EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Laura Nollen, (703) 305-7390, nollen.laura@epa.gov

Interregional 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

requesting, pursuant to section 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 methoxyfenozide, (3-methoxy-2-methylbenzoic acid 2-(3,5-

dimethylbenzoyl)-2-(1,1-dimethylethyl) hydrazide) including its metabolites and 

degradates in or on the raw agricultural commodities under paragraph (a) in or on herb 

subgroup 19A, except chive at 400 parts per million (ppm); date at 7 ppm; caneberry

subgroup 13-07A at 6 ppm; sorghum, grain, forage at 9 ppm; sorghum, grain, stover at 15 

ppm; sorghum, grain, grain at 4 ppm; sorghum, sweet, forage at 9 ppm; sorghum, sweet, 

stover at 15 ppm; sorghum, sweet, grain at 4 ppm; sorghum, sweet, stalk at 9 ppm; grain, 

aspirated grain fractions at 80 ppm; pea and bean, dried shelled, except soybean, 

subgroup 6C, except pea, blackeyed, seed and pea, southern, seed at 0.5 ppm; fruit, 

small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F at 1 ppm; berry, low 

growing, except cranberry, subgroup 13-07G at 1.5 ppm; fruit, pome, group 11-10 at 1.5 

ppm; vegetable, 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; soursop at 0.6 

ppm; and biriba 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 methoxyfenozide in or on rapeseed subgroup 20A at 1.0 ppm and sunflower 

subgroup 20B at 1.0 ppm. 

Upon approval of the tolerances 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 methoxyfenozide in or on pea, dry, seed at 2.5 ppm; bean, dry, seed at 0.24 

ppm; coriander, 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 upon 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 

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
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1. Plant metabolism. Per the EPA analytical summary for methoxyfenozide (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 

adequately understood. 

2. Analytical method. Per a recent 2012 decision on tolerances (M. Collantes, US 

EPA, D388978, May 23, 2012), EPA stated adequate single methods are available for 

tolerance enforcement in primary crops and animal commodities. Analytical 

methodology for the magnitude of residue studies was based on Dow AgroSciences 

method GRM 02.25 “Determination of Residues of Methoxyfenozide in High Moisture 

Crops by Liquid Chromatography with Tandem Mass Spectrometry Detection“.

3. Magnitude of residues. The proposed tolerances in Crop Subgroup 19A (except 

chives), dates, Crop Subgroup 13-07A, and sorghum commodities are all supported by 

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 Crop 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, respectively) 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. In addition, 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 adequately 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 days apart and marketable basil leaves and stems were collected 1 day after 

the final application for analysis 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. Some decline was noted over the 12 days 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, respectively for fresh basil, and 0.016 

ppm and 0.049 ppm, respectively 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 methoxyfenozide were determined following 3 foliar 

applications of Intrepid 2F insecticide at 4 field locations in California during the 2010 
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growing season. Methoxyfenozide was applied 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 days apart and marketable 

mature fruit was collected 7 days after the final application. Methoxyfenozide observed 

residues in date ranged from a maximum of 3.3 ppm to a minimum of 1.5 ppm with a 3.1 

ppm HAFT value at the PHI of 7 day. The LOD and LOQ values were calculated as 

0.0013 ppm and 0.0038 ppm, respectively for dates.

For Caneberry subgroup 13-07A, IR-4 recently completed trials in blackberry 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 during 

the 2010 growing season. Methoxyfenozide 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 days apart and 

marketable mature fruit was collected 3 days after the final application. 

Methoxyfenozide observed residues in blackberry ranged from a maximum of 2.5 ppm to 

a minimum of 0.62 ppm with a 2.5ppm 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 0.0040 ppm and 

0.012 ppm, respectively for caneberry.

For Sorghum, IR-4 recently completed trials with a 3 day PHI for forage and a 21 day

PHI for stover and grain (IR-4 PR No. 07241, March 23, 2012). Residues 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. 

Methoxyfenozide 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 9-14 days apart and forage was collected 2-3 days 

after the final application, and grain and stover were collected 11-23 days after the final 

application. Methoxyfenozide 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 

with 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 

unprocessed grain from the same trial had a residue of 0.48 ppm. The syrup 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 0.0071 ppm and 0.0213 ppm, 

0.0012 and 0.0037 ppm, 0.0026 and 0.0079 ppm, 0.0006 and 0.0019 ppm, 0.0003 and 

0.0008 ppm, respectively for sorghum forage, grain, stover, aspirated grain and syrup.

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, atemoya, custard apple, ilama, 

soursop, and biriba are based upon the existing avocado tolerances and registration.
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B. Toxicological Profile The toxicological profile for methoxyfenozide 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 associated with methoxyfenozide and for 

conducting a human health risk assessment.” EPA has not established an acute reference 

dose for methoxyfenozide and the chronic RfD is equivalent to the chronic PAD = 0.1 

mg/kg/day, because the FQPA SF has been reduced 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 including 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 Human Health review (Rate, EPA-HQ-OPP-2009-

0012-0004, D357983, July 22, 2009), methoxyfenozide demonstrated a “lack of 

genotoxicity in an acceptable battery of mutagenicity studies.”

