UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D .C. 20460 Office of Chemical Safety and Po ll ution Prevention MEMORANDUM Date: Oc t ober 24, 2013 SUBJECT: Common T r i azole Metabolites: Updated Aggregate Human H eal th Risk Assessment to Address The New Section 3 Registrations For Use ofPropiconazole on Rapeseed Crop Subgroup 20A; Use ofDifenoconazole on Rapeseed Crop Subgroup 20A; and Use ofTebuconazo le on Imported Oranges.

PC Codes : 600074 (1,2,4 - Triazole), 600011 (Triazolylalanine), 600082 (Triazolylacetic Acid), 625618 (Tri azolylpyruv ic Ac id) D ecis ion No . : 473635 Petition Nos.: 2F8134, 2F8135, & 2E8138 Ass es s ment T ype: Single Chemical, Aggregate TXR No. : None MRID No . : N one From: Thurston G. Morton, Senior Chem i st Risk Assessment Branch IV Health Effects Division (HED) 7509P Through: El i ssa Reaves, Ph.D., Branch Chief Risk Assessment Branch IV Health Effects Division ( HED) 7509P To: Rosemary Kearns/Tony Kish RM 22 Registration Division (RD; 7505P) 

### I . CONCLUSIONS DP Barcode : 414952
R egistration No.: None R egu latory Action: Section 3 R eg i stration Case No.: NA CAS N o . : M ultiple



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Based on conservative, h ealth-protective assumptions, aggregate risk estimates associated with 1

, 2 ,4-triazole (T) and the conjugated triazole metabolite s [i. e., combined residues of tria z olylalanine (TA), triazolylacetic acid (T AA), and triazolylpyruvic acid (TP)] are b e low 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.

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### II. ACTION REQUESTED Update the aggregate human health risk a ssessme nt s for T and the conjugated triazole metabolites to acco unt for the new uses of propiconazole , difenocon azo le, and tebuconazole. 

### III. BACKGROUND In 2006, HED issued aggregate human health risk assessments for T and th e co nju ga ted triazole metabolites (M. Doherty , 

### eta/., D322215 , 7 FEB 06). Tho s e assessments addressed a back- lo g oftriazole u se requests that had been he ld by the Agency pending r eso lution of various to xico logical and exposure concerns for the common triazole metabolites. The findings of that assessment were that risk estimates for all expo sure sc enarios were b e low HED's level of concern. Since that time, a number of reque sts for new uses of triazo le -d eri vative fungicides have been submitted to the Agency. As a resu lt of these requests , new di etary exposure estimates hav e bee n made for T and combined residues of TA, T AA , and T P, and new aggregate expos ure and ri sk estima t es are nece ssary . Ne ith er the toxico lo gical information nor the n ondi etary expos ure es tim ates detailed in the 2006 memorandum h ave changed ; thus the only alterations to the p reviou s aggregate expos ure and risk estima tes are due to changes in the di etary exposure estimates. For com plete hazard c h aracteriza tion and non- dietary expos ure assessments for the common triazole metabolite s, see the 2006 risk assessment. 

### IV. RES ULTS/DISCU SSION As not ed above , the only revisions to the co mp onents of the previ ous aggrega te exposure and risk estimate s are to the dietary exposure estimates. Fo r the common triazo l e metabo li tes, acute and chronic aggregate ri sk s consist only of dietary (foo d + water) components and, therefo re , are equ i vale n t to the dietary risk estima tes provided in the most recent di etary exposure assessment (T. Morton , 41 1 385 , May 1 , 2013). The revised aggregate estimates are summarized be low for short- and intermediate-term scenarios forT (Tab l es 2 and 3, respectively). T he conjugated triazol e me tabolites are form e d in plants by the conju gation of 1 ,2, 4-T to serine. The T A may then be further me tabolized to form TAA and/or TP. Because of the nature of thi s process, HED has assumed tha t i t occurs within the plant itself and not on leaf surfaces. Therefo r e, the res idue s are not avai l able for dermal , hand-to -mo uth , or ob ject- to- mouth exposures and HED has not conducted a residential exposure assessment f or the triazole conj ugate s. Residues o fT A, T AA , and TP may occur in soil. 1 , 2 , 4- Tr iaz ole is more toxic than T

### A!f 

### AAITP and exp osures to these via soil ingestion are unlikel y to exceed those of 1, 2,4-T. The asses s ment for so il inge stion of 1,2,4-T s hows that risk estimates are below HED's leve l of concern; therefore, ri s k estimates for s oil ingestion of the conjugate s will also be below HED's level of concern .

