Document ID: EPA-HQ-OPP-2007-0498-0029
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-10-15T04:00Z

AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

	OPEN MEETING

	

October 9 - 12, 2007

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2007-0498

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington,VA 22202

The Potential for Atrazine to Affect Amphibian Gonadal Development

Tuesday, October 9, 2007

  8:30 A.M.	Opening of Meeting and Administrative Procedures -- Joseph
E. Bailey, Designated Federal Official, Office of Science Coordination
and Policy, EPA

  8:40 A.M.	Introduction and Identification of Panel Members -- Steven
G. Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair  

  8:50 A.M.	Welcome and Opening Remarks -- William Jordan, Senior Policy
Advisor, Office of Pesticide Programs, EPA

  8:55 A.M.	Introduction - Goals and Objectives -- Arthur-Jean Williams,
Acting Division Director, Environmental Fate and Effects Division,
Office of Pesticide Programs, EPA 

  9:15 A.M	Introduction - Historical Perspective --Thomas Steeger,
Ph.D., Environmental Fate and Effects Division, Office of Pesticide
Programs, EPA

  9:45 A.M.	Break

10:00 A.M	Public Comment

12:00 P.M.	Lunch

  1:15 P.M.	Public Comment

  2:45 P.M.	Break

  3:00 P.M.	Public Comment

  5:00 P.M. 	Adjournment

AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

	OPEN MEETING

	

October 9 - 12, 2007

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2007-0498

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington,VA 22202

The Potential for Atrazine to Affect Amphibian Gonadal Development

Wednesday, October 10, 2007

  8:30 A.M.	Opening of Meeting and Administrative Procedures -- Joseph
E. Bailey, Designated Federal Official, Office of Science Coordination
and Policy, EPA

  8:40 A.M.	Introduction and Identification of Panel Members -- 

		Steven G. Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair  

  8:50 A.M.	Overview of Open Literature -- Thomas Steeger, Ph.D., Office
of Pesticide Programs, EPA 

  9:30 A.M.	Scientific Approach to the Design of the Data Call-In (DCI)
Studies -- Joseph Tietge, M.S., Office of Research and Development,
National Health and Environmental Effects Research Laboratory, EPA

10:15 A.M	Break

10:30 A.M.	Overview of the Atrazine DCI Studies -- Thomas Steeger,
Ph.D., Office of Pesticide Programs, EPA

11:15 A.M.	Overview of Statistical Analysis and Highlights of the
Results of the DCI Studies -- Mary Frankenberry, Office of Pesticide
Programs, EPA

11:45 P.M. 	Agency Conclusions --Thomas Steeger, Ph.D., Office of
Pesticide Programs, EPA

12:00 P.M.	Lunch

1:15 P.M.	Charge to Panel - Question 1

	In reviewing the available laboratory and field studies, the Agency
used a number of criteria to evaluate individual investigations. 
Criteria such as experimental design, test protocols, and quality
assurance information were used to evaluate the reliability of a
study’s ability to adequately assess a hypothesis that atrazine
elicits developmental effects in amphibians, and if so, the nature and
strength of associated dose-response relationships. 

(a)  	Please provide comments and recommendations regarding the EPA’s
approach and criteria used to evaluate the studies.   

	

	(b) 	Given the evaluation criteria employed by the Agency, please
comment on EPA’s overall application of these criteria to the
currently available studies.

2:15 P.M.	Charge to Panel - Question 2

	The Agency has concluded that the information contained in the open
literature published since the 2003 SAP does not provide any additional
information that could be used to refute or confirm the hypothesis that
exposure to atrazine alone causes adverse developmental effects in
amphibian gonads.

(a)  	Please comment on the comprehensiveness of the Agency’s
literature reviews relative to the potential effects of atrazine alone
on amphibian gonadal development.

(b) 	Please comment on the Agency’s evaluation of the open literature
studies and the Agency’s conclusion that the data derived from
laboratory studies, both individually and collectively, are not
sufficient to refute or confirm the hypothesis that atrazine exposure
causes developmental effects in amphibian gonads.

	(c) 	The Agency concluded that the field studies are not adequate for
assessing the hypothesis at hand.  Please comment on the Agency’s
conclusion.  If the SAP concludes one or more of the field studies do
provide the means to assess the hypothesis that atrazine exposure
results in effects on amphibian gonadal development, please suggest
interpretive and statistical methods that should be employed to evaluate
the data.

3:00 P.M.	Break

3:15 P.M.	Charge to Panel - Question 3

Please comment on the Agency’s evaluation of the final study design.
For example, the Agency concluded that the minor changes in the
experimental design [i.e., omitting atrazine degradate (DACT, DEA and
DIA) analysis and not conducting differential cell counts for ovarian
and testicular histology] did not compromise the means to assess the
hypothesis that atrazine exposure can affect amphibian gonadal
development.  If the SAP concludes that the alterations in the study
design preclude or significantly compromise the ability to assess the
hypothesis, please discuss to the extent possible, how the specific
design modifications could impact the means to assess the hypothesis. 
Please provide comments on other aspects of the Agency’s evaluation as
well.

