CONCLUSIONS AND RECOMMENDATIONS

Pioneer/DuPont addressed the recommendations made in BPPD (2011): the applicant artificially inflated the 

fecundity for European and southwestern corn borers to avoid population extinction in their modeling analyses, 

included some worst-case values for several sensitive parameters in their new simulations, conducted a 

probability analysis to be able to report a risk profile to the Agency, and addressed the most germane 

uncertainties described by the SAP (2011) for seed blends with pyramided PIPs targeting Lepidoptera.

However, Pioneer/DuPont did not include non-uniform oviposition by Lepidoptera in their main modeling 

analyses and explore greater female (southwestern corn borer) dispersal out of seed blends.

I. RISK CHARACTERIZATION

After careful review of the applicant’s new modeling submission, BPPD concludes that:

• The 20% single toxin block refuges had the lowest durability estimates of all options tested in 

Pioneer/DuPont’s model. Those durability results were, however, artificially reduced by higher 

fecundity assumptions. Pioneer/DuPont estimated blends to be between 6 and 60-fold more durable than 

20% blocks for single toxin PIPs.

• The proposed seed blends (5% and 10%) will likely be substantially less durable than a 5% block refuge 

for the same product (100% compliance assumed). This was also concluded by the SAP (2011). With 

realistic assumptions of non-compliance the estimated durability for the block scenario would likely be 

somewhat lower but still more durable than the blends. Pioneer/DuPont’s model estimated that a 5% 

block had close to double the durability of blends for both pests (benchmark assumptions). The 

durability of the pyramided blends is highly likely to fall in between the two block options. They can be 

expected to be more durable than the single toxins (especially under assumptions of low crossresistance). The uncertainties described below (effects of increased fecundity, no modeling of nonuniform oviposition and greater dispersal out of blends) can be expected to further erode the durability 

of blends. 

• A 10% blend is likely to be more durable than a 5% seed blend for the same product. Pioneer/DuPont 

reported, however, that the lower blend percentage had slightly greater durability than the higher blend 

percentage. Possible explanations for this unexpected outcome are discussed in the uncertainties section 

below.

• These conclusions are based on all available information, including Pioneer/DuPont’s modeling, the 

2011 SAP report, and EPA/ORD modeling analyses created for other seed blend products. 

Quantification of the risk (i.e. level of durability) for Optimum AcreMax and Optimum AcreMax Xtra is 

complicated by uncertainties in some biological parameters including uniform/non-uniform oviposition, 

effects of inflated fecundity, degree of female pre-ovipositional dispersal as well as aspects of the 

probability analysis. All these uncertainties together could functionally lower the durability of seed 

blends relative to block refuges.

• In consideration of the cumulative effect of the uncertainties and without additional modeling, BPPD is 

unable to completely quantify the relative durabilities of the various refuge options. BPPD expects, 

however, the relative durability relationship to hold true: 5% pyramid block > 10% pyramid seed 

blend > 5% pyramid seed blend > 20% single toxin block. 

• The 10% Optimum AcreMax 1 seed blend (expressing Cry34/35) targeting corn rootworm was 

approved in 2009. The applicant seeks to combine this single CRW gene with the pyramid PIP for 

Lepidoptera into a new 10% seed blend product (Optimum AcreMax Xtra). As stated above, the risk of 
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resistance development and relative durability cannot be quantified for any of the proposed blends; 

however, BPPD expects the risk of resistance evolution to be lower for a 10% seed blend expressing two 

pyramided PIPs than a 5% blend as proposed for the Optimum AcreMax product targeting Lepidoptera 

only.

II. UNCERTAINTIES:

BPPD has identified the following uncertainties in Pioneer/DuPont’s analysis:

1) Non-uniform oviposition behavior was not included into Pioneer/DuPont’s benchmark simulations 

although a sensitivity analysis for this parameter showed a trend of greater durability for the 10% seed 

blend over the 5% blend when conservative, yet realistic, assumptions of non-uniform oviposition 

favoring Bt plants were included. Based on the advice received by the SAP (2011) as well as 

information published in Hellmich et al. (1999), BPPD concludes that any durability analysis of a seed 

blend application targeting lepidoptera should conservatively incorporate non-uniform oviposition in 

order to address situations where greater insect damage to refuge plants in a seed mixture could result in 

greater oviposition onto Bt plants. One of Pioneer/DuPont’s proposed products (Optimum AcreMax 

Xtra) contains a corn rootworm protectant gene; for PIP plants that receive additional below ground 

protection, early crowding out of refuge plants by Bt plants is another reason why non-uniform 

oviposition needs to be addressed in modeling analyses. 

2) Pioneer/DuPont’s durability estimates for the 5% seed blend were greater than for the 10% seed blend

strategy. BPPD determined that this non-intuitive result may have been a consequence of having inflated 

the fecundity of the target pests by 6- and 4-fold for ECB and SWCB. This unexpected outcome of 

greater durability for a blend containing a lower non-Bt proportion was also the topic of discussion in 

the SAP report (2011) and Ives et al. (2011). It was demonstrated there that by inflating fecundity 

greatly that a two-toxin-pyramid in a seed blend with low non-Bt proportions could be driven to have 

increased durability over a blend with greater non-Bt proportions when target pests were mobile. In fact, 

the SAP demonstrated that at first the durability of seed blends increased with increasing proportion of 

non-Bt plants. Then a precipice was reached were durability began to decrease for blends with greater 

proportions of non-Bt plants. As fecundity was successively inflated, the precipice moved towards lower 

values of blends with non-Bt proportions (Figure 1). In other words, when fecundity was greatly 

increased, the effect was that there was greater mortality of susceptible genotypes as a result of densitydependence; this led to greater selection of resistant genotypes (Ives et al. 2011). “Because all sorts of 

variability are not considered in deterministic simulations, it is possible to push the model over the 

precipice, which marks the point on the graph where populations begin to head towards extinction and 

the density-dependent model becomes density-independent; accelerated resistance evolution can be 

observed at this point; the precautionary advice is to stay away from this precipice or boundary” (Ives, 

personal communication). 

Since the applicant’s durability estimates appear to be derived from beyond this boundary (precipice), 

BPPD concluded that it might be more meaningful to look at the sensitivity analysis conducted for nonuniform oviposition: when Bt plants were favored as oviposition sites, the fecundity of susceptible 

genotypes may have been indirectly reduced (of ECB but not so for SWCB) and density-dependence 

moved Pioneer/DuPont’s model back into the realm where durability estimates conformed to 

expectations under resistance evolution models and where seed blends with greater non-Bt proportions 

had greater durability than those with fewer non-Bt plants. Modeling analyses conducted in the past by 

EPA/ORD also predicted that a greater percentage (i.e. 10%) of refuge plants in a seed blend will be 
- 4 -

more durable than a lower percentage (i.e. 5%) of refuge plants (BPPD 2010a and BPPD 2010b). BPPD 

also considered Carriere et al. (2004) who reported that differences in Bt durability predicted by block 

and seed blends of equal refuge plant proportions (caused by a reduction in refuge insects in seed 

blends) could be overcome by increasing the proportion of non-Bt plants in seed mixtures.

