EPA REGI STRATION DIVISION COMPANY NOTICE OF FILING FOR PESTI CI DE

PETI TI ONS PUBLISHED IN THE FEDERAL REGI STER EPA Registration Division contact: Laura Nollen, (703) 305 - 7390, nollen.laura@epa.gov Interregion al Research Project Number 4 (IR - 4) Petition Number (PP#) 2E8118 EPA has received a pesticide petition , PP# 2E8118 from Interregional Research Project Number 4 (IR - 4) , 500 College Road East, Suite 201 W, Princeton, NJ 08540 request ing, pursuant to secti on 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 .544 by establishing a tolerance for residues of methoxy fenozide, (3 - methoxy - 2 - methylbenzoic acid 2 - (3,5 - dimethylbenzoyl) - 2 - (1,1 - dimethylethyl) h ydraz ide) including its metabolites and degradates in or on the raw agricultural commodit ies under paragraph (a) in or on h erb subgroup 19A, except chive at 400 parts per million (ppm ) ; d ate at 7 ppm ; c aneberry subgroup 13 - 07 A at 6 ppm ; s orghum, grain, forage at 9 ppm ; s orghum, grain, stover at 15 ppm ; s orghum, grain, grain at 4 ppm ; s o rghum, sweet, forage at 9 ppm; s or ghum, sweet, stover at 15 ppm; sorghum, sweet, grain at 4 ppm; s orghum, sweet, stalk at 9 ppm; grain, aspirated grain fractions at 80 ppm ; p ea an d bean, dried shelled, except soybean, subgroup 6C, except pea, blackey ed, seed and pea, southern, seed at 0.5 ppm ; f ruit, small, vine climbing , except fuzzy kiwifruit, subgroup 13 - 07F at 1 ppm; b erry , l ow growing , except cranberry , subgroup 13 - 07G at 1.5 ppm; f ruit, pome, group 11 - 10 at 1.5 ppm; v egetable, fruiting, group 8 - 10 at 2 ppm ; sugar apple at 0.6 ppm; cherimoya at 0.6 ppm; atemoya at 0.6 ppm; custard apple at 0.6 ppm; ilama at 0.6 ppm; s oursop at 0.6 ppm; and b iriba at 0.6 ppm . Additionally , the petition requested to amend 40 CFR 180.544, under paragraph (2)( d) by establishing a tolerance for indirect or inadvertent residues of methox yf

enozide in or on r apese ed subgroup 20A at 1.0 ppm and s unf lower subgroup 20B at 1.0 ppm. Upon approval of the t olerances in paragraph (a), the petition also requests to amend the tolerance in paragraph (2)(d) from herb and spice, group 19, except coriander, leaves at 4.5 ppm to spice subgroup 19B at 4.5 ppm. It is also proposed that the tolerance for residues of me thoxy fenozide in or on p ea, dry , seed at 2.5 ppm ; b ean, dry , seed at 0.24 ppm; c oriander, leaves at 30 ppm ; grape at 1.0 ppm; strawberry at 1.5 ppm; fruit, pome, group 11 at 1.5 ppm; vegetable, fruiting, group 8 at 2.0 ppm; and okra at 2.0 ppm be removed u

pon the approval of the proposed tolerances listed above. 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 submi tted 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 Chemistry2 1. Plant metabolism. Per the EPA anal yt ical summary for methox yf

enozide (D. Rate, US EPA, DP358341, June 10, 2009), the nature of the residue of methoxyfenozide in plants has been studied in several plants (apple, cotton, grape and rice) and is adequatel y understood. 2. Analytical method. Per a recent 2012 decision on tolerances (M. Collante s, US EPA, D388978, May

23, 2012), EPA stated adequate single methods are available for tolerance enforcement in primary crops and animal commodities. Analy tical methodology

for the magnitude of residue studies was based on Dow AgroSciences method GRM 02. 25 “Determination of Residues of Methoxy fenozide in High Moisture Crops by L iquid Chromatograph y with Tandem Mass Spectrometry Detection“. 3. Magnitude of residues. The proposed tolerances in Crop Subgroup 19A (except chives), dates, Crop Subgroup 13 - 07 A , and sorghum commodities are all supported b y magnitude of residue studies in basil, dates, caneberry , sorghum and processed sorghum. The proposed tolerances in Crop subgroup 13 - 07F (except fuzzy kiwifruit), Crop subgroup 13 - 07G, Crop Group 11 - 10 and C rop group 8 - 10 are all supported by existing tolerances on representative commodities for that crop or subgroup (Grape, Strawberry , Crop Group 11 and Crop Group 8, respectivel y) without the need for additional data. The proposed tolerances for inadvertent or indirect tolerances in oilseeds are supported by an EPA 2009 review of existing data (D. Rate, US EPA, D357983, July 22, 2009) and a 2012 EPA recommendation (W. Drew, US EPA, D396397, May 1, 2012) for reinstatement without the need for additional data. Inaddition, a request is made for international harmonization of tolerances for Pea and bean, dried shelled, except soybean, subgroup 6C, except pea, blackeyed, seed and pea, southern, seed . Thus, the requested tolerances are all adequatel y supported . For Herb subgroup 19A, except chives , IR - 4 recently completed trials in fresh and dried basil with a 1 day

