**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

> WASHINGTON, D.C. 20460![](media/image1.wmf){width="0.85in"
> height="0.925in"}
>
> OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: April 18, 2008

**[MEMORANDUM]{.underline}**

SUBJECT: *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.

  ---------------- ---------------------------- ------------------ --------------------
  **PC Code:**                                  **Registration     
  128997                                        No.:** 264-749,    
                                                264-752, 432-RUUU  

  **Regulatory                                  **MRID No.:** NA   
  Action:**                                                        
  Section 3                                                        
  Registrations,                                                   
  Tolerance                                                        
  Petition                                                         

  **Assessment                                  **Reregistration   
  Type:** Single                                Case No.:** NA     
  chemical                                                         
  aggregate                                                        

  **TXR No.:** NA                               **CAS No.:**       
                                                107534-96-3        

  **Case No.:** NA                              **40 CFR:**        
                                                180.474            

  **Petition       **DP Barcodes**: D256074,    **Petition Nos**:  **DP Barcodes**:
  Nos**:           D276447                                         D311536, D318247

  6F4668           D280899, D315967             0E6091             D262583, D315478

  7F4895           D313984, D315482, D332173,   0E6103             D263669, D315471
                   D315481, D332531, D318338,                      
                   D290263, D273238, D281343,                      
                   D281797                                         

  0F6086           D311602                      0E6117             D265115

  0F6129           D311592                      0E6153             D265745, D315467

  1F6289           D311619                      0E6158             D271514, D271687

  9E6045           D258383, D315749             0E6212             D271507, D271688

  9E6046           D258552, D315751             4F6854             D308967

  4E6842           D308836                      6E7036             D327031

  9E6048           D258559, D315752             6E7097             D332260
  ---------------- ---------------------------- ------------------ --------------------

+-------------------------------------+--------------------------------+
| FROM: Sarah Winfield, Biologist     | Sheila Piper, Chemist          |
|                                     |                                |
| Barry O'Keefe, Biologist            | Susan Stanton, Environmental   |
|                                     | Scientist                      |
| Registration Action Branch 3        |                                |
|                                     | Risk Integration, Minor Use    |
| and                                 | and Emergency Response         |
|                                     | (RIMUER) Branch                |
| Susan Hummel, Chemist               |                                |
|                                     | Registration Division (7505P)  |
| Reregistration Branch 4             |                                |
|                                     | and                            |
| and                                 |                                |
|                                     | Iwona Maher, Drinking Water    |
| Yung Yang, Toxicologist             |                                |
|                                     | Environmental Risk Branch 1    |
| Monica Hawkins, Environmental       |                                |
| Scientist                           | Environmental Fate and Effects |
|                                     | Division (7507P)               |
| Toxicology and Epidemiology Branch  |                                |
|                                     |                                |
| > Health Effects Division (7509P)   |                                |
+-------------------------------------+--------------------------------+
| THROUGH: Paula Deschamp, Branch     |                                |
| Chief                               |                                |
|                                     |                                |
| Registration Action Branch 3        |                                |
|                                     |                                |
| > and                               |                                |
|                                     |                                |
| Margarita Collantes and Jess        |                                |
| Rowland, Designated Reviewers       |                                |
|                                     |                                |
| > Risk Assessment Review Committee  |                                |
|                                     |                                |
| Health Effects Division (7509P)     |                                |
+-------------------------------------+--------------------------------+
| TO: Cynthia Giles-Parker, Mary      |                                |
| Waller and Robert Westin, Fungicide |                                |
| Branch                              |                                |
|                                     |                                |
| Barbara Madden, RIMUER Branch       |                                |
|                                     |                                |
| Tracy Keigwin, TRB                  |                                |
|                                     |                                |
| Registration Division (7505P)       |                                |
|                                     |                                |
| CC: Mark Hartman, Regulatory        |                                |
| Management Branch 2                 |                                |
|                                     |                                |
| Antimicrobials Division (7510P)     |                                |
+-------------------------------------+--------------------------------+

**Introduction**

**Note to RD**: This document addresses aggregate risk for all currently
proposed tolerances and existing and proposed non-food residential uses;
however, it only supports new registrations for wheat, barley, and tree
nuts. Occupational risk assessments for all other use sites will be
provided in a separate document (D315464).