4:15 P.M.	Charge to Panel - Question 4

The Agency has described the exposure profiles for studies conducted in
response to the DCI and has stated that mean-measured concentrations in
the studies were lower than target nominal concentrations.  However, the
Agency concluded that the frequent analytical measurements provide a
sufficiently comprehensive understanding of the exposure profile over
the course of the studies.  Please comment on the Agency’s conclusion
that the atrazine exposure concentration profile is reasonably
characterized and sufficient for documenting the potential effects of
atrazine over a broad range of exposure concentrations.  In addition,
provide comments on whether the actual concentrations were consistent
and sufficiently stable to establish the means to analyze exposure
concentration-response relationships.

5:00 P.M.	Adjournment



AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

	OPEN MEETING

	

October 9 - 12, 2007

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2007-0498

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington,VA 22202

The Potential for Atrazine to Affect Amphibian Gonadal Development

Thursday, October 11, 2007

  8:30 A.M.	Opening of Meeting and Administrative Procedures -- Joseph
E. Bailey, Designated Federal Official, Office of Science Coordination
and Policy, EPA

  8:40 A.M.	Introduction and Identification of Panel Members -- Steven
G. Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair  

  8:50 A.M.	Charge to Panel - Question 5

	The Agency described atrazine contamination of negative controls in one
out of the two studies and concluded that since the experimental design
had twice the number of controls relative to other treatments, the data
from these atrazine-contaminated controls could be removed from the
analyses without invalidating the statistical interpretation of the
results.

	

(a)	Please comment on the Agency’s decision to omit half of the
controls from the WLI study in the statistical analyses and on the
conclusion that the study is still scientific valid.  If the SAP has an
alternative approach to treating these control data in the statistical
analyses, please provide specific recommendations.

10:00 A.M.	Break

10:15 A.M.	Charge to Panel - Question 6

	The original White Paper (USEPA 2003) identified measurement endpoints
that included the possible enumeration of specific histological
structures such as the number of oogonia in ovaries and the number of
spermatids in testes.  Such a detailed analysis was not conducted in the
studies that are in response to the DCI.  Rather, a qualitative
assessment of the incidence of ovarian and testicular gonadocytes was
conducted. The Agency has concluded that the lack of these data does not
limit the means to assess the hypothesis that atrazine exposure affects
amphibian gonadal development.

	

	(a)	Please comment on whether the lack of these histological data
limits the utility of the available information to fail to support the
hypothesis that atrazine exposure affects amphibian gonadal development.

	(b) 	If the SAP concludes these data are necessary to adequately assess
the hypothesis, please provide options to processing and analyzing these
data in an efficient and robust manner.

11:15 A.M.	Charge to Panel - Question 7

	The Agency has described a number of measurement endpoints (e.g.,
translucent gonads, unpigmented ovaries, pigmented testes) based on
histology results that were reported in the studies. The Agency,
however, based on its understanding of relevant scientific literature,
could not conclude that these measurement endpoints are biologically
relevant indicators of effects on growth or reproductive success (i.e.,
the Agency did not interpret these responses as adverse effects per se)
nor was the Agency aware of any information that established these
responses as precursors to the apical endpoints of primary interest
(i..e., time to and size at metamorphosis, sex ratio, and the presence
of mixed and/or intersex animals).

	

(a)		Please comment on the biological relevancy of these endpoints and
the extent to which they may reflect reliable measures of developmental
abnormalities.

12:00 P.M.	Lunch

  1:15 P.M.	Charge to Panel - Question 8

	The Agency’s analysis of potential developmental effects in studies
responsive to the DCI has focused on histological data as opposed to
gross morphological data.  The histological data from these studies are
based on the analyses of a single certified pathologist.  While this
approach eliminates the potential variability associated with having
multiple pathologists analyze the histological slides, it may introduce
an avidity bias.

	

	(a)	Please comment on whether a single pathologist is sufficient for
interpreting the histology data.  If the SAP believes that a single
pathologist is not sufficient, please comment on the potential value of
convening a pathology review board to evaluate the findings of the DCI
study.  

	(b)	Please also comment on the potential value of having a pathology
review board evaluate materials (e.g., digital images of gross
morphology and microscope slides containing histological sections) from
studies published in the open literature.  These data could be submitted
voluntarily by the authors and could include slides to evaluate
similarities or differences in identifying or describing histological
features and/or describing and quantifying histological responses.

