DRAFT AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

December 8-9, 2010

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ- OPP-2010-0772

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington, VA 22202 

Scientific Issues Related to Insect Resistance Management for SmartStaxTM 

Refuge-in-the-Bag, a Plant-Incorporated Protectant (PIP) Corn Seed Blend

Please note that all times are approximate 

(See note at the end of the Agenda)

Wednesday, December 8, 2010

9:00 A.M. Opening of Meeting and Administrative Procedures – Sharlene 

Matten, Ph.D., Designated Federal Official, Office of Science Coordination 

and Policy, EPA

9:05 A.M. Introduction and Identification of Panel Members –

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

9:10 A.M. Welcome and Opening Remarks – Steven Bradbury, Ph.D., Director, 

Office of Pesticide Programs (OPP), EPA 

9:15 A.M. Introduction – W. Michael McDavit, Acting Director, Biopesticides and 

Pollution Prevention Division, OPP, EPA

9:20 A.M. Preliminary Risk Assessment of a 5% SmartStaxTM Seed Blend 

Targeting Lepidopteran and Corn Rootworm Pests – Jeannette 

Martinez, M.S., Biopesticides and Pollution Prevention Division, OPP, 

EPA

10:15 A.M. BREAK

10:30 A.M. PUBLIC COMMENTS

12:00 P.M. LUNCH
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Charge Questions Part A: Biology of European Corn Borer, Southwestern Corn 

Borer, Corn Earworm, and Corn Rootworm

1:00 P.M. Charge Question 1 

European corn borer (ECB) has both local and long distance dispersal 

capability. Currently, the proportion and frequency of individuals in a 

population engaging in dispersal before or after mating is unclear. While it 

has been established that ECB mate in aggregation sits near cornfields, 

mark-release-recapture studies in the U.S. have typically had a low 

recapture success (<1%). Recently it was suggested that 1-day old female 

ECB may engage in obligate pre-mating dispersal (Dorhout et al. 2008). 

Please comment on the uncertainties regarding ECB movement 

including mating sites, pre-mating dispersal, and the proportion of 

the population engaging in long-distance dispersal. How might these 

aspects of ECB movement affect a potential seed blend strategy?

2:00 P.M. Charge Question 2

Scientific Advisory Panels (1998 and 2000) discouraged the Agency from 

the use of Bt seed mixtures to control lepidopteran target pests because 

substantial larval movement could be expected between Bt and non-Bt

plants which could lead to more rapid selection of resistance. BPPD has 

reviewed new data developed by Dow and Monsanto simulating the 

effects of SmartStax on various instars of potentially mobile lepidoptera. 

These data provide evidence that SmartStax is highly toxic to 1st, 2nd, 

and 3rd instars. But, there was greater survivability among 4th and 5th

instars. While it has been established that ECB disperse as neonates, 

there is some uncertainty with respect to lepidopteran propensity for 

dispersal off non-Bt plants as later instars. BPPD notes that simulation 

models incorporating data on high larval mortality on SmartStax plants 

have (in some cases) predicted that seed blends may be as durable as 

structured refuges.

Please comment on ECB larval plant-to-plant movement including 

uncertainties about late-instar movement and the potential effect on 

the durability of a seed blend strategy.

3:00 P.M. BREAK

3:15 P.M. Charge Question 3

It is typically assumed that, since European corn borer (ECB) and 

southwestern corn borer (SWCB) are similar in many ways, ECB can serve 
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as a surrogate for SWCB to address uncertainties regarding biology and 

genetics. The applicants’ efficacy data, however, suggest that SmartStax is 

somewhat less toxic to older instars of SWCB. Results of a larval exposure 

study by Monsanto showed that SWCB survival was higher than ECB on 

SmartStax. Should some SWCB larvae disperse as older instars, the rate 

of adaptation to SmartStax could increase in a seed blend deployment. 

BPPD concluded that simulation models should incorporate such 

information in their analyses. There is currently a lack of data on the 

propensity of SWCB larval plant-to plant movement and on how ECB and 

SWCB differ in this respect, if at all.

