### UNITED STATES ENV IRO NMENT AL PROTECTION AGENCY WASHINGTON, D. C. 20460

OFF IC E OF C H EM ICAL SAFETY A N D POLL UTIO N PREVENTIO N 

### MEMORANDUM
DATE : Oc tober 1 , 20 1 5


### SUBJECT: Difenoconazole: Human Health Risk Scop in g Docum e nt in Support of R eg i s tration Review

P C Co d e: 128847 DP Barcode: 0429075 Decisio n No.: 50897 1 Re g ist r a ti o n No: N / A Petition No.: None Re g ul atory Act ion: Registrati o n Revi ew A ss e ss me nt Type: Scopi ng D ocume nt Reregi s t rat ion Case No.: 7014 TXR No.: None CAS No.: I 19446-68-3 M RID No.: None 40 C FR : § 1 80.475 

### FROM : Ivan Nieves , Ri sk Assessor 

# ._()4J .:__ .A B o nni e Cropp -Kohlli gian , E n v iro nm enta l Scie nti s 

## f

. T hur ston Morton , Chemist, Senior Sc ienti st ) Abdallah K.hasawinah , PhD. , Tox icologist 

### '/J**~** 

### Ri sk Assessme nt Branch 4

### ~ // Health Effects Division (7509 P )



### THROUGH: El issa Reave s , PhD. , Branch Chief

# ~7?~-**---~** Ri sk Assessment Bran ch 4 , H E D (7509 P)


### TO: Rosemary Kearns /Tony Kish (RM 22 ) F un gicide Branch R eg i stration Division (7505 P) And 

### Maria Piansay , Chemical Rev iew Mana ger Risk Manage ment and Impleme ntation Bran c h 5 P esticide R e -e v aluation Di v i s ion (7508P)

Attached in H E D 's human health scop in g document fo r difenoconazole to support Registration Review.

### Di fenoconazole/ 128847 Scoping Document 0429075


### Ex ecutiv e S ummary
The HED difenoconazole Registration Review team has evaluated the scientific database for the pesticide difenoconazo le 1 -[2-[2-ch l oro-4-( 4-c h loro

- phenoxy)

- pheny l]-4-methyl

- [ 1 ,3]di oxo lan-2-ylmethyl]- 1 

### H

- [ l ,2,4]tr iazo le to determi n e the scope of the work necessary to support the existing registrations.
Difenoconazole is a broad spectrum fungicide belonging to the triazole group of fungicides. [t i s currently reg i stered in the 

### U

. S. for use as a seed treatment on a number of cereal grain crops , cotton , canola , and potato seed pieces; for post-harvest use on members of tuberous and corm vegetables subgroup 1 C and pome fruit group 11-1 

### O ; and for multiple foliar applications on numerous crops including potatoes, stone fruit group 12 , and tree nut group 14. Difenoconazo le is also registered for use on golf course turf and treatment of ornamenta l plants in commercial and residential landscapes and interior plantscapes. Tolerances for difenoconazo le , currently established under 40 CFR 

### § 180.475 , range from 0.01-95 ppm. Difenoconazole acts by blocking demethy lation during sterol biosynthes i s w h ich, in turn , disrupts membrane synthesis. Difenoconazo le is availab l e as emulsifiab le co n ce n trate , so lub le concentrate, emu l s i o n [o il ] i n water , flowable suspension, and ready-to-use formu lations. As a seed treatme n t, it is applied with commerc ial grade seed treatment equipment. As a foliar treatment , i t i s applied to field and vegetable crops , landscape ornamentals and golf course turf by commercia l app l icators using aeria l and ground app li cation methods and equipme n t. It is app l ied to orname n ta l s by residentia l app l icato r s us ing hand he ld sp rayers.
The toxicology database for difenoconazole is complete for eval uating and characterizing toxicity and selecting endpoi n ts for purposes of this ri sk assessment. No new toxico logical data are r equired . H ED does n ot an ticipate the need to revise th e toxicological endpoints , points of departure , or safety factors for difenoconazole during Registration Review.
The difenoconazo le residue chemistry database is complete. The most recent acute and chronic dietary exposure ana lyses were conducted in 2015 u s ing the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID) Version 

### 3.16. The resulting acute and chronic food plus water dietary exposure estimate s were less than HED ' s Level of Concern (LOC) for the general U.S

. populat ion and aJI population sub

- groups. Quantificat ion of h uman cancer r i sk i s not required since it was determined the chronic dietary exposure assessment is protective of chronic risk including potentia l cancer. HED does not anticipate the need for a revised dietary assessment during Registration Review unless dietary exposure models or the Estimated Drinking Water Concentrations (EDWCs) are updated.
The re is sufficient information available to assess residential exposure resulting from residential uses of difenoconazole for Registration Review. Residential hand ler and postappl ication exposures were all re-evaluated and discussed in the most recent human health risk assessment dated February 24, 2015 (D421188; I. Nieves; 2 /24/2015) based
on the most current Standard Operating Procedures (SOPs) updated in 2012. All handler and post-app l ication exposure scenarios identified for the registered uses ( i.e. , applications to golf course turf and treatment of ornamental plants in commercial and
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### Difenoconazole/128847 Scoping Doc um ent D429075
residential landscapes and interior p lantscapes) resulted of no concern to the Agency. HED does not anticipate the need for a revised residential assessment during Registration Review

. A spray d ri ft and volatilization risk assessment fo r difenoconazole w ill be completed d u ring Registration Review

. There is suffic ient information avai lab le to assess occupational exposure resulting from occupati onal u ses of d i fenoconazo le for Registration Review. T he most rece n t quantitati ve occupational risk assessment that discusses these u se patterns was conducted in 2015 (D 421188; I. 

### Nieves; 2/24/20 1 5). No estimated risks of concern were identified for handlers with the require d Personal Protective Equipment (PPE) ( i .e., long shirt, long pants, sh oes, socks and gloves). No risk estimates of co nce rn were identified from postapp li cation exposure either. The Restricted Entry In terval (REI) specified o n proposed and registered label s is 12 hours based on difenoconazole 's acute toxicity. This is considered adequate to protect agric ultur a l workers from po st -application exposures to difenoconazole. HED do es not anticipate the need fo r a revised occupation a l assessme nt during Registration Review

. The acute and c hronic aggregate ri sk assessments take into acco unt expos ure estim ates from dietary consump tion of difenoconazole (food and drinking wate r). In th e 20 15 assessment, the ac ut e and c hronic dietary ri sk estim ates were not of concern to HED (<100% aPA D and cPA D , respectively) for the ge n eral U

. S

. population and all ot he r populatio n subgroups. Short term aggregate expos ur es acco unt for residential expos ur e plus average exposure l eve l s to food and water (co n sidere d to be a background expos ure level). 

## In the 2015 assess ment , s hort term aggregate risk estimates ranged from MOEs of 170 to 190 (targe t MO E is 100) and therefore not of concern to HED. HED do es not anticipate the need for a revised aggregate assessment during Registration Re view.
The previous agg regate tri azole human health ri s k assessment was rece ntl y updated for free triazo les and its con jugates and the aggregate estimates remain below HED 's l eve l of concern (T. Morton, D426493, 4/9/ 1 5). As part of Regi stration Review , updated aggregate risk assessmen ts may be necessary to re fl ec t revised di etary or residential exposure estimates.
No data deficiencies were id entified for d ifenoconazole however HED anticipates conducting the fo ll ow in g risk assessment updates during Registration Review:
D i etary Exposure:
• A rev ised dietary assessme nt during Regi s tration Review wou ld on ly be completed if di etary exposure models o r the Est im ated Drinkin g Water Co nce ntrations (E D WCs) are updated. Occupational and Residential Exposure:
• Th e need for spray drift and volatilization risk assessments for difenoconazole wi ll be comp leted during reg i stration re v iew.

P age 3 of29

### Difenoconazo le/12884 7 Sco pin g Document D429075



### . 1 Intr odu cti o n
D i fenoconazole i s a broad spectrum fu n gic ide belonging to th e triazole gro up of fu ng icid es. The re are c urrently 35 act i ve end-use products

. Sy nge nta Crop Protection , LLC , ha s 32o f these , and the other three are r eg i ste red with A lbaugh , L LC (2) , and N u f arm Ame rica s, In c ( 1 ). It 

### is currently registered in the U.S. for u se as a see d treatment on a number of cereal grain crops , cotto n , cano l a , and potato seed pieces and for postharvest u se on members of tub e rou s and corm vegetables subgroup IC and pome fruit gro up 1 1 -10 a nd for multip le foliar applications on numerou s c ro p s includ i ng s tone frui t gro up 12 and tr ee nut gro up 1 4

. Di fe noco nazole i s also registered for u se o n go lf course turf and treatment of ornamental plants in commercial and residential l andscapes and interior pl antscapes.


### 2 Haz ar d ld e ntifi ca ti o nffo x ic o l ogy
The toxicology database fo r difenoconazole is comple te for eva luating and characterizing toxicity and se l ecting endpo ints for ri s k assessme nt. S ubchro ni c and chronic toxic ity s tudies w i th d i fe noconazo le in m ic e and rats s how e d decrea se d body weights and effects o n th e li ver (e.g. hep atoce llular h ype rtro ph y , li ver nec ro s is, fatty c han ges in the li ver). Acute and subc hr o ni c neu rotox ici ty stud ie s s howed evi den ce of neuro toxi c effects. However , the observe d effects were transient and the d ose -respo n se was we ll c haracteri zed with identifi e d do se leve ls at which no observed adverse effects w e re see n
. Th e availab le developmental and r e production t ox ic it y studi es indi ca ted no increase d suscepti bilit y of rats or rabbits from 

### in utero or pos tn ata l exposu re to di fenoconazole. In an immunotoxicity study in mice , difenoconazole produced imm unotoxicity at doses that cause d sys te mi c toxicity. No evidence of carcinogenicity was see n in the c hro nic/ cancer rat s tudy. E vidence fo r carc inogeni c ity was seen in mi ce as indu c tion of liv e r tumors at doses which were consid e red to be excess ively hi g h fo r carcinogenicity test in g. Difenoconazole has been class ifi ed as " S u ggestive Evide n ce of Carcinogenic Potential'

. with risk quantified using a no n-lin ear (Margin of Expos ure) ap proac h (TXR 0054532). T he cancer c la ss ificati o n is ba se d on tumors occurring at excessive toxic d oses in mi ce , the absence of tumors at the lower do ses and the absence of ge notox i c effects. Th e FQPA Safety Facto r i s reduce d to 

### lX. Difenoconazole exhibits low acut e toxicity by the oral , dermal and inhalation routes of exposure. It is not an eye or skin irritant and is not a se n si ti zer. 

