UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: 

Subject: 

PC Code: 

Decision No.: 

Petition No.: 

April 7, 2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Methoxyfenozide. Occupational and Residential Exposure Assessment for 

Proposed Use on Pineapple. 

12l027 DP Barcode: 0413707 

478935 Registration No.: 62719-442 

3F8179 Regulatory Action: Section 3 

Assessment Type: OccupationaVResidential Case No.: 743 1 

TXRNo.:NA 

MRIDNo.:NA 

From: 

Through: 

To: 

Introduction 

CAS No.: 161050-58-4 

40CFR: 180.544 

Margarita Collantes, Biologist <--t'lizlftzufo!-e (2/1~..?.:­ Risk Assessment Branch (RAB) II 

Health Effects Division (7509P) 

Christina Swartz, Branch Chief 

Risk Assessment Branch (RAB) II 

Health Effects Division (7509P) 

Olga Odiott, Risk Manager 

Deborah McCall, Branch Chief 

Insecticide Branch 

Registration Division (7505P) 

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an 

exposure and risk assessment for proposed new use of the insecticide methoxyfenozide to control 

pests in pineapples. The proposed new use of methoxyfenozide on pineapples reflects the same 

application methods and agricultural practices as currently registered uses assessed in the most 

recent occupational risk assessment; however, the proposed use rate on pineapple is lower (0.1 lb 

ai/acre or 0.01 lb ai/gal) than the registered uses (0.25 lb ai/acre or 0.025 lb ai/gal). Therefore, 

the previous occupational exposure assessment for methoxyfenozide on citrus (M. Collantes, 

D389739, February 27, 2012) is expected to be protective of the proposed new use on pineapple. 

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Table of Contents 

1.0 Executive Summary ........................................................................ ...... ............................... 3 

2.0 Risk Assessment Conclusions and Recommendations ........................................................ 5 

3.0 Hazard Characterization ... ....... ....... ....... ........ .... ... ........... ..................................................... 5 

4.0 Use Profile ............................................................................................................... .... ........ 7 

5.0 Residential Exposure and Risk Estimates ............ ........... ..................................................... 7 

5.1 Residential Risk Estimates for Use in Aggregate Assessment ................... .... ................. 8 

6.0 Occupational Exposure and Risk Estimates ........................................................................ 9 

6.1 Occupational Handler Exposure/Risk Estimates .............................................................. 9 

6.2 Occupational Post-application Exposure/Risk Estimates ................. ...................... ~ ........ 9 

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1.0 Executive Summary 

Dow AgroSciences LLC has submitted a petition (PP#3F8179) proposing a new use for the 

active ingredient methoxyfenozide (benzoic acid, 3-methoxy-2-methyl-, 

2-(3,5-dimethylbenzoyl)-2- (1,1-dimethylethyl) hydrazide). The proposed new use allows 

application to pineapple, in Hawaii only, and will be added to the Intrepid® 2F (Reg. No. 62719-

442) label. Methoxyfenozide is an insecticide currently registered for use on ornamentals and on 

numerous agricultural crops, such as dried peas and beans, pomegranate, popcorn, and citrus 

(crop group 10). 

Intrepid 2F is formulated as a flowable concentrate containing 22.6% active ingredient (ai) or 2 

lb ai per gallon. The proposed use on pineapple allows application at a maximum rate of 0.10 lbs 

ai per acre (A) through a variety of methods including: aerial, ground (airblast and groundboom), 

and hand held equipment. The personal protective equipment (PPE) statement on the proposed 

label requires applicators and other handlers to wear long-sleeved shirt and long pants, socks, 

shoes, and chemical-resistant gloves. The proposed use is anticipated to result in short- and 

intermediate-term durations of exposure; long-term exposures are not expected. 

Methoxyfenozide is currently registered for use on ornamentals, the only potential scenario 

involving residential exposure; the residential handler exposure and risk estimates associated 

with use on ornamentals are presented in this document for the purpose of completing an 

aggregate risk assessment, and have not changed since the previous assessment (Memo, 

0388978, M. Collantes et al., 23 May 2012), which was completed using the 2012 Residential 

SOPs (Trees and Gardens). 

Hazard Characterization 

Methoxyfenozide shows low acute toxicity by all routes of exposure (Toxicity Category III for 

dermal, and Category IV for oral and inhalation). Although it is a very mild eye irritant, it is not 

a dermal irritant nor a dermal sensitizer. 

