UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHI NGTON D

. C ., 20460

OFFICE OF CHEMICAL SAFE TY AND POLLUTION PREVENTION


### MEMORANDUM SUBJECT: Review of Benefits for the Proposed Registration of a New Fungicide Act ive Ingredient Benzov indiflupyr (Solatenol) FROM:
THRU:

TO: Tara Cha nd goyal , Ph. D., Plant Pathologist Biological Analysis Branch Arnet Jones
. Chief Biological Analysis Branch Biological and Economic Analys i s Divis Shaunta 

### Hill , Chemical Review Manager Fungicide Branch Registration Division (7504P) 

### Product Review Panel: June 17, 2015
SUMMARY OPP is reviewing the application for registration of benzovindiflupyr as a new fungicide active ingredient with proposed uses on many crops [apples , peanuts , soybeans , cereals (wheat, barley), potatoes, turf and many minor crops (such as fruiting vegetables, beans, cucurbits , pome fruits)]. B EA D exam in ed subm itted 'information and product efficacy data provided by the registrant to detennine if potential benefits might be identi fied with the use of benzovindiflupyr. Because data are limited due to the nature of experimental use (i.e. , no corpmercia l-scale app licati ons) and limited number of seasons of data-gathering , any potential benefits that are identified by BEAD may not be reali ze d. Nevertheless , BEAD describes some potential attributes based on limited experimental data that could be offered to growers w ith the use of benzovinditlupyr. Benzovindiflupyr is a succinate dehydrogenase inhibitor (SDHI) fungicide
. The submitted data showed that benzovinditlupyr is more active in inhibiting SDH enzyme in fimgi (under contro ll ed conditions) than the registered alternatives (such as boscalid , carboxin , fluxapyroxad , penthiopyrad, sedaxane) indi catin g its efficacy at l ower rates than other SDHI fung icides (s uch as pentlufen , sedaxane, penthiopyrad , carboxin , boscalid) in contro llin g fungal pests.Benzovindiflupyr is effective in controlling fungal diseases on va ri ous crops (app les. peanuts. soy beans , wheat, barley. potatoes and turf). B e n zov indiflupyr might offe r a benefit to growers as a more effect ive SD I II fungic ide in an integrated fun g icide program where the efficacy of some S DHI fungicides h ave dec lined due to tolerance/ res is tance ( Ohkawa , Miyagawa and Lee , 2007). Under cond iti ons where S DI-II-resistance ha s been id entjfied in the field th e re i s the potential for increases in crop yie ld a nd/ o r quality with th e u se of bcnzovinditlupyr. Benefits might also be recognized for benzovindiflupyr treatments o n min or crops (e .g. . cucurbits. fruit ing vegetables. pome fruits) with limited registered alternatives. It is not anticipated that benzovind i Oupyr wou ld enhance yie ld a nd/ o r quality as compared to ctm ently reg i stered fungicides 

### in s ituati ons whe re SOH i-res is tance has not developed. 

### BACKGROUND The Fed e ral l nsecticid e. Fungicide. and Rodenticid e Act (FlFRA) authorizes EPA to register pesticides under 40 Code of Federal Regul ati o n s (CFR) Part 158. Fl FRA r eq uire s E P A to regulate the u se of a pesticide to the e xt e nt necessary to prevent unreaso nabl e adverse effects o n the env ironment. including human health , where ·unreasonable· js defined as taking into accoun t the economic. socia l, and enviro nmental costs a nd benefits of the use o f the pesticide. T he primary ri sks of concern fo r benzovinditlupyr a r e pe rs istenc e in th e env ironment a nd tox icity to aquatic li fe. The Agency wou ld like to p r opose mitigating th ese ri sks by reducing it s a pplication rate (lbs /A/ s pray) and imposing buffer zo nes for agricu ltu ra l crops v ia product labe l c hange s . The re g is trant has agreed to label amendments to mitigate these ri s ks. Benzovindiflupyr is being reviewed by OPP as a new fungicide active ingredient. OPP considers both the potential risks and benefi t s of a pesticide in its decision on th e requested registration. Here , BEAD provides infonnation. based on limit ed registrant

