1



# Environmental Fate, Ecological Risk and Endangered Species Assessment in Support of the Registration Review of Fomesafen Sodium (PC 123802)

O F 3 

## C

Cl NO 2 

## H N S O
O CH 3 

## O

Prepared by: Paige D. Doelling, PhD, Fisheries Biologist Stephen P. Wente, PhD, Biologist Reviewed by: Faruque Khan, PhD, Senior Fate Scientist U. S. E nvironmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division Environmental Risk Branch I 1200 Pennsylvania Ave., NW Mail Code 7507P Washington, DC 20460

Dec ember 20082 Table of Contents 1.0 Executive Summary

................................ ................................ ................................ 6 1.1 Nature of Stressor

................................ ................................ ............................... 6 1.2 Potential Risk

................................ ................................ ................................ ...... 6 1.3 Endangered Species Assessment

................................ ................................ ........ 7 2.0 Problem Formulation

................................ ................................ .............................. 9 2.1 Stressor Description

................................ ................................ ............................ 9 2.2 Environmental Fate Summary

................................ ................................ ............ 9 2.3 Mode of Action

................................ ................................ ................................ . 10 2.4 Use Characterization

................................ ................................ ......................... 10 2.5 Assessment Endpoints

................................ ................................ ...................... 12 2.5.1 Ecosystems Potentiall y at Risk

................................ ................................ . 13 2.5.2 Ecological Effects

................................ ................................ ..................... 13 2.5.2.1 D irect

................................ ................................ ................................ ......... 13 2.5.2.2 Indirect

................................ ................................ ................................ ...... 13 2.6 Risk Hy

potheses

................................ ................................ ................................ 15 2.7 Results of Previous Assessments

................................ ................................ ...... 15 2.8 Analysis Plan

................................ ................................ ................................ .... 16 3.0 Exposure Assessment

................................ ................................ ............................ 17 3.1 Label Application Rates and Intervals

................................ .............................. 17 3.2 Aquatic Exposure

................................ ................................ .............................. 18 3.2.1 PRZM

- EXAMS Modeling Inputs and Scenario Se lection

....................... 18 3.2.2 PRZM

- EXAMS Modeling Output

................................ ............................ 19 3.2.3 Registrant

- submitted Aquatic Exposure Modeling

................................ ... 20 3.2.4 SCIGROW Modeling for Ground Water

................................ .................. 20 3.2.5 Soil Accumulation

................................ ................................ .................... 21 3.3 National Surfac e Water Monitoring Data

................................ ......................... 23 3.3.1 Surface Water

................................ ................................ ............................ 23 3.3.2 Ground Water

................................ ................................ ............................ 23 3.4 Bird and Mammal Exposure (TREX)

................................ ............................... 24 3.5 Terrestrial Invertebrate Exposure

................................ ................................ ..... 26 3.6 Terrestrial Plant Exposure (TerrPlant & AgDrift)

................................ ............ 27 3.6.1 TerrPlant

................................ ................................ ................................ ... 27 3.6.2 AgDrift

................................ ................................ ................................ ...... 28 4.0 Effects Assessment

................................ ................................ ............................... 30 4.1 Specific Toxicological Concerns Associated with this Chemical

.................... 30 4.2 Aquatic Hazard Summary

................................ ................................ ................. 31 4.3 Summary of Aquatic Ecotoxicity Studies

................................ ......................... 33 4.3.1 Aquatic Guideline Data

................................ ................................ ............. 33 4 .3.2 Aquatic Data from ECOTOX

................................ ................................ ... 33 4.4 Terrestrial Hazard Summary

................................ ................................ ............. 35 4.5 Summary of Terrestrial Ecotoxicity Studies

................................ ..................... 36 4.5.1 Avian and Small Mammal Guideline Data

................................ ............... 36 4.5.2 Terrestrial Plant Data

................................ ................................ ................ 36 4.5.2.1 Guideline Studies

................................ ................................ ...................... 363

4.5.2.2 Additional Registrant

- Submitted Data

................................ ...................... 37 4.5.3 Terrestrial Insect Data

................................ ................................ ............... 38 4.5.4 ECOTOX Data

................................ ................................ .......................... 38 4.5.4.1 Biochemical Endpoints

................................ ................................ ............. 38 4.5.4.2 Aquatic Community- Level

................................ ................................ ....... 39 4.5.5 Carcinogenicity, Mutagenicity, and Endocrine Disruption

...................... 40 4.5.6 Toxic Effects of Multi

- Active Ingredient Label ed Products

.................... 40 4.6 In cident Database Review

................................ ................................ ................. 41 5.0 Risk Estimation

................................ ................................ ................................ ..... 42 5.1 Aquatic RQ Summary

................................ ................................ ....................... 43 5.2 Terrestrial RQ Summary

................................ ................................ ................... 44 5.2.1 Terrestrial Plants

................................ ................................ ....................... 44 5.2.1.1 TerrPlant

................................ ................................ ................................ ... 44 5.2.1.2 AgDrift

................................ ................................ ................................ ...... 46 5.2.2 Avian RQ Summary

................................ ................................ .................. 47 5.2.3 Small Mammal RQ Summary

................................ ................................ ... 48 5.2.4 Terrestrial Invertebrate Summary

................................ ............................. 48 6.0 Risk Description

................................ ................................ ................................ .... 50 6.1 Aquatic Risk

................................ ................................ ................................ ...... 50 6.2 Terrestrial Risk

................................ ................................ ................................ .. 53 6.2.1 Birds, Reptiles , and Amphibians

................................ .............................. 53 6.2.2 Mammals

................................ ................................ ................................ ... 54 6.2.3 Terrestrial Invertebrates

................................ ................................ ............ 54 6.2.4 Plants

................................ ................................ ................................ ......... 56 6.3 Endangered Species

................................ ................................ .......................... 58 6.3.1 Aquatic Listed Species

................................ ................................ .............. 58 6.3.2 Terrestrial Listed Species

................................ ................................ .......... 59 6.3.3 Plants

................................ ................................ ................................ ......... 65 6.3.4 Action Area

................................ ................................ ............................... 66 6.3.5 Probability of Individual Effects

................................ ............................... 68 6.4 Risk Conclusions

................................ ................................ .............................. 70 7.0 Uncertainties

................................ ................................ ................................ ......... 72 7.1 Exposure Assessment Uncertainties

................................ ................................ . 72 7.1.1 Aquatic Exposure

................................ ................................ ...................... 72 7.1.1.1 Mo deling Assumptions

................................ ................................ ............. 72 7.1.1.2 Monitoring Data

................................ ................................ ........................ 72 7.1.1.3 Impact of Vegetative Setbacks on Runoff

................................ ................ 72 7.1.1.4 PRZM Modeling Inputs and Predicted Aquatic Concentrations

.............. 73 7.1.2 Terrestrial Exposure Uncertainties

................................ ........................... 73 7.1.2.1 Residue Levels Selection

................................ ................................ .......... 74 7.1.2.2 Dietary Intake

................................ ................................ ............................ 74 7.2 Effects Assessment Uncertainties

................................ ................................ ..... 75 7.2.1 Age Class and Sensitivity of Effects Thresholds

................................ ...... 75 7.2.2 Use of Surrogate Species Data

................................ ................................ .. 75 7.2.3 Extrapolation of Effects

................................ ................................ ............ 75 7.2.4 Acute LOC Assumptions

................................ ................................ .......... 754

References

................................ ................................ ................................ ......................... 76 Guideline Study References

................................ ................................ .............................. 76 ECOTOX References

................................ ................................ ................................ ........ 81 Appendix A

– Exposure and Modeling Appendix B

– Ecological Effects Appendix C

– ECOTOX Bibiligraphy Appendix D

– RQ Method and LOCs Appendix E

– Analysis Summary Appendix F

– LOCATES (Endangered Species) Appendix G

– Spray Drift Analysis
Table of Figures
Figure 1 Chemical structure of fomesafen

................................ ................................ .......... 9 Figure 2 Conceptual model for fomesafen effects

................................ ............................ 14 Figure 3. Estimate of Fomesafen Loading in the Surface Soil

................................ ......... 235 Table of Tables Table 1 Summ ary of Direct and Indirect Effects

................................ ............................... 8 Table 2 Current Fomesafen Registrations

................................ ................................ ........ 11 Table 3 Summary of Assessment Endpoints and Measures of Ecological Effect

........... 12 Table 4 Label Application Rates and Intervals for Fomesafen Use on Soybeans, Cotton, Snap Beans and Dry Beans 1

................................ ................................ ........................... 17 Table 5 Label Application Rates and Intervals for Section 24c Uses of Fomesafen

....... 18 Tabl e 6. Input Parameters for PRZM

- EXAMS Modeling of Fomesafen on Cotton, Soy beans, Dry Beans, and Snap Bean

................................ ................................ ........... 19 Table 7. PRZM

- EXAMS Aquatic EECs for Fomesafen

................................ ................. 20 Table 8 PRZM

- EXAMS EECs for Fomesaf en at 0.50 lb ai/A

................................ ........ 20 Table 9. Input Parameters for SCIGROW Modeling for Fomesafen

.............................. 21 Table 10 Label Application Rates and Intervals for Fomesafen Use on Soybeans, Cotton, Snap Beans, and Dry Beans 1

................................ ................................ .......................... 21 Table 11 Input Parameters for TREX Modeling

................................ .............................. 24 Table 12 Bird Dose Estimates

................................ ................................ .......................... 25 Table 13 Mammal Dose Estimates

................................ ................................ .................. 26 Table 14 Terrestrial Invertebrate Exposure

................................ ................................ ..... 26 Table 15 Terrestrial Plant Exposure

................................ ................................ ................ 27 Table 16 Drift Deposition from Ground Applications

................................ ..................... 29 Table 17 Drift Depostion from Aerial Applications

................................ ........................ 29 Table 18 Aquatic Toxicity Profile for Fomesafen

................................ ........................... 32 Table 19 Terrestrial Toxicity Profile for Fomesafen

................................ ....................... 35 Table 20 Drift Deposition from Aerial Applications

................................ ....................... 46 Table 21 Drift Deposition from Ground Applications

................................ ..................... 46 Table 22 Avian RQ Summary

................................ ................................ .......................... 47 Table 23 Small Mammal RQ Summary

................................ ................................ ........... 48 Table 24 Terrestrial Invertebrate RQ Summary

................................ .............................. 49 Table 25 Summary of Risk to Non

- listed Aquatic Organisms

................................ ........ 52 Table 26 Comparison of Chronic Data for Acifluorfen, Fomesafen, and Oxyf luorfen.

.. 54 Table 27 Summary of Risk to Non

- Li sted Terrestrial Animals

................................ ....... 55 Table 28 Summary of Risk to Non

- listed Terrestrial Plants

................................ ............ 57 Table 29 Summary of Risk to Listed Aquati c Organisms

................................ ............... 58 Table 30 Summary of Risk to Listed Terrestrial Animals

................................ ............... 60 Table 31. Listed birds potentially at risk from fomesafen

................................ ............... 62 Table 32. Listed reptiles and amphibians potentially at risk from fomesafen

................. 63 Table 33 Summary of Risk to Listed Plants

................................ ................................ .... 64 Table 34 Endangered Plants by Crop and State

................................ ............................... 67 Table 35 Probability of Individual Effects

................................ ................................ ....... 69 Table 36 Summary of Direct and Indirect Effects

................................ ........................... 716



### 1. 0 Executive Summary 1.1 Nature of Stressor Fomesafen is an herbicide. It is applied as a foliar spray (both pre

- emergent and post

emergent) for control of broad

- leaved weeds, grasses, and sedges. Mode of action is via cellular membrane disruption

. It is highl y persistent in soil (aerobic soil metabolism half

lives of 2 9

- 99 weeks , dependent on soil ty pe) resulting in a potential for accumulation in terrestrial environments. The label suggests not planting sensitive crops in a fomesafen

treated field for a 3

- 18 month period, due to the persistence of fomesafen in the soil. Additionally, it is highly mobile, and is expected to leach into groundwater and be transported from the site via runoff into surface waters. Based on phys ical properties, bioaccumulation and long

- range transport are not expected to be of concern. It is extremely toxic to terrestrial plants, espe ciall y dicots, but of fairly low acute toxicity to fish and wildlife. Some chronic reproductive effects have been noted in mammals, and may also occur in birds. No major degradates of toxicological concern have been identified. 

### 1.2 Potential Risk Chemical Properties Fomesafen is highl y persistent and mobile in soil. These environmental fate properties are expected to promote year

- to

- ye ar accumulation in soil as well as off

- site movement by leaching and runoff. Because fomesafen is spray applied, there is a potential for drift onto non

- target plants. Prolonged phytotoxic effects on non

- target plants are expected based on the persistence of fomesafen. EFED has no data from which to determine how long it may be toxic, but the labels recommend not planting sensitive crops in the use site for 3 to 18 months following treatment. Ecological Risk Conclusions Ecologically, the organisms most at risk from fomesafen are terrestrial plants, especiall y dicots. Because terrestrial plants are important both ecologicall y (the y provide a critical part of both the structure and function that defines “habitat”) and economically (nearb y non - target, non

- treated crop plants may be affected), these potential impacts are an important consideration. No LOCs were exceeded for aquatic endpoints except the listed species LOC for freshwater non

- vascular plants. At the time of this assessment, there were no listed non

- vascular freshwater plants, and no listed species had been identified as having an obligate relationship with freshwater non

- vascular plants. For terrestrial organisms, chronic LOCs were exceeded for birds (and b y extension, reptiles and amphibians) at all but the lowest application rate. Chronic LOCs were exceeded for mammals only for small herbivorous mammals at the highest application rate. These LOC exceedences appl y to both listed and non

- listed species. Based on spray drift estimations, clearance distances for chronic exceedences are well within the clearance distances for terrestrial plants, thus if terrestrial plants are protected, then by virtue of sensitivity, other vulnerable organisms should be protected as well. Clearance distances for chronic effects on birds, reptiles, amphibians, and mammals are 10 ft from the7

application source for ground applications (based on low boom estimates) and 100 ft for aerial applications (based on application parameters used in AgDrift Tier I estimates). For terrestrial plants, using drift estimates based on the more sensitive dicots, effects should be anticipated as far as 850 ft for ground applications, and 1,000 ft for aerial applications. 

### 1.3 Endangered Species Assessment For listed animals, both aquatic and terrestrial, the primary risk posed b y us e of fomesafen as currentl y registered under Section 3 is due to potential de gradation of plant communities providing food, shelter, or protection from predators. On the basis of these indirect effects and the anticipated magnitude of such effect, an overall determination of may affect, likely to adversely affect applies to all li sted species located with 850 ft of the application location. The action area, based on the furthest extent at which an LOC is exceeded (dicots), is 1,000 ft away from agricultural land in geographic areas where fomesafen is registered for use. A list of potentially affected species is included as Appendix F

. No direct effects are anticipated for aquatic organisms, constituting a no effect determination for these organisms on the basis of direct effects. Based on available data, there is a chronic risk to birds, reptiles, and terrestrial

-phase amphibians. The Agency is unable to evaluate the potential magnitude of these chronic effects, thus the overall determination for these taxa is may affect, likely to adversel y affect.8

Table 1 Summary of Direct and Indirect Effects Evaluation Organism LOCA TE S Category Direct Effects Indirect Effects Critical Habitat Effects

Monocots Monocots Yes Ground ≤100 ft Aerial ≤100 ft from point of application No ? (only listed monocot affected is aquatic)

Other 1 No (No potentially affected species have designated critical habitat ) Dicots
Dicots Yes Ground ≤300 ft Aerial ≤900 ft from point of application Yes

Potential for effects on other plants in the community. Alteration of habitat ma y create environment unsuitable to the listed species

. Effects may occur up to Ground ≤300 ft Aerial ≤900 ft from point o f application Yes

(6 potentially affected species hav e designated critical habitat ) Birds Reptiles Birds Terrestrial

Phase Am phibians Mammals Mammals Yes Chronic Exceedences Ground ≤10 ft Aerial ≤100 ft from point of application FW Aquatic Plants 2 FW Aquatic

Plants SW Aquatic Plants SW Aquatic

Plants FW Crus tacea FW Bivalves FW Aquatic Invertebrates FW

Gastropods FW Fish FW Fish Aquatic

Phase Am phibians SW Crustacea SW Bivalves SW Aquatic Invertebrates SW

Gastropods SW Fish SW Fish No No LOC exceedences Yes

Potential for effects on other plants in the community. Alteration of habitat ma y create environment unsuitable to the listed sp ecies. Effects may occur up to Ground ≤300 ft Aerial ≤900 ft from point of application Yes

Potential for effects on other plants in the community. Alteration of habitat ma y create environment unsuitable to the listed species. Effects may occur up to Gro und ≤300 ft Aerial ≤900 ft from point of application

1 Cycads, Conifers, Fern Allies. These genera have no direct c orollary t est organism, and have been evaluated based on the most sensitive plant endpoint. 2 Evaluated based on both non

- vascular plants (algae) and vascular plants (duckweed)9



### 2. 0 Problem Formulation Problem formulation provides a strategic framework for the risk assessment. By identifying the important components of the problem, it focuses the assessment on the most relevant chemical properties, exposure routes, and endpoints. 

### 2.1 Stressor Description Fomesafen is applied as a pre

-plant, pre

- emergence, and post

- emergence herbicide in soy beans, snap beans, dry beans, and cotton for control of broadleaf weeds, grasses, and sedges. Fomesafen can be applied via ground and aerial sprays. Because fomesafen is persistent in soil ( aerobic soil degradation t 1/2 = 29 to 99 weeks at 0.50 lb ai/A application rate; MRID 00135660), residual in soil of the treated field is considered in this risk assessment as a secondary source.

O F 3 C

Cl NO 2 H N S O
O CH 3 O Figure 1 Chemical structure of fomesafen Empirical formula: C 15 H 10 ClF 3 N2 O 6 S Molecular weight: 438.77 g/mole CAS Registry Nos.: 72178

- 02

- 0 Chemical Class: Diphenyl ether 

### 2.2 Environmental Fate Summary Major routes of fomesafen dissipation are leaching, runoff, and microbial degradation. Because fomesafen is persistent and mob ile in soil, it is expected to move from the application site into groundwater and surface water. Additionally, off

- site movement of fomesafen is expected through spray drift from aerial and ground spray. The high persistence of fomesafen is expected to contribute to year- to

- ye ar accumulation in terrestrial and aquatic environments. Fomesafen is stable to abiotic hydrol ys is. It undergoes slow photodegradation in water (t 1/2 = 49 to 289 days). Fomesafen is persistent ( aerobic soil t 1/2 = 2 9 to 99 weeks) in aerobic soil and aquatic environments. However, it degrades rapidl y (t 1/2 <20 days) in anaerobic environments. The major degradation product of fomesafen is 5

- (2

- chloro

a , a , a - trifluoro

-p - tol yl oxy)

-N

- methylsulphonyl

-panthranilamide (fomesafen amine). A minor degradation product is 5

- (2

- chloro

- a , a , a - trifluoro

-p - tolyloxy) anthranilic acid (fomesafen amino acid). Neither degradate has been identified as a toxicological concern.10

Fomesafen is expected to be very mobile in soil. Simple partitioning coefficients range from 0.51 in loamy coarse sand to 2.45 in sandy cl ay loam soil. Regression anal ys is indicates fomesafen sorption is not dependent on soil organic matter content. Aged soil column leaching studies indicate degradation products of fomesafen are not mobile in soils; less than 0.06% of applied radioactivity was detected in the leachate samples. Field dissipation studies in NC, IL, MS, AR, AL, TX, LA, SD, MN, KY, IA, and MO indicate fomesafen is moderatel y persistent to persistent (t 1/2 = 50 to 150 days ) in surface soils under actual use conditions. Fomesafen was detected at depths up to 30 inches in the soil profile. Fomesafen amine was the only degradation product identified in field dissipation studies. Prospective ground water monitoring in NC indicates fomesafen moved through the soil profile into medium and deep ground water. Fomesafen has a low potential for bioaccumulation in fish tissues. Bioaccumulation factors for fosmesafen were 0.7 for whole fish, 0.2 for edible tissues, and 5.2 for nonedibl e tissue. Bioaccumulated residues decreased by 95% during a 14

- day depuration period. 

