AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

April 26 – 29, 2010

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2010-0125

The Hamilton Crowne Plaza Hotel

The Hamilton Ballroom

1001 14th Street, NW

Washington, DC 20005

202-682-0111

Reevaluation of the Human Health Effects of Atrazine: Review of
Experimental Animal and In Vitro Studies and Drinking Water Monitoring
Frequency

Please note that all times are approximate (see note at end of Agenda).

Day 1

Monday, April 26, 2010





1:00   P.M.	Opening of Meeting and Administrative Procedures – Joseph
Bailey, Designated Federal Official, Office of Science Coordination and
Policy, EPA

1:05   P.M. 	Introduction and Identification of Panel Members –
Kenneth Portier, Ph.D., FIFRA Scientific Advisory Panel Session Chair

1:15   P.M.	Welcome and Opening Remarks – Steven Bradbury, Ph.D.,
Acting Director, Office of Pesticide Programs, EPA

1:25   P.M.	Welcome and Introductions – Tina Levine, Ph.D., Director,
Health Effects Division, Office of Pesticide Programs, EPA

1:30   P.M.	Introduction:  Status of the Reevaluation of the Health
Effects of Atrazine – Anna Lowit, Ph.D., Health Effects Division,
Office of Pesticide Programs, EPA

1:45 P.M.	Reevaluation of Human Health Effects of Atrazine: Review of
Experimental Animal and In Vitro Studies and Drinking Water Monitoring
Frequency – Elizabeth Mendez, Ph.D., Health Effects Division, Office
of Pesticide Programs, EPA

2:00 P.M.	A Proposed MOA for Atrazine and Atrazine Metabolites – Ralph
L. Cooper, Ph.D., Endocrinology Branch, Toxicity Assessment Division,
National Health and Environmental Effects Research Laboratory, EPA.

3:00 P.M.	Break

3:15 P.M.	Review of Atrazine Immunotoxicity – Robert Luebke, Ph.D.,
Cardiopulmonary and Immunotoxicity Branch, Environmental Public Health
Division, National Health and Environmental Effects Research Laboratory,
EPA.

3:45 P.M.	Neurological Effects of Atrazine – John Liccione, Ph.D.,
Health Effects Division, Office of Pesticide Programs, EPA

4:15 P.M.	Summary of Non-Cancer Mammalian Toxicity Reevaluation –
Elizabeth Mendez, Ph.D., Health Effects Division, Office of Pesticide
Programs, EPA

4:30 P.M.	Approaches to Evaluating Water Sampling Strategies and
Frequency of Monitoring – Nelson Thurman, M.S., Environmental Fate and
Effects Division, Office of Pesticide Programs, EPA

5:00 P.M.	Evaluating the Performance of Sampling Strategies for
Estimating Maximum Concentrations of Different Durations – Mary
Frankenberry, Environmental Fate and Effects Division, Office of
Pesticide Programs, EPA

5:25 P.M.	Artificial Neural Network Modeling of Atrazine Occurrence
Patterns – Michael J. Messner, Ph.D., Standards and Risk Reduction
Branch, Office of Ground Water and Drinking Water, EPA

5:50 P.M.	Water Sampling Summary – Nelson Thurman, M.S., Environmental
Fate and Effects Division, Office of Pesticide Programs, EPA

5:55 P.M.	Summary and Conclusion – Anna Lowit, Ph.D., Health Effects
Division, Office of Pesticide Programs, EPA

6:00   P.M.	Adjourn

Day 2

Tuesday, April 27, 2010





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

8:35 A.M. 	Introduction and Identification of Panel Members – Kenneth
Portier, Ph.D., FIFRA Scientific Advisory Panel Session Chair