PHI (IR - 4 PR No. 07525, May 23, 2012 ) . Residues of methoxyfenozide were determined following 4 foliar applications of Intrepid  2F insecticide in at 5 field locations in Florida, North Carolina, New Mexico, Wisconsin and British Columbia during the 2009 growing season . Methoxyfenozide 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 9 - 11 day s apart and marketable basil leaves and stems were collected 1 day after the final application for analy sis of both fresh and dried samples . The methoxyfenozide residues in fresh basil ranged from a maximum of 47.2 ppm to a minimum of 9.26 ppm with a 43.4 ppm HAFT (Highest Average Field Trial) value at the PHI of 1 day . In dried basil observed residues ranged from a maximum of 194 ppm to a minimum of 56.3 ppm with HAFT value of 188 ppm. S ome decline was noted over the 1 2 day s within the decline trial . The limit of detection (LOD) and the limit of quantitation (LOQ) values were calculated as 0.0031 ppm and 0.0092 ppm, respectivel y for fresh basil, and 0.016 ppm and 0.049 ppm, respectivel y for dried basil. For Date, IR - 4 recently

completed trials in dates with a 7 day PHI (IR - 4 PR No. 10154, April 23, 2012). Residues of methoxy fenozide were determined following 3 foliar applications of Intrepid  2F insecticide at 4 field locations in California during the 20103

growing season. Methoxyfenozide was appli ed at a target rate of 0.31 lb ai/A, for a total of approximately

0.93 lb ai/A. Applications were made 9 - 11 day s apart and marketable mature fruit was collected 7 day s after the final application. Methoxyfenozide observed residues in date ranged from a m aximum of 3.3 ppm to a minimum of 1.5 ppm with a 3.1 ppm HAFT value at the PHIof 7 day . The LOD and LOQ values were calculated as 0.0013 ppm and 0.0038 ppm, respectivel y for dates. For Caneberry

subgroup 13 - 07 A, IR - 4 recentl y completed trials in blackbe rry and raspberry with a 3 day

PHI(IR - 4 PR No. 10470, February 6, 2012). Residues of methoxyfenozide were determined following 3 foliar applications of Intrepid  2F insecticide at 6 field locations in Michigan, North Carolina, California and Oregon durin g the 2010 growing season. Methox yf enozide was applied at a target rate of 0. 25 lb ai/A, for a total of approximately 0. 75 lb ai/A. Applications were made 6 - 8 day s apart and marketable mature fruit was collected 3 day s after the final application. Metho xyfenozide observed residues in blackberry ranged from a maximum of 2.5 ppm to a minimum of 0.62 ppm with a 2.5 ppm HAFT value at the PHI of 3 day . In raspberry observed residues ranged from a maximum of 2.3 ppm to a minimum of 1.6 ppm with HAFT value of 2 .2 ppm. The LOD and LOQ values were calculated as 0.00 40 ppm and 0.0 12 ppm, respectivel y for caneberry . For Sorghum, IR - 4 recently completed trials with a 3 day PHI for forage and a 21 day PHIfor stover and grain (IR - 4 PR No. 07241, March 23, 2012). Re sidues of methoxyfenozide were determined following 4 foliar applications of Intrepid  2F insecticide at 12 field locations in Arkansas, North Carolina, North Dakota, Nebraska, New Mexico, South Dakota, and Texas during the 2010 growing season. Methox yf en ozide was applied at a target rate of 0. 12 lb ai/A, for a total of approximately 0. 48 lb ai/A. Applications were made 9 - 1 4 day s apart and forage was collected 2 - 3 day s after the final application , and grain and stover were collected 11 - 23 day s after the f inal application . Methox yfenozide observed residues in forage ranged from a maximum of 5.6 ppm to a minimum of 0.7 ppm with a 5.0 ppm HAFT value at the PHI of 3 day . In stover observed residues ranged from a maximum of 9.7 ppm to a minimum of 0.29 ppm wi th HAFT value of 2.8 ppm. In grain observed residues ranged from a maximum of 2.6 ppm to a minimum of 0.15 ppm with HAFT value of 2.25 ppm. Aspirated grain fractions (AGF) processed from bulk grain samples had a residue of 17 ppm whereas the unprocesse d grain from the same trial had a residue of 0.48 ppm. The s yrup sample processed from sweet sorghum stalks had the same residue (1.1 ppm) as the unprocessed stalks. The LOD and LOQ values were calculated as 0.00 71 ppm and 0.0 213 ppm, 0.0012 and 0.0037 p pm, 0.0026 and 0.0079 ppm, 0.0006 and 0.0019 ppm, 0.0003 and 0.0008 ppm, respectivel y for sorghum forage, grain, stover, aspirated grain and sy rup . Tolerance requests for fruiting vegetable group 8 - 10, pome fruit group 11 - 10, subgroup 13 - 07F and subgroup 13 - 07G are crop group/subgroup revisions based upon established tolerances. Tolerances for sugar apple, cherimoya, atemo ya, custard apple, ilama, soursop, and biriba are based upon the existing avocado tolerances and registration.4

