### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D

. C

. 20460



### DATE: 05 -M ay - 20 1 5 OFF ICE OF C HEMICAL SAFETY AND POLLUTION PREV EN TION



### S ubj ect : Prohcxadione Ca lcium

. Sec ti on 3 Reg istra tion for Use on S tra w b e rry and Watercress. 

### C hronic Di etary Expos ure a nd Risk Assess m ent

. PC Code: I 12600 DP Ba r co d e: 0425890 Deci s io n No.: 489681 Petition No.: 4E8264 R isk Assess m e n t T Case No.: 7030 TXR No.: NA CAS No.: 1 27277

- 53-6 MRID No.: None 40 CFR: § 180.547 

### F r om:

T hrou g h :

To: William D. Wassell, Chemist 

# l}(;!J tf'. Ri sk Assessment Branch I ( R AB 1) H ea lth Effec t s Division (HED , 7509P)
Na nc y D o dd , Chemist

### ~~ D oug las Dotson, Ph.D. , Chemist

### ~.**~ ~**  Di etary Expos ure Science Adv isory Co uncil ( D ESAC) and George F. Kramer , Ph .D., Branch Senior Che mi st RAB l / II E D (7509 P )
Barbara Madden/Laura No ll e n , RM 05 R egistration Di v is io n (RO; 7505P) 

### Exec utiv e S umma ry The c hro nic agg regate dietary (foo d + drinking wate r) expos ure and risk assessmen t was conducted u s in g the Dietary Expos ure Eva lu at ion Model

- Food Co n sump ti o n Intake D atabase ( D EEM -FCID , ver. 3.16), wh ich us es food co n s umpti o n data from th e U.S. D epartment of Ag ri c ulture 's (USDA 's ) National Health and Nutrition Ex amination S urvey, What We Eat in America (N H ANES / WW E IA)

. Thi s dietary s urv ey was conducted from 2003 to 2008. The c urrent assessment is bein g co nducted in support of a proposed use of proh e xadione calcium on s trawberry and wate rc ress. This memorandum w as r eviewed by two p eer re vi ewe rs of the DESAC, per D ESAC SO P 20 12.1.
The unrefined chronic ana lys is assumed DEE M (ve r. 7.81) default processi ng factors, 100 % crop treated (C T ), and tol e rance-level re s idu es for a ll commod iti es. Th e c hroni c ana lys i s also in corporated the drinkin g water est imates provided by Environmental Fate a nd Effects Di v ision ( EF E D )

. The est im ated drinking water conce ntr a ti o n s (E DWC s) were ge n e ra t e d u s ing the ric e mod e l and are cons id e re d highly conservat ive. Th e assessment is ba se d on the maximum app li cation rate of 0. 1 3 75 lb ai/Napplica ti on fo r wate rcress , applied u s in g grou nd equipment Pa ge I of7Prohexadione Ca lc ium Dietary Exposure and Risk Assessment DP# 425890


### with a second app lication 7 days after the initial application. An 

### EDWC of 0.17 ppm was used in the chronic analysi s. The re su lting chronic food plus drinking water exposure es timate s are not of co ncern to HED (<100% chro ni c population-adjusted dose (c PA D ) for all population subgro up s of interest). The resulting ch ronic expos ure est imate for children 1

- 2 years (the subgroup with th e greatest ri sk) was 19% of th e cPAD.
There is no s tud y with a single dose and endpo int appropriate for the acute scenario and there is no evidence of carcinogen ic potential. Th erefo re , thes e risk assessments were not performed.

I. I n tr o du cti o n 

### Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute and chronic assessments, the risk is expressed as a percentage of a maximum acceptable dose ( i .e., the dose wh ich HED has conclu d ed will result in no unreasonable adverse health effects). This dose is referred to as the PAD. Th e PAD is equiva lent to a point-of-departure (PO D ; e.g., no-observable-adverse-effect-level (NOAEL)) divided by the required uncertainty o r safety factors.
For acute and non-cancer chronic exposu re s, HED is concerned when estimated dietary ri sk exceeds l 

### 00% of the PAD. References whic h discuss the acute and chronic risk assessmen ts in more detail arc available o n th e EP Npesticides web site: "A vailable Information on Assessing Exposure from Pesticid es, A User's Guide," 612 1100 , web link: htt p: //www.epa.gov/ fedrgstr/EPA-PEST/ 2000/July/ Da y- l 2 /606 l .pdf ; or see SOP 99.6 (8 / 20/ 99). The most recent prohexadione ca lcium dietary exposure assessme nt was conducted by G. Kramer (5 / 17/ 11 , D 384707).

