Organophosphates and the gulf war syndrome

Toxicology of Organophosphate & Carbamate Compounds

Volumn , Issue , 2006, Pages 69-78

  McCauley, Linda A ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 34548012771     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-012088523-7/50007-7     Document Type: Chapter

References (87)

1. Abdel-Rahman A.A., Shetty A.K., Abou-Donia M.B. Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf War syndrome. Neurobiol. Dis. 2002, 10:306-326.
2. Abdel-Rahman A.A., Dechkovskaia A.M., Goldstein L.B., et al. Neurological deficits induced by malathion, DEET, and permethrin, alone or in combination in adult rats. J. Toxicol. Environ. Health A 2004, 67:331-356.
3. Abdel-Rahman A.A., Abou-Donia M.B., El-Masry E.M., Shetty A.K., Abou-Donia M.B. Stress and combined exposure to low doses of pyridostigmine, bromide, DEET, and permethrin produce neurochemical and neuropathological alterations in cerebral cortex, hippocampus, and cerebellum. J. Toxicol. Environ. Health A. 2004, 67:163-192.
4. Abou-Donia M.B., Wilmarth K.R., Jensen K.F., Oehme F.W., Kurt T.L. Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET, and permethrin: implications of Gulf War chemical exposures. J. Toxicol. Environ. Health. 1996, 48:35-56.
5. Abou-Donia M.B., Wilmarth K.R., Abdel-Rahman A.A., Jensen K.F., Oehme F.W., Kurt T.L. Increased neurotoxicity following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos. Fundam. Appl. Toxicol. 1996, 34:201-222.
6. Abou-Donia M.B., Goldstein L.B., Jones K.H., et al. Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigine bromide, DEET, and permethrin, alone and in combination. Toxicol. Sci. 2001, 60:305-314.
7. Abou-Donia M.B., Goldstein L.B., Dechkovskaia A.M., et al. Effects of daily dermal application of DEET and permethrin, alone and in combination, on sensorimotor performance, blood-brain barrier, and blood-testis barrier in rats. J. Toxicol. Environ. Health A 2001, 62:523-541.
8. Abou-Donia M.B., Suliman H.B., Khan W.A., Abdel-Rahman A.A. Testicular germ-cell apoptosis in stressed rats following combined exposure to pyridostigmine bromide, N, N-diethyl m-toluamide (DEET), and permethrin. J. Toxicol. Environ. Health A 2003, 66:57-73.
9. Abou-Donia M.B., Dechkovskaia A.M., Goldstein L.B., Abdel-Rahman A.A., Bullman S.L., Khan W.A. Co-exposure to pyridostigmine bromide, DEET, and/or permethrin causes sensorimotor deficit and alterations in brain acetylcholinesterase activity. Pharmacol. Biochem. Behav. 2004, 77:253-262.
10. Abu-Qare A.W., Abou-Donia M.B. Combined exposure to sarin and pyridostigmine bromide increased levels of rat urinary 3-nitrotyrosine and 8-hyrdroxy-2'-deoxyguanosine, biomarkers of oxidative stress. Toxicol. Lett. 2001, 123:51-58.
11. Abu-Qare A.W., Abou-Donia M.B. Combined exposure to DEET (N, N-diethyl-m-toluamide) and permethrin-induced release of rat brain mitochondrial cytochrome c. J. Toxicol. Environ. Health A 2001, 63:243-252.
12. Abu-Qare A.W., Suliman H.B., Abou-Donia M.B. Induction of urinary excretion of 3-nitrotyrosine, a marker of oxidative stress, following administration of pyridostigmine bromide, DEET (N, N-diethyl-m-toluamide) and permethrin, alone and in combination in rats. Toxicol. Lett. 2001, 2001:127-134.
13. Baynes R.E., Halling K.B., Riviere J.E. The influence of diethyl-m-toluamide (DEET) on the percutaneous absorption of permethrin and carbaryl. Toxicol. Appl. Pharmacol. 1997, 144:332-339.
14. 14C] permethrin. Toxicol. Appl. Pharmacol. 2002, 181:164-173.
