UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

SUBJECT: Review of Benefits for the Proposed Registration of a New Fungicide Active 

Ingredient Benzovindiflupyr (Solatenol) 

FROM: 

THRU: 

TO: 

Tara Chandgoyal, Ph. D., Plant Pathologist 

Biological Analysis Branch 

Arnet Jones. Chief 

Biological Analysis Branch 

Biological and Economic Analysis 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)]. 

BEAD examined submitted 'information and product efficacy data provided by the registrant to 

detennine if potential benefits might be identified with the use of benzovindiflupyr. Because 

data are limited due to the nature of experimental use (i.e., no corpmercial-scale applications) 

and limited number of seasons of data-gathering, any potential benefits that are identified by 

BEAD may not be realized. Nevertheless, BEAD describes some potential attributes based on 

limited experimental data that could be offered to growers with 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 

controlled conditions) than the registered alternatives (such as boscalid, carboxin, fluxapyroxad, 

penthiopyrad, sedaxane) indicating its efficacy at lower rates than other SDHI fungicides (such 

as pentlufen, sedaxane, penthiopyrad, carboxin, boscalid) in controlling fungal pests. 
Benzovindiflupyr is effective in controlling fungal diseases on vari ous crops (apples. peanuts. 

soybeans, wheat, barley. potatoes and turf). Benzovindiflupyr might offer a benefit to growers as 

a more effective SDI II fungic ide in an integrated fungicide program where the efficacy of some 

SDHI fungicides have dec lined due to tolerance/resistance (Ohkawa, Miyagawa and Lee, 2007). 

Under conditions where SDI-II-resistance has been identjfied in the field there is the potential for 

increases in crop yield and/or quality with the use of bcnzovinditlupyr. Benefits might also be 

recognized for benzovindiflupyr treatments o n minor crops (e.g .. cucurbits. fruit ing vegetables. 

pome fruits) with limited registered alternatives. It is not anticipated that benzovindiOupyr 

would enhance yield and/or quality as compared to ctm ently registered fungicides in situations 

where SOH i-resistance has not developed. 

BACKGROUND 

The Federal l nsecticide. Fungicide. and Rodenticide Act (FlFRA) authorizes EPA to register 

pesticides under 40 Code of Federal Regulations (CFR) Part 158. FlFRA requires EPA to 

regulate the use of a pesticide to the extent necessary to prevent unreasonable adverse effects on 

the environment. including human health, where ·unreasonable· js defined as taking into account 

the economic. social, and environmental costs and benefits of the use of the pesticide. 

The primary risks of concern for benzovinditlupyr are persistence in the environment and 

toxicity to aquatic life. The Agency would like to propose mitigating these risks by reducing its 

application rate (lbs/A/spray) and imposing buffer zones for agricultura l crops via product labe l 

changes. The registrant has agreed to label amendments to mitigate these risks. 

Benzovindiflupyr is being reviewed by OPP as a new fungicide active ingredient. OPP considers 

both the potential risks and benefits of a pesticide in its decision on the requested registration. 

Here, BEAD provides infonnation. based on limited registrant-provided data. regarding the 

potential benefits of benzovindi flupyr use. 

Benzovindiflupyr is classified as a succinate dehydrogenase inhibitor (SDH I) of fungal 

pathogens by Fungicide Resistance Action Committee (FRAC) and be longs to group 7 (FRAC. 

20 15). These fungicides inhibit succinate dehyd rogenase (SDH, so-called complex JI in the 

mitochondrial respiration chain). which is a functional part of the rricarboxyl ic cycle and linked 

to the mitochondria l electron transport chain. SDH consists of four subunits (A. 8, C and D) and 

the binding site of the SDH ls is formed ~ subunits B. C and D. Cross-resistance between SDHls 

for different target sites are complex (FRAC. 20 15) and more studies are needed to understand 

this cross-resistance. Within group 7 there are 8 chemical groups [phenyl-bcnzamides (tlutolanil. 

mepronil), phenyl-oxo-ethyl-thiophene amide (isofetamid), pyridinyl-ethyl-benzamide 

(fluopyram), furan-carboxamide (fenfuram), oxathiin-carboxamides (carboxin and oxycarboxin). 

thi azole-carboxamides (thiafluzamide), pyrazole-carboxamides (benzovindi f1ypyr). Pyridinecarbozamides (bosca lid)] [FRAC. 2015: Sierotzki and Scalliet. 20131. 

Key attributes unique to benzovindiflupyr fungicide are strong biological activity against a broad 

spectrum of fungal plant pathogens. especially l'emuria inaequa/is (apple scab). Sclerorium 

ro/fsii (Southern stem blight of peanuts). Rhizocronia solani (potatoes and turf). I'hakospora 

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pachyrhizae. (Asian soybean rust), Puccunia spp. (wheat leaf rust). Septoria spp. (glume blotch 

of wheat and barley) and several fungal diseases on minor crops (Syngenta. 20 15) 

BIOLOGICAL BENEFITS 

Unique Properties of Benzovindiflupvr: 

The submitted data (Syngenta. 2015) showed that bcnzovindi nupyr inhibit 50% SDH enzyme in 

Rhizoctonia solani (pathogen on many hosts) with 0.9nM concentratio n whereas 1.3 to 8000nM 

concentration of other SDHI fungicides was required to achi eve same level of SDH inhibition. 

