UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Office of Chemical Safety and Pollution Prevention 

MEMORANDUM 

Date: October 24, 2013 

SUBJECT: Common Triazole Metabolites: Updated Aggregate Human Health 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 ofTebuconazole on Imported Oranges. 

PC Codes: 600074 (1,2,4-Triazole), 

600011 (Triazolylalanine), 

600082 (Triazolylacetic Acid), 

625618 (Triazolylpyruvic Acid) 

Decision No.: 473635 

Petition Nos.: 2F8134, 2F8135, & 2E8138 

Assessment Type: Single Chemical, Aggregate 

TXR No.: None 

MRID No.: None 

From: Thurston G. Morton, Senior Chemist 

Risk Assessment Branch IV 

Health Effects Division (HED) 7509P 

Through: Elissa 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 

Registration No.: None 

Regulatory Action: Section 3 

Registration Case No.: NA 

CAS No.: Multiple 

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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), triazolylacetic acid (T AA), and triazolylpyruvic acid (TP)] are below 

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 assessments for T and the conjugated triazole 

metabolites to account for the new uses of propiconazole, difenoconazole, and tebuconazole. 

III. BACKGROUND 

In 2006, HED issued aggregate human health risk assessments for T and the conjugated triazole 

metabolites (M. Doherty, eta/., D322215, 7 FEB 06). Those assessments addressed a back-log 

oftriazole use requests that had been held by the Agency 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 requests for new uses of triazole-deri vative fungicides 

have been submitted to the Agency. As a result of these requests, new dietary exposure 

estimates have been made for T and combined residues of TA, T AA, and TP, and new aggregate 

exposure and risk estimates are necessary. Neither the toxicological information nor the nondietary exposure estimates detailed in the 2006 memorandum have changed; thus the only 

alterations to the previous aggregate exposure and risk estimates are due to changes in the dietary 

exposure estimates. For complete hazard characterization and non-dietary 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 the previous aggregate exposure and 

risk estimates are to the dietary exposure estimates. For the common triazole metabolites, acute 

and chronic aggregate risks consist only of dietary (food + water) components and, therefore, are 

equivalent to the dietary risk estimates provided in the most recent dietary exposure assessment 

(T. Morton, 41 1385, May 1, 2013). 

The revised aggregate estimates are summarized below for short- and intermediate-term 

scenarios forT (Tables 2 and 3, respectively). The conjugated triazole metabolites are formed in 

plants by the conjugation of 1 ,2,4-T to serine. The T A may then be further metabolized to form 

TAA and/or TP. Because of the nature of this process, HED has assumed that it occurs within 

the plant itself and not on leaf surfaces. Therefore, the residues are not available for dermal, 

hand-to-mouth, or object-to-mouth exposures and HED has not conducted a residential exposure 

assessment for the triazole conjugates. Residues ofT A, T AA, and TP may occur in soil. 1 ,2,4-

Triazole is more toxic than T A!f AAITP and exposures to these via soil ingestion are unlikely to 

exceed those of 1 ,2,4-T. The assessment for soil ingestion of 1 ,2,4-T shows that risk estimates 

are below HED's level of concern; therefore, risk estimates for soil ingestion of the conjugates 

will also be below HED's level of concern. 

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Table I. Summary of Dietary (Food and Drinking Water) Exposure and Risk for the Common Triazole 

Metabolites Addingthe New Uses for Propiconazole, Difenoconazole, and Tebuconazole. 

Acute Dietary 

(95th Percentile) Chronic Dietary Cancer 

Population Subgroup Dietary Dietary Dietary 

Exposure %aPAD* Exposure %cPAD* Exposure Risk 

(mglkg/day) (mg/kg/day) (mg/kg/day) 

1,2,4-Triazole 

General U.S. Population 0.008240 27 0.001276 26 

All Infants(< I year old) 0.012026 40 0.001822 36 

Children 1-2 years old 0.022883 76 0.003629 73 

Children 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 + Triazolylacetic Acid+Triazolylpyruvic acid 

General U.S. Population 0.017658 20 

All Infants(< 1 year old) 0.02 1510 24 

Children 1-2 years old 0.054965 61 

Children 3-5 years old Not 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. 

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Table 2. Short-term Aggregate Exposure and Risk Estimates for 1,2,4-Triazole. 

Exposure Estimate, mglkglday1 

Dermal 

Dermal (Post- Hand-to- Object-to- Soil Aggregate 

Population Subgroup Dietary (MILIA) Applic.) Mouth Mouth Ingestion Aggregate 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 

Children 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 NIA 0.007966 3800 

Adults 20-49 yrs 0.001101 0.00183 0.0051 NIA N/A NIA 0.008031 3700 

Adults 50-99 yrs 0.001036 0.00183 0.0051 N/A N/A N/A 0.007966 3800 

Females 13-49 yrs 0.001073 0.00183 0.0051 N/A NIA N/A 0.008003 3700 . . Exposure est1mates for dermal, hand-to-mouth, ObJect-to-mouth, and s01l mgestiOn are from J. Arthur, DP 322240, 1219/05 . 1 Aggregate MOE = NOAEL (30 mg/kg/day) + Aggregate Exposure Estimate (mg/kg/day). Level of Concern= 1000. 

Table 3. Intermediate-term Aggre ate Exposure and Risk Estimates for 1,2,4-Triazole. 

Exposure Estimate, mg!k glday 

Population Subgroup Dietary Soil Ingestion1 Aggregate Aggregate MOE2 

U.S. Population (total) 0.001276 N/A 0.001276 12000 

All infants(< 1 year) 0.001822 0.000019 0.001841 8100 

Children l-2 yrs 0.003629 0.000019 0.003648 4100 

Children 3-5 yrs 0.002896 0.000019 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 14000 

Adults 50-99 yrs 0.001036 N/A 0.001036 14000 

Females 13-49 yrs 0.001073 N/A 0.001073 14000 . . S01l mgest1on estimates are from J. Arthur, DP 322240, 12/9/05 2 Aggregate MOE= NOAEL (15 mg/kg/day) + Aggregate Exposure Estimate (mg/kg/day). Level of Concern = 3000. 

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