Page 1 of 33 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 **OFFICE OF CHEMICA**  **L SA FETY**  **AND POLLUTION PREVENTION**  **MEMORANDUM Date**  **: December**  **9 ,**  **2013 SUBJECT:**  **Chlorantraniliprole:** Human Health Risk Assessment for Proposed Uses on

Green Onion Subgroup 3 - 07b, and Peanut; for the Requests to Update the Crop Groups of Stone Fruit, Tree Nut, and Spices; to Shorten the Pre - Harvest Intervals for Papaya, Passionfruit, and May haw ; and Evaluation of Condition of Registration Data on Rice, Coffee, Strawberry , and Tropical Fruits. **PC Code:** 090100 **DP Barcode s**  **:** D410513, D412173, D412170, D412171, D412169 **Decision No s**  **.:** 476038; 477960; 477964; 477967; 477972; 477962 ; 477952; 477965; 477970; 477963; 477954; 477966; 477971; 417413 **Registration No s**  **. :**  352 - 728; 352 - 729; 352 - 730; 352 - 820; 352 - 841; 352 - 838; 352 - 844 **Petition No s**  **.:** 3E8170; 3F8158 **Regulatory Action:** Section 3 Registration **Risk A**  **ss essment Typ**  **e :**  Single Chemical, Aggregate **Case No.:** NA **T XR No.:**  **NA CAS No.:**  500008 - 45 - 7 **MRID No.: NA**  **40 CFR:** 180.628 **FROM:** Kristin Rury , Risk Assessor

Steve Funk, Senior Chemist Minerva Mercado, Toxicologist Risk Assessment Branch III Health Effects Division (7509P) **THROUGH:** Christine Olinger , Branch Chief

Risk Assessment Branch III Health Effects Division (7509P) **TO:** Venus Eagle/Jennifer Urbanski, RM 01

Insecticide - Rodenticide Branch Registration Division (RD; 7505P) And Barbara Madden/Laura Nollen, RM 05 Risk Integration Minor Use, and Emergency Response Branch Registration Division (RD; 7505P)Page 2 of 33

**1.0 Executive Summary**  ................................ ................................ ................................ ........... 3 **2.0 Regulatory Conclusions and Recommendations**  ................................ ............................. 5 **2.1 Data Deficiencies/Conditions of Registration**  ................................ .............................. 5 **2.2 Tolerance Considerations**  ................................ ................................ .............................. 5 **2.2.1 Enforcement Analytical Method**  ................................ ................................ ............... 5 **2.2.2 International Harmonization**  ................................ ................................ ..................... 6 **2.2.3 Recommended Tolerances**  ................................ ................................ ......................... 7 **2.2.4 Revisions to Petitioned**  **- For Tolerances**  ................................ ................................ .... 7 **2.3 Label Recommendations**  ................................ ................................ ................................ 8 **3.0 Introduction**  ................................ ................................ ................................ ........................ 8 **3.1 Chemical Identity**  ................................ ................................ ................................ ........... 9 **3.2 Physical/Chemical Characteristics**  ................................ ................................ ............... 9 **3.3 Pesticide Use Pattern**  ................................ ................................ ................................ ...... 9 **3.4 Anticipated Exposure Pathways**  ................................ ................................ ................. 12 **3.5 Consideration of Environmental Justice**  ................................ ................................ .... 12 **4.0 Hazard Characterization and Dose**  **- Response Assessment**  ................................ .......... 13 **4.1 Summary of Toxicological Effects**  ................................ ................................ .............. 13 **4.2 Safety factor for Infants and Children (FQPA Safety Factor)**  ................................ 14 **4.2.1 Completeness of the Toxicology Database**  ................................ .............................. 14 **4.2.2 Evidence of Neurotoxicity**  ................................ ................................ ........................ 14 **4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Anim**  **al** ........ 15 **4.2.4 Residual Uncertainty in the Exposure Database**  ................................ ................... 15 **4.3 Toxicity Endpoint and Point of Departure Selections**  ................................ .............. 15 **5.0 Dietary Exposure and Risk Assessment**  ................................ ................................ ......... 16 **5.1 Residues of Concern Summary and Rationale**  ................................ .......................... 16 **5.2 Food Residue Profile**  ................................ ................................ ................................ .... 17 **5.3 Water Residue Profile**  ................................ ................................ ................................ .. 18 **5. 4**  **Dietary Risk Assessment** ................................ ................................ .............................. 18 **5.4.1 Description of Residue Data Used in Dietary Assessment**  ................................ .... 18 **5.4.2 Acute Dietary Risk Assessment**  ................................ ................................ ............... 19 **5.4.3 Chronic Dietary Risk Assessment**  ................................ ................................ ........... 19 **5.4.4 Cancer Dietary Risk Assessment**  ................................ ................................ ............. 19 **5.4.5 Summary Table**  ................................ ................................ ................................ ......... 19 **6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterization**  ............................. 19 **6.1 Residential Handler Exposure**  ................................ ................................ .................... 19 **6.2 Post**  **- Application Exposure**  ................................ ................................ .......................... 20 **6.3 Residential Bystander Post**  **- Application Inhalation Exposure**  ................................ 20 **6.4 Spray Drift**  ................................ ................................ ................................ .................... 20 **7.0 Aggregate Exposure/Risk Characterization**  ................................ ................................ .. 20 **8.0 Cumulative Exposure/Risk Characterization**  ................................ ............................... 21 **9.0 Occupational Exposure/Risk Characterization**  ................................ ............................ 21 **10.0 References**  ................................ ................................ ................................ ......................... 21 **Appendix A. Toxicology Profile** ................................ ................................ ................................ 23 **A.1 Toxicology Data Requirements**  ................................ ................................ ................... 23 **A.2 Toxicity Profiles**  ................................ ................................ ................................ ............ 24 **Appendix B. Physical/Chemical Properties** ................................ ................................ ............. 30Page 3 of 33

**1.0 Executive Summary**  Chlorantraniliprole is an anthranilic diamide insecticide that belongs to a class of compounds that acts on the ryanodine receptor (RyR) . It was developed and regis tered by E.I. d u Pont de Nemours and Company (DuPont) to control lepidopteran pests and insects primarily via interruption of normal muscle contraction pathway s, leading to paral ys is and eventual death. However, the relative absence of mammalian hazard fol lowing chlorantraniliprole exposure may be due in part to chlorantranilprole’s selectivity for insect RyR over mammalian counterparts . There are five proposed chlorantraniliprole registration actions evaluated in this risk assessment: 1. **D410513** - E.I. du Pont de Nemours and Company (DuPont) has requested a Section 3 registration and tolerances of chlorantraniliprole on peanuts . 2. **D412169**

– The Interregional Research Project No. 4 (IR - 4) of Rutgers University has requested crop group conversions for existin g tolerances on the stone fruit and tree nut crop groups to correspond with the crop group commodities update in 2012. 3. **D412173**

– The IR - 4 has requested to shorten the existing pre - harvest interval s (PHI s ) for papaya, passionfruit, and may haw . Additional ly , IR - 4 has requested to delete the existing separate may

haw tolerance because may haw will be supported by the existing pome fruit tolerance ( crop group 11 - 10). 4. **D412170**

–The IR - 4 requested to add greenhouse use directions to the existing chlorantranilip role labels for fruiting vegetables and cucurbits. The existing cucumber and tomato data will support the addition of greenhouse use directions on the labels for greenhouse tomato, pepper, and cucumber; there is no request for tolerances. 5. **D412717 –**  The IR - 4 has requested chlorantraniliprole use and tolerances on green onion ( crop subgroup 3 - 07B) and requested to raise the existing tolerance for spice subgroup 19B based on data on green onion and dill. Concomitant with these petitions, condition of reg istration field trial data were submitted for rice, coffee, and strawberry ; these data confirm the existing tolerances. Additionally, a study submitted as confirmatory data for crayfish supports lowering the current crayfish tolerance. Condition of registration residue decline data on cherry , papaya, and l yc hee were also submitted to support existing tolerances for certain tropical fruits and to propose lowering the PHIs from 10 day s to 1 day , with a tolerance increase of 2 ppm to 4 ppm for papaya and pass ionfruit. The new data for dried onions combined with previous data for alfalfa hay translated to dried basil support retention of the 90 ppm tolerance for herb subgroup 19A. Permanent tolerances are currentl y established in 40 CFR §180.628 for chlorantraniliprole in/on a variety of commodities . Use Profile The end - use product ( EP) formulations relevant to these request s are a 5 % active ingredient (ai) suspension concentrate (SC) , Prevathon ® Insect Control (0.43 lb ai per gallon, or 0.053 kg ai/l) , EPA Reg. No. 352 - 844 ; a 18.4% ai SC , Coragen ® In sect Control (1.67 lb ai/gallon or 0.200 kg ai/l) , EPA Reg. No. 352 - 729 ; a 35.0% ai water dispersible granular (WDG) , Altacor® (35 lb ai/100 lb) EPA Reg. No. 352 - 730 ; and a 50% ai Flowable Concentrate (FC) , Dermacor® X - 100Page 4 of 33