For Seploria spp. (glume blotch of wheat and barley). 3.0nm concentration of benzovindiflupyr 

was needed to inhibit 50% SDH enzyme whereas 8-950 nM concentratio n of other SDI-II 

fungicides was needed to achieve same level of inhibition. These results are indicative of high 

biological activity of benzovindiflypyr against these fungi in comparison to other SDl-ll 

fungicides. This permits lower application rates of benzovindi Oupry than the other registered 

SDHI fungicides (pcnthiopyrad, carboxin, boscalid. flupyram) in controlling these and possibly 

other fungal pests. The maximum single application rate of benzovindiflupyr on most crops 

ranges from 0.046 - 0.068 lbs ai acre. The application rates of other SDHT fungicides range from 

0.077 - 0.38 lbs ai/A. 

Efficacv of Bcnzovindiflupvr in Controlling Fungal Pests: 

The submitted data (Syngenta. 20 15) showed that benzovindiflupyr is as effective as standard 

apple scab control program. For apple scab control. the growers typically make 5 applications of 

mancozeb and 2 sprays of capran fungicide (Syngenta. 2015). Benzovindinupyr can replace 

some or captan and/or mancozeb sprays and still control the disease very effecti ve ly (Syngenta. 

2015). This practice would result in reduction of enviro nmental load of captan and/or mancozeb. 

In addition to captan a nd mancozeb. strobilurin fungic ides (such as azoxystrobin and 

trifloxystrobin) and triazole fungicides (such as myc lobutanil) are used for controlling apple 

scab. Resistance aga inst strobilurin and many tri azole fungicides is common (Rosenberger and 

Cox, 20 I 0) and benzovinditlupyr is expected to play significant role apple scab disease 

management and resistance management to maintain the efficacy or strobilurin and triazole 

fungic ides. 

On peanuts, southern stem blight (caused by Scleroti11ia rolj.;·ii) is managed by using 

azoxystrobi n, tebuconazole and flutolanil fungicides. The data submitted by the registrant 

(Syngenta. 20 I 5) showed that benzovindiflupyr premixed with azoxystrbin controls southern 

stem blight. In addition. it has secondary benefit of controlling and foliar disease (Cercospora 

leaf spots) in peanuts. This provides the grower more assurance that the fungal diseases will be 

less damaging when conditions are suitable for southern stem blight and foliar diseases. 

Currently used tebuconazole and flutolanil do not control foliar diseases on peanuts (Syngenta. 

2015). Resistance against azoxystrobin is present in most fungal pathogens. The results of 

efficacy trial showed that benzovindiflupyr addition into the disease control program resulted in 

better disease control and higher yields (Syngenta, 20 15). 

Benzovindinupyr is very effecti ve against Asian soybean rust caused by Phakospora 

pachyrhizae. In Brazil. this disease is a major limiting factor in soybean production. It is 

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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 resulted in better disease control, higher 

yields and resistance management against triazole fungicides (Syngenta, 2015). Asian soybean 

rust is present in the United States but to date it has been managed using triazole fungicides. 

Benzivindiflypyr 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 United States (Syngenta, 2015). 

On wheat and barley, leaf rust and glume blotch diseases are of high economic importance 

(Syngenta, 2015). They are controlled by triazole (propiconazole, tebuconazole) and strobilurin 

fungicides (azoxystrobin, pyraclostrobin). These fungal pests have developed resistance against 

strobilurins and tolerance against triazole fungicides is increasing (Syngenta, 2015). A 

benvovindiflypyr treatment may result in better control of these diseases and resistance 

management against currently 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 time of planting seeds (Syngenta. 

2015). The fungal pest has become less sensitive to azoxystrobin at many locations. 

Benzovinditlupyr, when used alone or in combination with azoxystrobin, provides an excellent 

control of this pest on potatoes (Syngenta, 2015). 

On golf course turf benzovinditlupyr provides excellent control of R. solani and other foliar 

fungal diseases (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 (2015) 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 significantly impact yields 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 triazole fungicides. Addition of 

benzovindiflupyr in the disease control program would help in reducing chlorothalonil 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). 

CONCLUSIONS 

BEAD examined experimental trial data provided by the registrant to determine if potential 

benefits might be identified \·Vith a future use ofbenzovinditlupyr. Benzovindiflupyr has higher 

biological activity against many fungi than other SDHI fungicides. This means that its lower 

application rates can achieve desired fungal disease control on many crops. As noted previously, 

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because data are limited due to the nature of experimental pesticide use and limited 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 SDHI fungicide where SDHI-resistant pathogen populations 

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, fruiting 

vegetables) where there are few registered fungicides. The benefits might include greater crop 

yield and quality compared to a situation where a SDHI fungicide has failed to control disease 

due to substantial resistant populations. However, because SDHI fungicides 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.sciencedirect.com/science/article/pii/S0261219410000554 

FRAC. 2015. Fungicide Resistance Action Committee Code List: Fungicides Sorted by Mode of 

Action. http://www. frac. in fo/docs/default-source/publ ications/frac-code-1 ist/frac-code-1 i st-20 I 5-

fi na I C2A 07 AA36764.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?i d=x 6t i 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 10. Apple scab management options for high inoculum 

orchards. http://W'v\rw.nyshs.org/pdf/ f g/ I Ospring/apple-scab-managemcnt-options-for-highinoculum-orchards.odf. Accessed on June 9, 20 15. 

Sierotzki, 1-I. and Scalliet, G. 2013. A review of cu1Tent knowledge of resistance aspects for the 

next-generation succinate dehydrogenase inhibitor fungicides. Phytopathology 103:880-887. 

http://apsjournals.apsnet.org/doi/pdf/ I 0.1094/PI-l YT0-01-13-0009-R VW 

Syngenta, 2015. Syngenta's response to EPA's questions on solatenol fungicide dated May 28, 

2015). 

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