UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Office of Chemical Safety and Pollution Prevention 

MEMORANDUM 

Date: April 9, 2015 

SUBJECT: Common Triazole Metabolites: Updated Aggregate 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 Established Foliar Uses/Tolerances for Stone Fruit and Tree Nut Crop Groups to 

Fruit, Stone, Group 12-12 and the Nut, Tree, Group 14-12.; and Use of Flutriafol on 

Hops. 

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

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 No.: None 

MRlD 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: 426493 & 426497 

Registration No.: None 

Regulatory 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 triazolylpyruvic acid (TP)] are below 

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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 uses of propiconazole, difenoconazole, and flutriafol. 

III. BACKGROUND 

In 2006, HED issued 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 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, 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, D426492, 4/15/15). 

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

scenarios for T (Tables 2 and 3, respectively). 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 ohhis 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 TAIT 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 Adding the New Uses for Difenoconazole and Propiconazole. 

Acute Dietary Chronic Dietary Cancer (95th Percentile) 

Population Subgroup Dietary Dietary Dietary 

Exposure %aPAD* Exposure %cPAD* Exposure Risk 

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

1,2,4-Triazole 

General U.S. Population 0.007866 26 0.001 148 23 

All Infants (< I year old) 0.012319 41 0.002097 42 

Children 1-2 years old 0.019571 65 0.003322 66 

Children 3-5 years old 0.016614 55 0.002647 53 Not Not Children 6-12 years old 0.009616 32 0.001431 29 Applicable Applicable Youth 13-19 years old 0.006806 23 0.000922 18 

Adults 20-49 years old 0.006353 21 0.000975 20 

Adults 50-99 years old 0.005589 19 0.000926 19 

Females 13-49 years old 0.006417 21 0.000941 19 

Triazolylalanine + Triazolylacetic Acid+Triazolylpyruvic acid 

General U.S. Population 0.015772 18 

All Infants(< 1 year old) 0.021525 24 

Children 1-2 years old 0.050647 56 

Children 3-5 years old Not Not 0.040826 45 Not Not Children 6-12 years old Applicable Applicable 0.021366 24 Applicable Applicable 

Youth 13-19 years old 0.013171 15 

Adults 20-49 years old 0.012807 14 

Adults 50-99 years old 0.012155 14 

Females 13-49 years old 0.073216 73 0.012355 14 

* The values for the highest exposed population for each type of risk assessment are bolded. 

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Table 2. Short-term A22regate Exposure and Risk Estimates for 1,2,4-Triazole. 

Exposure Estimate, mg/kg/day1 

Dermal 

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

Population Subgroup Dietary (M/UA) Aoolic.) Mouth Mouth Ingestion Ae.aregate 

U.S. Population (total) 0.00 1148 0.00 183 0.005 1 NIA NIA NIA 0.008078 

All infants(< I year) 0.002097 NIA 0.0086 0.0041 0.0010 0.000019 0.01581 6 

Children 1-2 yrs 0.003322 NIA 0.0086 0.0041 0.0010 0.000019 0.017041 

Children 3-5 yrs 0.002647 NIA 0.0086 0.0041 0.0010 0.000019 0.016366 

Children 6-1 2 yrs 0.00 143 1 NIA 0.0086 NIA NIA NIA 0.010031 

Youth 13-19 yrs 0.000922 0.00183 0.005 1 NIA NIA NIA 0.007852 

Adults 20-49 yrs 0.000975 0.00183 0.0051 NIA NIA NIA 0.007905 

Adults 50-99 yrs 0.000926 0.00183 0.0051 NIA NIA NIA 0.007856 

Females 13-49 yrs 0.000941 0.00183 0.0051 NIA NIA NIA 0.007871 . . ' Exposure estimates for dermal, hand-to-mouth, object-to-mouth, and so1l mgestion are from J. Arthur, DP 322240, 1219105 . 2 Aggregate MOE= NOAEL (30 mg/kg/day) + Aggregate Exposure Estimate (mg/kg/day). Level of Concern = I 000. 

Table 3. Intermediate-term A11'11're ate Exoosure and Risk Estimates for 1.2,4-Triazole. 

Exposure Estimate, mg/kg/day 

MOE2 

3700 

1900 

1800 

1800 

2900 

3800 

3800 

3800 

3800 

Population Subgroup Dietary Soil Ingestion' A1t2regatc A2trregate MOE2 

U.S. Population (total) 0.001148 NIA 0.0011 48 13000 

All infants(< I year) 0.002097 0.000019 0.00211 6 7100 

Children 1-2 yrs 0.003322 0.000019 0.003341 4500 

Children 3-5 yrs 0.002647 0.000019 0.002666 5600 

Children 6-12 yrs 0.00 1431 N/A 0.00143 1 10000 

Youth 13-19 yrs 0.000922 NIA 0.000922 16000 

Adults 20-49 yrs 0.000975 NIA 0.000975 15000 

Adults 50-99 yrs 0.000926 N/A 0.000926 16000 

Females 13-49 yrs 0.000941 NIA 0.000941 16000 .. 1 S01l mgesuon estimates are from J. Arthur, DP 322240, 1219/05 2 Aggregate MOE = NOAEL ( 15 mg/kg/day)+ Aggregate Exposure Estimate (mg/kg/day). Level of Concern = 3000. 

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