AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

February 23 – 25, 2009

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2008-0836

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington, VA 22202

Scientific Issues Associated with Evaluation of the Resistance Risks
from Using a Seed Mix Refuge with Pioneer's Optimum AcreMax1 Corn
Rootworm-Protected Corn

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

Monday, February 23, 2009

1:30 P.M.	Opening of Meeting and Administrative Procedures – Joseph
Bailey, Designated Federal Official, Office of Science Coordination and
Policy, EPA

1:40 P.M. 	Introduction and Identification of Panel Members – Steven
Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair 

1:50 P.M.	Welcome and Opening Remarks – Steven Bradbury, Ph.D., Deputy
Office Director for Programs, Office of Pesticide Programs, EPA

1:55 P.M.	Welcome and Introductions – Janet Andersen, Director,
Biopesticides and Pollution Prevention Division, Office of Pesticide
Programs, EPA 

2:00 P.M.	AcreMax Risk Assessment – Jeannette Martinez, M.S.,
Biopesticides and Pollution Prevention Division, Office of Pesticide
Programs, EPA

3:00 P.M.	Break

3:15 P.M.	Public Comment

5:30 P.M.      ADJOURN

	 

AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

February 23 – 25, 2009

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2008-0836

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington, VA 22202

Scientific Issues Associated with Evaluation of the Resistance Risks
from Using a Seed Mix Refuge with Pioneer's Optimum AcreMax1 Corn
Rootworm-Protected Corn

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

Tuesday, February 24, 2009

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

8:45 A.M.      Charge to Panel – Alan Reynolds, M.S., Biopesticides
and Pollution Prevention Divison, Office of Pesticide Programs, EPA

Charge Question 1 -  Pioneer suggested based on their host search
behavior results (MRID 473567-07) that Cry34/35Ab1 protects against corn
rootworm through deterrence and sub-lethal toxicity leading to death by
starvation. Pioneer’s larval recovery study demonstrated high survival
rate of CRW that were exposed to 59122 maize at any stage during their
development but allowed to recover on non-Bt corn (MRID 473567-01).
Conversely, larval exposure to 59122 maize without a recovery phase
resulted in a mortality rate of 0.05 for neonates and 0.01 for 2nd and
3rd instars. BPPD concluded that it cannot be determined whether
mortality or survival occurred due deterrence or some other mechanism. 

BPPD would like the panel to discuss whether there is evidence that
repellency or deterrence by 59122 maize could also be described as a
realistic mode of action, specifically for a non-high dose toxin such as
Cry34/35Ab1, and any implications for a seed blend refuge strategy.

10:00 A.M.	BREAK  	 

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

Charge Question 2 – Lefko et al. (2008) collected WCR individuals from
two geographically distinct and susceptible populations and introgressed
a non-diapausing trait from a WCR lab strain. The resulting offspring
were selected on 59122 maize for 11 generations. A number of
measurements were taken during the selection experiment to establish the
mean survival rate, fecundity, fertility, and percentage of females
produced for all cohorts of the 11 generations. Multiple greenhouse
experiments were conducted with 4 generations per selected lines to
determine if injury potential changed on 59122 roots. In addition, the
realized heritability (h2= R/S) of the tolerance trait was estimated.
Pioneer speculates that CRW tolerance for 59122 and apparent rarity of
resistance genes in the CRW population may support Lande’s (1983) less
popular hypothesis that “pest adaptation via a major resistance gene
can be prevented or delayed by a minor resistance gene despite strong
selection pressure; rarity of major resistance is an essential condition
for this interaction”. 

The Panel is asked to discuss the concept of major vs. minor gene as
hypothesized by Lefko et al. and the implications for selection of
resistance to 59122 and implications for a seed blend strategy.

11:15 A.M.	Charge to Panel (continued)

Charge Question 3 – In BPPD’s review it was concluded that varying
the selection pressure could have identified different resistance genes.
In corn fields across the country the selection pressure will likely be
different and more variable than in the lab because of, for example,
variability in host-pest interactions and environmental conditions. 

Please comment on BPPD’s conclusion that different selection
intensities could possibly select different genes, maybe a major
resistance gene. If different selection intensities could possibly
select different genes, maybe a major resistance gene, what does the
Panel think are the implications for resistance evolution to 59122 maize
in a seed blend environment?

12:00 P.M.	LUNCH

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

Charge Question 4 – In their selection experiment (Lefko et al. 2008),
Pioneer found that heritability of the tolerance trait first increased
and then decreased again. The tolerance trait could not get fixed by
generation 11; Lefko et al. hypothesized that this could be due to an
interaction between two tolerance genes. Pioneer did not address the
potential presence of more than one tolerance gene in the modeling
submission. Furthermore, CRW survival rate due to the tolerance trait
and off-type seed rate (0.00075) was assumed to be half of the survival
rate observed by Nowatzki et al. (2008, MRID 473567-05). 

Please comment on whether there is reason to believe that the relative
rate of adaptation could be affected by including more than one minor
gene in the model and whether the assumption of equal survival of
susceptible (AA) individuals with genotype XX (0.0125) and genotypes XY
and YY (0.0125) is realistic.