### Endpoints /

Points of D epa rture (PODs)fo r Risk Assessment. Toxico lo gica l points of departure ( P ODs) were selected for di e tary and drinking water expos ures ri sk assess me nt s
. An acute P O D for all p op ulatio n s was se lected from an acute neurotoxic ity study in ra ts based on red uc ed g rip s tre ngth. A chroni c POD was se lected from a chronic/ carcinogenic ity stud y in rats based on body we ight effec t s
. Short- a nd intermed iate-term incidental oral , derma l and inhalation POD s were selected from an oral
rat reproduction study based on decreased body weight effects in pups and parental ani mal s. A d e rmal absorption factor i s app lied w h e n dermal ex p os ure e ndp o i nt s are se lec ted from oral to x ic i ty studie s
. A d e rmal abso rption factor of 6%, ba sed o n triple pack data , was used for the dermal exposure assessment. Inh alat ion toxicity i s assumed to be equivale n t to oral toxicity. An uncertain ty factor of 1 

### OOX was applied endpoints

Page 4 of29

### Difenoconazole/128847 Scoping Do c um ent D4290 75
selected for 

### alI expos ures routes ( 

### 1 OX for in terspec ies extrapo lation , 1 

### OX for intraspec ies variati on, lX FQ P A SF)

. 

### FQPA Factor. The available Agency guid e line studi es indi ca ted no increased qualitati ve or quantitative s u sceptibili ty of rats or rabbits to 

### in utero and/or postnatal expos ure to d ife n oconazole

. In 

### the prenatal developmental tox ic ity stud ie s in rats and rabbits and the two

- generation reproduction study in rats , tox ici ty to the fetuses /offspring, when observed , occurred at equivalent or higher do ses than in the maternal / pare nta l animals

. Toge ther, the avai lab le data s upport the reduction of the FQPA factor to I X.
A s ummary of to x ico logical doses and po ints of departure for di fe noc o n azo le i s presented in Table 3 in the Append i x. A toxicity profile of difenoconazole i s presented in Tables 4 and 5, and guide line d ata requirements in Table 6 of th e Appe ndi x
. 

### Conclusions for Toxicology
Th e toxicology database for di fenoconazo l e i s complete. Based on a WOE approach cons id erin g a ll the avai lable difenoconazole hazar d and expos ure information, the Hazard and Sc ience Policy Counc il (HAS PO C) concluded that a 28 -d ay day inhalation st ud y is not required at this time (TXR # 0054074). HED doe s not anticipate the need to revise the toxico l ogical endpoints, points of departure, o r safety factors for d if enoconazole during R egistration R ev i ew
. 

### Residue Chemistry
The qua li tative nature of the residue of difenoconazole in/on crops and li ves tock i s adequately understood. The HE D R es idu es of Co nce rn Knowledgebase Sub- comm ittee ( ROCKS ) has det ermin ed (DP# 391350) that the residues of co nc ern for tol erance enforcement and risk assessment i n/on crop commodities i s parent on l y and in livestock commod i ti es are p arent and it s metabolite, CGA

- 205375 ( l-( 2

- ch lo ro
- 4

- (4

- chlorophenoxy)p he n y l]- 2 -[l ,2, 4]triazol-1-yl-ethanol). In addition , metabo l ite O H

- CGA

169374 shou l d be cons id ered as a res idu e of concern in milk for t he dietary ris k assessment. Metabo li tes CGA-205375 and OH-CGA-169374 are no m ore toxic than difenoconazo l e. Adequat e ana l yti cal enforceme nt me thod s are avai lable.
The HED ROCKS a lso determined (DP# 391350) that th e residues of co n ce rn in drinking water are parent and its metabolite , CGA-205375.


### Conclusions for Residue Chemistry The difenoconazole residue che mi stry database is complete. 

### Dietary Exposure and Risk Assessment
The most rece nt acute and chronic di etary expos ure analyses we re co ndu cted in 20 15 and considered a ll currently registered uses (D42649 1 , T. Morton , l-Jul y-20 1 5). The analyses we re co nduct ed using D EEM-F C ID (ve r. 3 .1 6) w hich in corporate d food consumption data from the 2003-2008 food consumption data from th e U.S

. Department of Agriculture's (USDA's) National H ealth and N utri t ion Examination S u rvey, What We

Page 5 of29

### Difenoconazole / 128847 Scoping Document D 429075
Eat in America, NHANES/WWE IA)

. T h e resulti ng unr efined (ass umi ng to lerance leve l residues and I 00 %CT) acute food plus water dietary exposure estimates were less than HED ' s level of concern ( < I 00% of the acute population

- adjusted dose 

### (aP AD)) at the 95th percenti l e of the exposure distribution for the general U.S. p opula ti on (I 

### 5% aP AD) and all pop u la ti o n s u b-groups; the m ost high ly exposed popu latio n subgroup was chi ldren 1-2 years old with 49% aPAD. The somewhat refined chronic analys i s assumed tolerance-level res i dues fo r some commodities, ave rage field tri a l residues and USDA Pesticide Data Program monitoring samples for the remaining commod it ies , the availab le em p irical or DEEM (ver. 7.8 1) default process ing facto rs, and% CT ass u mptio n s fo r some commodities. The resulting chronic food plus water dietary exposure estimates were less than HED ' s level of concern (<100% of the chronic population-adjusted dose (cPAD)) for the general U.S. population (26% cPAD) and all popu lation sub-groups; the most highly exposed populat ion subgroup was chi ldren 1

- 2 years o ld with 89% cPAD

. 

### Conclusions for 

### Dietwy Exposure
H ED d oes not anticipate the need for a revised dietary assessme n t duri ng Reg istration Review u nl ess th e Estimated Dri nki n g Wate r Conce n tra ti o n s (E D WCs) are updated.


### R es idential Ex posure a nd Ri s k Assess ment
R

esidentia l exposure is expec ted from reg i stered uses. There is ex p osure from handlers wo rking w ith ornamental plan t s, and residenti a l post-app l ication exposure from applications to golf course turf and treatment of ornamental plants in commercial and residential landscapes and interior plantscapes. Scenarios identified from these uses were all re
- eval ua ted and d iscussed i n the most recent hu man health r isk assessment da t ed Feb ru ary 24 , 20 1 5 (D42 1 188; I. 

### N ieves; 2/24/2 01 5) base d on the 2012

. At t hi s t ime no new nor p roposed residen t ia l u ses have been submitted to t he Agency.
The highest app l ication rate assessed for handlers was 0

. 13 1 b ail A. Exposure scenarios identifie d and assessed included mix ing/loading and app l ying l iquid form ul ations with the fo ll ow ing equipment: manually-p ressurized handwand; hose-end sprayer; backpack; and a ready to use hose-end sprayer. No estimated risks of concern were identified from residential handler exposure scenarios (MOEs > LOC of 100). Total MOEs (dermal and inha lation combined exposu re) ranged from 3,500 to 68,000. All exposure scenarios we r e considered to be of s hort -term duration ( 1 -30 days). Exposure scenarios were identified via the dermal route of exposure from postapplication activities. Rates of appl ication ranged from 0.13 to 0.25 lb ai/A. Risk est im ates from post-app li ca t ion exposure scenarios resu lted in MOEs above the Agency's LOC of 100. MOEs ranged from 250 to 31,000 (e.g. , fo r go l fers).
In conjunction with the 2007 40 CFR Part 158 Data Requirements , HED typically requires s u bm iss io n of a turf transferab le residue (TTR) study in order to determine exposure and risk associated w ith play in g o n treated tu rf. S in ce the es ti mated r esi d e nti a l turf post-applicat io n exposure for golf course usi n g default TTR val ues for difenoconazo le is mi n imal in comparison to the level of concern (i.e. , the calculated MOE is greater than 10 times higher than the level of concern , MOE= 2 , 100 compared to Page 6 of29

### Difenoconazole / 128847 Scoping Document D429075
the LOC of 100); EPA is waiving the 40CFR TTR data requirement. In this in stance, it is unlikely that chemical-specific TTR data would be needed to further refine exposure assessments or would add appreciably to our general understanding of the availability of turf transferable pesticide residues.
In accordance with 40CFR 158 , Dislodgeable Foliar Residue DFR data are required for residential (e.g., ornamentals) uses that could result in post-application exposure to foliage. Since the estimated residential post-app lic at ion exposure for ornamentals usi ng default DFR values for difenoconazole is minimal in comparison to the level of concern (i

. e ., the calculated MOE is greater than 2 times higher than the level of concern , MOE= 300 compared to the LOC of 100); EPA i s waiv ing the 40CFR DFR data requirement. In this instance , it is unlikely that chemical

- specific DFR data would be needed to further refine exposure assessments or would add appreciably to our overall understanding of the availability of dislodgeable foliar pesticide residues for difenoconazo le.
Residential bystander exposures resulting from off-site transport (e.g., spray drift or volatilization) may occur as a result of application s of difenoconazole. The potential for spray drift will be quantitative ly evaluated for each pesticide during the Registration Review process which ensures that all uses for that pesticide will be considered concurrent!y.
In terms of volatilization , the Agency has developed a Volati li zation Screening Tool and a subsequent Volatilization Screening Analys i s (http: //www .regulation s .go v/# !docketDetail;D = EPA-HO

- OPP

- 2014

- 0219 ). During Registration Review , the Agency will utilize this analysis to determine if data (i.e., flux studies , route-specific inhalation toxicological studies) or furthe r analysis is required for difenoconazole

. 

