title: Pyridostigmine, diethyltoluamide, permethrin, and stress: a double-blind, randomized, placebo-controlled trial to assess safety.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Combined, correct use of pyridostigmine, diethyltoluamide, and permethrin is well tolerated and without evidence of short-term physical or neurocognitive impairment.
authors.affiliation: Division of Military Internal Medicine, Department of Medicine, Room A3062, Uniformed Services University, 4301 Jones Bridge Rd, Bethesda, MD 20814, USA. mroy@usuhs.mil
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roy
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Kraus
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Seegers
authors.forename: Sylvia Y N
authors.initials: SY
authors.lastname: Young
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Kamens
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Law
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Cherstniakova
authors.forename: David N
authors.initials: DN
authors.lastname: Chang
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sato
authors.forename: William
authors.initials: W
authors.lastname: Matulich
authors.forename: David S
authors.initials: DS
authors.lastname: Krantz
authors.forename: Louis R
authors.initials: LR
authors.lastname: Cantilena
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Deuster
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000032:analysis; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D003671:DEET / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D004781:Environmental Exposure; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008889:Military Personnel; D026023:Permethrin / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D010575:Pesticides / Q000009:adverse effects* / Q000097:blood; D005082:Physical Exertion / Q000187:drug effects* / Q000502:physiology; D011446:Prospective Studies; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D012044:Regression Analysis; D013315:Stress, Psychological; D014481:United States
chemical_list: D001798:Blood Proteins; D002800:Cholinesterase Inhibitors; D010575:Pesticides; D003671:DEET; D026023:Permethrin; D011729:Pyridostigmine Bromide