3) Pioneer/DuPont conducted a sensitivity analysis for the “number of eggs produced in natal fields” by 

SWCB in block refuges (single and pyramided PIPs) but not for seed blend scenarios. The applicant 

reported that durability results for blocks were not very sensitive to changes in this parameter although a 

slightly decreasing trend in durability was noted for single PIPs as pre-ovipositional dispersal increased. 

For a 5% block refuge with a pyramided PIP (where no resistance evolved for the duration of the 

simulation – 400 yrs), the applicant reported that the final resistance allele frequency was slightly higher 

when there was more dispersal out of the fields. This result agrees with what the SAP (2011) reported, 

namely, that with high female dispersal, resistance would evolve faster. Pioneer/DuPont did not compare 

the durability of blends to blocks when varying this parameter. This would have been an important 

relative comparison, since dispersal in blends requires adults to only move short distances away from the 

refuge plant before having dispersed from their “natal field”. Hence the effects of female preovipositional dispersal out of seed blends can be expected to have a greater effect on resistance 

evolution in seed blends than block refuges. The SAP (2011) stated that “for seed mixtures dispersal 

rates will be 100%, and greater than between field refuges. The main consequence [of greater dispersal 

rates] is that seed mixtures will have faster resistance evolution than between field refuges”. 

III. RECOMMENDATIONS:

It is recommended that Pioneer/DuPont incorporate the following into their model:

a) Non-uniform oviposition for both generations of lepidoptera in a 10% seed blend (OAM Xtra);

b) Non-uniform oviposition for the second generation of lepidoptera in a 5% seed blend without a corn 

rootworm trait; and

c) Increased female (SWCB) pre-ovipositional dispersal out of seed blends.

It is recommended that Pioneer/DuPont further clarify the following about the modeling:

d) How was fecundity increased in seed blends? Does the 6-fold (and 4-fold) increase refer to the fecundity 

of susceptible insects on refuge plants relative to fecundity on Bt plants?

e) How was uniform oviposition dealt with in the model code? The methodology should be explained. Do 

adults form one big random mating pool in seed blends, and eggs are uniformly applied across the field 

(or else)? 

f) How was non-uniform oviposition dealt with in the model code of the sensitivity analysis? 

Pioneer/DuPont should explain the methodology used.

BPPD recommends research on:

g) Ovipositional behavior in seed blends under, for example, increased pest pressure;

h) The potential and degree of crowding out refuge plants by Bt protected plants in blends expressing corn 

rootworm traits under different environmental conditions;

i) Adult movement (related to mating and movement from refuges), larval movement, larval feeding (i.e., 

selective feeding within corn ears or on pollen), survival of heterozygote genotypes on OAM (markers 

may need to be determined for heterozygotes), and the potential for epistatic mechanisms of resistance 

(particularly with older instars).
- 5 -

I. BACKGROUND

BPPD reviewed biological data and simulation modeling for lepidoptera pest of corn that was submitted by 

Pioneer/DuPont to support a registration request for a 5% Optimum AcreMax (expressing Cry1F and Cry1Ab) 

and 10% Optimum AcreMax Xtra RIB (expressing Cry1F, Cry1Ab, and Cry34/35) (BPPD 2011a). In that 

review, BPPD identified a number of concerns and deficiencies with the proposed refuge strategies and was 

unable to quantify the relative durability of the proposed seed blends (BPPD 2011a). The following is a 

summary of the deficiencies and concerns listed in the Agency’s review and deficiency letter sent to the 

applicant (BPPD 2011b):

BPPD required that Pioneer/DuPont incorporate the following changes into their model, provide a comparative 

modeling analysis, and address some of the remaining biological uncertainties.

• Report final resistance allele frequency and actual estimates of durability rather than ‘greater than’ 

because relative comparisons between various strategies may be meaningful even if actual numbers are 

not.

• Artificially inflate fecundity of the pest to 1) avoid extinction, 2) avoid introducing the importance of 

genetic drift, and 3) determine relative durability for a seed blend and structured refuge.

• Incorporate a probability analysis to address uncertainties with various important parameter values and 

to provide the Agency with a risk profile (i.e., 0%, 5%, and 50%) for Optimum AcreMax and the 

modeled IRM strategies as well as a level of significance between estimated durability for different 

strategies.

• Provide comparative modeling (incorporating BPPD’s recommendations) to evaluate:

- 20% block refuge (single toxin)

- 5% block refuge (pyramid)

- 5% blended refuge (pyramid)

- 10% blended refuge (pyramid) 

• Correct the dominance value for pre-dispersal mortality/survival to be reflective of a low-dose exposure 

rather than a high-dose exposure.

• Include non-uniform oviposition parameter for first generation lepidoptera in Optimum AcreMax Xtra 

and second generation adults in Optimum AcreMax seed blends.

• Include NBI-movement hypothesis (SAP 2011) to address mortality associated with RS genotypes that 

originate and remain during most of their development on non-Bt but move as late-instars onto Bt where 

they have a certain probability of survival.

• Research on adult movement (related to mating and movement from refuges), larval movement, larval 

feeding (i.e., selective feeding within corn ears or on pollen), survival of heterozygote genotypes on 

OAM (markers may need to be determined for heterozygotes), and the potential for epistatic 

mechanisms of resistance (particularly with older instars).

On June 27, 2011, Pioneer/DuPont responded to the Agency’s review by resubmitting additional explanations 

and modeling (MRID 485219-01) to address the uncertainties and deficiencies noted in BPPD (2011a, b). The 

following review reflects BPPD’s summary of the applicant’s resubmission and the Agency’s analysis thereof.
- 6 -

II. PIONEER REVISED MODELING

Applicant’s Methods:

Pioneer/DuPont’s model was deterministic, spatially explicit, and consisted of a grid 100 m x 100 m cells (each 

cell = one hectare); simulations occurred on 400 cells for a total of size of 400 ha. The grid was divided into 10 

fields (4 x 10 cells, 40 ha), and each cell within each field was assigned to Bt, non-Bt, or Bt corn with a 5% 

blended refuge. The structured refuge was simulated by assigning two of the 40 cells in a field to non-Bt corn. 

The longest distance between refuge areas of each field was limited to < 600m; this placement favored block 

refuges and assumed random mating for ECB. Block refuges were all placed on the same short side of the ten 

rectangular fields and kept fixed at that location year after year (modeling scenario A) or switched to the 

opposite side each consecutive year (modeling scenario B). To simulate a 5% blended refuge, all 40 cells in 

each field were designated to have 5% non-Bt maize. A torus was simulated so that adults moving off of one 

side of the system arrived on the other side.

