Blood Cholinesterases as Human Biomarkers of Organophosphorus Pesticide Exposure

  • Herbert N. Nigg
  • James B. Knaak
Part of the Reviews of Environmental Contamination and Toxicology book series (RECT, volume 163)


The organophosphorus (OP) insecticides were developed before and during World War II. The history of their development has been reviewed (Holmstedt 1963; Karczmar 1970; Ursdin 1970; Koelle 1981). In 1936, Schrader synthesized paraoxon, parathion, and octamethylpyrophosphoramide (OMPA, schradan) in a search for an effective cockroach control agent (Ursdin 1970). Parathion use in agriculture began after World War II. In 1949, a mixer loader was killed by parathion in Lake Placid, FL (Griffiths et al. 1951). Monitoring red blood cell acetyl-cholinesterase (RBC AChE) of exposed workers was begun in 1950 in the Florida citrus industry (Griffiths et al. 1951), perhaps the first use of human blood esterase monitoring in agriculture.


PBPK Model Methyl Parathion Organophosphorus Pesticide Plasma Cholinesterase Brain AChE 
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  1. Aldridge WN (1950) Some properties of specific cholinesterase with particular reference to the mechanism of inhibition by diethyl p-nitrophenyl thiophosphate (E 605) and analogues. Biochem J 46: 451–460.PubMedGoogle Scholar
  2. Aldridge WN (1953a) Serum esterases. I. Two types of esterase (A and B) hydrolyzing p-nitrophenyl acetate, propionate, and butyrate, and a method for their determination. Biochem J 53: 110–117.PubMedGoogle Scholar
  3. Aldridge WN (1953b) Differentiation of true and pseudo cholinesterase by organophosphorus compounds. Biochem J 53: 62–67.PubMedGoogle Scholar
  4. Aldridge WN (1954a) Tricresyl phosphates and cholinesterase. Biochem J 56:185–189. Aldridge WN (1954b) Anticholinesterases. Inhibition of cholinesterase by organophosphorus compounds and reversal of this reaction. Mechanism involved. Chem Ind 473–476.Google Scholar
  5. Aldridge WN, Davison AN (1953) Mechanism of inhibition of cholinesterases by organo-phosphorus compounds. Biochem J 55: 763–765.PubMedGoogle Scholar
  6. Aldridge WN, Reiner E (1972) Enzyme inhibitors as substrates. In: Neuberger A, Tatum EL (eds) North-Holland Research Monographs, Frontiers of Biology, Vol. 26. North-Hollands, London, p 236.Google Scholar
  7. Alles GA, Hawes RC (1940) Cholinesterases in the blood of man. J Biol Chem 133: 375–390.Google Scholar
  8. Alozie SO, Sharma RP, Salunkhe DK (1978) Inhibition of rat cholinesterase isoenzymes in vitro and in vivo by the potato alkaloid, oc-chaconine. J Food Biochem 2: 259–276.Google Scholar
  9. Areekul S, Srichairat S, Kirdudom P (1981) Serum and red cell cholinesterase activity in people exposed to organophosphate insecticides. Southeast Asian J Trop Med Public Health 12: 94–98.PubMedGoogle Scholar
  10. Arpagaus M, Chatonnet A, Masson P, Newton M, Vaughan TA, Bartels CF, Nogueira CP, La Du BN, Lockridge O (1991) Use of the polymerase chain reaction for homology probing of butyrylcholinesterase from several vertebrates. J Biol Chem 266: 6966–6974.PubMedGoogle Scholar
  11. Atack JR, Perry EK, Bonham JR, Perry RH (1987) Molecular forms of acetylcholinesterase and butyrylcholinesterase in human plasma and cerebrospinal fluid. J Neurochem 48: 1845–1850.PubMedGoogle Scholar
  12. Atack JR, Yu QS, Soncrant TT, Brossi A, Rapoport SI (1989) Comparative inhibitory effects of various physostigmine analogs against acetyl-and butyrylcholinesterases. J Pharmacol Exp Ther 249: 194–202.PubMedGoogle Scholar
  13. Atkins EL, Rubins CH, Olsoni DR, Jackson RJ (1998) Rapid assessment of organophosphate-reduced cholinesterase depression: a comparison of laboratory and field kit methods to detect human exposure to organophosphates. Appl Occup Environ Hyg 15: 265–268.Google Scholar
  14. Augustinsson KB (1948) Cholinesterase: a study in comparative enzymology. Acta Physiol Scand Suppl 15: 1–182.Google Scholar
  15. Augustinsson KB (1949) Substrate concentration and specificity of choline ester-splitting enzymes. Arch Biochem 23: 111–126.PubMedGoogle Scholar
  16. Augustinsson KB (1955) The normal variation of human blood cholinesterase activity. Acta Physiol Scand 35: 40–52.PubMedGoogle Scholar
  17. Augustinsson KB (1960) Butyryl-and propionylcholinesterases and related types of eserine-sensitive esterases. In: Boyer PD, Lardy H, Myrbdck (eds) The Enzymes, 2nd Ed., Vol. 4. Academic Press, New York, pp 521–540.Google Scholar
  18. Bell JU, Van Petten GR, Taylor PJ, Aiken MJ (1979) The inhibition and reactivation of human maternal and fetal plasma cholinesterase following exposure to the organo-phosphate, dichlorvos. Life Sci 24: 247–254.PubMedGoogle Scholar
  19. Benjamini E, Metcalf RL, Fukuto TR (1959a) The chemistry and mode of action of the insecticide 0,0-diethyl 0p-methyl sulfinyl phenyl phosphorothionate and its analogues. J Econ Entomol 52: 94–98.Google Scholar
  20. Benjamini E, Metcalf RL, Fukuto TR (1959b) Contact and systemic insecticidal properties of 0,0-diethyl 0p-methyl sulfinyl phenyl phosphorothionate and its analogues. J Econ Entomol 52: 99–102.Google Scholar
  21. Berman HA (1995) Reaction of acetylcholinesterase with organophosphonates. In: Quinn DM et al. (eds) The Enzymes of the Cholinesterase Family. Plenum Press, New York, pp 177–182.Google Scholar
  22. Berman HA, Decker MM (1989) Chiral nature of covalent methylphosphonyl conjugates of acetylcholinesterase. J Biol Chem 264: 3951–3956.PubMedGoogle Scholar
  23. Berman HA, Leonard K (1989) Chiral reactions of acetylcholinesterase probed with enantiomeric methylphosphorothioates. J Biol Chem 264: 3942–3950.PubMedGoogle Scholar
  24. Bernsohn J, Barron KD, Hess A (1961) Cholinesterases in serum as demonstrated by starch gel electrophoresis. Proc Soc Exp Biol Med 108: 71–73.PubMedGoogle Scholar
  25. Bogusz M (1968) Influence of insecticides on the activity of some enzymes contained in human serum. Clin Chim Acta 19: 367–369.PubMedGoogle Scholar
  26. Bonham JR, Gowenlock AH, Timothy JAD (1981) Acetylcholinesterase and butyrylcholinesterase measurement in the pre-natal detection of neural tube defects and other fetal malformations. Clin Chim Acta 115: 163–170.PubMedGoogle Scholar
  27. Bowman JS, Casida JE (1957) Metabolism of the systemic insecticide 0,0-diethyl S-ethylthiomethyl phosphorodithioate (Thimet) in plants. J Agric Food Chem 5: 192–197.Google Scholar
  28. Brauer RW (1948) Inhibition of the cholinesterase activity of human blood plasma and ereythrocyte stromata by alkylated phosphorus compounds. J Pharmacol Exp Ther 92: 162–172.PubMedGoogle Scholar
  29. Brock A (1990) Immunoreactive plasma cholinesterase (EC substance concentration, compared with cholinesterase activity concentration and albumin: inter-and intra-individual variations in a healthy population group. J Clin Chem Clin Biochem 28: 851–856.PubMedGoogle Scholar
  30. Brock A (1991) Inter and intraindividual variations in plasma cholinesterase activity and substance concentration in employees of an organophosphorous insecticide factory. Br J Ind Med 48: 562–567.PubMedGoogle Scholar
  31. Brock A, Brock V (1993) Factors affecting inter-individual variation in human plasma cholinesterase activity: body weight, height, sex, genetic polymorphism and age. Arch Environ Contam Toxicol 24: 93–99.PubMedGoogle Scholar
  32. Bull DL (1970) Metabolism of organophosphorus insecticides. Presented at the Annual Meeting of the Entomological Society of America, Miami.Google Scholar
  33. Bull DL, Linguist DA (1964) Metabolism of 3-hydroxy-N,N-dimethyl-crotonamide dimethyl phosphate by cotton plants, insects and rats. J Agric Food Chem 12: 310–317.Google Scholar
  34. Bull DL, Linguist DA (1966) Metabolism of 3-hydroxy-N-methyl-cis-crotonamide dimethyl phosphate (azodrin). J Agric Food Chem 14: 105–109.Google Scholar
