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Agenda for FIFRA Scientific Advisory Panel (SAP) Open Meeting June 13 - 15, 2006

Final Agenda: 6/6/2006



FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

JUNE 13 - 15, 2006

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2006-0217

 

TUESDAY, JUNE 13, 2006

Holiday Inn - National Airport

2650 Jefferson Davis Highway

Arlington , VA 22202

(703) 684-7200

 

ANALYSIS OF A NATURAL REFUGE OF NON-COTTON HOSTS FOR MONSANTO'S BOLLGARD II COTTON

 

8:30 A.M.Introduction and Identification of Panel Members - Steven Heeringa, Ph.D., FIFRA SAP Chair

8:40 A.M. Administrative Procedures by Designated Federal Official – Myrta R. Christian

8:45 A.M. Welcome and Opening Remarks – Janet Andersen, Ph.D., Director, Biopesticides and Pollution Prevention Division, Office of Pesticide Programs, EPA

Leonard Cole, Biopesticides and Pollution Prevention Division, Office of Pesticide Programs, EPA

8:50 A.M. Tobacco Budworm Sampling and Gossypol Analysis – Alan Reynolds, Biopesticides and Pollution Prevention Division, Office of Pesticide Programs, EPA;

Effective Refuge Calculations and Modeling for Tobacco Budworm and Cotton Bollworm – Sharlene Matten, Ph.D., Biopesticides and Pollution Prevention Division, Office of Pesticide Programs, EPA

 

10:00 A.M.BREAK

 

10:15 A.M. Public Comments

 

12:00 P.M. LUNCH

 

1:00 P.M. Questions to the Panel

 

Sampling and Methodology

 

  • The Panel is asked to comment on the pheromone sampling strategy employed by Monsanto in which only male tobacco budworm (TBW) were trapped.

 

Is this an appropriate sampling strategy? Can inferences about female TBW be derived from data gathered exclusively with males?

 

  • Monsanto’s TBW sampling and gossypol analyses were conducted over a two year period (2004 and 2005). For several states ( Tennessee and E. Texas) data were collected in only one year. The trends between seasons were generally consistent, although no statistical/correlation analysis was performed.

 

The Panel is asked to comment on what uncertainties exist from using data collected from this time period (i.e., 2 years for North Carolina and Georgia and 1 year for Tennessee and E. Texas) to adequately assess the potential of natural refuge (i.e., non-cotton hosts) as a substitute for structured refuge (i.e., non-Bt cotton)?

 

3:00 P.M.BREAK

 

3:15 P.M. Panel Discussion (continued)

 

  • In some counties/states, extremely low numbers of TBW were trapped, with some traps collecting only one insect. In Tennessee, TBW numbers were so low that data were not reported at all for 2004. In addition, cotton monitoring efforts have been recently hampered by low availability of TBW samples (possibly due to a suppressive effect of Bt cotton).

 

Do low overall numbers of TBW trap captures in some areas affect the ability to assess the effectiveness of natural refuge for IRM? What conclusions, if any, should be drawn from the failure to capture Bt-susceptible TBW at particular sites?

 

Statistical Analyses

 

  • Monsanto used the Fisher’s Exact Test to determine whether the gossypol data could be pooled. Data were pooled for individual traps (i.e. for multiple collection dates for each month) and for counties (i.e. including all traps within a county for each month).

 

The Panel is asked to comment on Monsanto’s approach to pooling the gossypol data.

 

5:30 P.M.ADJOURNMENT

 

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

JUNE 13 - 15, 2006

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2006-0217

 

WEDNESDAY, JUNE 14, 2006

Holiday Inn - National Airport

2650 Jefferson Davis Highway

Arlington , VA 22202

(703) 684-7200

 

ANALYSIS OF A NATURAL REFUGE OF NON-COTTON HOSTS FOR MONSANTO'S BOLLGARD II COTTON.

 

8:30 A.M.Introduction and Identification of Panel Members - Steven Heeringa, Ph.D., FIFRA SAP Chair

8:35 A.M. Administrative Procedures by Designated Federal Official – Myrta R. Christian

8:40 A.M. Follow-up from Previous Day’s Discussion – Alan Reynolds and Sharlene Matten, Ph.D. Biopesticides and Pollution Prevention Division (Office of Pesticide Programs)

9:00 A.M. Panel Discussion (continued)

 

Statistical Analyses

 

  • Monsanto did not conduct any statistical analyses comparing the two sampling years (2004 and 2005). The Panel is asked to comment on whether valid comparisons (on a qualitative basis) can be made between the two years without statistical analyses? Please describe any meta-statistical analysis that could improve the overall understanding of the effectiveness of natural refuge across locations and across time.