Seed Treatment (FS, 5.210 lb ai/gal ), EPA Reg No. 352 - 820) . Chlorantraniliprole may be applied via drip irrigation, ground, handheld , seed treatment, and aerial application methods. Chlorantraniliprole is also registered for use in reside ntial settings on turf, landscape ornamentals , and interio rscapes. C hlorantraniliprole may also be used on golf courses and sod farms. Exposure Profile There is a potential for occupational short - and intermediate - term inhalation and dermal exposure to chlorantraniliprole during mixing, loading, application, and post - application activities. There is potential for short - term exposure from the registered residential uses on turf, golf courses landscape ornamentals, and interiorscapes. There is also expo sure expected through food and drinking water from the proposed and registered uses of chlorantraniliprole. Hazard Characterization There is sufficient toxicology information for selecting doses and endpoints for chlorantraniliprole risk assessment. Ins hort - term studies, the most consistent effects are those associated with non - adverse induction of liver enzy mes and subsequent increase in liver weights. Increased microvesiculation of the adrenal cortex was observed in several rat studies ; however detailed histopathology

and a special adrenal function study found no adverse adrenal effects in the rat . There was onl y one animal toxicity study (18 - month carcinogenicity study in mice) in the database that produced adverse effect s following chlorantraniliprole exposure. Chlorantraniliprole is not considered developmentally toxic, genotoxic, neurotoxic, immunotoxic, or carcinogenic. A subchronic inhalation toxicity study is not required for chlorantraniliprole at this time. Chlorantraniliprole is cl assified as Acute Toxicity Category IV for acute oral, dermal, and inhalation toxicity ; acute eye irritation ; and primary skin irritation. C hlorantraniliprole is not a dermal sensitizer. Based on the available hazard and exposure data, the Food Quality P rotection Act (FQPA) Safety Factor (SF) is reduced to 1x for all population subgroups and exposure scenarios. Dietary Risk Estimates (Food and water) An acute dietary

risk assessment was not performed because there was no acute hazard attributable to a single dose identified in the chlorantraniliprole toxicity database. The chronic dietary

(food and drinking water) exposure assessment is considered conservative and assumed tolerance - level residues and that 100% of the proposed and registered crop s were treated with chlorantraniliprole ( 100 %CT). Where processing data indicated a reduction (or no increase) in residue upon processing, the residue level of the raw agricultural commodity (RAC) was used without reduction. Where processing data indicated an increase in residue in the processed commodity , a tolerance was established and used, e.g., raisins from grapes. Where adequate processing data did not exist, default concentration factors w ere used if available. Estimated drinking water concentratio ns (EDWCs) from ground water from the Environmental Fate and Effects Division ( EFED ) were also included. The results of the chronic anal ys is indicate that the chronic dietary (food and drinking water) risk estimates utilized 2.3% of the chronic population adjusted dose (cPAD) for the general U.S. population and utilized 6.7% of the cPAD for children 1 - 2 years old, the most highly exposed population subgroup. Therefore, the chronic dietary

risk is not of concern (i.e., <100% of the cPAD).Page 5 of 33

Aggregate Risk Short - and intermediate - term aggregate risk assessments were not performed because there was n o hazard identified over short - or intermediate - term duration s . Therefore, the aggregate risk assessment for chlorantraniliprole only includes chronic exposures to residues in food and drinking water. The chronic dietary risk assessments for the U.S. population and all population subgroups are not of concern to HED (<100% cPAD). Occupational Risk Although there is potential for occupational handler and post - application exposure, the chlorantraniliprole toxicology database indicates there is no s ys temic hazard associated with short - and intermediate - term dermal and inhalation exposure, and therefore, no quantitative occupational exposure and risk assessment was conducted. Environmental Justice Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environment al Justice in Minority Populations and L ow - Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ). **2.0 Regulatory Conclusions and Recommendations**  HED has examined the residue chemistry , toxicity , and exposure database s for chlorantraniliprole and concluded that, provided a revised Section F is submitted, there are no deficiencies that would preclude granting a Section 3 registration on peanuts and green on ion subgroup 3 - 07B ; adding the greenhouse use directions for fruiting vegetables and cucurbits; and granting the requested crop group conversions . A crayfish tolerance of 8 ppm was previousl y established based on a fish bioconcentration study and the estimated residues in water, s ediment, and rice straw . The present crayfish study showed no residues (<0.01 ppm) at various sampling intervals from the use of chlorantraniliprole as a seed treatment on rice. This refl ects the actual use pattern. Therefore, a tolerance of 0.01 ppm is more appropriate and a modified Section F is required. The specific tolerance recommendations are discussed in Section 2.2.3 . **2.1 Data Deficiencies**  **/Conditions of Registration** There are no data deficiencies associated with the proposed uses of chlorantraniliprole. **2.2 Tolerance Considerations**  **2.2.1 Enforcement Analytical Method**  An adequate enforcement method (liquid chromatography/tandem mass spectrometry (L C/MS/MS), DuPont - 11374) is available for the determination of chlorantraniliprole residues in/on plant commodities. The limit of quantitation (LOQ) is reported at 0.01 ppm for parentPage 6 of 33

chlorantraniliprole. The method for the determination of chlorantraniliprole and its metabolites i n processed commodities is a L C/MS/MS method, DuPont - 14314, which is a slightly modified version of DuPont - 11374. These methods have been accepted by the Anal ytical Chemistry Branch (ACB)/Biological and Economical Anal ys is Division (BEAD; C . Stafford, D34 0358 , 02 / 0 6/20 0 8). An adequate enforcement method (L C/MS/MS) is available for the determination of residues of chlorantraniliprole and its metabolites in/on animal commodities. Atmospheric p ressure c hemical i onization (APCI) MS/MS detection operated in the positive ion mode is used . The LOQ is reported at 0.010 pp m for the parent and each of the metabolites. The method has been accepted b y ACB/BEAD (C. Stafford, D 340 358 , 02 / 0 6/20 0 8). **2.2.2 International Harmonization**  Residue definitions are harmonized among the US, Canada, and Codex, with the common definition chlorantraniliprole. The existing US tolerance for the tree nut group is 0.04 ppm, whereas the tolerance in both Canada and Codex is 0.02 mg/kg. The US tolerance is based upon the evaluation of field trial data for pecans and almonds with the use of the North American Free Trade Agreement (NAFTA) statistical spreadsheet (N. Tsaur, D357727, 03/03/2009). The data were reevaluated using the Organization for Economic Cooperation and Development (OECD) tolerance calculation procedures . The new tolerance estimate is 0.02 ppm. The refore, the tolerance for tree nuts, including pistachio, is lowered to 0.02 ppm, and harmonization with Canada and Codex is achieved. The existing US tolerance for the pome fruit group is 1.2 ppm. The Codex maximum residue limit ( MRL) for pome fruit is 0.4 ppm, and the Canada MRL for various pome fruits (apple, pear, may haw, and quince) is 0.4 ppm. The original US tolerance for pome fruits was 0.3 ppm, but it was adjusted upwards to 1.2 ppm to accommodate the use of adjuvants and a shortened PHI(D. Rat e, D361791, 01/08/2010). Therefore, the 1.2 ppm value cannot be lowered to harmonize with Codex and/or Canada. The existing US tolerance for the stone fruit group (except cherry , chickasaw plum, and damson plum) is 4.0 ppm. The Codex MRLfor stone fruit s is 1 mg/kg and the Canada MRL for various stone fruits (apricot, nectarine, peach, plum, plumcots, and cherries) is 2.5 mg/kg. The original US tolerance for stone fruits was 1.0 ppm, but it was adjusted upwards to 4.0 ppm to accommodate the use of adjuv ants and a shortened PHI(D. Rate, D361791, 01/08/2010). Therefore, the 4.0 ppm value cannot be lowered to harmonize with Codex and/or Canada. Codex has not established MRL s for passionfruit, papaya, peanuts, green onions, herbs, or spices. Therefore, there is no harmonization issue with Codex. Canada does not have MRL s for these same commodities, with the exception of green onions and peanuts. Canada and the US are conducting a joint review for green onions and peanuts and will work to harmonize the M RL s.Page 7 of 33

**2.2.3 Recommended Tolerances**  The current tolerance definition is found at 40CFR§180.628. Compliance with the tolerance is based on measuring onl y chlorantraniliprole for both plant and animal commodities. **Table 2.2.**  **3 . Tolerance Summary for**  **Chlorantraniliprole Comm**  **odity Established**  **Tolerance (ppm)**  **Proposed**

**Tolerance (ppm) HED**  **- Recommended**  **Tolerance (ppm) Comments**  **( correct commodity definition**  **)** Papaya 2.0 4.0 4.0 Passionfruit 2.0 4.0 4.0 Peanut, nutmeat - 0.06 0.06 Peanut, hay 0.20 (exp 04/10/14) 90 90 Translation from alfalfa hay Onion, green, subgroup 3 - 07B - 3 .0 3.0 Spice subgroup 19B 14 1 40 90 Nut, tree, group 14 - 12 0.04 - 0.02 Crop group conversion. International harmonization. Nut, tree, group 14 0.04 - Remove Replaced by crop group 14 - 12 Pistachio 0.04 - Remove Replaced by crop group 14 - 12 Fruit, pome, group 11 - 10 1.2 - 1.2 Crop group conversion Fruit, pome, group 11, except mayha w 1.2 - Remove Replaced by crop group 11 - 10 May ha w 0.6 - Remove Replaced by crop group 11 - 10 Fruit, stone group 12 - 12, except cherry, Chickasa w plum, and damson plum 4.0 - 4.0 Crop group conversion Fruit, stone group 12, except cherry, Chickasa w plum, and damson plum 4.0 - Remove Replaced by crop group 12 - 12 Crayfish 8.0 - 0.01 Onion, green 0.20 (exp 04/10/14) - Remove Replaced by Onion, green, subgroup 3 - 07B Onion, welsh 0.20 (exp 04/10/14) - Remove Replaced by Onion, green, subgroup 3 - 07B Shallots, fresh leaves 0.20 (exp 04/10/14) - Remove Replaced by Onion, green, subgroup 3 - 07B Leek 0.20 (exp 04/10/14) - Remove Replaced by Onion, green, subgroup 3 - 07B 1 A tolerance of 14 ppm was recommended (D361791, D. Rate, 01/08/2010), but is not listed in 40CFR§180.628 . This was based on the translation of alfalfa seed data, with adjustments for adjuvant use (2x) and application rate (2x). **2.2.4 Revisions to Petitioned**  **- For Tolerances**  The petitioned tolerances are the same as the recommended tolerances, except for spice subgroup 19B , crayfish , and increased /decreased tolerances for the crop group conversions due to international harmonization .Page 8 of 33

