Docket Number E PA-HQ-OPP- 2 015-0401 www .re gulation s .gov



## Difenoconazole Preliminary Work Plan Registration Review: Initial Docket Case Number 7014 December 2015

Approve d by: 

# 9 :t-d:JQ-LcL P

# ~~ Richard P. Keigwin, Jr. Director P est icid e Re-evaluation Di vision

Dat e : 

## / ;;l_j C2 I 

# I a. 0 Is

### Difenoconazole Prelimin a r y Work Plan- Tab le of Co ntents

OVERVIEW .................................................................................................................... ..... .......... 4 ANT ICIPATED DATA NEEDS .......................................................... ........... ............. ............ ...... 5 STATUTORY A D R EGU LATORY AUTHORITY ................................................................... 6 CHEMICAL FACTS ................................................. ...... ...................... . ........................................ 7 USE AND USAGE INFORMATION
...... ........... .................... ......... .............. ......... ................. ...... 8 RECENT ACTIO S ...................... ... .............................................................................................. 9 ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ............................. 10 TIMELINE
......... .. ......................................................................................................................... 13

EXT STEPS

. . .. . .... .... ... . .. . . .. . ... . ... . ... . . .. . . ... . ... . . ... .. .. .. ... . .... . ... . ... . .. . . .. . .... .... .. . .... .. . . .. . .... ... . .. . ... . ... . .. 1 3 Appendix

- Additional Areas Considered in the Amicarbazone Registration Review ................ 1 3

Reference s : This Pre lim inary Work Plan summarizes the Environmental Protection Agency's current position based on the fo ll owing documents:

I. D{(enoconazole Preliminary Proble m Formulation/or Environmental Fate, Ecological Risk , Endangered Species. and Drinking Water Exposure Assessments in Suppo rt of R egistration Review. Michael Lowit , Faruque Khan , Sujatha Sankula. November 5, 20 15. 2. Dif e noconazole. Human Health Risk Scop ing Document in Support of R eg ist ration Revi e w. Iv an Nieves, Bonnie C r opp -Kohlligian, Thurston Morton , Abdallah KJ1a saw inah. October I , 20 15. 3. Difenoconazole: Tier I (Scop ing) R eview of Human In ciden t s and Epidemiology. Shanna Reco re. September 15 , 2015

. -1. Common Triazole Metabolites: Updated Aggrega1e Human Health Risk Assessment to Address The New Section 3 Regi s tration s For Use of Propiconazole on Tea, Dill , Mustard Greens , Radish, and 1Varercress; Use of Difenoconazole on Globe Artichoke, Ginseng and Greenhouse Grown Cucumbe rs and Conversion ofrhe Es rablishe d Foliar Uses/Tole ran ces 2for Stone Fruit and Tree Nu t Crop Groups to Fruit , Stone, Group 12-12 and th e Nut, Tree , Group 1-1-12.: and Use ofF/utriafol on Hops. Thurston G. Morton. April9, 2015. 5. Co mmon Triazole Me tabol ites: Updated DietCIIy (Food + Wate1) Exposure and Risk Assessmen t to Address The New Section 3 Registrations For Use of Propiconazo le on Tea , Dill , Mustard Greens, Radish, and Watercress ; Use of Dif enoconazole on Globe Artichoke, Ginseng and Greenhouse Grown Cucumbe rs and Co nv e rsion of th e Established Foliar U-;es / Tolerancesfor Stone Frui t and Tree Nut Crop Groups to Fruit, Stone, Group 12-1 2 and the N111

. Tree, Group 1-1-12.; and Use ofF!utriq(ol on Hops. Thurston G. Morton. April 9, 2015. 6. BEAD Che111ica/ Pn?file (BCP) .fhr R eg i stra tion Review of Di{enoconazole ( 1288-17). Leonard Y o urrnan. Rafa e l Prieto . S t ep h e n Smcannan. Decemb e r 2, 2015 7. D((enoconazole (1288-1 7 ) Screening Level Usage Analysis (SLUA). Octob er 2, 2014. 8. Difenocona z ole (1 288-17) EFED Tabl e I Report. february 3, 20 1 5. 9. liED }vfaster Label Report: Difenoconazole ( 1 288-1 7 ). Febru ary 3, 2015. These and othe r s upportin g documents for th e difenoconazole registration review case may be found in the docket E PA-HQ-OPP-20 15-040 I at http: //www.rcgulations.gov.