15. Bourdette D.N., McCauley L.A., Barkhuizen A., Johnston W., Wynn M., Joos S.K., Storzbac D., Shuell T., Sticker D. Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness. J. Occup. Environ. Med. 2001, 43:1026-1040.
16. Buchholz B.A., Pawley N.H., Vogel J.S., Mauthe R.J. Pyrethroid decrease in central nervous system from nerve agent pretreatment. J. Appl. Toxicol. 1997, 17:231-234.
17. Chaney L.A., Wineman R.W., Rockhold R.W., Hume A.S. Acute effects of an insect repellent, N, N-diethyl-m-toluamide, on cholinesterase inhibition induced by pyridostig-mine bromide in rats. Toxicol. Appl. Pharmacol. 2000, 165:107-114.
18. Coker W.J., Bhatt B.M., Blatchley N.F., Graham J.T. Clinical findings for the first 1000 Gulf War veterans in the Ministry of Defence's medical assessment programme. Br. Med. J. 1999, 318:290-294.
19. Cook J.E., Wenger C.B., Kolka M.A. Chronic pyridostigmine bromide administration: Side effects among soldiers working in a desert environment. Mil. Med. 1992, 157:250-254.
20. Davis S.D., Kator S.F., Wonnett J.A., Pappas B.L., Sall J.L. Neurally mediated hypotension in fatigued Gulf War veterans: A preliminary report. Am. J. Med. Sci. 2000, 319:89-95.
21. Friedman A., Kaufer D., Shemer J., Hendler I., Soreq H., Tur-Kaspa I. Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response. Nat. Med. 1996, 2:1382-1385.
22. Fukuda K., Nisenbaum R., Stewart G., Thompson W.W., Robin L., Washko R.M., Noah D.L., Barrett D.H., Randall B., Herwaldt B.L., Mawle A.C., Reeves W.C. Chronic multisymptom illness affecting Air Force veterans of the Gulf War. J. Am. Med. Assoc. 1998, 20:981-988.
23. Gray G., Smith T., Knoke J., Heller J. The postwar hospitalization experience of Gulf War veterans possibly exposed to chemical munitions destruction at Khamisiyah, Iraq. Am. J. Epidemiol. 1999, 150:532-540.
24. Gray G.C., Gackstetter G.D., Kang H.K., Graham J.T., Scott K.C. After more than 10 years of Gulf War veteran medical evaluations, what have we learned?. Am. J. Prev. Med. 2004, 26:443-452.
25. Haley R.W. Excess incidence of ALS in young Gulf War veterans. Neurology 2003, 61:750-756.
26. Haley R.W., Kurt T.L. Self-reported exposure to neurotoxic chemical combinations in the Gulf War: A cross-sectional epidemiological study. J. Am. Med. Assoc. 1997, 277:231-237.
27. Haley R.W., Kurt T.L., Hom J. Is there a Gulf War syndrome? Searching for syndromes by factor analysis of symptoms. J. Am. Med. Assoc. 1997, 277:215-222.
28. Haley R.W., Billecke S., La Du B.N. Association of low PON1 type Q (type A) arylesterase activity with neurologic symptoms complexes in Gulf War veterans. Toxicol. Appl. Pharmacol. 1999, 157:227-233.
29. Haley R.W., Fleckstein J.L., Marshall W.W., McDonald G.G., Kramer G.L., Petty F. Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: Correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels. Arch. Neurol. 2000, 57:1280-1285.
30. Haley R.W., Marshall W.W., McDonald G.G., Daugherty M.A., Petty F., Fleckenstein J.L. Brain abnormalities in Gulf War syndrome: Evaluation of 1H MR spectroscopy. Neuroradiology 2000, 215:807-817.
31. Haley R.W., Vongpatanasin W., Wolfe G.I., Bryan W.W., Armitage R., Hoffman R.F., Petty F., Callahan T.S., Charuvastra E., Shell W.E., Marshall W.W., Victor R.G. Blunted circadian variation in autonomic regulation of sinus node function in veterans with Gulf War syndrome. Am. J. Med. 2004, 117:469-478.