### Con clusions of Residential Exp osure Assessment
HED does not anticipate the need for a revised residential assessment during Registration Re v iew. Spray drift and volatilization risk assessment for difenoconazole will be completed during Registration Review. 

### Aggregate Exposure and Risk Assessment
The acute and chronic aggregate risk assessments in the 2015 risk assessment take into account exposure estimates from dietary consumption of difenoconazole (food and drinking water). The acute and chronic dietary risk estimates were not of concern to HED ( < 100% aPAD and cPAD, respectively) for the general U.S. population and all other population subgroups.
Short term aggregate exposure takes into account residential exposure plus average exposure levels to food and water (considered to be a background exposure level). The short term aggregate risk included the estimated risk assoc iated with comb in ed risks from average food and drinking water exposures and dermal and inh al ation exposures from adults handling difenoconazole with a backpack sprayer and from post-application exposure to children 6 to 11 years old re-entering a treated garden scenario. Short term Page 7 of29

### Difenoconazole/128847 Sco ping D oc um e nt 042 9075
aggregate ri s k es timate s in the 2015 ri sk assessment ranged from MOEs o f 17 0 to 190 and therefore not of co ncern to HED.

T here are no res id ential u se sce nari os th a t will res ult in potenti a l in termediate t e rm ex posure to d ife noconazo le. Therefore , an interm ed iate-term aggregate was not performed.
A pplicati o n of difenoconazole a lso res ults in potent ia l expos ures to th e metabo lite s T (l ,2, 4-tria zo le), TA (tr iazoly la lanin e ) , T AA (triazo ly lacet ic acid ), and THP ( triazol y l hy droxypro pionic acid). T hese compounds are co n s idered to be toxicologicall y different from difen oconazole. The previous aggregate triazole human health ri sk assessment was recentl y updated for free triazoles and its conjugate s and th e aggregate es tim ates rem ai n below H ED 's l eve l of concern (T. Morton, 04 26493 , 4/ 9/15).


### Co11clusio11s for Aggregate Assessmen t H E D d oes not anticipate the need for a revised aggregate assessment during R egistration Review unl ess the Esti mated Drinkin g Water Concentrations (E DW Cs) are updated

. Revi s ed tri azo le risk assessme nts may be requir e d. 

### Occupationa l Ex po s ure a nd Risk Assessment Occupationa l h and ler and post-application exposures ar e expected based on the registe red uses of dif e noco naz ol e. The most rece nt quantitative occupational risk assessment th at discuss these use patterns was conducted in 20 1 5 (042 1188 ; I. 

### N ieves; 2/ 24/ 20 1 5)

. Difenoconazole is formu lated as e mul s ifiable concentrates , so lubl e concentrates , e mulsion s (oi l) in water, Oowable s u s pe n sions, and ready-to-use formulations. Foliar ag ri c ultural applicat io n s can be made by a ir , grou ndb oo m , airb last, chemigation , and handheld equip ment at app li cati on rat es ranging from 0.07 p ounds active in g redi ent per acre (lb ail A) to 0.13 lb ai / A. 

### Commercial applicati ons w ith l ow- press ure handheld eq uipment to o rnam en tal s can range fro m 0.0011 to 0.003 lb ai per gall on of so lution

. Golf course turf appl ications are made at a rat e of 0.25 lb ail A. 

### See d s ar e tr eated with spec i a li zed equ ipme n t at rates ran g ing from 0.025 to 0 .031 lb a i per hundred pounds of seed. P ost-harvest app li catio n are regi s tered at 0.00035 lb a i/ 100 lb s potato es. Occ upati o na l ex po su r e sce nario s applicable to difenoconazo l e ran ge from s ho rt-term ( I to 3 0 days) to intermediate- te rm (3 0 days to six mo nth s) durati o n.
The occupatio nal handl er assess ments indicate that , for the exis tin g registered uses , all of the potential exposure scena rios provide d e rmal and inhalation marg in s of expos ur e ( MOEs) greate r than o r e qual to th e LOC o f 100 at so me le ve l of pe rsona l protection and/o r engineering controls. T h e labe l s fo r mos t u ses req uire g loves in 

### ad di t ion to baseline clothing att ire of lo ng pants , long sleeved shirt and shoes plus socks and are conside red adequatel y p rotect ive.
Sev eral lev e l s of dermal po s t-application exposure acti v itie s have been identified ran g in g fro m l ow exposure activities such as weedi ng and scoutin g in immature plants to very high exposure acti vities such as harv esting o r thinning fruit from trees. The short

- and inte rmedi ate-term p os t- a ppli ca tion assess ment s indi cate that the MOEs reach the LO C of
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### Difenoconazole / 128847 Scoping Document D429075
100 within 1 day after application for all of the existing use scenarios. The restricted entry interval (RE I) listed on the applicab le labels is 12 hours and is adequately protective.
In accordance with 40CFR158 , Dislodgeable Foliar Residue DFR data are required for occupational (e.g., crops) uses that could result in post

- app li cation exposure to foliage. Since the highest estimated occupational post-application exposure using default DFR values for difenoconazole is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 2 times higher than the level of concern , MOE =370 compared to the LOC of 100); EPA is waiving the 40CFR DFR data requirement. In this instance , it is unlikely that chemical-specific DFR data wou ld be needed to further refine exposure assessments or would add appreciably to our overall understanding of the availability of dislodgeable foliar pesticide residues for difenoconazole.


### Co nclusions/or Occupational Exposure
H E D does not anticipate the need for a revised occupational assessment during Registration Review.


### Public Health and Pesticide Epidemiology Data
For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease Control and Prevention/National In stitute for Occupational Safety and Health ( CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides ( SENSOR) databases were consu l ted for pesticide incident data on the active ingredient difenoconazo le (D429081 ). The purpose of the database search is to identify potential patterns in the frequency and severity of the health effects attributed to difenoconazole and salts exposure. Difenoconazole is not included in the AHS , and , therefore , this study does not provide information for this report.
Based on the low frequency and severity of incident cases reported for difenoconazole in both IDS and SENSOR-Pesticide s ther e does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a concern is triggered , additional analysis will be included in the risk a ss essment.


### Tolerance Assessment and International Harmonization
U .S. permanent tolerances for residues of difenoconazole are estab li shed under 40 CFR § I 80.475(a)(l) in/on numerous c rop commodities and U.S. permanent tolerances for residues of difenoconaz ole and its me tabo lite , CGA-205375 , calculated as the stoichiometric equivalent of difenoconazole are established under 40 CFR 

### § l 80.475(a)(2) in milk , egg and ruminant tissue commodities. T he current tolerance expression is in accordance with the H E D Interim Guidance on To l erance Expressions (5 / 27 / 2009, S. Kni z ner). U.S. tolerances are harmonized with Codex and Canadian maximum residue limit (MRL) with regards to definition of residues as well as leve l s in/on a number of commodi ties. See Table 7 in the Appendix to this document for details. Additional harmoni z ation of residue levels will be cons idered under Registration Review. Page 9 of29

### Difenoconazo le/ 12884 7 Scoping Document D429075



### C umul ati ve Ri s k Assess m e nt
Difenoconazole is a memb e r of the triazole-c on tainin g class of pe st icides . A lthough conazoles act si milarl y in plants (fu n g i) by inhibiting ergosterol biosynthesis , there is not nece ssarily a re lationship between th e ir pesticidal activity and their mechani s m of toxicity in mammals. Str uc tural simi larities do not con s titute a common mechani s m of toxicity. Evidence i s neede d to es tabli s h that the chemicals operate by the same , or e sse ntiall y the sa m e, sequence of maj o r bio c he mical events (E PA , 2002). In conazoles , however, a vari able pattern of toxico logi cal re s ponses i s fou nd ; some are hepatotoxic and hepatocarcino ge nic in mic e. Some induce thyro id tumors in rats. Some indu ce developmental , rep roducti ve , and ne uro logical effec t s i n rodent s. Furthermore, the conazoles produc e a di ve rse range of biochem ical events including altered cholesterol

. lev e l s , s tress re s ponse s , and altered DNA meth ylation. I t is not cl early under s tood whethe r these biochemical eve nt s are directly co nnected to the to x ic o lo g ical o utc o me s. Thus , there i s curre nt ly n o ev idence to indicate that conazoles share co mmon mechanisms o f tox ic ity and E PA is not follow i ng a cumu lative ri s k approac h based on a common mechani s m of tox ic ity for the conazoles. For in fo rmati o n rega rdin g EPA's pro cedu re s for cumu latin g effec t s from s ub s tanc es found to have a co mm o n mechanism of toxic i ty, see EP A ' s website at ht tp: //www.epa.gov/ pe s tic i des/cumulative.


### Hum a n S tudi es
Th e 2002 RED and 2015risk assessment relied in part on data from s tud i es in which adult human s ubjects we re intentionall y ex posed to a pesticide or othe r chemical. These dat a , which include studies from PHED 1

. 1 , 

### the AHETF datab ase , the A RTF database , and Expo SAC Polic y 14 (SOPs for Seed Treatment) , are ( l ) 

### s ubject to e thics revi ew pursuan t to 40 CFR 26 , (2) have rece ived that rev iew , and (3) ar e co m p l ian t with app l icab le ethic s require ment s. For ce rtain stud ie s , the ethic s rev iew may have includ e d rev iew by the Hum an S tudi es Review Board. D e s criptio n s of data sou rces , as well as guidance on th e ir us e , can be found at the Agency w e b s ite 1 • 

### Data Requir e me nts
No data defici e nci es we re identi fied for d i fenoconazole however H ED anticipate s conducting the fo llowin g ri s k a ssess me nt upd ates durin g Registration Review:
Dietar y Expousre:
• HED do es not ant icipate th e nee d for a revised dietary asse ss ment durin g Registrati o n Re v iew unle ss dietary exposure mode l s or th e Estimated Drinkin g Wate r Co ncentration s (E DW Cs) are updated. Occupational and Residential Exposure:
• T he need for spray drift and vo latili zati o n ri sk assessments for difenoconazole will be c ompleted during regi s tration rev iew.