II. R es idu e In fo r ma t ion 

### Residu es of Concern: The HED Metabolism Assessment R eview Committee (MARC) concluded that only the parent compound needs to be included in the tolerance expression for pome fruit and peanuts and that it is th e only compound to be included in the dietary and drinking wate r risk assessments (DP# 263502 , 417 1 00, G. Kran1er). This conclus i on ha s been exte nd ed to st rawbe rry and watercress. 

### Established/Recommended Tolerances: Prohexadione calc ium tol erances are established in 40 CFR § 180.547. Tolerances fo r residues in/on a ll commod ities are expressed in terms of the parent only. B ase d on the re s u lts of th e strawbe rry and watercress field trials, the appropriate tolerance leve ls for residues of prohexadione calcium inion strawberry is 0.30 ppm and inion watercress is 4.0 ppm (Memo, pending , W. Wassell , D41998 l). 

### Residues Used in the Chronic Analysis: This analysis emp lo yed tolerance-level residues for a ll commodities. The DEEM (ve r . 7.81) default processing factor of 1.3 for apple juice was set to 1.0 because proh exad ion e calcium does not concentrate in this commodity ( M emo, 11 / 22/ 99, G. Kramer , D252547).

Page 2 of7Prohe xad ion e Calci um Dietary Exposu re and Ri sk Asse ss ment DP #425 890
Fish: Th e U SDA P es ticide D a ta Pro gram ( PDP ) monitored p esticid e residues in catfish in 2008, 200 9 , and 2010. In general , pe s ticid e res idue s would not b e ex p ec te d to be found in fi s h unl ess the p es ti c ide bi oaccumulates or has an aq u ati c u se . To d e te rmine whether or not res idue s are prese nt in fish , HED now rout in e ly ch ec ks PDP monitorin g data regardless of th e pesticide 's uses and phys icoche mic al properties. H owever, PDP did no t analyze catfi s h samples for proh exad i o ne calcium

. As a re s ult, res idues in fi s h were no t includ e d in the assess m e nt.



### III. Es tim a t ed Drinkin g Wa t e r Co n ce ntr a tion s Drinkin g water res idu es we re inc orpo rated dire ct ly into th e c h ro ni c di e tary analysis ("water , d irect, a ll so urces " and "wa t e r, indirect , a ll sources " ) and we re pro vided b y EFED ( Memo , 0 1 / 30 / 20 15 , E. Seifu , et al. , D419983). The E DW Cs were ge nerated u s ing the watercress ap plic at io n sce n ari o a nd the T ier 1 Ric e Model for prohex a di one calcium. Th e assess m en t is based on the maximum ap pli cati on rate o f0.1375 lb ai/A/application for waterc ress, appli ed u s ing g r o und equ ipme nt w i th a seco nd app licati on 7 days afte r the initial a ppli cat i o n.
Ta bl e I. Ti e r I E DW Cs R es ultin g F r o m Grou nd Ap pl ica ti o n s o f P r o hexad ione Calc ium

.

Drinking water source Use Acute EDWC Chronic EDWC 30

-year average (mode l) ( mode led r ate) ( ppb ) (ppb) ( ppb) Surface wate r (Ti e r I Wate rcress 170 1 70 NR 1 Ri ce Model) (0 .275 l b ai / Nyea r) G r o und water Turf 0. 137 0. 137 NR (SC I GROW ) ( 19.5 lb s ai/A /year)
1 NR = not reported.
A n EDWC of 0.17 ppm was u se d in the c hroni c ana lys i s.