  35. Bull DL, Lindquist DA, Grabbe RR (1967) Comparative fate of the geometric isomers of phosphamidon in plants and animals. J Econ Entomol 60: 332–341.Google Scholar
  36. Callaway S, Davies DR, Rutland JP (1951) Blood cholinesterase levels and range of personal variation in a healthy adult population. Br Med J 2: 812–816.PubMedGoogle Scholar
  37. Carter MK, Maddux B (1974) Interaction of dichlorvos and anticholinesterases on the in vitro inhibition of human blood cholinesterases. Toxicol Appl Pharmacol 27: 456–463.PubMedGoogle Scholar
  38. Casida JE (1956) Metabolism of organophosphorus insecticides in relation to their anties- terase activity, stability, and residual properties. J Agrc Food Chem 4: 772–785.Google Scholar
  39. Chambers JE (1992) The role of target site activation of phosphorothionates in acute toxicity. In: Chambers JE, Levi PE (eds) Organophosphates Chemistry, Fate, and Effects. Academic Press, New York, pp 229–239.Google Scholar
  40. Chambers JE, Ma T, Boone JS, Chambers HW (1994) Role of detoxification pathways in acute toxicity levels of phosphorothionate insecticides in the rat. Life Sci 54: 1357–1364.PubMedGoogle Scholar
  41. Chatonnet A, Lockridge O (1989) Comparison of butyrylcholinesterase and acetylcholinesterase. Biochem J 260: 625–634.PubMedGoogle Scholar
  42. Clemmons GP, Menzer RE (1968) Oxidative metabolism of phosphamidon in rats and a goat. J Agric Food Chem 16: 312–318.Google Scholar
  43. Cohen JA, Warringa MGPJ (1957) Purification and properties of dialkyl fluorophosphatase. Biochim Biophys Acta 26: 29–39.PubMedGoogle Scholar
  44. Cohen JA, Oosterbaan RA, Warringa MGPA (1955) Turnover number of ali-esterase, pseudo-and true cholinesterase and the combination of these enzymes with diisopropyl fluorophosphate (DFP). Biochim Biophys Acta 18: 228–235.PubMedGoogle Scholar
  45. Cohen SD, Williams RA, Killinger JM, Fredenthal RI (1985) Comparative sensitivity of bovine and rodent acetylcholinesterase to in vitro inhibition by organophosphate insecticides. Toxicol Appl Pharmacol 81: 452–459.PubMedGoogle Scholar
  46. Comroe JH Jr, Todd J, Gammon GD, Leopold IH, Koelle GB, Bodansky O, Gilman A (1946a) The effect of di-isopropyl-fluorophosphate (DFP) upon patients with myasthenia gravis. Am J Med Sci 212: 641–651.PubMedGoogle Scholar
  47. Comroe JH Jr, Todd J, Koelle GB (1946b) The pharmacology of di-isopropyl fluorophosphate (DFP) in man. J Pharmacol Exp Ther 87: 281–290.PubMedGoogle Scholar
  48. Cook JW, Yip G (1958) Malathionase. II. Identity of a malathion metabolite. J Assoc Off Agric Chem 41: 407–411.Google Scholar
  49. Cook JW, Blake JK, Yip G, Williams M (1958) Malathionase. I. Activity and inhibition. J Assoc Off Agric Chem 41: 399–407.Google Scholar
  50. Dauterman WC (1971) Biological and non-biological modification of organophosphorus compounds. Bull World Health Org 44: 133–150.PubMedGoogle Scholar
  51. Dauterman WC, Viado GB, Casida JE, O’Brien RD (1960) Persistence of dimethoate and metabolites following foliar application to plants. J Agric Food Chem 8: 115–119.Google Scholar
  52. Dawson RM (1990) Reversibility of the inhibition of acetylcholinesterase by tacrine. Neurosci Lett 118: 85–87.PubMedGoogle Scholar
  53. Dean RA, Christian CD, Barry Sample RH, Bosron WF (1991) Human liver cocaine esterases: ethanol-mediated formation of ethylcocaine. Fed Am Soc Exp/Biol Monogr 5: 2735–2739.Google Scholar
  54. de Jong LPA, Van Dijk C, Benschop HP (1989) Stereoselective hydrolysis of soman and other chiral organophosphates by mammalian phosphorylphosphatases. In: Reiner E, Aldridge WN, Hoskin FCG, Horwood E (eds) Enzymes Hydrolysing Organophosphorus Compounds. Limited, Chichester, England, pp 65–78.Google Scholar
  55. Domino EF (1988) Galanthamine: another look at an old cholinesterase inhibitor. In: Giacobini E, Becker R (eds) Current Research in Alzheimer Therapy. Taylor and Francis, New York, pp 295–303.Google Scholar
  56. Dong MH, Ross JH, Thongsinthusak T, Krieger RI (1996) Use of spot urine sample results in physiologically based pharmacokinetic modeling of absorbed malathion doses. In: Blancato JN, Brown RN, Dary CC, Saleh MA (eds) Biomarkers for Agrochemicals and Toxic Substances: Applications and Risk Assessment. ACS Symposium Series 643. American Chemical Society, Washington, DC.Google Scholar
  57. Donninger C, Hutson HD, Pickering BA (1967) Oxidative cleavage of phosphoric acid tri-esters to diesters. Biochem J 102: 26–27.Google Scholar
  58. Douch PGC, Hook CER, Smith JN (1968) Metabolism of Folithion (O,O-dimethyl O-(4-nitro-m-tolyl) phosphorothioate). Aust J Pharm 49: S70 - S71.Google Scholar
  59. Drevenkar V, Radic Z, Vasilic Z, Reiner E (1991) Dialkylphosphorus metabolites in the urine and activities of esterases in the serum as biochemical indices for human absorption of organophosphorus pesticides. Arch Environ Contam Toxicol 20: 417–422.PubMedGoogle Scholar
  60. Duncan RC, Griffith J, Konefal J (1986) Comparison of plasma cholinesterase depression among workers occupationally exposed to organophosphorus pesticides as reported by various studies. J Toxicol Environ Health 18: 1–11.PubMedGoogle Scholar
  61. Eckerson HW, Oseroff A, Lockridge O, La Du BN (1983) Immunological comparison of the usual and atypical human serum cholinesterase phenotypes. Biochem Genet 21: 93–108.PubMedGoogle Scholar
  62. Ecobichon DJ, Stephens DS (1972) Perinatal development of human blood esterases. Clin Pharmacol Ther 14: 41–47.Google Scholar
  63. El Bashir S, Oppenoorth FJ (1969) Microsomal oxidations of organophosphate insecticides in some resistance strains of houseflies. Nature (Lond) 223: 210–211.Google Scholar
  64. Ellman GL, Courtney KD, Andres V Jr, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88–95.PubMedGoogle Scholar
  65. Enslein K, Gombar VK, Shapero D, Blake BW (1998) Prediction of rat oral LD50 values of organophosphates by QSAR equations. Topkat Health Designs, Rochester, NY.Google Scholar
  66. Eto M (1974) Organophosphorus Pesticides: Organic and Biological Chemistry. CRC Press, Boca Raton, FL, p 164.Google Scholar
  67. Eyer P (1995) Neuropsychopathological changes by organophosphorus compounds: a review. Hum Exp Toxicol 14: 857–864.PubMedGoogle Scholar
  68. Frawley JP, Hagan EC, Fitzhugh OG (1952) A comparative pharmacological and toxicological study of organic phosphate anticholinesterase compounds. J Pharmacol Exp Ther 105: 156–164.PubMedGoogle Scholar
  69. Freedman AM, Willis A, Himwich HE (1949) Correlation between signs of toxicity and cholinesterase level of brain and blood during recovery from di-isopropyl fluorophosphate (DFP) poisoning. Am J Physiol 57: 80–87.Google Scholar
  70. Fukami J, Shishido T (1966) Nature of the soluble, glutathione-dependent enzyme system active in cleavage of methyl parathion to desmethyl parathion. J Econ Entomol 59: 1338–1346.PubMedGoogle Scholar
  71. Fukunaga K (1967) The in vitro metabolism of organophosphorus insecticides by tissue homogenates from mammals and insect. In: U. S.—Japan Seminar, Experimental Approaches to Pesticide Metabolism, Degradation, and Mode of Action, pp 197–207.Google Scholar
  72. Fukunaga K, Fukami J, Shishido T (1969) The in vitro metabolism of organophosphorus insecticides by tissue homogenates from mammal and insect. Residue Rev 25: 223–250.Google Scholar
  73. Fukuto TR (1971) Relationship between the structure of organophosphorus compounds and their activity as acetylcholinesterase inhibitors. Bull World Health Org 44: 3142.Google Scholar
  74. Fukuto TR, Metcalf RL (1956) Structure and insecticidal activity of some diethyl substituted phenyl phosphates. J Agric Food Chem 4: 930–935.Google Scholar
  75. Fukuto TR, Metcalf RL, March RB, Maxon MG (1955) Chemical behavior of systox isomers in biological systems. J Econ Entomol 48: 347–354.Google Scholar
