Pyridostigmine, Diethyltoluamide, Permethrin, and Stress: A Double-Blind, Randomized, Placebo-Controlled Trial to Assess Safety

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.