- provided data. regarding the potential benefits of benzovindi flup y r use. Benzovind iflup y r is cla ss ifi ed as a succinate dehydrogenase inhibitor (SDH I ) of fungal pathoge n s by Fungicide Res istance Action Comm ittee (FRAC) and b e lo ngs to group 7 (FRAC. 20 15 )
. T hese fungicid es inhibit s uccinate dehyd r oge na se (S DH, so-ca ll ed complex JI in the mitochondrial respiration chain). which is a functional part of the rricarboxyl i c cycle and linked to the mitochondria l electron transport chain. SD H co n sists of fou r subunits (A. 8, C and D) and the binding si te of the SDH l s is fo rmed**~** subunits B. C and D. Cross-resistance between SDH l s for different target s i tes a re complex (FRA C. 20 1 5) and more st udi es are needed to understand this c ross -resi s tanc e . Within gro up 7 there are 8 c hem ical groups [ph e n y l-b cnzam ides ( tlut o lanil. m epro nil ), phen y l-o xo-e th y l-thiophene amide ( iso f e ta mid ), pyridinyl-ethyl-benzamide (fluopyram), f ur an-carboxam ide (fenfuram), oxa thiin- carboxamides (ca rbox in and oxycarbox in ). thi azo le-carboxamide s ( thiaflu z amide), pyrazo le-carboxamides (benzov in d i f1ypyr). Pyridineca rbo za mid es (bosca lid )] [FRAC. 2015: Sierotzki and Sca lliet. 20131. Key att ributes unique to benzovindiflupyr fungicide are strong biological activity agai nst a broad spectrum of fungal plant pathogens
. especially 

### l'emuria inaequa/is (apple scab). 

### Sclerorium ro/fsii (Southe rn s tem b li g ht of peanuts). 

### Rhi zocronia solani (potatoes and turf). 

### I'hakospora

2

### pachyrhizae. (As ia n soybean ru s t ), 

### Pu ccun ia s pp. (w heat leaf ru st). 

### Sep to r ia spp. (g lume bl o tch of wheat and bar ley) a nd several fungal diseases o n minor crops (Sy nge nt a. 20 1 5) 

### BIOLOGI CA L BENEFITS U nique Properties of Benzovindiflupvr: The subm itted da ta (Sy ngenta. 2015) s howed that bc nzovindi nu pyr inhibit 50% S DH e n zy me in 

### Rhizoctonia solani (pat hoge n o n many hos t s) w ith 0.9 n M concen tra ti o n w he reas 1.3 to 8000nM co nce ntrat io n of othe r S DHI fungic ide s was required to ac hi eve same leve l of SDH inhibition. For 

### Sep loria spp . (g lum e blotc h of w heat and bar ley)
. 3.0 nm co nce ntrati o n of benzov indiflup y r was needed to inhibit 50% S DH enzyme w he reas 8-950 nM concent ra ti o n of other S DI-II fun g icide s was nee d ed to ac hieve sa m e level of inhibiti o n. These res ult s a re indicative of high biologica l ac tivit y o f benzov indifl ypy r a gain st th ese fun g i in co mpari so n to o th e r SD l-ll fungicides. Th is permits l ower application rate s of benzov ind i Oupr y th a n th e other registe re d S DHI fun g ic id es (pc nthiop yrad , carboxin, b osca lid. flup yram) in con tro llin g the se and po ss ibl y o th er fu nga l pests. The m ax imum s ingl e application ra te of benzov indiflup y r on m os t crops ranges from 0.046

- 0.068 lbs a i acre . The application ra tes of othe r SD HT f un g icides range from 0.077

- 0.38 lb s a i / A. 