  76. Fukuto TR, Wolf JP, Mecalf RL, March RB (1956) Identification of the sulfoxide and sulfone plant metabolites of the thiol isomer of systox. J Econ Entomol 49: 147–151Google Scholar
  77. Gage JC (1953) A cholinesterase inhibitor derived from O, O-diethyl O p-nitrophenyl. Biochem J 54: 426–430.PubMedGoogle Scholar
  78. Gage JC (1955) Blood cholinesterase values in early diagnosis of excessive exposure to phosphorus insecticides. Br Med J 1: 1370–1372.PubMedGoogle Scholar
  79. Gage JC (1967) The significance of blood cholinesterase activity measurements. Residue Rev 18: 159–173.PubMedGoogle Scholar
  80. Ganelin RS (1964) Measurement of cholinesterase activity of the blood. Ariz Med 21: 710–714.PubMedGoogle Scholar
  81. Gearhart JM, Jepson GW, Clewell HJ, Andersen ME, Connolly RB (1990) Physiologically based pharmacokinetic and pharmacodynamic model for the inhibition of acetylcholinesterase by diisopropylfluorophosphate. Toxicol Appl Pharmacol. 106: 295–310.PubMedGoogle Scholar
  82. Geller I, Stebbins WC (1979) Introduction and overview. In: Geller I, Stebbins WC, Wayner MJ (eds) Proceedings of the Workshop on Test Methods for Definition of Effects of Toxic Substances on Behavior and Neuromotor Function. Neurobehav Toxicol 1: 7.Google Scholar
  83. Geller I, Stebbins WC, Wayner MJ (1979) Proceedings of the Workshop on Test Methods for Definition of Effects of Toxic Substances on Behavior and Neuromotor Function. Neurobehavioral Toxicology 1. Ankho International, Fayetteville, NY 225 ppGoogle Scholar
  84. Glick D (1937) Properties of choline esterase in human serum. Biochem J 31: 521–525.PubMedGoogle Scholar
  85. Gnatt A, Ginzberg D, Lieman-Hurwitz J, Zamir R, Zakut H, Soreq H (1991) Human acetylcholinesterase and butyrylcholinesterase are encoded by two distinct genes. Cell Mol Neurobiol 11: 91–104.PubMedGoogle Scholar
  86. Goldberg ME, Johnson HE, Knaak JB (1965) Inhibition of discrete avoidance behavior by three anticholinesterase agents. Psychopharmacologia 7: 72–76.PubMedGoogle Scholar
  87. Goldberg ME, Johnson HE, Knaak JB, Smyth HF (1963) Psychopharmacological effects of reversible cholinesterase inhibition induced by N-methyl 3-isopropyl phenyl carbamate (compound 10854). J Pharmacol Exp Ther 141: 244–252.PubMedGoogle Scholar
  88. Goldstein A (1951) Properties and behavior of purified human plasma cholinesterase. III. Competitive inhibition by prostigmine and other alkaloids with special reference to differences in kinetic behavior. Arch Biochem Biophys 34: 169–188.PubMedGoogle Scholar
  89. Griffiths JT, Sterns CR, Thompson WL (1951) Parathion hazards encountered spraying citrus in Florida. J Econ Entomol 44: 160–163.Google Scholar
  90. Grob D (1950) The anticholinesterase activity in vitro of the insecticide parathion (p-nitrophenyl diethyl thionophosphate). Bull Johns Hopkins Hosp 87: 95–105.PubMedGoogle Scholar
  91. Grob D (1956) The manifestations and treatment of poisoning due to nerve gas and other organic phosphate anticholinesterase compounds. Arch Intern Med 98: 221–239.Google Scholar
  92. Grob D, Harvey AM (1949) Observations on the effects of tetraethyl pyrophosphate (TEPP) in man, and on its use in the treatment of myasthenia gravis. Bull Johns Hopkins Hosp 84: 532–566.PubMedGoogle Scholar
  93. Grob D, Harvey JC (1958) Effects in man of the anticholinesterase compound sarin (isopropyl methyl phosphonofluoridate). J Chem Invest 37: 350–368.Google Scholar
  94. Grob D, Lilienthal JL Jr, Harvey AM, Jones BF (1947a) The administration of di-isopropyl fluorophosphate (DFP) to man. I. Effect on plasma and erythrocyte cholinesterase; general systemic effects; use in study of hepatic function and erythropoiesis; and some properties of plasma cholinesterase. Bull Johns Hopkins Hosp 81: 217–245.Google Scholar
  95. Grob D, Lilienthal JL Jr, Harvey AM (1947b) The administration of di-isopropyl fluoro-phosphate (DFP) to man. II. Effect on intestinal motility and use in the treatment of abdominal distention. Bull Johns Hopkins Hosp 81: 245–256.PubMedGoogle Scholar
  96. Grob D, Harvey AM, Langworthy OR, Lilienthal JL Jr (1947c) The administration of di-isopropyl fluorophosphate (DFP) to man. III. Effect on the central nervous system with special reference to the electrical activity of the brain. Bull Johns Hopkins Hosp 81: 257–292.PubMedGoogle Scholar
  97. Grob D, Garlick WL, Harvey AM (1950) The toxic effects in man of the anticholinesterase insecticide parathion (p-nitrophenyl diethyl thionophosphate). Bull Johns Hopkins Hosp 87: 106–129.PubMedGoogle Scholar
  98. Hada T, Ohue T, Imanishi H, Nakaoka H, Hirosaki A, Shimomura S, Fujikura M, Matsuda Y, Yamamoto T, Amuro Y, Higashino K (1990) Discrimination of liver cirrhosis from chronic hepatitis by analysis of serum cholinesterase isozymes using affinity electrophoresis with concanavalin A or wheat germ agglutinin. Gastroenterol Jpn 25: 715–719.PubMedGoogle Scholar
  99. Hansen ME, Wilson BW (1999) Oxime reactivation of RBC acetylcholinesterases for biomonitoring. Arch Environ Contam Toxicol 37: 283–289.PubMedGoogle Scholar
  100. Harris MH, Harris RS (1944) Effect in vitro of curare alkaloids and crude curare preparations on “true” and pseudo-cholinesterase activity. Proc Soc Exp Biol Med 56: 223–225.Google Scholar
  101. Harris H, Robson EB (1963) Fractionation of human serum cholinesterase components by gel filtration. Biochim Biophys Acta 73: 649–652.PubMedGoogle Scholar
  102. Harris H, Whittaker M (1959) Differential response of human serum cholinesterase types to an inhibitor in potato. Nature (Lond) 183: 1808–1809.Google Scholar
  103. Harris H, Whittaker M (1962) Differential inhibition of the serum cholinesterase phenotypes by solanine and solanidine. Ann Hum Genet 26: 73–76.PubMedGoogle Scholar
  104. Hart GJ, O’Brien RD (1973) Recording spectrophometric method for determination of dissociation and phosphorylation constants for the inhibition of acetylcholinesterase by organophosphates in the presence of substrate. Biochem 12: 2940–2945.Google Scholar
  105. Hartwell WV, Hayes GR Jr, Funckes AJ (1964) Respiratory exposure of volunteers to parathion. Arch Environ Health 8: 820–825.PubMedGoogle Scholar
  106. Harvey AM, Lilienthal JL Jr, Grob D, Jones BF, Talbot SA (1947) The administration of di-isopropyl fluorophosphate to man. IV The effects on neuromuscular function in normal subjects and in myasthenia gravis. Bull Johns Hopkins Hosp 81: 267–292.PubMedGoogle Scholar
  107. Hassan RM, Pesce AJ, Sheng P, Hanenson IB (1981) Correlation of serum pseudocholinesterase and clinical course in two patients poisoned with organophosphate insecticides. Clin Toxicol 18: 401–406.PubMedGoogle Scholar
  108. Hawkins RD, Mendel B (1949) Studies on cholinesterase. VI. The selective inhibition of true cholinesterase in vivo. Biochem J 44: 260–264.Google Scholar
  109. Hayes GR Jr, Funckes AJ, Hartwell WV (1964) Dermal exposure of human volunteers to parathion. Arch Environ Health 8: 829–833.PubMedGoogle Scholar
  110. Hayes WJ (1983) Pesticides Studied in Man. Williams and Wilkins, Baltimore, pp 284–435. Hayes WJ Jr (1969) Pesticides and human toxicity. Ann NY Acad Sci 160: 40–54.Google Scholar
  111. Heath DF, Park PO (1953) An irreversible choline-esterase inhibitor in white clover. Nature (Lond) 172: 206.Google Scholar
  112. Hellenäs K-E, Nyman A, Slanina P, Lvvf L, Gabrielsson J (1992) Determination of potato glycoalkaloids and their aglycone in blood serum by high-performance liquid chromatography. Application to pharmacokinetic studies in humans. J Chromatogr 573: 69–78.PubMedGoogle Scholar
  113. Hess AR, Angel RW, Barron KD, Bernsohn J (1963) Proteins and isozymes of esterases and cholinesterases from sera of different species. Clin Chim Acta 8: 656–667.PubMedGoogle Scholar