Pioneer/DuPont adjusted the previously chosen values for cross-resistance, fecundity rate, dominance, and 

proportion of eggs produced in the natal field. New benchmark and worst-case parameter values are provided in 

Tables 1 and 2 below. 

The dominance value for Cry1Ab and Cry1F were increased. For Cry1Ab vegetative stage maize the new 

worst-case value was set at to 0.27 for reproductive stage maize. Because of the assumption that there is a twofold difference between dominance values of reproductive and vegetative stage maize, a new dominance value 

for vegetative stage maize was also calculated (0.27/2=0.135). For Cry1F the dominance value for vegetative

stage maize was increased to 0.23 and 0.1 for reproductive stage maize. The new coefficient of dominance was 

calculated based on these new values (0.1/0.23=0.435). 

To avoid extinction in the majority of fields and the impact of genetic drift (as a result of low population 

densities), the applicant increased fecundity of ECB and SWCB by 6-fold and 4-fold, respectively. 

Additionally, pre-ovipositional dispersal was increased for SWCB females by decreasing the benchmark 

parameter value “Proportion of Eggs Produced in Natal Field” from 0.75 to 0.5; the sensitivity of this parameter 

was explored for a range of values (0, 0.1, 0.25, 0.4, 0.5, and 0.75).

The duration of the deterministic model runs was extended from 200 years to 400 years. For IRM scenarios 

where resistance did not evolve within the set time limit, final resistance allele frequencies were reported.

Resistance was assumed to have evolved when the resistance allele frequencies for both loci had reached 0.50.

Pioneer conducted a sensitivity analyses for ‘non-uniform oviposition’ in seed blends. The impact on durability 

of blends from different oviposition ratios was explored (favoring Bt over non-Bt 1:1, 2:1, and 4:1) (see Tables

3 and 4).

Pioneer/DuPont conducted a probability analysis using a stochastic module written in R statistics software and 

provided estimates for 0%, 5%, and 50% level of risk that resistance would evolve within a certain time. The 

PERT-distribution was skewed toward worst-case parameter values to additional conservatism. Refuge blocks 

were randomly placed between two locations. A total of 1000 runs were conducted for each simulation.

Parameters used in the probability analysis are displayed in Table 5.
- 7 -

The following refuge scenarios were modeled using the probability analysis:

• 1507 and MON810 single toxins with a 20% block refuge (moved randomly) every year;

• 1507xMON810 with a 5% block refuge (moved randomly) every year;

• 1507xMON810 with a 5% blended refuge; and

• 1507xMON810 with a 10% blended refuge.

Table 1. Benchmark and Worst-Case Parameter Values for Revised Modeling of ECB Resistance to Optimum AcreMax

Changed 

Parameters

Original Model: 

Benchmark

Revised Model:

Benchmark

Original Model:

Worst-Case

Revised Model:

Worst-Case

Cross-resistance of 

Cry1Ab  Cry1F 0.2 0.2 0.3 0.3

Cross-resistance of 

Cry1F  Cry1Ab 0 0.1 0.1 0.1

Fecundity (eggs/female) 288 1728 288 1728

Dominance of R-allele 

for Cry1Ab (vs) 0.01 0.01 0.05 0.135

Coefficient of 

Dominance for Cry1Ab 2-fold 2-fold 2-fold 2-fold

Dominance of R-allele 

for Cry1F (rs) 0.01 0.07 0.05 0.23

Coefficient of 

Dominance for Cry1F 2-fold 0.435 2-fold 0.435

Dominance value for 

pre-dispersal tasting 

survival (spdt)

0.01 0.5 0.05 0.5

Proportion of eggs 

produced in natal field 0 0 0 0

Table was modified from Table 1 in Pioneer/DuPont’s submission, p.10 (MRID 485219-01) 1 These were the original benchmark parameter values as referenced by BPPD in their risk assessment dated May 18th, 2011.
- 8 -

Table 2. Benchmark and Worst-Case Parameter Values for Revised Modeling of SWCB Resistance to Optimum AcreMax

Changed 

Parameters

Original Model1:

Benchmark

Revised Model: 

Benchmark

Original Model:

Worst-Case

Revised Model:

Worst-Case

Cross-resistance of 

Cry1Ab  Cry1F 0.1 0.1 0.3 0.3

Cross-resistance of 

Cry1F  Cry1Ab 0 0.1 0.1 0.1

Fecundity 

(eggs/female) 441 1764 441 1764

Dominance of R-allele 

to Cry1Ab (vs) 0.02 0.02 0.1 0.135

Coefficient of 

Dominance for 

Cry1Ab

2-fold 2-fold 2-fold 2-fold

Dominance of R-allele 

to Cry1F (rs) 0.02 0.07 0.1 0.23

Coefficient of 

Dominance for Cry1F 2-fold 0.435 2-fold 0.435

Dominance value for 

pre-dispersal tasting 

survival (spdt)

0.02 0.5 0.1 0.5

Proportion of eggs 

produced in natal field 0.75 0.5 0.75 0.5

Table was modified from Table 1 in Pioneer/DuPont’s submission, p.10 (MRID 485219-01) 1 These were the original benchmark parameter values as referenced by BPPD in their risk assessment dated May 18th, 2011.

Table 3. Effects of ECB non-uniform oviposition on the durability of different seed blend percentages

Seed blend 

Percentage

Gen1: 1:1

Gen2: 1:1

Gen1: 1:1

Gen2: 2:1

Gen1: 2:1

Gen2: 2:1

Gen1: 2:1

Gen2: 4:1

Years to Resistance Years to Resistance Years to Resistance Years to Resistance

5% 217 174 145 124

10% 199 183 178 162

Table was modified from Table 4 in P/DP submission, p.14 (MRID 485219-01)

*Highlighted sections are durabilities predicted under Pioneer/DuPont’s model construct with non-uniform oviposition assumptions believed to be 

more conservative by BPPD

Ratio 1:1; females oviposit eggs equally onto Bt and refuge plants

Ratio 2:1; females oviposit 2/3 of eggs onto Bt and 1/3 of eggs onto refuge plants

Ratio 4:1; females oviposit 4/5 of eggs onto Bt and 1/5 onto refuge plants

Table 4. Effects of SWCB non-uniform oviposition on the durability of different seed blend percentages

Seed blend 

Percentage

Gen1: 1:1

Gen2: 1:1

Gen1: 1:1

Gen2: 2:1

Gen1: 2:1

Gen2: 2:1

Gen1: 2:1

Gen2: 4:1

Years to Resistance Years to Resistance Years to Resistance Years to Resistance

5% 232 263 300 310

10% 136 159 163 180

Table was modified from Table 4 in P/DP submission, p.14 (MRID 485219-01)