3

### OVERVIEW The docket for difenoconazole is now open, initiatin g the first public comment period for thi s r eg is tration revi ew (docket number EPA-HQ-OPP-20 15-040 I). Di fenocona zo le, 1- [2-[2-chlo ro4-(4-chloro -ph enoxy) -phen yl)-4 -meth yl-[ I , 3)dioxolan-2-ylmethyl)-l /-1-( 1 ,2,4] tri azo le , is a broad

- spectrum fungicide. with registered uses on many fruits, vegetables, ce rea ls, field crops , and golf course turfgrass, and ornament a l plants, includin g roses. T hi s Preliminary Work Plan ( PWP) docum en t explains what EPA's Office of Pes ticide Pro g ram s knows abou t difenoconazole, highlighting anticipated data and assessment needs , identifying the types of in fo m1 ati on that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing the r eg istration review for difenoconazole. The re g is trati on review process was designed to include a public participation compone nt to solicit input from interested stake hold ers. The Agency intends, by s haring this inf o rmati on in th e docket, to inf orm the public of wha t it knows about di fenoconazole and what types of ne w data or o the r inform ation wou ld be helpful fo r the Agency to receive as it moves toward a decision on difenoconazole. The Agency encou ra ges all interested s takehold ers to review th e PWP and Appendix and to provide comme nts and additional information that will help th e Agency's decision-making process for this chemical. In addition to gene ra l areas o n wh ich persons may wish t o comment, there arc so me areas identified in the PWP and Append ix about which the Agency specifica ll y seeks comments and information. Int erested s t akeholders could in clude: environmental non-profit o r interes t groups; pesticide manufacturers; agricultural labor or commod it y groups; commerciill, institutional, resid entia l. and other users of pesticides; or the public at large. The Pr e liminar y Work Plan beg in s by li s tin g the anticipated data needs for difen oco nazole. ext. it discusses the statuto ry and regulatory authority for Re g istratio n Review. Th e n the document provides chemical facts, use and usage inf ormatio n , recent actions, the anticipated risk assessments, and a projected regis tration rev iew timelin e for d ifenoconazole. fina ll y, the Appendix to this document in c lud es id entification and discuss ion of so me areas that a re conside red genera ll y in re g i s tration re v iew a lon g with some additional chemical case -specifi c information.

4ANTICIPATED DATA NEEDS Table I below s ummari zes an ticipated data needs for d i fenoconazole. For additional di scussion of the anticipated data need s, see the D ifenoconazole Prelimincuy Problem Formulation for Environm en tal Fate, Ecological Risk, Endangered Species. and Drinking Water Exposure Assessments in Suppo rt of Reg i st ration Review. Tab l e 1: Anticipated Data Nee d s for the Difcnoc o nazo l e Re g i s tration Revi ew Es tim ated G uid e lin e Numb e r Stud y Tit l e 2 Test Mate rial 1 Timefram e (Months from re ce ipt of D C I) Anticipated Dat a Ne ed s for Dif e no co n azo le Non

-GDL

_ N Tier I H oneybee adult acute oral exposure TGA I 12 Non-GDLN Tier I Hone ybee adult chronic oral exposure TGAI 12 Non-GDLN Tier I Honeybee larva l acu te exposure TGAI 1 2 Non-G DL N Tier I Hon ey bee larval c hro ni c o r a l exposu re TGA I 1 2 Re s idue in pol l en and nectar on-GDLN Tier II (recommendat ion pending risks identified in TE P 24 Tier I studies) Semi-fie ld testing for pol lin ators (tu nn el and feed ing s tudies) Non-GDLN Tie r II TE P 24 (recommendation pendin g ri s ks identified in Tier I s tudies ) Full-field te s ting for pollinators 850.3040 Tier Ill (recom m endati o n pending ri s ks identified in TEP 24 Ti er II s tudi es) In dependent labor atot y va lid ati o n report for 850.6100 ( !LV ) ana l y tical method in soi l for difenoconazo le TGA I 12 and its metabolites (CGA-205375, CGA

142856 , and CGA-71019). Environmen ta l chemistry method and ind ependen t labo ratory valida ti on for 850 .6100 (ECM / ILV) a nal y ti ca l m ethod in water f o r TGA I 12 difenoconazo le and its metabol it es (CGA205375, CGA -1 42856, and CGA -71 0 1 9).

