UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON D.C., 20460

CHEMICAL SAFETY AND POLLUTION PREVENTION

March 9, 2020 MEMORANDUM

SUBJECT: Review of Benefits of Using Inpyrfluxam (A New ) to Control Fungal Diseases on Many (DP# 444798, PC# 090114, MRID# 201700356).

FROM: Tara Chandgoyal, Ph. D., Pathologist Biological Analysis Branch

THRU: Monisha Kaul, Chief Biological Analysis Branch Biological and Economic Analysis Division (7503P)

TO: Heather A Garvie, Senior Regulatory Specialist Fungicide Branch Registration Division (7505)

Product Review Panel: November 7, 2018

SUMMARY

The Office of Programs (OPP) is reviewing the application for the registration of a new active ingredient, inpyrfluxam. Inpyrfluxam is a succinate dehydrogenase inhibitor (SDHI) fungicide and belongs the Fungicide Resistance Action Committee (FRAC) code 7. The proposed use sites include: , canola, cereal grains, corn (field, pop, and sweet), legume vegetables, peanut, rice, sorghum, soybean and sugarbeet.

BEAD reviewed the submitted information and product performance data provided by the registrant to determine potential benefits of inpyrfluxam. Potential benefits may vary considerably under large scale commercial field conditions in different parts of the United States. BEAD determined that the high benefits of inpyrfluxam use are on soybean and sugarbeet, where it adds a new mode of action (MOA) against key fungal pests. On soybean, it provides a new MOA to control Rhizoctonia Aerial Blight disease that can cause high yield losses. Only two other fungicide MOAs - strobilurins (FRAC Code 11 - azoxystrobin, pyraclostrobin, trifloxystrobin) and (FRAC Code 3 - propiconazole, difenoconazole, tetraconazole) are registered to control this pest. On sugar beet, inpyrfluxam provides a new MOA to control Rhizoctonia Root and Crown Rot (RRCR) for which only strobilurins and are registered. On soybean and sugarbeet, inpyrfluxam is likely to play a role in fungicide resistance management. On other crops (, corn, peanut and rice), inpyrfluxam does not appear to have any obvious benefits compared to registered alternatives in controlling fungal pests. In this review, the benefits of using inpryfluxam on canola, cereal grains, legume vegetables and sorghum are not discussed as no information was submitted by the registrant.

BACKGROUND

EPA registers under section 3(c) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). A registration is granted unconditionally under section 3(c)(5) of FIFRA or conditionally under 3(c)(7) of FIFRA if the appropriate safety criteria are met. Each authority available to EPA for registering a pesticide under section 3(c) involves a finding related to whether the pesticide poses unreasonable adverse effects on the environment. “Unreasonable adverse effects on the environment” is defined in section 2(bb) of FIFRA to include “any unreasonable risk to man or the environment considering the economic, social, and environmental costs and benefits of the use of the pesticide. Therefore, in cases where a pesticide presents risks of concern, EPA assesses the benefits of the pesticide to determine whether those risks would lead to unreasonable adverse effects.

METHODOLOGY

BEAD assesses benefits of a pesticide based on several factors such as: its efficacy in managing a pest or pests in comparison with registered alternatives on different crops, yields, produce quality improvement, higher economic return, its role in management and/or integrated pest management. BEAD assessed the benefits of inpyrfluxam fungicide based on information submitted by the registrant (Valent, 2017). The registrant submitted information on the efficacy of inpyrfluxam in comparison with market leader fungicides in controlling fungal diseases on apple, corn (field, pop and sweet), peanut, rice, soybean, and sugarbeet. In some cases, the yield benefits and its role in fungicide resistance management was discussed. In addition, BEAD used publicly available information for review of the registrant submitted claims, as cited in the reference section of this document for benefits assessment.

INTRODUCTION

Valent, U.S.A., LLC (Walnut Creek, CA 94596) applied for the registration of inpyrfluxam fungicide for controlling fungal diseases on many crops, including: apples, cereal grains, corn, peanut, rice, sorghum, sugar beet and many legume vegetables within crop group 6. Inpyrfluxam is a succinate dehydrogenase inhibitor (SDHI) fungicide belonging to FRAC code 7 (FRAC, 2018). It belongs to subgroup pyrazole-4-carboxamide and there is medium to high risk of fungi developing resistance against to fungicides in Code 7 (FRAC, 2018). Inpyrfluxam use rates on labeled crops, are generally lower (0.044 – 0.089 lbs. a.i./A/Application) than other fungicides (such as azoxystrobin, benzovindiflupyr, fluxapyroxad, penthiopyrad with use rate ranging from 0.036 – 0.391 lbs. ai/A/Application on these crops. The registrant claims that inpyrfluxam does

8 not have cross resistance with other fungicides having different mode of action and therefore benefiting growers in fungicide resistance management.

