# Environmental Fate and Ecological Risk Assessment for the Registration of Penflufen

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Penflufen N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1 H -pyrazole-4-carboxamide CAS Registry Number: 494793-67-8

PC Code: 100249

Prepared by:
Reuben D. Baris, Environmental Scientist Brian D. Kiernan, Biologist
U. S. Environmental Protection Agency Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch IV

1200 Pennsylvania Ave., NW

Mail Code 7507P Washington DC 20460 Reviewed by: Melissa Panger, Ph.D, Senior Biologist ERB III
William P. Eckel, Ph.D, Senior Science Advisor, ERB VI
Mark Corbin, Branch Chief, ERB VI

Date: November 23, 2011-Page 2 of 115- Table of Contents

1. Executive Summary ........................................................................................................................... 4

1.1. Nature of Chemical Stressor ........................................................................................................ 4

1.2. Potential Risks to Non-target Organisms .................................................................................... 4

1.3. Conclusions - Exposure Characterization .................................................................................... 5

1.4. Conclusions - Effects Characterization ....................................................................................... 6

2. Problem Formulation ......................................................................................................................... 8

2.1. Nature of Regulatory Action ....................................................................................................... 8

2.2. Stressor Source and Distribution ................................................................................................. 8

2.2.1. Nature of Chemical Stressor ................................................................................................. 8

2.2.2. Overview of Pesticide Usage .............................................................................................. 10

2.3. Receptors

.............................................................................................................................. ..... 10

2.3.1. Aquatic and Terrestrial Effects ........................................................................................... 10

2.3.2. Ecosystems Potentially at Risk ........................................................................................... 11

2.4. Assessment Endpoints ............................................................................................................... 11 2.5. Conceptual Model ...................................................................................................................... 11

2.5.1. Risk Hypotheses .................................................................................................................. 12

2.5.2. Conceptual Diagram ........................................................................................................... 12 2.6. Analysis Plan ............................................................................................................................ 1 4

2.6.1. Residues of Concern ........................................................................................................... 14

2.6.2. Preliminary Identification of Data Gaps and Uncertainties ................................................ 14

2.6.3. Evaluation of Multiple Active Ingredients and Mixtures .................................................... 15

2.6.4. Measures of Exposure ......................................................................................................... 15

2.6.5. Measures of Effect .............................................................................................................. 16

2.6.6. Integration of Exposure and Effects .................................................................................... 18 3. Analysis

.............................................................................................................................. ............. 19

3.1. Use Characterization .................................................................................................................. 19

3.2. Exposure Characterization ......................................................................................................... 20

3.2.1. Environmental Fate and Transport Characterization .......................................................... 20

3.2.2. Measures of Aquatic Exposure ........................................................................................... 29

3.2.3. Measures of Terrestrial Exposure ....................................................................................... 35

3.3. Ecological Effects Characterization .......................................................................................... 36

3.3.1. Aquatic Toxicity Assessment .............................................................................................. 37

3.3.2 Terrestrial Effects Characterization .................................................................................... 46

4. Risk Characterization ...................................................................................................................... 56

4.1. Risk Estimation ......................................................................................................................... 56

4.1.1. Aquatic Organisms .............................................................................................................. 57

4.1.2. Terrestrial Organisms .......................................................................................................... 58

4.2. Risk Description........................................................................................................................ 60

4.2.1 Exposure to Aquatic Organisms ......................................................................................... 60

4.2.2 Risks to Aquatic Animals ................................................................................................... 61

4.2.3 Risks to Aquatic Plants ....................................................................................................... 63

4.2.4. Risks to Mammals ............................................................................................................... 64

4.2.5. Risk to Birds ....................................................................................................................... 64

4.2.6. Potential Effects on Terrestrial Invertebrates ...................................................................... 65

4.2.7. Risk to Terrestrial Non-target Plants ................................................................................... 66

4.3. Uncertainties and Data Gaps ..................................................................................................... 67

4.3.1. Fate and Transport .............................................................................................................. 67-Page 3 of 115- 4.3.2. Effects Uncertainties ........................................................................................................... 67

4.3.3. Aquatic Exposure ................................................................................................................ 68

5. Federally Threatened and Endangered (Listed) Species Concerns ............................................. 69

5.1. Action Area

.............................................................................................................................. . 70

5.2. Taxonomic Groups Potentially at Risk ...................................................................................... 70

5.2.1. Probit Dose-Response Analysis .......................................................................................... 72

5.2.2. Listed Species Occurrence Associated with Penflufen Use ................................................ 73

6. References

.............................................................................................................................. ........... 74

6.1. Submitted Product Chemistry and Environmental Fate Studies ................................................ 75

6.2. Submitted Ecotoxicity Studies ................................................................................................... 77 Appendix A. Chemical Names, Structures, and Maximum Reported Amounts of Penflufen and Its Degradates.

.............................................................................................................................. .................. 86 Appendix B. Tier 2 Summary Catalog of Submi tted Ecological Effects Studies for Penflufen. ....... 91 Appendix C. Catalogue of Submitted Environmental Fate Studies for Penflufen. ............................ 96 Appendix D. Product Chemistry and Envi ronmental Fate Summary of Penflufen ........................ 100 Appendix E. Aquatic Model Input/Output Data. ................................................................................ 108 Appendix F. Federally Listed Species Potentially at Risk from the Proposed Uses of Penflufen ... 111-Page 4 of 115- 1. Executive Summary

1.1. Nature of Chemical Stressor

Bayer CropScience is seeking registration for the new chemical fungicide penflufen (BYF
14182; N -[2-(1,3-dimethylbutyl)pheny l]-5-fluoro-1,3-dimethyl-1 H -pyrazole-4-carboxamide ; CAS#: 494793-67-8; PC code: 100249). Penflufen is a succinate dehydrogenase inhibitor (SDHI) in the pyrazole carboxamide class of chemical s. It is proposed for use as a fungicide seed treatment for protection against certain soilborne, seedborne, a nd post-emergence diseases of crop plants.

This assessment is for a national registration request for the following seed treatment uses: alfalfa, beans and peas (including soybeans), ca nola, mustard (oilseed and condiment), rapeseed, cotton, cereal grains, corn, sorghum, sunflower, sa fflower, potato seed pieces, and rice (not for application to flooded fields). In addition, Bayer is proposing an in-furrow spray application for potato and other tuberous corm vegetables at plan ting in combination with the treatment of seed pieces or seed. Maximum application rates range from 0.001 to 0.28 lbs a.i./A/yr. This assessment is based on proposed maximu m application rates for all uses.

Seven end-use formulations of penflufen are pr oposed for registration in the United States. Some of the proposed labels include multiple co-formulated currently registered active ingredients for use as seed treatments ( e.g., penflufen plus clothi anidin, trifloxystrobin, metalaxyl, or prothioconazole). The Agency does not routinely include an evaluation of mixtures of active ingredients in its risk assessments. In the cas e of the product formulations of active ingredients (that is, a regi stered product containing more than one active ingr edient), each active ingredient is subject to an individual risk assessment for regulatory decision regarding the active ingredient for a particular use site. Howe ver, acute mammalian toxicity data are available for several combinations of active ingredients us ed in proposed products and no toxic effects are reported. Data on coformulants are not available for any other taxa.

Major transformation products resulting from the environmental degradation of penflufen are penflufen-3-hydroxy-butyl (pen-3HB), penflu fen-pyrazolyl-AAP (AAP), and under certain circumstances, BYF 14182-fluoro acidand carbon dioxide. Eco-toxicity data are available for pen-3HB and AAP showing that pen-3HB and AAP are no more, and often less, toxic compared to the technical grade active ingr edient (TGAI), based on the most sensitive taxa tested. Aquatic exposure estimates are thus based on exposure fr om penflufen penflufen alone. Terrestrial exposure estimates are based on the residue levels of the parent compound alone.

1.2. Potential Risks to Non-target Organisms

The results of this screening-level assessment on th e proposed penflufen uses indicate that risk of adverse effects to non-target organisms is gene rally not expected. However, because a NOAEC was not determined in the available mallard duck ( Anas platyrhynchos ) reproduction study, risk from chronic exposure to listed and non-listed bird s, reptiles and terres trial-phase amphibians-Page 5 of 115- cannot be precluded. Additionally, the proposed use as a treatment for rice seed results in an RQ equal to the listed species acute LOC for fish a nd surrogates (aquatic-phase amphibians).

Table 1.1. Potential Effects to Federally List ed Taxa Associated with Direct or Indirect Effects from the Proposed New Uses of Penflufen.

Listed Taxon Direct Effects Indirect Effects a

Terrestrial and semi-aquatic plants - monocots No Yes

Terrestrial and semi-aquatic plants - dicots No Yes

Birds Yes Yes Terrestrial-phase amphibians and reptiles Yes Yes

Mammals No Yes Aquatic nonvascular plants No Yes

Aquatic vascular plants No Yes

Freshwater fish Yes Yes Aquatic-phase amphibians Yes Yes

Freshwater crustaceans No Yes

Mollusks No Yes

Marine/estuarine fish No Yes

Marine/estuarine invertebrates No Yes

a until an endangered species assessment is complete, indirect effects to all species cannot be precluded

1.3. Conclusions - Exposure Characterization

Penflufen is expected to persis t in both terrestrial and aquati c environments under aerobic and anaerobic conditions, an d is considered moderately m obile, lipophilic, and nonvolatile. Penflufen is persistent in soil, with half-lives ranging from 11 5 to 433 days in aerobic soil and extrapolated half-lives of nearly two and a half years in anaerobic soil. Th ere is no evidence of degradation via hydrolysis, which was studied across environmental pHs. Laboratory data show that penflufen degraded slowly by aerobic aqua tic metabolism with half-lives ranging from 267 to 301 days. A potentially major route of degradation in shallow, clear waters ( e.g., applications to flooded rice paddies) may be aqueous photolys is (environmental half-life of 83 days); however photolysis is slow and plays a significant role in shallow clear waters. Penflufen does

not bioconcentrate in aquatic organisms.

Aquatic exposure estimates are based on the expo sure of the parent compound penflufen only. There were significant amounts of unextracted residues reported in the metabolism studies, and multiple extraction solvents were not explore d. The applicant submitted supplemental data characterizing the unextracted residues addres sing the uncertainty about whether or not the unextracted residues are parent. The study compared extractions in sterile (gamma-irradiated) and non-sterile (viable) soils (M RID 48652501). These data suggest that a large portion of the unextracted residues reported in the metabolis m studies are biological ly mediated and are hypothesized to be irreversibly bound. Therefore, conservative aquatic exposure estimates were generated using environmental half -lives for the parent only.

Modeled uses include the potato seed piece treatm ent and combined in-furrow spray, peas and bean seed treatment (including legumes and soybean s), and the rice seed treatment. These uses result in the maximum exposure for each type of application method. Therefore, they provide-Page 6 of 115- conservative estimates of exposure for the proposed uses with lower application rates and similar application methods that were not modeled. The range of all proposed us es are listed in Table

3.1.

Acute 1-in-10 year estimated environmental concentr ations (EECs) in surface water (for parent + unextracted residues) for all modeled uses of penflufen ranged from 1.13 μg/L to 4.71 μg/L.

Use for rice seed resulted in an exceedence of th e level of concern (LOC) for listed fish (an EEC of 4.71 μg/L for rice). A reduction in the application rate for rice from 0.006 lbs a.i./A to 0.005 lbs a.i./A would reduce the peak EEC from 4.71 μg/L to 3.93 μg/L, whic h would mitigate the

exceedance for listed fish desc ribed above in Section 1.2.

Terrestrial exposure estimates are based on the re sidue levels of penflufen on seed alone, as described above. The in-furrow treatment for seed pieces is treated as an additional seed treatment in this assessment, in that the seed pi ece per acre rate and the in-furrow per acre rate are added together to generate a conservative estimate of exposure. Seeding rates were used to calculate a dose on a per area basis of treated se ed that terrestrial animals may use as forage items. Penflufen is locosystemic and is not tr ansported acropetally in foliage as the plants emerge and grow; therefore the greatest exposure is expected from animals directly ingesting

treated seed.

1.4. Conclusions - Effects Characterization

Aquatic Organisms

Results of acute toxicity studies in freshwater and estuarine/marine fish indicate that penflufen is highly to very highly toxic to fish on an acute ex posure basis. Dose-dep endent sublethal effects observed in fish studies included surfacing, leth argy, erratic swimming, loss of equilibrium, loss of vertical orientation, labored respiration, and lying on the bottom. Reduced fish length was observed in the F1 generation of the available early life-stage (ELS) st udy. Acute toxicity studies indicate that penflufen is moderately toxic to freshwater and estuarine/marine invertebrates on an acute exposure basis. Quie scence, pale color and abnormal positioning were the reported sublethal effects in invertebrates. Penflufen has effects on aquatic vascular and nonvascular plants, with biomass and ce ll density being adversely affected.

Degradate toxicity data on fis h, aquatic invertebrates and gree n algae indicate that penflufen degradates are less toxic than the parent and eff ects are not expected at environmentally relevant

concentrations.

Terrestrial Organisms

Penflufen is practically n on-toxic to Norway rat ( Rattus norvegicus ) on an acute exposure basis. A two-generation study on reproduction and fertility in the rat showed penflufen to cause chronic toxicity effects in the parents and F 1 and F 2 generations that would impact adult body weights

and reduced litter size.-Page 7 of 115- Studies of acute oral (dose-base d) toxicity in bobwhite quail ( Colinus virginianus ) and canary ( Serinus canaria ) indicated that penflufen is practical ly nontoxic to bobwhite quail and canary when administered as a single or al dose. Two subacute dietary toxicity studies indicate that penflufen TGAI is also practic ally nontoxic to mallard duck and bobwhite quail on a subacute dietary exposure basis. For ch ronic effects, there were treatme nt-related effects on the number of eggs hatched per live embryo at all tested conc entrations in the reprodu ction toxicity study of penflufen TGAI in mallard duck; no endpoint ( i.e. , NOAEC) was derived in the study. No effects were reported in the bobwhite quail study. No studies of the formulations or the degradates were submitted for birds; all meas urement endpoints for avian species are based on technical grade penflufen.

Results of available toxicity studies indicate that penflufen TGAI is practically nontoxic to honey bees ( Apis mellifera ) on an acute exposure basis, though th ere are effects on the fecundity of Aphidius rhopalosiphi , a parasitoid wasp, and earthworms ( Eisenia foetida ) on an acute contact exposure basis. It is not clear from the available data whether there would be effects on larval bee pollinators or what the rout e of exposure would likely be. However, a study on larval bees would reduce this uncertainty.

Tier I limit studies of the effect of the penf lufen formulation PEN 240FS on seed emergence and vegetative vigor in terrestrial plants were s ubmitted, indicating that terrestrial plants are relatively insensitive to penflufen at applicati on rates slightly less than the maximum per acre application rate for the proposed registration uses.-Page 8 of 115- 2. Problem Formulation

The purpose of problem formulation is to provid e the foundation for the environmental fate and ecological risk assessment for the registration of the new chemical penflufen, (BYF 14182; N -[2- (1,3-dimethylbutyl)phenyl] -5-fluoro-1,3-dimethyl-1 H -pyrazole-4-carboxamide ; CAS#: 494793- 67-8; PC code: 100249). The problem formulation sets the objectives for the risk assessment, establishes a risk hypothesis and conceptual mode l depicting potential ri sk, and provides a plan for analyzing the data and characterizing the risk associated with the proposed use of penflufen (USEPA, 1998).

2.1. Nature of Regulatory Action

The U.S. Environmental Protection Agency (EPA or the Agency) is required under the Federal Insecticide, Fungicide, and Rode nticide Act (FIFRA) to ensure that the newly proposed use of penflufen as a fungicide does not have the potenti al to cause unreasonable adverse effects to the environment. In addition to non-target animals an d plants, potential effect s to listed species ( i.e.

, species on the Federal list of endangered and thr eatened wildlife and plan ts) and their designated

critical habitat are also considered under the Endangered Species Act (ESA) in order to ensure that the registration of penflufe n is not likely to jeopardize th e continued existence of listed species or adversely modify their critical habitat. In order to meet the requirements of FIFRA and the ESA, this assessment follows EPA guidance on conducting ecologi cal risk assessments (USEPA, 1998) and Office of Pesticide Progr am’s Overview Docume nt, which contains guidance for assessing pesticide risks to non- target and listed or ganisms (USEPA, 2004).

The end result of the EPA pesticide registration process ( i.e. , the FIFRA regulatory action) is an approved (or disapproved) product la bel. The label is a legal doc ument that stipulates how and where a given pesticide may be used. Product labe ls (also known as end-use labels) describe the formulation type ( e.g. , liquid or granular), acceptable methods of application, approved use sites, and any restrictions on how applications may be c onducted. Therefore, the us e, or potential use, described by the pesticide’s labels is consider ed “the action” being assessed. This assessment was prepared to support evaluation of the propos ed new chemical registration of penflufen.

2.2. Stressor Source and Distribution

2.2.1. Nature of Chemical Stressor

Bayer CropScience is seeking registration for the use of the new chemical fungicide penflufen (BYF 14182), N-[2-(1,3-dimethylbutyl )phenyl]-5-fluoro-1,3-dimethyl-1 H -pyrazole-4- carboxamide. According to Bayer, penf lufen is a locosystemic fungicide ( i.e., is available in the cells of new sprouts but is not transported in xylem or phloem) that is intended to inhibit mitochondrial respiration by blocki ng electron transport in the re spiratory chain of succinate dehydrogenase ( i.e. , the compound is a succinate dehydrogenase inhibitor or SDHI). Penflufen is intended to provide protection to seedlin gs against fungal pat hogens by acting on spore germination, germ tube elongation, and mycelium gr owth. This assessment is part of a national-Page 9 of 115- registration request for a fungici de seed treatment for protecti on against certain soilborne, seedborne, and post-emergence fung al diseases of crop plants.

Penflufen is in the pyrazole carboxamide family of fungicides. Bayer is proposing the following seed treatment uses: alfalfa, beans and peas (i ncluding soybeans), canola, mustard (oilseed and condiment), rapeseed, cotton, cere al grains, corn, sorghum, sunf lower, safflower, potato seed pieces, and rice (not for use in flooded fields). In addition, Bayer is proposing an in-furrow spray application for potato and other tuberous corm ve getables at planting in combination with the treatment of seed pieces or seed. This asse ssment is based on proposed maximum application

rates for all uses.

Seven end-use formulations of penflufen are propos ed for registration in the United States. They include the following:

1. PEN 240FS: 22.7% penflufen, used as a seed treatment for alfalfa, beans and peas (including soy), canola and other oilseed crops, cotton, cereal grains, corn (field, sweet, popcorn), sorghum, sunflower and safflower , rice, potato (seed piece and in-furrow application).

2. PENCLO 273.5FS: 6.0 % penflufen (co-formulated with clothianidin (18.6%)), used to treat potato seed pie ces, and cotton seed.

3. PENCLOTRIME 310.68FS: 0.82 % penflufen (co-fo rmulated with clothianidin (22.3%), trifloxystrobin (0.55%), and metalaxyl (0.55%)), used to treat canola, rapeseed and mustard (oilseed and condiment) seed.

4. PENPRO 118FS: 9.35 % penflufen (co-formulated with prothioconazole (1.68 %)), used to treat potato seed pieces and wheat seed.

5. PENPROME 177FS: 3.59 % penflufen (co-form ulated with prothi oconazole (7.18%), and metalaxyl (5.74%)), used to treat alfalfa, beans and peas (including soybean), cereal grains, and rice seed.

6. PENRED 240FS: 22.4% penflufen, used as a s eed treatment for alfalfa, beans and peas (including soy), canola and other oilseed crops, cotton, cereal grains, corn (field, sweet, popcorn), sorghum, sunflower and safflower , rice, potato (seed piece and in-furrow application).

7. PENTRI 308FS: 13.3% penflufen (co-formulated with trifloxystrobin (13.3 %), used as a seed treatment for alfalfa, beans, wheat, corn, sorghum, cotton, and rice.

Penflufen is formulated as a flowable concentrate for seed treatment. It is applied primarily to seed or potato seed pieces, although the propos ed labels recommend an additional in-furrow spray for seed piece plantings. The in-furrow a pplication is applied as a near-surface spray before the seed pieces (and the in-furrow applied material) are covered in soil.

The proposed maximum annual application rates are on potato seed pieces. The seed pieces are treated at a rate of 0.14 lbs ai/A (based on a seed ing rate of 6,969 lbs/A and an application rate of 0.13 fl oz product/100 lbs of seed). An additiona l 0.14 lbs ai/A can be applied in-furrow, for a total mass applied (on a per acre basis) of 0.28 lbs. Other seed treatments are proposed at lower proposed rates as discussed in Section 3.1.-Page 10 of 115- 2.2.2. Overview of Pesticide Usage

Usage data are not available for penflufen because it is a new active ingredient proposed for use

in the United States.

2.3. Receptors

2.3.1. Aquatic and Terrestrial Effects

In ecological risk assessment, a receptor is a biological entity that is exposed to a stressor (USEPA, 1998). Consistent with the process described in the Overvi ew Document (USEPA, 2004), this risk assessment uses a surrogate speci es approach in its ev aluation of penflufen. Toxicity data generated using surr ogate test species, which are inte nded to be representative of broad taxonomic groups, are used to infer potential effects on a variety of speci es (receptors)

included under these broa der taxonomic groupings. Table 2.1 provides the general taxonomic groups and surrogate species tested to evaluate po tential ecological effects of penflufen to broad classes of non-target organisms. Within each of these taxonomic groups, a measure of effect is selected from among the avai lable test data.

Table 2.1. Taxonomic Groups and Test Sp ecies Evaluated for Assessing Potential Ecological Effects of Penflufen.

Taxonomic Group Typical Species

Birds 1 Mallard duck ( Anas platyrhynchos ) Bobwhite quail ( Colinus virginianus )

Mammals Norway rat ( Ratus norvegicus )

Invertebrates Honey bee ( Apis mellifera L. )

Freshwater fish 2 Bluegill sunfish ( Lepomis macrochirus ) Rainbow trout ( Oncorhynchus mykiss ) Fathead minnow ( Pimephales promelas )

Freshwater invertebrates Water flea ( Daphnia magna ) Midge ( Chironomus riparius )

Estuarine/marine fish Sheepshead minnow ( Cyprinodon variegatus )

Estuarine/marine invertebrates Mysid ( Americamysis bahia ) Eastern oyster ( Crassostrea virginica ) Terrestrial plants 3 Monocots – Crop species, such as corn ( Zea mays ) Dicots – Crop Species, such as soybean ( Glycine max ) Aquatic plants and algae Duckweed ( Lemna gibba ) Freshwater Algae ( Pseudokirchneriella subcapitata )

1 Birds represent surrogates for terrest rial-phase amphibians and reptiles.

2 Freshwater fish may be surroga tes for aquatic-phase amphibians.

3 Four species of two families of monocots, of which one is corn; six species of at least four dicot families, of which one is s oybeans.-Page 11 of 115- 2.3.2. Ecosystems Potentially at Risk

The ecosystems potentially at risk are often extensive in scope; therefore, it may not be possible to identify specific ecosystems during the deve lopment of a nation-wide ecological risk assessment. However, in general terms, terrest rial ecosystems potentially at risk could include the treated field and immediately adjacent areas th at may receive drift or runoff. Areas adjacent

to the treated field could incl ude cultivated fields, fencerow s and hedgerows, meadows, fallow fields or grasslands, woodlands, riparian habitats, and other un cultivated areas.

Aquatic ecosystems potentially at risk include wa ter bodies adjacent to or downstream from use sites, and might include impounded bodies such as ponds, lakes and reservoirs, or flowing waterways such as streams or rivers includi ng all adjacent off-channel habitats that are permanently or intermittently connected to flowin g waters. For uses in coastal areas, aquatic habitat also includes marine ecosystems, in cluding estuaries, embayments, and near-shore

environments such as tidal marshes.

Given that the proposed penflufen use is primar ily as a seed treatment, exposure to ecosystems through spray drift is expected to be minimal, as the in-furrow tr eatment is sprayed close to the ground and immediately covered in 3”-6” of soil. Although the Agency is aware that some exposure via dust from abraded seed coat can occur, transport in runoff is likely to be the dominant route of ecosystem exposure.

2.4. Assessment Endpoints

Assessment endpoints represent the ac tual environmental value that is to be protected, defined by an ecological entity (species, community, or othe r entity) and its attri bute or characteristics (USEPA, 1998). For penflufen, eco logical entities of potential concern include the following: birds, amphibians, reptiles, mammals, freshwater fish and invertebrates, estuarine/marine fish and invertebrates, non-target terres trial plants, terrestrial inverteb rates, and aquatic vascular and non-vascular plants. The attributes for each of these entities may include growth, survival, and reproduction ( Table 2.2 in Section 2.6.4 ).

2.5. Conceptual Model

For a pesticide to pose an ecological risk, it mu st reach ecological receptors in biologically significant concentrations. An exposure pathway is the means by which a pesticide moves in the environment from a source to an ecological recepto r. For an ecological pathway to be complete, it must have a source, a release mechanism, an environmental transport mechanism, and a feasible route of exposure.

The conceptual model is intended to provide a wr itten description and visual representation of anticipated relationships between penflufen, pot ential routes of exposure, and the predicted effects for the assessment endpoints. The concep tual model consists of two major components: risk hypotheses and a conceptual diagram (USEPA, 1998).-Page 12 of 115- 2.5.1. Risk Hypotheses

For penflufen, the following generic ecological risk hypothesis is being employed for this screening-level risk assessment:

Given the proposed uses of penflufen and its environmental fate pr operties, there is a likelihood of exposure to non-target te rrestrial and aquatic organisms.

When used in accordance with the label, pe nflufen results in poten tial adverse effects upon the survival, growth, and reproduction of non-target terrestrial and aquatic organisms.

2.5.2. Conceptual Diagram

The conceptual model is a graphical representati on of predicted relationships between ecological receptors, both listed (threatened and endangered) and non-listed, and the st ressors to which they may be exposed. A conceptual model specifies po tential routes of exposur e, biological receptor types, and effects endpoints of potential concern.

Penflufen is expected to persis t in both terrestrial and aquati c environments under aerobic and anaerobic conditions, and is cons idered moderately mobile, lipoph ilic, and nonvolatile. There is no evidence of degradation via hydrolysis. A poten tially major route of degradation in shallow, clear waters ( e.g., applications to flooded rice paddi es) may be aqueous photolysis; however photolysis is slow and plays a si gnificant role in sha llow clear waters. Penflufen has not been shown to bioconcentrate in aquatic organisms.

Penflufen is applied to seeds as a seed treatment. For seed pieces, it is also applied as an infurrow spray, which is covered immediately with 3” -6” in soil. Many seeds are incorporated, but given the persistence and mobility of penflufen, th e chemical and/or its major degradates may be transported off-site in runoff. Ecologically sign ificant spray drift is not expected, the in-furrow spray due to its proximity to the soil surface, and is not expected for seed treatments. Figure 2.1 depicts the stressors, exposure pathways, and pot ential effects to terrestrial organisms from proposed uses of penflufen. Figure 2.2 depicts the stressors, exposur e pathways, and potential effects to aquatic organisms from proposed uses of penflufen. For both figures, dotted lines indicate exposure pathways that are expected to have a low likeli hood of contributing to ecological risk.-Page 13 of 115- 

### Stressor

Source

Receptors

Attribute Change Direct application

Birds / Terrestrialphase amphibians / reptiles /

mammals Seeds

Individual organisms

Reduced survival Reduced growth Reduced reproduction Food chain Reduction in prey Habitat integrity Reduction in primary productivity

Reduced cover Community change Terrestrial/riparian plants grasses/forbs, fruit, terrestrial

invertebrates Runoff

Mammals 

### Exposure

Media Soil

Ingestion Ingestion

Ingestion Ingestion Dermal uptake/Ingestion

Root uptake

Wet/dry deposition

Birds / Amphibians

Ingestion Penflufen treated seeds and in-furrow spray applied to use site

Figure 2.1. Conceptual model for penflufen seed treatment effects on terrestrial organisms.-Page 14 of 115- Figure 2.2. Conceptual model for penflufen seed treatment effects on aquatic organisms. Penflufen treated seeds and in-furrow spray applied to use site

Fish/aquatic-phase amphibians Eggs

Larvae

Juveniles / Adults

Individual organisms

Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Habitat integrity Reduction in primary productivity

Reduced cover Community change Surface water/

Sediment Runoff

Uptake/gills or integument Aquatic Animals

Invertebrates

Vertebrates

Ingestion Ingestion Wet/dry deposition Soil Groundwater

Uptake/gills or integument

Aquatic Plants

N on-vascular

Vascular Uptake/cell, roots, leaves Riparian plant

terrestrial

exposure pathways see

Figure 2.1 

### Stressor

Source

Exposure

Media

Receptors

Attribute Change

2.6. Analysis Plan

2.6.1. Residues of Concern

Major degradates of penflufen ( i.e. those constituting greater than 10% of the applied radiation from environmental fate studies) are pen- 3HB, AAP, carbon dioxide, and under certain circumstances BYF 14182-fluoro acid (chemical na mes, chemical structures, and data on the formation of these degradates are provided in Appendix A ). BYF 14182-fluoro acid was detected approaching 10% of the applied radioa ctivity in a submitted aqueous photolysis study.

Pen-3HB and AAP were not included as residues of concern because available toxicity data suggest these degradates are less to xic than the parent such that risk would not be indicated at environmentally relevant concentr ations. While no toxicity data are available for the fluoro-acid, exposure to organisms is expected to be limited, as this degradate was only shown to form via aquatic photolysis. Therefore, penflufen alone is the residue of concern in this assessment.

2.6.2. Preliminary Identification of Data Gaps and Uncertainties-Page 15 of 115- For the purposes of this assessment, data gaps refer to the absence of necessary data for a complete risk assessment. Without eco-toxicity da ta or evidence to demonstrate otherwise, risk to non-listed and listed species of a taxon is pres umed. An area of considerable uncertainty for this assessment surrounds poten tial chronic risk to birds. Current data on mallard duck are inadequate to derive a definitive NOAEC or make a definitive determination of risk (effects were

noted at all test concentrati ons). A second avian reproduction study on mallard duck that results

in derivation of a NOAEC would reduce uncertaint y, and potentially obviat e the need to assume risk to this taxon. Additionally, three species of nonvascular aquatic plants have not been submitted for penflufen, but these data are not thought to be critical to the risk conclusions based on data for other carboximide pyrazoles. The adequ acy of data for making risk determinations is

discussed in the context of all lines of evidence in the Risk Characterization.

For the purposes of risk assessment the submitted environmental fate data are not adequate. The quality of the submitted data is generally adequate, however some uncertainties exist and are

discussed in section 4.3. Furthe r a catalog of submitted environmen tal fate studies for penflufen and its degradates, along with justified review classifications, can be found in Appendix C . A complete summary of all submitted environmental fate data is included in Appendix D

.

2.6.3. Evaluation of Multiple Acti ve Ingredients and Mixtures

The Agency does not routinely include in its risk assessments an evaluation of mixtures of active ingredients, either those mixtures of multiple ac tive ingredients in product formulations or those in the applicator’s tank. In the case of the pr oduct formulations of active ingredients (that is, a registered product containing more than one active ingredient), each active ingredient is subject to an individual risk assessment for regulator y decision regarding the active ingredient on a particular use site. If effects data are availa ble for a formulated product containing more than one active ingredient, they may be used qualitati vely or quantitatively in accordance with the Agency’s Overview Document and the Services’ Evaluation Memorandum (U.S. EPA 2004; U.S. FWS/NMFS 2004).

In the case of penflufen, data on the produc t PEN 240FS are available for fish, aquatic invertebrates, nonvascular aquatic plants and mammals. Additionally, data on penflufen and

coformulants are available for mammals. These are discussed in the eff ects section (Section 3.3) and later in the risk descrip tion section (Sect ion 4.2.).

2.6.4. Measures of Exposure

Measures of exposure are based on aquatic and te rrestrial models that estimate environmental concentrations of penflufen using labeled app lication rates and methods. For aquatic exposure the Tier II model Pesticide Root Zone Model (PRZM v3.12.2; May 12, 2005) linked with EXposure Analysis Modeling System (EXAMS v2.98.4.6; Apr. 25, 2005) via the PRZM/EXAMS model shell (PE v5.0, Nov. 15, 2006), i.e. , PRZM/EXAMS) and the Tier I Rice Model (v1.0, May 8, 2007) were used to estimate screening-level exposure concentrations in aquatic environments. The measure of exposur e for aquatic species in surface water bodies receiving runoff and/or spray dr ift is a return freq uency of 1-in-10 years of the estimated-Page 16 of 115- environmental concentrations (EEC), based on 30 -year simulations. The maximum 1-in-10 year return frequency concentration is used for es timating acute exposures to aquatic organisms (plants and animals); the 1-in-10 year 21-day mean concentration is used for assessing aquatic invertebrate chronic exposure; and the 1-in-10 year 60-day mean concentration is used for assessing chronic exposure for fish (and aquati c-phase amphibians for which fish serve as surrogates). Exposure to benthic organisms from sediment concentrations in water bodies was assessed; pore-water 1-in-10 year EECs were calculated for maximum use patterns.

Terrestrial exposure estimates for avian and mamma lian risk assessments were derived using the T-REX model (version 1.4.1, 10/08/2008). The assu mption of the model is that mammals and birds may be exposed via their consumption of tr eated seeds on or immedi ately adjacent to the site of application. The seed treatment work sheet in T-REX calculate s the avian and mammalian dose (mg a.i. bw -1 day -1 ) and available pesticide (mg a.i. ft -2 ). Risk quotients (RQ) are calculated using the adjusted LD 50 for the smallest weight class of animal (20 g for birds and 15 g for mammals). Acute RQs are calculated using two methods:

Method 1 (EEC/LD 50 method) : Acute RQ = mg a.i./kg -1 day -1 /adjusted LD 50
Method 2 (analogous to the LD 50 ft -2 method) : Acute RQ = mg/kg -1 a.i. ft -2 / (adjusted

LD 50 x body weight (kg))

Chronic RQs are calculated us ing the following equation:

Chronic RQ = mg a.i. kg -1 seed / NOAEC (mg/kg-diet).

Exposure for terrestrial plants inha biting dry and semi-aquatic areas ( e.g. , low-lying wet areas that may dry up at times throughout the year), using TerrPlant v 1.2.1, is based on the following:

(1) the pesticide's water solubility and the am ount of pesticide presen t on the soil surface and its top one centimeter, (2) potential "sheet runoff" (one treated acre to an adjacent acre) for dry areas, (3) potential "channel runoff" (10 acres to a distant low-lying acre) for semi-aquatic or wetland areas, (4) fractional runoff values of 0.01, 0.02, and 0.05 for pesticide water solubilities of <10, 10-100, and <100 ppm, respectively

The S creening I mbibition P rogram (SIP v.1.0) was used to cal culate an upper bound estimate of wildlife exposure via drinking water using penflu fen’s solubility avian and mammalian toxicity endpoints.

2.6.5. Measures of Effect

Measures of effect are obtained from a suite of registrant-submitted guideline studies that were

conducted with a limited number of surrogate test species ( Table 2.1) . No additional ecotoxicity data on penflufen were located, based on an August 2011 query of the open literature in the publically available version of the ECOTOX database (http://c fpub.epa.gov/ecotox/).-Page 17 of 115- The acute measures of effect used in this baseline assessment are the LD 50 (median Lethal Dose),

LC 50 (median Lethal Concentration) or EC 50 (median Effects Concentration). These are measures of acute toxicity which result in 50% of the respective effe ct in tested organisms. The endpoints for chronic measures of exposure are the no observed adverse effect concentration (NOAEC) and the no observed adverse effect le vel (NOAEL). Toxicity studies were submitted for freshwater fish and invertebrates, estuarine/ marine fish and inverteb rates, aquatic plants, birds, mammals, bees, and other terrestrial invertebrates. The e ndpoints used for risk

characterization are derived from studies whic h underwent review and were classified as “acceptable” (conducted under guideline conditions and considered to be scientifically valid) or “supplemental” (conditions deviated from guidelin es but the results are considered to be scientifically valid).

