Project Details


The long-term objective of this project is to supply information which will
aid in the identification of conditions under which individuals might be
susceptible to organothiophosphate pesticide-induced toxicity. It seeks to
accomplish this objective by focusing on how hepatic and extrahepatic
metabolic activation and detoxification of these pesticides mediate their
toxicity. The relative activation and detoxification of
organothiophosphate pesticides at sites of entry and, after absorption, at
various internal organs could greatly influence the severity and time
course of their toxicity. Understanding the interactions of other foreign
compounds with organothiophosphates following different routes of exposure
requires knowledge of the relationships of metabolism of these pesticides
by different tissues. This research will not only provide information
helpful in the safety assessment of pesticides, but will also contribute to
the fundamental knowledge of those metabolic systems involved in the
biotransformation of these pesticides. Specific aims to be addressed in
this research are: 1. To evaluate if the toxic oxygen analogs produced
hepatically from organothiophosphates escape the liver, thereby entering
the general circulation, or are these potent cholinesterase inhibitors
further biotransformed hepatically, inactivating them before they exit the
liver; 2. If the toxic oxygen analogs of organothiophosphates escape the
liver and enter the blood, can they survive long enough to reach
extrahepatic organs, or will they quickly be detoxified by plasma
A-esterases; 3. To evaluate the toxicological significance of extrahepatic
activation of organothiophosphate pesticides with particular emphasis on
the brain.
Effective start/end date1/1/901/1/90


  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences


  • Toxicology


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.