*Highlighted sections are durabilities predicted under Pioneer/DuPont’s model construct with non-uniform oviposition assumptions believed to be 

more conservative by BPPD

Ratio 1:1; females oviposit eggs equally onto Bt and refuge plants

Ratio 2:1; females oviposit 2/3 of eggs onto Bt and 1/3 of eggs onto refuge plants

Ratio 4:1; females oviposit 4/5 of eggs onto Bt and 1/5 onto refuge plants
- 9 -

Table 5. Parameters used in Pioneer/DuPont's PERT distribution

Parameter ECB SWCB

Min Mode1 Max Min Mode1 Max

Cross-resistance of 

Cry1Ab  Cry1F 0.1 0.2 0.3 0.05 0.1 0.3

Cross-resistance of 

Cry1F  Cry1Ab 0.05 0.1 0.15 0.05 0.1 0.15

Initial R-allele 

frequency for Cry1Ab 0.0005 0.001 0.05 0.0005 0.001 0.005

Initial R-allele 

frequency for Cry1F 0.005 0.01 0.05 0.0005 0.001 0.005

Dominance of R-allele 

to Cry1Ab 0.005 0.01 0.05** 0.01 0.02 0.1 

Dominance of R-allele 

to Cry1F 0.005 0.07 0.23 0.005 0.07 0.23

Survival on Cry1Ab of 

SS larva – early instar 0 0.001 0.01 0 0.001 0.01

Survival on Cry1F of 

SS larva – early instar 0 0.001 0.01 0 0.001 0.01

Survival on Cry1Ab of 

SS larva – late instar 0.01 0.025 0.2 0.02 0.05 0.2

Survival on Cry1F of 

SS larva – late instar 0.01 0.025 0.2 0.125 0.25 0.75

Table was modified from Table 1 in P/DP submission, p.12 (MRID 485219-01) 1 Mode of each parameter is the same as the benchmark value in Tables 1 and 2 above.

** According to Pioneer/DuPont’s submission these max values should have adjusted to 0.135

Applicant’s Sensitivity Analyses:

Sensitivity analyses were conducted for the parameters ‘non-uniform oviposition’ and ‘proportion of eggs 

produced in natal fields’. As oviposition for first and second generations of ECB became less uniform, the 

durability for both the 5% RIB and the 10% RIB decreased. However, the 10% RIB became more durable than 

the 5% blend option when non-uniform oviposition was included. This shift in greater durability from the 5% to 

the 10% blend was attributed to the fact that density-dependence became less important as the overall 

population density declined. Pioneer/DuPont contended that although they explored the effects of non-uniform 

oviposition, there was no evidence in the literature to support that ECB preferentially oviposit onto Bt 

(Hellmich et al. 1999; Pilcher and Rice 2001). This appears to be the reason why this recommendation was not 

incorporated into the actual benchmark simulations (BPPD comment).

When the number of SWCB eggs laid in natal fields was decreased for block refuge scenarios, the durability 

increased slightly, and the applicant determined that this parameter was not sensitive.

Applicant’s Results:

Pioneer/DuPont cautioned that inflating the fecundity of ECB and SWCB to avoid extinction and effects of 

genetic drift, as recommended by BPPD, lead to unrealistically small durability estimates as was evident for the 

single toxin simulations. For single PIPs deployed with a 20% structured refuge, estimated durabilities were less 

than the actual time the products had been commercialized. The applicant recommended that results be 

considered relative to each other rather than viewed as absolute predictions.
- 10 -

The applicant concluded that a 5% Optimum AcreMax RIB was more durable against ECB and SWCB than 

either single gene PIP deployed with a 20% structured refuge irrespective of the fact whether the refuge was 

kept in the same location each year or randomly assigned between two possible locations. When benchmark and 

worst-case assumptions were considered, the 5% RIB scenarios were estimated to be between 7-36 fold and 4-6 

fold more durable than the single toxins MON810 (Cry1Ab) and 1507 (Cry1F), respectively, deployed with a 

20% block refuge. When the same comparisons were made for SWCB under the same benchmark and worstcase assumptions, then the durabilities for a 5% RIB were 18-58 and five-fold more durable than the single 

toxins MON810 and 1507, respectively.

Furthermore, Pioneer/DuPont reported that a 5% MON810 x 1507 RIB was more durable than a 10% RIB using

the same pyramided toxins. The applicant reasoned that this was not unexpected based on the inflated fecundity 

levels chosen and the resulting increase in density dependent mortality on refuge plants in scenarios with a 

higher blend percentage compared to a lower blend percentage and cited to discussions in Ives et al. (2011) and

SAP (2011) for support. A 5% RIB targeting ECB was only moderately more durable than the 10% RIB, while 

for SWCB the durability decreased nearly by half when the blend percentage increased from 5% to 10%. The 

applicant had set the (per-plant) carrying capacity at 18 larvae (Gen1) and 22 larvae (Gen2) for ECB and 1 larva 

(both generations) for SWCB and noted that if was difficult to determine whether the differences in durability 

seen between the two species was only a function of the different carrying capacities chosen (and DD-mortality) 

or whether differences in mating behavior could have also influenced the results.

The applicant stated that increasing the dominance value for the “pre-dispersal tasting mortality” value from 

0.02 to 0.50 created a survival differential between SS and RS individuals that was not supported by the latest 

research (manuscript in process). 

The 5% block refuge scenario had the greatest durability of all simulated refuge options. But the applicant noted 

that compliance was modeled at 100% and that any compliance less than that would decrease the durability of 

the block refuge. The difference in durability between the 5% block and 5% RIB scenario would therefore be 

reduced if non-compliance was considered. 

Table 6. Relative durability comparison between different IRM and PIP strategies (incorporating BPPD's recommendations)

PIPs IRM Strategy

Durability in Years

ECB SWCB

Benchmark Worst-Case Benchmark Worst-Case

1507 20% block-fixed 6 2 5 2

20% block-moved 6 2 4 2

MON810 20% block-fixed 32 3 13 2

20% block-moved 31 3 7 2

1507xMON810

5% block-fixed 362 17

>400*

FRAF(Cry1A) =0.001009

FRAF(Cry1F) =0.001012

5

5% block-moved 357 16

>400*

FRAF(Cry1A) =0.001101

FRAF(Cry1F) =0.001122

5

5% RIB 217 13 232 11

10% RIB 199 12 136 11

All block refuge comparisons assume 100% compliance (MRID 485219-01)

All scenarios were run with the assumption of uniform oviposition

Table was modified from Table 3 in Pioneer/DuPont’s submission, p.14

*When resistance did not evolve within the timeframe modeled, Pioneer/DuPont reported the final resistance allele frequencies.
- 11 -

Table 7. Probability analysis for relative duration of durability under different refuge and PIP strategies

PIPs IRM Strategy

Durability in Years

Different Probability Estimates for Resistance Evolution

ECB SWCB

0% 5% 50% 0% 5% 50%

1507 20% block-moved 3 3 5 2 3 4

MON810 20% block-moved 8 11 18 2 3 4

1507xMON810

5% block-moved 50 91 211 80 332 400

5% RIB 44 63 124 36 60 117

10% RIB 33 61 117 25 40 85

(MRID 485219-01)