Table 2.2 lists the measures of environmental exposur e and ecological effects used to assess the potential risks of penflufen to non-target organisms. The methods used to assess the risk are

consistent with those outlined in the document “Overview of the Ecological Risk Assessment

Process in the Office of Pes ticide Programs” (USEPA, 2004).-Page 18 of 115- Table 2.2. Measures of Exposure and Measures of Effect Used in Assessing Potential Risks Associated with the Proposed Uses of Penflufen.

Assessment Endpoint Surrogate Species and Measures of Ecological Effect 1 Measures of Exposure

Birds 2 Survival Lowest acute LD 50 (single oral dose test)

and LC 50 (subacute dietary test) Upper-bound residues on

food items

Reproduction

and Growth Lowest NOAEC (21-week reproduction test)

Mammals Survival Lowest acute LD 50 (single oral dose test)

Reproduction

and Growth Lowest NOAEC (2-generation reproduction test)

Aquatic Animals (Fish and invertebrates) 3 Survival Lowest tested LC 50 or EC 50 (acute toxicity test) Peak EECs 4

Reproduction

and Growth Lowest NOAEC (early life-stage or full life-cycle tests) 21-day EECs for invertebrates and 60-day EECs for fish 4

Terrestrial plants 5 Survival and growth Lowest EC 25 (for non-listed plants) and corresponding NOAEC (for listed plants)

(endpoints derived for monocots and dicots from seedling emergence and vegetative vigor studies) Estimates of runoff and spray drift to non-target areas

Insects 6 Survival (not quantitatively

assessed) Lowest honeybee LD 50 (acute contact test)

Lowest Earthworm LC 50 Maximum application rate for honeybees and estimates of

soil concentrations for

earthworms

Aquatic plants (vascular and non-vascular) Survival and growth Lowest EC 50 (for non-listed plants) and corresponding NOAEC or EC 05 (for listed plants) Peak EECs 4

1 The most sensitive species tested within taxonomic groups is used for screening-level risk assessments.

2 Birds represent surrogates for terrest rial-phase amphibians and reptiles.

3 Freshwater fish represent surroga tes for aquatic-phase amphibians.

4 Aquatic EECs are based on modeling described in Section 3.2.2.1

. 5 Four species of two families of monocots - one is corn, six speci es of at least four dicot families, of which one is soybeans.

6 Risk to terrestrial invertebrates from penflufen use is not evaluated, rather the potential h azard to honey bees and earthworm s (i.e. the available data) are qualitatively assessed.

2.6.6. Integration of Exposure and Effects

Exposure and toxicity data are integrated in or der to evaluate the risks of adverse ecological effects on non-target species. For the screening-level risk assessment of penflufen, the deterministic risk quotient (RQ) method is used to compare estimated exposure concentrations with measured toxicity values. The RQ method involves dividing point estimates of environmental concentrations by acute and chroni c toxicity values. The resulting unitless RQs are then compared to the Agency’s Le vels of Concern (LOC) (USEPA, 2004) ( Table 2.3 ).

These criteria are used to indicate when applications of pe nflufen, as directed on the proposed labels, have the potential to cau se adverse effects to listed an d non-listed non-target organisms.-Page 19 of 115- Table 2.3. Agency Risk Quotient (RQ) Metr ics and Levels of Concern (LOC) Per Risk

Class.

RISK CLASS RISK DESCRIPTION RQ LOC

Aquatic Animals (fish and invertebrates)

Acute Potential for effects to non-listed animals from acute

exposures Peak EEC/LC 50 1 0.5

Acute

Restricted Use Potential for effects to an imals from acute exposures Risks may be mitigated through restricted use classification Peak EEC/LC 50 1 0.1

Acute Listed Species Listed species may be potentially affected by acute

exposures Peak EEC/LC 50 1 0.05

Chronic Potential for effects to non-listed and listed animals from chronic exposures 60-day EEC/NOAEC (fish) 1 21-day EEC/NOAEC (invertebrates)

Aquatic Plants

Non-Listed Potential for effects to non-listed plants from exposures Peak EEC/LC 50 1 1

Listed Potential for effects to listed plants from exposures Peak EEC/NOAEC 1

Terrestrial Animals (mammals and birds)

Acute Potential for effects to non-listed animals from acute

exposures EEC 2 /LC 50 (Dietary) 0.5 EEC/LD 50 (Dose)

Acute

Restricted Use Potential for effects to an imals from acute exposures Risks may be mitigated through restricted use classification EEC 2 /LC 50 (Dietary) 0.2 EEC/LD 50 (Dose)

Acute Listed Species Listed species may be potentially affected by acute

exposures EEC 2 /LC 50 (Dietary) 0.1 EEC/LD 50 (Dose)

Chronic Potential for effects to non-listed and listed animals from chronic exposures EEC 2 /NOAEC 1

Terrestrial and Semi-Aquatic Plants

Non-Listed Potential for effects to non-target, non-listed plants from

exposures EEC/ EC 25 1

Listed Plant Potential for effects to non-target, listed plants from

exposures EEC/ NOAEC 1 EEC/ EC 05

1 LC 50 or EC 50

. 2 Based on upper bound seeding rates.

3. Analysis

3.1. Use Characterization

Penflufen is proposed primarily for use as a se ed treatment. Proposed maximum application rates and use patterns listed by use according to the proposed la bels are provided in a mass per

unit area basis in Table 3.1 . The in-furrow application, used with seed piece treatment only ( e.g. potatoes) is immediately incorporat ed to a depth of 3-6 inches, pe r the proposed label and USDA Crop Profiles for potato cultivation (USDA, 2000). For the purpose of this screening-level risk assessment, the entire per-acre rate for the in-fur row treatment is assumed to be additive to the per-acre rate for the seed piece treatment ( i.e. 0.14 lbs a.i./A for seed piece and 0.14 lbs a.i./A for-Page 20 of 115- the in-furrow applications for a total penflufen application rate of 0.28 lbs a.i./A). Given that the

entire acre would not be treate d, this is likely a conservative assumption. Surface applied seed (beans and peas, cereal grains, wheat, alfalfa, canola, and other oil seed crops) are broadcast on the soil surface. Alfalfa and beans are applied as a “slurry treatment.” The slurry treatment principle involves suspension of wettable powde r treatment material in water. The treatment material applied as a slurry is metered through a sample mechanism composed of a slurry cup and seed dump pan. The cup introduces a given mass of slurry with each dump of seed into a mixing chamber where seed are blended. The seed s are then moved into a hopper for application

to the field surface..

Table 3.1. Proposed Maximum Use Patterns of Penflufen.

Crop/Use Formulated Product Maximum Application

Rate (lbs a.i./A) * Maximum

Number of Applications

(interval) Maximum Yearly Application (lbs a.i./A/yr) Method of Application

Potato other tuberous corm vegetables (in-furrow app with seed pieces) PEN 240 FS 0.14 NS NS Ground infurrow (with

seed piece application)

Potato seed pieces PENCLO, PEN 240FS 0.14 NS NS Treated seed pieces Beans (slurry) PENTRI 308 FS 0.0384 NS NS Treated seed Cereal grains PENRED, PEN 240FS, 0.0078 NS NS Treated seed

Wheat PENTRI 308FS,

PENPRO 118FS 0.0078 NS NS Treated seed

Rice PENRED, PEN 240FS,

PENPROME 177FS 0.00645 NS NS Treated seed

Corn PENRED, PEN 240FS 0.0033 NS NS Treated seed

Alfalfa (slurry) PENRED, PEN 240FS,

PENTRI 308FS 0.00225 NS NS Treated seed

Cotton PENRED, PENCLO, PEN 240FS, PENTRI

308FS 0.0019 NS NS Treated seed

Canola and other oilseed crops PENRED, PEN 240FS,

PENCLOTRIME 0.00123 NS NS Treated seed

*USEPA, 2011a, Acres Planted per Day and Seed ing Rates of Crops Grown in the United States, Memorandum from Beck and Ratnayake, Biological and Economic Analysis Division, to Deschamp (HED) and Spatz (EFED), March 2011.

3.2. Exposure Characterization

3.2.1. Environmental Fate and Transport Characterization

The general physical/chemi cal properties of penflufen are summarized in Table 3.2

. Environmental fate and transport pr operties of penflufen are characte rized in further detail in the following sections. The Agency’s understanding of these properti es is limited by the available dataset. Many of the chemical properties and envi ronmental fate parameters of penflufen listed in

Table 3.3 are based on studies classified as suppl emental. Additional de tail on each study is provided in Appendix D.

Based on the chemical structure of the co mpound, the compound has a stereocenter and may-Page 21 of 115- show enantiomeric selection in the degrada tion studies. This was not addressed in the degradation studies submitted to the Agency. Additional data on this issue to address enantiomeric selection would reduce the uncertainty of the degradation of penflufen isomers.

Table 3.2 General Physical and Chemical Properties of Penflufen

Parameter Value Reference

PC code 100249

--

CAS No. 494793-67-8

--

Structure

N H N

N O

F CH

3

CH 3

CH 3 CH 3 CH

3 --

Chemical name (IUPAC) (RS)-N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1 H

pyrazole-4-carboxamide --

Chemical name (CAS) 1 H -Pyrazole-4-carboxamide, N-[2-(1,3-dimethylbutyl)phenyl]-5- fluoro-1,3-dimethyl- --

Common name Penflufen (BYF14182)

--

Chemical formula C 18 H 24 F N 3 O

-- Molecular weight 317.41 g/mol 48023535

Water solubility (20oC, pH 7) 10.9 mg/L 48023535

Vapor pressure (25oC) 9.0 x 10 -9 torr 48023537

Henry's law constant 1.04 x 10 -10 atm·m 3 /mol 48023539

Octanol-water partitioning coefficient Log K OW (20oC, pH 7) 3.3 48023534

Dissociation Constant (pK

a ) No dissociation constant was found in aqueous solution of penflufen in the range of 1 < pH < 12. The molecule has no structural moieties which are prone to dissociate. 48023532

Penflufen is persistent in aer obic and anaerobic cond itions, and is moderately mobile based on the FAO soil mobility classifications (mean Koc = 365; MRID 48023546) (USEPA, 2006a). The compound is nonvolatile, lipophilic, and does not bioconcentrate in aquatic organisms. Penflufen is persistent in soil with half-lives ranging from 115 to 433 days in aerobic soil from two studies conducted in six soils (MRI D 48023552, 48023553). The compound degrades very slowly in anaerobic soil, with an extrapolated half-life of 886 days (MRID 48023555). There is no evidence of degradation via hydrolysis, whic h was studied across environmental pHs (pH 5, 7, and 9 at 50oC; MRID 48023547). Penflufen al so degrades slowly by aerobic aquatic metabolism, with half-lives ranging from 267 to 301 days (MRID 48023556). There is no evidence of degradation in anaerobic aqua tic systems (MRID 48023557). A potentially major route of degradation may be aqueous photolysis (environmental half- life of 83 days; MRID 48023548); however photolysis is slow and only likely to play a significant role in shallow, clear-Page 22 of 115- waters. A summary of the submitted environmental fate and transport data is summarized below

in Table 3.3

.

Penflufen is expected to persist in both terrest rial and aquatic environm ents. The degradate Pen3HB is much more mobile than the parent, bu t the AAP degradate is comparatively immobile. Under aerobic conditions, AAP can be slowly metabolized, but it is stable to anaerobic metabolism. AAP persists, with half-lives ra nging from 116-260 days (there are no metabolism data for Pen-3HB). Penflufen was detected in su bmitted terrestrial field dissipation studies above the level of quantitation (LOQ) at depths up to 60 cm, however the majority of reported detections were from the upper soil layers (0-15 cm).

Table 3.3 Environmental Fate Data Summary for Penflufen

OPPTS

Guideline Data Requirement Data Summary Source

835.2120 Hydrolysis t 1/2 at 50°C Stable MRID 48023547

835.2240 Aqueous photolysis t 1/2 at 25°C 83 days (36 days in river water) MRID 48023548 (MRID 48023549)

835.2410 Soil photolysis t 1/2 at 22°C No data (soil incor porated/seed treatment use)

--

835.4100 Aerobic soil metabolism t 1/2 at 25°C 249 days (silt loam) 433 days (sandy loam)* MRID 48023553

Aerobic soil metabolism t 1/2 at 20oC 117 da ys (silt loam) 165 days (sandy loam)* 243 days (loam)* 129 (loam)* MRID 48023552,

AAP (degradate) 257 days (sandy loam)* 116 days (silt loam) 231 days (loam)* 128 days (clay loam)* MRID 48023554

835.4200 Anaerobic Soil Metabolism t 1⁄2 at 20°C 866 days* MRID 48023555

835.4300 Aerobic aquatic metabolism t 1/2 at 20°C (sandy loam:sediment system) 301 days* MRID 48023556

835.4400 Anaerobic aquatic metabolism t 1/2 at 20°C (combined labels) Stable MRID 48023557

835.1230 Organic carbon partitioning coefficient (K oc, mL/g oc) 404 (sandy loam) 283 (silt loam) 257 (loam) 475 (Goldsboro loamy sand) 407 (Oska-Martin clay loam) MRID 48023546

pen-3HB (transformation product) 30 (sandy loam) 40 (silt loam) 37 (sandy loam) 63 (Goldsboro sandy loam) 69 (Oska-Martin clay loam)

AAP (transformation product)

1954 (sandy loam) 1868 (silt loam) 1906 (silt loam) 3553 (Goldsboro sandy loam) MRID 48023544

MRID 48023545-Page 23 of 115- OPPTS

Guideline Data Requirement Data Summary Source

9313 (Oska-Martin silty clay)

Freundlich adsorption value, K f , mL/g oc (1/n) 4.9 (0.89), sandy loam 4.7 (0.89), silt loam 2.6 (0.94), loam 5.4 (0.95), Goldsboro loamy sand 6.0 (0.86), Oska-Martin clay loam MRID 48023546

pen-3HB (transformation product) 0.62 (0.95), sandy loam 0.98 (0.95), silt loam 0.63 (0.96), sandy loam 0.44 (0.91), Goldsboro sandy loam 1.36 (0.98), Oska-Martin clay loam AAP (transformation product) 14.9 (0.76), sandy loam 24.4 (0.77), silt loam 18.7 (0.79), silt loam 10.9 (0.69), Goldsboro sandy loam 127.7 (0.89), Oska-Martin silty clay MRID 48023544

MRID 48023545

835.6100 Terrestrial field dissipation DT 50 US soils 11 days (Tifton loamy sand, GA) 340 days (Delco loam, ID) MRID 48023559

MRID 48023560

Terrestrial field dissipation DT 50 Canadian soils 14 days (Harriston loam, ON) 202 days (Weyburn sandy loam, SK) 15 days (Alberry sandy loam, PE) MRID 48023561

MRID 48023562

MRID 48023563

Terrestrial field dissipation DT 50 European soils 187 days (clay loam, France) 100 days (clay, UK) 133 days (sandy loam/sandy clay loam, Sweden) 193 days (loam, Germany) 77 days (loam, Italy) 53 days (loam/sandy clay loam, Spain) MRID 48023564

850.1730 Fish bioconcentration (BCF) (steady state BCF ) Edible, viscera, whole Low dose (0.45 ug/L): 35, 186, 100 High does (4.5 ug/L): 37, 187, 103 MRID 48023589

*Indicates the half-life was extrapolated beyond the termination of the study.

3.2.1.1. Transport and Mobility

Penflufen is not volatile, with a partial vapor pressure of 9.0 x 10 -9 torr at 25oC (MRID 48023537). The molecule has no structural moieties that are prone to dissociate. The reported

K
ow for penflufen at 25oC for pH 7 was 1,995 (LogK

ow = 3.3; MRID 48023534).

Penflufen is moderately mobile to mobile ba sed on FAO Soil Mobility Classification Guidance (USEPA, 2006a), with reported organic carbon pa rtitioning coefficients ranging from 257 to 475 (Freundlich adsorption constants (K f ) from five soils ranging from 2.6 to 6.0; corresponding adsorption isotherms 0.86 to 0.95) (MRID 48023546). Batch equilibrium data for penflufen show that adsorption to soil is not we ll correlated with or ganic carbon content (r 2 = 0.578, p = 0.14), pH (r 2 = 0.272, p = 0.37), clay content (r 2 = 0.183, p = 0.47), or CEC (r 2 = 0.487, p = 0.19). However, the coefficient of variation for Koc values (25%) is less than that for Kf values (27%); therefore, the mobility of penflufen in so il may be partially affected by the soil fraction of organic carbon.-Page 24 of 115- Leaching and adsorption/desorption studies were conducted on the two major degradates 1 : pen3HB and AAP. Pen-3HB is much more mobile than the parent, however AAP reported high sorption values compared to the parent indicatin g that it has a higher bindi ng affinity (correlated with % clay content) (MRID 48023544, 48023545).

3.2.1.2. Degradation

Penflufen is stable to hydrolysis; there was no evidence of degradation at pH 4, 7, and 9 at 50oC (MRID 48023547). It is slowly photolab ile in clear water (environmental half-life of 83 days at pH 7; MRID 48023548). In the presence of natura l compounds found in river water, penflufen may more quickly photolyze in water (environmental half-life of 36 days).

Penflufen biodegrades slowly in aerobic soil, wi th reported half-lives ranging from 117 to 433 days (parent-only half-lives; MRID 48023552, 48023553). Un-extracted residues were substantial (as high as 26%) in all aerobic metabolism studies. Multiple solvent systems were not employed in the extraction scheme, and it is uncertain to what exte nt unextracted residues consist of bound or available parent compound or degradates. Supplemental data characterizing the extraction of parent residues from sterile an d non-sterile soils was submitted by the registrant following the Agency’s review of the metabo lism studies. The study was submitted November 8, 2011 and was assigned MRID 48652501. The re sults from the comparison between extractions from sterile (gamma-i rradiated) and non-sterile (viable) soils showed that a portion of the unextracted residues reported in the metabo lism half-lives are biol ogically mediated and potentially irreversibly bound. Th erefore, for risk assessment exposure estimates were based on half-lives calculated for the parent-only.

Results from the two aerobic soil metabolism studi es on six different soil types show penflufen degrades via hydroxylation at the alkyl side chain in the 3-position to form pen-3HB, which further oxidizes to AAP and multiple unidentif ied minor compounds. Apparently irreversible sorption of unextracted residue is substa ntial, and in general formation of CO 2 is minimal. Figure 3.1 illustrates a predicted degradation pathway under aerobic conditions

.

1 A major degradate is defined as a compound that is detected in the fate studies at > 10% of the applied radiation.-Page 25 of 115- N H N

N O

F CH 3

CH 3

CH

3 CH 3 CH

3

N H N

N O

F CH 3

CH 3

CH

3 CH 3 CH 3

OH

N H N

N O

O F CH 3

CH 3 CH 3 BYF 14182-3-hydroxy-butyl

BYF 14182-pyrazolyl-AAP (AE 2300037) Penflufen

BYF 14182

Non-extractable residues + CO 2 Figure 3.1 Predicted Transformation Pathway under Aerobic Conditions

An aerobic aquatic metabolism study was c onducted for penflufen investigating the biotransformation of penflufen in two water-sed iment systems from Germany: a sand-gravel pit lake water system (Angler Weiher), and a loam-pond water system (Hoenniger Weiher). However, due to unexplained variab ility in the material recovery from the Angler system, only calculated half-lives from the Hoenniger system are acceptable for risk a ssessment. The rate of biodegradation of penflufen was slower in aquatic environments than terrestrial environments (parent-only single first-order half-life of 301 days (DT 90 of 942 days) in the water-sandy loam sediment system; MRID 48023556; parent plus unextra cted residues, single first-order half-lives of 978 days). The compound dissipated from the water column compara tively quickly (water dissipation half-life of 5.9 days), and was dete cted in the sediment. In anaerobic aquatic environments, penflufen is apparently stable to biodegradation; ther e was no evidence of degradation (MRID 48023558).-Page 26 of 115- 3.2.1.3. Field Studies

Seven terrestrial field dissipation studies were conducted for penflufen at three sites in the United States (Georgia, Idaho, and Califor nia), three sites in Canada (O ntario, Saskatchewan, and Prince Edward Island), and six sites in the European Union (France, UK, Sweden, Germany, Italy, and Spain). It is important to note that the Calif ornia field dissipation study was found unacceptable because the dissipation route(s) were not well characterized. All North American studies were conducted with broadcast applications to bare ground (MRID 48023569, 48023560, 48023561, 48023562, 48023563), each site included four bare ground plots that had <1% slope (except Georgia, where the slope was 2.8%) and no runoff collection equipment. Penflufen was applied at an exaggerated broadcast rate in all of the North American field studies; up to 171% of the proposed maximum application rate. The method of application in these studies was inconsistent with the proposed uses ( i.e. , proposed uses are seed treatment uses, with one in-furrow spray, not surface/foliar applied ground sprays as were used in the field studies). These factors increase the uncertainty of the reported dissipation rates in the submitted field studies compared to the proposed uses of penflufen ( i.e ., the rate of dissipation from broadcast applications may be greater than for seed treatmen t and in-furrow application methods, where less material is available for runoff and photolysis). Additional data describing th e dissipation patterns from use patterns similar to the proposed us es (seed treatments) are needed to decrease the uncertainty surrounding the dissipation routes fo r penflufen and its degradates.

Penflufen residues were primarily detected in the top 0-30cm soil laye rs. The parent compound was detected as deep as 60cm, but was often re ported below the limit of quantification. Pen-3HB and AAP were only detected in the 0- 15cm soil layers. Dissipation rates (DT 50 ) for penflufen from the North American field studies ranged from 11-340 days. This wide range encompasses the variability observed in the laboratory studies (half-lives ranging from 116-257 days), however, the laboratory studies on ly measure biodegradation, wher eas the field studies measure dissipation due to transport loss pathways as well ( e.g. , runoff, leaching, etc.).

An additional study of six sites in Europe (Fra nce, Italy, Spain, Sweden, Germany, and the UK) was conducted to study the dissipation in European soils (MRID 48023564). Penflufen was broadcast applied to bare soil at an exaggerated rate (0.223 lbs a.i./A), incorporated to an unknown depth, and grass was sown into soil foll owing application. Dissipa tion half-lives from the European studies ranged from 52 to 193 da ys, comparable to the North American field studies that reported a simila r range of dissipation times.

There was significant carryover of penflufen residu es on an annual basis in the North American studies; carryover ranged from 18% (Georgia) to 39% (Idaho), with an average of 29%. Dissipation rates (DT 50 ) from Prince Edwards Island, Ontari o, and Georgia were <15 days, however Saskatchewan and Idaho reported DT 50 s >200 days. Carryover percentages were approaching 40% for Saskatchewan and Idaho co mpared to Ontario and Georgia which reported

carryover percentage s closer to 20%.-Page 27 of 115- 3.2.1.4. Bioconcentration

A flow-through bioconcentration study of bluegill sunfish ( Lepomis macrochirus ) exposed to penflufen in pH 7.5-8.0 water for 28 days indicates that bioconcentration of the compound in fish

does not exceed levels of concern. The 28- day exposure period was followed by a 14 day depuration period. Bioconcentration factor s (BCF) were 35, 186, and 100x for whole fish, edible, and non-edible fish ti ssues, respectively, in low-dose samples (0.45 μg/L), and 37, 187, and 103 for whole fish, edible, and non-edible fi sh tissues, respectively, in high-dose samples (4.5 μg/L) (98% of mean total residues were de purated after 14-days). BCF values less than 1000 do not trigger criteria for further ev aluation of bioaccumulative compounds.

3.2.1.5. Environmental Degradates

The major degradates resulting from environm ental degradation processes are pen-3HB and AAP ( Table 3.4 ). These transformation products were identified in the en vironmental fate

studies at concentrations >10% of the applied radioactivity (all major and minor degradates are

listed in Appendix A , identifying the study in which it was reported). In all six soils studied (four German soils, two US soils) pen-3HB was reported at increasing concentrations at the study termination (120 days for German soils, 365 days for US soils; 9-18% of the applied). AAP was reported in the two U.S. soils, however it was only reported as a major degradate in the sandy loam soil. In this study AAP was detected at 61 days after treatment (DAT) and increased in concentration through the termination of th e study (365 DAT). In the silt loam soil, AAP was only detected in the final sampling time period (365 DAT). This suggests that the AAP degradate may form after a considerable amount of time has passed ( i.e. , the study duration for the German soils may have been insufficient to capture the fo rmation of AAP). Pen-3HB was also detected as a major degradate in the aerobic aquatic metabol ism study (13% of the applied radiation), and was still increasing in co ncentration at the termination of the study. Pen-3HB and AAP were also

both detected in the terrestria l field dissipation studies; howev er detections were largely restricted to the 0-15 cm range of the soil prof ile. Pen-3HB was detected in the aquatic field dissipation study as well.

Other major degradates detected in the envi ronmental fate studie s include BYF 14182-fluoro acid (detected in the aqueous phot olysis study using river water), and carbon dioxide (both were up to 9.9%AR at study termination).

The environmental degradates of penflufen that are considered to be of exposure concern are pen-3HB and AAP. These degradates were formed at increasing concen trations through the

termination of the environmental fate studies in which they were formed. Therefore, there is uncertainty about the formation and decline of these major degradates in the environment. BYF 14182 fluoro acid may also be a degradate of exposure concern (9.9% of the AR). Due to the proposed label methods (primarily as a seed tr eatment) and because this degradate was only detected in the aqueous photolysis study, environmental exposure to this degradate is more likely where penflufen is applied to ri ce paddies, or is transported to shallow, clear water bodies via

runoff.-Page 28 of 115- Batch equilibrium data for pen-3HB and AAP show that pen-3HB will be much more mobile than the parent (highly mobile based on FAO St andardized Soil Mobility Classifications), and that AAP will be much less mobile (hardly mobile based on FAO classifications) (USEPA, 2006a). Aerobic soil metabolism data from studies using AAP as the starting material show that the transformation product will pe rsist under aerobic conditions after it is formed (half-lives ranged from 115 to 231 days in three soils; MRID 48023554).

Minor degradation products may be of exposure concern; however their structures were not reported in any study, and their percent of forma tion was frequently below 2%, except for BYF 14182-pyrazole-4-carboxamide which was detected at nearly 7% in a submitted aqueous photolysis study (MRID 48023548; Appendix A ).

Two degradates were detected in plant tissue (ric e plants) in the aquatic field dissipation study; pen-3HB and penflufen-bis-desmethyl-3-carboxylic acid. Pen-3HB was detected in other fate studies (aerobic soil and aerobi c aquatic metabolism, as well as anaerobic soil metabolism); however penflufen-bis-desmethyl -3-carboxylic acid was only dete cted in the plant tissue.

Table 3.4. Table of Transformation Products Formed in Environmental Fate Studies

Common Name Chemical Name Study in Which Found (Maximum % of Parent, or equivalent) Reference

MRID

Pen-3HB (penflufen-3- hydroxy-butyl; M01)

N H N

N O

F CH 3

CH 3

CH

3 CH 3 CH 3

OH 5-fluoro-N-[2-(3-hydroxy-1,3- dimethylbutyl)phenyl]-1,3- dimethyl-1 H -pyrazole-4-

carboxamide Aerobic soil metabolism (17.5%) Aerobic aquatic metabolism (13.3%) Anaerobic soil metabolism (7.1%) Terrestrial field dissipation (9.0 ng/g) Aquatic field dissipation (0.7 ng/g) 48023553

48023556

48023555

48023564

48023565

AAP (penflufenpyrazolyl-AAP; M02)

N H N

N O

O F CH 3

CH 3 CH 3 N-(2-acetylphenyl)-5-fluoro-1,3- dimethyl-1 H -pyrazole-4-

carboxamide Aerobic soil metabolism (13.4%) Terrestrial field dissipation (1.6 ng/g) 48023553

48023564

Penflufen-fluoro acid (M60)

OH

N

N O

F CH

3

CH

3 5-fluoro-1,3-dimethyl-1 H-pyrazole4-carboxylic acid Aqueous photolysis, river water (9.9%) 48023549

Carbon dioxide Carbon dioxide

-- --

Degradates of penflufen found in plant ti ssue during Aquatic Field Dissipation study-Page 29 of 115- Pen-3HB (penflufen-3- hydroxy-butyl; M01)

N H N

N O

F CH 3

CH 3

CH

3 CH 3 CH 3

OH 5-fluoro-N-[2-(3-hydroxy-1,3- dimethylbutyl)phenyl]-1,3- dimethyl-1 H -pyrazole-4-

carboxamide Aquatic field dissipatio n, rice tissue (11.5 ng/g) 48023565

BYF 14182-bisdesmethyl-3- carboxylic acid (M64)

N

N

H F

O OH 5-fluoro-1H-pyrazole-3-carboxylic

acid Aquatic field dissipation, rice tissue (6.1 ng/g) 48023565

3.2.2. Measures of Aquatic Exposure

3.2.2.1. Surface Water Exposure

The Tier II model Pesticide Root Zone Model (PRZM v3.12.2; May 12, 2005; Carousel et al.

, undated) linked with EXposure Analysis M odeling System (EXAMS v2.98.4.6; Apr. 25, 2005; Burns, 2004) via the PRZM/EXAMS model shell (PE v5.0, Nov. 15, 2006), i.e.

, PRZM/EXAMS) and the Tier I Rice Model (v1.0, Ma y 8, 2007) were used to estimate screeninglevel exposure concentrations in aquatic environments. The PRZM model simulates pesticide

movement and transformation on and across th e agricultural field resulting from crop applications. The EXAMS model simulates pesticid e concentrations in wa ter due to loading via runoff, erosion, and spray drift, assumi ng a standard 1-ha pond, 2-m deep (20,000 m 3 ) with no outlet that borders a 10-ha treated field. Simulations are for multiple (usually 30) years, from which the Agency estimates peak values that are expected to recur on average once every ten years, based on time series of daily estimated concentrations. The coupled PRZM and EXAMS

models and user’s manuals are available from the U.S. Environmental Protection Agency Water Models web-page (USEPA, 2011b).

Exposure estimates generated using the standard pond are intended as surrogates for potential

concentrations in a wide vari ety of vulnerable water bodies, in cluding prairie potholes, playa lakes, vernal pools, other wetlands, man-made a nd natural ponds, and ephemeral and first-order streams. Innumerable site-specific factors wi ll tend to make such water bodies more or less vulnerable than the standard pond. Static water bodies that have la rger ratios of pe sticide-treated drainage area to water body volume are generally expected to ha ve higher peak concentrations than the standard pond’s EECs. Su ch water bodies may be smaller in size, and/or have larger drainage areas. However such water bodies may be more likely to overflow and discharge pesticide in their effluent, whereas the standa rd pond has no discharge. As watershed size increases, it becomes increasingly unlikely that th e entire watershed is pl anted with a single crop that is all treated simultaneously with a pe sticide. Headwater streams may have peak concentrations that are higher th an those predicted for the standa rd pond, but such concentrations-Page 30 of 115- will likely persist for only short periods of time or distance, as they are carried downstream and diluted with water originating elsewhere.

The Tier I Rice Model was used to estimate sc reening-level exposure to penflufen that may occur in water bodies receiving re leased water from rice paddies th at were seeded with rice seed treated with penflufen. This model was used to assess the proposed use on rice seed because the PRZM/EXAMS exposure models do not specif ically address the unique rice growing environment and the model is approved for use in risk assessment. The model produces a single exposure value that represents a di ssolved concentration within a rice paddy. This single value is used to approximate both acute and chronic exposures.

The Tier I Rice Model relies on an equilibrium partitioning concept to provide conservative exposure estimates resulting from ap plication of pesticides to rice paddies. When a pesticide is applied to a rice paddy, the model assumes inst antaneous partitioning between the water and sediment phases. The model does not account for pesticide degradation, mass transfer between the aqueous phase and the sediment, volatilizat ion, dilution, or other potentially important attenuation processes; theref ore the model provides an upper- bound estimate of exposure for penflufen which is proposed for use on rice as a dry-seeded application (seed treatment). The Tier I Rice Model was calibrated to generate estima tes that are consistent with or conservative

for dissolved concentrations measured within ri ce paddies and in discharged paddy water. The

model was not evaluated or calibrated for concen trations measured in sediment and does not account for residues bound to suspended sediment. A description of and guidance for using the Tier I Rice Model may be found on the U.S. E nvironmental Protection Agency (EPA) Water Models web-page (USEPA, 2011b).

The general chemical and environmental fate data for penflufen listed in Table 3.2-3.3 were used for generating model input parameters for PRZM and EXAMS (listed in Table 3.5 ). Chemical specific and model input values were chosen in accordance with current divisional guidance (USEPA, 2009).-Page 31 of 115- Table 3.5. PRZM and EXAMS Surface Water Chem ical Input Parameters for Penflufen.

Input Parameter Value Comment Source

Molecular Mass (g·mol -1 ) 317.41 Product chemistry 48023535

Vapor Pressure at 25°C (torr) 9.0 x 10 -9 Product chemistry 48023535

Solubility in Water at 20oC, pH7 (mg·L -1 ) 10.9 Product chemistry 48023537

Organic carbon partition coefficient (K

oc , mL/g oc) 290 Parent only (mean of 5 soils) 48023546

48023544

48023545

Aerobic Soil Metabolism Half-life (days) 293.3 Parent only half-life (upper 90 th
percentile on the mean of 6 soils) 48023552

48023553

Aerobic Aquatic

Metabolism Half-life (days)

639 Parent only half-life from one water:sediment system. Adjusted to 25oC using a Q10 of 2 (measured T1⁄2 is 301 days from one water:sed system). Value is multiplied by 3 to account for potential variability in different water:sediment systems. 48023556

Anaerobic Aquatic

Metabolism Half-life (days) Stable No evidence of degradation. 48023557

Hydrolysis Half-lives (days) Stable No evidence of degradation at 50oC, pH 4, 7, 9. 48023547

Aqueous Photolysis Half-life (days) 83 Corrected environmental half-life 48023548

The model input parameters used in PRZM to simulate penflufen application and management practices are provided in Table 3.6 . The initial application date was selected in order to reflect when the crop is planted, since the penflufen applic ations are for seed trea tments or for a single in-furrow spray at planting for potato and other tuberous corm vegetables. Timing of planting was determined by consulting the crop-profile information provided by the United States Department of Agriculture (USDA, 2000). The modeled bean/legume use represents the realm of penflufen seed treatments for crops that are seeded at the surface, and the modeled potato use represents crops that are seeded below the surface. The potato a nd bean uses were selected for aquatic modeling purposes because they have the highest proposed applica tion rates, and are two different application methods of penflufen as a seed treatment (potato seed piece treatment plus an in-furrow spray, and a “slurry type” seed treatment application method). These model runs are used as upper-bound estimates of exposure an d represent the exposure from other uses of penflufen that are permitted at lower rates (for use as a seed treatment fungicide on vegetable, turberous and corm, alfalfa, grains, cereal, rice , vegetables, legume, including soybeans, canola, borage, crambe, cuphea, echium, flax seed, gold of pleasure, hare’s ear mustard, lesquerella,-Page 32 of 115- lunaria, meadowfoam, milkweed, mustard seed, o il radish, poppy seed, rapeseed, sesame, sweet rocket, calendula, castor o il plant, Chinese tallow tree, euphorbia, evening primrose, jojoba, niger seed, rose hip, safflower, stokes aster, sunflower, tallowwood, tea oil plant, veronia, cottonseed). Application rates for modeling purposes were sel ected in accordance with the proposed labels to generate the most conservative es timates of aquatic exposure.

Table 3.6 PRZM/EXAMS Model Input Parame ters for Penflufen Application Methods

Use Scenario Application

Rate lbs a.i./A

(kg a.i./ha) Applications per Year Application

Interval

(days) Date of

Initial Application Application

Method (CAM)

Potato 1 IDNpotato_WirrgST

D.txt 0.28 (0.31) 1 NA May 1 Granular incorporated,

3 inches 3
(4)

MEPotatoSTD.txt 0.28 (0.31) 1 NA May 1 Granular incorporated,

3 inches 3
(4) Beans and peas including including soybean 2 MSsoybeanSTD.txt 0.04 1 NA March 16 Granular

broadcast (2) 4

NA = not applicable

1 Includes a seed piece application at 0.14 lb a.i./A, and an in-f urrow application that occurs at planting for potato and other tuberous and corm vegetables at a rate of 0.14 lb a.i./A for a to tal single maximum application of 0.28 lb a.i./A.