  114. Hitchcock M, Murphy SD (1967) Enzymatic reduction of O,O-(4-nitrophenyl) phosphorothioate, 0,0-diethyl O-(4-nitrophenyl) phosphate, and 0-Ethyl O-(4-nitrophenyl) benzene thiophosphonate by tissues from mammals, birds, and fishes. Biochem Pharmacol 16: 1801–1811.PubMedGoogle Scholar
  115. Hodgkin WE, Giblett ER, Levine H, Bauer W, Motulsky AG (1965) Complete pseudocholinesterase deficiency: genetic and immunologic characterization. J Clin Invest 44: 486–493.PubMedGoogle Scholar
  116. Hodgson E, Levi PE (1992) The role of the flavin-containing monooxygenase (EC in the metabolism and mode of action of agricultural chemicals. Xenobiotica 22: 1175–1183.PubMedGoogle Scholar
  117. Hodgson E, Levi PE (1994) Introduction to Biochemical Toxicology. Appleton and Lange, Norwalk, CT.Google Scholar
  118. Hodgson E, Rose RL, Ryu DY, Falls G, Blake BL, Levi PE (1995) Pesticide-metabolizing enzymes. Toxicol Lett 82 (83): 73–81.PubMedGoogle Scholar
  119. Hollingworth RM (1969) Dealkylation of organophosphorus esters by mouse liver enzymes in vitro and in vivo. J Agric Food Chem 17: 987–996.PubMedGoogle Scholar
  120. Hollingworth RM (1970) The dealkylation of organophosphorus triesters by liver enzymes. In: O’Brien RD, Yamamoto I (eds) Biochemical Toxicology of Insecticides, Vol. 70. Academic Press, New York, pp 75–92.Google Scholar
  121. Hollingworth RM (1971) Comparative metabolism and selectivity of organophosphate and carbamate insecticides. Bull World Health Org 44: 155–170.PubMedGoogle Scholar
  122. Hollingworth RM, Metcalf RL, Fukuto TR (1967) The selectivity of sumithion compared with methyl parathion. Metabolism in the white mouse. J Agric Food Chem 15: 242–249.Google Scholar
  123. Hollingworth RM, Alstott RL, Litzenberg RD (1973) Glutathione S-aryl transferase in the metabolism of parathion and its analogs. Life Sci 13: 191–199.PubMedGoogle Scholar
  124. Holmstedt B (1963) Structure-activity relationships of the organophosphorus anticholinesterase agents. In: Eichler O, Farah A, Koelle GB (eds) Handbuch Der Experimentellen Pharmakologie. Springer, Heidelberg, pp 428–485.Google Scholar
  125. Houwelingen RV, Nordoy A, van der Beek E, Houtsmuller U, de Metz M, Hornstra G (1987) Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males. Am J Clin Nutr 46: 424–436.Google Scholar
  126. Hutson DH, Pickering BA, Donniger C (1968) Non-hydrolytic detoxification of insecticidal phosphate triester. In: Abstracts of the 5th Meeting of the Federation of European Biochemical Societies, Prague.Google Scholar
  127. Johns RJ (1962) Familial reduction in red-cell cholinesterase. New Engl J Med 267: 1344–1348.Google Scholar
  128. Juul P (1968) Human plasma cholinesterase isoenzymes. Clin Chim Acta 19: 205–213.PubMedGoogle Scholar
  129. Kalow W, Davies RO (1958) The activity of various esterase inhibitors towards atypical human serum cholinesterase. Biochem Pharmacol 1: 183–192Google Scholar
  130. Kalow W, Genest K (1957) A method for the detection of atypical forms of human serum cholinesterase. Determination of dicubaine numbers. Can J Biochem Physiol 35: 339–346.PubMedGoogle Scholar
  131. Kalow W, Gunn DR (1959) Some statistical data on atypical cholinesterase of human serum. Ann Hum Genet 23: 239–250.PubMedGoogle Scholar
  132. Kalow W, Staron N (1957) On distribution and inheritance of atypical forms of human serum cholinesterase, as indicated by dibucaine numbers. Can J Biochem Physiol 35: 1305–1321.PubMedGoogle Scholar
  133. Karczmar AG (1970) Reactions of cholinesterases with substrate inhibitors and reactivators. In: International Encyclopedia of Pharmacology and Therapeutics: Anticholinesterase Agents. Pergamon Press, New York, pp 20–44.Google Scholar
  134. Karczmar AG (1984) Acute and long lasting central actions of organophosphorus agents. Fundam Appl Toxicol 4: S1 - S17.PubMedGoogle Scholar
  135. Knaak JB, O’Brien RD (1960) Effect of EPN on in vivo metabolism of malathion by the rat and dog. J Agric Food Chem 8: 198–203.Google Scholar
  136. Knaak JB, Maddy KT, Gallo MA, Lillie DT, Craine EM, Serat WF (1978a) Worker reentry study involving phosalone application to citrus groves. Toxicol Appl Pharmacol 46: 363–374.PubMedGoogle Scholar
  137. Knaak JB, Maddy KT, Jackson T, Fredrickson AS, Peoples SA, Love R (1978b) Cholinesterase activity in blood samples collected from field workers and nonfield workers in California. Toxicol Appl Pharmacol 45: 755–770.PubMedGoogle Scholar
  138. Knaak JB, Peoples SA, Jackson TA, Fredrickson AS, Enos R, Maddy KT, Bailey JB, Düsch ME, Gunther FA, Winterlin WL (1978c) Reentry problems involving the use of dialifor on grapes in the San Joaquin Valley of California. Arch Environ Contam Toxicol 7: 465–481.PubMedGoogle Scholar
  139. Knaak JB, Iwata Y, Maddy KT (1989) The worker hazard posed by reentry into pesticide-treated foliage: development of safe reentry times, with emphasis on chlorthiophos and carbosulfan. In: Pautenbach DJ (ed) The Risk Assessment of Environmental Hazards: A Textbook Case of Studies. Wiley, New York.Google Scholar
  140. Knaak JB, Al-Bayati MA, Raabe OG (1993a) Physiologically based pharmacokinetic modeling to predict tissue dose and cholinesterase inhibition in workers exposed to organophosphorous and carbamate pesticides. In: Wang GM, Knaak JB, Maibach HI (eds) Health Risk Assessment. Dermal and Inhalation Exposure and Absorption of Toxicants. CRC Press, Boca Raton, FL, pp 3–29.Google Scholar
  141. Knaak JB, Al-Bayati MA, Raabe OG, Blancato JN (1993b) Development of in vitro Vmax and Km values for the metabolism of isofenphos by P-450 enzymes in animals and humans. Toxicol Appl Pharmacol 120: 106–113.PubMedGoogle Scholar
  142. Knaak JB, Al-Bayati MA, Raabe OG, Blancato JN (1994) Prediction of anticholinesterase activity and urinary metabolites of isofenphos. In: Saleh MA, Blancato JN, Nauman CH (eds) Biomarkers of Human Exposure to Pesticides. ACS Symposium Series. American Chemical Society, Washington, DC, pp 284–300.Google Scholar
  143. Knaak JB, Al-Bayati MA, Raabe OG, Blancato IN (1996) Use of a multiple pathway and multiroute physiologically based pharmacokinetic model for predicting organophosphorus pesticide toxicity. In: Blancato JN, Brown RN, Dary CC, Saleh MA (eds) Biomarkers for Agrichemicals and Toxic Substances: Applications and Risk Assessment. ACS Symposium Series 643. American Chemical Society. Washington, DC, pp 206–228.Google Scholar
  144. Koelle GB (1981) Organophosphate poisoning—an overview. Fundam Appl Toxicol 1: 129–134.PubMedGoogle Scholar
  145. Kozikowski AP, Xia Y, Reddy ER, Tickmantel W, Hanin I, Tang XC (1991) Synthesis of huperzine A and its analogues and their anticholinesterase activity. J Org Chem 56: 4636–4645.Google Scholar
  146. Krause A, Lane AB, Jenkins T (1988) A new high activity plasma cholinesterase variant. J Med Genet 25: 677–681.PubMedGoogle Scholar
  147. Krieger RI (1995) Pesticide exposure assessment. Toxicol Lett 8283: 65–72.Google Scholar
  148. Kunstling TR, Rosse WF (1969) Erythrocyte acetylcholinesterase deficiency in paroxysmal nocturnal hemoglobinuria (PNH)—A comparison of the complement-sensitive and insensitive populations. Blood 33: 607–616.PubMedGoogle Scholar
  149. Kurono Y, Maki T, Yotsuyanagi Y, Ikeda K (1979) Esterase-like activity of human serum albumin: structure-activity relationships for the reactions with phenyl acetates and p-nitrophenyl esters. Chem Pharm Bull (Tokyo) 27: 2781–2786.Google Scholar
  150. Kurono Y, Kondo T, Ikeda K (1983) Esterase-like activity of human serum albumin: enantioselectivity in the burst phase of reaction withp-nitrophenyl a-methoxyphenyl acetate. Arch Biochem Biophys 227: 339–341.PubMedGoogle Scholar
  151. Kurono Y, Yamada H, Hata H, Okada Y, Takeuchi T, Ikeda K (1984) Esterase-like activity of human serum albumin. IV. Reactions with substituted aspirins and 5-nitrosalicyl esters. Chem Pharm Bull (Tokyo) 32: 3715–3719.Google Scholar