### I V. D EEM-FC ID P r og r a m a nd Co n s umpti o n Inform at io n A pro hexad ione calc i um ch ro n ic d ie tary ex posure and r isk assessment was conducted u s in g DEEM-FC ID (ver. 3. 1 6), w hi ch uses food co n su mpti o n data from th e U S D A 's N HAN E S/ WWEJA. This di e tary survey was conducted from 2003 to 20 08

. Foods 

### " as co n su m e d " (e.g., ap pl e pi e) a re li nked to E P A

- defined food commodities (e.g., app les, p ee le d fruit

- cooke d ; fre s h o r N / S ; b a ked ; o r w heat flour

- coo k ed; fresh or N / S , bake d ) u s in g publi c l y ava i lab le rec ipe translatio n fil es d eve l oped joint ly by USDA/ARS and E P A. For c hroni c ex posure assess m e nt , consump ti on data are averaged for th e e ntire U.S. population and w ithin popul ation s ubgroup s. Ba se d on analys is of the consumption data , wh i ch took into account d ietary patterns and s urvey re spo nd e nt s, H E D concluded th at it is mo s t ap propri ate to r eport risk for th e following p op ulation s ub g roup s: the gen e ral U .S

. population , all in fants ( < I year o ld), c hildre n 1- 2, childr e n 3

- 5, children 6-12 , yo uth 1 3- 19 , adult s 20 -49 , fe ma les 1 3-49, and adu lt s 50-9 9 years old.
For chronic dietary ex posur e assess m en t , an estim ate of the resi due leve l in eac h foo d or food

form (e. g., o range or o range juice) on th e food commod ity res idue li st i s m u ltip li e d by t he ave rage d a il y con s ump t ion est im ate fo r that food/food form to produce a residue intake es tim ate. The re s ultin g residu e intake es timate for eac h food / food fo rm is su mmed w ith th e res idu e int ake es timate s fo r a ll o th e r food/food forms o n the commodity residue l i st to arrive at th e total Page 3 of7Prohexadione Calcium Dietary Exposure and Risk Assessment DP# 425890
average es tim ate d exposure. Exposure is expressed in mg/kg body weight / d ay and as a percent of the cPAD. This procedure i s performed for eac h p op ul at ion subgroup.



### V. Toxi co l o g ica l Informati o n Th e toxicologi cal endpoints are s umm ariz ed below in Table 2

. Ta bl e 2. S umm a ry o f T oxicologica l Doses a nd End p o in ts for Pro hexad ione Ca lcium fo r Use in D iet a ry Hum a n H ea lth Ri sk A ss ess m e nts'. Exposure Do se Used in Risk RfD , PAD , LOC for Risk Sce nari o Assessment, UFs Assessmen t Study and Toxicological Effects Acute Die tary NA NA There is no study with a sing le dose and endpoint appropriate for this scenario. Th erefore , this risk assessme nt was not performed. Ch ronic Dietary NOAEL = 20 C hr on ic R ID = c PA D = Chronic to xic ity

- dog. mg/kg/day 0

.20 mg/kg/da y LOA EL = 200 m g/

kg/day based on UF A = IOX hisropathological changes in th e kidney s UF11 = IO X (dilated ba s ophilic tubule s ) and increa se d FQPASF = IX urin ary vo lume and Na • ion concentrations. Cancer (o ral, Not likely human NA No ev iden ce of carcinogenic p otential , dermal , inhalation) carcinogen. therefore , cancer ri s k as se ss ment is not required

. 1 UF = uncertainty fac tor , FQPA SF = FQPA safety factor , NOAEL = no-observed advers e- effect level , LO AEL = lowest-observed adve rse-effect level , UFA = extrapo lation from animal to human (inters pecie s ) , UF11 = potential variatio n in sen s itivity among members of th e hum an populat ion ( intra species) , PAD = population-adjusted dose (c = chronic) , Rm = reference do se , LOC = level of concern.



### VI. R es ults /Di sc u ss io n A n unrefined chron ic an alysis was performed using DEE M

- FCI D (ver. 3. 1 6) which estimates the dietary expos ure of th e U.S. population and various populati o n subgroups

. Th e re s ults repo rted are for the ge neral U.S. population, all infant s (< I year old), chi ldre n 1-2 years old , childre n 3-5 yea rs old , children 6-12 years o l d , youth 13-19 years old, fema les 1 3

- 49 years old, adults 20-49 years old , and adu lt s 50

- 99 years ol d

. The resulting chronic risk estimates are not of concern to H ED

. The most hi g hl y exposed popu lat io n was c hildren 1- 2 years old ut ili z ing 1 9% of the cPAO. See Table 3 bel ow fo r a su mm ary of the results of the dietary assessme nt.

