EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITION EPA Registration Division contact: Sidney Jackson (703) 305 - 7610 Interregional Research Project Number 4 PP# 1E7842 EPA has received a pesticide petition ( PP) 1E7842) from Interregional Research Project #4 (IR - 4), IR - 4 Project Headquarters, Rutgers, The State University of New Jersey , 500 College Road East, Suite 201 W, Princeton, NJ 08540 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFD CA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing tolerances for residues of methoxyfenozide, including its metabolites and degradates, in or on the raw agricultural commodities Fruit, citrus, group 10 - 10 at 1.9 parts per million (ppm); Lemo n, oil at 45 ppm ; Citrus, oil (except lemon) at 100 ppm; Vegetable, root, except sugar beet, subgroup 1B at 0.8 ppm; Beet, sugar at 0.5 ppm. The petition also proposes to remove the established tolerances for Vegetable, root, subgroup 1A and citrus oil at 100 ppm from table in paragraph (a) as well as Fruit, citrus, group 10 from the table in paragraph (c) upon the approval of the pr oposed tolerances listed above, and a dditionally , the petition proposes to revise the tolerance expressions in 40 CFR part 180.544 to read as follows: (a)(1) Tolerances are established for residues of the insecticide methox yf enozide, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only methoxy fenozide [benzoic acid, 3 - methoxy - 2 - methyl - , 2 - (3,5 - dimethylbenzoyl) - 2 - (1,1 - dimethylethyl) h ydrazide]. (a)(2) Tolerances are established f or residues of the insecticide methox yf enozide, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of methoxyfenozide [ benzoic acid, 3 - methoxy - 2 - methyl - , 2 - (3,5 - dimethylbenzoy l) - 2 - (1,1 - dimethylethyl) h ydrazide] and its glucuronide metabolite (β - D Glucopy ranuronic acid, 3 - [ [2 - (1,1 - dimethylethyl) - 2 - (3,5 - dimethylbenzoyl) - hy drazino]carbonyl ] - 2 - methylphen yl - ), calculated as th e stoichiometric equivalent of methoxyfenozide. b) Section 18 emergency exemptions . Time - limited tolerances specified in the following table are established for residues of the insecticide methoxyfenozide , including its metabolites and degradates , in or on the specified agricultural commodities, resulting from use of the pesticide pursuant to FFIFRA section 18 emergency exemptions. Compliance with the tolerance levels specified below is to be determined by measuring only methoxy fenozide [benzoic acid, 3 - methoxy - 2 - methyl - , 2 - (3,5 - dimethylbenzoyl) - 2 -(1,1 - dimethylethyl) h ydrazide]. The tolerances expire and will be revoked on the date

specified in the table. d) Indirect or inadvertent residues. (1) Tolerances are established for the indirect or ina dvertent residues of the insecticide methox yf enozide, including its metabolites and degradates, in or on the raw agricultural commodities in the table below, when present therein as a result of the application of methox yfenozide to growing crops as listed in paragraph (a) of this section. Compliance with the tolerance levels specified below is to be determined b y measuring onl y methox yfenozide [benzoic acid, 3 - methoxy - 2 - methyl - , 2 - (3,5 - dimethylbenzoyl) - 2 - (1,1 - dimethylethyl) hydrazide]. (2) Tolerances are established for the indirect or inadvertent residues of the insecticide methoxyfenozide, including its metabolites and degradates, in or on the raw agricultural commodities in the table below, when present therein as a result of the application of methoxyfenozide to growing crops as listed in paragraph (a) of this section. Compliance with the tolerance levels specified below is to be determined b y measuring only the sum of methox yfenozide [benzoic acid, 3 - methoxy - 2 - methyl - , 2 - (3,5 - dimethylbenzoyl) - 2 - (1,1 - dimethylethyl) h ydrazide] and the following metabolites (all calculated as the stoichiometric equivalent of methoxy fenozide): free phenol of methox yf enozide [3,5 - dimethylbenzoic acid N - tert - but yl - N ′ - (3 - hy drox y - 2 - methylbenzoyl) h ydrazide], the glucose conj ugate of the phenol [3,5 - dimethyl benzoic acid N - tert - but yl - N' - [3 (β - D glucop yr anos yl oxy) - 2 - methylbenzoyl] - hy drazide] and the malonylg ly cosy l conjugate of the phenol [3,5 - dimethyl benzoic acid N - tert - butyl - N' - [3 (β - D - 6 - malonyl glucop yr anos yl - 1 - oxy) - 2 - methy lbenzoyl] - hy drazide]. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism. Per the most recent EPA analytical summary for methoxyfenozide (D. Rate, US EPA, DP358341, June 10, 2009), the nature of the residue of methox yfenozide in plants has been studied in several plants (apple, cotton, grape and rice) and is adequately

