Page 2 of 7

Background Cyantraniliprole is a second generation ryanodine receptor insecticide being jointly developed by DuPont and Syngenta. It is being reviewed as part of a global work share project. The crops proposed in the U.S. include berries, citrus, cotton, oilseeds, ornamentals, pome fruit, potatoes, stone fruit, tree nuts, turf, and various vegetables. Application methods include foliar spray, drip irrigation, soil drench and seed treatment. Metabolism studies were conducted on rice, cotton, tomato and lettuce as p rimary crops; lettuce, red beet, soybean and wheat as rotational crops; laying hens and lactating ruminants . In addition, soil and aquatic metabolism studies under aerobic and anaerobic conditions, aqueous photolysis and hydrolysis studies, and terrestrial field dissipation studies were conducted to understand the environmental fate of cyantraniliprole . Committee Recommendation Table 1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression Matrix Residues included in Risk Assessment 1 Residues included in Tolerance Expression Plants Primary Crop Cyantraniliprole Cyantraniliprole

Rotational Crop Cyantraniliprole Cyantraniliprole Processed Commodities Cyantraniliprole and IN - J9Z38 Cyantraniliprole Livestock Ruminant Cyantraniliprole , IN - N7B69, IN - MLA84, IN - MYX98 , and /or IN - J9Z38 2 Cyantraniliprole Poultry Cyantraniliprole Drinking Water Cyantraniliprole and the degradates listed below 3 Not Applicable 1 Cyantraniliprole is 3 - Bromo - 1 - (3 - chloro - 2 - pyridinyl) - N - [4 - cyano - 2 - methyl - 6 - [(methylamino)carbonyl]phenyl] - 1 H - pyrazole - 5 - carboxamide. The names and chemical structures of the metabolites can be found in A ppendix 1 . 2 Parent cyantraniliprole is recommended as residue of concer n in all commodities along with the metabolites that are at significant amount in the commodity under consideration. 3 IN - J9Z38, IN - NXX69, IN - QKV54, IN - RNU71, IN - JSE76, IN - JCZ38, IN - K5A78, IN - K5A77, IN - K5A79, and IN - PLT97. Summary of Briefing Material s Considered Cyantraniliprole is an anthranilic diamide insecticide which acts through unregulated activation of ryanodine receptor (RyR) channels leading to calcium depletion and impair ed regulation of muscle contraction. The major findings following repeated oral administration in rats, mice and dogs were changes in the liver, thyroid gland, and adrenal cortex. The thyroid toxicity observed was likely a result of increased hepatic enzyme activities and perturbation of the thyroid hormone homeostasis , and minor changes in the adrenal cortex were not considered biologically significant . Therefore , the primary mode of toxicity to mammals is hepatotoxicity. Cyantraniliprole was not observed to cause genotoxicity, neurotoxicit y or immunotoxicity in rats and/or mice . No increase in tumor incidence was observed in adequately conducted carcinogenicity studies in rats and mice. Acute oral toxicity and m utagenicity studies are available for several metabolites including IN - JSE76, IN - PLT97, IN - F6L99 and IN - N5M09 . While the acute studies did not indicate significant increases in toxicity for any of the metabolites, the primary mode of action for cyantraniliprole , liver toxicity, is n ot likely to manifest after a single exposure . However, in a 28 - day feeding study with IN - JSE76 in rats , noPage 3 of 7

