UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASH IN GTON , D

. C

. 2046 0 

### MAY 0 5Z014

MEMORANDUM OFFICE OF CH E MICAL SAFETY AND POLLUTIO N PREVE N TIO N

SUBJECT: BEAD Chemical Profile for Regi stration Revi ew: Etoxazole , 107091 FROM:

THRU:



### TO: Nikhil Mallampalli, Entomologist Biological Analysis Branch Cynthia Doucoure, Environmental Protection Specia list 

### (!**~~** Science Information and Analysis Branch Monisha Kaul, Environmental Protection Specialist Economic Analysis Branch Biological and Economic Analysis Division (7503P) Arnet J ones , Chief

# ~~ Biological Analysis Branch 

# U
Diann Sims, C hief

# ~ Science Information and Analysis Branch Timothy Kiely , Chief

# ~ LQ Economic Analysis Branch \/\.\..._'-' Biological and Economic Analysis ivision P) Julia Stokes, Chemical Revi ew Manager Risk Management and Implementation Branch V Pesticide Re-evaluation Division (750 8P) 

# tJlo HAu 

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Product Review Panel date: April16, 2014

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### 10INTRODUCTION The purpose of this document is to convey usage information and a broad o v erview of the pest management roles of pesticides that are beginning to undergo registration review. The anticipated audience consists of the team of EPA staff cur rentl y evaluating the registration status of etoxazole, and eventually the general public. This document builds upon the data BEAD provides in the Label Use Information System (LU IS) reports and the Screen ing Level Usage Analysis (SLUA) to Registration Revie w teams. The document is based on information and data available to BEAD as of January 2014. Etoxazole was conditionally registered in August 2002 as a miticide/ovicide. The Insecticide Resistance Action Committee (IRAC), a group of industry technical experts, classifies etoxazole in Group 1 OB , with a mode of action that is described as " mite growth inhibition". Hollingworth and Treacy (2006) describe etoxazole's activity on mites as follows:"
... primarily active against tetranychid mites in the egg and larval stages, but it has no effect on adult s and is rather slow acting. It has translaminar but no systemic activity. The half-life for dissipation in the field is a few days to a few weeks".
HISTORY OF BEAD ASSESSMENTS FOR ETOXAZOLE In 2011, BEAD conducted a re view ofthe registrant 's request to extend exclusive use of registration data. In that assessment, BEAD co ncluded that etoxazole met benefits-related criterion IV for a three year extension of exclusive use of data by the registrant, in that it played a useful role in managing mites as part of an integrated pe st management (I PM) program for nine minor crops included in the registrant's exclusive use request (pear, cherries, plums, peaches, strawberry , hops , walnuts, mint, and muskmelons). In addition, BEAD concluded that etoxazole met the requirement for Criterion III (compelling evidence that etoxazole can be used to manage

. resistance to acaricides with different Modes of Action) for muskmelon, because this crop did

not have the very similar acaricides clofentezine and hexythiazox registered (Mallampalli, 2011 ).
COMMON FORMULATIONS AND APPLICATION METHODS Etoxazole i s commonly formulated as water dispersible granu les, emulsifiable concentrates, and wettable powders. It i s applied aerially or by ground applications using compressed air sprays , hydrauli c sprayers, or ground boom sprayers.

USE SITES Agricultural Use Sites: Etoxazole is registered for use on the 8-10B Pepper/Eggplant subgroup , Cucurbit Crop Group 9, Pome Fruit Group 11 , 13-07 A Caneberry subgroup, 13-07F Small fruit vine climbing subgroup , except fuzzy kiwifruit, and 13-07G Low growing berry s ubgroup. Etoxazole is also used on Page 

### 2 of 

### 10alfalfa, carrots, corn, cotton, non-bearing fruit trees, hops, mint, stone fruits, subtropical/tropical fruit, tomato, tree nuts and Christmas tree plantings. Non-Agricultural Use Sites: Etoxazo le is registered for use on ornamentals and in greenhouses
.
ETOXAZOLE USAGE BEAD prepared a Screening Level Usage Analysis (SLUA) in May 2013 that provided data on use of etoxazole on nuts (almond and walnuts), pome fruit, stone fruit, grapes, melons, strawberries, and cotton in the U.S. during the 2004-2011 timeframe. The crops with the highest average percent crop treated include strawberries (15%) and pears (10%). The crops with the highest average pounds a.i. applied include almonds (6,000 lbs a.i.), grapes (5,000 lbs a.i.), and cotton (2,000 lbs a.i.). Agricultural Usage Trend According to proprietary market research surveys, reported use of etoxazole in the U.S
. , in t erms of pounds a.i. applied and total area trea ted , has continued to increase following a sharp decrease in use in the middle of the period shown in Figures 1 and 2. The overall average a.i. rate of application during this period was 0.09 lbs a.i. per acre. Figure 1. Etoxazole Usage: Pounds AI Applied, 2004-2012 40,000 -,-------------

