Page 2 of 22 

### 1. Summary

The U.S. Environmental Protecti on Agency, referred to hereafter as EPA, is proposing to grant the unconditional registration under section 3(c)(5) of the Federa l Insecticide, Fungicide, and Rodenticide Act (FIFRA) for the new active in gredient, flupyradifur one, 2(5H)-furanone,4-[[(6- chloro-3- pyridinyl)methyl](2,2- difluoroethyl)amino. Flupyradifurone is formulated as a technical and two end use products. It is a ne w butenolide insecticide that targets piercing, sucking insects such as aphids and whiteflies. The proposed uses for this new chemical include Bushberry, Except Cranberry (Crop Subgroup 13- 07B); Low Growing Berry Except Cranberry (Crop Subgroup 13-07G); Bulb Vegetables (Crop Group 3-07); Cereal Grains Except Rice (Crop Group 15); Citrus Fruits (Crop Group 10-10) ; Cottonseed (Crop Subgroup 20C); Cucurbit Vegetables (Crop Group 9); Edible Podded Legum e Vegetables (Crop Su bgroup 6A); Succulent Shelled Pea and Bean (Crop Subgroup 6B); Dr ied Shelled Pea and Bean (except Soybean); Foliage of Legume Vegetables (except Soybean ) (Crop Subgroup 7A); Non-grass Animal Feeds (Alfalfa and Clover only); Forage, Fodder, and St raw of Cereal Grains (Crop Group 16); Fruiting Vegetables (Crop Group 8-10); Hops; Head and Stem Brassica Vegetables (Crop Subgroup 5A); Leafy Brassica Greens (Crop Subgroup 5B); Leaf y Vegetables (Except Brassica) (Crop Group 4); Peanuts; Pitaya; Pome Fru its (Crop Group 11-10); Prickly P ear Cactus; Root Vegetables Except Sugar Beet (Crop Subgroup 1B); Small Fr uit Vine Climbing (Except Fuzzy Kiwifruit) (Crop Subgroup 13-07F); Soybean (Seed); Taro Leaves; Tree nuts (Crop Group 14-12); Turnip Greens; and Tuberous and Corm Vegetables (Crop Subgroup 1C).

The Agency is not granting uses proposed fo r Crop Group 18, the non-grass animal feeds (forage fodder, straw and hay) group. Uses of flupyradif urone for non-grass animal feeds will only be granted for clover exclusively in Washington, Or egon, and Idaho, and for alfalfa nationally; an

insufficient number of clover trials was submitted to support the entire crop group.

The end use product formulations are Si vantoTM 200 SL and BYI 02960 480 FS. Proposed methods of application include seed treatment (soybean only) , soil drench, and foliar. The maximum annual application ra te is 0.365 lb a.i./A/year.

The database submitted to support the Human Hea lth Risk assessment is complete with the exception of insufficient field-trial data to support a Crop Group 18 tolerance (see Section 7.2.3 for additional details). There are no aggregate or occupational risks of concern for human health.

The screening-level Ecological Ri sk Assessment identified potent ial risk concerns for direct effects to several taxonomic categor ies (outlined in Section 5.4). To address the risks identified in the screening-level assessment, the draft labeling has been update d to minimize potential exposure thus effectively reducing risk. Labelin g updates include a requirement for vegetative buffer strips, limitations on the number of cr op cycles, and the updated label language for pollinator stewardship and best management practices that will minimize the exposure to

terrestrial invertebrates. While flupyradifurone is toxic to honeybees ( Apis mellifera ) on an acute oral exposure basis, the compound is practically nontoxic to adult bees on an acute contact exposure basis and to honeybee larvae on an acu te exposure basis. Therefore, the primary exposure route of concern is thr ough ingestion of residues in polle n/nectar rather than direct contact. However, honey bee colonies exposed to flupyradifurone did not exhibit any detectablePage 3 of 22 long-term effects 1 . Further, overwinter success was not adve rsely affected in field studies. The incorporation of label language for best practi ce stewardship is direct ed at protecting food resources for pollinating insects to further reduce expos ure and thereby reduce potential risk. For example, the label includes language that advi ses foliar sprays be performed late in the afternoon/evening/night hours, outside of peak foraging periods. Additional details on risk mitigation labeling language are included in Section 7.2.3.

EPA’s Reduced Risk Committee approved flupyradif urone as a reduced ri sk candidate for the proposed uses. Based on the committee's evalua tion of the information provided, the human health and ecological hazard prof iles for flupyradifurone are favorable compared to currently registered alternatives. Currently registered pest icides, such as those containing neonicontinoids, organophosphates, pyrethroids, and one compound be longing to the mectin family, are labeled for similar uses; comparatively, flupyradifurone presents a less hazardous ecological and human health profile.



### 2. Requested Action

On October 5, 2012, EPA received an application from Bayer CropScience to register products containing the insecticide flupyradifurone, a ne w active ingredient, for use on: Bushberry, Except Cranberry (Subgroup 13-07B); Cereal Grai ns Except Rice (Group 15); Citrus Fruits (Group 10-10); Cottonseed (Subgroup 20C); Cucu rbit Vegetables (Gr oup 9); Edible Podded Legume Vegetables (Subgroup 6A); Succulent Shelled Pea and Bean (Subgroup 6B); Dried Shelled Pea and Bean (except S oybean); Non-grass Animal Feeds (Forage, Fodder, Straw and Hay (Group 18); Forage, Fodder, and Straw of Ce real Grains (Group 16) ; Fruiting Vegetables Group 8-10); Hops; Head and Stem Brassica Vege tables (Subgroup 5A); Leafy Brassica Greens (Subgroup 5B); Leafy Vegetables (Except Brassi ca) (Group 4); Taro Leaves; Turnip Greens; Low Growing Berry Except Cranberry (Subgroup 13- 07G); Peanuts; Pome Fruits (Group 11-10); Prickly Pear Cactus; Root Vegetables Excep t Sugar Beet (Subgroup 1B ); Small Fruit Vine Climbing (Except Fuzzy Kiwifruit) (Subgroup 13- 07F); Soybean (Seed); Tree nuts (Group 14- 12); Bulb Vegetables (Group 3-07); Foliage of Legume Vegetables (except Soybean) (Subgroup 7A); Pitaya; and Tuberous and Corm Vegetables (Subgroup 1C). Reduced risk classification was requested for cereal grains, cotton, non-grass anim al feeds, peanuts, tr ee nuts, vine and berry crops, citrus, pome fruits, prickly pear cacti, root and tuberous corm vegetables, leafy brassica, legumes, fruiting vegetables, and cucurbit vegetables.



### 3. Chemical Information

Chemical Name: Flupyradifurone, 2(5H)-furanone,4- [[(6-chloro-3- pyridinyl)methyl](2,2- difluoroethyl)amino

EPA PC Code: 122304

1 Data generated from semi-field studies (e.g., tunnel st udies using whole colonies and a single nutrition/forage source), where applications were made at maximum foliar rates while bees were actively foraging at full bloom, only identified relatively transient increases in adult bee mortality hours to several days following treatment.Page 4 of 22 Chemical Abstracts Service (CAS) Number: 951659-40-8

IRAC MoA Classification: Group 4D - Butenolide Insecticide

Mode of Action: Flupyradifurone is the first chemical th at belongs to the Insecticide Resistance Action Committee (IRAC) Mode of Action Classi fication Group 4D (Bute nolide Insecticide).