- ..

**~** 1 TGA I

- techlllcal grade acuvc mgred1cnt: I EP 

### = typ1cal end-use product !O n June 27. 2012. EPA announced cenain revisions in harmonized guideline seri e s 850

- Ecological Effec ts Tests- includin g renumbering and / or removal of the Tier designations for some guideli ne stud ie s. cc "Final Test Guidelines: OCSPP 850 Series: Notice of 1\ vailabi lity" 77 FR 38282. June 27. 20 1 2. http : // ,, . ,, w .rcg ulations.gov/ 11

**!ducumcntDctaii:D EP/\-**  **110-0PPT-2 009-**  0 154-002S



### 5STATUTORY AND R EGU L ATORY AUTHORITY The Food Quality Prote c ti o n Ac t ( FQPA ) of 1996 mandated a r eg istration re v i ew program. All pesticides distributed or so ld in the United States (U .S. ) gene ra ll y must be reg is tered by the Environmental Protecti o n Agency (E PA o r the Agency), b ased on scientific data showing that they will no t cause unreasonab le risk s to human health o r the environment when used as direct ed on product lab e ling. The reg ist ration review program is intended to make s ure that , as the ability to assess ri s k evo lves and as policies and practices change , all r egistered pe s ticides continue to meet the s t a tutor y standard of no unreason ab le adve rse effects t o human he a lth or the environment. C hanges in sc ience , publi c po lic y , and pesti cide use practice s will occur over time. Thro u gh th e registration r ev iew program , the Agency periodically reevalu a te s pesticides to m ake sure th at as change occur s, products in th e marketplace can be used safely. In formation on thi s program is provided on EPA 's webs ite. 1 The Age ncy is implementing the registrati o n re v iew pro g ram pursuant to Sec ti on 3(g) of th e Federal In sect icide , Fungicide, and Rod e nti c ide Act (FIFRA ) , and will re v iew eac h registered pesticide every 15 years t o determine whether it continues to meet the FIFR A s tandard for registra tion. The reg ul ations govern in g r eg is tration review beg in at 40 CFR 1 55.40. The Agency wi ll consider benefits information a nd data as requi red by FIFRA. The public phase of registra ti o n rev iew begin s when the initial docket is opened for each case. The docket is the Age ncy"s opportunit y to s t a te w hat it knows about the pe s ticide and what additional risk analyses and data o r inf or

mati o n it believes are nee ded to make a re g i s tr ation revie w dec i sio n . After review i n g and respondin g to comments and data re ceived in the docket durin g this initial comment period , the Agency will deve lop a Final Work Plan (fWP) and an ti c ipated schedu le f o r th e r egist r a ti on review of di fenoconazo le. C H EM I CAL FAC T S Table 2 provides a summary of the chemica l facts for difen oco nazole

. Table 2: Chemica l Facts for Dif c noconazol e PC code 128847 Case Numbe r 7014 CAS Number 119446-68- 3 Year first registered 1994 Pes ti cide Type Fungicide Chemic a l cla ss Triazolc Reregi s trat io n Eligibility No Rere g is tra ti o n Eligibility Dec is ion (RED ) was issued for Deci sio n difenoconazole. Tol e ra nc e Reass essment Difenocona zo le was not s ubj ect to tolerance reassess ment. E li g ib ilit y Decision (TRED) Cumulative group Difenoconazo l e has not been id ent ified as a membe r of a cumulative g r o up that shares a common mechanism of toxicit y . 40 CF R Ci t at io n To l erances for difenoconazole a re es tablished in 40 CFR § 180.4 75.

1 http ://www2

. cpa.gov / pcsticidc-rccvaluation 6Ta ble 2: C h e mical Facts fo t · Dif e nocon azo l c Dual-use Difenocon azole is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses. Non-pesticidal u ses There are no identified non-pesticidal uses of difenoconazole. Pesticide Re-evaluati o n Mar ia Rivera Pian say Di v i sio n , C hemical Rev ie w Pian say.mar ia @ epa .gov Manager (703 )308-8063 Registration Division , Tony Kish Product Manage r Kish.ton v(@ cpa.gov (703)308-9443

USE AND USAGE I NFO RM ATI ON Table 3 summarizes the use and usage information for difenoconazole. Please see the 

### BEAD Chemical Profile for Registration Review: Difenoconazole, 1288-1 7 in the registration review docket for more details.