Residue data on dill seed was presented in support of a spice subgroup 19B tolerance. HED had previously

recommended for a spice subgroup 19B tolerance of 14 ppm. The petitioner requested 40 ppm, but evaluation of the dill seed data indicates that 90 ppm is appropriate. Condition of registration data on field trial residue decline for cherry , papaya, and leechee support existing tolerances for certain tropical fruits and al low for lowering of the PHIs from 10 day s to 1 day , with an increase in tolerance from 2 ppm to 4 ppm, for papaya and passionfruit. A crayfish tolerance of 8 ppm was previousl y established based on a fish bioconcentration study and the estimated residues in water, s ediment, and rice straw . The present crayfish study showed no residues (<0.01 ppm) at various sampling intervals from the use of chlorantraniliprole as a seed treatment on rice. This reflects the actual use pattern. A tolerance of 0.01 ppm is a ppropriate. A modified Section F is required. A crop group conversion for tree nut group 14 to tree nut group 14 - 2 was requested. This is acceptable, but the tolerance will be changed from 0.04 ppm to 0.02 ppm to harmonize with Canada and Codex. The registrant must submit a revised Section F requesting tolerances of 90 ppm and 0.01 ppm for the spice subgroup 19B and crayfish, respectively . **2.3 Label Recommendations**  There are no label recommendations for this petition. **3.0 In**  **troduction** The ai, chl orantraniliprole, is an anthranilic diamide insecticide that belongs to a class of compounds that acts on the RyR . It was developed and registered by E.I. du Pont de Nemours and Company

(DuPont) to control lepidopteran pests and insects primarily via interruption of normal muscle contraction pathway s, leading to paraly sis and eventual death.Page 9 of 33

**3.1 Chemical Identity**  **Table 3.1. Chlorantraniliprole Nom**  **enclature.** Chemical structure

Common name Chlorantraniliprole Com pany experimental name DPX - E2Y45 IUPAC name 3 - bromo - 4 ′ - chloro - 1 - (3 - chloro - 2 -py ridyl) - 2 ′ - methyl - 6 ′ - (methylcarbamoyl)pyrazole - 5 - carboxanilide CAS name 3 - b romo -N - [4 - chloro - 2 - methyl - 6 - [(methylamino)carbonyl]phenyl] - 1 - (3 - chloro - 2 - p yridinyl) - 1 H

-py razole - 5 - carboxamide CAS registry number 500008 - 45 - 7 End -use product (EP) DuPontTM Altacor® WD G (35%; EPA Reg. No. 352 - 730) DuPontTM Coragen® SC Insect Control ( 1.67 lb ai/gal; EPA Reg. No. 352 - 729) DuPontTM Prevathon® Insect Control ( 0.43 lb ai/gal; EPA Reg No. 352 - 844 ) DuPontTM Dermacor® X - 100 Seed Treatment (FS, 5.210 lb ai/gal; EPA Reg No. 352 - 820) **3.2 Physical/Chemical Characteristics**  The phy sical/chemical properties of chlorantraniliprole are summarized in Appendix B. Based on the low vapor pressure ( 6.3 x 10 - 12 Pa at 20 o C ) and KOW (~3 at pH ranges 4 to 9), chlorantraniliprole is not expected to volatilize , pass lipid barriers (consistent with dermal absorption findings in mammals) , or bioaccumulate. Environmental fate data indicate chlorantraniliprole is persistent and mobile in t errestrial and aquatic environments. Major routes of chlorantraniliprole dissipation are expected to be alkaline - catal yz ed h ydrolysis, photodegradation in water, leaching, and runoff. **3.3 Pesticide Use Pattern**  For the proposed Section 3 registrations addressed herein there are four EPs , two SCs , one FC, and one WDG . The proposed changes will also apply to the technical product label (EPA Reg. No. 352 - 728). Proposed labels have been provided for a 5% ai SC , Pre vathon ® Insect Control (0.43 lb ai per gallon, or 0.053 kg ai/l) EPA Reg. No. 352 - 844 ; a 18.4% ai SC , Coragen ® Insect Control (1.67 lb ai/gallon or 0.200 kg ai/l) EPA Reg. No. 352 - 729 ; a 35% ai WDG , Altacor® (35 lb ai/100 lb) EPA Reg. No. 352 - 730 ; and a 5 0% ai Flowable Concentrate (FC) Dermacor® X - 100 Seed Treatment (FS, 5.210 lb ai/gal ), EPA Reg No. 352 - 820) . Changes to the Altacor® label involve only

crop conversions , and changes to Dermacor® only involves the conditional data related to seed treatment use on rice . The WDG formulation is not proposed for use on cereal grains. The summary of the relevant proposed uses is presented in Table 3 .3 . **N N**  **N N**  **H O**  **Cl Br**  **N H**  **O Cl** Page 10 of 33

**Table 3.3. Summ ary of Proposed** **/ Relevant**  **Existing Chlorantraniliprole Use Directions**  Applic. Timing, Ty

pe, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Season Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations Proposed Use: Peanut Foliar (ground; aerial) 18.4% SC

1.67 lb ai/gal Coragen [ 352 - 729 ] 0.045

–

0.065 4 0.2 (from all

chlorantranili prole sources) 1 Minimum interval between treatments is 3 days. Foliar (ground; aerial) 5% SC

0.43 lb ai/gal Prevathon [ 352 - 844 ] 0.047 -

0.067 Proposed Use: Bulb Vegetables (including green onion subgroup) Foliar (ground; aerial) 18.4% SC

1.67 lb ai/gal Coragen [ 352 - 729 ] 0.045

–

0.065 4 0.2 per crop

0.6 per year (from all chloroantranili

-prole sources) 1 Minimum interval between treatments is 4 days. Proposed Use: Greenhouse Cucumbers, Greenhouse Peppers, Greenhouse Tomatoes

Foliar 18.4% SC

1.67 lb ai/gal Coragen [ 352 - 729 ] 0.031

tomato 0.045 pepper, cucumber 3 (per

crop cycle) 0.134 per crop

cycle 1 Minimum interval between treatments is 7 days. Mix 1.6 fl oz per 100 gal spray volume (0.0209 lb ai/100 gal) Maximum application is 150 gal spray solution per acre for tomato and 214 gal spray solution per acre for cucumber and pepper. Updated Use: Tropical Fruits (Papaya, Passionfruit, Lychee ) 1 , 2

Foliar 35.0%

WDG Altacor [ 352 - 730 ] 0.066 -

0.099 3 0.2 (from all chloroantranil iprole sources) 1 2

10 (acero la, jaboti caba, and lychee) Minimum interval

between treatments is 7 days. Do not apply dilute solutions of more than 200 gal water per acre. Do not apply less than 30 gal water per acre . Updated Use: Lo w growing berry (subgroup 13 - 07G ) 1 Foliar 35.0%

WDG Altacor [ 352 - 730 ] 0.066 -

0.099 3 0.2 (from all chloroantranil prole sources) 1 Minimum interval between treatments is 7 days. Do not apply dilutePage 11 of 33

**Table 3.3. Summ ary of Proposed** **/ Relevant**  **Existing Chlorantraniliprole Use Directions**  Applic. Timing, Ty

pe, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Season Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations solutions of more than 200 gal water per acre. Do not apply less than 30 gal water per acre. Do not apply to straw berry or cranberry.

Foliar 18.4% SC

1.67 lb ai/gal Coragen [ 352 - 729 ] 0.045 -

0.065 4 0.2 per crop (from all chloroantranili

-prole sources) 0.4 per year (from all chloroantranili

-prole sources) 1 Minimum interval between treatments is 7 days. Updated Use: Rice 1

Seed treatment 50% FS

5.21 lb ai/gal Dermacor [ 352 - 820 ] 0.084 1 N/S N/S Do not use DERMACOR® X - 100 treated rice field for the aquaculture of edible fish or Crustacea (including crawfish) during the rice production cycle (planting through harvest). Updated Use: Coffee 1

Foliar 35.0%

WDG Altacor [ 352 - 730 ] 0.066 -

0.099 3 0.2 (from all

chloroantranili

-prole sources) 7 Minimum interval between treatments is 14days. Do not apply dilute solutions of more than 200 gal water per acre. Do not apply less than 30 gal water per acre. Updated Use: Herb Subgroup 19A 1

Foliar 18.4% SC

1.67 lb ai/gal Coragen [ 352 - 729 ] 0.045

–

0.065 4 0.2 per crop (from all chloroantranili

-prole sources) 0.8 per year (from all chloroantranili

-prole sources) 1 Minimum interval between treatments is 3 days. Updated Use: Spices Subgroup 19B 1 Foliar 18.4% SC 0.045

– 4 0.2 per crop 1 Minimum intervalPage 12 of 33

**Table 3.3. Summ ary of Proposed** **/ Relevant**  **Existing Chlorantraniliprole Use Directions**  Applic. Timing, Ty

pe, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Season Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations 1.67 lb ai/gal Coragen [ 352 - 729 ] 0.065 (from all chloroantranil iprole sources) 0.8 per year (from all chloroantranil iprole sources) between treatments is 3 days.