32. Horner R.D., Kamims K.G., Feussner J.R., Grambow S.C., Hoff-Linquist J., Harati Y., Mitsumoto H., Pascuzzi R., Spencer P.S., Tim R., Howard D., Smith T.C., Ryan M.A.K., Coffman C.J., Kasarskis E.J. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology 2003, 61:742-749.
33. Hotoph M., Mackness M.I., Nikolaou V., Collier D.A., Curtis C., David A., Durrington P., Hull L., Ismail K., Peakman M., Unwin C., Wessely S., Mackness B. Paraoxonase in Persian Gulf War veterans. J. Occup. Environ. Med. 2003, 45:98-405.
34. Hotoph M., Mackness M.I., Nikolaou V., Collier D.A., Curtis C., David A., Durrington P., Hull L., Ismail K., Peakman M., Unwin C., Wessely S., Mackness B. Paraoxonase in Persian Gulf War veterans. J. Occup. Environ. Med. 2003, 45:668-675.
35. Hoy J.B., Cornell J.A., Karlix J.L., Schmidt C.J., Tebbett I.R., van Haaren F. Interactions of pyridostigmine bromide, DEET, and permethrin alter locomotor behavior in rats. Vet. Hum. Toxicol. 2000, 42:65-71.
36. Hoy J.B., Cornell J.A., Karlix J.L., Tebbett I.R., van haaren F. Repeated coadministration of pyridostigmine bromide, DEET, and permethrin alter locomotor behavior of rats. Vet. Hum. Toxicol. 2000, 42:72-76.
37. Husain K., Somani S. Delayed toxic effects of nerve gas sarin and pyridostigmine under physical stress in mice. J. Burns Surg. Wound Care (online journal) Available at www.journalof burns.com 2003 January 18.
38. Hyams K.C., Wignall F.S., Roswell R. War syndromes and their evaluation: From the US Civil War to the Persian Gulf War. Ann. Intern. Med. 1996, 125:398-405.
39. Institute of Medicine Gulf War and Health: Volume 1-Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccines 2000, National Academy Press, Washington, DC.
40. Self reported illness and health status among Gulf War veterans. J. Am. Med. Assoc. 1997, 277:238-245. Iowa Persian Gulf Study Group.
41. Jamal G.A., Hansen S., Apartopoulos F., Peden A. The "Gulf War syndrome". Is there evidence of dysfunction in the nervous system?. J. Neurol. Neurosurg. Psychiatr. 1996, 60:449-451.
42. Joseph S. The Comprehensive Clinical Evaluation Program Evaluation Team: A comprehensive clinical evaluation of 20,000 Persian Gulf War veterans. Mil. Med. 1997, 162:149-155.
43. Kaufer D., Friedman A., Seidman S., Soreq H. Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature 1998, 393:308-309.
44. Keeler J.R., Hurst C.G., Dunn M.A. Pyridostigmine used as a nerve agent pretreatment under wartime conditions. J. Am. Med. Assoc. 1991, 266:693-695.
45. Lallement G., Foquin A., Baubichon D. Heat stress, even extreme, does not induce penetration of pyridostigmine bromide into the brain of guinea pigs. Neurotoxicology 1998, 19:759-766.
46. Mackness B., Durrington P.N., Mackness M.I. Low paraoxonase in Persian Gulf War veterans self-reporting Gulf War syndrome. Biochem. Biophys. Res. Commun. 2000, 276:729-733.
47. Martin J. Deputy Director, Persian Gulf Veterans' Illnesses Investigative Team, Department of Defense, testimony before the Presidential Advisory Committee on the Gulf War Veterans' Illnesses, April, May, July, and August, 1996.
48. McCain W.C., Lee R., Johnson M.S., Whaley J.E., Ferguson J.W., Beall P., Leach G. Acute oral toxicity study of pyridostigmine bromide, permethrin and DEET in the laboratory rat. J. Toxicol. Environ. Health 1997, 50:113-124.
49. McCauley L.A., Joos S.K., Spencer P.S., Lasarev M.R., Shuell T., other members of the Portland Environmental Hazards Research Center Strategies to assess validity of self-reported exposures during the Persian Gulf War. Environ. Res. A 1999, 81:195-205.