8:45 A.M.	Follow-up from Previous Day’s Presentations

9:15 A.M.	Public Comments

10:00 A.M.	Break

10:15 A.M.	Public Comments

12:15 P.M.	Lunch Break

1:30 P.M.	Charge to Panel – Question 1 

In Vivo & In Vitro Experimental Toxicology in Mammals

In 2003, the human health risk assessment was based on a mode of action
in which exposure to atrazine leads to a reduced release of gonadotropin
releasing hormone (GnRH) from the hypothalamus thereby lessening the
afternoon pituitary luteinizing hormone (LH) surge in female Sprague
Dawley rats.  As a result, the estrus cycle lengthens.  This, in turn,
leads to increased estrogen levels and an increased incidence of mammary
tumors in female Sprague Dawley rats.  EPA determined that atrazine’s
cancer mode of action (i.e., premature reproductive aging) in the
Sprague-Dawley rat is not likely to be operative in humans (a conclusion
consistent with the SAP recommendation in 2000).  The Agency will be
evaluating the cancer classification further as the experimental
toxicology data are integrated with the epidemiology literature; new
experimental toxicology studies (Section 3.6 of the draft issue paper)
do not suggest a change to the Agency’s previous conclusion that
atrazine is “not likely to be carcinogenic to humans.”   

Although the cancer mode of action may not be operative in humans, it is
not unreasonable to assume that atrazine might cause adverse effects on
hypothalamic-pituitary function in humans.  Thus, the same endocrine
perturbations that induce tumors in rats may play a role in at least
some reproductive/developmental effects (not associated with
reproductive aging) that may be relevant to humans.  Accordingly, the
Agency identified disruption of estrous cyclicity and delays in puberty
onset (males and females) occurring as a consequence of disruptions to
the hypothalamic-pituitary-gonadal (HPG) axis as the critical endpoints
of concern (Sections 2.0 & 3.2 of the draft issue paper).  

The Agency continues to believe that this disruption of the HPG axis is
critical to affecting estrous cyclicity

and delayed puberty onset.  However, as discussed in Questions 1.2-1.6
(See Figure 3 of the draft issue

paper), new information has been published that indicates a more
expanded understanding of how atrazine

may perturb the pathway leading to reproductive effects. These new data
indicate that atrazine disrupts the

hypothalamic-pituitary-adrenal (HPA) axis altering the central nervous
system’s control of the pituitary 

and adrenal which, in turn, disrupts the HPG axis. Furthermore, a
hypothesis for a direct effect of atrazine

on the adrenal cortex and the gonads which may impact steroidogenesis
directly is also supported by the

available data.

Question 1.1 – With the caveat that the review of the epidemiological
literature is still on-going, please comment on the Agency’s
preliminary conclusion that new experimental data from in vitro and in
vivo laboratory animal studies do not support a change in the
conclusions from the 2003 risk assessment that atrazine is unlikely to
be a human carcinogen.

2:15 P.M. 	Charge to Panel – Question 1 (continued)

Question 1.2 – Based on an evaluation of the studies examining the
mode of action of atrazine on neuroendocrine function (Section 3.2 of
the draft issue paper), the Agency has preliminarily concluded that
atrazine affects both the HPG axis and the HPA axis.  With respect to
the temporal concordance, 

recent studies show that atrazine induces a rapid (within minutes)
increase in ACTH and adrenal cortical hormones (corticosterone and
progesterone) in both male and female rats (Fraites et al., 2009; Laws
et al., 2009; Pruett et al., 2009), while changes in the HPG axis, such
as the suppression of the LH surge, may take up to 2-3 days (Cooper et
al., 2009).  This sequence of HPA alterations followed by HPG changes
indicates that the suppression of the surge may be, in part, mediated by
activation of the HPA axis (i.e., a corticosterone suppression of the
GnRH and LH release).  In addition, with respect to dose-response
concordance, atrazine-induced increases in ACTH, corticosterone and
adrenal progesterone are seen following a single dose of atrazine (50
mg/kg).   In contrast, the HPG is not altered following a single dose up
to 200 mg/kg. However, when treated for multiple days, the dose
necessary to alter the HPA axis is lower than or equal to the one needed
to affect the HPG axis.  

Please comment on the Agency’s preliminary hypothesis for the mode of
action involving atrazine’s alteration of both the HPA and HPG axes. 
Does the document adequately and clearly describe the hypothesis in the
context of a “toxicity pathway” (i.e. cellular response pathways
that, when sufficiently perturbed, are expected to result in adverse
health effects)?  Does the document clearly describe the data used to
test the proposed hypothesis? To what extent do the available data
establish key events in the proposed mode of action hypothesis?  What
are the strengths and limitations of the data available on this
hypothesis?  