The butenolide insecticide has a mode of action si milar to nicotine and neonicotinoid insecticides in that it is an agonist binding to nicotinic acety lcholine receptors (nAchR), blocking the receptor causing insect death; however, its chemical structure diffe rs from the nitroguanidine neonicotinoids thus is a separate sub-class of IRAC Group 4. The compound is systemic in plants and targets piercing, sucking insects such as aphi ds and whiteflies. Flupyradifurone is expected to be an important tool in IPM programs, as it has a different mechanism of action than nitroguanidine neonicotinoids.



### 4. Human Health Risk Assessment

A summary of the human health risks of flupyradifurone is provided below.



### 4.1 Hazard Characterization

The acute toxicity of flupyradif urone was low for all routes of exposure (oral, dermal, and inhalation). The oral LD 50 for rats was estimated to be >2,000 mg/kg bw, with some mortalities reported at 2,000 mg/kg bw but none at 300 mg/kg bw (Toxicity Category III ). The acute dermal

LD 50 for rats was >2,000 mg/kg (Toxicity Ca tegory III). The acute inhalation LC 50 for rats was >4,671 mg/m 3 (4.67 mg/L), which was the highest achie vable concentration (Toxicity Category IV). Flupyradifurone was not irri tating to rabbit skin and caused only slight ocular irritation (redness of the conjunctivae) whic h was reversed within 48 hours.

The most sensitive effect seen in mammals was skeletal muscle atrophy/degeneration in dogs. With dietary administration, reductions in body weight and food consum ption were commonly

seen in all test animal species (rats, mice, dogs, and rabbits). The liver and thyroid were also common targets of flupyradifurone toxicity. The liver effects ofte n consisted of increased liver weight, hepatocellular hy pertrophy, liver enzyme increases (cytochrome P 450 upregulation), and

decreases in total cholesterol. Some of the liv er effects were judged to be adaptive responses

while others were correlated with vacuolations and changes in clin ical chemistry parameters (i.e., increases in alkaline phosphata se (ALP) and alanine aminotrans ferase (ALT), and cholesterollevel changes indicative of liver effects which extended beyond th e adaptive stage). The thyroid effects consisted of thyroid follicular cell hyper trophy and were observed mainly in rats. In addition, the thyroid effects we re generally found in conjunction with liver effects.

The developmental toxicity data in rats and ra bbits showed that flupyrad ifurone caused delayed

bone ossification in fetal rats and increased incidence of fetal deat h in rabbits. These effects were observed in the rat developmental study at the ma ternal lowest observed adverse effect level (LOAEL, 150 mg/kg/day). No advers e maternal effects were observe d at the highest dose testedPage 5 of 22 (80 mg/kg/day) in the main and range findi ng rabbit developmental studies. The increased

incidence of fetal death in rabbits was considered to be a quantitative increase in susceptibility in the developing fetuses. However, clear no obs erved adverse effect levels (NOAELs) were

established for both rat and rabbit developmental toxicity studies.

The results of a 2-generation reproduction study showed that flupyradifurone reduced the number of estrus cycles, decrease d the number of implantations in P 2 dams, and reduced the litter size in the presence of decreased body weight and food consumption in maternal animals. In addition, the body weight of F 2 pups was decreased at a dose ( 37.8 mg/kg/day) where no effect was seen in the parental animals; this finding suggests a quantitative increase in susceptibility in the young rat.

Carcinogenicity studies in rats and mice did not yield a compound-relate d increase in tumor incidence, and the genotoxicity battery di d not show flupyradifurone to produce any genotoxicity.

The acute neurotoxicity study showed that or al administration of flupyradifurone caused increases in the incidence of piloerection and d ilated pupils at 50 mg/kg bw. At the next higher dose level (200 mg/kg bw) and above, it produced a large number of clin ical signs that are indicative of neurotoxicity; these included lowe r muscle tone, rapid re spiration, low arousal, tremors, myoclonic jerks, chew ing, repetitive licking of lips, gait incoordination, flattened or hunched posture, dilated pupils, impaired (uncoor dinated or slow) righting reflex, impaired flexor and tail pinch responses, and reduced rectal temperature. However, none of these clinical signs were found in the dietary feeding studies , including the 90-day ne urotoxicity study. The

effects seen in the acute neurot oxicity study are likely related to stimulation of the nicotinic acetylcholine receptors (nAchRs), however ther e is limited additional evidence in mammalian studies that the pesticidal mode of action is important to mammals. The differences in the findings between the acute oral neurotoxicity st udy and other studies using subacute dietary administration might be explai ned by the rapid absorption an d excretion of flupyradifurone. Flupyradifurone was absorbed rapidly in the me tabolism study where rats were dosed by gavage. Peak plasma levels were reached within 1-4 hours of dosing depending on the dose, and flupyradifurone was almost completely eliminat ed approximately 24 hours after administration. With subacute dietary administration, the rode nt test animal consumed the compound mostly during the entire night, and the internal flupyradifurone concen tration required to produce clinical signs of toxicity was probably seldom reached due to metabolism and rapid elimination from the body. As a result, clinical signs were not reported. No neurotox icity or other adverse effects were seen in 90-day di etary neurotoxicity study in rats at dose levels as high as 174 mg/kg bw/day.

No immunotoxicity was found in rats tested at the highest dose of 230 mg/kg bw/day.

Several metabolites were found in plants and ra t metabolism studies; some of these metabolites were tested in mutagenicity stud ies and subchronic oral toxicity studies. The results showed that most of the flupyradifurone metabolites had lowe r toxicity than the parent compound, except for difluoroacetic acid (DFA). DF A may be found in food and drinking water as a result of the proposed uses; dermal and inhala tion exposures to DFA are not e xpected. DFA was found in thePage 6 of 22 rat metabolism study at approximately 6% of th e administered dose. The registrant provided limited toxicity data on DFA so the Agency scre ened the literature and databases of similar chemicals to identify any additional toxicity concerns resulting from exposure to DFA. A literature search did not identify any studies that demonstrated th at DFA was more toxic than the parent compound at any duration of exposure. Furthermore, a st ructure-activity relationship analysis did not reveal any new concerns for DFA.

The most sensitive flupyradifurone effects seen in the database were skeletal muscle myofiber atrophy/degeneration, d ecreases in body weight, and decrea ses in body weight gain at the LOAEL of 33 mg/kg/day in the 90-day dog or al toxicity study (NOA EL = 12 mg/kg/day). However, in a 90-day oral feeding study in rats DFA produced a different effect (black foci in the glandular part of the stomach with correla ted histopathology findings of focal glandular erosion/necrosis at 66.2/78.8 mg/kg/day). These dose levels and effects confirm that DFA and flupyradifurone produce different effects on target different ti ssues. Although these effects occurred at similar potencies (similar comparable NOAELs and LOAELs on a molar basis 2 ), the effects are different. Therefore, the toxicity to DFA should be evaluated separately from flupyradifurone.

