### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 Office of Chemical Safety an d Pollution Prevention 

### MEMORANDU M Date : April 9, 2015 SUBJECT: Common Tr iazole Metabolites: Updated Aggr egate Human Health Risk Assessment to Address The New Section 3 Registrations For Use of Propiconazole on Tea, Dill, Mustard Greens, Radish, and Watercress; Use ofDifenoconazole on Globe Artichoke, Ginseng and Greenhouse Grown Cucumbers and Conversion of the Es tablished Foliar Uses/Tolerances for Stone Fruit and Tree N ut Crop Groups to Fruit, Stone, Group 12-12 and the Nut, Tre e , Group 14-12.; and Use of Flutriafol on Ho ps. PC Codes: 600074 (1,2,4 -Triazo le), 600011 ( Triazolylalanine), 600082 (Triazolylacetic Acid), 625618 (Triazolvlovruvic Acid) Decision No.: 491006 & 

### 496175 Petition Nos.: 2F8134, 2F8135, & 

### 2E8138 Assessment Type: Single Chemical, A2'2'regate TXR N o .: None MRlD No.: No n e 

### From : Thurston G. Morton , Senior Chemist Risk Assessment Branch IV Health Effects Division (HED) 7509P Through: E lissa Reaves, Ph.D., Branch Chief Risk Assessment Branch IV Health E ffects Division (HED) 7509P To: Rosemary Kearns/Tony Kish RM 22 Registration Division (RD; 7505P) 

## I. CONCLUSIONS DP Barcode: 426493 & 

### 426497 Registration No.: None Regu latory Action: Section 3 Registration Case No.: NA CAS No.: Multiole



### Based on conservative, health-protective assumptions, aggregate risk estimates associated with 1,2,4-triazole (T) and the conjugated triazole metabolites [i . e., combined residues of triazolylalanine (TA), triazolylayetic acid (TAA), and triazo l ylpyruvic acid (TP)] are below Page 1of 4

### HED 's level of concern . There are no human heath risk issues for these metabolites that would preclude the requested uses of propiconazole, difenoconazole, and tebuconazole. 

### II. ACTION REQUESTED Update the aggregate human health risk assessments for T and the conjugated triazole metabolites to account for the new use s of propiconazole , difenoconazole , and flutriafo l. 

## III. BACKGROUND In 2006, HED issu e d aggregate human health risk assessments for T and the conjugated triazole metabolites (M. Doherty, 

## et al . , 0322215 , 7 FEB 06). Those assessments addressed a back-log oftriazole use requests that had been h el d by the Age ncy pending resolution of various toxicological and exposure concerns for the common triazole metabolites. The findings of that assessment were that risk estimates for all exposure scenarios were below HED 's level of concern. Since that time, a number of reque sts for new uses of triazole-derivative fungicides have been sub mitted to the Agency. A s a result of these requests, new dietary exposure estimates have b een made for T and combined re sid ues of TA, T AA, and TP, and new aggregate exposure and risk estimates are necess ary. Neither the toxicological information nor the nondietary expos ure estimates detailed in the 2006 memorandum have changed ; thus the only alter ations to the previous aggregate exposure and risk estimates are due to changes in the dietary exposure estimates. For comp l ete hazard characterization and non-di etary exposure assessments for the common triazole metabolites, see the 2006 risk assessment. 

### IV. RESULTS/DISCUSSION As noted above, the only revisions to the components of th e previous aggre gate expos ur e and risk estimates are to the dietary exposure estimates. For the common triazo le metabo li tes, acute and chronic aggregate risks consist only of dietar y (food + water) components and, therefore , are equ i valent to the dietary risk estimates provided in the most recent dietary exposure assessment (T . Morton, D426492, 4/15/15). The revi sed aggregate estimates are summarized below for short- and intermedi ate-term scenar i os for T (Tables 2 and 3, respectively). The conjugated triazole metabolites are formed in plants by the conjugation of 1 ,2 ,4-T to se rine. The TA may then be further metabolized to form TAA and/or TP . Because of the nature o hhis process, HED has assumed that it occurs within the plant itself and not on leaf surfaces. Therefore, the res i dues are not avail able for dermal , hand -to -mo uth , or object-to-mouth exposures and HED ha s not conducted a residential exposure assessment for the triazole conjugates. Residues of TA, TAA , and TP may occur in soil. 1 ,2, 4- Triazole is more to x ic th an TAITAAITP and exposures to these v i a soil ingestion are unlikely to exceed those of 1,2,4-T. The assessment for soi l inges t ion of 1,2,4-T s hows that risk estimates are below HED's l evel of concern; there fore, risk est imates for soi l ingestion of the conjugates wi ll also be be low HED 's le vel of conce rn.