 

Please include in your comments a discussion of the Agency’s
interpretations of the data linking the initial perturbations in HPA
axis to changes in the HPG axis.  

Please comment on the evidence that the initial perturbations in the HPA
axis may lead to impairment in reproductive function and/or
developmental consequences.  Which event(s) is/are viewed as critical in
leading to health consequences? Are there data on other substances that
would inform this question?

3:15 P.M. 	Break

3:30 P.M.	Charge to Panel – Question 1 (continued)

Question 1.3 – The Agency has preliminarily concluded that atrazine
directly targets cells within the HPA axis (Sections 3.2 & 3.3.2.3 of
the draft issue paper) and that the increased activity of the adrenal
axis does not reflect nonspecific stress.  Evidence for this conclusion
is based on the following observations.  

Several studies report increased adrenocorticotropic hormone (ACTH) and
corticosterone levels immediately following a single exposure to
atrazine and its two metabolites (deisopropyl-atrazine, DIA;
deethyl-atrazine, DEA) but not diamino-s-chlorotriazine (DACT; Laws et
al., 2009; Fraites et al., 2009; Pruett et al., 2009). 

A single intravenous administration of DEA in vivo (Fraites et al.,
2009) also causes an immediate increase in ACTH and adrenal hormone
release, indicating that a chlorotriazine-induced gastrointestinal
distress is not driving the hormonal response.

The adrenal corticosterone response to continued oral exposure to
atrazine did not habituate in rats (Fraites et al., 2009; Laws et al.,
2009) or mice (Pruett et al., 2009).  

Although, atrazine induced a rapid increase in ACTH, prolactin secretion
was not affected in the same animals (Laws et al., 2009).  This is
unusual in that an increase in both ACTH and prolactin are typically
observed in response to a number of physiological and psychological
stressors.

Please comment on the extent to which the available evidence supports
the preliminary conclusion that atrazine and its intermediate
metabolites (DIA and DEA) induce changes in the HPA axis as a result of
a direct action on the HPA tissue and such changes are not due to a
generalized or non-specific stress response.  Are there data on other
substances that would support this conclusion?

4:15 P.M.	Charge to Panel – Question 1 (continued)

Question 1.4 – Based on a review of in vitro studies evaluating the
effects of atrazine on estrogen production, the Agency has preliminarily
concluded that atrazine does not have a direct effect on the catalytic
activity of aromatase.  However, with continued exposure (> 24 hrs)
atrazine can cause increased estrone and estradiol production in the
H295R and JEG-3 cell lines (Sanderson et al., 2000; Laville 2006; Higley
et al., 2010).   These changes in estrogen production have been
associated with increased cAMP and CYP19 mRNA (Sanderson et al., 2000,
2001) that are part of a complex mode of action through which atrazine
up-regulates the gene expression of aromatase and possibly other enzymes
within the steroidogenic pathway (Section 3.3.2.3 & Figure 3, Arrow 7of
the draft issue paper).  The hypothesis that atrazine alters multiple
steroids is supported by  increased testosterone concentrations in H295R
cells following exposure to atrazine (Higley et al., 2010), and in vitro
studies demonstrating that atrazine affects a number of signal
transduction pathways and/or transcription factors in a variety of cell
lines (Suzawa and Ingraham, 2008; Albanito et al., 2008).  Up-
regulation of the expression of a group of major steroidogenic genes has
been observed in JEG-3 cells (Suzawa and Ingraham, 2008).  In vivo,
there is little evidence that atrazine alters aromatase per se (Modic,
2004) and the evidence associating atrazine exposures to increases in
serum estrogens appears to be related to a general increase in gonadal
and adrenal progesterone and androstanedione (Modic 2004; Laws et al.,
2009).  

Please comment on the extent that the available data do or do not
support the Agency’s preliminary

conclusion that atrazine has a general stimulatory effect on
steroidogenesis, as opposed to a direct effect 

on aromatase.

