Grant Details
Grant Number: |
1R01ES010503-01 Interpret this number |
Primary Investigator: |
Keating, Garrett |
Organization: |
University Of Calif-Lawrnc Lvrmr Nat Lab |
Project Title: |
Improved Exposure Assessment for Organophosphate Pestici |
Fiscal Year: |
2000 |
Abstract
DESCRIPTION: (Adapted from Investigator's Abstract)
The objective of the proposed research is to improve exposure assessment of
pesticides by developing a methodology for measuring acetylcholinesterase
(AChE) inhibition that includes determinations of free and total enzyme in the
same blood sample. The research will develop a methodology for preparing
whole blood samples so that these measurements can be made sequentially using
currently available methods for measuring cholinesterase activity that are
used in clinical monitoring of pesticide exposure. The research proposes to
calibrate colorimetric measurements of these AChE activities with specific
binding of a radiolabeled probe to AChE in blood samples partially inhibited
by an organophosphate (OP) pesticide. Once analyzed by standard AChE assays,
the samples will be processed to reactivate the OP-inhibited AChE followed by
determination of this reactivated fraction through binding of the AChE-
specific probe and colorimetric assay. This parallel AChE measurement
approach is intended to validate the sequential colorimetric determinations so
that the methodology can be performed without the radioactive assay. This
capability will improve exposure assessment of pesticides in several ways.
First, knowledge of the total AChE activity in a blood sample will permit a
more accurate estimate of the level of inhibition by utilizing individual-
specific information. Secondly, measurement of AChE activity is considered to
be a more relevant endpoint for the neurological effects of pesticides than
other cholinesterase activities. Finally, the ratio of inhibited-to-total
AChE will provide an internal standard to normalize the different ChE assays
currently used to monitor pesticide exposure.
Publications
None