50. McCauley L., Rischitelli G., Lambert W., Lasarev M., Sticker D. Symptoms of Gulf War veterans possibly exposed to organophosphate chemical warfare agents at Khamisiyah, Iraq. Int. J. Occup. Environ. Health 2001, 7:79-89.
51. McCauley L.A., Lasarev M.R., Sticker D., Rischitelli D.G., Spencer P.S. Illness experience of Gulf War veterans possibly exposed to chemical warfare agents. Am. J. Prev. Med. 2002, 23:200-206.
52. Menon P.M., Nasrallah H.A., Reeves R.R., Ali J.A. Hippocampal dysfunction in Gulf War syndrome. A proton MR spectroscopy study. Brain Res. 2004, 1009:189-194.
53. Murata K., Arak S., Yokoyama K., Okumura T., Ishimatsu S., Takasu N., White R.F. Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack. J. Neurol. 1997, 244:601-606.
54. Murphy F.M. Gulf War syndrome. Br. Med. J. 1999, 318:274-275.
55. Nakajima T., Ohta S., Fukushima Y., Yanagisawa N. Sequelae of sarin toxicity at one and three years after exposure in Matsumoto, Japan. J. Epidemiol 1999, 9:337-343.
56. National Academy of Sciences Possible Long-Term Health Effects of Short-Term Exposure to Chemical Agents: Volume 1-Anticholinesterases and Anticholinergics 1982, National Academy Press, Washington, DC.
57. Olgun S., Gogal R.M., Adeshina F., Choudhury H., Misra H.P. Pesticide mixtures potentiate the toxicity in murine thyrmocytes. Toxicology 2004, 196:181-195.
58. Peckerman A., LaManca J.J., Smith S.L., Taylor A., Tiersky L., Pollet C., Korn L.R., Hurwitz B.E., Ottenweller J.E., Natelson B.H. Cardiovascular stress responses and their relationship to symptoms in Gulf War veterans with fatiguing illness. Psychosom. Med. 2000, 62:509-516.
59. Peden-Adams M.M., Eudaly J., Eudaly E., et al. Evaluation of immunotoxicity induced by single or concurrent exposure to N, N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel. Toxicol. Ind. Health 2001, 17:192-209.
60. Presidential Advisory Committee on Gulf War Veterans' Illnesses Final Report 1996, U.S. Government Printing Office, Washington, DC.
61. Presidential Advisory Committee on Gulf War Veterans' Illnesses Interim Report 1996, U.S. Government Printing Office, Washington, DC.
62. Presidental Advisory Committee on Gulf War Veterans' Illnesses Special Report 1997, October, U.S. Government Printing Office, Washington, DC.
63. Riviere J.E., Baynes R.E., Brooks J.D., Yeatts J.L., Monteiro-Riviere N.A. Percutaneous absorption of topical N, N-diethyl-m-toluamide (DEET): Effects of exposure variables and coadministered toxicants. J. Toxicol. Environ. Health A 2003, 66:133-151.
64. Roland P.S., Haley R.W., Yellin W., Owens K., Shoup A.G. Vestibular dysfunction in Gulf War syndrome. Otolaryngol. Head Neck Surg. 2000, 122:319-329.
65. Scremin O.U., Shih T.-M., Huynh L., Roch M., Booth R., Jenden D.J. Delayed neurologic and behavioral effects of subtoxic doses of cholinesterase inhibitors. J. Pharmacol. Exp. Ther. 2003, 304:1111-1119.
66. Shapiro S.E., Lasarev M.R., McCauley L. Factor analysis of Gulf War illness: What does it add to our understanding of possible health effects of deployment?. Am. J. Epidemiol. 2002, 156:578-585.
67. Sharief M.K., Priddin J., Delamont R.S., et al. Neurophysiologic analysis of neuromuscular symptoms in UK Gulf War veterans: A controlled study. Neurology 2002, 59:1518-1525.
68. Sinton C.M., Fitch T.E., Petty F., Haley R.W. Stressful manipulations that elevate corticosterone reduce blood-brain barrier permeability to pyridostigmine in the rat. Toxicol. Appl. Pharmacol. 2000, 165:99-105.