### 2.3 Mode of Action Fomesafen is a diphenyl ether. It disrupts the cell membrane of the plant (www.s yn gentacroprot ection

-us.com) by penetrating into the cy toplasm and causing formation of peroxides and free electrons (http://www.ces.purdue.edu/extmedia/WS/WS

23

- W.html). The specific mode of action is inhibition of protoporphy rinogen oxidase (Roberts 1998 ) . Fomesafen generally acts quickl y, and does not translocate. It has both foliar and soil activity . Other herbicides in this group include aciflourfen, lactofen, and oxyfluorfen. 

### 2.4 Use Characterization Fomesafen is used primarily as a pre -plant, pre

- emergence, and post

- emergence herbicide to control broadleaf weeds, grasses, and sedges in soy beans, snap beans, dry beans, and cotton. Methods of application are ground spray and aerial spray (maximum 0.375 lb ai/A, soy beans, dry beans, snap beans, and cotton). Application is limited to once a year, or in alternate years, depending on location. Application rates are regionally specific. A search of OPPIN on 4/24/2008 (PDD) located 20 active Section 3 and Section 24 registratio n numbers associated with the active ingredient fomesafen. Of these, 5 were end

-use products, 4 were technicals or formulation intermediates (with no associated crops), and 11 were state

- specific special local needs (Sec. 24c), all of which were associated with a single parent Section 3 label. Only 2 registrants (S yn genta and BASF) hold current fomesafen registrations , and as of this writing, BASF has submitted a Request for Voluntary Cancellation for its fomesafen containing products. Three of the end

-use products include a second active ingredient.11

Table 2 Current Fom e safen Re gistrations Product Name (Registrant) EPA Registration Number (latest label date) Active Ingredients (% w/w) Crops Section 3 End Use Products Reflex (Syn genta) Em ulsifiable concentrate 100

- 993 (02/08/08) Fomesafen 22.8% Cotton, dry beans, snap beans, soybeans Flexstar (Syngenta) Em ulsifiable concentrate 100

- 1101 (03/20/07) Fomesafen 22.1% So ybeans Prefix (Syngenta) Em ulsifiable concentrate 100

- 1268 (4/13 /07) Fomesafen 10.2%

s- me tolachlor 46.4% So ybeans BAS 530 04 (BASF) Soluble concentrate 7969

- 82 10/22/97 Fomesafen 12.9%

Bentazon 29% So ybeans Faster (BASF) Soluble concentrate 7969

- 83 10/22/97 Fomesafen 7.2%

Bentazon 29.8% So ybeans Section 24 Registrat ions AL030003 AR030006 GA880005 MS980002 NC950010 SC030006 TX040002 Pine seedlings in nurseries

NC870005 SC900004 So ybeans, idle cropland
SC900004 So ybeans, idle cropland, non cropland (USDA eradication program only) NE060002 Dry beans Reflex (Syngenta) Em ulsifiable concentrate

AR080004 Fomesafen 22.8%

Cotton

Section 3 Technicals and Formulation Intermediates Fomesafen paste 100

- 1016 Fomesafen technical 100

- 1017 100

- 1092 Fomesafen salt aqueous concentrate 100

- 1103 Manufacturing intermediates with no registered crop uses. Not anticipated to be environmentally relevant exce pt in case of spill.12



### 2.5 Assessment Endpoints Assessment endpoints are selected based on ecos ystems ty picall y at risk from pesticide applications. Specific ecologi cal effects are evaluated based on toxicity information from guideline tests and open literature data, and focus on the general categories of survival, growth, and reproduction. Information regarding sub

- lethal effects, if available, is discussed in the risk characterization. EFED assesses behavioral or biochemical endpoints if they are quantitatively linked to effects on survival or fecundity

. Table 3 Summary of Assessment Endpoints and Measures of Ecological Effect Assessment E ndpoint Me asures of Ecological Effect a Aquatic Environments
1. Survival, growth, and reproduction of fish and aquatic phase amphibians Freshwater 1a. Rainbow trout acute LC 50 1 1b. NOAEC estimated from sheepshead minnow ACR 1 Saltwater 1c. Sheepshead m innow acute LC 50 1 1d. Sheepshead minnow chronic NOAEC
2. Survival, growth, and reproduction of aquatic invertebrates Freshwater 2a. W ater flea EC 50 1 2b. W ater flea chronic NOAEC 1 Saltwater 2c. Mysid s hrimp acute EC 50 1 2d. Mysid s hrimp chronic NOAEC 1

3. Survival, growth, and reproduction of aquatic plants Freshwater 3a. Non

- vascular plant (freshwater algae) acute EC 50 1 and NOAEC 1 3 b

. Non

- vascular plant (freshwater algae) acute EC 50 2 and NOAEC Saltwater 3c. Non

- va scular plant (saltwater diatom) ac ute EC 50 2 and NOAEC 3 Terrestrial Environments 4 . Survival, growth, and reproduction of ma mmals 4a. Guinea pig acute LC 50 1 4b. Rat chronic NOAEC 1 5 . Survival, growth, and reproduction of birds, terrestrial phase amphibians, and reptiles 5a. Mallard duck acute oral LC 50 1 5b. Mallard duck acute dietary LC 50 1 5c. Mallard duck chronic NOAEC 1 6 . Survival, growth, and reproduction of terrestrial invertebrates 6a. Honey bee acute contact LC 50 7 . Survival, growth, and reproduction of terrestrial plants 7a. Monocot (onion) seedling emergence EC 25 1 7b. Dicot (radish) vegetative vigor EC 25 1
a All toxicity data reviewed for this assessment are tabulated in Appendix B. 1 Guideline study 2 ECOTOX study13 2.5.1 Ecosystems Potentially at Risk For typical fomesafen applications, th e ecos ys tem at risk is the application site itself, including organisms that might be sprayed during application, organisms affected b y residual fomesafen in the soil; and the adjacent aquatic and terrestrial environments affected due to runoff, spray drift, or groundwater contamination. In water bodies receiving runoff from the treatment site , fish, aquatic

-phase amphibians, aquatic invertebrates, and aquatic vascular and non

- vascular plants are considered. Terrestrial organisms assessed include non

- target plants, insects, amphibians, reptiles, birds, and mammals. Because fomesafen is an herbicide, potential affects on non

- target plants have been addressed at length. 2.5.2 Ecological Effects Evaluation of ecological effects fo cuses initiall y o n direct effects to the groups of organisms residing in the ecos ys tems at risk, based on ratios (risk quotients) of the estimated environmental concentration (EEC) to a designated toxicity endpoint for a surrogate test organism. If pre

- es tablished levels of concern (LOCs) are exceeded for direct effects, indirect effects to endangered species ( e.g ., food chain, decrease in community diversity) are evaluated based on the group of organisms exceeding the LOC. Details on the RQ method and LO Cs are in Appendix G. 2.5.2.1 Direct Direct effects evaluated are the survival, growth, and reproduction of various taxa of organisms potentially exposed to fomesafen . Taxonomic groups evaluated include aquatic plants (algae and vascular), aquatic inver tebrates, aquatic vertebrates, terrestrial plants, terrestrial invertebrates, birds, and mammals. There are currently no guideline tests for reptiles or amphibians, so these taxa are evaluated using bird data as a surrogate for reptiles and terrestrial ph ase amphibians, and fish as a surrogate for aquatic phase amphibians. Both acute and chronic effects are considered. 2.5.2.2 Indirect When herbicides are applied, indirect effects may include a decline in primary productivity , or change in composition of plant communities proximate to the treated area or systems (wetlands and water bodies) receiving runoff from the site. If LOCs are exceeded for any taxa, potential indirect effects to endangered species are assessed.14

Figure 2 Conceptual model for fomesafen effects 

### Fomesafen applied to crop 

## Stressor

Source Runoff

Direct application Spray drift



## Receptors Birds and Mammals Terrestrial insects

Individual organisms Reduced survival Reduced growth Reduced reproduction Food chai n Reduction in primary productivity Reduction in prey Shift in community composition Habitat integrity Reduced cover Community change 

## Attribute Change Aq uatic plants invertebrates vertebrates Terrestrial plants Soil accumulation, leaching and runoff

Soil invertebrates15



### 2. 6 Risk Hypotheses

· Fomesafen transported in runoff from treated areas may affect the survival, growth, or reproduction of aquatic plants, aquatic invertebrates, aquatic

- phase amphibians o r fish.
· Fomesafen may affect the survival, growth, or reproduction of non - target plants proximate to the treatment site

. · Fomesafen residues in plant and animal dietary sources may affect growth, surviv al, or fecundity of birds, terrestrial

-phase amphib ians, or small mammals ingesting these materials

. · Fomesafen residues o n plant s may affect surviv al of terrestrial invertebrates. 

### 2. 7 Results of Previous Assessments A Section 3 new use ecological risk assessment was conducted for fomesafen in 2006 (DP302 766) when it was proposed for use on cotton, dry beans, and snap beans. Two proposed rates (0.5 lb ai/A, ground only) and 0.375 lb ai/A (ground and aerial) were evaluated. An alternative lower rate (0.2 lb ai/A) was also evaluated. Key findings of this assessment included:

· The greatest acute risk associated with fomesafen use was for non

- target terrestrial plants.
· The persistence and mobility of fomesafen in soil and the persistence in aquatic environments is a concern

. · Accumulation in the soil of a field repeatedly treated with fomesafen may adversel y affect crops subsequently planted in the field. Effects from a single treatment may persist for 3

- 18 months.
· Concentrations of fomesafen in shallow groundwater used for irrigation purposes may be high enough to adversel y affect crops subsequently planted in the field.
· Fomesafen is practicall y non - toxic to slightly toxic to aquatic animals, both freshwater and estuarine/marine. No adverse effects to aquatic animals are anticipated based on proposed application rates.
· Fomesafen does exert toxic effects on aquatic plants but risk quotients (RQs) for the scenarios modeled were below the level of concern (LOC).16

· Fomesafen is practicall y non - toxic to slightly toxic to birds and mammals on an acute basis. Chronic reproductive effects were noted in rats. A chronic LOAEC for birds was not established. No acute risk LOCs were exceeded, but acute endangered species LOCs were exceeded for small mammals at application rates of 0.5 and 0.375 lb ai/A

. Some chronic RQs for both birds and mammals exceeded the LOC at all application rates. The meaning of the exceedence for birds is uncertain, as the guideline study submitted did not determine a LOAEC. Better data may significantl y affect the chronic ris k picture for birds. Endangered Species

· Based on LOC exceedences, the following taxa of endangered species were identified as potentially being at risk from fomesafen use: amphibians (terrestrial phase), birds, dicotyledon plants, mammals, monocotyledon plants, and reptiles
· Fomesafen is likely to affect plants near the treated areas, with potential effects extending to >900 ft away from the treatment source in the case of aerial application. Direct effects (reduction of growth, survival, or fecundity) may occur for endangered plants in the drift zone. Effects on non

- endangered plants in the drift zone may constitute indirect effects (reduction of food or cover) to endangered animals. Fomesafen was registered for use on all proposed crops, with a maximum application of 0.375 lb ai/A via both aerial and ground applications. 

### 2. 8 Analysis Plan This assessment was conducted in accordance with the methods, and using the models described in the Overview Document (USEPA 2004). Some additional methods were use d to more specificall y determine which listed species might be at risk as a result of fomesafen use. These methods build on existing models and were as follows:

● Terrestrial animals were grouped into “Kenaga categories” based on diet and size informatio n available in the natureserve database (www.natureserve.org) and species recovery plans developed by the Services in order to determine which animals were likely to be at risk. 1
● The AgDrift model was used to determine how far away from the point of appli cation that estimated fomesafen concentrations on terrestrial food items were high enough for RQs to exceed LOCs. The point at which the concentration is low enough that the RQ drops below the LOC is referred to as the “clearance estimate” and is presented in the appropriate tables.

1 The classificatio n is currently undergoing the QA/QC process within EFED.17



### 3. 0 Exposure Assessment EFED conducted the exposure assessment using standard exposure modeling methods, as described in the Overview Document (USEPA 2004). 

### 3.1 Label Application Ra tes and Intervals Fomesafen is registered under Section 3 as a pre

- plant, pre

- emergence, and post

emergence herbicide for control of broadleaf weeds, grasses, and sedges in soy beans, cotton, snap beans, and dry beans. Additional uses covered under Section 24c (special local needs, or SLN) registrations are for use on pine seedlings in nurseries (AL, AR, GA, MS, NC, SC, TX), for control of weeds in dry beans in Nebraska, and for control of witchweed in so ybeans and idle cropland in North Carolina and South Carolina. Use in South Carolina also includes non

- cropland, although the South Carolina uses are limited to areas included in the USDA witchweed eradication program. Section 3 labels belonging to the primary registrant, Sy ngenta, include regionally speci fic application rates, shown in T able 1

. Based on these labels , fomesafen can be applied via aerial and ground spray at a maximum application rate of 0.375 lbs ai/A. Section 3 labels belonging to BASF do not provide regionall y specific application rates, but “are intended for use” in the areas included in Regions 1

- 4, and application rates (0.19

- 0.23 lb ai/A) are lower than those on the Sy ngenta labels.
Table 4 Label Applic ation Rates and Intervals for Fomesafen Use on Soybeans, Cotton, Snap Beans and Dry Beans 1 Region States in Region Ap p Rate (lbs/A) Ap plication Interval 1 AL, AR , GA, LA, MS, MO 2
,

NC, OK2 , SC, TN, TX 2 0.375 1 year
2 DC, DE, IL 2 , IN 2
, KY, MD, ,

OH 2 , PA3 , WV , VA, 0.375 2 year
3 CT, IA, ME, MA, MI 3 , NH,

NJ, NY , PA3 , RI, WI , VT 0.312 2 year
4 KS 2 , MI 3 , MN 2
, ND 3
, NE 2

SD 3
, WI 2 0.25 2 year
5 ND 3
, MN 3
, SD 3 0.170 2 year
1 REFLEX 2.5 Gallon â (EPA Reg. No. 100

- 993) 2 Does not include entire state 3 Portions of state are in multiple regions Application rates on some of the Section 24c labels (pine seedling use, also belonging to the primary registrant) are slightly higher, with a maximum application rate of 0.5 lbs ai/A for pre

- emergence applications. The higher rate does not appl y in all states. States included under pine seedling uses are in Region 1 as defined on the parent label, although the Section 24c label for Texas is assumed to include the entire state.18

Table 5 Label Ap plication Rates and Intervals for Section 24c Uses of Fomesafen Use Site States Ap plication Technique Max App Rate (lbs ai/A) Ap plication

Interval AR, GA, MS, NC, SC, Aerial or Ground 0.5 1 year Pine seedlings in nurseries AL, TX Aerial or Ground 0.375 1 year So ybeans, idle cropland, non

cropland SC (Horry and

Mar ion counties) Aerial or Ground 0.375 1 year

So ybeans, idle cropland NC (Robeson,

Cumberland, Sam pson, Bladen, and Pender counties) Aerial or Ground 0.375 1 year Dry beans NE Aerial or Ground 0.25 2 years 1 Based on areas currently infested with witchwee d, as noted on www.ncagr.com/plantindustry/plant/weed/witchnc.htm , accessed May 16, 2008 

### 3.2 Aquatic Exposure Tier II EFED aquatic exposure modeling use s the linked P esticide Root Z one M odel and Exposure Analysis M odel S ys tem (PRZM/EXAMS). PRZM uses the chemical’s physical and environmental fate properties and the site characteristics to predict the concentration of pesticide in runoff and entrained sediment from the field. EXAMS e stimates the concentration of pesticide in an edge

- of

- field small water

-body receiving runoff from the field. The water

-body has a constant volume (20 million liters) with no outflow and is intended to represent an upper

- end occurrence concentration. 3.2. 1 PRZM

-EXAMS Modeling Inputs and Scenario Selection The aquatic exposure assessment for fomesafen was conducted to assess use on soybeans, dry beans, snap beans, and cotton. The Mississippi soy beans scenario was used as both a scenario representing MS soy b eans as well as a surrogate for dry beans and snap beans, as EFED currently has no standard scenarios for these crops in this region. Standard scenarios were selected to assess runoff potential from vulnerable use sites in MS (soy bean and cotton), NC (cotton), and TX (cotton). The MI beans scenario from region 4 was selected to provide more geographical balance to the analysis since all of the other scenarios occur in region 1. No other EFED scenarios had combinations of crop and location relevant to this a ssessment. Input parameters for fomesafen were selected according to EFED Input Parameter Guidance for PRZM/EXAMS 1 . Input parameters are shown in Table 6

.

