1,2,4-Triazole and Conjugated Metabolites Human-Health Risk Assessment D388544

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

MEMORANDUM

Date: 14-April-2011

Subject: Common Triazole Metabolites. Updated Aggregate Human-Health Risk Assessment 

to Address Tolerance Petitions for Tetraconazole.

PC Code: 120603 (Tetraconazole), 600074 (1,2,4-Triazole), 

600011 (Triazolylalanine), 600082 (Triazolylacetic Acid), 

625618 (Triazolylpyruvic Acid)

DP Barcode: D388544

Decision No.: 435873 Registration Nos.: 80289-7 and 80289-8

Petition Nos.: 0E7735 (13-07F and 03-07G) and 0F7737

(field corn and popcorn)

Regulatory Action: Section 3

Risk Assessment Type: Aggregate Case No.: 7043 (Tetraconazole)

TXR No.: not applicable CAS No.: Tetraconazole - 112281-77-3; T -

288-88-0; TA - 86362-20-1; and TAA - 28711-29-7

MRID Nos.: none 40 CFR: none

From: Tom Bloem, Chemist

Risk Assessment Branch 1, Health Effects Division (RAB1/HED); 7509P

Through: Dana Vogel, Branch Chief

George F. Kramer, Ph.D., Senior Chemist

RAB1/HED (7509P)

To: Mary Waller/Lisa Jones (RM 21)

Barbara Madden (RM 05)

Registration Division (7505P) 

I. Conclusions

Based on conservative, health-protective assumptions, aggregate risk estimates associated with 

1,2,4-triazole (T) and the conjugated triazole metabolites are below HED’s level of concern. 

There are no human-heath risk issues for these metabolites that would preclude the requested 

uses of tetraconazole to field corn, popcorn, small fruit vine climbing (except fuzzy kiwifruit) 

subgroup 13-07F, and low-growing berry subgroup 13-07G (except cranberry).
1,2,4-Triazole and Conjugated Metabolites Human-Health Risk Assessment D388544

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II. Detailed Considerations

T and its conjugates are residues of concern in primary crops, livestock, rotational crops, and/or 

water following the application of several triazole-derivative fungicides including tetraconazole. 

In 2006, HED issued an aggregate human-health risk assessments for T and for the combined 

residue of its conjugates (D322215, M. Doherty et al., 7-Feb-06). This assessment has been 

updated as needed with the most recent assessment conducted on 28-Oct-2009 (D370435, M. 

Negussie). Based on the proposed tetraconazole application scenarios, new dietary and aggregate 

risk estimates for T and its conjugates are required (see below). HED notes that neither the 

toxicological information nor the non-dietary 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 (refer to D322215 memo for 

information concerning the toxicological and nondietary exposure assessments). 

Dietary: HED completed an updated dietary exposure and risk analysis for T and its conjugated 

metabolites which included residues resulting from the proposed tetraconazole uses (D386652, T. 

Morton, 16-Feb-2011). These analyses were conducted using the Dietary Exposure Evaluation 

Model DEEM-FCIDTM (ver. 2.03) which incorporates food consumption data from the U.S. 

Department of Agriculture’s (USDA) Continuing Surveys of Food Intakes by Individuals (CSFII; 

1994-1996 and 1998). Four assessments were conducted: acute and chronic durations for T, and 

acute and chronic durations for combined residues of the conjugated T metabolites. As with the 

previous triazole metabolite assessments, this assessment includes exposure estimates resulting 

from direct consumption of T or its conjugated metabolites as well as indirect exposure resulting 

from consumption of parent fungicides followed by in vivo conversion to these compounds. For 

each food form in the acute assessment, the residue used is the maximum estimate from the 

various food/triazole fungicide combinations combined with the average indirect residue estimate. 

For the chronic assessments, the residue estimates are the average residue from the food-specific 

food/triazole combinations combined with the average indirect residue estimates. All four 

assessments assume 100% crop treated and include conservative estimates for residues of the 

metabolites in drinking water. The resulting exposure and risk estimates are based on healthprotective assumptions and should be characterized as conservative. For all four analyses, risk 

estimates are below HED’s level of concern for all population subgroups (see Table 2.1). 

Aggregate: The revised T short- and intermediate-term aggregate estimates are summarized 

below (see Tables 2.2 and 2.3, respectively). The resulting short-and intermediate-term risk do 

not exceed HED’s level of concern. 