adverse effects were observed up to the highest dose tested (20,000 ppm , equivalent to1445 mg/kg/day) . Although this is still considered a short - term study, 28 days is sufficient to indicate pote ntial hepatic injury. Therefore , assuming equal toxicity between parent and similarly structured metabolites/degradates is likely a conservative estimation. Metabolism studies were conducted with cyantraniliprole radio labeled in the cyano group or in the carbonyl adjacent to the pyrazole ring . The metabolism of cyantraniliprole applied to ri ce, lettuce, cotton and tomato were similar after foliar and soil applications ; cyantraniliprole w as the major residue in addition to the formation of many minor metabolites . Results in c r op field trials confirm parent as the predominant residue. In addition to parent cyantraniliprole, s everal residues have also been identified in processing studies. Nature of the residue in processing studies showed formation o f degradates IN - J9Z38, IN - N5M09, and IN - F6L99 under conditions of heat and/or hydrolysis. Magnitude of the residue studies showed formation of these degradates in certain processed commodities. For example, IN - J9Z38 was present in cooked spinach, orange oil, tomato paste, cotton seed oil, and cotton seed meal. Indeed, m ost of the cyantraniliprole was degraded to IN - J9Z38 in cooked spinach. IN - N5M09 and IN - F6L99 were each about 1 - 2 % of the IN - J9Z38 concen tration in cooked spinach. All three degradates were generated in apple sauce, with IN - J9Z38 approximating the concentration of cyantraniliprole and IN - N5M09 and IN - F6L99 each being < 10 - 20 % of the combined cyantraniliprole plus IN - J9Z38 concentration in the apple sauce . Degradates IN N5M09 and IN - F6L99 were <LOQ (<0.01 ppm each) in commodities from processing studies with tomato, orange, plum, cottonseed, grapes, and olives. In confined rotational studies , parent cyantraniliprole was the major residue pr esent in soybean, wheat grain, lettuce, and beet root . Some metabolites were found at levels greater than 10% of the TRR only in livestock feedstuffs. In feedstuff commodities including wheat forage, hay, and straw, parent and IN - J9Z38 accounted for the majority of the residues. In soybean foliage, parent, IN - JSE76 and IN - MLA84 accounted for the majority of the residues. In field rotational crop studies, low levels of parent and metabol ites were observed at the 30 - day plant back interval except for animal feeds. In hay, forage, and straw of several crops, in addition to cyantraniliprole, significant amounts of metabolites such as IN - JCZ38, IN - J9Z39 and IN MLA84 were also present. T hese metabolites are at significan t levels in feedstuff commodities only . Livestock metabolism studies were conducted on laying hen s and lactating ruminants. For hens, most of the dose was excreted as unchanged parent compound (68 - 77% TRR). R esidues in mus cle, fat, and skin with fat were <0.01 ppm. Finite residues were found in eggs and liver . Cyantraniliprole, IN - HGW87, IN - J9Z38, and IN - MLA84 were major residues in eggs. However, feeding studies conducted by dosing laying hens at levels of 3, 10 and 30 m g/kg for 28 days show significant levels of parent cyantraniliprole and metabolites IN - MYX98, IN - J9Z38, and /or IN - MLA84 in eggs, muscle, liver and skin (with fat) . For ruminants, cyantraniliprole was the major residue in milk, liver, kidney, muscle and fat. Also present in milk were 2 other maj or metabolites, IN - N7B69 and IN - MYX98 . Feeding studies conducted with lactating cow at levels of 3, 10, 30 and 100 mg/kg for 2 8 days show significant levels of parent cyantraniliprole, and metabolites IN - N7B69, IN - J9Z38, IN - MLA84 and/or IN - MYX98 in cream, skim mi lk, muscle, liver, kidney and fat.Page 4 of 7