4.1.1 Food Quality Protection Act (FQPA) Safety Factor

Based on the currently available toxicity and ex posure data, EPA has concluded that the FQPA Safety Factor for flupyradifurone can be redu ced to 1X. Flupyradifurone is supported by a complete toxicological database . Although there are clinical signs which indicated neurotoxicity in adult rats, quantitative increases in suscep tibility demonstrated by decreased body weights in

F 2 rat pups, and quantitative and qu alitative suscep tibility demonstrated by increased incidence of dead rabbit fetuses, ther e are clear NOAELs for these effects. The NOAEL for offspring toxicity in the 2-generation re production study is equiva lent to the point of departure (POD)

selected for risk assessment while the NOAELs for neurotoxicity (cli nical signs) and rabbit development toxicity are greater than the NOAE L selected as the POD for risk assessment. Therefore, the POD is protective of the eff ects which are indicative of neurotoxicity and susceptibility in rats and rabbits. Overall, the data support the determination that an additional safety factor is not needed.

The flupyradifurone toxicology databa se is adequate to characterize any potential for prenatal or postnatal risk for infants and children, and in cludes acceptable rat and rabbit developmental toxicity studies and a rat re productive toxicity study, as well as acute and subchronic neurotoxicity studies. EPA waived the require d subchronic inhalation toxicity study for the following reasons: flupyradifurone has a low va por pressure, low acut e inhalation toxicity (Toxicity Category IV). Further, based on a screening level risk assessment using a conservative chronic oral POD, margins of exposure (MOEs) do not exceed the target MOE 10 times the level of concern (LOC).

2 Calculation of Equivalent Dose Between DFA and the Parent Compound: MW flupyradifurone = 289 g/mol MW DFA = 97 g/mol. 289 g/mol ÷ 97 g/mol = ~ 3 g/mol. NOAEL in 90 day rat oral toxicity study with flupyradifurone = 30/38 (M/F) mg/kg/day. NOAEL in 14 day rat oral toxicity study with DFA = 12.7/15.6 (M/F) mg/kg/day. 30 mg/kg/day ÷ 3 = ~10 mg/kg/day (which is similar on a molar basis to the DFA NOAEL of 12.7 mg/kg/day).Page 7 of 22 4.1.2 Cumulative Effects

Unlike other pesticides for which EPA has fo llowed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for flupyradifurone and any other subs tances. Therefore, for the purposes of this action EPA has assumed that flupyradifurone does not have a common mechanism of toxicity with other

substances.

4.1.3 Toxicological Endpoints

Table 1. Summary of Toxicity Endpoints and Points of Departure for Use in Dietary, NonOccupational, and Occupational Human Health Risk Assessments.

Exposure/ Scenario Point of Departure Uncertainty/ FQPA Safety

Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Acute Dietary (All populations) NOAEL =

35 mg/kg/day UF A = 10x

UF H =10x

FQPA SF= 1x aRfD =0.35 mg/kg/day Acute neurotoxicity study –rat LOAEL = 50 mg/kg/day. At the next higher dose level (200 mg/kg) or above, lower muscle tone, rapid respiration, low arousal, tremors, myoclonic jerks, chewing, repetitive licking of lips, gait incoordination, flattened or hunched posture, dilated pupils, impaired righting reflex, impaired flexor and tail pinch responses and reduced rectal temperature. Automated measures of motor activity were also reduc ed in both sexes, compared to controls.

Chronic Dietary (All Populations) NOAEL =

7.8 mg/kg/day UF A = 10x

UF H =10x

FQPA SF= 1x cRfD = 0.078 mg/kg/day

cPAD = 0.078 mg/kg/day 1-year oral toxicity study-dog LOAEL= 28 mg/kg/day based on minimal to slight, focal to multifocal areas of skeletal muscle degeneration in gastrocnemius and/or biceps

femoris muscle.

Dermal Short-(1-30 days)

and Intermediateterms (1-6 months) NOAEL =

12 mg/kg/day

DAF =

7.42% a UF A = 10x

UF H =10x LOC = 100 90-day oral toxicity study-dog LOAEL= 33 mg/kg/day ba sed skeletal muscle atrophy/degeneration.2-generation reproduction study- rat as a cocritical study. NOAEL= 7.7 mg/kg/day Offspring LOAEL=38.7 mg/kg/day based on pup body weight decrease.

Inhalation Short-(1- 30 days) and

Intermediate-terms (1-6 months) NOAEL =

12 mg/kg/day UF A = 10x

UF H =10x LOC = 100 90-day oral toxicity study-dog LOAEL= 33 mg/kg/day based on skeletal muscle atrophy/degeneration2-generation reproduction study- rat as a cocritical study. NOAEL= 7.7 mg/kg/day Offspring LOAEL=38.7 mg/kg/day based on pup body weight decrease.

Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on data s howing no treatment-related

increase in tumors incidence in rat and mouse carcinogenicity studies. No mutagenic concern was reported in the genotoxicity studies. Point of Departure (POD) = A data point or an estimated point that is derived from observed dos e-response data and used to mark the beginning of extrapolation to determine risk associ ated with lower environmentall y relevant human exposures. NOAEL

= no observed adverse effect level. L OAEL = lowest observed adve rse effect level. UF = uncertainty factor. UF A = extrapolationPage 8 of 22 from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (c = chronic). RfD = reference dose. LOC = level of concern. Dermal Absorption Factor = DAF. Toxicity via the inhalation route of exposure is assumed to be equivalent to toxicity via the oral route. a : This DAF was calculated based on the dermal absorpti on values from the 24 hours measurements of

the most dilute test formulation used in the in vivo rat and in vitro human and rat skin dermal penetration studies. To estimate the human dermal absorption factor (DAF ), the following equation is used:

Human DAF = (in vitro human % absorption ) x [(in vivo rat % absorption / (in vitro rat % absorption )]

.



### 4.2 Exposure and Risk Characterization

4.2.1 Dietary Exposure and Risk

For dietary exposure and risk as sessment, unrefined acute and chronic dietary analyses were conducted for flupyradifurone. The assessments incorporated recommended tolerance-level residues, default or empirical processing factors, and conservative drinking water estimates, and assumed that 100% of the proposed crops were treated.

4.2.1.1 Acute Dietary Risk

The acute dietary (food and drinking water) expo sure and risk estimates do not exceed the Agency’s LOC (i.e., <100% acute population adju sted dose (aPAD)) for the U.S. population and all population subgroups. At the 95 th percentile of exposure, the resulting acute dietary risk estimates represented 24% of the aPAD for the general U.S. population and 38% of the aPAD for children 1-2 years old, the most highly exposed population subgroup.

4.2.1.2 Chronic Dietary Risk

The chronic dietary (food and drinking water) exposure and risk estimates do not exceed the Agency’s LOC (i.e., <100% chronic population adju sted dose (cPAD)) for the U.S. population or any population subgroups. The resulting chronic diet ary risk estimates represented 39% of the cPAD for the general U.S. population and represen ted 84% of the cPAD for children 1-2 years old, the most highly exposed population subgroup. Based on the lack of refinement in the assessment, actual dietary exposure is e xpected to be significantly lower.

4.2.1.3 Cancer Dietary Risk

Flupyradifurone is classified as “not likely to be carcinogenic to humans.” Therefore, a cancer dietary exposure assessment was not performed.