1 http :// www.eoa
. gov/pest icide s/s cience/handler

-exposure-data.html and http : //www.epa.gov/ pesticides/s cience / post-app-exposure-data.html 

### Page 1 0of2 9

### Difenoconazole/128847 Scoping Document D429075
References
Difenoconazole: Tier I (Scoping) Review of Human Incidents and Epidemiology. S. Recore , 0429081 , 9/ 15 / 2015
Difenoconazole. Human Health Risk Assessment for proposed new foliar uses on legume subgroup 6C and bushberry subgroup 13-07B ; post-harvest uses on pome fruit group 11-1 

### O ; and ornamental plants and vegetab le transplants grown in both indoor and outdoor production facilities.

- I. 

### N ieves , D4 22992 , D421429, D421216, 0421201, 0421208 , 0421188 , and D41 3471, 2/ 24/ 2015
Oifenoconazole. New Foliar Uses on P ea and Bean , Dried Shelled, Except Soybean, Subgroup 6C and Bu shberry Subgroup 13-07B. Summary of Analytical Chemistry and Residue Data.

- B. Cropp-Kohll ig ian , D418479 and D421194, 10 115 /20 14
Difenoconazole. Request to Register New Multip le Active Ingredient (MAI) End-Use Product (AcademyTM Fungicide) for New Po st-Harvest Uses on Pome Fruit Group 11-10. Summary of Analytical Chemistry and Residue Data.

- B. Cropp-Kohlligian , 0417611 , 10/17/ 2014
Oifenoconazole. Acute and Chronic Aggregate Dietary Exposure and Ri sk Assessments for the Petition for Use of Difenoconazole on Pea and Bean , Dri ed Shelled , Excep t Soybean , Subgroup 6C , Bushberry Subg r o up I 3-07B and an amended use on Pome Fruit to add Post-Harvest Use of Difenoconazole.

- T. 

### Morton , 0421430 , 2/ 24/15 Drinking Water Exposure Assessment in s upp ort of the new use registration of multiple difenoconazole formulated products on Artichoke , Berry Bushberry Subgroup 13-07B , Ginseng , and Bean and Pea, Dri ed Shelled (except Soybean) Subgroup 6C as well as Conversion of Stone Fruit Crop Group 12-12 and Tree Nuts Crop Group 14-12

.. - F. Khan , D421092 , I 1/13/14
Difenoconazole. Occupational and Residential Exposure Assessment for a Proposed Use on Canela and Oilseed Subgroup 20A.

- T. 

### Nieves, 041 281 1 , 09 / 13 / 2013
Difenoconazole. Occupational and Residential Exposure Assessment to Eval uate the Risk from Proposed Uses on Post-Harvest Potatoes , and the Expansion of Various Crop Groups Including : Citrus Fruit Group 10-10; Fruiting Vegetable Subgroups 8-10; Lo w Growing Berry Subgroup 13-07G , except cranberry; Pome Fruit, Crop Group 11-10 and Fruiting Vegetable , Crop Group 8-10).

- I. 

### Nieves, D 398608, 5/ 30 / 20 12
Difenoconazole. Occupational and Residential Exposure Assessment for the Propos ed New Use of Difenoconazole on Strawberry , Carrot , Chickpeas , Soybean, Stone Fruit: Group 12 and Golf Course Turfgrass. - R ebecca D aiss ; 0371037 ; February 24, 2011

. Di fenoconazole. Occupational and Residential Exposure/Risk Assessment for the Propo sed New Uses of Difenoconazole on Fruiting Vegetables, Tuberous and Conn Vegetab le s , P ome Fruit , Sugar Beets and Ornamentals

- Mark I. 

### Dow; D340044; Jul y 27 , 2007

. Page 11 of 29

### Di fenoconazole/128847 Sco pin g Document 0429075

Di fenoconazole: Report of the Residues of Co ncern Knowledgebase Subcommittee ( RO CKS). Will i am Irwin ; 0 39 1 350 ; Septemb er 19, 2011
Interim Guidance on Tolerance Expressions. Steve Knizner ; May 27 , 2009.

Page 12 of29

### Difenoconazole/12884 7 Scop in g Do cument D4 29075 Append i x 

### A.

Tab le 1. Difenoconazo l e Nomenc lat ur e. Chem ical structure of parent**~** 

# o'Q**~N** 

# I**~**

# I~ N 

### I Cl

## N 0 0 

# L_\ Cl**c~** mol. wt. 406

. 3 Co mmon nam e Di fenoconazole Co mpany experimental name CGA-169374 IUPAC name 1-(2-(2-chloro-4-( 4-chloro-phenox y) -ph eny 1)-4-meth y l-[ 1 , 3 ]dioxolan-2- ylmethyl]-1H-[ 1,2,4]triazole CAS name 1-[[2-[2-ch lo ro -4-( 4-c h lorophenoxy)phenyl]-4-methy 1-1 ,3 -dioxolan-2-yl]methyl]- I H-1 , 2,4-tria zole CAS reg istry numb er I 19446-68-3 C hemical structure of 

# Ou

CGA

- 205375 livestock 

### "': metabolite, 1-(2-chloro-4-( 4- 0N 

# I**~**

# ~ chlo ro-phenoxy)phenyl]-2

- [ 1,2, 4 ]triazol-1- yl -ethanol N 

## I Cl

# ~N O H Cl mol. wt. 349.2 Chem ic al structure of

### N~ 1 ,2,4-Triazole (I ,2,4 -T ) 

## I N 

# HN--...Y

Chemical st ructure of NH 2**N~** Triazo l yla lan ine (TA)

# ~IN HO**N~**
0 C he mical str ucture of 0**N~** Triazo ly lacetic acid (TAA)

# ~/ N

### N~ H O



### Page 1 3of29

### Di fenoconazole/ 128847 Scop in g Document D429075

Table 2. Ph ys icochemica l Pr o p e rt ies o f D i fe n oconazo l e. Parameter Value Refere nce Melting po int 78.6 °C DP# s 1 72067 an d 178394 , I 0 / 26/ 92, R. pH 6-8 at 20 °C (saturated so luti on) Lascola Density 1.37 g/ cm 3 at 20 °C Water solubility 3.3 ppm at 20 °C So lvent so lubili ty g/ 100 mL at 25 °C : n-h exane: 0.5 1-octanol: 35 toluene: 77 acetone : 88 ethanol: 89 Vapor pre ss ure 2.5 x I0
· 10 mm Hg at 25 °C Dissociation constant , pK

. pure grade (99.3% ± 0.3%) DP# 375159 , 5/ 26/10, B. Croppdifenoconazole in water (with 4% Kohlligian methanol) at 20°C is I

. I Octanol/water partition 4.2 at 25 °C DP# s 17206 7 and 1 78394, I 0 /26/ 92 , R. coef fi c ient, Log(K ow) Lasco la UV/ visible absorption spectrum 

### Amu at about 200 and 238 nm PMRA Propo se d Regulatory Decision (in methanol at 26 °C) Document on Difenoconazole , 4/ 14/ 99 ( PRDD99-0 I)



### Page 14 of29

### Difenoconazo l e/128847 Scoping Document D429075

Table 3a. Summary of Toxico l ogica l Doses and Endpoints for Difenoconazo l e for Use in Dietary and NonOccupationa l Human Hea lth R is k Assessments D422992 Februarv 24 2015 , PC Code: 12884 7 Expos ur e Point of U nce r tainty/FQPA RfD , PAD , Study and Relevant LOC for Risk Scena rio Departu re Safety F actors A ssess ment Toxicologica l E ffect s Acute Dietary NOAEL =25 UFA = I OX aRID = aPAD Acute Neurotoxic ity Study in (A ll populations) mg/kg UFH = IOX = 0.25 Rats (M RJD 46950327) UFFQPA = IX mg/kg/day LOAEL = 200 m g/kg in male s based on reduced fore-limb grip st

rength in ma les on day 1. Chronic Dietary NOAEL = 0.96 UFA = !OX cRfD = cPAD Combined chronic ( All populations) mg/k g/day UFH = IOX = toxicity / carcinogenicity (ra t ; UF FQPA = IX 0.0 I mg/kg/day dietary , MRJD 42090019 , 427100 I0) LOAEL = 24.1 / 32

. 8 mg/kg/day (M/ F) based on cumulative decreases in body

weight gai n s
. Incidental Oral Oral NOAEL = UF A= IOX R es id ent ial Repro duction and fertility Study Short-Term ( 1- 1.25 UFH = IOX LO C for (rat; dietary, MRlD 42090018) 30 days) mg/kg/day UF FQPA = IX MOE< IOO Parental/Offspring LOAEL = 12.5 mg/kg/day based on decreased pup weight in males
on day 21 and reduct ion in bodyweight gain of Fo fema les prior to mating , gestation and lactation. Dermal Oral NOAEL = UFA = IOX Residential Reproduction and fertility Study Short

- and 1.25 UFH = IOX LOC for (rat; dietary, MRID 42090018) lntem1ediate- mg/kg/day UFFQPA = IX MOE < IOO Parental/Offspring LOA E L = Term (1

- 30 days 12.5 mg/kg/day based on and 1-6 months) decreased pup we ight in mal es DAF =6% on day 21 and r e duction in bodyweight gain of Fo females prior to mating, gestation and lactation. Inhalation Oral NOAEL = U F A= IOX Re side ntial Reproduction and fertility Study (Short

- and 1. 25 UFH = IOX LOC for (rat; dietary, MRID 42090018) lntennediate- m g/kg/day UFFQPA = IX MOE < IOO Parental/Offspring LOAEL = term) 12.5 mg/kg/day based on Inhalation and decreased pup weight in male s oral absorption on day 21 and r ed uction in bodyassumed we ight ga in of F o females prior
e quivalent to mating, gestation a nd lactation

. Cancer (oral, Difenoconazo le is classified "Suggestive Evidence of Carci nogenic Potential " with a nondennal , lin ear (MOE) approach for human risk characterization (CP R C Document, 7/ 27/ 94, Memo, inhalation) P. V

