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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [insert name and telephone number with area 

code]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert “NA-Remove” and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., “[insert 

company name],” with the information specific to your action.

TEMPLATE:

[Dow AgroSciences, LLC]

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from [Dow 

AgroSciences, LLC], [9330 Zionsville Rd., Indianapolis, IN 46268] 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

by establishing a tolerance for residues of

[methoxyfenozide, including its metabolites and degradates. Compliance 

with the tolerance levels is to be determined by measuring only the active 

ingredient: methoxyfenozide [3-methoxy-2-methylbenzoic acid 2-(3,5-

dimethylbenzoyl)-2-(1,1-dimethylethyl) hydrazide]] in or on the raw agricultural 

commodity [under paragraph (a) as Pineapple] at [0.7] parts per million (ppm). 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 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.
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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 tolerance in pineapple is supported 

by magnitude of residue studies in pineapple. Thus, the requested tolerance is

adequately supported.

Dow AgroSciences recently completed trials in pineapples with 3 and 10 day PHIs

(Dow AgroSciences Study No. 110317, March 14, 2012). Residues of 

methoxyfenozide were determined following 4 foliar applications of GF-837 at 4 

field locations in Costa Rica and 4 field locations in Hawaii during the 2011 growing 

season. Methoxyfenozide was applied at a target rate of 0.107 lb ai/A, for a total of 

approximately 0.428 lb ai/A. A surfactant was included in each tank mix. 

Marketable mature fruit was collected 3 and 10 days after the final application. For 

the 3-day PHI, methoxyfenozide observed residues in pineapple ranged from 0.0808-

0.365 ppm with a HAFT of 0.346 in the Hawaii trials and 0.0276-0.0824 ppm with a 

HAFT of 0.0626 in the Costa Rica trials. For the 10-day PHI, methoxyfenozide 

observed residues in pineapple ranged from 0.109-0.374 ppm with a HAFT of 0.355 

ppm in the Hawaii trials and 0.0189-0.0277 ppm with a HAFT of 0.0266 ppm in the 

Costa Rica trials. The LOD and LOQ values were calculated as 0.003 ppm and 

0.001 ppm, respectively for pineapple.]

B. Toxicological Profile [The toxicological profile for methoxyfenozide which 

supports this petition to revise tolerances was reviewed in 2009 (Rate, EPA-HQOPP-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-OPP2009-0012-0004, 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-
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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-HQOPP-2009-0012-0004, 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.]

6. Animal metabolism. [Per the 2009 Human Health review (Rate, EPA-HQOPP-2009-0012-0004, 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 
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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 exposure of the U.S. population subgroups to residues of methoxyfenozide. 

These analyses cover all registered crops, as well the proposed tolerance. 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 

methoxyfenozide-specific processing factor for orange juice (0.2X).]

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 were

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 DEEMFCID 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 
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mg/kg/day. The Tier-I DEEM exposure for food and water with revised proposed 

tolerances resulted in an estimated exposure of 0.023719 mg/kg/day for the US 

general population which is 23.7% of the chronic RfD. For the most highly exposed 

population subgroup, children 1 to 2 years old, the estimated exposure is 0.063427

mg/kg/day at 63.4% 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 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 current assessment resulted in slightly lower estimates of adult dietary exposure 

(due to changes in the DEEM-FCID dietary intake model). Thus the small change 

in the dietary contribution resulted in a slight increase in the MOE for adults from 

670 to 700; 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

[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 23.7% of the chronic RfD for the US 
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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 700, 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-HQOPP-2009-0012-0004, 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 63.4% 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. The 

residential uses are not anticipated to result in exposure to children, so the 

aggregate exposure is equivalent to the dietary exposure, and therefore is not of

concern.]

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; Dow AgroSciences makes no claim regarding the verification 

of these values relative to the individual national authoritative sources. Listed 

tolerance on pineapples, seem to have been driven by positive lists which are set at 

the method LOQ level. 

Commodity Existing MRLa

(ppm)

Regulatory 

Authority

Pineapple 0.02 EU SANCO

Other Fruits 0.1 Japan

Pineapple 0.02 Chile

]