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

Methoxyf enozide. 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 Healt h 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 ofthe 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 regi stered uses assessed in the mo st 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 ofthe proposed new use on pineapple.

Page 

### 1 oflOTa ble of Contents 

### 1 .0 Execut i ve Summary

..... . .. ..... ..... . .. .. .. .. .. . ................. ......... .. .. .. .. .. .. .. .. ... . .. .. .. .. .. ... . ..... . ...... ....... 3 2. 0 Ri sk Assessment Co nclusions and Recommendations

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

. .. . ... . .. .. .. . .. .. .. . .. ...... .. . ... . .. .. .. .. . .. .. ..................................................... 5 4.0 Use Profile

.............. . .. .. .. . .. .. .......................................................................... ... . ... . ... .. .. .. .. .... 7 5.0 Re sidential E xposure and Ri sk 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

Page 2 ofl O

### 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 lb s 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 inhala tion 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 Page 

### 3 oflOinhalation 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 1OX each for interspecies 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 i s classified as not likel y 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 previou sly reassessed to reflect updates to HED's 2012 Residential SOPs 1 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 resul ts are presented herein for the aggregate assessment associated with the new food use on pineapple. Residential handler risk estimates resulted in MOEs ;::76,000. I n 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 re s idential handler inhalation exposure from applications to ornamentals via backpack sprayer. The exposure estimate for this scenario resulted in a MOE of 76 ,00 0, 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 mo st recently assessed (0.2 5 lb ai/acre or 0.025 lb ai/gal). Therefore , the previous occupational exposure assessment for methoxyfenozide on citrus (M
. Collantes, D389739 , February 27, 20 12) 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 Page 4 oflOand 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 po st-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 la bel, and thus classifies methoxyfenozide as a reduced ri sk candidate. Human Studies Review This risk assessment relies in part on data from studies in which adult human subjects were intentionall y exposed to a pesticide or other chemical.· These data, which include s tudies from PHED 1 .1 ; the A HETF 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 s tudies, 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 re sidential/occupational risk estimates of concern associated with the registered ornamental or propo sed new agricultural uses of methoxyfenozide on pineapple. Occupational exposure scenarios resulted in inhalation handler MOEs that were not ofconcern (i.e., short- and intermediate-term MOEs**~** 100) for methoxyfenozide, at the label-specified PPE (e.g., no respira tor). 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 Page 5 oflOdermal, 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] 441444 1 5 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] 441444 22 Very mild irritant IV 870.2500 Acute dermal irritation (rabbit] 44144424 Not an irritant IV 870.2600 Skin sen si tization [Guinea pig] 44144426 Not a sens itizer N/A 

### 3.1 Toxicological PODs Used for Risk Assessment and Uncertainty Factor Considerations A summary of the toxicological dose s and endpoints for occupational and residential exposure scenario s is provided in 

### Table 3 .1.

Table 3.1. Summary ofToxicological 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 s hort- and intermediate-term durations of exposure via the dermal Intermediate- route ; therefore, there's no ri sk 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 increas ed 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 Page 6 oflOexposures . NOAEL = no observed adverse effect level. L OAEL = 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 = leve l of concern. 

### 4.0 Use Profile Dow AgroSciences LLC is requesting a new Section 3 registration for use of the in sect icide 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 chemiga tion 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 potentia l method of application. The PPE statement on the proposed label requires applicators and other handlers to wear long

sleeved shi rt and long pants, socks , shoes, and chemical

-resistant gloves. There is also a currently registered res idential 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 infesta tion 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
Page 7 oflOS0Ps 3 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 p roposed 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. A ll 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. Furthermor e, the potential for post-application oral exposure to child ren is not expected for residential ornamentals. Theref ore , 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 ri sk cs ttmates should co ntnbute to the restdentlal expos ure portton of the aggreg ate assessment. 2 Res ide nti al Handler Dose = th e hi ghes t handler dose for each appli c able lifestage o f all s cenarios assess ed in T abl e 4. 1

.2 in 038973 9
. 3 Re s ide ntial Handler MO E = th e MOEs associated with th e hi ghes t d oses identifi ed in Table 4

. 1

.2 in 0 3 89739

.

3 Available: http: / / www.epa .gov/pes ticides/ science /residential- exposure -sop.html Page 8 oflO

### 6.0 Occupational Expo sure 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 low er 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 ofpersonal 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 p ineapples re sulted 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 ofa 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 Page 9 oflOThe criteria for reducing REi s 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.

Page 10 of 10