### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C

. 20460



### Date: Jan uary 3 1

, 20 13

MEMORANDUM OFFICE OF

CHEMICAL SAFETY AND
POLLUTION PREVENTION



### SUBJECT: Tebuconazole: Human Health Ri s k Assessment for Tolerance Increases Based

on Submission of Condition of Registration Requirements for Barley and Cantaloupe; and Crop Group Expansion for Fruiting Vegetable Crop Group 8-10.

PC Code: 128997

Decision No.: 464543

Petition No.: 2E8012

Risk Assessment Type : Single Chemical/ Aggregate

TXRNo.: NA

MRIDNo.: NA DP Barcode : D402457 Registration No.: 264-752, 264-748

Re gulatory Action: Tolerance Reassessment

CaseNo.: NA

CAS No.: 107534-96-3

40 CFR: §180.474

FROM: Barry O'Keefe, Sen ior Biologist

# IJ~ 

# 0 

# :J/.4

Meheret Negussie, Chemist 

# ffi:J!y 0 '/(**~** 

### Whang Phang, Senior Toxicologist**frt:;'~** 

### Risk Assessment Branch III 

## F (X



### Health Effec ts Division (7509P)

THROUGH : JeffDawson, Acting Branch Chief

Risk Assessment Branch III

Health Effec t s Division (7509P)

TO: Sidney Jack son, RM Team 05

Introduction Risk In tegration

, Minor Use and Emergency Response Branch Registration Division (7505P)

The Interregional Research Project No. 4 (IR-4) submitted additional field trial data (for barley

and cucurbits) as required to satisfy pre v ious conditions of registration. The IR-4 also requested

an expansion of the established tolerance for the fruiting vegetables, group 8. The Regis trat ion

Division (RD) reques ted that the HED evaluate toxico logy and residue chemistry data and

conduct dietary and aggregate exposure and risk assessments, as needed, to estimate the risk to

human health resulting from the changes i n tol era nces. Since no new uses, or changes to existing

Page 1 

### of39

### uses, are being proposed by these actions

, the tebuconazole use pattern is unchanged. Therefore

,

new occupational and residential risk assessments are not needed. HED ha s however, conducted

new dietary and aggregate risk assessments to reflect the changes in tolerances.

A summary of the findings and an assessm e nt of human risk resulting from these changes in

tolerances of tebuconazole are provided in this document. The ri sk assessment was provided by Barry O'Keefe, the hazard characterization by Whang Phang, the residue chemistry data review

and the dietary assessment by Meheret Negussie. The drinking water assessment was provided by William Eckel of the Environmental Fate and Effects Division (EFED).

Page 2 of39

### Page 3 of 39 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ .......... 5

2.0 Regulatory Conclusions and Recommendations

................................ ............................ 8

2.1 Data Deficiencies/Conditions of Registration

................................ ..................... 8

2.2 Tolerance Considerations

................................ ................................ ..................... 8

2.2.1 Enforcement method

................................ ................................ ................ 8

2.2.2 International Harmonization

................................ ................................ ... 8

2.2.3 Recommended Tolerances

................................ ................................ ........ 9

2.2.4 Revisions to Petitioned

- For Tolerances

................................ ................ 10

2.3 Label Modifications

................................ ................................ ............................ 10

3.0 Ingr edient Profile

................................ ................................ ................................ ............ 10

3.1 Summary of Proposed Uses

................................ ................................ ................ 10

3.2 Structure and Nomenclature

................................ ................................ ............. 10

3.3 Physical and Chemical Properties

................................ ................................ ..... 10

3.4 Anticipated Exposure Pathways

................................ ................................ ........ 10

3.5 Consideration of Environmental Justice

................................ .......................... 11

4.0 Hazard Characterization/Assessment

................................ ................................ ........... 11

4.1 Toxicology Studies Available for Analysis

................................ ........................ 11

4.2 Summary of Toxicological Effects (including ADME and Absorption)

........ 11

4.3 Safety Factor for Infants and Children (FQPA Safety Factor)

...................... 13

4.3.1 Completeness of Toxicology Database

................................ .................. 13

4.3.2 Evidence of Neurotoxicity

................................ ................................ ...... 13

4.3.3 Evidence of Sensitivity/Susceptibility in the Developing or Young

Animal

................................ ................................ ................................ .................. 13

4.3.4 Residual Uncertainty in the Exposure Database

................................ .. 14

4.4 Toxicity Endpoint and Point of Departure Selections

................................ ..... 14

4.4.1 Dose

- Response Assessment

................................ ................................ .... 16

4.4.2 Recommendation for Combining Routes of Exposures for Risk

Assessment

................................ ................................ ................................ ........... 16

4.4.3 Cancer Classification and Risk Assessment Recommendation

.......... 17

5.0 Dietary Exposure/Risk Characterization

................................ ................................ ..... 17

5.1 Pesticide Metabolism and Environmental Degradation

................................ .. 17

5.1.1 Metabolism in Primary and Rotational Crops

................................ ..... 17

5.1.2 Metabolism in Livestock

................................ ................................ ......... 17

5.1.3 Drinking Water Residue Profile

................................ ............................ 18

5.1.4 Food Residue Profile

................................ ................................ ............... 19

5.2 Di etary Exposure and Risk

................................ ................................ ................ 21

5.2.1 Acute Dietary Exposure/Risk

................................ ................................ . 22

5.2.2 Chronic Dietary Exposure/Risk

................................ ............................. 23

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

............................ 24

6.1 Residential Handler Exposure/Risk Characterization

................................ .... 25

6.2 Residential Post

- Application Exposure and Risk Characterization

.............. 25

6.3 Other (Spray Drift, etc. )

................................ ................................ ..................... 26

7.0 Aggregate Risk Assessments and Risk Characterization

................................ ............ 27

7.1 Acute & Chronic Aggregate Risk

................................ ................................ ...... 27

7.2 Short

- Term Aggregate Risks

................................ ................................ ............. 27

### Page 4 of 39

8. 0 Cumulative Risk Characterization/Assessment

................................ ........................... 29

9.0 References

................................ ................................ ................................ ........................ 30 Appendix A: Toxicology Assessment

................................ ................................ ....................... 32 Appendix B: EPA Review of Human Research

................................ ................................ ...... 37 Appendix C: Structure, Nomenclature, and Physical and Chemical Properties

................. 38 Appendix D: International Residue Limit Status

................................ ................................ ... 39

### Page 5 of 39

1.0 Executive Summary

Tebuconazole is a triazole fungicide currently registered for disease control on a variety of fruit and field crops. The triazoles act by inhibiting C14

- d e methylase, an enzyme which plays a role in sterol production in fungi.

This document evaluates requests from IR

- 4 and Bayer CropScience (Bayer) to

The IR

- 4

, on behalf of the Agricultural Experiment Stations of California, Idaho, Oklahoma, Oregon, South Carolina, Tennessee, Texas and Washington 

### previously submitted a request for amended registration of the 3.6 lb ai/gal suspension concentrate (SC) ( EPA Reg. No. 264

- 752;

Folicur 3.6 F ® 

### ) to add uses on cucurbit vegetables; and tolerances were proposed under PP#

9E3045. The submitted data were evaluated by HED 1 

### . Field trials were conducted on the Crop Group 9 representative crops: squash (summer), cucumbers, and cantaloupe. As a conditi on of registration, HED required a dditional crop field trial data on melons ( two trials in Region 10, one trial each in Region 2 and in Region 5, with a pre

- harvest interval (PHI) of 3 days, or two additional field trials in Region 10, with a revised label specifying a PHI of 6 days )

.

Currently, the IR

- 4 request s amending the established tolerances for the residues of the fungicide tebuconazole on cucurbit vegetables from 0.09 ppm to 0.4 pm, on barley grain from 0.15 ppm to 0.3 ppm, and expanding the fru iting vegetables, group 8 to fruiting vegetables, group 8

- 10.



### Bayer CropScience ( Bayer ) previously submitted a request for amended registration of the 3.6 lb ai/gal SC ( EPA Reg. No. 264

- 752; Folicur 3.6 F ® 

### ) to add use on barley; tolerances were proposed u nder PP# 7F4895

. The submitted data were evaluated by HED 2 

### . Additional crop field trial data were required for barley grain, hay, and straw from regions 10 and 11, accompanied by concurrent storage stability data on barley straw.

IR

- 4 has now submitte d three crop field trials on barley in the United States ( US ) encompassing North American Free Trade Agreement (NAFTA) Growing Zones 10 and 11during the 2009 and 2010 growing season and two field trials 

### on melons conducted during the 2009 growing season in California (EPA region 10) conducted at PHI of 6

- 7 days.



### Toxicity/Hazard

The toxicological database for tebuconazole is essentially complete with the exception of an immunotoxicity study, which is currently under review

. A preliminary evaluation shows no concerns, i.e., the results of the immunotoxicity study will not alter the values of the points of departure (POD) currently selected for risk assessment. With repeated dosing, the main target organs are the liver, the

adr enals, the hematopoetic system and the nervous system. Effects on these target organs were seen in

both rodent and non

- rodent species. In addition, ocular lesions are seen in dogs (including lenticular

1 Tebuconazole. IR

- 4 Request for Tolerances on Cuc urbits. Summary of Analytical Chemistry and Residue Data. Petition Number #9E6048. DP258559, G. Otakie, 7/20/06.

2 Tebuconazole on Barley Comm odities. Summary of Analytical Chemistry and Residue Data. DP344178, S.
Hummel, 4/10/08.

### Page 6 of 39

degeneration and increased cataract formation) follo wing subchronic or chronic exposure

. The toxicological effects of tebuconazole are consistent with those of other triazole

- derivative chemicals. In particular, developmental toxicity and hepatocellular tumors are effects common to a number of these pesti cides. R eliable data show that it would be safe for infants and children to red uce the Food Quality Protection Act ( FQPA ) safety factor to 3 x for all potential exposure scenarios

. The level of concern ( LOC ) for residential risk is for margins of exposure (MOEs) less than 300, based on the uncertainty factors of 10x for interspecies extrapolation, 10x for intraspecies variation, and a 3x uncertainty factor to account for LOAEL to NOAEL extrapolation.

Tebuconazole is considered a “possible human carcinog en , Group C .” For the purpose of carcinogenic risk assessment, the chronic risk assessment is considered protective of any cancer effects; therefore, a separate quantitative cancer risk assessment is not required.

Tebuconazole has low acute toxicity by the oral and dermal route s of exposure (Toxicity Category III), and moderate toxicity by the inhala tion route (Toxicity Category II). It is not a

dermal sensitizer

, n or a dermal irritant; however, it is slightly

, to mildly irritating to the eye.

Drinking Water

Since new uses, or changes to existing uses, are not being proposed by these actions, the

e stimated drinking water concentrations (EDWCs) from the latest dr inking water assessment conducted by the Environmental Fate and Effects Division ( E FED) were used and incorporated directly into the acute and chronic dietary assessments. The EDWCs are based on the maximum application rates specified on the existing label s . The surface water model estimates resulted in the highest acute EDWC of 96.6 μg/L from the existing use on turf ; however

, a 30

- year distribution of daily surface water concentrations based on this turf use was incorporated into the acute dietary assessment . The highest ch ronic EDWC of 59 μg/L

, from the existing use on

commercial ornamentals

, was incorporated into the chronic dietary assessment . The assessment was performed using Tier II (PRZM/EXAMS) modeling for surface water and Tier I (SCI

GROW) for ground water.