1 Uses associated with condition of registration data evaluated in association with the Section 3 and crop group conversion requests. 2 The PHI for papaya and passionfruit has been reduced from 10 days to 1 day. **3.4 Anticipated Exposure Pathways**  Humans may

be exposed to chlorantraniliprole in food and drinking water, since chlorantraniliprole may

be applied directly

to growing crops and application may result in chlorantraniliprole reaching surface and ground water sources of drinking water. There are registered residential uses of chlorantraniliprole, so there is likely to be exposure in residential or non - occupational settings. In an occupational setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is a potential for post - application exposure for workers re - entering treated fields. This risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of chlorantraniliprole, but also considers the existing uses as well, particularl y for the dietary assessment. **3.5 Consideration of Environmental Justice**  Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and L o w - Income Populations," http://www.epa.gov/environmentaljustice/resources/policy /exec_order_12898.pdf

. As a part of every pesticide risk assessment, O PP considers a large variety of consumer subgroups according to well - established procedures. In line with OPP policy , HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consump tion, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the U.S. Department of Agriculture’s National Health and Nutrition Examination Survey , What We Eat in America, (NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are anal yz ed and categorized by subgroups based on age and ethnic group. Additionally , OPP is able to assess dietary exposure t o smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non - dietary

exposures based on home use of pesticide products and associated risks for adult applicators and for children 1 - 2 years , youths , and adults entering or playing on treatedPage 13 of 33

areas post - application are evaluated. Further considerations are currentl y in development as OPP has committed resources and expertise to the development of specialized software and models th at consider exposure to by standers and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups. **4.0 Hazard Characterization and Dose**  **- Response Assessment**  No new toxicity

and/or metabolism data have been received since the last risk assessment. This assessment includes summaries of prior assessments ( S . Healy , D399493 , 05/17/2012 ). The Hazard and Science Policy council waived the required subchronic inhalation toxicity study (TXR# 0056851 ). **4.1 Summary of**  **Toxicological Effects** Chlorantraniliprole is an anthranilic diamide insecticide that belongs to a class of compounds that acts on the RyR . It control s lepidopteran pests and insects primaril y via interruption of normal muscle contraction pathway s, which leads to paral ys i s and eventual death. The relative absence of mammalian hazard may be due in part to chlorantranilprole’s selectivity for insect Ry R over mammalian counterparts . In short - term mammalian studies, the most consistent effects are increase d liver weights and mild induction of liver enzy mes. In oral and dermal toxicity studies in rats, increased incidence of adrenal cortex microvesiculation was observed (usually in males onl y). H owever, an additional special study to assess the capacity

of th e adrenal gland to produce corticosterone found no effects in male rats (with or without microvesiculation) following ACTH stimulation. Therefore, adrenal cortex microvesiculation observed in rat studies was not considered adverse. Chlorantraniliprole doe s not exhibit pre - or postnatal toxicity

as there were no maternal or fetal effects in studies conducted in rats and rabbits. Chlorantraniliprole is not genotoxic, neurotoxic, immunotoxic, carcinogenic, or developmentall y toxic. Chlorantraniliprole is cl assified as “Not likel y to be Carcinogenic to Humans ”. No treatment - related tumors were reported in the submitted chronic and oncogenicity studies in rats and mice (18 - month carcinogenicity study) or in the subchronic studies in mice, dogs and rats. Based on the results of short - term and acute dermal studies, chlorantraniliprole has relatively low dermal toxicity . Chlorantraniliprole is not acutel y toxic via the oral, or inhalation routes of exposure. The LD 50 for both oral and dermal acute exposure is > 5000 mg/kg/day and the LC 50 for acute inhalation exposure is > 5.1 mg/L . Chlorantraniliprole is not an eye or skin irritant and does not cause skin sensitization. The acute inhalation study did not report any portal of entry effects or acute irritation via the inhalation route of exposure . Absorption, Distribution, Metabolism, Excretion (ADME) Chlorantraniliprole metabolism was studied extensively in rats, mice , and dogs. In rats, absorption of chlorantraniliprole was rapid with peak concentrations occurring at 5 - 12 hours after low or high (10 or 200 mg/kg) oral single dose administration. The plasma elimination half - lives after single dose ranged from 41 hours in males to 79 hours in female rats. Tissue distribution of the absorbed dose was extensive and indicated low potential for accumulation. The tissue residues were higher in female rats than in male rats, which is consistent with femalePage 14 of 33

rats having a longer elimination half - life. Rapid excretion was observe d via bile (49 - 53%) within 48 hours and 88 - 97% total excretion was observed within 7 day s after single or multiple dose s . Fecal excretion was the primary route of elimination followed by excretion in the urine with no significant excretion occurring b y exhalation. Metabolism of the absorbed dose was extensive and involved sex differences (greater hydrox yl ation in males). Results also suggest possible species differences in the primary metabolites formed in all three species tested. Metabolites represent ed in the rat metabolism cascade were : IN - K9T00, IN - HXH44, IN - KAA24, IN - H2H20, and IN - GAZ70 (chemical nomenclature and molecular structures for these compounds can be found in: S . Healy , D381810 , 02/28/2011 ) . Based on studies conducted in rats, dermal penetration of chlorantraniliprole formulations is approximately ≤ 1.09% for undiluted concentrates and 2.10 - 2.79% for 0.75 g/L aqueous dilutions of the concentrates. **4. 2**  **Safety factor for Infants and Children (FQPA Safety Factor)** Based on the hazard and exposure data, the HED chlorantraniliprole risk assessment team recommend s that the FQPA SF be reduced to 1x . The rationale for this recommendation is provided in the following sections. **4. 2**  **.1 Completeness**  **o f**  **the Toxicology Database**  The toxicity

databa se for this chemical is complete for the purposes of this risk assessment and considered adequate for the characterization of potential pre - and post - natal risks to infants and children. Acceptable developmental toxicity, 2 - generation reproduction toxicity, acute neurotoxicity, subchronic neurotoxicity, and immunotoxicity studies have been submitted and reviewed . The Hazard and Science Policy council waived the required subchronic inhalation toxicity study based on chlorantraniliprole’s phy sical chemical properties, including low vapor pressure; low acute inhalation toxicity (Toxicity Category IV); and the use of a conservative, chronic oral POD that results in screening - level MOEs > 12,000 (TXR# 0056851 ). **4. 2**  **.2 Evidence of N**  **eurotoxicit y**  There is no indication that chlorantraniliprole is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional uncertainty factors (UFs ) to account for neurotoxicity . The no observed adverse effect level (NOAEL ) in an acute oral gavage neurotoxicity

study was 2000 mg/kg, the limit dose. In a subchronic neurotoxicity study , the NOAEL was 1313/1586 mg/kg/day (M/F), the maximum dietary concentration administered (greater than the limit dose). The NOAELs were based on the absence of treatment related effects on sy stemic toxicity and neurotoxicity

parameters, including microscopic neuropathology . Neurological assessments conducted in conjunction with the 18 - month oncogenicity study in mice following 45, 60, and 90 days of dietary administration of chlorantraniliprole confirmed the lack of potential neurotoxicity . Further, no treatment related clinical signs indicative of potential neurotoxicity were observed in short - term or long - term exposure studies in rats, mice, or dogs.Page 15 of 33

**4. 2**  **.3 Evidence**  **o f Sensitivity/Su**  **sceptibility in the Developing o r Young Animal**  There is no evidence that chlorantraniliprole results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2 - generation reproduction study . There were no effects on prenatal fetal growth or postnatal development up to the limit dose of 1000 mg/kg/day

in rats or rabbits. There were no treatment - related effects on the numbers of litters, fetuses (live or dead), resorptions, sex ratio, or post - implantation loss. There were no effects on fetal body weights ; skeletal ossification ; and external, visceral, or skeletal malformations or variations. **4. 2**  **.4 Residual**  **Uncertainty in the Exposure Datab ase**  There are no residual uncertainties identified in the exposure databases. The chronic dietary assessment utilized tolerance - level residues for all crops and assumed 100 % CT of the proposed and registered crops were treated with chlorantraniliprole. Where processing data indicated a reduction (or no increase) in residue upon processing, the residue level of the RAC was used without reduction. Where processing data indicated an increase in residue in the processed commodity , a tolerance was established and used, e.g., raisins from grapes. Where adequate processing data did not exist, default concentration factors w ere used if available. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to chlorantraniliprole in drinking water. Moreover, there is a lack of toxicity via the dermal route, as well as the lack of toxicity over the acute - , short - and intermediate - term via the oral route. These assessments will not underestimate the exposure and risks posed by chlorantraniliprole. **4. 3**  **Toxicity Endpoint and Point of D**  **eparture Selections** The details for selecting toxicity endpoints and points of departure for various exposure scenarios are presented in the original risk assessment for Section 3 Registration (S. Winfield, DP336983, 03/07/20 08). There have been no changes to the prior dose - response assessment or recommendations for combining routes of exposure and/or cancer classification. Refer to Table 4.3.1.Page 16 of 33

**Table 4.3.1**  **. Summary of Toxicological Doses and Endpoints for Chlorantraniliprole for Use in Dietary ,**  **Non**   ** Occupational** **, and Occupa tional**  **Hum an Health Risk Assessments**  **Exposure/ Scenario**  **Point of**

**Departure Uncertainty/FQPA** 

**Safety Factors RfD, PAD,** 

**Level of Concern for**  **Risk Assessment**  **Study and Toxicological Effects** Ac ute Dietary (All Populations) N/A N/A N/A No acute hazard attributable to a single dose wa s identified; therefore, an acute dietary endpoint was not selected for quantitative risk assessment. Chronic Dietary (All Populations) NOAEL=

