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Toxic Interactions of Prophylactic Drugs and Pesticides

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Annual rept. 21 Dec 2000-20 Dec 2001

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The key goal of this project is to test the hypothesis that exposure to mixtures of the test compounds, PB oral, DEET dermal, and permethrin dermal reduces the bodys ability for their detoxification, resulting in increased bioavailability of the parent compounds and of their enhanced delivery to the toxicity sites, leading to pronounced toxicity. The results reported in this Annual Report support this hypothesis as follows 1 Although exposure to single compounds caused locomotor and sensorimotor performance deficit in rats, combined exposure resulted in greater deficit even at one-tenth of real-life exposure doses. 2 Combined exposure to the three test compounds with stress increased the permeability of the blood-brain barrier BBB as shown by the uptake of 3Hhexamethonium iodide, penetration of horseradish peroxidase and immunostaining for endothelial-barrier antigen EBA, and inhibition of brain acetylcholinesterase. 3 Exposure to DEET and or permethrin for 60 days, and PB, DEET, and permethrin in combination with stress for 28 days caused neuronal cell death in cerebral cortex and hippocampus, and Purkinje cells in the cerebellum. These alterations are consistent with the neurobehavioral changes and breakdown of the BBB. 4 Combined exposure to chemicals and stress caused liver damage and decreased detoxification of test compounds. 5 Combined exposure increased the bioavailability of test compounds because liver damage and because of competition for the diminished amount of available enzymes in the plasma and liver. These results are consistent with recent DOD report that Gulf war veterans are prone to neurologic diseases such as amyotrophic lateral sclerosis ALS.

Subject Categories:

  • Medicine and Medical Research
  • Toxicology
  • Pharmacology

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