Summary of Use

Use Site s

Summary ofUsage Table 3: Difenoconazolc Use and Usage Informati o n Difenoconazole is a broad-spectrum triazole fungicide that works by inhibitin g demethylation and o th er processes in sterol biosynthesis. Difenoconazole is a penetrating system ic fungicide whic h is rapid ly abso rb ed by leaves a nd i s then d istributed w ithin plant tis sue by tr ans laminar movement. Ag ri c ultun l l Use S ites: Difenoconazole i s registered for use on pla nt s o r seeds of a number of fruits, vegetables. cereals, and field crops . C rops include citrus , pome fruits, lo w g rowing berries , tuberous and co rm vege tabl es , fruiting vegetables, cucurbit vegetables, s ton e fruits, tree nut s, and co le c rops. More spec ificall y, thi s chemical is registered for a lmonds, barley, canola , carrots , sweet corn , cotton , filbert (haze lnut ) , garba nzos / chick peas , garlic , grapes , leeks, oats , onions , pecan, pepper , pistachio , potatoes, rye, shallot , soybeans , suga r beets, tomatoe s, tri t ica le, and wheat. Non-agricultura l Use S it es : Ou td oor applicat ion t o estab li s he d orna men tal s in l andscaped areas, inc luding (bu t not limited to) recreational parks , institutional sites , go lf courses and residential properties by commerc ial and non-professional (i.e., homeowner) applicators. Agricultural Usage: From 2008 to 2013, ann ual usage of clifenocona zo l e ave r aged 1 40,000 po und s of active in gre d ie nt (A. I.) treat in g an an nual average of 6.4 million acres, with an overa ll ave ra ge application rate of 0.021 pounds A. I. per acre. Usage may be higher because our data sources do not captu re all registered ag ri cultural use sites suc h as leeks , shallot , triti ca le, etc. The use 7Tabl e 3 : Difcnocona zo lc Usc and Usage Information of difenocona zo le has steadily increased s in ce 2008 as measured by pounds A. I. and to tal area treated. In addi ti on . as seed treatment data fo r various crop s are not surveyed. their usage es timat e i s I ikc l y an underestimate of actual percent crop tr eated. Non-agricultural Us age: There arc no availab l e non-agricultura l usage data fo r difenoconazole. Formul a tion Type(s ) Difenocona zo le is formul ated as a tlowab le concen trate , e mul sion (o il ) in water , emuls ifiable conce ntr ate, ready-to-use so lution , and liquid solub le co n centrate. Appl ica ti o n M e th od(s) This h e rbi c id e i s app li e d as a g ro und and aerial s pra y or as a seed treatm e nt. It i s a l so app l ied as broadcast sp r ay an d by che mi gat ion. Other ap plic atio n methods include broadcast spray, chemigat io n , bin/truck drench or in-line dip/ drench or flooder , and/o r in-lin e aqueo u s o r fruit coatin g spray application. Tec hni ca l Reg i s trant (s) Syngen ta Cr op, LLC A lbau g h , LL C N ufarm Americas , Inc

. Numbe r of Registration s Th irt y fi ve Sectio n 3 registrations 1 R estricted Use No

.. 1 Secu o n 3 product labels can b.: obt a an ed from the Pe s ucadc Pro duct Labe l Systl.!m (PPLS) wcb s nt:

**(h ttr**  **// oa**  **puh .c**  **pa.** gov/ pes t

**hl ppl**  **homc)** Guidanc e for Co mmcntcrs: Additiona l areas of use and usage re lat ed in formation requ es t ed for thi s re g i s tration review , and of particular int erest to EPA , are described below.