III. BPPD REVIEW

Pioneer/DuPont provided additional modeling simulations to address BPPD’s concerns expressed in the original 

review of their new product application (BPPD 2011a). In this revised submission, the applicant focused on 

providing the Agency with simulations for an additional seed blend percentage (10%), which is directly relevant 

to the application for Optimum AcreMax Xtra maize (Reg. No. 29964-RR) that expresses both two Lepidoptera 

and one Coleoptera Bt toxin. Additionally, the applicant submitted to the Agency simulation modeling for 

single gene PIPs (the two toxins expressed in the pyramid) deployed with a 20% block refuge. All simulations 

were run with several new parameter values as suggested by BPPD. During the original review of the 

applicant’s new product application (BPPD 2011a), an analysis of data and modeling showed that a 5% seed 

blend with a pyramid of Cry1Ab and Cry1F would be substantially less durable than a 5% structured refuge for 

the same product and likely more durable than a single gene product deployed with a 20% block refuge. Since 

some scenarios were not provided at that time, however, BPPD was unable to quantify the relative gain or loss 

in durability of a pyramided product deployed as a 5% seed blend compared to a 20% block and 10% seed 

blend strategy.

BPPD’s discussion in this review will focus primarily on the relative comparison between the 5% and 10% seed 

blend as well as between a 5% blend and 20% block refuge for a single PIP and the probability analysis 

conducted by the applicant. In conclusion, BPPD will discuss the remaining uncertainties and revisit the SAP’s 

(2011) recommendations (as discussed in BPPD, 2011) to determine whether the applicant addressed those 

concerns.

BPPD discussion of reported results:

For the following reported durability results derived with benchmark and worst-case parameter values, the 

applicant assumed that oviposition was uniform for both generations of lepidoptera. Other parameters that went 

into the model to derive these results were listed in Table 1 and Table 2.

SWCB results:

In Table 6, Pioneer/DuPont reported that the durabilities for a 5% and 10% blend targeting SWCB were much 

lower than for a 5% block refuge under benchmark assumptions. No resistance was reported after 400 years for 

a 5% block, and the final resistance allele frequencies had only reached 0.001, while SWCB evolved resistance 
- 12 -

in the blends in significantly less time. However, the 5% blend was more durable (1.7 times) in these 

simulations than the 10% blend. This is contradictory to the results reported by BPPD (2010a) that blends with 

greater refuge proportions are more durable (although the simulations in that review were for a different target 

pest). This unexpected result of greater durability for the lower blend percentage is discussed in detail in the 

uncertainties section below.

When Pioneer/DuPont used worst-case parameter assumptions, the 5% and 10% seed blends had double the 

durability of the 5% block and almost four times the durability compared to the 20% block deployed with a 

single gene. BPPD is unable to determine from the submission what parameter combination, aspect of model 

structure, or other assumptions influenced the outcome in which the 5% and 10% blend had equal durability 

under worst-case assumptions.

ECB results:

When benchmark assumptions were used, Pioneer/DuPont estimated that the 5% block for the pyramid was 1.7 

times and 1.8 times more durable than the 5% and 10% blend respectively. These lower durability results for 

greater refuge proportions in blends are a consequence of the inflated fecundity numbers (as discussed in 

uncertainties section).The 20% block refuge was significantly less durable than the other three strategies. When 

oviposition was assumed to be non-uniform in the first and/or second generation, then the durability for the 10% 

blend was slightly higher than for the 5% blend and approximately 2 times lower than the estimated durability 

of the 5% block. The difference between the 10% and 5% blend would likely be greater with normal fecundity 

assumptions. The 5% blend was approximately 2.5 times less durable than the 5% block.

Probability analysis:

The reported 0%, 5%, and 50% levels of risk reported for ECB and SWCB were greatest for the single gene 

20% block refuge, followed by the 10% seed blend, 5% seed blend, and 5% block refuge, respectively, under

Pioneer/DuPont’s model construct. BPPD recognizes and commends the effort that was put into this analysis by 

Pioneer/DuPont. Unfortunately, the actual risk profile is complicated by the overwhelming effect of increased 

fecundity on the results, which BPPD had recommended the registrant explore in order to avoid rapid (<10 yrs) 

population extinction in their prior modeling submission (see BPPD 2011). However, the larger point is that 

relatively speaking, single toxin PIPs, even with a 20% refuge, are less durable than pyramided PIPs (under 

assumptions of low cross-resistance) deployed in seed blends with lower refuge proportions. 

Discussion of uncertainties:

a) Uniform oviposition:

When Pioneer/DuPont presented their benchmark and worst-case durability estimates for a 1507 x MON810 

RIB (see Table 6), they incorporated uniform oviposition onto Bt and non-Bt plants for both generations of 

ECB and SWCB. Presumably this assumption was made based on an article published by Hellmich et al. 

(1999). BPPD notes that this study analyzed results of different cage experiments in the field to evaluate 1) 

whether adult ECB could detect the presence or absence of different Bt toxins (Cry1Ab, Cry1Ac) expressed in 

vegetative corn and 2) whether second generation adults would be deterred from laying egg masses onto 

reproductive refuge corn that had evidence of first generation infestation/damage. Hellmich et al. found that 

ECB adults did not select non-Bt over Bt expressing maize in the first generation meaning that adults could not 

detect the expressed toxins in the genetically modified plants. The authors also stated that injuries to 
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reproductive (non-Bt) maize from first generation larvae were not severe enough to affect oviposition of second 

generation adults. BPPD has concerns that in cases of greater pest pressure significant damage to refuge plants 

in seed mixtures could occur and lead to non-uniform oviposition behavior by ECB adults onto Bt plants. This 

concern was also voiced by the SAP (2011) and discussed in BPPD’s review of Pioneer/DuPont’s original 

submission (BPPD 2011a). The SAP stated that this was more likely a concern in seed mixtures (rather than 

block refuges) where Bt and non-Bt plants were in close proximity. Additionally, 1507 x MON810 x Cry34/35 

is designed to also protect Bt corn plants from below-ground pests (such as corn rootworm), which could allow

Bt plants to outgrow (crowd out) unprotected refuge plants that incurred rootworm damage in such seed blends. 

In light of the uncertainties regarding uniform oviposition behavior for adult ECB (and SWCB), BPPD 

continues to support the recommendation of the SAP to incorporated non-uniform oviposition for first and 

second generation lepidoptera when Bt maize receives protection from feeding damage of above and below 

ground pests and for second generation lepidoptera when protection in the blend is received from damage of 

above ground pests only.

