Document ID: EPA-HQ-OPP-2011-0300-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-07-19T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
	WASHINGTON D.C., 20460

	OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

                                                                PC Code: 128847
                                                             DP Barcode: 390040
MEMORANDUM								

DATE:	June 23, 2011

SUBJECT: 	The Drinking Water Degradates Identification Memorandum for Difenoconazole

FROM:	Faruque Khan, Ph.D.,Senior Scientist
		Environmental Risk Branch I
		Environmental Fate and Effects Division (7507P)

TO:		Christine Olinger, Co-chair
		Edward Scollon, Co-chair
		Residues of Concern Knowledgebase Subcommittee

THRU: 	Katrina White, Ph.D., EFED ROCKS Representative
		William Shaughnessy., Ph.D,, EFED ROCKS Representative
		Residues of Concern Knowledgebase Subcommittee
		
		Nancy Andrews, Ph.D., Branch Chief
		Sujatha Sankula, Ph.D., Lead Biologist
		Environmental Risk Branch I
		Environmental Fate and Effects Division

This memorandum identifies the environmental degradates of difenoconazole.  These data are provided to help determine which environmental degradates are of risk concern for conducting a drinking water assessment to support a human health risk assessment.  If you have questions concerning this memorandum, please contact Faruque Khan at 703-305-6127.

 Difenoconazole is a fungicide in the conazole chemical class.  Fungicidal activity of the conazole class of compounds is attributed to the inhibition of ergosterol biosynthesis.  There are several active registrations for formulations of difenoconazole (including mixtures) and one for the technical grade product.  Based on the field and laboratory studies, the active ingredient difenoconazole is persistent in soil and slightly mobile.  Difenoconazole is likely to reach surface water sources of drinking water via spray drift and runoff.  Detailed description of fate and transport properties of difenoconazole can be obtained from previous section 3 assessment (U.S. EPA, 2010; D378927+).
 
 Mobility, Volatility, and Propensity to Move into Surface and Ground Water 
 
Based on a low vapor pressure of 2.5 x 10[-10] mm Hg and a Henry's Law constant of 8.9 x 10[-12] atm-m[3]/mol, difenoconazole has a low propensity to volatilize from application site and surface water.  It has a low solubility (15 mg/L) in water.  Difenoconazole appears to be slightly mobile to hardly mobile in the soil; its Koc values range from 3,471-11,202 L/kg.  Difenoconazole has potential to reach surface water via run-off, erosion, and spray drift, and is less likely to reach ground water except in soils of high sand and low organic matter content.

 Degradation 
 
Environmental fate data indicate that difenoconazole is relatively stable to aerobic and anaerobic soil metabolisms and aerobic and anaerobic aquatic metabolism. When applied at 0.1-0.23 ppm to an aerobic soil, difenoconazole appears to degrade with half-lives ranging from 84.5 to 533 days based on laboratory studies conducted on a variety of foreign and domestic soils.  At concentrations of 10 ppm, difenoconazole degraded with the half-lives of 1059-1600 days in aerobic, and 947 days anaerobic loam soil, respectively.  In aquatic environment under aerobic conditions, difenoconazole microbially degraded with half-lives ranging from 315 to 565 days at concentrations up to 0.17 mg ai/L, and 860 days in a concentration of 10 mg ai/L. Under anaerobic conditions, difenoconazole degraded in 370 days at a concentration of 0.04 mg ai/L, and 1245 days at concentrations of 10 mg ai/L.  The longer half-life values obtained for those higher concentration rates may imply that the rate of difenoconazole microbially mediated degradation may be concentration dependent.  In laboratory studies on difenoconazole a significant amount of radioactivity was nonextractable (14.4 to 48.9%) from soils. 

 Considering abiotic degradation, difenoconazole is photolyzed in water (half-life of 6 to 228 days), but stable in soil.  The half-life of 228 days was extrapolated from a 15-day study in which difenoconazole slowly photolyzed from 100% to 91% under artificial light conditions (MRID 46950105). Also, the compound is stable to hydrolysis at pH values from 4 to 9. 
 
Difenoconazole degraded with half-lives ranging from 139 to 462 days in the terrestrial field dissipation studies.  The overall stability of the compound in the terrestrial environment suggests that difenoconazole may accumulate in soil with successive applications from year to year. 