understood. For primary crops and drinking water, the tolerance expres sion is methox yfenozide per se . 2. Analytical method. Per the most recent EPA analy tical summary

for methoxyfenozide (D. Rate, US EPA, DP358341, June 10, 2009), adequate enforcement methods are available for determination of methoxy fenozide residues in p lant commodities. Analy

tical methodology

for the magnitude of residue studies in citrus was based on a procedure based on Dow AgroSciences method GRM 02.25 “Determination of Residues of Methox yf

enozide in High Moisture Crops by L iquid Chromatography with Tandem Mass Spectrometry Detection“. The limit of detection (L OD) and the limit of quantitation (LOQ) values in citrus were calculated as 0.0072 ppm and 0.022 ppm,respectivel y. Anal yt ical methodology for the magnitude of residue studies in root crops us ed a procedure based on the Rohm and Haas Technical Report No. 34 - 98 - 87, “Tolerance enforcement method for Parent RH - 2485 in Pome Fruit” with minor modifications. The LOD and LOQ values were calculated as 0.0028 ppm and 0.0084 ppm, respectivel y. 3. Magn itude of residues. For carrots, IR - 4 recently completed trials in carrot (I R 4 PR No. 09884, May

28, 2010) to support reduction of the PHI on root crops in subgroup 1B from 14 day s to 1 day . Residues of methoxy fenozid e were determined following 4 foliar applications of Intrepid  2F insecticide in 8 field locations in the EPA Regions 3, 5, 6, and 10 during the 2007 and 2008 growing season. Methoxyfenozide was applied at a target rate of 0.25 lb ai/A, for a total of app roximately 1.0 lb ai/A. Applications were made 14 (  2) day s apart and samples collected 1 day after the final application. A decline trial also included samples at 0, 1, 3, 6, 7, and 10 days after the last application. The methoxyfenozide residues in carrot roots ranged from a maximum of 0.130 ppm to a minimum of 0.0266 ppm with a 0.1245 HAFT (Highest Average Field Trial) value at the PHI of 1 day and some decline was noted over the 10 day s within the decline trial. For radish, I R - 4 recentl y completed trials (IR - 4 PR No. 09895, June 14, 2010) to support reduction of the PHI on root crops in subgroup 1B from 14 day s to 1 day . Radish trials are limited to fewer applications based on the short growing season. Residu es of methoxyfenozide were determined following 2 foliar applications of Intrepid  2F insecticide across 4 Regions. Methox yf enozide was applied at a target rate of 0.25 lb ai/A, for a total of approximately 0.5 lb ai/A. Applications were made 14 to 15 days apart and samples collected 1 day after the final application. A decline trial also included samples at 0, 1, 3, 5, 7, and 9 day s after the last application. The methoxy fenozide residues in radish roots ranged from a maximum of 0.601 ppm to a minimum of 0.0442 ppm with a 0.453 ppm HAFT value at the PHI of 1 day and there was no significant decline over 9 day s. For citrus, IR - 4 recently

completed additional trials in orange, grapefruit and lemon (I R - 4 PR No. A9367, August 25, 2010) to expand the currentl y approved regional use to a national registration for use of methox yfenozide in citrus with a 1 day PHI. Residues of methoxyfenozide were determined following four foliar applications of Intrepi d  2F insecticide in 14 field locations in California, Florida and Texas during the 2008 growing season. Methox yfenozide was applied at a target rate of 0.25 lb ai/A, for a total of approximately