. Shah dated March 3, 2007, HE D Doc. No. 0054532). Point of Departur e ( POD) = A data point or an estima t ed p o int that 1 s derived from observed do se-resp onse data and u sed to mark th e beginning of ex trapo lati o n to determine ri sk assoc iat ed with l o wer e nvironmentally relevant human expos ur es. NOA EL = no observe d adverse effect level. LOAE L = lowest observed adverse e ffect l evel. UF = unce rtaint y factor. UFA = extrapolation from anima l to human ( int ers pec i es). UF11 = potential variation in se n s itivi ty am on g members of the human populati o n ( intraspecies OAF= Demial A bso rpti o n Facto r



### Page 15 of29

### Di fenoconazole/ l 2 884 7 Sc opin g D ocument 0429075

Table 3 b . S umma ry o f T ox i cologica l Do ses a nd Endpoint s for Difen oco n azo le for U se O cc u patio nal Hum a n Health Risk A sses sme n ts 0422 992 , February 24 2015 , P C Co de: 128847 

### Ex posure Point of Uncertainty/FQPA RID, PAD, Study and Toxicological Scenario Departure Safety Factors Level of Effects Concern for Risk Assessment D e rmal Rep ro duction and ferti li ty Short

- and Study (ra t ; di e tary , M RlD Intermediate- Oral U FA= IOX 42090018) Parental/Offspring Term ( 1 -30 NOAEL = U FH = IO X Occupationa l LOAE L = 12.5 m g/kg/day days and 1 -6 1. 25 LOC for base d on decreased pup weight months) mg/k g/day MOE< IOO in males on day 21 and OAF=6% reduction in body-we ight gain of F o females pri o r t o matin g, gestation and lactation

. Inhalation Reproduction and fertility (S hort- and Study ( rat ; dietary , MRlD Intermed iate- Oral UFA= I OX 420900 18 ) Parenta l / Off s prin g te nn) NOAEL = UF11 = I OX Occupational LOA E L = 12.5 mg/kg/day Inhal ation and 1.25 LOC for based on decrea sed pup weight oral absorption mg/k g/da y MOE< IOO in males on day 21 and
assu med reduction in body-weight gai n eq uival e nt of F o females prior to mating, ges t at ion and lactation. Cancer (ora l, Difenoconazole is classified "Suggestive Evidence of Ca rcinogenic Potential " with a nondermal , linear ( MOE) approach for human ri sk characteri zation (C PR C Document, 7/ 27/ 94, M emo , P. inhalation) V

. S h a h dated M arc h 3, 2 00 7, H E D Doc. No. 0054 532).

T a bl e 4

. Acute Toxici ty Pro fil e
- Dif e nocona zo le: February 20 15 G uid e lin e No. Stud y Type MRID No. Re s ult s Tox ici ty Ca tegor y 870.1 1 00 Acute oral 42090006 ( 1987) LD so = 1450 m g/kg Ill 870.1200 Acute dermal 42090007 ( 198 7) LD so > 20 I 0 mg/k g 111 870.1300 Acu te inhalation 42090008 ( 1991 ) LC so > 3.3 m g/L Ill 870.2400 Eye irritation 42090009 ( 1991 ) Mild irritation r eve rsibl e in 7 days 111 870

. 2500 Dermal irritation 4 20900 10 (199 1) Sl ig ht irritati o n IV 870.26 00 Skin se n sitization 42090011 (1987), Negati ve N I A 4 27 10004 (1992)

Tabl e 5. S ub ch r on ic , Ch ronic , Other Toxicit y Profile

- Difenocona zo le: Fe b rua r y 20 1 5 G uid e lin e No. MRID No. (ye ar) / Re s u lts Stu d y T y pe C la ss ifi catio n !Doses 870.3 1 00 42090022 ( 1987) N OA EL = 20 ppm (I mg/k g/ day) 90-Day oral toxicity Acce pt a bl e/g u ide lin e LOAEL = 200 ppm ( IO m g/kg/da y) based on th e I 0% (rat) 0, 20, 200 , 750, 1500 or 3000 decrease in body weight in the 200 ppm fe mal es (as we ll pp m as a negativ e trend in feed consumption) and In c reases in 0, I , 10,37.5 , 75and 1 50 abso lut e live r we ights in both sexes mg/kg/d 870.3100 42090021 ( 1987) NOA EL = 20 ppm (2.9 mg/kg/day) 90- Day o ral t ox icity Acceptab le/gu ide li ne LOAEL = 200 ppm (30.8 mg/kg/d ay) based on body ( m ouse) 0, 20 , 200, 250 0 , 7500 or 15 , 000 weig ht chan ges & li ver histopatholo gy. ppm



### Page 1 6 of29

### Difenoconazole/128847 Scop i ng Document D429075

Table 5. S ub c hronic , Chronic, Other Toxic i tv Profil e
- Dif e nocon azo l e : Fe bruar y 2015 G ui de lin e No

. MRID No. (yea r ) / Results S tud y T y p e C l ass ifi catio n /Do ses M: 0 , 2.9, 30.8, 383.6 , 11 25 and 2250 mg/ kg/d F: 0 , 4.1 , 4

.1 .5, 558.9 , 1125 and 2250 mg/kg/d 870.3150 420900 12 (1987) NOAEL = 3000 ppm (3 1.3 mg/kg/day in males/ 34.8 26-Week oral toxicity Acceptable I g uid e lin e mg/kg/day in females) 0 , 100 , I 000 , 3000 or 6000 ppm LOAEL = 6000 ppm (96 .6 mg/kg/day in males/ 110.6 M: 0 , 3

. 6 , 31.3, 96.6 and 157.8 mg/kg/day in females), based primarily on microscopic mg/kg/d examination of CGA 169 374-related lenticular cataracts. F: 0 , 3.4, 34.8, 110.6 and 203.7 mg/kg/d 870.3200 42090013 ( 1987) NOA EL = I0 mg/kg/day 2 1

/ 28 -Day dermal Acceptab le I g u ideline LOA EL = I 00 mg/kg/day based o n statisticall y toxicity (rat) 0, IO, 100 and 1000 mg/k g/d significant decrements in body weight , body weight gain , and food consumption. 870.3200 46950310 (2000) NOAEL (sys temic) = 1000 mg/k g/day 21 / 28 -Day dermal Acceptab le/ gu id e lin e L OA E L (system ic) was not determined. toxicity (rat) 0 , I 0 , I00 and I000 mg/kg/d N OA EL (dermal) = 100 mg/kg/day LOAEL (dermal) = I 000 mg/kg/day based on hyperkeratosis at the s kin application site. 870.3465 Waived HASPOC TXR # 0054074 2 8/ 90-Day I nhalation 870.3700a 42090016, 42710007 (1987) Maternal NOA EL = 16 mg/kg/day Pre natal Acceptab le I g uid e line LOA E L = 85 mg/kg/ day based on decreased body weight deve lopm e ntal in (rat) 0 , 2, 20, 100 or 200 mg/kg/d gain and food consumption. from GD 6-15 (nominal doses D eve lopme nt a l NOA E L = 85 m g/kg/day differed wide ly from theoretical, LOA E L = 171 mg/k g/day based on alterations in fetal this requ ired altering ossification. NOAEL/LOAEL va lu es) 870.3700b 420900 17 ' 42710008 (1987) Materna l N OAEL = 25 mg/kg/day Prenatal Acceptab le I g uid e lin e LOA EL = 75 mg/ kg/ day based on decreased body weight developmenta l in 0 , I , 25 or 75 mg/kg/ d from GD ga in and food co n sumption

. (ra bbit) 7-19 Deve l opmental N O A EL = 25 mg/kg/day LOA E L = 75 mg/kg/ day based on non sig nificant increases in postimplantation loss and resorptions/ doe and a significant decrease in fetal weiaht. 870.3800 42090018 ( 1988) P are ntal/Syste mi c NOA EL = 25 ppm ( 1 .25 mg/kg/day) Reproduction and Acceptable I g ui deline LOAEL = 250 ppm ( 12.5 mg/kg/day) based on fertility effects 0 , 25, 250 or 2500 ppm reductions (statistically nonsignificant) in body weight (rat) 0, 1.25 , 12.5 and 125 mg/ k g/d ga in wh ich appear to be part of a do se- related trend days 70-77 prior to mating , days 0-7 of gestation , and days 7- 14 of lactation Offspring N OAE L = 25 ppm ( 1.25 m g/ kg/day) LOAEL = 250 ppm (12.5 m g/ kg/day) ba sed on a s ignificant reduction in the body weight of FI male pups at day 21 in the 25 0 ppm group. 870.41 OOb 42090012 , 42710005(1988) N OAEL = 100 ppm (3.4 m g/ kg/ day in males/ 3.7 C hronic toxicity Acce p tab le I g uid e lin e mg/kg/day in female s) (dog) 0 , 20 , I 00 , 500 or 1500 ppm LOA EL = 500 ppm (16.4 m g/ k g/day in males/19.4 M: 0, 0.71, 3.4 , 16.4 and 51.2 mg/k g/day in females) , based on significant inhibition of mg/kg/d body weight gain in females. F: 0 , 0.63 , 3.7, 19 .4 and 44.3 mg/k g/d 

### Page 17of29

### D ife n oco nazo l e/ 12884 7 Sc opin g Doc um e n t 0 4 29075

Table 5

. Subc hr onic , C hr o nic , Other Tox i c i ty Pro fil e
- Di f e n ocona zo l e: Februar y 2015 G uideline No
. MRID No

. ( ye ar)/ Re s ult s S tud y Type C la ss ificati on /Doses 870.4200 42090019 , 427100 10( 1989) NOAEL 

## = 20 ppm (0.96 mg/kg/day in ma les/ 1.27 Carcinogenicity Acc eptab le I g uidelin e mg/kg/day in females) ( ra t ) 0, I0, 20, 500 o r 2500 ppm LOAEL 

## = 500 ppm (24. I mg/kg/day in males/ 32.8 M: o , 0.48 , 0.96, 24. 12 and 123

. 7 mg/kg/day i n fema les) base d o n reduct ions in c um u lative mg/ kg/ d body w eig ht gains in th e 500 and 2500 ppm groups. F: 0 , 0.64 , 1.27, 32.79 and 169.6 mg/kg/d No evidence of carcinogenicity 870.4300 42090015,427 10006( 1989) NOAEL 