Cyantraniliprole’s major routes of dissipation include alkaline - based hydrolysis (w ith DT 50 values of 0.86 days at pH 9, 31 days at pH 7, and 222 days at pH 4), photodegradation in aqueous and moist soil environments (with DT 50 values of 7.9 hours and 12.5 days, respectively), and aerobic and anaerobic biotransformation in terrestrial an d aquatic environments (with DT 50 values from 2.4 to 89 days). In terrestrial field studies, cyantraniliprole dissipated with DT 50 s ranging from 3.4 to 44 days. Cyantraniliprole appears not to volatilize and is characterized as being moderately mobile. S ome degradates are more mobile than the parent and some are less mobile than the parent. Based on laboratory studies, the major (≥10% of the applied) environmental degradates of cyantraniliprole include IN - J9Z38 ( hydrolysis and biotransformation in aerobi c and anaerobic soil and aquatic systems), IN - NXX69 ( aqueous phototransformation ), IN - QKV54 (moist soil phototransformation), IN - RNU71 (moist soil phototransformation), IN - JSE76 (aerobic soil biotransformation), IN - JCZ38 (aerobic soil biotransformation), a nd IN - K5A78 (aerobic soil biotransformation). IN - J9Z38 formed under both microbial mediated and abiotic processes. Major degradates that continued to increase over time to study termination in various fate studies include IN - J9Z38, IN - RNU71, IN - JSE76, IN JCZ38, and IN - K5A78. It should be noted that additional aerobic soil biotransformation studies were conducted with transformation products. Degradate half - lives ranged from 3.5 to 1800 days , depending on transformation product and soil type. In addition, IN - K5A77, IN - K5A79, and IN - PLT97 were also detected in terrestrial field dissipation studies. Post - meeting Note: Regarding TP (IN - NXX69), it is the opinion of the Canadian reviewer that it may be relevant for surface water modeling (although it is formed at pH 4 and perhaps pH 7 is more “environmentally relevant” but not for groundwater modeling since it is not a relevant pathway (not formed in soil). Rationale Parent cyantraniliprole was detected as a main residue in the metabolism studies, crop field trials and livestock feeding studies. Based on this , it is consider ed an appropriate marker for primary crops, rotational crops and livestock commodities and is recommended as the residue of concern (ROC) for tolerance enforcement. The followin g discussion is for the selection of the residue of concern for risk assessment purposes only . P rimary Crops : Metabolism studies show parent cyantraniliprole as a major residue in rice, lettuce, cotton and tomato, and IN - J9Z38 as a major residue in ri ce and lettuce. T he crop field trials show the presence of several metabolites at levels below the limit of quantitation or at significantly lower amounts than parent cyantraniliprole. T he ROCKS recommends inclusion of parent only for risk assessment pur poses. Rotational Crops: Parent cyantraniliprole was the main residue in all the commodities for human consumption. Other metabolites were present at similar or lower levels than parent cyantraniliprole in feedstuff commodities only . Since the metabolites will not be significant contributors to the overall livestock dietary burden inclusion of the metabolites in the residue of concern will not significantly affect the dietary risk assessment. The refore, the ROCKS recommends including only the parent cyantraniliprole as the residue of concern for rotational crops .Page 5 of 7

Processed Commodities: Although degradates IN - J9Z38, IN - N5M09, and IN - F6L99 were formed under conditions of heat and/or hydrolysis , in general, only IN - J9Z38 was observed at significant concentrations in a few processed commodities (e.g. cooked spinach , apple sauce ). IN - N5M09 and IN - F6L99 were found at low levels in apple sauce and cooked spinach, but were absent (<LOQ) in a variety of other processed commodities. B ased on this the ROCKS recommends parent cyantraniliprole and IN - J9Z38 as ROC . Livestock: Feeding studies show that parent cyantraniliprole, IN - N7B69, IN - MLA84, IN MYX98, and/or IN - J9Z38 are likely to be present in significant amount in some commodities. These metabolites are assumed to have similar toxicity to parent cyantraniliprole. The ROCKS recommends inclusion of parent cyantraniliprole for risk assessment purposes in all the commodities. In addition, inclusion of the metabolites that are significa nt levels in specific commodities ( e.g. IN - N7B69, IN - MYX98 in milk ; IN - MYX98 in muscle of poultry; IN - MLA84 and IN - MYX98 in liver; IN - MLA84, IN - N7B69, and IN - MYX98 in kidney ) is recommended and should be considered on a matrix - specific basis . Water : Cyan traniliprole is likely to degrade extensively in the environment through several degradation routes to form IN - J9Z38, IN - NXX69, IN - QKV54, IN - RNU71, IN - JSE76, IN JCZ38, IN - K5A78, IN - K5A77, IN - K5A79, and IN - PLT97. These degradates were either major degradat es in relevant laboratory studies, formed in the field, or both. In the absence of toxicity data and similar analogs, these degradates are considered no more toxic than the parent compound and a total residue approach is recommended for risk assessment pu rposes. Therefore, the recommended ROC in water include cyantraniliprole, IN - J9Z38, IN - NXX69, IN QKV54, IN - RNU71, IN - JSE76, IN - JCZ38, IN - K5A78, IN - K5A77, IN - K5A79, and IN - PLT97. R ecommended Tolerance Expression The ROCKS recommends the following language for the tolerance expression for p lant and livestock commodities: Tolerances are established for residues of the insecticide cyantraniliprole , including its metabolites and degradates, in or on the commodities listed below. Compliance with the t olerance levels specified below is to be determined by measuring only cyantraniliprole (3 - b romo - 1 - (3 - chloro - 2 - pyridinyl) - N - [4 - cyano - 2 - methyl - 6 - [(methylamino)carbonyl]phenyl] - 1 H - pyrazole - 5 - carboxamide) , in or on the commodity.Page 6 of 7