158 mg/kg/day UF A= 10x

UF H =10x FQPA SF= 1x Chronic RfD

= 1.58 mg/kg/day cPAD = 1.58 mg/kg/day 18 - Month Oral (feeding)/mouse

LOAEL = 935 mg/kg/day based on eosinophilic foci accompanied by hepatocellular hypertrophy and increased liver weight (males only) . Incidental Oral Short - /Intermediate Term N/A N/A N/A There was no hazard identified via the oral route over the short - and intermediate term and , therefore, no endpoint was selected for quantitative risk assessment. Dermal Short - /Intermediate Term N/A N/A N/A There was no hazard identified via the dermal route (and no concerns for developmental, reproductive or neurotoxic effects) and , therefore, no dermal endpoint wa s selected for quantitative risk

assessment. Inhalation Short - /Intermediate Term N/A N/A N/A Based on the lack of hazard identified in the acute inhalati on study, lack of acute irritation, and extremely low oral toxicity , no inhalation endpoint was selected for quantitative risk assessment. Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on weight of evid ence of data:

no treatment - related tumors reported in the submitted chronic and oncogenicity studies in rats and mice, subchronic studies in mice, dogs and rats and 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 dose - response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. RfD = Referen ce Dose. PAD = Population Adjusted Dose. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. N/A = not applicable. **5.0 Dietary Exposure and Risk Assessment**  **5.1 Residues of Concern Summary and Rationale**  The residue s of concern for tolerance enforcement and risk assessment in plants, livestock, and water are summarized below in Table 5.1 . See Appendix B for names and structures. HED also recalculated the dietary

burdens for beef and dairy cattle (S. Funk, D416101, 11/ 12 /2013 ) . The resulting residue estimates were below the established tolerances for ruminants; therefore, tolerance - levels were used in the dietary risk assessment for cattle.Page 17 of 33

**Table 5.1. Summ ary of Metabolites and Degradates to be**  **included in the Risk Assessment and Tolerance Expression**  Matrix Residues included in Risk Assessment Residues included in Tolerance Expression Plants Primary Crop Chlorantraniliprole Chlorantraniliprole

Rotational Crop Chlorantraniliprole Chlorantraniliprole Livestock Ruminant Chlorantraniliprole, IN HXH44, IN - K9T00. Chlorantraniliprole Poultry Chlorantraniliprole Eggs: Chlorantraniliprole, IN - H2H20, IN - K7H29, IN GAZ70 , IN - F9N04 Chlorantraniliprole Drinking Water Chlorantraniliprole N/A **5 .2**  **Food Residue**  **Profile** The submitted magnitude of the residue data are adequate for risk assessment and tolerance assessment. For all crops, the number and locations of field trials are adequate . Greenhouse tomato, greenhouse pepper, greenhouse cucumber, rice, coffee, and strawberry trials reflect the proposed label maximum application rate and other conditions and demonstrate that the existing tolerances are adequate. The crayfish trials show that the existing tolerance may be reduced. Residues in passionfruit, papaya, and may haw will increase with decreased PHI s, but the existing respective group tolerances are protective. Trials for proposed uses on green onions and peanuts are adequate both i n number of trials and geographic distribution and are conducted under conditions reflective of the proposed labels. The new feed item, peanut hay, does not increase the calculated dietary

exposure of ruminants and therefore does not change the existing t olerances for ruminant commodities. The dill seed trials provide a tolerance estimate of 90 ppm for the spices subgroup 1 9B. This is an increase from the previous recommendation of 14 ppm, and the registrant request for 40 ppm. The new data for dried oni ons combined with previous data for alfalfa hay

translated to dried basil support retention of the 90 ppm for herb subgroup 19A . The field trial studies are supported by adequate storage stability data. The existing cotton seed processing study is transl ated to peanut, and no concentration of residue occurs in the oil or meal. Adequate confined and limited field rotational crop data are available. HED previously concluded that the residue of concern in rotational crops is parent onl y. All necessary rotational crop tolerances were established previously or appropriate label restrictions were implemented . Several inadvertent tolerances will now be replaced with primary crop commodity

tolerances. Extensive primary

crop or crop group tolerances have b een established, and therefore there are very few inadvertent tolerances needed.Page 18 of 33

**5.3 Water Residue Profile**  The EDWC for groundwater from the assessment evaluating the proposed uses is greater than the surface and groundwater estimates from the previous assessment. Thus, the groundwater concentration of 207 ppb (one - in - ten - year annual mean) based on the Wisconsin corn scenario was used in the dietary

exposure ass essment (C. Koper, D414839, 09/23/2013) . **Table 5.3. Summ ary of Estimated**  **Surface Water and Ground Water Concentrations for Chlorantraniliprole.** Surface Water Concentration

(ppb a) Ground Water Concentration (ppb b ) Ac ute 55.30 207 Chronic (non - cancer, 1 in 10 year annual average) 39.87 Chronic (cancer, 30 - year annual average) 39.87 a Pesticide Root Zone Model (PRZM v3.12.2, May 12, 2005) and Exposure Analysis Modeling System (EXAMS v2.98.04.06, April 25, 2005), simulation models, were coupled with the input PE5.pl.shell. The Provisional Cranberry Model was used to assess cranberry. The model does incorporate a degradation component b From the PRZM - GW model **5.4 Dietary Risk Assessment**  **5.4.1 Description of Residue Data Used in Dietary Assessment**  HED used tolerance - level residues for the proposed and registered crops and 100% crop treated w as assumed for all commodities included in th is assessment ; therefore, this assessment is considered conservative . Where processing data indicated a reduction (or no increase) in residue upon processing, the residue level of the RAC was used without reduction, for example mint oil from spearmint. Where processing data indicated an increase in residue in the processed commodity , a tolerance was established and used, e.g., raisins from grapes. Where adequate processing data did not exist, def ault concentration factors w ere used if available. D efault concentration factors were used for the following: dried apple, apple juice, dried apricot, dried banana, dried beef meat, cherry juice, field corn sy

rup, cranberry

juice, grape juice, grapefruit juice, lemon juice, lime juice, dried l ych ee, dried (dehydrated) bulb onion, orange juice, dried peach, dried pear, peanut butter, dried pineapple, pineapple juice, dried plantain, dried plum prune, plum juice, dried potato (flakes, granules), potato flour, tangerine juice, tomato paste, tomato puree, dried tomato, and tomato juice. The drinking water residues used in the dietary risk assessment were provided by EFED ( C. Koper, D414839, 09/23/2013 ) and incorporated directly into this dietary

assessment. Water residues were incorporated in the Dietary Exposure Evaluation Model software with the Food Commodity

Intake Database ( DEEM - F CID TM ) into the food categories “water, direct, all sources” and “water, indirect, all sources.” The estimated groundwater concentration of 207 ppb was used for this assessment .Page 19 of 33

**5.4.2 Acute Dietary Risk Assessment**  No acute dietary

toxicity endpoint could be identified based on the toxicology data currentl y available for chlorantraniliprole; therefore, an acute assessment was not performed . **5.4.3 Chronic Dietary Risk Assessment**  The results of the chronic anal ys is indicate that the chronic dietary (food and drinking water) risk estimates utilized 2.3% of the cPAD for the general U.S. population and utilized 6.7% of the cPAD for children 1 - 2 years old, the most highl y exposed population subgroup. Therefore, the chronic dietary

risk is not of concern (i.e., <100% of the cPAD). A summary of these results is shown in Table 5.4.5. **5.4.4 Cancer Dietary Risk Assessment**  C hlorantraniliprole is classified as “n ot likely to be carcinogenic to humans”; therefore, a cancer assessment was not performed . **5.4.5 Summary Table**  **Table 5.4**  **. 5.**  **Summary of Dietary (Food and Drinking Water)**  **Exposure and Risk for Chlorantraniliprole.** 

**Population Subgroup Chronic Dietary**  **Dietary Exposure (m**  **g/kg/day) % cPAD** * General U.S. Population 0.036207 2.3 All Infants (<1 year old) 0.060811 3.8 Children 1 - 2 years old* **0.105269 6.7**  Children 3 - 5 years old 0.081499 5.2 Children 6 - 12 years old 0.046110 2.9 Youth 13 - 19 years old 0.027234 1.7 Adults 20 - 49 years old 0.030559 1.9 Adults 50+ years old 0.030166 1.9 Females 13 - 49 years old 0.029398 1.9 *T he subpopulation with the highest risk estimate . **6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterization**  **6.1 Residential Handler Exposure**  Although there are existin g residential uses for chlorantraniliprole, residential exposure to chlorantraniliprole was not quantitatively assessed due to the lack of toxicity via inhalation and dermal route s. No risk is expected from residential handler exposure to chlorantraniliprol e.Page 20 of 33

**6.2 Post**  **- Application Exposure**  D ue to the lack of toxicity via inhalation and dermal route s of exposure , as well as the lack of toxicity over the acute, short - and intermediate - term via the oral route , a residential post application risk assessment i s not required. **6. 3**  **Residential Bystander Post -** **A pplication Inhalation Exposure**  Based on the Agency's current practices, a quantitative post - application inhalation exposure assessment was not performed for chlorantraniliprole at this time primarily because of the low acute inhalation toxicity

(Toxicity Category IV), low vapor pressure (6.3 x 10 - 12 Pa @ 20  ̊C), and the low proposed use rate (0.099 lb ai/A). However, volatilization of pesticides may be a source of post - application inhalation exposure to individuals nearb y pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 1 . The Agency is in the process of evaluating the SAP report and may , as appropriate, develop policies and procedures to identify the need for and, subsequently , the way to incorporate post - application inhalation exposure into the Agency's risk assessments. I f new policies or procedures are deve loped, the Agency may revisit the need for a quantitative post - application inhalation exposure assessment for chlorantraniliprole . **6. 4**  **Spray Drift** Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularl y the case with aerial application, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundboom and airblast) emplo yed for chlorantraniliprole **.** The Agency has been working with the S pray Drift Task Force (a task force composed of various registrants which was developed as a result of a Data Call - In issued b y EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency ’s Spray