Bioaccumulation

The octanol water partition coefficient, log Kow of 4.4, suggests that defienoconazole has a potential to bioaccumulate.  Difenoconazole accumulated rapidly in edible and non-edible bluegill sunfish tissues with bioconcentration factors of 170x for edible tissues, 570x for non-edible tissues, and 330x for whole body.  Depuration was also rapid with a depuration half-life of approximately 1 day and 96-98% clearance after 14 days of depuration.  From both edible and non-edible tissues, one metabolite was recovered, CGA-205375, and accounted for 51-64% of the applied.

 
 Possible Degradates of Toxic and Exposure Concern

Difenoconazole  may break down to CGA205375, (1-[2-Chloro-4-(4-chlorophenoxy)-phenyl]-2-[1,2,4]triazol-1-yl-ethanol), next to triazolyl acetic acid and further to triazole methanol and triazole. 1,2,4-triazole and its conjugates (triazole alanine and triazole acetic acid) are common metabolites to the class of compounds known as the triazole-derivative fungicides (T-D fungicides, conazoles).  A separate drinking water assessment was conducted on 1,2,4-triazole degradates ((U.S. EPA, 2006; D D320682).  The majority of the major degradates formed under both abiotic and biotic processes.  

 A summary of ecotoxicity data for degradates has been submitted (MRID 453427-01) from several submitted studies including data in birds (45284015), earthworms (MRID 45297201), daphnids (MRID 00133381), fish (MRID 45284017), and algae (MRID 00133382).  The data suggest that 1,2,4-triazole may be less toxic than difenoconazole to fish, daphnids, and aquatic plants, but more toxic to earthworms.  No toxicity data are available on the other major degradates of difenocozole at this time.    

Residues of possible exposure concern for drinking water include the parent and its degradates.  The submitted environmental fate data for difenconazole and its degradates are summarized in Table 1. 

 Table 1.  Difenconazole and Its Major and Minor Environmental Degradates.
 
Code Name/ Synonym
Chemical Name
Chemical Structure
Study Type
MRID
Maximum %AR (day)
Final %AR (study length)
                                    PARENT
Difenconazole

CGA-169374

IUPAC Name: 3-Chloro-4-[(2RS,4RS;2RS,4SR)-4-methyl-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-2-yl]phenyl 4-chlorophenyl ether.

CAS Name: 1-[2-[2-Chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole.

CAS Number: 119446-68-3
Formula: C19H17Cl2N3O3
MW: 406.3 
SMILES:  O1CC(C)OC1(Cn2ncnc2)c3c(Cl)cc(Oc4ccc(Cl)cc4)cc3
                                       
                                       
Hydrolysis     pH 5
42245127

                                    ---[1]

                                       
Hydrolysis     pH 7

                                      ---

                                       
Hydrolysis     pH 9

                                      ---

                                       
Aqueous Photolysis
42245128

2.50 (30 days)

                                       

46950104

1.21+-0.5
 (30 days)

                                       

46950105

94.1 (15 days)

                                       
 Soil Photolysis
46950106-
46950107

91.4 (30 days)

                                       
Aerobic Soil Metabolism
4695109

18.4  +-0.1
 (293 days)

                                       

46950110

13.6(293 days)

                                       

46950111

51.0(228 days)

                                       

46950112-
46950113

54.2  +-4.8
 (360 days)

                                       

46950114
46950115

58.8 +-1.1
(372 days)

                                       
Aerobic Aquatic Metabolism
46950116

71.2 (183 days)

                                       

46950117-
46950118

81.53+-3.22
(112 days)

                                       
Anaerobic Aquatic Metabolism
46950119-46950120

42.72  0.88 
(350 days)

                                       
Terrestrial Field Dissipation
46950126

44 ppb  (531 days)

                                       

46950127

14 ppb (535 days)

                                       

46950129

302 ppb (422 days)
                                       
                    MAJOR (>10%) TRANSFORMATION PRODUCTS
CGA-179500
[CGA 205375,  
CGA 211391 and M1]