5:00 P.M. 	Adjourn

Day 3

Wednesday, April 28, 2010





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

8:35 A.M. 	Introduction and Identification of Panel Members – Kenneth
Portier, Ph.D., FIFRA Scientific Advisory Panel Session Chair

8:45 A.M.	Charge to Panel – Question 1 (continued)

Question 1.5 – A series of studies evaluating the effect of either
peripubertal or gestational exposure of atrazine in the male rat
indicate that atrazine decreases testosterone concentrations and may
lower androgen dependent tissue weights but that it has little effect on
basal LH secretion in the male.  This response generally occurs at doses
of 50 mg/kg and above.  In contrast, atrazine in vitro has been found to
consistently increase steroid hormone production.  Thus, there is an
apparent discrepancy between the in vivo and in vitro data.  However,
our understanding of the interplay between the adrenal and the gonadal
axes may provide an explanation.   At the doses used in the in vivo
studies, atrazine induces an activation of the adrenal axis (increased
ACTH and corticosterone) and the increase in corticosterone does not
habituate (i.e., it does not lessen with repeated dosing). There are a
number of studies in the literature demonstrating that prolonged
corticosterone stimulation will impair testosterone production by a
direct action on steroidogenesis in the Leydig cells. Therefore, the in
vivo effects on testosterone synthesis are likely the result of an
adrenal hormone-mediated down regulation of HPG axis (through
corticotropin releasing hormone [CRH] modulation of GnRH pulsatility) or
directly on the testis (through a glucocorticoid receptor mediated
change in steroidogenesis).  

Please comment on the degree to which the proposed mode of action
(Figure 3 of the 

draft issue paper) provides a biologically plausible explanation for the
decrease in serum 

and testicular testosterone identified in the in vivo studies.  Please
comment on the extent 

that the available data do or do not support this hypothesis.

10:00 A.M.	Break

10:15 A.M.	Charge to Panel – Question 1(continued)

Question 1.6 - Based on a review of the neurotoxicity studies (Section
3.4 of the draft issue paper), the Agency has preliminarily concluded
that several recent studies provided further support for the concern
that dopaminergic neurotransmission may be affected by atrazine, a
concern that was raised by studies prior to 2003.  However, the Agency
has also concluded that several aspects of these studies of the
dopaminergic neuronal pathways, in particular the changes noted in
stereological evaluations and the observed changes in behavior, should
be considered as preliminary findings.  This conclusion is based on the
notable limitations identified in the data including:  (1) lack of clear
dose-response relationships, (2) lack of inclusion of suitable positive
controls to confirm the competency and reliability of the procedures 

utilized in examining dopaminergic systems in the brain, (3) limited
data to corroborate stereological findings, (4) limited or no supporting
histological and behavioral assessments, and (5) no consideration of the
potential role of the HPA axis (e.g. alterations in corticosterone).  
EPA has further determined that two non-dopaminergic neurotoxicity
studies--one on brain somatostatinergic systems and the other on
neurobehavior in mice -- also have significant limitations (e.g., lack
of details on source and purity of atrazine, and age and body weights of
the mice; poor quality of amino cupric silver staining photomicrographs;
limited presentation of reverse-transcriptase polymerase chain results;
lack of data to corroborate conclusion of neuronal degeneration;
reference citations did not support statements made in the text; no
explanation of biological plausibility of alterations in
somatostatinergic receptor subtypes; inappropriate statistical
evaluation of data (litter vs. pup); discrepancies in number of pups
examined for behavioral endpoints, and lack of objective and validated
behavioral tests).  Please comment on these preliminary conclusions
regarding the neurotoxicity findings.  

The Agency has preliminarily concluded that the available studies
indicate that the neurotoxicity endpoints

examined are not more sensitive than those evaluated for neuroendocrine
function following atrazine

exposure (e.g., attenuation of LH surge and estrous cycle disruptions in
female Sprague-Dawley rats which

form the basis for the current chronic RfD).  In addition, the Agency
has concluded that there is no

association between atrazine exposure and development of Parkinson’s
Disease on the basis of non-

specificity of effects on brain dopaminergic systems, lack of
histological and behavioral features

characteristic of Parkinson’s Disease, and results of epidemiological
studies. Please comment on this

preliminary conclusion.