Page 4 of7Prohexadione Calcium Dietary Ex p osure and Risk Assessme nt DPf/425890

Ta bl e 3. S umm a r y o f Di etary ( Foo d a nd Drin kin g W ate r ) Ex p os ure Ri s k fo r P ro h exa d ion e Ca lcium .' Acute Dietary (95 1 h Pe rce ntil e) Population Subgroup Dietary Exposure %a P A D (mg/kg/day) General U.S. Population A ll Infant s (<I yea r old) C h ild r e n 1 -2 ye ars o ld Chi l dren 3-5 years old Children 6-12 years old 

### N I A N I A You th 13- 19 years old Adults 20-49 years old Adults 50-99 years old Females 13-49 years o l d 1 The values for the highe s t exposed popul a tion arc bolded. NA 

### = not app li cab le. 

### V II

. C h arac t e riz atio n o f Input s/Outpu t s Chronic Di etary Ca ncer Dietary Dietary Exposure %c PAD Ex po s ure Ri sk (mg/kg/day) (mg/kg/day)

0.007637 3.8 0.029740 15 0 .03820 1 1 9 0.022459 II 0.010 1 20 5.1 

### N I A N I A 0.005035 2.5 0.005172 2.6 0.005198 2 .6 0.005329 2.7

The c hronic analysis ass um e d to le ran ce - l eve l residues , DEEM (ver. 7.81 ) defau lt p rocessi ng factors, and I 00% CT. This analysi s is considered very conservative and could be refined through th e u se of anticip a t e d-res idue es timate s (A R s) for a ll commodities , %C T data for registered commodities, and/or ad diti ona l empirical processing fac tors.



### V III. 

### Co nclu s i o n s A chron ic expos ure an d r i s k assessment was conducted u s ing D EEM -F C I D (ver. 3. 16), w hi ch incorporates food consumpt io n data from the USDA's N H AN E S/ WWE IA

. This dietary s urv ey was cond ucted from 20 0 3 to 2008.
The unrefined c hronic analysis ass um ed D EEM (ver. 7.8 1) d efault processing facto rs, 100% CT , and tolerance-level r es idues for all commodi ti es. Th e chro ni c analysis a lso in cor p orated the drinking wate r est imates provid e d by EFED

. Th e res ultin g chro ni c food plu s w ater expos ure estimates are not of concern to HED ( < I 00% chronic c P AD) fo r a ll populat ion subgroups of interest , and the re su lting c hroni c exposure es tim a t e fo r children 1- 2 years (the subgroup with the grea test risk) was 19 % of the c P AD.



### IX

. Li s t o f Att ac hm e nt s Attachment 1: DEEM -F C ID Chronic Residue File. Attachmen t 2: D EEM-FC ID Chronic Expos ure an d Risk Es tim ates

.

cc: W.Wa sse ll (RA BI ) RO I : DE SAC Reviewers: 5 / 2

/ 20 1 1
Page 5 of7Prohexadione Calcium Di etary Exposure and Risk A ssess ment
Attachment 1: DEEM-FC ID C hronic Re s idue File.

Filename : J : \Work Files\$ Prohexadione\DEEM\PROHEXADIONE.R08 Chemical: Prohexadione RfD(Chronic) : . 2 mg/kg bw/day NOEL(Chronic): O mg/kg bw/day RfD(Acute): O mg/kg bw/day NOEL{Acute): O mg/kg bw/day DP# 425890

Date created/last modified: 01

- 07-2015/16 : 54:50 Program ver. 3.16, 03-08-d Crop EPA Code Grp Commodity Name Def Res (ppm) 1100007000 11 1100008000 11 110000800 1 11 1100009000 11 1100009001 11 1100010000 11 1100010001 11 1100011000 11 1100011001 11 1100129000 11 1100210000 11 11 00266000 11 1100266001 11 1100267000 11 1100268000 11 1100268001 11 1100310000 11 1201090000 12A 1201090001 12A 1201091000 12A 1201091001 12A 1307359000 13G 1307359001 13G 1307360000 13G 1307360001 13G 31000 46 00 1 31 3100048000 31 3100049000 3 1 3100049001 31 3200170000 32 3200172000 32 3200173000 32 3 4 00292000 34 3400292001 34 3400294000 34 3400295000 34 3500340000 35 3500342000 35 35003 4 3000 35 8601000000 86A 8602000000 86B 9500263000 0 9500264000 0 9500265000 0 9500398000 0 Apple, fruit with peel Apple, peeled fruit Apple, peeled fruit

- babyfood App le , dried Apple, dried

- babyfood Apple, juice Apple, juice -baby food App le , sauce Apple, sauce-babyfood Crabapple Loquat Pear Pear

