Deriving toxicity values for organophosphate nerve agents: A position paper in support of the procedures and rationale for deriving oral RfDs for chemical warfare nerve agents

Human and Ecological Risk Assessment (HERA)

Volumn 5, Issue 3, 1999, Pages 589-634

  Young, Robert A ^a   Opresko, Dennis M ^a   Watson, Annetta P ^a   Ross, Robert H ^a   King, Joe ^b   Choudhury, Harlal ^c  

^a OAK RIDGE NATIONAL LABORATORY   (United States)

^b U S ARMY   (United States)

^c U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

Anticholinesterase; Cholinesterase inhibitor; Sarin; Soman; Tabun; VX

Indexed keywords

EID: 26444491193     PISSN: 10807039     EISSN: None     Source Type: Journal    
DOI: 10.1080/10807039991289554     Document Type: Article

References (143)

1. Aas, P. 1988. The toxic effect of an AChE-inhibitor on the cholinergic nervous system in airway smooth muscle. Toxicology 49, 91-97.
2. Albuquerque, E.X., Alkondon, M., Pereira, E.F.R., Castro, N.G., Schrattenholz, A., Barbosa, C.T.F., Bonfante-Cabarcas, R., Aracava, Y., Eisenberg, H.M., and Maelicke, A. 1997. Properties of neuronal nicotinic acetylcholine receptors: Pharmacological characterization and modulation of synaptic function. J. Pharmacol. Exp. Ther. 280: 1117-1136.
3. Albuquerque, E.X., Deshpande, S.S., Kawabuchi, M., Aracava, Y., Idriss, M., Rickett, D.L., and Boyne, A.F. 1985. Multiple actions of anticholinesterase agents on chemosensitive synapses: Molecular basis for prophylaxis and treatment of organophosphate poisoning. Fundam. Appl. Toxicol. 5, S182-S203.
4. Albuquerque, E.X., Swanson, K.L., Montes, J.G., and Aracava, Y. 1994. Molecular targets and synaptic effects of carbamates, organophosphates, oximes, and pyridiniums: Implications for prophylaxis and therapy of organophopshate toxicity. Final Report. U.S.Army Medical Research and Development Command. DAMD-17-81-C-1279, DAMD-17-84-C-4219, DAMD-17-88-C-8119.
5. Aronstam, W.N. and Buccafusco, J.J. 1985. Clonidine protection from soman and echothiophate toxicity in mice. Life Sci. 39: 2097-2102.
6. Ashani, Y., Shapira, S., Levy, D., Wolfe, A.D., Doctor, B.P., and Raveh, L. 1993. Cholinesterase Prophylaxis against Organophosphorus Poisoning. AD-A277 096. U.S. Army Medical Research, Development, Acquisition, and Logistics Command, Fort Detrick, MD
7. Augustinsson, K.-B. 1959. Electrophoresis studies on blood plasma esterases. I. Mammalian plasmata. Acta Chem. Scand. 13, 571-592.
8. Bakry, N.M.S., El-Rashidy, A.H., Eldefrawi, A.T., and Eldefrawi, M.E. 1988. Direct actions of organophosphate anticholinesterases on nicotinic and muscarinic acetylcholine receptors. J. Biochem. Toxicol. 3, 235-259.
9. Bajgar, J. 1993. Action of nerve agents to cholinesterases. Sb. Ved. Pr. Lek. Fak. Univ. Karlovy Hradci Kralav. 36, 63-72.
10. Benschop, H.P., Konings, C.A.G., and de Jong, L.P.A. 1981. Gas Chromatographic separation and identification of the four stereoisomers of 1,2,2-trimethylpropyl methylphosphonofluoridate (soman). Stereospecificity of in vitro "detoxification" reactions. J. Am. Chem. Soc. 103, 4260-4262. (As cited in Nordgren et al., 1984.)
11. Benschop, H.P. Konings, C.A.G., Van Genderen, H.P.M., and de Jong, L.P.A. 1984. Isolation, anticholinesterase properties, and acute toxicity in mice of the four stereoisomers of the nerve agent soman. Toxicol. Appl. Pharmacol. 72, 61-74.
12. Blick, D.W., Weatherby, F.R., Jr., Brown, G.C., and Murphy, M.R. 1994. Behavioral toxicity of anticholinesterases in primates: Effects of daily repeated soman exposure. Pharmacol. Biochem. Behavior 48: 643-649.
13. Bonderman, R.P. and Bonderman, D.P. 1971. A titrimetric method for differentiating between atypical and inhibited human serum pseudocholinesterase. Arch. Environ. Health 22, 578-581.
