Re-Evaluation of Human Hea

of Atrazine: Review of Expe

Animal and In vitro Studies an

Water Monitoring Frequ

Elizab

Senior Scientist, Heal

Office of P

mendez.e
Outline

z Introductionz Peer Review Historyz 2003 Human Health Risk Assessmen

 Mode of Action (MOA) & Points of Depa

(PODs)

z Current reevaluation

 Mammalian toxicity and in vitro studies Drinking water sampling frequency
Introduction

z Atrazine widely used in the U.S.

 Approximately 70 million pounds  Used primarily on corn

z Interim Reregistration Eligibility 

(IRED) finalized in 2003

z RED finalized in 2006
Peer Review History

z 1988 SAP: Evaluation of rat mammary gz 2000 SAP: Evaluation of MOA

 Mammary gland tumors, reproductive 

developmental findings in rats

 Human relevance

z 2003 SAP: Evaluation of prostate cancer

 Epidemiology study on relationship bet

exposure and prostate cancer in workemanufacturing plant

z 2009 SAP: Re-opening Atrazine Human 

Evaluation

z Feb. 2010 SAP: Draft framework for inc

epidemiology and humain risk assessment
2003 Human Health Risk As
Mode of Action (1)

z Mode of Action: Perturbation of hypoth

pituitary-gonadal (HPG) axis

z 2003 Key events:

 Hypothalamic effects resulting in chan

catecholamine function and regulation release of GnRH

 Attenuation of the LH surge Cessation of ovulation with the ensuin

release of estrogen

 Increased prolactin release by the pitu

secondary consequence resulting from estrogen levels

 Prolactin and estrogen-induced prolife

in the mammary gland leading to tum
Mode of Action (2)

z HPG axis perturbation

 Attenuation of LH surge Mammary gland tumorigenesis Delayed puberty onset

z Not relevant for mammary tumor 

development in humans

z Relevant to assess potential non-

adverse reproductive effects in hu
Non-cancer Effects

z Acute exposures: Delayed ossificatio

fetuses and decreased body weight (NOAEL/LOAEL of 10/70 mg/kg/day)

z Short exposures: Delayed puberty o

(NOAEL/LOAEL of 6.25/12.5 mg/kg/

z Intermediate and long-term exposur

attenuation of Luteinizing Hormone 
Current Analysis
Objective

z Conduct objective and thorough reviez Integrate new information with existi

evaluate hazard identification and dorelationships

z Determine the extent to which new s

a need for the Agency to develop a nhealth risk assessment 

z Re-consider, as appropriate, the freq

drinking water monitoring conducted the atrazine registrant
Scope of Current Analy

z Mammalian toxicity and in vitro studi

 Three databases searched (EMBASE, Pu Approximately 100 studies since 2003 Additional information on atrazine’s MOA Various types of toxicities reported in the 

reproductive/developmental, immunotoxgenotoxicity, carcinogenicity as well as M

z Drinking water sampling frequency

 Two approaches for monitoring drinking  Integrates the temporal aspects of the t

the sampling frequency
Presentations

z Mode of Action Analysis: Dr. Ralph Cooperz Immunotoxicity Analysis: Dr. Robert Luebz Neurotoxicity Analysis: Dr. John Liccionez Summary of Mammalian Toxicity: Dr. Eliza

 Next steps

z Approaches to Evaluating Water Sampling 

Frequency of Monitoring: Dr. Nelson Thur

z Evaluating the Performance of Sampling St

Dr. Mary Frankenberry

z Artificial Neural Network Modeling: Dr. Mic