A dermal endpoint was not selected since the rat 28-day dermal toxicity study did not 

demonstrate systemic toxicity up to the limit dose ( 1,000 mg/kg/day). Furthermore, the 

developmental toxicity studies in the rat and rabbit showed no maternal or developmental 

toxicity, and the rat subchronic dietary neurotoxicity showed no toxicity up to the limit dose 

(1000 mg/kg/day). Therefore, the rat 28-day dermal toxicity study was considered protective of 

sensitive populations, including potential developmental effects, and a dermal assessment is not 

required. 

In the absence of a route-specific inhalation study, a two-week dietary study in the dog was 

selected to assess both short- and intermediate-term inhalation exposure because it provided the 

most sensitive dose and endpoint available (no observable adverse effect level (NOAEL) of 16.8 

mg/kg/day, based on hematological effects at the lowest observable adverse effect level 

(LOAEL) of90.8 mg/kg/day. The Hazard and Science Policy Council (HASPOC) determined 

that based on a weight of evidence (WOE) approach, a 28-day inhalation toxicity study is not 

required for methoxyfenozide. Since no route-specific data are available, toxicity by the 

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inhalation route is considered to be equivalent to toxicity by the oral route of exposure. Since the 

inhalation endpoint was not based on developmental or reproductive effects, the average adult 

body weight of 80 kilograms (kg) was used to estimate inhalation exposure. 

The potential for post-application incidental oral exposure to children is not expected for 

registered residential ornamental use sites; therefore, an incidental oral endpoint was not 

selected. 

For risk assessment purposes, the level of concern (LOC) for all occupational and residential 

scenarios is based on the combined uncertainty factors of 1 OX each for inter species extrapolation 

and intraspecies variability. The required lOX Food Quality Protection Act (FQPA) safety factor 

(SF) for the protection of infants and children has been reduced to 1 X. Therefore, margins of 

exposure (MOEs) less than 100 represent risks of concern, and MOEs equal to or greater than 

100 are not of concern. 

Methoxyfenozide is classified as not likely to be carcinogenic to humans. 

Residential Exposure 

There are no new proposed residential uses at this time; however, the existing residential use on 

ornamentals was previously reassessed to reflect updates to HED's 2012 Residential SOPs1 

along with policy changes for body weight assumptions (M. Collantes, D389739, 02/27/12). 

There has been no change to the residential exposure and risk assessment since the 2012 review, 

and therefore the results are presented herein for the aggregate assessment associated with the 

new food use on pineapple. Residential handler risk estimates resulted in MOEs ;::76,000. 

In the absence of a dermal endpoint and POD, a dermal post-application exposure assessment 

was not conducted, and there is no risk associated with dermal exposure for individuals entering 

treated areas. Based on the Agency's current practices, a quantitative post-application inhalation 

exposure assessment was not performed for the use of methoxyfenozide on ornamentals. 

The recommended residential exposure scenario for use in the adult aggregate assessment 

reflects residential handler inhalation exposure from applications to ornamentals via backpack 

sprayer. The exposure estimate for this scenario resulted in a MOE of 76,000, which is greater 

than the LOC of 100 and is not of concern. · 

Occupational Exposure 

The proposed new use of methoxyfenozide on pineapples reflects the same application methods 

and agricultural practices as currently registered uses assessed in the most recent occupational 

risk assessment; however, the proposed application rate is lower (0.1 lb ai/acre or 0.01 lb ai/gal) 

than the registered uses most recently assessed (0.25 lb ai/acre or 0.025 lb ai/gal). Therefore, the 

previous occupational exposure assessment for methoxyfenozide on citrus (M. Collantes, 

D389739, February 27, 2012) is expected to be protective of the proposed new use on pineapple. 

A new quantitative occupational exposure assessment was not performed for the proposed use on 

pineapple. Short-term inhalation risk estimates for occupational handlers resulted in MOEs 

ranging from 28,000 to 2, 700,000 at the baseline level of personal protection (i.e., no respirator) 

1 Available: http:l/www.epa.gov/pesticides/science/residential-exposure-sop.html 

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and were not of concern. Given the lower application rate for use on pineapple, MOEs for the 

new use would be even higher. 