## = 30 pp m (4.7 mg/kg/day in males/ 5.6 Carc ino ge n ic ity Acceptable I g uid e lin e mg/ kg/d ay in fema les) (mouse) 0 , I0 , 30 , 300, 2500 or 3000 ppm LOAEL 

## = 300 pp m (46.3 mg/kg/day in male s / 57.8 M: 0, 1.51 , 4.65, 46.29, 423.1 mg/kg/day in females) based on reductions in the and 818.9 mg/kg/d cumulative body weight gai n s and hepatoce ll ular F: 0, 1. 9 , 5.63 , 57

. 79 and 5 12. 6 hype rtroph y , liv er n ecros is, fatty c h an ges in th e li ve r a nd mg/kg/d bi le s t as is in the 300 , 2500 & 4500 ppm groups.
Evidence of carcinogenicity (liver adenoma/carcinoma in bo th sexes) 870.5 100 42090019,427100 10( 1989) T he re we re sufficie nt and valid data to conclude that In v itr o bacterial gene Acceptabl e I g uideline CGA 169374 technical was negative in the microbial mutation (Sa lmonella 340

- 5447 μ g/ plate ; gene mutation assay. typhimuriuml £. coli) / 85

- 1362 μ g/ p late ( r epea t assay mam m al ia n with TA l 537 a nd TA98) activation gene mutation assa y 870.5300 42090024 ( 1986) No co nc lusio n can be reac hed fro m the three nonac ti va t ed in vitro ma m ma l ian U n acce p tab le/ gu id e lin e and two S9 activate d mouse ly mph oma forward mutation cell gene muta t ion assays co nducted with difenoconazo le technical. The assay in mou se s tudy was se riously compromised. lymphoma cells
870.5375 469503 19 (200 I) There was evidence of a weak induction of structural In v itro Mammalian A c ceptab l e / g uidelin e chromosomal aberrations ove r background in the C ytogenetic s 0 , 21

. 99 , 27.49, o r 34.36 μg/mL presence ofS9-mix. (c hrom oso ma l (-S9) aberra ti o n s) assay in 0, 34.36, 53.69 o r 67. 1 1 μg/m L Chinese ham s ter ( + S9) C HO cells 870

. 5375 4695 0 32 1 (200 I) T he r e was evi d e nce of a weak indu ct io n o f s tru c tu ral I n vitro Mammalia n Acceptab le/ g uideline chro m osomal aberration s ove r backgroun d

. Cytogenetics 0, 26.3, 39.5 or 59.3 μ g/ m L (

- S9) (chromosomal 0, 11.7 or 17.6 μg/mL ( + S9) aberra tions) assay i n Chinese h amste r C HO cell s 870.5375 46950323 (2 00 I) There was no evide n ce of s tructural ch romosomal In vitro Mam m alian Acce p tab le/ gu id eline aberra ti ons induce d over background. Cytoge netics 0 , 5, 30 or 75 μg/ mL (-S9) (chromosomal 0 , 5 , 30 or 62 μg/ mL ( + S9) aberrations) assay in human lymphocytes 87 0 .53 8 5 42 0 90023 ( 1986) T here was no evi d e nce of a cytotox ic effec t o n the ta rget I n vivo mammalian U n accept a b lc/guide lin e organ o r significant increase in the frequency of nuclear chromosomal 25 0 , 500 or I000 mg/kg anomalies (micronuclci). However , the s tud y wa s comp ro m ised.


### P age 1 8 of2 9

### Dif enoco n azole/128847 Scopi n g Document 04290 75

Tab l e 5. S ub c hron i c, C hro ni c, Other To xicity Profile

- Dif e nocona zo le: February 2015 G uidelin e No. MRID N o. (year) / Resu lt s St ud y T y p e C l ass ifi cation /Doses aberrat ion test Assay in Mice 870.5395 41710011 (1992) Mice bone marrow
- No increase in m icronucleated In vivo mammalian A ccep table/ g ui de lin e polychromatic erythrocytes occurred with CGA -1 69374 cytogenetics

- Do ses up to 1600 mg/kg (91.2% a.i). erythrocyte micronucleus assay in mice 870.5550 4210012 ( 1992) CGA -i69374 tech

. (92.2% a.i.) was considered to be Unscheduled DNA Acceptable/ guideline negative in the unscheduled DNA synthesis assay in rat Synthesis in Doses up to 50 μg/mL primary hepatocytes as measured by an autoradiographic Mammalian Cells in method at concentrations up to 50.0 μg/mL. Culture 870.5550 42090027 ( 1985) No conclusion can be reached from the unschedu l ed Unscheduled DNA U n acce pt a bl e/ g uideline DNA synthesis (U D S) primary rat hepa tocyte assay Synthesis in 0.25-3 I .25 μg/mL conducted with difenoconazole technical at Mammalian Cells in concentrations ranging from 0.25 to 3 1 .25 μg / mL. The Culture sensitiv ity of the study was seve rely compromised.

870.5550 42090026 ( 1985) No conclusion can be reached from the un sche duled U nscheduled DNA U naccepta ble/ g uid e lin e DNA synthesis (UDS) human fibroblast assay conducted Synthesis in 0.08-10 μg/mL with difenoconazole tech. at cone. ranging from 0.08 to Mammalian Cells in JO**~ig mL.**  Culture 870

. 6200a 46950327 (2006) N OA EL (M) 

### = 25 mg/kg/day Acute neurotoxicity Acceptable/ g uideline LOAEL (M) 

### = 200 mg/kg/ day based on reduced forescreeni ng battery 0 , 25, 200 or 2000 mg/kg/d limb grip strength in ma les on day I and increased motor activity on Day I. NOA E L (F) 

### = 200 mg/kg/day LOAEL (F) 

### = 2000 mg/kg/day based on decreased body weight , the following clin ical s ig n s: upward curvature of the s pine , tip-toe gait , decreased activity, piloerection and s ide s pinched in and decreased motor activity. 870.6200b 46950329 (2006) NOAEL (M) 

### = 40 ppm (2.8 mg/kg/day) Subchronic Acceptab l e / g uid el in e LOAE L (M) 

### = 250 ppm ( 17 .3 mg/kg/day) based on neuroroxicity 0, 40, 250, or 1500 ppm M ; 0 , decreased hind limb strength.
sc reening battery 2.8 , I7 .3 or I07 .0 mg/kg/d NOA EL (F) 

### = 250 ppm ( 19.5 m g/kg/day) F:0 , 3.2 , 19.5 , or 120.2 m g/kg/d LOAEL (F) 

### = 1500 ( 120. 2 m g/kg/day) based on decreased body we ight, body weight gain and food effic ienc y. 870.7800 48696701 (201 1) Syste mic to x icity NOAEL 

### = 200 ppm (35 mg/k g/day) Immunotoxicity Acceptab le/ g u ide lin e System i c tox icity LOAEL 

### = I 000 ppm (177 mg/kg/day) [dietary]

- Mouse 0, 20 , 200, I000, or 1500 pm (0 , based on decreased body weight ga ins and li ver toxicity 3 , 35, I 77, or 247 mg/kg/day) for 28 days. l mm un ot oxici ty NOAEL 

### = 200 ppm (35 mg/kg/day) lmmun otoxic ity LOA EL 

### = 1000 ppm (177 mg/k g/day) based on decreased mean ant i-SRBC l gM levels. 870.7600 In vivo 47453201 (2007) See TXR 00564 73 Dermal Penetration

- rat 870.7600 In vivo 46950333 (2003) See TXR 00564 73 Dermal Penetration

- rat


### Page 

### 19 of29

### Difenoconazo le/ 1 2 8847 Scopi ng Do cume nt D 429075

Table 5. S ubchro n ic , C hron ic, Other Toxicity Profile

- Dife n oco na zo l e: Februa r y 2015 Guid e lin e No. MRID No. (year)/ R es ult s St ud y T y pe C l assi fication /Do ses 870.7600 In vi rro 47453202 (2007) See TXR 00564 73 Dermal Penetration 870.7600 I n virro 47453203 (2007) See TXR 005647 3 Dermal Penetration 870.7485 42090028 ( 1990) Male and female Sprague-Dawley rats. Animals were Metabo li s m and Acceptab l e / g uid e lin e adminis tered a sing le oral gavage dose of0.5 or 300 pharmacokinet ic s 14 daily dose s of 0.5 or 300 mg/kg ( 14 C]CGA

- 169374 , or 0.5 mg/kg unlabeled GGA- (rat) mg/kg 169374 by gavage for 14 days followed by a single gavage dose of 0.5 mg/kg [ 14 C)CGA- l 69374 on day 15

. The te s t compound was labeled with C 1 4 at either the phen y l or triazole ring. 870.7485 42090028 ( 1990) Male a nd female Sprag u e-Dawley rats. Animals were Metaboli s m and 42090029 ( 1987) administered a si ng le oral gavage dose of0.5 or 300 pharmacokinetic s 42090030 ( 198 7) mg/kg ( 14 C]CGA- 169374 , or 0.5 m g/kg unlabeled GGA- (rat) 42090031 ( 1988) 169374 by gavage for 14 days followed by a single Acceptab l e / g uidelin e ga va ge dose of0.5 mg/kg [ 14 C) CGA-169374 on day 15

. Sing le oral dose 0.5 or 300 The te st compound was labeled with C 14 at either the mg/kg phenyl or triazol e ring. 14 daily do ses of 0 .5 or 300
m g/kg [ 14 C] CCA 169 374 was rap idl y and extensively distributed , metabolized , and excreted in rats for all dosin g regimens. The metabolism of difenoconazole appears to be ex tens ive because the metabolites accounted for mo s t of th e recovered radioactivity in the excreta