1.0 lb ai/A. Applications were made 12 to 15 day s apart an d marketable citrus fruit was collected 1 day after the final application. This new data is in addition to the 7 citrus trials (6 harvest trials and one processing trial) conducted from Regions 6 and 10 during 2005 and 2006 (I R - 4 ID 09367, MRID 47556401, August 1, 2008; F ederal Register of September 2, 2009 74 FRL - 8433 - 8 ) . Based on the combined set of methox yfenozide residues in citrus ranged from a maximum of 1.72 ppm to a minimum of 0.112 ppm with a 1.67 ppm HAFT value at the PHIof 1 day

and there was no significant decline over the 14 day s. Residues ranges bysample ty pe were: 0.191 to 0.1.72 ppm in oranges, from 0.112 to 0.312 ppm in grapefruit, and from 0.140 to 0.933 ppm in lemons). The requested tolerances are adequatel y supported. B. Toxicologi cal Profile The toxicological profile for methox yfenozide which supports this petition to revise tolerances is assessed in the 2009 Human Health review (Rate, EPA - HQ - OPP - 2009 - 0012 - 0004, D357983, July 22, 2009), and the endpoints for risk assessment are re iterated in EPA’s most recent dietary assessment (EPA, Hanson, DP361376, July

7, 2009). EPA has concluded “The toxicological database is adequate for the purpose of risk ass essment and tolerance setting.” 1. Acute toxicity. Per the 2009 Human Health re view (Rate, EPA - HQ - OPP - 2009 - 0012 - 0004, D357983, July 22, 2009) , no significant acute hazards were attributable to a single exposure in the available toxicology studies on methoxyfenozide including the acute neurotoxicity

study in rats, the developmental t oxicity studying rats and the developmental toxicity

study in rabbits. Since no acute toxicological endpoints were established, no acute assessment is required. 2. Genotoxicty. [ Per the 2009 Human Health review (Rate, EPA - HQ - OPP - 2009 - 0012 - 0004, D357983, July 22, 2009) , methoxy fenozide demonstrated a “lack of genotoxicity

in an acceptable battery

of mutagenicity

studies.” 3. Reproductive and developmental toxicity. P er the 2009 Human Health review (Rate, EPA - HQ - OPP - 2009 - 0012 - 0004, D357983, July 22, 2009 ), methox yfenozide “is not a developmental or reproductive toxicant”. The toxicology data base available for methoxyfenozide included acceptable developmental toxicity studies in both rats and rabbits as well as a 2 - generation reproductive toxicity study in rats. The data provided no indication of increased sensitivity of rats or rabbits to in utero and/or postnatal exposure to methoxyfenozide. EPA determined that an additional safety factor was not needed for the protection of infants and children (FQPA SF = 1x). 4. Subchronic toxicity. P er the 2009 Human Health review (Rate, EPA - HQ - OPP 2009 - 0012 - 0004, D357983, July 22, 2009), in subchronic and chronic oral studies in rats, the most toxicologicall y significant effects were mild anemia and mild effects on the liver, thy roid gland, and adrenal gland. In subchronic and chronic oral studies in dogs, the predominant toxic effect was anemia, which was often accompanied b y signs of a compensatory

response. 5. Chronic toxicity. Per the 2009 Human Health revie w (Rate, EPA - HQ - OPP 2009 - 0012 - 0004, D357983, July 22, 2009), the chronic population - adjusted dose (cPAD) is 0.1 mg/kg/day

based on hematological changes, liver toxicity , histopathological changes in th yroid and possible adrenal toxicity observed at the LOA EL of 411 mg/kg/day

in a chronic toxicity

study in rats.6. Animal metabolism. Per the 2009 Human Health review (Rate, EPA - HQ - OPP 2009 - 0012 - 0004, D357983, July 22, 2009), in a metabolism study in rats, 14 C methoxyfenozide was rapidly absorbed, distributed, metabolized and almost completely excreted within 48 hours. The major route of excretion was feces (86 - 97%) with lesser amounts in the urine (5 - 13%). Metabolism of methoxyfenozide in other animals (poul try and ruminants) appears to be similar to its metabolism in rats. Per the most recent EPA anal yt ical summary

for methoxyfenozide (D. Rate, US EPA, DP358341, June 10, 2009), the qualitative nature of methox yf enozide residues in livestock are adequately understood based on ruminant and poultry metabolism studies. The residue of concern is parent in milk and ruminant tissues (except meat by products), poultry