14. Bonierbale, E., Debordes, L., and Coppet, L. 1997. Application of capillary gas chromatography to the study of hydrolysis of the nerve agent VX in rat plasma. J. Chromat. B, 688, 255-264.
15. Boter, H.L., Ooms, A.J.J., Van Den Berg, G.R., and Van Dijk, C. 1966. The synthesis of optically active isopropyl methylphosphonofluoridate (Sarin). Rec. Trav. Chim. PaysBas 85, 147-150. (Cited in Somani, 1992.)
16. Bowman, W.C. and Rand, M.J. 1980. Textbook of Pharmacology, pp. 10.37-10.41, Oxford, Blackwell Scientific Publications.
17. Bucci, T.J., Parker, R.M., and Gosnell, P.A. 1991. Toxiaty Studies on Agents GB and GD (Phase II), 90 Day Subchronic Study of GB (Sarin Type I) in CD-Rats. Defense Technical Information Center Report No. AD-A248617, prepared by the National Center for Toxicological Research, Jefferson, AR, for the US Army Biomedical Research and Development Laboratory, Fort Detrick, MD.
18. Bucci, T.J. and Parker, R.M. 1992. Toxicity Studies on Agents GB and GD (Phase II), 90 Day Subchronic Study of GB (Sarin Type II) in CD-Rats. Defense Technical Information Center Report No. AD-A248618, prepared by the National Center for Toxicological Research, Jefferson, AR, for the US Army Biomedical Research and Development Laboratory, Fort Detrick, MD.
19. Bucci, T.J., Parker, R.M., and Gosnell, P.A. 1992a. Toxicity Studies on Agent GA (Phase II): 90 Day Subchronic Study of GA (Tabun) in CD Rats. Defense Technical Information Center Report No. AD-A258020, prepared by the National Center for Toxicological Research, Jefferson, AR, for the US Army Biomedical Research and Development Laboratory, Fort Detrick, MD.
20. Bucci, T.J., Parker, R.M., and Gosnell, P.A. 1992b. Delayed Neuropathy Study of Sarin, Type I, in SPF White Leghorn Chickens. Technical Report, prepared by the National Center for Toxicological Research, Jefferson, AR, for the US Army Biomedical Research and Development Laboratory, Fort Detrick, MD.
21. Bucci, T.J., Parker, R.M., and Gosnell, P.A. 1992c. Delayed Neuropathy Study of Sarin, Type II, in SPF White Leghorn Chickens. Technical Report, prepared by the National Center for Toxicological Research, Jefferson, AR, for the US Army Biomedical Research and Development Laboratory, Fort Detrick, MD.
22. Callaway, S., Davies, D.R., and Rutland, J.P. 1951. Blood cholinesterase levels and range of personal variation in a healthy adult population. Br. Med. J. 2:812-816.
23. Carnes, S.A. and Watson. A.P. 1989. Disposing of the US chemical weapons stockpile: an approaching reality. J. Am. Med. Assoc. 262, 653-659.
24. Carney, J.M. 1989. Biological Determinant of the Behavioral Effects of Acelylcholinesterase Inhibitors. Defense Technical Information Center, AD-A277 096. Final report, prepared by the University of Oklahoma Health Science Center, Oklahoma City, OK, for the U.S. Army Medical Research and Development Command, Fort Detrick, MD.
25. Cashman, J.R., Perotti, B.Y., Berkman, C.E., and Lin, J. 1996. Pharmacokinetics and molecular detoxication. Environ. Health Perspect. 104, 23-40.
26. CDC (Centers for Disease Control). 1988. Final recommendations for protecting the health and safety against potential adverse effects of long-term exposure to low doses of agents: GA, GB, VX, mustard agent (H, HD, T), and lewisite (L). Federal Register 55 (50), 8504-8507.
27. Chen, S.-M. and Chi, M.-G. 1986. Direct effect of VX and soman on nicotinic receptors. Acta Pharmacol. Sinica 7, 401-406.
28. Christen, P.J. and van den Muysenberg, J.A.C.M. 1965. The enzymatic isolation and fluoride catalyzed racemisation of optically active sarin. Biochim. Biophys. Acta. 110, 217-220.
29. Cicmanec, J.L., Dourson, M.L., and Hertzberg, R.C. 1996. Noncancer risk assessment: present and emerging issues. In: Fan, A.M. and Chang, L.W. Eds., Toxicology and Risk Assessment: Principles, Methods, and Applications. Marcel Dekker, New York, pp. 293-310.