1 Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides. Version II, 2/28/02.19

Table 6 . Input Parameters for PRZM - EXA MS Modeling of Fomesafen on Cotton, Soybeans, Dry Beans, and Snap Bean

Parameter Value Comments Source Application Rates (kg ai /ha) 0.19

- 0.56 Varies by Region Label 1 Molecular W eight (grams/mole) 420 EPA 2020220 Solubility (mg/L) 1200 @pH = 7; 20 0 c MRID 45048207 Vapor Pressure (torr) <7.5 × 10 - 7 @ 50 o C HSDB Henry’s Constant (atm m 3/m ol) 7.5 × 10 - 13 Estimated HSDB Kd (L/kg) 0.68 Lowest non

- sand K d Acc

. No. 259413 Aerobic Soil Metabolism Half

- life (days) 511 Upper 90 th percentile of mean 2 Acc

. No. 071059 Acc. No. 00135660 Aerobic Aquatic Metabolism Half

life (days) 129.4 Upper 90 th percentile of mean 3 Acc. No. 72158 Anaerobic Aquatic Metabolism Half

- life (days) 1000 Conservative Assumption No Data Available Photodegradation in W ater (days) 289 @pH = 7 MRID 40451101 Hydrolysis Half

- life (days) Stable @pH = 7 Acc

. No. 071059 1 Reflect application rates on the REFLEX 2LC, REFLEX 2.5, and REFLEX labels 2 Calculated from half

- lives of 187.6, 630, 57, 693, 349.3, 527.1, 207 days using a mean of 387.84 days and standard deviation of 242.90 days. 3 Calculated from half

- lives of 139.9, 60.9, 92.4, and 115.5 days using a mean of 102 days and standard deviation of 33.44 days. The MI beans scenario from region 4 was selected to provide more geographi cal balance to the anal ys is since all of the other scenarios occur in region 1. No other EFED scenarios had combinations of crop and location relevant to this assessment. Because applications in Region 4 are restricted to every other year, a modified cop y of the PE5 shell was created to only apply the pesticide in alternate years (odd years). This can be seen in the Appendix A PRZM/EXAMS outputs for Michigan beans in which the even year EECs are always lower than the odd years. 3.2.2 PRZM

-EXAMS Modeling Out

put For aerial applications ( Table 7 ), peak 1 in 10 year estimated environmental concentrations (EECs) ranged from 2.3 ppb (beans, MI) to 12. 0 ppb (cotton, TX). Chronic 1

- in

- 10 year (21

- day average and 60

- day average) EECs ranged from 1.7 ppb (bean s , MI , 60

- day average) to 11.4 ppb (cotton, MS &TX, 21

- day average).20

Table 7 . PRZM - EXA MS Aquatic EECs for Fomesafen Peak 21 days 60 days Region Crop State Ap p. Date Aerial/

G round m g/L (pp b) Region 1: Annual Applications at 0.375 lb a.i/A A 8.99 8.57 7.74 1 So ybean MS 5/1 G 8.19 7.77 6.9 5 A 11.83 11.37 10.07 1 Cotton MS 5/15 G 11.20 10.79 9.56 A 8.99 8.7 2 8.0 3 1 Cotton NC 5/10 G 8. 20 7.9 6 7.3 4 A 11.9 6 11 .39 10.31 1 Cotton TX 5/10 G 11.44 10. 90 9.85

Region 4: Every

- other

-year Applications at 0.28 lb a.i/A A 2.27 2.15 1.9 4 4 Beans MI 6/15 G 2.3 7 2.2 5 2.0 2
Peak 1

- in

- 10 year EECs for ground spray applications ( Table 8 ) ranged from 10.9 ppb (cotton, NC) to 15.3 ppb (cotton, TX). Chronic 1 in 10 year (21

- day average and 60

- day average) concentrations ranged from 9.8 ppb (cotton, NC, 60

- day average) to 14.5 ppb (cotton, TX, 21

- day average). Table 8 PRZM - EXA MS EECs for Fomesafen at 0.50 lb ai/A Peak 21 days 60 days Region Crop State Ap p. Date m g/L 1 Cotton MS 5/15 14.9 14. 4 12.7 1 Cotton NC 5/10 10.9 10.6 9. 8 1 Cotton TX 5/10 15. 3 14.5 13.1 1

- Concentrations were derived for 0.50 lb ai/A u sing ground spray 3.2.3 Registrant

-submitted Aquatic Exposure Modeling The registrant submitted Tier II PRZM/EXAMS modeling assessments for fomesafen use on cotton and soy

beans (MRID 450482

- 04, 450482

- 05, 450482

- 06). The modeling scenarios used were deve loped to assess fomesafen runoff from vulnerable use sites (H ydrologic D soils) with high rainfall. Selected scenarios represent sites in Tensas County , LA (MRLA 131) for cotton; Leflore, MS (MRLA 131) for soy beans; and Dodge, NE (MRLA 102B) for soybeans, and Shebo ygan, WI (MRLA 95B). Maximum application rates were 0.31 lbs for snap beans, 0.5 lbs ai/A for cotton, and 0.375 lbs ai/A for so ybeans. Onl y ground spray was considered, although the labels allow aerial spray. The sources (study identification numbers) of environmental fate data are not reported. Additionally, there are no explanations for selection of the environmental fate data in the exposure assessment. The registrant estimated environmental concentrations are similar in magnitude to, but slightly higher than, those calculated b y EFED. 3.2.4 SCIGROW Modeling for Ground W ater Because fomesafen is mobile and persistent in soil, a screening level groundwater assessment using SCIGROW (ver. 2.3) was conducted to estimate the concentration of fom esafen in shallow groundwater, which could potentially be used for crop irrigation. Input parameters for SCIGROW are listed in Table 10.21

Table 9 . Input Parameters for SCIGROW Modeling for Fomesafen

Parameter Value Comments Source Application Rate (kg ai/ha)

- Cotton 0.375

– 0.17 Varies by Region Label 1 Koc (L/kg) 68 Estimated 2 Acc No. 259413 Aerobic Soil Metabolism Half

- life (days) 387.84 Mean 3 Acc No. 071059 Acc. No. 00135660 1

- Reflect maximum application rates on the REFLEX 2 LC , REFLEX 2.5 and REFLEX labels 2

- Koc estimated using Kd/SOC=Koc; where Kd=0.68 and SOC=1% SOC percentage 3

- Calculated from half

- lives of 187.6, 630, 57, 693, 349.3, 527.1, 207 days using a mean of 387.84 days and standard deviation of 242.90 days. Base d on the SCIGROW estimate, the concentration of fomesafen in shallow ground water in sand soils ( Table 10 ) is not expected to exceed 5.01 m g/L (Region 1).
Table 10 Label Application Rates a nd Intervals for Fomesafen Use on Soybeans, Cotton, Snap Beans , and Dry Beans 1 Region Ap plication Rate (lbs/A)

(A pplication Interval) SCIGROW - estimated Groundwater Concentrations (μg/L) Fomesafen A pplication Due Solely to Irrigation (lbs ai/A) 1 0.375 (1 year) 5.01 2.27 × 10 - 3 2 0.375 (2 year) 2.5 1.13 × 10 - 3 3 0.312 (2 year) 2.08 9.42 × 10 - 4 4 0.25 (2 year) 1.67 7.56 × 10 - 4 5 0.17 (2 year) 1.14 5.16 × 10 - 4 1 REFLEX 2.5 Gallon â (EPA Reg. No. 100

- 993) Because fomesafen is expected to leach to groundwater, EFED has calculated the maximum application rate of fomesafen from two inches of irrigation water. This calculation assumes that two inches of irrigation water is required for optimum plant growth. The application rate of fomesafen in terms of lbs ai/A in 2 inches of groundwater is calculated as follows:

lbs / g 454 g μg 10 L

μg ft in 12 ft

L 32

. 28 in 2 A ft 560 , 43 ai/A lbs 6 3 2
 ́

 ́  ́  ́ = EEC fomesafen where: fomesafen is the estimated application rate of fomesafen in lbs ai/A in 2 in/A of

groundwater; and EEC is the region

- specific SCIGROW EEC in groundwater from Table 5. Based on two inches of irrigation and the SCIGROW estimate, the application rate of fomesafen is estimated to vary from 0.00227 to 0.000516 lbs ai/A. 3.2.5 Soil Accumulation Because of the persistence of fomesafen in soil, a screening level assessment was conducted to quantify the accumulation of fomesafen residues in soil. This screening

level assessment does not consider loss of pesticide to run

- off and leaching (only degradation b y a erobic soil metabolism is considered). A first

- order decay model was22

u sed to estimate fomesafen soil concentrations over 20 years. This model is based on first

- order decay of a single application:

kt e A A - = 0 where: A is the soil fomesafen concentration at any point in time; A 0 is the original soil fomesafen co ncentration at the time that it was applied; k is the upper 90 th percentile of the mean aerobic soil metabolism half

- life (t 1/2 = 511 days; k = 1.356452 × 10 - 3 days - 1 ), which was used to represent the microbial mediated decay rate of fomesafen in soil; and t is the time since the fomesafen application. Because multiple applications occur over this 20 year timeframe, this equation is modified to account for multiple applications: 

## å

= - = n

i kt i i e A A 1 ,

0
where: i is a counter variable that denotes the firs t fomesafen application when i = 1 and the second when i = 2, etc .; n is the last application; A 0, i is the soil fomesafen concentration contributed by the i th application; and ti is the time since the i th fomesafen application. The soil fomesafen concentration contributed to the upper 15 cm of soil by the i th application (

A 0, i) in mg/Kg is calculated as:

3 2 2 2 , 0 g/cm cm 15 /m cm 000 10 /ha m 000 10 g/Kg 1000 mg/g 1000 A/ha 47105381 2 g/lbs 454 ai/A lbs density

, , . AppRate A i  ́  ́  ́  ́  ́  ́  ́ =
where: AppRate is the regional maximum application rate from Table 3 and density is the bulk density of soil. The bulk density o f soil varies from 1.0 g/cm 3 for clay soils to 1.8 g/cm 3 for sandy o r compacted soils (http://www.cdpr.ca.gov/docs/emon/pubs/sops/fsso001.pdf ). The modeling scenario assumes that 100% of fomesafen residue is applied to the soil as recommended for a pre

emergent application. The model scenario also assumes that microbial degradation is the only route of dissipation from the application site. These assumptions are expected to exaggerate predicted formesafen soil concentrations. Figure 3 illustrates the fomesafen concentrations in soil reach a plateau after approximately 10 years regardless of the application rate or soil bulk density. An application rate of 0.375 lbs/A applied every ye ar (Region 1) can theoretically result in a maximum fomesafen concentration of 0.71 mg/kg in soils with a low bulk density (1.0 g/cm 3 ). The same application rate (0.375 lbs ai/A applied every ye ar) can theoreticall y result in a maximum fomesafen concentration of 0.4 mg/kg in soils with a high bulk density (1.8 g/cm 3 ). Applying fomesafen every other year (Region 2 to 5) and at lower application rates also reduces residual soil fomesafen concentrations.23 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

0 5 10 15 20 YearsSoil Concentration (mg/Kg)

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

0 5 10 15 20 YearsSoil Concentration (mg/Kg) Region 1 Region 2 Region 3 Region 4 Region 5

Figure 3 . Estimate of Fomesafen Loading in the Surface Soil (0 - 15 cm depth) in Clay Soils (a; bulk density = 1.0 g/cm 3 ) and Sandy or Compacted Soils (b; bulk density = 1.8 g/cm 3 ) of Regions 1 through 5.


### 3.3 National Surface Water Monito ring Data 3.3.1 Surface Water The USGS National Water Quality Assessment (NAWQA) database was accessed (6/9/08, SPW). No data for fomesafen was located in the database, but this appears to be because fomesafen is not included in the schedules of chemicals quantified by the laboratory . Therefore, a lack of data should not be construed as meaning there are no detectable fomesafen residues in surface waters. 3.3.2 Ground W

ater A groundwater monitoring study was submitted (MRID 42247001), but the shallow groundwater wells were dry during the study . Fomesafen was detected in soil porewater at concentrations ranging from 1 m g/L (at 4 months) to 17 m g/L (at 1 month). It was detected at a concentration of 1 m g/L in the medium

- to deep

- depth wells. These observed porewater concentrations are much higher than the SCIGROW EECs for groundwater. Using the porewater concentrations of 1 mg/L and 17mg/L (from the groundwater study) as outer bounds of the fomesafen groundwater concentrations that might be applied in irrigation water, concentrations of fomesafen in irrigation water could range from 0.45 to 7.7 lbs ai/A, respectivel y. a b24



### 3. 4 Bird and Mammal Exposure (TREX) EFED estimates exposure of birds and mammals using the Terrestrial Exposure Model (TREX). TREX uses the Kenaga nomagram, as modified by Fletcher et al (1994) to determine pesticide residues on several categories of food items, then calculates the potential dose an organism might receive from ingesting contaminated items using allometric equations. Dose estimates are based on the upper bound dose and assumptions that the organism exclusively eats one type of food item and forages only in the treated and/or overspray areas. Table 11 Input Parameters for TREX Modeling Input Parameters Value Source
Application Rate 0.5 lb ai/A 0.375 lb ai/A 0.312 lb ai/A 0.25 lb ai/A 0.17 lb ai/A Label Reflex 100

- 9 93 Foliar Half

- life 35 days EFED Default Number of Applications 1 per year Label Reflex 100

- 993 Avian LD 50 5,000 mg/kg bw (mallard duck) MRID 163168 Avian LC 50 20,000 mg/kg diet (mallard duck) MRID 163381 Avian NOAEC 46 m g/k g diet (mallard duck) MRID 135639 Mammal LD 50 607 m g/kg bw (guinea pig) MRID 164901 Mammal NOAEC 1,000 mg/kd diet (rat) MRID 144862 For birds, dose estimates for the 0.50 lb ai/A application rate range from 2.1 mg/kg bwt (1000 g frugivores, granivores, and insectivores) to 134.0 mg/kg bwt (20 g herbivores). At the 0.375 lb ai/A application rate, estimated doses range from 1.6 mg/kg bwt (1000 g frugivores, granivores, and insectivores) to 102.5 mg/kg bwt (1000 g fruit and pods). Dose estimates for the 0.17 lb ai/A application rate range from 0.7 mg/kg bwt (1000 g frugivores, granivores, and insectivores) to 46.5 mg/kg bwt (20 g herbivores).25

Table 12 Bird Dose Estimates Kenaga Upper Bound Dose (mg/kg bwt) Feeding Categories Small (20 g) Me dium

(100 g) Large

(1000 g) 0.50 lb ai/A Application Rate(pine seedlings, Region 1) Short grass 133.93 76.38 34.19 Tall grass 61.39 35.01 15.67 Broadleaf plants/small insects 75.34 42.96 19.23 Fruits/pods/seeds/large insects 8.37 4.77 2.14 0.375 lb ai/A Applicat

ion Rate (Region 1 & 2 ) Short grass 102.5 58.45 26.17 Tall grass 46.98 26.79 11.99 Broadleaf plants/small insects 57.66 32.88 14.72 Fruits/pods/seeds/large insects 6.41 3.65 1.64

0.17 lb ai/A Application Rate (Lowest Rate, Region 5) Short grass 46.47 26.50 11.86 Tall grass 21.30 12.14 5.44 Broadleaf plants/small insects 26.14 14.90 6.67 Fruits/pods/seeds/large insects 2.90 1.66 0.74 For mammals dose estimates for the 0.50 lb ai/A application rate range from 0.25 mg/kg bwt (1000 g granivore) to 11 2 mg/kg bwt (20 g short grass). At the 0.37 5 lb ai/A application rate, estimated doses range from 0.2 mg/kg bwt (1000 g granivore) to 85.8 mg/kg bwt (20 g short gras s). Dose estimates for the 0.17 lb ai/A application rate range from 0.1 mg/kg bwt (1000 g granivore) to 38.9 mg/kg bwt (20 g short grass)

.26

Table 13 Ma mmal Dose Estimates Kenaga Upper Bound Dose (mg/kg bwt) Feeding Categories Small (15 g) Me dium

(35 g) Large

(1000 g) 0.50 lb ai/A Application Rat e(P ine seedlings, R egion 1) Herbivores/Insectivores Short grass 112.12 77.49 17.97 Tall grass 51.39 35.52 8.23 Broadleaf plants/small insects 63.07 43.59 10.11 Fruits/pods/seeds/large insects 7.01 4.84 1.12 Granivores Fruits/pods/seeds/large insects 1.56 1.08 0.25 0. 375 lb ai/A Application Rate (Region 1,2 ) Herbivores/Insectivores Short grass 85.81 59.30 13.75 Tall grass 39.33 27.18 6.30 Broadleaf plants/small insects 48.27 33.36 7.73 Fruits/pods/seeds/large insects 5.36 3.71 0.86 Granivores Fruits/pods/seeds/l arge insects 1.19 0.82 0.19

0.17 lb ai/A Application Rate (Lowest Rate, Region 5 ) Herbivores/Insectivores Short grass 38.90 26.88 6.23 Tall grass 17.83 12.32 2.86 Broadleaf plants/small insects 21.88 15.12 3.51 Fruits/pods/seeds/large insects 2.43 1. 68 0.39 Granivores Fruits/pods/seeds/large insects 0.54 0.37 0.09


### 3. 5 Terrestrial Invertebrate Exposure Exposure of terrestrial invertebrates was estimated using the dietary

-based EECs produced b y TREX for the two insect categories (small and large). The value produced by TREX, mg ai/kg insect, is equivalent to m g ai/g insect. The fomesafen residue for a bee (μg ai/bee) is calculated by multiplying the residue by the assumed weight of a honey bee (0.128 g) to establish a dose per bee. This method assumes that contact is the relevant route of exposure, rather than ingestion. This method of estimation is believed to be adequate for fomesafen

. Table 14 Terrestrial Invertebrate Exposure Application Rate (lb ai/A) Insect Size Category EECs

(m g ai/kg insect) Dose per Bee ( mg ai/bee) Sm all insects 67.50 8.64 0.50 ( Pine seedlings, Region 1) Large insects 7.50 0.96 Sm all insects 50.63 6.48 0.375 (Regions 1,2 ) Large insects 5.63 0.72 Sm all insects 22.95 2.94 0.017 (Region 5) Large insects 2.55 0.3227



### 3.6 Terrestrial Plant Exposure (Terr Plant & AgDrift) Currently , EFED uses the TerrPlant Model (Version 1.2.1) to evaluate exposure of terrestrial plants to pesticides applied on agricultural fields. In cases where spray drift may be of concern in the risk assessment EFED also uses the AgDri ft model.

3. 6.1 TerrPlant TerrPlant has two basic exposure scenarios. The first is an adjacent upland area, which is exposed to the pesticide via drift and dissolved concentrations in sheet runoff. The second is an adjacent semi

- aquatic (wetland) area, which is exposed to the pesticide via drift and to dissolved concentrations in channelized runoff. Drift is calculated as a percentage of the application rate (1% for ground and 5% for aerial, airblast, or spray chemigation) and is not adjusted for distance from the application site. The amount of dissolved pesticide in the runoff component is estimated based on solubility of the active ingredient.
Table 15 Terrestrial Plant Exposure Total Loading (Runoff + Drift) (lb ai/A) Drift EEC (lb ai/A) Application Method Upland Areas We tland Areas All Areas

Application Rate 0.5 lb ai/A (Pine seedlings, Region 1) Aerial 0.05 0.275 0.025 Ground 0.03 0.255 0.005

Application Rate 0.375 lb ai/A (Region 1 & 2) Aerial 0.0375 0.20625 0.0 1875 Ground 0.0225 0.19125 0.00375

Application Rate 0.312 lb ai/A (Region 3) Aerial 0.0312 0.1716 0.0156 Ground 0.01872 0.15912 0.00312

Application Rate 0.25 lb ai/A (Region 4) Aerial 0.025 0.1375 0.0125 Ground 0.015 0.1275 0.0025

Application Rate 0.17 lb ai/A (Region 5) Aerial 0.017 0.0935 0.0085 Ground 0.0102 0.0867 0.001728 3. 6.2 AgDrift Because of concerns about effects on non

- target plants located in th e overspray or spray drift area , EFED elected to perform an anal ys is of potential deposition of fomesafen using AgDrift modeling software. AgDrift was developed using extensive field

measured data sets, and provides a method of estimating deposition of the compound of concern at a specified distance away from the application source. Depositi on is heavily dependent on the method of application and droplet size. The AgDrift modeling reported in Table 16 and Table 17 is AgDrift Tier I, with associated defaults. It should be completel y repro ducible by anyone else using the model with the same settings, as the only required inputs are the application rate and distance from the field. Please note, however, that “fraction of applied” results were put into an Excel spreadsheet in order to more efficiently calculate RQs for different endpoints and application rates. Some of the values being calculated are based on very low concentrations of fomesafen, and there could be minor variations in output depending on how values for the input or from the output are rounded. The Tier I modeling extends to approximately 1,000 ft away from the point of application. At this point, the mathematical curve that represents the deposition is asy mptotic. Thus, evaluations past this point were not performed. It is possible to estimate deposition at longer distances using higher tiers of AgDrift, but the greater distances add substantial uncertainty. For aerial applications, the deposition at 950 ft ranges from 0.3% to 4%, depending on droplet size. Deposition was estimated in 50 ft increments for droplet spectrums ranging from very fine to very coarse (ASTM standard designation, 4 different ranges as implemented in the modeling software). For ground applications, estimates were done every 10 ft for the first 100 ft and at 50 ft increments thereafter. Estimates were done for both high and low boom application methods, in the 2 droplet ranges implemented in AgDrift (very fine to fine, fine to medium, ASTM standard designation). All values reported are based on the 90 th percentile estimate. Complete modeling output is included in Appendix G. Values in the table are reported at the distance where deposition is slightl y l ower than the NOAEC for the most sensitive plant, or at the limit of the Tier I modeling, designated as >950 ft . The actual furthest extent of the Tier I m odel varies slightl y depend s on the method of application and droplet size.29

Table 16 Drift Deposition from Ground A pplications Low Boom High Boom Very Fine to Fine Fine to Medium Medium to Coarse Coarse to Very Coarse Application Rate (lb ai/A) Distance

(ft) Deposition

(lb ai/A) Distance

(ft) Deposition

(lb ai/A) Distance

(ft) Deposition

(lb ai/A) Distance

(ft) Deposition

(lb ai/A) 0.5 300 0.0018 150 0.0017 450 0.0020 250 0.0017 0.375 200 0.0019 80 0.0020 400 0.0020 150 0.0019 0.312 200 0.0016 70 0.0020 350 0.0019 150 0.0016 0.25 150 0.0017 50 0.0019 300 0.0019 90 0.0019 0.17 80 0.0020 30 0.0019 250 0.0016 60 0.0018

Table 17 Drift Depostion from Aerial Applications

Very Fine to Fine Fine to Medium Medium to Coarse Coarse to Very Coarse Application Rate (lb ai/A) Distance

(ft) Deposition

(lb ai/A) Distance

(ft) Deposition

(lb ai/A) Distance

(ft) Deposition

(lb ai/A) Distance

(ft) Deposition

(lb ai/A) 0.5 950 0.0214 950 0.0060 950 0.0028 700 0.0020 0.375 950 0.0161 950 0.0045 950 0.0021 550 0.0019 0.312 950 0.0134 950 0.0037 950 0.0021 550 0.0019 0.25 950 0.0107 950 0.0030 600 0.0019 350 0.0020 0.17 950 0.0073 950 0.0020 400 0.0019 250 0.001930



### 4. 0 Effects Assessment Toxicity endpoints are established based on data generated from guideline studies submitted by the registrant, and from open literature studies that meet the criteria for inclusion into the ECOTOX database maintained by EPA/ORD. EFED policy is to use the effects endpoint from the most sensitive tested species for each taxa evaluated. In aquatic s ys tems, taxa evaluated include aquatic plants, invertebrates, and fish. Fish serve as a surrogate for aquatic

-phase amphibians when amphibian data are unavailable or unacceptable for quantitative use . Where data are available, separate endpoints are used for freshwater and estuarine/marine organisms. In terrestrial s ys tems, taxa evaluated include birds and mammals. B ird endpoints are generall y derived from guideline studies on bobwhite quail and/or mallard duck. Bird data are used as a surrogate for reptiles and terrestrial

-phase amphibians when data for these taxa are unavailable or unacceptable for quantitative use

. Mammal data are derived from guideline studies conducted on laboratory rats, mice, or rabbits.