Please comment on the assumption that ECB is a suitable biological 

surrogate for SWCB and BPPD’s concerns that a SmartStax seed 

blend may affect SWCB differently than ECB.

4:00 P.M. Charge Question 4

Corn earworm (CEW) was not considered in the applicants’ and 

EPA/ORD’s analyses for a 5% SmartStax seed blend based on the 

assumption that the insect does not overwinter in the Corn Belt where the 

blend has been proposed. BPPD is concerned, however, that there could 

be areas in the southern portion of the Corn Belt where CEW may be able 

to successfully overwinter, particularly in less severe winters. Such areas 

may need to be identified because they could contribute to increased 

selection for CEW resistance to Bt corn (including the proposed 5% 

SmartStax seed blend).

Please comment on the assumption that corn earworm does not 

successfully overwinter in the Corn Belt and poses less of a risk for 

resistance. If CEW can potentially overwinter in parts of the Corn Belt, 

should the insect be considered in the analysis of the proposed 5% 

SmartStax seed blend?

5:30 P.M. Adjourn
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DRAFT AGENDA

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

December 8-9, 2010

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ- OPP-2010-0772

U.S. Environmental Protection Agency

Conference Center - Lobby Level

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington, VA 22202 

Scientific Issues Related to Insect Resistance Management for SmartStaxTM 

Refuge-in-the-Bag, a Plant-Incorporated Protectant (PIP) Corn Seed Blend

Please note that all times are approximate 

(See note at the end of the Agenda)

Thursday, December 9, 2010

9:00 A.M. Opening of Meeting and Administrative Procedures – Sharlene 

Matten, Ph.D., Designated Federal Official, Office of Science Coordination 

and Policy, EPA

9:05 A.M. Introduction and Identification of Panel Members –

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

9:10 A.M. Follow-up from Previous Day’s Discussion – Jeannette Martinez, M.S., 

Biopesticides and Pollution Prevention Division, OPP, EPA

9:30 A.M. Charge Question 5

To assess dose expression for corn rootworm (CRW) Bt toxins, the level 

of survival (adult emergence) is typically compared between artificially 

infested Bt and non-Bt corn plots. However, density-dependent mortality in 

non-Bt plots can potentially confound the comparison by reducing overall 

survival and adult emergence. (Density-dependent mortality is not 

expected in Bt plots due to effects of the toxin on young larvae.) To 

account for this effect, the dose calculation can be adjusted by removing 

density-dependent mortality from the control plots. This effectively 

increases the dose mortality estimate by raising the number of larvae
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present in non-Bt plots relative to the surviving larvae in Bt plots.

For the SmartStax toxins, Dow/Monsanto made a density-dependent 

adjustment to their dose estimates based on density/survival relationships 

developed by Onstad et al. (2006). The resulting dose mortality profile 

was: Cry34/35Ab1 (99.75%), Cry3Bb1 (99.75%), and 

Cry34/35Ab1/Cry3Bb1 pyramid (99.95%). On the other hand, BPPD has 

also considered separate work by Hibbard et al. (2010), which suggests 

that density-dependent mortality occurs at higher egg density levels than 

those assumed by Dow/Monsanto. In light of this research, BPPD 

recommended in its 2009 risk assessment of SmartStax that dose should 

also be evaluated without a density-dependent adjustment. The nonadjusted dose profile for the SmartStax toxin is: Cry34/35Ab1 (94.2%), 

Cry3Bb1 (97.5%), and Cry34/35Ab1/Cry3Bb1 pyramid (98.2%).

Please comment on dose estimates for the SmartStax toxins 

(Cry34/35Ab1 and Cry3Bb1) targeting corn rootworm given the 

different interpretations of density-dependent mortality.

10:15 A.M. BREAK

10:30 A.M. Charge Question 6

Northern and western corn rootworm studies have shown that male 

emergence in 5% seed blends can be variable and may be up to 60 times

lower compared to emergence in non-Bt plots (Data submitted by 

Monsanto). This information was not included in any of the models used in 

the SmartStax seed blend analysis. The SAP (2009) concluded that a 

reduction in the number of males from Bt seed blends could have a 

negative impact on the effective refuge. BPPD is concerned with the 

potentially negative effects a reduction in male emergence might have on 

product durability.

