### Fomesafen Endangered Species Risk Assessment Syngenta Meeting With EPA 

### September 24, 2009 Monty Dixon, Jeff Perine, Richard Brain2 

## Key Messages ● Fomesafen is key agricultural tool ● New avian data show no direct effects on birds, reptiles, amphibians ● Additional information indicate no indirect effects on endangered species ● Higher Tier refinement required to assess the potential direct effects on terrestrial plants3 

# Fomesafen Endangered Species Assessment

● Fomesafen Background ● Review of New Data and Rationale Submitted in Our Comments ● Discussion of Next Steps for the Fomesafen Registration Review4 

### Current Regional Use Rate Map

Region 1 (0.375 lb. a.i./A/Yr) Region 2 (0.375 lb. a.i./A/

Alternate Yr) Region 3 (0.313 lb. a.i./A/

Alternate Yr) 

### Crops Beans, dry Beans, snap Cotton Soybeans5 

## Reflex Herbicide 24(c) State Crop Method No. Applic. Rates (lb. a.i/A) AL Pine Seedling Nurseries Pre or Post 1 0.375 AR Pine Seedling Nurseries Pre (Coarse Soil Only) or Post 1 Pre 0.5, Post 0.375 GA Pine Seedling Nurseries Pre or Post 1 Pre 0.5, Post 0.375 MS Pine Seedling Nurseries Pre or Post 1 Pre 0.5, Post 0.375 NC Pine Seedling Nurseries Pre or Post 1 Pre 0.5, Post 0.375 SC Pine Seedling Nurseries Pre or Post 1 Pre 0.5, Post 0.375 TX Pine Seedling Nurseries Pre or Post 1 Pre 0.375, Post 0.3756 

## Reflex Herbicide 24(c) – cont. State Crop Method No. Applic. Rates (lb a.i./A

AR Cotton Early pre- plant to medium/fine texture soils 1 0.250 NC Soybeans Post to Witchweed 1 0.375 Fallow Cropland Post to Witchweed 1 0.375 NE Dry beans Post 1 0.250 SC Soybeans Post to Witchweed 1 0.375 Fallow Cropland Post to Witchweed 1 0.375 Non -Cropland Post to Witchweed 1 0.3757 

## Additional Uses Pending or Trials Underway By IR-4 In Support of Specialty Crops Crop Lb ai/A Comments Cantaloupe 0.375 Pre or prior to transplant. Broadcast or shielded / hooded sprayer to row middles before vine running Cucumber 0.25 – 0.375 Pre prior to emergence or transplanting. Peas 0.375 Preemergence Peppers 0.375 Prior to transplanting to bell and non - bell types: submission planned October 2009 Potato 0.25 Delayed preemergence 10- 14 days after planting: submitted by Syngenta 4/27/09 Squash 0.25 - 0.375 Summer squash pre before emergence or before transplanting. Tomato 0.375 Transplant within 7 days of preemergence application: submitted by Syngenta 4/27/098 

# Current and Future Uses of Fomesafen

State Approval Pending 

### Crops Beans, dry Beans, snap Cotton Soybeans Potatoes (7/10)* Tomatoes (7/10)* Peppers* (other specialty crops*) * Pending9 

## Fomesafen Background ● Controls or partially controls over 70 broadleaf, grass and sedge weeds selectively in cotton, dry bean, snap bean and soybeans. ● Provides both preemergence and postemergence activity ● Excellent crop selectivity ● Effective in all tillage systems – conventional, minimum and no-till ● Alternative mode of action to ALS - inhibitor and glyphosate herbicides

- Critical active ingredient that provides management of glyphosate - resistant Palmer amaranth and other glyphosate - resistant weeds • Cotton and soybean growing states (Georgia, Southeast, Mid -south and Delta) face increased spread of glyphosate - resistant Palmer amaranth and other glyphosate - resistant weeds • Majority of 2009 Georgia cotton acreage was treated with Reflex® 