• Certain difenoconazole labels are un c lear wi th respect to applica ti on parameters s uch as m ax imum number of app li cat io n s, minimum app li cation int e r va l s, and m axi mum app l ication rat es per ac re ( m axim um lb a i / A/year) fo r labels th a t refe r o nl y to pe r -c r op or per-season rates (see Difenoconazo l e (1288 -1 7) EFED Table 1 Repo rt ). • The Agency does not have n o n-a g ri cultural usage d a t a and infonnation on th e use or usage of difenoconazole on golf course turfgra ss, orname nt al plant s, eith e r commercial or residential. Information that might clari fy th e relative importance of d if e n oconazo le in co mp ari son to a lt e rn a ti ves wo uld be h elpf ul if the Age n cy co nduct s benefits o r imp act assess m e nts. • Usage data on see d tr ea tm e nt c rops n o t s urv eye d by ava il ab le databa ses. • P ou nd s of act ive in gredient app lied , percent c r o p treated , a nd app li cat io n r ates on r egis t e r ed use s ite s. • Addit iona l information on the occurrence of res i s tan ce to dife n oco n azole would be useful in es t ab li s hing benefits and developing re s i s tance man agemen t lan g ua ge.



### 8RECENT ACTIONS

• Recently a pproved new uses o n peas an d beans, ar ti c h o ke, p ost -ha rves t to pome fruits (May I 0, 20 15). • Recently ap proved new uses o n gi n se n g artich o ke green h ouse cucumber co n vers io n s to c rop g roup s 1 2- 12 s t o n e fruits and tree nuts 14-1 2 ( D ece mber 14, 20 1 5)

. • Data associated wi th new uses arc re quir e d as condition of r eg i stration with the exce pti o n of honey b ee da t a. ANT I C I PATED RI SK ASSESSMENTS FOR REGISTRATION REV I EW The m os t r ece nt eco lo g ica l a nd env ironm e nt a l fa t e ri sk assessments we re cond ucted in 2014. Findin gs and conc lu s io n s f r o m these ri s k assess m e nt s are s ummarized in D ife no conazo l e Preliminar y Problem Formula tion for Environmen tal Fate , Ecolog i cal Risk , Endangered Species

. and Drinking Water Exposure Assessments in Support of Registration Rev iew. Durin g reg istration review , th e Agency an ti cipates the n eed t o co nduct a comprehensive eco log ica l ri s k assessment , i n c lud ing an e n da n ge red species assess ment , fo r a ll u ses of dif e n oco n azo le. The Agency also an ticipates th e n eed to d e t e rmin e 

### if addi tional data a re n ee d e d to address possible co n cerns abo ut bystander exposures to vola tili ze d difenoconazole. I f t oxicological e ndpo int s , poi nt s of departure, s tandard operating proce dures , or default exposure assumptions are revised , n ew human h ea lth ri s k assessments may be needed. A dietary assessment for com mon tri azo le de gradates/ metabolites m ay also be need ed. Tab le 4 b e low s ummari zes the a nticip a t ed r eg i s tr a t ion rev iew ri s k assessmen ts b ase d o n the EFED Problem For mul a ti on and HED Scop in g D oc um e nt a nd Draft Hum an ll ea lth Ri sk Assessment.



### 9T a bl e 4: A nti c i p a t e d Ri s k Assess m e nts fo r th e Dif e n oco n az ol e R eg i s tr a ti o n R ev i ew Type of Ri s k Assess m e nt Co ndu c t' ? No t es E colo gical and E nviro nm e nt a l F a te Co mprehensive eco logical 

### y The Age n cy will conduct a comprehensive (spec ies t o be assessed ecological risk assessment for the parent i nclude terrestria l and di , fenoconazole, including an endangered aquatic organisms), species assessmen t. including endange red species Incidents Will check for updates F or a discussion of reported ecological incid ents for difenoconazole, see page 21 of th e Problem formul a ti o n . Human He a l th •• 1 ·or Dietary Food N A n ew dietary risk assessment for ( difenocona z ole difenoconazole residues of concern is not residues of concern) anticipated to be ne eded during re gis tr a ti on r ev iew. 

### y A dietary assessment for commo n tri azole (common degradates / metabolites may be needed. degradates/ metabolites) Drinking water 

### y A drinking water assessment will be (difenoconazo le conducted, if wan·anted , to s upport future r esi due s of concern) hum a n hea lth dietary ri sk assessments of difenoconazole. Th e residues of concern are anticipated to be difenoconazo le and CGA205375 unless information becomes available th a t indic ates that other degradates should be includ ed

. 