meat and fat. The residues of concern in meat b yproducts and eggs are methox yf enozide and the RH - 1 41,518 metabolite. 7. Metabolite toxicology . Per the 2009 Human Health review (Rate, EPA - HQ OPP - 2009 - 0012 - 0004, D357983, July 22, 2009), in a metabolism study in rats, methoxyfenozide is metabolized principally by O - demethylation of the A - ring methox y gr oup and oxidative hy droxylation of the B - ring methyl groups followed by conjugation with glucuronic acid. No significant sex - related or dose - dependent differences in metabolic disposition were noted. The methox yfenozide glucuronide conjugates are considere d to be less toxic than the parent compound because glucuronide conjugation is well known to be a commonly occurring detoxification mechanism in mammalian species since it results in the formation of more polar, more water - soluble metabolites which are rea dil y and easily excreted from the bod y (in this case, in the bile and urine). Further, based on similarities of chemical structure, the non - conjugated metabolites would be expected to be no more toxic than the parent compound. Furthermore, HED has covered potential metabolite exposure b y inclusion of RH - 141,518 along with the parent methoxyfenozide in the residue of concern for certain commodities: ruminant liver and kidney , eggs, poultry

live and poultry

meat by products. 8. Endocrine disruption . The avai lable mammalian toxicity and toxicokinetic studies on methoxyfenozide, including a 2 - generation reproduction study , developmental toxicity studies in two species, and repeat dose toxicity studies ranging from 28 day s to 2 ye ar studies in three species (rat , mouse, and dog), do not demonstrate that methoxyfenozide possesses endocrine disrupting properties that are relevant to humans. C. Aggregate Exposure 1. Dietary exposure. The starting point for this assessment was the DEEM file from the 2009 EPA dietary assessment (EPA, Hanson, DP361376, July 7, 2009). The Dietary Exposure Evaluation ModelTM (DEEM - FCI D, ver. 2.16, Exponent, Inc., Washington, DC - 20036) software was employ ed. DEEM contains food consumption data as reported b y respondents in the USDA Continuing Survey s of Food Intake by Individuals (CSFII) conducted in 1994 - 1996 and 1998 and food translation to RACs, as indicated b y EPA/USDA FCID recipe set as of August, 2002.i. Food. A chronic assessment was conducted to evaluate potential chronic die tary

exposure of the U.S. population subgroups to residues of methox yfenozide. These anal ys es cover all registered crops, as well as revised proposed tolerances. The current dietary assessment is an unrefined Tier I assessment using tolerance values and 100% crop - treated assumption to estimate dietary exposure to methoxy fenozide. DEEM (ver 7.81) default processing factors for all food commodities, with the exception of a methoxyfenozide - specific processing factor for orange juice (0.2X). The proposed ci trus, and root crop uses do not alter the livestock burden calculations; assessment of livestock tolerances is not required. ii. Drinking W

ater. There are no water - related exposure data from monitoring to complete a quantitative drinking water exposure analy sis and risk assessment for methoxyfenozide. The previous EPA estimates of 33.1 ppb for potential drinking water exposures have been directly incorporated in the DEEM - FCID into the food categories “water, direct, all sources” and “water, indirect, all sources.” Per the 2009 Human Health review (Rate, EPA - HQ - OPP - 2009 - 0012 - 0004, D357983, July 22, 2009), the established chronic endpoints are cRfD = cPAD = 0.10 mg/kg/day . The Tier - I DEEM exposure for food and water with revised proposed tolerances result ed in an estimated expos ure of 0.023895 mg/kg/day for the US general population which is 23.9% of the chronic RfD. For the most highly exposed population subgroup, children 1 to 2 y ears old, the estimated exposure is 0.056857 mg/kg/day at 56.9% of cPAD. These results are conservative (health protective) risk estimates. Refinements such as use of percent crop - treated information and/or anticipated residue values would y ield lower estimates of chronic dietary exposure. 2. Non - dietary exposure . A new use in ornamentals was recently approved for methoxyfenozide in 2009. Residential uses are limited to commercial applications on ornamentals for use in areas such as parks, recreation areas and residential propert y. Because there is no homeowner use, the pot ential exposure is limited to a post application scenario. To account for this additional use in the aggregate assessment, an estimate of the potential exposure according to the residential SOPs was conducted. Per the ornamental use label for Intrepid  2 F Insecticide, the maximum label rate is 0.25 lb/A. Per the 2009 Human Health review (Rate, EPA - HQ - OPP - 2009 - 0012 - 0004, D357983, July