2 Beans and Legumes include a “slurry type” seed treatment that i nvolves suspension of wettable powder treatment material in wat er. The treatment material applied as a slurry is accurately metered thr ough a sample mechanism composed of a slurry cup and seed dump pan.

3 Potatoes are planted at depths ranging fr om 3 – 6”. 3” was selected as the conser vative end of this range (USDA, 2000). Application was modeled as a granular application due to the seed piece treatment.

4 Modeled as a granular, broadcast, unincorporated application per DRAFT guidance for Recommende d Input Parameter for Simulating Various Pesticide Application Practices, R. David Jone s, through the WQTT. Provisional Guidance.

Two scenarios were used to represent the potato use because they represent different potato producing regions of the country. The field used to represent Id aho potato production is located in Bingham County, Idaho. This is an approve d standard PRZM scenario for potatoes (IDNpotato_WirrgSTD.txt). Accord ing to the 2000 Census of Agri culture, Idaho is the leading potato producing state in the Unite d States, producing greater than 29% of the total U.S. crop. The field has Malm fine sandy loam soil, which ha s a volcanic origin ideal for growing potatoes. This is a hydrologic soil group C soil. The w eather data are from w eather station W24156, Pocatello, Idaho. The field used to represent po tato production in Maine is located in Aroostook County (#1 producing county in Maine) in Northeas tern Maine (MLRA143/146). This is also an approved standard PRZM scenario for potat oes (MEPotatoSTD.txt). Aroostook County produces approximately 90 percent of Maine’s potatoes. According to the 1997 Census of Agriculture, Maine is the 3 rd largest producer of potatoes in the United States behind Idaho and Pennsylvania. The soil selected to simulate the fi eld is a Conant silt loam. Conant silt loam is a fine loamy, isotic, frigid Aquic Ha plorthods. These soils are extens ively used for potatoes, oats and peas. This is a hydrologic soil group C soil. The weather data are from weather station W14607, Caribou, ME.

The field used to represent beans and peas (i ncluding soybean) is in Yazoo County, Mississippi. This is one of the approved standard PRZM scenarios used for modeling legumes (MSsoybeanSTD.txt). The field has Loring silt loam soil, which is a fine-silty, mixed, active,-Page 33 of 115- thermic Oxyaquic Fragiudalfs. Th is is a hydrologic soil group C soil. The weather data are from weather station W03940, Jackson, Mississippi.

The Tier I Rice Model was used to estimate sc reening-level exposure to penflufen that may occur in water bodies receiving re leased water from rice paddies th at were seeded with rice seed treated with penflufen. This model uses the ap plication rate for rice ( 0.006 lb a.i./A) and the organic carbon partitioning coefficient for penflufen (290 mL/g oc).

The modeled aquatic EECs resulting from the proposed penflufen uses (listed in Table 3.7 ) were used for risk estimation in this screening-level assessment. The model input and output filenames supporting these values are listed in Appendix E

.

Table 3.7. Modeled Aquatic Surface Water 1-in -10-year EECs for Proposed Uses of

Penflufen 1

Uses Scenario Max. App. rate (lbs a.i./A/yr) Peak (ppb) 21-day (ppb) 60-day (ppb)

Potato MEpotato 0.28 3.52 3.50 3.47

IDpotato 0.28 1.13 1.10 1.07

Beans and Peas MSsoybean 0.04 2.39 2.36 2.32

Rice Tier I Rice Model 0.006 4.71 <4.71 <4.71

1 Range in model estimates represent the uppe r bound of estimated environmental concentr ations completed using half-lives for pa rent-only.

The ecological pond modeled with EXAMS is a st atic water body of fixed volume and no outlet ( i.e. no flow-through). Penflufen is persistent in aquatic environments and since the ecological pond has no outlet to discharge chemical, the mo deling indicates penflufen accumulates in the pond throughout the 30-year simulations. Exposure endpoints, in this assessment, are based on yearly peak concentrations. In the case of persistent compounds in the farm pond, a 1-in-10 year EEC does not only reflect varyi ng meteorological conditions that are expected once every 10 years, since material carries over from year to year. Thus the yearly pe aks are not independent, but are partially functions of the previous year’s concentrations. The graph below ( Figure 3.2 ) of the daily PRZM/EXAMS EECs from the Ma ine potato model run shows that because penflufen is persistent, there is a buildup of the compound over th e entire simulation. It should be noted that the peak from the first modeled year of application is estimated to be less than 1.0 ug/L compared to the reported peak acute value of 3.52 ug/L. This is a result of the buildup from year to year due to the persis tence of penflufen and the EXAM S farm pond is a static water body. Carry-over of residues in the rice paddy over multiple years was not considered.-Page 34 of 115- Figure 3.2. Daily PRZM/EXAMS Ou tput for Maine Potatoes 0.00E+00 5.00E

‐ 01 1.00E+00 1.50E+00 2.00E+00 2.50E+00 3.00E+00 3.50E+00 4.00E+001/1/19611/1/19631/1/19651/1/19671/1/19691/1/19711/1/19731/1/19751/1/19771/1/19791/1/19811/1/19831/1/19851/1/19871/1/19891/1/1991DailyAquaticEEC(ug/L)

Date (mm/dd/yyyy) 

## Penflufen: Maine Potato Daily Output

3.2.2.2. Sediment Pore Water Exposure

Environmental fate data show that penflufen dissipates from the water column but not from aquatic systems in their entirety, as it has been detected in sediment; therefore sediment exposure may be a concern for sediment-dwelling organism s. Benthic sediment pore water EECs were calculated for the proposed maximum use patterns for penflufen. Pore-water EECs are provided

in Table 3.8. The rice model does not estimate pore water concentrations.

Table 3.8. 1-in-10 year Pore Water EECs for Proposed Uses of Penflufen

Uses Scenario Max. App. rate (lbs a.i./A/yr) Peak (ppb) 21-day (ppb) 60-day (ppb)

Potato MEpotato 0.28 3.45 3.44 3.43

IDpotato 0.28 0.97 0.97 0.97

Beans and Peas MSsoybean 0.04 2.21 2.20 2.19-Page 35 of 115- 3.2.3. Measures of Terrestrial Exposure

3.2.3.1. Terrestrial Wildlife

Terrestrial wildlife exposure estimates are typically calculated for birds and mammals, emphasizing a dietary exposure route for uptake of the pesticide active ingredient. Birds are considered surrogates for terrestrial-phase amphi bians as well as reptiles. For exposure to terrestrial organisms from seed treatments, estimation of pesticid e residues in or on seeds as food items assumes organisms are exposed to a single pesticide residue in a given exposure scenario and focuses on the possible dietary ingestion of re sidues. For seed applications, estimation of loadings of penflufen per unit ar ea is calculated based on known or estimated seeding rates. This approach, which intends to represent exposures vi a multiple routes and not just direct ingestion, considers observed acute effects (acute oral LD 50 ) in terrestrial toxico logy studies and relates

them to the surface area where the pesticide is applied (LD 50 /ft 2 ).

T-REX is used to calculate dose-based EECs of penflufen for mammals and birds consuming treated seeds. Seeding rates as well as maximu m penflufen application rates according to the proposed label for the major uses of penflufen are provided in Table 3.9 . Other seed treatment use patterns are an order of magnitude belo w on a per acre basis. Estimated avian and mammalian doses of penflufen as determined using T-REX are also provided in the table. Risk quotients (RQs) are calculat ed using the adjusted LD 50 for the smallest weight class of animal (20 g for birds and 15 g for mammals).

Table 3.9. Penflufen application rates and corresponding avian and mammalian doses as determined using maximum proposed treatment rates and T-REX.

Crop Penflufen application

rate (lbs. a.i./A) Maximum Seeding Rate (lbs seed/acre) 1 Maximum Seed Application Rate (mg ai/kg seed) Avian Dose(mg ai/kgbw/day) Mammalian Dose (mg ai/kg-bw/day) Available AI (mg ai

/ft 2 )

Bean 3 0.02 436 47.27 11.96 10.02 0.22

Canola 0.00123 15 141.82 35.89 30.05 0.10

Corn 0.0033 33 94.55 23.93 20.03 0.03

Cotton 0.0019 19 94.55 23.93 20.03 0.02

Potato 0.13 6969 19.20 4.86 4.07 1.40

Potato 2 0.28 6969 38.41 9.72 8.14 2.79

Rice 0.006 129 47.27 11.96 10.02 0.06

Sunflower 0.00123 4 141.82 34.89 30.05 0.01

Wheat 0.0078 156 47.27 11.96 10.02 0.08

1 USEPA, 2011a, Acres Planted per Day and Seed ing Rates of Crops Grown in the United States, Memorandum from Beck and Ratnayake, Biological and Economic Analysis Division, to Deschamp (HED) and Spatz (EFED), March 2011.

2 Succluent beans have the highest seeding ra te, therefore present the greatest exposure

3 Including the in-furrow treatment-Page 36 of 115- Penflufen exposures to terrestrial invertebrates are not quantitativ ely calculated for derivation of deterministic RQs. However, risk to this taxon is assessed qualitatively in the Risk Description,

Section 4.2.

Additionally, the model SIP v1.0 is used to evaluate whether risk to terre strial animals is of concern for drinking water alone. The model a ssumes those terrestrial animals are getting 100% of their drinking water from the treated field. The model uses the solubility of the compound and weight-adjusted toxicity values. Results of th e model are discussed in the Risk Description.

3.2.3.2. Terrestrial Plants

Exposure of naturally-occurring te rrestrial and semi-aquatic (wetla nd) plant species is typically estimated using OPP’s TerrPlant (v1.2.2; USEP A, 2006b) model and is assumed to encompass

areas outside the immediate use site. The TerrPla nt model is used to derive EECs in runoff and drift for terrestrial and semi-aqua tic plants near areas where penf lufen has been applied. Runoff exposure is assessed in two scenar ios: sheet and channel runoff. In the sheet runoff scenario, the treated area generating runoff is assumed to dr ain into an area with equal size containing seedlings, resulting in 1, 2, or 5% of the amount applied being deposited. In the channel runoff scenario, a ten-to-one ratio of treatment area to receiving area re sults in 10, 20, or 50% of the amount applied being deposited on soil with emerging or emerged seedlings. Spray drift is also a source of pesticide loading to non-target areas. There is an assumption that no spray drift is

associated with seed treatment. The in-furrow treatment is narrowly sprayed close to the ground and spray drift from this application is consider ed negligible. TerrPlantestimates EECs based on application rate, application method, chemical sol ubility in water, type of runoff and default assumptions of drift (which is zero in the case of penflufen). The EECs for terrestrial and semiaquatic plants for a single appli cation of penflufen at the maximu m label rate for the two highest proposed uses are presented in Table 3.10

.

Table 3.10 EECs* for Terrestrial and Semi-Aquatic Plants Near Penflufen Use

Areas.

Use and Application Single Max. Application

Rate (lbs a.i./A) EECs (lbs a.i./A)

Total Loading to Semi-Aquatic Areas Dry Areas (Total)

Potato seed piece Seed treatment

withincorporated infurrow spray 0.28 0.0028 0.028

Beans* Seed treatment 0.0384 0.000768 0.00768

*all other uses are applied at a rate at least an order of ma gnitude lower than beans and potatoes resulting in much lower EECs

.

3.3. Ecological Effects Characterization

In screening-level ecological risk assessments, effects characterization describes the types of effects a pesticide can have on aquatic and terrest rial organisms. To da te, toxicity tests for-Page 37 of 115- amphibian or reptiles are not requ ired; birds are used as surrogates for reptiles and terrestrialphase amphibians and freshwater fish are used as surrogates for aquatic-phase amphibians. This characterization is based on the registrant-submitted toxicity data for birds, mammals, fish, invertebrates, and plants for penflufen, two major degradates and a typical formulated product (PEN 240FS). No data were available in the public literature for penflufen effects characterization (see below).

In addition to the data submitted in support of registration, the public version of ECOTOX (ECOTOXicity) database (USEPA, 2011) was searched for additional toxicity data from the open literature. The ECOTOX database is a pu blicly-available, quality -assured, comprehensive tool for locating toxicity data from the open li terature and is maintained by EPA Mid-Atlantic Ecology Division. More information on ECOTOX can be found at: http://www.epa.gov/ecotox. Research papers are thoroughly screened using sta ndard procedures before being accepted into ECOTOX thereby ensuring consistent, high qua lity information. For penflufen and its degradates, no studies were identified in ECOTOX as of September 18, 2011.

Given that penflufen is a new ac tive ingredient with no previous registration in the U.S. or any other country, it is assumed that no eco logical incidents exist for penflufen.

3.3.1. Aquatic Toxicity Assessment

The most sensitive acute and chronic effects me asurement endpoints associated with penflufen exposure to freshwater and estuarine/ marine species are summarized in Table 3.11. All acceptable and supplemental studies submitted for the registration of penflufen are described

below

.

Results of acute toxicity studies in freshwater and estuarine/marine fish indicate that penflufen is highly to very highly toxic to fish on an acute ex posure basis. Dose-dep endent sublethal effects observed in fish studies included surfacing, leth argy, erratic swimming, loss of equilibrium, loss of vertical orientation, labored respiration, and lying on the bottom. Reduced fish length was observed in the F1 generation of the available EL S study. Acute toxicity studies indicate that penflufen is moderately toxic to freshwater and estuarine/marine invertebrates on an acute exposure basis. Quiescence, pale color and a bnormal positioning were reported sublethal effects

in invertebrates. In some studi es the pooled control was used by the primary reviewer (Canada). In cases where it was judged to not impact th e derived endpoint, the statistics were not reassessed by the Agency.-Page 38 of 115- Table 3.11. Most Sensitive Acute and Chronic Toxicity Data for A quatic Organisms and Plants Exposed to Penflufen Technical
Exposure

Scenario Species Affected Endpoint Toxicity Measurement MRID (Classification)

Freshwater Fish

Acute Common carp ( Cyprinus carpio ) Mortality 96-hr LC 50 = 90 μg a.i./L Slope: N/A MRID 48023583 (Acceptable)

Chronic Common carp ( Cyprinus carpio ) Acute-toChronic

Ratio NOAEC = 18.1 μg a.i./L Acute-to-Chronic

Ratio based on [Fathead minnow;

116/23.4 = an ACR of 4.96; 90/ 4.96 = 18.1].

Freshwater Invertebrates

Acute Water flea ( Daphnia spp.) Immobility 48 hr EC 50 >4660 μg a.i./L 1
Slope: N/A MRID 48023574 (Acceptable)

Chronic Water flea ( Daphnia spp.) Reproduction

& Growth 21-day NOAEC = 1530 μg a.i./L MRID 48023587 (Supplemental)

Subacute Midge ( Chironomus

tentans ) Mortality

Growth Pore Water Exposure 10 day NOAEC = 780 μg a.i./L MRID 47443238 (Supplemental)

Estuarine/Marine Fish

Acute Sheepshead minnow ( Cyprinodon variegatus ) Mortality 96-hr LC 50 = 1150 μg total a.i./L Slope: N/A MRID 48023586 (Acceptable)

Chronic No studies available

Estuarine/Marine Invertebrates

Acute Eastern oyster ( Crassostrea virginica ) Shell Deposition 96-hr EC 50 = 1300 μg a.i./L Slope: NA MRID 48023578 (Acceptable)

Chronic No studies available Aquatic Plants
7-day

exposure Duckweed ( Lemna gibba ) None 7-day EC 50 >4700 μg a.i./L NOAEC = 2400 μg a.i./L MRID 48023603 (Acceptable)

72-hour

exposure Green algae ( Pseudokirchneriella subcapitata ) None 96-hr EC 50 >5100 μg a.i./L NOAEC = 520 μg a.i./L MRID 480243604 (Supplemental)

3.3.1.1 Toxicity to Freshwater Fish

Acute Effects

An acute toxicity study (MRID 48023580; Acceptable) with rainbow trout ( Oncorhynchus mykiss ) is available for penflufen. Fish were exposed under static conditions for 96-hour to

mean measured concentrati ons of <0.006 (control and so lvent control), 0.066, 0.110, 0.22, 0.51 and 0.93 mg a.i./L. Sublethal effects were obser ved in fish in the 0.22, 0.51, and 0.93 mg a.i./L treatment groups. Sublethal effects noted in the fish included loss of equilibrium, labored respiration, abnormal position at the bottom of the water column or at the surface, and-Page 39 of 115- quiescence. No sublethal effects were observed in fish in the c ontrol, solvent control, 0.066, and 0.110 mg a.i./L groups. Fish mortality wa s 10, 100, and 100% in the 0.22, 0.51 and 0.93 mg a.i./L groups, respectively. There was no mortalit y in the controls or in the two lowest test concentrations (0.066 and 0.110 mg a.i./L). The 96-hour LC 50 for rainbow trout was 0.31 mg a.i./L (95% confidence interval 0.22 to 0.51 mg a.i./L). The NOAEC was 0.110 mg a.i./L based on mortality and clinical signs of to xicity. Penflufen is classified as highly toxic to rainbow trout on an acute exposure basis.

An acute toxicity study (MRID 48023581; Acceptable) with bluegill sunfish ( Lepomis

macrochirus ) is available for penflufen. Fish were e xposed to mean measured concentrations of <0.006 (control and solvent control), 0.065, 0.129, 0.28, 0.51 and 1.00 mg a.i./L. Sublethal effects noted in fish in the 0.51 and 1.00 mg a.i./L treatment groups included loss of equilibrium, labored respiration, abnormal position at the bott om of the water column and quiescence. No

sublethal effects were observed in fish in the control, solvent c ontrol, 0.065, 0.129, and 0.28 mg a.i./L groups. Fish mortality was 70 a nd 100% in the 0.51 and 1.00 mg a.i./L groups, respectively. There was no mortality in the cont rols or in the other test groups. The 96-hour

LC 50 for bluegill exposed to penflufen was 0.45 mg a.i./L (95% confidence interval 0.28 to 1.00 mg a.i./L). The NOAEC was 0.285 mg a.i./L and the LOAEC was 0.51 mg a.i./L based on mortality. Penflufen is classified as highly toxic to bluegill sunfish on an acute exposure basis.

An acute toxicity study (MRID 48023582; Acceptable) with fathead minnow ( Pimephales promelas ) is available for penflufen. Fish were e xposed to mean measured concentrations of <0.006 (control and solvent control), 0.055, 0.106, 0.22, 0.46 and 0.90 mg a.i./L. Sublethal

effects were noted in the fish in the 0.106 mg a.i./L group included loss of equilibrium and quiescence. No sublethal effects were observed in fish in the c ontrol, solvent control, and 0.055 mg a.i./L groups. Fish mortality was 40, 100, 100, and 100% in treatment groups 0.106, 0.22, 0.46, and 0.90 mg a.i./L, respectively. There was no mortality in the controls or the 0.055 mg a.i./L group. The 96 hour LC 50 for fathead minnow was 0.116 mg a.i./L (95% confidence interval 0.055 to 0.220 mg a.i./L). The NOAE C was 0.055 mg a.i./L based on mortality and clinical signs of toxicity. Penf lufen is classified as very high ly toxic to fathead minnow on an acute exposure basis.

An acute toxicity study (MRID 48023583; Acceptable) with common carp ( Carpinus carpio ) is available for penflufen. Fish were exposed to mean measured concentrations of <0.006 (control and solvent control), 0.061, 0.117, 0.196, 0.475 and 0.751 mg a.i./L. No sublethal effects were observed in fish in the control, solvent cont rol and 0.061 mg a.i./L gr oup. Sublethal effects including loss of equilibrium or fish lying on side or back, quiescent, inactive or abnormally low activity, and labored respiration were observed in fish in the 0.117 mg a.i./L group. No mortality was observed in the control, so lvent control and 0.061 mg a.i./L group. Mortality after 96-hours was 90, 100, 100 and 100% in the 0.117, 0.196, 0.475, a nd 0.751 mg a.i./L groups, respectively.

Binomial distribution with untransformed data was used to obtain a 96-hour LC 50 of 0.090 mg a.i./L and a NOAEC of 0.061 mg a.i./L. Penflufen is classified as very highly toxic to common carp on an acute exposure basis.-Page 40 of 115- Degradates

An acute toxicity limit study (MRID 48023584; Acceptable) with common carp ( Cyprinus carpio ) is available for the degr adate penflufen-3-hydroxy-butyl. Carp were exposed, under static conditions, to mean meas ured test concentration of 36.3 mg a.i./L. No mortalities or sublethal effects were observed to common carp ( Cyprinus carpio ) in either the control or treatment groups. The 96h-LC 50 was, therefore, greater than 3 6.3 mg a.i./L (mean measured).

An acute toxicity limit study (MRID 48023585; Acceptable) with common carp ( Cyprinus carpio ) is available for the degradat e penflufen-pyrazolyl-AAP. Carp were exposed, under static conditions, to mean measured te st concentration of 0.799 mg a.i./L. No mo rtalities to common carp ( Cyprinus carpio ) were observed in either the control or treatment groups. All fish in the test group (0.799 mg a.i./L) displayed sli ght reduced vigor. Therefore, the 96h-LC 50 was greaterthan 0.799 mg a.i./L and the NOAEC was 0.799 mg a.i./L. This 96-h LC50 value for penflufenpyrazolyl-AAP is at least one or der of magnitude greater than the LC50 reported for carp (0.09 mg/L).

Formulation

An acute toxicity study (MRID 48024004; Acceptable) with common carp ( Cyprinus carpio ) is available for a representative formulation of penflufen (240FS; 22.4%). Carp were exposed, under static conditions, to mean measured test concentration <0.00511 (control), 0.0134, 0.0281,0.0620, 0.166, 0.316, 0.641 and 1.46 mg a.i./L.. At study termination, no mortalities or sublethal effects were observed in the cont rol, 0.0134, 0.0281, and 0.0620 mg a.i./L treatment groups. Fish mortality was 100% in the 0.166 mg a. i./L treatment group and higher. Sub-lethal effects in the 0.166 mg a.i./L and higher treatment groups incl uded abnormally low activity, laboured respiration, fish remaining either on th e surface or the bottom of the tank, and loss of equilibrium followed by death. The 96h-LC 50 was 0.101 mg a.i./L and the NOAEC was 0.062 mg a.i./L, which is roughly equivale nt in toxicity to the TGAI.

Chronic Effects

A fish early-life stage study (MRID 48023588; Acceptable) was conducted using the fathead minnow ( Pimephales promelas ). The exposure period was 35-days under flow-through

conditions. The mean measured concentrations were: control and solv ent control (<0.6), 6.21, 12.2, 23.4, 47.6 and 95.7 μg a.i./L. Hatching starte d on day 4 and was completed by day 5. There was a significant difference in time to ha tch between the pooled controls and the 95.7 μg a.i./L treatment group on day 4, however, this delay in time to hatch was no longer evident by day 5. There was also no statistical difference in larval survival between the pooled controls and any of the treatment groups. Both the percent hatc hed and percent larval survival ranged between 92 and 97%. The growth parameter of fish lengt h was the most sensitive endpoint in this study (3% at NOAEC). The 35-day chronic NOAEC and LOAEC were 23.4 and 47.6 μg a.i./L, respectively.

No chronic toxicity studies of penflufen’s formul ations or degradates in freshwater fish were

submitted.-Page 41 of 115- 3.3.1.2. Toxicity to Freshwater Invertebrates

Acute Effects

An acute toxicity study (MRID 48023574; Acceptable) using Daphnia magna (neonates, <24 hours old) is available for pe nflufen. Daphnids were exposed under static conditions for 48 hours to mean measured concentrations of < 0.025 (control and solven t control), 0.30, 0.61, 1.26, 2.33 and 4.66 mg a.i./L. Due to limited solubility of penflufen in the labo ratory dilution water, no concentrations higher than nominal 5 mg a.i./L could be tested. Dimethylformamide was the solvent used to prepare the test solutions (0.1 mL /L). The only treatment related effects were at the highest concentration where 20% immobilization (4 of 20) was reported. The 15 of the surviving waterfleas exhibited one or more clin ical symptoms (only 1 normal daphnid). Clinical symptoms included quiescence, abnormal position on th e bottom of the vessel, and pale in color.

The 48-h EC 50 for Daphnia magna was determined to be greater than 4.66 mg a.i./L. Penflufen is classified as moderately toxic to daphnids on an acute exposure basis. The observed NOAEC is 2.33 mg ai/L.

An acute toxicity study (MRID 48023577; Accep table) using juvenile crayfish ( Procambarus

clarkii ) is available for penflufen. One replicat e of 10 crayfish were exposed under static

conditions for 96 hours to mean measured concentr ations of <0.03 (control and solvent control), 0.31, 0.64, 1.16, 2.3 and 4.5 mg a.i./L. The organisms were not fed during the test. Due to limited solubility of penflufen in the laboratory dilution water, no concentrations higher than nominal 5 mg a.i./L could be test ed. Dimethylformamide was the solvent used to prepare the test solutions (0.1 mL/L). The crayfish were observed for mortalities and sublethal effects at 4, 24, 48, 72 and 96 hours. All surviving crayfish were nor mal. There were only two mortalities during the study and both mortalities were suspected to be due to cannibalism. On Day 4, one crayfish

in the solvent control and one in the 4.5 mg a.i./L concentratio n group were noted as dead. The

96-hour LC 50 for crayfish was determined to be great er than 4.5 mg a.i./L). Penflufen is classified as moderately toxic to crayfish on an acute exposure basis.

Degradates

An acute toxicity study (MRID 48023575; Acceptabl e) with the degradate penflufen-pyrazolylAAP is available. Six replicates of Daphnia magna (neonates, <24 hours old) were exposed

under static conditions for 48 hour s to mean measured concentr ations of <0.0104 (control), 0.709, 1.42, 1.52, 1.33, and 3.12 mg a.i./L. No solvent was used in this study. There were no treatment related effects at any test concentration. The 48h EC 50 of penflufen-pyrazolyl-AAP on Daphnia magna was determined to be greater than 3.12 mg a.i./L

A 48h acute toxicity study (MRID 48023576; Accep table) with the degradate penflufen-3- hydroxy-butyl. Daphnids were exposed to mean m easured concentrations of < 0.5 (control), 3.30, 6.8, 14, 28 and 62 mg a.i./L. There were no treatment related effects at any test

concentration. The 48h EC 50 of penflufen-3-hydroxy-butyl on Daphnia magna was determined to be greater than 62 mg a.i./L.-Page 42 of 115- Although the existence of non-definitive values for Daphnia EC 50 with parent penflufen and its degradates prevents precise comparisons from being made, there is no evidence to indicate greater toxicity of degradates to Daphnia compared to parent chemical. There are no data on the effect of formulations on daphnids.

Chronic Effects

A chronic life-cycle study (MRID 48023587; S upplemental) is available for daphnids. Daphnia

magna (1 st instars <24 hours old, 25 animals per study group) were exposed in a static-renewal test system (3 renewal intervals per week) for 21 days to mean measured test concentrations of <0.006 (control and solvent control), 0.10, 0.18, 0.37, 0.74, and 1.53 mg a.i./L. No dose related

behavioral/sublethal effects were observed in any of the parental test groups and controls. One daphnid each in the control and 0.10 mg a.i./L group were found to be immobilized. The daphnid in the 0.10 mg a.i./L group was killed due to handling error. At study termination, mean lengths ranged between 5.11 and 5.26 mm while mean dry weights ranged between 1.266 to 1.545 mg. There were no statistica lly significant difference in the growth end-points between the pooled control group and any of the treatment groups . Time to first brood was six days for all control and test groups except the 1.53 mg a.i./L group, where time to first brood was at day seven. Penflufen did not negatively affect the time to first brood for daphnids. Therefore, the NOAEC is 1.53 mg ai/L and the LOAEC is >1.53 mg ai/L

No chronic toxicity studies of penflufen formul ations or degradates using freshwater aquatic

invertebrates were submitted.

Benthic Organisms

A 10-day study (MRID 48023590; Acceptable) evaluati ng benthic stage survival and growth of the midge ( Chironomus dilutus ) was performed with hard water a nd artificial sediment in a flowthrough test system which renewed the overlying water. The exposure to penflufen was via spiked sediment. The sediment concentrations we re mixed and equilibrated over a 21-day period at the nominal concentrations of control, solvent control, 6.25, 12.5, 25, 50 and 100 mg a.i./kg dry weight sediment. There were 10 replicates per treatment leve l; 8 for biological observations and 2 for measured concentration analysis. E ach test vessel/glass beaker received a 100-mL aliquot of spiked sediment and then a 175-mL aliquot of clean, overlying water was added.

On Day 0, the organisms were impartially selected and added to each of the 8 replicates which were designated for biological observations. E ach vessel contained 10 second- and third-instar larvae (with at least 50% of the organisms at 3 rd instar) that were co llected 11 days after hatching. The 10-day study included observations of midge behavior and survival and measurements of ash-free dry weight. Th ese data were used to determine the LC 50 or IC 50 , NOAEC and LOAEC based on pore water concentrati ons and sediment concentrations. Mean measured concentrations for sediment, pore wa ter and overlying water were conducted on Day-0 and a Day-10 of the study. The compound was st able in the sediment over the 10-day midge exposure. The mean measured concentrations in the sediment were control and solvent control-Page 43 of 115- (<0.60), 3.99, 8.51, 17.7, 34.4 and 63.8 mg a.i./kg dry we ight sediment. The mean measured concentrations in the pore water were c ontrol and solvent cont rol (<0.01), 0.38, 0.78, 1.97, 4.07 and 8.28 mg a.i./L; and in the mean overlying wa ter concentrations were control and solvent control (<0.01), 0.02, 0.04, 0.09, 0.16, and 0.35 mg a.i./L.

During 10-days of flow-through exposure to th e spiked sediments there were no clinical symptoms of toxicity noted in the surviving larvae in any control or treatment group. One dead midge was found on the sediment surface on day 8 in the 34.4 mg a.i./kg dry weight sediment group. At study termination (day 10), mortality wa s 2% in the controls and 0% in the solvent control. Mortality in the treatment groups was 5, 2, 5, 6, and 7% in the 0.38, 0.78, 1.97, 4.07 and 8.28 mg a.i./L pore water concentrations, resp ectively. Midge survival in the highest concentration was significantly reduced when compared with the pooled control. The LC 50 was greater than 8.28 mg ai/L pore water. The NOAEC for survival was 4.07 mg a.i./L pore water

concentration.

Midge growth at study termination, as measured by ash-free dry weight , was inhibited -13, 7.0, 20, -2.0, and 21% in the 0.38, 0.78, 1.97, 4.07 and 8.28 mg a.i./L pore water concentrations, respectively, when compared to the pooled control. The IC 50 for growth is greater than 8.28 mg ai/L pore water; the NOAEC for growth was 0.78 mg a.i./L based on pore water concentrations. The most sensitive endpoint in the 10-day study was midge growth.

3.3.1.3. Toxicity to Estuarine/Marine Fish

Acute Effects

An acute toxicity study (MRID 48023586; A cceptable) with sheepshead minnow ( Cyprinodon variegatus ) is available for penflufen. Fish were e xposed to mean measured concentrations of <0.012 (control and solvent control), 0.116, 0.21, 0.43, 0.82, 1.92 and 3.45 mg a.i./L. Dimethylformamide was used as solvent at the concentration of 0.1 mL/L in each test level except for the water control. There were no prec ipitates in any of the test solutions. No mortality or clinical si gns of toxicity were observed in th e control, solven t control, 0.12, 0.21, and 0.43 mg a.i./L groups. Mortality was 10, 100, and 100% in the 0.82, 1.92, and 3.45 mg a.i./L groups. Clinical signs of toxicity were also noted in th e 0.82, 1.92 and 3.45 mg a.i./L groups. The symptoms noted included vertical orientation, on bottom, at surface, labored respiration and quiescence. The 96-hour NOAEC was 0.43 mg a.i./L and the 96-hour LC 50 calculated by binomial probability was 1.15 mg a.i./L. Penflu fen is classified as moderately toxic to sheepshead minnow on an acute exposure basis.

Chronic Effects

No chronic toxicity tests in estuarine/ma rine fish with the TGAI, formulations, or degradates were submitted.-Page 44 of 115- 3.3.1.4. Toxicity to Estuarin e/Marine Invertebrates

Acute Effects

An acute toxicity study (MRID 48023578; A cceptable) using Eastern oysters ( Crassostrea virginica ) is available for penflufen. Oysters were exposed under flow-through conditions for 96

hours to mean measured concentrations of < 0.1 (control and solven t control), 0.23, 0.44, 0.90, 1.4 and 3.2 mg a.i./L. There were no mortali ties among oysters in any treatment or control groups during the test. All oys ters appeared normal thr oughout the 96-hour exposure period. After 96 hours, the mean shell deposition were 3.3, 3.3, 2.3, 2.9, 2.1, 1.3, and 1.4 mm in the control, solvent control, 0.23, 0.44, 0.90, 1.4 and 3.2 mg a.i./L treatment groups, respectively. Percent inhibition of shell gr owth relative to the pooled c ontrol data in the 0.23, 0.44, 0.90, 1.4 and 3.2 mg a.i./L treatment groups was 30, 11, 35, 61 and 57%, respectively. There was no statistical difference in growth between the pooled control and the 0.44 mg a.i./L treatment group. There was a statistically significant redu ction in shell growth in the 0.23, 0.90, 1.4 and 3.2 mg a.i./L treatment groups in relation to the pooled control. Although th ere was a statistically significant reduction in growth in the 0.23 mg a.i./L treatment group relative to the pooled control, this reduction was not considered to be treatment related as shell growth was not statistically significantly reduced in the next highest test group (0.44 mg a.i./L). The 96-hour

EC 50 was calculated to be 1.3 mg a.i./L. The NO AEC was considered to be 0.44 mg a.i./L. The

96-hour EC 50 was calculated to be 1.3 mg a.i./L. Penflu fen is classified as moderately toxic to Eastern oysters on an acute exposure basis.

A 96h acute toxicity study (MRID 48023579; Acceptable) using mysid shrimp ( Americamysis

bahia ) is available for penflufen. Mysids were exposed under flow-through conditions to mean measured concentrations of < 0.025 (contro l and solvent control), 0.45, 0.76, 1.4, 2.6 and 4.7 mg a.i./L.. Due to limited solubility of penflufen in the laboratory dilution water, no concentrations higher than nominal 5 mg a.i./L could be teste d. Dimethylformamide was the solvent used to prepare the test solutions (0.1 mL/L). At study termination, one mysid was dead (5% mortality) in the negative control group. No mortalities were observed in the solvent control, 0.45, 0.76, and 1.4 mg a.i./L groups. Mortality was 55% (11 dead) and 100% in the 2.6 mg a.i./L and 4.7 mg a.i./L test groups, respectively. Clinical symptoms of toxicity includi ng erratic swimming, lying on the bottom of the chamber, and reduced growth compared to the controls were noted in the 2.6 and 4.7 mg a.i./L test groups. One mysid wa s noted with erratic swimming in the 0.76 mg a.i./L group only on day 3. All mysid shrimp app eared normal in the 0.76 mg a.i./L group at study termination. No other sublethal eff ects were noted in the study. The 96-hour LC 50 value was 2.5 mg a.i./L and the 96-hour NOAEC was 1.4 mg a.i./L. Penflufen is classified as moderately toxic to mysids on an acute exposure basis.

3.3.1.5. Toxicity to Aquatic Plants

Studies were submitted for a freshwater vascular plant (duckweed, Lemna gibba ) and a green algae ( Pseudokirchneriella subcapitata ). Species typically used to evaluate risk to also include a cyanobacteria ( Anabaena flos-aquae) , a freshwater diatom ( Navicula pelliculosa ) and a marine alga ( Skeletonema costatum ). That studies on these three taxa have not been submitted increases-Page 45 of 115- the uncertainty in the risk assessment.

Four studies on green algae were submitted: one on technical penflufen, one on the formulated product PEN 240FS, one each on the degradates AAP and pen-3HB.