### 4.1 Specific Toxicological Concerns Associated with this Chemical Fomesafen is a diphenyl

- ether, one of a class of herbicides sometimes referred to as light

dependent peroxidizing herbicides (LDPHs), which have enhanced toxicity in the presence of solar ultra

- violet radiation. Because toxicity of the LDPHs is affected b y the presence of ultraviolet (UV) radiation, toxicity tests used in this assessment, which were conducted under standard laboratory lighting conditions, may underestimate the toxicity of fomesafen to some taxa under natural sunlight conditions. The Agency is currentl y in the process of developing a protocol for aquatic studies that evaluate the effect of UV light on the toxicity of these herbicides, but at the time of this assessment, it had not been finalized ( EFED 2007 ) . Preliminary studies have been submitted for some chemicals, but not fomesafen. Fish early life

- cycle studies on oxyfluorf en conducted under UV light indicate larval fish LD 50 s are approximately an order of magnitude lower than LD 50 s based on standard lighting conditions (MRID 46585104 ). In this study , the larval fish appeared to hatch prematurely compared to the controls, and then die. Based on the mode of action, it is possible that disruption of the egg cell membrane caused the premature hatch. The extent to which UV light enhances the toxicity of fomesafen is unknown. However, existing studies may underestimate the tox icity . Potential impacts of the underestimation are discussed in the Risk Description (Section 6)

. Fomesafen, along with other chemicals in this class have been associated with peroxisome proliferation, which can induce hepatocellular carcinomas in rodent s. (Smith and Elcombe 1989, Ashby et al as cited in Krijt et al 1999 . A discussion of potential for carcinogenicity, based on EFED’s review of open literature information and the HED’s review of mammalian guideline studies, is included in the terrestrial effects section.31



### 4.2 Aquatic Hazard Summary Fomesafen was originally registered for use in the 1980s. Guideline studies from that time were available for aquatic invertebrates and fish, both freshwater and marine/estuarine. Although some of the studies were conducted on formulated product, and would not be acceptable under current standards, they were classified as core or supplemental under the guidelines at the time they were submitted , and have been used in this assessment . When necessary , endpoints for these tests were re - calculated and/or data were converted to express toxicity on the basis of active ingredient

. Overall, fomesafen is slightly toxic to practically nontoxic to invertebrates and practicall y non - toxic to fish on an acute basis. Chronic tests were conducted under standard laboratory lighting, and as noted in Section 4.1, may underestimate toxicity by approximately an order of magnitude.32

Table 18 Aq uatic Toxicity Profile for Fomesafen Assessment Endpoint Surrogate

Species Toxicity Value Used Source Citation Comments Freshwater Acute Toxicity to Fish and Aquatic

- phase Am phibians Rainbow trout LC 50 =126 mg/L 95%CI=117

- 135 mg/L Slope=14.6 MRID 103023 Form ulation 1 ,2

(practically nontoxic) Chronic Toxicity Fish and Aquatic

- phase Am phibians Calculated

based on ACR (Sheepshead mi nnow/sheeps

- head m innow LC 50 =9.4 mg/L (ACR=13.4) Estimated Estimated from formulation data. Daphnia ACR=7.5 Mysid ACR=35.7 Acute Toxicity to Aquatic Invertebrates Wa ter flea LC 50 =376 mg/L 95%CI=323

- 437 mg/L Slope=5.6 MRID

1631169 Form ulation 1 ,2

(practically nontoxic) Chronic Toxicity Aquatic Invertebrates Wa ter flea NOAEC=50 mg/L LOAEC=100 mg/L MRID 135642 Form ulation 1 ,2

Reduced growth, and # of offspring Acute Toxicity to Aquatic Plants (non

- vascular) Green alga LC 50 = 0.092 mg /L 3 NOAEC = 0.010 mg /L 3 MRID 46673804 Technical

Biom ass most sensitive endpoint Acute Toxicity to Aquatic Plants (vascular) Duckweed LC 50 = 0.210 mg /L NOAEC = 0.064 mg/L MRID 46673803 Technical

Dry weight most sensitiv e endpoint Saltwater Acute Toxicity to Fish Sheepshead

mi nnow LC 50 = >163mg/L

95%CI=ND Slope=ND MRID 135651 Form ulation 1 ,2

(practically nontoxic) Chronic Toxicity to Fish Sheepshead

mi nnow NOAEC=12.2 mg/L

LOAEC=20.1 mg/L MRID 135644 Form ulation 1 ,2

Reduc ed larval survival Acute Toxicity to Aquatic Invertebrates Mysid shrimp LC 50 = 25 mg /L 95%CI= 19

- 38 mg /L Slope= ND MRID 135647 Form ulation 1 ,2

(slightly toxic) Chronic Toxicity Aquatic Invertebrates Mysid shrimp NOAEC=0.70 mg/L LOAEC=1.7 mg/L MRID 135648 Form ulation 1 ,2

Parental mortality Acute Toxicity to Aquatic Plants SW diatom LC 50 = 1.51 mg/L NOAEC=0.94 mg/L MRID 46673806 Technical

Biom ass most sensitive endpoint 1 Data are from studies originally reviewed and classified in 1984, some of which used formu lated product. 2 For purposes of this risk assessment, test concentrations were adjusted for percent ai if necessary, and endpoints were re

- calculated using TOXANAL software. 3 Endpoints have been revised since those reported in problem formulation, which were based on provisional data. ND

not determined.33



### 4. 3 Summary of Aquatic Ecotoxicity Studies 4. 3

. 1 Aquatic Guideline Data Fomesafen was originally registered for use in the 1980s. Guideline studies from that time were available for aquatic invertebrate s and fish, both freshwater and marine/estuarine. Although some of the studies were conducted on formulated product, and would not be acceptable under current standards, they were classified as core or supplemental under the guidelines at the time they were submitted. When necessary , endpoints were re

- calculated and/or data were converted to express toxicity on the basis of active ingredient

. Aquatic plant data are from studies conducted on the technical ingredient

. Acute toxicity (LC 50 s) for fish and invertebrates ranges from 25 mg ai/L (mysid shrimp, MRID 135647) to 1,507 mg/L (bluegill, MRID 163169). No sub

- lethal effects were reported in the acute studies. Overall, fomesafen is slightly toxic to practicall y nontoxic to invertebrates and practically non - toxic to fish on an acute basis. Chronic toxicity (NOAECs) for fish and invertebrates range from 0.7 mg ai/L (mys id shrimp, parental mortality, MRID 1354648) to 50 mg ai/L (Daphnia magna, reduc ed growth, total number of offspring , MRID 1354642). Becaus e of fomesafen’s l ow toxicity to aquatic animals based on the available data, additional studies were not requested at the time of problem formulation, and this risk assessment was conducted using existing data. More recent studies on aquatic plants were conducted on the technical active ingredient (ai). LC 50 s for aquatic plants range from 0.092 mg ai/L (green alga, MRID 46673804) to 71 mg ai/L (bluegreen alga, MRID 46673807). NOAECs range from 0.0095 mg ai/L (green alga, MRID 46673804) to 27.3 mg ai/L (bluegreen alga, MRID 46673807). 4. 3 .2 Aquatic Data from ECOTOX Several studies were available in ECOTOX evaluating the effects of fomesafen on aquatic organisms, including mesocosm studies that addressed effects on community structure and primary productivity (Caquet et al 2005 (E87334) and Caquet 2006 (E95935) ; Perschbacher et al 1997 (E53095 ) )

. Other studies evaluated effects on the hematocy tes of snail exposed to fomesafen in solution Russo et al ( 2007 ) (E95100) and Russo and Medec ( 2007 ) (E95590)

. T aken together, Caquet et al ( 2005 ) (E87334) and Caquet ( 2006 ) (E95935) show that fomesafen applied to mesocosm s in aquatic concentrations of approximately 30

- 60 m g/L can cause perturbations in the ecos ys tem. These perturbations appear to be mostly associated with shifts in species composition and abundance, rather than reductions in overall primary productivity and biomass (of either plants or animals). Stable i sotope anal ys is of predators in the system, ny mphs of the common backswimmer ( Notonecta glauca L .), confirm there are some modifications in both trophic level and initial carbon source when treatments were compared to controls. Treatments with a nonylphenol

containing surfactant, Agral 90, and fomesafen (applied at the same nominal concentration as the fomesafen onl y treatment) produced slightl y different effects on the mesocosms. Based on the structure of the experiments and the data presented in the34

pap ers, it cannot be determined if differences in response were associated with the surfactant alone or some interactive effect between fomesafen and the surfactant. Application of the fomesafen

- surfactant mixture reduced water concentrations of fomesafen in the mesocosoms. At termination of treatment, fomesafen concentrations were given b y authors as 62.5 ±5.3 m g/L (mean) in the fomesafen

- onl y ponds and as 19.4 ±7.6 m g/L (mean) in the fomesafen

- Agral 90 ponds. The authors make no mention of measuring concentrations in other compartments in the mesocosm or performing any mass balance calculations to determine fate of fomesafen in the mixture mesocosms, although they speculate (Caquet et al 2005) it may have accumulated at the interfaces. Currently , the EFED assumption for spray drift in aerial applications is 5%, and it is assumed to be the product (or whatever a pplication mix) deposited directly on the surface of a water body adjacent to a treated field. Study authors have essentially made the same assumption, and evaluated the short

- term effects (deposition

- 72 hrs) of a 1% and 10% drift rate associated with aerial application to soy beans on the phy

toplankton community of a small (500

- L) pond. Based on this work, one could interpret that short

- term effects on the phy

toplankton abundance and production from concentrations of fomesafen ≤0.06 mg/L are not anticipated. This should be caveated with the fact that the community was dominated by cyanobacteria (which appear to be less sensitive to fomesafen than green algae). Also, measurement endpoints reported b y authors evaluate overall primary productivity of the s ystem, rather than community structure, which may be more responsive. Authors noted statistically significant increases in production of reactive oxygen species (ROS) in snails exposed to water concentrations of fomesafen ≥10 m g/L (Russo et al 2007). Cellular membrane permeability was increased at exposure concentrations of ≥10 m g/L (Russo et al 2007, Russo and Madec 2007). Increased cellular permeability may lead to higher percentages of apoptotic and necrotic cells in the population of circulating hemocy tes in the snails, but these cells do not necessarily proceed to death (Russo and Madec 2007). Responses vary across the time course of exposure (24

- 504 hours) with a lower response generall y noted at 504 hours (Russo et al 2007, Russo and Madec 2007). It is unclear in both works whether the reduced response is due to a c ompensatory response b y the cells, or overwhelming of cellular processes following extended exposure. At concentrations of ≤270 m g/L for durations ≤504 hours (21 days) there was no observable abnormal behavior, mortality, or reduction of hemocy te cell viability in the snails (Russo et al 2007, Russo and Madec 2007). Based on this work , it appears that fomesafen induces an immune response in freshwater snails at concentrations that may occur in the environment, but how these responses translate to measurable effects at an organism level ( e.g. , reduced growth, tumor activation, increase susceptibility to disease) are unknown.35



### 4. 4 T errestrial Hazard Summary Guideline studies evaluating effects on birds, mammals, and terrestrial invertebrates were available for fomesafen. Several ECOTOX studies suitable for risk assessment purposes were available. On an acute basis, fomesafen is slightly toxic to mammals and practically non - toxic to birds and honey bees. Open literature studies indicate fomesafen may induce homolysis and formation of hepatic carcinomas in some strains of mice, but these o ccur at concentrations and durations of exposure far higher than likel y to occur in the environment based on current registrations. HED (USEPA 2006) has determined fomesafen is neither mutagenic nor carcinogenic for humans, nor does it appear to be associ ated with endocrine

- disrupting effects.
Table 19 Terrestrial Toxicity Profile for Fomesafen Assessment Endpoint Surrogate

Species Toxicity Value Used Source Citation Comments Vertebrates Acute Risk to Mammals Guinea pig LC 50 =60 7 m g/k g 95%CI=ND Slope=ND MRID

164901 Slightly toxic Chronic Risk to Mammals Rat NOAEC=1,000 mg /k g LOAEC= ND MRID

144862 No reproductive

effects Mallard duck (oral dose) LC 50 =>5,000 mg/kg 95% CI=ND Slope=ND MRID

163168 Practically non

- toxic Acute Risk to Birds, Terrestrial

phase Am phibians, and Reptiles Mallard duck

(dietary) LC 50 =>20,000 mg/kg

NOAEC=20,000 mg/kg MRID 163384 Practically non

- toxic Chronic Risk to B irds, Terrestrial phase Am phibians, and Reptiles Mallard duck NOAEC=46 mg/kg LOAEC= >46 mg/kg MRID 135639 No endpoints

affected

Invertebrates Acute Risk to Invertebrates Honey bee

(acute contact) LD 50 =>100 mg/bee MRID 135651 Practically non

- toxic Plants Acute Risk to Monocots Onion

(seedling em ergence) EC 25 = 0.084 lb ai/A

NOAEC=0.030 lb ai/A MRID 46673801 Acute Risk to Dicots Lettuce

(vegetative vigor) EC 25 = 0.002 lb ai/A

NOAEC=< 0.002 lb ai/A MRID 46673802 Form ulation

(Reflex 2 LC)36



### 4. 5 Summary of Terrestrial Ecotoxicity Studies 4. 5 .1 Avian and Small Mammal Guideline Data Guideline acute toxicity studies were available for birds (both dose and dietary), and small laboratory mammals (dose). The oral LD 50 for mallard ducks was greater than the highest dose tested (LD 50 >5,000 mg/kg , MRID163168 ). Sub

- acute dietary L C 50 s for both mallards and bobwhite quail were also greater than the highest dose tested (>20,000 mg/kg, MRIDs 163384, 164901) Acute oral dose LD 50 s were available for guinea pigs (F 607 mg/kg, MRID 164901), mice (F 745 mg/kg, M 766 mg/kg, MRID164901) and rats (F 1499 mg/kg, M 1858 mg/kg, MRID 164901). On the basis of both dose and dietary values, fomesafen is practically non - toxic to bird s and slightly toxic to mammals. Endpoints for female guinea pigs and mallard ducks were the most sensitive and were used to develop risk quotients. Chro nic guideline studies were available for birds (mallard duck , MRID 135639 ) and small laboratory mammals (rat , MRID 144862 ). The b ird guideline 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. La ck of a LOAEC contributes significant unc ertainty to the evaluation of chronic risk to birds. The mallard duck NOAEC (46 ppm) is used in the determination of chronic risk to birds, but it may over - estimate the risk to birds. In some cases, calculated exposure is near or above the maximum tested concentration. In the rat study, no treatment related reproductive parameters were affe cted at the highest dose tested , resulting in a reproductive NOAEC of 1,000 mg/kg (MRID 144862). Changes in the liver histopathology of both the parents and the offsp ring were noted at 1,000 mg/kg. Histology changes are difficult to link with the assessment endpoints of growth, survival and fecundity ev aluated by the Agency . The reproductive NOAEC of 1,000 mg/kg was used to develop endpoints for mammals. Because of fomesafen’s low toxicity to terrestrial organisms based on the available data, additional studies were not requested at the time of problem formulation, and this risk assessment was conducted using existing data. 4. 5 .2 Terrestrial Plant Data 4.5.2.1 Guideline Studies Terrestrial plant guideline studies were available

. Fomesafen is effective, both pre

- and post

- emergent, against a variety of plants, although dicots appear to be more sensitive than monocots for both endpoints (seedling emergence and vegetative vigor) . The product is marketed as a c ontrol for broad

- leafed weeds. Guideline studies for seedling emergence (MRID 46673801, acceptable) and vegetative vigor (MRID 46673802, acceptable) were available at the time of this assessment. Both studies evaluated the effects of fomesafen formulated product (REFLEX 2LC) on 10 plant species. Species tested included 4 monocots (onion, barnyard grass, corn, and oats)37

and 6 dicots (radish, lettuce, tomato, soy bean, oilseed rape, and sugarbeet). Two concentratio ns were tested: 0.25 lb ai/A and 0.50 lb ai/A. For monocots, the seedling emergence EC 25 s ranged from 0.084 lb ai/A to >0.48 lb ai/A (no effect at highest concentration tested). Dicots were more sensitive, with the seedling emergence EC 25 s ranging from 0.005

- 0.35 lb ai/A, with the exception of soy beans, with an EC 25 of >0.48 lb ai/A (no effect at highest concentration tested)

. Currently , soy beans are the crop for which fomesafen is most commonly used. For dicots, the sensitivity range for the vegetativ e vigor endpoint is similar to the seedling emergence endpoint. EC 25 s for the dicot vegetative vigor endpoint range from 0.002

- 0.24 lb ai/A, with the exception of soy beans, with an EC 25 of >0.47 lb ai/A (no effect at highest concentration tested). For monocot vegetative vigor endpoint EC 25 s ranged from 0.29 lb ai/A to >0.47 lb ai/A (no effect at highest concentration tested). Based on this data, dicots appear more sensitive than monocots, and the vegetative vigor and seedling emergence endpoints appear to be equally sensitive. 4.5.2.2 Additional Registrant

-Submitted Data Efficacy data (MRID 135656 ) were part of the data package submitted for the original registration of fomesafen, and were considered in this assessment. The efficacy data included pre

- emergence and post

- emergence treatment of 24 plant species, at two concentrations (0.25 and 1.0 kg ai/ha , or when converted , 0.42 and 0.54 lb ai/A). The two concentrations are greater than most currentl y registered rates

. The plant species tested included bo th monocots (11 species) and dicots (13 species). Both crop (7 species) and non