### Herbicide primarily to control glyphosate - resistant Palmer amaranth10 

## Glyphosate Resistant Palmer amaranth in cotton11 

## Additional Data Submitted By Syngenta ● Wall S, 2009, Fomesafen - Summary of Fomesafen Use on Woody Plant Species, Syngenta Report Number T008243- 08 ● Edwards et.al, 1989: Edwards P.J., Collins I. G., Coulson J. M., 1989, Fomesafen – A Laboratory Investigation of the Toxicity to Two Beneficial Arthropods, a Ground Beetle, Pterostichus cupreus (Carabidae) and a Wolf Spider Pardosa spp. ( Lycosidae) Syngenta Report Number RJ0604B ● Henry et.al,2009: Henry K, Overmyer J, 2009, Fomesafen - Preliminary Results of Chronic Bob White Quail Study Interim Report Syngenta Report Number TK0016777 ● Frank A.R., 2009: Fomesafen - Analysis of Potential Direct Effects on Threatened and Endangered Plants , Syngenta Report Number TK0019939 ● Overmyer et.al, 2009: Overmyer J , Henry K, 2009, Fomesafen - Summary of Efficacy Screening Data for Herbicide Discovery and Development Interim Report Syngenta Report Number TK0019940 ● Peters J, 2002: Fomesafen - Anaerobic Aquatic Metabolism of [14C - Nitrophenyl] - Fomesafen Final Report Syngenta Report Number Syngenta Number 1318 - 01 ● Overmyer et.al, 2009: Overmyer J , Sutton P, Murdock J, 2009, Fomesafen - Evaluation of the Recovery of Non -Target Plants Exposed to Potential Drift Rates - Final Report Syngenta Report Number TK001667512 

# Fomesafen Endangered Species Assessment

● Fomesafen Introduction ● Review of New Data and Rationale Submitted in Our Comments ● Discussion of Next Steps for the Fomesafen Registration Review13 

## Direct Effects Assessment (Birds)

● Acute toxicity

- Practically non -toxic • Oral LD 50 > 5000 mg/kg bw (mallard) • Sub - acute dietary LC 50 > 20,000 mg/kg diet (mallard and bobwhite) ● Chronic toxicity [mallard study – 135639]

- No effects at the highest dose tested (46 mg/kg diet) (mallard) • NOEC = 46 mg/kg diet • LOEC (not determined) • LOC was exceeded in the EPA draft assessment “The bird guideline [mallard study – 135639] study did not establish a LOAEC, only determining that there were no effects at the highest (mean - measured) concentration tested for birds. No sub - lethal effects were noted. Lack of a LOAEC contributes significant uncertainty to the evaluation of chronic risk to birds.”
– US EPA 200814 

## Direct Effects Assessment (Birds) ● Bobwhite considered more appropriate surrogate for this class of chemistry ● New bobwhite quail reproduction study currently being conducted

- Dose levels = 0, 150, 300, 600, 1200 mg/kg diet

- Interim data submitted indicate no effects are expected (egg shell thickness not yet analyzed)

● With new data, no LOC exceedances

- No direct effects on birds (amphibians and reptiles) ● Submission of final report – December 200915 

## Direct Effects Assessment (Mammals)
● Acute toxicity

- LD 50 = 607 mg/kg (guinea pig)

- No LOCs exceeded ● Chronic toxicity

- No reproductive effects at the highest dosed tested (1000 mg/kg) (rat)

- Dose - based, small mammal (15 g) feeding exclusively on short grass nominally exceeded the LOC (RQ = 1.04) • This was from pine seedling SLN rate of 0.5 lbs ai/A. • No other rate exceeds LOC ● Alternative Approaches

- Dietary- based chronic RQ for small mammals = 0.12 or

- If a small mammal spends 95% of its time exclusively feeding on short grass immediately adjacent to pine seedlings receiving the maximum rate of fomesafen, the RQ = 0.9816 

## Direct Effects Assessment (Mammals)
● Additional alternative approach

- If residues in near field environments (1 ft off the field margin) were of similar magnitude to those modeled by T- Rex, screening level drift estimates demonstrate that the chronic RQ is < LOC for small mammals

● Based on any of these alternative approaches and other supporting evidence, chronic effects to mammals are not anticipated to occur Distance (ft) Estimate Resulting EEC (mg/kg-bw) RQ Default aerial drift assumption Near field 5% 5.7 0.05 Default ground drift assumption Near field 1% 1.1 0.01 AgDRIFT (aerial, very fine/fine droplet) 1 48% 54.9 0.5 Ground (high boom, very fine/fine droplet) 1 86% 98.4 0.9 2 71% 81.2 0.74 Table 5. RQs resulting from drift assumptions in near field environments based on a maximum application rate of 0.5 lb ai/A and an extrapolated NOEC of 50 mg/kg - bw (converted from 1000 mg/kg -diet via T- REX).17 