IUPAC Name: 4-[ Not reported 
CAS Name: alpha-[2-Chloro-4-(4-chlorophenoxy)phenyl]-1H-1,2,4-triazole-1-ethanol.
1-[2-Chloro-4-(4-chlorophenoxy)phenyl]-2-[1,2,4]-triazol-1-yl-ethanol.
CAS Number: 117018-19-6

                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
Aqueous Photolysis
42245128
2.9 (5 days)
0.1 (30 days)

46950104
2.04 (14 days)
0.96 (30 days)

46950105
NA
NA

Aerobic Soil metabolism
46950109
5.1+- 1.4
(84days)
3.7+- 0.1
(293 days)

46950110
4.6+- 0.1
(56days)
2.7+- 0.5
(293 days)

46950111
9.4+- 05
(120days)
9.0(228 days)

46950112-
46950113
14.8+-1.8 (360days)

14.8+- 1.8
 (360 days)

4695114-
4695115
9.4+- 0.1
 (372 day)
9.4+- 0.1
 (372 day)

Aerobic Aquatic Metabolism
46950116

11.4 (183 days)
11.4 (183 days)

Anaerobic Aquatic Metabolism
46950119-46950120
12.60+- 0.42
 (175days)
6.2 +- 0.76
 (350 days)

Terrestrial Field Dissipation
46950126
11 ppb (358 days)
6.2ppb (531days)

46950127
12 ppb (123 days)
5.6 ppb (531days)

46950129
18ppb (364 days)
12.0 2ppb (535days)
CGA-71019

IUPAC Name: 4-[ Not reported 

CAS Name: 1H-1,2,4-Triazole 
CAS Number: 288-88-0
                                       
                                       
Aqueous Photolysis
42245128
13.4 (9 days)
10.9 (30 days)

                                       

46950104
12.27 +- 0.7 (30days)
12.27 +- 0.7 
(30 days)

                                       

46950105
NA[2]
NA

                                       
Aerobic  Soil Metabolism
4695110

20.6
 (190 day)
17.8+- 2.8
 (293 day)

                                       

4695111

1.6+-0.4
 (120 day)
0.9
 (228day)

                                       

4695114-
4695115
7.8+- 0.1
 (372 day)
7.8+- 0.1
 (372 day)

                                       
Anaerobic Aquatic Metabolism
46950119-46950120
25.62+- 0.35
 (350 day)
25.62+- 0.35
 (350 day)

                                       
Terrestrial Field Dissipation
46950129
3.5 ppb (36 days)
< LOQ (535days)
CGA-142856
IUPAC Name: 4-[ Not reported 

CAS Name: 1H-1,2,4-Triazole-1-acetic acid
CAS Number: 28711-29-7
                                       
                                       
Aqueous Photolysis
46950104
41.83 +-0.9 (30days)
41.83+-0.9 
 (30 days)

                                       
Terrestrial Field Dissipation
 46950126
<LOQ[3]
11 ppb 
(358 days)
CGA-107069
IUPAC Name: 4-[ Not reported 

CAS Name: 1H-1,2,4-Triazole-1-methanol
CAS Number: 74205-82-6

                                       
Aqueous Photolysis
46950104
Reported as combined residue with CGA 71019

Carbon
Dioxide
CAS Number:  124-38-9
Formula: CO2
MW: 44.1 g/mol
                                       
Aqueous Photolysis
46950104
2.01 (30 day)
2.01+- 2.5(30 days)

                                       

46950105
0.01 (3days)
<0.1 (15 days)

                                       
Soil Photolysis
46950106
46950107
0.02 (30days)
0.2 (30 days)

Aerobic Soil Metabolism
46950109
23.4 +- 1.9
  (293 days)
23.4 +- 1.9
  (293 days)

46950110
4.5 +- 2.4
  (293 days)
4.5 +- 2.4
  (293 days)

46950111
19.2
  (228 days)
19.2
  (228 days)

46950112
46950113
15.0 +- 1.3
  (360 days)
15.0 +- 1.3
  (360 days)

46950114
46950115
4.2 +- 0.1
  (372 days)
4.2 +- 0.1
  (372 days)

Aerobic Aquatic Metabolism
46950116
3.9(183 days)
3.9 (183 days)