Dieta ry Exposure (food and drinking water)

Refined acute and chronic dietary (food and drinking water) exposure analyses were performed for tebuconazole. The analyses indicate that acute and chronic dietary exposure to tebuconazole from food and drinking wate r are below HED’s LOC. Combined acute dietary exposure from food and drinking water at the 99.9 th 

### percentile of exposure is estimated to be 0.009 5 mg/kg/day for the general U.S. population, equivalent to 33% of the acute population adjusted dose (aPAD). The population subgroup with the highest estimated acute dietary exposure to tebuconazole is

children 1

- 2 years old , with an estimated exposure at the 99.9 th 

### percentile of 0.01 6 mg/kg/day, equivalent to 55 % of the aPAD. Chronic dietary exposure estimates for food and drinking water

are below HED’s LOC for all population subgroups. The chronic dietary exposure from food and drinking water is estimat ed at 0.0026 mg/kg/day for the general U.S. population ( 9 % of the chronic population adjusted dose (cPAD)) and 0.004 2 mg/kg/day (1 4 % of the cPAD) for

children 1

- 2 years old , the population subgroup with the highest estimated dietary exposure to

tebuconazol e.

### Page 7 of 39

Dietary Assessment of Free Triazole and its Conjugates

Tebuconazole is among the group of pesticides which generate the common triazole metabolites 1,2,4

- triazole (T), triazolylalanine ( triazole alanine; TA), triazolylacetic acid ( triazole acetic acid ; TAA), and triazolylpyruvic acid (TP). These triazole residues have been evaluated for the entire class of triazole compounds. In connection with the pending tolerance increases for barley , grain and vegetable, cucurbits

, group 9 , HED has reviewed the previous triazole dietary assessments to

include the se changes to tebuconazole. HED has determined that dietary risk (food and drinking water) remains unchanged and below HED’s LOC

. There are no dietary exposure considerations

for the common triazole met abolites that would preclude granting the tolerance increase requests.

Residential Exposure

No new residential uses are being requested at this time. However, a dults, adolescents and children may be exposed to tebuconazole from its currently registered use s on turf

, ornamentals

and treated wood surfaces

.

Aggregate Risk

The dietary route (food and water) alone is relevant to assess acute and long

- term aggregate exposure to tebuconazole; therefore, the dietary exposure and risk assessment s described above

eval u ate aggregate exposure for these durations. However , there are residential uses of

tebuconazole that result in short

- term exposure that should be considered with background dietary exposure. The aggregate assessment result s in MOE s that do not exceed the LOC of an

MOE of 300 or less , and ranged from 3 1 0 to 1,5 00.

Updated Aggregate Assessment of Free Triazole & its Conjugates

HED has completed an updated aggregate human health risk assessment for 1,2,4

- triazole and the conjugated tr iazole metabolites (TA, TAA and TP). 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 components and, therefore, are equivalent to the dietary risk estimates. For short

- and

intermediate

- term aggregate scenarios, the revised aggregate estimates are below HED’s level of

concern.

Occupational Exposure and Risk

This document present s the risk assessment of the proposed tolerance increases of tebuconazole

on cucurbits and barley . Occupational exposure from tebuconazole application to cucurbits and barley ha s been previously assessed. No new occupational uses are being requested at this time.

### Page 8 of 39

Environmental Justice Considerations

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment. Dietary and non

- dietary exposures were considered.

Review of H

uman Rese arch

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies (listed in Appendix B ) have been determined to require a review of their ethical conduct, and have received that review.

2.0 Regulatory Conclusions and Recommendations

HED has reviewed the new cucurbits and barley residue field trials for tebuconazole. HED

concurs with the IR

- 4’s proposal that the barley, grain tolerance be raised to 0.3 ppm and the vegetable

, cucurbit, group 9 tolerance be raised to 0.4 ppm. Additionally, HED concurs that the tolerance on vegetabl e , fruiting, group 8 be expanded to vegetable, fruiting, gro up 8

- 10.

The specific tolerance recommendations are discussed in Section 2.2.

2.1 Data Deficiencies/Conditions of Registration

There are no outstanding data deficiencies or conditions of registr ation that would preclude the establishment of the tolerance changes outlined in this document.

2.2 Tolerance Considerations

2.2.1 Enforcement method

The data collection and enforcement method s for tebuconazole w ere previously discussed (D373948, B. O’Keefe, 12/28/09). A gas chromatography/Nitrogen Phosphorus Detector (GC/NPD) enforcement method for dete rmin ing tebuconazole residues is available and adequate (Method 101341).

2.2.2 International Harmonization

The US and Canadian tolerance expressions for plants and livestock are in harmony ; w hereas

, the US and Codex tolerance expressions are in harmony for plants only. The Codex tolerance expression for livestock commodities includes parent only. Residue definition in the US includes parent and the metabolite; therefo re
, harmonization of tolerances/ MRLs ( maximum residue limits) for livestock commodities is not possible.

Codex MRLs have been proposed for residues of tebuconazole in/on barley grain at 2 ppm and barley straw and fodder, dry at 4 0 ppm. The US tolerances at 0.3 ppm for barley grain and at 3.5 ppm for barley straw are not in harmony. The US tolerances cannot be harmonized with the

### Page 9 of 39

Codex MRL’s since there are significant differences in MRL values. There is a Canadian MRL on barley grain at 0.15 ppm which is also not in harmony with the US.

Codex MRL s are established on cucumber (0.15 ppm), summer squash (0.2 ppm) , melons ( except watermelon ) (0.15 ppm)

, sweet peppers (1 ppm)

, and tomatoes at 0.7 ppm.

Harmonization is an issue for cucurb it vegetables (Crop Group 9) and fruiting vegetables (Crop group 8) since tolerances are established at 0.4 ppm and 1.3 ppm, respectively

. Harmonization

cannot be achieved since Codex MRL s are established on individual crops rather than on crop

group s and have lower MRLs . There are no Canadian tebuconazole MRLs for any cucurbit vegetables and fruiting vegetables

.

An International Residue Limit (IRL) status sheet is appended to this document as Appendix D.

2.2.3 Recommended Tolerances

The existing uses and the submitted data support the following tolerances for residues of

tebuconazole i n/on the following raw agricultural commodities.

Barley, grain

................................ ............................. 0. 3 p pm Barley, hay

................................ ............................... 7

. 0 p pm Barley, straw

................................ ............................ 3.5 p pm Vegetable, cucurbit, group 9

................................ .... 0. 4 p pm Vegetable, fruiting, group 8

- 10

................................ 1

. 3 p pm

Note to RM: The established tolerance on barley grain at 0.15 ppm should be changed to 0.3 ppm and on cucurbit vegetables at 0.09 ppm should be changed to 0.4 ppm in 40 CFR §180.474(a) .

Note to RM: The established tolerance on the vegetable fruiting group 8 at 1.3 ppm can be extended to the vegetable fruiting group 8

- 10 at 1.3 ppm.

Note to RM: In conjunction with the establishment of the vegetable fruiting group 8

- 10 tolerance, the exi sting tolerance for okra needs to be removed from 40 CFR §180.474(a) .

The established and changed tolerances relevant to the current petition are summarized in Table

2.2.3 below.

Table 2.2.3. Tolerance Summary for Tebuconazole

. 

### Crop Commodity Established

Tolerance (ppm) Proposed

Tolerance (ppm) Recommended

Tolerance (ppm) Comments

(Correct Commodity Definition)

Barley, grain 0.15 0.3 0.3 The established tolerance (0.15 ppm) should be increased to 0.3 ppm.

Barley, hay 7.0 7.0 7.0 Adequate residue data are available ; the established tolerance is sufficient.

Barley, straw 3.5 3.5 3.5 Adequate residue data are available;

the established tolerance is sufficient.

### Page 10 of 39

Table 2.2.3. Tolerance Summary for Tebuconazole

. 

### Crop Commodity Established

Tolerance (ppm) Proposed

Tolerance (ppm) Recommended

Tolerance (ppm) Comments

(Correct Commodity Definition)

Vegetable, cucurbit, group 9 0.09 0.4 0.4 The established tolerance (0.09 ppm) should be increased to 0.4 ppm. Vegetable, fruiting, group 8

- 10 1.3 1.3 1.3 Adequate residue data are available;

the established tolerances are

sufficient. Vegetable, fruiting, group 8

- 10 Okra 1.2 None None



### 2.2.4 Revisions to Petitioned

- For Tolerances

HED conclude s that there are no revisions needed to the petitioned for tolerance changes.

2.3 Label Modifications

There are no label modifications needed

.

3.0 Ingredient Profile

3.1 Summary of Proposed Uses

T e IR

- 4 submitted additional field trial data (for barley and cucurbits, respectively) as required to satisfy previous conditions of registration. IR

- 4 also requested an expansion of the established tolerance for the fruiting vegetables, group 8. Therefore, n o new uses, or changes to existing uses, are being proposed by these actions.

3.2 Structure and Nomenclat ure

Structure and nomenclature are reported in Appendix C.

3.3 Physical and Chemical Properties

The physicochemical properties of tebuconazole are reported in Appendix C

.

3.4 Anticipated Exposure Pathways

Humans may be exposed through their diet from applications to agricultural crops . Humans may also be exposed to residues in drinking water, since application s may result in residues reaching surface and ground water sources. There are residential uses of tebuconazole, so exposure to tebuconazole may occur in residential or non

- occupational settings during application and as a result of residues present after application. In an occupational setting, handlers may be exposed while handling the pesticide prior to application, as well as during application. There is also a potential for post

- application exposure for workers re

- entering treated sites.

### Page 11 of 39

Risk assessments have bee n completed for the existing uses of tebuconazole . This risk assessment considers all of the aforementioned exposure pathways based on the proposed changes in tolerances of tebuconazole, but also considers existing uses of tebuconazole, particularly in th e dietary exposure assessment.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://www.eh.doe.gov/oepa/guidance /justice/eo12898.pdf

. As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposure s that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the U.S. Department of Agric ulture’s National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, se ason of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- d ietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently in developme nt as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characteriza tion/Assessment

Tebuconazole is a member of the triazole fungicide g r oup . The triazoles act by inhibiting, C14

- demethylase, an enzyme which plays a role in sterol production in fungi. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Hence, in hi bition of sterol production leads to abnormal fungal growth and eventually death.

4.1 Toxicology Stu dies Available for Analysis

The toxicity studies on tebuconazole are essentially complete ; an immunotoxicity study has been

submitted and is under review. A preliminary evaluation of the immunotoxicity study shows no concerns, i.e., the results will not alter the values of the points of departures currently selected for

risk assessment. Refer to the last HED risk assessment for further details (DP 384949, K. Rury, 5/24/11).

4.2 Summary of Toxicological Effects (including ADME and Absorption)

### Page 12 of 39

The toxicological profile of tebuconazole is presented in the Appendix A. With repeated dosing, the main target organ s are the liver, the adrenals, the hematopoetic system and the nervous system. Effects on these target organs were seen in both rodent and non

- rodent species. In addition, ocular lesions are seen in dogs (including lenticular degeneration and increased c ataract formation) following subchronic or chronic exposure (D256074 & D276447, S

. Winfield,

0 4/18/08).

Oral administration of tebuconazole caused developmental toxicity in all species evaluated (rat, rabbit, and mouse), with the most prominent effects se en in the developing nervous system. In developmental toxicity studies, these effects were manifested as increases in malformations of the nervous system and skull (including exencephaly and acrania, skull bone and vertebral anomalies). Similar types of malformations were seen in all species evaluated. The developmental toxicity studies, including the developmental neurotoxicity study, demonstrate

increase d susceptibility in developing fetuses both quantitatively and qualitatively. In the reproductive t oxicity study, adverse effects on offspring were manifested only as decreased pup body weight. However, prolonged gestation and dystocia, as well as decreased offspring survival (fewer pups born alive, more stillborn pups, and more pup deaths during the f irst week after birth), were seen in the developmental neurotoxicity study.