22, 2009), methoxyfenozide has not shown significant toxicity by dermal and/or inhalation routes; endpoints were deemed unnecessary for dermal or inhalation exposure. Therefore, only the combined oral exposure for toddlers was estimated. Without a dermal endpoint, there is no assessment necessary for adult post - application exposure from ornamental uses. For toddlers, the c ombined potential oral exposure from hand to mouth, soil ingestion and object to mouth as 0.003747 mg/kg/day . Potential exposure was conservatively assessed against the chronic dietary NOAEL of 10.2 mg/kg/day

which was determined in the 2 - ye ar chronic rat study . The resulting MOE value of 2669 for the combined oral routes in toddlers is well above the 100 value threshold of concern for the EPA.For children, the potential post - application short term exposure from the ornamental use

pattern were combined with chronic dietary (food and water) exposure for determination of aggregate short - term exposure. The combined exposures were conservatively assessed against the chronic dietary endpoint with an assumed level of concern for incidental oral exposure of 10 0, for an aggregate risk assessment. The table below is a summary of the short - term aggregate exposures and risk estimates. Because the aggregate MOE values are 170 or greater, short - term aggregate exposure to methoxyfenozide is not of concern. Based on EPA’s conclusion that no dermal or inhalation endpoints were necessary , no aggregate risk assessment was conducted for adult . Short - Term

Aggregate Risk Calculations for Children Population NOAEL

(m g/kg/day) Target

MOE Chronic Food

and Water Exposure (m g/kg/day) Residential Oral

Exposure (m g/kg/day) Aggregate

Exposure (m g/kg/day) Aggregate

MOE (food, w ater, and residential) Children 1 - 2 yrs old 10.2 ) Target MOE 0.056857 0.003747 0.060604 170 Children 3 - 5 yrs old 0.044916 0.003747 0.048663 210 Children 6 - 12 yrs old 0.028025 0.003747 0.031772 320 D. Cumulative Effects Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify , or revoke a tolerance, the Agency considers “available information” concerning the cumulative effects of a particular pesticide’s residues and “other substances that have a common mechanism of toxicity .” EPA does not have, at this time, available data to determine whether methoxyfenozide has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity , methoxyfenozide does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, therefore, it is assumed that methox yfenozide does not have a common mechanism of toxicity with other substances. E. Safety Determination 1. U.S. population. Using the DEEM exposure assumptions described above, the dietary and water exposure to methoxyfenozide from the current and proposed new tolerances will utilize 23.9% of the chronic RfD for the US population. EPA generall y has no concern for exposures below 100% of the chronic RfD. It is concluded that there is a reasonable certainty

that no harm will res ult to US - general population from exposure to methoxyfenozide residues. 2. Infants and children . P er the 2009 Human Health review (Rate, EPA - HQ - OPP 2009 - 0012 - 0004, D357983, Ju ly 2 2, 20090, EPA has previously d etermined that an additional safet y factor wa s not needed for the protection of infants and children (FQPA SF = 1x). U sing the DEEM exposure assumptions described above for the dietary andwater exposure to methoxyfenozide with the current and proposed new tolerances, the

highest exposed subpopulati on is children 1 - 2 ye ars at 56.9% of the cPAD. E PA generall y has no concern for exposures below 100% of the cPAD because the cPAD represents the level at or below which daily a ggregate dietary

e xposure over a lifetime will not pose appreciable risks to human health. W hen the food, water and residential exposures are aggregated for children, the resulting MOEs are 170 or greater, which are well above the LOC of 100. Therefore, there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to methoxy fenozide exposure to methoxyfenozide residues. F. International Tolerances Several governing bodies have established Maximum Residue L evels (MRLs) for methoxyfenozide in a variety of crops. The germane international MR Ls for root crops and citrus fruits are found in the following table based on a MRLs compiled by searches in Homologa ( http://www.homologa.com/ ) , the EU SANCO website (http://ec.europa.eu/sanco_pesticides/public/index .cfm ) and the Australian MRLwebsite ( http://www.foodstandards.gov.au/foodstandards/foodstandardscode/standard142maximu mre4244.cfm ) . Homologa is a third part y database; I R - 4 makes no claim regarding the verification of these values relative to the individual national authoritative sources. The proposed change from 10 ppm to 1.9 ppm for citrus is congruent with other international tolerances. C ountry Crop Amount Unit Australia CI TRUS FRUITS 1 PPM Australia CI TRUS: PUL P - DRY 10 PPM CODEX Citrus 0.7 PPM EU Harmonized Citrus fruit 1 PPM EU Harmonized Root and tuber vegetables 0.02 PPM