 

10:00 A.M.BREAK

 

10:15 A.M. Panel Discussion (continued)

 

Effective Refuge Calculation and Modeling

  • Monsanto has corrected their calculation of effective refuge size presented in Gustafson and Head, 2004 based on the Agency’s (BPPD, 2004b) and June 2004’s Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel’s (SAP) recommendations (SAP, 2004). Modifications to the calculation of the effective refuge size involved removing the assumption of constant effective refuge size and explicitly accounting for the lower production of CBW and TBW in cotton where survival of these insects is reduced. Estimation of the effective refuge now assumes a regionally specific annual cycle of effective refuge size, according to data collected in alternative host studies of CBW (Head and Voth, 2004) and TBW (Head and Gustafson, 2005). These data were combined with corn planting estimates on either the regional scale for CBW, or county-scale for TBW, to estimate effective (i.e., current (structured non-Bt cotton + non-cotton) and natural (non-cotton only) refuge sizes for each of what were conservatively assumed to be six annual generations for each pest.
  • Estimation of the relative number of CBW adult moths produced by each of the five sub-compartments is given by the following equation: M ij = A ij E ij LB ij LS ij (Equation 1).

[M is the number of adult moths produced per unit area of the region; A is the proportion of the region occupied by the crop type of interest; E is the relative (to cotton, i.e. E cotton=1) number of effective eggs (eggs that would produce adults in the absence of B.t. or pyrethroid sprays) laid in the crop type; LB is the fraction of larvae surviving in the presence of the B.t. crop; LS is the fraction of larvae surviving a pyrethroid insecticide spray on the crop; the subscript i refers to the compartment (B for B.t. or R for refuge); and the subscript j refers to the particular crop type within the compartment (1 = cotton, 2 = corn, 3 = other C3 host crop).]

The effective refuge, R eff , is defined as the proportion of adult moths that would have been produced in the refuge compartment (non-Bt cotton, non-Bt corn, non-cotton C3 crops) in the absence of any induced larval mortality:

R eff = M subscript R1 plus M subscript R2 plus M subscript R3, all divided by M subscript R1 plus M subscript R2 plus M subscript R3 plus M subscript B1 plus M subscript B2 (Equation 5; used when CBW populations were actively feedings in cotton, Generations 3-5)

Effective refuge estimations for all of the “non-cotton” generations are given by:

R with n c over e f f = M subscript R2 plus M subscript R3 all divided by M subscript R2 plus M subscript R3 plus M subscript B2(Equation 6)

The natural refuge component (i.e., non-cotton C3 crops + non-Bt corn components) of the total effective refuge is as follows:

R with CBW  over n a t = M subscript R2 plus M subscript R3 all divided by M subscript R2 plus M subscript R3 plus M subscript B2 (Equation 7)

The Agency asks the SAP to comment on the estimated CBW effective and natural refuge calculations.

  • Pooled, county-level estimates of the percent cotton-reared TBW moths were combined with county-level landcover information to estimate the current effective refuge and natural refuge for each county per month. The relative TBW productivity of non-cotton areas within a county for a specific month is given as:

E NC = Open parenthesis A subscript NBTC all divided by P NBTC close parenthesis, minus A subscrit NBTC, all divided by A subscript NC(Equation 8)

The current effective refuge (non-Bt cotton + non-cotton hosts) for TBW is defined as the proportion of TBW moths actually produced in the effective refuge compartment prior to selection by Bt cotton:

R twith TBW over e f f = A subscript NBTC plus open parenthesis A subscript NC E subscript NC, close parenthesis all divided by A subscript BTC plus A subscript NBTC plus open parenthesis A subscript NC E subscript NC (Equation 9)

The estimated natural refuge (non-cotton hosts) for TBW is given by the following equation:

R with TBW over n a t = A subscript NC E subscript NC all divided by A subscript BTC plus A subscript NBTC plus open parenthesis A subscript NC E subscript NC (Equation 10)

The Agency asks the SAP to comment on the estimated TBW effective and natural refuge calculations.

12:00 P.M. LUNCH

 

1:00 P.M.Panel Discussion (continued)

 

  • Monsanto examined the durability of each of the three Bt cotton products (i.e., Bollgard, WideStrike, and Bollgard II) individually and together in the marketplace using a three-gene model. The Bt protein, Cry1Ac, is common to all three products. The presence of each of these products in the marketplace selects for potential resistance to Bollgard cotton, expressing only the Cry1Ac protein, and also selects for resistance to the other two products through the common selection for Cry1Ac resistance. The products vary greatly in the rate at which they select for resistance to Cry1Ac because of the presence of additional insecticidal proteins in Bollgard II (Cry2Ab2) and in WideStrike (Cry1F).