30. Clement, J.G. 1982. Plasma cholinesterase - a possible depot for soman (pinacolyl methylphosphonofluoridate) in the mouse. Biochem. Pharmacol. 31, 4085-4088. (As cited in Clement, 1984.)
31. Clement, J.G. 1983. Effect of pretreatment with sodium phenobarbital on the toxicity of soman in mice. Biochem. Pharmacol. 32, 1411-1415.
32. Clement, J.G. 1984. Role of aliesterase in organophosphate poisoning. Fund. Appl. Toxicol. 4, S96-S105.
33. Clement, J.G. 1985. Hormonal consequences of organophosphate poisoning. Fundam. Appl. Toxicol. 5, S61-S77.
34. Cook, J.W. 1957. In vitro destruction of some organophosphate pesticides by bovine rumen fluid. Agric. Food Chem. 5, 859-863.
35. Cohen, E.M., Christen, P.J., and Mobach, E. 1971. The inactivation by oximes of sarin and soman in plasma from various species. I. The influence of diacetylmonoxime on the hydrolysis of sarin. J.A. Cohen Memorial Issue, North Holland Publishing Co., Amsterdam, pp. 113-131.
36. Costa, L.G., Schwab, B.W., and Murphy, S.D. 1982. Tolerance to anticholinesterase compounds in mammals. Toxicology 25, 79-97.
37. Dacre, J.C. 1984. Toxicology of some anticholinesterases used as chemical warfare agents - a review. In Cholinesterases: Fundamental and Applied Aspects, pp. 415-426 (Brzin, M., Barnard E.A., and Sket, D., Eds.), New York, Walter de Gruyter.
38. Davies, D.R., Holland, P., and Rumens, M.J. 1960. The relationship between the chemical structure and neurotoxicity of alkyl organophosphorus compounds. Brt. J. Pharmacol. 15, 271-278.
39. Davies, D.R. and Holland, P. 1972. Effect of oximes and atropine upon the development of delayed neurotoxic signs in chickens following poisoning by DFP and sarin. Biochem. Pharmacol. 21, 3145-3151.
40. Davies, H.G., Richter, R.J., Keifer, M., Broomfield, CA., Sowalla, J., and Furlong, C.E. 1996. The effect of human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nat. Genet. 14, 334-336.
41. de Jong, L.P.A. and Wolring, G.Z. 1978. Effect of 1-(AR)alkyl-2-hydroxyiminomethyl-pyridinium salts on reactivation and aging of acetylcholinesterase inhibited by ethyl dimethylphosphoramidocyanidate (tabun). Biochem. Pharmacol. 27, 2229-2235.
42. D'Mello, G.D. 1993. Behavioral toxicity of anticholinesterases in humans and animals - a review. Human Exp. Toxicol. 12, 3-7.
43. Doctor, B.P., Blick, D.W., Caranto, G., Castro, C.A., Gentry, M.K., Larrison, R., Maxwell, D.M., Murphy, M.R., and Schutz, M. 1993. Cholinesterases as scavengers for organophosphorus compounds: protection of primate performance against soman toxicity. Chem.-Biol. Interact. 87, 285-293.
44. Duffy, F.H., Burchfiel, J.L., Bartels, P.H., Gaon, M., and Sim, V.M. 1979. Long-term effects of an organophosphate upon the human electroencephalogram. Toxicol. Appl. Pharmacol. 47, 161-176.
45. Dulaney, M.D., Hoskins, B., and Ho, I.K. 1985. Studies on low dose sub-acute administration of soman, sarin, and tabun in the rat. Acta Pharmacol. Toxicol. 57, 234-241.
46. Ellin, R.I. 1981. Anomalies in Theories and Therapy of Intoxication by Potent Organophosphorus Anticholinesterase Compounds. Special Publication USABML-SP-81-003, Defense Technical Information Center Report No. AD A101364. US Army Medical Research and Development Command, Biomedical Laboratory, Aberdeen Proving Ground, MD.
47. Fernando, J.C.R., Lim, D.K., Hoskins, B., and Ho, I.K. 1985. Variability of neurotoxicity of and lack of tolerance to the anticholinesterases soman and sarin in the rat. Res. Commun. Chem. Pathol. Pharmacol. 48, 415-430.
48. Filbert, M.G., Dochterman, L.W., Smith, C.D., Forster, J.S., Phann, S., and Cann, F.J. 1993. Effect of mannitol treatment on soman-induced brain and heart lesions in the rat. Drug Develop. Res. 30, 45-53.