The results o f the carcinogenicity study in mice showed that tebuconazol e induced an increase in the incidence of hepatocellular adenomas, carcinomas and combined a denomas/carcinomas in

male and female mice. Tebuconazole was classified as a Group C “possible human carcinogen”. Submitted mutagenicity studies did not demonstrate any evidence of mutagenic potential for

tebuconazole.

The toxicological effects of tebuc onazole are consistent with those of other triazole

- derivative chemicals. In particular, developmental toxicity and hepatocellular tumors are effects common to a number of these pesticides. Tebuconazole also shares common metabolites with other

chemicals in this group, including free triazole (1,2,4

- triazole) and triazole

- conjugated plant metabolites (such as triazole alanine). These common metabolites were the subject of a recent risk assessment document ( D380512, B. O’Keefe, 05/24/11) updated to incorp orate new uses of

triazole

- derivative fungicides.

It should be noted that tebuconazole has low acute toxicity by the oral or dermal route of exposure, and moderate toxicity by the inhalation route. It is not a dermal sensitizer or a dermal irritant; however, it is slightly to mildly irritating to the eye

.

Following o ral administration to rats

, tebuconazole was rapidly and extensively absorbed (approximately 98% of the administered dose), metabolized, and eliminated. At 72 hours post

dosing, >94% of the administered radioactivity was recovered. Approx imately 11

- 33% of the

administered dose was eliminated in urine and 61

- 82% was eliminated in the feces. At sacrifice, total radioactivity in the body, excluding the GI tract, amounted to 0.3 to 0.5% of the

administered dose. The data also showed that teb uconazole unde rwent enterohepatic circulation

. Elimination via expired air accounted for 0.03% of the administered dose over a 72

- hour collection period. A total of 10 compounds (metabolites) were identified in the excreta, amounting to 51

- 58% of the adm inistered dose. The parent compound was present in relatively

### Page 13 of 39

small amount (0.5

- 2.2% of the administered dose).

Previously, a dermal absorption factor of 23.1 % was derived from a dermal absorption study in

the monkey

. HED recently re

- examined the data f rom this study and determined the absorption factor appropriate for route

- to

- route extrapolation is 13%, rather than 23.1% ( DP397518 , B. O’Keefe, 4/30/12), and the DER has been updated with a new Executive Summary (DP399045, J. Ryman, 2/23/12).

4.3 Safety F actor for Infants and Children (FQPA Safety Factor)

The RAB3 risk assessment team has determined that reliable data show that it would be safe for

infants and children to red uce the FQPA safety factor to 3X for all potential exposure scenarios. That decision is based on the following findings (Sections 4.4.1 through 4.4.4.) :

4.3.1 Completeness of Toxicology Data b ase

The toxicity dat abase for tebuconazole is considered complete . The registrant has submitted an immunotoxicity study in rats, and the study is currently under review. With preliminary evaluation, tebuconazole tested up to 1000 ppm (78.4 mg/kg/day) produced no immunotoxicity under the conditions of this study.

4.3.2 Evidence of Neurotoxicity

Tebuconazole demonstrated neurotoxicity in the acute neurotoxicity study in rats ; the LOAEL of 100 mg/kg/day was based on increased mot or activity in male and female rats and decreased footsplay in female rats ; however, the subchronic neurotoxicity study was unacceptable due to inadequate dosing. Malformations indicative of nervous system development disruption were seen in developmental toxicity studies in mice, rats, and rabbits. Neurotoxicity was also seen in offspring in the developmental neurotoxicity study in rats the LOAEL of 8.8 mg/kg/day was based on decreases in body weights, decreases in absolute brain weights, changes in brai n morphometric parameters, and decreases in motor activity. A NOAEL could not be established. However, the LOAEL (8

. 8 mg/kg/day) was employed as the point of departure in assessing the risk for all exposure scenarios

, and the FQPA SF is retained as a UF L 

### . A Benchmark Dose (BMD) analys i s of the datasets relevant to the adverse offspring effects (decreased body weight and brain weight) seen at the LOAEL in the DNT study was conducted. All of the BMDLs (benchmark dose limit ) modeled successfully on statist ically significant effects are 1

- 2X lower

than the LOAEL. The results also indicate that an extrapolated NOAEL is not likely to be 10 X

lower than the LOAEL and that use of an UF L 

### of 3 X would not underestimate risk. Therefore, the analysis supports reducing the UF L 

### from 10X to 3X . Using an UF L 

### of 3 X in risk assessment (8.8 mg/kg/day ÷ 3x = 2.9 mg/kg/day) is further supported by other studies in the tebuconazole toxicity database [with the lowest NOAELs being 3 and 2.9 mg/kg/day, from a developmental toxicity study in mice and a chronic toxicity study in dogs, respectively (respective LOAELs 10 and 4.5 mg/kg/day)].

4.3.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

### Page 14 of 39

Although there is qualitative evidence of increased susceptibility in the prenatal developmental studies in rats, the risk assessment team did not identify any residual uncertainties after establishing toxicity endpoints and traditional UFs to be used in t he risk assessment of

tebuconazole. The degree of concern for residual uncertainties for prenatal and/or postnatal toxicity is low.

4.3.4 Residual Uncertainty in the Exposure Database

EPA utilized a tiered approach in estimating exposure to tebuconazole. While some refinements were incorporated into dietary and residential exposure calculations, EPA is confident that the aggregate risk from exposure to tebuconazole in food, water and residential pa thways will not be underestimated. The acute and chronic dietary exposure assessments incorporated refined estimates of residues in food commodities from reliable field trial data reflecting maximum use conditions, recent monitoring data from USDA’s Pesti cide Data Program (PDP), and relevant market survey data on the percentage of crops treated. Estimated concentrations of tebuconazole in drinking water were incorporated into the chronic dietary analysis as the upper bound point estimate and into the prob abilistic acute dietary analysis as a distribution. For the residential exposure pathway (ornamentals, golf course turf, and treated wood products), potential exposure resulting from tebuconazole outdoor uses in the residential setting was assessed using screening

level inputs that assumes an adult or child will come in contact with turf and other surfaces immediately after application.

4.4 Toxicity Endpoint and Point of Departure Selections

At this time, the toxicity endpoints and points of depart ure previously selected for risk

assessment (D256074 and D276447, S Winfield, 04/18/08) are valid and will be employed for

this risk assessment

. A full discussion of the endpoints selected for risk assessment may be

found in the above referenced risk assessment. The summary of toxicity endpoints and points of departu re are presented in Table 4. 4 .1

.

### Page 15 of 39

Based on the available toxicity database and the Agency's current practices, the inhalation risk

for tebuconazole was assessed using an oral toxicity st udy. The Agency sought expert advice and input on issues related to this route to route extrapolation approach (i.e. the use of oral toxicity studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and

Rodenticide Act Scientific A dvisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the Table 4

. 4 .1

. Summary of Toxicological Doses and Endpoints for Tebuconazole for Use in Dietary and N on

Occupational Human Health Risk Assessments

Exposure/

Scenario Point of Departure Uncertainty/FQPA

Safety Factors RfD, PAD, Level

of Concern for

Risk Assessment Study and Toxicological Effects

Acute Dietary (General Population, including Infants

and Children) LOAEL = 8.8

mg/kg/day

UF = 300 UF A = 10x

UF H =10x FQPA(UF L )= 3x Acute RfD = 0.029 mg/kg/day

aPAD = 0.029 mg/kg/day Developmental Neurotoxicity Study

- Rat.

LOAEL = 8.8 mg/kg/day based on decreases in body weights, absolute brain weights, brain measurements and motor activity in offspring.

Chronic Dietary (All Populations) LOAEL = 8.8

mg/kg/day

UF = 300 UF A = 10x

UF H =10x FQPA(UF L )= 3x Chronic RfD =

0.029 mg/kg/day

cPAD =0.029 mg/kg/day Developmental Neurotoxicity Study

- Rat.

LOAEL = 8.8 mg/kg/day based on decreases in body weights, absolute brain weights, brain measurements and motor activity in offspring.

Incidental Oral

Short

- Term (1

- 30 days) LOAEL = 8.8

mg/kg/day

UF = 300 UF A = 10x

UF H =10x FQPA(UF L )= 3x Residential LOC

for MOE = 300 Developmental Neurotoxicity Study

- Rat.

LOAEL = 8.8 mg/kg/day based on decreases in body weights, absolute brain weights, brain measurements and motor activity in offspring.

Dermal Short

- Term (1

- 30 days) LOAEL = 8.8

mg/kg/day

UF = 300 UF A = 10x

UF H =10x

UF L = 3x

DAF = 1 3% Residential LOC

for MOE = 300 Developmental Neurotoxicity Study

- Rat.

LOAEL = 8.8 mg/kg/day based on decreases in body weights, absolute brain weights, brain measurements and motor activity in offspring.

Inhalation Short

Term (1

- 30 days) LOAEL = 8.8

mg/kg/day

UF = 300 UF A = 10x

UF H =10x

UF L = 3x Residential LOC

for MOE = 300 Developmental Neurotoxicity Study

- Rat.

LOAEL = 8.8 mg/kg/day based on decreases in body weights, absolute brain weights, brain

measurements and motor activity in offspring.

Cancer (oral, dermal, inhalation) Classification: Group C

- possible human carcinogen based on statistically significant increase in the incidence of

hepatocellular adenoma, carcinoma, and combined adenoma/carcinomas in both s exes of NMRI mice. The chronic risk assessment is considered to be protective of any cancer effects; therefore, a separate quantitative cancer risk assessment is not required.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no ob served adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = referenc e dose.

MOE = margin of exposure. LOC = level of concern. N/A = not applicable. DAF = dermal absorption factor.

### Page 16 of 39

process of evaluating the SAP report and may, as appropriate, re

- exa mine and develop new policies and procedures for conducting inhalation risk assessments, including route to route extrapolation of toxicity data. If any new policies or procedures are developed, the Agency may revisit the need for an inhalation toxicity s tudy for tebuconazole and/or a re

- examination of the inhalation toxicity risk assessment.

4.4.1 Dose

- Response Assessment

Some of the data relevant to this section have been discussed in Section 4.4.2, but they are essential details for this section as well. The repetition helps to emphasize that reducing the FQPA safety factor in the form of a UF L 

### from 10X to 3X is protectiv e of all the adverse effects demonstrated in the tebuconazole toxicity database.

The tebuconazole risk assessment team selected the most sensitive and protective endpoints from the tebuconazole database (from the rat developmental neurotoxicity study) to employ in the risk assessment for acute and chronic dietary exposure scenarios and for relevant occupational and residential exposure scenarios following dermal, incidental oral and inhalation exposures. In this developmental neurotoxicity (DNT) study, t he maternal NOAEL was 22.0 mg/kg/day and the LOAEL was 65 mg/kg/day based on decreased body weights, body weight gains, and food consumption, prolonged gestation with mortality ; and an increased number of dead fetuses. T he offspring LOAEL was 8.8 mg/kg/day (the lowest dose tested) based on decreases in body weights, decreases in absolute brain weights, changes in brain morphometric parameters, and decreases in motor activity. An offspring NOAEL was no t established. BMD analyses were

conducted usi ng the critical datasets of the developmental neurotoxicity (DNT) study with tebuconazole (TXR# 0054776). The analyses do not provide a new POD for risk assessments. It does, however, provide scientific support for reducing the default 10 X Uncertainty Fa ctor applied to a LOAEL when a NOAEL is not identified in the critical study used in risk

assessments. All of the BMD Ls modeled successfully on statistically significant effects are 1

- 2 X

lower than the established LOAEL. The results indicate that an extr apolated NOAEL is not likely to be 10 X lower than the LOAEL and that use of an Uncertainty Factor of 3 X would not

under estimate risk. Using an UF L 

### of 3 X would yield a POD of 2.9 mg/kg/day (8.8 mg/kg/day ÷

3 X = 2.9 mg/kg/day) which is further supported by the NOAELs established in other studies in the tebuconazole toxicity database [ i.e. , 3 and 2.9 mg/kg/day, from a developmental toxicity study in mice and a chronic toxicity study in dogs, respectively (respective LOAELs 10 and 4.5 mg/kg/day)].