In the absence of a dermal endpoint and POD, a dermal post-application exposure assessment 

was not conducted, and there is no risk associated with dermal exposure to workers either 

treating pineapple or re-entering treated areas. Based on the Agency's current practices, a 

quantitative non-cancer occupational post-application inhalation exposure assessment was not 

performed in conjunction with the proposed use. If new policies or procedures are put into place, 

the Agency may revisit the need for a quantitative occupational post-application inhalation 

exposure assessment for methoxyfenozide. 

Restricted Entry Interval (REI) 

The proposed 4-hour REI which appears on the proposed supplemental label is consistent with 

the 4-hour REI on the master label, and thus classifies methoxyfenozide as a reduced risk 

candidate. 

Human Studies Review 

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical.· These data, which include studies from 

PHED 1.1 ; the AHETF database; and the Outdoor Residential Exposure Task Force (ORETF) 

database are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, 

and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review 

may have included review by the Human Studies Review Board. Descriptions of data sources, 

as well as guidance on their use, can be found at the Agency website2• 

2.0 Risk Assessment Conclusions and Recommendations 

There are no residential/occupational risk estimates of concern associated with the registered 

ornamental or proposed new agricultural uses of methoxyfenozide on pineapple. Occupational 

exposure scenarios resulted in inhalation handler MOEs that were not of concern (i.e., short- and 

intermediate-term MOEs ~ 100) for methoxyfenozide, at the label-specified PPE (e.g., no 

respirator). Furthermore, there are no label recommendations or data deficiencies that must be 

resolved prior to allowing the proposed new use on pineapple. 

3.0 Hazard Cha.racterization 

Methoxyfenozide is a diacylhydrazine insecticide active against lepidopterous insects (moths and 

butterflies) by competitively binding to receptors of the molting hormone in larvae. Many of the 

available short-term or subchronic toxicity studies on methoxyfenozide showed little or no 

toxicity. The main targets were the liver, thyroid, and red blood cells. 

Acute Toxicity 

Methoxyfenozide shows low acute toxicity by all routes of exposure (Toxicity Category III for 

2 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html 

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dermal, and Category IV for oral and inhalation); although a very mild eye irritant, 

methoxyfenozide is not a dermal irritant nor is it a dermal sensitizer. A summary of the acute 

toxicity for methoxyfenozide is provided in Table 3. 

Table 3. Acute Toxicity Profile- Methoxyfenozide Technical. 

Guideline No. Study Type MRID(s) Results Toxicity Category 

870.1100 Acute oral [rat] 44144415 LDso >5000 IV 

mglkg, both sexes 

870.1100 Acute oral [mouse] 44144416 LDso >5000 IV 

mglkg, both sexes 

870.1200 Acute dermal [rat] 44144418 LDso >2000 III 

mglkg, both sexes 

870.1300 Acute inhalation [rat] 44144420 LCso >4.3 mg!L, IV 

both sexes 

870.2400 Acute eye irritation [rabbit] 44144422 Very mild irritant IV 

870.2500 Acute dermal irritation (rabbit] 44144424 Not an irritant IV 

870.2600 Skin sensitization [Guinea pig] 44144426 Not a sensitizer N/A 

3.1 Toxicological PODs Used for Risk Assessment and Uncertainty Factor 

Considerations 

A summary of the toxicological doses and endpoints for occupational and residential exposure 

scenarios is provided in Table 3.1. 

Table 3.1. Summary of Toxicological Doses and Endpoints for Methoxyfenozide for Use in Occupational 

and Residential Risk Assessments. 

Exposure/ Point of Uncertainty Level of Concern 

for Risk Study and Toxicological Effects Scenario Departure Factors Assessment 

Dermal ShortTerm (1-30 

days) or No hazard was identified for short- and intermediate-term durations of exposure via the dermal 

Intermediate- route; therefore, there's no risk associated with these exposures. 

Term ( 1-6 

months) 

Occupational Two-week oral range-finding study-dog 

Inhalation 

Short-Term (I- UFA=10x LOCforMOE = 

NOAEL = UFH= lOx 100 LOAEL = 90.8 mg/kglday based on 

30 days) and 16.8 hematological changes (decreased RBC 

Intermediate- mglkglday FQPA Residential parameters, increased Heinz body count, Term ( 1-6 SF= IX LOC for MOE = reticulocyte counts, erythrocyte 

months) 100 morphology and methemoglobinemia) 

and increased spleen weights. 