### E fficacv of Bcnzo v indiflupvr in Controlling Fungal Pe s ts: The s ubm itted data (Sy n gen ta. 20 1 5) showed that be nzovindi flup yr is as effecti ve as standard apple scab contro l program. For apple scab contro l. the growers typically make 5 applications of mancozeb and 2 sp rays of cap r a n fu ng ic id e (Syngenta. 2015). Benzovi nd inu pyr can replace some or cap tan and/o r mancozeb sprays and s till con trol the d isease very effec ti ve ly (Syngen ta. 2015). T hi s practice wou ld r es ult in reduction of e nvi r o nm e nt a l load of ca ptan and / or man cozeb
. In add iti on to ca ptan a nd m a ncoze b. s tro bilurin fun g i c id es (suc h as azoxys trobin a nd trifloxystrobin) a nd triazo le fungicides (such as m yc lobutanil) are u sed for controlling apple scab. Resistance aga in s t s tro bilurin and man y tri azo le fun g ic id es is co mmon (Rosenberger and Cox, 20 I 0) and benzov inditlupy r is expected to play s ig nificant rol e apple sca b di seas e m a nage m e nt and resis ta nce manag e ment to maintain th e ef fic acy 

# o rs trobilurin and triazol e fungic ides. On peanuts, so uthern stem blight (cau sed by 

### Scle r oti11 ia rolj.; ·ii) is managed by using azoxystrobi n , teb uco n azo le a nd flutolanil fun g icides. The data submi tted by the reg istrant (Sy ngenta. 20 I 5) showed that benzovind i flupyr premixed with azoxystrbin contro ls southern stem b li ght. In additio n. it has seco nd ary benefit of co n tro llin g and foliar disease 

### (Cercospora leaf spots) in pean u ts. This provides the grower more assurance that the fungal diseases will be le ss damaging when cond iti ons are suitable for southern stem blig h t a nd foliar diseases
. Currently u se d tebuconazole and flut olani l do not control foliar diseases o n peanu t s (Synge nta . 2015). Re sis tance against azoxys trob in is present in mo st fungal pathogens. The results of efficacy trial s howed that be n zov indiflup yr addition int o the disease cont r ol program resu lted in better d isease co nt rol and higher yie ld s (Syngenta , 20 1 5). B e nzovi nd inup yr is very effec ti ve a gain st Asian soybea n rust caused by 

### Phakospora pachyrhizae. In B razil. thi s di sease is a major lim iting factor in soybea n production. It is 

### 3

### controlled by using triazole fungicides (such as propiconazole and tebuconazole) but recently there have been reports of decline in the efficacy of these fungicides. The addition of benzovinditlypyr to the disease control program has resu lted in better disease control , higher yields and resistance management against triaz ole fungicides (Syngenta, 2015). Asian soybean rust is present in the United States but to date it has been managed using triazole fungicides. Benz ivindiflypyr has the potential to play a role in better control of the disease and resistance management against triazole fungicides if soybean rust deve lops tolerance/resistance against triazole fungicides (like Brazil) in the U nited States (Syngenta , 2015). On wheat and barley , leaf rust and glume blotch diseases are of high economic impo rtance (Syngenta , 2015). They are controlled by triazole (propiconazole , tebuconazole) and strobilurin fungicides (azoxystrobin , pyraclostrobin). These fungal pests have developed resistance against strobi lurins and tolerance against triazole fungicides is increasing (Syngenta , 2015)
. A benvovindiflypyr treatment may result in better control of these diseases and resistance management against currentl y used fungicides
. On potatoes soil-borne 

### Rhizoctonia solani (causing stem canker and black scurf disease) can be a major problem and managed by using azoxystrobin at the t ime of planting seeds (Syngenta. 2015). The fungal pest has become les s sensitive to azoxystrobin at many locations. Benzovinditlupyr, when used a lone or in comb i nation with az oxystrobin , prov ides an excellent control of this pest on potatoes (Syngenta , 2015). On golf course turf benzovinditlupyr provides exce ll ent control of 

### R. solani and other foliar fungal d i seases ( such as leaf spots, rust , and powdery mildews). On turf fluto lanil and fluxapyroxad (another SDHI fungicide) appear to be less effective in managing fungal diseases than benzovindiflupyr (Syngenta , 2015). Syngenta (2 015) provided studies to support the registration of benzovindiflupyr on more than I 00 minor crops . The registrant (Syngenta , 2015) claims that on minor crops benzovindiflupyr will control diseases caused by 

