Document ID: EPA-HQ-OPP-2010-0583-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-08-29T04:00Z

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).

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-FCID(TM) (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 health-protective 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-to-mouth 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.  

 Table 2.1.  Summary of Dietary (Food and Drinking Water) Exposure and Risk for T and its Conjugate Metabolites.
                              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
                                 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/day[1]
                               Aggregate MOE[2]
                                       
                                    Dietary
                                    Dermal
                                    (M/L/A)
                             Dermal (Post-Applic.)
                                 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).  Level of Concern = 1000.

Table 2.3.  Intermediate-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.