11:00 A.M.	Charge to Panel – Question 1(continued)

Question 1.7 – Based on a review of two studies of the potential
effects of atrazine on the prostate (Section 3.3.2.2 of the draft issue
paper), the Agency has concluded that the results of the Rayner et al.
(2007) study of pregnant rats treated during gestation support previous
observations (Stoker et al., 1999) that atrazine treatment to the rat
dam either perinatally or early postnatally can increase prostate
weights (due to an increase in inflammatory infiltrate) in the male
offspring.  This effect on the offspring was shown to be due to a
suppression of prolactin in the atrazine-exposed dams during lactation,
and is consistent with the mode of action of atrazine on neuroendocrine
function.   The Agency also preliminarily concluded that further
research is needed to provide more convincing evidence that
atrazine-mediated suppression of prostate cancer in the probasin/SV40T
antigen transgenic rat (androgen-dependent prostate cancer rodent model)
 may possibly be due to caloric restriction rather than
endocrine-related as postulated by Kandori et al. (2005).  Please
comment on these preliminary conclusions regarding the recent prostate
findings.

Please comment on the extent to which the available data support the
proposed mode of action for

prostatitis and the appropriateness of the rodent model in the context
of human health.

12:00 noon	Lunch	

1:15 P.M.	Charge to Panel – Question 1 (continued)

Question 1.8 – Based on data obtained in studies to assess the effects
of atrazine on the immune system following developmental and adult
exposure, as well as in vitro mechanistic studies, EPA concluded that
atrazine has the potential to affect the immune system (Section 3.5 of
the draft issue paper).  However, the Agency has also concluded that
underlying mechanisms of atrazine-mediated immunotoxicity and its
relevance to potential adverse health effects in humans are still not
thoroughly understood.  It is well established that products of the
endocrine system modulate immune function.  However, adult rodent
studies have not determined whether immune system effects are caused by
direct effects of atrazine and/or its metabolites or whether they are
the result of modulated endocrine hormone production, which in turn
affects immune cells.  Two published studies indicate that exposure to
atrazine during immune system development may result in altered immune
function in offspring, although no conclusions were drawn on the
potential adversity of the effects, because immunosuppression was
observed in one study and immunoenhancement was observed in the other.  
Please comment on potential explanations for the disparate findings
reported by Rooney et al. and Rowe et al.  Many immunotoxicologists
consider immunomodulation, i.e., suppression or enhancement of immune
function, as a potentially adverse alteration of homeostasis, because
both have been associated with disease states.   Thus, while the results
Rooney et al. and Rowe et al. may appear to be contradictory, together
the data indicate unintended immunomodulation at approximately the same
dose in two species.  Please comment on characterizing the effects of
gestational atrazine exposure as immunomodulation, when describing the
immunotoxicological outcome of developmental immunotoxicity studies.

Appendix B of the draft issue paper describes experiments conducted by
EPA scientists on the potential developmental immunotoxicity of
atrazine.  The results of the experiments provide conflicting results. 
Additional studies did not provide a suitable explanation of the
differences.  The Agency believes both sets of data are of high quality.
 However, in the context of hazard assessment, such differences are
difficult to interpret.  Please comment on the information contained in
Appendix B and provide suggestions for interpreting such data as part of
the atrazine re-evaluation.

The available data do not indicate that atrazine-induced immunotoxicity
is a more sensitive endpoint than

the atrazine-induced effects on neuroendocrine function, (e.g.,
attenuation of LH surge and estrous cycle 

disruptions which form the basis for the current chronic RfD) in female
Sprague-Dawley rats.  Please

comment on the degree to which these preliminary conclusions are
supported by the available data.

2:00 P.M.	Charge to Panel – Question 1 (continued)

Question 1.9 – After the April 2010 SAP, the Agency will evaluate the
weight of evidence (WOE) for atrazine by integrating the experimental
toxicology data with the epidemiological studies.  As part of this work,
the Agency will consider the available data on hormonal changes and
functional outcomes that may be used as endpoints for deriving PoDs
across different durations of exposure and for different populations
(including potentially sensitive ones).  Important studies evaluating
the dose-response relationships for hormones involved in the HPA axis
are still on-going.  These studies are expected to provide high quality
data that can be used to characterize the entire dose response curve. 
With the caveat that these data are not available now, given the current
understanding of atrazine’s mode of 

action, please comment on what would be appropriate endpoints to
consider for use in deriving points of departure in a possible future
risk assessment.