HED determined that the conjugated T metabolites are formed within the plant itself and not on 

leaf surfaces. Therefore, these residues are not available for dermal, hand-to-mouth, or object-tomouth exposure. However, residues of the conjugated T metabolites may occur in soil. For the 

following reasons, HED concludes that exposure to the conjugate T metabolites via soil ingestion 

is insignificant: exposure to T via soil ingestion was insignificant (see Table 2.2 and 2.3); it is 

unlikely that exposure via soil ingestion of the conjugate T metabolites will exceed that of T; and 

T has lower incidental oral endpoints than those for conjugated T. 
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Table 2.1. Summary of Dietary (Food and Drinking Water) Exposure and Risk for T and its Conjugate 

Metabolites.

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

T

General U.S. Population 0.006517 22 0.001185 24

not applicable

All Infants (< 1 year old) 0.011889 40 0.002065 41

Children 1-2 years old 0.014564 49 0.003112 62

Children 3-5 years old 0.011865 40 0.002542 51

Children 6-12 years old 0.007790 26 0.001614 32

Youth 13-19 years old 0.005358 18 0.001002 20

Adults 20-49 years old 0.005085 17 0.000974 20

Adults 50+ years old 0.004724 16 0.000916 18

Females 13-49 years old 0.004903 16 0.000964 19

Conjugated T Metabolites

General U.S. Population

not applicable

0.013915 16

not applicable

All Infants (< 1 year old) 0.020264 23

Children 1-2 years old 0.039889 44

Children 3-5 years old 0.031321 35

Children 6-12 years old 0.019106 21

Youth 13-19 years old 0.012076 13

Adults 20-49 years old 0.011326 13

Adults 50+ years old 0.010308 12

Females 13-49 years old 0.051668 52 0.011136 12

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

Table 2.2. Short-term Aggregate Exposure and Risk Estimates for T.

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) 0.001185 0.00183 0.0051 N/A N/A N/A 0.008088 3700

All infants (< 1 year) 0.002065 N/A 0.0086 0.0041 0.0010 0.000019 0.015744 1900

Children 1-2 yrs 0.003112 N/A 0.0086 0.0041 0.0010 0.000019 0.016769 1800

Children 3-5 yrs 0.002542 N/A 0.0086 0.0041 0.0010 0.000019 0.016205 1800

Children 6-12 yrs 0.001614 N/A 0.0086 N/A N/A N/A 0.010177 2900

Youth 13-19 yrs 0.001002 0.00183 0.0051 N/A N/A N/A 0.007904 3800

Adults 20-49 yrs 0.000974 0.00183 0.0051 N/A N/A N/A 0.007881 3800

Adults 50+ yrs 0.000916 0.00183 0.0051 N/A N/A N/A 0.007828 3800

Females 13-49 yrs 0.000964 0.00183 0.0051 N/A N/A N/A 0.00787 3800

1 Exposure estimates for dermal, hand-to-mouth, object-to-mouth, and soil ingestion are from J. Arthur (D322240, 9-Dec-2005).

2 Aggregate MOE = NOAEL (30 mg/kg/day) ÷ Aggregate Exposure Estimate (mg/kg/day). Level of Concern = 1000.

Table 2.3. Intermediate-term Aggregate Exposure and Risk Estimates for T.

Population Subgroup Exposure Estimate, mg/kg/day Aggregate MOE2

Dietary Soil Ingestion1 Aggregate

U.S. Population (total) 0.001185 N/A 0.001158 13000

All infants (< 1 year) 0.002065 0.000019 0.002044 7200

Children 1-2 yrs 0.003112 0.000019 0.003069 4800

Children 3-5 yrs 0.002542 0.000019 0.002505 5900

Children 6-12 yrs 0.001614 N/A 0.001577 9300

Youth 13-19 yrs 0.001002 N/A 0.000974 15000

Adults 20-49 yrs 0.000974 N/A 0.000951 15000

Adults 50+ yrs 0.000916 N/A 0.000898 16000

Females 13-49 yrs 0.000964 N/A 0.000940 16000

1 Soil ingestion estimates are from J. Arthur (D322240, 9-Dec-2005). 

2 Aggregate MOE = NOAEL (15 mg/kg/day) ÷ Aggregate Exposure Estimate (mg/kg/day). Level of Concern = 3000.