46950117
46950118
0.59 +- 0.28
  (98 days)
0.29 +- 0.03
  (112 days)

Anaerobic Aquatic Metabolism
46950119-46950120
0.55+- 0.33
 (245days)
0.25 +- 0.02
 (350 days)
Non-extractable Residues

Soil Photolysis
46950106/
46950107
0.55+- 0.33
 (245days)
0.25 +- 0.02
 (350 days)

Aerobic Soil Metabolism
4695109
38.0 +-1.3
(293days)
38.0 +-1.3
(293days)

46950110
48.9 +-0.6
(293 days)
48.9 +-0.6
(293 days)

46950111
22.9
(228 days)
22.9
(228 days)

46950112
46950113
14.4 +-1.0
(360 days)
14.4 +-1.0
(360 days)

46950114
46950115
18.4 +-1.0
(372 days)
18.4 +-1.0
(372 days)

Aerobic Aquatic Metabolism
46950116
8.7  (183 days)
8.7 (183 days)

46950117
46950118
8.87 +- 3.04
  (112 days)
8.87 +- 3.04
  (112 days)

Anaerobic Aquatic Metabolism
46950119-46950120
8.06+- 1.24
 (302days)
7.11 +- 0.32
 (350 days)
Unidentified Unknowns[4]

Aqueous Photolysis
42245128
20.0 (15days)
6.5  (30 days)

46950104
29.02 +- 2.9 (30days)
29.02 +- 2.9
(30days)

46950105
16.7(15 days)
11.1 (15 days)

Aerobic Soil Metabolism
4695111
0.4
(228 days)
0.4
(228 days)

Aerobic Aquatic Metabolism
46950116
5.5
 (127days)
5.7
 (183day)

46950117-46950118
5.56+- 0.03
(98days)

4.26+- 1.34
(112days)

46950119-46950120
0.77+- 0.23
 (245 day)
<LOQ (350 days)

Anaerobic Aquatic Metabolism
46950119-46950120
5.69+- 0.57
 (302 day)
5.21+- 0.98
 (350 day)
                    MINOR (<10%) TRANSFORMATION PRODUCTS
CGA-205374 [CGA176459]
IUPAC Name: 2-(4-Cyclopropyl-2,4-dioxo-butyl)-succinic acid

 CAS Name: 1-[2-Chloro-4-(4-chlorophenoxy)phenyl]-2-(1H-1,2,4-triazol-1-yl)-ethanone.

CAS Number: 136815-80-0
                                       
                                       
                                       
Aqueous Photolysis
42245128
1.5 (0 day)
< LOQ (30 days)

46950104
1.11+- 0.11
 (14 days)
0.13 +- 0.1
 (30 days)

46950105
NA
NA

Aerobic  Soil Metabolism
46950114-
46950115
2.1 +- 0.4
 (272days)
1.4 +- 0.1
(293 days)

Anaerobic Aquatic Metabolism
46950119-46950120
0.77+- 0.23
 (245 day)
<LOQ (350 days)
M2

Aerobic  Soil Metabolism
46950109
1.5
(28days)
1.4 +- 0.1
(293 days)

46950110
2.1+- 1.81
(293days)
2.1+- 1.81
(293days)

46950111
1.5
(228days)
1.5
(228days)

Anaerobic Aquatic Metabolism
46950119-46950120
5.79+- 1.42
 (245 days)
< LOQ (350 days)
M4

Aerobic  Soil Metabolism
46950109
1.2
(190days)
1.0 +- 0.4
(293 days)
 [1] =  Stable
 [2] = Not Analyzed
 [3] = Limit of Quantitation
 [4] Unidentified unknowns may consists of M4, M5, M6, M7 and several other unidentified components with no zone exceeding 5.68% of applied radioactivity.

References:

      US EPA, 2011.  Ecological Risk Assessment for the Proposed New Uses of Difenoconazole as a Foliar Spray for Carrot, Chickpea, Soybean, Stone Fruit (Group 12), and Strawberry and as a Seed Treatment for Oat and Rye
. 	February 22, 2011. (378927+)

      US EPA, 2006.  1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid:  Drinking Water Assessment in Support of Reregistration and Registration Actions for Triazole-derivative Fungicide Compounds. February 28, 2006. (D320682)