Cancer (oral, 

dermal, Classification: not likely to be carcinogenic to humans. 

inhalation) 

Pomt 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 

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exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UF A = extrapolation from animal to human (interspecies). UFH =potential variation among 

members of the human population (intraspecies). FQPA SF= Food Quality Protection Act Safety Factor (for 

residential only). MOE = margin of exposure. LOC = level of concern. 

4.0 Use Profile 

Dow AgroSciences LLC is requesting a new Section 3 registration for use of the insecticide 

methoxyfenozide on pineapple to be added to the Intrepid 2F (Reg. No. 62719-442) label. 

Intrepid 2F is formulated as a flowable concentrate containing 22.6% active ingredient (ai) or 2 

lb ai per gallon. The proposed use instructions for Intrepid 2F allow application by aerial, 

groundboom, airblast and hand held equipment. The master label specifies that the product is 

not to be applied by chemigation unless specified in crop-specific directions on the label or 

supplemental labeling. Therefore, since the supplemental labels did not specify use of 

chemigation for the proposed use on pineapple, it was not assessed as a potential method of 

application. 

The PPE statement on the proposed label requires applicators and other handlers to wear longsleeved shirt and long pants, socks, shoes, and chemical-resistant gloves. 

There is also a currently registered residential use for methoxyfenozide on ornamentals. The 

proposed and existing use directions are summarized in Table 4.1. 

Table 4.1. Summary of Directions for Proposed Uses of Methoxyfenozide and Registered Residential Use 

Method of Application Maximum Maximum Use Directions, Application 

Application Rate No. Seasonal PHI (Days) Timing, Type and 

Applications Application Limitations 

per Season Rate 

_(lb ail A)_ 

Pineapples 

Ground 0.06 - 0.10 Apply as a foliar spray. Heavy 

(Airblast), lb ai/A 4 0.44 lb ail A 3 infestation may require repeat 

Aerial and (4-7 fl ozJA) applications. 

hand held 

equipment .OOllb 

ail gal 

Ornamentals (Registered Residential Use) 

0.25 Ib ai/A 0.5lb Repeat applications on a l 0-14 

(4-16 4 ai!A/yr NA day interval. When applying 

Handheld flozJA) with hand sprayers apply until 

Equipment (32 fl ozJA runoff. 

0.025 lb yr) 

ai/gal 

5.0 Residential Exposure and Risk Estimates 

There are no new proposed residential uses at this time; however, the is an existing residential 

ornamental use that was previously reassessed to reflect updates to HED's 2012 Residential 

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S0Ps3 along with policy changes for body weight assumptions (M. Collantes, 0389739, 

02/27/12). There has been no change to the residential exposure and risk assessment since the 

2012 review, and therefore the results are presented herein for the aggregate assessment 

associated with the proposed food use on pineapple. 

HED's level of concern (LOC) for residential handler and post-application exposure is an MOE 

of 100. Scenarios resulting in MOEs greater than or equal to a margin of exposure (MOE) of 

100 are not a risk concern. MOEs less than 100 represent risks of concern. All residential 

handler inhalation exposure risk estimates for handheld mixer/loader/application to ornamentals 

resulted in MOEs greater than 76,000 and were not of concern. 

Although there is potential for post-application dermal exposure to adults and children (6 to 11 

years of age) as a result of the use on ornamentals, a dermal endpoint was not selected. 

Therefore, a dermal post-application exposure assessment was not conducted. Furthermore, the 

potential for post-application oral exposure to children is not expected for residential 

ornamentals. Therefore, an oral endpoint was not selected and an oral post-application exposure 

assessment was not conducted. 

5.1 Residential Risk Estimates for Use in Aggregate Assessment 

The recommended residential exposure for use in the adult aggregate assessment has not 

changed since the 2012 assessment (M. Collantes, 0389739, 02/27/12). HED selected the most 

conservative residential adult scenario to be included in the aggregate, based on the lowest 

overall MOE (i.e., highest risk estimate). The recommended residential exposure scenario for 

use in the adult aggregate assessment reflects residential handler inhalation exposure from 

applications to ornamentals via backpack sprayer. The estimated risk estimate for this scenario 

resulted in a MOE of76,000, which is greater than the LOC of 100 and is not of concern. Table 

5.1 reflects the residential risk estimate that is recommended for use in the aggregate assessment 

for methoxyfenozide. 