- crop (17 species) plants were evaluated. With the exception of soybeans, all plants tested experienced >20% “damage” when treated pre

- emergence, with a significant number (65 %) experiencing >80% damage when treated with the lower concentration (0.25 kg ai/ha). Applied post

- emergence, fomesafen is slightly less effective, with “damage” typicall y in the 0

- 40% range for monocots and 40

- 80% range for dicots. The report did not specify how damage was quantified. Additional plant data was submitted by the registrant during the registration review process (MRID 47587101). This submission was not reviewed b y EPA for acceptability, and raw data were not included, thus values reporte d herein do not represent any thing statistically generated b y the Agency . Inclusion of these data is intended to provide a broader view of potential effects on plants than is provided b y guideline data alone. These data do not represent a regulatory endp oint. The submission included an estimation a 10 th percentile EC 25 , based on EC 25 s for a range of plant species tested b y the registrant. The registrant’s database included 210 efficacy tests addressing 35 common crop and weed, with multiple application rates ranging from 0.01

- 0.45 lb ai/A . Effects on the plants are rated on a visual scale of 1 to 10 compared to control plants, then converted to a percent effects scale (0%=no damage, 100%=complete efficacy).38 4. 5 .3 Terrestrial Insect Data Guideline te sts for honeybees were submitted (MRID 135651, Core), as was a field chronic effects study on earthworms (MRID 135652). The acute oral LD 50 for honey bees was >50 m g ai/bee , and the acute contact LD 50 was >100 m g ai/bee. The field test for earthworms included two applications of fomesafen, applied at one

- ye ar intervals. Fields were treated with 0.5 kg ai/ha and 5.0 kg ai/ha. No adverse effects on total numbers, total weights, or numbers of individual species were noted at the 0.5 kg ai/ha treatment level

. A significant change in numbers of one species of earthworm (Allolobophura nocturna ) was noted at the higher treatment level, but authors attributed this to modifications in grass cover caused b y the herbicide treatment rather than direct toxic effects. Studies were also submitted (MRID 135656) for eight species of invertebrates, from the orders Acarina, Hemiptera, Diptera, Lepidoptera, Coleoptera, and Nemotoda. Fomsafen was applied to multiple life stages at concentrations of 250 and 500 ppm. The gre atest level of mortality in these tests was 9%. Aphids (Aphis fabae) experienced mortality rates of 9% at concentrations of 250 ppm and 500 ppm. 4.5.4 ECOTOX Data Some information regarding toxicity of fomesafen was available in the open litereature. Ful l reviews of studies with endpoints potentially useful for this risk assessment are located in Appendix B. No studies contained endpoints lower than those derived from guideline studies. Summaries of studies evaluating biochemical and community

- level end points are presented below. 4.5.4.1 Biochemical Endpoints Several studies (Krijt et al 1993 (E95026); Krijt et al 1994a (E95399); Krijt et al 1994b (E95589); Krijt et al 1999 (E95400); Krijt et al 2003 (E95588 )) evaluating the effects of fomesafen on mammalian hematocy tes were located and reviewed

. The work of Krijt et al demonstrates that fomesafen ingested b y mice at concentrations ranging from 100

- 2,500 ppm diet for 10 days causes elevated liver and fecal porphy rins, primarily via inhibition of the 7 th enzy

me of the heme bios ynthesis protoprophyrin III oxidase (Krijt et al 1993). Body wei ght gain is statistically significantly affected when fomesafen is administered at concentrations of 2,500 ppm in diet for 10 days ( Krijt et al 1993). The treatment groups in all investigations are small (n=3 or 4). Mice used in the experiments were generally in the size range of 30

- 35 grams. In some cases, fomesfen may also inhibit uroporphy

rinogen III decarboxyl ase, but specific biochemical responses may vary dependent on the strain of mouse (Krijt et al 1994m, Krijt et al 2003). Consumption of high doses (2,300

- 3,000 ppm) for extended periods of time (50 weeks to 14 months) caused development of precancerous cells in the liver (Krijt et al 1999). Even with extende d exposure, mice appeared to recover following a period of clean diet (3months) with liver porphy

rins decreasing, and liver histology not noticeably different from controls (Krijt et al 1999). In both studies that included a recovery period, liver porphy rin concentrations decreased rapidly following withdrawal from fomesafen, but did not return to the same levels as controls during the observation period (Krijt et al 1999).39

Two studies described the effects of fomesafen on the hemocy tes of the freshwater snail Lymnaea stagnalis (Russo et al 2007, Russo and Madec 2007). Authors noted statistically significant increases in production of reactive oxygen species (ROS) in snails exposed to water concentrations of fomesafen (≥10 m g/L) (Russo et al 2007). Cellular membrane permeability was increased at exposure concentrations of ≥10 m g/L (Russo et al 2007, Russo and Madec 2007). Increased cellular permeability may lead to higher percentages of apoptotic and necrotic cells in the population of circulating hemoc yt es in the snails, but these cells do not necessarily proceed to death (Russo and Madec 2007). Responses vary across the time course of exposure (24

- 504 hours) with a decrease response generall y noted at 504 hours as compared to 24 hours (Russo et al 200 7, Russo and Madec 2007). It is unclear in both works whether the reduced response is due to a compensatory response by the cells, or overwh elming of cellular processes following extended exposure. At concentrations of ≤270 m g/L for durations ≤504 hours (21 days) , there was no observable abnormal behavior, mortality , or reduction of hemocy te cell viability in the snails (Russo et al 2007, Rus so and Madec 2007). Based on this work, it appears that fomesafen induces an immune response in freshwater snails at concentrations that may occur in the environment, but how these responses translate to measurable effects at an organism level ( e.g. , redu ced growth, tumor activation, increase susceptibility to disease) are unknown. 4.5.4.2 Aquatic Community

- Level Mesocosm studies ( Caquet et al 2005 , Caquet 2006 ) show that fomesafen applied in concentrations of approximately 30

- 60 m g/L can cause perturbations in the ecos ys tem. These perturbations appear to be mostly associated with shifts in species composition and abundance, rather than reductions in overall primary productivity and biomass (of either plants or animals). Stable i sotope anal ys is of predators in the system, ny mphs of the common backswimmer (Notonecta glauca L

. ), confirm there are some modifications in both trophic level and initial carbon source when treatments were compared to controls. Treatments with a nonylphenol

- containing surfactant, Agral 90, and fomesafen (applied at the same nominal concentration as the fomesafen only treatment) produced slightly different effects on the mesocosms. Based on the structure of the experiments and the data presented in the pap ers, it cannot be determined if differences in response were associated with the surfactant alone or some interactive effect between fomesafen and the surfactant. Application of the fomesafen

- surfactant mixture reduced water concentrations of fomesafen in the mesocosoms. At termination of treatment, fomesafen concentrations were given b y authors as 62.5 ±5.3 m g/L(“maximum mean”) in the fomesafen only ponds and as 19.4 ±7.6 m g/L (“maximum mean”) in the fomesafen

- Agral 90 ponds Pershbarger et al (1997) examines the effect of spray drift on aquatic mesocosms. Study authors evaluated the short

- term effects (depo sition to 48 hrs) of a 1% and 10% drift rate associated with aerial application to soy beans on the phy

toplankton community of a small (500

- L) pond. Based on this work, one could interpret that short

- term effects on the phy toplankton abundance and producti on from concentrations of fomesafen ≤0.06 mg/L are not anticipated. This should be caveated with the fact that the mesocosm community was dominated b y c yanobacteria (which appear to be less sensitive to fomesafen than40

green algae based on registrant

- submitted studies: MRID 46673806, green alga EC 50 92 m g/L; MRIDs 46673807, blue

- green alga EC 50 710 m g/L). Also, measurement endpoints reported b y authors evaluate overall primary productivity of the s ys tem, rather than community structure, which may be more responsive. 4. 5 .5 Carcinogenicity

, Mutagenicity, and Endocrine Disruption Based on data submitted for use in human health risk assessments, the Health Effects D ivision (HED) evaluates potential for carcinogenicity . Fomesafen was classified as “not likely to be carcinogenic to humans.” This decision was “based on the weight

- of

evidence which supports activation of perox isiome proliferator

- activated alpha (PPAR a) as the mode of action for fomesafen

- induced hepatocarcinogeneisis in mice. The data did not support either mutagensis or cy totoxicity followed by regenerative proliferation as alternative modes of action.” (USEPA 2006 ). EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) “may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or oth er such endocrine effects as the Administrator may designate.” Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA determined that there were scientific bases for including, as part of the program, androgen and thy roid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential effects in wildlife. When the appropriate screening and/or testing protocols b eing considered under the Agency ’s Endocrine Disrupter Screening Program (EDSP) have been developed and vetted, fomesafen may be subjected to additional screening and/or testing to better characterize effects related to endocrine disruption. 4. 5 .6 Toxic Ef

fects of Multi

-

Active Ingredient Labeled Products Mammalian toxi city data were available for several formulated products, including one containing onl y fomesafen and all those containing multiple active ingredients. Based on female guinea pig data (used as the assessment endpoint LD 50 = 607 mg/kg bw), rats are less sensitive to fomesafen (female LD 50 = 1,499 mg/kg bw). For the formulations, rat data was compared to minimize variability associated with interspecies variation. Flexstar (reg#100

- 1101) , which contains only fomesafen (22.1%) has an LD 50 o f 3863 mg/kg (female, 95% CI not reported , MRID44030101 ). Prefix (reg # 100

- 1268), which contains both fomesafen and s - metolachlor (10.1% and 46.5% respectively) has an LD 50 of 5,000 mg/kg (combined, 95% CI 2, 865

- 8,390 , MRID46952103 ). Metolachlor has an LD 50 o f 2780 mg/kg (combined, 95% CI 2,180

- 3,545, MRID00015523). Formulations containing bentazon (BAS 530 04 (29%) , reg#7969

- 82 and Faster (29.8%) , reg#7969

- 83) have an LD 50 of >1210 mg/kg and 1470 mg/kg ( 95% CI 1,000

- 2,160, MRIDs 40340502, 40031302 ) . Bentazon has an LD 50 o f 1480 mg/kg (MRID s 92065, 64314).41

Although guideline studies are not designed to elucidate such effects, there do not appear to be additive or s ynergistic acute toxicity effects between fo mesafen and any of the currentl y co - formulated active ingredients based on available data

. Toxic effects to mammals from ingestion of the formulated products containing fomesafen alone or fomesafen in conjunction with s - metolachlor or bentazon are not anticipated to exceed toxic effects estimated based on the technical active ingredient (Appendix H)

. 

### 4. 6 Incident Database Review EFED maintains EIIS, a database containing reported incidents of damage to non

- target species caused b y pestici de use. There are a total of 65 reported incident s (Appendix F) for fomesafen, 64 of which are damage to agricultural crops. Incident s reported cover a range of 13 ye ars ( 1992

- 2005), but many of them (83%) were reported in 2001

- 2003

. Corn was the crop most frequentl y rep orted damaged, accounting for 86% of the total plant damage reports. The most frequentl y reported routes of exposure for corn were direct treatment, drift, and carryover. In many cas es (36%) the legality was classified as registered use . In other cases (55% ), the legality o f application is unknown. The certainty that the incident was related to fomesafen use was generall y classified as probable

. Other crops damaged included green peas, cotton, and so ybeans under registered use conditions. Only 5 cases of misuse or accidental misuse were reported. There is one report of a fish kill (I007601

- 001) . In this incident, there was a report of approximately 200 fish (channel catfish, crappie, largemouth bass, and redear sunfish) dying following a legal appli cation to a soy bean site. The certainty of the kill being related to fomesafen runoff is classified as possible. Application was in accordance with registered use.42



### 5. 0 Risk Estimation Risk is estimated by calculating the ratio of the expected environmental concentration and the appropriate toxicity endpoint. This value is the risk quotient (RQ), which is then compared to pre

- established levels of concern (LOC) for each category evaluated. The RQ methodology , LOCs, and specific details of calculation are contained in Appendix G. The highest EECs and most sensitive endpoints are used to determine the screening level RQ. Using these two values , theoretically, results in a conservative estimate of risk.43



### 5.1 Aquatic RQ Summary Based on scenario s modeled for Section 3 label rates (0.17

- 0.375 lb ai/A) and existing Section 24 label rates, no acute or chronic RQs for animals exceeded any LOCs

. Acute RQs for freshwater and saltwater fish and invertebrates ranged from <0.0 1 to 0.02

. Chronic RQs for freshwater and saltwater fish and invertebrates were ≤ 0.02. Acute risk RQs for fresh

- and saltwater plants, both vascular and non

- vascular, ranged from <0.01 to 0.16. In no cases did RQs for plants exceed the acute risk LOC. Listed species RQs for fresh

- and saltwater aquatic plants ranged from <0.01 to 1. 6

. At the 0.5 lb ai/A application rate, RQs for freshwater non

- vascular plants exceed the listed species LOC. For some, but not all of the scenarios modeled, RQs for freshwater non

- vascular plants exceed the listed species LOC at the application rate of 0.375 lb ai/A (RQs for all scenarios modeled are included in Appendix A)

. In no cases did the modeled concentrations of fomesafen exceed the LOAEC for freshwater non

- vascular plants. Fomesafen appears to pose very low risk to aquatic ecos ys tems based o n the data currentl y av ailable.
Table 21 Summary of Aquatic RQs

Taxa Acute RQ Chronic RQ 1 Endangered Species RQ 2 Highest Section 24 Use on Cotton at 0.5 lb ai /A (MS scenario, ground application) FW Aquatic Plants (algal) 0.16 NA 1 1.6 a FW Aquatic Plan ts (vascular) 0.07 NA 1 0.24 FW Aquatic Invertebrates <0.01 <0.0 1 <0.0 1 FW Fish <0.0 1 NC <0. 0 1 SW Aquatic Plants 0.01 NA 1 0.02 SW Aquatic Invertebrates <0.0 1 <0.01 <0.0 1 SW Fish <0.0 1 <0.01 <0.0 1 Highest Section 3 EEC : Use on Cotton at 0.375 lb ai /A ( TX scenario, aerial application) FW Aquatic Plants (algal) 0.13 NA 1 1.2 a FW Aquatic Plants (vascular) 0.06 NA 1 0.19 FW Aquatic Invertebrates <0.01 <0.01 <0.01 FW Fish <0.01 <0.01 <0.01 SW Aquatic Plants <0.01 NA 1 0.01 SW Aquatic Invertebrates <0.01 0 .02 <0.01 SW Fish <0.01 <0.01 <0.01 Lowest EEC: Us e on Beans at 0.17 lb ai /A (MI scenario, aerial application) FW Aquatic Plants (algal) 0.03 NA 1 0.24 FW Aquatic Plants (vascular) 0.01 NA 1 0.04 FW Aquatic Invertebrates <0.01 <0.01 <0.01 FW Fish <0.0 1 <0.01 <0.01 SW Aquatic Plants <0.01 NA 1 <0.01 SW Aquatic Invertebrates <0.01 <0.01 <0.01 SW Fish <0.01 <0.01 <0.01 1 There are no chronic aquatic plants tests. 2 Endangered species RQ for plants are calculated based on NOAEC. Endangered species RQ s for animals are calculated in the same way as acute risk values, but compared to a different LOC. NA

– not applicable, NC

– Not calculated, data not available. a Exceeds endangered species LOC.44



### 5.2 Terrestrial RQ Summary 5.2.1 Terrestrial Plants Risk quo tients were calculated based on the exposures estimated b y both TerrPlant and AgDrift. Calculations were made using data from both ty pes of guideline studies (vegetative vigor and seedling emergence). Evaluations were done for both monocots and dicots. The most sensitive endpoint was dicot vegetative vigor (EC 25 =0.0016 lb ai/A, NOAEC=0.00098 lb ai/A). For the seedling emergence tests, calculated EC 05 was unavailable, and the reported NOAEC was greater than the calculated EC 25 , so the EC 25 was used as th e toxicity endpoint for the endangered species anal ys is. 5.2.1.1 TerrPlant Because fomesafen is highly toxic to terrestrial plants, RQs for all application rates, both aerial and ground, are presented below. It is especially toxic to dicots, and RQs excee d the LOC for both non

- listed and listed species of plants in upland and wetland areas, as well as on the basis of spray drift alone

. RQs for non

- listed dicots range from 4.3 (drift only , 0.17 lb ai/A) to 59.8 (wetland, 0.5 lb ai/A). RQs for listed dicot s range from >0.85 (drift only , 0.17 lb ai/A) to 59.8 (wetland, 0.5 lb ai/A). For non

- listed monocots, RQs exceed the LOC onl y in the wetland area. Non

- listed monocot RQs range from <0.1 (drift only , 0.17 lb ai/A) to 3.3 (wetland, 0.5 lb ai/A). RQs for listed monocots range from <0.1 (drift only , 0.17 lb ai/A) to 3.3 (wetland, 0.5 lb ai/A).45

Table 22 Terrestrial Plant Risk Quotients Based on TerrPlant

Total Loading RQ (Seedling Emergence) Total Loading RQ (Seedling Emergence) Drift Only (Vegetative Vigor) Upland Areas We tland Areas Drift Only Application Rate ( lb ai/A) Monocot Dicot Monocot Dicot Monocot Dicot Aerial Applications Non

-listed Plants 0.5 Region 1 pine 0.60 10.87 a 3.27 a 59.78 a 0.30 12.50 a 0.375 Region 1 & 2 0.45 8.15 a 2.66 a 44.84 a 0.22 9.38 a 0.312 Region 3 0.37 6.78 a 2.04 a 37.30 a 0.19 7.80 a 0.25 Region 4 0.30 5.43 a 1.64 a 29.89 a 0.15 6.25 a 0.17 Region 5 0.20 3.70 a 1.11 a 20.33 a 0.10 4.25 a Ground Applications Non

-listed Plant s 0.5 Region 1 pine 0.36 6.52 a 3.04 a 55.43 a <0.1 2.50 a 0.375 Region 1 & 2 0.27 4.89 a 2.28 a 41.58 a <0.1 1.88 a 0.312 Region 3 0.22 4.07 a 1.87 a 34.59 a <0.1 1.56 a 0.25 Region 4 0.18 3.26 a 1.52 a 27.72 a <0.1 1.25 a 0.17 Region 5 0.12 2.22 a 1.03 a 18.85 a <0.1 0.85 Aerial Applications L isted Plants 0.5 Region 1 pine 1.67 a 10.87 a 9.17 a 59.78 a 0.83 > 12.50 a 0.375 Region 1 & 2 1.25 a 9.87 a 6.88 a 54.28 a 0.63 > 9.38 a 0.312 Region 3 1.04 a 8.21 a 5.72 a 45.16 a 0.52 > 7.80 a 0.25 Region 4 0.83 6.58 a 4.58 a 36.18 a 0.42 > 6.25 a 0.17 Region 5 0.57 4.47 a 3.12 24.61 a 0.28 > 4.25 a Ground Applications L isted Plants 0.5 Region 1 pine 1.00 a 7.89 a 8.50 a 67.11 a 0.17 > 2.50 a 0.375 Region 1 & 2 0.75 5.92 a 6.38 a 50.33 a 0.13 > 1.88 a 0.312 Region 3 0.62 4.93 a 5.30 a 41.87 a 0.10 > 1.56 a 0.25 Region 4 0.50 3.95 a 4.25 a 33.55 a <0.1 > 1.25 a 0. 17 Region 5 0.34 2.68 a 2.89 a 22.82 a <0.1 > 0.85

a Exceeds or equals LOC of 146 5.2.1.2 AgDrift Acute risk RQs and listed species RQs were calculated for aerial and ground applications (low boom and high boom) using the EC 25 and NOAEC for the most sensitive dicot (lettuce EC 25 0.0002 lb ai/A, NOAEC <0.00019 lb ai/A)