4.2.1.4 Dietary Exposure Evaluation - DFA

Exposure to DFA as a result of flupyradifurone application is expected in food (plant- and animal- based) and drinking water. DFA was not a major metabolite in most plant commodities, but was significant for the following uses: seed tr eatment (soybean), soil drench (tomato), andPage 9 of 22 foliar (succulent legume vegetables, especially gr een beans and lima beans, and cucurbits). DFA was a major degradate on a relative basis in poult ry commodities; but on an absolute basis, only very small concentrations of DFA and parent are anticipated at the calculated livestock feeding (exposure) levels. Therefore, dietary exposure to DFA is expected to be relatively low compared to exposure to parent flupyradifurone.

Additionally, the Agency conducte d a conservative screening-leve l dietary exposure evaluation. This evaluation assumed conservative drinking wa ter concentrations, that 100% of the crops

contained DFA based on measured residue data found in crop field tr ials. The screening exposure evaluation of DFA showed 5-7X less e xposure to DFA than to flupyradifurone from the proposed uses. Since there is similar potency (albeit with different toxic effects) between flupyradifurone and DFA but less exposure expected to DFA than flupyradifurone, and there are no risk concerns from exposure to flupyradifur one, there should also be no concerns from exposure to DFA.

4.2.2 Residential Exposure and Risk

There are no proposed residential uses of flupyr adifurone; therefore, a residential exposure

assessment has not been conducted.

4.2.3 Aggregate Exposure and Risk

In accordance with the FQPA, the Agency must consider aggregate pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or th e risks themselves can be aggregated. When aggregating exposures and risks from various so urces, EPA considers both the route and duration of exposure. There are no residential uses of flupyradifurone; therefor e, the aggregate risk includes only exposure from food and drinking water. Acute and chronic dietary risks do not exceed EPA’s LOC for the U.S. population or any population subgroups.

4.2.4 Occupational Exposure and Risk

There is potential for short- and intermediate-term occupatio nal exposure to flupyradifurone during both handler (mixing, loadin g, and application via the derm al and inhalation routes) and post-application activ ities (via the dermal route) based on the proposed uses.

For both dermal and inhalation exposures, the PODs selected are considered protective of both

short- and intermediate-term durations.

The quantitative exposure/risk a ssessment developed for occupati onal handlers is based on the following scenarios:Page 10 of 22  mixing/loading liquid formulations for aer ial, airblast, chemigation, and ground boom application;

 applying sprays with aerial, ai rblast, and ground boom equipment;

 flagging for aerial applications;

 mixing/loading/applying using a backpack sprayer and mechanically pressurized handgun;

 primary handling for seed treatment (loa ding/applying, sewing, bagging treated seed; multiple activities); and

 secondary handling for seed treatment (planters).

The proposed BYI 02960 480 FS label (seed treatment for soybean only) requires seed treaters and workers cleaning the treatment facilities to wear long-sleeved shirts, long pants, shoes, socks, and chemical resistant gloves. Baggers an d others involved in the packaging of treated seed are required to wear long-sleeved shirts , long pants, shoes, and socks. The proposed SivantoTM label requires occupati onal handlers to wear long-sleeved shirts, long pants, shoes, socks, and chemical resistant gloves.

There are no risk estimates of concern at baseline PPE (long-sleev ed shirts, long pants, shoes, and socks). For the agricultural uses of flupyr adifurone, the short- and intermediate-term combined (dermal + inhalation) occupationa l handler MOEs ranged from 260 to 17,000 with

baseline PPE. With the addition of chemical-resi stant gloves, as required on the flupyradifurone label, the short- and intermediate-term combin ed (dermal + inhalation) occupational handler MOEs ranged from 800 to 57,000. For the proposed seed treatment use of flupyradifurone, the combined (dermal + inhalation) short- and intermediate-term MOEs ranged from 2,000 to 14,000.

There was no dislodgeable foliar residue (DFR) study submitted with the application. Since the Day zero target MOE 3 for a DFR study waiver was exceeded for certain activities following foliar applications in grapes, the restricted en try interval (REI) was in creased to 48 hours for girdling or cane turning activities to achieve an MOE >200. Si nce the increased REI for specific activities in grapes addresse s the MOE exceedance, the DFR study requirement was waived since all other proposed uses re sulted in MOEs greater than 200. Section 7.2.3 includes specific label language to address the REI for gird ling and cane turning ac tivities in grapes.



### 5. Ecological Risk Assessment

The environmental fate and ecological ri sk assessment is summarized below.



### 5.1 Environmental Fate

Flupyradifurone is characterized as being persistent to very persistent and is moderately mobile to mobile depending on soil conditions. Therefore, it has the potential to reach aquatic environments, including surface and groundwater , for several months or more following

3 An MOE of at least 200 is required in absence of the required DFR study.Page 11 of 22 application. Flupyradifurone is nonvolatile, and thus movement through air will not constitute a major transport pathway. The available fate data suggest that flupyradif urone is likely to dissipate from the point of a pplication through various transpor t mechanisms, including runoff, erosion, and leaching to groundwater. Times to 50% dissipation of pesticide mass (DT50) in 12 terrestrial field dissipation st udies ranged from 8.3 to 310 da ys,with DT50 being less than 56 days in eight of the studies. Times to 90% declin e of pesticide mass (DT90) from surface soils in terrestrial field dissipation studies also show a wide range in pers istence from <3 months to one year, highlighting the variability in the persis tence of flupyradifurone under certain conditions. Since flupyradifurone is mobile to moderately mob ile and persistent in th e aquatic environment, there is the potential for both short-term and long-term exposure to aquatic organisms.



### 5.2 Ecological Exposure

Measures of exposure are based on aquatic and terrestrial models that calculate estimated environmental concentrations (EECs) using proposed application rates and methods.

5.2.1 Exposure to Aquatic Life

The environmental fate properties of flupyradifurone indicate that for foliar applications, spray drift, runoff, and leaching are potential trans port mechanisms to aquatic habitats where nontarget organisms may be exposed. A sensitivit y analysis was completed to determine the contribution of each route of exposure. When the contribution from spray drift is removed from aquatic exposure estimates, many proposed uses stil l exceeded the acute risk to federally listed threatened/endangered species (hereafter referred to as “listed” species) and chronic risk LOCs. This indicates that exposure exceedances in mo st cases are driven by residues in runoff. The requirement for a maintained vegetative buffer intercepting runoff before entering water bodies neighboring application sites is expected to re duce the potential exposur e in aquatic systems. While any setback buffer between an aquatic wa terbody and the treated field is expected to reduce exposure, methodologies are not available to determine the specific distance that is needed to eliminate the risk concern from transport in runoff.

Compounds with a log octanol-w ater partition coefficient (K ow ) of three and above are generally considered to have the potential to bioconcentrat e in aquatic organisms. The partition coefficient for flupyradifurone (log K ow =0.08) falls well below this thre shold and therefore the compound is not expected to bioconcentrat e in aquatic organisms.