Page 2 of4Table I. Summary of Dietary (Food and Drinking Water) Exposure and Risk for the Common Triazole Metabolites Addingthe New Uses for Propiconazole , D ife noconazole, and T ebuconazole. Acute Dietary (95th Percentile) Chronic Dietary Cancer Population Subgroup Dietary Dietary Dietary Exposure %aPAD* Exposure %c PAD * Exposure Risk (mglkg/day) (mg/kg/day) (mg/k g/day) 1,2,4-Triazole Genera l U.S. Population 0.008240 27 0.001276 26 All Infant s(< I year old) 0.012026 40 0 . 001822 36 Ch ildren 1-2 years old 0.022883 76 0.003629 73 Chi ldren 3 -5 years old 0.018815 63 0 . 002896 58 Not Not Children 6-12 years old 0.010932 36 0.001588 32 Youth 13-19 years old 0.007167 24 0.001036 21 Applicable Applicable Adults 20-49 years old 0.006581 22 0.001101 22 Adults 50 -99 years old 0.005808 19 0.001036 21 Females 13 -49 years old 0.006730 22 0.001073 22 Triazolylalanine + Tr iazolylacetic Acid +Triazolylpyruvic acid General U . S . Population 0.017658 20 All Infants(< 1 year old) 0.02 1 510 24 Children 1 - 2 years old 0.054965 61 Ch ildren 3-5 years old No t Not 0.044098 49 Not Not Children 6-12 years old Applicable Applicable 0.023459 26 Youth 13 - 19 years old 0.014759 16 Applicable Applicable Adults 20-49 years old 0.014662 16 Adults 50-99 years old 0.013721 15 Females 13-49 years old 0.078443 78 0.014260 16 * The values for the highest exposed populatiOn for each type of nsk assessment are bolded .

Page3 of4Tab le 2. Short- term Aggregate E xposure and Risk Estimates for 1 , 2 , 4 - Triazole . Exposure Estimate, mglkglday 1 Dermal Dermal (Post- Hand-to- Object-to- So il Ag gregate Population Subgro up Dietary (MILIA) App lic.) Mouth Mouth Inges tion Aggreg ate MOE2 U.S. Population (total) 0.001276 0.00183 0.0051 N/ A N/A N/A 0 . 008206 3700 All infants( < I year) 0.001822 

### N!A 0.0086 0.0041 0.0010 0 . 000019 0.015541 1900 Chi ldren 1-2 yrs 0.003629 N/A 0.0086 0 . 0041 0.0010 0.000019 0 . 017348 1700 Children 3 - 5 yrs 0.002896 N/A 0.0086 0 . 0041 0 . 0010 0.000019 0.016615 1800 Children 6-12 yrs 0.001588 N/A 0 . 0086 

### NIA N/A 

### NIA 0 . 010188 2900 Youth 13- 19 yrs 0.001036 0.00183 0 . 0051 

### NIA N / A 

### N I A 0 . 007966 3800 Adults 20-49 yrs 0 . 001101 0 .0 0183 0 . 0051 

### N I A N / A 

### N I A 0 .0 08031 3700 A dults 50-99 yrs 0 . 001036 0 . 00183 0.0051 N/A N / A N/A 0.007966 3800 F emales 13 - 49 yrs 0.001073 0 . 00183 0 . 0051 N / A 

### NIA N / A 0.008003 3700

. . Exposure est1mates fo r dermal , hand -to-mouth , ObJect-to-mouth , and s01l mgestiOn are from J. Arthur, DP 322240, 1219/ 05 . 1 Aggregate MOE = NOAE L (30 mg/kg/day) + Aggregate Exposure Estimate ( mg/kg/day). Level of Concern= 1000.

Table 3 . Interm ediate-term Aggre ate Exposure and Risk Estimates for 1,2,4 -T riazol e . Exposu r e Estimate, m g!k glday Population Subgroup Dietary Soil Ingestion 1 Aggr egate Aggregate MOE 2 U . S . Populat ion (total) 0.001276 N /A 0.001276 12000 All infants(< 1 year ) 0.001822 0.000019 0.001841 8100 Ch ild ren l-2 yrs 0.003629 0.0000 1 9 0 . 003648 4100 Children 3-5 yr s 0.002896 0.0000 19 0.002915 5100 Children 6- 12 yrs 0.001588 N/A 0.001588 9400 Youth 13- 19 yrs 0.001036 N/A 0.001036 14000 Adults 20-49 yrs 0.001101 N / A 0.001101 14 000 Adu l ts 50-99 yrs 0.001036 N /A 0.001036 14 000 Females 13 -49 yrs 0.001073 N/ A 0.001073 14000

. . S01l mgest1on estimates ar e from J. Arthur, DP 322240, 12/9/05 2 Aggregate MOE= NOAEL (15 mg/kg/day) + Aggregate E xposure Estim ate (mg/kg/day). Level of Con cern = 3000 .

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