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

### MEMORANDUM Date: October 24 , 20 1 3 SUBJECT: Common Triazole Metabolites: Updated Aggregate Human Health Risk

Assessment to Address The New Section 3 Registration s For Use of Propiconazole on Rapeseed Crop Subgroup 20A; Use of Difenoconazole on Rapeseed Crop Subgroup 20A; and Use of Tebuconazole on Imported Oranges . PC Codes: 600074 (1,2,4 - Triazole),

600011 (Triazolylalanine), 600082 (Triazolylacetic Acid), 625618 (Triazolylpyruvic Acid) DP Barcode: 414952 Decision No.: 4 73635 Registration No. : None Petition Nos.: 2F8134, 2F8135, & 2E8138 Regulatory Action: Section 3 Assessment Type: Single Chemical, Aggregate Registration Case No.: NA T XR No.: None CAS No.: Multiple 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**  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 (TAA), and triazolylpy ruvic ac id (TP) ] are below HED’s level of concern. There are no human heath risk issues for these metabolites that would preclude the requested use s of propiconazole, difenoconazole , and tebuconazole .Page 2 of 4



### 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, et al . , D322215, 7 FEB 06 ). Those assessments addressed a back- log of triazole 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 - derivative 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, TAA, and TP, and new aggregate exposure and risk estimates are necessary . Neither the toxicological information nor the non dietary exposure estimates detaile d 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 onl y 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 , 411385 , May 1 , 20 1 3 ). The revised aggregate estimates are summarized below for short- and intermediate - term scenarios for T (Tables 2 and 3 , respectivel y) . The conjugated triazole metabolites are formed in plants by the conjugation of 1,2,4 - T to serine. The TA 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 of TA , TAA, and TP may occur in soil. 1,2,4 - Triazole is more toxic than TA/TAA/TP and exposures to these via soil ingestion are unlikel y 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.Page 3 of 4

Table 1 . Summary of Dietary (Food and Drinking Water) Exposure and Risk for the Common Triazole Metabolites Adding the New Uses for Propiconazole, Difenoconazole, and Tebuconazole . Population Subgroup Ac ute Dietary ( 95 th Percentile) Chronic Dietary Cancer Dietary Exposure (mg/kg/day) % aPAD* Dietary Exposure (mg/kg/day) % cPAD* Dietary Exposure (mg/kg/day) Risk 1,2,4 - Triazole General U.S. Population 0.00 8240 27 0.001 276 26 Not Applicable Not

Applicable All Infants (< 1 year old) 0.01 2026 40 0.00 1822 36 Children 1 - 2 years old **0.0 22883**  **76 0.00**  **3629 73**  Children 3 - 5 years old 0.01 8815 63 0.00 2896 58 Children 6 - 12 years old 0.0 10932 36 0.001 588 3 2 Youth 13 - 19 years old 0.00 7167 24 0.001 036 2 1 Adults 20 - 49 years old 0.00 6581 22 0.00 1101 2 2 Adults 50 - 99 years old 0.00 5808 19 0.00 1036 21 Females 13 - 49 years old 0.00 6730 22 0.00 1073 22 Triazolylalanine + Triazolylacetic Acid+Triazolylpyruvic acid General U.S. Population Not Applicable Not

Applicable 0.01 7658 20 Not Applicable Not

Applicable All Infants (< 1 year old) 0.0 21510 2 4 Children 1 - 2 years old **0.0 54965**  **61** Children 3 - 5 years old 0.0 44098 49 Children 6 - 12 years old 0.0 23459 26 Youth 13 - 19 years old 0.01 4759 16 Adults 20 - 49 years old 0.01 4662 1 6 Adults 50 - 99 years old 0.0 13721 1 5 Females 13 - 49 years old **0.0 78443**  **78** 0.01 4260 1 6 * The values for the highest exposed population for each type of risk assessment are bolded.Page 4 of 4

Table 2 . Short- term Aggregate Exposure and Risk Estimates for 1,2,4 - Triazole. Population Subgroup Exposure Estimate, mg/kg/day 1 Aggregate MOE 2 Dietary Dermal

(M/L/A) Dermal

(PostApplic.) Hand - to Mouth Object- to Mouth Soil

Ingestion Aggregate U.S. Population (total) 0.001 276 0.00183 0.0051 N/A N/A N/A 0.0082 06 3 7 00 All infants (< 1 year) 0.00 1822 N/A 0.0086 0.0041 0.0010 0.000019 0.0155 41 1900 Children 1 - 2 yrs 0.003629 N/A 0.0086 0.0041 0.0010 0.000019 0.017 348 1700 Children 3 - 5 yrs 0.00 2896 N/A 0.0086 0.0041 0.0010 0.000019 0.016 615 1800 Children 6 - 12 yrs 0.001 588 N/A 0.0086 N/A N/A N/A 0.01 0188 2900 Youth 13 - 19 yrs 0.001 036 0.00183 0.0051 N/A N/A N/A 0.00 7966 3 8 00 Adults 20 -49 yrs 0.00 1101 0.00183 0.0051 N/A N/A N/A 0.0080 3 1 3700 Adults 50 - 99 yrs 0.00 1036 0.00183 0.0051 N/A N/A N/A 0.00 7966 3 8 00 Females 13 - 49 yrs 0.00 1073 0.00183 0.0051 N/A N/A N/A 0.0080 03 3700 1 Exposure estimates for dermal, hand- to -mouth, object- to -mouth, and soil ingestion are from J. Arthur, DP 322240, 12/9/05. 2 Aggregate MOE = NOAEL (30 mg/kg/day) ÷ Aggregate Exposure Estimate (mg/kg/day). Level of C oncern = 1000.

Table 3 . Intermediate - term Aggregate Exposure and Risk Estimates for 1,2,4 - Triazole. Population Subgroup Exposure Estimate, mg/kg/day Aggregate MOE 2 Dietary Soil Ingestion 1 Aggregate U.S. Population (total) 0.001 276 N/A 0.00 1276 12 000 All infants (< 1 year) 0.00 1822 0.000019 0.0018 4 1 8 1 00 Children 1 - 2 yrs 0.003629 0.000019 0.003 648 41 00 Children 3 - 5 yrs 0.00 2896 0.000019 0.00 2915 51 00 Children 6 - 12 yrs 0.001 588 N/A 0.001 588 9 4 00 Youth 13 - 19 yrs 0.001 036 N/A 0.0010 36 14000 Adults 20 -49 yrs 0.00 1101 N/A 0.0011 0 1 1 4 000 Adults 50 - 99 yrs 0.00 1036 N/A 0.0010 36 14000 Females 13 - 49 yrs 0.00 1073 N/A 0.001 073 1 4 000 1 Soil ingestion 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.