B. Toxicological Profi le The toxicological profile for methox yfenozide which supports this petition to revise tolerances was reviewed in 2009 (Rate, EPA - HQ - OPP - 2009 - 0012 - 0004, D357983, July

22, 2009) and again in the the 2012 Human Health review (Collantes, US EPA, D388978, May 23, 2012), and the endpoints for risk assessment are reiterated in EPA’s most recent dietary assessment (EPA, Holman, D389738, March 2, 2012). EPA has concluded “The toxicity database is considered complete for the purposes of characterizing the hazard a ssociated with methoxyfenozide and for conducting a human health risk assessment.” EPA has not established an acute reference dose for methox yf

enozide and the chronic RfD is equivalent to the chronic PAD = 0.1 mg/kg/day , because the FQPA SF has been reduc ed to 1X. 1. Acute toxicity. Per the 2009 Human Health review (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 includin g the acute neurotoxicity

study in rats, the developmental toxicity 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 Hum an 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. Per the 2009 Human Health revi ew (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 rab bits 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. Per 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 toxicologic all 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

respo nse . In 2012 (Colantes, US EPA, D388978, M ay 2012), new inhalation endpoints for Short - Term (1 - 30 day s) and Intermediate Term (1 - 6 months) were established with a NOAEL of 16.8 mg/kg/day for use in residential and occupational assessments . 5. Chronic toxicity. Per the 2009 Human Health review (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 possi ble adrenal toxicity observed at the LOAEL of 411 mg/kg/day

in a chronic toxicity

study in rats .5 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, 14C methoxyf enozide 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 (poultry and ruminants) appears to be similar to its metabolism in rats. Per the EPA anal yt ical summary for methoxy fenozide (D. Rate, US EPA, DP358341, June 10, 2009), the qualitative nature of methox yf enozide residues in livestock are adequatel y understood based on rum inant 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 - 141,518 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 group and oxidative hydr oxylation 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 considered 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 readil y and easily excret ed from the body (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 e xposure 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 r and poultry

meat b yproducts . 8. Endocrine disruption . The available mammalian toxic ity 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 2012 EPA dietary assessment (EPA, H olman , D389738 , March 2 , 20 12 ). The Dietary Exposure Evaluation ModelTM (DEEM - FCID, ver. 3.14 ) software was employ ed. DEEM contains food consumption data based on NHANES 2 - day food Consumption data for 2003 to 2008 and food translation to RACs, as indicated by EPA/USDA FCID recipe se t as of February

2012 . i. Food. A chronic assessment was conducted to evaluate potential chronic dietary6

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 tol erances. 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 and default processing factors for all food commodities, with the exception o f a methoxy fenozide specific processing factor for orange juice (0.2X). Although the proposed sorghum uses alter the MRBD livestock burden calculations very slightly , existing tolerances for meat and milk are sufficient to cover the very small change and no increase in tolerance for animal commodities is needed . ii. Drinking water. 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 have recentl y been conservativel y increased by EFED based on new model assumptions in 2012 (Gebken, US EPA, D388876, May