For surface water, the highest peak EEC was de rived for the use on alfalfa and clover (0.18 lbs a.i./A, 2 applications, 7-day retreatment interval, foliar and aerial application) where 1-in-10 year peak, 21-day, and 60-day average flupyradifurone EECs are 25.2, 24.0, and 22.1 μg/L, respectively, and are not substant ially different from one another in terms of the magnitude of

residues in water.Page 12 of 22 5.2.2 Exposure to Terrestrial Wildlife, Plan ts, and Beneficial Invertebrates

It is expected that non-target terrestrial organisms can be expo sed to foliar applications of flupyradifurone through consumption of exposed pl ants and invertebrates on the treated field. Additionally, flupyradifurone may reach terrestrial e nvironments off the field via spray drift, and via application of irrigation wate r containing residues of flupyradifur one. With regard to the seed treatment, flupyradifurone may reach aquatic habita ts via leaching of the chemical from the seed coat, and subsequent transport via runoff and/or infiltration. It is e xpected that non-target terrestrial organisms can be exposed to flupyrad ifurone through consumption of treated seeds which may remain on the surface. Standard cons ervative, unrefined exposure modeling was used to estimate exposure to non-target terrestria l organisms, with the exception of the honeybee where refined modeling approaches were used because screening-level LOCs were exceeded.



### 5.3 Ecological Effects

5.3.1 Aquatic Organisms

Flupyradifurone is slightly to practically non-toxi c to aquatic vertebrates (fish and aquatic-phase amphibians for which fish serve as surrogates) on an acute exposure basis. Acute toxicity values for freshwater and estuarine/marine fish are non-definitive (i.e., LC 50 values are greater than the highest concentration tested). Estimated peak ex posure concentrations in surface water for all proposed uses are several orders of magnitude lo wer than the highest co ncentration tested in available fish acute toxicity stud ies; therefore, the likelihood of ac ute mortality in freshwater or estuarine/marine fish following exposure to fl upyradifurone from any of the uses evaluated is presumed to be low.

Flupyradifurone is very highly toxi c to both freshwater insects a nd estuarine/marine crustaceans on an acute exposure basis. Flupyradifurone is slightly toxic to water fleas ( Daphnia magna ) and the Eastern oyster ( Crassostrea virginica ) with non-definitive acute toxicity estimates; however, the compound is very highly toxic to non-biting midges ( Chironomus riparius ) and highly toxic to mysid shrimp ( Americamysis bahia ) on an acute exposure basis. Based on toxicity tests for several transformation products of flupyradifur one using the most sensitive freshwater invertebrate, C. riparius , M47, M48, and 6-CNA degradates ar e less toxic than the parent compound by several orders of magnitude.

The NOAEC of flupyradifurone on freshwater vascular plants and nonvascular plants was determined to be 34.2 mg a.i./L (frond number) a nd 80 mg a.i./L, respectively. It should be noted that 80 mg a.i./L was the highest concentration tested for growth of freshwater green algae ( Pseudokirchnerie lla subcapitata ) and was reported to be at the practical limit of solubility for flupyradifurone. The effects of several transfor mation products of flupyradifurone were also tested on green algae; none of the studies showed adverse effects at any of the concentrations

tested.Page 13 of 22 5.3.2 Terrestrial Wildlife, Plants a nd Beneficial Invertebrates

Based on the available data, flupyradifurone is mode rately toxic to birds (a nd to terrestrial-phase amphibians and reptiles for which birds serve as surrogates) on an acute oral exposure basis and slightly toxic to birds on a subacute dietary exposure basis. Several of the acute oral and subacute dietary toxicity studi es indicate effects on feed consumption, body weight, or body weight gain, suggesting that the chemical can a ffect either the willingne ss of birds to consume diets containing elevated levels of flupyradifurone (i.e., pala tability) or to consume food (i.e., anorexia).

Flupyradifurone is classified as practically nontox ic to mammals on an acute oral exposure basis. No mortality was observed at the limit dose (2000 mg/kg bw) in an acute oral toxicity study with the rat, which was the most sensitive mammalian species tested; therefore, the 96-hr LD 50 is nondefinitive (i.e., LD 50 >2,000 mg a.i./kg bw). As indicated above, EPA has concluded that flupyradifurone exhibits low acute toxicity to mammals by all e xposure routes (EPA Toxicity Category III or IV).

Flupyradifurone is practically non-toxic to young adult honeybees on an acute contact basis; however, the compound is highly to xic to young adult bees on an acute oral exposure basis. Flupyradifurone is practically non-toxic to larval bees following repeat oral exposure. In the acute contact toxicity test, some bees showed movement coordina tion problems or lethargy at the two highest concentrations (100 and 200 μg a.i. /bee) starting at 48 hours of exposure. In the acute oral toxicity test, behavioral abnormalities ( e.g., movement coordination problems and lethargy) were observed in bees at doses >0.34 μg a.i./bee within only th e first four hours of dosing. In addition, the acute oral toxicity test resulted in a st eep dose-response relationship in which 0 and 100 percent mortalit y were observed at 0.34 and 2.8 μg a.i./bee, respectively.

For terrestrial plants there were no adverse effects on survival in any of th e eleven species tested in the vegetative vigor study. Sli ght phytotoxicity was observed in tomato, oat, and corn, and moderate effects were observed in soybean. Sim ilarly, effects on emergence, survival, and shoot length did not exceed 25% in any of the eleven species tested in the seedling emergence study; therefore, a definitive endpoint was not establishe d at the maximum proposed application rate for flupyradifurone.



### 5.4 Ecological Risk

5.4.1 Aquatic Organisms

Fish and Aquatic-Phase Amphibians

Flupyradifurone is slightly to practically non-toxi c to aquatic vertebrates (fish and aquatic-phase amphibians). Since acute toxicity values for fr eshwater and estuarine/marine fish are nondefinitive (i.e., greater than the highest concentrat ion tested), RQ values could not be calculated. However, estimated peak exposure concentratio ns in surface water for all proposed uses are several orders of magnitude lowe r than the highest concentration tested in available fish acutePage 14 of 22 toxicity studies; therefore, the li kelihood of acute mortal ity in freshwater or estuarine/marine fish following exposure to flupyradifurone from any of the uses evaluated is presumed to be low. Chronic RQ values for freshwater fish for all proposed uses are ≤ 0.01, and therefore do not exceed the chronic risk LOC (RQ ≥ 1) for fish.

Invertebrates

Acute and chronic RQ values were derived for freshwater and estuarine/marine invertebrates inhabiting both water column and benthic aq uatic environments using surface water and sediment pore water EECs, respectively. For freshw ater invertebrates inhabiting surface waters, all proposed uses exceed the acute risk to listed species LOC (RQ = ≥ 0.05), while the acute risk to non-listed species LOC (RQ ≥ 0.5) is only exceeded for foliar applications when there are ≥ 2 crop cycles per season. For estuarine/marine in vertebrates inhabiting surface waters, most proposed uses exceed the acute risk to lis ted species LOC (RQ range: 0.01-0.26), but none exceed the LOC for risk to non-listed species. Chr onic RQ values for freshwater invertebrates (RQ range: 0.27- 5.9) and estuarine/marine i nvertebrates (RQ range: 0.22-4.70) inhabiting

surface waters exceed th e chronic risk LOC (RQ ≥ 1.0) for the majority of uses. For most uses, exceedances are driven by the contribution of runo ff as compared to spray drift. For some uses (legume vegetables, pome fruit, low growing berrie s, hops) when the cont ribution of spray drift to exposure levels is removed or when ground sp ray is modeled as compared to aerial spray, acute risk to listed species and/or chronic LOCs are no longer exceeded for freshwater and/or

estuarine/marine invertebrates.