REGISTRANT CLAIMS AND BEAD’s ASSESSMENT

The registrant submitted information to support their claims of benefits and public interest of using inpyrfluxam on apples, corn (field, pop and sweet), peanut, rice, soybean, and sugarbeet. No data was submitted on canola, cereal grains, sorghum, and legume vegetables. BEAD reviewed the registrant’s submitted data and verified their claims using publicly available information (cited in references part of this memorandum) for review of inpyrfluxam benefits and claims that this registration would be in the public interest as discussed below.

APPLES

Registrant Claim

Apple Scab and : Apple scab (caused by ) and powdery mildew (caused by Podosphaera leucotricha) are important disease of apples and can cause significant yield and quality losses. The leading fungicides used in controlling apple scab include captan, cyprodinil+difenoconazole, flupyram+pyrimethanil, fluxapyroxad+pyraclostrobin, ziram and benzovindiflupyram (Valent, 2017). The leading fungicides used in controlling powdery mildew include sulfur, sterol biosynthesis inhibitors (fenbuconazole, myclobutanil, tebuconazole), strobilurins (trifloxystrobinand kresoxim-methyl) and succinate de-hydroginase inhibitors (benzovindiflupyr, boscalid, flupyram, fluxapyroxad) fungicides. The registrant claimed that inpyrfluxam is a valuable succinate de-hydrogenase inhibitor fungicide (FRAC code 7) for a season-long disease management and a rotational partner with other fungicides in controlling these diseases.

BEAD Review

BEAD agrees that apple scab and powdery mildews can cause significant yield and quality losses to apples if no fungicides are used. BEAD agrees with the list of fungicides used by growers in controlling apple scab and powdery mildew (MRD, 2013-2017). The registrant did not compare the efficacy of inpyrfluxam in controlling apple scab and powdery mildew with the leading fungicides. For apple scab control, inpyrfluxam efficacy was compared with penthiopyrad only. The data shows that inpyrfluxam and penthiopyrad reduced scab severity from 11 percent in untreated control to 2 and 4 percent, respectively. These differences between inpyrfluxan and penthiopyrad in controlling apple scab were not significantly from each other. For powdery mildew control, inpyrfluxam efficacy was compared with penthiopyrad and kresoxam-methyl. The data showed that inpyrfluxam, penthiopyrad and kresoxam-methyl reduced powdery mildews from 20 percent in untreated control to 2, 6 and 6 percent respectively. Inpyrfluxam was significantly more effective than penthiopyrad and kresoxam-methyl in controlling powdery mildew. BEAD agrees that inpyrfluxam efficacy in controlling scab

8 and powdery mildew on apple is at par with penthiopyrad and kresoxam-methyl; however, BEAD is unable to determine benefits of using inpyrfluxam because penthiopyrad and kresoxam-methyl are not the leading fungicides for these uses.

CORN (FIELD, POP and SWEET)

Registrant Claim

Corn (field, pop and sweet) is susceptible to Rhizoctonia solani that causes seed decay, damping-off and seedling blight diseases. The registrant claimed that sedaxane and fluxapyroxad are registered and widely used as seed treatment for controlling this pest. In addition, trifloxystrobin, pyraclostrobin and ipconazole fungicides are registered and used by growers for corn seed treatment and in-furrow application to control this pest. The registrant submitted product performance data in comparison with registered alternatives and claimed that inpyrfluxam will be a valuable fungicide because it is a new active ingredient for controlling R. solani on corn.

BEAD Assessment

BEAD agrees with the list of registered alternatives available to growers for corn seed treatment to control R. solani (MRD, 2013-2017, CDMS, 2018). The results of submitted experimental trials showed that seed treatment and in-furrow applied inpyrfluxam provided protection to corn against Rhizoctonia pest and protection was comparable to widely used alternatives (sedaxane and fluxapyroxad). The efficacy of inpyrfluxam in controlling the pest was also compared by mixing inpyrfluxam with other registered fungicides (trifloxystrobin, pyraclostrobin, ipconazole). The results showed no significant differences in plant stand count between these treatments. On corn (field, pop and sweet), inpyrfluxam was as effective as registered alternatives in controlling R. solani seed decay, damping-off and seedling blight diseases. BEAD agrees that inpyrfluxam is a new active ingredient for controlling this fungal pest on corn.