Pioneer/DuPont did not include this recommendation into their benchmark and worst-case simulations when 

reporting final durabilities for different IRM strategies. Their sensitivity analysis showed, however, that a 10% 

seed blend for ECB was relatively more durable than a 5% blend under moderately conservative assumptions of 

non-uniform oviposition. Whether the differences were actually significant was unclear. The sensitivity analysis 

for this parameter in SWCB did not show this same trend of increased durability with increased percentage (i.e. 

10%) of refuge plants in a blend. 

b) Increased fecundity and lower durability for the greater blend percentage:

When Pioneer/DuPont increased the fecundity for ECB and SWCB to avoid population extinction and the 

importance of genetic drift, as suggested by BPPD, they observed that under some circumstances (i.e. when 

oviposition was held uniform for ECB) the durability of the 10% blend was somewhat lower than the durability 

of the 5% blend despite their being more refuge plants available and the potential for greater total refuge 

population in a 10% blend. This behavior was also observed and discussed by the SAP (2011) as well as Ives et 

al. (2011). During the SAP meeting, Dr. Ives demonstrated in his presentation of a density-dependent analysis 

for a two toxin pyramid (in a seed blend) that for some special cases this result of having lower durability for a 

greater blend percentage may not be unexpected. In fact, Figure 1 (extracted from the SAP report) shows that at 

first the durability of the blend increases with increasing proportion of non-Bt plants. Then a point (or precipice) 

is reached (see arrows) were durability begins to decrease for blends with greater proportions of non-Bt plants. 

As fecundity is successively inflated (see lower to upper graph), the precipice is moving towards lower values

(see arrows). In other words, as fecundity increases (while all other parameters are held constant), the speed of 

resistance evolution increases for the same proportion of refuge that lies past this precipice. When fecundity is 

increased, the effect is that there is greater mortality of susceptible genotypes as a result of density-dependence; 

this leads to greater selection of resistant genotypes (Ives et al. 2011).”The precipice then marks the point on the 

graph where a population begins to head towards extinction and the density-dependent model becomes densityindependent; the model behavior changes from what one would expect, and accelerated resistance evolution can 

be observed at this point; the precautionary advice is to stay away from this precipice or boundary” (Ives, 

personal communication). BPPD notes that the increasing fecundity for ECB and SWCB (6 and 4-fold) may 

have moved Pioneer/DuPont’s simulated populations past this ‘precipice’ described by the SAP, which explains 

their decreased durability for a 10% blend compared to a 5% blend. This lower durability for higher blends is 

then likely a phenomenon due to inflating fecundity artificially.
- 14 -

The applicant’s sensitivity analysis suggests that when assumption of uniform oviposition were relaxed and

adults favored Bt plants over refuge plants 2:1 in the first and/or second generation, that fecundity of the 

susceptible genotypes was reduced indirectly. This had the effect of increasing the durability estimates for the 

10% blend over the lower blend percentage. This relative difference in durability was enhanced when 

oviposition onto Bt was increased for both generations of ECB, which might be expected in a seed blend that 

expresses both corn rootworm and lepidoptera active toxins (see discussion above on ‘Bt plants crowding out 

refuge plants’). IRM analyses conducted in the past by EPA/ORD also predicted that a greater percentage (i.e. 

10%) of refuge plants in a seed blend will be more durable than a lower percentage (i.e. 5%) of refuge plants 

(BPPD 2010a and BPPD 2010b).

Figure 1. Generations to resistance failure (frequency of both alleles >0.5) for density-dependent model for F=100, 50, and 20 (labeled) when 

larval movement is 0, 0.3, and 0.6. Arrows mark the proportion of seed mixtures below which the population decreases towards extinction. 

Baseline parameter values are: S1SS = S2SS=0.01; h1=h2= 0.05; survival is divided equally between pre-and post larval movement; and initial 

allele frequency = 0.005. (This figure was extracted from the SAP report (2011) and modifies Fig.A2-11 (p.134) to show the density-dependent 

model runs only. Frequency dependent results were removed for the purpose of this report.)

c) Probability analysis:

The applicant improved their original modeling analysis by conducting a probability analysis (PERT 

distribution) for both lepidoptera pests to address uncertainties with important parameters and to provide the 

Agency with a risk profile for resistance evolution. BPPD noted that in Table 2 of the applicant’s submission 
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(MRID 485219-01), the maximum values for dominance of the resistance allele for Cry1Ab was 0.05 (original 

benchmark) instead of 0.135 (the newly adjusted value for current modeling submission). The dominance value 

for the resistance allele is typically one of several sensitive parameters. It is unclear how much the risk profile 

would change (if at all) had this maximum value been adjusted as outlined in the applicant’s report. The 

applicant also stated that they skewed the distribution of the PERT analysis towards the higher values for the 

purpose of deriving a conservative risk profile (but weighting the mean by a factor of four and therefore placing 

more confidence into that value). It is not clear to BPPD how skewing the distribution in this manner increased 

the probability of sampling the extreme values; it appears that the mean value was changed by skewing the 

distribution. Also, Pioneer/DuPont did not state how many simulations were run to derive their probability

distribution. The SAP concluded that unless simulations were increased to close to 100,000 runs, it was unlikely 

that extreme values were sampled from a predetermined range used to derive a PERT Beta distribution (SAP 

2011).

d) Female dispersal out of natal fields:

Pioneer/DuPont conducted a sensitivity analysis for the “number of eggs produced in natal fields” by SWCB 

(one of the parameters for which BPPD suggested more conservative values) and reported that model results 

were not very sensitive to changes in this parameter. However, a slightly increasing trend in durability was 

noted for single PIPs as the percentage of eggs in the natal (block refuge) field increased from 0% to 50% 

(analogous to decreasing durability with increasing pre-ovipositional dispersal). For a 5% block (no resistance 

evolved in 400 yrs), the applicant reported that the resistance allele frequency was slightly higher with more 

dispersal out of the fields compared to when 50% of the eggs were laid in the natal field. This result matches up 

with what the SAP (2011) reported, namely, that with high female dispersal, resistance would evolve faster. 

Pioneer/DuPont did not compare the durability for blends to blocks when varying this parameter. This would 

have been an important comparison since dispersal in blends requires adults to only move short distances away 

from the refuge plant before having dispersed from their “natal field”. The SAP (2011) stated that “for seed 

mixtures dispersal rates will be 100%, and greater than between field refuges. The main consequence [of greater 

dispersal rates] is that seed mixtures will have faster resistance evolution than between field refuges”. BPPD 

notes that Pioneer’s durability estimates for seed blends would likely be lower than what is currently reported if 

greater dispersal had been incorporated into the benchmark and worst-case assumptions for SWCB as was done 

for block refuge simulations.

SAP (2011) recommendations:

• Larval movement: explicit vs. implicit

Pioneer/DuPont included both the NBI and BNI hypothesis in their model, which addresses the SAP’s (2001) 

recommendation to include larval movement explicitly and to address pathways of selection before and after Bt 

exposure. The applicant included early instar (varied dominance as well as late instar exposure and mortality 

into their model construct.