## Direct Effects Assessment (Terrestrial Invertebrates)
● Acute toxicity

- Contact LD 50 >100 μg/bee

- Screening level RQs marginally exceeded the interim LOC (0.05) for small insects potentially exposed to the 0.5 or 0.375 lbs/A rate. (RQs <0.09 and <0.07 respectively). ● 6.2.3 Terrestrial Invertebrates, page 54 of EPA’s draft assessment: “Based on available data, effects on terrestrial invertebrates, while possible, do not appear likely. Lack of indicated toxicity in guideline bee studies, guideline aquatic invertebrate studies, and non guideline studies on soil invertebrates, arthropods, and in aquatic mesocoms support this conclusion.” ● Additional data support low toxicity and thus minimal risk

- Similar to bees, fomesafen is not acutely toxic to other terrestrial invertebrates (wolf spider and ground beetle (newly submitted) at higher rates (1.11lbs/A) ● No effects on terrestrial invertebrates are anticipated18 

## Indirect Effects Assessment (Algae)
● No LOC exceedances on aquatic vascular plants ● Acute toxicity

- EC 50 = 92 μg/L

- NOEC = 10 μg/L

- Some screening level RQs exceeded the LOC (1.0) for non -vascular aquatic plants • 0.5 lbs/A (RQ = 1.6) • 0.375 lbs/A (RQ = 1.2) ● However

- There are no endangered algae

- If lowest EC 50 or LOEC values are used the LOC is not exceeded

- If other algae EC 50s/NOECs are used the LOC is not exceeded

- These factors are similar to the clomazone assessment where non -vascular plants were considered not relevant - US EPA Clomazone Assessment Table 47 ● No effects on aquatic algae are anticipated19 

## Indirect Effects Assessment (Animals) ● A total of 298 species of animals were assessed

- 152 from EPA Appendix F plus146 from Nature Serve Data sets (including mollusks & crustaceans)

- 207 endangered species potentially located within 1000ft of NLCD 82 (National Land Cover Database for cultivated crops) areas • 1000 ft based upon EPA draft assessment

- 189 species either do not require plants for their habitat or as a food source or if they do rely on plants, the plants are not sensitive to fomesafen (i.e. upland monocots or aquatic plants)

- 16 species require plants for their habitat or food but do not rely on a specific type of plant to meet their requirements ● 2 species are exclusively reliant on specific plant species for food and/or habitat

- Karner Blue ( Lycaeides melissa samuelis)

- Dakota Skipper ( Hesperia dacotae) ● Indirect effects unlikely: obligate plant species are unlikely to be affected by fomesafen20 

## Indirect Effects Assessment (Riparian Zones and Wetlands) ● Indirect effects to aquatic organisms based on potential effects on riparian and wetland plant communities are not likely to occur

- Riparian zones are typically composed of both woody and herbaceous monocots and dicots • Woody plants and several monocot species are not sensitive to fomesafen (data submitted 11/23/08 and 09/21/09)

- Recovery study indicated the potential for both monocots and dicots to recover from exposure to fomesafen

- Plants were exposed to fomesafen at rates between 0.002 and 0.071 lbs ai/A (based upon screening level modeled potential drift)

- Plants were assessed at 7, 14, 21 and 28 days after application

- Evidence of necrosis, leaf curl in recovery study,

- All plants showed signs of recovery 28 day post application

- No plants died in study21 

## Plants demonstrated recovery by day 28 compared to day 7 Dicots (0.071 lbs ai/A) Monocots (0.071 lbs ai/A)

0 10 20 30 40 50 60 70 80 90 100

7DAA 14DAA 21 DAA 28DAA% Plant Damage CHEAL STEME KSCHS ABUTH IPOHE
0 5 10 15 20 25 30 35 40 45 50

7DAA 14DAA 21 DAA 28DAA% Plant Danage ORYSA CYPES BROTE PANMI LOLPE ALOMY22 

## Indirect Effects Assessment (Riparian Zones and Wetlands)
● Guideline vegetative vigor study

- All plant species except Raphanus sativus (radish) demonstrated viability and continued to grow throughout the 21 day experiment Species Application Rate (lbs ai/A) Mean Height (cm) Mortality (%) Day 0 Day 21 Allium cepa 0.5 8.4 21.4 0 Avena sativa 0.5 11.3 50.9 0 Echinochloa crus-galli 0.5 13.3 60.0 0 Zea mays 0.5 11.7 68.8 0 Glycine max 0.5 5.5 20.3 0 Lycopersicon

esculentum 0.5 5.4 16.2 0 Beta vulgaris 0.25 5.4 16.0 6.7 Lactuca sativa 0.062 3.3 7.2 70.0 Brassica napus 0.031 7.7 12.7 30.0 Raphanus sativus 0.031 7.1 3.7 26.7 Table 12. Growth and mortality of plant species used in the vegetative vigor study (Porch, et.al., 2001b, MRID 46673802) at specified rates of application.23 