 

The three-gene model for insect resistance evolution used in this study is based on a conceptual model similar to that proposed by Dow AgroSciences (DAS) for its product, WideStrike cotton, and was reviewed by a recent U.S. EPA Scientific Advisory Panel (SAP) (SAP, 2004). However, the SAP questioned some of the mathematical details of the DAS model and Monsanto has made some changes to address the SAP’s concerns. As shown in schematic form in Figure 3, Appendix 2, the three-gene model is based on the following assumptions concerning the mechanism of activity of the three commercial Bt cotton products (Bollgard, Bollgard II, and WideStrike cotton):

 

  • The Cry1Ac toxin, present in all three products, binds to two receptors, 60% to receptor A and 40% to receptor B.
  • The Cry1F toxin, present only in WideStrike cotton, binds exclusively to receptor A.
  • The Cry2Ab2 toxin, present only in Bollgard II cotton, binds exclusively to receptor C.

 

a) CBW. Based both on the intrinsic durability of each of the three B.t. cotton products (Figure 4, Appendix 2) and the three-gene modeling analyses for all three Bt cotton products together in the marketplace (Table 14, Appendix 2), Bollgard II retained the highest level of efficacy against CBW in all scenarios (all regions). Given the assumptions of the three-gene model and its limitations, there is likely enough effective natural refuge to be sufficient to delay the evolution of resistance to Bollgard II cotton for more than 25 years (not a precise number of years) under all plausible scenarios in all four regions (Table 14, Appendix 2). This is because of the relatively high mortality of individuals heterozygous to Cry1Ac resistance in the presence of Cry2Ab2, as compared to WideStrike. WideStrike is intermediate in many scenarios because of the shared binding receptor between Cry1F and CryAc and the likelihood of cross-resistance is greater. Bollgard is weakest in all scenarios because there is no high dose for CBW and it is a single-gene product. Monsanto’s models predict that CBW resistance to Bollgard cotton will evolve in less than the 30 year horizon in the Georgia, Mississippi, and E. Texas regions in most scenarios except for 2-C (Bollgard = 0.1; Bollgard II = 0.8; WideStrike = 0.1). Resistance always took at least 30 years to evolve to all three Bt cotton products in the North Carolina region in all scenarios, even the natural refuge scenarios. When Bollgard cotton acreage is minimized, Bollgard II and WideStrike longevity is maximized (Table 14). Large amounts of Bollgard II cotton in the marketplace increased the durability of both Bollgard and WideStrike (Table 14, Appendix 2). Uncertainties in the pheromone captures, estimation of adult productivity, carbon isotope analyses, spatial analysis, estimation of effective refuge calculation, degree of shared binding affinity of Cry1Ac to receptor A and B, genetics of resistance, resistance mechanism, initial resistance allele frequency, and other modeling assumptions affect the precision and accuracy of the modeling predictions. Monsanto’s modeling also does not consider pre-selection for Cry1Ac resistance. Ten years of selection pressure (since 1996) for resistance to Cry1Ac has already occurred. Field resistance to Cry1Ac places additional selection pressure on the Cry2Ab2 component of Bollgard II cotton.

 

Given the assumptions and uncertainties in Monsanto’s CBW modeling efforts, the Agency asks the SAP to comment on the utility of the modeling to predict the effectiveness of natural (non-cotton C3 crops + non-Bt corn) vs. current effective refuge (non-Bt Cotton + non-Bt corn + non-cotton C3 crops) to manage CBW resistance to the toxins expressed in Bollgard II. Discuss the impact of pre-selection for Cry1Ac resistance on the modeling output.

 

b) TBW. The intrinsic durability of all three Bt cotton products is much greater for TBW than for CBW because of the “high dose” of Cry1Ac for TBW expressed in all three products. In virtually all cases, all three products retained their efficacy (i.e., no resistance) for more than 30 years (maximum time for the simulation) even if all cotton in a region is planted to that product and no structured refuge is required (i.e., all natural refuge). The only exceptions occur for Bollgard cotton in Tennessee and Mississippi. Given the assumptions of the three-gene model and its limitations, there is likely enough effective natural refuge to be sufficient to delay the evolution of resistance to Bollgard II cotton for more than 30 years (i.e., the time horizon of the model, not to be interpreted as a precise number of years) under all plausible scenarios in all four regions. This is due to the extremely high efficacy of Cry1Ac against TBW, and the fact that Cry1Ac is present in all three Bt cotton products. In the state with the lowest natural refuge for TBW, Mississippi (see Table 13, Appendix 2), resistance to Cry1Ac and Cry1F evolved after 21 years in scenario 1-N if the structured refuge requirements for Bollgard and WideStrike cotton were removed. Uncertainties in the pheromone captures, gossypol analyses, spatial analysis, estimation of effective refuge calculation, degree of shared binding affinity of Cry1Ac to receptor A and B, genetics of resistance, resistance mechanism, initial resistance allele frequency, and other modeling assumptions affect the precision and accuracy of the modeling predictions. Monsanto’s modeling also does not consider pre-selection for Cry1Ac resistance. Ten years of selection pressure (since 1996) for resistance to Cry1Ac has already occurred. Field resistance to Cry1Ac places additional selection pressure on the Cry2Ab2 component of Bollgard II cotton.