. Three major metabolites were identified in the feces (i.e. metab oli te s A , B , and C). Two of the metabolite s were se parate d into isom er s (i.e. , Al , A2 , B I , and B 2). Metabolite C was detected only in the highdose groups, indicating that metaboli s m of difenoconazole is dose-related and involves sa turation of the metabolic pathway. Fr ee triazole metabolite was detected in the urine of triazole-labeled groups and its byproduct was detected in the liver of phenyl labeled groups on ly
. Other urinary metabolit es were not characterized. 870.7485 42090028 ( 1990) The ab so rption, di s tribut i on, metaboli s m , and excretion 42090029 ( 198 7) of CGA 169374 were studi ed in groups of male and 42090030 ( 1987) female Sprague-Dawley rat s. Animal s were administered 4209003 1 ( 1988) a single oral gavage dose of0.5 or 300 mg/kg [ 14 C]CGAAcceptab le/ g uid e lin e in 169374 , or 0.5 mg/kg unlabeled GGA-169374 b y gavage conjunct io n with MRJDs fo r 14 days followed by a s in gle gavage dose of 0.5 420710013 , 427 1001 4 li sted mg/kg [ 14 C) CGA- l 69374 on day 15. The test compound below was labeled wi th C 14 at either the phen yl or triazole ring

. Single oral dose 0.5 or 300 mg/kg [ 14

### CI CCA 169374 was rap idl y and ex ten s ivel y 14 daily doses of 0.5 or 300 di s tribut ed, m etabolized , and excreted in rats fo r a ll mg/kg dosing regimen s. The extent of absorption is und e t e rmin ed pending determination of the extent of biliary excretion. The 4-day recoveries were 97

. 94- 107. 75% of the administered dose for all dosin g g roup s. The e limination of radioactivity in the feces (78.06- 94.61 % of administered dose) and urine (8.48-21.86%) were almost comparable for all oral do se group s, with slightly higher radioactivity found in the feces of the


### Page 20 of29

### Difenoconazo le/ 12 8 84 7 Scoping D ocument 

### 0429075

Ta bl e 5 . S ubchroni c, C hro ni c, Oth e r To x ic i ty Pro file

- Oif e no co n azo le: F ebru ary 2015 G uid e lin e No. M R ID No. (year)/ R es ults S tud y T y p e C lass ifi ca tion / D oses h i gh-dose group than the low-dose groups. This was probably due to biliary excretion, poor absorpt ion or saturation of the metabo l ic pathway. The radioactivity in the blood peaked at about 24-48 hours. H a lf- l ives of elimination appear to be approximately 20 hours for the low-dose groups and 33-48 h our s for the h igh

- dose group. The study results a lso ind icate that d i fenoconazole and/or its metabo l ites do not bioaccumu late to an appreciable extent fo ll owi ng oral exposure since all the tissues contained negligible leve l s( < 1%) of rad ioactivity 7 days post exposure.
The metabo l ism of difenoconazole appears to be extens ive because the metabo lites accounted for most of the recovered radioactivity in the excreta. Three major metabol ites were identified in the feces (i

. e. metabol ites A , B , and C). Two of the metabol ites were separated into isomers (i.e. , Al , A2, BI , and 82). Metabolite C was detected only in the high-dose groups, indicating that metabo l ism of d i fenoconazo le is dose

- related and invo lves saturat ion of the metabolic pathway . Free triazole metabolite was detected in the u ri ne of tr iazolelabe led groups and its byproduct was detected in the liver of phenyl labeled groups only. Other ur inary metabolites were not characterized.
These studies in d icate that distr ibutio n , metabo l ism , and e l iminat ion of CGA- 1 69374 were not sex related. There was a s l ight dose d i fference in the metabolism a nd eliminat ion of CGA

- 169374. I n phenyl and triazole labeling studies , fecal excretion of radioactiv ity was h igher in the hi gh dose an imals compared to the low dose an imals , and an addit ional metabo li te was found in the feces of the high dose animals compared to the low dose animals. There was no major d i fference in the d istribution and excretion of radioactivity with labe l ing at the phenyl and triazole r ing positions , however , there were some d i fferent metabo l ite s identified. The studies also showed that admi n istration of 0.5 and 300 mg/kg CGA- 1 69314 did not induce any treatment related cl inica l effects.



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### Difenoconazol e/ 12884 7 Scoping Docum ent D4 29075

Table 6
. Guideline Data Requirements : Difenocon azo le: Februa r y 2015 Test Technical Req uired Satis fi e d 870.1100 Acute Oral To xicity yes yes 8 70. 1200 Acute D ennal Toxicity yes yes 870

. 1300 Acute Inhalati on Toxic i ty yes yes 870.2400 Primary Eye Irritation yes yes 870. 25 00 Primary Dennal Irritation yes yes 870. 2 600 Dennal Sen sitization yes ves 8 70.3 100 Oral S ubchronic (ro dent ) yes yes 870. 3 150 Oral Subchronic ( non-rodent) yes yes 870. 32 00 21-Day Dennal no yes 870. 325 0 90- D ay Dennal no 

# - 870.3465 28/90- Da y Inh a lation waived*



### - 870 .37 00a Developmental Toxic ity (rodent) yes yes 870 .3 700b Deve lop mental To xicity (non-rodent) yes yes 870 .3 800 Reproduction yes ves 870.41 OOa C hro ni c Toxici ty (ro dent) yes yes 870.41 OOb Chr o nic To xicity (no n-rod ent) yes yes 870.4200a carcinogen ic ity (rat) yes yes 870.4200b carcino g enici ty ( mouse ) yes yes 8 70.4300 Chronic / carcinoge nicity yes yes 870 .5 100 Mutage nicity -Ge ne Mutation

- bacterial yes yes 870.5300 Mutagen ic ity

- Ge ne Mutation

- mammali an yes yes 870 .537 5 Muta ge nicity

- Srructural C hromosomal Aberrations yes yes 870. 5900 Mutagenicitv -O ther Genot ox ic Effects yes yes 870 .6 1 OOa Acute Dela ye d Ne urotox . ( hen ) no 

# - 870.6 1 OOb 90-Day Neurotoxicity (hen) no 

# - 870.6200a Acut e Neurotox. Screening Battery (rat) yes yes 8 70.62 00b 90-Da y Neuro. Sc ree ning Batt ery ( rat) yes 

# - 870 .6300 Deve l oo. Neuro no 

# - 870.7485 General Metaboli s m yes yes 870.7600 D ermal Penetration yes yes 8 70.7 800 lmmunotoxicity yes yes * waived per HASPOC TXR 0054074



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### Difenoconazole/128847 Scoping Document D429075



### Ta bl e 7. International Residue Limits
Difenoconazole (128847; 8 / 3/15)


### Table 7. Summary of US and Interna tional To lerances and Maximum R esidue Limit s 

### Residue Definition: 

# us Canada Mexico 1 Codex2 40 CFR 180.475: 1-[[2-[2

- ch loro-4-(4- Difenoconazole Plant: difenoconazole , l-[2-[2-chloro-4- ch lorophenoxy )phenyl]-4- (4-ch lorophenoxy)pheny l]-4-methyl- methyl- I , 3-dioxolan-2- The residue is fatI , 3-dioxolan-2-ylmethyl]

- I H- I ,2 ,4- ylmethyl]- I H- I ,2 , 4-triazole soluble. triazole


### Commodit y Tolerance (ppm ) !Maximum Residue limit**(mvk~)** 

# us Canada Mexico 1 Co d ex 2 Almond , hull s 7.0 Apple , wet pomace 25 Aspirated grain fractions 95 Banana ' 0.2 0.2 0.1 Barley, grain 0

. 1 0.0 1 Barl e v , hav 0

. 05 Barley , straw 0.05 Beet , sugar 0.3 0.2 Beet, sugar , dried pulp 1.9 1.9 Berry , low g rowing , 2.5 2.5 bearberries , bilberries , subgroup I 3-07G, except lowbush blueberries , cranberry cloudberries, lingonberries, muntries , partridgeberries , strawberries Brassica , head and stem , 1.9 I .9 broccoli , brussels 2
s ubgroup SA sprouts, cabbages, cauliflowers , broccoli , Chinese broccoli, Chinese mustard cabbages, kohlrabies , napa C hin ese cabbages Brassica , leafy green , 35 35 broccoli raab, bok choy subgroup SB Chinese cabbages , collards , kales , mustard greens , mustard spinach , rape leaves Bushberrv subgroup I 3-078 4.0 Carrot 0.50 0.5 carrot roots 0.2 Citrus, dried pulp 2.0 Citru s, oil 25 25 Com , sweet, forage 0.01 Corn , sweet , kernel p lu s cob 0

. 01 0.01 with husks removed Corn , sweet, stover 0.01 Cotton , gin byproducts 0.05 Cotton , undelinted seed 0.05 0.05 Dragonfruit 1 1.5


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### Difenoconaz ole/1 2 8847 Sco pin g Do cwnent 0429075


### Table 7. Su mm ary o f US and Intern ati onal Tolerances a nd Ma xi mum R e s idu e Limits Residue Definition: 

# us Canad a Mex i co 1 

### Codex2 Fruit, citru s, group I 0-10 0.60 0.8 Australian (dese rt limes , 0.6 linger limes, round lime s) , brown river finger lim es , c alamondin , citru s citron , ci tru s hyb rid s, graperrui t s , kumquats , lemon s , limes , Mediterranean Mandarin , Mount White lime , New Guinea wild lim es , oranges, pummelos , Ru ssell Rive r limes , Satsuma mandarins s wee t limes , tachibana oran ges , tahiti limes , tangeloa , tangerines , tangors, trifol iate oranges , U

niq rruits Frui t, pome , gro up I 1-10 5.0 I appl e s, Asia n pears , 0.8 azarole s, Chinese quinces , crabapp l e s, Japane s e quinces , l oq uats , mayhaws , medlar s, pears , quinces , teiocotes Fruits, stone, group 12 2.5 2.5 American plum s, 0.2 c he rrie s , plums Apricots, beach plums , (inc ludin g prunes) black che rr ies , Canada 0.5 nectarine s, peach plums , capu lin s , cherry plum s , chick s aw plums, damson plums , fres h prun e plums , Japanese apricots , Japanese plum s, jujubes, klamath plums , nanking cherri es
. nec tarin e s, peache s, plumcots , plums , s loe s , swee t cherries, tart cherrie s Grape 4.0 4 