4.4.2 Recommendat ion for Combining Routes of Exposures for Risk Assessment

As per FQPA, 1996, when there are potential residential exposures to a pesticide, aggregate risk

assessment must consider exposures from three major sources: oral, dermal and inhalation exposures. The toxicity endpoints selected for short

- , intermediate

- and long

- term risk

assessments are identical; the oral, dermal

, and inhalation exposures can be combined due to t he presence of a commo n toxicity endpoint

.

### Page 17 of 39

4.4.3 Cancer Classification and Risk Assessment Recommendation

The Carcinogenicity Peer Review Committee concluded that tebuconazole should b e classified as a Group C

- possible human carcinogen (TXR No. 0052724). This conclusion was based on

results of a 91

- week carcinogenicity study in NMRI mice (MRID 42175001, 42469301) in which the following effects were observed: 1) a statistically signi ficant increase in the incidence of hepatocellular adenomas, carcinomas and combined adenomas/carcinomas in male mice both by positive trend and pairwise comparison at the highest dose tested (279 mg/kg/day); and 2) a statistically significant increase in the incidence of hepatocellular carcinomas and combined adenomas/carcinomas in female mice both by positive trend and pairwise comparison at the highest dose tested (366 mg/kg/day). The structural relationship of tebuconazole to at least six

other triazol e fungicides that also produce hepatocellular tumors in male and/or female mice supported the Committee's conclusion. These compounds include triadimefon, triadimenol, uniconazole, propiconazole, cyproconazole and etaconazole. For the purpose of carcinog enic risk assessment, t he chronic risk assessment is considered to be protective of any cancer effects; therefore, a separate quantitative cancer risk assessment is not required.

5.0 Dietary Exposure/Risk Characterization

5.1 Pesticide Metabolism and Environmental Degradation

5.1.1 Metabolism in Primary and Rotational Crops

No new metabolism data were submitted with the subject petition. Adequate plant metabolism studies are available reflecting the metabolism of [ 14 

### C] tebuconazole in grapes and [U

14 

### C

triazole] tebuconazole in wheat and peanuts. The residue of concern in p lants for tolerance and

risk assessment is tebuconazole

. Refer to the last HED risk assessment for further details (DP384949, K. Rury, 5/24/11).

5.1.2 Metabolism in Livestock

The nature of tebuconazole residues in livestock is adequately understood based on acceptable goat and poultry metabolism studies. The residues of concern in livestock commodities for the tolerance expression include both tebuconazole and free and conjuga ted t

- butylhydroxy tebuconazole (HWG

- 2061). In addition to tebuconazole and free and conjugated t

- butylhydroxy

tebuconazole , triazole degradates may occur in livestock from the use of tebuconazole and other triazole pesticides . Exposure to these degradat es was assessed independently as part of the triazole aggregate risk assessment, and therefore, need not be included as a residue of concern for risk assessment or tolerance expression in the tebuconazole risk assessment.

### Page 18 of 39

5.1.3 Drinking Water Residue Profil e

The tebuconazole risk assessment team determined that the residue of concern in drinking water for this single chemical risk assessment is tebuconazole

. The EDWCs for tebuconazole were calculated for ground and surface drinking water using the Tier II (PRZM/EXAMS) surface water modeling and Tier I (SCI

- GROW) ground water modeling based on the proposed

maximum use rates of tebuconazole on turf and ornamentals ( D P 385878, W. Eckel, 05/10/11 )

. The drinking wate r models and their descriptions are available at the EPA internet site: http://www.epa.gov/oppefed1/models/water/

. Surface water EDWCs were used in the dietary assessment, since they were higher than those for ground water. For the human health risk assessment, the highest relevant EDWCs are recommended. Water residues were incorporated in the Dietary Exposure Evaluation Model (DEEM

- FCID) into the food categories “water, direct,

all sources” and “wa ter, indirect, all sources.”

Triazole degradates ( 1,2,4

- triazole and triazole conjugates ) may occur in drinking water from the use of tebuconazole and other triazole pesticides; thus, HED has conducted aggregate human

health risk assessments for these deg radates ( D P403618

, T. Morton, 0 8 / 01 /1 2 )

. The requested

increases in tebuconazole tolerances did not result in an increase in dietary exposure ; therefore

, the last dietary exposure analyses of the triazole metabolites have not changed.

Drinking Water Residues Used in the Dietary Assessment:

The entire 30

- year distribution of estimated daily surface water concentrations based on tebuconazole being aerially applied to FL turf was used probabilistically for the acute assessment. For chronic dietary expo sure assessment

, the 1 in 10 yr annual mean (chr onic)

concentration of 59 μg/L was used, which was based on tebuconazole being aerially applied to

commercial ornamentals.

Table 5.1.3 .1 provides a summary of the estimated concentrations of tebuconazole in surface

water.

Table 5.1.3.1. Estimated Drinking Water Concentrations (EDWCs) R esulting from A pplications of Tebuconazole

Scenario Application Type/Annual Fungicide Application Rate (kg ai/ha) 1 in 10 yr annual peak (μg/L) 1 in 10 yr annual

mean (μg/L) 30 yr annual mean (μg/L)

FL Turf Aerially applied

1.65 x 3 = 4.95 96.6 a 51.4 33.7

Commercial

Ornamentals simulated

with PA T urf Aerially applied

0.56 x 8 = 4.48 77.4 59.0 46.2

PA A pples Airblast

0.25 x 6 = 1.50 27.4 16.6 10.9

Bold values denote maximum Estimated Drinking Water Concentrations (EDWCs)

a: A 30

- year distribution of daily surface water concentrations was used in the acute assessment

### Page 19 of 39

Drinking Water Data for Free Triazoles

Residues of 1,2,4

- triazole in drinking water were provided to HED by the Environmental Fate and Effects Division (D P 320682, I. Maher, 02/ 28 / 06). EFED stated in electronic communication (F. Khan, 04/07/2011) that registered tebuconazole uses are covered by the previous drinking water assessment for 1,2,4

- triazole.

Due to the inter

- conversion between 1,2,4

- triazole, triazole alanine, and triazole acetic acid that may occur in the environment, the residue estimates used in these assessments are a summation

o f all three residues and, therefore, represent an overestimate of actual concentrations of the common triazole metabolites in drinking water. The Tier II PRZM/EXAMS (surface water) and SCIGROW (ground water) residue estimates are summarized in Table 5.1.3.2 . HED notes that there were no detects of 1,2,4

- triazole in any of the 271 water samples analyzed by PDP, with a limit of quantification of 730 parts

- per

- trillion (0.73 ppb). The surface water estimates are significantly greater than those for gro und water, and were used in the assessments for free triazole as well as the conjugated metabolites.

Table 5.1.3.2

. Summary of Estimated Drinking Water Concentrations of 1,2,4

- Triazole. Exposure Duration Surface Water Concentration, ppm Ground W ater Concentration, ppm

Acute 0.041 0.001

Chronic 0.011 0.001



### 5.1.4 Food Residue Profile

Residues of Concern

The nature of the residue in plants and livestock is adequately understood. HED has concluded that the residue of concern in plants is tebuconazole per se for both regulatory and risk assessment purposes ( D P 186731 , G. Otakie, 02/19/93 ). The residues of concern in animal commodities include tebuconazole and free and conjugated t

- butylhydroxy tebuconazole, HWG

2061 (D P 170444 , G. Otakie, 02/19/93 ).

Crop Field Trials

Crop Field Trial Data in Support of Proposed Increase in Tolerance s

F ield trial data were submitted to support the uses of tebuconazole on cantaloupe (MRID 48778702) and barley (MRID 48778701) , including concurrent storage stability data on barley

straw. Analysis of residues of 1, 2,4

- triazole and its conjugates were also included in the

submissions.

The field trial data are adequate and support the existing use patterns. Samples were analyze d for residues of tebuconazole using adequate analytical methods, and the sample storage conditions and intervals from these field trials are supported by the available storage stability

data.

### Page 20 of 39

The submitted data for barley (hay, grain, and straw) and cant aloupe in conjunction with the data that were previously submitted under DP344178 and DP258559, respectively

, are sufficient

. T he previously established tolerances of 7.0 ppm on barley hay and 3.5 ppm on barley straw will

not be exceeded

. Based on all av ailable data, and using the Organization for Economic Cooperation and Development ( OECD ) statistical calculation procedure s
, tolera nce adjustment is required for barley grain and cucurbit vegetables. The proposed tolerances of 0.3 ppm for barley grain a nd 0.4 ppm for cucurbit vegetables are adequate. HED recommends increasing the US

tolerance s to reflect this determination.

Cantaloupe

The results from the submitted field trials are summarized in Table 5.1.4. 1

. These data adequately satisfy the deficiencies previously identified.

Table 5

. 1 4 1. Summary of Residue Data from Cantaloupe Field Trials with T ebuconazole

. Commodity Analyte Total

Rate (lb ai/A) PHI

(days) Residue Levels (ppm) 1

n Sample

Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std

. Dev.

Cantaloupe Tebuconazole 0.684

- 0.695 6

- 7 2 0.05 0.24 0.06 0.20 0.13 0.13 0.10

Tebuconazole (all available data) 6 <0.01 0.24 0.06 0.20 0.04 0.06 0.07

T 2 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

TA 2 0.04 0.09 0.04 0.09 0.07 0.07 0.04

TAA 2 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Comb. TA+TAA 2 <0.05 <0.10 <0.05 <0.10 0.08 0.08 0.04

1 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.01 ppm for all analytes) was used for any results reported as <LOQ. N/A = Not applicable.

2 LAFT = lowest

- average

- field

- trial; HAFT = highest

- a verage

- f ield

- t rial.



### Barley

The results from the submitted field trials are discussed below and summarized in Table 5.1.4. 2

. These data adequately satisfy the deficiencies previously identified.

Table 5

. 1.4.2. Summary of Residue Data from Barley Field Trials with T ebuconazole

. Commodity Analyte Total

Rate (lb ai/A) PHI

(days) Residue Levels (ppm) 1

n Sample

Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std

. Dev.

Barley hay Tebuconazole 0.1088

- 0.1147 7

- 11 3 0.390 3.68 0.452 3.31 1.07 1.61 1.50

T 3 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

TA 3 <0.07 <0.07 <0.07 <0.07 0.07 0.07 N/A

TAA 3 <0.04 0.047 <0.04 <0.043 0.040 0.041 0.002

Comb. TA+TAA 3 <0.11 <0.117 <0.11 <0.113 0.110 0.111 0.002

Barley

Grain Tebuconazole 0.1088

- 0.1147 29

- 31 3 0.067 0.280 0.068 0.247 0.106 0.140 0.094

### Page 21 of 39

Table 5

. 1.4.2. Summary of Residue Data from Barley Field Trials with T ebuconazole

. Commodity Analyte Total

Rate (lb ai/A) PHI

(days) Residue Levels (ppm) 1

n Sample

Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std

. Dev.

