1,2,4 - Triazole and Conjugated Metabolites Human - Health Risk Assessment D3 8 8544



### Page 1 of 3 **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 ( T etraconazole), 600074 (1,2,4 - Triazole), 600011 (Triazolylalanine), 600082 (Triazolylacetic Acid), 625618 (Triazolylpyruvic Acid) **DP Barcode:** D38 8544 **Decision No.:** 435873 **Registration No s**  **. :**  80289 - 7 and 80289 - 8 **Petition No s**  **.:** 0E7735 (13 - 07F and 03 - 07G) and 0F7737 (field corn and popcorn) **Regulatory Action:** Section 3 **Risk Assessment Type:** Aggregate **Case No.:** 7043 (Tetraconazole) **T XR No.:**  not applicable **CAS No.:** Tetraconazole - 112281 - 77 - 3 ; T - 288 - 88 - 0; TA - 86362 - 20 - 1; and TAA - 28711 - 29 - 7 

### MRID No **s .:**  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. C**  **onclusions** 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 f ield c orn, popcorn, s mall f ruit vine c limbing ( except f uzzy kiwifruit) subgroup 13 - 07F, and l ow - growing b erry subgroup 13 - 07G (except cranberry).1,2,4 - Triazole and Conjugated Metabolites Human - Health Risk Assessment D3 8 8544



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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 onl y 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 anal ys is 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 the se 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 health protective assumptions and should be characterized as conservative. For all four analys es, 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, respectivel y). 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- to mouth exposure. However, residues of the conjugated T metabo lites 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 .1,2,4 - Triazole and Conjugated Metabolites Human - Health Risk Assessment D3 8 8544



### Page 3 of 3 **Table 2**  **.1. Summ ary of Dietary**  **(Food and Drinking Water) Exposure and Risk for**  **T and its Conjugate Me** **tabolit es.**  Population Subgroup Acute 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 **T** General U.S. Population 0.006517 22 0.001185 24

n ot a pplicable 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

n ot a pplicable 0.013915 16

n ot a pplicable 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 Estim ates for T.**  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) 0.001185 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). L evel of C oncern = 1000. 

### Table **2 .3. Interm** **ediate -**  **term Aggregate Exposure and Risk Estimates for T.**  Population Subgroup Exposure Estimate, mg/kg/day Aggregate MOE 2 Dietary Soil Ingestion 1 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.