. As the endpoints are so similar, RQs presented below apply to both listed and non

- listed species. Because the droplet size is an important parameter in determining spray drift, clearance distances and RQs were calculated for all droplet spectrum available in AgDrift. The maximum extent of AgDrift Tier I modeling is approximately 1,000 ft from point of application for aerial applications, but the specific distance varies slightly dependent on the droplet spectrum. For the sake of consistency, modeling was terminated at 950 ft for all spectra. At this distance, the mathematical curve which describes the deposition is asymptotic, there are only small declines for greater linear distances

. For aerial applications, fomesafen applied with a very fine to fine or fine to medium droplet spectrum exceeds the terrestrial plant LOC at all application rates. For coarser droplet spectra, RQs range from 0.96 to 1.4, and clearance distances range from 250 ft to >950 ft. Ground applications require a n arrower buffer to clear the LOC , especially a low boom. Clearance distances for ground applications range from 30 ft to 450 ft.
Table 20 Drift Deposition from Aerial Applications

Very Fine to Fine Fine to Medium Medium to Coarse Coarse to Very Coarse Ap plication Rate (lb ai/A) Clearance

Distance (ft) RQ

unitless Clearance

Distance (ft) RQ

unitless Clearance

Distance (ft) RQ

unitless Clearance

Distance ( ft) RQ

unitless 0.5 >950 10 .7 >950 3.0 >950 1.4 700 0.98 0.375 >950 8.0 >950 2.3 >950 1.1 550 0.94 0.312 >950 6.7 >950 1.9 >950 1.1 550 0.94 0.25 >950 5.4 >950 1.5 600 0.96 350 0.98 0.17 >950 3.6 >950 1.0 400 0.94 250 0.96 Bold designates an exceedence (LOC=1) Table 21 Drift Deposition from Ground A pplications Low Boom High Boom Very Fine to Fine Fine to Medium Medium to Coarse Coarse to Very Coarse Application Rate (lb ai/A) Clearance

Distance (ft) RQ

unitless Clearance

Distance (ft) RQ

unitless C learance

Distance (ft) RQ

unitless Clearance

Distance ( ft) RQ

unitless 0.5 300 0.88 150 0.83 450 0.98 250 0.83 0.375 200 0.96 80 0.98 400 0.95 150 0.96 0.312 200 0.80 70 0.90 350 0.97 150 0.85 0.25 150 0.83 50 0.93 300 0.94 90 0.95 0.17 80 0.98 30 0.9 3 250 0.79 60 0.8847 5.2.2 Avian RQ Summary For birds, no acute LOCs were exceeded at any ap plication rates. Chronic RQs are reported as <RQ, due to the fact that the NOAEC established in the guideline study was not definitive. At the application rate of 0.5 lb ai/A, chronic LOCs for birds in three out of the four food categories (short grass, tall grass, and bro adleaf plants/small insects) were exceeded. At the application rate of 0.375 lb ai/A, chronic LOC s for birds consuming the food categories of short grass and broadleaf plants/small insects were exceeded

. At the application rate of 0.17 lb ai/A, chronic LOC s for birds in the short grass food category were exceeded.
Table 22 Av ian RQ Summary Acute dose - based RQs 1 Acute dietary based RQs 1 Chronic

RQs Risk quotients based on Kena ga upper bound EECs 20g 100g 1000g Al l birds Al l birds

Maximum Application Rate 0.5 lb ai/A (pine seedlings, states in region 1) Short grass 0.05 0.02 0.01 0.01 < 2.61 c Tall grass 0.02 0.01 <0. 01 <0.01 < 1.20 c Broadleaf plants/small insects 0.03 0.01 <0.01 <0.01 < 1.47 c Fruits/pods/seeds/lg insects <0.01 <0.01 <0.01 <0.01 < 0.16

Common Application Rate 0.375 lb ai/A (all crops, regions 1, 2 ) Short grass 0.04 0.02 0.01 <0.01 < 1.96 c Tall grass 0 .02 0.01 <0.01 <0.01 < 0.90 Broadleaf plants/small insects 0.02 0.01 <0.01 <0.01 < 1.10 c Fruits/pods/seeds/lg insects <0.01 <0.01 <0.01 <0.01 < 0.12

Minimum Application Rate 0.17 lb ai/A (all crops, region 5) Short grass 0.02 0.01 <0.01 <0.01 < 0.89 c Tall grass 0.01 <0.01 <0.01 <0.01 < 0.41 Broadleaf plants/small insects 0.01 <0.01 <0.01 <0.01 < 0.50 Fruits/pods/seeds/lg insects <0.01 <0.01 <0.01 <0.01 < 0.06 a exceeds acute risk LOC (0.5) b exceeds endangered species acute risk LOC (0.1) c exceeds chronic risk LOC (1.0)48 5.2.3 Small Mammal RQ Summary For mammals, no acute LOCs were exceeded at any application rates. The chronic LOC was exceeded onl y for small (15g) mammals eating short grass at the highest rate (0.5 lb ai/A, pine seedlings in AR, GA, MS, NC , and SC).
Table 23 Small Mammal RQ Summary Acute dose - based RQs Chronic dose - based RQs Chronic dietary based RQs Risk Quotients based on Kenaga upper bound EEC 15 g 35 g 1000 g 15 g 35 g 1000 g Al l mammals Maximum Appl

ication Rate 0.5 lb ai/A (pine seedlings, states in region 1) Short grass 0.09 0. 07 0.04 1.04 c 0.89 0.48 0.48 Tall grass 0.04 0.03 0.02 0.48 0.41 0.22 0.22 Broadleaf plants/ sm all insects 0.05 0.04 0.02 0.59 0.50 0.27 0.27 Fruits/pods/seeds/ lg insects 0.01 < 0.01 < 0.01 0.07 0.06 0.03 0.03 Seeds (granivores) <0.01 <0.01 < 0.01 0.01 0.01 0.01 NA

Common Application Rate 0.375 lb ai/A (all crops, regions 1&2 ) Short grass 0. 06 0.05 0.03 0.78 0.67 0.36 0.36 Tall grass 0.03 0.03 0.01 0.36 0.31 0.16 0.17 Broadleaf plants/ sm all insects 0.04 0.03 0.02 0.44 0.38 0.20 0.20 Fruits/pods/seeds/ lg insects <0.01 <0.01 <0.01 0.05 0.04 0.02 0.20 Seeds (granivores) <0.01 <0.01 <0.01 0.01 0.01 <0.01 NA

Minimum Application Rate 0.17 lb ai/A (all crops, region 5) S hort grass 0.0 3 0.02 0.01 0.35 0.30 0.16 0.16 Tall grass 0.01 0.01 0.01 0.16 0.14 0.07 0.07 Broadleaf plants/ sm all insects 0.02 0.01 0.01 0.20 0.17 0.09 0.09 Fruits/pods/seeds/ lg insects <0.01 <0.01 <0.01 0.02 0.02 0.01 0.01 Seeds (granivores) <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 NA a Equals or exceeds acute risk LOC (0.5) b Equals or exceeds listed species acute risk LOC (0.1) c Equals or exceeds chronic risk LOC (1.0) 5 .2.4 Terrestrial Invertebrate Summary F omesafen appears to be of relativel y l ow toxicity to bees, based on submitted guideline tests. Estimated dose per bee for an organism in the treatment are a ranged from 0.96 m g ai/bee (based o n large insect estimator , 0.5 lb ai/A) to 8.64 m g ai/bee (based on small insect estimator) . Using the acute contact LD 50 of >100 m g ai/bee, anticipated exposure at the treatment site would not be greater than approximately 9% of the LD 50 . RQs calculated on this basis are shown below. At the time of this assessment, OPP has an interim listed species acute risk LOC for terrestrial insects, but does not have a corresponding LOC for non

- listed species.49

Table 24 T e rrestrial Invertebrate RQ Summary Ap plication Rate (lb ai/A) Insect Size Category RQ Dose per Bee ( m g ai/bee) Sm all insects < 0.09 a 8.64 0.50 (Pine seedlings, Region 1) Large insects < 0.01 0.96 Sm all insects < 0.07 a 6.48 0.375 (Regions 1, 2 ) Large insects <0.01 0.72 Sm all insects < 0.03 2.94 0.017 (Region 5) Large insects <0.01 0.32 a Equals o r exceeds interim listed species acute risk LOC (0. 0 5) Non

- guideline field tests on earthworms submitted by the registrant showed that fomesafen did not have observable adverse effects on total numbers, total weights, or numbers of individual species at a treatment level of 0.45 lb ai/A. Decline in the population of one species of earthworms in the test plots was attributed to the change in plant cover on the plot as a result of the herbicide application.50



### 6. 0 Risk Description 6.1 Aquatic Risk Based on currently available data, fomesafen appears to be of relativel y l ow toxicity to aquatic animals in freshwater and estuarine/marine systems. Both acute and chronic effects were considered. Fomesafen is a light

- dependent peroxidizing herbicide (LDPH) , and may b e more toxic under conditions of natural sunlight than in laboratory lighting (Matringe 1989) . The Agency has proposed testing this class of compounds under ultraviolet (UV) light conditions (EFED 2007) , but as of the time of this risk assessment, such data were not available for fomesafen. Based on fish earl y- life cycle tests submitted for oxyfluorfen, another chemical in this class , UV light conditions appear to increase the toxicity by approximately an order of magnitude (MRID 46585104 ). To evaluate the effect of this increase in toxicity, fish earl y l ife cycle endpoints were adjusted by an order of magnitude and RQs were recalculated for all scenarios modeled. In all cases, RQs were <0.015. It should be noted, however, that the freshwater fish earl y l ife cycle endpoint was based on an ACR calculated from the saltwater fish studies, thus considerable uncertainty surrounds this endpoint. Based on the effects noted in the oxyfluorfen study (decreased hatching time and reduced larval survival) and the mode of action of LDPHs, it seems possible that oxyf luorfen may have affected the viability of the egg cell m embrane surrounding the larva. Given this possibility, extrapolation of the enhanced toxicity to the fish life stages used in the acute toxicity te sts was not judged to be appropriate. No tests conducted under UV light conditions were available for aquatic invertebrates , thus the type or magnitude of phototoxic effects on these typ es of organisms is unknown. Given that many z ooplankters have translucent bodies, and are present in the surface layers of water bodies where UV rays might penetrate (Barron et al 2000, Diamond et al 2005), photoenhanced toxicity to these taxa is a possibility

. In aquatic ecos ys tems, aquatic plants are the taxa most sensitive to fomesafen. Aquatic plants (both vascular and non

- vascular) are the primary producers, and may serve as the primary energy base in some aquatic s ys tems either via consumption by herbivores or energy input to the detrital food web. Perturbations to the base of the food chain have the potential to modify community structure and/or productivity of the affected system. There are no acute risk LOC exceedences for any application rates. RQs exceed the listed species LOC for freshwater non

- vascular plants for the application rate of 0.375 lb ai/A in some scenarios modeled, and for the application rate of 0.5 lb ai/A in all scenarios modeled. However, EECs (2

- 25 m g/L) do not exceed the LOAEC (23 m g/L) , which is based on a 9% inhibition in biomass (MRID46 673804). Mesocosm studies (Caquet et al 2005, Caquet 2006) show that fomesafen concentrations of 30

- 60 m g/L can cause perturbations in the s ys tem, but these perturbations are primarily associated with shifts in species composition and abundance rather than primary productivity . Mesocosm studies conducted b y P ershbarger et al (1997) indicate short

- term effects on phytoplankton abundance and composition from concentrations of fomesafen ≤60 m g/L are not measurable, but it must be noted that their experimental system was dominated by blue

green alga (EC 50 = 71,000 m g/L, MRID 46673807), which are less sensitive to fomesafen51

than the green alga (EC 50 = 92 m g/L, MRID 46673804). The mesocosm studies were both conducted outdoors under natural sunlight conditions, thus any photoenhancement of fomesafen toxicity for these taxa would be implicitly incorporated into study results. Measurable differences in the algal composition and productivity of water bodies receiving runoff from fields treated with fomesafen at the application rates evaluated in this document are not anticipated. At the time of this assessment, there were no listed freshwater non

- vascular plants, and no indications of any obligate relationships between a listed species and freshwater algae. Fome safen may indirectly affect aquatic s ys tems by damaging plants in adjacent wetland or riparian zones. Modification of the vegetation in wetlands or riparian zones could cause decreased allochthonous input, increased sediment input, destabilization of the stream bank, or changes in the structural components (plant). Effects on waterbody associated plant communities can be minimized by ensuring an adequate offset distance is maintained between the application site and the wetland or riparian zone. Appropri ate offset distance s are discussed in the terrestrial plants section.52

Table 25 S ummary of Risk to Non - listed Aq uatic Organisms Assessment Endpoint Crops Estimator LOC Exceedence Freshwater Acute Toxicity to Fish and Aquatic

pha se Amphibians Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Chronic Toxicity Fish and Aquatic

phase Amphibians Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Acute Toxicity to Aquatic Invertebrates Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Chronic Toxicity Aquatic Invertebrates Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Ac ute Toxicity to Aquatic Plants (non

- vascular) Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Acute Toxicity to Aquatic Plants (vascular) Pine seedli ngs

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Saltwater Acute Toxicity to Fish Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Chronic Toxicity to Fish Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Acute Toxicity to Aquatic Invertebrates Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Chronic Toxicity Aquatic Invertebrates Pine seedlings

Cotton , Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Acute Toxicity to Aquatic Plants Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton ( 0.5lb ai) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No53



### 6.2 Terrestrial Risk In general, fomesafen presents low risk to terrestrial animals on an acute basis, with no acute LOC exceedences for either birds or mammals. However, there are chronic L OC exceedences for both bird s and mammals at all application rates. Fomesafen poses a risk to terrestrial plants, especially dicots, in areas which may be subject to drift or runoff from the application site. Due to the sensitivity of dicots to fomesafen , effect from drift may occur as far away from the use site as 1,000 ft for aerial applications and 300 ft for ground applications. 6.2.1 Birds, Reptiles, an d Amp h ibians In the avian reproduction study on mallard ducks (MRID 135639) , no endpoints were affe cted, thus the NOAEC was established as the highest dose tested (46 mg/kg diet). No LOAEC was determined, so based on the available data, the meaning of the chronic LOC exceedences for birds is difficult to interpret, either in terms of which endpoints mi ght be affected, or if chronic exposure to fomesafen is at levels that would trigger these effects. It should also be noted that generally bobwhite quail, which were not tested for fomesafen , are more sensitive than mallard ducks. Avian data for fomesa fen and several structurally similar compounds, acifluorfen (PCs 114401

- 114404), oxyfluorfen (PC 111601), and lactofen (PC 128888), is presented below. The data available for the other chemicals suggests reproductive effects of fomesafen may include reduction in embryo survival, number of hatchlings, and/or number of eggs laid. The data also suggests that bobwhite quail are the more sensitive species for this class of chemicals, thus the mallard data used in the risk assessment may underestimate the risk to more sensitive species. Mammalian data were also considered in an attempt to characterize the potential chronic toxicity for birds. Reproductive effects were noted in the lactofen and oxyfluorfen tests. Because the reported NOAECs and LOAECs are in part an artifact of the test concentrations selected and sufficient data points are not available to generate chronic dose

- response curves, no specific conclusions should be drawn regarding relative toxicity of the compounds. In the absence of more definitive chronic avian data for fomesafen, the Agency concludes that there is a chronic risk to insectivorous or herbivorous birds, reptiles, and/or terrestrial

-phase amphibians foraging in or near the treated area for all application rates. Potential effects on the fecundity of frugivorous birds foraging in or near the treated area should be anticipated for the 0.5 lb ai/A application rate.54

Table 26 Compar ison of Chronic Data for Acifluorfen, Fomesafen, and O xyfluorfen. Chemical Test Organism NOA EC (mg/kg diet) LOA EC

(mg/kg diet) Endpoints A ffected Avian Bobwhite quail (MRID 107491) 20 100 Reduced number of em bryos Acifluorfen (PC114401) Mallard duck

(MRID 107492) 100 >100 No endpoint affected Fomesafen Mallard duck

(MRID 135639) 46 >46 No endpoint affected Lactofen (PC128888) No chronic data available

Bobwhite quail (MRID 46070102) 124 256 Survivor weight, embryo survival, number of hatchlings Oxy fluorfen (PC111601) Mallard duck

(MRID 46070101) 506 751 Eggs laid, embryo survi val, number of hatchlings Mammalian Acifluorfen (PC114401) Rat

(MRID155548) 2500 ND No reproductive effects Fomesafen Rat

(MRID144862) 1000 ND No reproductive effects Lactofen (PC128888) Rat

(AC73859) 50 500 Reduced pup weight Oxy fluorfen (PC111601) R at

(MRID42014901) 400 1600 Decreased body weight, # live pups/litter 6.2.2 Mammals For mammals, no acute LOCs were exceeded at any application rate. The chronic LOC was exceeded onl y for small (15g) mammals eating short grass at the highest application rate (0.5 lb ai/A, pine seedlings in AR, GA, MS, NC , and SC). Thus effects on the endpoints of growth, survival, and fecundity are not anticipated at the 0.375 lb ai/A application rate. Open literature data demonstrated elevated levels of liver and fecal porphy rins in mice fed 100 mg/kg diet for 10 days (Krijt et al 1994b ). Based on TREX estimates of dietary EECs, only the 0.5 lb ai/A rate exceeds 100 mg/kg rate

. Given the existing body of data regarding fomesafen effects on the liver porphyrins of small mammals, effects on this biochemical endpoint appear unlikel y, although there is a difference in sensitivity amongst strains of mice ( Krijt et al 1994a). Where laboratory mice strains are in a species sensitivity distribution as compared to small wild mammals is unknown. 6.2. 3 Terrestrial Invertebrates 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

- gui deline studies on soil invertebrates, arthropods, and in aquatic mesocoms support this conclusion.55

Table 27 Summary of Risk to Non - Listed Terrestrial A nimals Clearance estimate Assessment Endpoint Application

Rate lb ai/A Size Class

(g) LOC Exceede nce 1 Distance from site (ft) Rate

(lb ai/A) Vertebrates 0.5 15

35 1000 No

No No Clears at current rate

0.375 15

35 1000 No

No No Clears at current rate Acute Risk to Mammals
0.17 15 35 1000 No

No No Clears at current rate

0.5 15

35 1000 Yes (SG)

No N o Aerial 0 2

Ground 10 0.47 3

Clear Clear 0.375 15

35 1000 No

No No Clears at current rate Ch ronic Risk to Mammals
0.17 15 35 1000 No

No No Clears at current rate

0.5 20

100 1000 No

No No Clears at current rate

0.375 20

100 1000 No

No No Clears at current rate Acute Risk to Birds, Terrestrial

phase Am phibians, and Reptiles 0.17 20 100 1000 No

No No Clears at current rate

0.5 All Yes (SG, TG, BL, SL) Aerial 10 0 Ground 10 0.19 2

0.375 All Yes (SG, BL) Aerial 100 Ground 10 0.19 2 Chronic Risk to B irds, Terrestrial

phase Am phibians, and Reptiles 0.17 All Yes (SG) Aerial 100 Ground 10 0.19 2 Invertebrates Acute Risk to Invertebrates All rates All Risk appears unlikely Not applicable 1 LOC exceedences using more conservative d ose - based estimates 2 AgDrift clearance estimate is ~45% deposition directly below aircraft 3 Clearance level is for short grass estimate 4 OPP does not currently have an acute risk LOC for non

- listed terrestrial invertebrates Feeding categories: short g rass (SG), tall grass (TG), broadleaf plants, small insects (BL), seeds, large insects (SL), granivore