Vascular Aquatic Plants

A study (MRID 48023603; Acceptable) examining th e effect of technical penflufen on the aquatic macrophyte duckweed ( Lemna gibba G3) was submitted. Three replicates with an initial cell density of 1 x 10 4 cells/mL were exposed to penflufen, under static (shaken cultures) conditions, for 96 hours. Mean measured concen trations were contro l and solvent control <0.015, 0.27, 0.54, 1.1, 2.4 and 4.7 mg a.i./L. The test solutions were renewed on Day 3 of the study and the compound was stable in the te st system. There were no compound related phytotoxic effects noted in the st udy. All fronds appeared normal during observations on days 0 and three. On study day five and seven, several fr onds in one of the control vessels (replicate A) appeared brown and/or transparent. This effect was isolated to this re plicate vessel and did not appear to have an effect on the frond number or dry weights of the plants in this test replicate.

Plants were normal in all other test vessels and test levels.

After seven days, the mean frond numbers were 184.2, 167.7, 169.3, 174.0, 166.0, and 142.3 in the pooled control, 0.27, 0.54, 1.1, 2.4, and 4.7 mg a.i. /L treatment groups, respectively. Percent inhibition of frond numbers were 9.0, 8.1, 5.5, 9.9, and 22.7% in the 0.27, 0.54, 1.1, 2.4, and 4.7 mg a.i./L treatment groups, respectively, as compared to the pooled control. Inhibition of mean cumulative biomass was 9.5, 7.8, 5.9, 9.5, and 18.6% in the 0.27, 0.54, 1.1, 2.4, and 4.7 mg a.i./L treatment groups, respectively, as co mpared to the pooled control, and inhibition of mean growth rate was 3.4, 3.1, 2.3, 3.8, and 9.5% for the corresponding treatment groups , respectively, when compared to the solvent cont rol group. Mean frond count in the 4.7 mg a.i./L group was statistically significant reduced when compared to the pooled controls. Mean dry weight was 1.012, 1.036, 1.021, 1.014, 1.018, and 1.014 g in the pooled control, 0.27, 0.54, 1.1, 2.4, and 4.7 mg a.i./L treatment groups, respectively. There were no statistically significant difference between the pooled control and any of the trea tment groups for mean dry weight. The 7-day EC 50 values for all endpoints in the duckweed study we re >4.7 mg a.i./L which was the functional limit of solubility in the test system. The NOAEC for frond count/number, cumulative biomass and growth rate were all 2.4 mg a.i./L. Frond c ount/number, cumulative biomass and growth rate were the most sensitive endpoints in this study.

Nonvascular Aquatic Plants

A study (MRID 48024007; Supplemental due to only being 72h) examining the effect of formulated penflufen (PEN240FS; 22.7% a.i.) on green algae, Pseudokirchneriella subcapitata

, was submitted. Three replicates with an initial cell density of 1 x 10 4 cells/mL were exposed to penflufen, under static (shaken cultures) conditions, for 72 hours. Mean measured

concentrations were contro l and solvent control (<0.015 mg a.i./L), 0.510, 1.51, 3.90, 9.42, and 24.8 mg a.i./L. Cell density was determined daily in each of the three test replicates at each test concentration. Inhibition of gr owth rate relative to the cont rol growth rate was 0.0, -1.4, 4.3, 2.3,-Page 46 of 115- and 41.0% for the 0.510, 1.51, 3.9, 9.42, and 24.8 mg a.i. /L treatment groups, respectively. The

72-hour EC 50 and NOAEC for cell density inhibition were 7.5 and 1.51 mg a.i./L, respectively.

The 72-hour EC 50 and NOAEC for the inhibition of growth rate were > 24.8 and 1.51 mg a.i./L, respectively.

A study (MRID 48023604; Acceptable) examining the effect of penflufen technical on green algae, Pseudokirchneriella subcapitata , was submitted. Three replicates with an initial cell density of 1 x 10 4 cells/mL were exposed to penflufen, unde r static (shaken cu ltures) conditions,

for 96 hours. Mean measured concentrations were control and solv ent control (<0.015 mg a.i./L), 0.14, 0.28, 0.52, 0.99, 2.3 and 5.1 mg a.i./L. Mean measured recoveries were within the range of 91-95% of the nominal co ncentrations. Cell density was de termined daily in each of the three test replicates at each test concentration. Parameters measured included cumulative biomass, growth rate, and cell de nsity at 96 hours. The 96-hour EC 50 value values for growth rate and cumulative biomass were >5.1 mg a.i./L with the NOAEC value of 0.52 mg a.i./L, based on biomass and cell density inhibition.

Degradates

A study (MRID 48023606; Supplemental because th e study was conducted for 72h) examining the effect of the degradate penflufen-pyrazolyl-AAP on green algae, Pseudokirchneriella subcapitata , was submitted. Three replicates with an initial cell density of 1 x 10 4 cells/mL were exposed to penflufen, under static (shaken cultures) conditions, for 72 hours. Mean measured

concentrations were contro l and solvent control (LOQ 5.2 μg a.i./L), 9.42, 34.4, 98.3, 320, and 1071.5 μg a.i./L. Mean measured recoveries were within the range of 91-95% of the nominal

concentrations. The 72 EC 50 values were calculated based on th e mean measured concentrations. At the highest test concentration (1071.5 μg a.i./L ), the inhibition of growth rate and % biomass were only 3 and 11.9% respectively. As a result , reliable confidence intervals could not be

calculated. The 72-hour EC 50 values for growth rate and cumulative biomass were >1071.5 μg a.i./L. The NOAEC was 98.3 μg a.i./L.

A study (MRID 48023605; Supplemental because th e study was conducted for 72h) examining the effect of the degradate penf lufen-3-hydroxy-butyl on green algae, Pseudokirchneriella subcapitata , was submitted. Three replicates with an initial cell density of 1 x 10 4 cells/mL were exposed to penflufen, under static (shaken cultures) conditions, for 72 hours. Mean measured

test concentrations were c ontrol, 4.3, 8.4, 16.8, 35.8, and 71.9 mg a.i./L. No solvent was used in the preparation of the test solutions. Based on the limited solubility of the pure metabolite in algal media, the highest possible test concentration was 75 mg/L. The 72-hour EC 50 value for cell density was 60.8 mg a.i./L, the most sens itive endpoint. The NOAEC was 16.8 mg a.i./L.

3.3.2 Terrestrial Effects Characterization

The most sensitive acute and chronic toxicity reference values associated with penflufen exposure to mammals, birds, and terrestri al invertebrates ar e summarized in Table 3.12 . The most sensitive measurement endpoints for terrestrial plants are presented in Table 3.13

.-Page 47 of 115- Penflufen is practically n on-toxic to Norway rat ( Rattus norvegicus ) on an acute exposure basis. A two-generation study on reproduction and fertility in the rat showed penflufen to cause chronic toxicity effects in the parents and F 1 and F 2 generations that would impact adult body weights

and reduced litter size.

Studies of acute oral (dose-base d) toxicity in bobwhite quail ( Colinus virginianus ) and canary ( Serinus canaria ) indicated that penflufen is practical ly nontoxic to bobwhite quail and canary when administered a single oral dose. Two s ubacute dietary toxicity studies indicate that penflufen TGAI is also practic ally nontoxic to mallard duck ( Anas platyrhynchos ) and bobwhite quail on a subacute dietary exposure basis. For chronic effects, no effects were observed in the bobwhite quail study, but treatment-r elated effects on number of eggs hatched per live embryo in the reproduction toxicity study of penflufen TGAI in mallard du ck were noted at all test concentrations; therefore, a definitive NOAEC valu e was not derived in th e study. No studies of the formulations or the degradates were submitted; all measurement endpoints for avian species are based on technical grade penflufen.

Results of available toxicity studies indicate that penflufen TGAI is practically nontoxic to honey bees ( Apis mellifera ) on an acute exposure basis, though th ere are effects on the fecundity of Aphidius rhopalosiphi , a parasitoid wasp, and earthworms ( Eisenia foetida ) on an acute contact exposure basis.

Tier I limit studies of the effect of the penf lufen formulation PEN 240FS on seedling emergence and vegetative vigor in terrestrial plants were submitted, indicating that terrestrial plants are relatively insensitive to penflufen at applicati on rates slightly less than the maximum per acre application rate for the pr oposed registration uses.

Table 3.12. Penflufen Technical Grade Toxici ty Measurement Endpoints for Terrestrial

Animals.
Exposure

Scenario Species Exposure

Duration Toxicity Reference Value MRID (Classification)

Mammals

Acute (Dose-based) Laboratory rat Single oral dose LD50 > 2000 mg a.i./kg bw MRID 40823749 Acceptable

Chronic (Dietary-based) Laboratory rat Two-generation NOAEL = 1000 mg/kg diet LOAEL = 4000 mg/kg diet

Endpoints based on decreased parental, decreased litter size MRID 48023812 Acceptable

Birds

Acute (Dose-based) Bobwhite quail

Colinus virginianus 14-day single

oral dose LD 50 >4000 mg a.i./kg bw NOAEL: 2000 mg a.i./kg bw (based on female body weights) MRID 48023591 (Acceptable)

Acute (Dose-based) Canary

Serinus

canaria 14-day single

oral dose LD 50 >2000 mg a.i./kg bw NOAEL: 2000 mg a.i./kg bw MRID 48023592 (Supplemental)-Page 48 of 115- Table 3.12. Penflufen Technical Grade Toxici ty Measurement Endpoints for Terrestrial

Animals.
Exposure

Scenario Species Exposure

Duration Toxicity Reference Value MRID (Classification)

Acute (Dietary-based) Bobwhite quail

Colinus virginianus 8-day dietary LC 50 : >8944 mg ai/kg diet NOAEC: 8944 mg ai/kg diet MRID 48023593 (Acceptable)

Mallard duck

Anas platyrhynchos 8-day dietary LC 50 : >9923 mg ai/kg diet NOAEC: 4613 mg ai/kg diet (based on treatment related effects on body weight and feed consumption) MRID 48023594 (Acceptable)

Chronic (Dietary-based) Mallard duck

Anas platyrhynchos ca. 22 week

avian reproduction study LOAEC: 292 mg ai/kg diet NOAEC: < 292 mg ai/kg diet (based on %hatch /live embryo and %hatch/eggs set) MRID 4823596 (Supplemental)

Bobwhite quail

Colinus virginianus ca. 21 week

avian reproduction study LOAEC: >946 mg ai/kg diet NOAEC: 946 mg ai/kg diet MRID 48023595 (Acceptable)

Terrestrial Invertebrates

Acute (Contact) Honeybee 48-hour LD 50 >100 μg a.i./bee NOAEL: 100 μg ai/bee MRID 40823597 (Acceptable)

Acute (Oral) Honeybee 48-hour LD 50 >108 μg a.i./bee NOAEC: 108 μg ai/bee MRID 40823597 (Acceptable)

Acute Earthworm 14-day LC 50 > 1,000 mg a.i./kg dw soil NOAEC: 316 mg a.i./kg dw soil LOAEC: 562 mg a.i./kg dw soil MRID 48023611 (Supplemental) 3

Table 3.13. Penflufen Toxicity Measurem ent Endpoints for Terrestrial Plants.
Exposure

Scenario Formulation Species Exposure

Duration Toxicity Reference Value Reference (Classification)

Seedling Emergence PEN 240FS None

affected 21-day test - single application EC 25 >0.22 lbs a.i./A

NOAEC = 0.22 lbs a.i./A MRID 48023601 (Acceptable)

Vegetative Vigor PEN 240FS None

affected 21-day test - single application EC 25 >0.22 lbs a.i./A

NOAEC = 0.22 lbs a.i./A MRID 448023598 (Acceptable)

3.3.2.1. Toxicity to Mammals

Acute Effects

An acute oral toxicity study is available for us ing female rats were submitted for penflufen. The study (MRID 48023749; Acceptable) derived a 14-day oral LD 50 value of > 2,000 mg a.i./kg bw. The study was conducted after OECD 423, with rat each given a single or al dose of 2,000 mg/kg bw. No clinical signs or toxicological effects on body weight or weight gain were observed, and no gross pathological changes in anim als sacrificed were observed.-Page 49 of 115- Additional product mixtures were tested in cluding PEN 24FS (MRID 48024102), penflufen plus prothioconazole plus metalaxyl (MRID 48024302), penflufen plus pr othioconazole (MRID 48024402) penflufen plus trifloxystrobin (MRID 4824502) and penflufen plus clothianidin (MRID 48024602). While none were an actual final product formulation, they represent a suite of ‘typical’ coformulants, each in relative amounts found in products, mixed in water and administered by gavage. Each study resulted in an LD 50 > 2000 mg mixture/kg-bw.

Chronic Effects

An acceptable 2-generation Wistar rat ( Ratus norvegicus ) reproduction and fertility effects study using penflufen technical was submitted to establish the toxicity of penflufen to mammals over prolonged periods (MRID 48023812). Thirty rats/sex/dose via the diet at nominal dietary concentrations of 0, 200, 1000, or 4000 ppm [e quivalent to 0, 12.8, 64.1, or 252.2 mg/kg/day (males)/ 0, 15, 75.9, or 294.5 mg/kg/day (females )] throughout the 10-w eek pre-mating period and to the dams through gestation and lactation. There was one set of litters per generation. The parental systemic LOAEL is 4000 ppm based on decreased body weight, decreased body weight gain (both generations). The parental system ic NOAEL is 1000 ppm. The offspring LOAEL is 4000 ppm based on a slight decrease in litter size in both generations, decreased pup body weight and pup body-weight gain. The offspring NOAEL is 1000 ppm. There was no treatment-related effect on reproductive performance in either the P or the F 1 -generation. The reproductive NOAEL is 4000 ppm, the highest dose tested.

3.3.2.2. Toxicity to Birds

Acute and Subacute Dietary

An acute oral toxicity study (MRID 48023591; Acceptable) was conducted with16-week old adult northern bobwhite quail ( Colinus virginianus ). Penflufen technical (purity 95.6%) was applied via single oral administra tion in gelatin capsules, ten birds per treatment level (five males and five females), caged by dose and by sex. The treatments incl uded a control (empty gelatin capsule), and three dose leve ls of 1000, 2000 and 4000 mg a.i./kg-bw. All birds were given equivalent numbers of gelatin capsules ( i.e. , four capsules) as determined by the number needed to accommodate the test material for the highest tr eatment group. No solvents were used for the treatments and no regurgitation was observed fo llowing treatment. The study duration was 14 days. There were no clinical symptoms of toxicity, no mortality a nd no gross pathological symptoms at necropsy in any dose group or the controls. There was reduced food consumption and reduced body weight and growth in the fema les at the highest treatment level of 4000 mg a.i./kg bw. The 14-day acute oral LD 50 of penflufen in northern bobwhite was >4000 mg a.i./kgbw. The NOAEL, based on reduced female body weights and feed consumption, was 2000 mg a.i./kg-bw. Penflufen is classified as practica lly nontoxic to bobwhite quail on an acute exposure

basis.

An acute oral toxicity study (MRI D 48023592) was conducted with canaries ( Serinus canaria ). The study is classified as Supplemental due to a prolonged pre-test fasti ng period; however this-Page 50 of 115- did not seem to adversely affect the control bird s. Penflufen was admini stered via single oral dose (in a gelatin capsule) to adu lt canaries. Ten birds (five males and five females) were dosed in the control and in the limit dose group at 2000 mg a.i./kg-bw. The control was dosed with empty gelatin capsules. The gelatin capsule was co ated with corn oil before administering to the birds. No regurgitation was observed following dose administration. The study duration was 14 days. No symptoms of toxicity were observed in the control and treatment group. No mortality occurred in the treatment group. There was one d eath in the control group (female) on day 3. This mortality was attributed to injuries su stained during dose admini stration. The 14-day acute

oral LD 50 of penflufen in canary was >2000 mg a.i./kg-bw. The NOAEL was 2000 mg a.i./kgbw. Penflufen is classified as practically nontoxic to canary on an acute exposure basis.

A subacute dietary study (MRID 48023593; Accepta ble) was conducted with northern bobwhite quail (10-day-old hatchlings, 10 hatc hlings per test level). Birds were exposed for five days to feed with mean measured dietary test c oncentrations of 0 (control), 659, 1106, 2319, 5394, and 8944 mg a.i./kg diet, which was equivalent to a daily dietary dose of 0, 125, 212, 445, 1005, and 1697 mg a.i/kg bw/day, respectively. The exposur e period was followed by a 3-day subsequent recovery phase on untreated feed. No clinical signs of toxicity or treatment-related mortalities were noted at any treatment level. There we re no statistically signi ficant reductions in body weight or growth during the e xposure period at any treatment level. There was no treatment related reduction in feed consumption at any trea tment level. Post-mortem examinations revealed no treatment related gross le sions or unusual observations . The sub-acute dietary LC 50 of technical penflufen in northern bobwhite was > 8944 mg a.i./kg-diet or >1697 mg a.i./kg-bw. Based on all parameters measured, the NOAEC was 8944 mg a.i./kg-diet. Penf lufen is classified as practically nontoxic to bobwhite quail on an acute dietary exposure basis.

A subacute dietary study (MRID 48023594; Accep table) was conducted with mallard ducks ( Anas platyrhynchos ). Ten-day-old ducklings, 10 per di et group were exposed to measured concentrations of 0 (<LOQ), 692, 1337, 2698, 4613 and 9923 mg a.i./kg-diet and were equivalent to a dietary dose of 0 (cont rol), 144, 308, 586, 1046, and 2208 mg a.i./kg bw/day, respectively. No clinical signs of toxicity or treatment-relate d mortalities were noted at any

treatment level. There was no treatment related reduction in feed consumption at any treatment

level. Post-mortem examinations revealed no treatment related gross lesions or unusual observations. There were no body weight or food consumption effects at treatment levels 692, 1337, 2698 and 4613 mg a.i./kg diet as compared to the controls. During the Day 5 exposure period, mean growth and body mass were signifi cantly lower in the 9923 mg a.i./kg feed treatment level as compared to the control group. Feed cons umption in the 9923 mg a.i./kg treatment level was also decreased as compared to the control group during the exposure periods. All birds recovered in body mass and growth when given untreated diet. The food consumption was less as compared to the control by the end of the recovery period (Day 8). The sub-acute dietary LC 50 for mallard duck was >9923 mg a.i./kg di et or >2208 mg a.i./kg body weight. Based on body weight and food consumption during th e exposure phase of the study, the NOAEC was 4613 mg a.i./kg diet (1046 mg a.i. /kg body weight/day). Penflufen is classified as practically

nontoxic to mallard duck on an acu te dietary exposure basis.-Page 51 of 115- Chronic

A one generation avian repr oduction toxicity study (M RID 48023595; Acceptable) was

conducted with the northern bobwhite quail. Young (17-week old) qua il were acclimated to test conditions for two weeks prior to th e start of the study. Eighteen pa irs of birds were introduced to penflufen treated feed at 19-week s of age and were exposed for a pproximately 22 weeks to mean measured dietary concentrations of 0 (control), 226, 461 and 946 mg a.i./kg-diet. These values correspond to daily dietary dose levels of 0, 23, 47 and 96 mg a.i./kg body weight/day, respectively. There were no treatment related adverse effects on the health or reproductive capacity of adult bobwhite quail. Additionall y, no treatment related effects were noted on hatchling health, growth, or survival of bobwh ite quail. The NOAEL was 946 mg a.i./kg feed (96 mg a.i./kg bw/day). The LOA EL was >946 mg a.i./kg feed (>96 mg a.i./k g bw/day).

A one generation avian repr oduction toxicity study (MRI D 48023596; Supplemental) was

conducted with mallard duck. The birds were 18 weeks old when introduced to penflufen-treated feed and were exposed for approx imately 21 weeks to mean measured dietary concentrations of control 0, 262, 502, 1049 mg a.i./kg feed. These values corres pond to daily dietary dose levels of 0, 27, 45, and 95 mg a.i./kg body we ight/day, respectively. There were no treatment related adverse effects on the health or reproductive capac ity of adult mallard duck. For hatchling effects, initial hatchling body wei ght and percentage of 14-day surviv al of eggs set were significantly lower in hatchlings in the 45 mg a.i./kg body weight/day treatment group when co mpared to the controls (Dunnett’s Test). As there were no significant difference in the corresponding hatchling end-points in the 95 mg a.i./kg body weight/day, these differences were not considered to be treatment related. The percent hatching survival of eggs set was significantly different for the 45 mg a.i./kg body weight/day treatment group when compared to the controls (Mann-Whitney Test). As there was no significant difference in the 27 and 95 mg a.i./kg body weight/day treatment groups when compared to the controls, this differ ence in the percent hatching survival of eggs set was not considered to be biologi cally relevant. The percent hatch of live embryo was significantly

different for the 27 and 95 a.i./ kg body weight/day treatment groups when compared to the controls (Mann-Whitney test) while all test groups were si gnificantly different (9%) than the control group for percent hatch of eggs set (Jonckheere test). For the ratio of hatchlings to live embryos, reductions from control ranged from 9 to 18%, with significant e ffects at the 262 (p=0.007) and 1049 (p=0.029) mg ai/kg diet levels . For the ratio of hatchling su rvivors to eggs set, reductions ranged from 10 to 15% of control with only a si gnificant effect (p=0.033) at the 502 mg ai/kg diet level, but a trend toward a significant effect was noted at the 263 (p=0.059) and 1049 (p=0.091) mg ai/kg levels. A reduction in hatchl ing weight was only apparent at the 502 mg ai/kg diet level (5%; p=0.044). These results when taken togeth er indicates an NOAEC <262 mg ai/kg diet and a LOAEC of 262 mg ai/kg diet. No other treatme nt related effects were noted on hatchling health, growth, or survival of mallard duck.-Page 52 of 115- 3.3.2.3. Toxicity to Terrestrial Invertebrates

Acute Effects

Honey bee

The oral and contact toxicity of penflufen towards honey bees ( Apis mellifera ) was studied over a 48 hour period (MRID 48023597; Acceptable). Honey bees (5 replicates of 10 bees per group) were exposed to penflufen formulation topically vi a the thorax (contact) or in the feed solution (oral) in a limit test. The dose for the contact test was 100 μg a.i. /bee while the test item dose for the oral test, based on the actual intake was 108.2 μg a.i./bee. A cetone was used as the organic solvent. A test with a toxic reference (Per fekthion, a formulation of the active substance dimethoate) was conducted in parallel. Endpoint s were mortality and behavior of the bees compared to control up to 48 hours after application.

In the contact toxicity test 0% mortality wa s observed at 100 μg a.i./bee after 48 hours. No mortality occurred in the solven t control and the water control, respectively. There were no behavioral abnormalities in the exposed bees or th e controls at any time during the test. In the oral toxicity test no mortality or behavioral abnormalities occurred in the treated bees or controls at any time during the study. The 48-h NOEL and LD 50 of penflufen technical were 100 and >100 μg a.i./bee in the contact toxicity test, respectively. The 48-h NOEL and LD 50 in the oral toxicity test were 108.2 and > 108.2 μg a.i./bee, respectively.

Parasitoid wasp

The formulated product PEN 240FS (containing 22.8% w/w penflufen) was studied on 48-hour old adults of the parasitoid wasp Aphidius rhopalosiphi under laboratory conditions (MRID 48023607; Supplemental). Glass plates were treated at rates of 0.01, 0.03, 0.05, 0.11 and 0.22

lbs a.i./A in 200 L deionized water and allowed to dr y. The parasitoid wasp Aphidius rhopalosiphi were then exposed to the spray residu es. The control group was treated with deionized water (200 L/ha). Dimethoate EC 400 ( 0.1 g a.i./ha in 200 L water/ha) was used as a toxic reference item. Four repl icates of 15 wasps (per treatm ent group) were exposed to the residues of the test item, re ference item and control treatme nts, respectively. During the mortality test, the wasps were fed ad libitum with aqueous honey solution (25 % w/w honey). The condition of the adult wasps was assessed at 2, 24 and 48 hours after exposure. At the end of the 48 hours 15 impartially chosen females from the water control and treatment groups 15, 30, 61, 124 and 250 g a.i./ha were transferred to a cylinder containing untr eated barley plants

infested with Rhopalosiphum padi for a period of 24 hours. The number of mummies was assessed 11 days later to ev aluate the potential fecund ity effects of PEN 240 FS.

The rate of mortality of wasps after 48-h expos ure to PEN 240FS was 3.3% (two deaths out of 60) in the control group. The uncorrected ra te of mortality was 3.3, 3.3, 3.3, 0.0, and 6.7% in treatment groups 0.01, 0.03, 0.05, 0.11 and 0.22 lbs a.i./A , respectively. Corr ected mortality was 0, 0, 0, 0, -3.4, and 3.4% for the control, 15, 30, 61, 124, and 250 g a.i/ha treatment groups, respectively. Statistical analysis (FISHER`s Exact test, 1-sided, p-values adjusted according to-Page 53 of 115- Bonferroni-Holm, p<0.05) revealed no significant differe nces concerning the mortality after 48

hours between the control and all te st item treatment groups. The LD 50 of PEN 240 FS on the predatory wasp was, therefore, greater than 250 g a.i./ha.

In the fecundity assessment after 48-h exposure of PEN 240FS, the mean number of mummies produced per wasp was 6.5, 5.3, 2.5, 2.8, 2.8, and 2.3 in the control, 0.01, 0.03, 0.05, 0.11 and 0.22 lbs a.i./A treatment groups, respectively. The percent reduction in mean number of mummies produced per wasp between the control and the 0.01, 0.03, 0.05, 0.11 and 0.22 lbs a.i./A treatment groups were 18.4, 61.2, 57.1, 57.1, and 64.3%, respectively. There was a significant statistical difference between control and the 0.22 g ai/ha treatment level regarding

the reduction of the number of parasitized aphids per female (Wilcoxon test, 2-sided, p-values adjusted according to Bonferroni-Holm, p<0.05). The lower treatments (0.01, 0.03, 0.05, and 0.11 lbs a.i./A) resulted in no statistical difference as compared to the control. While this is not a guideline USEPA study, the data do i ndicate that there ar e reproductive effects at all rates tested, but that variability in the replicates (or the use of the Bonferroni correct ion) precluded sufficient statistical power to detect these effects. There are inhibitions of roughly 60% in the highest four

rates.

Predatory mites

A study with protonymphs of the predatory mite Typhlodromus pyri is available for penflufen (48023609; Supplemental). The protonymphs were exposed to spray residues of PEN 240FS (22.8% a.s. w/w on glass plates). The sp ray application rates were 10.01, 0.03, 0.05, 0.11 and

0.22 lbs a.i./A in 200 L deionized water/ha. The control was treated with deionized water (200 L/ha). Dimethoate EC 400 (4 g a.i./ha in 200 L water/ha) was used as a toxic reference item.

Protonymphs of T. pyri were exposed in 5 replicates of 20 mites (per treatment group) to the spray residues of the test item, reference item and control treatment, respectively. During the assessments the predatory mites were fe d with pollen (birch – pine mixture).

Mortality of 100 protonymphs was assessed 1, 4, 7, 10, 12 and 14 days after exposure by counting the number of living and dead mites. The number of escaped mites was calculated as the difference from the total number exposed. The reproduction rate of su rviving mites was then evaluated over the period of 7- 14 days after treatment by counting the total number of offspring (eggs and larvae) produced.

All OECD TG226 validity criteria for conducting the laboratory test with Typhlodromus pyri were met: The results of the control group indica ted that the test organisms were in a good condition (mortality: 11%, reproduction: 5.8 eggs /female). The results of the toxic standard group indicated that the test system was sensitiv e to harmful substances (corrected mortality: 83.1%).

Seven days after study initiation, mortality of mites in the control group was 11%. The corrected mortality of mites were -2.2, 3.4, 7.9, 6.7, and 10.1% in the 0.01, 0.03, 0.05, 0.11 and 0.22 lbs a.i./A treatment groups, respectively. There were no statistically signi ficant differences in-Page 54 of 115- mortality after 7 days between the contro l and all test item treatment groups. The LD 50 was, therefore, > 0.22 lbs ai/A.

The mean number of offspring produced per female after 14 days was 5.76, 6.69, 4.95, 5.31, 5.97, and 3.62 in the control, 0.01, 0.03, 0.05, 0.11 and 0.22 lbs a.i./A treatment groups, respectively. The reduction of m ean number of offspring relativ e to the control group was -16, 14, 7.8, -3.6, and 37 for the 15, 30, 61, 124, and 250 g a.i./ha treatment groups, respectively. There was a statistically signifi cant effect of the test item on reproduction at the highest application rate, only when compared to th e control group, resulting in a NOAEC of 0.11 lbs

ai/A.

Earthworms

A 14-day earthworm study is available for penflufen (MRID 48023611; Supplemental). Adult earthworms ( Eisenia fetida Andrei) (4 x 10 animals per concen tration, the overall average weight was 0.35 g) were exposed for 14 days in artific ial soil at nominal concentrations of 100, 178, 316, 562 and 1000 mg ai/kg dry weight soil. Th e earthworms were observed for mortality, weight changes and abnormalities ( e.g. changes in behavior). The animals were not fed during the study.

No morphological or behavioral effects were observed. No morta lity was observed in either the control or any of the treatment groups. At study termination, mean weights of the earthworms were 0.35, 0.36, 0.35, 0.33, 0 .31, and 0.28 in the cont rol, 100, 178, 316, 562, and 1000 mg a.i./kg dry weight soil groups, respectively. Earthworm weights in the 562 and 1000 mg a.i./kg dry soil groups were statistically significantly reduced relative to the control weights. The 14-day LC 50 of penflufen technical on earthworms was >1000 mg a.i./kg dry weight soil and the NOAEC was 316 mg a.i./kg dry weight soil.

Formulation

The effect of the formulated product Pen 240 FS on the survival, growth and reproduction of earthworms, Eisenia fetida , was studied over an eight w eek (56 day) period (MRID 48023612; Supplemental). Adult earthworms (approx. 7 m onths old, 8 x 10 animals for the control group and 4 x 10 animals per application rate of the treatment group) were exposed in an artificial soil (with 5 % peat content) to application rates of 57.8, 101.7, 180.3, 321.3, and 573.2 mg a.i./kg dry weight soil. After 28 days, the number of survivin g adult animals and their weight alteration was

determined. The adult earthworms were then re moved from the artificial soil and after an additional 28 days, the number of offspring was determined. After 28 days of exposure, no adverse behavioral and morphol ogical effects, and no mortalit y were observed in the adult earthworms in any of the control or treatment groups. Mean weight s were statistically significantly reduced in the 312.3 and 573.2 mg a.i./kg dry weight soil treatment groups with respect to the control gr oup (Dunnett’s method). No statistica lly significant difference in mean earthworm weights were observed between th e control and the 57.8, 101.7 and 180.3 mg a.i./kg dry weight soil groups.-Page 55 of 115- After eight weeks, there was no statistically significant difference in reproduction between the control and 57.8 mg a.i./kg dry weigh soil groups. There was a st atistically significant reduction in mean number of juvenile earthworms found in the 101.7, 180.3, 312.3, and 573.2 mg a.i./kg dry weight soil groups when compared to the co ntrol. The 28-day NOAEC related to growth was 180.3 mg a.i./kg dry weight soil. The 56-day NOAEC relate d to reproduction was 57.8 mg a.i./kg dry weight soil.

Additionally, there were no effects on the reproduction of the collembola species Folsomia

candida at the highest concentration tested (M RID 48023625). There were also no effects on mortality and reproduction on the soil mite species Hypoaspis aculeifer (MRID 48023626).

Degradates

The effect of penflufen-3-hydroxy-butyl, a tran sformation product of penflufen on the survival, growth and reproduction of earthworms, Eisenia fetida , was studied over an eight week (56 day) period (MRID 48023613; Supplemental). Adult earthwor ms were exposed in an artificial soil to application rates of 62.5, 125, 250, 500 and 1000 mg a.i. /kg dry weight soil. After 28 days of exposure, no adverse behavioral and morphological effects, and no mortality were observed in the adult earthworms in any of the control or treatment groups. After eight weeks, there was no statistically significant differen ce in reproduction between the cont rol and any of the treatment groups. The 28-day NOAEC related to growth was gr eater than 1000 mg a.i./ kg dry weight soil. The 56-day NOAEC related to repr oduction was greater than 1000 mg a.i./kg dry weight soil.

The effect of penflufen-pyrazolyl-AAP, a transformation product of penflufen on the survival, growth and reproduction of earthworms, Eisenia fetida , was studied over an eight week (56 day) period (MRID 48023614; Supplemental). Adult earthwor ms were exposed in an artificial soil to application rates of 63, 125, 250, 500 and 1000 mg a. i./kg dry weight so il. The 28-day NOAEC related to growth was 1000 mg a.i./kg dry we ight soil. The 56-day NOAEC, based on the statistically significant differen ce related to reproduction was 500 mg a.i./kg dry weight soil.

There were no effects of the 3-hydroxy-butyl degradate on Folsomia candida (MRID 48023627) or

Hypoaspis aculeifer (MRID 48023628) at the highest concentration tested. There were also no effects of
the pyrazolyl-AAP on either species at the highest concentration tested (MRIDs 48023629 and48023630,
respectively).

3.3.2.4. Toxicity to Terrestrial Plants

A limit study (MRID 48023601; Acceptable) was conducte d to evaluate the phytotoxic effects of PEN 240FS on the vegetative vigor of non-target terrestrial plant species following a postemergence application of 0.22 lbs ai/A onto the foliage of plants at the 2-4 leaf stage. The plants of eleven species were te sted, including seven dicoty ledonous species: sugar beet ( Beta vulgaris ), oilseed rape ( Brassica napus ), cucumber ( Cucumis sativus ), buckwheat ( Fagopyrum

esculentum ), soybean ( Glycine max ), sunflower ( Helianthus annuus ) and tomato ( Lycopersicon

esculentum ) plus four monocotyledonous species: oat ( Avena sativa ), onion ( Allium cepa ), ryegrass ( Lolium perenne ) and corn ( Zea mays ).-Page 56 of 115- After 21-days, survival for the el even species tested was 97 to 100% for the control and 100% in the treated groups. No adverse phytotoxicity eff ects were observed in either the control or treatment groups. Inhibition of shoot dry weight for the eleven species tested ranged between -

16 and 2% in relation to the control. Oilseed ra pe and corn were the only species exhibiting a reduction in shoot dry weight; s hoot dry weight inhi bition was 2% for both oilseed rape and corn, respectively. Reductions in plant height for the eleven species tested ranged between -11 and 5%. Tomato, onion, and oat were the only speci es exhibiting reductions in plant height of 1, 1, and 5%, respectively, when comp ared to the controls. The EC 25 for all plants is >0.22 lbs ai/A;

the limit rate will be us ed in lieu of a NOAEC.

A limit study (MRID 48023598; Acceptable) was to evaluate the effects of PEN 240 FS on the seedling emergence and seedling growth on non-targ et terrestrial plant species. PEN 240 FS was applied as a pre-emergence application on soil surface at an application rate of 0.22 lbs ai/A. Eleven species were tested, including seven dicotyledonous sp ecies: sugar beet ( Beta vulgaris ), oilseed rape ( Brassica napus ), cucumber ( Cucumis sativus ), buckwheat ( Fagopyrum

esculentum ), soybean ( Glycine max ), sunflower ( Helianthus annuus. ) and tomato ( Lycopersicon

esculentum ), and four monocotyl edonous species: oat ( Avena sativa ), onion ( Allium cepa ), ryegrass ( Lolium perenne ) and corn ( Zea mays ).

At test termination (21 days), seedling emer gence for the 11 crop species ranged between 72.5 and 100% in the untreated control group, and 62.5 to 97.5% in the treated group. Emergence

was inhibited relative to cont rol emergence only in oilseed rape, corn, and onion seedlings; percent inhibition in emergence was 11, 5, a nd 14% for oilseed rape, corn, and onion, respectively. Emergence in the other treated sp ecies was greater than the control emergence. Percent seedling survival for the 11 crops ranged from 97 to 100% in the control group and was 100% in all treated groups. Pen 240 FS was not s hown to have any negative effects on survival of emerged seedlings. Reductions in plant height for the eleven crops ranged from -10 to 5%

between the controls and trea ted group. Soybean, tomato, onion, and ryegrass were the only species with reductions in plant he ight relative to the respective controls with re ductions of 3, 5, 4, and 1%, respectively. Reductions in shoot dry weight to the el even crops ranged from -22 to 13% between the controls and treated group. O ilseed rape, buckwheat, soybean, tomato, and onion were the only species with reductions in shoot dry weight relati ve to their respective controls with reductions of 5, 10, 12, 6, and 13%, respectively. The EC 25 for all plants is >0.22 lbs ai/A; the limit rate will be used in lieu of a NOAEC.