PEANUT

Registrant Claim

Peanut is an important and high-value crop grown primarily in Georgia, Alabama, Texas, Florida, and Carolinas (Valent, 2017). Rhizoctonia Limb and Pod Rot (RLPR) disease is caused by Rhizoctonia solani and stem rot is caused by Sclerotium rolfsii. These diseases can cause significant yield losses without the use of fungicides (Valant, 2017). To manage these fungal diseases tebuconazole, flutolanil, azoxystrobin, prothioconazole+tebuconazole, penthiopyrad, flutolanil+propiconazole, pyraclostrobin, , azoxystrobin+benzovindiflupyr are available to the growers (Valent 2017). Inpyrfluxam will be used via foliar application prior to disease development at 14-

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21 days interval. The registrant claims that inpyrfluxam will be a new active ingredient to control these diseases on peanut.

BEAD Assessment

BEAD agrees that on peanut tebuconazole, flutolanil, azoxystrobin, prothioconazole+tebuconazole, penthiopyrad, flutolanil+propiconazole, pyraclostrobin, cyproconazole, azoxystrobin+benzovindiflupyr are dominantly used to control RLPR disease is caused by Rhizoctonia solani and stem rot is caused by Sclerotium rolfsii (MRD, 2013-2017). The submitted efficacy data showed that inpyrfluxam provides RLPR and stem rot disease control equivalent to the registered alternatives. BEAD agrees that inpyrfluxam will be an additional new active ingredient to manage these diseases on peanut.

RICE

Registrant Claim

On rice, sheath blight (caused by Rhizoctonia solani) is a yield limiting disease for rice growers in Louisiana (Lunos, 2016, Valent 2017). Rice grain yield losses ranging from 4 to 50 percent have been attributed to sheath blight, under disease favorable weather conditions (Groth and Bond, 2007). Sheath blight is found in 50 to 66 percent of rice fields in Arkansas and yield losses of 5-15 percent are common (Wamishe et al., 2017). Azoxystrobin, fluxapyroxad and propiconazole are widely used fungicides on rice to control the disease (Valent, 2017). The registrant claims that inpyrfluxam efficacy in controlling the pest is equal to the registered alternatives (azoxystrobin, fluxapyroxad) based on submitted field trial results. The registrant also claims that inpyrfluxam will be an excellent rotational partner for season long disease control and help in resistance management as its mode of action is different than commercially used fungicides.

BEAD Assessment

The results of the registrant submitted experimental trials showed that inpyrfluxam, azoxystrobin and fluxapyroxad reduced sheath blight incidence from 68 percent in untreated control to 25, 30 and 32 percent, respectively, and there was no significant difference in disease control provided by these fungicides. Propiconazole was ineffective in reducing disease incidence. Crop yield differences between inpyrfluxam, azoxystrobin and fluxapyraxad were not significant. Inpyrfluxam and fluxapyroxad fungicide belong to same FRAC code 7 and have similar mode of action (FRAC, 2018) and therefore inpyrfluxam is unlikely to play a major role in resistance management. Inpyrfluxam is a new active ingredient and some growers may find it useful in managing sheath blight of rice.

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SOYBEAN

Registrant Claim

Seedling Blight: Soybean seedling blight is caused by R. solani. Soybean seeds are treated with a base fungicide treatment consisting of fludioxonil+ethaboxam+metalaxyl for protection against soil-borne fungal pests (Valent, 2017). The efficacy benefits of inpyrfluxam, sedaxane and fluxapyroxad were compared by adding these fungicides into the base seed-treatment mixture. The data showed that inpyrfluxan, sedaxane and fluxapyroxad resulted in significant increase (approximately 19 percent) in yield over base treatment.

Rhizoctonia Aerial Blight: This disease has been reported to cause significant losses (up to 50 percent) in some fields in North Dakota (Valent, 2017). Strobilurin (azoxystrobin, pyraclostrobin, trifloxystrobin) and triazole (propiconazole, difenoconazole, tetraconazole) fungicides are used to control this pest (Valent, 2017). Strobilurin and triazole fungicides belong to FRAC code 11 and 3, respectively (FRAC, 2018). The registrant claims that inpyrfluxam has excellent efficacy against this pest and because it has a different mode of action than the registered alternatives it would play a role in resistance management.