For sediment-dwelling (benthic) freshwater inve rtebrates, represented by non-biting midges, all proposed uses except for prickly pears exceed the acute risk to listed species and chronic risk LOCs, while the acute risk to non-listed species LOC is only exceeded for foliar applications

when there are ≥ 2 crop cycles per season. For sediment-dwe lling estuarine/marine invertebrates, represented by mysid shrimp, the majority of pr oposed uses exceed the acute risk to listed species LOC, and approximately half of the propos ed uses exceed the chronic risk LOC; all of the uses are below the LOC for non-listed species.

Aquatic Plants

For both vascular aquatic plants and algae, there are no exceed ances of the Agency’s LOC for listed species. Risk to non-listed species RQ values could not be cal culated since available values are non-definitive (i.e., greater than the highest concentrations tested); however, EC 50 values for both vascular and nonvascular plan ts are at least two orders of magnitude higher than peak surface water EECs. Therefore, th e likelihood for adverse effects to non-listed aquatic plants from the proposed uses of flupyradifurone is presumed to be low.

5.4.2 Terrestrial Organisms

Birds, Reptiles, and Terr estrial-Phase Amphibians

For all foliar or drench uses of flupyradifurone evaluated, the acute dose-based RQ values for birds exceed the Agency’s LOC for acute risk to listed species (RQ ≥ 0.1) for three or more typesPage 15 of 22 of dietary items. In addition, for all foliar or drench uses excep t for hops, the acute dose-based RQ values for birds exceed the Agency’s LO C for acute risk to non-listed species (RQ ≥ 0.5) for the smallest size class of birds (20 g) feedi ng on short grasses. The modeling of multiple crop cycles generally increases the number of dietar y items for which the acute risk to non-listed species are exceeded. The chronic risk LOC (RQ ≥ 1) is not exceeded for birds, and by extension to reptiles or terrestrial-phas e amphibians for which birds serve as surrogates, for any proposed use, including when multiple crop cycles are taken into account.

Mammals

Chronic, dietary-based RQ values for mammal s only exceed the chronic risk LOC for those mammals foraging on short grass (i.e., a single food item) when flupyradifurone is applied in two or more crop cycles; see Section 7.2.3 for speci fic label language to address potential risks identified in the risk assessment. Conversely, dose-based chronic RQs exceed the chronic risk LOC for multiple dietary items and size classes for all proposed uses evaluated. These risk quotients were conservatively calculated by assu ming 100% of the animal’s diet comes from the treated site. Proximity of home range of the mammalian species to the treated site drives the exposure that an individual orga nism would receive. For those mammals where the treated site does not represent 100% of their diet, the exposure is reduced and thereby th e potential for risk is reduced as well. RQ values were not calculated for acute risk to mammals because the toxicity endpoints were greater than the highest c oncentration/dose test ed in each study.

Terrestrial Plants

For terrestrial plants, all RQs are below the risk to listed and non-listed terrestrial plants LOC (RQ ≥ 1).

Terrestrial Invertebrates

On a conservative, unrefined dietary exposure ba sis (Tier I), all proposed foliar uses exceed the honeybee acute risk and chronic ri sk LOCs of 0.4 and 1.0, respec tively. However, neither acute

nor chronic LOCs are exceeded for foliar uses on a contact exposure basis or for soil drench or soybean seed treatment uses on an oral exposure basis.

Since LOCs are exceeded at the Tier I screeni ng level using model-generated exposure estimates, a refinement was conducted using empirical residue data from po llen and nectar from multiple crop types. Refined EECs were ge nerated based on measured residue s in pollen and nectar using known food consumption rates for bees. The data i ndicate that residues for most crops were at their daily maximum immediately following the bloom application and declined thereafter.

Residues taken from whole flowers were substantia lly higher than residues in nectar obtained from flowers or honeybee stomachs and theref ore may overestimate actual exposure values. Although flower residue data for most crops exceed the LOC threshold for acute risk to honeybees (RQ ≥ 0.4), nectar-specific residues are below the LOC.

The incorporation of label language for pesticide a pplicators best practice stewardship is directed at protecting food resources for pollinating insects to further re duce exposure and thereby reducePage 16 of 22 potential risk. For example, the label incl udes language recommending that foliar sprays be made late in the afternoon/evening/night hours outside of peak foraging periods.



### 6. Benefits and Alternatives

Flupyradifurone demonstrates efficacy against a variety of piercing, sucking insects, including species that are challenging to control (e.g., scales, whiteflies) and/or transmit disease (Asian citrus psyllid). It is a member of a new subc lass of chemicals in the IRAC Group 4D and has a new mechanism of action. Registration of flupyrad ifurone can provide growers with a new pest management tool that meets the criteria for EP A’s Reduced Risk Classification. It poses lower risk to agricultural workers relative to other curren tly registered pesticides with similar uses. The two end use products are classified as Toxicity Category III with Caution as the signal word. The REI for early entry into treated areas is set at the minimum time fram e of 4 hours (12 hours in California), except when girdling and cane turning in grapes (48 hours).

Flupyradifurone is proposed for use on a wide va riety of crops, includi ng cereal grains, cotton, peanuts, radish, carrot, brassica, legumes, fruitin g vegetables cucurbit vegetables, hops, citrus fruits, bushberries, low growing berries, small cl imbing vine fruits, tree nuts, and prickly pears.

The main alternative in secticides include chemicals in th e organophosphate class (chlorpyrifos, acephate), IRAC Group 4A of the neonico tinoid class (acetamiprid, imidacloprid, thiamethoxam), and the pyrethroid class (bifenth rin, fenpropathrin, zeta-cypermethrin), as well

as abamectin.

Organophosphates, such as acephate and chlorpyrif os, pose a greater risk to applicators than flupyradifurone and are currently undergoing a cumulative assessm ent for dietary risk. These alternatives are classified as Toxicity Cate gory II, requiring additional PPE and longer REIs. These chemicals are also more toxic to birds, terrestrial-phase amphi bians, reptiles, and mammals than flupyradifurone. Abamectin also pos es a greater human health risk through both worker and dietary exposure.

As is typical with most insecticides, flupyradif urone may pose a risk to aquatic invertebrates. The pyrethroids, however, are significantly more t oxic to these organisms. The cyano-substituted neonicotinoid acetamiprid is three times as toxic as flupyradifurone to freshwater invertebrates, and the nitroguanidine-substituted neonicotinoid thiamethoxam is approximately twice as toxic.

