TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

Project Details

Description

The overall objective of this proposal is to provide information
which will aid in the identification of conditions in which
individuals might be unusually susceptible (or resistant) to the
toxic actions of pesticides. The project will focus on the
organophosphorus insecticides since they represent the major class
of chemicals used as insecticides, and since they have potential
for serious toxic effects in humans. Research will be directed
towards characterizing those factors which affect the mammalian
biotransformation reactions of organophosphorus insecticides, as
well as the consequences of such reactions. It is expected that
these studies will provide information useful in assessing the
health hazards of organophosphorus insecticides, as well as their
potential for toxic interactions with certain other foreign
chemicals. Additionally this proposed research will contribute to
the fundamental knowledge of those metabolic systems involved in
the biotransformation of these insecticides. The specific aims in
this research are as follows: 1) To continue to investigate the
toxicological significance of extrahepatic activation of certain
organothiophosphorus insecticides. 2) To investigate why
glutathione-dependent detoxification of numerous
dimethyl-substituted organophosphorus insecticides occurs in vitro
but not in vivo. 3) To identify and characterize factors which
affect hepatic and serum A-esterase activities. Included in this
aim will be the investigation of kinetic and physiochemical
differences between "high activity" and "low activity" forms of
human serum A-esterase. 4) To characterize biochemically the two
forms of A-esterase purified from mouse hepatic microsomes in this
laboratory. 5) To characterize the factors affecting secretion of
A-esterase(s) from liver. These studies will also focus on
comparisons of the secreted form(s) of A-esterase(s) with those
forms found in hepatic microsomes.
StatusFinished
Effective start/end date1/1/908/31/96

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

  • Toxicology

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