49. Fitzgerald, B.B. and Costa, L.G. 1993. Modulation of muscarinic receptors and acetylcholinesterase activity in lymphocytes and in brain areas following repeated organophosphate exposure in rats. Fundam. Appl. Toxicol. 20, 210-216.
50. Fonnum, F. and Sterri, S.H. 1981. Factors modifying the toxicity of organophosphorus compounds including soman and sarin. Fund. Appl. Toxicol. 1, 143-147.
51. Goldman, M., Rosenblatt, L.S., Wilson, B.W., Kawakami, T.G., Culbertson, M.R., Schreider, J.P., Remsen, J.F., and Shifrine, M. 1988. Toxicity Studies on Agent VX. Defense Technical Information Center Report No. AD A201397, prepared by the Laboratory for Energy-Related Health Research for the US Army Medical Research and Development Command, Fort Detrick, MD.
52. Goldstein, B.D., Fincher, D.R., and Searle, J.R. 1987. Electrophysiological changes in the primary sensory neuron following subchronic soman or sarin: alterations in sensory receptor function. Toxicol. Appl. Pharmacol. 9, 55-64.
53. Goldstein, B.D. 1989. Changes in spinal cord reflexes following subchronic exposure to soman and sarin. Toxicol. Lett. 47, 1-8.
54. Gordon, J.J., Inns, R.H., Johnson, M.K., Leadbetter, L., Maidment, M.P., Upshall, D.G., Cooper, G.H., and Rickard, R.L. 1983. The delayed neuropathic effects of nerve agents and some other organophosphorus compounds. Arch. Toxicol. 52, 71-82.
55. Grob, D. and Harvey, J.C. 1958. Effects in man of the anticholinesterase compound sarin (isopropyl methyl phosphonofluoridate). J. Clin. Invest. 37, 350-368.
56. Gupta, R.C., Patterson, G.T., and Dettbarn, W-D. 1987. Acute tabun toxicity: biochemical and histochemical consequences in brain and skeletal muscles of rat. Toxicology 46, 329-341.
57. Halbrook, R.S., Shugart, L.R., Watson, A.P., Munro, N.B., and Linnabary, R.D. 1992. Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophopshate nerve agent exposure. J. Am. Vet. Med. Assoc. 201, 714-725.
58. Harris, L.W., Heyl, W.C., Stitcher, D.L., and Broomfield, C.A. 1978. Effects of 1,1-oxydimethylene-bis-(4-tert-butyl pyridinium chloride) (SAD-128) and decamethonium on reactivation of soman- and sarin-inhibited cholinesterase by oximes. Biochem. Pharmacol. 27, 757-761.
59. Harris, H. and Whittaker, M. 1962. The serum cholinesterase variants: study of twenty-two families selected via the "intermediate" phenotype. Ann. Hum. Genet. 26, 59-72.
60. Hartgraves, S.L. and Murphy, M.R 1992. Behavioral effects of low-dose nerve agents. In Chemical Warfare Agents, pp. 125-154 (Somani, S.M., Ed.), New York, Academic Press.
61. Henderson, J.D., Higgins, R.J., Rosenblatt, L., and Wilson, B.W. 1989. Toxicity Studies on Agent GA: Delayed Neurotoxicity - Acute and Repeated Exposures to GA (Tabun). Defense Technical Information Center Report No. AD A219457. US Army Medical Research and Development Command, Fort Detrick, MD.
62. Henderson, J.D., Higgins, R.J., Dacre, J.C., and Wilson, B.W. 1992. Neurotoxicity of acute and repeated treatments of tabun, paraoxon, diisopropyl fluorophosphate and isofenphos to the hen. Toxicology 72, 117-129.
63. Ho, I.K. and Hoskins, B. 1983. Basal Ganglia Dopamine-Gamma Aminobutyric Acid-Acetylcholine Interaction in Organophosphate-Induced Neurotoxicity. Defense Technical Information Center Report No. AD B091748. US Army Medical Research and Development Command, Fort Detrick, MD.
64. Ho, I.K. and Hoskins, B. 1987. Biochemical and pharmacological aspects of neurotoxicity and tolerance to organophosphorus cholinesterase inhibitors. In Handbook of Toxicology, pp. 44-73 (Haley, T.J. and Berndt, W.O., Eds.), New York, Hemisphere Publ. Corp.
65. Holmstedt, B. 1951. Synthesis and pharmacology of dimethylamidoethoxyphosphoryl cyanide (tabun) together with a description of some allied anticholinesterase compounds containing the NP bond. Acta Physiol. Scand. 25 (Suppl. 90), 1-120.
