 17%. 

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