Neurotoxic esterase

Phosphonothioate Esters of Phenols. Phosphonates with a single P—C bond are highly toxic and persistent iasecticides but have not been used extensively because some compounds produce delayed neuropathy leading to irreversible paralysis ia higher animals, including humans. Such compounds specifically inhibit an enzyme, neurotoxic esterase, that is responsible for the growth and maintenance of long nerve axons (31,32). 

Ohkawa H, Oshita H, Miyamoto J. 1980. Comparison of inhibitory activity of various organophosphorus compounds against acetylcholinesterase and neurotoxic esterase of hens with respect to delayed neurotoxicity. Biochem Pharmacol 29 2721-2727. 

Gd gestational day (Gl) = gastric intubation (GO) = gavage in oil Hemato - hematological incr. = increased IPTPP = isopropyl triphenyl phosphate LD = lethal dose, 50% kill LOAEL = lowest-observed-adverse-effect level M = male MCV = mean corpuscular volume MCHC = mean corpuscular hemoglobin concentration mo = month(s) Musc/skel = musculoskeletal NOAEL = no-observed-adverse-effect level NS = not specified NTE = neurotoxic esterase RBC red blood cell Resp = respiratory TBEP = tributoxyethyl phosphate TBP = tributyl phosphate TMP = trimethyl phosphate TNBP = tri-n-butyl phosphate TOP = trioctyl phosphate wk = week(s) x = times yr = year(s). 

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... 

Padilla S, Veronesi B. 1985. The relationship between neurological damage and neurotoxic esterase inhibition in rats acutely exposed to tri-ortho-cresyl phosphate. Toxicol Appl Pharmacol 78 78-87. 

Richardson RJ, Moore TB, Kayyali US, et al. 1993. Chlorpyrifos Assessment of potential for delayed neurotoxicity by repeated dosing in adult hens with monitoring of brain acetylcholinesterase, brain and lymphocyte neurotoxic esterase, and plasma butyrylcholinesterase activities. Fundam Appl Toxicol 21 89-96. 

Schwab BW, Richardson RJ. 1986. Lymphocyte and brain neurotoxic esterase Dose and time dependence of inhibition in the hen examined with three organophosphorus esters. Toxicol Appl Pharmacol 83 1-9. 

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). 

M. Lotti, M.K. Johnson, Repeated small doses of neurotoxic organophosphate. Monitoring of neurotoxic esterase in brain and spinal cord. Arch. Toxicol. 45 263, 1980. 

Online file. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH. Vranken, M.A., H.C. DeBisschop, J.L. Willems. 1982. In vitro inhibition of neurotoxic esterase by organophosphorus nerve agents. Arch. Int. Pharmacodyn. Ther. 260 316-318. (Cited in Munro et al., 1994)... 

Pope, C.N., Tanaka, D., Jr., Padilla, S. (1993). The role of neurotoxic esterase (NTE) in the prevention and potentiation of organophosphorus-induced delayed neurotoxicity (OPIDN). Chem. Biol. Interact. 87 395-406. 

Clothier, B., Johnson, M.K. (1979). Rapid aging of neurotoxic esterase after inhibition by di-isopropylphosphorofluoridate. Biochem. J. 177 549-58. 

Dudek, B.R., Richardson, R.J. (1978). Occurrence of neurotoxic esterase in various tissues of hen. Toxicol. Appl. Pharmacol. 45 269-70 (abstract). 

Johnson, M.K. (1970). Organophosphoms and other inhibitors of brain neurotoxic esterase and the development of delayed neurotoxicity in hens. Biochem. J. 120 523-31. 

Johnson, M.K. (1975). Stmcture-activity relationships for substrates and inhibitors of hen brain neurotoxic esterase. Biochem. Pharmacol. 24 797-805. 

Johnson, M.K. (1977). Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential. Toxicol. 37 113-15. 

Johnson, M.K., Lotti, M. (1980). Delayed neurotoxicity caused by chronic feeding of organophosphates requires a high point of inhihition of neurotoxic esterase. Toxicol. Lett. 5 99-102. 

Kayyali, U.S., Moore, T.B., Randall, J.C., Richardson, R.J. (1991). Neurotoxic esterase (NTE) assay optimized conditions based on detergent-induced shifts in the phenol/4-aminoantipyrine chromophore spectrum. J. Anal. Toxicol. 15 86-9. 

Novak, R., Padilla, S. (1986). An in vitro comparison of rat and chicken hrain neurotoxic esterase. Fundam. Appl. Toxicol. 6 464-71. 

Padilla, S.S., Grizzle, T.G., Lyerly, D. (1987). Triphenyl phosphite in vivo and in vitro inhibition of rat neurotoxic esterase. Toxicol. Appl. Pharmacol. 87 249-56. 

Richardson, R.J. (1984). Neurotoxic esterase normal and pathogenic roles. In Cellular and Molecular Neurotoxicology (T. Narahashi, ed.), pp. 285-95. Raven Press, New York. 

Richardson, R.J. (1992). Interactions of organophosphorus compounds with neurotoxic esterase. In Organophosphates Chemistry, Fate, and Ejfects (J.E. Chambers, P.E. Levi, eds), pp. 299-323. Academic Press, San Diego. 

Richardson, R.J., Dudek, B.R. (1983). Neurotoxic esterase characterization and potential for a predictive screen for exposure to neuropathic organophosphates. In Pesticide Chemistry Human Welfare and the Environment, Vol. 3 (J. Miyamoto, P.C. Kearney, eds), pp. 491-5. Pergamon Press, Oxford. 

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