- baby food Pear, dried Pear, juice Pear, juice -b abyfood Qu ince Cherry Cherry-babyfood Cherry, juice Cherry, juice-babyfood Strawberry Strawberry-babyfood Strawberry, juice Strawberry, juice-babyfood Beef, meat byproducts-babyfood Beef, kidney Beef, liver Beef, liver -b abyfood Goat, meat byproducts Goat, kidney Goat, liver Pork, meat byproducts Pork, meat byproducts-babyfood Pork, kidney Pork, liver Sheep, me at byproducts Sheep, kidney Sheep, liv er Water, direct, all s ources Water, indirect, a ll s ources Peanut Pe anut , butter Peanut, oil Watercress

Page 6 of7 Adj

. Factors Ill 112 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 3.000000 0.400000 0

. 400000 0.400000 0 .40 0000 0.300000 0.300000 0.300000 0.300000 0.050000 0.100000 0.050000 0.050000 0.050000 0

. 100000 0.050000 0.050000 0.050000 0.100000 0

. 050000 0.050000 0

. 100000 0.050000 0.170000 0.170000 1.000000 1.000000 1.000000 4

. 000000 1.000 1.000 1.000 8.000 8.00 0 1

. 000 1.000 1

. 000 1. 000 1

. 000 1. 000 1.000 1. 000 6.250 1.000 1.000 1

. 000 1

. 000 1.000 1

. 500 1. 500 1.000 1. 000 1.000 1.00 0 1.000 1

. 000 1.000 1 .000 1

. 000 1.000 1.000 1.000 1.000 1.000 1.000 1

. 000 1.000 1

. 000 1

. 000 1

. 000 1.000 1.890 1.000 1. 000 Comment

1

. 000 1.000 1 .0 00 1

. 000 1. 000 1.000 1. 000 1.000 1. 000 1.000 1. 000 1.000 1

. 000 1.000 1 .0 00 1.000 1. 000 1.000 1. 000 1.000 1. 000 1

. 000 1

. 000 1

. 000 1

. 000 1.000 1.000 1.000 1. 000 1.000 1. 000 1.000 1. 000 1

. 000 1

. 000 1. 000 1

. 000 1.000 1. 000 1. 000 1.000 1. 000 1. 000 1.000 1. 000Prohexadione Calci um Die t ary Exposure and Ri sk Assessment DP#425890 

### Attachment 2: DEEM-FCID Chronic Exposure and Risk Estimates.

US EPA DEEM-FCID Chronic analy si s Residue file name: J: \W ork Ver

. 3

. 16 , 03-08- d for PROHEXADIONE NHANES 2003-2008 2-day Files \$ Prohexadione\DEEM\PROHEXADIONE.R08 Adjustment factor ff2 NOT used

. Analysis Date 01-07

- 2015/16:56:47 Residue file dated : 01

- 07

- 2015/16:54:50 Reference dose (RfD, Chronic) = . 2 mg / kg bw/day


### ======================================== = === = === == == = == === == = ======= = === == == =

Population

Subgroup Total US Population Hispanic Non-Hisp-White Non-Hisp

- Black Non-Hisp-Other Nursing Inf ants Non-Nursing Infants Female 13+ PREG Children 1-6 Children 7

- 12 Male 13-19 Female 13-19/NP Male 20+ Female 20+/NP seniors 55+ All Infants Female 13-50 Children 1-2 Children 3-5 Children 6-12 Youth 13-19 Adults 20-49 Adults 50-99 Female 13-49 Total exposure by population subgroup To tal Exposure mg/kg body wt/day 0.007637 0

. 009236 0.007249 0.007429 0.009151 0.016200 0

. 035788 0

. 006493 0.027070 0.008968 0.004745 0

. 005287 0

. 004921 0.005382 0.005163 0.029740 0.005340 0

. 038201 0

. 022459 0.010120 0.005035 0

. 005172 0

. 005198 0

. 00 53 29

Page 7 of7 Percen t of Rf d 3.8% 4.6% 3.6% 3. 7% 4 .6% 8.1% 17.9%

3.2% 13.5%

4

. 5% 2. 4% 2.6% 2.5% 2.7% 2

. 6% 14.9%

2

. 7% 19 .1% 11. 2%

5 .1% 2

. 5% 2.6% 2

. 6% 2. 7%