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# Office of Pesticide Programs & The Agricultural **Health Study**

**, Comparison O**  **f 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 2011Page 2 of 5 In t his document , EPA describe s the steps completed subsequent to the February 2010 meeting of the FIFRA Scientific Adviso ry Panel (SAP) concerning the evaluation of exposure assessment methods in epidemiologic research as described in Case Study B presented at th at 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 t he meeting minutes of the February 2010 SAP , the panel recommended that the Agency consider a variety of actions including a broader examination of epidemiologic al 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 large r scale analysis, and addressing issues related to the generalizability of epidemiological findings in the risk assessment process.

T he Agency agrees with these general recommendations, and has start ed this process with a focus on the Agricultural Healt h Study (AHS) ( http://aghealth.nci.nih.gov/ ) . EPA will foc us on AHS due to its high

- quality methods and de sign 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 perspective s

. Ultimately, the current exercise will inform the use of other e pide miological 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 c omplete a comparison of the exposure determi nants used in the AHS and EPA approaches for pesticide applicator exposure assessment to understand potential similarities and differences. Limited progress has been made ; t he key components of this step which have been completed i nclud e a review of the appropria te questionnaires, examination of the
exposure

- related information c ollected 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 b uild 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 facilitat e a one

- to

- one comparison of exposure variables for these individuals (e.g., diary i nformation, 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.Page 3 of 5 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 wa s to complete a large r

- 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 b elow

. 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 cas e 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 20 09

. Additional data were received in 2010 based on subsequent requests. From the Phase I Enrollment and Farmer Applicator questionnaire s , 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 P estici de Use Module

– Private Pesticide Applicator questionnaire will also be used because application method is linked to pesticide use and crop s 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.Page 4 of 5 Another ongoi ng 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 initia l 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 complet ing Steps 1 and 2 of the case study because it illustrate s of the exposure characteristics of the privat e applicators in the AHS cohort ; h owever, 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.

P rocedures 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 o utlined 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 t he February 2010 SAP meeting have developed a basic understanding of the AHS data st ructure to quickly proceed once the information
becomes available

.

4 http://aghealth.nci.nih.gov/guidelines.htmlPage 5 of 5 **•** 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.