Document ID: EPA-HQ-OPP-2013-0151-0010
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2015-02-04T05:00Z

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.

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 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.  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.

 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
                              (95[th] 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.

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 2.  Short-term Aggregate Exposure and Risk Estimates for 1,2,4-Triazole.
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)
0.001276
                                    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 MOE[2]

                                    Dietary
                               Soil Ingestion[1]
                                   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.