2:00 P.M.	Charge to Panel - Question 9

	After an evaluation of the laboratory-based studies submitted in
response to the DCI, the Agency has concluded that these studies do not
provide sufficient evidence to support the hypothesis that atrazine
causes adverse gonadal developmental effects in amphibians.

	

	(a)	In light of the responses to Questions 3 – 8, please comment on
whether the results from the study in response to the DCI are
sufficiently robust to address the hypothesis that atrazine exposure
causes gonadal abnormalities in X. laevis.   If the SAP concludes these
results are not sufficiently robust, what recommendations can the SAP
provide to efficiently and reasonably address remaining uncertainties? 
For example, if the SAP does not believe the DCI study is sufficiently
robust to assess the hypothesis, does the SAP believe either the two
experiments or a specific component of the two experiments should be
reanalyzed or repeated?  Please provide the rationale for recommending
any additional analyses and/or experiments.

	(b)	Please comment and provide recommendations on alternate statistical
analyses, if any, to evaluate the data derived from the study.  If
alternative approaches are suggested, please comment, to the extent
possible, on the rationale for these approaches and how they represent
improvements in the existing statistical interpretations.

2:45 P.M.	Break

3:00 P.M.	Charge to Panel - Question 10

	Is the SAP aware of any other laboratory-based or field-based studies
not included in this White Paper that contradict the Agency’s
conclusions that 1) the designs associated with current studies
available in the open literature are not appropriate for evaluating the
hypothesis that atrazine affects amphibian gonadal development and 2)
the available data in the open literature combined with the results of
DCI study indicate that atrazine does not cause adverse effects on
gonadal development in X. laevis when investigated under conditions
consistent with those recommended by the SAP in its previous report (SAP
2003).  If so, please identify the studies and briefly outline how the
results from these studies would contradict the conclusion that atrazine
at concentrations up to 100 μg/L does not cause adverse effects on
amphibian gonadal development.

4:00 P.M.	Charge to Panel - Question 11

	The Agency is not aware of data that establish a mechanistic basis for
how atrazine could affect amphibian gonadal development.  Please
identify and comment on any studies that demonstrate the mechanistic
steps by which amphibian gonadal development could be affected by
atrazine, and thereby contradict the Agency’s overall conclusions
based on the studies evaluated for this SAP review.  If the SAP is aware
of any relevant study(ies), please comment on the data from this
study(ies) and how the data indicate and quantify a mechanistic pathway
from atrazine’s molecular site of action to histological and apical
endpoints associated with adverse effects on amphibian gonadal
development.  Please also comment on any dose-response relationships
associated with the steps in the reported toxicity pathway.

5:00 P.M.	Adjournment



AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

	OPEN MEETING

	

October 9 - 12, 2007

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2007-0498

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington,VA 22202

The Potential for Atrazine to Affect Amphibian Gonadal Development

Friday, October 12, 2007

  8:30 A.M.	Opening of Meeting and Administrative Procedures -- Joseph
E. Bailey, Designated Federal Official, Office of Science Coordination
and Policy, EPA

  8:40 A.M.	Introduction and Identification of Panel Members -- Steven
G. Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair  

  8:50 A.M.	Charge to Panel - Question 12

	In its 2003 White Paper the Agency proposed a research approach using
focused, empirical laboratory studies based on initial investigations
with X. laevis, potentially followed by selective, confirmatory
laboratory studies with frog species native to North America.  However,
the 2003 SAP did not identify any important differences between
amphibian species to conclude that any affected developmental and/or
mechanistic processes observed in X. laevis would not be applicable to
indigenous ranid species. 

	

	(a)  	Please comment on the Agency’s recommendation that data derived
from X. laevis in the studies evaluated for this review are sufficient
to conclude that additional testing with indigenous species is not
warranted.

10:00 A.M.	Break

10:15 A.M.	Charge to Panel - Question 13

	Based on the available data provided by the DCI studies, the Agency has
concluded that atrazine does not adversely affect amphibian gonadal
development.  The Agency has further concluded that no additional
studies are required to address the hypothesis that atrazine adversely
affects amphibian gonadal development.

	Please comment on the Agency’s recommendation that the current body
of data is sufficient to refute the hypothesis that atrazine by itself
can adversely affect amphibian gonadal development and that no
additional data are required to address this hypothesis.

11:15 A.M.	Continued Panel Discussion (as needed)

12:00 P.M.	Lunch

  1:15 P.M.	Continued Panel Discussion (as needed)

  2:45 P.M.	Break

  3:00 P.M.	Continued Panel Discussion (as needed)

  5:00 P.M.	Adjournment

Please be advised that agenda times are approximate; when the discussion
for one topic is completed, discussions for the next topic will begin. 
For further information, please contact the Designated Federal Official
for this meeting, Joseph Bailey, via telephone:  (202) 564-2045; fax:
(202) 564-8382; or email: bailey.joseph@epa.gov

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