Table5.1.: 

Residential Handler 

Lifestage Dose (mglkglday)2 MOE3 

Dermal Inhalation Total Dermal Inhalation Total 

Adult Male N/A 0.00022 N/A N/A 76,000 N/A 

Adult Female N/A NIA N/A N/A 

Child N/A 

I Bolded risk csttmates should contnbute to the restdentlal exposure port ton of the aggregate assessment. 

2 Residential Handler Dose = the highest handler dose for each applicable lifestage of all scenarios assessed in Table 4. 1.2 in 0389739. 

3 Residential Handler MOE = the MOEs associated with the highest doses identified in Table 4.1.2 in 0 389739. 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html 

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6.0 Occupational Exposure and Risk Estimates 

6.1 Occupational Handler Exposure/Risk Estimates 

The proposed new use of methoxyfenozide on pineapple allows the same application methods 

and agricultural practices as the currently registered uses assessed in the most recent 

occupational risk assessment (for use on citrus and root vegetables); however, the proposed use 

on pineapple reflects a lower application rate (0.1 lb ai/acre or 0.01 lb ai/gal) than the registered 

uses (0.25 lb ai/acre or 0.025 lb ai/gal). Short-term handler inhalation risk estimates for 

methoxyfenozide use on citrus resulted in MOEs ranging from 28,000 to 2,700,000 at the 

baseline level of personal protection (i.e., no respirator) and were not of concern (M. Collantes, 

0389739, February 27, 2012). 

The short- and intermediate-term handler exposure and risk estimates for the use of 

methoxyfenozide in pineapples resulted in inhalation MOEs ranging from 34,000 to 7,800,000. 

HED's level of concern (LOC) for occupational handler exposure is an MOE of 100. Scenarios 

resulting in MOEs greater than or equal to a margin of exposure (MOE) of 100 are not of 

concern. The previous occupational exposure assessment for methoxyfenozide on 

citrus is expected to be protective of the proposed new use on pineapples and a new 

occupational exposure assessment was not performed. Because estimated MOEs are all ~ 100 

there are no risks of concern. 

6.2 Occupational Post-application Exposure/Risk Estimates 

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for methoxyfenozide at this time primarily because of the low 

acute inhalation toxicity (Toxicity Category IV), vapor pressure (I x 10·7 mm Hg), and the low 

proposed use rate (0.25 lb ai/ A). In the absence of a dermal point of departure, a dermal postapplication exposure assessment was not conducted, and there is no risk associated with dermal 

exposure to workers re-entering treated areas. 

Restricted Entry Interval 

The REI specified on the proposed label is based on the acute toxicity of methoxyfenozide. 

Methoxyfenozide is classified as Toxicity Category III via the dermal route and Toxicity 

Category IV for skin irritation potential. It is not a skin sensitizer. Under 40 CFR 156.208 (c) 

(2) (iii), ai' s classified as Acute III or IV for acute dermal, eye irritation and primary skin 

irritation are assigned a 12-hour REI. Therefore, the (156 subpart K] Worker Protection 

Statement interim REI of 12 hours is adequate to protect agricultural workers from postApplication exposures to methoxyfenozide. 

However, REis may be further reduced from 12 hours if certain criteria are met for both the 

technical material and the different end-use products in accordance with the Pesticide 

Registration (PR) Notice 95-3 [Reduction of Worker Protection Standard (WPS) Interim 

Restricted Entry Intervals (REis) for Certain Low Risk Pesticides] .

4 

4 Available: http://www.epa.gov/PR Notices/pr95-3.html 

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The criteria for reducing REis include the following: 

(1) The active ingredient is in Toxicity Category III or IV based upon data for acute dermal 

toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irritation. 

(2) The active ingredient is not a dermal sensitizer. 

(3) The active ingredient is not a cholinesterase inhibitor. 

( 4) The active ingredient is not associated with known reproductive, developmental, 

carcinogenic, or neurotoxic effects. 

(5) EPA does not possess incident information that are "defmitely" or "probably" related to 

the post-application exposures to the active ingredient. 

With respect to methoxyfenozide, it is not classified as a carcinogen or a neurotoxicant, nor is it 

associated with known reproductive or developmental effects, which classifies it as a reduced 

risk candidate. Therefore, the proposed 4-hour REI which appears on the proposed supplemental 

label is consistent with 4-hour REI on the master label and is a candidate for a reduce risk 

chemical. 

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