Tebuconazole (all available data) 20 0.01 0.280 0.01 0.247 0.023 0.044 0.056

T 3 <0.01 <0.01 <0.01 < 0.01 0.01 0.01 N/A

TA 3 <0.03 0.059 <0.03 0.057 0.035 0.041 0.015

TAA 3 <0.01 0.015 <0.01 0.014 0.010 0.011 0.003

Comb. TA+TAA 3 <0.04 0.073 <0.04 0.072 0.045 0.052 0.017

Barley

S traw Tebuconazole 0.1088

- 0.1147 29

- 31 3 0.113 1.24 0.467 1.01 0.611 0.696 0.281

T 3 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

TA 3 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

TAA 3 <0.01 0.019 <0.01 0.017 0.013 0.013 0.004

Comb. TA+TAA 3 <0.02 <0.029 <0.02 <0.027 0.023 0.023 0.004

1 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ s w ere used for any results reported as < LOQ. LOQs were 0.01 ppm for tebuconazole and T in hay, grain, and straw, for TA in straw, and for TAA in grain and straw; 0.07 and 0.03 ppm for TA in hay and grain; 0.04 ppm for TAA in hay; and 0.11, 0.04, and 0.02 ppm, respectively for TA + TAA in hay, grain, and straw . N/A = Not applicable.

2 LAFT = lowest

- avera ge

- field

- trial; HAFT = highest

- average

- field

- trial.



### Fruiting Vegetables Crop Group 8

Tolerances have been established for tebuconazole on fruiting vegetables at 1.3 ppm and on okra at 1.2 ppm

. The available data on fruiting vegetables group 8 and okra are adequate to establish tolerances on fruiting vegetables group 8

- 10. No new residue data are needed for these changes. Therefore, t he established tolerance on the vegetable
, fruiting

, group 8 at 1.3 ppm could be extended to vegetable
, fruiting

, group 8

- 10 at 1.3 ppm

.

Processed Food and Feed

The previously reviewed pepper reduction study and tomato processing studies are adequate ( DP362720, W. Cutchin, 9/14/09)

.

Meat, Milk, Poultry, and Eggs

The livestock feedstuffs associated with this petition are barley grain, hay, and straw; in addition, there are established tolerances for numerous livestock feedstuffs. The additional data for barley hay and grain will not increase the previously estim ated dietary burden (DP287292 etc, S. Hummel, 11/27/06). The existing t olerances for animal commodities do not need to be reassessed for this petition.

5.2 Dietary Exposure and Risk

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments

were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCID) Version 3.16. This software uses 2003

- 2008 food consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health and

### Page 22 of 39

Nutrition Examinatio n Survey, What We Eat in America, (NHANES/WWEIA).

Refined acute probabilistic and chronic dietary exposure assessments were conducted for all existing food uses of tebuconazole

. For both the acute and chronic dietary analyses, the

exposure assessment inc orporated the same input parameters used in the previous assessment ( DP384950, C. Walls, 05/31/2011)

. Please refer to this document for detailed information of the

assessment. The only change s made to the previous dietary assessment are in the acute

anti cipated residues from field trial data ( in the residue distribution file; RDF) for cantaloupe, the average residue input on cantaloupe for chronic assessment, and input s for gojiberry and tomato tree for crop group expansion. No changes were made to barle y residues since PDP data were used for acute and chronic dietary assessments.

Livestock commodities:

The livestock feedstuffs associated with this petition are barley grain, hay, and straw; in addition,

there are established tolerances for numerous livestock feedstuffs. The additional data for barley hay and grain will not increase the previously estimated dietary burden

. Based on these calculations, the existing tolerances for meat and milk remain adequate, while tolerances in poultry and eggs are still not required ( D 384787 , L. Cheng, 04/01/11)

.

5.2.1 Acute Dietary Exposure/Risk

The estimated acute dietary exposure to tebuconazole from food and drinking water at the 99.9 th


### percentile of exposure is estimat ed to be 0.009 5 mg/kg/day for the general U.S. population, equivalent to 33% of the acute Population Adjusted Dose (aPAD). The population subgroup with the highest estimated acute dietary exposure to tebuconazole is children 1

- 2 years, with an

estimated e xposure at the 99.9 th 

### percentile of 0.016 mg/kg/day, equivalent to 55% of the aPAD.

Table 5.2.1. Results of Acute Dietary (Food + Drinking Water) Exposure Analysis Using DEEM

- FCID

. Population Subgroup aPAD

(mg/kg/day) 95 th Percentile 99th Percentile 99.9 th Percentile

Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD

General U.S. Population

0.029 0.003007 10 0.004957 17 0.009549 33

All Infants

(< 1 year old) 0.005564 19 0.008649 30 0.013549 47

Children 1

- 2 years old 0.004914 17 0.008155 28 0.015881 55

Children 3

- 5 years old 0.004294 15 0.007114 24 0.014256 49

Children 6

- 12 years old 0.003219 11 0.005390 19 0.011692 40

### Page 23 of 39

Table 5.2.1. Results of Acute Dietary (Food + Drinking Water) Exposure Analysis Using DEEM

- FCID

. Population Subgroup aPAD

(mg/kg/day) 95 th Percentile 99th Percentile 99.9 th Percentile

Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD Exposure (mg/kg/day) % aPAD

Youth 13

- 19 years old 0.002372 8.2 0.003929 14 0.007612 26

Adults 20

- 49 years old 0.002841 9.8 0.004348 15 0.007862 27

Adults 50+ years old 0.002598 9.0 0.004341 15 0.008363 29

Females 13

- 49 years old 0.002639 9.1 0.004153 14 0.007533 26

Note: The bolded values represent the subgroup with the highest food and water exposure

.



### 5.2.2 Chronic Dietary Exposure/Risk

The chronic dietary exposure estimates for food and drinking water for the general U.S.

p opulation is 0.0026 mg/kg/day

, equivalent to 9.0% of the cPAD. The population subgroup with the highest estimated chronic dietary exposure to tebuconazole is children 1

- 2 years with an estimated exposure of 0.042 mg/kg/day, equivalent to 14% of the cPAD.

Table 5. 2.2. Summary of Chronic Dietary (Food + Drinking Water) Exposure and Risk for Tebuconazole Using DEEM

- FCID

.

Population Subgroup Exposure (mg/kg/day) % cPAD

General U.S. Population 0.002622 9.0

All Infants (< 1 year old) 0.004024 14

Children 1

- 2 years old 0.004200 14

Children 3

- 5 years old 0.003877 13

Children 6

- 12 years old 0.002746 9.5

Youth 13

- 19 years old 0.002046 7.1

Adults 20

- 49 years old 0.002567 8.9

Adults 50+ years old 0.002471 8.5

Note: The bolded values represent the subgroup with the highest food and water exposure.

### Page 24 of 39

5.3 Dietary Assessment of Free Triazole and its Conjugates

Tebuconazole is a triazole fungicide. A separate updated dietary exposure and risk analysis (D P403618

, T

. Morton

, 0 8 / 01 /1 2 ) for the common triazole metabolites 1,2,4

- triazole (T), triazolylalanine (TA), triazolylacetic acid (TAA), and triazolylpyruvic acid (TP) was conducted previously ; the review was associated with a registration request for the triazole fungicide, propic onazole

. The increased tolerances for tebuconazole in/on barley, grain and v egetables, cucurbits, group 9 are not expected to change the risk of exposure to the triazoles.

For all four analyses, risk estimates were below HED ’s LOC for all population subgroups. There are no dietary exposure considerations for the common triazol e metabolites th at would preclude granting the tolerance requests for tebuconazole

.

Table 5.3. Summary of Dietary (Food and Drinking Water) Exposure and Risk for the Common Triazole Metabolites Adding the Amended Use for Propiconazole.

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 0.00 8282 28 0.001 327 2 7

Not Applicable Not

Applicable All Infants (< 1 year old) 0.01 2115 40 0.00 1843 37

Children 1

- 2 years old 0.0 23117 77 0.00 3832 77

Children 3

- 5 years old 0.01 8974 63 0.00 3064 61

Children 6

- 12 years old 0.0 10992 37 0.001 665 3 3

Youth 13

- 19 years old 0.00 7222 24 0.001 085 2 2

Adults 20

- 49 years old 0.00 6609 22 0.00 1137 2 3 Adults 50+ years old 0.00 5820 19 0.00 1073 22

Females 13

- 49 years old 0.00 6747 22 0.00 1110 22 Triazoly lalanine + Triazolylacetic Acid+Triazolylpyruvic acid General U.S. Population

Not Applicable Not

Applicable 0.01 8547 21

Not Applicable Not

Applicable All Infants (< 1 year old) 0.0 21851 2 4

Children 1

- 2 years old 0.0 58600 65

Children 3

- 5 years old 0.0 47124 52

Children 6

- 12 years old 0.0 24837 28

Youth 13

- 19 years old 0.01 5657 17

Adults 20

- 49 years old 0.01 5272 1 7 Adults 50+ years old 0.0 14323 1 6

Females 13

- 49 years old 0.0 79772 80 0.01 4900 1 7 * The values for the highest exposed population for each type of risk assessment are bolded.



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

No new residential uses are being requested at this time. However, a dults, adolescents

, and children may be exposed to tebuconazole from its currently registered use s on turf

, flower gardens, trees, ornamentals, and pressure

- treated wood. Each of these existing residential use patterns has previously been assessed and the resulting exposures and risk estimates did not

exc eed HED’s LOC (see DP346795, B. O’Keefe, 11/27/07 and DP349926, B. O’Keefe,

### Page 25 of 39

3/13/08). Additionally, HED has recently updated the residential standard operating procedures (SOPs; see http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html for specifics) and body weights to be used in all human health assessments. Therefore, all of the existing residential use patterns were reassessed for handler and post

- applicati on exposures to adults and children using the updated procedures and data, since the residential exposures can impact the aggregate assessment for tebuconazole (see DP397518, B. O’Keefe, 4/30/12).

6.1 Residential Handler Exposure/Risk Characterization

Residential h andler exposure is expected to be short

- term

. Intermediate

- term exposures are not likely because of the intermittent nature of applications by homeowners. Dermal and inhalation exposures were combined since the same endpoint and POD is used for both routes of exposure.

Table 6 .1 summarizes the residential handler exposures and risk estimates for tebuconazole. All

combined risk estimates are not of concer n to HED with MOEs ranging from 2

, 8 00 to 91,000.

1 Application rates are based on maximum values found on existing labels.

2 Daily Exposure (mg/kg/day) = (Unit Exposure * % Absorption * Application rate * Amount handled daily) / Body Weight of 6 9

- kg; where dermal absorption is 1 3%. and inhalation absorption is 100%.

3 Short

- /Intermediate

- Term MOE = NOAEL / Daily Exposure. The dermal/inhalation NOAEL is 8.8 mg/kg/day. The LOC is 300.



### 6.2 Residential Post

- A pplication Exposure and Risk Characterization

Adults and children golfing, working in gardens, and performing physical activities on pressure

treated wood after application of tebuconazole may receive exposu re to tebuconazole residues. Exposure is expected to be short

- term in duration. Short

- term dermal and incidental oral

exposure and risk estimate s have been previously assessed and indicate no risk estimates of

concern. Table 6.2 summarizes the residential post

- application exposure and risk estimates for

tebuconazole. Residential dermal post

- application MOEs for all life stages range from 3 40 to 6,200. The residential exposure for 1 to 2 year olds coming in contact with pressure treated wood resulted in a dermal MOE of 460, an oral hand

- to

- mouth MOE of 2,600, and a combined dermal plus oral MOE of 390.

Table 6.2 . Residential Post

- Application Short

- Term Exposure and Risk Estimates for Tebuconazole.