The fungicidal active ingredient (ai) tebuconazole was first registered
in 1983, and is currently registered for use in/on: food use-sites
\[bananas, barley (seed treatment), cherries, grapes, grasses (grown for
seed), nectarines, oats (seed treatment), peaches, peanuts, plantain,
triticale (seed treatment), wheat (seed treatment)\], residential
use-sites \[on residential ornamentals, as a paint preservative, and
in/on wood (construction, flakeboard, particleboard, aquatic structures,
doors, fence posts, frames, jambs, joints, millwork, poles/posts,
pressure treatment, products, siding, sills, surfaces, windows)\], as
well as in adhesives, coatings, glues, lumber, metalwork cutting fluids,
paper/paperboard, particleboard, plastics, plywood, polymers,
polyurethane, styrene and vinyl. Although registered as a paint
preservative (*i.e.*, for use to prevent mildew formation on newly
painted surfaces), due to identified risk issues, this use has been
voluntarily cancelled. Therefore, residential paint use is not
considered in this document (and is addressed in a separate document*,*
D346795, Barry O'Keefe, 11/26/07).

Furthermore, there have been Section 18 emergency exemptions for use of
tebuconazole on: asparagus (MI 2001, 2003), barley (CA 1997 and 1998;
MN, ND, SD 2003), garlic (CA 2003), irrigation supply systems (water
treatment, FL 1998), leatherleaf fern (FL 1998), sunflower (CO, ND 1997;
NE 2001; KS, CO 2003), and wheat (LA, MS, AR, MN, ND 1997; TX, MI, ID
1998; OR 1999; ND, MI, SD 2003).

Currently, there are a number of pending tolerance petitions (including
import tolerances) and proposed new uses that both Bayer CropScience
(Bayer) and the USDA Inter-Regional Project Number 4 (IR-4) have
submitted to the Agency. In the early 2000s, the review of these actions
was delayed due to uncertainty surrounding the risk posed by the common
metabolites/degradates of the triazole fungicides. In 2006 the Agency
addressed this issue in a separate HED document (D322215, Michael
Doherty, 2/7/06; this assessment is updated in D350315, Michael Doherty,
3/27/08, to incorporate new uses of triazole-derivative fungicides).

The sites and tolerances with no U.S. registration (import tolerances)
for which Bayer and/or IR-4 have proposed new uses/tolerances on are:
asparagus (domestic use and import), barley, beans, beets, *Brassica*
leafy greens, bulb vegetables, coffee (import), commercial ornamentals,
corn, cotton, cucurbits, garlic (import), hops, lychee, mango, okra,
onions (import), pome fruit, soybean, stone fruit, sunflower, tree nut
crop group, turf, turnips and wheat. Associated with these proposed uses
are the formulations ELITE® 45 DF (a 45% ai dry flowable; EPA Reg. No.
264-749), FOLICUR® 3.6 F (a 3.76 lb ai/gal flowable concentrate; EPA
Reg. No. 264-752) and Lynx® 2 (another liquid formulation with a
concentration of 2 lb ai/gal; EPA Reg. No. 432-RUUU).

Subsequently, Bayer is proposing tolerances for tebuconazole on the
following crop groups and/or commodities (includes revised tolerance
proposals dated August 21, 2006):

> Stone fruits (group 12) 1.0 ppm
>
> Pome fruits (group 11) 0.05 ppm
>
> Soybean, seed 0.06 ppm
>
> Soybean, hay 45.0 ppm
>
> Soybean, forage 17.0 ppm
>
> Soybean, hulls 0.06 ppm
>
> Grain, aspirated fractions 15.0 ppm
>
> Bean, succulent 0.1 ppm
>
> Bean seed 0.1 ppm
>
> Cotton undelinted seed 2.0 ppm
>
> Cotton gin byproducts 16.0 ppm
>
> Corn field, grain 0.01 ppm
>
> Corn field, forage 3.0 ppm
>
> Corn field, stover 3.0 ppm
>
> Corn pop, grain 0.01 ppm
>
> Corn pop, stover 3.0 ppm
>
> Corn sweet, K+CWHR 0.5 ppm
>
> Corn sweet, forage 6.0 ppm
>
> Corn sweet, stover 5.0 ppm
>
> Hop, dry cone\* 30.0 ppm
>
> Wheat forage 3.0 ppm
>
> Wheat hay 6.0 ppm
>
> Wheat straw 1.4 ppm
>
> Barley hay 6.0 ppm
>
> Barley straw 1.4 ppm
>
> Tree nut crop group (Group 14) including pistachios 0.05 ppm
>
> Almond hulls 6.0 ppm
>
> Asparagus (stems)\* 0.01 ppm
>
> Coffee, bean, green\* 0.1 ppm
>
> Coffee, bean, roasted\* 0.2 ppm
>
> Garlic (bulb)\* 0.2 ppm
>
> Onion (bulb)\* 0.1 ppm