• Cross-resistance

The applicant addressed the SAP’s (2011) and BPPD’s concern about cross-resistance and incorporated a 10% 

and 20% cross-resistance for Cry1F to Cry1Ab and Cry1Ab to Cry1F, respectively. Additionally, the applicant 

assumed a worst-case maximum of 30% cross-resistance for Cry1Ab to Cry1F in their probability analysis. It is 

uncertain, however, whether enough simulations were run to sample extreme values from the parameter range 

(see discussion in probability analysis above).
- 16 -

• Non-uniform oviposition

The applicant explored non-uniform oviposition and its effects on the durability of seed blends in a sensitivity 

analysis only. Their main modeling results were not derived with assumptions of non-uniform oviposition (both 

benchmark and worst-case simulations). Hence, when looking at Pioneer/DuPont’s estimated durability results 

in Tables 6 and 7, this point needs to be considered. Based on the advice received by the SAP (2011) as well as 

information published in Hellmich et al. (1999), BPPD concludes that any durability analysis of a seed blend 

application should conservatively incorporate non-uniform oviposition favoring Bt plants to address situations 

where greater insect damage to refuge plants in a seed mixture could result in preferring Bt plants as oviposition

sites or where CRW protected maize could crowd out refuge plants.

BPPD Conclusions:

Pioneer/DuPont addressed the recommendations made in BPPD (2011): the applicant inflated the fecundity of 

the target pests by 6 and 4-fold to avoid population extinction for European and southwestern corn borers in 

their modeling analyses, included some worst-case values for several sensitive parameters in their new 

simulations, conducted a probability analysis to be able to report a risk profile to the Agency, and addressed the 

most germane uncertainties described by the SAP (2011) for seed blends with pyramided PIPs targeting 

Lepidoptera. However, Pioneer/DuPont did not include non-uniform oviposition by Lepidoptera in their main 

modeling analyses and explore greater female (southwestern corn borer) dispersal out of seed blends.

After careful review of the applicant’s new modeling submission, BPPD concludes that:

• The 20% single toxin block refuges had the lowest durability estimates of all options tested in 

Pioneer/DuPont’s model. Those durability results were, however, artificially reduced by higher 

fecundity assumptions. Pioneer/DuPont estimated blends to be between 6 and 60-fold more durable than 

20% blocks for single toxin PIPs.

• The proposed seed blends (5% and 10%) will likely be substantially less durable than a 5% block refuge 

for the same product (100% compliance assumed). This was also concluded by the SAP (2011). With 

realistic assumptions of non-compliance the estimated durability for the block scenario would likely be 

somewhat lower but still more durable than the blends. Pioneer/DuPont’s model estimated that a 5% 

block had close to double the durability of blends for both pests (benchmark assumptions). The 

durability of the pyramided blends is highly likely to fall in between the two block options. They can be 

expected to be more durable than the single toxins (especially under assumptions of low crossresistance). The uncertainties described below (effects of increased fecundity, no modeling of nonuniform oviposition and greater dispersal out of blends) can be expected to further erode the durability 

of blends. 

• A 10% blend is likely to be more durable than a 5% seed blend for the same product. Pioneer/DuPont 

reported, however, that the lower blend percentage had slightly greater durability than the higher blend 

percentage. Possible explanations for this unexpected outcome are discussed in the uncertainties section 

below.

• These conclusions are based on all available information, including Pioneer/DuPont’s modeling, the 

2011 SAP report, and EPA/ORD modeling analyses created for other seed blend products. 

Quantification of the risk (i.e. level of durability) for Optimum AcreMax and Optimum AcreMax Xtra is 

complicated by uncertainties in some biological parameters including uniform/non-uniform oviposition, 

effects of inflated fecundity, degree of female pre-ovipositional dispersal as well as aspects of the 
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probability analysis. All these uncertainties together could functionally lower the durability of seed 

blends relative to block refuges.

• In consideration of the cumulative effect of the uncertainties and without additional modeling, BPPD is 

unable to completely quantify the relative durabilities of the various refuge options. BPPD expects, 

however, the relative durability relationship to hold true: 5% pyramid block > 10% pyramid seed 

blend > 5% pyramid seed blend > 20% single toxin block. 

• The 10% Optimum AcreMax 1 seed blend (expressing Cry34/35) targeting corn rootworm was 

approved in 2009. The applicant seeks to combine this single CRW gene with the pyramid PIP for 

Lepidoptera into a new 10% seed blend product (Optimum AcreMax Xtra). As stated above, the risk of 

resistance development and relative durability cannot be quantified for any of the proposed blends; 

however, BPPD expects the risk of resistance evolution to be lower for a 10% seed blend expressing two 

pyramided PIPs than a 5% blend as proposed for the Optimum AcreMax product targeting Lepidoptera 

only.

BPPD has identified the following uncertainties in Pioneer/DuPont’s analysis:

1) Non-uniform oviposition behavior was not included into Pioneer/DuPont’s benchmark simulations 

although a sensitivity analysis for this parameter showed a trend of greater durability for the 10% seed 

blend over the 5% blend when conservative, yet realistic, assumptions of non-uniform oviposition 

favoring Bt plants were included. Based on the advice received by the SAP (2011) as well as 

information published in Hellmich et al. (1999), BPPD concludes that any durability analysis of a seed 

blend application targeting lepidoptera should conservatively incorporate non-uniform oviposition in 

order to address situations where greater insect damage to refuge plants in a seed mixture could result in 

greater oviposition onto Bt plants. One of Pioneer/DuPont’s proposed products (Optimum AcreMax 

Xtra) contains a corn rootworm protectant gene; for PIP plants that receive additional below ground 

protection, early crowding out of refuge plants by Bt plants is another reason why non-uniform 

oviposition needs to be addressed in modeling analyses. 

2) Pioneer/DuPont’s durability estimates for the 5% seed blend were greater than for the 10% seed blend

strategy. BPPD determined that this non-intuitive result may have been a consequence of having inflated 

the fecundity of the target pests by 6- and 4-fold for ECB and SWCB. This unexpected outcome of 

greater durability for a blend containing a lower non-Bt proportion was also the topic of discussion in 

the SAP report (2011) and Ives et al. (2011). It was demonstrated there that by inflating fecundity 

greatly that a two-toxin-pyramid in a seed blend with low non-Bt proportions could be driven to have 

increased durability over a blend with greater non-Bt proportions when target pests were mobile. In fact, 

the SAP demonstrated that at first the durability of seed blends increased with increasing proportion of 

non-Bt plants. Then a precipice was reached were durability began to decrease for blends with greater 

proportions of non-Bt plants. As fecundity was successively inflated, the precipice moved towards lower 

values of blends with non-Bt proportions (Figure 1). In other words, when fecundity was greatly 

increased, the effect was that there was greater mortality of susceptible genotypes as a result of densitydependence; this led to greater selection of resistant genotypes (Ives et al. 2011). “Because all sorts of 

variability are not considered in deterministic simulations, it is possible to push the model over the 

precipice, which marks the point on the graph where populations begin to head towards extinction and 

the density-dependent model becomes density-independent; accelerated resistance evolution can be 

observed at this point; the precautionary advice is to stay away from this precipice or boundary” (Ives, 

personal communication). 
- 18 -

Since the applicant’s durability estimates appear to be derived from beyond this boundary (precipice), 

