Toxic Interactions of Prophylactic Drugs and Pesticides
Abstract
The goal of this project is to evaluate the possible interaction between DEET, permethrin and pyridostigmine bromide (PB) and the biological and pathological consequences of such interactions. Our standing hypothesis is that combined exposure to a mixture of chemicals would have enhanced, and in some cases deterimental toxicological effects than exposure with single chemical. We have been testing the stated hypothesis that interactions between combined chemical exposure would result in greater toxicological and pathological changes, and certain environmental modifying factors such as stress would modulate the toxic effects in combined exposure scenario. In the previous year we have carried out dose-response studies ranging from 0.1-10 x the estimated human exposure on DEET, permethrin and PB. In those studies we carried out neurobehavioral as well as neurochemical assessment following exposure to a single or multiple chemicals (See the manuscripts in Appendix). In the current studies, we have focused on the pathological consequences of sub-chronic exposure to single chemical or combined%concurrent exposure. Additionally, we studied the effect of one environmental modifier, stress on the neurotoxicity associated with concurrent exposure to PB, DEET and permethrin. The pathological changes were studied by immunohistochemical evaluation of microtubule-associated protein-2 (MAP-2), glialfibrillary acidic protein (GFAP), and microglial activation by lectin binding. Furthermore, we evaluated the possible mechanism(s) of neurotoxic effects of single or combined exposure by assessing the permeability of blood-brain barrier (BBB) and evaluating 8-hydroxy-2'-deoxyguanosine by HPLC. In the current studies, we also established the pharrnacokinetic interaction between DEET and permethrin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2001
- Accession Number
- ADA396374
Entities
People
- Mohamed B. Abou-donia
Organizations
- Duke University Hospital