  152. Kurono Y, Miyajima M, Tsuji T, Yano T, Takeuchi T, Ikeda K (1991) Esterase-like activity of human serum albumin. VII. Reaction with p-nitrophenyl 4-guanidinobenzoate. Chem Pharm Bull (Tokyo) 39: 1292–1294.Google Scholar
  153. Kusic R, Jovanovic D, Randjelovic S, Joksovic D, Todorovic V, Boskovic B, Jokanovic M, Vojvodic V (1991) HI-6 in man: efficacy of the oxime in poisoning by organophosphorous insecticides. Hum Exp Toxicol 10: 113–118.PubMedGoogle Scholar
  154. La Du BN, Bartels CF, Nogueira CP, Hajra A, Lightstone H, Van Der Spek A, Lockridge O (1990) Phenotypic and molecular biological analysis of human butyrylcholinesterase variants. Clin Biochem 23: 423–431.Google Scholar
  155. La Du BN, Bartels CF, Nogueira CP, Arpagaus M, Lockridge O (1991) Proposed nomenclature for human butyrylcholinesterase genetic variants identified by DNA sequencing. Cell Mol Neurobiol 11: 79–89.Google Scholar
  156. LaMotta RV, Woronick CL (1971) Molecular heterogeneity of human serum cholinesterase. Clin Chem 17: 135–144.PubMedGoogle Scholar
  157. LaMotta RV, Williams HM, Wetstone HJ (1957) Studies of cholinesterase activity. II. Serum cholinesterase in hepatitis and cirrhosis. Gastroenterology 33: 50–56.PubMedGoogle Scholar
  158. LaMotta RV, McComb RB, Wetstone HJ (1965) Isozymes of serum cholinesterase: a new polymerization sequence. Can J Physiol Pharmacol 43: 313–318.PubMedGoogle Scholar
  159. LaMotta RV, McComb RB, Noll CR Jr, Wetstone HJ, Reinfrank RF (1968) Multiple forms of serum cholinesterase. Arch Biochem Biophys 124: 299–305.PubMedGoogle Scholar
  160. Lapidot-Lifson Y, Prody CA, Ginzberg D, Meytes D, Zakut H, Soreq H (1989) Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: correlation with various leukemias and abnormal megakaryocytopoiesis. Proc Natl Acad Sci USA 86: 4715–4719.PubMedGoogle Scholar
  161. Layer PG, Willbold E (1995) Novel functions of cholinesterases in development, physiology and disease. Prog Histochem Cytochem, 29:1–94 reverse Fischer, Stuttgart.Google Scholar
  162. Li Y, Camp S, Rachinsky TL, Getman D, Taylor P (1991) Gene structure of mammalian acetylcholinesterase. J Biol Chem 266: 23083–23090.PubMedGoogle Scholar
  163. Li Y, Camp S, Taylor P (1993a) Tissue-specific expression and alternative mRNA process- ing of the mammalian acetylcholinesterase gene. J Biol Chem 268: 5790–5797.PubMedGoogle Scholar
  164. Li Y, Camp S, Rachinsky TL, Bongiorno C, Taylor P (1993b) Promoter elements and transcriptional control of the mouse acetylcholinesterase gene. J Biol Chem 268: 3563–3572.PubMedGoogle Scholar
  165. Linguist DA, Bull DL (1967) Fate of 3-hydroxy-n-methyl-cis-crotonamide dimethyl phosphate in cotton plants. J Agric Food Chem 15: 267–272.Google Scholar
  166. Lockridge O (1990) Genetic variants of human serum cholinesterase influence metabolism of the muscle relaxant succinylcholine. Pharm Exp Ther 47: 35–60.Google Scholar
  167. Lockridge O, La Du BN (1978) Comparison of atypical and usual human serum cholinesterase. J Biol Chem 253: 361–366.PubMedGoogle Scholar
  168. Lockridge O, Eckerson HW, LaDu BN (1979) Interchain disulfide bonds and subunit organization in human serum cholinesterase. J Biol Chem 254: 8324–8330.PubMedGoogle Scholar
  169. Lockridge O, Adkins S, LaDu BN (1987a) Location of disulfide bonds within the sequence of human serum cholinesterase. J Biol Chem 262: 12945–12952.PubMedGoogle Scholar
  170. Lockridge O, Bartels CF, Vaughan TA, Wong CK, Norton SE, Johnson LL (1987b) Complete amino acid sequence of human serum cholinesterase. J Biol Chem 262: 549557.Google Scholar
  171. Loft AGR (1990) Determination of amniotic fluid acetylcholinesterase activity in the antenatal diagnosis of foetal malformations: the first ten years. J Clin Chem Clin Biochem 28: 893–911.PubMedGoogle Scholar
  172. Loft AGR, Mortensen V, Hangaard J, Norgaard-Pedersen B (1991) Ratio of immunochemically determined amniotic fluid acetylcholinesterase to butyrylcholinesterase in the differential diagnosis of fetal abnormalities. Br J Obstet Gynaecol 98: 52–56.PubMedGoogle Scholar
  173. Long KR (1975) Cholinesterase activity as a biological indicator of exposure to pesticides. Int Arch Occup Environ Health 36: 75–86.PubMedGoogle Scholar
  174. Lucier GW, Menzer RE (1968) Metabolism of dimethoate in bean plants in relation to its mode of application. J Agric Food Chem 16: 936–945.Google Scholar
  175. Lucier GW, Menzer RE (1970) Nature of oxidative metabolites of dimethoate formed in rats, liver microsomes and bean plants. J Agric Food Chem 18: 698–704.PubMedGoogle Scholar
  176. Ludwig PD, Kilian DJ, Dishburger HJ, Edwards HN (1970) Results of human exposure to thermal aerosols containing dursban insecticide. Mosq News 30: 346–354.Google Scholar
  177. Lynch TJ, Maltes CE, Singh A, Bradley RM, Brady RO, Dretchen KL (1997) Cocaine detoxification by human plasma by tyrylcholinesterase. Toxicol Appl Pharmacol 145: 363–371.PubMedGoogle Scholar
  178. Ma T, Chambers JE (1994) Kinetic parameters of desulfuration and dearylation of parathion and chlorpyrifos by rat liver microsomes. Food Chem Toxicol 32: 763–767.PubMedGoogle Scholar
  179. Main AR (1960a) The purification of the enzyme hydrolyzing diethyl p-nitrophenyl phosphate (paraoxon) in sheep serum. Biochem J 74: 10–20.PubMedGoogle Scholar
  180. Main AR (1960b) The differentiation of the A-type esterases in sheep serum. Biochem J 75: 188–195.PubMedGoogle Scholar
  181. Main AR (1964) Affinity and phosphorylation constants for the inhibition of esterases by organophosphates. Science 144: 992–993.PubMedGoogle Scholar
  182. Main AR (1969) Kinetic evidence of multiple reversible cholinesterases based on inhibition by organophosphates. J Biol Chem 244: 829–840.PubMedGoogle Scholar
  183. Main AR (1973) Kinetics of active-site directed irreversible inhibition. In: Hayes WL (ed) Essays in Toxicology. Academic Press, New York, p 59.Google Scholar
  184. Main AR, Iverson F (1966) Measurement of the affinity and phosphorylation constants governing irreversible inhibition of cholinesterases by di-isopropyl phosphorofluoridate, Biochem J 100: 525–531.PubMedGoogle Scholar
  185. Masson P (1979) Formes moleculaires multiples de la butyrylcholinesterase du plasma humain. I. Parametres moleculaires apparents et ebauche de la structure quaternaire. Biochim Biophys Acta 578: 493–504.PubMedGoogle Scholar
  186. Masson P (1989) A naturally occurring molecular form of human plasma cholinesterase is an albumin conjugate. Biochim Biophys Acta 988: 258–266.Google Scholar
  187. Masson P (1991) Molecular heterogeneity of human plasma cholinesterase. In: Massoulii J, Bacou F, Barnard E, Chatonnet A, Doctor B Quinn DM (eds) Cholinesterases: Structure, Function, Mechanism, Genetics, and Cell Biology. American Chemical Society, Washington DC, pp 42–46.Google Scholar
  188. Matsumura R (1975) Toxicology of Insecticides, Plenum Press, New York.Google Scholar
  189. Matsumura F, Hogendijk CJ (1964) The enzymatic degradation of parathion in organophosphate-susceptible and -resistant houseflies. J Agric Food Chem 12: 447–452.Google Scholar
  190. Matsuzaki S, Iwamura K, Katsunuma T, Kamiguchi H (1980a) Separation of serum cholinesterase isozymes by an improved polyacrylamide gel electrophoresis and its application for the study of liver diseases (Part I). Gastroenterol Jpn 15: 33–40.PubMedGoogle Scholar
  191. Matsuzaki S, Iwamura K, Katsunuma T, Kamiguchi H (1980b) Abnormalities of serum cholinesterase isozyme in liver cirrhosis and hepatoma (Part II). Gastroenterol Jpn 15: 543–549.PubMedGoogle Scholar
  192. Mattes CE, Lynch TJ, Singh A, Bradley RM, Kellaris PA, Brady PO, Dretchen KL (1997) Therapeutic use of butyrylcholinesterase for cocaine intoxication. Toxicol Appl Pharmacol 145: 372–380.PubMedGoogle Scholar
