OBJECTIVE
To determine whether short-term human exposure to pyridostigmine bromide, diethyltoluamide,
and permethrin, at rest or under stress, adversely affects short-term physical or
neurocognitive performance.
PARTICIPANTS AND METHODS
A multicenter, prospective, double-blind, placebo-controlled crossover trial exposing
64 volunteers to permethrin-impregnated uniforms, diethyltoluamide-containing skin
cream, oral pyridostigmine, and corresponding placebos was performed. Each participant
had 4 separate sessions, ensuring exposure to all treatments and placebos under both
stress and rest conditions in random order. Outcomes included physical performance
(handgrip strength and duration, stair climbing, and pull-ups [males] or push-ups
[females]), neurocognitive performance (computerized tests), and self-reported adverse
effects.
RESULTS
Permethrin was undetectable in the serum of all participants; pyridostigmine levels
were higher immediately after stress (41.6 ng/mL; 95% confidence interval, 35.1-48.1
ng/mL) than rest (23.0 ng/mL; 95% confidence interval, 19.2-26.9 ng/mL), whereas diethyltoluamide
levels did not significantly differ by stress condition. Heart rate and systolic blood
pressure increased significantly with stress compared with rest but did not vary with
treatment vs placebo. Physical and neurocognitive outcome measures and self-reported
adverse effects did not significantly differ by exposure group.
CONCLUSION
Combined, correct use of pyridostigmine, diethyltoluamide, and permethrin is well
tolerated and without evidence of short-term physical or neurocognitive impairment.
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REFERENCES
- Pretreatment for nerve agent exposure.in: Sidell FR Takafuji ET Franz DR Medical Aspects of Chemical and Biological Warfare. Borden Institute, Walter Reed Army Medical Center, Washington, DC1997: 181-196
- Pyridostigmine used as a nerve agent pretreatment under wartime conditions.JAMA. 1991; 266: 693-695
- Chronic pyridostigmine bromide administration: side effects among soldiers working in a desert environment.Mil Med. 1992; 157: 250-254
- Interactive effects of pyridostigmine and altitude on performance.in: Proceedings of the Sixth Medical Chemical Defense Bioscience Review. US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Md1987: 605-607
- Pyridostigmine bromide effects of performance of tactical transport aircrews.in: Proceedings of the Sixth Medical Chemical Defense Bioscience Review. US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Md1987: 609-611
- The use of therapeutic mixtures in the treatment of cholinesterase inhibition.Fundam Appl Toxicol. 1981; 1: 214-216
- The influence of pyridostigmine administration on human neuromuscular functions—studies in healthy human subjects.Fundam Appl Toxicol. 1991; 16: 288-298
- The effect of pyridostigmine on bronchial hyperreactivity.Chest. 1993; 103: 1755-1758
- A Review of the Scientific Literature as it Pertains to Gulf War Illnesses. Vol 2. Pyridostigmine Bromide. RAND, Santa Monica, Calif1999
- Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response.Nat Med. 1996; 2: 1382-1385
- Stress does not enable pyridostigmine to inhibit brain cholinesterase after parenteral administration.Toxicol Appl Pharmacol. 2000; 164: 301-304
- 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
- Self-reported illness and health status among Gulf War veterans: a population-based study.JAMA. 1997; 277: 238-245
- Unexplained illness among Persian Gulf War veterans in an Air National Guard unit: preliminary report—August 1990-March 1995.MMWR Morb Mortal Wkly Rep. 1995; 44: 443-447
- Symptoms in 18,495 Persian Gulf War veterans: latency of onset and lack of association with self-reported exposures.J Occup Environ Med. 1998; 40: 520-528
- War syndromes and their evaluation: from the U.S. Civil War to the Persian Gulf War.Ann Intern Med. 1996; 125: 398-405
- Gulf War illnesses: causes and controversies.Mayo Clin Proc. 2000; 75: 811-819
- In the borderland between health and disease following the Gulf War.Mayo Clin Proc. 2000; 75: 777-779
Bolton HT. Use and safety of pesticides (repellents) in Persian Gulf. Presented at: Department of Veterans Affairs Update on Health Consequences of Persian Gulf Service: Baltimore, Md; July 18, 1995.
- Review of the biodistribution and toxicity of the insect repellent N,N-diethyl-m-toluamide (DEET).J Toxicol Environ Health. 1986; 18: 503-525
- Comparative percutaneous absorption of lindane and permethrin.Arch Dermatol. 1996; 132: 901-905
- Self-reported exposure to neurotoxic chemical combinations in the Gulf War: a cross-sectional epidemiologic study.JAMA. 1997; 277: 231-237
- Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET, and permethrin.J Toxicol Environ Health. 1996; 48: 35-56
- Acute oral toxicity study of pyridostigmine bromide, permethrin, and DEET in the laboratory rat.J Toxicol Environ Health. 1997; 50: 113-124
- Initial evaluation of N,N-diethl-m-toluamide and permethrin absorption in human volunteers under stress conditions.Mil Med. 2006; 171: 122-127
- Personal Protective Measures Against Insects and Other Arthropods of Military Significance. Defense Pest Management Information Analysis Center, Forest Glen Section, Walter Reed Army Medical Center, Washington, DC1996 (Technical Guide No. 36.)
- Acute psychophysiologic reactivity and risk of cardiovascular disease: a review and methodologic critique.Psychol Bull. 1984; 96: 435-464
- Automated Neuropsychological Assessment Metrics Documentation. Vol. 1. Test Administration Guide. Office of Military Performance Assessment Technology, Silver Spring, Md1992
- Increased neurotoxicity following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos.Fundam Appl Toxicol. 1996; 34: 201-222
- Neurochemical effects of DDT in rat brain in vivo.Arch Toxicol Suppl. 1986; 9: 14-26
Article Info
Footnotes
This study was supported by a competitive grant from the US Army Medical Research Materiel Command under the Congressionally Directed Medical Research Programs, DAMD17-00-1-0715.
None of the authors have any financial or other conflicts of interest regarding the subject matter addressed in this article.
The opinions or assertions contained herein are the private views of the authors and are not to be considered as official or as reflecting the views of the Department of the Army, Department of the Navy, or Department of Defense.
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© 2006 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