0 ··- ,**-- --** **~----·-T--·--· --·** **, ----·-·-** **------- -----** **--- --** **........-,- ---·** **--** 2004 2005 2006

Source: EPA Proprietary Data, 2004-20l2 2007 2008 Year
Page 3 oflO 2009 2010 2011 2012Figure 2: Etoxaz ole Usage: Total Area Treated Applied , 2004-2012 400,000

2004 2005 2006 2007 2008 2009 2010 2011 2012 Year Source: EPA Proprietary Data, 2004-2012
Agricultural Usage Trend: Top Crops, 2008-2012 Following a sharp decline in at the beginning ofthe period, reported use of etoxazole increased s teadily during the remainder of the 2008-2012 time frame. The crops with the highest proportion of total pounds a.i. applied were almonds (37%), wine grapes (19%) and cotton (13'9, followed by table grapes (8%), strawberries (7%) , and pears (6%) , as shown in Table I. The average annua l pounds a.i. applied during this period was 23 , 000 and the overall average a.i. application rate was 0.09 lb s a.i
. per acre. Etoxazole was applied at higher than overall average application rates on all crops except cotton and table grapes.

Page 4 of 10T bl 1 Et lU a e oxazo e se on 

### T C op rops, 2008 2012


## - 2008-2012 Average= 23,128 lbs/yr Crop %of Total Lbs A.I. %of Total Area Avg. A.l. Rate of Applied Treated Application (lb a.i. /acre) Almonds 37 31 0.11 Wine Grapes 19 14 0.13 Cotton 13 29 0.04 Table Grapes 8 9 0.08 Strawberries 7 5 0.13 Pears 6 4 0.12 Other* 10 8 0.09-0.14 *Other crops include apples , apricots, cantaloupes , cherries , corn, raisin grapes, peache s, walnuts , and watermelons. Source: Propnetary Data , 2008-20 12
Agricultural Usage Trend: Top States, 2008-2012 The states with the highest proportion of pounds a.i. applied during the 2008-2012 t imefra me were Ca_lifornia (80%) , Louisiana (5%) and Washington (5%). Etoxazole was applied at hi gh er than overall average application rates in all states except Louisiana.

T bl 2 E I U

. T S

a e toxazo e se m op tates , 2008 2012

- 2008-2012 Average= 23,000 lbs/yr State % of Total Lbs A.I. % of Total Area Treated Avg. A.I. Rate of Applied A pplication (lb a.i.lacre) California 80 69 0.10 Louisiana 5 10 0.04 Washington 5 4 0.12 Other* 10 17 0.03-0.14 *Other s tates include AZ , AR, FL , MI , MS , MO , N Y , NC, OH , OR, PA , TN , TX , VA , a nd WV Source: Proprietar y Data, 2008-2012
Agricultural Use Intensity of Etoxazole Use in the U.S
. Another measure of usage is the us e intensity. 

### In this analysis, the use int ensity is expressed as the average annual amount (in pounds) of the active ingredient applied per 

### 1,000 acres of crop acres grown. This differs from the application rate , which is expressed as the pounds a.i. applied per treated area. Figure 3 spatially represents etoxazole ' s use intensity in C alifornia on several 