Drift website for more information). 2 The Agency is also taking means to qualitatively

and qualitatively

address spray

drift as a potential source of exposure in risk assessments for pesticides through existing p rograms such as Ag Drift and chemical specific properties of pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during the Registration Review process which ensures that all uses for that pesticide will be consid ered concurrentl y. **7.0 Aggregate Exposure/Risk Characterization**  In accordance with the FQPA, HED must consider and aggregate (add) 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 the risks themselves can be aggregated. When 1 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html 2 Available: http://www. epa.gov/opp00001/factsheets/spraydrift.htmPage 21 of 33

aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. An acute aggregate risk assessment was not performed because no appropriate endpoint was available to determine the aRfD for the general U.S. population or any population subgroup . Short - and intermediate term aggregate risk was not performed because n o hazard was identified over short - or intermediate - term durations . Therefore, the aggregate risk assessment for chlorantraniliprole onl y includes chronic exposures to residues in food and drinking water. The chronic dietary risk assessments for the U.S. population and all population subgroups are not of concern to HED (<100% cPAD). The results of the chronic anal ys is indicate that the chronic dietary (food and water) risk estimates utilized 2.3% of the cPAD for the general U.S. population and utilized 6.7% of the cPAD for children 1 - 2 years old, the most highly exposed population subgroup. **8.0 Cumulative Exposure/Risk Characterization**  Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common me chanism of toxicity finding as to chlorantraniliprole and any other substances and chlorantraniliprole does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, therefore, EPA has not assumed th at chlorantraniliprole has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the pol icy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/. **9.0 Occupational Exposure/Risk Characterization**  There is potential for short - and intermediate - term occupational exposure to chlorantraniliprole during both handler [mixing, loading, and application (via the dermal and inhalation routes)] and post - application activities (via the dermal route) based on the proposed uses. However, the chlorantraniliprole toxicology database indicates there is no hazard associated with short - and intermediate - term dermal and inhalation exposure, and , therefore, no quantitative occupational exposure and risk assessment was conducted. **10.0 References**  Kristin Rury , D416093, 12/03/2013. Chlorantraniliprole: Chronic Dietary (Food and Drinking Water) Exposure and Risk Asses sment for the Section (3) Registration Actions on Green Onion Subgroup 3 - 07b, and Peanut; and for the Requests to Update the Crop Groups of Stone Fruit, Tree Nut, and Spices; and to Shorten the Pre - Harvest Intervals for Papaya, Passionfruit, and May haw.Page 22 of 33

Christopher Koper, D414839, 09/23/2013. Tier II Drinking Water Assessment to Establish Tolerances of Chlorantraniliprole on Various Crops with Multiple Seasons. Steve Funk, D416101, 11/ 12 /2013. Chlorantraniliprole . Petition for the Establishment of Permanent Tolerances and Registration for Use on Peanuts and on Green Onion, Addition of Use on Greenhouse Tomato and Greenhouse Pepper and Greenhouse Cucumber, Crop Group Conversions for Stone Fruit and Tree Nuts, and L abel Amendment to Shorten the PHI for Passionfruit, Papaya, and May haw. Condition of Registration Data for Rice, Crayfish, Coffee, Strawberry , and Live s tock Analy tical Methods. Summary of Anal ytical Chemistry

and Residue Data.Page 23 of 33

**A ppendix**  **A .**  **Toxicology Profile**  **A.1 Toxicology Data Requirements**  The requirements (40 CFR 158.500 ) for food use for chlorantraniliprole are in Table A.1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used. **Test Technical**  **Required Satisfied**  870.1100 Acute Oral Toxicity ................................ ....................... 870.1200 Acute Dermal Toxicity ................................ .................. 870.1300 Acute Inhalation Toxicity ................................ .............. 870.2400 Primary Eye Irritation ................................ .................... 870.2500 Primary Dermal Irritation ................................ .............. 870.2600 Dermal Sensitization ................................ ...................... y es yes yes yes yes yes yes

yes yes yes yes yes 870.3100 Oral Subchronic (rodent) ................................ ............... 870.3150 Oral Subchronic (non - rodent) ................................ ........ 870.3200 21 - Day

Dermal ................................ .............................. 870.3250 90 - Day

Dermal ................................ .............................. 870.3465 90 - Day

Inhalation ................................ .......................... y es yes yes no no * yes

yes yes

-

- 870.3700a Developmental Toxicity (rodent) ................................ ... 870.3700b Developmental Toxicity (non - rodent) ........................... 870.3800 Reproduction ................................ ................................ . y es yes yes yes

yes yes 870.4100a Chronic Toxicity (rodent) ................................ .............. 870.4100b Chronic Toxicity (non - rodent) ................................ ....... 870.4200a Oncogenicity (rat) ................................ .......................... 870.4200b Oncogenicity (mouse) ................................ .................... 870.4300 Chronic/Oncogenicity ................................ .................... y es yes yes yes no yes **

yes yes ** yes yes ** 870.5100 Mutagenicity

—Gene Mutation - bacterial ..................... 870.5300 Mutagenicity

—Gene Mutation - mammalian ................ 870.5385 Mutagenicity

— Structural Chromosomal Aberrations ... 870.5395 Mutagenicity

—Micronucleus ................................ ........ y es yes yes yes yes

yes yes yes 870.6100a Acute Delayed Neurotox. (hen) ................................ ..... 870.6100b 90 - Day

Neurotoxicity (hen) ................................ ........... 870.6200a Acute Neurotox. Screening Battery (rat) ....................... 870.6200b 90 - Day

Neuro tox . Screening Battery (rat) ..................... 870.6300 Develop. Neuro tox ................................ ........................ n o no yes yes no -

- yes yes

- 870.7485 General Metabolism ................................ ...................... 870.7600 Dermal Penetration ................................ ........................ 870.7 8 00 Immunotoxicity ................................ ............................. y es no yes yes

- yes * Based on a weight of evidence approach a subchronic inhalation toxicity study is not required for the current uses (TXR#0056851 ). ** Submittal of 870.4300 fulfills the requirement for 870.4100a and 870.4200 a .Page 24 of 33

**A.2 Toxicity Profile**  **s Table A.2.1**  **Acute Toxicity Profile of Chlorantraniliprole**  **Guideline No. Study Type**  **MRID(s) Results**  **Toxicity Category**  870.1100 Ac ute oral - rat 46889112 LD 50 > 5000 mg/kg IV 870.1200 Ac ute dermal - rat 46889113 LD 50 > 5000 mg/kg IV 870.1300 Ac ute inhalation - rat 46889121 LC 50 > 5.1 mg/L IV 870.2400 Ac ute eye irritation - rabbit 46889115 Iritis score of 1 in 1/3 rabbits, conjuctival redness score of 1 in 2/3 rabbits. All eyes returned to normal after 72 hours. IV

870.2500 Ac ute dermal irritation - rabbit 46889114 No dermal irritation, clinical signs or body weight loss IV 870.2600 Skin sensitization - mo use 46889221 Not a dermal sensitizer Negative **Table A.2.2 Subchronic, Chronic and Other Toxicity Profile**  **of Chlorantraniliprole**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  870.3050 28

–Day oral t oxicity

(rat) 46979941, 46979942

(2006) Acceptable

–

Nonguideline 0, 300, 1500, 8000 ppm (M: 0, 20.7, 106, 584 mg/kg/d ; F: 24, 128, 675 mg/kg/d) NOAEL = 584 / 675 (M/F) mg/kg/d LOAEL not established. F had dose - dependent increase in liver weight and hepatocellular hypertrophy without corresponding histopathological evidence of adverse liver effects. 870.3050 28

–Day oral t oxicity

(mouse) 46979303 (2003)

Acceptable

–

Nonguideline 0, 300, 1000, 3000, 7000 ppm (M: 0, 52, 182, 538, and 1443 mg/kg/d; F: 0, 64, 206, 658, and 1524 mg/kg/d) NOAEL = 1443 / 1524 (M/F) mg/kg/d LOAEL not established. F had dose - dependent increase in liver weight ; M and F had dose dependent increase in CYP content and decreased hepatic β - oxidation at HDT; these effects occurred without corresponding histopathological evidence of adverse liver effects. 870.3100 90 - Day

oral toxicity (rat) 46889010 (2005)

Acceptable

– Guideline 0, 600, 2000, 6000, or 20, 000 ppm (M : 0, 36.9, 120, 359, 1188 mg/kg/d; F: 0, 47, 157, 460, 1526 mg/kg/d) NOAEL = 1188 / 1526 ( M/F ) mg/kg/d LOAEL not established. F had s light increase in liver weight at HDT and dose - dependent decreased bilirubin without corresponding histopathological evidence of adverse liver effects .Page 25 of 33

**Table A.2.2 Subchronic, Chronic and Other Toxicity Profile**  **of Chlorantraniliprole**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  870.3100 90 - Day

oral toxicity (mouse) 46889013 (2006)

Acceptable

– Guideline 0, 200, 700, 2000, or 7000 ppm (M: 0, 32.6, 115, 345, 1135 mg/kg/d; F: 0, 40.7, 158, 422, 1529 mg/kg/d) NOAEL = 1135 / 1529 ( M/F ) mg/kg/d LOAEL not established . M and F had slight increase in liver weight at HDT but no corresponding histopathological evidence of adverse liver effects. Hyperactivity/ hyperreactivity seen in 1529 mg/kg/d F near end of study and convulsions in one male were not reproducible in 18 - mo nth mou se study with FOB (MRID 46979720). 870.3150 90 - Day

oral toxicity (dog) 46889012 (2004)

Acceptable

– Guideline 0, 1000, 4000, 10,000, and 40,000 ppm (M: 0, 32.2, 119, 303, 1163 mg/kg/d; F: 0, 36.5, 133, 318, 1220 mg/kg/d) NOAEL = 1163 / 1220 (M/F) mg/kg/d LOAEL not established. M had slight increase in liver weight at HDT but no corresponding histopathological evidence of adverse liver effects.

