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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 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.: 473635 Registration No.: None

Petition Nos.: 2F8134, 2F8135, & 2E8138 Regulatory Action: Section 3

Assessment Type: Single Chemical, Aggregate Registration Case No.: NA

TXR 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 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, 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 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, 411385, May 1, 2013). 

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 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 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 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

Acute Dietary

(95th 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 0.008240 27 0.001276 26

Not 

Applicable

Not 

Applicable

All Infants (< 1 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

Children 6-12 years old 0.010932 36 0.001588 32

Youth 13-19 years old 0.007167 24 0.001036 21

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

Not 

Applicable

Not 

Applicable

0.017658 20

Not 

Applicable

Not 

Applicable

All Infants (< 1 year old) 0.021510 24

Children 1-2 years old 0.054965 61

Children 3-5 years old 0.044098 49

Children 6-12 years old 0.023459 26

Youth 13-19 years old 0.014759 16

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

Population Subgroup

Exposure Estimate, mg/kg/day1

Aggregate 

MOE2 Dietary

Dermal

(M/L/A)

Dermal 

(PostApplic.)Hand-toMouthObject-toMouthSoil 

Ingestion Aggregate

U.S. Population (total) 0.001276 0.00183 0.0051 N/A N/A N/A 0.008206 3700

All infants (< 1 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 N/A N/A N/A 0.010188 2900

Youth 13-19 yrs 0.001036 0.00183 0.0051 N/A N/A N/A 0.007966 3800

Adults 20-49 yrs 0.001101 0.00183 0.0051 N/A N/A N/A 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 N/A N/A 0.008003 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 Concern = 1000.

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

Population Subgroup

Exposure Estimate, mg/kg/day

Aggregate MOE2 Dietary Soil Ingestion1 Aggregate

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

All infants (< 1 year) 0.001822 0.000019 0.001841 8100

Children 1-2 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

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.