### crops including almonds and wine grapes. For more inf ormation about thi s map ; see Appendix A. Page 5 oflO

### Figure 3. Annual Average Agricultural Use Intensity of Etoxazole (2008-2012).

Pounds Active Ingredient per 1.000 Crop Acres Grown 0NoDalll < 0 11 011
. 023

- 02• · 032

- >032 (Source: Proprietary Data, 2008-2012)
Non-Agricultural Usage BEAD reviewed avai !able data sources and found two years of reported use of etoxazole in nursery and floriculture as shown in Table 3 below. While national-level use in nursery and floriculture is relatively low (Table 3), use in California on ornamentals (in terms of area treated) appears quite high , based on CDPR data (Table 4).
Table 3. Etoxazole Use in N ursery & Floriculture Year Total Lbs A.I. Avg. A.I. Rate of Applied Application {lb a.i./acre) 2006 800 0.06 2009 200 0.04 Source: USDA NASS Agncultural Chemical Usage Reports , 2006 and 2009 Page 6 oflOTable 4. Etoxazole Use in California on Ornamental Plants 2010- 2012 

### ' Co mmodity 2010 2011 2012 Lbs Area Lbs Area Lbs Area A.I
. Treated A. I. Treated A.l. Treated Applied (Acres) Applied (Acres) Applied (Acres) Greenhouse Fl ower s & 

### 34 76 32 13 

### 67 125 Plants in Containers Outdoor F lower s & 33 

### 6 14 11 140 35 Plants in Containers Total 

### 67 82 46 139 

### 207 160

.. Source : California DPR, Annual Statewide Pesticid e Use Reports , 2010-2012


### BIOLOGICAL ASPECTS RELEVANT TO ETOXAZOLE The publicly accessible database of publi shed scientific literature on arthropod resistance that is maintained by Michigan State University (available at http: //www.pesticideresistance.com/index.php ) li sts only one publication documenting resistance to etoxazole. This item reports reduced susceptibil ity to etoxazole in two-spotted spider mites in Korea (KiSu et al. 2004). However, other studies have provided some ev idence that resistance to clofentezine can lead to cross-resistance to etoxazo le in European red mite (Pree et al. 2005) , and that resistance to hexythiazox and etoxazole are genetica lly linked in spi der mites (Asahara et al. 2008). Both clofentezine and hexythiazox are classified in the Mode of Action Group 1 OA, and are mite growth inhibitors similar to etoxazole. The extent of such cross-res i stance in U.S. crops is not clear to BEAD. Pree et al. (2005) obtained their resu lts using laboratory colonies established from mites collected in Canadian apples and peaches; Asahara et al. (2008) used spider mites collected in Japan. As mentioned earlier in this document, for at least some minor crops etoxazole appears to be a usefu l component in IPM programs, largely because its efficacy appears to be very mite-specific , and thus has lower toxicity to some non-mite beneficial insects than alternatives such as some synthetic pyrethroids , propargite, dicofol, and pyridaben. For example , As hley et al. (2006) found that etoxazole did not affect minute pirate bugs as much as either fe npropat hrin or propargite. Pirate bugs are common predators of the eggs and larvae of many agricultural pests , including mites and ap hi ds.


### ROLE OF ETOXAZOLE IN PEST MANAGEMENT Based on the avai lable usage data, etoxazole appears to p lay an important ro le in the production of major crops in California, including strawberries, pears, almonds, and wine grapes. The available data also s hows considerable use of etoxazole in California on greenhouse, containerized, and outdoor plants and flowers (Table 4)
. Etoxazole appears to be an effective mite growth inhibitor and has lower toxicity to some non-mite beneficial in s ects such as the
Page 7 oflOpirate bugs , which are predators of agricultural pests. It is also a useful component in IPM programs. BEAD is unsure why there is greater use of eto xazole in California ornamental production as compared to national-level data. Quinn et al. (2009) mention etoxazole and hexythiazox ( a very similar insecticide) among several options useful in nursery and greenhouse IPM programs that target spider mites. However, hexythiazox is l imited to one app li cation in California production of these crops , while etoxazole can be appli ed up to two times per season. This may be a factor in its greater use. Other factors, such as lower product cost, product availability, or localized resistance , may be driving factors as well.
INFORMATION THAT MAY BE USEFUL FOR BEAD'S FUTURE WORK ON ETOXAZOLE Obtaining the following usage information may improve future assessments conducted by the Agency related to the u se and importance of etoxazole: 1) Typical application timing in each registered crop. 2) Details on the pest management importance of etoxazole in California ornamental production. 3) 

### If more than one application is typically made , the typical re-application interval (per crop). 4) Recent resistance reports for etoxazole in populations of imp ortant target pests, in particular cases of cross-resistance to both hexythiazox , clofentezine , and etoxazole.