BPPD concluded that it might be more meaningful to look at the sensitivity analysis conducted for nonuniform oviposition: when Bt plants were favored as oviposition sites, the fecundity of susceptible 

genotypes may have been indirectly reduced (of ECB but not so for SWCB) and density-dependence 

moved Pioneer/DuPont’s model back into the realm where durability estimates conformed to 

expectations under resistance evolution models and where seed blends with greater non-Bt proportions 

had greater durability than those with fewer non-Bt plants. Modeling analyses conducted in the past by 

EPA/ORD also predicted that a greater percentage (i.e. 10%) of refuge plants in a seed blend will be 

more durable than a lower percentage (i.e. 5%) of refuge plants (BPPD 2010a and BPPD 2010b). BPPD 

also considered Carriere et al. (2004) who reported that differences in Bt durability predicted by block 

and seed blends of equal refuge plant proportions (caused by a reduction in refuge insects in seed 

blends) could be overcome by increasing the proportion of non-Bt plants in seed mixtures.

3) Pioneer/DuPont conducted a sensitivity analysis for the “number of eggs produced in natal fields” by 

SWCB in block refuges (single and pyramided PIPs) but not for seed blend scenarios. The applicant 

reported that durability results for blocks were not very sensitive to changes in this parameter although a 

slightly decreasing trend in durability was noted for single PIPs as pre-ovipositional dispersal increased. 

For a 5% block refuge with a pyramided PIP (where no resistance evolved for the duration of the 

simulation – 400 yrs), the applicant reported that the final resistance allele frequency was slightly higher 

when there was more dispersal out of the fields. This result agrees with what the SAP (2011) reported, 

namely, that with high female dispersal, resistance would evolve faster. Pioneer/DuPont did not compare 

the durability of blends to blocks when varying this parameter. This would have been an important 

relative comparison, since dispersal in blends requires adults to only move short distances away from the 

refuge plant before having dispersed from their “natal field”. Hence the effects of female preovipositional dispersal out of seed blends can be expected to have a greater effect on resistance 

evolution in seed blends than block refuges. The SAP (2011) stated that “for seed mixtures dispersal 

rates will be 100%, and greater than between field refuges. The main consequence [of greater dispersal 

rates] is that seed mixtures will have faster resistance evolution than between field refuges”. 

RECOMMENDATIONS:

It is recommended that Pioneer/DuPont incorporate the following into their model:

a) Non-uniform oviposition for both generations of lepidoptera in a 10% seed blend (OAM Xtra);

b) Non-uniform oviposition for the second generation of lepidoptera in a 5% seed blend without a corn 

rootworm trait; and

c) Increased female (SWCB) pre-ovipositional dispersal out of seed blends.

It is recommended that Pioneer/DuPont further clarify the following about the modeling:

d) How was fecundity increased in seed blends? Does the 6-fold (and 4-fold) increase refer to the fecundity 

of susceptible insects on refuge plants relative to fecundity on Bt plants?

e) How was uniform oviposition dealt with in the model code? The methodology should be explained. Do 

adults form one big random mating pool in seed blends, and eggs are uniformly applied across the field 

(or else)? 

f) How was non-uniform oviposition dealt with in the model code of the sensitivity analysis? 

Pioneer/DuPont should explain the methodology used.
- 19 -

BPPD recommends research on:

g) Ovipositional behavior in seed blends under, for example, increased pest pressure;

h) The potential and degree of crowding out refuge plants by Bt protected plants in blends expressing corn 

rootworm traits under different environmental conditions; and

i) Adult movement (related to mating and movement from refuges), larval movement, larval feeding (i.e., 

selective feeding within corn ears or on pollen), survival of heterozygote genotypes on OAM (markers 

may need to be determined for heterozygotes), and the potential for epistatic mechanisms of resistance 

(particularly with older instars).
- 20 -

IV. REFERENCES

Carriere, Y, MS Sisterson, and BE Tabashnik. 2004. Resistance management for sustainable use of Bacillus 

thuringiensis crops in integrated pest management, p. 65-95. Book chapter in “Insect Pest Management: Field 

and Protected Crops”, Springer, 2004.

Hellmich RL, LS Higgins, JF Witkowski, JE Campbell, and LC Lewis. 1999. Oviposition by European corn 

borer (Lepidoptera: Crambidae) in response to various transgenic events. Journal of Economic Entomology, 

Vol. 92(5): 1014-1020

Ives AR, PR Glaum, NL Ziebarth, and DA Andow. 2011. The evolution of resistance to two-toxin pyramid 

transgenic crops. Ecological Applications, Vol. 21(2): 503-515

AR Ives. 2011, personal (phone) communication with J.C. Martinez on August 3rd, 2011.

Pan Z, K Tran, H Zeng, and others (2011). Responses to EPA’s letter dated June 7, 2011 regarding Pioneer’s

Lepidopteran blended refuge products. Unpublished study submitted to the Agency by Pioneer Hi-Bred

International, Inc. (MRID 485219-01).

Other:

BPPD, 2011a. EPA Review of Pioneer’s new product registration request, Optimum AcreMax Insect 

Protection, expressing Cry1F and Cry1Ab in a 5% seed blend to control lepidopteran pests of corn. Memo from 

JC Martinez to M. Mendelsohn dated May 18, 2011.

BPPD, 2011b. Agency deficiency letter sent by Dr. Sheryl Reilly in June, 2011 addressed to Tracy Rood from 

Pioneer/DuPont. 

BPPD, 2010a. Science Assessment of Pioneer’s modeling addenda in support of their application of registration 

for Optimum AcreMax1 Insect Protection. Memo from JC Martinez to M. Mendelsohn dated February 4, 2010.

BPPD, 2010b. Science risk assessment to evaluate the durability of a 10% Cry34/35 seed blend refuge 

deployment of Cry34/35 corn relative to the durability predicted for a 20% block in regards to Pioneer/DuPont’s 

Optimum AcreMax1. Memo from JC Martinez to M. Mendelsohn dated April 22, 2010.

EPA Scientific Advisory Panel. 2011. Transmittal Meeting Minutes of the FIFRA Scientific Advisory Panel 

Meeting Held December 8-9, 2010 to Address Scientific Issues Associated with Insect Resistance Management 

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

from Dr. Sharlene Matten (DFO) to Dr. Steven Bradbury (Director of OPP) on March 3, 2011.