### y Dif enoconazo le may be considered in an (com m on d egradat es) updated drinking water assessment for common triazole degradates. Occupational Handler s (mixers, loaders , N A new occupationa l handler risk assessment is app lic ato rs) not anticipated to be needed during re g i st ration review. Post-application N A ne\v occu p at ional post-application exposure is not a nti c ipated to be needed during re g i st r at io n review. R es idential Handlers N A new residential handl e r ri sk assessment is not anticipated to be needed during registration review.

10T ab l e 4: A n t i c i pa t ed Ri sk As s ess me n ts f o r t h e D if e n oco n azo l e R e g is t..ati o n R ev i ew T y pe of R is l< Assess m e nt Co n d u ct ? Notes Pos t- ap pli ca ti on y Durin g r eg is tration rev iew, the Agency wi ll det ermine if data (e.g. , nux s tudies ) or f urther analy s i s i s re qui red fo r a bystande r risk asse ss me nt. Other Agg r ega t e y As pa rt of re g is tra t io n r ev iew, updat ed aggregate ri s k assessments for d i fenoconazole re s idu es of concern may be necessary to re fl ec t rev ised d ie t ary o r reside nti a l exposure es timate s. A dditi ona ll y , a di e tar y assess ment f o r common triazole deg r ada te s / metabolit es may be nee ded

. C um u lati ve N EPA has not made a common mec hani s m of toxic ity fin d in g for dif e noconazole and any o t h e r s ub s tances
. Tolerances y U.S. to lerances are ha rm o n ized w ith Codex and Canadian maximum r es idue limit (MRL) w ith rega rds to definiti o n of residues as well as leve ls in / o n a nu m be r of com mod it ie s. Add it io na l harmoni zati o n of resid ue leve ls wi ll be co ns idered und er reg i s trat i on r ev iew. Incidents Will check f o r updates B ased o n the low frequency and severity o f incid e nt cases report ed for difenoconazolc in both IDS and SENSO R-Pest ic ides there doe s not appea r to be a co nce rn at this t ime th at wou ld wa r ra nt f urth e r inv es t i gat io n. Th e Agency will continue t o mo nitor incident inf o rm a tion and if a conce rn is tri gge r ed, additiona l analysis will be included in th e risk a ssess ment ; see page 9 of the Scoping D oc u ment / D r aft Ri sk As sess me nt a nd Dif e n oco nazole: Tier I (Sco p ing) Rev i e w of Hum an In c id en t s and Ep id e miology. G ui danc e fo r C o mm e nt crs: Additional eco logical inform a ti on reque s ted for thi s registration review , and o f part icular inte r est to EPA , i s d es cribed below.

• Eco log ical incidents no t already repo r ted to the Agenc y. • Water quality mo nit o rin g data ( see Appendix for further details).

IIT IM EL I NE 

### EPA has c reated the following estimated tim eli ne for the comple ti on of the d i fenoco nazo l e regi s tration review in T ab l e 5 below.
Tabl e 5: Pr ojected Difcn oco na zo l e Registrat i o n R ev i ew T im e li ne Activ iti es Es timated Date 

### Opening the Docket Open Docke t and 60

- day Pub li c Comment Period 20 15

- D ecember Clo se Public Co mm ent 20 16

- February Case Deve lopment Fina l Work Plan 20 16- Ap ril- Jun e Issue DC I 20 16

- Jul y- Septembe r Data S ubmi ss io n 20 18- July- September 60

- da y Publi c Comment Period fo r Draft R isk 2020- January - Marc h Asses s m ent s 1 

### R

eg istra ti on Revi ew Dec is io n 60-da y Pub li c Co mm e nt P e ri od for Proposed 2020- October- Dece mber Re g ist ra ti o n Revi ew Deci s ion Re g ist ra ti o n R ev i ew Decis io n and Be g in P ost- Decision 202 1- April -J une Follow-up Total (y ea rs) 6 'The re g ul auon s gove m in g regi s tr a tio n rev iew ge ne r al ly require th e Age ncy t o provide a p ub l ic co mment peri o d o f 111 lcu s t JO cn lcn dar day s l o r drall ri sk a ss es s men t s; sec 40 CFR Par t 155 .53(c). For conventi o na l pes tici des. the Agency plans to provide a 60 ca l e ndar da y public comm en t period genera ll y for draft risk assessments
.
NEXT S T E PS 

### After the 60 -day public co mm ent period clo ses, th e Agency will r ev i ew and r es pond to any comm ent s r ece ived in a t im e ly manner and then iss ue a Fina l Wo r k Pl an for th e r egis trati on re v iew of di fenoconazole.