Appendix 1 . Cyantraniliprole and it major metabolites/ degradates. Common Name Chemical Name Structure Cyantraniliprole SYN545377 DPX - HGW86 CAS Name: 3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - N - [4 - cyano - 2 - methyl - 6 [(methylamino)carbonyl]phenyl] - 1 H - pyrazole 5 - carboxamide

IN - MLA84 CAS Name: 2 - [3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - 1 H - pyrazol - 5 - yl] - 1,4 - dihydro - 8 - methyl - 4 - oxo - 6 - quinazolinecarbonitrile

IN - N7B69 CAS Name: 3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - N

- [4 - cyano - 2 - (hydroxymethyl) - 6 - [(methylamino)carbonyl]phenyl] - 1 H - pyrazole 5 - carbonitrile

IN - MYX98 CAS Name: 3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - N

- [4 - cyano - 2 - [[(hydroxymethyl) amino]carbonyl] - 6 - [(methylphenyl] - 1 H pyrazole - 5 - carboxamide

IN - J9Z38 CAS Name: 2 - [3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - 1 H - pyrazol - 5 - yl] - 3,4 - dihydro - 3,8 - dimethyl - 4 - oxo - 6 - quinazolinecarbonitrile IN - NXX69 CAS Name: 2 - [[(4Z) - 2 - bromo - 4H pyrazolo[1,5 - d]pyrido[3,2 - b][1,4]oxazin - 4 - ylidene]amino] - 5 - cyano - N,3 - dimethylbenzamide IN - QKV54 CAS Name: 2 - (3 - Bromo - 1H - pyrazol - 5 - yl) - 1,4 -

dihydro - 3,8 - dimethyl - 4 - oxo - 6 - quinazolinecarbonitrilePage 7 of 7

Appendix 1 . Cyantraniliprole and it major metabolites/ degradates. Common Name Chemical Name Structure IN - RNU71 CAS Name : 2 - (2 - Bromo - 4 - oxopyrazolo[1,5 -

a]pyrido[3,2 - e]pyrazin - 5(4H) - yl) - 5 - cyano - N,3 - dimethylbenzamide

IN - JSE76 CAS Name : 4 - [[[3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - 1H - pyrazol - 5 - yl]carbonyl]amino] - 3 - methyl - 5 - [(methylamino)carbonyl]benzoic acid IN - JCZ38 CAS Name : 4 - [[[3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - 1H - pyrazol - 5 - yl]carbonyl]amino] - N'3',5 - dimethyl - 1,3 - benzenedicarboxamide

IN - K5A78 CAS Name : 2 - [3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - 1H - pyrazol - 5 - yl] - 3,4 - dihydro - 3,8 - dimethyl - 4 - oxo - 6 - quinazolinecarboxylic acid IN - K5A77 CAS Name : 2 - [3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - 1H - pyrazol - 5 - yl] - 3,4 - dihydro - 3,8 - dimethyl - 4 - oxo - 6 - quinazolinecarboxamide

IN - K5A79 CAS Name : 3 - (Aminocarbonyl) - 4 - [[[3 -

bromo - 1 - (3 - chloro - 2 - pyridinyl) - 1H - pyrazol - 5 - yl]carbonyl]amino] - 5 - methylbenzoic acid

IN - PLT97 CAS Name: 2 - [3 - Bromo - 1 - (3 - chloro - 2 -

pyridinyl) - 1 H - pyrazol - 5 - yl] - 1,4 - dihydro - 8 - methyl - 4 - oxo - 6 - quinazolinecarboxylic acid