No terrestrial plant studies were submitted for technical grade penflufen or the degradates.

4. Risk Characterization

4.1. Risk Estimation

Toxicity data and exposure estimates are used to evaluate the potential for adverse ecological effects on non-target species. This screening-leve l assessment for penflufen relies on the-Page 57 of 115- deterministic RQ method to provide a metric of potential risks. The RQ provides a comparison of exposure estimates to toxicity endpoints ( i.e. , the estimated exposure concentrations are divided by acute and chronic toxicity values). The resulting unitless RQs are compared to the Agency’s LOCs, as shown in Table 2.3 . LOCs are used by the Agency to indicate when the use of a pesticide, as directed by th e label, has the potential to cause adverse effects to non-target organisms.

4.1.1. Aquatic Organisms

The highest screening-level a quatic EECs based on the maximum application rates for each proposed use pattern were used to derive RQs. These exposure estimates represent concentrations in surface water ( Table 3.7 ). Peak EECs are used to represent acute exposure to fish, aquatic invertebrates, and aquatic plants, and the highest 21-day and 60-day average EECs represent chronic exposure to aquatic invert ebrates and fish, respectively. Because of penflufen’s persistence, each subsequent year may be affected by the previous year’s application. The PRZM-EXAMS modeling demonstr ates year-to year carry ove r for the first 20 years of modeling (see Figure 3.2 ).

4.1.1.1. Fish and Invertebrates

Fish

Table 4.1 lists RQs calculated for fish (freshwate r and estuarine/marine) and aquatic-phase amphibians exposed to penflufen, based on th e acute EECs generated from PRZM/EXAMS and Tier I Rice Model modeling scenarios. Results of acute toxicity studies in freshwater and estuarine/marine fish ( Table 3.13 ) indicate that penflufen is “highly toxic” to freshwater fish on an acute exposure basis. Ho wever, most RQs for proposed uses of penflufen fall below the Agency’s acute risk to listed species LOC (0.05), as well as the Agency’s acute risk to non-listed species LOC of 0.5. The RQ from the proposed rice is equal to the listed sp ecies LOC. No other

scenarios exceed the LOCs.

RQs for chronic exposures also fell below the Ag ency’s chronic risk to listed and non-listed species LOC (1.0).-Page 58 of 115- Table 4.1. Risk Quotients for Freshwat er Fish and Aquatic-phase Amphibians Exposed to Penflufen at the Highest EECs Us ing the Most Sensitive of the Available Endpoints.

Use EECs (ppb) Fish and Aquatic-phase Amphibian RQs

LC 50 = 90 μg ai/L NOAEC = 18.1 μg ai/L

Peak 60-day Acute 1,2 Chronic 3

Potato 3.52 3.47 0.039 0.19

1.13 1.07 0.014 0.06

Beans and Peas 2.39 2.32 0.027 0.13

Rice 4.71 <4.71 0.052 <0.26

1 Acute risk to non-listed species LOC for aquatic fish is 0.5

2 Acute risk to listed species LOC for aquatic fish is 0.05

3 Chronic risk to listed and nonlisted aquatic animals is 1.0

Aquatic Invertebrates

Definitive acute toxicity endpoints from studies on the TGAI were unavailable for freshwater invertebrates and thus RQs were not calculated and risk is expected to be low as the EC50 is greater than the highest concentr ation tested. The relationship be tween the highest endpoints in the studies and the estimated exposure will be disc ussed in the Risk Description section. Based on all available acute studies, penflufen is categorized as moderately toxic to aquatic

invertebrates. A definitive estuarine/marine e ndpoint is available for Eastern oyster (1300 μg ai/L), but the RQ is <0.01. A definitive chr onic exposure toxicity e ndpoint is available for freshwater invertebrates and the RQ is <0.01, at least two orders of magnitude below the Agency’s level of concern (1.0).

The 10- day NOAEC based on growth for benthic i nvertebrates through pore water exposure is 780 μg ai/L. The RQ calculated with the maximum 21d pore water EEC (3.44 μg ai/L) is <0.01. Therefore, risk is assumed to be low. The relationship between the toxicity endpoints and the exposure estimates will be discussed furthe r in the Risk Description section.

4.1.1.2. Aquatic Plants

Although penflufen does exhibit effects on both Lemna gibba and Pseudokirchneriella subcapitata , these effects are at much higher concentrations than those estimated for the highest proposed penflufen uses. For both taxa, both listed and nonlisted RQs are <0.01, while the

LOCs are 1.0.

4.1.2. Terrestrial Organisms

4.1.2.1. Mammals

Acute RQs were not calculated for mammals because only non-definitive acute oral toxicity data are available. Based on the available acute toxic ity data, no mortality was observed in any of the mammalian studies conducted on penf lufen technical or its formulated products at-Page 59 of 115- the highest concentrations/doses tested; as such, penflufen is categorized “practically nontoxic” to mammals on an acute exposure basis. Furthe r discussion of the predicted exposure values relative to the levels at which no mortality was observed is provided as part of the risk description in Section 4.2.4.

Based on the proposed maximum application rates, combined with the amount of seed per acre, the highest exposures occurred fo r the canola and alfalfa uses, re sulting in the highest chronic RQs across all uses of 0.14, less than the chronic risk LOC of 1.0. Even adding the in-furrow treatment to the seed piece treatment, the ch ronic exposure RQ for the potato use is 0.04. Table

4.2 lists maximum chronic exposure mammal RQs for all of the proposed uses based on the upper 90 th percentile Kenaga values. These RQs all fall below the Agency’s mammalian chronic risk to listed and non-listed speci es chronic risk LOC (1.0).

Table 4.2. Chronic Mammalian Risk Quotients for Penflufen Proposed Uses

Crop Penflufen application

rate (lbs. a.i./A) Maximum Seeding Rate (lbs seed/acre) 1 Maximum

Seed Application

Rate (mg ai/kg seed) Mammalian Dose (mg ai/kg-bw/day) Mammalian RQs

Alfalfa 0.00225 15 141.82 30.05 0.14

Bean 3 0.0384 436 47.27 10.02 0.05

Canola 0.00123 15 141.82 30.05 0.14

Corn 0.0033 33 94.55 20.03 0.09

Cotton 0.0019 19 94.55 20.03 0.09

Potato 0.13 6969 19.20 4.07 0.02

Potato 2 0.28 6969 38.41 8.14 0.04

Rice 0.006 129 47.27 10.02 0.05

Sunflower 0.00123 4 141.82 30.05 0.14

Wheat 0.0078 156 47.27 10.02 0.05

1 USEPA, 2011a, Acres Planted per Day and Seeding Rates of Crops Grown in the United States, Memorandum from Beck and Ratnayake, Biological and Economic Analysis Divisi on, to Deschamp (HED) and Spatz (EFED), March 2011.

2 Including the in-furrow treatment

3 Succluent beans have the highest seeding ra te, therefore present the greatest exposure

4.1.2.2. Birds

Acute RQs were not calculated for birds becaus e only non-definitive acute and sub-acute toxicity endpoints are available. Penflufe n is categorized as practically non-toxic to canary, mallard duck and bobwhite quail on an acute and subacute oral a nd dietary basis. Trea tment-related sublethal

effects were observed in mallard duck and bobwhite quail studies at the hi ghest concentrations tested; however these concentra tions were above the typical li mit dose for avian acute and subacute dietary toxicity studies. These effects (noted previously) will be disc ussed further, relative to potential exposure, in the Risk Description sec tion, but acute risk to avian species is expected

to be low.-Page 60 of 115- The measure of effect for chronic risk to bi rds was a non-definitive en dpoint (NOAEC <292 mg a.i./kg-diet. Therefore, chronic RQs for bi rds are not calculated. The nondefinitive endpoint relevant EECs are discussed qualitative ly in the Risk Description section.

4.1.2.3. Terrestrial Invertebrates

Risk assessments are not conducted for terrestrial inve rtebrates at the screeni ng-level at this time. Characterization of exposure rela tive to known toxicity endpoints fo r terrestrial invertebrates will

be discussed in the Risk Description section.

4.1.2.4. Non-target Terrestrial Plants

Potential effects to riparian and upland vegeta tion are assessed deriving RQs from terrestrial plant seedling emergence and vegetative vigor EC 25 and NOEAC endpoints. Based on the results of the submitted terrestrial plant toxicity tests for the typical formulated product Penflufen 240FS, there were no effects reported at the highes t rate tested (0.22 lbs a i/A). Based on the runoff exposure calculations in TerrPlant, using the greatest per acre rate from the potato use (0.28 lbs ai/A; 0.14 lbs ai/A for piec es plus 0.14 lbs ai/A), both nonlisted and list plant RQs are <0.01 for dry areas and 0.25 for low-lying areas vulnera ble to run-off, well below the LOC of 1.0. Therefore, risks to terrestrial plants from the proposed uses of penflufen are expected to be low.

4.2. Risk Description

The results of risk estimation i ndicate that proposed uses of pe nflufen are unlikely to adversely affect non-listed fish or aquati c invertebrates or aqua tic plants on either an acute or chronic exposure basis. Similarly, with the exception of assumed risk to bird s from chronic exposure, terrestrial animal and plant risks appear to be below the Agency’s levels of concern. Therefore, the risk hypothesis for this risk assessment is only partially supported (risk from chronic exposure is presumed for birds).

4.2.1 Exposure to Aquatic Organisms

Surface water EECs resulting from applications of seeds treated with penflufen for potato and bean uses are conservative estimates of exposure for the proposed uses of penflufen as a seed treatment fungicide. Application rates were ca lculated based on the be st available data for seeding rates for particular uses, which may re sult in low relative pounds of active ingredient applied on a per acre basis. The potato seed pi ece application was modele d as an incorporated application where seed pieces are planted at a depth of 3-6 inches (USDA, 2000); an additional in-furrow spray was made at the time of planting, also at a depth of 3-6 inches (the combined modeled application rate, 0.28 lbs a.i./A, was used as an input for PRZM). The bean/legume use represents the realm of penflufen seed treatments for crops th at are seeded at the surface, where the potato use represents crops that are seeded below the surface.

The Tier I Rice model was used to estimate exposur e from rice seed treated with penflufen. The EECs resulted in an RQ >0.05 for listed fish, whic h is an exceendence fo r listed fish. The label-Page 61 of 115- proposes the application of treated seed to dry fields, however the exact planting method is not specified, nor is water holding times. Info rmation on the holding times for paddy water, and permitted planting methods ( e.g. , drilling) would better inform the risk assessment for the rice

use. The model estimate is a conservative estimate of exposur e, considering the Tier I Rice Model assumes that when a pesticide is applied to a rice paddy it instantaneously partitions between the water phase and the sediment phase . The model does not account for pesticide degradation, mass transfer between the aqueous phase and the sediment , volatilization, dilution, or other dissipation processes; therefore the model provides an upper bound estimate of exposure for penflufen which is proposed for use on rice as a dry seeded application. Further, for modeling purposes we assumed that 100% of the chem ical on the seed coat is available. It is possible that only a percentage of the chemical on the seed coat is available and will partition

from the sediment to the water column. It is unknown what the available percentage is, but this uncertainty could be addressed with the submissi on of additional data supporting the release rate of penflufen from the seed coat into the soil ( i.e. , partitioning from the seed coat). Also there

will be some amount of the chemical that is taken up by the plant during emergence, and some amount that is degraded prior to, and duri ng, the flooded phase of rice production. These information may help to mitigate the potential ri sk to listed fish resulting from the use of penflufen.

Another potential mitigating action is a reduction in the application rate for rice seed from 0.006

lb a.i./A to 0.005 lb a.i./A re duces the peak exposure value from 4.71 to 3.93 ug/L, which results

in no acute risk LOC exceedance.

Model uncertainties are discussed in greater detail in Section 4.3

.

4.2.2 Risks to Aquatic Animals

Freshwater Fish

For acute exposure studies were submitted to the Agency for penflufen TGAI, as well as one for each of the two primary degradates. Studies on penflufen-3-hydroxy-butyl and penflufen pyrazolyl-AAP were conducted using common carp, the species most acute ly sensitive to the TGAI. The toxicity endpoints derived in these studies are much less sensitive than any from the TGAI studies. Additionally, there is a study, also with the common carp, that was conducted using the PEN 240FS product (a single ai formul ation). This study resulted in an endpoint similar to the TGAI study (0.101 μg ai/L vs 0.090 μg ai/L), indicating that inert ingredients in the formulation do not enhance penflufen’s toxicity to fish.

The most sensitive endpoint derived from the available studies was compared to the highest expected aquatic exposure values , and almost all are below the Agency’s levels of concern. Common carp was the most sensitive species to penflufen among those studied, with an LC 50 of 0.090 μg ai/L, and resulted in an RQ equal to the listed species LOC. The other freshwater fish tested, rainbow trout, bluegill sunfish and fa thead minnow, although appare ntly less sensitive, were within an order of 4X of the carp and so th e range in sensitivity appears to be quite narrow.-Page 62 of 115- However, the sheepshead minnow was quite a b it less sensitive to penflufen with an LC 50 of 1150 μg ai/L. Therefore, risk to estuarine/mari ne fish is generally expected to be low.

The RQ for acute exposure to freshwater fish from the proposed rice use is 0.052, indicating the potential for risk to listed freshwat er fish from this use (LOC for listed species is 0.05). There is uncertainty in the exposure value for this use, as described above. However, a reduction in application rate from 0.006 lbs ai/A to 0.005 lb s ai/A would reduce the RQ to 0.044, below the listed species acute risk LOC.

The EECs derived from PRZM/EXAMS are selected from the 30-year modeling scenario. However, the ecological pond modeled with EXAMS is a static water body of fixed volume and no outlet. Penflufen is persistent and sin ce the ecological pond has no outlet, the modeling indicates penflufen accumulates in the pond th roughout the 30-year simulations. EECs from flowing water bodies may be less than those esti mated in the static pond. Exposure endpoints in this assessment are based on yearly peak c oncentrations from th e static pond, per USEPA modeling guidance for ecological risk assessment (USEPA, 2004). In the case of persistent compounds, a 1-in-10 year EEC does not only reflect varying meteorological conditions that are expected once every 10 years, since materi al carries over from year to year. Figure 3.2 shows that there is a buildup of the co mpound over the first 20+ years of application, due to penflufen’s persistence.

Although there is a definitive endpoint for chronic exposure to freshwater fish from a study with fathead minnow, fathead minnow is not quite as acutely sensitive to penflufen as the common carp. Therefore, an acute to chronic ratio (A CR) from the fathead minnow studies (5X) was applied to the common carp. The chronic RQ fo r the rice use, which results in the highest estimated exposure, is 0.26, only about a quart er of the Agency’s level of concern.

Based on a water column exposure study, penflufen is not expected to bioaccumulate in fish. Due to its low log Kow (3.3), penf lufen is not expected to bioaccu mulate in aquatic invertebrates or bioaccumulate up the food chain (confirmation with the model KABAM is not shown).

Aquatic Invertebrates

Acute RQs were not calculated for freshwater in vertebrates due to the non-definitive endpoint for daphnid (>4660 μg total ai/L), crayfish (>450 0 μg ai/L) and for th e benthic chironomid (>8280 μg ai/L)

. RQ-values calculated with the highest concentration tested in these studies result in RQs <0.01, and there is no way to know from these studies how much greater than the highest dose test the concentration would need to be to achieve a definitive LC 50 value. Sublethal effects were noted in the daphnid stud y at the highest dose tested, making the observed NOAEC 2.33 mg ai/L The highest RQ-value calc ulated using that co ncentration would be 0.001, more than two orders of magnitude below the listed species LOC of 0.05.

The estuarine/marine invertebrates, mysid shri mp and Eastern oyster studies also reported sublethal effects at the higher concentrati ons. Using the observed NOAECs (440 and 1440 μg ai/L, respectively), the highest RQ-value woul d be 0.01, 5X lower than the listed species acute-Page 63 of 115- risk LOC.

Chronic risk to freshwater invertebrates was assessed base d on one reproductive study on Daphna magna ; the actual highest RQ is 0.003 several or ders of magnitude below the Agency’s chronic risk LOC of 1.0. However, estuarine/ma rine invertebrates exhi bited slightly greater sensitivity to penflufen than daphnids on an acute exposure basis. Because the daphnid acute value is nondefinitive, an ACR cannot be used to estimate the potential for effects from penflufen on a chronic exposure basis. But, the mysid NOAEC would need to be several orders of magnitude lower than the daphnid NOAEC for there to be an exceedance of the LOC.

While the benthic chironomid NOAEC, based on por e water concentration, was greater than 780 μg ai/L, based on growth. This value result s in an RQ-value of 0.004, several orders of magnitude below the current LOC for benthic orga nisms of 1.0. The RQ-value was calculated using the 1-in-10-year 21-day pore water c oncentrations from PRZM/EXAMS, although the study was only of a 10-day duration. Because pe nflufen’s concentrations do not change much between the peak and the 60-day values, risk to benthic invertebrates is expected to be low regardless of which value is considered.

Based on the 40 CFR Part 158 data requirements, penflufen should have a chronic sediment toxicity study submitted, since the half-life is greater than 10 da ys. The absence of this study introduces uncertainty as to the long-term effect of penflufen on sediment dwelling invertebrates. Given the metabolism half lives of up to 866 days , multiple years of penflufen application would result in increasingly high levels of exposure to these organisms. Howe ver, as indicated above, the NOAEC for growth in the 10-day study is seve ral orders of magnitude below the LOC. While the absence of this study represents an un certainty in the risk as sessment, requiring these data are unlikely to affect the risk conclusions for the proposed uses.

4.2.3 Risks to Aquatic Plants

Based on the available information on Lemna gibba and Pseudokirchneriella subcapitata , the proposed uses of penflufen do not exceed the Agency’s LOC for aquatic plant (1.0) for nonlisted or listed plants. While RQs were not calculated in the Risk Estimation section due to the lack of

definitive IC 50 values, there were effect s noted in the studies. The lowest NOAEC among the

vascular and nonvascular studies involving the TGAI or formula tion is 520 μg ai/L for green algae (based on biomass and cell density). At that concentration, the RQ = 0.006 whereas the LOC is 1.0. Therefore, potential risk to aquatic plants from th e proposed uses of penflufen is expected to be low.

However, risk to aquatic nonvascular species is typically evaluated with not only the green algae that was submitted, but also with a cyanobacteria, a centric diatom and a pinnate diatom. These additional species have not been submitted and ar e an appreciable source of uncertainty in the risk assessment. These planktonic taxa form the very basis of the aquatic food web and are frequently more sensitive to pesticides than gr een algae. However, any of these species would need to have a NOAEC of 3 μg ai/L to exceed the listed species LOC. Given that the green algae NOAEC is 520 μg ai/L, this would seem unlikely. For sedaxane, also a pyrazole-Page 64 of 115- carboximide, the NOAEC for green algae is 990 μg a i/L. The next most sensitive nonvascular plant species, the diatom Navicula pellicosa , has a NOAEC of 1200 μg ai/L.

In addition to studies on TGAI and the PEN 24F S formulation, degradate studies with green algae were submitted. Green alga was shown to be more sensitive to penflufen-pyrazolyl-AAP and penflufen -3-hydroxy-butyl than to the parent. However, even if the degradates were present in the water column at 100% of the parent, the highest RQ-value (based on the penflufenpyrazolyl-AAP NOAEC of 98.3 μg ai/L) would be 0.03, well below the listed species LOC of

1.0.

4.2.4. Risks to Mammals

Acute RQs were not derived for mammals in the Risk Estimation section of this assessment because no mortality to rats was observed at th e highest treatment level in the acute oral mammalian study ( i.e. >2000 mg ai/kg-bw) of penflufen tec hnical. Based on the seed treatment calculations in T-REX and the highe st dose tested in the acute rat study, the highest RQ-value for 15 gram mammals is 0.04 for potatoes with treated seed pieces plus the in-furrow treatment for the PEN 240FS product, which results in the high est exposure estimates for penflufen. Given that the 15 gram mammal is considered the most vulnerable and the RQ-value is less than half the listed species LOC (0.1), the potential for risk to mammals from acute exposure appears to be

low.

As presented in the Risk Estimation, chronic ma mmalian RQs for all applications of penflufen fell below the Agency’s risk to listed and nonlisted species LOC of 1.0, with a calculated maximum RQ of 0.14 for the propose d canola and sunflower uses.

Based on results of the screening model SIP, dr inking water exposure alon e is not a concern for mammals. Penflufen has a relatively low solubility in water, which is th e only parameter used in estimating potential exposure, and mammals are not particularly sensitive to penflufen on either

an acute or chronic basis.

4.2.5. Risk to Birds

Because the LD 50 and LC 50 values exceeded the highest treatm ent levels tested in the submitted

acute oral and sub-acute dietar y avian studies, standard RQs fo r acute and sub-acute exposure

were not calculated in the Risk Estimation section of this assessment. However, sublethal effects were observed on female body weights in the acute oral study with bobwhite quail at the highest dose tested (NOAEC=2000 mg ai/kg-bw). Th e maximum acute exposure RQ-value for a 20 gram bird (considered the most vulnerable in T-REX) is calculated from the proposed potato seed piece plus in-furrow treatme nt is 0.13, greater than the listed species LOC of 0.1. However,

this number reflects the bobwhite NOAEC and the canary nondefinitive LD 50 value, and not the median lethal dose for either species. A dditionally, potato seed pi eces (and the in-furrow treatment) are covered with at least 3” of soil, reducing potentia l exposure appreciably. The next highest RQ-value is for the proposed bean use, 0. 01. Therefore, while the calculated RQ-value is <0.13, acute risk to avian species from the proposed uses is considered to be low.-Page 65 of 115- Chronic RQs were derived as a screening exerci se in the Risk Estimation section of this

assessment for the non-definitive ri sk measure of effect to bird s (NOAEC < 292 mg ai/kg-diet). As a minimum level of risk, none of the RQs fo r any proposed uses of penflufen exceeded the Agency’s chronic risk to birds LOC of 1.0. Th e highest RQ-value (0.49) is for the proposed canola and sunflower uses. However, the maximu m direct chronic risk to nonlisted and listed bird species is unknown and cannot be precluded with the availabl e data. The study from which this endpoint is derived wa s conducted on mallard duck over ca. 22 weeks based on reduction in percent hatch per live embryo (9% at the lowest concentration), which is a frank effect with direct implication for the reproductive success of av ian species. No effects were observed in the bobwhite quail reproduction study. Based on the calculated RQ-value using the LOAEC in the mallard study, the mallard would need to be twice as sensit ive to penflufen ( i.e. the NOAEC would need to be half the LOAEC) for the chr onic LOC to be exceeded. The next highest RQvalues (corn and cotton; 0.32) indicate the NOAEC woul d need to be 3X lower for there to be an exceedance. However, direct chronic risk to listed and nonlisted av ian species cannot be precluded and is presumed for proposed uses of penflufen. A second study on reproductive effects in mallard duck in which a definitive NOAEC is derived would greatly reduce uncertainty in making a chronic ri sk call to birds.

The potential for direct mortalit y of nonlisted and listed birds (and to terrestrial-phase amphibian and reptiles for which birds serve as surrogates) from acute and s ubacute exposures of penflufen for all proposed uses is not expe cted. Direct risk is presumed for nonlisted and listed birds and surrogates from chronic exposures to all proposed uses and application methods of penflufen.

Based on results of the screening model SIP, dr inking water exposure alon e is not a concern for birds. Penflufen has a relatively low solubility in water, which is the only parameter used in estimating potential exposure, and birds are not pa rticularly sensitive to penflufen on either an acute or chronic basis. However, there is no t a NOAEC available for mallard duck (as discussed previously), and so risk to bi rds from drinking water alone is presumed. However, the mallard

duck NOAEC would need to be half of the lowest rate tested in the av ailable study for drinking water exposure alone to be a route of concern.

4.2.6. Potential Effects on Te rrestrial Invertebrates

The available toxicity data for honey bees indi cate that direct contac t and oral exposure to penflufen is not likely to adversely affect honey bee pollinators (young adu lt forage bees) in and around proposed use areas for penflufen. There is uncertainty in the amount of exposure that honey bees would be subject to fr om the proposed uses, but the lack of effects at 100 μg ai/ bee is expected to account for some, if not all, uncertainty in exposure. However, penflufen is coformulated in two products with clothianidin (PC Codes 044309 (stereochemistry unspecified); 660108 (E-isomer)), a systemic neonicotinic insecticid e that is associated with high bee toxicity and reported incidents with honey bees. Some of the incidents reported for clothianidin are

associated with dust from abraded seed coats from drilled seed appli cations (USEPA 2011).

There are no available data on the effect of this coformulation on honey bees.-Page 66 of 115- Mortality in parasitoid wasps was negligible, ho wever effects on reproduction were observed at

all concentrations. Percent re duction relative to the control was roughly 60% between 0.026 lbs

ai/A and 0.22 lbs ai/A. At 0.013 lbs ai/A the redu ction was 18%. Although the degree to which these species are likely to be exposed to penflufe n is uncertain, and mortality does not appear to be an issue at the highest proposed rates, reprodu ction of these species may be affected at some of the higher proposed rates. However, while the maximum proposed per acre rate is 0.28 lbs ai/A, the majority of applicati ons are 0.04 lbs ai/A or less. Again, being co-formulated with clothianidin should pose a greater potential for effects on to bene ficial insects than penflufen

alone.

Affects to body weight were obser ved in earthworms from a 14-da y study at concentrations of 562 and 1000 mg a.i./kg dw soil. Reproductive effects, i.e. number of offspring produced, were observed in a 56-day study at concentrations of as low as 101.7 mg a.i./kg dw soil (NOAEC 57.8 mg ai/kg soil). Given that penflufen is proposed as a seed treatment, the degree of exposure to earthworms is uncertain. The most likely exposure scenario is the potato s eed piece with the infurrow treatment. But even this proposed use cove rs a relatively small percentage of the field. As an exercise to characterize this toxicity at relevant environmental concentrations, an estimate was made as to the expected concentration of penflufen in soil at the maximum single application rate of 0.22 lbs a.i./A, assuming a so il depth of 15 cm and bulk density of 1.3 g/cm 3

. Given this scenario, although r ough, the predicted maximum soil concentration of penflufen would be 0.128 mg a.i./kg dw soil, which is orders of magnitude lower than the most sensitive effects endpoint from earthworm toxicity studie s (57.8 mg a.i./kg dw soil). Therefore, the potential for direct risk to earthworms from e xposure to penflufen in soil is not expected.

Screening-level risk assessments do not typically evaluate risks to terrestrial invertebrates; however, toxicity information for beneficial in sects is used to deve lop precautionary label language where necessary. Based on the availabl e data, precautionary label language for bees does not appear necessary for end-use products with penflufen as the on ly active ingredient.

4.2.7. Risk to Terrestrial Non-target Plants

Limit tests were submitted for both vegetative vigor and seedling emergence, at the rate of 0.22

lbs ai/A. No effects >25% were observed in e ither study. Minimal measured inhibitions were observed in biomass and shoot length, up to 5% in the vegetative vigor study, none statistically significant. In the seedling emergence study, measured inhibition of 14% emergence was

observed in onion and 10% and 12% biomass in buckwheat and soybean, respectively, none statistically significant. For the purpose of this risk assessment, the limit rate of 0.22 lbs ai/A is

used in lieu of a NOAEC. The highest per acre application rate of 0.28 lbs ai/A results in a listed species RQ of 0.25 for low lying areas vulnerable to run off and <0.1 for higher areas. Although the limit studies did not test up to the highest per acre application ra te, this rate is for the potato seed piece plus in-furrow treatment, which is an incorporated applic ation. The RQ of 0.25 represents the rate of 0.28 lbs ai/A unincorporated. Applying an incorporation depth of 3” reduced the RQ to 0.13. The 0.28 lbs ai/A application rate is an or der of magnitude greater than the per acre rate for a ny other proposed use.-Page 67 of 115- Because all the proposed uses are seed treatmen ts, no drift exposure is expected to nontarget plants. The in-furrow applica tion is generally sprayed extrem ely close to the soil and the application is immediately covered. Usually the nozzle is shielded to protect it from the soil. However, even if a 1% spray drift assumption is applied, the highest RQ is 0.13 for spray drift and 0.38 for low lying areas vulnerable to runoff.

While there is uncertainty due to the observed inhibitions in study endpoints, exacerbated by the study not being conducted up to the maximum per acre application rate , potential risk to nontarget terrestrial plants is expe cted to be low. The need for additional data for this risk assessment thought to have minimal on the risk conclusions in this risk assessment.

4.3. Uncertainties and Data Gaps

4.3.1. Fate and Transport

There is considerable variability in the aerobic degradation rate, contributing to the uncertainty of the degradation rate of penflufen. Two studi es were submitted that encompass six soils to fulfill the aerobic soil metabolism data requir ement for the parent penflufen (OPPTS 835.4100) for all outdoor pesticides use. Both studies were classified as Supplementa l for various scientific reasons ( e.g. , study duration was insufficient to charac terize the degradatio n of the parent, formation and decline of majo r degradates was not well characterized, half-lives were extrapolated beyond the study durat ion). Additional acceptable st udies, or supplemental data addressing the scientific issues identified in the studies would help reduce the uncertainty in the study results. Further uncertainty regarding the half-lives of penf lufen and its degradates would

be reduced with additiona l studies conducted for a sufficient dur ation to accurate ly characterize the formation and decline of all major degradates.

There was significant variability in the reported data for the aerobic aquatic metabolism study; the Anglerweiher water:sand system reported an unc haracterized decline of the parent and major degradates. This system was not be used for ri sk assessment purposes since the half-lives are of uncertain value. Therefore for modeling pur poses the single half-life from the Hoeniger water:sediment system was multiplied by three to account for the potential variability in degradation between aquatic system s. Additional data for anothe r water:sediment system would reduce the uncertainty and may reduce model input values.

4.3.2. Effects Uncertainties

There are no chronic exposure toxicity data on common carp, the most acutely sensitive fish species. Therefore, an ACR was applied to common carp based on the fathead minnow, for which there are both acute and chronic toxicity da ta. The ACR is considered protective of fish for the purpose of this risk assessment; however, the application of an ACR in the absence of

actual data does introduce uncerta inty to the risk assessment.

For the purpose of this risk assessment, the per acre in-furrow application was considered additive to the per acre potato s eed piece application rate. While the nature of this application-Page 68 of 115- results in the total application to be covered by soil, the actual e xposure to species that forage on potato seed pieces may be higher than estimated. Birds and mammals likely to forage on buried potato seed pieces are likely to be larger animals that would fa ll into the fruit/pods/seeds/large insect forage category, one of the less sensitive categories in the TREX model. However, this still represents an uncertainty in the assessment.

As discussed previously, there is uncertainty regarding potential effects from chronic exposure to

birds due to the lack of a NOAEC in one of th e available avian reproduc tion studies. There was a statistically significant 9% reduc tion in the ratio of hatchlings to live embryos at the lowest

concentration tested. It is unknown at what conc entration a there would be no significant effect and so risk is presumed. The NOAEC would need to be half of the LOAEC (292 mg ai/kg-diet) for there to be an RQ exceedance for chronic expo sure to birds. Other pyrazole compounds such as penthiopyrad (NOAEC =1520 mg ai/kg-diet) and pyroxasulfone (NOAEC=60 mg ai/kg-diet) do not show any consistency in toxicity from chronic exposure to birds.

Degradate Toxicity

Toxicity of the major degradates penflufe n-3-hydoxy-butyl and penflu fen-pyrazolyl-AAP are available for multiple taxa (fish, aquatic plants, earthworms) and in all cases were found to be less toxic than parent penflufen. The degree to which these toxic ity studies are applicable to other taxa is an uncertainty in the risk assessment. However, given that fish are the most sensitive taxa to the parent, this risk assessmen t assumes that these degradates are equally less toxic than the parent across all taxa.

No toxicity data on the degradat e penflufen fluoro-acid are availabl e. The lack of such data represents an uncertainty in the risk assessmen t. However, as it only forms from photolysis, exposure to this degradate is expected to be minimal.

4.3.3. Aquatic Exposure

Uses on potatoes and beans were simulated in the environment as granular applications, based on the assumption that seed, or seed piece, is trea ted with penflufen prior to planting (potato), or broadcasting seed on the surface of the soil (beans and peas, canola, etc. ). Draft guidance for Recommended Input Parameter for Simulating Vari ous Pesticide Application Practices (USEPA, 2011a) instructs the model user to increase the application effici ency in PRZM to 1.0, and reduce the drift to 0.0 for granular appl ications. This is again based on the assumption that penflufen is adsorbed to the seed prior to planting and does not dr ift as dust or in a slurry. To the extent that actual use patterns and amount of treated seed differ from the modeling assumptions, actual environmental concentrations could be lower, and additional non-target organisms could be exposed to penflufen ( e.g. , if drift is a factor). EFED used the best available data to make a reasonably conservative estimate of the amount of crop that could receive applications of penflufen based on current seedi ng rates for the crops modeled.

For the rice seed treatment, the la bel proposes the application of treated seed to a dry fields; however the planting method ( e.g. , drilling vs. broadcast) and water holding times are not-Page 69 of 115- specified on the label. Information on the holding times for paddy water, and permitted planting

methods would better inform th e risk assessment for the rice use. The model estimate is a conservative estimate of exposure, considering the Tier I Rice Model assumes when a pesticide is applied to a rice paddy it will instantaneous ly partition between a water phase and a sediment phase. The model does not account for pesticide degradation, mass transfer between the aqueous phase and the sediment, volatilization, dilution, or other dissipation proc esses; therefore the model provides an upper bound estimate of exposu re for penflufen. Further, for modeling purposes we assumed that 100% of the chemical on the seed coat is available. It is likely that only a percentage of the chemical on the seed coat is available and will partition from the

sediment to the water column. Also there will be some amount of the chemical that is taken up by the plant during emergence, and some amount th at is degraded prior to and during the flooded phase of rice production.

There is also uncertainty associated with the ab ility of the aquatic exposure modeling to simulate aquatic exposures as well as with the selection of input parameters. In this regard, one of the potentially important parameters that can impact concentration estimates is the selection of appropriate application dates. Al though the pesticide application da tes were selected to be most appropriate with considerations for labeled application recommendations ( e.g. , at the time of planting), model simulated cropping dates, and label restrictions, variability neve rtheless results because the time span that a pesticide may be applied may be large and the actual application dates are unknown, or vary for diffe rent regions of the country. Su ch variability is caused by the temporal proximity of a pesticid e application to rain events. As with all model estimates, the values presented here should not be viewed as precise estimates.

5. Federally Threatened and Endang ered (Listed) Species Concerns

Section 7 of the Endangered Species Act, 16 U. S.C. Section 1536(a)(2), requires all federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and anadromous listed species, and/or the United States Fish and Wildlife Service (USFWS) for listed wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species or their designated critic al habitat. Each federal agen cy is required under the Act to ensure that any action they aut horize, fund, or carry out is not likely to jeopardize the continued existence of a listed species or result in the destruction or adverse modification of designated critical habitat. To jeopardize the continued existence of a listed species means "to engage in an action that reasonably would be expected, directly or indirect ly, to reduce appreciably the likelihood of both the survival and recovery of a listed species in th e wild by reducing the reproduction, numbers, or distribution of the species" (50 C.F.R. § 402.02).

To facilitate compliance with the requirements of the Endangered Species Act (subsection (a)(2)), the Office of Pesticide Programs has es tablished procedures to evaluate whether a proposed registration action may directly or indi rectly appreciably reduc e the likelihood of both the survival and recovery of a listed species in the wild by re ducing the reproduction, numbers, or distribution of any listed sp ecies (USEPA, 2004). After the Agency’s screening level risk assessment is conducted, if any of the Agency’s listed species’ LOCs are exceeded for either

direct or indirect effect s, an analysis is conducte d to determine if any lis ted or candidate species-Page 70 of 115- may co-occur in the area of the proposed pesticide use or areas downstream or downwind that

could be contaminated from drift or runoff/erosi on. If listed or candidate species may be present in the proposed action area, further biological as sessment is undertaken. The extent to which listed species may be at risk is considered, whic h then determines the ne ed for the development of a more comprehensive consultation package, as required by the Endangered Species Act.