\*proposed tolerance with no U.S. registration (import tolerance)

In the petition for use on corn, Bayer also proposed the following
tolerances for inadvertent residues of tebuconazole in soybeans planted
in rotation with treated wheat. However, since these tolerances were
proposed, Bayer has proposed the above tolerances on soybeans reflecting
the direct application of tebuconazole to soybeans. Once these
tolerances (listed above) are established tolerances for inadvertent
residues in soybeans (listed below) will be unnecessary.

> Soybean, seed (rotational crop) 0.01 ppm
>
> Soybean, forage (rotational crop) 0.01 ppm
>
> Soybean, hay (rotational crop) 0.05 ppm

IR-4 is proposing tolerances for tebuconazole on the following
commodities okra, mango, lychee, sunflower, turnips, cucurbits, domestic
asparagus, and hops (domestic):

> Asparagus (domestic use) 0.02 ppm
>
> Mango, post-harvest treatment 0.2 ppm
>
> Lychee 1.5 ppm
>
> Okra 1.0 ppm
>
> Plum, post-harvest treatment 1.0 ppm
>
> Sunflower, seed 0.05 ppm
>
> Sunflower, meal 0.2 ppm
>
> Sunflower, refined oil 0.2 ppm
>
> Turnip tops 8 ppm
>
> Turnip roots 0.4 ppm
>
> Cucurbit vegetables (Crop Group 9) 0.1 ppm
>
> Hops (domestic use) 5.0 ppm

The tolerance proposal for hops, domestically grown, in Petition No.
4E6046, will be superseded by the proposal for hops, dry cone (based on
data for imported hops) in Petition No. 4E6842, since the proposed
import tolerance is higher. Additionally, Petition No. 6E7036 supersedes
Petition No. 0E6091 \[import tolerances on asparagus (and also coffee,
garlic and onion) since the proposed domestic tolerance is higher.

IR-4 is also proposing the following permanent tolerances in Petition
No. 6E7097 for tebuconazole:

> Vegetable, bulb, group 3 1.3 ppm
>
> *Brassica*, leafy greens, subgroup 5B 2.5 ppm
>
> Beet, garden, root 0.70 ppm
>
> Beet, garden, leaves 5.0 ppm

Petition No. 6E7097 supersedes Petition No. 0E6091 \[import tolerances
on garlic and onion (and also on asparagus and coffee)\] since the
proposed tolerances are for the crop group.

These proposed uses and tolerances result in new dietary exposures as,
as well as new occupational and residential exposures. This Health
Effects Division (HED) document addresses the exposures and risks
expected from the new use patterns/tolerances and incorporates currently
registered residential uses that are considered in the aggregate
assessment. Occupational exposure and risk resulting from Petition No.
7F4895 (tree nuts, wheat and barley) are addressed in this document. All
other occupational exposures and risks associated with the proposed uses
outlined in this document are addressed in a separate document (D315464,
Barry O'Keefe).

Pending the resolution of issues associated with the 1,2,4-triazole and
conjugated triazole metabolites aggregate assessment (Section 10.4), the
submission of a revised Section B (label modifications -- see Section
10.2 and 10.3 of this document), the submission of conditional data
requirements concerning the data on barley, field corn forage, pears,
melons, turnip tops and mustard greens (see Section 10.2), the
submission of a revised Section F (see below), and resolution of
recommendations/issues identified in D315464 by Barry O'Keefe, there are
no residue chemistry, toxicology, and/or exposure issues that would
preclude granting permanent tolerances and conditional registrations for
the requested uses of tebuconazole on the crops, crop groups and/or use
sites addressed in this document. Registration should be made
conditional pending adequate resolution of the data gaps listed in
Section 10.0.