66. Holmstedt, B. 1959. Pharmacology of organophosphorus cholinesterase inhibitors. Pharmacol. Reviews 11, 567-688.
67. Hoskins, B. and Ho, I.K. 1992. Tolerance to organophosphorus cholinesterase inhibitors. In Organophosphates, Chemistry, Fate and Effects, pp. 285-297 (Chambers, J.E. and Levi, P.E., Eds.), New York, Academic Press.
68. Husain, K., Kumar, P., Vijayaraghavan, R., Singh, R., and Das Gupta, S. 1993. Delayed neurotoxic effect of sarin in mice after repeated inhalation exposure. J. Appl. Toxicol. 13, 143-145.
69. Husain, K. 1994. Phenylvalerate and choline ester hydrolases in the platelets of human, hen, rat and mouse. Human Exper. Toxicol. 13, 157-159.
70. Hymowitz, N., Brezenoff, H.E., McGee, J., Campbell, K., and Knight, V. (1985). Effect of repeated intraperitoneal injections of soman on schedule-controlled behavior in the rat. Psychopharmacology 86, 404-408.
71. Idriss, M.K., Aguayo, L.G., Rickett, D.L., and Albuqueque, E.X. 1986. Organophosphate and carbamate compounds have pre- and postjunctional effects at the insect glutamatergic synapse. J. Pharmacol. Exp. Ther. 239, 279-285.
72. Jimmerson, V.R., Shih, T-M., and Mailman, R.B. 1989. Variability in soman toxicity in the rat: correlation with biochemical and behavioral measures. Toxicology 57, 241-254.
73. Johnson, M.K., Willems, J.L., De Bisshop, H.C., Read, D.J., and Benschop, H.P. 1988. High doses of soman protect against organophosphorus-induced polyneuropathy but tabun does not. Toxicol. Appl. Pharmacol. 92, 34-41.
74. Johnson, M.K. 1992. Molecular events in delayed neuropathy: experimental aspects of neuropathy target esterase. In Clinical and Experimental Toxicology of Organophosphates and Carbamates, pp. 90-113 (Ballantyne, B., Marrs, T.C., Eds.), Oxford, Butterworth Heinemann.
75. Jokanovi'c, M. and Maksimovi'c, M. 1989. Role of carboxylesterase in soman, sarin, and tabun poisoning in rats. Pharmacol. Toxicol. 65, 181-184.
76. Jokanovi'c, M., Kosanovi'c, M., and Maksimovi'c, M. 1996. Interaction of organophosphorus compounds with carboxylesterases in the rat. Arch. Toxicol. 70, 444-450.
77. Jokanovi'c, M. and Maksimovi'c, M. 1997. Abnormal cholinesterase activity, understanding and interpretation. Eur. J. Clin. Chem. Clin. Biochem. 35, 11-16.
78. Kaliste-Korhonen, E., Torronen, R., Ylitalo, P., and Hanninen, O. 1987. Inhibition of cholinesterase by DFP and induction of organophosphate-detoxicating enzymes in rats. Gen. Pharmacol. 21, 527-533.
79. Koelle, G.B. 1976. Cholinesterases and anticholinesterase agents. Springer-Verlag, Berlin, pp. 123-154.
80. Koelle, G.B. 1981. Organophosphate poisoning - an overview. Fundam. Appl. Toxicol. 1, 129-134.
81. Lallement, G., Carpenteir, P., Pernot-Marino, I., Baubichon, D., Collet, A., and Blanchet, G. 1991a. Involvement of the different rat hippocampal glutamatergic receptors in development of seizures induced by soman. Neurotoxicogy 4, 655-664.
82. Lallement, G., Carpenteir, P., Collet, A., Pernot-Marino, I., Baubichon,. A., and Blanchet, G.. 1991b. Effects of soman-induced seizures on different extracellular amino acid levels and on glutamate uptake in rat hippocampus. Brain Res. 563, 234-340.
83. Lehmann, H. and Liddell J. 1969. Human cholinesterase genetic variants and their recognition. Br. J. Anaesth. 41, 235-244.
84. Lenz, D.E., Maxwell, D.M., and Austin, L.W. 1996. Development of a rat model for subacute exposure to the toxic Organophosphate VX. J. Am. Coll. Toxicol. 15 (Suppl. 2), S69-S77.
85. Little, J.S., Broomfield, C.A., Fox-Talbot, M.K., Boucher, L.J., MacIver, B., and Lenz, D.E. 1989. Partial characterization of an enzyme that hydrolyzes sarin, soman, tabun and diisopropyl phosphonofluoridate (DFP). Biochem. Pharmacol. 38, 23-29. (As cited in Somani et al., 1992.)