69. Smith T.C., Gray G.C., Weir J.C., Heller J.M., Ryan M.A. Gulf War veterans and Iraqi nerve agents at Khamisiyah: Postwar hospitalization data revisited. Am. J. Epidemiol. 2003, 158:457-467.
70. Spencer P.S., McCauley L.A., Lapidus J.A., Lasarev M., Joos S.K., Storzbach D. Self-reported exposures and their association with unexplained illness in a population-based case-control study of Gulf War veterans. J. Occup. Environ. Med. 2001, 43:1041-1056.
71. Steele L. Prevalence and patterns of Gulf War illness in Kansas veterans: Association of symptoms with characteristics of person, place, and time of military service. Am. J. Epidemiol. 2002, 152:992-1002.
72. Storzbach D., Campbell K.A., Binder L.M., McCauley L., Anger W.K., Rohlman D.S., Kovera C.A. Psychological differences between veterans with and without Gulf War unexplained symptoms. Psychosom. Med. 2001, 62:726-735.
73. Unwin C., Blatchley N., Coker W., Ferry S., Hotopf M., Hull L., Ismail K., Palmer I., David A., Wessely S. Health of U.K. servicemen who served in Persian Gulf War. Lancet 1999, 353:169-178.
74. U.S. Department of Defense, Office of the Special Assistant to the Under Secretary of Defense (Personnel and Readiness) for Gulf War Illnesses, Medical Readiness, and Military Deployment Environmental exposure report: Pesticides-Final report 2003, Available at, Accessed March 20, 2005. http://www.gulflink.osd.mil.
75. U.S. Department of Veterans Affairs Research Advisory Committee on Gulf War Veterans' Illnesses (2004, September 4).
76. Scientific progress in understanding Gulf War veteran's illnesses: Report and recommendations. Available at www.ngwrc.org. Accessed March 20, 2005.
77. Research Advisory Committee on Gulf War Veterans' Illnesses Scientific progress in understanding Gulf War Veterans' illnesses: Report and recommendations 2004, September, Available at, Accessed March 20, 2005. http://www.ngwrc.org.
78. U.S. General Accounting Office Gulf War illnesses: DOD's conclusions about U.S. troops' exposure cannot be adequately supported, GAO-04-159 2004, Available at, Accessed March 20, 2005. http://www.gao.gov.
79. van Haaren F., Cody B., Hoy J.B., et al. The effects of pyridostigmine bromide and permethrin, alone or in combination, on response acquisition in male and female rats. Pharmacol. Biochem. Behav. 2000, 66:739-746.
80. van Haaren F., Haworth S.C., Bennett S.M., et al. The effects of pyridostigmine bromide, permethrin, and DEET alone, or in combination, on fixed-ratio and fixed-interval behavior in male and female rats. Pharmacol. Biochem. Behav. 2001, 69:23-33.
81. Vlahov D., Galea S. War and anxiety disorders. Epidemiology 2004, 15:129-130.
82. Vogel J.S., Keating G.A., Buchholz B.A. Protein binding of isofluorophate in vivo after coexposure to multiple chemicals. Environ. Health Perspect. 2002, 110:1031-1036.
83. Vojdani A., Thrasher J.D. Cellular and humeral immune abnormalities in Gulf War veterans. Environ. Health Perspect. 2004, 112:840-846.
84. Walpole R., Rostker B. Modeling the chemical warfare agent release at the Khamisiyah pit 1997, September, Available at, Central Intelligence Agency and Department of Defense, Washington, DC. http://www.gulflink.osd.mil.
85. Martin J. Deputy Director, Persian Gulf Veterans' Illnesses Investigative Team, Department of Defense, testimony before the Presidential Advisory Committee on the Gulf War Veterans' Illnesses, April, May, July, and August, 1996.
86. U.S. Department of Veterans Affairs Research Advisory Committee on Gulf War Veterans' Illnesses (2004, September 4).
87. Scientific progress in understanding Gulf War veteran's illnesses: Report and recommendations. Available at www.ngwrc.org. Accessed March 20, 2005.