### Rhizoctonia solani. Sclerotium ro/f'>ii, Puccinia spp . , and many more fungi that may significant ly impact yie lds and quality of produce. On cucurbits (watermelon , melon , cucumber and others) gummy stem blight is a major disease and currently managed by using chlorothalonil , strobilurins and triazo le fungicides. Addition of benzovindiflupyr in the disease control prog r am would help in reducing chlorothaloni l use, resistance management against strobilurins and triazole fungicides in addition to better disease management (Syngenta, 2015)
. Benzovindiflupyr has been demonstrated to be effective against powdery disease on cucurbits (Syngenta , 2015)
. Powdery mildews can be better managed using a rotation of program comprised of multiple fungicides (such as benzovindiflupyr , mancozeb , chlorothalonil , strobilurins and traizoles)
. 

### C O NCLUS IO NS B E AD examined experimental trial data provided by the registrant to determine if potential benefits might be identified \· Vith a future use ofbenzovinditlupyr. Benzovi ndiflupyr has higher biologica l activity against many fungi than o t her SDHI fungicides. This means that its lower application rates can achieve desired fungal disease control on many crops . As noted previous ly, 4because data are limited due to the nature of experimental pesticide use and lim ited number of seasons of data-gathering , any potential benefits that are identified by BEAD may or may not be realized upon commercial use of benzovindiflupyr. That stated , the use of benzovindiflupyr could offer benefits as an alternative SDH I fungicide where SDH I-resistant pathogen popu lat ions have resulted in disease control failures. Benefits might also be recognized for benzovnditlupyr treatments on registered crops with minor pesticide uses on minor crops (e
. g . , cucurbits, fruit in g vegetables) where there are few registered fungicides. The benefits might includ e greater crop yield and quality compared to a s itu ation where a SDHI fungicide has failed to contro l disease due to substantial resistant populations. However, because SDHI fungic ides are often used as part of a rotation program or mixed with other fungicides with different mode of action , the season long benefits regarding yield or enhanced revenue may be difficult to assess. 

### REFERENCES Avenot, H.F
. and Micha ilides , 

### T. J. 2010. Progress in understanding molecular mechanisms and evolution of resistance to succinate dehydrogenase inhibiting (SDHI) fungicides in phytopathogenic fungi. Crop Protection 29:643

- 651. http ://www . sc iencedirect.com/ science / article/ pii/ S0261219410000554 FRAC. 2015
. Fungic ide Resistance Action Committee Code List: Fungic ides Sorted by Mode of Action
. http :// www. frac
. in fo/ docs /default-source/ pub lications/frac-code-1 ist / frac-code-1 ist-20 

### I 5- fi na 

### IC2A 07AA36764
. pdf?sfvrsn = 4 Ohkawa , 

### J., Miyagawa , Hand Lee , PW. 2007. Pesticide Chemistry: Crop protection, Public Health , Environmental safety. John Wiley & Sons
. https ://books. googl e .com / books?id=x 6ti

### YI rwhgC&dq=carboxi n+resistance+app 1 e + scab&sourc e = gbs navlinks s . Accessed June 19 , 2015. Rosenberger, D.A and Cox, K.D. 20 1 0. App le scab management options for high in oculum orchards. http ://W'v\rw
. nyshs
. org/ pdf / f

g/ I Ospring/apple-scab-managemcnt

- options-for

- high

inoculum-orchards.odf. Accessed on June 9, 20 1 5
. Sierotzki , 1-I. and Scalliet, G. 2013. A review of cu1Tent knowledge of resistance aspects for the next-generation succinate dehydrogenase inhibi tor fungicides. Phytopathology 103:880-887. http: //apsjournals.apsnet.org/ doi/ pdf / 

### I 0.1094/ PI-l YT0-01-13-0009-RVW Syngenta , 2015. Syngenta's response to EPA ' s questions on solateno l fungicide dated May 28 , 2015)
.

5