Given the assumptions and uncertainties in Monsanto’s TBW modeling efforts, the Agency asks the SAP to comment on the utility of the modeling to predict the effectiveness of natural (non-cotton hosts) vs. current effective refuge (non-Bt cotton + non-cotton hosts) to manage TBW resistance to the Bt toxins expressed in Bollgard II cotton. Discuss the impact of pre-selection for Cry1Ac resistance on the modeling output.

 

3:00 P.M.BREAK

 

3:15 P.M. Panel Discussion (continued)

 

  • Modeling suggests that the overall durability of Bollgard II cotton can be enhanced if Bollgard cotton is removed from the marketplace. This conclusion is supported by other researchers who examined the benefit of managing resistance evolution to two toxins with dissimilar modes of action using a pyramided approach (Zhao et al., 2005; Roush, 1998; Livingston et al., 2004; Hurley, 2000; Caprio, 2005). On the other hand, the concurrent use of single- and two-gene Bt plants can offer exposed populations a “stepping stone” to develop resistance to both proteins. Bollgard, Widestrike, and Bollgard II cotton exist in a mosaic in southeastern cotton growing regions, with Bollgard dominating the total acreage. In 2004, Bollgard cotton acreage accounted for >95% of all Bt cotton acreage in the U.S. (see Head et al., 2005, MRID# 467172-03). Encouraging the adoption of Bollgard II will increase the overall durability of all three Bt cotton products. From an insect management point of view, removal of Bollgard cotton from the marketplace would benefit the two-gene products, Bollgard II and WideStrike.

 

The Panel is asked to address the implications for selection for CBW and TBW resistance if the mosaic of single gene and dual gene products remains in the marketplace for a number of years. How would selection pressure be reduced if the single gene product is removed from the marketplace gradually (e.g., >3 years) or rapidly (e.g., ≤3 years) over a period of years?

 

5:00 P.M.ADJOURNMENT

 

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

JUNE 13 - 15, 2006

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

OPP Docket Telephone: (703) 305-5805

Docket Number: EPA-HQ-OPP-2006-0217

 

THURSDAY, JUNE 15, 2006

Holiday Inn - National Airport

2650 Jefferson Davis Highway

Arlington , VA 22202

(703) 684-7200

 

ANALYSIS OF A NATURAL REFUGE OF NON-COTTON HOSTS FOR MONSANTO'S BOLLGARD II COTTON.

 

8:30 A.M.Introduction and Identification of Panel Members - Steven Heeringa, Ph.D., FIFRA SAP Chair

8:35 A.M. Administrative Procedures by Designated Federal Official - Myrta R. Christian

8:40 A.M. Follow-up from Previous Day’s Discussion - Alan Reynolds and Sharlene Matten, Ph.D. Biopesticides and Pollution Prevention Division (Office of Pesticide Programs)

9:00 A.M. Panel Discussion (continued)

 

Overall Data/Results Interpretation

 

  • There are three major variables to evaluating structured refuge for Bt crops: a) production of a sufficient number of susceptible insects relative to any resistant survivors of the Bt crop, b) proximity of the refuge to the transgenic crop to facilitate random mating between susceptible (from the refuge) and resistant (from the Bt crop) insects, and c) developmental synchrony of the refuge with the transgenic crop to promote random mating.

 

Given Monsanto’s sampling, gossypol analysis, spatial and temporal analyses, and modeling evaluation, the Agency asks the panel to comment on whether Monsanto’s analysis scientifically supports the conclusion that natural refuge will be comparable to the effectiveness of structured refuge for management of TBW resistance to the Bt proteins expressed in Bollgard II cotton for each of the four regions: the Carolinas, Georgia, Mississippi Delta, and Texas.

 

11:00 A.M.ADJOURNMENT

 

Please be advised that agenda times are approximate. For further information, please contact the Designated Federal Official for this meeting, Ms. Myrta Christian, via telephone: (202) 564-8450; fax: (202) 564-8382; or email: christian.myrta@epa.gov


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