12

### Appendix - Additional Areas Considered in the Difenoconazol e Re g istration Revi ew P U BLI C C OMM EN TS AN D FEEDBA C K: Guidance for Co mm c nt e rs: Th e areas below hi g hli g ht top ics of s pecial int erest to the Agency w h ere yo ur co mment s, da t a s ubm issions , or r efere nce to so urces of add i t i o na l informat ion co uld be of particular use. Trade lrriwnts: Through th e reg i strati on rev iew process , th e Agency inte nd s to solic it information o n trade init ants a nd , to the exte n t feas ib le, take steps toward facili t a tin g irri tant reso lution. Th e Agency will work to harmonize tolerances a nd international maximum r esidue li mits (MRLs) and may modify t o lerance leve ls t o do so, when possible. Growe rs a nd other s takeholders a re aske d to co mm e nt on any trade irrit an t issues resulting f rom lack of MRLs or dispariti es between U.S. toleran ces and MRLs in key expo rt markets , provi din g as much spec ifi city as possible regardin g the nature of th e concern. Water Quality: Difeno conazo le is not identified as a cause of impairment for any water bodies li s t ed as impaired under section 303(d) of the Clean Water Ac t. 2 In addi ti o n , no To tal Maximum Daily Loads (TMD L) h ave bee n d eve l oped f or dif e n oco nazo l e. More inf o rmati o n on impaired wa ter bod ies and TMDL s ca n be f ound a t the Age ncy's webs ite. 3 Th e Age nc y invit es s ubmi ss ion of water quality data f o r thi s p e s ticid e. To the ex t e nt possib l e, data s hould co nf orm to the quality standards in Ap pend i x A of the OP P Standard Operating Procedure: inclusion of impair ed Water Body and Other Wat e r Quality Data in OPP ' s R egis tration R eview Risk Assessment and Manag e ment Process "' in order to ens ur e th ey can be u sed qua ntit at ively or qualitatively i n pes ticide ri s k assessments. Environmental Justice: EPA seeks to achieve environmental justice , the fair treatm e nt and meani n gful involvement of a ll people , regard less of race , co lo r, national origi n , or income , in the developm e nt , impl eme nt a ti o n , and e n fo rce me nt of e n v i ronmenta l laws, regu lati o ns, and po li c ies. To he l p address po t ent ia l e n v ironmental justice issue s, the Agency seeks inf o rm at io n o n a ny g roup s or seg ments of the population who , as a result of the ir location , cultural practice s, or other factor s, may h ave atyp ical. unusually h i gh ex posure to difenoconazole compared to the general populatio n . Pl ea se co mm e n t if yo u a rc aware of any s ub -popu la tion s that ma y h ave atypical , unu s u a ll y hi g h ex p os ur e co mp a red to the ge neral populati o n.

1 hup :// iaspub.epa.govltmdl waters I 0 / aua in s nation cy.ca u se detail 303 d ? p cause group id = 885 3 http: //www.epa.gov / o wow/tmd II