The federal action addressed herein is the propos ed new registration of penflufen on agricultural use sites it is expected that its use could occur nationwide.

5.1. Action Area

For listed species assessment pur poses, the action area is consider ed to be the area affected directly or indirectly by penflufen use and not merely the immediate area where penflufen is applied. At the initial baselin e, the risk assessment consid ers broadly described taxonomic groups and conservatively assumes that listed species within those broad groups are co-located with the pesticide treatment area. This means that listed terrestrial plants and wildlife are assumed to be located on or adjacent to the treat ed site and listed aquatic organisms are assumed to be located in a surface water body adjacent to th e treated site. The assessment also assumes that the listed species are located within an assumed area, which ha s the relatively highest potential exposure to the pesticide, and that ex posures are likely to decrease with distance from

the treatment area. Section 3.1 of this risk assessment presen ts the proposed pesticide use sites

that are used to establish initial co-l ocation of species with treatment areas.

5.2. Taxonomic Groups Po tentially at Risk

If the assumptions associated with the baseline action area result in RQs that are below the listed species LOCs, a "no effect" determination conclusion is made with respect to listed species in that taxa, and no further refinement of the acti on area is necessary. Furt hermore, RQs below the listed species LOCs for a given ta xonomic group indicate no concern for indirect effects on listed species that depend upon the taxonomic group for wh ich the RQ was calculated. However, in situations where the screening assumptions lead to RQs in excess of the listed species LOCs for a given taxonomic group, a potential for a "may aff ect" conclusion exists a nd may be associated with direct effects on listed sp ecies belonging to that taxonomic group or may extend to indirect effects upon listed species that depend upon that ta xonomic group as a resource. In such cases, additional information on the biology of listed sp ecies, the locations of these species, and the

locations of use sites are considered to determ ine the extent to which screening assumptions regarding an action area apply to a particular listed organism. Th ese subsequent refinement steps will consider how this information would impact the action area for a particular listed organism and potentially include areas of exposure that are downwind and downstream of the pesticide use

site.

Assessment endpoints, exposure pathways, and the conceptual models addressing proposed new penflufen uses, and the associated exposure a nd effects analyses conducted for the penflufen

baseline risk assessment are in Sections 2 to 3 . The assessment endpoints used in the baseline risk assessment include those defined operati onally as reduced survival and reproductive-Page 71 of 115- impairment for both aquatic and te rrestrial animal spec ies and survival, reproduction, and growth of aquatic and terrestrial plan t species from both direct acute and chronic exposures. These assessment endpoints are intended to address the standard set fo rth in the Endangered Species Act requiring federal agencies to ensure that any action they author ize does not appreciably

reduce the likelihood of both the surv ival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of the species. Risk estimates (RQs) which, integrating exposure and effects, are calcul ated for broad based taxonomic groups in the screening-level risk assessment presented in Section 4.

Both acute endangered species and chronic risk LOCs are considered in the baseline risk assessment to identify direct and i ndirect effects to taxa of listed species. This section identifies direct effect concerns, by taxa that are trigge red by exceeding endangered LOCs in the baseline risk assessment, with an evaluation of the potentia l probability of individu al effects for exposures that may occur at the estab lished endangered species LOC. Data on exposure and effects

collected under field and laborat ory conditions are evaluated to make determinations on the predictive utility of the direct effect screeni ng assessment findings to listed species. For penflufen, risk from chronic exposure is presumed for birds, reptiles and terrestrial-phase amphibians. Potential acute risk to listed fish and aquatic-phase amphibians is indicated based on marginal exceedance of the LOC.

Table 5.1. Potential Effects to Federally List ed Taxa Associated with Direct or Indirect Effects from the Proposed New Uses of Penflufen.

Listed Taxon Direct Effects Indirect Effects a

Terrestrial and semi-aquatic plants - monocots No Yes

Terrestrial and semi-aquatic plants - dicots No Yes

Birds Yes Yes Terrestrial-phase amphibians and reptiles Yes Yes

Mammals No Yes Aquatic nonvascular plants No Yes

Aquatic vascular plants No Yes

Freshwater fish Yes Yes Aquatic-phase amphibians Yes Yes

Freshwater crustaceans No Yes

Mollusks No Yes

Marine/estuarine fish No Yes

Marine/estuarine invertebrates No Yes

a until an endangered species assessment is complete, indirect effects to all species cannot be precluded-Page 72 of 115- 5.2.1. Probit Dose-Response Analysis

The Agency uses the probit dose-response rela tionship as a tool fo r providing additional information on the potential for acute direct effects to aquatic and terrestrial animals (USEPA, 2004). As part of this evaluation, the acute RQ for listed species is pres ented in terms of the chance of an individual event ( i.e. , mortality or immobilization) should exposure at the EEC actually occur for a species with sensitivity to penflufen on par w ith the acute toxicity endpoint selected for RQ calculation. To accomplish this in terpretation, the Agency uses the slope of the dose-response relationship availabl e from the toxicity study used to establish the acute toxicity measures of effect for each taxonomic group that is relevant to this assessment. The individual effects probability associated with the acute RQ is based on the mean estimate of the slope and an assumption of a probit dose-response relationsh ip. In addition to a single effects probability estimate based on the mean, upper and lower esti mates of the effects probability are also provided to account for variance in the slope, if available. Based on the available acute toxicity for penflufen, a summary of the probit dose-response analysis is provided in Table 5.2 . If no dose response information is available to estim ate a slope for this analysis, a default slope assumption of 4.5 (with lower and upper bounds of 2 to 9) (Urban and Cook, 1986) is used.

Individual effect probabilitie s are calculated based on an Ex cel spreadsheet tool IECV1.1 (Individual Effect Chance Model Version 1.1) deve loped by the U.S. EPA, OPP, Environmental Fate and Effects Division (June 22, 2004). The m odel allows for such calculations by entering the mean slope estimate (and the 95% confidence bounds of that estimate) as the slope parameter for the spreadsheet. The desired threshold for the pr obability of an individual effect is entered as the listed species LOC. In addi tion, the probability of an individua l effect is also derived based on the calculated acute RQ, if available.

Table 5.2. Summary of Penflufen Probit Dose Response Analysis for Listed Species

Taxa (study type) Acute Effect Slope (95% C.I.) Chance of Individual Effect at Listed Species LOC (95% C.I.) Chance of Individual

Effect at Derived Acute RQ 1,2, (95% C.I.)

Bird oral dose No mortality observed 1 in 2.9E+05 (1 in 44 to 1 in 8.86E+18) Not calculated; no mortality observed

Bird dietary No mortality observed 1 in 2.9E+05 (1 in 44 to 1 in 8.86E+18) Not calculated; no mortality observed

Mammal oral dose No mortality observed 1 in 2.9E+05 (1 in 44 to 1 in 8.86E+18) Not calculated; no mortality observed

Freshwater Fish Mortality Default Slope = 4.5 (2 – 9) 1 in 4.18E+08 (1 in 216 to 1 in 1.75E+31) 1 in 2.4E+10 (1 in 515 to 1 in

1.50E+38) 1

Freshwater invertebrates Immobilization Default Slope = 4.5 (2 – 9) 1 in 3.34E+40 (1 in 6.32E+14 to 1 in 9.03E+78) 1 in 3.29E+33 (1 in 2.97E+7 to 1 in 8.14E+129) 2

1 Acute RQ for fish = 0.03.

2 Acute RQ for invertebrates = 0.002.

As shown in Table 5.2 , the probability for acute direct effects ( i.e. , mortality) to individual listed fish (based on the most sensitive species, common carp) and the highest de rived RQ value is 1 in

2.4X10 10 . This reflects an average slope of 4.5. If the true dose response curve were steeper, the-Page 73 of 115- chance of an individual increas es (e.g. slope of 9, chance is 1 in 515). The chance of an individual effect for aquatic inve rtebrates, based on the most sensitive species, Eastern oyster, is

1 in 3.29X10 33

.

5.2.2. Listed Species Occurrence Associated with Penflufen Use

The goal of the co-location analysis is de termine whether sites of pesticide use are geographically associated with known locations of listed species [following the convention of the Services, the word ‘species’ in this assessment may apply to a ‘species’, ‘subspecies’, or an Evolutionary Significant Unit (ESU)]. At the screening level, this analysis is accomplished using the LOCATES database (version 2.10.3). The database uses location information for listed species at the county level and compares it to agricultural census data (from 2002) for crop production at the same county level of resolution . The product is a lis ting of Federally-listed species that are located in c ounties known to produce the crops upon which the pesticide will be used. A list of potentially direc tly affected species associated with the proposed new uses of penflufen is provided in Appendix F. Species potentially indirectly affected include all listed species.

This preliminary analysis indicates that there is a potential for penflufen use to overlap with listed species and that a more refined assessmen t is warranted. The more refined assessment

should involve clear delineation of the action area associated with proposed uses of penflufen and the best available information on the temporal and spatial co-location of listed species with respect to the action area. This analysis has not been conducted for this assessment.-Page 74 of 115- 6. References

Carousel, R.F., J.C. Imhoff, P.R. Hummel, J.M. Cheplick, A.S. Donigian, Jr., L.A. Suarez. Undated. PRZM-3, A Model for Predicting Pes ticide and Nitrogen Fate in the Crop Root

and Unsaturated Soil Zones: Users Ma nual for Release 3.12.2. National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Athens, GA; AQUA TE RRA Consultants, Mountain View, CA;

Waterborne Environmenta l, Inc., Leesburg, VA.

USEPA 1998. Guidelines for Ecological Risk A ssessment. EPA/630/R-95/002F. Published in 63 FR 26846; May 14, 1998. U.S. Environmen tal Protection Agency, Washington, DC. April, 1998.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental Protection Ag ency. Endangered and Threatened Species Effects Determinations. Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, D. C. January 23, 2004. Online at: http://www.epa.gov/oppfead1/endanger /consultation/ecorisk-overview.pdf

USEPA 2006a. Standardized Soil Mobility Cl assification Guidance. U.S. Environmental Protection Agency, Office of Prevention, Pes ticides and Toxic Substances, Office of Pesticide Programs, Environmental Fate and Effects Division, Memorandum. Apr. 21,

2006.

USEPA. 2006b. User’s Guide: Te rrPlant Version 1.2.2 (Terrestrial Residue Exposure model).

United States Environmental Protection Agency. Environmental Fate and Effects Division. Office of Pesticide Programs. U.S. Environmental protection Agency. Washington, D.C. December 26, 2006.

USEPA 2008. White Paper on Methods for Assessi ng Ecological Risks of Pesticides with Persistent, Bioaccumulative and Toxic Charact eristics. Submitted to the FIFRA Scientific Advisory Panel. October 28-31, 2008. Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, D.C.

USEPA 2009. Guidance for Selecting Input Paramete rs in Modeling the Environmental Fate and Transport of Pesticides. U.S. Environmen tal Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Environmental Fate and Effects Division, Oct. 22, 2009. Online at: http://www.epa.gov/oppefed1/models/w ater/input_parameter_guidance.htm

USEPA. 2011a. Acres Planted per Day and Seedi ng Rates of Crops Grown in the United States, Memorandum from Beck and Ratnayake, Biolog ical and Economic Analysis Division, to Deschamp (HED) and Spatz (EFED), March 2011. US Environmental Protection Agency, OCSPP, Office of Pesticide Programs.-Page 75 of 115- USEPA. 2011b. Water Models. U.S. Environm ental Protection Agency, Pesticides: Science and Policy, Models and Databases. Last updated Aug. 8, 2011. Online at: http://www.epa.gov/oppefed1/models/water/

USEPA. 2011c. DRAFT: Regi stration Review: Problem Formulation for the Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Exposure

Assessments of Clothianidin " DP barcode 391491.

USDA. 2000. USDA Crop Profiles. Hosted by the Integrated Pest Management Centers.

Available online at: http://www.ipmcenters.org/cropprofiles/index.cfm

.

USFWS/NMFS. 2004. 50 CFR Part 402. Joint C ounterpart Endangered Species Act Section 7 Consultation Regulations; Final Rule. FR 47732-47762.

Urban, D.J. and N.J. Cook, 1986. Hazard Evalua tion Division Standard Evaluation Procedure Ecological Risk Assessment . EPA 540/9-85-001. U.S. Environmental Protection Agency, Office of Pesticide Programs, Washington D.C.

6.1. Submitted Product Chemistry and Environmental Fate Studies

MRID Reference

48023544 Fent, G. 2007. [Pyrazole-3- 14 C]BYF14182-3-hydroxy-butyl (BCS-AA10006): Adsorption/desorption in five different soils. Unpublished study performed by RLP AgroScience GmbH, Weinstrabe, Germany; sponsored and submitted by Bayer CropScience AG, Monheim am Rhein, Germany. Experiment initiation June 12, 2007 and termination July 31, 2007. Final report issued September 10,

2007. 48023545 Stupp, H. and M. Telscher. 2009. [Pyrazole-3- 14 C]BCS-AF73126 (BYF 14182-pyrazolyl-AAP): Adsorption/desorption on five soils. Study No. M131 1802-6. Unpublished study performed, sponsored, and submitted by Bayer CropScience AG, Monheim am Rhein, Germany. Experiment initiation August 25, 2008 and termination July 28, 2009 (p. 6). Final report issued September 17,

2009. 48023546 Heinemann, O. and D. Dehner. 2006. [Phenyl-UL- 13 C 6 / 14 C]BYF14182: Adsorption/desorption on five soils. Study No. M1311493-2. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim am Rhein, Germany, and submitted by Bayer CropScienc e LP, Research Triangle Park, North Carolina. Experiment initiation May 30, 2005 and termination June 29, 2005 (p. 9). Final report issued May 5, 2006. 48023547 Koehn, D. [Phenyl-UL- 13 C 6 / 14 C] and [pyrazole-3- 14 C]BYF 14182: Hydrolytic degradation. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim am Rhein, Germany, and submitted by Bayer CropScience LP , Research Triangle Park, North Carolina. Experiment initiated March 28, 2007, and terminated April 4, 2007. Final report issued July 18, 2008. 48023548 Menke, U. 2009. [Phenyl-UL- 13 C 6 / 14 C]BYF 14182 and [pyrazole-3- 14 C]BYF 14182: Phototransformation in aqueous buffer. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim am Rhein, Germany, and submitted by Bayer CropScience LP, Research Triangle Park, North Carolina. Experiment initiate d June 26, 2007, and terminated August 9, 2007. Final report issued August 27, 2009. 48023549 Menke, U. 2009. [Phenyl-UL- 13 C 6 / 14 C] and [pyrazole-3- 14 C]BYF 14182: Photolysis in natural water. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim am Rhein, Germany, and submitted by Bayer CropScience LP , Research Triangle Park, North Carolina.-Page 76 of 115- Experiment initiated July 25, 2007 and terminated November 28, 2007. Final report issued August 31,

2009. 48023550 Heinemann, O. 2009. BYF14182: Determination of the quantum yield and assessment of the environmental half-life of the direct photo-degradation in water. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim am Rhein, Germany, and submitted by Bayer CropScience LP, Research Triangle Park, North Ca rolina. Experiment initiated May 5, 2009 and terminated June 4, 2009. Final report issued June 30, 2009. 48023552 Sneikus, J. [Phenyl-UL- 14 C]BYF14182: Aerobic soil metabolism/degradation and time-dependent sorption in four soils. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim, Germany, and submitted by Bayer Cr opScience LP, Research Triangle Park, North Carolina. Experiment initiated September 26, 2005 , and terminated March 21, 2006. Final report issued March 22, 2007. 48023553 Mislankar, S.G. and K.A. Dallstream. 2009. [Phenyl-UL- 14 C] and [pyrazole-3- 14 C] BYF 14182: aerobic soil metabolism in two US soils. Unpublis hed study performed by Bayer CropScience AG, Monheim, Germany; AGVISE Laboratories, Northw ood, North Dakota, Bayer CropScience, Stilwell, Kansas and sponsored and submitted by Bayer CropScience, Research Triangle Park, North Carolina. Experiment started February 20, 2007, and completed March 12, 2008. Final report issued September 15, 2009. 48023554 Stupp, H-P. and M. Telscher. [Pyrazole-3- 14 C]BCS-AF73126 (BYF 14182-pyrazolyl-AAP): degradation and time-dependent sorption in soils. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim, Germany; and subm itted by Bayer CropScience, Research Triangle Park, North Carolina. Study Completion Date July 31, 2009. 48023555 Sneikus, J. 2009. [Pyrazole-3- 14 C] and [phenyl-UL- 14 C]BYF14182: anaerobic soil metabolism. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim, Germany; and submitted by Bayer CropScience, Research Triang le Park, North Carolina. Study Completion Date May 30, 2008. 48023556 Sneikus, J. [Pyrazole-3- 14 C]& [phenyl-UL- 14 C]BYF14182: Aerobic aquatic degradation. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim, Germany; and submitted by Bayer CropScience, Research Triangle Park, Nort h Carolina. Study Initiation Date March 30, 2007. Study Completion Date August 5, 2008. 48023557 Meyer, B.N. 2008. [Phenyl-UL- 14 C] and [pyrazole-3- 14 C]BYF 14182: anaerobic aquatic metabolism. Unpublished study performed by Bayer CropScience, Stilwell, Kansas; and sponsored and submitted by Bayer CropScience, Research Triangle Park, North Carolina. Experiment started June 28, 2007, and completed January 25, 2008. Final report issued December 15, 2008. 48023558 Lenz, M. 2010. Terrestrial Field Dissipation of BYF 14182 in a California Soil, 2007. Unpublished study performed by Bayer CropScience, Stilwell, KS; AGVISE Laboratories, Northwood, ND; and California Agricultural Research, In c., Kerman, CA; sponsored and submitted by Bayer CropScience, Research Triangle Park, NC. Mar. 10, 2010. 48023559 Lenz, M. 2010. Terrestrial Field Dissipation of BYF 14182 in Georgia Soil, 2007. Unpublished study performed by Bayer CropScien ce, Stilwell, KS; AGVISE Labo ratories, Northwood, ND; and Southeast Ag Research, Inc., Chula, GA; sponsored and submitted by Bayer CropScience, Research Triangle Park, NC. Mar. 10, 2010. 48023560 Lenz, M. 2010. Terrestrial Field Dissipation of BYF 14182 in Idaho Soil, 2007. Unpublished study performed by Bayer CropScience, Stilwell, KS; AGVISE Laborato ries, Northwood, ND; and Miller Research, Inc., Rupert, ID; sponsored and submitted by Bayer CropScience, Research Triangle Park, NC. Mar. 10, 2010. 48023561 Lenz, M. 2010. Terrestrial Field Dissipation of BYF 14182 in Ontario, Canada Soil, 2007. Unpublished study performed by Bayer CropScience, Stilwell, KS; AGVISE Laboratories, Northwood, ND; and Bayer CropScience, Rockwood, Ontario, Canada; sponsored and submitted by Bayer CropScience, Research Triang le Park, NC. Mar. 10, 2010. 48023562 Lenz, M. 2010. Terrestrial Field Dissipation of BYF 14182 in Saskatchewan, Canada Soil, 2007. Unpublished study performed by Bayer CropScience, Stilwell, KS; AGVISE Laboratories, Northwood, ND; and Bayer CropScience, Regina, Saskatchew an, Canada; sponsored and submitted by Bayer CropScience, Research Triang le Park, NC. Mar. 10, 2010. 48023563 Lenz, M. 2010. Terrestrial Field Dissipation of BYF 14182 in Prince Edward Island, Canada Soil,-Page 77 of 115- 2007. Unpublished study performed by Bayer Crop Science, Stilwell, KS; AGVISE Laboratories, Northwood, ND; and Atlantic Agritech, Hunter River, Prince Edward Island, Canada; sponsored and submitted by Bayer CropScience, Research Triangle Park, NC. Mar. 10, 2010. 48023564 Telscher, M. 2009. Determination of the Residues of BYF 14182 in/on Soil after Spraying of BYF 14182 SC 100 (100 SC) in the Field in Northern France, United Kingdom, Sweden, Germany, Italy, and Spain. Report No. RA-2147/06; Document No. M-350568-01-2. Unpublished study performed by Bayer CropScience AG, Monheim, Germany; sponsored and submitted by Bayer CropScience AG, Monheim am Rhein, Germany. July 1, 2009. 48023565 Lenz, M. 2010. Aquatic Dissipation of BYF 14182 FS 240 in a Cropped Arkansas Rice Field, 2008. Report No. RAELP039; Document No. M-365281-01-1. Unpublished study performed by Bayer CropScience, Stilwell, KS; AGVISE Laboratories, Northwood, ND; Mid-South Ag Research, Inc., Proctor, AR and Bayer Crop Science, Research Triangle Park, NC; sponsored and submitted by Bayer CropScience, Research Triangle Park, NC. Final report issued Mar. 15, 2010. 48023719 Freitag, T. and M. Hoffmann. 2009. Determin ation of the storage stability of BYF14182 and its metabolites BYF14182-3-hydroxybutyl (BCS- AA10006) and BYF14182- pyrazolyl-AAP (AE 2300037) in soil - Results for an interval of 0 to 12 and 24 months. Unpublished study performed and sponsored by Bayer CropScience AG, Monheim am Rhein, Germany and submitted by Bayer CropScience LP, USA. Experiment initiated September 21, 2007, and terminated October 22, 2009. Final report issued October 30, 2009. 48023722 Wade, J.M. 2010. Storage Stability of BYF 14182 and its metabolites BYF 14182-3- hydroxy-butyl and BYF 14182-p yrazolyl-AAP in Raw Surface Water Du ring Frozen Stor age, USA, 2009. Unpublished study performed by Bayer CropScien ce, Stilwell, Kansas and sponsored by Bayer CropScience, Research Triangle Park, North Carolin a. Experiment initiated June 4, 2009, termination date not reported. Final report issued March 8, 2010. 48652501 Woodard, D. 2011. [Pyrazole-3-14C]BYF 14182: Determination of Bound Residue Formation in Sterile Aerobic Soil and Aerobic Aquatic Water/Sediment Test Systems. Unpublished study performed by Bayer CropScience, Stilwell, Kansas. Study completed on Nov. 8, 2011.

6.2. Submitted Ecotoxicity Studies

Guideline: 850.1010 Aquatic inverteb rate acute toxicity, test, freshwater daphnids

------------------------------------------------------------------------------------- MRID: 48023574 Roberts, J.; Lam, C. (2008) Acute Toxicity of BYF 14182 Technical to Daphnia magna Under Static Conditions. Project Number: M/296362/01/1, EB ELP005, M/296362/01/1/OCR. Unpublished study prepared by Bayer CropScience. 43 p.

MRID: 48023575 Banman, C.; Hoffmann, J.; Lam, C. (2009) Acute Toxicity of BYF 14182-3-Hydroxy-Butyl to Daphnia magna Under Static Conditions. Project Numb er: M/346259/01/1, EBELP027, M/346259/01/1/OCR. Unpublished study prepared by Bayer CropScience. 41 p.

MRID: 48023576 Bruns, E. (2009) Acute Toxicity of BYF14182-Pyrazolyl-AAP (Tech.) to the Waterflea Daphnia magna in a Static Laboratory Test System. Project Number: M/357192/01/2, EBELP102, E/320/3613/8. Unpublished study prepared by Bayer CropScience. 43 p.

MRID: 48023577 Banman, C.; Daly, R.; Lam, C. (2009) Acute Toxicity of BYF 14182 Technical to Crayfish Under Static Conditions. Project Number: M/350813/01/1, EB ELP047, M/350813/01/1/OCR. Unpublished study prepared by Bayer CropScience. 44 p.-Page 78 of 115- MRID: 48024003 Bruns, E. (2009) Acute Toxicity of BYF 14182 FS 240 G to the Waterflea Daphnia magna in a Static Laboratory Test System. Project Number: M/345436/01/2/OCR, EBELP079, M/345436/01/2. Unpublished study prepared by Bayer CropScience. 49 p.

Guideline: 850.1025 Oyster acute toxicity test (shell deposition)

------------------------------------------------------------------------------------- MRID: 48023578 Gallagher, S.; Kendall, T.; Krueger, H. (2009) BYF 14182: A 96-Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica). Project Number: M/343505/01/1, EBELP014, M/343505/01/1/OCR. Unpublished study prepared by Wildlife International, Ltd. 63 p.

Guideline: 850.1035 Mysid acute toxicity test

------------------------------------------------------------------------------------- MRID: 48023579 Gallagher, S.; Kendall, T.; Krueger, H. (2008) BYF 1 4182: A 96-Hour Static Acute Toxicity Test with the Saltwater Mysid (Americamysis bahia): Amendment. Project Number: M/303018/01/1, EBELP012, 149A/233. Unpublished study prepared by Wildlife International, Ltd. 62 p.

Guideline: 850.1075 Fish acute toxicity test, freshwater and marine

------------------------------------------------------------------------------------- MRID: 48023580 Banman, C.; Hoffmann, J.; Lam, C. (2009) Acute Toxicity of BYF 14182 Technical to the Rainbow Trout (Oncorhynchus mykiss) Under StaticCond itions. Project Number: M/343491/01/1, EBELP002, M/343491/01/1/OCR. Unpublished study prepared by Bayer CropScience. 46 p.

MRID: 48023581 Banman, C.; Hoffmann, J.; Lam, C. (2009) Acute To xicity of BYF 14182 Technical to Bluegill (Lepomis macrochirus) Under Static Conditions. Project Number: M/343846/01/1, EBELP037, M/343846/01/1/OCR. Unpublished study prepared by Bayer CropScience. 46 p.

MRID: 48023582 Matlock, D.; Hoffmann, J.; Lam, C. (2009) Acute Toxicity of BYF 14182 Technical to the Fathead Minnow (Pimephales promelas) U nder Static Conditions. Project Number: M/346776/01/1, EBELP026, M/346776/01/1/OCR. Unpublished study prepared by Bayer CropScience. 49 p.

MRID: 48023583 Ruhland, M. (2009) Acute Toxicity of BYF 14182 (T ech.) to Fish (Cyprinus carpio) Under Static Conditions. Project Number: M/344774/01/2, EBELP077, E/280/35559/2. Unpublished study prepared by Bayer CropScience. 51 p.

MRID: 48023584 Bruns, E. (2009) Acute Toxicity of Penflufen-3-Hydr oxy-Butyl to Fish (Cyprinus carpio) Under Static Conditions - Limit Test. Project Number: M/ 357272/01/2, EBELP039, E/280/3739/2. Unpublished study prepared by Bayer CropScience. 49 p.

MRID: 48023585 Bruns, E. (2009) Acute Toxicity of Penflufen-Pyr azolyl-AAP to Fish (Cyprinus carpio) Under Static Conditions - Limit Test. Project Number: M/ 357274/01/2, EBELP103, E/280/3719/0. Unpublished study prepared by Bayer CropScience. 49 p.-Page 79 of 115- MRID: 48023586 Banman, C.; Hoffmann, J.; Lam, C. (2009) Acute Toxicity of BYF 14182 Technical to the Sheepshead Minnow (Cyprinodon variegatus) Under Static Conditions. Project Number: M/343499/01/1, EBELP003, M/343499/01/1/OCR. Unpublished study prepared by Bayer CropScience. 47 p.

MRID: 48024004 Bruns, E. (2009) Acute Toxicity of BYF 14182 FS 240 G to Fish (Cyprinus carpio) Under Static Conditions. Project Number: M/345941/01/2/OCR, EBELP078, M/345941/01/2. Unpublished study prepared by Bayer CropScience. 55 p.

Guideline: 850.1300 Daphnid chronic toxicity test

------------------------------------------------------------------------------------- MRID: 48023587 Banman, C.; Lam, C. (2009) Chronic Toxicity of BYF 14182 Technical to the Daphnia magna Under

Static Renewal Conditions: Am ended Report. Project Number: M/328667/02/1, EBELP006/1, M/328667/02/1/OCR. Unpublished study prepared by Bayer CropScience. 75 p.

Guideline: 850.1400 Fish early-life stage toxicity test

------------------------------------------------------------------------------------- MRID: 48023588 Matlock, D.; Lam, C. (2009) Early Life Stage Toxicity of BYF 14182 Technical to the Fathead Minnow (Pimephales promelas) Under Flow-Through Cond itions. Project Number: M/329464/01/1, EBELP004, M/329464/01/1/OCR. Unpublished study prepared by Bayer CropScience. 96 p.

Guideline: 850.1730 Fish BCF

------------------------------------------------------------------------------------- MRID: 48023589 Justus, K. (2009) [Phenyl-UL-(Carbon 13)/( Carbon 14)]BYF 14182: Bioconcentration and Biotransformation in Fish (Le pomis macrochirus). Project Number: M/356580/01/2, MEF/09/100, M2881755/6. Unpublished study prepared by Bayer CropScience AG. 173 p.

Guideline: 850.2100 Avian acute oral toxicity test

------------------------------------------------------------------------------------- MRID: 48023591 Stoughton, T.; Christ, M. (2009) Toxicity of BYF 14182 Technical During an Acute Oral LD50 with the Northern Bobwhite Quail (Colinus virginianus). Project Number: M/357031/01/1, EBELP015, M/357031/01/1/OCR. Unpublished study prepared by Bayer CropScience. 33 p.

MRID: 48023592 Fredricks, T.; Stoughton, T.; Christ, M. (2010) Toxicity of BYF 14182 Technical During an Acute Oral LD50 with the Canary (Serinus canaria): Am ended Report. Project Number: M/361570/02/1, EBELL004/1, M/361570/02/1/OCR. Unpublished study prepared by Bayer CropScience. 86 p.

MRID: 48024005 Barfknecht, R. (2009) Acute Oral Toxicity for BYF 14182 FS 240 G with Northern Bobwhite Quail (Colinus virginianus). Project Number: M/348863/01/2/OCR, BAR/LD/100, M/348863/01/2. Unpublished study prepared by Bayer CropScience. 31 p.

Guideline: 850.2200 Avian dietary toxicity test-Page 80 of 115- ------------------------------------------------------------------------------------- MRID: 48023593 Stoughton, T.; Christ, M.; Lam, C. (2009) Toxicity of BYF 14182 Technical During an Acute Dietary LC50 with the Northern Bobwhite Quail (Colinus virginianus). Project Number: M/358055/01/1, EBELP017, M/358055/01/1/OCR. Unpublished study prepared by Bayer CropScience. 44 p.

MRID: 48023594 Stoughton, T.; Lam, C. (2009) Toxicity of BYF 14182 Technical During an Acute Dietary LC50 with the Mallard Duck (Anas platyrhynchos). Project Number: M/348230/01/1, EBELP018, M/348230/01/1/OCR. Unpublished study prepared by Bayer CropScience. 46 p.

Guideline: 850.2300 Avian reproduction test

------------------------------------------------------------------------------------- MRID: 48023595 Stoughton, T.; Christ, M.; Lam, C. (2009) Toxicity of BYF 14182 Technical on Reproduction to the Northern Bobwhite Quail (Colinus virginianus). Project Number: M/358260/01/1, EBELP019, M/358250/01/1/OCR. Unpublished study prepared by Bayer CropScience. 79 p.

MRID: 48023596 Christ, M.; Lam, C. (2009) Toxicity of BYF 14182 Technical on Reproduction to the Mallard Duck (Anas platyrhynchos). Project Number: M/358529/ 01/1, EBELP020, M/358529/01/1/OCR. Unpublished study prepared by Bayer CropScience. 74 p.

Guideline: 850.3020 Honey bee acute contact toxicity

------------------------------------------------------------------------------------- MRID: 48023597 Schmitzer, S. (2007) Effects of BYF 14182 (Acute Contact and Oral) on Honey Bees (Apis mellifera L.) in the Laboratory: Final Report. Project Number: M/292797/01/2, 36581035, M/292797/01/2/OCR. Unpublished study prepared by Institut fuer Biol ogische Analytik und Consulting IBACON. 32 p.

MRID: 48024006 Schmitzer, S.; Sekine, T. (2009) Effects of BYF 14 182 FS 240 G (Acute Contact and Oral) on Honey Bees (Apis mellifera L.) in the Laboratory: Final Report. Project Number: M/350450/01/2/OCR, 48191035, M/350450/01/2. Unpublished study prepared by Ins titut fuer Biologische Analytik und Consulting IBACON. 32 p.

Guideline: 850.4100 Terrestrial plant toxicity, Tier 1 (seeding emergence)

------------------------------------------------------------------------------------- MRID: 48023598 Gosch, H. (2009) BYF 14182 FS 240 g/L: Effects on Eleven Species of Non-Target Terrestrial Plants: Seedling Emergence and Growth Test (Tier 1). Project Number: SE08/005/TIER/1, EBELP045, M/353590/01/2/OCR. Unpublished study prepar ed by Bayer CropScience AG. 61 p.

MRID: 48023599 Gosch, H. (2009) Non-Target Terrestrial Plants: An Evaluation of the Effect of BYF 14182 FS 50 g/L in the Seedling Emergence and Growth Test. Project Number: SE09/013/TIER/1, EBGLP152, M/348694/01/2/OCR. Unpublished study prepar ed by Bayer CropScience AG. 23 p.

Guideline: 850.4150 Terrestrial plant toxicity, Tier 1 (vegetative vigor)-Page 81 of 115- ------------------------------------------------------------------------------------- MRID: 48023601 Gosch, H. (2009) BYF 14182 FS 240 g/L: Effects on Eleven Species of Non-Target Terrestrial Plants: Vegetative Vigour Test (Tier 1). Project Numb er: M/353600/01/2/OCR, VV08/006/TIER/1, EBELP046. Unpublished study prepared by Bayer CropScience AG. 57 p.

MRID: 48023602 Gosch, H. (2009) Non-Target Terrestrial Plants: An Evaluation of the Effects of BYF 14182 FS 50 g/L in the Vegetative Vigour Test. Project Number: M/348690/01/2/OCR, VV09/014/TIER/1, EBELP151. Unpublished study prepared by Bayer CropScience AG. 23 p.

Guideline: 850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II

------------------------------------------------------------------------------------- MRID: 48023603 Banman, C.; Hoffmann, J.; Lam, C. (2009) Toxicity of BYF 14182 Technical to Duckweed (Lemna gibba G3) Under Static-Renewal Conditions. Proj ect Number: M/343501/01/1/OCR, EBELP038/OCR, M/343501/01/1. Unpublished study prepared by Bayer CropScience. 51 p.

Guideline: 850.5400 Algal toxicity, Tiers 1 and II

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MRID: 48024007 Ruhland, M. (2009) Pseudokirchneri ella Subcapitata Growth Inhibition Test with BYF 14182 FS 240 G. Project Number: M/333595/01/2/OCR, EBELP080, M/ 333595/01/2. Unpublished study prepared by Bayer CropScience. 65 p.

Guideline: 870.1100 Acute oral toxicity

------------------------------------------------------------------------------------- MRID: 48023749 Schungel, M. (2007) BYF 14182: Acute Toxicity in the Rat after Oral Administration. Project Number: M/294194/01/2, AT04001, T/3077694.

Unpublished study prepared by Bayer HealthCare AG. 28 p.

MRID: 48024008 Rupprecht, K. (2010) Bridging Rationale for Acute Toxicology of PEN 240FS. Project Number: M/365029/01/1/OCR, M/365029/01/1, G202164. Unpublished study prepared by Bayer CropScience LP. 10 p.

MRID: 48024102 Gillissen, U. (2009) BYF 14182 FS 240 (Red): Acute Toxicity in the Rat after Oral Administration. Project Number: M/356564/01/2/OCR, AT05520, M/356564/01/2. Unpublished study prepared by Bayer Ag Inst. of Toxicology. 29 p.