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

Charge Question 5 – After having completed the review of the modeling
submission, BPPD has identified several uncertainties and/or weaknesses
of the model. Please comment on which of these uncertainties and/or
modeling weaknesses are important to explore the risk of resistance
evolution to 59122 maize in a seed blend environment. 

A. Initial frequency of major resistance gene (0.005) and dominance
(0.05): Pioneer determined initial gene frequency based on the selection
results and modeling comparison conducted in Lefko et al. (2008). Major
resistance was assumed to be almost completely recessive despite the
fact that Cry34/35 does not express a high-dose against CRW. 

B. Lack of inclusion of emergence delays: delays of up to 13 days in
initial emergence and eight days in median emergence were observed
between adults from 5% seed blends and 59122 maize. Delays of up to 19
days in initial emergence and 12 days in median emergence were observed
between adults from 100% refuge fields and 59122 maize (MRID 473567-05).

C. Lack of inclusion of uneven sex ratios: the field study (MRID
473567-05) showed that the production of female adult CRW was favored
over the production of male adults, while in the lab study, the
production of males was favored (MRID 473567-01). An inequality in sex
ratios results in a special sort of bottleneck in which random genetic
drift is enhanced and the effective population size is reduced. For
example, if the number of males emerging from Bt plants decreases, then
females emerging early from refuge plants could be more likely to mate
with refuge males rather than 59122 males, especially when one considers
that females have been shown to mate once only. 

D. Lack of inclusion of density-dependent dispersal: Hibbard et al.
(2004) reported that in their experiment conducted from 2000-2002, CRW
larval movement was dependent upon egg density per plant (independent of
Bt plants). 

E. Lack of inclusion of non-random mating: delayed emergence and uneven
sex ratios are likely to affect the random mating between adult CRW
emerging from refuge maize and adults emerging from 59122 maize. 

F. Lack of exploratory modeling: Pioneer’s model did not explore the
production of different percentages of males and females and non-random
mating and, ultimately, their effects on the relative rate of adaptation
to 59122 maize. 

3:15 P.M.	Break

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

Charge Question 6 – The delay in evolution of resistance in
Pioneer’s model when the tolerance gene, major resistance gene, and
off-type seed rate were included was driven by the rapid increase in
frequency of the susceptible genotypes carrying the Y-allele (mostly
AAYY). The proportion of susceptible individuals heterozygous for the
tolerance trait (AAXY) peaked at 0.62 after generation 2; the proportion
of susceptible individuals homozygous for the tolerance trait (AAYY)
reached 0.5 by generation 3. The population was 90% homozygous for the
Y-allele after generation 7 with an interaction emerging between the Y
and B allele around generation 9 when AAYY genotypes declined at a
similar rate to its earlier rate of increase. The proportion of
population homozygous for both the major resistance gene and the
tolerance (BBYY) gene reached 0.5 and 0.9 around generation 17 and 19,
respectively.

 

Please comment on whether it is realistic to assume that the minor
tolerance trait, specifically the AAYY genotype, might drive the delay
of major resistance to 59122 maize in a seed blend environment.

5:00 P.M.	Adjourn

AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

February 23 – 25, 2009

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2008-0836

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington, VA 22202

Scientific Issues Associated with Evaluation of the Resistance Risks
from Using a Seed Mix Refuge with Pioneer's Optimum AcreMax1 Corn
Rootworm-Protected Corn

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

Wednesday, February 25, 2009

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 – Steven
Heeringa, Ph.D., Scientific Advisory Panel Chair

8:45 A.M. 	Charge to Panel (continued) - Alan Reynolds, M.S.,
Biopesticides and Pollution Prevention Divison, Office of Pesticide
Programs, EPA

end (≥2%) for corn rootworm, all the supporting studies, and the model
with its general assumptions, parameters and their values, as well as
modeling analyses and concludes the following: At this point, BPPD
believes that the proposed seed blend of ≥2% for Optimum® AcreMax™
1 Insect Protection has many uncertainties with respect to biological
and genetic parameters and lack of exploratory modeling. BPPD believes
these uncertainties must be resolved before a seed blend refuge is a
viable long-term alternative to a structured refuge for corn rootworm.
In the interim, BPPD has concluded that no less than 10% refuge seed
blend is appropriate. BPPD bases its conclusion on: 1) the Relative Rate
of Adaptation (RRA) at the 10% refuge proportion (value ~ 0.7) compared
to the higher RRA values at lower proportions of refuge as estimated in
Pioneer’s model (MRID 473567-08), 2) root protection results for the
10% seed blend (Nowatzki and Meinke, 2008, MRID 473567-06), 3) efficacy
results (Davis and MacIntosh, 2008, MRID 473567-10), 4) CRW emergence
curve similarities for the 10% seed blend and 100% refuge maize
(Nowatzki et al., 2008, MRID 473567-05), 5) similarity in fitness
results between females emerging from the 10% seed blend and the 100%
refuge maize, and 6) modeling uncertainties. 

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10:00 A.M.	Break

10:15 A.M.	Charge to Panel (continued as needed)

12:00 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) 564-0130; fax:
(202) 564-8382; or email: bailey.joseph@epa.gov.	

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