Given that the duration of the toxicological concern is a key factor in
evaluating the frequency of drinking water monitoring, please include in
your response a consideration of the magnitude and duration of changes
in key events in the toxicity pathway that are sufficient perturb normal
function and comprise human health.   In defining the exposure window of
interest, please comment on the toxicokinetic/dynamic considerations
with respect to atrazine's effects on the HPA/HPG axis.

3:00 P.M. 	Break

3:15 P.M.	Charge to Panel – Question 2 

Approaches to Evaluating Water Sampling Strategies & Frequency of
Monitoring

In conjunction with the toxicological review presented in the issue
paper, the Agency has also discussed methods for re-evaluating the
sampling frequency that is necessary for determining, with confidence,
concentrations of the pesticide in water that sources drinking water. 
These have included different methods for estimating pesticide
concentrations between known sampling events and examining the
performance of different sampling strategies for averaging periods of
different durations.  The Agency seeks feedback from the Panel with
regard to how the uncertainty and variability in both the monitoring
data and in the toxicity data (i.e., point of departure) can be
integrated to characterize and to interpret the potential significance
of atrazine concentrations in drinking water.  

Question 2.1 – Given the nature of the temporal patterns of pesticide
occurrence in surface waters described in Section 5.2, including serial
correlations from day to day, periodicity in elevated concentrations
within seasons and from year to year, below quantitation data, and
uncertainty in the shape of the pesticide distributions in surface
waters--what statistical approaches should the Agency 

consider in determining confidence bounds on exposure estimates from
monitoring data? Please comment on how the approach may vary depending
on the duration of concern.

4:00 P.M. 	Charge to Panel – Question 2 (continued)

Question 2.2 – The first two simulation methods presented in Section
5.5 are applicable to the specific data sets they describe, although
some generalities regarding shape patterns appear to exist.  Given this
information, please comment on the strengths and weaknesses of the
approaches and on the practical merits of pursuing them or some other
numerical approach with a larger set of higher concentration systems. 
Please comment on how the methods for determining confidence bounds
might apply given these considerations.    

5:00 P.M.	Adjourn

Day 4

Thursday, April 29, 2010





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

8:35 A.M. 	Introduction and Identification of Panel Members – Kenneth
Portier, Ph.D., FIFRA Scientific Advisory Panel Session Chair

8:45 A.M.	Charge to Panel – Question 2 (continued)

Question 2.3 – As described in Section 5.4.2, the Agency is
considering the use of a confidence interval or prediction interval
approach to characterize the uncertainty of exposure estimates derived
from monitoring data of varying sampling frequencies.  Please comment on
the strengths and weaknesses of either placing confidence bounds on the
rolling average estimates and comparing the upper limit from monitoring
against the level of concern (LOC) or, conversely, placing confidence
bounds on the LOC.  

9:45 A.M.	Charge to Panel – Question 2 (continued)

Question 2.4 – Please comment on the relative merits of the various
modeling approaches the Agency described in Section 5.4.1 and 5.6 for
interpolating pesticide concentrations between sampling points and, in
particular, on the strengths and weaknesses of these methods as the
frequency of samples decreases. Considering the health endpoint(s) being
considered for atrazine, particularly data for the HPA axis, and the
exposure time frame needed to induce the health effect(s) which is
shorter than that used in the 2003 risk assessment, please comment on
the advantages and disadvantages of each model for 

evaluating the likely occurrence and exposure via drinking water of
short, moderate, and long duration concentrations.  Please comment on
the Agency’s proposed approach for evaluating these methods, as 

described in Section 5.7.1.  To what extent should the Agency consider
other factors, such as the shape of the chemograph (Section 5.5.3),
weather patterns, stream flow, and/or pesticide use patterns in
evaluating the modeling approaches?

10:30 A.M.	Break

10: 45 A.M.	Charge to Panel – Discussion continued as needed

12:00 noon	Lunch

1:15 P.M.	Charge to Panel – Discussion continued as needed

3:00 P.M. 	Break

3:15 P.M.	Charge to Panel – Discussion continued as needed 

5:00 P.M.	Adjourn

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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