Scenario Formulati on Application

Rate Amount

Treated Activity Exposure Route Daily Dose (mg/kg/day) MOE 1 Table 6.1. Residential Handler Short

- term Exposure and Risk Estimates for Tebuconazole.

Scenario Formulation Equipment/ Application

Method Application

Rate 1 Amount

Treated Exposure

Route Daily Dose

(mg/kg/day) 2 MOE Combined

MOE 3

Residential

Handler for

flower gardens,

trees,
ornamentals Liquid Manually

Pressurized

Handwand 0.0053 lb

ai/gal 5 gal Dermal 0.00314 2,800 2,800 Inhalation 0.00000690 1.3E+6

Hose

- End Sprayer 0.0014 lb

ai/gal 11 gal Dermal 0.00168 5,200 5,200 Inhalation 0.000000312 2.8E+7

Backpack 0.0014 lb

ai/gal 5 gal Dermal 0.00171 5,100 5,100 Inhalation 0.0000142 6.2E+5

Ready To Use (RTU) Liquid Trigger Sprayer 0.0003 lb

ai/bottle 2 bottles Dermal 0.0000961 92,000 91,000 Inhalation 0.000000530 1.7E+7

### Page 26 of 39

Table 6.2 . Residential Post

- Application Short

- Term Exposure and Risk Estimates for Tebuconazole.

Scenario Formulati on Application

Rate Amount

Treated Activity Exposure Route Daily Dose (mg/kg/day) MOE 1

Golf Course

Turf Liquid 1.35 lb ai/A NA Adults Golfing Dermal 0.020 440

Children 11 to <16 yr old Dermal 0.0201 440

Children 6 to <11 yr old Dermal 0.0217 370

Gardens,

Tress &

Ornamentals Liquid 0.27 lb ai/ A 1 can Adults to Gardens Dermal 0.0261 340

Adults to Trees Dermal 0.0024 3700

Children 6 to <11 yr old

to Gardens Dermal 0.0155 570

Children 6 to <11 yr old

to Trees Dermal 0.00143 6200

Pressure

Treated

Wood 1 Liquid 1 μg/cm 2 NA Children 1

- 2 yr old Dermal 0.0191 460

Children 1

- 2 yr old Oral hand

- to

- mouth 0.0034 2600

Children 1

- 2 yr old Oral HTM & Dermal 0.0225 390

1 Wood surface residue adjusted for dermal transfer or “transfer efficiency” (EPA high end assumption of 1 μg/cm 2 ) (DP Barcode 330159, 6/20/06, T. Leighton)

.



### 6.3 Other (Spray Drift, etc. )

Residential Bystander Post

- A pplication Inhalation Exposure Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for tebuconazole at this time because the chemical has low vapor

pressure ( 9.75 x 10 - 9 

### m m Hg (20oC) ) and is not applied via airblast or a ircraft . However, volatilization of pesticides may be a potential source of post

- application inhalation exposure to individuals nearby to pesticide applications. The Agency sought expert advice and input on

issues rel ated to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ) and is in the process of evaluating the SAP report. The Agency may, as appropriate, develop policies and procedures to identify the need for and, subsequently , the way to incorporate post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative post

- application inhalation exposure assessment

for tebu conazole.

Spray Drift Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the g round application method employed for the previously

registered uses of tebuconazole . The Agency has been working with the Spray Drift Task Force, EPA Regional Offices

, and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new data base submitted by the Spray Drift T ask Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for

### Page 27 of 39

pesticides applied by air, orchard airblast

, and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce

off

- target drift and risk estimates associated with aerial as well as other application types where appropriate.

7.0 Aggregate Risk Assessmen ts and Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard ( e.g. , a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure.

7.1 Acute & Chronic Aggregate Risk

Refer to Section 5.2, which discusses acute and chronic dietary (food and drinking water) exposure in detail. The dietary route alone is relevant for acute exposure and risk assessment; and the acute dietary exposure and risk assessment conducted for tebuconazole is a refined, probabilistic assessment. The dietary route alone is also relevant for long

- t erm/chronic exposure and risk assessment; and the chronic dietary exposure and risk assessment conducted for tebuconazole is a refined, deterministic assessment.

7.2 Short

- Term Aggregate Risk s

The short

- term aggregate risk assessments in this document use a deterministic approach, in that point estimates of exposure from each source are added together; and each of the point estimates used are in turn deterministic [dietary exposure estimates use point estimates for food and drinking water residue s (anticipated residues based o n field trial and PDP data, and tolerance level residues) and the residential scenarios also employ point estimates (central to high

- end values considered protective)]. Exp osures are assumed to occur over the same time frame, and no use frequency data is considered. There is the potential for residential exposure to co

- occur with background dietary exposure over the short

- term (1

- 30 days) , whereas co

- occurring

intermediate exposures (1

- 6 months) are less likely. However, since the POD employed for both durations are the same, the aggregate assessments address both exposure durations. Although there are two adult residential exposure scenarios considered in this document, t he likelihood of a residential handler treating ornamentals with tebuconazole and then playing golf on a

tebuconazole

- treated course is considered low; therefore, each scenario is considered separately with background dietary exposure. In sum, these aggre gate risk assessments are considered protective. Aggregate risk estimate s for all examined population subgroups were not of concern to HED, and above the level of concern (LOC = 300).

These aggregate exposure assessments are considered conservative est imates, that should not underestimate risks, for the following reasons : 1) the dietary analysis used refined dietary exposure inputs for its acute and chronic dietary assessments, including crop specific (turf) screening level drinking water modeling data (i.e., surface water model ing ); 2) maximum

### Page 28 of 39

application rates and minimum application intervals were used; and 3) conservative SOPs and upper level estimates of exposure were employed.

Table 7.2 .1

. Short

- Term Aggregate Risk Calculations

Population Residential Scenario Short

- Term Scenarios

LOAEL LOC 1 Max

Allowable Exposure 2
(mg/kg/day) Average Food

& Water Exposure (mg/kg/day) Residential

Exposure 3
(mg/kg/day) Aggregate

MOE 4

( dietary and residential)

Residential Handler

Adult Manually Pressurized

Handwand to gardens, trees, ornamentals 8.8 300 0.029 0.0026 22 0.0 031469 1,500

Residential Post

- Application

Children 11 to <16 yr old Golfer, Turf 8.8 300 0.029 0.00 2046 0.0 201 400

Children 6 to <11 yr old Golfer, Turf 8.8 300 0.029 0.002746 0.0217 360

Adults Gardens 8.8 300 0.029 0.002622 0.0261 310

Children (3

- 5) Activities on pressure

treated wood surfaces 8.8 300 0.029 0.003 877 0.0 225 330

1. The basis for the LOC are the standard inter

- and intra

- species uncertainty factors totaling 100, as well as an additional uncertainty factor for LOAEL to NOAEL extrapolation (UF L = 3X)
2. Maximum allowable exposure (mg/kg/day) = LOAEL / LOC 3. Residential Exposure = [Oral Exposure + Dermal Exposure + Inhalation Exposure]. See Section 6.0 for derivation of residential exposure

assessments. 4. Aggregate MOE = [LOAEL/(Average Food & Water Exposure + Residential Exposure)]



### Updated Aggregate Assessment of Free Triazole & its Conjugates

In 2006, HED issued aggregate human health risk assessments for 1,2,4

- triazole ( T ) and the conjugated triazole metabolites ( DP322215, M. Doherty, et al., 0 2/ 0 7/ 06). In 201 2 , HED reviewed the dietary and residential exposure of T and the triazole metabolites for a petition

associated with propic onazole (D P403619 , T. Morton, 0 8 / 01 /1 2 ). The findings of the

assessment s were that risk estimates for all exposure scenarios were be low HED’s level of concern. 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 in 201 2 are due to chan ges in the dietary exposure estimates. For complete hazard characterization and non

- dietary exposure assessments for the common triazole metabolites, see the 2006 and 201 2 risk assessment s

.

The revised aggregate estimates are summarized below for short

- and intermediate

- term scenarios for T (Tables 7.2.2 and 7.2.3 , 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

### Page 29 of 39

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 ass essment 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 7.2. 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) 0.001327 0.00183 0.0051 N/A N/A N/A 0.008257 3600

All infants (< 1 year) 0.001843 N/A 0.0086 0.0041 0.0010 0.000019 0.015562 1900

Children 1

- 2 yrs 0.003832 N/A 0.0086 0.0041 0.0010 0.000019 0.017551 1700

Children 3

- 5 yrs 0.003064 N/A 0.0086 0.0041 0.0010 0.000019 0.016783 1800

Children 6

- 12 yrs 0.001665 N/A 0.0086 N/A N/A N/A 0.010265 2900

Youth 13

- 19 yrs 0.001085 0.00183 0.0051 N/A N/A N/A 0.008015 3700

Adults 20

- 49 yrs 0.001137 0.00183 0.0051 N/A N/A N/A 0.008067 3700
Adults 50+ yrs 0.001073 0.00183 0.0051 N/A N/A N/A 0.008003 3700

Females 13

- 49 yrs 0.001110 0.00183 0.0051 N/A N/A N/A 0.00804 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 7.2.3. 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) 0.001 327 N/A 0.001 327 1 1 000 All infants (< 1 year) 0.00 1843 0.000019 0.001862 81 00

Children 1

- 2 yrs 0.003832 0.000019 0.003851 39 00

Children 3

- 5 yrs 0.00 3064 0.000019 0.003083 49 00

Children 6

- 12 yrs 0.001 665 N/A 0.001 665 90 00

Youth 13

- 19 yrs 0.001 085 N/A 0.001 085 14 000

Adults 20

- 49 yrs 0.00 1137 N/A 0.00 1137 1 3 000 Adults 50+ yrs 0.00 1073 N/A 0.00 1073 1 4 000

Females 13

- 49 yrs 0.00 1110 N/A 0.00 1110 1 4 000

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.



### 8.0 Cumulative Risk Characterization/Assessment

Tebuconazole is a member of the triazole

- containing class of pesticides. Although conazoles act similarly in plants by inhibiting ergosterol biosynthesis, there is not necessarily a relationship between their pesticidal activity and their mechanism of toxicity in mam mals. Structural similarities do not constitute a common mechanism of toxicity. Evidence is needed to establish that the chemicals operate by the same, or essentially the same, sequence of major biochemical events (EPA, 2002). In conazoles, however, a v ariable pattern of toxicological responses is

found ; s ome are hepatotoxic and hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some induce developmental, reproductive, and neurological effects in rodents. Furthermore, the conazoles produc e a diverse range of biochemical events including altered

### Page 30 of 39

cholesterol levels, stress responses, and altered DNA methylation. It is not clearly understood whether these biochemical events are directly connected to their toxicological outcomes. Thus,

there is currently no evidence to indicate that conazoles share common mechanisms of toxicity and EPA is not following a cumulative risk approach based on a common mechanism of toxicity for the conazoles. For information regarding EPA’s procedures for cumulati ng effects from substances found to have a common mechanism of toxicity, see EPA’s website at http://www.epa.gov/pesticides/cumulative

.

Tebuconazole is a triazole

- derived pesticide. This class of compounds can form the common metabolite 1,2,4

- triazole an d two triazole conjugates ( triazolylalanine and triazolylacetic acid ). To support existing tolerances and to establish new tolerances for triazole

- derivat ive pesticides, including tebuconazole , U.S. EPA conducted a human health risk assessment for exposur e to 1,2,4

- triazole, triazolylalanine, and triazolylacetic acid resulting from the use of all current and pending uses of any triazole

- derived fungicide. The risk assessment is a highly conservative, screening

- level evaluation in terms of hazards associat ed with common metabolites (e.g., use of a maximum combination of uncertainty factors) and potential dietary and non

- dietary exposures (i.e., high end estimates of both dietary and non

- dietary exposures). In addition, the Agency

retained the additional 10 X FQPA safety factor for the protection of infants and children. The assessment includes evaluations of risks for various subgroups, including those comprised of infants and children. The Agency’s complete risk assessment is found in the propiconazole

re registration docket at http://www.regulations.gov , Docket Identification (ID) Number EPA

HQ

- OPP

- 2005

- 0497.