MRID: 48024202 Gillissen, U. (2009) BYF 14182 + Clothianidin + Me talaxyl + Trifloxystrobin FS 10,7+290+7,15+7,15: Acute Toxicity in the Rat After Oral Administration. Project Number: M/356568/01/2, AT05522, M/356568/01/2/OCR. Unpublished study prepared by Bayer Schering Pharma AG. 31 p.-Page 82 of 115- MRID: 48024302 Gillissen, U. (2009) BYF 14182 + Prothioconazole + Metalaxyl FS 38.4+76.8+61.4: Acute Toxicity in the Rat after Oral Administration. Project Number: M/356701/01/2/OCR, AT05537, M/356701/01/2. Unpublished study prepared by Bayer Ag Inst. of Toxicology. 29 p.

MRID: 48024402 Gillissen, U. (2010) BYF 14182 + Prothioconazole FS 100+18 g/L: Acute Toxicity in the Rat after Oral Administration. Project Number: M/362429/01/2/OCR, AT05723, M/362429/01/2. Unpublished study prepared by Bayer Ag Inst. of Toxicology. 29 p.

MRID: 48024502 Gillissen, U. (2009) BYF 14182 & Trifloxystrobin FS 154 + 154 (Blue): Acute Toxicity in the Rat after Oral Administration. Project Number: M/357051/01/2, AT05553, M/357051/01/2/OCR. Unpublished study prepared by Bayer HealthCare AG. 29 p.

MRID: 48024602 Gillissen, U. (2010) BYF 14182 + Clothianidin FS 66.5+ 207 g/L: Acute Toxicity in the Rat After Oral Administration. Project Number: M/362454/01/2, AT05725, M/362454/01/2/OCR. Unpublished study prepared by Bayer Schering Pharma AG. 29 p.

Guideline: 870.3800 Reproduction and fertility effects

------------------------------------------------------------------------------------- MRID: 48023812 Milius, A. (2009) Technical Grade BYF 14182: A Tw o-Generation Reproductive Toxicity Study in the Wistar Rat: Final Report. Project Number :M/357261/01/1, 07/R72/MK, M/357261/01/1/OCR. Unpublished study prepared by Bayer CropScience and Xenometrics, LLC. 1693 p.

MRID: 48248902 Milius, A. (2009) Technical Grade BYF 14182: A Do se Range-Finding Reproductive Toxicity Study in the Wistar Rat: Final Report. Project Number: 07/P72/JW, M/357262/01/1. Unpublished study prepared by Bayer CropScience. 480 p.

Guideline: 850.1735 Whole sediment: acute freshwater invertebrates

------------------------------------------------------------------------------------- MRID: 48023590 Banman, C.; Matlock, D.; Lam, C. (2009) Spiked Whole Sediment 10-Day Toxicity Test of BYF 14182 Technical to Chironomus dilutus (Formerly Known as Chironomus tentans). Project Number: M/353945/01/1, EBELP011, M/353945/01/1/OCR. Unpublis hed study prepared by Bayer CropScience. 71 p.

Non-Guideline Study

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MRID: 48023604 Citation: Banman, C.; Hoffmann, J.; Lam, C. (2007) Toxicity of BYF 14182 Technical to the Green Alga Pseudokirchneriella subcapitata. Project Number: M/295850/01/1/OCR, EBELP007/OCR, M/295850/01/1. Unpublished study prepared by Bayer CropScience. 55 p.

MRID: 48023605-Page 83 of 115- Citation: Banman, C.; Hoffmann, J.; Lam, C. (2009) Toxicity of BYF 14182-3-Hydroxy-Butyl to the Green Alga Pseudokirchneriella subcapitata. Pr oject Number: M/347970/01/1/OCR, EBELP028/OCR, M/347970/01/1. Unpublished study prepared by Bayer CropScience. 53 p.

MRID: 48023606 Citation: Bruns, E. (2009) Pseudokirchneriella subcapitata Growth Inhibition Test with BYF 14182- Pyrazolyl-AAP. Project Number: M/346267/02/2/ OCR, EBELP101/OCR, E/323/3618/6. Unpublished study prepared by Bayer CropScience. 69 p.

MRID: 48023607 Citation: Waibel, J. (2008) BYF 14182 FS 240 G: Toxici ty to the Parasitoid Wasp Aphidius rhopalosiphi (DeStephani-Perez) (Hymenoptera: Braconidae) in the Laboratory. Project Number: M/311401/01/2/OCR, CW08/040/OCR, EBELP068. Unpub lished study prepared by Bayer CropScience AG. 30 p.

MRID: 48023608 Citation: Waibel, J. (2009) Toxicity to the Par asitoid Wasp Aphidius rhopalosiphi (DeStephani-Perez) (Hymenoptera: Braconidae) Using a Laboratory Test BYF 14182 FS 50 G. Project Number: M/346081/01/2/OCR, CW09/009/OCR, EBELP148. Unpub lished study prepared by Bayer CropScience AG. 30 p.

MRID: 48023609 Citation: Waibel, J. (2008) BYF 14182 FS 240 G: Toxicity to the Predatory Mite Typhlodromus pyri Scheuten (Acari, Phytoseiidae) in the Laboratory. Project Number: M/311411/01/2/OCR, CW08/039/OCR, EBELP069. Unpublished study prepared by Bayer CropScience AG. 35 p.

MRID: 48023610 Citation: Waibel, J. (2010) BYF 14182 FS 50 G: Toxicity to the Predatory Mite Typhlodromus pyri Scheuten (Acari, Phytoseiidae) Using a Laboratory Test. Project Number: M/349193/01/2/OCR, CW09/008/OCR, EBELP147. Unpublished study prepared by Bayer CropScience AG. 35 p.

MRID: 48023611 Citation: Leicher, T. (2009) BYF 14182 (Tech.): Acute Toxicity to Earthworms (Eisenia fetida) Tested in Artificial Soil with 5 Percent Peat. Project Number: M/294423/01/2/OCR, LRT/RG/A/95/07/OCR, E/310/3378/5. Unpublished study prepared by Bayer CropScience. 24 p.

MRID: 48023612 Citation: Leicher, T. (2007) BYF 14812 FS 240: Effects on Survival, Growth and Reproduction on the

Earthworm Eisenia fetida Tested in Artificial Soil with 5 Percent Peat. Project Number: M/295772/01/2/OCR, LRT/RG/R/40/07/OCR, E/312/3383/3. Unpublished study prepared by Bayer CropScience AG. 38 p.

MRID: 48023613 Citation: Leicher, T. (2008) BYF 14182-3-Hydroxy-Butyl: Effects on Survival, Growth and Reproduction on the Earthworm Eisenia fetida Tested in Artificial Soil with 5 Percent Peat. Project Number: M/304291/01/2/OCR, LRT/RG/R/48/08/OCR, E/312/3439/5. Unpublished study prepared by Bayer CropScience AG. 44 p.

MRID: 48023614 Citation: Friedrich, S. (2009) BYF 14182-Pyrazoly l-AAP: Sublethal Toxicity to the Earthworm Eisenia-Page 84 of 115- fetida in Artificial Soil with 5 Percent Peat: Final Report. Project Number: M/349225/01/2/OCR, 09/10/48/033/S/OCR, EBELP100. Unpublished stud y prepared by Biochem Agrar, Labor fuer Biologische und Chemische. 32 p.

MRID: 48023615 Citation: Leicher, T. (2009) BYF 14182 FS 50 G: Effects on Survival, Growth and Reproduction on the

Earthworm Eisenia fetida Tested in Artificial Soil with 5 Percent Peat. Project Number: M/354676/01/2/OCR, LRT/RG/R/58/09/OCR, EBELP073. Unpublished study prepared by Bayer CropScience AG. 46 p.

MRID: 48023625 Citation: Frommholz, U. (2007) BYF 14182 FS 240 G: Influence on the Reproduction of the Collembola Species Folsomia candida Tested in Artificial Soil with 5 Percent Peat. Project Number: M/291241/01/2/OCR, FRM/COLL/56/07/OCR, E/314/3318/3. Unpublished study prepared by Bayer CropScience AG. 26 p.

MRID: 48023626 Citation: Kratz, M. (2007) BYF 14182 FS 240: Influence on Mortality and Reproduction on the Soil Mite Species Hypoaspis aculeifer Tested in Artificia l Soil with 5 Percent Peat. Project Number: M/294547/01/2/OCR, KRA/HR/5/07/OCR, E/428/3306/6. Unpublished study prepared by Bayer CropScience AG. 34 p.

MRID: 48023627 Citation: Frommholz, U. (2009) Metabolite BYF 14182-3-Hydroxy-Butyl: Influence on the Reproduction of the Collembola Species Folsomia candida Tested in Artificial Soil with 5 Percent Peat. Project Number: M/348154/01/2/OCR, FRM/COLL/ 72/09/OCR, E/314/3620/9. Unpublished study prepared by Bayer CropScience AG. 25 p.

MRID: 48023628 Citation: Kratz, M. (2009) BYF 14182-3-Hydroxy- Butyl: Influence on Mortality and Reproduction on the Soil Mite Species Hypoaspis aculeifer

Tested in Artificial Soil with 5 Percent Peat. Project Number: M/329899/01/2/OCR, KRA/HR/14/09/OCR, E/428/3601/4. Unpublished study prepared by Bayer CropScience AG. 32 p.

MRID: 48023629 Citation: Frommholz, U. (2009) Metabolite BYF 14182-Pyrazolyl-AAP: Influence on the Reproduction of the Collembola Species Folsomia candida

Tested in Artificial Soil with 5 Percent Peat. Project Number: M/348117/01/2/OCR, FRM/COLL/73/09/OCR, E/314/3621/0. Unpublished study prepared by Bayer CropScience AG. 25 p.

MRID: 48023630 Citation: Kratz, M. (2009) BYF 14182-Pyrazolyl-AA P: Influence on Mortality and Reproduction on the Soil Mite Species Hypoaspis aculeifer Tested in Ar tificial Soil with 5 Percent Peat. Project Number: M/329902/01/2/OCR, KRA/HR/13/09/OCR, E/428/3600/3. Unpublished study prepared by Bayer CropScience AG. 32 p.

MRID: 48023631 Citation: Frommholz, U. (2009) BYF 14182 FS 050 G: Influence on the Reproduction of the Collembola-Page 85 of 115- Species Folsomia candida Tested in Artificial Soil with 5 Percent Peat. Project Number: M/344200/01/2/OCR, FRM/COLL/70/09/OCR, E/314/3603/0. Unpublished study prepared by Bayer CropScience AG. 25 p.

MRID: 48023632 Citation: Kratz, M. (2009) BYF 14182 FS 050: Influence on Mortality and Reproduction on the Soil Mite Species Hypoaspis aculeifer Tested in Artific ial Soil with 5 % Peat. Project Number: M/329498/01/2/OCR, KRA/HR/12/09/OCR, E/428/3598/9. Unpublished study prepared by Bayer CropScience AG. 32 p.Appendix A. Chemical Names, Structures, and Maximum Reported Amounts of Penflufen and Its Degradates.Table 1. Penflufen and Its Major Environmental Degradates.Code Name/SynonymChemical NameChemical StructureStudy TypeMaximum%AR (day)Final Ave. %AR(studytermination)PARENTPenflufenBYF 14182IUPAC:(RS)-N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro1,3-dimethyl-1H-pyrazole-4-carboxamideCAS:1H-Pyrazole-4-carboxamide,N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethylCAS-no:494793-67-8Formula:C18H24F N3OMW:317.41 g/moleNHNNOFCH3CH3CH3CH3CH3MAJOR (>10%) TRANSFORMATION PRODUCTSM01BYF 14182-3-hydroxy-butylPenflufen-3-hydroxy-butylPen-3HB(RS)-5-fluoro-N-[2-(3-hydroxy-1,3-dimethylbutyl)phenyl]-1,3-dimethyl-1H-pyrazole-4-carboxamideFormula:C18H24F N3O2MW:333.41 g/molNHNNOFCH3CH3CH3CH3CH3OHAerobicsoilMRID48023552Silt loam15.2(120)15.2(120)Sandy loam10.1(120)10.1(120)Loam7.2(120)7.2 (120)Laacherhof AIII aLoam13.8(120)13.8(120)MRID48023553Silt loam (phenyl label)16.5(273)14.5(365)Silt loam (pyrazolelabel)17.5(365)17.5(365)Sandy loam (phenyllabel)9.8(271)9.4 (365)Sandy loam (pyrazolelabel)9.4(271)8.9(365)-Page 86 of 115-Final Ave. %ARCode Name/MaximumSynonymChemical NameChemical StructureStudy Type(study%AR (day)termination)AnaerobicsoilMRID48023555Water (phenyl label)2.9 (51)2.3 (214)Sediment (phenyllabel)6.7 (30)3.6 (214)System (phenyl label)7.1 (45)5.9 (214)Water (pyrazole label)3.0 (51)2.4 (214)Sediment (pyrazolelabel)6.9 (30)4.0 (214)System (pyrazole label)6.9 (154)6.5 (214)AerobicaquaticAnglerweiherMRID48023556Water (phenyl label)11.2(120)11.2(120)Sediment (phenyllabel)2.1 (120)2.1 (120)System (phenyl label)13.3(120)13.3(120)Water (pyrazole label)10.5(120)10.5(120)Sediment (pyrazolelabel)1.7 (120)1.7 (120)System (pyrazole label)12.2(120)12.2(120)HoennigerWeiherMRID48023556Water (phenyl label)0.8 (76)0.5 (120)Sediment (phenyllabel)0.9 (76)0.7 (120)System (phenyl label)1.7 (76)0.9 (120)Water (pyrazole label)0.8 (120)0.8 (120)Sediment (pyrazolelabel)1.3 (120)1.3 (120)System (pyrazole label)2.1 (120)2.1 (120)FieldstudiesTerrestrialMRID 480235580.33 ppb (29)nd1(182)MRID 480235590.2 ppb (7, 28,59, 178)nd1(269)MRID 480235601.9 ppb (120)1.0 ppb (532)MRID 480235610.3 ppb (125,168)0.3 ppb (168)MRID 480235620.5 ppb (345,378)0.4 ppb (509)MRID 480235631.7 ppb (367)1.0 ppb (538)MRID48023564France5.3 ppb (490)3.0 ppb (749)UK5.9 ppb (62)4.4 ppb (733)Sweden3.7 ppb (589)2.5 ppb (719)Germany9.0 ppb (119)2.3 ppb (720)Italy3.3 ppb(361)1.2 ppb (720)Spain2.9 ppb (62)nd1(735)-Page 87 of 115-Final Ave. %ARCode Name/MaximumSynonymChemical NameChemical StructureStudy Type(study%AR (day)termination)AquaticMRID 480235650.7 ppb (14)0.3 ppb (365)M02BYF 14182-pyrazolyl-AAPPenflufen-3-pyrazolyl-AAPAAPN-(2-acetylphenyl)-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamideFormula:C14H14F N3O2MW:275.28 g/molNHNNOOFCH3CH3CH3AerobicsoilMRID 48023552Not identified but not majorMRID48023553Silt loam (phenyl label)13.4(273)9.2 (365)Silt loam (pyrazolelabel)10.3(365)10.2(365)Sandy loam (phenyllabel)1.9 (365)1.9(365)Sandy loam (pyrazolelabel)1.6 (365)1.6 (365)FieldstudiesTerrestrialMRID 480235580.37 ppb (29)0.2 ppb (182)MRID 480235590.3 ppb (1-7)nd1(269)MRID 480235600.7 ppb (7, 58,532)0.7 ppb (532)MRID 480235610.4 ppb (15,125)0.3 ppb (168)MRID 480235620.2 ppb (345)nd1(509)MRID 480235631.6 ppb (4)0.8 ppb (538)MRID48023564France1.3 ppb (581)nd1(749)UK1.6 ppb (572)1.4 ppb (733)Germany1.4 ppb (539)nd1(720)Italy1.2 ppb (361;10-20 cm)nd1(720)M60BYF 14182-fluoro acid5-fluoro-1,3-dimethyl-1H-pyrazole4-carboxylic acidFormula:C6H7F N2O2MW:158.13 g/molOHNNOFCH3CH3AqueousphotolysispH 7 (phosphate buffer)Not identified but not majorpH 7.8 (river water; pyrazole label)9.9(2.9)9.9(2.9)-Page 88 of 115--Page 89 of 115-Code Name/SynonymChemical NameChemical StructureStudy TypeMaximum%AR (day)Final Ave. %AR(studytermination)Carbon dioxideCarbon dioxideFormula:CO2Aerobic soilMRID48023552Silt loam6.5 (120)6.5 (120)Sandy loam3.9 (120)3.9 (120)Loam1.5 (120)1.5 (120)LaacherhofAIIIa loam5.0 (120)5.0 (120)MRID48023553Silt loam(phenyl label)9.9(365)9.9(365)Silt loam(pyrazole label)7.9 (365)7.9 (365)Sandy loam(phenyl label)8.1 (365)8.1 (365)Sandy loam(pyrazole label)7.7 (365)7.7 (365)Anaerobic soilPhenyl label1.0 (0-214)1.0 (214)Pyrazole label0.4 (0-214)0.4 (214)Aerobic aquaticAnglerweiherPhenyl label3.3 (120)3.3 (120)Pyrazole label0.8 (120)0.8 (120)HoennigerWeiherPhenyl label1.2 (120)1.2 (120)Pyrazole label0.7 (120)0.7 (120)Anaerobic aquaticPhenyl label0.1 (7-120)0.1 (120)Pyrazole label0.1 (7-120)0.1 (120)Aqueous photolysispH7 (phosphate buffer;phenyl label)1.97 (5.7)1.97 (5.7)pH 7 (phosphate buffer;pyrazole label)0.24 (5.7)0.24 (5.7)pH 7.8 (river water;phenyl label)0.7 (2.9)0.7 (2.9)pH 7.8 (river water;pyrazole label)0.013 (2.9)0.013 (2.9)The table includes only those degradates that were addressed in the studies. Degradatesthat appear in the registrant's structure file that were used as reference standards or were not found in theenvironmental fate studies are not included in the table.C OOnd means “not detected.”-Page 90 of 115-Table 2. Minor Environmental Degradate of Penflufen (<10% of the Applied Radioactivity).CodeChemical nameChemical structureStudy TypeMaximum %AR(day)Final %AR (studylength)M58BYF 14182-pyrazole-4-carboxamide5-fluoro-1,3-dimethyl-1H-pyrazole4-carboxamideFormula:C6H8F N3OMW:157.15 g/molNNOFCH3CH3NH2Aqueous photolysispH 7 (phosphate buffer)AqueousphotolysispH 7.8(riverwater;pyrazolelabel)6.8 (2.9)6.8 (2.9)Table 3. Degradates of Penflufen Found in Plant Tissue During theAquatic Field Dissipation Study.Code Name/ SynonymChemical NameChemical StructureStudy TypeMaximum%AR (day)Final%AR(studylength)M01BYF 14182-3-hydroxybutyl(RS)-5-fluoro-N-[2-(3-hydroxy-1,3-dimethylbutyl)phenyl]-1,3-dimethyl-1H-pyrazole-4-carboxamideFormula:C18H24F N3O2MW:333.41 g/molNHNNOFCH3CH3CH3CH3CH3OHAquatic field dissipation (riceplants)11.5 ppb (28)nd1(120)M64BYF 14182-bisdesmethyl-3-carboxylic acid5-fluoro-1H-pyrazole-3-carboxylic acidFormula:C4H3F N2O2MW:130.08 g/molAquatic field dissipation (riceplants)6.1 ppb (28)nd1(120)OOHNNHF1 nd means “not detected.”Appendix B. Tier 2 Summary Catalog of Submitted Ecological Effects Studies for

Penflufen.

Table of ecotoxicological endpoints

Birds

Test species Test design Ecot oxicological endpoint Reference
Penflufen (BYF 14182)

Bobwhite quail acute, oral LD 50 [mg a.i./kg bw] >4000 Stoughton & Christ; 2009

M-357031-01-1

KIIA 8.1.1/01 Canary acute, oral LD 50 [mg a.i./kg bw] >2000 Fredricks, et.al. 2010

M-361570-01-2

KIIA 8.1.1/02

Bobwhite quail 5-day feeding LC 50 [mg a.i./kg feed] >8944

= LDD 50 [mg a.i./kg bw/d] >1697 Stoughton, Christ, &Lam;

2009

M-358055-01-1

KIIA 8.1.2/01

Mallard duck 5-day feeding LC 50 [mg a.i./kg feed] >9923

= LDD 50 [mg a.i./kg bw/d] >2208 Stoughton & Lam, 2009

M-348230-01-1

KIIA 8.1.3/01

Bobwhite quail 22-weeks feeding chronic, reproduction NOEC [mg a.i./kg feed] 946 = NOEL [mg a.i./kg bw/d] 96 Stoughton, Christ & Lam,

2009

M-358260-01-1

KIIA 8.1.4/01

Mallard duck 21-weeks feedingchronic, reproduction NOEC [mg a.i./kg feed] <292 = NOEL [mg a.i./kg bw/d] <27 Christ & Lam; 2009

M-358529-01-1

KIIA 8.1.4/02 PEN 240FS (representative formulation)

Bobwhite quail Acute, oral LD 50 [mg a.i./kg bw] >456 Barfknecht, 2009

Aquatic organisms: Fish

Test species Test design Ecot oxicological endpoint Reference
Penflufen (BYF 14182)

Rainbow trout acute, 96h,

static LC 50 [mg a.i./L] 0.31 NOEC [mg a.i./L] 0.110 (mean measured) Banman, Hoffmann, Lam, 2009

M-343491-01-1

KIIA 8.2.1.1/01 Bluegill sunfish acute, 96h,

static LC 50 [mg a.i./L] 0.45 NOEC [mg a.i./L] 0.285 (mean measured) Banman, Hoffmann, Lam, 2009

M-343846-01-1

KIIA 8.2.1.2/01

Fathead minnow acute, 96h,

static LC 50 [mg a.i./L] 0.116 NOEC [mg a.i./L] 0.055 (mean measured) Matlock, Hoffmann, Lam, 2009

M-346776-01-1

KIIA 8.2.1.2/02 Carp ( Cyprinus carpio ) acute, 96h,

static LC 50 [mg a.i./L] 0.090 NOEC [mg a.i./L] 0.061 (mean measured) Ruhland, 2009

M-344774-01-2

KIIA 8.2.1.2/03

-Page 91 of 115-Test species Test design Ecot oxicological endpoint Reference
Sheepshead

minnow ( Cyprinodon variegatus ) acute, 96 h,

static LC 50 [mg a.i./L] 1.15 Banman, Hoffmann, Lam, 2009

M-343499-01-1

KIIA 8.11.1/01

Fathead minnow ( Pimephales promelas ) chronic, 35d, flow-through (ELS) NOEC [mg a.i./L] 0.0234 (based on growth as length) Matlock & Lam, 2009

M-329464-01-1

KIIA 8.2.4/01 Bluegill sunfish bioconcentration in

fish BCF (whole fish wet weight) 100 Bruns & Justus, 2009

M-356580-01-2

KIIA 8.2.6.1/01
BYF 14182-3-hydroxy-butyl (metabolite)
Carp ( Cyprinus carpio ) acute, 96h,

static LC 50 [mg metabolite/L] >36.3 Bruns, 2009

M-357272-01-2

KIIA 8.2.1.3/01
BYF 14182-pyrazolyl-AAP (metabolite)
Carp ( Cyprinus carpio ) acute, 96h,

static LC 50 [mg metabolite/L] >0.799 Bruns, 2009

M-357274-01-2

KIIA 8.2.1.3/02 PEN 240FS (representative formulation) Carp ( Cyprinus carpio ) acute, 96h,

static LC 50 [mg a.i./L] between 0.0620 and

0.166 0.101 Bruns, 2009

Aquatic organisms: Invertebrates

Test species Test design Ecot oxicological endpoint Reference
Penflufen (BYF 14182)
Daphnia magna acute, 48h,

static EC 50 [mg a.i./L] >4.66 (mean measured) Roberts & Lam, 2008

M-296362-01-1

KIIA 8.3.1.1/01

Chironomus

dilutus acute, 10 d, spiked sediment NOEC 10 d survival 34.4 [mg a.s./kg sediment] NOEC growth 8.51 [mg a.i./kg sediment] NOEC 10 d survival overlying 0.16 water [mg a.i./L] NOEC growth pore water 0.78 [mg a.i./L] Banman, Matlock, Lam, 2009

M-353945-01-1

KIIA 8.5.1/01

Crayfish, ( Procambarus

clarkia ) acute, 96 h,

static EC 50 [mg a.i./L] >4.5 (mean measured) Banman, Daly, Lam,

2009

M-350813-01-1

KIIA 8.3.1.3 /01 Daphnia magna chronic, 21d,

static-renewal NOEC [mg a.i./L] 1.53 (mean measured) Banman & Lam, 2009

M-328667-01-2

KIIA 8.3.2.1/01 Oyster ( Crassostrea virginica , marine species) acute, 96h flow-through EC 50 [mg a.i./L] 1.3 Gallager et al, 2009

M-343505-01-1

KIIA 8.11.1/02

-Page 92 of 115-Test species Test design Ecot oxicological endpoint Reference
Mysid shrimp ( Americamysis

bahia , marine species) acute, 96h flow-through LC 50 [mg a.i./L] 2.5 Gallager et al, 2008

M-303018-01-1

KIIA 8.11.1/03

BYF 14182-3-hydroxy-butyl (metabolite)
Daphnia magna acute, 48h,

static EC 50 [mg metabolite/L] >62.0 (mean measured) Banman, Hoffmann, Lam, 2009

M-346259-01-1

KIIA 8.3.1.1/02
BYF 14182-pyrazolyl-AAP (metabolite)
Daphnia magna acute, 48h,

static EC 50 [mg metabolite/L] >3.12 (mean measured) Bruns, 2009

M-357192-01-2

KIIA 8.3.1.1/03
PEN 240FS (representative formulation)
Daphnia magna acute, 48h,

static EC 50 [mg a.i./L] 4.928 (mean measured) Bruns, 2009

Aquatic organisms: Algae and Plants

Test species Test design Ecot oxicological endpoint Reference
Penflufen (BYF 14182)

Pseudokirchneriella subcapitata chronic, 96h,

static 96h-E

r C 50 [mg a.i./L] >5.1

96h-E b C 50 [mg a.i./L] >5.1

96h-EC 50 cell density[mg a.i./L] >5.1 Banman, Hoffman, Lam, 2007

M-295850-01-1

KIIA 8.4/01 Lemna gibba chronic, 7d,

static renewal 7d-EC 50 values [mg a.i./L] > 4.7 Banman, Hoffmann, Lam, 2009

M-343501-01-1

KIIA 8.6/01
BYF 14182-3-hydroxy-butyl (metabolite)

Pseudokirchneriella subcapitata chronic, 72 h,

static 72h-E

r C 50 [mg/L] >71.9

72 h-E b C 50 [mg/L] 66.5

72h- EC 50 cell density [mg/L] 60.8 Banman, Hoffmann, Lam, 2009

M-347970-01-2

KIIA 8.4/03
BYF 14182-pyrazolyl-AAP (metabolite)

Pseudokirchneriella subcapitata chronic, 72 h,

static 72h-E

r C 50 [μg/L] >1071.5 Bruns, 2009

M-346267-02-2

KIIA 8.4/02
PEN 240 FS (representative formulation)

Pseudokirchneriella subcapitata chronic, 72 h,

static 72h-E

r C 50 [mg a.i./L] >24.8

72h- EC 50 cell density [mg a.i./L] 7.5 Ruhland, 2009

Soil macro-organisms

Test species Test design Ecot oxicological endpoint Reference
Penflufen (BYF 14182)

-Page 93 of 115-Test species Test design Ecot oxicological endpoint Reference
Eisenia fetida acute, 14 days (5% peat in test soil) LC 50 [mg a.i./kg d.wt.s.] >1000 Leicher, 2007

M-294423-01-2

KIIA 8.9.1/01
PEN 240FS (representative formulation)
Eisenia fetida chronic, 28 d (5% peat in test soil) NOEC growth 180 [mg a.i./kg d.wt.s.] NOEC reproduction 57.8 [mg a.i./kg d.wt.s.] Leicher, 2007

M-295772-01-2

KIIA 8.9.2/01

Folsomia candida chronic, 28 d (5% peat in test soil) NOEC reproduction 231.1 [mg a.i../kg d.wt.s.] Frommholz, 2007

M-291241-01-2

KIIA 8.16.1/01
Hypoaspis aculeifer chronic, 14 d (5% peat in test soil) NOEC reproduction 2000 [mg a.i./kg d.wt.s.] Kratz, 2009

M-294547-01-2

KIIA 8.16.1/02
BYF 14182-3-hydroxy-butyl (metabolite)
Eisenia fetida chronic, 28 d (5% peat in test soil) NOEC growth and reproduction [mg/kg d.wt.s.] 1000 Leicher, 2008

M-304291-01-2

KIIA 8.9.2/02

Folsomia candida chronic, 28 d (5% peat in test soil) NOEC [mg/kg d.wt.s.] 1000 Frommholz, 2009

M-348154-01-2

KIIA 8.16.1/03
Hypoaspis aculeifer chronic, 14 d (5% peat in test soil) NOEC [mg/kg d.wt.s.] 1000 Kratz, 2009

M-329899-01-2

KIIA 8.16.1/04
BYF 14182 pyrazolyl-AAP (metabolite)
Eisenia fetida chronic, 28 d (5% peat in test soil) NOEC growth [mg/kg d.wt.s.] 1000 NOEC reproduction 500 [mg/kg d.wt.s.] Friedrich, 2009

M-349225-01-2

KIIA 8.9.2/03

Folsomia candida chronic, 28 d (5% peat in test soil) NOEC [mg/kg d.wt.s.] 1000 Frommholz, 2009

M-348117-01-2

KIIA 8.16.1/05
Hypoaspis aculeifer chronic, 14 d (5% peat in test soil) NOEC [mg/kg d.wt.s.] 1000 Kratz, 2009

M-329902-01-2

KIIA 8.16.1/06

Bees

Test species Test design Ecot oxicological endpoint Reference
Penflufen (BYF 14182)
Apis mellifera acute, 48 h, oral acute, 48 h, contact LD 50 [μg a.i./bee] >108.2

LD 50 [μg a.i./bee] >100 Schmitzer, 2007

M-292797-01-2

KIIA 8.7.1/01
PEN 240 FS (representative formulation)
Apis mellifera acute, 48 h, oral acute, 48 h, contact LD 50 [μg a.i./bee] >111.7

LD 50 [μg a.i./bee] >100 Schmitzer, 2009

-Page 94 of 115-Non-target arthropods: Parasitoids + Predatory mites

Test species Test design Ecot oxicological endpoint Reference
PEN 240 FS (representative formulation)
Aphidius rhopalosiphi

, adults laboratory, glass plates LR 50 [g a.i./ha] >250 effect on reproduction at 250 g a.i./ha:

64% Waibel, 2008

M-311401-01-2

KIIA 8.8.1.1/01 Typhlodromus pyri laboratory, glass plates LR 50 [g a.i./ha] >250 effect on reproduction at 250 g a.i./ha:

37% Waibel, 2008

M-311411-01-2

KIIA 8.8.1.2/01

-Page 95 of 115-Appendix C. Catalogue of Submitted Envi ronmental Fate Studies for Penflufen.

Submitted Environmental Fate Studies for Penf lufen, their Review Classifications, and

Classification Justifications.

Guideline Study Title MRID Classification Comments Are data adequate for

Risk

Assessment? Current Additional

Data Need

835.2120 Hydrolysis 48023547 Acceptable Study was conducted at 50oC.

Penflufen was stable at pHs 4, 7, and

9. Yes None

835.2240 Photodegradation

in Water 48023548 Supplemental Study duration was not sufficient. A large amount of parent remained undegraded at the termination of the study. Half-lives are of uncertain

value.

Yes An acceptable aqueous photolysis study

conducted for a

sufficient duration is

recommended to

confirm the results reported from the

reviewed studies. Photodegradation

in River Water 48023549 Supplemental Study duration was not sufficient. A large amount of parent remained undegraded at the termination of the study. Half-lives are of uncertain

value.

Quantum Yield

of Penflufen 48023550 Supplemental Dark controls were not used. Irradiation lamp was not compared to natural sunlight (mercury vapor lamp was used).

835.2410 Photodegradation

on Soil -- -- Study not required since this is a seed

treatment. -- --

835.4100 Aerobic Soil

Metabolism 48023552 Supplemental German soils. Study duration was not

sufficient to characterize the degradation of the parent and formation and decline of major degradates. Half-lives were extrapolated beyond the study

duration and thus are of uncertain value. Comparison to intended use sites in the US was not provided.

Yes An acceptable aerobic soil metabolism study

conducted for a

sufficient duration to

characterize the decline of the parent and

formation and decline of major degradates is

recommended to reduce the uncertainty regarding the aerobic degradation of

penflufen 48023553 Supplemental US soils. Study duration was insufficient to completely characterize the degradation of the parent and formation and decline of major degradates.

48023554 Supplemental Study was conducted using a penflufen-pyrazolyl-AAP as the starting material. Extraction methods were not exhaustive, multiple

extraction methods should have been explored. Major degradates were not identified. Comparison to intended use sites in the US was not provided.

-Page 96 of 115-Are data

Guideline Study Title MRID Classification Comments adequate for Current Additional

Risk Data Need

Assessment?

835.4200 Anaerobic Soil

Metabolism 48023555 Acceptable A large amount of parent material remained undegraded at the study termination (70-74%). Half-lives are extrapolated beyond the duration of the study. An additional study conducted for a longer duration will not likely improve the results. German soils were used in the study and were not compared to intended

use sites in the US. No None

835.4300 Aerobic Aquatic

Metabolism 48023556 Supplemental Unexplained variability in the reported data (uncharacterized decline of the parent and major degradates). Anglerweiher water:sand system should not be used for risk assessment. Hoenniger Weiher water :sandy loam system is acceptable for risk assessment. Yes An additional acceptable aerobic aquatic study that

includes a different water: sediment system

is recommended to address the potential variability that exists

between multiple aquatic systems.

835.4400 Anaerobic Aquatic

Metabolism 48023557 Supplemental A large amount of parent material remained undegraded at the study termination (86-90%; 120 DAT). Penflufen was just beginning to dissipate from the sediment; a study

conducted for a sufficient determination may determine whether penflufen was in factdissipating from the sediment. Halflive are extrapolated and are of uncertain value. System was only moderately reducing. Only a single water:sediment system was studied. Yes Two water:sediment

systems are
recommended from

studies conducted for a

sufficient duration to reduce the uncertainty regarding the anaerobic degradation. However, it is unlikely that

additional studies

would produce significantly different

results.

835.1230 Mobility - Adsorption / Desorption 48023546 Supplemental Residues were not accounted for in

the intercalated solution in the initial adsorption step and each desorption step. Registrant-calculated percent adsorption values could not be

confirmed due to lack of raw data.

None of the test soils had OM

content < 1%. Foreign soils were used for the study, comparison

information to intended US use sites was not provided. Yes An acceptable adsorption/desorption study is recommended

to address uncertainties identified in the study

reviews.

48023544 Supplemental Study was conducted using a majortransformation product (penflufenhydroxy butyl). Registrant-calculated percent adsorption values could not

be confirmed due to lack of raw data.

None of the test soils had an OM

content < 1%. Foreign soils were used for the study, comparison

information to intended US use sites was not provided.

-Page 97 of 115-Are data

Guideline Study Title MRID Classification Comments adequate for Current Additional

Risk Data Need

Assessment?

48023545 Supplemental Study was conducted using a majortransformation product (penflufenpyrazolyl-AAP). Registrantcalculated percent adsorption values

could not be confirmed due to lack of

raw data. None of the test soils had

an OM content < 1%. Foreign soils were used for the study, comparison

information to intended US use sites was not provided.

835.6100 Terrestrial Field Dissipation 48023558 Unacceptable Reported dissipation half-lives are comparatively shorter than other field studies (orders of magnitude). Additional dissipation routes (e.g., runoff) were not m easured, therefore there is some other dissipation route occurring that has not been accounted

for. Exhaustive extraction methods were not investigated. Depth of sampling was insufficient.