870.3200 21/28 - Day dermal

toxicity (rat) 46889128 (2006)

Acceptable

– Guideline 0, 100, 300 , 1000 mg/kg/d **Systemic** NOAEL = 1000 mg/kg/d LOAEL not established. I ncreased incidence of adrenal cortex microvesiculation in males wa s not associated with changes in adrenal function (MRID 488892 14 ) and is not considered adverse . **Derm al irritation**  NOAEL= 1000 mg/kg/d L OAEL not established. 870.3700a Prenatal

developmental in rat 46889108 (2004)

Acceptable

– Guideline 0, 20, 100, 300, 1000 mg/kg/d **Maternal** NOAEL = 1000 mg/kg/d LOAEL not established due t o the absence of maternal effects at any dose. **Developm ental**  NOAEL = 1000 mg/kg/d LOAEL not established due to the absence of developmental effects at any dose. 870.3700b Prenatal

developmental in rabbit 46889109 (2005)

Acceptable

– Guideline 0, 20, 100, 300, 1000 mg/kg/d **Maternal** NOAEL = 1000 mg/kg/d LOAEL not established due t o the absence of maternal effects at any dose. **Developm ental**  NOAEL = 1000 mg/kg/d LOAEL not established due to the absence of developmental effects at any dose.Page 26 of 33

**Table A.2.2 Subchronic, Chronic and Other Toxicity Profile**  **of Chlorantraniliprole**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  870.3800 Reproduction and

fertility effects

– 2 generation (rat) 46889107 , 46979722

(2006) Acceptable

– Guideline 0, 200, 1000, 4000, or 20,000 ppm (M: 0, 12.0, 60.4, 238, 1199 mg/kg/d; F: 0, 15.5, 77.8, 319, 1594 mg/kg/d) **Parental/System ic**  NOAEL = 1199/ 1594 (M/F) mg/kg/d LOAEL not established. Increase in adrenal wei ghts and microvesiculation incidence (M/F) wa s not associated with changes in adrenal function (MRID 48889214) and is not considered adverse. Increase in liver weight ( F ) wa s not associated with adverse effects (MRID 46889010 ). **Reproductive** NOAEL = 1000 mg/kg/day L OAEL not established due to the absence of reproductive effects at any dose. **Offspring** NOAEL = 1199/1 594 (M/F) mg/kg/day LOAEL not established due to absence of adverse effects in pups during lactation. 870.4100a Chronic toxicity

(rodents) C om bined chronic / carcinogenicity study available (see below) 870.4100b Chronic toxicity

(dog) 46979718 (2006)

Acceptable

– Guideline 0, 1000, 4000, 10000, or 40000 ppm (M: 0, 32, 112, 317, 1164 mg/kg/d; F: 0, 34, 113, 278, 1233 mg/kg/d) NOAEL = 1164/1233 (M/F) mg/kg/day LOAEL not established. M and F had slight increase in liver weight at HDT but no corresponding histopathological evidence of adverse liver effects.

870.4300a Chronic /

Carcinogenicity (rat) 46979719 (2006)

Acceptable

– Guideline 0, 200, 1000, 4000, 20000 ppm (M: 0, 7.71, 39.0, 156, 805 mg/kg/d; F: 0, 10.9, 51.0, 212, 1076 mg/kg/d) NOAEL = 805/1076 (M/F) mg/kg/d LOAEL not established. Increase incidence of adrenal microvesiculation (M ) was not associated with changes in adrenal function (MRID 48889214) and is not considered adverse. Increase in relative liver weight (F) without corresponding histopathological evidence of adverse liver effects. **No evidence of carcinogenicity** 870.4200 Carcinogenicity

(mouse) 46979720 (2006)

Acceptable

– Guideline 0, 20, 70, 200, 1200, 7000 ppm (M: 0, 2.60, 9.20, 26.1, 158, 935 mg/kg/d; F: 0, 3.34, 11.6, 32.9, 196, 1155 mg/kg/d) NOAEL = 158 /1155 (M/F) mg/kg/d LOAEL = 935 (M) mg/kg/d based on mild eosinophilic foci in 5/70. A LOAEL in F was not established. M and F ( ≥ 158/196 mg/kg/d) had increase in absolute and relative liver weight and minimal - mild hepatocellular hypertrophy . **No evidence of carcinogenicity**Page 27 of 33

**Table A.2.2 Subchronic, Chronic and Other Toxicity Profile**  **of Chlorantraniliprole**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  870.510 0 Bacterial Reverse

Mutation Test 46889103 (2004)

Acceptable

– Guideline Initial assay: 8 conc s. ( 2.5 to 5000 μg/plate ) C onfirmatory assay : 5 concs . ( 50 to 5000 μg /plate ) Negative with and without metabolic activation (S9) in Salmonella strains TA 98, TA 100, TA 1535 and TA 1537 , and in E. Coli WP2 uvrA strain.

870.5100 Bacterial Reverse

Mutation Test 46979921 (2006)

Acceptable

– Guideline Initial assay: 8 conc s. (33.3 to 5000 μg/plate ) C onfirmatory assay : 5 concs . (333 to 5000 μg /plate ) Negative with and without metabolic activation (S9) in Salmonella strains TA 98, TA 100, TA 1535 and TA 1537 , and in E. Coli WP2 uvrA strain.

870 .5300 In vitro Chinese

Ham ster Ovarian Cell Gene Mutations at HGPRT L ocus Test 46889106 (2004)

Acceptable

– Guideline 0, 15.6, 31.3, 62.5, 125, 250 g/mL Negative with and without metabolic activation (S9). 870.5375 In vitro Human

Lymphocyte Chromosome Aberration Test 46979922 (2006)

Acceptable

– Guideline 0, 50, 100, 500 μg/mL (no S9); 1, 10, 25 μg/mL (w

/ S9) Negative with and without metabolic activation (S9).

870. 53 75 In vitro Human

Lymphocytes Chromosome Aberration Test 46889105 (2004)

Acceptable

– Guideline 0, 125, 250, 500 μ g/mL Negative with and without metabolic activation (S9). 870. 53 75 In vitro Human

Lymphocytes Chromosome Aberration Test 46979922 (2006)

Acceptable

– Guideline 0, 1, 10, 25, 50, 100, 500, 1000, 2000, 4831.5 μ g/mL Negative with and without metabolic activation (S9).

870.5395 Mouse Erythrocyte

Micronucleus Assay 46889104 (2006)

Acceptable

– Guideline 0, 500, 1000, or 2000 mg/kg/d Negative in the bone marrow of M and F Crl:CD - 1 ® (ICR)BR mice. 870.6200a Ac ute neurotoxicity

screening battery (rat) 46979312 (2004 )

Acceptable

– Guideline 0, 200, 700, 2000 mg/kg/d NOAEL = 2000 mg/kg/day LOAEL not established due to absence of adverse systemic or neurological effects .Page 28 of 33

**Table A.2.2 Subchronic, Chronic and Other Toxicity Profile**  **of Chlorantraniliprole**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  870.6200b Subchronic

neurotoxicity screening battery (rat) 46979721 (2006 )

Acceptable

– Guideline 0, 200, 1000, 4000, 20,000 ppm (M: 0, 12.7, 64.2, 255, and 1313 mg/kg/d; F: 0, 15.1 , 77.3 , 304 , 1586 mg/kg/d) NOAEL = 1313/1586 ( M/F ) mg/kg/d LOAEL not established due to absence of adverse systemic or neurological effects.

870.7485 Metabolism and

pharmacokinetics (rat) 46979330 (2006)

Acceptable

– Guideline 10 or 200 mg/kg single dose Readily absorbed after low (10 mg/kg bw) or high (200 mg/kg bw) single oral gavage. P lasma levels p eak 5 - 12 hours after dosing. E xtensive tissue distribution and low tissue:plasma ratios ( <1 ) show low potential for accumulation . Tissue levels slightly greater in F th an M. Distribution 7 days after low dose : 24 - 29% urine, 62 - 64% fe ces, 0.8 - 3.3% tissues ; a fter high dose, 3.8 - 5.2% urine, 91 - 92% feces , 0.2 - 0.5% tissues. Urinary excretion slightly greater in M than F. Extensive metabolism characterized by methylphenyl and N - methyl hydroxylation, followed by N - demethylation, nitrogen - to carbon cyclisation , alcohols oxidation to carboxylic acids, amide bridge cleavage, amine hydrolysis, and O - glucuronidation. 870.7485 Metabolism and

pharmacokinetics (rat) 46979331 (2006)

Acceptable

– Guideline 10 mg/kg/d for 4, 8, 11, or 14 days T max 14 days administration in male rats; female rats were near steady stat e. After cessation of dosing, readily eliminated from the plasma and tissues. T issue distribution at 1 and 7 days similar to that found after single dose and confirmed minimal accumulation potential . F eces was the predominate route of elimination. E xtensive metabolism consistent with that observed for the single dose study. 870.7800 Immunotoxicity (rat) 46979343 (2006) 0, 1000, 5000, or 20,000 ppm (M: 0, 74, 3 63, 1494 mg/kg/d ; F: 0, 82, 397, 1601 mg/kg/d) NOAEL = 1494 / 1601 (M/F) mg/kg/d LOAEL not established due to absence of a dverse systemic or immune effects . 870.7800 Immunotoxicity