## Indirect Effects: Exposure Refinement ● Alternative to TerrPLANT screening assessment

- PRZM edge of field runoff flux data • Refinements based on standard crop scenarios

- 10,957 daily values from 1961 to 1990 used to derive peak EEC (worst- case) • Adjustable to regional application rates, species-specific ER 25 

### values 

### • 90th 

### centile of highest peak EECs captured for each of 30 years (1961 - 1990) compare to ER 25 

### ● Of 10,957 daily values for 0.375 lb/acre/year

- 42 values (0.38%) > ER 25 

### (wetland), 9 values (0.08%) > ER 25 

### (upland) • All 42 wetland values fall between May 10 and June 21 • All 9 upland values fall between May 10 and May 2124 

## Indirect Effects Assessment (Riparian Zones and Wetlands) Summary ● Overall stability and function of the riparian zone and adjacent wetlands are not likely to be compromised considering the mixed plant community; demonstrated ability of many plants to be tolerant to fomesafen; and ability to recover ● As stated in the clomazone assessment (USEPA 2009, page 137) “...offfield decreased short-term growth in a diverse plant community is not expected to impact erosion above baseline levels”. ● Applying the same reasoning, no indirect effects of fomesafen due to potential impact on riparian zones or adjacent wetlands will occur ● Exposure refinements indicate terrestrial plant communities in riparian and wetland areas will not be adversely affected from potential fomesafen exposure.25 

# Potential for Direct Effects: Plants ● 222 species encompassed within the entire U.S. identified in EPA draft assessment (Appendix F) ● 105 species identified within label area according to counties listed in EPA draft assessment ● 87 species identified as being in <1000 ft proximity to cultivated crops (NLCD - 82) according to IMS and MJD databases ● 28 species identified as co- occurring with fomesafen labeled crops and less than1,000 ft to agricultural land use areas, with appropriate considerations of habitat (characteristics and use site conditions) and species protections (e.g federal, state, and local protections)

- These species were further evaluated using taxonomic relatedness 222 Plant Species (EPA Draft Assessment Appendix F)

28 Plant Species (Evaluated Using Taxonomic Relatedness)26 

## Potential for Direct Effects: Taxonomic Evaluation Rationale 

# ● Plant ESA should consider taxonomic relatedness ● EPA draft assessment:

- Uses most sensitive species (lettuce; a dicot) as surrogate for all endangered species

- Delineates sensitivity at Class taxonomic level “monocot species are considerably less sensitive than many dicot species to fomesafen” Kingdom Subkingdom Superdivision Division Class Subclass Order Family Genus Species Monocots vs. Dicots Taxonomic Comparison EPA Draft Assessment 

## Taxonomic Strata27 

# Taxonomic Evaluation: Approach ● Taxonomic relatedness assessed at the Family level ● Comparison between 28 endangered species (6 monocots, 22 dicots) and all available species effects data (28 monocots, 22 dicots)

- Percent damage and EC 25 

### values obtained from recovery studies, fomesafen screening data, and seedling emergence, vegetative vigor and Syngenta’s annual herbicide Primary Profiling Screening (PPS) program • Data include newly submitted studies ● Taxonomic data compiled from USDA Natural Resources Conservation Service Plants Database28 

# Taxonomic Evaluation: Results ● Family level assessment encompassed over half of the identified endangered species ● Monocots, the dicot pea Family (Fabaceae), and several target dicot crop species from the Mallow (Malvaceae), Pea, and Potato (Solanaceae) Families, display low sensitivity ● Sensitivity varied markedly among remaining dicot Families ● Unlikely that fomesafen would have a significant impact on the viability of 5 endangered species taxonomically related to assessed tolerant species

- Includes 1 monocot (swamppink) and 4 dicots (Virginia jointvetch, Jesup's milkvetch, prairie lespedeza, and running buffalo clover)29 