The proposed uses and the submitted data support the following
tolerances for residues of tebuconazole *per se* in/on the following raw
agricultural and processed commodities:

  -------------------------------------------------------------------------------
  **Crop Commodity**        **Recommended   **Crop Commodity**    **Recommended
                            Tolerance                             Tolerance
                            (ppm)**                               (ppm)**
  ------------------------- --------------- --------------------- ---------------
  Almond, hulls             6.0             Fruit, pome, group 11 0.05

  Apple, wet pomace         0.1             Fruit, stone, group   1.0
                                            12, except cherry     

  Asparagus                 0.05            Grain, aspirated      16.0
                                            fractions             

  Barley, grain             0.05            Hop, dry cone         35

  Barley, hay               7.0             Lychee                1.6

  Barley, straw             1.5             Mango                 0.15

  Bean, succulent           0.1             Nut, tree, group 14   0.05

  Bean, dry                 0.1             Okra                  1.2

  Beet, garden, root        0.70            Onion, bulb, subgroup 0.2
                                            3-07A                 

  Beet, garden, leaves      7.0             Onion, green,         1.3
                                            subgroup 3-07B        

  *Brassica*, leafy greens, 2.5             Soybean, forage       25.0
  subgroup 5B                                                     

  Cherry                    5.0             Soybean, hay          50.0

  Coffee, bean, green       0.15\*          Soybean, seed         0.08

  Coffee, bean, roasted     0.3\*           Sunflower, seed       0.05

  Corn, field, grain        0.05            Sunflower, meal       0.2

  Corn, field, forage       4.0             Sunflower, refined    0.2
                                            oil                   

  Corn, field, stover       3.5             Turnip, tops          7.0

  Corn, pop, grain          0.05            Turnip, roots         0.5

  Corn, pop, stover         3.5             Vegetable, cucurbit   0.09
                                            group 09              

  Corn, sweet, K+CWHR       0.5             Wheat, forage         3.0

  Corn, sweet, forage       7.0             Wheat, grain          0.05

  Corn, sweet, stover       6.0             Wheat, hay            7.0

  Cotton, undelinted seed   2.0             Wheat, straw          1.5

  Cotton, gin byproducts    25.0                                  
  -------------------------------------------------------------------------------

\* Import tolerances

This HED document provides a summary of the findings from the data
evaluation and subsequent assessment of human health risk resulting from
this submission. The hazard assessment and characterization was
conducted by Kathleen Raffaele and Yung Yang; the occupational and
residential exposure data review and assessment were conducted by Barry
O'Keefe; the residue chemistry data was reviewed and analyzed by Susan
Hummel, Jerry Stokes, Gary Otakie, Linda Kutney, Yan Donovan and Leung
Cheng; Susan Stanton and Sheila Piper conducted the dietary exposure
assessments; Monica Hawkins and Hans Allender prepared the Incidents
Report; and the human health risk assessment was conducted by Sarah
Winfield (RAB3); additionally, the drinking water assessment was
conducted by Iwona Maher of OPP's Environmental Fate and Effects
Division (EFED).