9.0 References

Tebuconazole: Human Health Risk Assessment to support tolerances in/on Asparagus, Barley,
Beans, Beets, Brassica leafy greens, Bulb Vegetables, Coffee (import), Commercial Ornamentals, Corn, Cotton, Cucurbits, Hops, Lychee, Mango, Okra, Pome fruit, Soybean, Stone fruit, Sunflower, Tree Nut Crop Group, Turf, Turnips and Wheat. DP 256074 and DP276447 , S.

Winfi eld, 4/18/08.

Tebuconazole: Human Health Risk Assessment to Harmonize Tolerances of Tebuconazole in/on Oats and Wheat with Canada. DP384949, K.Rury, 5/24/11.

Tebuconazole: Occupational Exposure and Risk Assessment for Proposed Increase in Application Ra te for Golf Course Turf. DP397518, B. O’Keefe, 4/30/12

Tebuconazole. IR

- 4 Request for Tolerances on Cucurbits. Summary of Analytical Chemistry and Residue Data. Petition Number #9E6048. DP258559, G. Otakie, 7/20/06.

Tebuconazole on Barley Commodities. Summary of Analytical Chemistry and Residue Data. DP344178, S. Hummel, 4/10/08.

Tebuconazole. Supplemental Residue Data for Barley and Cantaloupe. Response to Condition of Registration Requirements Specified Under DP #s 258559 and 344178 and Crop Group Expansions to Fruiting Vegetable Crop Group 8

- 10. Summary of Analytical Chemistry and

### Page 31 of 39

Residue Data. M. Negussie, DP402456, 01/31/13.

Tebuconazole. Petition for the Establishment of a Tolerance on Fruiting Vegetables ( Crop Group 8). Summary of Analytical Chemistry and Residue Data. DP362720, W. Cutchin, 9/14/09

Tebuconazole: Acute and Chronic Aggregate Dietary Exposure and Risk Assessments for Condition of Registration Requirements Specified Under DP#s D258559 and D344 178 and Crop Group Expansions to Fruiting Vegetable Crop Group 8

- 10. DP408526, 01/31/13. M. Negussie, DP408526, 01/29/13.

Drinking Water Assessment for Tebuconazole: Fluopyram/Tebuconazole 400 SC Fungicide (EPA Reg. No. 264

- RNOR), DP 385878, W. Eckel

, 05/10/11.

Common Triazole Metabolites: Updated Dietary (Food + Water) Exposure and Risk Assessment to Address The Amended Propiconazole Section 3 Registration to Add Foliar Use on Sugarcane.

T. Morton. DP403618. 8/1/2012.

Common Triazole Metabolit es: Updated Aggregate Human Health Risk Assessment to Address The Amended Propiconazole Section 3 Registration to Add Use on Sugarcane. T. Morton.

DP403619. 8/1/2012.

### Page 32 of 39 

## Appendix A: Toxicology Assessment

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food and non

- food uses for Tebuconazole are in Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protoc ols were used.

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ....................... 870.1200 Acute Dermal Toxicity

................................ .................. 870.1300 Acute Inhalation Toxicity

................................ .............. 870.2400 Primary Eye Irritation

................................ .................... 870.2500 Primary Dermal Irritation

................................ .............. 870.2600 Dermal Sensitization

................................ ...................... yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

................................ ............... 870.3150 Oral Subchronic (nonrodent)

................................ ......... 870.3200 21

- Day Dermal

................................ .............................. 870.3250 90

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

................................ .......................... yes

yes

yes

no

yes yes

yes

yes

no

yes +

870.3700a Developmental Toxicity (rodent)

................................ ... 870.3700b Developmental Toxicity (nonrodent)

............................. 870.3800 Reproduction

................................ ................................ . yes

yes

yes yes

yes

yes

870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Oncogenicity (rat)

................................ .......................... 870.4200b Oncogenicity (mouse)

................................ .................... 870.4300 Chronic/Oncogenicity

................................ .................... no

yes

yes

yes

yes no

yes

yes

yes

yes

870.5100 Mutagenicity

— Gene Mutation

- bacterial

..................... 870.5300 Mutagenicity

— Gene Mutation

- mammalian

................ 870.5xxx Mutagenicity

— Structural Chromosomal Aberrations

... 870.5xxx Mutagenicity

— Other Genotoxic Effects

....................... yes

yes

yes yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen)

................................ ..... 870.6100b 90

- Day Neurotoxicity (hen)

................................ ........... 870.6200a Acute Neurotox. Screening Battery (rat)

....................... 870.6200b 90

- Day Neuro. Screening Battery (rat)

.......................... 870.6300 Develop. Neuro

................................ .............................. no

no

yes

yes

yes -

- yes

yes

yes

870.7485 General Metabolism

................................ ...................... 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity............................................... yes

no

yes yes

yes

yes *

Special Studies for Ocular Effects

Acute Oral (rat)

................................ ........................... Subchronic Oral (rat)

................................ .................. Six

- month Oral (dog)

................................ .................. no

no

no no

no

no

* The study has been received and is currently under review

.
+ An acceptable 21

- day inhalation toxicity study in rats was submitted.



### A.2 Toxicity Profiles

### Page 33 of 39

Table A.2.1 Acute Toxicity Profile

- Tebuconazole

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [rat] 40700917 LD 50 (fasted) = > 5000 mg/kg (M); 3933 mg/kg (F); (unfasted)=4264 mg/kg (M); 3352 mg/kg (F) III

870.1200 Acute dermal [rat] 40700917

41290801 LD 50 = >5000 mg/kg (M & F) III

870.1300 Acute inhalation [rat] 40700922 LC 50 (4 h, aerosol)= >371 mg/m 3

LC 50 (4 h, dust)= >5093 mg/ m 3 II

870.2400 Acute eye irritation [rabbit] 40700925

40700917 Slight to Mild irritant III

870.2500 Acute dermal irritation [rabbit] 40700917

40995910 Non

- irritant IV

870.2600 Skin sensitization

[guinea pig] 40700928

41290802 No evidence of skin sensitization using

the Buehler test NA

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.3100

90

- Day oral toxicity

- r at 40700930 (1986) ( 0, 100, 400, 1600 ppm in diet ) ; 0, 8.6, 34.8, 171.7 mg/kg/d (m) ; 0, 10.8, 46.5, 235.2 mg/kg/d (f) Acceptable/guideline Male: NOAEL = 34.8 mg/kg/d ; LOAEL= 171.7 mg/kg/d

based on decreased body wt., body wt. gain, and histopathology findings. Female: NOAEL=10.8 mg/kg/d, LOAEL= 46.5 mg/kg/d

based on histopathological changes in the adrenal gland

.

870.3150

90

- Day oral toxicity

- dog 40700934 (1987) (0, 200, 1000, 5000 ppm in diet); 0, 73.7, 368.3, 1749.1 mg/kg/d (m); 0, 73.4, 351.8, 1724.8 mg/kg/d (f) Acceptable/guideline NOAEL = 73.4/73.7 mg/kg/d (m/ f)

LOAEL = 368.3/ 351.8 mg/kg/d ( m/ f) based on decrease d body wt. gain , food consumption and increased liver enzyme activities.

870.3200

21 /28

- Day dermal toxicity

- rabbit 40700937 (1984) 0, 50, 250, 1000 mg/kg/day Acceptable/guideline NOAEL = 1000 mg/kg/day. No dermal or systemic toxicity was seen.

870.3465

2 1

- Day inhalation toxicity

- rat 40700938 (1985) 0, 1.2, 10. 6, 155.8 mg/m 3
Acceptable/guideline NOAEL = 10.6 mg/m 3 /d (0.0106 mg/L/day)

LOAEL = 155.8 mg/m 3 /d (0.1558 mg/L/day) based on clinical signs and induction of liver microsomal

enzymes.

870.3700a Prenatal developmental

- rat 40700943 (1988) 0, 30, 60 , 120 mg/kg/d, GD 6

- 15 Acceptable/guideline Maternal NOAEL = 3 0 mg/kg/day LOAEL=60 mg/kg/d based on increased liver wt and liver/body weight ratios. Developmental NOAEL=3 0 mg/kg/day

LOAEL =60 mg/kg/d based on delayed ossification of

several bones and increased numbers of fetuses with supernumerary ribs.

870.3700a Prenatal developmental

- rat (Dermal) 41450801 (1988) 0, 100, 300, 1000 mg/kg/d, GD 6

- 15 Acceptable/guideline Maternal NOAEL= 1000 mg/kg/d Developmental NOAEL= 1000 mg/kg/d No evidence of maternal or developmental toxicity seen

via dermal route.

### Page 34 of 39

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.3700a Prenatal developmental

- mouse 40821501 (1988) 0, 10, 30, 100 mg/kg/d, GD 6

- 15 40821500 (1988) Supplementary study 0, 10, 20, 30, 100 mg/kg/d GD 6

- 15 Acceptable/guideline Maternal NOAEL = 30 mg/kg/d LOAEL = 100 mg/kg/d based on increased hepatic triglycerides, pale lobular liver, increased severity of hepatic vacuoles and lipidosis. Developmental NOAEL = 10 mg/kg/d LOAEL = 30 mg/kg/d bas ed on increased number of

runts.

870.3700a Prenatal developmental

- mouse 43776201, 43776202(1995) 0, 10 , 30, 100 mg/kg/d, GD 6

- 15 Supplementary group 0, 1, 3 mg/kg/d GD 6

- 15 Acceptable/ guideline Maternal : NOAEL = 3 mg/kg/d LOAEL = 10 mg/kg/d based on increased hepatic enzyme induction and severity of vacuolization in liver

cells. Developmental : NOAEL= 3 mg/kg/d LOAEL=10 mg/kg/d based on increased external,

visc eral, and skeletal malformation/variation in the head

and skull.

870.3700a Prenatal developmental

- mouse (Dermal) 42010301 (1990) 0,100,300,1000 mg/kg/d GD 6

- 15 Acceptable/guideline Maternal NOAEL= 1000 mg/kg/d Developmental NOAEL= 1000 mg/kg/d

No evidence of maternal or developmental toxicity seen

via dermal route.

870.3700b Prenatal developmental

- rabbit 40700945 (1987) 0, 10, 30,100 mg/kg/d, GD 6

- 18 Acceptable/ guideline Maternal NOAEL = 30 mg/kg/d LOAEL = 100 mg/kg/d based on decreased body weight gain and food consumption. Developmental NOAEL = 30 mg/kg/d LOAEL = 100 mg/kg/d based on increased resorptions and post

- implantation losses, decreased live fetuses/doe,

and external and skeletal abnormalities

.

870.3700b Prenatal developmental

- rabbit 43776201 (1995) 0, 10, 30, 100 mg/kg/day GD 6

- 18 Acceptable/guideline Maternal NOAEL = Not established (<10 mg/kg/d) LOAEL = 10 mg/kg/d based on increased incidence of single cell necrosis in liver cells. Developmental NOAEL = 1 0 mg/kg/d

LOAEL = 3 0 mg/kg/d based on increased external and

visceral malformation/variations.