REFERENCES Asahara, M., R. Ues ugi , and M.H
. Osakabe. 2008. Linkage between one o f the polygenic hexythiazox resis tance genes and an etoxazole resistance gene in the two spotted spider mite (Acar i: Tetranychidae)
. J
. Econ. Entomol. 101(5): 1704-1710. Ashley , J.A. , D.A. Herbert, E.E. Lewis, C.C. Brewster, and R. Huckaba. 2006. Toxicity of three acaricides to Tetranychus urticae (Tetranychidae: Acari) and Orius insidiosus (Anthocoridae: Hemiptera). J. Econ. Entomol. 99(1): 54-59. EPA Proprietary Data, 2004-2012 EPA , Etoxazole Screening Level Usage Analysis (SLUA), May 2013 Hollingworth , R. M. and M.F. Treacy. 2006. Classification and Properties of Commerci al Insecticides and Acaricdes. Pp 36-67 In : Use and Management of I nsecticides, Acaricdes, and Transgenic Crops. J.N. All and M.F. Treacy (eds). Joint publication ofthe Entomo lo gy Society ofAmerica and the American Phytopathological Society. Page 8 oflOK i Su, A. , K. Gilhah , L. Soyoung , K. Chul su , and S
. Sangchul. 2004. Inheritance and stability of etoxazole resistance in two
- spotted spider mi te, 

### Tetranychus urtica e, and it s cross re sistance
. Kore an J. Appl. Entomol. 43: 4 3 -48. Mall ampalli , N. 20 l l
. Review of a Request for Exten s ion ofthe Exclus ive Us e Perio d for Etoxazole (DP # 384053). B EAD Officia l Record. Pree , D.J
. , K.J. Whitty , and L. VanDr iel. 2005. Bas elin e su sceptibi lit y and cross re sistances of some new acaricides in the Europ ean red mite , 

### Panonychus ulmi. Experimenta l and App li ed Acarology (2005) 37: 1 65

- 1 71. Quinn, J. , D. T ri nkle in , and R.A. C loyd. 2009. Integrated Pest Manageme n t in Greenhouses and Herbaceous Nurseri e s. Publication IPM0 1 26 from the University of Missouri Exten sion Service
. Avai lable on the web at http :// extension
.missouri
.edu/p/IPM1026
. [Accessed April2014]. U SDA N ASS Agricultural Chemica l Us age Reports , 2006 and 2009.

Page 9 of l OAPPENDIX A The map included herein is primarily for the use of the risk assessors in the Environmental Fate and Effects Division. The map provides a very broad geographical view of the average annual amount (in pounds) of the active ingredient applied per 1 , 000 acres of crop acres grown. These data are included in the maps because risk assessors are interested in the amount of a pesticide used across agricultural land. The calculated values presented in the map are not equivalent to an application rate ( lb a.i ./ A). The data used to make these maps have several limitation s. Any interpretation of the maps should consider the underlying data and the associated limitatio n s carefully. The numerator (annual average pounds applied) is based on private market surveys of pesticide us e in agriculture averaged over the last five years (Proprietary Data, 2008-2012). These surveys cover about 60 crops and are targeted in states that produce the majority of the crop. Alth ough the surveys capture most of the use of a particular active ingredient in agriculture, there are severa l limi tat ions to these surveys.
• States with minor production of a surveyed crop are not sampled • Not all types of pesticides are surveyed in every crop in every year • Many specialty crops with very small acreages are not included in the survey The result of these limitations is that states that show no usage may actually have a small amount ofthe active ingredient being used. In some cases the displayed use intensity may be disto rted because the surveyed crops and the reported pesticide usage may not accurately represent the actual pesticide usage on the crops produced in the state. The denominator 

### (1 ,000 crop acres grown) was also obtained from the same private market survey database. The "Crop Acres Grown" variable represents the total acres grown in a given state of all ofthe s urveyed crops . This value is independent ofpesticide usage and pesticide registration. It is important to note that the surveyed crops (about 60) are s ampled from states that are major producers of each crop. Therefore, there are cases where the actual crop acreage in a state i s hi g her than that reported by crop acres grown in the survey because either that state and/or crop was not :included in the survey. The reader sho uld pay particular attention to the figure legends and realize that a map prepared for a particular chemi cal is not directly comparable to a map prepared for a different chemical as the legend bins will likely be different.

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