Atrazine Re Atrazine Re

-Evaluation:

Introduction & Status

Atrazine Re

-Evaluation:

Introduction & Status

Presentation to Scientific Advisory Panel

July 26 July 26

-29 2011 29, 2011

Elizabeth Méndez, Ph D. . 

Health Effects Division

USEPA Office of Pesticide Pro

grams
Peer Review Peer Review

• 1988 SAP: Evaluation of rat mammary gland • 2000 SAP: Evaluation of MOA

• Mammary gland Mammary gland tumors reproductive tumors, reproductive and

developmental findings in rats

• Human relevance Human relevance

• 2003 SAP: Evaluation of prostate cancer

• Epidemiology study on relationship betwe

atrazine exposure and prostate cancer in 

atrazine manufacturing plant
Atrazine Human Health 

Re-Evaluation

• Goals of the Re-Evaluation

• Determine if the risk assessment for atrazine sh

revised

• E l t d i t lt i l d t ( Evaluated experimental toxicology data (non-cancer a

effects)

• Evaluated epidemiology data

• Integrate experimental toxicology and epidemiology d• Ascertain if critical lifestages are adequately assesse• Ascertain if durations of exposure assessed are the m

appropriate

• Identify methods for analyzing uncertainty in dri

water monitoring data water monitoring data
Atrazine Atrazine 2010 SAP Meeting

2010 SAP Meeting

Human Health

•Draft Framework: Incorporating epidemiolo

Human Health

February 2010

and human health incident data in risk asse•Two atrazine case studies

April 2010

•Preliminary evaluation of in vitro & in vivo la

studies (non-cancer)

•Frequency of atrazine monitoring in drinkinsources (proposed approaches)•Epidemiology studies: non-cancer

September 2010

•Integration of epidemiology & experimentainto hazard characterization for non-cancer•Frequency of atrazine monitoring in drinkinsources (updated analyses)
Atrazine 2010 SAP Meeting

Panel Conclusions & Recommen

• February 2010 SAP

• In general, concurred with Agency’s 

proposed approach for evaluating

• September 2010 SAP

• Concurred with Agen

proposed approach for evaluating conclusions/approach

epidemiology data

• April 2010 SAP

• Reaffirmed conclusions of previous 

SAPs regarding cancer classification

conclusions/approachrange of issues. 

• Mammary gland • Use of internal do

SAPs

• LH suppression p

regarding cancer classification

for atrazine as “not likely to be carcinogenic to humans.”

• Concurred with Agency’s conclusions 

• LH suppression p

other effects

• Use of Cooper et 

to establish PoD

• No evidence of a 

that atrazine-induced effects on neuroendocrine function are the most sensitive effects

• Recomm

e

nded usin

g intern

al 

No evidence of

a 

sensitivity of the to adults

• Non-cancer findin

epidemiology stu

eco e ded us g te a

dosimetry rather than externally administered dose

• Noted that the toxicological duration 

of concern is key to determining sampling frequency identifying

• Recommended a com

statistical and modeliconsider in quantifyinexposure estimates f

data sampling frequency, identifying

methods for estimating exposure from monitoring

data
July 2011 SAP: Human Hea

Non-Cancer Cancer

July 2011 SAP: Human Hea

Review of new experimental toxicology studies Species extrapolation from rat to 

Epidemiology studies

human—duration of exposureLifestage sensitivity analysis

Approaches for analyzing atrazine Approaches for analyzing atrazine

monitoring data in drinking water sources

Udt t p a e on exposure assessment

collaborative project with AHS Integ ated e g t o t e e de ce t ep de o ogy & e pe 

rated weight of the evidence with epidemiology & expe

toxicology
M d f A ti Chemical

Dose Response 

Assessment

C d

Population Based

Studies

Mode of Action Characterization

Compounds

Assess

Biological 

Perturbation

Affected

Pathway Dose Response Analysis for 

Perturbations

of Toxicity 

Pathways

Calibrating 

in vitro and human

Dosimetry

Perturbation

Measures of

dose in vitro

Human Exposure

Data 

Metabolite(s)

Hazard Characterization

Exposure Assessment

Risk Characterization
Presentations

Atrazine: Adverse Outcomes and MOA 

Dr. Ralph C. Cooper

Review of Atrazine Cancer Epidemiology 

Dr. Carol H. Christensen

Integration of Epidemiology and Toxicity Data into Health Risk AssesIntegration of Epidemiology and Toxicity Data into Health Risk Asses

Dr. Elizabeth Méndez

Atrazine: Updates to Dose-Response Assessment with Implications for W

Fre

q y uenc

y

Dr. Chester Rodriguez

Evaluating Atrazine Drinking Water Monitoring Data For Use in Human Healt

Mr. Nelson Thurman

Atrazine Re-Evaluation: Scientific Considerations in Potential Sensitivity of In

Dr. Elizabeth Méndez

Case Study: Implications of MOA and Toxicity Profile on Water MonCase Study: Implications of MOA and Toxicity Profile on Water Mon

Dr. Chester Rodriguez and Mr. Nelson Thurman