- ma mmals only (G) NA

– Not applicable56 6.2. 4 Plants The non

- target organisms of greatest concern for fomesafen are plants in the overspray, runoff, and sp ray drift zones. Fate data do not indicate fomesafen is likel y to be subject to long

- range atmospheric transport, thus this route of exposure has not been addressed in the assessment. It is, however, persistent in soil, and may affect plants growing in the soil of treated fields or overspray areas for an extended period (approximately a year) following application. Because of the persistence, it is also likely to accumulate in fields repeatedly treated with fomesafen, even if the field is only treated in alternate years. The theoretical maximum concentration occurs in about 10 years if the field is treated in alternate years. Maximum residual concentration for an application rate of 0.375 lb ai/A is 0.29 lb ai/A, and for an application rate of 0.5 lb ai/A is 0.38 lb ai/A. These concentrations are greater than the seedling emergence EC 25 s of the most sensitive dicot (tomato, EC 25 0.005 lb ai/A) and the most sensitive monocot (onion, EC 25 0.084 lb ai/A). Shallow groundwater used for irrigation of agricul tural fields could potentially contain sufficient fomesafen to affect some crops. Based on estimated concentrations delivered to a field receiving 2 inches of irrigation water (0.0004

- 0.0077 lbs ai/A, based on application rate of 0.5 lb ai/A to field), sensitive crop species such as radish, lettuce, oilseed rape, and tomato (EC 25 s of 0.002

- 0.008 lb ai/A) could be affected. How long fomesafen will persist in the groundwater is not well defined. Fomesafen has the potential to adversel y a ffect plant communities of concern beyond the edges of the treated field. Plants potentially affected by fomesafen include crops in neighboring fields, hedgerows, riparian zones, and wetlands. Using AgDrift (Tier 1), EFED was unable to calculate the distance required for the acute plant risk to fall below the LOC for aerial applications, with toxicity predicted to occur at least to 900 ft beyond the application point for aerial applications and 300 ft for ground applications. Potential runoff effects to wetlands near the treatment site are difficult to evaluate, as the amount of runoff is greatl y influenced b y s lope, presence of buffers, and degrees of channelization in runoff swales. Wetlands receiving direct runoff from treated sites are likely to be affected. Because fomesafen is an herbicide, it may affect the primary productivity , community composition, and/or structure of herbaceous communities located near the margins of the treated fields. EFED has no data with which to evaluate the potential effect on woody plants, although given the mode of action for fomesafen (cell membrane disruption), woody plants may be more resistant. Modifications to the plant community may have significant effects on the populations of animals dependent on those communities.57

Table 28 Summary of Risk to Non - listed Terrestrial Plants Clearance estimate 1 Assessment Endpoint Ty pe of

Plant Ap plication

Rate lb ai/A LOC Exceedence 2 Distance from site (ft) Rate

(lb ai/A) Aerial Application 0.5 No 0.375 No 0.312 No 0.25 No Upland 0.17 No Clears at current rate (Based on runoff and drift) 0.5 Yes 0.375 Yes 0.312 Yes 0.25 Yes We tland 0.17 Yes 100 0.084
Ground Application 0.5 No 0.375 No 0.312 No 0.25 No Upland 0.17 No Clears at curren t rate (Based on runoff and drift) 0.5 Yes 0.375 Yes 0.312 Yes 0.25 Yes Acute Risk to Monocots

We tland 0.17 Yes 10 0.084
Aerial Application 0.5 Yes 0.375 Yes 0.312 Yes 0.25 Yes Upland 0.17 Yes

0.5 Yes 0.375 Yes 0.312 Yes 0.25 Yes We tland 0.17 Yes >900 0.002

Ground Application 0.5 Yes 300 0.375 Yes 200 0.312 Yes 200 0.25 Yes 150 Upland 0.17 Yes 80

0.5 Yes 3 00 0.375 Yes 200 0.312 Yes 200 0.25 Yes 150 Acute Risk to Dicots

We tland 0.17 Yes 80 0.002

1 Based on drift estimates from AgDrift, does not include runoff58



### 6.3 Endangered Species 6.3.1 Aquatic Listed Species No aquatic endangered species are at risk for direct effects f rom fomesafen. Although there are listed species LOC exceedences for freshwater non

- vascular plants, there were no listed freshwater non

- vascular plants at the time of this assessment. Additionally, no listed species have been identified as having an obl igate relationship with freshwater non

vascular plants. This results in a determination of no effect for aquatic organisms on the basis of direct effects. In direct effects to aquatic organisms are possible, based on potential effects on riparian and wetl and plant communities . For an evaluation of indirect effects, please see the section on endangered plants.
Table 29 Summary of Risk to Listed Aq uatic Organisms Assessment Endpoint Crops Estimator LOC Exceedence Freshwater Acute Toxicity to Fish and Aquatic

phase Amphibians Pine seedlings Cotton , Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Chronic Toxicity Fish and Aquatic

phase Amphibians Pi ne seedlings Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Acute Toxicity to Aquatic Invertebrates Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (so y, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Chronic Toxicity Aquatic Invertebrates Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Acute Toxicity to Aquatic Plants (non

- vascular) Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) Yes Yes No Acute Toxicity to Aquatic Plants (vascular) Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Saltwater Acute Toxicity to Fish Pine seedlings

Cotton, Beans (soy, snap, d ry ) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Chronic Toxicity to Fish Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Acute Toxicity to Aquatic Invertebrates Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Chronic Toxicity Aquati c Invertebrates Pine seedlings

Cotton, Beans (soy, snap, dry) Cotton, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No Acute Toxicity to Aquatic Plants Pine seedlings

Cotton, Beans (soy, snap, dry) Cotto n, Beans (soy, snap, dry) MS cotton (0.5lb ai ) TX cotton (0.375 lb ai) MI beans (0.375 lb ai) No No No59 6.3.2 Terrestrial Listed Species There are no listed species acute risk LOC exceedences for birds or mammals. Chronic risk LOCs were exceeded for herbivorous birds at all a pplication rates except the 0.17 lb ai/A rate (Region 5). Chronic risk LOCs were exceeded for insectivorous birds at applications rates of 0.375 lb ai/A and higher (Region 1 & 2). As birds are the surrogate for reptiles and terrestrial

-p hase amphibians, these exceedences also appl y t o those taxa. Exceedences are based on a non

- definitive endpoint from a guideline study, and thus may overestimate risk. In absence of a definitive endpoint , the Agency assumes effects may occur at any exposure concentrations about the established NOAEC. The AgDrift model was used to estimate the distances from the application site for exposure to drop below the level of concern based on the most conservative estimator (short grass). The resulting clearance distances were 10 ft for ground applications and 100 ft for aerial applications. Thus, for listed insectivorous and herbivorous birds, reptiles, or amphibians nesting or foraging within 100 ft of the application source, the direct effects determination i s may affect, likely to adversely affect. For organisms located greater than 100 ft away from the field , the direct effects determination is no effect. Table 31 and Table 32 show which species have been identified as potentially at risk, based on application rate, geographic location, and dietary habits. Indirect effects on listed birds, reptiles, and terrestrial

-phase amphibians are possible, based on potential effects o n plant communities and/or designated habitat . For an evaluation of indirect effects, please see the section on endangered plants. For mammals, there were no listed species acute risk LOC exceedences or chronic risk LOC exceedences for any of the existing Section 3 application rates. For application rates of 0.375 lb ai/A or less, the effects determination for mammals is no effect. Chronic risk LOCs were exceeded for the small herbivorous mammals (15g) at the 0.5 lb ai/A application rate, which applies only to pine seedlings in AR, GA, MS ,NC, and SC

. Based on the available data ( LOCATES and dietary information), no listed small herbivorous mammals occur in these locations.60

Table 30 Summary of Risk to Listed Terrestrial A nimals Clearance estimate Assessment Endpoint Ap plication

Rate lb ai/A Size

Class (g) LOC Exceedence 1 Distance from site (ft) Rate

(lb ai/A) Vertebrates 0.5 15

35 1000 No

No No Clears at current rate

0.375 15

35 1000 No

No No Clea rs at current rate Acute Risk to Mammals
0.17 15 35 1000 No

No No Clears at current rate

0.5 15

35 1000 Yes (SG)

No No Aerial 0 2

Ground 10 0.47 3

Clear Clear 0.375 15

35 1000 No

No No Clears at current rate Chronic Risk to Mammals
0.17 15 35 1000 No

No No Clears at curren t rate

0.5 20

100 1000 No

No No Clears at current rate

0.375 20

100 1000 No

No No Clears at current rate Acute Risk to Birds, Terrestrial

phase Am phibians, and Reptiles 0.17 20 100 1000 No

No No Clears at current rate

0.5 All Yes (SG, TG, BL, SL) Aerial 100 Ground 10 0.19 2

0.375 All Yes (SG, BL) Aerial 100 Ground 10 0.19 2 Chronic Risk to Birds, Terrestri al

phase Am phibians, and Reptiles 0.17 All No Clears at current rate Invertebrates 0.5 All Yes 0.375 All Yes Aerial 0 Ground 10 0. 28 Acute Risk to Invertebrates 0.17 All No Clears at current rate 1 LOC exceedences using more conservative dose

- based estimates 2 AgDrift clearance estimate is ~45% deposition directly below aircraft 3 Clearance level is for short grass estimate 4 OPP does not currently have an acute risk LOC for non

- listed terrestrial invertebrates Feeding categories: short grass (SG), tall grass (TG), broadleaf plants, small insects (BL), seeds, large insects (SL), granivore

- ma mmals only (G)61

Indirect Effects and Critical Ha bitat Effects (Birds, Reptiles, Amphibians, and Mammals) The most likely indirect effect on listed animals is modification of habitat as a result of damage to plants. The habitat modification could include reduced food supply, locations for nesting or bur

rowing, and/or reduced cover for predator avoidance

. Both monocots and dicots are affected by fomesafen, although based on available data, effects on sensitive species of dicots occur at lower concentrations. The assessment endpoint used for non

- listed p lant species is the EC 25 , a measure of a 25% reduction in the most sensitive endpoint for the most sensitive plant. Although plant sensitivity to fomesafen varies, determining the range of sensitivities in plant communities near application sites is beyond the scope of this assessment. For fomesafen, the most sensitive endpoints are ty picall y biomass and percent survival. While it is difficult to predict community

- level effects on the plant community supporting the listed plants, a 25% reduction in these endpoints is likely to reduce the viability of any affected population. Degradation of habitat could indirectl y a ffect listed species in a number of ways. Thus, for purposes of this assessment, exceedence of the non

- listed plant LOC is considered a “may affect, likely to adversel y affect” for listed animals, and has the potential to modify designated critical habitat for habitat located within 1 , 000 ft of aerial applications and 850 ft of ground applications. Potential mitigation measures include but are not limited to: 1) restricting applications of fomesafen within 1,000 ft of populations of endangered plants, and 2) restricting applications of fomesafen at sites where runoff to wetland areas is likely

. Removal of aerial application methods from the label is another possibility . However, in light of the fact that anticipated effects zones are almost as wide for ground applications, this may not be the most beneficial mitigation.62

Table 31 . Listed birds potentially at risk from fomesafen Common Name Scientific

Name Pine Soybean Cotton Dry Beans Snap

Beans Flycatcher, Southwestern Wi llow Empidonax

trailii extimus R1 R1 R1 Plover, Piping Charadrius

melodus R1 R1, R2 R1, R2 R1, R2 R1, R2 Tern, California Least Sterna

anti llarum browni R1 R1 R1 Tern, Interior Least Sterna

antillarum R1 R1, R2 R1 R1, R2 Wa rbler, Bachman’s Vermivora

bachmanii R1 R2 R1, R2 Wa rbler, Golden

cheeked Dendroica

chrysoparia R1 R1 R1 R1 R1 Wa rbler, Kirtland’s Dendroica

kirtlandii R1 R1, R2 R 1 R1, R2 Wo odpecker, Red

- cockaded Picoides

borealis R1 R1, R2 R1, R2 R1 R1, R2 Wo odpecker, Ivory- billed Campephilus

principalis R2 R263

Table 32 . Listed reptiles and amphibians potentially at risk from fomesafen Common Name Scientific

Name Pine Soybean Cotton Dry Beans Snap

Beans Frog, Dusk y Gopher Rana capito

sevosa R1 R1 Salamander, Cheat Mountain Plethodon

nettingi R2 R2 Salamander, Flatwoods Ambystoma

cingulatum R1 R1 R1 R1 Salamander, Red Hills Phaeognathus

hubrichti R1 R1 R1 R1 Salamander, Shenandoah Plethodon

shenandoah R2 R2 Toad, Houston Bufo

houstonensis R1 R1 R1 R1 R1 Tortoise, Gopher Gopherus

polyphemus R1 R1 R1 R1 R1 Turtle, Alabama Red

bellied Pseudemys

alabamensis R1 R2 R1 R1 Turtle, Norther n Bog Clemmys

muhlenbergii R1 R2 R2 Turtle Flattened Musk Sternotherus

depressus R1 R3 R1 R1 R1 Turtle Ply mo uth Red

bellied Pseudemys

rebriventris bangsi R3 Turtle, Ringed Sawback Graptemys

oculifera R1 R1 R1 R1 R1 Turtle, Yellow

blotched Map Graptemys

flavimaculata R1 R2 R1 R1 R164

Table 33 Summary of Risk to Listed Plants Clearance estimate 1 Assessment Endpoint Ty pe Ap plication Rate lb ai/A LOC Exceedence 2 Distance from site (ft) Rate

(lb ai/A) Aerial Application 0.5 Yes 0.375 Yes 0.312 Yes 100 0.03 0.25 No Upland 0.17 No Clears at current rate

0.5 Yes 0.375 Yes 0.312 Yes 0.25 Yes 100 0.03 We tland 0.17 No Clears at current rate Ground Application 0.5 Yes 20 0.03 0.375 No 0.312 No 0.25 No Up land 0.17 No Clears at current rate

0.5 Yes 20 0.375 Yes 0.312 Yes 0.25 Yes Acute Risk to Mono cots

We tland 0.17 Yes 10 0.03
Aerial Application 0.5 Yes 0.37 5 Yes 0.312 Yes 0.25 Yes Upland 0.17 Yes

0.5 Yes 0.375 Yes 0.312 Yes 0.25 Yes We tland 0.17 Yes >900 <0.002

Ground Application 0.5 Yes 300 0.375 Yes 200 0.312 Yes 200 0.25 Yes 150 Upland 0.17 Yes 80

0.5 Yes 300 0.375 Yes 200 0.312 Yes 200 0.25 Yes 150 Acute Risk to Dicots

We tland 0.17 Yes 80 <0.00265 6. 3

. 3 Plants Using LOCATES, a list of plants co

- occurring with labeled crops was generated. For crops listed only on S yn genta labels, which contain wording such that appl ication outside the designated regions would be considered misuse 2 , search parameters were constrained to only states listed on the label. BASF labels (soybeans onl y) contained less specific language, thus the search was nationwide, resulting in the inclu sion of Florida and Hawaii. Table 30 shows the number of species potentially affected by crop and state. Numbers of monocots and dicots are shown separately . Ferns, cycads, and lichens, for which no data were available, are listed with dicots, which are more sensitive to fomesafen. Direct Effects Exceedences of endangered species LOC (based on NOAECs) for the most sensitive plants tested constitute a “may affect” determination. Based on this definition, use of fomesafen may affect listed plants of all varieties located near the application site. Spray drift anal ys is using AgDrift (Tier I, Terrestrial Assessment, Point Deposition, ASAE fine to medium spray) resulted in clearance distances of approximately 1,000 ft for dicots, and 200 ft for monocots for aerial applications at a maximum rate of 0.375 lb ai/A. For ground applications, clearance distances were estimated at 850 ft for dicots and 20 ft for monocots. As no data are available to evaluate the sensitivity of endangered plants to fomesafen, all are conservatively assumed to be as sens itive as the most sensitive species tested. While plants are not subject to the same “take” definitions as animals, the dicot listed species clearance distances for fomesafen are approximately the same as the dico t clearance distances for non

- listed species, which are based on a 25% reduction in the most sensitive endpoint for the most sensitive plant. For fomesafen, the most sensitive endpoints are typicall y bi omass and percent survival. While it is difficult to predict community

- level effects on the plant community supporting the listed plants, a 25% reduction in these endpoints is likely to reduce the viability of any affected population. Thus, fomesafen is likely to adversel y a ffect dicots up to 1,000 ft away from the application point, and likely to adversel y affect monocots up to 100 ft away from the application point for aerial applications, based on the maximum application rate of 0.375 lb ai/A. For ground applications, the respective distances would be 85 0 ft for dicots, and 10 ft for monocots. Note that spray drift estimates do not take into the account the effects of runoff from the treated site . Because runoff conditions and the quality of vegetated buffers vary widel y from site to site, these effects are difficult to estimate in a general sense. However, except in cases of extreme channelization or nearly bare ground, runoff across a 1,000 ft

2 Clarification of label language provided in email from James Stone, Registration Division, OPP on May 1, 2008. BASF labels (7969

- 82, 7969

- 83) contain the phrase “intended for use” in certain geographic areas, which is too vague for use outside the listed areas to be construed as misuse.66

buffer is likel y to be low. Because fomesafen is less toxic to monocots, a grassy buffer would likely be more effective. Potential mitigation measures include but are not limited to: 1 ) restricting applications of fomesafen within 1,000 ft of populations of endangered plants, and 2 ) restricting applications of fomesafen at sites where runoff to wetland areas is likely

. Removal of aerial application methods from the label is another possibility . However, in light of the fact that anticipated effects zones are almost as wide for ground applications, this may not be the most beneficial mitigation. Indirect Effec ts Pesticide

- mediated indirect effects to plants are usually the loss of an important pollinator or dispersal species. Given the relativel y l ow toxicity of fomesafen to animals in general, the likelihood of these types of effects appears to be extremely l ow. Some endangered plant species may require the presence of other non

- endangered plant species to create a suitable habitat. Fomesafen effects on the habitat plants could constitute an indirect effect, but without detailed information on the plant’s li fe history and distribution, EFED is unable to even qualitatively evaluate this ty pe of effect. 6.3.4 Action Area The action area is determined based on the furthest range of anticipated effects. Based on the work of Russo et al (2007) and Russo and Madec (2007), it appears that fomesafen induces an immune response in freshwater snails and no definitive NOEC for this effect has been experimentall y determined . Therefore for purposes of the ESA, the action area is considered to be the entire U.S. Other than this sub

- lethal snail immune response, the most sensitive organisms evaluated are terrestrial dicots. Based on an analysis with AgDrift, deposition from aerial applications at the highest Section 3 rate (0.375 lb ai/A) at 950 ft away from the point of app lication will be 0.004 lb ai/A. The most sensitive endpoint is the dicot NOAEC of 0.002 lb ai/A. At approximately 1,000 ft, the decline curve in AgDrift based empirical measurements is as ympto tic. For a fine

- to

- medium droplet size spray , only 1.2% of applied will be deposited on the downwind side of the field, presuming no interception. Thus, for practical reasons, the extent of these dicot effects is estimated at 1,000 ft from point of application. This applies to all agricultural land in the regions where fomesafen is registered for use under the existing Sy ngenta labels.67