23, 2012). F or potential drinking water exposures the new value of 43.4 ppb ha s 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 resulted in an estimated exposure of 0.024775 mg/kg/day for the US general population which is 2 4.8 % of the chronic RfD. For the most highly exposed population subgroup, children 1 to 2 y ears old, the estimated exposure is 0.06666 mg/kg/day at 66.7 % of cPAD. These results are conservative (health protective) risk estimates. Refinements such as use of percent crop - treated information and/or anticipated residue values wou ld yield lower estimat es of chronic dietary exposure. 2. Non - dietary exposure . A new use in ornamentals was recently approved for methoxyfenozide in 2009. Per the 2012 review (Collantes, US EPA, D388978, May 23, 2012), EPA made the conservative interpre tation that the label did not preclude homeowner use on ornamentals. Thus in accordance with FQPA, EPA conducted an aggregate assessment to include residential handler exposure for adults. The dietary exposure of the general adult US population was aggreg ated with exposure estimates from residential use of a backpack spray er treatment of ornamentals. The calculated exposure resulted in an aggregate MOE of 670, which is significantl y higher than the stated LOC of 100 for methox yf enozide, and thus is not of concern. The proposed tolerances in this petition do not make significant contributions to the dietary consumption patterns. Thus the small change in the dietary contribution did not result in a change in MOE for adults; it remains 670 and hence the ris k estimate is not of concern for adults . It is also noted that for children, the EPA concluded that: “there are no residential uses of methoxyfenozide that would result in significant postapplication exposure to children, based on ornamental use only. Th erefore the aggregate exposure and risk for children is equivalent to those from food and water.” D. Cumulative Effects7 Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify , or revoke a tolerance, the Agency considers “av ailable 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 a ppear 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 3.14 exposure assumptions described above, the dietary

and water exposure to methoxy fenozide from the current and proposed new tolerances will utilize 24.8 % of the chronic RfD for the US population. EPA generally has no conce rn for exposures below 100% of the chronic RfD. It is concluded that there is a reasonable certaint y that no harm will result to US - general population from dietary exposure to methoxyfenozide residues . When the food, water and residential exposures are agg regated for adults , the resulting MOEs are 670 , which are well above the LOC of 100 ; values above the LOC are t ypicall y not of a concern for the Agency . 2. Infants and children . Per the 2009 Human Health review (Rate, EPA - HQ - OPP 2009 - 0012 - 0004, D357983, July 22, 20090, EPA has previousl y determined that an additional safet y factor was not needed for the protection of infants and children (FQPA SF = 1x). Using the DEEM exposure assumptions described above for the dietary and water exposure to methoxyfenoz ide with the current and proposed new tolerances, the highest exposed subpopulation is children 1 - 2 y ears at 66.7 % of the cPAD. EPA generall y has no concern for exposures below 100% of the cPAD because the cPAD represents the level at or below which dail y aggregate dietary exposure over a lifetime will not pose appreciable risks to human health . F. International Tolerances Several governing bodies have established Maximum Residue L evels (MRLs) for methoxyfenozide in a variety of crops. The related inte rnational MRL s are found in the following table based on a review of MRL s compiled by searches in the USDA MRL database ( http://www.mrldatabase.com/results.cfm ), Homologa ( http://www.homologa.com/), the EU SANCO website ( http://ec.europa.eu/sanco_pesticides/public/index.cfm), Japan MRLlisting ( http://www.m5.ws001.squarestart.ne.jp/foundation/agrdtl.php?a_inq=75700 ) and the Australian MRLwebsite ( http://www.comlaw.gov.au/Series/F2008B00619 ) . Homologa is a third party

database; IR - 4 makes no claim regarding the verification of these values relative to the individual national authoritative sources.8

Commodity Existing MRL a (ppm) Regulatory

Authority Beans (dry) 0.5 CODEX Cowpea (dry) 5 CODEX Beans, dried 4 Japan Other herbs 30 Japan Other fruits 0.1 Japan Beans (Broad beans, navy beans, flageolets, jack beans, lima beans, field beans, cowpeas) 5 EU SANCO Peas (Chickpeas, field peas, chickling vetch) and Pulse, dry

others 0.02* EU SANCO Cane fruit, Dates, Herbs 0.02* EU SANCO Sorghum 0.05* EU SANCO Rape seed (Bird rapeseed, turnip rape) 0.05* EU SANCO Sunflower seed 0.05* EU SANCO Herbs T20 Australia Cherimoya (Custard apple, sugar apple (sweetsop), Il ama and other medium sized Annon aceae) 0.6 EU SANCO Soursop (guanabana) 0.02* EU SANCO Custard apple 0.3 Australia a T he * and T notations are direct translations from the country website listings.