  193. McCurdy SA, Hansen ME, Weisskopf CP, Lopez RL, Schneider F, Spencer J, Sanborn JR, Krieger RI, Wilson BW, Goldsmith DF, Schenker MB (1994) Assessment of azinphosmethyl exposure in California peach harvest workers. Arch Environ Health 49: 289–296.PubMedGoogle Scholar
  194. Menzer R, Casida JE (1965) Nature of toxic metabolites formed in mammals insects and plants from 3-(dimethoxyphosphinyloxy)-N, N-dimethyl-cis-crotonamide and its N-methyl analog. J Agric Food Chem 13: 102–112.Google Scholar
  195. Menzie CM (1966) Metabolism of pesticides. Special Scientific Report—Wildlife No. 96. U. S. Department of the Interior, Fish and Wildlife Service, Washington, DC.Google Scholar
  196. Menzie CM (1969) Metabolism of pesticides. Special Scientific Report—Wildlife No. 127. U.S. Bureau of Sport Fisheries and Wildlife, Washington, DC.Google Scholar
  197. Mertens HW, Lewis MF, Steen JA (1974) Some behavioral effects of pesticides: phosdrin and free-operant escape-avoidance behavior in gerbils. Aerospace Med 45: 1171–1176.PubMedGoogle Scholar
  198. Metcalf RL, March RB (1953) The isomerization of organic thiophosphate insecticides. J Econ Entomol 46: 288–294.Google Scholar
  199. Metcalf RL, Fukuto TR, March RB (1957) Plant metabolism of dithio-systox and thimet. J Econ Entomol 50: 338–345.Google Scholar
  200. Michel HO, Krop S (1951) The reaction of cholinesterase with diisopropyl fluorophosphate. J Biol Chem 190: 119–125.PubMedGoogle Scholar
  201. Mileson BE, Chambers JE, Chen WL, Dettbarn W, Ehrich M, Eldefrawi AT, Gaylor DW, Hamernik K, Hodgson EA, Karczmar G, Padilla S, Pope, CN, Richardson RJ, Saunders DR, Sheets LP, Sultatos LG, Wallace KB (1998) Common mechanism of toxicity: a case study of organophosphorous pesticides. Toxicol Sci 41: 8–20.PubMedGoogle Scholar
  202. Moeller HC, Rider JA (1962) Plasma and red blood cell cholinesterase activity as indications of the threshold of incipient toxicity of ethyl-p-nitrophenyl thionobenzenephosphonate (EPN) and malathion in human beings. Toxicol Appl Pharmacol 4: 123–130.PubMedGoogle Scholar
  203. Moore DH, Clifford CB, Crawford IT, Cole GM, Baggett JM (1995) Review of nerve agent inhibitors and reactivators of acetylcholinesterase. In: Quinn, et al. (eds) Enzymes of the Cholinesterase Family. Plenum Press, New York.Google Scholar
  204. Morgan DP (ed) (1982) Recognition and Management of Pesticide Poisonings, 3rd Ed. U.S. Environmental Protection Agency, Washington, DC pp 1–8.Google Scholar
  205. Moriearty PL, Becker RE (1993) Inhibition of human brain and RBC acetylcholinesterase (AChE) by heptylphysostigmine (HPTL). Methods Find Exp Clin Pathol 14: 615–621.Google Scholar
  206. Morris SC, Lee TH (1984) The toxicity and teratogenicity of Solanaceae glycoalkaloids, particularly those of the potato (Solanum tuberosum): a review. Food Technol Aust 36: 118–124.Google Scholar
  207. Moss DE, Kobayashi H, Pacheco G, Palacios R, Perez RDG (1988) Methanesulfonyl fluoride: A CNS selective cholinesterase inhibitor. In: Giacobini E, Becker R (eds) Current Research in Alzheimer Therapy. Taylor and Francis, New York, pp 305–314.Google Scholar
  208. Mounter LA (1956) Identity of diisopropylfluorophosphatase and acylase. Fed Proc 15: 317–318.Google Scholar
  209. Mücke W, Alt KO, Esser O (1970) Degradation of 14C-labelled diazinon in the rat. J Agric Food Chem 18: 208–212.PubMedGoogle Scholar
  210. Murphy SD (1966) Liver metabolism and toxicity of thiophosphate insecticides in mammalian, avian and piscine species. Proc Soc Exp Biol Med 123: 392–398.Google Scholar
  211. Murphy SD (1972) The toxicity of pesticides and their metabolites. In: Degradation of Synthetic Organic Molecules in the Biosphere. National Academy of Science, Washington, DC, pp 313–335.Google Scholar
  212. Murphy SD (1980) Pesticides. In: Casarett U, Doull J (eds) Casarett and Doull’s Toxicology: The Basic Science of Poisons, 2nd Ed. Macmillan, New York, pp 357–375.Google Scholar
  213. Murphy SD, Lauwerys RR, Cheever KL (1968) Comparative anticholinesterase action of organophosphorus insecticides in vertebrates. Toxicol Appl Pharmacol 12: 22–35.PubMedGoogle Scholar
  214. Nakatsugawa T, Dahm PA (1967) Microsomal metabolism of parathion. Biochem Pharmacol 16: 25–38.Google Scholar
  215. Namba T (1971) Cholinesterase inhibition by organophosphorus compounds and its clinical effects. Bull Org Mond Sante (Bull World Health Org) 44: 289–307.Google Scholar
  216. Namba T, Hiraki K (1958) PAM (pyridine-2-aldoxime methiodide) therapy for alkylphosphate poisoning. JAMA 166: 1834–1839.Google Scholar
  217. Namba T, Nolte CT, Jackrel J, Grob D (1971) Poisoning due to organophosphate insecticides. Am J Med 50: 475–492.PubMedGoogle Scholar
  218. Neal RA (1967a) Studies on the metabolism of diethyl 4-nitrophenyl phosphorothionate (Parathion) in vitro. Biochem J 103: 183–191.PubMedGoogle Scholar
  219. Neal RA (1967b) Studies of the enzymic mechanism of the metabolism of diethyl 4-nitrophenyl nitrophenyl phosphorothionate (parathion) by rat liver microsomes. Biochem J 105: 289–297.PubMedGoogle Scholar
  220. Neitlich HW (1966) Increased plasma cholinesterase activity and succinylcholine resistance: a genetic variant. J Clin Invest 45: 380–387.PubMedGoogle Scholar
  221. Neville LF, Gnatt A, Loewenstein Y, Soreq H (1990) Aspartate-70 to glycine substitution confers resistance to naturally occurring and synthetic anionic-site ligands on in-ovo produced human butyrylcholinesterase. J Neurosci Res 27: 452–460.PubMedGoogle Scholar
  222. Nigg HN, Olexa M (1986) Safety and health maintenance. In: IFAS Pesticides Policies and Procedures. University of Florida, Gainesville.Google Scholar
  223. Nigg HN, Ramos LE, Graham ME, Sterling J, Brown S, Cornell JA (1996) Inhibition of human plasma and serum butyrylcholinesterase (EC by Oc-chaconine and a-solanine. Fundam Appl Toxicol 33: 272–281.PubMedGoogle Scholar
  224. NIOSH (1990) Pocket Guide to Chemical Hazards. DHHS (NIOSH) publication no. 90117. Publications Dissemination, NIOSH, Cincinnati, OH.Google Scholar
  225. O’Brien RD (1957) Properties and metabolism in the cockroach and mouse of malathion and malaoxon. J Econ Entomol 50: 159–164.Google Scholar
  226. O’Brien RD (1960) Toxic Phosphorus Esters: Chemistry, Metabolism, and Biological Effects. Academic Press, New York.Google Scholar
  227. O’Brien RD, Kimmel EC, Sferra RP (1965) Toxicity and metabolism of famphur in insects and mice. J Agric Food Chem 13: 366–372.Google Scholar
  228. O’Malley MA, McCurdy SA (1990) Subacute poisoning with phosalone, an organophosphate insecticide. West J Med 153: 619–624.PubMedGoogle Scholar
  229. Oosterbaan RA, Kunst P, Cohen JA (1955) Nature of the reaction between diisopropyl fluorophosphate and chymotrypsin. Biochem Biophys Acta 16: 299–300.PubMedGoogle Scholar
  230. Orgell WH (1963) Inhibition of human plasma cholinesterase in vitro by alkaloids, glycosides, and other natural substances. Lloydia (Cinci) 26: 36–43.Google Scholar
  231. Orgell WH, Hibbs ET (1963) Cholinesterase inhibition in vitro by potato foliage extracts. Am Potato J 40: 403–405.Google Scholar
  232. Orgell WH, Vaidya KA, Dahm PA (1958) Cholinesterase inhibition in vitro by extracts of potato. Iowa Acad Sci 65: 160–162.Google Scholar
  233. Orgell WH, Vaidya KA Hamilton EW (1959) A preliminary survey of some midwestern plants for substances inhibiting human plasma cholinesterase in vitro. Proc Iowa Acad Sci 66: 149–154.Google Scholar
  234. Padilla S, Lassiter L, Crofton K, Moser VC (1996) Blood cholinesterase activity: Inhibition as an indicator of adverse effect. In: Blancato JN, Brown RN, Dary CC, Saleh MA (eds) Biomarkers for Agrochemicals and Toxic Substances: Applications and Risk Assessment. ACS Symposium Series 643. American Chemical Society, Washington, DC, pp 70–78.Google Scholar