Asian Soybean Rust: This is a sporadic disease on soybeans in the United States. Triazole fungicides (cyproconazole, propiconazole, tebuconazole), the strobilurin fungicides (azoxystrobin, pyraclostrobin, trifloxystrobin) and succinate dehydrogenase inhibitor fungicide (code 7 fungicide; fluxapyraxad) are registered for its control. The registrant claims inpyrfluxam is effective without providing efficacy data. The registrant also claims that rotating different modes of action if inpyrfluxam is registered will benefit growers.

BEAD Assessment

Inpyrfluxam efficacy in controlling soybean seedling blight was at par with registered alternatives (sedaxane and fluxapyroxad) when applied with base fungicide treatment to soybean seeds. The registrant submitted data (Valent, 2017) also showed that inpyrfluxam and registered alternatives provided similar yield benefits and belong to same FRAC code 7.

For controlling Rhizoctonia aerial blight on soybean, strobilurin (azoxystrobin, pyraclostrobin, trifloxystrobin) and triazole (propiconazole, difenoconazole, tetraconazole) fungicides belonging to FRAC code 11 and 3, respectively, are widely used (Valent, 2017, MRD, 2013-2017). However, the fungal pests are developing resistance against strobilurin fungicides (Gisi, et al., 2002). BEAD cannot determine the value of inpyrfluxam in controlling aerial blight without comparative efficacy data. BEAD agrees that inpyrfluxam belongs to FRAC code 7 and has different mode of action

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(FRAC, 2018) than the registered alternatives and therefore likely to play a role in fungicide resistance management.

BEAD agrees with the registrant that Asian soybean rust is a sporadic disease in the United States. To control this disease many fungicides are registered and used (Valent, 2017, MRD, 2013-2017). BEAD is unable to determine inpyrfluxam value in managing Asian soybean rust disease control without comparative efficacy data with registered alternatives.

SUGARBEET

Registrant Claim

Seed Treatment: According to the registrant, inpyrfluxam targets soil-borne fungi especially Rhizoctonia solani that causes seed decay and damping-off. For sugarbeet, standard base seed treatment for protection against soil-borne fungal pests is a combination of hymexazole and metalaxyl (Valent, 2017). Penthiopyrad, fluxapyroxad and sedaxane are also registered for treating sugarbeet seeds and can be added to the base seed treatment for disease control. Inpyrfluxam can be added to the standard base treatment for protection against this pest. The results of three experimental trial in North Dakota showed that sugarbeet seed treatment with inpyrfluxam+base seed treatment and penthiopyrad+base treatment produced 9 and 7 percent higher count per acre than untreated control, respectively. The results were not analyzed statistically. In another experimental trial in Idaho, inpyrfluxam+base seed treatment and penthiopyrad+base seed treatment produced 9 and 17 percent higher number of plants than the untreated control. The results were not analyzed statistically.

Post-Emergence Treatment: RRCR of sugarbeet is caused by R. solani during plant emergence. It can cause yield loss up to 50 percent (Haverson, 2008) and in recent years it has become more problematic (Kahn and Bolton, 2017). Fungicide seed treatment (as discussed above) is used to protect seeds from fungal . To control RRCR disease, azoxystrobin, pyraclostrobin and prothioconazole are registered and used (Valent, 2017). Azoxystrobin or pyroclostrobin is applied as in-furrow treatment to provide early season control of R. solani. Prothioconazole may be applied as post emergence treatment (Valent, 2017). The registrant claimed that the growers will benefit from using inpyrfluxam as it has different mode of action than the registered alternatives for controlling RRCR. It will also help in fungicide resistance management (Valent, 2017).

BEAD Assessment

Based on the submitted fungicide performance trials, BEAD agrees with the registrant that inpryfluxam was as effective as penthiopyrad in increasing sugarbeet plant per acre (Valent, 2017) when applied with base seed treatment consisting of hymexazole and metalaxyl. The other code 7 fungicides (fluxapyroxad and sedaxane) were not included in 8

the efficacy trials. Therefore, it is unclear if inpyrfluxam will outperform or will be as effective as fluxapyroxad and sedaxane in controlling the disease.