(mice) 47231202 (2007)

0, 300, 1700, or 7000 ppm (M: 0, 48, 264, 1144 mg/kg/d ; F: 0, 64, 362, 1566 mg/kg/d) NOAEL = 1494 / 1601 (M/F) mg/kg/d LOAEL not established due to absence of adverse systemic or immune effects .Page 29 of 33

**Table A.2.2 Subchronic, Chronic and Other Toxicity Profile**  **of Chlorantraniliprole**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  Special Study 28 - d ay repeated - d ose

dermal mechanistic study in males (rat) 46889214 (2006)

Acceptable

–

Non Guideline 1000 mg/kg/d C hlorantraniliprole had no effect on adrenal function after ACTH challenge in male rats at a dermal dose that resulted in an increase incidence of

adrenal cortical microvesiculation. Special Study Development of

methods for evaluation of adrenal cortex (rat) 46979749 , 46979927

(2006) Acceptable

–

Non Guideline Method wa s able to detect a reduction of ACTH - stimulated serum corticosterone level at a positive control dose that did not alter basal serum corticosterone. I n some rat s from several studies (28 - day

dermal , 90 - day oral, multigeneration reproduction , 2 - year chronic ) a slight , treatment - related increased in microvesiculation was observed in zona fasciculata cells of the adrenal cortex. Special Study 14 - day toxicity,

metabolism and pharmacokinetics (rat) 46979935 (2006)

Acceptable

–

Non Guideline 0, 25, 100, 1000 mg/kg/d NOAEL = 1000 mg/kg/day LOAEL not established due to absence of adverse effects. D ecreased absorption wa s observed at higher doses. E stimated T 1/2 wa s 3.4 - 4.0 hr. T max wa s 0.25 - 2.75 hr . C max wa s similar at all dose levels . Weak induction of CYP3A in F only. Total CYP in M and β - oxidation in M or F were not altered. Special Study 28

–Day oral (capsule)

toxicity ( dog ) 46979711 (2003)

Acceptable

–

Nonguideline 0, 300 or 1000 mg/kg/d NOAEL = 1000 mg/kg/d LOAEL not established. An increase in hepatic CYP content at HDT without corresponding histopathological evidence of adverse liver effects. T 1/2 = 8.1 - 9.3/13.3 - 17.2 hr (M/F). C max = 2.5 - 3.0 μ g/mL (M and F) Special Study 28

–Day oral (feed)

toxicity ( dog ) 46979713 (2003)

Acceptable

–

Nonguideline Group 1: 1000 (Wk 1), 5000 (Wk 2), 10,000 (Wk 3 - 4) ppm ; Group 2: 30, 000 (Wk 1 - 2) 40,000 (Wk 3 - 4) ppm (M: 0, 26, 138, 266, 797, 1302 mg/kg/d; F: 0, 28, 138, 298, 888, 1240 mg/kg/d) NOAEL = 1302 / 1240 (M/F) mg/kg/d LOAEL not established due to absence of adverse effects. P alatability of the diet was not affected by inclusion of the test material

F = females; M = males ; HDT = highest dose tested; dose - dependent = a change was observed in at least the two highest doses; CYP = cytochrome P450 enzymes; CYP3A = CYP is oenzyme 3A; C ma x = maximum (i.e. steady - state) serum concentration; T ma x = time at maximum serum concentration; T 1/2 = half - life in serum, i.e. time at half of maximum serum concentration. Wk = weekPage 30 of 33

**Appendix B**  **. Physical/Chemical Properties**  **Table B.**  **Physicochemical Properties of Tec hnical Grade of Chlorantraniliprole**  **.** Parameter Value Reference (MRID) Melting point/range (°C) 200 - 202 (95.9%)/208

– 210 (99.2%) 46889033 pH 5.77 ± 0.087 at 20°C 46889031 Relative Density 1.5189 (95.9%)/1.507 (99.2%) at 20°C 46889033 Water solubility (20°C) Deionized Water 1.023 mg/L pH 4 0.972 mg/L pH 7 0.880 mg/L pH 9 0.971 mg/L 46889026 Solvent solubility (20°C) Acetone 3.446 ± 0.172 g/L Acetonitrile 0.711 ± 0.072 g/L Ethyl Acetate 1.144 ± 0.046 g/L Dichloromethane 2.476 ± 0.058 g/L Dimethylformamide 124 ± 4 g/L n - Octanol 0.386 ± 0.01 g/L Methanol 1.714 ± 0.057 g/L n - Hexane <0.0001 g/L o - Xylene 0.162 ± 0.01 g/L 46889030

Vapor pressure 6.3 x 10 - 12 Pa @ 20 ° C, 2.1 x 10 - 11 Pa @ 25 ° C 46889130 Dissociation constant, pKa 10.88 ± 0.71 46889034 Octanol/water partition coefficient, KOW (20°C) Deionized Water 589 pH 4 588 pH 7 721 pH 9 654 46889032 UV/visible absorption (max) pH <2 no absorption max >200 nm, at 290 ε = 3941 pH 7 no absorption max >200 nm, at 290 ε = 4185 pH >10 absorption max at ~320 nm which may be due to decomposition of DPX - E2Y45 , at 290 ε = 6082 46889027

**Structures of Chlorantraniliprole and Possible Metabolites** 

**Structures of C**  **hlorantraniliprole and P**  **ossible M**  **etabolites .**  Chemical Name; Company Code Structure 3 - Bromo -N

- [4 - chloro - 2 - methyl - 6 - [(methylamino)carbonyl]phenyl] - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

- py razole - 5 - carboxamide Chlorantraniliprole DPX - E2Y45 **N N**  **N N**  **H O**  **Cl Br**  **N H**  **O Cl** Page 31 of 33 **Structures of C**  **hlorantraniliprole and P**  **ossible M**  **etabolites .**  Chemical Name; Company Code Structure 3 - Bromo - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

- py razole - 5 - carbox yl ic acid IN - DBC80

2 - [3 - Bromo - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

- py razol - 5 - yl ] - 6 - chloro - 3, 8 - dimethyl - 4(3 H ) - quinazolinone IN - EQW78

5 - Bromo -N

- methyl - 1 H

- py razole - 3 - carboxamide IN - F6 L99

N - [2 - (Aminocarbonyl ) - 4 - chloro - 6 - methylphenyl] - 3 - bromo - 1 - (3 - chloro - 2 - py

ridinyl)1 H

- py razole - 5 - carboxamide IN - F9N04

2 - [3 - Bromo - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

- py razol - 5 - yl ] - 6 - chloro - 8 - methyl - 4(3 H

) - quinazolinone IN - GAZ70

3 - Bromo -N

- [4 - chloro - 2 - [[(hydrox ym eth yl )amino]carbonyl] - 6 - methylphenyl] - 1 - (3 - chloro - 2 - py

ridinyl) - 1 H

- py razole - 5 - carboxamide IN - H2H20 **N N**  **N O** 

**Cl Br**  **O H** 

**N N**  **N N**  **N Br**  **O**

**Cl Cl** 

**N**

**H N**  **H O**  **N Br** 

**N N**  **N N**  **H O**  **Cl Br**  **O Cl**  **N H**  **2**

**N**

**N H**  **N N**  **N Br**  **O**

**Cl Cl** 

**N N** 

**N N** **H O**  **Cl Br**  **N H**  **O Cl**  **O H** Page 32 of 33 **Structures of C**  **hlorantraniliprole and P**  **ossible M**  **etabolites .**  Chemical Name; Company Code Structure N - [2 - Aminocarbonyl ] - 4 - chloro - 6 - (hydroxy methyl)phenyl] - 3 - bromo - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

- py razole - 5 - carboxamide IN - HXH40

3 - Bromo -N

- [4 - chloro - 2 - (hydrox ym ethyl) - 6 - [(methylamino)carbonyl]phenyl] - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

- py razole - 5 - carboxamide IN - HXH44

2 - [3 - Bromo - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

- py razol - 5 - yl ] - 6 - chloro - 8 - (h ydrox ym ethyl) - 4(3 H ) - quinazolinone IN - K7H29 3 - Bromo -N

- [4 - chloro - 2 - (hydrox ym ethyl) - 6 - [[(hydrox ym eth yl )amino)carbonyl ]phenyl] - 1 - (3 - chloro - 2 - py

ridinyl) - 1 H

- py razole - 5 - carboxamide IN - K9T00

6 - Chloro - 1, 2, 3, 4 - tetrahydro - 2, 4 - dioxo - 8 - quinazolinecarbox yl ic acid IN - K9X71 **N N**  **N N** **H O**  **Cl Br**  **N H**  **2 O**  **Cl**

**O H** 

**N N**  **N N** **H O**  **Cl Br**  **N H**  **O Cl** 

**O H** 

**N**

**N H**  **N N**  **N Br**  **O**

**Cl Cl** 

**O H** 

**N N**  **N N** **H O**  **Cl Br**  **N H**  **O Cl** 

**O H**  **O H** 

**N H**  **N H**  **O**

**O Cl** 

**O H**  **O**Page 33 of 33 **Structures of C**  **hlorantraniliprole and P**  **ossible M**  **etabolites .**  Chemical Name; Company Code Structure 2 - [[[3 - Bromo - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

- py razol - 5 - yl ]carbonyl]amino] - 5 - chloro - 3 - [(methylamino)carbonyl]benzoic acid IN - KAA24

2 - Amino - 5 - chloro - 3 - [(methylamino)carbonyl ]benzoic acid IN - L8 F56

IN - E5F18 Not provided **N N**  **N N** **H O**  **Cl Br**  **N H**  **O Cl**  **O H**  **O**

**O Cl** 

**O H**  **O N** 

**N H**  **2**