  235. Pardue JR, Hansen EA, Barron RP, Chen JYT (1970) Diazinon residues on field-sprayed kale. Hydroxydiazinon—a new alteration product of diazinon. J Agric Food Chem 18: 405–408.PubMedGoogle Scholar
  236. Parke DV (1968) Radioisotopes in the study of the metabolism of foreign compounds. In: Roth LJ (ed) Isotopes in Experimental Pharmacology 1965: 315–342.Google Scholar
  237. Pasquet J., Mazuret A, Fournel J, Koenig FH (1976) Acute oral and percutaneous toxicity of phosalone in the rat, in comparison with azinphosmethyl and parathion. Toxicol Appl Pharmacol 37: 85–92.PubMedGoogle Scholar
  238. Patil BC, Sharma RP, Salunkhe DK, Salunkhe K (1972) Evaluation of solanine toxicity. Food Cosmet Toxicol 10: 395–398.PubMedGoogle Scholar
  239. Peakall D (1992) Animal Biomarkers as Pollution Indicators. Chapman and Hall, London, pp 1–290.Google Scholar
  240. Pesticide and Toxic Chemical News (1991) Cholinesterase assay recommendations may come by year end. Pesticide and Toxic Chemical News, December 11, 1991, pp 2932.Google Scholar
  241. Polhuijs M, Langenberg JP, Benschop HP (1997) New method for retrospective detection of exposure to organophosphorous anticholinesterases: application to alleged satin victims of Japanese terrorists. Toxicol Appl Pharmacol 146: 156–161.PubMedGoogle Scholar
  242. Prester L, Simeon V (1991) Kinetics of the inhibition of human serum cholinesterase phenotypes with the dimethylcarbamate of (2-hydroxy-5-phenylbenzyl)-trimethylammonium bromide (Ro 02–0683). Biochem Pharmacol 42: 2313–2316.PubMedGoogle Scholar
  243. Raabe OG, Knaak JB, Al-Bayati MA, Enslein K, Gombar VK (1994) Mechanistically-based alternative methods in toxicology structure-activity and PBPK/PBPD models in toxicology, Research proposal, University of California at Davis, Davis, CA.Google Scholar
  244. Radie Z, Quinn RD, Vellom DC, Camp S, Taylor P (1995) Amino acid residues in acetyl-cholinesterase which influence fasciculin inhibition. In: Quinn DM, et al (eds) Enzymes of the Cholinesterase Family. Plenum Press, New York, pp 183–188.Google Scholar
  245. Raffaele KC, Rees C (1990) Neurotoxicology dose/response assessment for several cho- linesterase inhibitors: use of uncertainty factors. Neurotoxicology 11: 237–256.PubMedGoogle Scholar
  246. Reiner E, Aldridge WN, Hoskins FCG (1989) Enzymes Hydrolysing Organophosphorus Compounds. Ellis Horwood, Chichester, England.Google Scholar
  247. Reiter LW, Talens GM, Woolley DE (1975) Parathion administration in the monkey: time course of inhibition and recovery of blood cholinesterases and visual discrimination performance. Toxicol Appl Pharmacol 33: 1–13.PubMedGoogle Scholar
  248. Rider JA, Hodges JL Jr, Swader J, Wiggins AD (1957) Plasma and red cell cholinesterase in 800 “healthy” blood donors. J Lab Clin Med 50: 376–383.PubMedGoogle Scholar
  249. Rider JA, Moeller HC, Puletti EJ, Swader JI (1969) Toxicity of parathion, systox, octamethyl pyrophosphoramide, and methyl parathion in man. Toxicol Appl Pharmacol 14: 603–611.PubMedGoogle Scholar
  250. Rubinstein HM, Dietz AA, Hodges LK, Lubrano T, Czebotar V (1970) Silent cholinesterase gene: variations in the properties of serum enzyme in apparent homozygotes. J Clin Invest 49: 479–486.PubMedGoogle Scholar
  251. Sanderson DM, Edson EF (1964) Toxicological properties of the organophosphorous insecticide dimethoate. Br J Ind Med 21: 52–64.PubMedGoogle Scholar
  252. Schaffer NK, Michel HO, Bridges AF (1973) Amino acid sequence in the region of the reactive serine residue of eel acetylcholinesterase. Biochemistry 12: 2946–2950.PubMedGoogle Scholar
  253. Schumacher M., Maulet Y, Camp S, Taylor P (1988) Multiple messenger RNA species give rise to the structural diversity in acetylcholinesterase. J Biol Chem 263: 18979–18987.PubMedGoogle Scholar
  254. Schüürman G (1992) Ecotoxicology and structure-activity studies of organophosphorus compounds. In: Rational Approaches to Structure, Activity, and Ecotoxicity of Agro-chemicals, eds. Draber W and Toshia F, CRC Press, Boca Raton, Fl, 1992.Google Scholar
  255. Sheets LP, Hamilton BF, Sangha GK, Thyssen JH (1997) Subchronic neurotoxicity screening studies with six organophosphate insecticides: an assessment of behavior and morphology related to cholinesterase inhibition. Fundam Appl Toxicol 35: 101–119.PubMedGoogle Scholar
  256. Sherman KA, Kumar V, Ashford JW, Murphy JW, Elble RJ, Giacobini E (1988) Effect of oral physostigmine in senile dementia patients: utility of blood cholinesterase inhibition and neuroendocrine responses to define pharmacokinetics and pharmacodynamics. In: Strong R, Wood WG (eds) Central Nervous System Disorders of Aging: Clinical Intervention and Research. Raven Press, New York, pp 71–90.Google Scholar
  257. Sinden SL, Webb RE (1972) Effect of variety and location on the glycoalkaloid content of potatoes. Am Potato J 49: 334–338.Google Scholar
  258. Smith RL, Williams RT (1966) Implications of the conjugation of drugs and other exogenous compounds. In: Dutton GJ (ed) Glucuronic Acid, Free and Combined. Academic Press, New York, pp 457–491.Google Scholar
  259. Soreq H, Zakut H (1993) Human Cholinesterases and Anticholinesterases. Academic Press, New York.Google Scholar
  260. Spencer EY, O’Brien RD, White RW (1957) Permanganate oxidation products of schradan. J Agric Food Chem 5: 123–127.Google Scholar
  261. Srinivasan R, Karczmar AG, Bernshon J (1976) Rat brain acetylcholinesterase and its isoenzymes after intracerebral administration of DFE Biochem Pharmacol 25: 2739–2745.Google Scholar
  262. Stefanini M (1985) Enzymes, isozymes, and enzyme variants in the diagnosis of cancer. Cancer (Phila) 55: 1931–1936.Google Scholar
  263. Strelitz F (1944) Studies on cholinesterase. IV Purification of pseudocholinesterase from horse serum. Biochem J 38: 86–88.PubMedGoogle Scholar
  264. Sultatos LG (1990) A physiologically based pharmacokinetic model of parathion based on chemical-specific parameter determined in vitro. J Am Coll Toxicol 9: 611–619.Google Scholar
  265. Sultatos LG, Gagliardi CL (1990) Desulfuration of the insecticide parathion by human placenta in vitro. Biochem Pharmacol 39: 799–801.PubMedGoogle Scholar
  266. Sultatos LG, Murphy SD (1983) Kinetic analyses of the microsomal biotransformation of the phosphorothioate insecticides chlorpyrifos and parathion. Fundam Appl Toxicol 3: 16–21.PubMedGoogle Scholar
  267. Sumerford WT, Hayes WJ Jr, Johnston JM, Walker K, Spillane J (1953) Cholinesterase response and symptomatology from exposure to organic phosphorus insecticides. Arch Ind Hyg Occup Med 7: 383–398.Google Scholar
  268. Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman L (1991) Atomic structure of acetylcholinesterase from Torpedo californcia: a prototypic acetylcholine-binding protein. Science 253: 872–879.PubMedGoogle Scholar
  269. Sutton LD, Froelich S, Hendrickson HS, Quinn DM (1991) Cholesterol esterase catalyzed hydrolysis of mixed micellar thiophosphatidylcholines: a possible charge-relay mechanism. Biochemistry 30: 5888–5893.PubMedGoogle Scholar
  270. Svensmark O (1963) Enzymatic and molecular properties of cholinesterases in human liver. Acta Physiol Scand 59: 378–389.PubMedGoogle Scholar
  271. Tammelin LE (1958a) Choline esters. Substrates and inhibitors of cholinesterase. Svensk Kem Tidskr 70: 157–181.Google Scholar
  272. Tammelin LE (1958b) Dialkoxyphosphorylthiocholines, alkoxymethylphosphorylthiocholines and analogous choline esters. Synthesis, pKa of tertiary homologs and cholinesterase inhibition. Acta Chem Scand 11: 1340–1349.Google Scholar
  273. Tammelin LE (1958c) Organophosphorylcholines and cholinesterases. Arkiv Kemi 12: 287–298.Google Scholar
  274. Tang XC, Zhu XD, Lu WH (1988) Studies on the nootropic effects of huperzine A and B: two selective AChE inhibitors. In: Giacobina E, Becker R (eds) Current Research in Alzheimer Therapy. Taylor and Francis, New York, pp 289–293.Google Scholar