Table 34 Endangered Plants by Crop and State

Pine So ybeans Cotton Dry Beans Snap Beans State Monocot Dicot 1 Monocot Dicot 1 Monocot Dicot 1 Monocot Dicot 1 M onocot Dicot 1 AL 3 13 3 11 3 13 1 1 3 12 AR 0 3 0 2 0 3 CT 1 0 0 2 1 1 DC 2 0 DE 2 0 2 0 GA 6 12 6 12 4 12 6 11 IA 2 4 2 3 2 4 IL 2 7 1 7 IN 1 4 0 1 1 4 KS 1 1 1 1 1 1 KY 0 10 0 9 LA 0 2 0 2 MA 1 0 1 0 2 1 ME 2 1 2 1 2 1 MD 2 4 1 2 2 4 MI 3 3 3 2 3 5 MN 2 1 1 2 2 2 MO 1 7 0 3 0 1 2 2 MS 0 3 0 3 0 3 0 1 0 3 NC 5 21 5 21 3 16 1 5 5 22 ND 1 0 1 0 1 0 NE 1 1 1 2 1 0 NH 1 0 1 1 NJ 3 2 3 0 3 2 NY 1 5 1 5 1 5 OH 2 4 1 1 2 4 OK 2 0 2 0 PA 2 0 2 0 2 0 RI 0 1 1 1 SC 6 14 6 14 3 11 1 5 6 14 SD 1 0 1 0 1 0 TN 2 18 0 5 1 3 TX 2 5 2 14 2 24 2 11 2 13 VA 1 3 2 7 0 1 4 13 VT 0 1 0 1 WI 2 4 2 4 WV 0 1 1 4 BASF Labels only (soybeans nationwide) FL 1 25 HI 11 74 Dicot 1 This category also includes fern, lichens, and cycads, which are reported separately in LOCATES. Blank rows or section of rows indicate that crop does not co

- occ ur with any endangered plants in that state.68 6.3. 5 Probability of Individual Effects Generally , available toxicity data provides an LC 50 or an EC 50 , (the concentration at which 50% of the test populati o n exhibits the designated endpoint, usually mortality). Because the Endangered Species Act (ESA) requires determination of potential effects at an individual level, this information must be extrapolated from existing data. The Agency uses the probit dose response relationship as a tool for deriving the probability of effects on a single individual (U.S. EPA, 2004). The individual effects probability associated with the acute RQ is based on the mean estimate of the probit dose response slope and an assumption that that probit model is appropriate for the data set. In some cases, probit is not the appropriate model for the data, and EFED has low confidence in extrapolations from these types of data sets. In addition to a single effects probability estimate based on the mean, upper , and lower estimates of th e effects probability are also provided to account for variance in the slope, if available. The upper and lower bounds of the effects probability are based on available information on the 95% confidence interval of the slope. Individual effect probabilities are calculated based on an Excel spreadsheet tool IECV1.1 (Individual Effect Chance Model Version 1.1) developed b y the U.S. EPA, OPP, Environmental Fate and Effects Division (June 22, 2004 ). Probability of individual effects for the various assessment endpoints , if the acute RQ equals the endangered species LOC , is provided below in Table 35 . Probablity of individual effects is onl y evaluated for animals on an acute basis. For plant endangered species risk quotients and animal chronic risk quotients, the endpoint used is a no effect level, thus an evaluation of the probability of individual effects is not applicable.69

Table 35 Probability of Individual Effects Assessment Endpoint Surrogate

Species LC 50 and Slope Fits Probit Chance of

Individual Effect Acute Toxicity to FW Fish Rainbow

trout 126 m g/L and 9.7 (lower bound)

126 m g/L and 14.6 126 m g/L and 19.5 (upper bound)

At LOC of 0.05 Yes <1 in 10 16 <1 in 10 16 <1 in 10 16 1 in 4.2 × 10 8 Acute Toxicity to FW Aquatic Invertebrates Wa ter flea 376 m g/L and 3.9 (lower bound) 376 m g/L and 5.6 376 m g/L and 7.3 (upper bound) At LOC of 0.05 Yes 1 in 5.1x10 6 1 in 6.3x10 12 <1 in 10 16 1 in 4.2 × 10 8 Acute Toxicity to SW Fish Sheepshead

mi nnow >163 mg /L and 4.5 (default slope) At LOC of 0.05 No 1 in 2.9x10 5 NA Acute Toxicity to SW Aquatic Invertebrates Mysid

shrimp >163 mg/L and 4.5 (default slope) At LOC of 0.05 No 1 in 2.9x10 5 NA Acute Toxicity to Mammals Guinea pig 607 m g/kg and 4.5 (default slope ) At LOC of 0. 1 No 1 in 2.9x10 5 1 in 2.9 × 10 5 Acute Toxicity to Birds, Terrestrial phase Am phibians and Reptiles Mallard

duck Dose

>5,000 mg/kg and 4.5(default slope)

At LOC of 0. 1 Diet >20,000 mg/kg and 4.5(default slope)

At LOC of 0. 1 No 1 in 2.9x10 5 NA 1 in 2.9x10 5 NA N.A.

– No n - definitive endpoint.70



### 6. 4 Risk Conclusions Fomesafen is per sistent in surface and ground water, and has high potential to leach to ground water, given its mobility in soil. Ecologically , the organisms most at risk from fomes afen are terrestrial plants, especiall y dicots. Because terrestrial plants are important both ecologicall y (the y p rovide a critical part of both the structure and function that defines “habitat”) and economically (nearb y non - target, non

- treated crop plant s may be affected), these potential impacts are an important consideration. No LOCs were exceeded for aquatic endpoints except the listed species LOC for freshwater non

- vascular plants. At the time of this assessment, there were no listed non

- vascular freshwater plants, and no listed species had been identified as having an obligate relationship with freshwater non

- vascular plants. For terrestrial organisms, chronic LOCs were exceeded for birds (and b y extension, reptiles , and amphibians) at all but the lowest application rate

. Chronic LOCs were exceeded for mammals only for small herbivorous mammals at the highest application rate. These LOC exceedences appl y to both listed and non

- listed species. Based on spray drift estimations, clearance distances for chronic exceedences are well within the clearance distances for terrestrial plants, thus if terrestrial plants are protected, then b y virtue of sensitivity, other vulnerable organisms should be protected as well. Clearance distances for chronic effect s on birds, reptiles, amphibians, and mammals are 10 ft from the application source for ground applications (based on low boom estimates) and 100 ft for aerial applications (based on application parameters used in AgDrift Tier I estimates). For terrestrial plants, using drift estimates based on the more sensitive dicots, effects should be anticipated as far as 850 ft for ground applications, and 1,000 ft for aerial applications.71

Table 36 Summary of Direct and Indirect Effects Eva luation Organism LOCA TE S Category Direct Effects Indirect Effects Critical Habitat Effects

Monocots Monocots Yes Ground ≤100 ft Aerial ≤ 100ft from point of application No ? (only listed monocot affected is aquatic)

Other 1 No (No potentially affected species have designated critical habitat Dicots
Dicots Yes Ground ≤300 ft Aerial ≤ 900ft from point of application Yes

Potential for effects on other plants in the community. Alteration of habitat ma y create environment unsuitable to the listed species. Effects may occur up to Ground ≤300 ft Aerial ≤ 900ft from point of application Yes

(6 potentially affected species have designated critical habitat Birds Reptiles Birds Terrestrial

Phase Am phibians Mammals Mammals Yes Chronic Exceedences Ground ≤10 ft Aerial ≤ 100ft from point of application FW Aquatic Plan ts 2 FW Aquatic

Plants SW Aquatic Plants SW Aquatic

Plants FW Crustacea FW Bivalves FW Aquatic Invertebrates FW

Gastropods FW Fish FW Fish Aquatic

Phase Am phibians SW Crustacea SW Bivalves SW Aquatic Invertebrates SW

Gastropods SW Fish SW Fish No No LOC exceedences Yes

Potential for effects on other plants in the community. Alteration of habitat ma y create environment unsuitable to the listed species. Effects may occur up to Ground ≤300 ft Aerial ≤ 900ft from point of application Yes

Potential for effects on other plants in the community. Alteration of habitat ma y create environment unsuitable to the listed species. Effects may occur up to Ground ≤300 ft Aerial ≤ 900ft from point of application

1 Cycads, Conifers, Fern Allies. These genera have no direct corollary t est organism, and have been evaluated based on the most sensitive plant endpoint. 2 Evaluated based on both non

- vascular plants (algae) and vascular plants (duckweed)72



### 7.0 Uncertainties Risk assessment, by its very nature, is not exact, and requires the risk assessor to make assumptions regarding a number of parameters, to use data which may or may not accuratel y reflect the spe cies of concern, and to use models which are a simplified representation of complex ecological processes. In this risk assessment, EFED has attempted to locate the best available data regarding use and toxicity of fomesafen

. Frequently , such information are better expressed as ranges rather then points, and when this is the case, EFED has opted to make use of the end of range which would result in a conservative estimate of risk. These uncertainties, and the directions in which they may bias the risk estimate, are described below. 

### 7.1 Exposure Assessment Uncertainties 7.1.1 Aquatic Exposure Overall, the uncertainties inherent in the aquatic exposure assessment tend to result in over- estimation of exposures. This is apparent when comparing modeling result s with monitoring data. E stimated peak exposures are generall y 1

- 2 order s of magnitude above the highest detection s in the monitoring data . In general, the monitoring data should be considered a lower bound on exposure, while modeling represents an upper bound. The modeling conser

vativel y assumes that the receiving water body and the application site are adjacent

. 7.1.1.1 Modeling Assumptions The uncertainties incorporate d in the exposure assessment cannot be quantitatively characterized. However, given the available data and EFED’s policy to rely on conservative modeling assumptions, it is expected that the modeling results in an over

prediction in exposure. Qualitatively , conservative assumptions which may affect exposure include the following:

· The a ssessment assumes all applications within the modeled watersheds occur concurrently (same time and same day) at th e maximum application rate.
· The assessment assumes all applications are at maximum label rate. 7.1.1.2 Monitoring Data No surface water monito ring data was identified for fomesafen.

. Groundwater data was only available from the registrant submitted prospective groundwater study. 7.1.1.3 Impact of Vegetative Setbacks on Runoff EFED does not currently have an effective tool to evaluate the impact of vegetative setbacks on runoff and pesticide loadings. The effectiveness of such setbacks is highl y dependent on the condition of the vegetative strip. A well

- established, healthy vegetative73

setback can be a very effective means of reducing runoff and erosion from agricultural fields and may substantially reduce loading to aquatic ecos ys tems. However, a setback that is narrow, of poor vegetative quality, or channelized is likely to be ineffective at reducing loadings. The presence and quality of setbacks are site

- specific, and may vary widely , even within a small geographic area. EFED does not currently incorporate any “buffer reduction” in its runoff exposure estimates. Until such time as quantitative methods to estimate the effect of vegetative set backs of various conditions on pesticide loadings become available, EFED’s aquatic exposure predictions are likel y to overestimate exposure where healthy vegetative setbacks exist and may underestimate exposure where poorly developed, channelized or no set backs exist. 7.1.1.4 PRZM Modeling I nputs and Predicted Aquatic Concentrations EFED use d the linked PRZM/EXAMS model in this assessment , which produces estimated aquatic concentrations based on site conditions and historical mete orological files (generall y 30

- ye ar). The “peak” pesticide concentration used in the assessment is probability

-based, and is expected to be exceeded once within a ten

- ye ar period. PRZM is a process

-based "simulation" model, which calculates what happens to a pesticide in a farmer' s field on a day

- to

- day basis. It considers factors such as rainfall and plant transpiration of water, as well as how and when the pesticide is applied. The two major components are hydrology and chemical transport. Water movement in and off the field i s simulated by the use of generalized soil parameters, including field capacity, wilting point, and saturation water content. Soils in each scenario are selected to represent high availability conditions for the pesticide. The chemical transport component simulates the method of pesticide application on the soil or on the plant foliage and the environmental processes acting on the pesticide. Dissolved, adsorbed, and vapor

-phase concentrations in the soil are estimated by simultaneousl y considering the processes of pesticide uptake by plants, surface runoff, erosion, decay , volatilization, foliar wash

- off, advection, dispersion, and retardation. Uncertainty associated with each of these individual components adds to the overall uncertainty of the modele d concentrations. Equations in the model have not been shown to exert any directional bias. M odel inputs from the required environmental degradation studies are chosen to represent the upper confidence bound of the mean, and are not exp ected to be exceeded in the environment 90 % of the time. Mobility input values are selected to be representative of conditions in the open environment. N atural variation in soils adds to the uncertainty of modeled values. Factors such as application date, crop emergence date, and canopy cover can affect estimated concentrations

. Ambient environmental factors, such as soil temperatures, sunlight intensity , antecedent soil moisture, and surface water temperatures may cause actual aquatic concentrations to differ from the m odeled values

.
7.1.2 Terrestrial Exposure Uncertainties For terrestrial exposure estimates, the T

- REX model is used to estimate exposure and calculate RQs.74 7.1.2.1 Residue Levels Selection The Agency relies on the work of Fletcher et al (1994) for setting the a ssumed pesticide residues in wildlife dietary items. These residue assumptions are believed to reflect a realistic upper

-bound residue estimate, although the degree to which this assumption reflects a specific percentile estimate is difficult to quantify

. It is important to note that the field measurement efforts used to develop the Fletcher estimates of exposure involve highl y varied samp ling techniques. It is possible that much of these data reflect residues averaged over entire above ground plants in the case of grass and forage sampling. 7.1.2.2 Dietary Intake It was assumed that ingestion of food items in the field occurs at rates commensurate with those in the laboratory . Although the screening assessment process adjusts dry

weight estimates of food intake to reflect the increased mass in fresh

- weight wildlife food intake estimates, it does not allow for gross energy differences. Direct comparison of a laboratory dietary concentration

- based effects threshold to a fresh

- weight pesticide residue estimate would result in an underestimation of field exposure b y f ood consumption by a factor of 1.25

–2.5 for most food items. Differences in assimilative efficiency between laboratory and wild diets suggest that current screening assessment methods do not account for a potentiall y important aspect of food requirements. Depending upon species and dietary matrix, bird assimilation of wild diet energy ranges from 23

– 80%, and mammal’s assimilation ranges from 41

– 85% (U.S. Environmental Protection Agency , 1 993). If it is assumed that laboratory chow is formulated to maximize assimilative efficiency (e.g., a value of 85%), a potential for underestimation of exposure may exist by assuming that consumption of food in the wild is comparable with consumption during laboratory testing. In the screening process, exposure may be underestimated because metabolic rates are not related to food consumption.75



### 7.2 Effects Assessment Uncertainties 7.2 .1 Age Class and Sensitivity of Effects Thresholds It is generall y recognized that test organism age may have a significant impact on the observed sensitivity to a toxicant. For guideline tests, young ( and theoretically more sensitive) organisms are used

. Testing of juveniles may overestimate toxicity at older age classes fo r active ingredients of pesticides which act directl y (without metabolic transformation) on the organism, because younger age classes often have not developed enzy matic s ys tems associated with the detoxification of xenobiotics. When the available toxicity data provide s a range of sensitivity information with respect to age class, the risk assessors use the most sens itive life

- stage information as measures of effect

. 7.2.2 Use of Surrogate Species Data Currently , there are no FIFRA guideline toxicity tests for amphibians or reptiles

. Therefore, in accordance with EFED policy , data for the most sensitive freshwater fish are used as a surrogate for aquatic

-phase amphibians, and data for the most sensitive bird are used as a surrogate for terrestrial

-phase amphibians and reptiles. Use of data from the most sensitive organism is assumed to be protective of the majority of other organisms which may encounter the pesticide. 7.2.3 Extrapolation of Effects Length of exposure and concurrent environmental stressors will likely affect the response of the organism to fomesafen . Because of the complexity of an organism’s response to multiple stressors, the overall direction of the response is unknown. Additional environmental stressors may decrease or increase the sen sitivity to the herbicide. Timing, peak concentration, and duration of exposure are critical in terms of evaluating effects, and these factors will vary both temporall y and spatially . Overall, the effect of this variability may result in either an overes timation or underestimation of risk 7.2.4 Acute LOC Assumptions The risk characterization section of this assessment includes an evaluation of the potential for individual effects. The individual effects probability associated with the acute RQ is based o n the assumption that the dose

- response curv e fits a probit model. It uses the mean estimate of the slope and the LC 50 to estimate the probability of individual effects.76



### References Barron, MG, Little EE, Calfee R, and S. D iamond. 2000. Quantifying solar spectral irradiance in aquatic habitats for the assessment of photoenhanced toxicity

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- 925. Diamond, SA, Trenham, PC, Adams MJ, Hossack, BR, Knapp, RA, Stark, SL , Bradford, D, Corn PS, Czarnowski, K, Brooks, P D Fagre, D, Breen , B, Detenbeck NE, and K Tonessen. 2005. Estimated Ultraviolte radiation doeses in wetlands in six national parks. Ecosystems . 8:462

- 477. EFED. 2007. Memo on: Environmental Fate and Effects Division recommendation regarding the light dependent peroxidizing herbicides (LDPHs), DP Barcode D333803, dated 4/16/2007. Fletcher, J.S., J.E. Nellesson and T. G. Pfleeger. 1994. Literature review and evaluation of the EPA food

- chain (Kenaga) nomogram, an instrument for estimating pesticide resi dues on plants. Environ. Tox. And Chem . 13(9):1383

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. HED 2006. Fomesafen sodium human health risk assessment for a proposal to amend se on soy beans and proposals to add uses on cotton, dry beans, and snap beans. DP Barcode D325797, dated 2/28/06. Matringe, M, Camadro, J

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- 235. Roberts , T. (Ed.). 1998. Metabolic Pathways of Agrochemicals, Part One: Herbicides and Pl ant Growth Regulators. Royal Society of Chemistry, Cambridge. 849pp. Smith, L .L . and Elcombe, C.R., 1989. Mechanistic studies: their role in the toxicological evaluation of pesticides. Food Addit. Contam. 6 Suppl. 1, pp. S57

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### Guideline Study References 71
- 1 Avian Single Dose Oral Toxicity77

163168 Roberts, N.; Fairley , C. (1981) The Acute Oral Toxicity (LD50) of PP021 to the Mallard Duck: ICI/370/WL/80792. Unpublished study prepared by Huntingdon Research Centre. 16 p 71
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72
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- ous Sodium Salt (GFU060) to the Sheepshead Minnow: Report No. TMUE0019/B. (Unpublished study received Nov 22, 1983 under 10182

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- ous Sodium Salt (GFU 060) to the Pink Shrimp: Report No. TMUE0021/B. (Unpublished study received Nov 22, 1983 under 10182

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64314 Hofmann, H.T.; Freisberg, K.O. (1974) Acute Oral Toxicity of the Sodium Salt of 3

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- 1H

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- Butyl/Fomesafen: Acute Oral Toxicity to the Rat of a 0.75/1.0 lb/US gal Formulation: Rept. No. CTL/P/ 1971. Unpublished study prepared b y Imperial Chemical Industries, Ltd. 27 p. 43236202 Duerden, L. (1994) Fomesafen: Acute Oral Toxicity to the Rat of a 120g/l ME Formulation: Lab Project Number: CTL/P/4371: AR5709. Unpublished study prepared by Zeneca Central Toxicology Lab. 49 p. 43949801 Lees, D.; Connolly , H. (1996) Fomesafen: Acute Oral Toxicity to the Rat of a 240 g/l SL Formulation: Lab Project Number: AR6152: CTL/P/4912. Unpublished study prepared b y Zen eca Central Toxicology Lab. 59 p. 44030101 Robinson, P. (1996) Flexstar HL (Fomesafen): Acute Toxicity Study in Rats of a 225.57 g/l ME Formulation: Lab Project Number: AR6173: CTL/P/4949. Unpublished study prepared by Zeneca Central Toxicology Laboratory . 62 p. 44032401 Rob inson, P. (1996) Fomesafen Sodium Salt Aqueous Concentrate: Acute Oral Toxicity Study in Rats of a 316.1 g/L MUP Formulation: Lab Project Number: AR6155: CTL/P/4979. Unpublished study prepared by Zeneca Central Toxicology Lab. 62 p. 44036702 Robinson, P. (1996) Twister: Fomesafen/Fenoxaprop/Fluazifop

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