As an insecticide, flupyradifurone is unusual in that it demonstrates lit tle to no acute contact toxicity to honeybees. A comparison of LD 50 values is shown below in Table 2 for the above noted compounds and several other alternatives.Page 17 of 22 Table 2. Honeybee acute 96-hr contact LD 50 values

Chemical LD 50

μg a.i./bee

Bifenthrin 0.015

Zeta -cypermethrin 0.023

Thiamethoxam 0.024 Spinetoram 0.024 Chlorpyrifos 0.059 Imidacloprid 0.078

Abamectin 0.54 Acephate 1.2 Acetamiprid <12.5 Flupyradifurone 122 Pyriproxyfen >100 Spirotetramat >100
Fenpropathrin N/A

N/A = Data are Not Available



### 7. Proposed Regulatory Decision

Under Section 3(c)(5) of the Fe deral Insecticide, Fungicide a nd Rodenticide Act (FIFRA), the Agency is proposing to unconditionally register the new active ingredient flupyradifurone for use on Bushberry, Except Cranberry (Subgroup 13-07B); Cereal Grains Exce pt Rice (Group 15); Citrus Fruits (Group 10-10); Cotton seed (Subgroup 20C) Cucurb it Vegetables (Group 9); Legume Vegetables (succulent or dried) (Group 6); Forage, Fodder and St raw of Cereal Grains (Group 16); Fruiting Vegetables (Group 8-10); Hops; Brassica (Col e) Leafy Vegetables (Group 5); Leafy Vegetables (Except Brassica) (G roup 4); Low Growing Berry Except Cranberry (Subgroup 13-07G);Alfalfa; Clover; Peanuts; Pome Fruits (Gr oup 11-10); Prickly Pear Cactus; Root Vegetables (Subgroup 1B); Small Fruit Vi ne Climbing (Except Fuzzy Kiwifruit) (Subgroup 13-07F); Soybean (Seed); Bulb Onion (Subgroup 3-07A); Green Onion (Subgroup 3-07B); Tree Nuts (Group 14-12); Foliage of Legume Vegetabl es (Group 7); Pitaya; Turnip Greens; Taro Leaves; and Tuberous and Corm Vegetables (Subgroup 1C). The end-use products under

consideration for the new uses are Sivant oTM and BYI 02960 480 FS . Methods of application include seed treatment, soil drench, and foliar.

The Agency is not granting all of the uses proposed for Crop Group 18, the non-grass animal feeds (forage fodder, straw and hay) group. Uses will only be granted for clover in Washington, Oregon, and Idaho, and for alfalfa nationally; an insufficient number of clover trials were submitted to support a tolerance for the entire crop group.

For the food uses, Canadian Maximum Residue Levels (MRLs) and U.S. tolerances are harmonized for primary crop commodities.



### 7.1 Public Comments

On May 29, 2013, EPA published a Notice of Receipt in the Federal Register of an application for registration of flupyradifur one and announced a public comme nt period of 30 days. TwoPage 18 of 22 comments were received. The first expressed co ncern that neonicotinoid chemicals and other toxic substances are poisoning the environment, specifically citing concerns over cancer (generally) and concerns regarding pollinator e xposure to toxic substances. This comment was not specifically addressing the application to register flupyradifurone but generally directed at the registration of pesticides.

The second comment was from The City of Sacramen to Department of Utilities. They expressed concern that registering the chemical flupyradif urone for use on rice will affect drinking water quality in Sacramento.

In regard to the second comment, the applicant did not apply for a use on rice and a rotation crop interval for rice was not adequately supported. In response to the first comment, flupyradifurone is not classified as a carcinogen. As an inse cticide, flupyradifurone is unusual in that it

demonstrates little to no acute contact toxi city to honeybees. While the compound does show acute oral toxicity, it is comparatively better than the available registered alternatives, specifically the nitroguanidine-ne onicotinoids which are members of a different sub-class of chemicals as defined by IRAC thathave a different mechanism of action.

On June 5, 2013, EPA published a Notice of Fi ling in the Federal Register announcing the receipt of the initial filing of the flupyradifurone petiti on requesting the establishment of regulations for residues of flupyradifurone on various commodities. This publication also announced a public comment period of 30 days; no comments were received on the Notice of Filing.



### 7.2 Regulatory Rationale

Flupyradifurone is classified as a Reduced Risk chemical and the risk profile is favorable for both human health and non-target organisms compared to the main alternative compounds. Further, there were no human hea lth risks identified for dietary or occupational worker exposures resulting from the proposed use patterns. There are no proposed residential uses of flupyradifurone.

The screening-level Ecological Ri sk Assessment identified potent ial risk concerns for direct

effects to several taxonomic cate gories (outlined above in Sec tion 5.4). EPA believes the label changes made after the initial risk assessm ent minimizes potential exposure to non-target organisms thus effectively reduces potential risk. Specific label changes imposed by the Agency

to address identified risk ar e included in Section 7.2.3.

Consistent with the chemical’s mode of acti on (blocking the nicotinic acetylcholine receptors causing insect death), there are risk s of concern for terrestrial invertebrates. However, relative to the alternative registered produc ts (neonicontinoids and abamec tin), flupyradifurone has a lower toxicity profile. Further, semi-field/tunnel studies only identified relatively transient increases in adult bee mortality. Colonies exposed to flupyradif urone did not exhibit a ny detectable long-term effects, and field studies examining colonies through overwintering di d not demonstrate any

adverse effects in the treated co lonies. Currently registered alte rnatives such as neonicotinoid

class chemicals for the same uses are more acutely toxic to bees than flupyradifurone.Page 19 of 22 Flupyradifurone is practically non-t oxic to adult bees on an acute contact exposure basis and it is practically non-toxic to larval b ees on an acute contact/oral expos ure basis. Currently registered pesticides such as organophosphates, for which this chemical is an alternative, pose a greater risk to non-target organisms (birds and mammals) than flupyradifurone.

7.2.1 Endangered Species Act Considerations

The NAS report, available at http://www.nap.edu/catalog.php?record_id=18344, outlines recommendations on specific scientific and tech nical issues related to the development of pesticide risk assessments that are compliant with the Endangered Species Act and the Federal Insecticide, Fungicide, and Rode nticide Act. In November 2013, the EPA, along with the U.S. Fish & Wildlife Service (USFWS), the National Ma rine Fisheries Service (NMFS) (collectively, the Services), and the U.S. Department of Agri culture (USDA), released a summary of their joint Interim Approaches for a ssessing risks to listed species from pesticides. The Interim Approaches were developed jointly by the Agen cies in response to the NAS’s recommendations and reflect a common approach to risk assessment shared by the Agencies as a way of addressing

scientific differences between EPA and the Servi ces. The joint Interim Approaches were released prior to the stakeholder workshop held on November 15, 2013 ( http://www.epa.gov/espp/2013/interagency.pdf ). EPA presented the joint Interim Approaches at the December 2013 PPDC (Pesticide Program Dialogue Committee; http://www.epa.gov/pesticides/ppdc/2013/decem ber/dec2013-mtg.html) and SFIREG (State

FIFRA Issues Research and Ev aluation Group) meetings, allowing additional opportunities for stakeholders to comment on the Interim Appr oaches. As discussed at the November 2013 workshop, and consistent with the March 2013 st akeholder engagement process for FIFRA-ESA consultations, the Agencies have invited comment on the Interim A pproaches as preparations are made to apply these new approaches in the co ntext of upcoming registration review decisions. The Agencies intend to jointly implement these a pproaches as part of a phased iterative process that takes account of the input received and the le ssons learned from the initial efforts to work with the Interim Approaches.