Sugarbeet RRCR is effectively controlled using registered alternatives (azoxystrobin, pyraclostrobin and prothioconazole) (Valent, 2017, MRD, 2013-2017). The registrant did not provide inpyrfluxam efficacy data in controlling RRTC. BEAD agrees that inpyrfluxam has a different mode of action than the registered alternatives and therefore it is likely to play a role in fungicide resistance management.

CONCLUSIONS

Inpyrfluxam is a new fungicide that belongs to SDHI fungicides belonging to code 7 (FRAC, 2018; Valent 2018). According to registrant submitted data, inpyrfluxam is effective in controlling various fungal diseases on apple, corn (field, pop and sweet), peanut, rice, soybean and sugarbeet. BEAD finds that inpyrfluxam’s benefits are obvious on soybean and sugarbeet crops only. On soybean, inpyrfluxam provides a new mode of action to control aerial blight disease and therefore it is likely to play a role in resistance management. Similarly, on sugarbeet inpyrfluxam provides a new mode of action for controlling RRCR and it is likely to play a role in disease control and resistance management. On other crops, inpryfluxam appears to be at par with registered fungicides in controlling various diseases and increasing crop yields.

REFERENCES

CDMS. 2018. Crop Data Management System. Accessed September 3, 20189. http://premier.cdms.net/webapls/FormsLogin.asp?/webapls/

Cools, HJ., Hawkins, NJ and Fraaije, BA. 2013. Constraints on the evolution of azole resistance in plant pathogenic fungi. Accessed on January 30, 2019. https://onlinelibrary.wiley.com/doi/full/10.1111/ppa.12128

EPA. 2019. Suggestions for Applicants on Information Considered When Evaluating Benefits of New Conventional Active Ingredients/Significant New Use Site Requests. Accessed January 2019. https://www.epa.gov/pesticide-registration/suggestions-applicants-information- considered-when-evaluating-benefits-new

FRAC. 2018. Fungicide Resistance Action Committee Code List: Fungicides Sorted by Mode of Action. http://www.frac.info/docs/default-source/publications/frac-code- list/frac_code_list_2018-final.pdf?sfvrsn=6144b9a_2. Accessed on April 11, 2017.

Gisi, U., Sierotzki, H., Cook, A and McCaffery, A. 2002. Mechanisms influencing the evolution of resistance to QoI inhibitor fungicides. Plant Management Science 58:859-867.

Groth, DE and Bond, JA. 2007. Effects of Cultivars and Fungicides on Rice Sheath Blight, Yield, and Quality. Plant Disease Vol. 91. No. 12:1647-1650. Accessed October 17, 2018. http://apsjournals.apsnet.org/doi/pdf/10.1094/PDIS-91-12-1647. 8

Haverson, R.M. 2008. Rhizoctonia Root and Crown Rot of Sugar Beet, G1841. University of Nebraska Extension. http://extensionpublications.unl.edu/assets/pdf/g1841.pdf. Accessed September 19, 2017.

Lunos, A.G. 2016. Geographic Distribution and Severity of Strobilurin Fungicide Resistance among Rhizoctonia Solani on Rice in Southwestern Louisiana. Thesis. Page 67. Louisiana State University. Accessed on October 26, 2018. http://digitalcommons.lsu.edu/cgi/viewcontent.cgi?article=4063&context=gradschool_the ses.

Market Research Data (MRD). 2013-2017. Data collected and sold by a private market research firm. Data collected on pesticide use for about 60 crops by annual surveys of agricultural users in the continental United States. Survey methodology provides statistically valid results, typically at the state level.

NASS (National Agricultural Statistics Service). 2014. 2012 Census of . Accessed October 18, 2019. https://www.agcensus.usda.gov/

PPLS. U.S. EPA Pesticide Product Label accessed September 13, 2019. https://www3.epa.gov/pesticides/chem_search/ppls/000352-00834-20140225.pdf

Valent. 2017. A public interest document supporting the registration of inpyrfluxam to control economically important diseases in Apple, canola, cereal grains, corn, legume vegetables, peanut, rice sorghum, soybean and sugarbeet. A package submitted by Valent U.S.A. LLC to USEPA in support of registration of inpyrfluxan in 2017. MRID 50312817.

Wamishe, Y., Cartwright, R and Lee, F. 2017. Management of Rice Sheath Blight and Blast in Arkansas. University of Arkansas Extension Accessed on October 26, 2018.. https://www.uaex.edu/farmranch/ crops-commercial-horticulture/docs/Sheath%20Blight%20and%20Blast.pdf.

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