## Terrestrial Plant Exposure: Drift Refinements 

# ● EPA draft assessment (Sec. 3.6.2)

- Used an early, beta version of AgDRIFT®



## - Tier I only, no refinements

- AgDRIFT over- predicts deposition in the far field (>50 m) by as much as 4x

- Overestimated deposition fractions for fomesafen30 

## Terrestrial Plant Exposure: Drift Refinements (Aerial Spray) ● AGDISP v8.15 is latest, most developed version, offering improved accuracy in the far field (Andrew Hewitt, “Atomization and Drift Models”) ● Spray volume : Product label - “A minimum of 5 gallons per acre of spray mixture should be applied...” ● Evaporation rate : Default is 84.76 **μ** m 2

### / ° C/sec, but salts are much lower

- Honcho® 

### = 38.39 **μ** m 2

### / ° C/sec , Roundup® 

### = 36.69 **μ** m 2

### / ° C/sec

- 1⁄2 of default rate = 42.38 **μ** m 2

### / ° C/sec is more appropriate for fomesafen sodium than the default rate, yet still conservative 

### ● Regional application rates : per product label31 

## Terrestrial Plant Exposure: Drift Refinements (Ground Spray) ● AgDRIFT® 

### v2.0.09 is latest, most developed version ● Low boom : Approved ground applications are low boom (preplant surface, pre - emergence and/or post- emergence) ● F- M/C spray : Product label - “Use nozzles that are set up to deliver medium quality spray (ASAE Standard S -572).” ● 50th 

### data percentile : Refer to EPA September 10, 2009, Response to NMFS November 18, 2008, Final Biological Opinion ● Regional application rates : per product label32 

## Terrestrial Plant Exposure: Drift Refinements (Example) Region Application Rate (lb ai/acre) Clearance Distance (feet)* 1 (pine seedlings) 0.5 55 1,2 0.375 40

3 0.312 35 4 0.25 25 5 0.17 20 

### Ground spray (AgDrift v2.0.09): Distance to deposition = 0.0020 lb/A

* Tier 1 deposition at 50th percentile using low boom, ASAE Fine to Medium/Coarse

spray33 

## Geo-spatial Proximity Analysis: Ground Boom1 

## Slide #34 Contains Confidential Business Information2 

## Slide #35 Contains Confidential Business Information36 

# Evaluation of Direct Effects on Terrestrial Plants and Other Species ● Stage 1.

- Current : Calculate RQ’s based on most sensitive species from the VV and SE studies and EEC’s from TerrPlant and AgDRIFT

- Refined : More refined exposure modeling should be considered, such as higher tier AgDRIFT , AGDISP and PRZM ● Stage 2.

- Current : Spatial bounds established and applied to the action area to define the potential co - occurrence and overlap of listed species

- Refined : Consider National Land - cover Dataset for crop production areas (NLCD 82) at the county level in conjunction with spatial database information for listed species derived from FIFRA Endangered Species Task Force (FESTF) - Multi -Jurisdictional Dataset (MJD) - Information Management System (IMS) and NatureServe to define the listed species to be considered37 

# Evaluation of Direct Effects on Terrestrial Plants and Other Species ● Stage 3.

- Additional Refinements : • Incorporate refined biological considerations such as species specific data from guideline studies, efficacy trials, recovery studies, literature studies, etc. • If a taxonomically related plant is identified at the Family/Genus level then this value should be used as a surrogate • If no taxonomically related plants are available then the most appropriate values based on class, nature of the effect in the study, and temporal considerations should be used ● Stage 4.

- Additional Refinements :

- Further refinements: spatial, analyses at the sub - county level, and temporality of coincidence of application time to critical stage of plant development38 

## Key Messages ● Fomesafen is key agricultural tool ● New avian data show no direct effects on birds, reptiles, amphibians ● Additional information indicate no indirect effects on endangered species ● Higher Tier refinement required to assess the potential direct effects on terrestrial plants39 

# Fomesafen Endangered Species Assessment

● Importance of fomesafen to agriculture ● Review of New Data and Rationale Submitted in Our Comments ● Discussion of Next Steps for the Fomesafen Registration Review40 

## Contact Information Person Phone Number Email Monty Dixon 336.632.7055 monty.dixon@syngenta.com Jeff Perine 336.632.2374 jeff.perine@syngenta.com Richard Brain 336.632.6011 richard.brain@syngenta.com Steven Wall 336.632.2285 steven.wall@syngenta.com Dan Campbell 336.632.7627 dan.campbell@syngenta.com 

### Thank you for your time.