Please comment on the potential effects of lowered male emergence 

of Northern and Western corn rootworm on the durability of the seed 

blend and whether this information should be incorporated into the 

risk assessment.

Charge Questions Part B: Modeling of Resistance Evolution

11:15 A.M. Charge Question 7

The durability of the proposed 5% SmartStax seed blend strategy was 

compared to the durability of a 5% structured refuge for lepidoptera and 
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corn rootworm target pests. Monsanto developed a deterministic three 

locus model for ECB/SWCB and Dow created a stochastic two locus 

model for CRW. Separate analyses were conducted using EPA/ORD’s 

two locus and three locus deterministic, probabilistic model to estimate the 

risk of resistance evolution with a 5% seed blend and structured refuge. 

The applicants and EPA/ORD each made conservative assumptions, 

though of differing degrees, for parameters determined to be sensitive in 

the models. For example, more conservative initial resistance allele 

frequencies and fitness assumptions significantly lowered the time to 

resistance in EPA/ORD’s model for ECB and SWCB. In Monsanto’s 

modeling of ECB and SWCB, a greater degree of dispersal between 

compliant and non-compliant fields significantly affected the estimated 

time to resistance.

Please comment on the appropriateness of the assumptions and 

inputs used for the following parameters in the Monsanto, Dow, and 

EPA/ORD models:

• Initial resistance allele frequency for single traits 

Cry1A.105, Cry2Ab2, Cry1F, Cry34/35Ab1, and Cry3Bb1 

for all modeled pests;

• Survival/fitness for all modeled pests; and

• Dispersal for ECB and SWCB as modeled by Monsanto 

and EPA/ORD. 

12:00 P.M. LUNCH

1:00 P.M. Charge Question 8

EPA/ORD encountered challenges in the lepidopteran modeling with 

partitioning non-multiplicative interactions that occurred between more 

than two resistance genes since the mortality caused by each locus was 

not independent. With two gene pyramids this non-additivity can be 

assigned to the single two locus interaction, but in a three gene pyramid 

there are three possible two locus interactions. In the absence of data, this 

non-additivity was partitioned equally among the three two locus 

interactions. As more than two Bt genes are pyramided, this problem will 

have to be addressed so that resistance evolution in the target pests to 

these products can be more accurately simulated.

Does the Panel have any recommendations for distributing nonmultiplicative interactions in models to evaluate multi-gene 

pyramided products?
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2:00 P.M. Charge Question 9

Based on a review of the submitted simulation modeling, the preliminary 

conclusions are:

1) For CRW, a 5% seed mixture and a 5% structured refuge had 

comparable durability in both the EPA and Dow models;

2) For ECB, a 5% seed mixture was less durable than a 5% structured 

refuge in simulations with EPA’s model. However, ECB resistance did not 

evolve within 158 generations in any of the simulations with the 5% seed 

mixture, similar to the level of durability predicted by Monsanto’s model. 

There was no difference in durability between the 5% seed mixture and 

the 5% structured refuge in Monsanto’s model. Resistance did not evolve 

to either refuge option within 100 generations (the extent to which the 

model was run); 

3) For SWCB, a 5% seed mixture was less durable (78 generations) than 

a 5% structured refuge (118 generations) in EPA’s model simulations. 

Conversely, with Monsanto’s model there was no difference in the 

prediction for durability between the 5% seed mixture and the 5% 

structured refuge. Resistance did not evolve to either refuge option within 

100 generations (the limit of the model simulations).

Please comment on the reliability of the estimates of resistance 

evolution by each of the three models in light of the biological and 

parameter uncertainties identified by BPPD. 

3:30 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, Dr. Sharlene Matten, via telephone: (202)-564-

0130; fax: (202) 564-8382; or email: matten.sharlene@epa.gov.