86. Maxwell, D.M. 1992. The specificity of carboxylesterase protection against the toxicity of Organophosphate compounds. Toxicol. Appl. Pharmacol. 114, 306-312.
87. Maxwell, D.M., Brecht, K.M., and O'Neil, B.M. 1987. The effect of carboxylesterase inhibition on interspecies differences in soman toxicity. Toxicol. Lett. 39, 35-42.
88. McDonough, J.H. 1997. Detection of anticholinesterase effects: EEG and sleep studies. The Health Effects of Low-Level Chemical Warfare Nerve Agent Exposure, Satellite Symposium of the 36th Society of Toxicology Annual Meeting, March 7-8. Dept. of Veterans Affairs, Cincinnati, OH.
89. McDonough, J.H., Jr., McLeod, C.G., Jr., and Nipwoda, M.T. 1987. Direct microinjection of soman or VX into the amygdala produces repetitive limbic convulsions and neuropathology. Brain Res. 435, 123-137.
90. Mendel, B., Mundell, D.B., and Rudney, H. 1943. Studies on cholinesterase. I. Cholinesterase and pseudocholinesterase. Biochem. J. 37, 59-63.
91. Morgan, D.P. 1989. Recognition and Management of Pesticide Poisonings, 4th ed., EPA-540/ 9-88-001. US Environmental Protection Agency, Washington, DC.
92. Munro, N.B., Ambrose, K.R., and Watson, A.P. 1994. Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: implications for public protection. Environ. Health Perspect. 102, 18-38.
93. Munro, N.B., Talmage, S.S., Griffin, G.D., Waters, L.C., Watson, A.P., King, J.F., and Hauschild, V. 1999. The sources, fate, and toxicity of chemical warfare agent degradation products. Environ. Health Perspect. (accepted for publication).
94. Murata, K., Araki, S., Yokoyama, K., Okumra, T., Ishimatsu, S., Takasu, N., and White, R.F. 1997. Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack. J. Neurol. 244, 601-606.
95. Nordgren, I., Lundgren, G., Puu, G., and Holmstedt, B. 1984. Stereoselectivity of enzymes involved in toxicity and detoxification of soman. Arch. Toxicol. 55, 70-75.
96. Opresko, D.M., Young, R.A., Faust, R.A., Talmage, S.S., Watson, A.P., Ross, R.H., Davidson, J.A., and King, J. 1998. Chemical warfare agents: estimating oral reference doses. Reviews in Environmental Contamination and Toxicology 156, 1-183.
97. Osweiler, G.D. et al. 1985. Clinical and Diagnostic Veterinary Toxicology, 3rd ed., Dubuque, Iowa, Kendall/Hunt Publ. Co.
98. Pond, A.L., Chambers, H.W., and Chambers, J.E. 1995. Organophosphate detoxication potential of various rat tissues via A-esterase and aliesterase activities. Toxicol. Lett, 78, 245-252.
99. Prendergast, M.A., Terry, A.V., Jr., and Buccafusco, J.J. 1998. Effects of chronic, low-level organophosphate exposure on delayed recall, discrimination, and spatial learning in monkeys and rats. Neurotoxicol. Teratol. 20, 115-122.
100. Raveh, L., Grauer, E., Grunwald, J., Cohen, E., and Ashani, Y. 1997. The stoichiometry of protection against soman and VX toxicity in monkeys pretreated with human butyrylcholinesterase. Toxicol. Appl. Pharmacol. 145, 43-53.
101. Rice, G.B., Lambert, T.W., Haas, B., and Wallace, V. 1971. Effect of Chronic Ingestion of VX on Ovine Blood Cholinesterase. DTC 71-512. US Army Desert Test Center, Dugway Proving Ground, Dugway, UT.
102. Rocha, E.S., Pereira, E.F.R., Swanson, K.L., and Albuquerque, E.X. 1996. Novel molecular targets in the central nervous system for the actions of cholinesterase inhibitors: alterations of modulatory processes. Med. Def. Biosci. Rev. Proc. 3, 1635-1643.
103. RTECS (Registry of Toxic Effects of Chemical Substances). 1995. MEDLARS, online Information Retrieval System, National Library of Medicine, Washington, DC.
104. Russell, R.W., Booth, R.A., Lauretz, S.D., Smith, C.D., and Jenden, D.J. 1986. Behavioral, neurochemical and physiological effects of repeated exposures to subsymptomatic levels of anticholinesterase, soman. Neurobehav. Toxicol. Teratol. 8, 675-685.
