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Office of Pesticide Programs & The Agricultural 

Health Study, Comparison Of Exposure 

Assessment Approaches – An Update On 

Recent Activities

Submitted to the FIFRA Scientific Advisory Panel

For Review and Comment

July 26-29, 2011

Office of Pesticide Programs

Office of Chemical Safety and Pollution Prevention

U.S. Environmental Protection Agency

Washington, DC

June 2011
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In this document, EPA describes the steps completed subsequent to the February 2010 

meeting of the FIFRA Scientific Advisory Panel (SAP) concerning the evaluation of 

exposure assessment methods in epidemiologic research as described in Case Study B

presented at that meeting.

1

 While necessary differences in exposure assessment 

methodology between epidemiologic research and quantitative risk assessment are 

understood and acknowledged, the uncertainties that result from these differences are not 

as well understood at this time. The purpose of this project is to enhance EPA’s 

understanding as to how epidemiology may be used to inform the regulatory process. 

In the meeting minutes of the February 2010 SAP, the panel recommended that the 

Agency consider a variety of actions including a broader examination of epidemiological 

research regardless of study design, continued evaluation of the differences in exposure 

metrics, clarity with regard to the Agency’s exposure assessment approach, use of 

pertinent biological monitoring data as a basis for comparison followed by a larger scale 

analysis, and addressing issues related to the generalizability of epidemiological findings 

in the risk assessment process. 

The Agency agrees with these general recommendations, and has started this process 

with a focus on the Agricultural Health Study (AHS) (http://aghealth.nci.nih.gov/). EPA will 

focus on AHS due to its high-quality methods and design as well as the number of 

anticipated studies as previously discussed at the February 2010 SAP. EPA expects to 

learn lessons specific to its use of AHS study results, as well as to identify examples that

are useful from both general methodological and policy development perspectives. 

Ultimately, the current exercise will inform the use of other epidemiological findings in the 

pesticide regulatory process.

The three step process proposed by EPA at the February 2010 SAP is briefly described 

below. An update on the progress made to date follows. 

Step 1: The EPA goal was to complete a comparison of the exposure 

determinants used in the AHS and EPA approaches for pesticide applicator 

exposure assessment to understand potential similarities and differences. Limited 

progress has been made; the key components of this step which have been 

completed include a review of the appropriate questionnaires, examination of the 

exposure-related information collected by the survey questionnaires, and 

identifying limitations associated with the available information. 

Step 2:

 

1 2010 SAP information available at 

The EPA goal was to build on the findings from Step 1 using separately 

collected data from a field study on a subset of pesticide applicators in the AHS 

cohort. These data can be used to facilitate a one-to-one comparison of exposure 

variables for these individuals (e.g., diary information, biomonitoring data, AHS 

http://www.epa.gov/scipoly/sap/meetings/2010/020210meeting.html 

the Case Study B document and the SAP panel report are key primers for this discussion.
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survey responses, and calculated AHS exposure intensity scores). This step has 

not been conducted because all needed data are not yet available since the data 

transfer agreement between the AHS and EPA has not yet been completed. This

is discussed further below. 

Step 3: The EPA goal was to complete a larger-scale comparative analysis using 

information pertaining to specific pesticide users in the AHS cohort based on the 

findings of Steps 1 and 2. Prior to conducting this step, a feasibility of this analysis 

will be evaluated by the Agency and investigators from the AHS. 

Data to complete Steps 1 and 2 are encompassed within the AHS Phase I and Phase II 

questionnaires, as well as certain AHS sub-studies described below.

2

In addition to the questionnaire data, a small group of sub-studies that developed more 

detailed exposure information for members of the AHS cohort have been completed. Step 

2 of the case study will include use of the results from Bakke et al 2008 which was 

selected from the group of available studies that were considered for this process.

 The Phase I and II 

data originally requested were received by EPA in December 2009. Additional data were 

received in 2010 based on subsequent requests. From the Phase I Enrollment and 

Farmer Applicator questionnaires, EPA has abstracted information regarding use of 

herbicides as a group, triazines, and atrazine including application methods, use of 

personal protection equipment (PPE), and farm size, among other relevant pesticide use 

and usage information. Phase II data from the Pesticide Use Module – Private Pesticide 

Applicator questionnaire will also be used because application method is linked to 

pesticide use and crops treated by an individual, which is not possible using Phase I 

information. This additional information is likely to allow for a more direct comparison with 

EPA’s methods. 

3

Bakke et al. (2008) conducted a longitudinal study of atrazine users before, during, and 

following a growing season, measured urinary biomarkers of pesticide exposure, and 

collected diary information to supplement the AHS questionnaires. The study population 

consisted of thirty farmers from the AHS Iowa cohort who had completed both the Phase I 

and Phase II questionnaires. Using the Bakke study will allow for a direct comparison to 

see how well the intensity scores predict the monitoring results and to examine the 

correlation between different types of exposure metrics. 

 

2 Questionnaires available at http://aghealth.nci.nih.gov/questionnaires.html 3

Bakke, B., A.J. De Roos, D.B. Barr, P.A. Steward, A. Blair, L. Beane-Freeman, C.F. Lynch, R.H. Allen, M.C.R. 

Alavanja, and R. Vemeulen. 2008. Exposure to atrazine and selected non-persistent pesticides among corn farmers 

during a growing season.
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Another ongoing aspect related to this effort is to develop a temporal characterization of 

how farming practices evolve over time as a critical aspect of understanding how 

conditions prevailing during the time frame of the epidemiological study compare to 

current conditions (e.g., efficacy of a risk mitigation measure or the ability to extrapolate 

results to a broader user population). To this end, EPA is also seeking use information 

from AHS to be able to evaluate such factors. 

To date, EPA has completed initial exploratory analyses using the currently available 

data. Specifically, the Agency has compared AHS intensity scores by application method, 

PPE use and pesticide use, or some combination of the above factors as described in 

Step 1 of the 2010 SAP materials. This is an important step in completing Steps 1 and 2 

of the case study because it illustrates of the exposure characteristics of the private 

applicators in the AHS cohort; however, given the complexities of the data collected and 

large size of the AHS dataset, EPA is still in the process of refining these analyses in 

conjunction with AHS researchers.

Procedures and guidelines have been established for collaborative research with the 

AHS.4 The National Institutes of Health (NIH) has recently implemented new procedures 

guiding the transfer of materials and data to collaborators. The new procedures have 

affected the transfer of sub-study data related to Bakke et al that are needed to complete

Step 2 of the analysis plan described above. Both agencies are working to achieve 

consensus on the terms of the data transfer that meet EPA’s statutory needs for 

transparency and NIH requirements for collaboration. Pending completion of the 

agreement EPA will continue to pursue the process outlined above for Step 1. Work on 

Step 2 will begin following data transfer. 

A list of milestones that EPA plans on moving forward with relative to the goals of this 

analysis is provided below for consideration:

• Achieve consensus regarding the conditions of the data transfer agreement for the 

sub-study dataset. 

• Proceed with the case study process once the Bakke et al data become available. 

The efforts since the February 2010 SAP meeting have developed a basic 

understanding of the AHS data structure to quickly proceed once the information 

becomes available.

 

4 http://aghealth.nci.nih.gov/guidelines.html
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• Proceed with the evaluation of the use information for the selected chemicals in order 

to develop standard approaches for evaluating the influence of differences in 

assumptions related to farming practices and use patterns on findings by AHS relative 

to EPA.

Future SAP presentations are possible but such a need will be determined based on the 

outcome of these efforts. Possible topics would also be determined based on the results 

of these efforts.