870.3800 Reproduction and fertility

effects

- rat 40700946 (1987) 0, 100, 300, 1000 ppm in diet ( equivalent to 0, 5, 15, 50 mg/kg/day ) Acceptable/guideline Parental/Systemic NOA EL = 15 mg/kg/day (m & f) LOAEL = 50 mg/kg/day based on increased severity of splenic hemosiderosis (m & f), increa sed incidence of splenic hematopoiesis (m), and decreased weight gain during gestation (f) Reproductive NOAEL = 50 mg/kg/day

LOAEL = not determined Offspring NOAEL = 15 mg/kg/day LOAEL = 50 mg/kg/day based on decreased pup body

wt.

870.4300

Chronic/ carcinogenicity

- rat 40700939 , 40816401 (1988) 0, 100, 300, 1000 ppm in diet; M: 0, 5.2, 15.9, 55 mg/kg/d; F: 0, 7.4, 22.8, 86.3 mg/kg/d Acceptable /guideline Males: NOAEL = 15.9 mg/kg/d; LOAEL=55 mg/kg/day based on decreased testes weight.

Females: NOAEL= 7.4 mg/kg/d ; LOAEL=22.8 mg/kg/day based on decreased body wt. & wt. gain, decreased erythrocyte parameters and increased incidence of splenic hemosiderosis (incr eased erythrocyte clearance). No evidence of carcinogenicity at the doses tested.

### Page 35 of 39

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.4100b Chronic toxicity

- dog 40700940 (1987) 0, 40, 200, 1000/2000 ppm in diet ; 0, 15.5, 77.3, 483 mg/ kg/ d Acceptable/guideline NOAEL = 15.5 mg/ kg/ d ay LOAEL = 77.3 mg /kg /d ay based on ocular lesions and changes in erythrocyte morphology (anisocytosis)

870.4100b Chronic toxicity

- dog 42030601 (main) (1989) & 42537201 (suppl.) (1992); 0, 100, 150 ppm; M: 0, 2.96, 4.39 mg/kg/d F: 0, 2.94, 4.45 mg/kg/d

A cceptable/guideline together with

40700940 NOAEL = 2.96 mg/kg/day (m), 2.94 mg/kg/d (f )

LOAEL = 4.39 mg/kg/day (m), 4.45 mg/kg/d (f) based

on lesions in the adrenal gland

.

870.4200b Carcinogenicity

- mouse 40700941 (1988) 0, 20, 60, 180 ppm in diet; M: 0, 5.9, 18.2, 53.1 mg/kg/d F: 0, 9.0, 26.1, 80.5 mg/kg/d

42175001 0, 500, 1500 ppm M: 0, 84.9, 279 mg/kg/day F: 0, 103.1, 365.5 mg/kg/day Acceptable/guideline M ale mice had statistically significant, dose

- related increasing trends in hepatocellular adenomas,

carcinomas and c ombined adenomas and/or carcinomas. There were also statistically significant differences in the pair

- wise comparisons of the controls with the 1500 ppm dose group for hepatocellular adenomas (29% vs. 5% controls), hepatocellular carcinomas (21% vs. 0%

con trols) and combined adenomas and/or carcinomas (47% vs. 5% controls).

870.5100 Salmonella point mutation 40700947 & 40700948 (1988) Acceptable/guideline Negative with or without activation at doses ranging from 39.5 to 450 μg/plate

870.5300

CHO

- HGPRT forward

mutation 40700949 (1988) Unacceptable/guideline Negative with or without activation at concentrations ranging from 12.5

- 200 and 80

- 100 μg/mL, respectively; highest concentration tested did not produce high level of cytotoxicity

.

870.5375

In vitro Cytogenetics (human lymphocytes) 40700953 (1988) Acceptable with activation; Unacceptable without activation Negative for chromosome aberrations with activation (30

- 300 μg/mL) and without activation (10

- 300 μg/mL); highest dose not cytotoxic without activation

.

870.5395 Mammalian erythrocyte

micronucleus 40700951 (1985) Acceptable/guideline Negative at all doses up to 2000 mg/kg bw

870.5450 Mouse dominant lethality 40700950 (1986) Unacceptable/guideline Negative at 2000 mg/kg bw (only dose tested) during 12 serial mating periods; positive control was not included

870.5500 DNA damage and repair ( E.coli) 40700955 (1983) Unacceptable/guideline Negative with or without activation at concentrations ranging from 625

- 10,000 μg/plate); no growth inhibition

zone detected

870.5550

Unscheduled DNA synthesis (rat hepatocytes) 40816402 (1988) Acceptable/guideline No evidence of an increase in unscheduled DNA synthesis at 0.504

- 25.2 μg/mL

870.5900 Sister chromatid exchange (CHO cells in vitro ) 40700952 (1987) Acceptable/guideline Negative with and without activation with S9 at concentrations ranging from 4

- 30 μg/mL and 15

- 120 μg/mL, respectively.

870.6200a

Acute neurotoxicity screening battery

- rat 44449301, 44545701 (1997)

0, 21, 50, 103, 497, 950 mg/kg

Unacceptable/Guideline

(Upgradeable) NOAEL = 50 mg/kg/day

LOAEL = 100 mg/kg/day based on increased motor activity in males and females and decreased footsplay in

females.

### Page 36 of 39

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.6200b

Subchronic neurotoxicity screening battery

- rat 44588001 (1998)

0, 100, 400, or 1600 ppm

M: 0.00, 7.57, 29.2, 107 mg/kg/day F: 0.00, 8.81, 34.0, 122 mg/kg/day

Unacceptable/Guideline

(Not upgradeable) NOAEL = 107 mg/kg/day

LOAEL = Not determined [>107 mg/kg/day]

870.6300

Developmental neurotoxicity

- rat 45074301 (2000)

0, 100, 300, 1000 ppm

[GD/LD 0/0, 8.8/16.3, 22/41.3, 65/125.4 to dams], GD6 to LD11

Acceptable/Guideline Maternal NOAEL = 22 mg/kg/day LOAEL = 65 mg/kg/day based on decreased body weight, body weight gain, and food consumption; prolonged g estation with mortality, increased number of

dead fetuses. Offspring NOAEL = <8.8 mg/kg/day

LOAEL = 8.8 mg/kg/day based on decreased body weight, decreased absolute brain weights and brain measurements, and decreased motor activity.

870.7485

Metabolism

- rat 40995911, 40995912 (1987)

Acceptable/guideline 98.1% of oral dose is absorbed. Over 87% of dose excreted in urine & feces within 72 hours after dosing. At sacrificed (72 hrs postdosing) total residue (minus GI tract) amounted to 0.63% of the dose. A total of 10 compounds were identified in excreta. A large fraction of the identified metabolites corresponded to successive oxidation steps of a methyl group of tebuconazole. At higher dose 920 mg/kg) changes in detoxification patterns may result from meta bolic saturation.

870.7600

Dermal penetration

- monkey 46634901 (2003)

132 μg/cm 2 tebuconazole in Folicur EW250, single 8 hr administration

A cceptable/non guideline Estimated dermal absorption 23.1%. (including the

fraction of the dose absorbed and the amount of dose remaining in the skin after washing).

Literature study: Developmental neurotoxicity /immunotoxicity 45486901 (2001), 45591701 (2002), 46146701 (2003)

0, 6, 20, 60 mg/kg (gavage) GD14

- PND7 to dams, PND7

- 42 to offspring Study evaluated reproductive, immuno

- , and neurotoxicity in offspring. Identified one effect of concern: learning deficits in high dose offspring, evaluated starting on PND74. Neuropathological effects identified in the original study were retracted based on a patholog y peer

- review.

### Page 37 of 39

Appendix B: EPA Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies (which compose PHED, listed below) were determined to require a review of their ethical conduct, have received that

review and have been determined to be ethical.

Data from the Outdoor Residential Exposure Task Force (ORETF).

H ED Residential Standard Operating Procedures (2012).

### Page 38 of 39

Appendix C: Structure, Nomenclature, and Physical and Chemical Properties

Table C. 1. Tebuconazole Nomenclature

. Chemical structure

Common name Tebuconazole

Company experimental name HWG 1608

IUPAC name ( RS )

- 1

- p

- C hlorophenyl

- 4,4

- dimethyl

- 3

- (1 H

- 1,2,4

- triazol

- 1

- ylmethyl)pentan

- 3

- ol

CAS name α

- [2

- (4

- C hlorophenyl)ethyl]

- α

- (1,1

- dimethylethyl)

- 1 H

- 1,2,4

- triazole

- 1

- ethanol

CAS registry number 107534

- 96

- 3

End

- use product (EP) Folicur 3.6 F Foliar Fun gicide (EPA File Symbol 264

- 752 )

Chemical structure of

t

- butylhydroxy

- tebuconazole ; HWG 2061

1

- (4

- C hlorophenyl)

- 4,4

- dimethyl

- 3

- (1 H

- 1,2,4

- triazole

- 1

- yl

- methyl)

- pe n tane

- 3,5

- diol

Table C. 2. Physicochemical Properties of Tebuconazole

. Parameter Value Reference

Melting point/range 104.7 °C PP#9F3724/9F3818, 5/9/91,

G. Otakie pH Not soluble enough

Specific gravity (20 oC) 1.202 g/mL

Water solubility (20 °C) 32 mg/L

Solvent solubility (g/L at 20oC) n

- hexane 2

- 5

dichloromethane >200

2

- propanol 100

- 200

toluene 50

- 100

Vapor pressure 1.3 x 10 - 3 mPa (20 oC)

3.1 x 10 - 3 mPa (25 oC)

Dissociation constant, pK

a does not dissociate

Octanol/water partition coefficient, Log(K OW ) 3.7 at 20 oC

UV/visible absorption spectrum Not available

### Page 39 of 39

Appendix D : International Residue Limit Status



## Tebuconazole (PC Code; 01/04 /2012)

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 2 

### Codex 3

40 CFR 180.474:

Plant: (1) tebuconazole [α

- [2

- (4

- chlorophenyl) ethyl]

- α

- (1,1

- dimethylethyl)

- 1H

- 1,2,4

- triazole

- 1

- ethanol]

Livestock: sum of tebuconazole (alpha

- [2

- (4

- chlorophenyl)ethyl]

- alpha

- (1,1

- dimethylethyl)

- 1 H

- 1,2,4

- triazole

- 1

- ethanol) and its diol metabolite (1

- (4

- chlorophenyl)

- 4,4

- dimethyl

- 3

- (1 H

- 1,2,4

- triazole

- 1

- yl

- methyl)

- pentane

- 3,5

- diol), calculated as the

stoic hiometric equivalent of

tebucon a zole Plants: (+)

- α

- [2

- (4

- chlorophenyl)ethyl]

- α

- (1,1

- dimethylethyl)

- 1 H

1,2,4

- triazole

- 1

- ethanol

Livestock: (±)

- α

- [2

- (4

- chlorophenyl)ethyl]

- α

- (1,1

- dimethylethyl)

- 1H

1,2,4

- triazole

- 1

- ethanol, including the metabolite

5

- (4

- chlo rophenyl)

- 2,2

- dimethyl

- 3

- (1H

- 1,2,4

- triazol

- 1

- ylmethyl)

- 1,3

- pentanediol Tebuconazole

The residue is fat

soluble.



### Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 

### Codex 3

Barley, grain 0.3 0.15 barley 2 barley Barley, hay 7.0 Barley, straw 3.5 40 barley straw and fodder, dry

Vegetable, cucurbit, group 9 0.4 0.15 cucumber; melons, except watermelon 0.2 summer squash

Vegetable, fruiting, group 8

- 10, except okra 1.3 0.1 eggplant

0.7 tomato 10 peppers chili, dried 1 peppers, sweet (including pimento or pimiento) Completed: M. Negussie; 01/07/2013

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fa t) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.