# .. .) Grape , rai s in 6.0 6 6 dried g rap es ( = currants , rai s ins and s ultana s ) Mango • 0.07 0

. 09 0.07



### P age 24 of29

### Difenoconazole/128847 Scoping Document 0429075
Table 7. Summary of 

### US and Intern at i o nal Tolerances and Maximum Residue Limits 

### R es idue Definition: 

# us Canada Mexico 1 Codex2 Nut , tree , g roup 14 0.03 0.03 Afr ica n tr ee nut s, 0.0 3 almond nuts , beechnut s, black wa lnu ts , Bra zil nuts, Brazi l ian pine nut s, bunya nut s, bur oak nuts , butternuts , Caj ou nut s , candlenuts , cashew nuts, chestnuts , ch inqu ap in nut s, coconuts , coquito nu ts, dika nuts, En g li s h walnuts, g inkgo nut s , Gu iana chestnuts , h aze lnut s (filbe rt) , heartnuts , hi cko ry nut s, Japan ese hor se
chestnuts , macadamia nuts , m o ng on go nuts, monk eypot nut s, monkey puzzl e nuts , okari nuts , pachira nut s, peach palm nuts , pecan nuts, pequi nut s, pili nuts , pine nuts , pi stach io nuts , sapuc a ia nuts, tropic al almo nd nuts , ye llo w ho rn nuts Oat , forage 0.15 Oat, grain 0.01 0.01 Oat , hay 0.05 Oat , straw 0.05 Onion , bulb , s ub group 3-07 A 0.20 0.2 C hine se , on ions, 0

. 02 ga rlic(' ") Dayli li es, dry bulb on io n s, 0 .1 on ion bulb fritillari a bu lb s, ga rlic , grea t-h ea d e d garli c , l il ies, p earl o ni ons , pot ato o nion s , serpe nt ga rlic , s h a llot bulb s On io n , green, subgroup 3

- 6.0 6 Beltsvi lle bunchin g 0.3 l eek 078 onions , e lega n s ho sta , fresh 9 sp rin g on ion (C hin ese chive leaves, chive leaves) , fresh onions , frit ill aria leaves, gree n onions, kurrats , lady's leeks , leeks, macroste m onions, shallot leaves, tree o nion top s, W e lsh onio n tops , w ild leeks Papaya 1 0.30 0.3 0.2 0.3 ( propo sed)



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### Difenoconazole / 128847 Scoping Document 0429075


### Tab le 7

. Summary of US and International Tolerances and Maximum Re si due Limits 

### Residue Definition: 

# us Canada Mex ico 1 Codex 2 Pea and bean , dried s helled , 0.20 0.03 Dry (adzuki beans , 0.7 beans , except except s oybean , subgroup 6C beans , blackeyed peas , broad bean and s o y a broad beans , catja ng seeds , bean chickpeas, cowpea seeds , field peas , guar seeds, kidney beans , lablab beans , lima beans , moth beans , mung bean s , navy beans , pigeon peas, pink beans , pinto beans , rice beans , soybeans , southern peas, tepary beans, urd beans, lenti ls) grain lupin Pea, field, hay 40 Pea , field, vines 10 Pistachio 0.03 0.03 0.03 lTee nuts Potato , wet pe el 7.3 Rapeseed subgroup 20A 0.10 0.1 Seeds (Bo rage , crambe. 0.05 rapeseed cuphea; echium , flax seed , go ld of pleasure , hare's ear mustard , lesq uerella, lunaria , meadowfoam , milkweed , mustard seed (cond im ent type and oi l seed type) , oi l radi s h, popp y seed , rapeseed , sesame , sweet rocket) Rye , forage 0. 15 Rye, gra in 0.01 0.01 Rye, s traw 0.05 Soybean , hulls 0.20 Soybean , seed 0.15 0.15 0.02 (*)soybean (dry) Turnip , greens 35 Vegetable , cucurbit , group 9 0.70 0.7 balsam apples , balsam 0.2 cucumber, pears , cantaloupes , chayotc gherkin , squash fruit, C hin ese cucumbers , s umm e r C hinese waxgourds, citron 0.7 melons , except melons. cucumbers, edible watermelon gourds , muskmelons (other than those listed in this item) pumpkins , summer squash , watermelons , west Indian gherkins, winter squas h



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### Difenoconazole/128847 Scoping Document D429075

Table 

### 7

. Summary of US and Internati onal Tol erance s and Maximum Residue Limits R esidue Definilion: 

# us Canada Mexico' Codex2 Vegetable, fruiting , group 8- 0.60 0.6 Arrican eggplants , bell 0.6 rruiting 10 peppers , bush tomatoes, vegetables other than
coconas , currant tomatoes , cucurbits (except eggplants , garde n sweet com and huckleberries , goji berries, mushroom) groundcherries, martyn ias, 5 peppers chili, dried naranj ill as, nonbell peppers , okras, pea eggp lants , pepinos , roselles , scarlet eggp lants, sunberries , tomatillos , tomatoes , tree tomatoes Vegetable , tuberous and 4.0 4 arracacha, arrowroot , 4 potato corm , subgroup 1 C cassava roots , chayote roots , Chinese a rti chokes , chufa , edible canna , ginger roots, Jerusalem art ichokes , lerens, potatoes , sweet potato roots , tanier conns , taro conns, true yam tubers , turmeric roots, yam bean roots Wax jambu 1 1.5 Wheat , forage 0.1 Wheat, grain 0.1 0.1 wheat 0.02 (*) Wheat, hav 0.05 Wheat , straw 0.1 3 wheat straw and fodder, dry MRLs with NO US Equivalent Buckwheat 0.01 Pearl millet 0.01 Popcorn grain 0.01 Proso millet 0.0 1 Rice 0.01 Sorghum 0.01 Teosinte 0.01 Triticale 0.01 Wild ri ce 0.01 A s paragus 0.03 Celeriac 0.5 Celery 3 Ginseng 0

. 08 Gin seng , dried includin g red 0.2 ginseng Ginseng , extracts 0

. 6 Lettuce , head 2 Lettuce , leaf 2 Olives 2 Passion rruir 0.05 Peas (pods and 0.7
s ucculent=immature seeds) Sunflower seed 0.02


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### Difenoconazole / 128847 Scop in g Docum ent 04 29075


### Table 7. Summary of 

### US a n d Lnternat io n al T o lera nce s a nd Maximum R es idu e Limi ts 

### R es idue D e fin ition: 

# us Ca nada Mexico• Codex 2 US 40 CFR 180.475 C anada Mexico• Codex 2 Livestock: sum of d i fenoconazo le. 1-[2- 1-[[2-[2-c hloro-4-(4- Animal commodities: [ 2 -chloro-4-( 4-chlorophenoxy)phenyl]

- chlorophenoxy)phenyl)-4- sum of 4-methyl-1,3-dioxolan-2

- ylmethy l]-1 H- methyl-1 ,3 -dioxolan-2

- difenoconazole and 1 ,2, 4-triazole, and its metabolite , CGA

- ylmethyl]-1 H- 1,2 ,4-triazole, 1-[ 2-c hloro-4 -(4- 205375, l-[2-chloro-4- (4

- chloro- includin g the metabolite 

### a
- chloro-phenoxy)- phenoxy)phenyl)-2-( 1 ,2, 4)triazol- l- y l- [2-chloro-4-(4

- phen y l]-2

- ( 1.2.4-
e thanol , calculated as the stoichiometric c hloroph e noxy)phenyl]-1 H- triazol)-1-yl-ethanol) , equivalent of difenoconazole 1 ,2,4-t r iazole

- I-ethanol expressed as di fenoconazole. 

### Commodity Toleran ce (pvm) / Maximum Residue Limit (mf!/kf!) 

# us Ca n ada M ex ico• Codex2 Catt le , fat 0.10 Canle, liver 0.40 0.1 1.5 edible offa l mammalian Cattle, meat 0.05 0.05 0.2 meat (from mammals other th an marine mammals ) (fat) Can le, meat byproduct 0

. 10 0.05 1.5 edible offal (except liver) mammalian E1rn. 0.02 0.05 0.03 Goat, fat 0.01 Goat, liver 0.40 0.1 1.5 edible offal mammalian Goat, meat 0.05 0.05 0.2 meat (from mammals other than marine mammals) (fat) Goat , me at byproduct (except 0. 10 0.05 1 .5 edible offal liver) mammalian Hog, fat 0.10 H og, li ver 0.40 0. 1 1.5 edible offa l mammalian Hog, mea t 0.05 0.05 0.2 meat (from mammals other than marine mammals) ( fat ) Hog , meat byproduct (except 0.10 0.05 1.5 edible offal li ver) mammalian H orse, fat 0.10 Horse , liver 0.40 0.1 1.5 edible offal mammalian H orse , meat 0.05 0.05 0.2 meat (fi-orn mammals other than marine mammals) (fat) Horse , meat byproduct 0.10 0.05 1.5 edible offal (except li ver) mammalian Milk 0.02 0.0 1 0.02 Sheep, fat 0.10 Sheep, liver 0.40 0.1 1.5 edible offal mammalian 

### Page 28 of29

### Difenoconazole/128847 Scoping Document 

### 0 429075


## Tab le 7. S umm ary of US a nd In ternat i o n a l To lera n ces and M ax i m um R es idu e Lim i t s 

### Residue Definition: 

# us Ca n ada Mexico 1 Codex2 Sheep , meat 0.05 0

. 05 0.2 meat (from mammals other than marine mammals) (fat) Sheep , meat byprod uct 0. 1 0 0.05 1 .5 ed ible offa l (excep t liver) mammal ian MRLs with NO US £q11ival e nt Poultry , meat 0.0 I (*)(fat) Poultry. edible offal of 0.01 (* ) Completed: M. Negus s ie; 08 / 12/ 15 1 Mexico adopts US to lerances and/or Codex MRLs fo r its ex p ort pu rposes.

2 

## * = ab s ent at the limit of quantitation; Po = po s tharvest treatment , s uch as treatment of stored grains. P oP

= proc ess ed postharve s t treated commodity , such as processing of treated stored wheat. ( fa t) = to be
mea s ure d on the fat porti o n of the sample. MRL s indicated as propo s ed have not been finalized by the CCPR and the CAC.



### Page 29 of29