  275. Thomsen T, Kewitz H (1990) Selective inhibition of human acetylcholinesterase by galanthamine in vitro and in vivo. Life Sci 46: 1553–1558.PubMedGoogle Scholar
  276. Tietz NW, Finley PR, Pruden EL (eds) (1990) Clinical Guide to Laboratory Tests, 2°d Ed. Saunders, Philadelphia. U.S. Environmental Protection Agency (1991) Pesticide assessment guideline, subdivision E. Hazard evaluation: human and domestic animals. Addendum 10: Neurotoxicity, series 81, 82, and 83. USEPA 540/09–91–123.Office of Prevention, Pesticides and Toxic Substances. Washington, DC.Google Scholar
  277. U.S. Environmental Protection Agency (1992) Worker protection standards. USEPA, Washington, DC, p. 36.Google Scholar
  278. Uchida T, O’Brien RD (1967) Dimethoate degradation by human liver and its significance for acute toxicity. Toxicol Appl Pharmacol 10: 89–94.PubMedGoogle Scholar
  279. Uchida T, Dauterman WS, O’Brien RD (1964) The metabolism of dimethoate by vertebrate tissues. J Agric Food Chem 12: 48–52.Google Scholar
  280. Ursdin E (1970) Reactions of cholinesterases with substrate inhibitors and reactivators. In: International Encyclopedia of Pharmacology and Therapeutics: Anticholinesterase Agents, Pergamon Press, New York, pp 49–354.Google Scholar
  281. Vandekar M (1980) Minimizing occupational exposure to pesticides: cholinesterase determination and organophosphorus poisoning. Residue Rev 75: 67–80.PubMedGoogle Scholar
  282. Van Lith HA, Herman S, Zhang X, Van Der Palen JGP, Van Zutphen LFM, Beynen AC (1990) Influence of dietary fats on butyrylcholinesterase and esterase-1 (ES-1) activity in plasma of rats. Lipids 25: 779–786.PubMedGoogle Scholar
  283. Vincent D, Parant M (1956) Atropine, apo-atropine et cholinestirases. Comptes Rendus Seances Soc Biol Toulouse 150: 444–447.Google Scholar
  284. Walker CH (1989) The development of an improved system of nomenclature and classification of esterases. In: Reiner E, Aldridge WN, Hoskin FCG (eds) Enzymes Hydrolyzing Organophosphorus Compounds. Halsted Press, New York, 266 pp.Google Scholar
  285. Wallace KB, Dargan JE (1987) Interinsic metabolic clearance of parathion and paraoxon by livers from fish and rodeasts. Toxicol Appl Pharmacol 90: 235–242.PubMedGoogle Scholar
  286. Wallace KD (1992) Species-selective toxicity of organophosphorus insecticides: a pharmacodynamic phenomenon. In: Chambers JE, Levi PE (eds) Organophosphates, Chemistry, Fate, and Effects. Academic Press, San Diego, pp 79–105.Google Scholar
  287. Wang C, Murphy SD (1982) Kinetic analysis of species difference in acetylcholinesterase sensitivity to organophosphate insecticides. Toxicol Appl Pharmacol 66: 409419.Google Scholar
  288. Wester RC, Maibach HI, Melendres J, Sedik L, Knaak JB, Wang R (1992) In vivo and in vitro percutaneous absorption and skin evaporation of isofenphos in man. Fundam Appl Toxicol 19: 521–526.PubMedGoogle Scholar
  289. Wetstone HJ, LaMotta RV (1965) The clinical stability of serum cholinesterase activity. Clin Chem 11: 653–663.PubMedGoogle Scholar
  290. Whetstone RR, Phillips DD, Sun YP, Ward LF, Shellenberger TE (1966) 2-Chloro-1-(2,4,5-trichlorophenyl) vinyl dimethyl phosphate, a new insecticide with low toxicity to mammals. J Agric Food Chem 14: 352–356.Google Scholar
  291. Whittaker M (1986) Cholinesterase. Monographs in Human Genetics, Vol. II. Karger, Basel, Switzerland.Google Scholar
  292. Wilkinson GN (1961) Statistical estimations in enzyme kinetics. Biochem J 80: 324–332.PubMedGoogle Scholar
  293. Wilson BW, Hooper M, Chow E, Higgins R, Knaak JB (1984) Antidotes and neuropathie potential of isofenphos. Bull Environ Contam Toxicol 33: 386–394.PubMedGoogle Scholar
  294. Wilson BW, Sanborn JR, O’Malley MA, Henderson JD, Billitti JR (1997) Monitoring the pesticide-exposed worker. Occup Med State of the Art Reviews, 12: 347–363.Google Scholar
  295. Wilson BW, Billitti JE, Henderson JD, McCarthy SA, O’Malley MA, Sanborn JR, McCurdy SA (1998) Optimizing cholinesterase assays for monitoring humans. Bull Environ Contam Toxicol (in press).Google Scholar
  296. Wilson GS (1959) A small outbreak of solanine poisoning. Monthly Bull Med Res Counc 18: 207–210.Google Scholar
  297. Wilson IB (1951) Acetylcholinesterase. XI. Reversibility of tetraethyl pyrophosphate inhibition. J Biol Chem 190: 111–117.PubMedGoogle Scholar
  298. Wilson IB (1960) Acetylcholinesterase. In: Boyer PD, Lardy H, Myrbdck K (eds) The Enzymes, 2nd Ed. Academic Press, New York, pp 501–520.Google Scholar
  299. Wilson IB, Bergmann F (1950) Acetylcholinesterase. VIII. Dissociation constants of the active groups. J Biol Chem 186: 683–692.PubMedGoogle Scholar
  300. Wilson IB, Bergmann F, Nachmansohn D (1950) Acetylcholinesterase. X. Mechanism of the catalysis of acylation reactions. J Biol Chem 188: 781–790.Google Scholar
  301. Witter RF (1963) Measurement of blood cholinesterase. Arch Environ Health 6:537–563. Wolthius OL, Vanwersch RAP (1984) Behavioral changes in the rat after low doses of cholinesterase inhibitors. Fundam Appl Toxicol 4: S195 - S208.Google Scholar
  302. Wustner DA, Fukuto TR (1974) Affinity and phosphorylation constants for the inhibition of cholinesterase by the optical isomers of O-2-butyl S-2-(dimethylammonium) ethyl ethylphosphorothioate hydrogen oxalate. Pestic Biochem Physiol 4: 365–376.Google Scholar
  303. Yang RSH, Dauterman WC, Hodgson E (1971a) Metabolism in vitro of diazinon and diazoxon in rat liver. J Agric Food Chem 19: 10–13.PubMedGoogle Scholar
  304. Yang RSH, Dauterman WC, Hodgson E (1971b) Metabolism in vitro of diazinon and diazoxon in susceptible and resistant houseflies. J Agric Food Chem 19: 14–19.Google Scholar
  305. Yoshida A, Motulsky AG (1969) A pseudocholinesterase variant (E Cynthiana) associated with elevated plasma enzyme activity. Am J Hum Genet 21: 486–498.PubMedGoogle Scholar
  306. Yoshida K, Kurono Y, Mori Y, Ikeda K (1985) Esterase-like activity of human serum albumin. V. Reaction with 2,4-dinitrophenyl diethyl phosphate. Chem Pharm Bull (Tokyo) 33: 4995–5001.Google Scholar
  307. Yu Q-S, Liu C, Brzostowska M, Chrisey L, Brossi A, Greig NH, Atack JR, Soncrant TT, Rapoport SI, Radunz H-E (1991) Physovenines: efficient synthesis of (-)- and (+)-physovenine and synthesis of carbamate analogues of (-)-physovenine. Anticholinesterase activity and analgesic properties of optically active physovenines. Helv Chim Acta 74: 761–766.Google Scholar
  308. Zakut H, Lieman-Hurwitz J, Zamir R, Sindell L, Ginzberg D, Soreq H (1991) Chorionic villus cDNA library displays expression of butyrylcholinesterase: putative genetic disposition for ecological danger. Prenatal Diagn 11: 597–607.Google Scholar
  309. Zavon MR (1965) Blood cholinesterase levels in organic phosphate intoxication. JAMA 192: 137.Google Scholar
  310. Zeller von EA, BisseggerA (1943) Uber die Cholin-esterase des gehirns und der Erythrocytes. Zugleich 3. Mitteilung uber die beeinflussung von fermentreaktionen durch. Chemotherapeutica und pharmaka. Helv Chim Acta 26: 1619–1630.Google Scholar
  311. Zhang HX, Sultatos LG (1991) Biotransformation of the organophosphorus insecticides parathion and methyl parathion in male and female rat livers perfused in situ. Drug Metab Dispos 19: 473–477.PubMedGoogle Scholar
  312. Zimmerman JK, Grothusen JR, Bryson PK (1989) Partial purification and characterization of paraoxonase from rabbit serum. In: Reiner E, Aldridge WN, Hoskin FCG (eds) Enzymes Hydrolysing Organophosphorus Compounds. Ellis Horwood, Chichester, England, pp 128–142.Google Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Herbert N. Nigg
    • 1
  • James B. Knaak
    • 2
  1. 1.Citrus Research and Education CenterUniversity of FloridaLake AlfredUSA
  2. 2.Department of Pharmacology and Toxicology, School of MedicineSUNY at BuffaloBuffaloUSA

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