Understanding the Pharmacokinetics of Atrazine in Cynomolgus Monkeys: Implications for Human Biomonitoring Open Access
George, Elizabeth K (2012)
Abstract
Abstract
Understanding the Pharmacokinetics of Atrazine in Cynomolgus
Monkeys: Implications for Human Biomonitoring
By: Elizabeth K. George
Background: Several studies suggest harmful effects
caused by exposure to the widely used
herbicide, atrazine (ATZ) however, little is known regarding the
pharmacokinetics of ATZ.
Purpose: To understand the metabolism and elimination
kinetics in an animal model by
identifying a biomarker of exposure, determining the elimination
half life of ATZ, an ideal
serum sample collection time and inter- animal variation of the
pharmacokinetics of atrazine.
Methods: Plasma samples were analyzed using a solid-phase
extraction-high-performance
liquid chromatography-tandem mass spectrometry method with isotope
dilution
quantification to measure four chlorinated atrazine metabolites in
plasma;
diaminochloroatrazine [DACT], desethyl atrazine [DEA], desisopropyl
atrazine [DIA] and
atrazine [ATZ].
Results: The metabolite diaminochloroatrazine [DACT] was
identified as an appropriate
biological marker for atrazine exposure due to its extended
presence in serum as well as the
fact that DACT proves to be present in the highest concentration
relative to the other
metabolites. The half live of DACT was determined to be
approximately 17 hrs.
Conclusion: Based on the information determined through
this project, a better understanding
of the activities of ATZ post exposure will aid in laying a
foundation for knowledge
regarding the pharmacokinetics of ATZ.
Table of Contents
TABLE OF CONTENTS
I.
INTRODUCTION...............................................................................................................1
II.
METHODS.......................................................................................................................6
a. Experimental Subjects and Dosing
Scheme...........................................................................6
b. Sample
Collection..............................................................................................................6
c. Sample Preparation and
Analysis.........................................................................................6
d. Data
Analysis...................................................................................................................8
III.
RESULTS......................................................................................................................8
a. Identify a
biomarker..........................................................................................................9
b. Determine the elimination half
life.......................................................................................9
c. Determine ideal serum sample collection
time.....................................................................10
d. Identify inter-animal
variation...........................................................................................10
IV.
DISCUSSION...............................................................................................................11
a. Major
Findings................................................................................................................11
b.
Limitations.....................................................................................................................14
V. CONCLUSION AND
RECCOMENDATIONS.......................................................................15
VI.
REFERENCES...............................................................................................................17
VII. TABLES AND
FIGURES...............................................................................................19
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