105. Sheets, L.P., Hamilton, B.F., Sangha, G.K., and Thyssen, J.H. 1997. Subchronic neurotoxicity studies with six organophosphate insecticides: an assessment of behavior and morphology relative to cholinesterase inhibition. Fundam. Appl. Toxicol. 35, 101-119.
106. Sidell, F.R. 1992. Clinical considerations in nerve agent intoxication. In: Chemical Warfare Agents, pp. 155-194 (Somani, S.M., Ed.), New York, Academic Press.
107. Sidell, F.R. and Groff, W.A. 1974. The reactivatibility of cholinesterase inhibited by VX and sarin in man. Toxicol. Appl. Pharmacol. 27, 241-252.
108. Sidell, F.R. and Kaminskis, A. 1975. Temporal intrapersonal physiological variability of cholinesterase activity in human plasma and erythrocytes. Clin. Chem. 21, 1961-1963.
109. Sim, V.M., McClure, C., Jr., Vocci, F.J., Feinsilver, L., and Groff, W.A. 1964. Tolerance of Man to VX-Contaminated Water. CRDLR 3231. US Army Chemical Research and Development Laboratories, Edgewood Arsenal, MD.
110. Somani, S.M., Solana, R.P., and Dube, S.N. 1992. Toxicodynamics of nerve agents. In: Chemical Warfare Agents, pp. 67-123 (Somani, S.M., Ed.), New York, Academic Press, Inc.
111. Sterri, S.H., Lyngaas, S., and Fonnum, F. 1980. Toxicity of soman after repetitive injection of sublethal doses in rat. Acta Pharmacol. Toxicol. 46, 1-7.
112. Sterri, S.H., Lyngaas, S., and Fonnum, F. 1981. Toxicity of soman after repetitive injection of sublethal doses in guinea pig and mouse. Acta Pharmacol. Toxicol. 49, 8-13.
113. Stevens, J.T., Stitzel, R.E., and McPhillips, J.J. 1972. Effects of anticholinesterase insecticides on hepatic microsomal metabolism. J. Pharmacol. Exp. Ther. 181, 576-583.
114. Sumerford, W.T., Hayes, W.J., Jr., Johnston, J.M., Walker, K., and Spillane, J. 1953. Cholinesterase response and symptomatology from exposure to organic phosphorus insecticides. AMA Arch. Ind Hyg. Occup. Med. 7, 383-398.
115. Talbot, B.G., Anderson, D.R., Harris, L.W., Yarbrough, L.W., and Lennox, J.W. 1988. A comparison of in vivo and in vitro rates of aging of soman-induced erythrocyte acetylcholinesterase in different animals species. Drug Chem. Toxicol. 11, 289-305.
116. Taylor, P. 1985. Anticholinesterase agents. In The Pharmacological Basis of Therapeutics, pp. 110-129 (Gilman, A.G., Goodman, L.S., Rall, T.W., and Murad, F., Eds.), New York, MacMillan Publishers.
117. Tryphonas, L. and Clement, J.G. 1995. Histomorphogenesis of soman-induced encephalocardiomyopathy in Sprague-Dawley rats. Toxicol. Pathol. 23, 393-409.
118. USEPA (U.S. Environmental Protection Agency). 1989. Risk Assessment Guidance for Superfund. Volume 1. Human Health Evaluation Manual EPA/540/1-89/002. Office of Emergency and Remedial Response, Washington, DC.
119. USEPA (U.S. Environmental Protection Agency). 1990. Integrated Risk Assessment System (IRIS) Reference Guide. Office of Health and Environmental Assessment, National Center for Environmental Assessment, Cincinnati, OH.
120. USEPA (U.S. Environmental Protection Agency). 1991a. Oral RfD Assessment for Silver. Integrated Risk Assessment System (IRIS), online file. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH.
121. USEPA (U.S. Environmental Protection Agency). 1991b. General Quantitative Risk Assessment Guidelines for Noncancer Health Effects. External Review Draft. ECAO-CIN-538. U.S. Environmental Protection Agency, Office of Research and Development, Cincinnati, OH.
122. USEPA (U.S. Environmental Protection Agency). 1992. Oral RfD Assessment for Pirimiphosmethyl Integrated Risk Assessment System (IRIS), online file. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH.
123. USEPA (U.S. Environmental Protection Agency). 1994. Methods for the Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry. EPA/600/8-90/066F. Environmental Criteria and Assessment Office, Research Triangle Park, NC.
124. USEPA (U.S. Environmental Protection Agency). 1995. Proposed Guidelines for Neurotoxicity Risk Assessment. Federal Register 60, 52032-52056.