Page 2 of4Tabl e I . Summary of D ietary (Food and Drinkin g Water) Expos ure and Ri sk for the Common Tri azo l e Metabo lite s Adding the New Uses for D ifenoc onazole and Pro pi conazo le . Ac ute Diet ary Chronic D ietary Cancer (95th Percenti le) Population Subgroup Dietary Di etary D ietary Exposure %aPAD* Exposure %cPAD* Exposure Risk (mg/kg/day) (mg/kg/day) (mg/kg/day) 1,2,4-Triazole Genera l U.S . Pop ulat ion 0.007 866 26 0.001 1 48 23 All In fants (< I year old) 0.012319 41 0.002097 42 C hildren 1 - 2 year s old 

### 0.019571 65 0.003322 66 Chi ldren 3-5 years old 0 . 0166 14 55 0.002647 53 No t Not Childr en 6-12 years old 0.009616 32 0.001431 29 App li cab l e Applicab l e Youth 13-19 years old 0 .006806 23 0.000922 18 Adult s 20-49 years o ld 0.006353 21 0.00097 5 20 Adults 50-99 years old 0 . 005589 19 0.000926 19 Fe ma les 13 - 49 years old 0 . 006417 21 0.00094 1 19 Tr iazo ly l alanine + Tr iazo ly lacetic Ac id+ Tr iazolylpyruvic acid General U.S. Populat ion 0.015772 18 All Infants(< 1 year o ld) 0 . 02152 5 24 Ch ildren 1-2 years old 

### 0.05064 7 56 Children 3-5 years old Not No t 0 . 040826 45 Not Not Child ren 6-12 years old Applica b le Applicable 0.021366 24 App li cab le Appl icable Youth 13 - 19 years old 0.01317 1 15 Adults 20 - 49 years old 0.012807 14 Adults 50-99 years old 0.01215 5 14 Females 1 3-49 years o ld 

### 0.073216 

### 73 0 . 01235 5 1 4 * The values for the highes t exposed population for each type of risk assessment are bolded .

Page 3 of4T a ble 2 . S h ort- term A2 2r egat e Exp osure an d Ri sk Esti mates fo r 1,2, 4 - Triazole. Expos ur e Es ti m a t e, mg/kg/day 1 D

erm a l Dermal (Po st- Hand- t o- O bj ect-to - Soil Aggregate Popul at ion S ubgroup Dietary (M/U A

) A o olic.) Mouth Mouth Inge stio n Ae.arega te U . S. Popul at ion (total) 0. 00 1 1 4 8 0 . 0 0 1 8 3 0 . 0 05 1 

### N I A N I A N I A 0 .00807 8 All in fant s(< I year ) 0.00 2 0 97 

### NIA 0 . 008 6 0 . 0041 0 . 00 1 0 0 .0 0 0019 0. 0 1 581 6 Chil d ren 1- 2 y rs 0.003 32 2 

### N I A 0.0086 0 . 0041 0.0010 0.000019 0.0 1 7041 Chi ldren 3-5 yrs 0 . 00 2 64 7 

### N I A 0.0086 0.0041 0 . 0010 0 . 000019 0 . 0 163 66 C hildren 6 -1 2 yrs 0.00 1 4 3 1 

### N I A 0 . 0086 

### N I A N I A NI A 0 .0 10031 Yo u t h 13-19 yrs 0 . 0 0 0 922 0 . 0018 3 0.00 5 1 

### N I A NI A N I A 0 . 0078 5 2 Adults 20-49 y rs 0.0009 7 5 0.0018 3 0 . 00 5 1 

### N I A N I A N I A 0. 0 0

7905 Adu lts 5 0 - 99 yrs 0.0009 2 6 0.0018 3 0.0051 

### N I A N I A N I A 0.007 856 F

e male s 1 3- 49 y rs 0.000941 0.0018 3 0.0051 

### N I A N I A N I A 0. 00787 1

. . ' E

xposur e es timates fo r dermal , hand -to -m o uth , o b ject -to- m o u

t h , and so 1l mgestio n are fr om J . Arthur , DP 3 22240 , 1 219 105 . 2 Aggregate MO E= NO AEL (3 0 m g/kg/ d ay) + Aggregate E xpos ur e Es ti mate (m g/

k g/

d ay) . Level of Con ce rn = I000 .

Table 3. Inte rmediate-te rm A11'11're ate Exoosure and Ris k Estimates for 1.2,4-Triazole. Ex p osu r e Est im a t e, m g/kg/day M O

E 2 37 0 0 19 00 1 8 0 0 1800 2 900 38 00 3 80 0 3 800 380 0

Populati on Subgro up Di etary So i l I ng es tio n' A1t2r egatc A2trreg ate MOE 2 U. S . Popul a ti o n (t o t

al) 0 . 00 11 48 NIA 0.00 11 48 13000 All infants( < I y ear) 0 . 002097 0 .0000 19 0 . 002 11 6 71 00 C

hi ld ren 1- 2 yrs 0 . 003 3 22 0 . 0000 19 0. 00334 1 4500 Child r en 3 -5 yrs 0. 00 2 64 7 0 . 000019 0.00 266 6 560 0 C

hildre n 6- 12 yrs 0 . 00 14 31 N /A 0 .00 1 43 1 1 0000 Y

o uth 13- 1 9 yrs 0 . 00092 2 

### N I A 0.00 0922 16000 Adults 20-4 9 y rs 0 . 00 097 5 N IA 0.000 975 1 5 0 00 Ad ul ts 50 - 99 y r s 0 . 00 092 6 N /A 0 . 00 09 26 1600 0 Fe mal es 13 -49 y r s 0 . 000 9 41 N IA 0. 0009 4 1 16000



### .. 1 S01l mges u on es timat es are fro m J . Arth ur , DP 322240 , 1219 /05 2 A

ggre gat e MOE = NOAEL ( 1 5 mg/k g/d ay)+ A ggrega t e E xp os ure Es t i m

a t e ( mg/kg/d ay). Le vel o f Co n cern = 3000 .



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