Yes An acceptable

terrestrial field dissipation study that studies the proposed

use patterns (seed

treatment) is

recommended to

address the

uncertainties identified

in the study reviews. 48023559 Supplemental Test application ra te was conducted at an exaggerated rate (10x proposed maximum labeled rate). Exhaustive

extraction methods were not investigated. Depth of sampling was

insufficient.

48023560 Supplemental Test application ra te was conducted at an exaggerated rate (10x proposed maximum labeled rate). Exhaustive

extraction methods were not investigated. Depth of sampling was insufficient. Reported LOQ did not compare to validated LOQ.

48023561 Supplemental Test application ra te was conducted at an exaggerated rate (10x proposed maximum labeled rate). Exhaustive

extraction methods were not investigated. Reported LOQ did not compare to validated LOQ.

48023562 Supplemental Test application ra te was conducted at an exaggerated rate (10x proposed maximum labeled rate). Exhaustive

extraction methods were not investigated. Reported LOQ did not compare to validated LOQ.

48023563 Supplemental Test application ra te was conducted at an exaggerated rate. Exhaustive

extraction methods were not investigated. Reported LOQ did not compare to validated LOQ.

-Page 98 of 115-Are data

Guideline Study Title MRID Classification Comments adequate for Current Additional

Risk Data Need

Assessment?

48023564 Supplemental Study was conducted in ecoregions

dissimilar to the intended use sites in the US. Comparisons to intended use sites in the US were not provided. Application rates were not verified using data from the monitoring devices (e.g., filter paper).

835.6200 Aquatic Field Dissipation 48023565 Supplemental Test application ra te was conducted at an exaggerated rate. Exhaustive

extraction methods were not investigated. Reported LOQ did not compare to validated LOQ. Study

was conducted on ri ce. Plant samples were analyzed for parent and degradates. Hydroxy butyl and a carboxylic acid degradate were detected in plant samples at low levels. Storage stability was not demonstrated for the longest storage period (MRID 48023722) Yes Although not required for current action,

future actions with aquatic uses would require a second study in an aquatic system.

850.1730 Fish

Accumulation 48023589 Acceptable Low BCFs indicate that penflufen will not bioconcentrate in aquatic

food webs. Mean TRR values were

used in the calculation of BCFs. EPA typically uses maximum TRR values from whole fish, edible, and viscera tissues when calculating BCFs,

however mean TRR values do not change the conclusi ons that would be drawn by using maximum values. Yes None

860.1380 Storage stability

in soil 48023719

48176601 Acceptable Initial study MRID 48176601was not

conducted for sufficient duration. Together these two studies satisfy the guideline requirement.

Yes None

Storage Stability 48023722 Supplemental Study duration was insufficient. Stability was demonstrated through 222 days, however it should have

been conducted for at least as long as the longest storage period (362 days). An acceptable storage stability study in water

conducted for a sufficient duration, using water from the aquatic field dissipation study.

-Page 99 of 115-Appendix D. Product Chemistry and Envi ronmental Fate Summary of Penflufen

Product Chemistry of Penflufen

Chemical Name: Penflufen (BYF 14182)

IUPAC: N -[2-(1,3-dimethylbutyl)phenyl ]-5-fluoro-1,3-dimethyl-1 H -pyrazole-4-carboxamide

CAS: 1H-Pyrazole-4-carboxamide, N-[2-(1,3-dime thylbutyl)phenyl]-5-fl uoro-1,3-dimethylChemical Abstracts registry number: 494793-67-8

Synonyms: BYF 14182, Penflufen

Molecular Formula: C 18 H 24 F N 3 O

Molecular Weight: 317.41 g/mol

Chemical Structure:



## N H N

N O

F CH 3



## CH 3



## CH 3 

## CH 3 

## CH 3

Environmental Fate Summaries of Penflufen (BYF 14182)

Detailed information regarding the fate and trans port of penflufen in the environment is provided in the study summaries below. Data evaluation records were completed in cooperation with Canada (PMRA) and Australia (APVMA) as pa rt of the Global Joint Review framework.

Hydrolysis - - EPA Guideline: 161-1 (835.2120)

MRID: 48023547 Penflufen was stable in sterile aqueous buffer soluti ons (pH 4, 7 and 9) that were incubated in the dark at 50°C for 7 days.

-Page 100 of 115-Since penflufen was stable under th e conditions of this study, the e xperiment was not repeated at a lower temperature or with a second pos ition of radiolabel. Although USEPA and OECD guidelines require laboratory hydr olysis studies be conducted at environmentally relevant temperatures (20-25oC), there wa s little to no degradation via hydr olysis at 50oC, therefore an additional study at a lower temperatur e is not required at this time.

Study Acceptability : This study is classified ACCEPTABLE

.

Photolysis in Water - - EP A Guideline: 161-2 (835.2240)

MRID: 48023548 Penflufen is moderately degraded by photolytic processes at 25°C in aqueous buffer solution of pH 7, with a calculated combined label half-life of 17 days; corrected environmental half-life for Phoenix, Arizona and Athens, Greece of 83 and 131 days, respectively. No major transformation products are formed. Penflufen degrades to numerous very minor transformation products and

CO 2 (Figure 2, p. 66)

USEPA Study Acceptability : This study is classified SUPPLEMENTAL

.

MRID: 48023549 In sterilized river water, penflu fen is degraded by photolytic pro cesses at 25°C, with a calculated half-life of 3.85 days; corrected environmental half-life in Tokyo, Japan is 36 days. The only major transformation product, BYF 14182-fluoro acid, is degraded to the only identified minor transformation product, BYF 14182-pyrazole-4-c arboxamide. Numerous unidentified minor transformation products are formed. Formation of CO 2 and organic volatiles is negligible.

USEPA Study Acceptability : This study is classified SUPPLEMENTAL

.

Adsorption, Desorption and Mobility in Soil - - EPA Guideline: 163-1 (835.1230)

MRID: 48023546 Overall medium values of adsorption were dete rmined for the active substance penflufen. Except for organic carbon content (a weak correlation), the coeffients for adsorption and desorption did not correlate with other physico- chemical properties of soil.

Using the Standardized Soil Mobility Classi fication Guidance according to the Food and Agriculture Organization (FAO) of the United Nations adopted by USEP A and using reviewer calculated adsorption K

oc values presented in Table 7 of this DER, penflufen is characterized as being moderately mobile in the test soils.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

MRID: 48023544 BYF 14182-3-hydroxy-butyl

-Page 101 of 115-Overall low values of adsorption were dete rmined for metabolite BYF14182-3-hydroxy-butyl. Except for organic carbon, there was also no obvi ous dependence of Freundlich coefficients K F for adsorption and desorption to correlate with other physico-chemical properties of soil. The same applies for a dependence of adsorption or desorption on pH of soil. The desorption

constants K F(des) were higher by a factor of 1.3 compared to the respective ad sorption constants, indicating some enhanced sorption of the compound once adsorbed to soil.

Using the Standardized Soil Mobility Classi fication Guidance according to the Food and Agriculture Organization (FAO) of the United Nations adopted by USEP A and using reviewer calculated adsorption K

oc values presented in Table 6 of this DER, BYF14182-3-hydroxy-butyl is characterized as being m obile in the test soils.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

MRID: 48023545 BYF 14182-pyrazolyl-AAP Overall high values of adsorption were de termined for metabolit e BYF14182-pyrazolyl-AAP. Coefficients for adsorption did not correlate wi th other physico-chemical properties of soil. There was also no obvious dependence of adsorption or desorption on pH of soil.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

Aerobic Soil Metabolism EPA Guideline: 162-1 (835.4100)

MRID: 48023552 Penflufen dissipated with reviewer-calculated half-lives of 118-239 days in the four German soils. The only major transformation product was BYF14182-3-hydroxy- butyl, with maximum concentrations of 7.2-15.2% of the applied at 120 days posttreatment (study termination). No minor transformation products were identifi ed, and no distinct HPLC peaks totaled ≥ 2.1% of the applied. Unidentified [ 14 C]compounds totaled up to 6.0% of the applied. All degradation products appeared to be transi ent with either further tran sformation to their metabolic downstream products or substantially integrated into the soil matr ix as nonextract able residues.

A transformation pathway was provided by the study author. Based on the study results, the route of aerobic degradation of penflufen in soil is characterized by the following major

processes:

• Hydroxylation at the alkyl side chain in the 3-position to form BYF14182-3-hydroxybutyl;

• Formation of nonextractable (bound) residues; and

• Mineralization (formation of CO 2 ).

This study is acceptable for delineating the rout e of transformation of penflufen; however, extrapolation past the study duration for calculati ng half-lives leads to uncertainty in those extrapolated values.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

-Page 102 of 115-MRID: 48023553 Penflufen dissipated with reviewer-calculated non linear half-lives of 249 days in the silt loam soil and 432 days in the sandy loam so il. BYF14182-3-hydroxy-butyl was a major transformation product in both soils, with maximu m concentrations of 9.4-17.5% of the applied at 271-365 days posttreatment. BYF 14182-pyrazol yl-AAP was a major transformation product

in the silt loam soil with maximum concentra tions of 11.3-13.4% of the applied at 273-365 days posttreatment, and was a minor transformation product in the sandy loam soil with maximum

concentrations of 1.9-2.2%. At 365 da ys posttreatment, nonextractable [ 14 C]residues averaged 17.6-25.8% of the applied and CO 2 totaled 7.7-9.9%.

Based on the study results, the rout e of aerobic degradation of penf lufen in soil is characterized by the hydroxylation at the alkyl side chain in the 3-posit ion to form BYF 14182-3-hydroxybutyl, which further oxidizes to BYF 14182-pyrazolyl-AAP (F igure 31, p. 82). Degradation

results in formation of nonextractable residues and CO 2

.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

MRID: 48023554 BYF 14182-pyrazolyl-AAP BYF 14182-pyrazolyl-AAP dissipated with reviewe r-calculated half-lives of 115.5 in the silt loam soil, 256.7 days in the sandy loam soil, 231.0 days in the loam soil, and 128.4 days in the clay loam soil. No major or minor transfor mation products were iden tified. Unknown C was a major transformation product in the loam soil, re aching maximum concentrations of 7.3% of the applied in the silt loam soil, 5.2% in the sandy loam soil, 10.0% in the loam soil, and 6.1% in the clay loam soil (maximum averages 6.5%, 4.9%, 9.1%, and 5.6%, respectively) at 3-14 days posttreatment and decreasing to averages of 0.4- 2.6% at 122 days. In all four soils, four unidentified components (A, B, D, and E) each averaged ≤ 5.9% of the applie d throughout the experiment. At 122 days posttreatment, total ex tractable residues averaged 51.4-73.4% of the applied, nonextractable residues averaged 22.6-38.2%, and 14 CO 2 averaged 3.7-8.7%. Formation of other volatile radioactivity was insignifican t for all soils at any sampling interval ( ≤ 0.1% AR).

A transformation pathway was not provided by the study author. Ba sed on the study results, BYF 14182-pyrazolyl-AAP degrades to several unid entified and mostly minor compounds and CO 2 , and is bound to the soil.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

Anerobic Soil Metabolism EPA Guideline: 162-2 (835.4200)

MRID: 48023555

-Page 103 of 115-Penflufen degrades very slowly under the conditions of anaerobic so il degradation testing in the laboratory, with reviewer-calculate d half-lives in the water-silt lo am soil system of 866 days in the total system, 990 days in th e soil, and 173 days in the wa ter layer. Dissipation was by adsorption of residues to the soil. Volatilization is minimal. The only transformation product, BYF14182-3-hydroxy butyl, was present in equivalent concentrations prio r to flooding and was stable post-flooding.

USEPA Study Acceptability : This study is classified ACCEPTABLE

Aerobic Aquatic Metabolism EP A Guideline: 162-4 (835.4300)

MRID: 48023556 Penflufen degraded slowly under the conditions of aerobic aquatic degrad ation testing in the laboratory, with reviewer-calculate d single first-order half-lives of 267 and 301 days in the total system. Only one system (Hoenniger) should be used for risk assessment due to unexplained variability in the tota l recovery in the Anglerweiher system. One transformation product, BYF14182-3-hydroxy-butyl, was identified at maxi mum average concentrations of 12.1-12.8% of the applied in the Anglerweiher water:sa nd sediment total system and 1.7-2.1% in the Hoenniger Weiher water:sandy loam se diment system. Nonextractable [ 14 C]residues averaged 10.1-19.8% of the applied at 120 days postt reatment. Volatilization was minimal.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

Anerobic Aquatic Metabolism EPA Guideline: 162-3 (835.4400)

MRID: 48023557

Penflufen is stable in an an aerobic water-sediment system, with a non-transformed (SFO) halflife of greater than 6 years in th e total system. Penflufen applied to the water surface dissipates with a nonlinear half-life of approximately 48 days , with elimination due to movement into the

sediment.

A transformation pathway was not proposed by th e study author and could not be developed based on the study results.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

Terrestrial Field Dissipation EPA Guideline: 164-1 (835.6100)

MRID: 48023558 Penflufen (BYF 14182) dissipated with a review er-calculated dissipation time of 1.88 days (DFOP) and a DT 90 of 138 days, with residues not detected above the LOQ below the 15-30 cm depth. The transformation products BYF 14182-3-hydroxy-butyl and BYF 14182-pyrazolylAAP were both detected in the top soil la yer only, at levels below the LOQ.

-Page 104 of 115-USEPA Study Acceptability: This study is classified UNACCEPTABLE

.

MRID: 48023559 Penflufen (BYF 14182) dissipated with a reviewer-calculated DT50 of 11 days (DFOP), a DT90 of 598 days (DFOP), with residues generally not detected above the LOQ below the 0-15 cm depth. Carryover of residues at 269 days posttreatment was ca . 20% of the zero-time recovery of BYF 14182 (detected as BYF 14182). The tran sformation products BYF 14182-3-hydroxy-butyl and BYF 14182-pyrazolyl-AAP were both detected in the top soil layer only, at levels below the LOQ.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

MRID: 48023560 Penflufen (BYF 14182) dissipated with a reviewe r-calculated dissipation half-life of 308 days (DFOP) for the total soil profile, DT 90 >2000 days. The DT90 was extrapolated beyond the study duration, however it illustrate s the potential for penflufen to persist at low concentrations must longer than the estimated 1 st half-life. Penflufen was detected above the LOQ to a maximum depth of 45-60 cm. Carryover of re sidues at 532 days posttreatment was ca . 29% of the target application rate ( ca . 27% detected as BYF 14182) and 39.3% of the zero-time recovery of BYF 14182. The transformation produc ts BYF 14182-3-hydroxy-butyl and BYF 14182- pyrazolyl-AAP were both detected above the LOQ in the top soil layer only, at individual replicate maximum concentrations of 2.16 ppb (at 166 days) and 1.23 ppb (at 7 days), respectively (1.4% and 0.9% of the BYF 14182 target application ra te, respectively).

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

MRID: 48023561 Penflufen (BYF 14182) dissipated with a reviewe r-calculated DT50 of 14 days (IORE), DT90 of 436 days, with residues not detected above th e LOQ below the 0-15 cm depth. Carryover of residues at 168 days posttreatment was ca . 13% of the target application rate ( ca . 10% detected as BYF 14182), and ca . 14% of the zero-time recovery of BYF 14182. The transformation products BYF 14182-3-hydroxy-butyl and BYF 14182- pyrazolyal-AAP were both detected in the top soil layer only, at levels below the LOQ.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

MRID: 48023562 Penflufen (BYF 14182) dissipated with a revi ewer-calculated dissipation half-life of ca . 200 days (DFOP), with residues not detected a bove the LOQ below the 0-15 cm depth. A DT90 was calculated at 1480 days indicating that although the compound dissipate s with an initi al half-life of 200 days, subsequent half-lives are much longer and penflufen may persist at low concentrations for a long time. Carryover of resi dues at 509 days posttreatment was 17.5% of the target application rate (15.0% detected as BYF 14182) and ca . 25% of the zero-time recovery of BYF 14182. The transformation products BYF 14182-3-hydroxy-but yl and BYF 14182- pyrazolyl-AAP were both detected in the top so il layer only, at levels below the LOQ.

-Page 105 of 115-US EPA Study Acceptability: This study is classified SUPPLEMENTAL

.

MRID: 48023563 Penflufen (BYF 14182) dissipated with a reviewer-calculated half-life of ca . 15 days (DFOP), a DT90 of 1,270 days for the total soil profile, w ith residues not detected below the 15-30 cm depth (with one exception). This clearly s hows that although the fi rst half-life may be comparatively short to subsequent half-lives th e compound will persist at low concentrations for a long time. Carryover of residue s at 538 days posttreatment was ca . 18% of the target application rate ( ca . 16% detected as BYF 14182), and 22.4% of the zero-time recovery of BYF 14182. The transformation products BYF 14182- 3-hydroxy-butyl and BYF 14182-pyrazolylAAP were both detected above the LOQ in th e top soil layer only, at individual replicate maximum concentrations of 2.43 ppb (at 367 days) and 2.17 ppb (at 7 days), respectively (1.3% and 1.4% of the BYF 14182 target a pplication rate, respectively).

US EPA Study Acceptability: This study is classified SUPPLEMENTAL

.

MRID: 48023564 Penflufen (BYF 14182) dissipated with a review er-calculated SFO half-life of 100-193 days (non-transformed regression) from Northern Europe study sites (Fra nce, United Kingdom, Sweden, Germany) and 53-77 days (nonlinear regression) from Southern Europe study sites (Italy and Spain), based on residues in the 0- 10 cm soil depth. Residues of BYF 14182 were generally not detected below the 20-30 cm depth. BYF 14182 declined to 12.9-17.1% of the target application rate at th e end of the 719-749 day study period for the Northern Europe study sites, and to 3.06-5.41% of the target applicati on rate at the end of the 720-735 day study period for the Southern Europe study sites. The transformation product BYF 14182-3-hydroxy-butyl was detected in the 0-10 cm depth at an indi vidual replicate maximu m concentration of 5.37-9.13 ppb at the France, United Kingdom, and Germany study sites and below the LOQ at the Sweden, Italy, and Spain study sites and BYF 14182-pyrazolyl-AAP was not detected above the LOQ at any study site.

USEPA Study Acceptability: This study is classified SUPPLEMENTAL.

Fish Accumulation EPA Guideline 165-4 (850.1730)

MRID: 48023589 BYF 14182 accumulated in bluegill sunfish with a to tal residue bioconcentration factor of about
100 to 103 X for whole fish (sum of radio la beled compounds, BYF 14182 parent, metabolites and
mineralization products). After 14 days in uncontaminat ed water, 98% of the radioactivity was depurated
from whole fish at both concentrations (nominal concentrations of 0.45 μg/L and 4.50 μg/L).

USEPA Study Acceptability: This study is classified Acceptable.

Storage Stability EPA Guideline (860.1380)

-Page 106 of 115-MRID: 48023719 Penflufen and BYF 14182-3-hydroxybutyl are stable when stored frozen at <-18 °C for 761 days.

BYF 14182-pyrazolyl-AAP may be stable when stored frozen at <-18 °C for 844 days.

USEPA Study Acceptability: This study is classified ACCEPTABLE

.



### MRID: 48023722
Penflufen and its transformation produc ts BYF 14182-3-hydroxy- butyl and BYF 14182- pyrazolyl-AAP were stable in frozen wa ter for a minimum of 222 days (p. 17).

USEPA Study Acceptability: This study is classified SUPPLEMENTAL

.

-Page 107 of 115-Appendix E. Aquatic Model Input/Output Data.

Summary of Input/Output Files.

File name Date Location/Simulation

Input Files for PRZM/EXAMS Potato.prz Sept. 6, 2011 Potato Use Beans.prz Sept. 6, 2011 Beans and Peas Use

Crop Scenario Files for PRZM/EXAMS IDNpotato_WirrgSTD.txt Dec. 20, 2004 Bingham, County, ID/Potato and tuberous corm MSsoybeanSTD.txt Aug. 9, 2001 Yazoo, County, MS/Beans and Peas

Weather Data Files for PRZM/EXAMS

W12844.dvf July 3, 2002 West Palm Beach, Florida

W03812.dvf July 3, 2002 Asheville, North Carolina

Example Input/Output Data for Individual Simulations

PRZM/EXAMS Example Input/Output File.

stored as Pen_potato_unex.out Chemical: penflufen PRZM environment: IDNpotato_WirrigSTD.txt modified Tueday, 29 May 2007 at 13:55:22 EXAMS environment: pond298.exv modified Tueday, 26 August 2008 at 06:14:08 Metfile: w24156.dvf modified Tueday, 26 August 2008 at 06:15:52 Water segment concentrations (ppb)

Year Peak 96 hr 21 Da y 60 Day 90 Day Yearly

1961 0.1895 0.1873 0.1791 0.1717 0.1662 0.09502

1962 0.1416 0.1415 0.141 0.1397 0.1387 0.1358

1963 0.3339 0.3314 0.3256 0.3217 0.3161 0.2378

1964 0.4667 0.4644 0.4555 0.4478 0.4462 0.3774

1965 0.4213 0.4208 0.42 0.4158 0.4132 0.4059

1966 0.4535 0.453 0.4516 0.447 0.4463 0.4212

1967 0.6288 0.6262 0.6167 0.6094 0.6029 0.5243

1968 0.6364 0.635 0.6312 0.6231 0.6176 0.5805

1969 0.7028 0.7008 0.6951 0.6872 0.6788 0.6238

1970 1.309 1.3 1.273 1.244 1.216 0.9492

1971 1.081 1.081 1.08 1.078 1.076 1.045

1972 1.008 1.008 1.007 1.006 1.004 0.9773

1973 0.9816 0.9801 0.9762 0.9653 0.9568 0.9369

1974 1.334 1.329 1.308 1.273 1.251 1.088

1975 1.293 1.291 1.281 1.264 1.251 1.185

1976 1.171 1.171 1.17 1.169 1.167 1.138

1977 1.228 1.226 1.217 1.202 1.19 1.13

1978 1.405 1.401 1.385 1.356 1.337 1.22

1979 1.243 1.243 1.242 1.24 1.238 1.204

1980 1.204 1.203 1.201 1.193 1.184 1.154

1981 1.433 1.429 1.417 1.387 1.367 1.241

1982 1.343 1.341 1.334 1.325 1.318 1.275

1983 1.339 1.337 1.331 1.325 1.318 1.27

1984 1.272 1.271 1.268 1.258 1.248 1.23

-Page 108 of 115-1985 1.2 1.2 1.199 1.198 1.196 1.163

1986 1.137 1.136 1.131 1.126 1.12 1.1

1987 1.146 1.144 1.137 1.125 1.115 1.074

1988 1.054 1.054 1.054 1.052 1.05 1.017

1989 0.9775 0.9774 0.9768 0.9755 0.974 0.9485

1990 1.012 1.01 1.003 0.988 0.9798 0.9349

Sorted results

Prob. Peak 96 hr 21 Day 60 Day 90 Day Yearly

0.032258064516129 1.433 1.429 1.417 1.387 1.367 1.275

0.0645161290322581 1.405 1.401 1.385 1.356 1.337 1.27

0.0967741935483871 1.343 1.341 1.334 1.325 1.318 1.241

0.129032258064516 1.339 1.337 1.331 1.325 1.318 1.23

0.161290322580645 1.334 1.329 1.308 1.273 1.251 1.22

0.193548387096774 1.309 1.3 1.281 1.264 1.251 1.204

0.225806451612903 1.293 1.291 1.273 1.258 1.248 1.185

0.258064516129032 1.272 1.271 1.268 1.244 1.238 1.163

0.290322580645161 1.243 1.243 1.242 1.24 1.216 1.154

0.32258064516129 1.228 1.226 1.217 1.202 1.196 1.138

0.354838709677419 1.204 1.203 1.201 1.198 1.19 1.13

0.387096774193548 1.2 1.2 1.199 1.193 1.184 1.1

0.419354838709677 1.171 1.171 1.17 1.169 1.167 1.088

0.451612903225806 1.146 1.144 1.137 1.126 1.12 1.074

0.483870967741936 1.137 1.136 1.131 1.125 1.115 1.045

0.516129032258065 1.081 1.081 1.08 1.078 1.076 1.017

0.548387096774194 1.054 1.054 1.054 1.052 1.05 0.9773

0.580645161290323 1.012 1.01 1.007 1.006 1.004 0.9492

0.612903225806452 1.008 1.008 1.003 0.988 0.9798 0.9485

0.645161290322581 0.9816 0.9801 0.9768 0.9755 0.974 0.9369

0.67741935483871 0.9775 0.9774 0.9762 0.9653 0.9568 0.9349

0.709677419354839 0.7028 0.7008 0.6951 0.6872 0.6788 0.6238

0.741935483870968 0.6364 0.635 0.6312 0.6231 0.6176 0.5805

0.774193548387097 0.6288 0.6262 0.6167 0.6094 0.6029 0.5243

0.806451612903226 0.4667 0.4644 0.4555 0.4478 0.4463 0.4212

0.838709677419355 0.4535 0.453 0.4516 0.447 0.4462 0.4059

0.870967741935484 0.4213 0.4208 0.42 0.4158 0.4132 0.3774

0.903225806451613 0.3339 0.3314 0.3256 0.3217 0.3161 0.2378

0.935483870967742 0.1895 0.1873 0.1791 0.1717 0.1662 0.1358

0.967741935483871 0.1416 0.1415 0.141 0.1397 0.1387 0.09502

0.1 1.3426 1.3406 1.3337 1.325 1.318 1.2399 Average of yearly averages:

0.889417333333334

Inputs generated by pe5.pl - Novemeber 2006

Data used for this run: Output File: Pen_potato_unex

Metfile: w24156.dvf

PRZM scenario: IDNpotato_WirrigSTD.txt EXAMS environment file: pond298.exv

Chemical Name: penflufen Description Variable Name Value Units Comments Molecular weight mwt 317.41 g/mol Henry's Law Const. henry atm-m^3/mol Vapor Pressure vapr 9e-9 torr

-Page 109 of 115-Solubility sol 10.9 mg/L

Kd Kd mg/L

Koc Koc 290 mg/L Photolysis half-life kdp 83 days Half-life Aerobic Aquatic Metabolism kbacw 978 days Halfife Anaerobic Aquatic Metabolism kbacs 0 days Halfife

Aerobic Soil Metabolism asm 577 days Halfife Hydrolysis: pH 7 0 days Half-life

Method: CAM 4 integer See PRZM manual Incorporation Depth: DEPI 7.6 cm Application Rate: TAPP 0.31 kg/ha Application Efficiency : APPEFF 1.0 fraction Spray Drift DRFT 0.00 fraction of application rate applied to pond Application Date Date 01-05 dd/mm or dd/mmm or dd-mm or dd-mmm

Record 17: FILTRA

IPSCND 1

UPTKF

Record 18: PLVKRT

PLDKRT

FEXTRC 0.5 Flag for Index Res. Run IR EPA Pond Flag for runoff calc. RUNOFF none none, monthly or total(average of entire run)

-Page 110 of 115-Appendix F. Federally Listed Species Potent ially at Risk from the Proposed Uses of

Penflufen

Bird counts by state associated with the highest two exposure scenarios



## Species Counts by St ate and Generic Taxon

No species were excluded.

Minimum of 1 Acre. All Medium Types Included

canola, corn for grain, corn for silage or gr eenchop, corn-popcorn & sweet corn, corn-sweet for seed, cotton-all, safflower, sunflower seed-all

AL, AK, AS, AZ, AR, CA, CO, CT, DE, DC, FM, FL, GA , GU, HI, ID, IL, IN, IA, KS, KY, LA, ME, MH, MD,

MA, MI, MN, MS, MO, MT, NE, NV, NH, NJ, NM, NY , NC, ND, MP, an, OA, an, OP, OH, OK, OR, PW,
Alabama

The Generic Taxon Amphibian has 10 species co-occurring with the indicated crops

The Generic Taxon Bird has 52 species co-occurring with the indicated crops

The Generic Taxon Reptile has 17 species co-occurring with the indicated crops

Arizona

The Generic Taxon Amphibian has 12 species co-occurring with the indicated crops

The Generic Taxon Bird has 47 species co-occurring with the indicated crops

The Generic Taxon Reptile has 2 species co-occurring with the indicated crops

Arkansas

The Generic Taxon Bird has 44 species co-occurring with the indicated crops

California

The Generic Taxon Amphibian has 93 species co-occurring with the indicated crops

The Generic Taxon Bird has 125 species co-occurring with the indicated crops

The Generic Taxon Reptile has 52 species co-occurring with the indicated crops

Colorado

The Generic Taxon Bird has 88 species co-occurring with the indicated crops

Connecticut

The Generic Taxon Bird has 12 species co-occurring with the indicated crops

The Generic Taxon Reptile has 2 species co-occurring with the indicated crops

Delaware

The Generic Taxon Bird has 1 species co-occurring with the indicated crops

The Generic Taxon Reptile has 1 species co-occurring with the indicated crops

Florida

The Generic Taxon Amphibian has 23 species co-occurring with the indicated crops

The Generic Taxon Bird has 252 species co-occurring with the indicated crops

The Generic Taxon Reptile has 95 species co-occurring with the indicated crops

-Page 111 of 115-Georgia

The Generic Taxon Amphibian has 24 species co-occurring with the indicated crops

The Generic Taxon Bird has 324 species co-occurring with the indicated crops

The Generic Taxon Reptile has 57 species co-occurring with the indicated crops

Guam

The Generic Taxon Bird has 5 species co-occurring with the indicated crops

The Generic Taxon Reptile has 4 species co-occurring with the indicated crops

Hawaii

The Generic Taxon Bird has 50 species co-occurring with the indicated crops

Illinois

The Generic Taxon Bird has 7 species co-occurring with the indicated crops

Indiana

The Generic Taxon Bird has 1 species co-occurring with the indicated crops

The Generic Taxon Reptile has 3 species co-occurring with the indicated crops

Iowa

The Generic Taxon Bird has 5 species co-occurring with the indicated crops

Kansas

The Generic Taxon Bird has 71 species co-occurring with the indicated crops

Kentucky

The Generic Taxon Bird has 29 species co-occurring with the indicated crops

Louisiana

The Generic Taxon Bird has 31 species co-occurring with the indicated crops

The Generic Taxon Reptile has 5 species co-occurring with the indicated crops

Maine

The Generic Taxon Bird has 10 species co-occurring with the indicated crops

Maryland

The Generic Taxon Bird has 1 species co-occurring with the indicated crops

The Generic Taxon Reptile has 4 species co-occurring with the indicated crops

Massachusetts

The Generic Taxon Bird has 19 species co-occurring with the indicated crops

The Generic Taxon Reptile has 4 species co-occurring with the indicated crops

Michigan

The Generic Taxon Bird has 35 species co-occurring with the indicated crops

The Generic Taxon Reptile has 6 species co-occurring with the indicated crops

Minnesota

The Generic Taxon Bird has 1 species co-occurring with the indicated crops

Mississippi

-Page 112 of 115-The Generic Taxon Amphibian has 2 species co-occurring with the indicated crops

The Generic Taxon Bird has 30 species co-occurring with the indicated crops

The Generic Taxon Reptile has 47 species co-occurring with the indicated crops

Missouri

The Generic Taxon Bird has 6 species co-occurring with the indicated crops

Montana

The Generic Taxon Bird has 29 species co-occurring with the indicated crops

Nebraska

The Generic Taxon Bird has 135 species co-occurring with the indicated crops

Nevada

The Generic Taxon Bird has 4 species co-occurring with the indicated crops

The Generic Taxon Reptile has 4 species co-occurring with the indicated crops

New Hampshire

The Generic Taxon Bird has 1 species co-occurring with the indicated crops

New Jersey

The Generic Taxon Bird has 23 species co-occurring with the indicated crops

The Generic Taxon Reptile has 17 species co-occurring with the indicated crops

New Mexico

The Generic Taxon Amphibian has 5 species co-occurring with the indicated crops

The Generic Taxon Bird has 58 species co-occurring with the indicated crops

The Generic Taxon Reptile has 1 species co-occurring with the indicated crops

New York

The Generic Taxon Bird has 63 species co-occurring with the indicated crops

The Generic Taxon Reptile has 22 species co-occurring with the indicated crops

North Carolina

The Generic Taxon Bird has 153 species co-occurring with the indicated crops The Generic Taxon Reptile has 48 species co-occurring with the indicated crops

North Dakota

The Generic Taxon Bird has 78 species co-occurring with the indicated crops

Northern Mariana Islands

The Generic Taxon Bird has 15 species co-occurring with the indicated crops

Ohio

The Generic Taxon Bird has 8 species co-occurring with the indicated crops

The Generic Taxon Reptile has 5 species co-occurring with the indicated crops

Oklahoma

The Generic Taxon Bird has 220 species co-occurring with the indicated crops

The Generic Taxon Reptile has 1 species co-occurring with the indicated crops

-Page 113 of 115-Oregon

The Generic Taxon Bird has 41 species co-occurring with the indicated crops

Pennsylvania

The Generic Taxon Bird has 1 species co-occurring with the indicated crops

The Generic Taxon Reptile has 15 species co-occurring with the indicated crops

Puerto Rico

The Generic Taxon Amphibian has 10 species co-occurring with the indicated crops

The Generic Taxon Bird has 57 species co-occurring with the indicated crops

The Generic Taxon Reptile has 29 species co-occurring with the indicated crops

Rhode Island

The Generic Taxon Bird has 10 species co-occurring with the indicated crops

South Carolina

The Generic Taxon Amphibian has 4 species co-occurring with the indicated crops

The Generic Taxon Bird has 108 species co-occurring with the indicated crops

The Generic Taxon Reptile has 2 species co-occurring with the indicated crops

South Dakota

The Generic Taxon Bird has 79 species co-occurring with the indicated crops

Tennessee

The Generic Taxon Bird has 24 species co-occurring with the indicated crops

Texas

The Generic Taxon Amphibian has 21 species co-occurring with the indicated crops The Generic Taxon Bird has 309 species co-occurring with the indicated crops

The Generic Taxon Reptile has 11 species co-occurring with the indicated crops

Utah

The Generic Taxon Bird has 23 species co-occurring with the indicated crops

The Generic Taxon Reptile has 1 species co-occurring with the indicated crops

Virgin Islands

The Generic Taxon Reptile has 1 species co-occurring with the indicated crops

Virginia

The Generic Taxon Amphibian has 3 species co-occurring with the indicated crops

The Generic Taxon Bird has 7 species co-occurring with the indicated crops

The Generic Taxon Reptile has 4 species co-occurring with the indicated crops

Washington

The Generic Taxon Bird has 45 species co-occurring with the indicated crops

West Virginia

The Generic Taxon Amphibian has 5 species co-occurring with the indicated crops

Wisconsin

-Page 114 of 115--Page 115 of 115- The Generic Taxon Bird has 6 species co-occurring with the indicated crops

Wyoming

The Generic Taxon Amphibian has 1 species co-occurring with the indicated crops

The Generic Taxon Bird has 27 species co-occurring with the indicated crops



### Fish and surrogates count by State associated with rice



## Species Counts by St ate and Generic Taxon

No species were excluded.

Minimum of 1 Acre. All Medium Types Included

rice AL, AK, AS, AZ, AR, CA, CO, CT, DE, DC, FM, FL, GA , GU, HI, ID, IL, IN, IA, KS, KY, LA, ME, MH, MD,

MA, MI, MN, MS, MO, MT, NE, NV, NH, NJ, NM, NY , NC, ND, MP, an, OA, an, OP, OH, OK, OR, PW,
Arkansas

The Generic Taxon Fish has 15 species co-occurring with the indicated crops

California

The Generic Taxon Amphibian has 31 species co-occurring with the indicated crops

The Generic Taxon Fish has 55 species co-occurring with the indicated crops

Florida

The Generic Taxon Fish has 1 species co-occurring with the indicated crops

Illinois

The Generic Taxon Fish has 2 species co-occurring with the indicated crops

Louisiana

The Generic Taxon Fish has 27 species co-occurring with the indicated crops

Mississippi

The Generic Taxon Fish has 16 species co-occurring with the indicated crops

Missouri

The Generic Taxon Fish has 8 species co-occurring with the indicated crops

Tennessee

The Generic Taxon Fish has 4 species co-occurring with the indicated crops

Texas

The Generic Taxon Amphibian has 3 species co-occurring with the indicated crops