125. USEPA (U.S. Environmental Protection Agency). 1997. Office of Pesticide Programs Science Policy on The Use of Data on Cholinesterase Inhibition for Risk Assessments of Organophosphate and Carbamate Pesticides. Office of Pesticide Programs, USEPA, April 30, 1997.
126. Valdes, J.J., Chester, N.A., Menkning, D., Shih, T-M., and Whalley C. 1986. Regional Sensitivity of Neuroleptic Receptors to Subacute Soman Intoxication. CRDC-TR-86011. U.S. Army Armament, Munitions and Chemical Command, Aberdeen Proving Ground, MD.
127. Van Dongen, C.J. and Wolthuis, O.L. 1989. On the development of behavioral tolerance to organophosphates. I. Behavioral and biochemical aspects. Pharmacol. Biochem. Behav. 34, 473-481.
128. Van Kampen, K.R., Shupe, J.L., Johnson, A.E., James, L.F., Smart, R.A., and Rasmussen, J.E . 1970. Effects of nerve gas poisoning in sheep in Skull Valley, UT. J Am Vet Med Assoc 156, 1032-1035.
129. Van Helden, H.P.M. and Wolthuis, O.L. 1983. Evidence for an intramuscular depot of the cholinesterase inhibitor soman in the rat. Eur. J. Pharmacol. 89, 271-274. (As cited in Clement, 1984.)
130. Wahllander, A. and Szinicz, L. 1990. Detoxification of soman in the perfused rat liver: quantitative uptake and stereoisomer metabolism. Arch. Toxicol. 64, 586-589.
131. Watson, A.P., Ambrose, K.R., Griffin, G.D., Leffingwell, S.S., Munro, N.B., and Waters, L.C. 1989. Health effects of warfare agent exposure: implications for stockpile disposal. Environ. Prof. 11, 335-353.
132. Willems, J.L., Nacaise, M., and De Bisschop, H.C. 1984. Delayed neuropathy by the organophosphorus nerve agents soman and tabun. Arch. Toxicol. 55, 76-77.
133. Wills, J.H. 1972. The measurement and significance of changes in the cholinesterase activities of erythrocytes and plasma in man and animals. CRC Crit. Rev. Toxicol. 1, 153-202.
134. Wilson, B.W., Henderson, J.D., Kellner, T.P., Goldman, Higgins, R.J., and Dacre, J.C. 1988. Toxicity of repeated doses of organophosphorus esters in the chicken. J. Toxicol. Environ. Health 23, 115-126.
135. Wilson, I.B. and Sondheimer, F. 1957. A specific antidote against lethal alkyl phosphate intoxication. Arch. Biochem. 69, 468-474.
136. Wolthuis, O.L., van Helden, H.P.M., Melchers, B.P.C., Busker, R.W., and de Groot, D.M.G. 1994. Search for a therapy against soman-intoxication. Neurosci. Biobehav. Rev. 18, 469-486.
137. Woodward, C.L., Calamaio, C.A., Kaminskis, A., Anderson, D.R., Harris, L.W., and Martin, D.G. 1994. Erythrocyte and plasma cholinesterase activity in male and female rhesus monkeys before and after exposure to sarin. Fund. Appl. Toxicol. 23, 342-347.
138. Worek, F., Kleine, A., Falke, K., and Szinicz, L. 1995. Arrhythmias in organophosphate poisoning: effect of atropine and behavioral bispyridium oximes. Arch. Int. Pharmacodyn. 329, 418-435.
139. Yager, J., McLean, H., Hudes, M., and Spear, R.C 1976. Components of variability in blood cholinesterase assay results. J. Occup. Med. 18, 242-244.
140. Yamasaki, Y., Sakamoto, K., Watada, H., Kajimoto, Y., and Hori, M. 1997. The Arg 192 isoform of paraoxonase with low sarin-hyrolyzing activity is dominant in the Japanese. Japan. Hum. Genet. 10, 67-68.
141. Yang, C.M., Dwyer, T.M., and Farley, J.M. 1991. Muscarinic receptors and mucus secretion in swine tracheal epithelium: effects of subacute organophosphate treatment. Fundam. Appl. Toxicol. 17, 34-42.
142. Yilmazlar, A. and Özyurt, G. 1997. Brain involvement in organophosphate poisoning. Environ. Res. 74, 104-109.
143. Zhao, D-L., Wang, Z-X., Pei, S-Q., and Liu, C-H. 1983. Effects of soman, sarin, and VX on the specific binding of 3H-QNB in rat cerebral cortex homogenates. Acta Pharmacol. Sinica 4, 225-228.