It is important to understand th at the development of the Inte rim Approaches does not by its terms suggest that existing or recently developed ri sk assessments using the criteria articulated in OPP’s 2004 Overview document (http://www.epa .gov/espp/consultation/eco risk-overview.pdf) are necessarily “under-pro tective.” The Interim Approaches are intended to identify interim thresholds for interagency review as the Agencies jointly work to implement the recommendations of the NAS on certain specific re gistration review actions . The Agencies have

made no determination that these thresholds are necessary to prevent ta ke and preclude likely jeopardy and, in any case, the In terim Approaches do not establis h legally binding thresholds for consultation under the Services’ implementing re gulations. As EPA and the Services work through the initial actions that are being reviewed unde r the Interim Appro aches, the Agencies

will determine whether these thresholds should be modified before they are extended more broadly to additional regulatory actions. The de tails of the joint Interim Approaches are contained in the white paper “Interim Appro aches for National-Leve l Pesticide Endangered Species Act Assessments Based on the Recommenda tions of the National Academy of Sciences April 2013 Report,” dated November 1, 2013, available at http://www.epa.gov/espp/2013/nas.html.Page 20 of 22 As the Agency has emphasized in multiple forums, EPA is focusing most of its resources for assessing impacts to listed speci es on its registration review pr ogram for currently registered pesticides. EPA believes that, as a general matter, currently registered pesticides present a greater degree of risk to listed speci es than most new chemistries coming to market, including flupyradifurone, and that it is th erefore environmentally preferab le in most circumstances for EPA to assess the impacts of existing pesticides sooner in the process than newer pesticides that are designed to compete with more risky altern atives. As a result, EPA does not believe the environment or the public would be best served by delaying the registration of flupyradifurone to complete consultation. Focusing EPA’s and th e Services’ limited resources on completing a consultation on the effects of flupyradifurone woul d by necessity come at the expense of putting more resources into evaluating – and consequen tly regulating, where appropriate – what EPA believes to be more toxic compounds, that, among other things, pose greate r risk to endangered species than does flupyradifurone. With respect to the evaluation of flupyradifurone specifically, it is important to understand that under any internal or interagency review, the ecological risk evaluation will continue to rely on the body of information used in the current EPA ecological

assessment.

For the reasons explained above, EPA is not cons ulting with the Services on the issuance of the flupyradifurone registration. However, EPA is curre ntly working to prioritize its consultation

activities with Services and will evaluate the appropriate timing and scope of consultation on flupyradifurone in connection with those efforts. In addition, to the extent EPA receives new information indicating that flupyr adifurone may pose a greater risk to listed species than indicated by the existing scientific database for this pesticide, EPA will re-evaluate the terms of registration and determine whether additional use restrictions to protect listed species are

necessary

7.2.2 Data Requirements

There are no outstanding data requirements for flupyradifurone.

7.2.3 Mitigation and Labeling Requirements

In order to address risks that we re identified in the human health and ecological risk assessments, the following labeling language has been upda ted following the completion of the risk assessments. The updated labeling is intended to reduce the potential risk by minimizing the potential for exposure to flupyradifurone resi dues and/or or reduce exposure to humans.

General Label Requirements

 The draft labeling has been upda ted to include a restriction for uses in greenhouses. Use in greenhouses is not permitted because there is no supporting field trial data.Page 21 of 22 Label changes related to establishing tolerances

 A rotational crop interval of 30 days for rice is not adequately supported by adequate rotational crop data. The appropriate interval is 12-months. The exception for rice has

been removed from the label.

 The original petition reques ted a tolerance on Crop Group 18 (non-grass animal feeds). EPA is unable to establish the Crop Group 18 to lerances at this time for forage and hay because the registrant submitted an insufficient number of field trials for clover, one of the representative commodity crops. Based on the available data, EPA is establishing tolerances for alfalfa forage and hay, in addition to tolerances for clover; however, registration for flupyradifurone use on clover is restricted to use in Washington, Oregon, and Idaho, the areas where the field trials were conducted. A crop group tolerance could

be considered if additional field trials for clover from diverse areas of the US are supplied. The draft labeling has been upda ted to remove the uses on Crop Group 18.

 The draft labeling has been updated to specify flupyradifur one use on alfalfa grown for seed in Washington, Idaho, Oregon, Nevada, an d Montana only where state restrictions on alfalfa seed production prev ent the release of alfalfa seed into the food and feed commodity markets. No tolerance was establ ished for alfalfa grown for seed because residue studies were only c onducted on forage and hay.

 The proposed label pre-harvest interval (PH I) for prickly pear is 14 days, but the crop trials were conducted with a 21- day PHI. Therefore the draft labeling has been updated to include a PHI of 21 days.

Worker Exposure Risk

Since the day 0 MOE was exceeded for certain activ ities following foliar applications in grapes, the restricted entry interval (REI) was incr eased to achieve an MOE >200 (required in the absence of dislodgeable foliar resi due data). The draft labeling has been upda ted to include the following statement for girdling or cane turning activities in grapes following application of flupyradifurone:

Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) of 4 hours with the following exceptions: 1) the REI is 48 hours when girdling or cane turning in grapes; 2) in California the REI is 12 hours.

This change adequately reflects that all pos t-application MOEs, incl uding cane turning and girdling in grapes, are not of c oncern and are therefore acceptable.

Ecological Risk

The draft labeling has been updated to address risks identified in the screening-level assessment by minimizing potential exposure thus effectivel y reducing risk. Labeling updates occurring after risk assessment include a requirement for vegeta tive buffer strips, and limitations on the number of crop cycles. Risks were identif ied for a number of crop uses where multiple crop cycles perPage 22 of 22 season were permitted. Exceedances are addresse d by limiting the number of crop cycles to a single cycle per field per year. These changes have been incor porated on the proposed label.

Environmental Hazard Statements : These are required based on the physical-chemical properties of flupyradifurone.

The following Groundwater Advisory has been included on the label:

 This chemical has properties and characteristi cs associated with chemicals detected in groundwater. This chemical may leach into groun dwater if used in areas where soils are permeable, particularly where the water table is shallow.

The following Surface Water Advisory statement is triggered because the proposed uses are outdoor uses. The following two statements were updated on the label:

 This product may impact surface water quality due to runoff of rain water. This is especially true for poorly draining soils and soils with sh allow groundwater.

 This product is classified as having high pot ential for reaching surface water via runoff

for several months or more af ter application. A level, well -maintained vegetative buffer strip between areas to which this product is applied and surface water features such as ponds, streams, and springs will reduce the potential loading of flupyradifurone and difluoroacetic acid (a residue of concern of flupyradifurone). Runoff of this product will be reduced by avoiding applications when rain fall or irrigation is expected to occur

within 48 hours.

The following environmental hazard statement a nd best management practice statement have been included on the label in response to the e ffects (or lack thereof) of flupyradifurone on pollinators:

 Flupyradifurone is practically non-toxic to ad ult bees on an acute contact exposure basis and it is practically non-toxic to larval bees on an acute contact/oral exposure basis. Flupyradifurone is classified as toxic to a dult bees on an acute oral exposure basis in laboratory studies. Field studies with this product, Sivanto, when used at the maximum labeled rates, show no long-term impact to bee colonies.

 General Pollinator Best Management Practice: In order to minimize exposure to pollinators, it is recommended that foliar insecticides are applied late in the afternoon, evening, or at night outside of daily peak foraging periods.