·• hnp : //www2.cpa. gov / pe st ic icle-rccva luation / opp-gu idance

- s ubm i ss ion- tat e-a nd-triba 1-w a tcr-g ua Iity

- monitoringdata 1 3EN D AN G E R E D S P EC I ES: A risk assessment that s upporis a comp lete e ndan ge red species determina ti on has not been conducted for difenoconazo le. T he ecolog ical ris k assessment p lanned dur i ng regis tration review wi ll allow the Agency to determine whether use of difenocona zo lc ha s " no effect" or ··may affect" federally li s t ed tlu·eatened or endange r ed spec ies (listed spec i es) or their desi g nated critical habitats. When an assessment concludes that a pesticide's use "may affect " a listed species or its designated c riti cal habitat , the Agency wi ll consu lt with th e U.S. Fish and Wildlife Service and / or Nat io na l Marine Fisherie s Service (the Services) , as appropriate. EN DO C RI NE Dl S R U PTOR SC RE EN IN G PRO G RA M: As requ ired by FTFRA and FFOCA , EPA revi ews numero us stud i es to assess potential adve rse ou tcomes from expos ure to chemica ls. Collectively , these stud ies includ e acute , subchronic and ch r o nic toxicity, including assessments of carcinogenicity, neurotoxicity , developmental, reproductive , and general o r syste mic toxicity. These s tudies include endpoi nt s which may be s usceptible to endocrine influence, includin g effects on endoc rin e target organ histopathology , organ \ veights , estrus cyclicity, sexual maturation , fertility , pregnancy rates , reproductive loss. and sex ratio s in offsprin g. for eco logical hazard assessme nt s, EPA eva lu ates acu te tests and chronic studies that assess growth, developm e nt a l and reproductive effects in different taxonomic groups. /\s pa rt of its most recent reg is tration decision for difen oco nazole , EPA r ev iewed these data and selected the most sensitive endpo ints for re levant risk assessment scena rios from the ex is tin g ha za rd databa se. Howeve r, as requi r ed by FFD CA section 408(p), am ic arbazo ne is subject to the endocrine screeni ng part of the Endocrine Di srup tor Screening Program (E DSP ). EPA has developed the EDSP to determine whether certain subs tances (i ncluding pestic ide active and other in gred ients) may have an effect in humans or wildlife s imil ar to an effect produced b y a " naturally occurring estrogen , o r ot her such endocrine effec ts as the Administrator may designate." The EDSP employs a two- t iered approach to making the statutoril y required determinations. Tier 

### 1 cons ists of a battery of 

### II sc reeni ng assays to ident ify the potential of a c he mic a l substance to inte ract with the estrogen , a ndrogen , or thyroid (E , /\ , or T) hormonal syste ms. Chemicals th a t go through Tier 1 screen in g and are found to have th e potential to interact w ith E. A, or T hormonal systems will proceed to the next stage of th e EDSP where EPA will determine whi ch, if any, of the Tier 2 te sts are necessary based o n the available data. Tier 2 testing is designed to id e ntif y any adverse endocrine-related effects caused by the substance , and estab li s h a dose-response relations hip between the dose and theE , A , or T effec t. Under FFDCA section 408(p), the Agency must sc reen a ll pes ticide chemica ls. Between October 2009 and Feb r ua r y 20 1 0, EPA issued te s t orde rs / data call-ins for th e first gro up of 67 c hem ic a ls , which contains 58 pesticide active in g r ed ients and 9 inert ingredients. A second list of chemicals identifi ed for E DSP screening was published on Jun e 14 , 20 13 5 and includes some pesticides scheduled for registration review and chemicals found in water. Ne ither of the se li sts

s Sec b.!.!Q: // www.regulntion s. gov / # !documentDetai i ;D = EPA-HQ-OPPT
- 2009 - 0477-0074 for the final second li st of chem i ca Is. 14should be co ns trued as a li s t o f known o r lik e ly e ndocrin e dis r uptors. D i fenoconazo le doe s not appear on ei ther li st. For further information on the status of th e EDSP , the pol icies and procedu res , the lists of chemicals, futu re lists , the test guide lin es and the T ier I screeni ng battery , plea se v i s it ou r websi te. 1 

### HUMAN S T UDI ES : Occupational and Residen tial P ast difcnoconazole ri s k assess ments r ely in part on data from studie s in which adult human s ubjec ts we r e intention a ll y ex po se d to a pes ti c id e to de termin e th e ir dermal and inhalation exposure. Many such stud ies , involving exposure to many different pe stic id es , co mpri se ge ne ri c pesticide exposure databa ses such as the P es ticide Handl ers Expos ure Databa se (PHED) , the Agricultural Reentry Task Force (A RTF ) Database , and the Outdoor Residential Exposure Ta sk Force (O RETF) Database. EPA has reviewed a ll the s tudi es s upp or tin g th ese multi-pesticid e ge ne ri c exposu re databases , a nd ha s found no c lear and convincing evidence that the conduct o f any of th e m was either fu nd amenta ll y un e thi ca l o r s ign i ficantly d efic ient r e lat ive to the ethical standards prevailing at th e tim e the research was co nduct ed. A ll app licabl e r equ ire me nt s of EPA 's Rule for the Prote c tion of Human Subjects of Researc h (40 CFR Part 26) have been satisfied. and there is no reg u lato ry barrier to con tinu ed reliance on these studies.

1 h!lp :// www2

.epa.gov /endocrinc-d i s ruplion 1 5