3. Reproductive and developmental toxicity. Per the 2009 Human Health review 

(Rate, EPA-HQ-OPP-2009-0012-0004, D357983, July 22, 2009), methoxyfenozide “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. Per the 2009 Human Health review (Rate, EPA-HQ-OPP2009-0012-0004, D357983, July 22, 2009), in subchronic and chronic oral studies in rats, 

the most toxicologically significant effects were mild anemia and mild effects on the 

liver, thyroid gland, and adrenal gland. In subchronic and chronic oral studies in dogs, the 

predominant toxic effect was anemia, which was often accompanied by signs of a 

compensatory response. In 2012 (Colantes, US EPA, D388978, May 2012), new 

inhalation endpoints for Short-Term (1-30 days) 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-OPP2009-0012-0004, 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 thyroid and possible adrenal toxicity observed at the LOAEL of 411

mg/kg/day in a chronic toxicity study in rats.
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6. Animal metabolism. Per the 2009 Human Health review (Rate, EPA-HQ-OPP2009-0012-0004, D357983, July 22, 2009), in a metabolism study in rats, 14Cmethoxyfenozide 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 analytical 

summary for methoxyfenozide (D. Rate, US EPA, DP358341, June 10, 2009), the 

qualitative nature of methoxyfenozide 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 byproducts), poultry meat and fat. The residues 

of concern in meat byproducts and eggs are methoxyfenozide and the RH-141,518 

metabolite.

7. Metabolite toxicology. Per the 2009 Human Health review (Rate, EPA-HQOPP-2009-0012-0004, D357983, July 22, 2009), in a metabolism study in rats, 

methoxyfenozide is metabolized principally by O-demethylation of the A-ring methoxy 

group and oxidative hydroxylation 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 methoxyfenozide 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 

readily and easily excreted 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 exposure by inclusion of RH-141,518 along with the parent 

methoxyfenozide in the residue of concern for certain commodities: ruminant liver and 

kidney, eggs, poultry liver and poultry meat byproducts.

8. Endocrine disruption. The available 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 days to 2 

year 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, Holman, D389738, March 2, 2012). The 

Dietary Exposure Evaluation ModelTM (DEEM-FCID, ver. 3.14) software was employed. 

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 set as of February 2012.

i. Food. A chronic assessment was conducted to evaluate potential chronic dietary
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exposure of the U.S. population subgroups to residues of methoxyfenozide. These 

analyses 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 methoxyfenozide and default 

processing factors for all food commodities, with the exception of a methoxyfenozidespecific 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 analysis and risk assessment for 

methoxyfenozide. The previous EPA estimates of 33.1 ppb have recently been 

conservatively increased by EFED based on new model assumptions in 2012 (Gebken, 

US EPA, D388876, May 23, 2012). For potential drinking water exposures the new 

value of 43.4 ppb has 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 

24.8% of the chronic RfD. For the most highly exposed population subgroup, children 1 

to 2 years 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 would yield lower 

estimates 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 interpretation 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 aggregated with exposure estimates 

from residential use of a backpack sprayer treatment of ornamentals. The calculated 

exposure resulted in an aggregate MOE of 670, which is significantly higher than the 

stated LOC of 100 for methoxyfenozide, 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 risk 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. Therefore the aggregate exposure 

and risk for children is equivalent to those from food and water.”

D. Cumulative Effects
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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 by other substances. For the purposes of this tolerance action, therefore, it is 

assumed that methoxyfenozide 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 methoxyfenozide from the current and proposed new 

tolerances will utilize 24.8% of the chronic RfD for the US population. EPA generally

has no concern for exposures below 100% of the chronic RfD. It is concluded that there 

is a reasonable certainty that no harm will result to US-general population from dietary

exposure to methoxyfenozide residues. When the food, water and residential exposures 

are aggregated for adults, the resulting MOEs are 670, which are well above the LOC of 

100; values above the LOC are typically not of a concern for the Agency.

2. Infants and children. Per the 2009 Human Health review (Rate, EPA-HQ-OPP2009-0012-0004, D357983, July 22, 20090, EPA has previously determined that an 

additional safety 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 methoxyfenozide with the current and proposed new tolerances, the 

highest exposed subpopulation is children 1-2 years at 66.7% of the cPAD. EPA 

generally has no concern for exposures below 100% of the cPAD because the cPAD 

represents the level at or below which daily aggregate dietary exposure over a lifetime 

will not pose appreciable risks to human health.

F. International Tolerances

Several governing bodies have established Maximum Residue Levels (MRLs) for 

methoxyfenozide in a variety of crops. The related international MRLs are found in the 

following table based on a review of MRLs 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 MRL listing 

(http://www.m5.ws001.squarestart.ne.jp/foundation/agrdtl.php?a_inq=75700) and the 

Australian MRL website (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. 
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Commodity Existing MRLa

(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), Ilama and other medium sized 

Annonaceae)

0.6 EU SANCO

Soursop (guanabana) 0.02* EU SANCO

Custard apple 0.3 Australia

a

The * and T notations are direct translations from the country website listings.