TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

Project Details

Description

The long-term objective of this proposal 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
determining the relative roles of hepatic and extrahepatic
biotransformation of these chemicals in mediating their acute
toxcicities. Implicit in this approach is the evaluation of
numerous factors which affect these critical metabolic pathways.
It is expected that these studies will provide information useful
in assessing the health hazards of organothiophosphate
insecticides, as well as their potential for toxic interactions
with certain other zenobiotics. Furthermore these studies will
contribute to the fundamental knowledge of those metabolic systems
involved in the biotransformation of organothiophosophate
insecticides. The specific aims to be addressed in this research
are as follows: 1. To further investigate whether the toxic
oxygen analogs produced intrahepatically from organothiophosphate
pesticides enter the general circulation, or whether they undergo
extensive intrahepatic detoxification thereby preventing their
escape from the liver. 2. To determine if the A-esterase in blood
has the capacity to prevent the passage of those oxons escaping
liver to target tissues such as brains and lungs. 3. To
investigate the toxicological significance to extrahepatic
activation of certain organothiophosphate insecticides. 4. To
identify and characterize the metabolic activation and
detoxification of organothiophosphate insecticides by human
placenta. 5. To evaluate the role of gluthathione-mediated
biotransformation of dimethyl-substituted organothiophosphates in
vivo in the detoxification of these pesticides.
StatusFinished
Effective start/end date12/31/898/31/96

Funding

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

ASJC

  • Environmental Science(all)
  • Medicine(all)
  • Toxicology

Fingerprint

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.