Understanding the Pharmacokinetics of Atrazine in Cynomolgus Monkeys: Implications for Human Biomonitoring Open Access

George, Elizabeth K (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/hm50ts01f?locale=en
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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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