**Table of Contents**

**1.0** **Executive Summary** [9](#__RefHeading___Toc196283098)

**2.0** **Ingredient Profile** [15](#__RefHeading___Toc196283099)

2.1 Summary of Registered/Proposed Uses
[15](#__RefHeading___Toc196283100)

2.1.1 Residential Proposed/Registered Uses
[16](#__RefHeading___Toc196283101)

2.1.2 Occupational Proposed Uses [17](#__RefHeading___Toc196283102)

2.2 Structure and Nomenclature [21](#__RefHeading___Toc196283103)

2.3 Physical and Chemical Properties [22](#__RefHeading___Toc196283104)

**3.0** **Hazard Characterization/Assessment**
[22](#__RefHeading___Toc196283105)

3.1 Hazard and Dose-Response Characterization
[22](#__RefHeading___Toc196283106)

3.1.1 Database Summary [22](#__RefHeading___Toc196283107)

3.1.1.1 Studies Available and Considered (animal, human, general
literature**)** [22](#__RefHeading___Toc196283108)

3.1.1.2 Mode of Action, Metabolism, Toxicokinetic Data
[23](#__RefHeading___Toc196283109)

3.1.1.3 Sufficiency of Studies/Data [23](#__RefHeading___Toc196283110)

3.1.2 Toxicological Effects [23](#__RefHeading___Toc196283111)

3.1.3 Dose-Response [24](#__RefHeading___Toc196283112)

3.2 Absorption, Distribution, Metabolism, Excretion (ADME)
[25](#__RefHeading___Toc196283113)

3.3 FQPA Considerations [26](#__RefHeading___Toc196283114)

3.3.1 Adequacy of the Toxicity Database
[26](#__RefHeading___Toc196283115)

3.3.2 Evidence of Neurotoxicity [26](#__RefHeading___Toc196283116)

3.3.3 Developmental Toxicity Studies [26](#__RefHeading___Toc196283117)

3.3.4 Reproductive Toxicity Study [26](#__RefHeading___Toc196283118)

3.3.5 Additional Information from Literature Sources
[26](#__RefHeading___Toc196283119)

3.3.6 Pre-and/or Postnatal Toxicity [27](#__RefHeading___Toc196283120)

3.3.6.1 Determination of Susceptibility
[27](#__RefHeading___Toc196283121)

3.3.6.2 Degree of Concern Analysis and Residual Uncertainties for Pre-
and/or Postnatal Susceptibility [27](#__RefHeading___Toc196283122)

3.3.7 Recommendation for a Developmental Neurotoxicity Study
[28](#__RefHeading___Toc196283123)

3.4 Safety Factor for Infants and Children
[28](#__RefHeading___Toc196283124)

3.5 Hazard Identification and Toxicity Endpoint Selection
[29](#__RefHeading___Toc196283125)

3.5.1 Acute Reference Dose (aRfD) - Females age 13-49 and General
Population including Infants and Children
[29](#__RefHeading___Toc196283126)

3.5.2 Chronic Reference Dose (cRfD) [29](#__RefHeading___Toc196283127)

3.5.3 Incidental Oral Exposure (Short- and Intermediate-Term)
[30](#__RefHeading___Toc196283128)

3.5.4 Dermal Absorption [30](#__RefHeading___Toc196283129)

3.5.5 Dermal Exposure (Short- and Intermediate-Term)
[31](#__RefHeading___Toc196283130)

3.5.6 Inhalation Exposure (Short- and Intermediate-Term)
[31](#__RefHeading___Toc196283131)

3.5.7 Level of Concern for Margin of Exposure
[32](#__RefHeading___Toc196283132)

3.5.8 Recommendation for Aggregate Exposure Risk Assessments
[32](#__RefHeading___Toc196283133)

3.5.9 Classification of Carcinogenic Potential
[33](#__RefHeading___Toc196283134)

3.5.10 Summary of Toxicological Doses and Endpoints for Tebuconazole for
Use in Human Risk Assessments [34](#__RefHeading___Toc196283135)

3.6 Endocrine Disruption [35](#__RefHeading___Toc196283136)

**4.0** **Public Health and Pesticide Epidemiology Data**
[36](#__RefHeading___Toc196283137)

4.1 Incident Reports [36](#__RefHeading___Toc196283138)

4.2 National Health and Nutritional Examination Survey (NHANES)
[36](#__RefHeading___Toc196283139)

4.3 Agricultural Health Study (AHS) [37](#__RefHeading___Toc196283140)

4.4 Other Pesticide Epidemiology Published Literature
[37](#__RefHeading___Toc196283141)

**5.0** **Dietary Exposure/Risk Characterization**
[37](#__RefHeading___Toc196283142)

5.1 Pesticide Metabolism and Environmental Degradation
[37](#__RefHeading___Toc196283143)

5.1.1 Metabolism in Primary Crops [37](#__RefHeading___Toc196283144)

5.1.2 Metabolism in Rotational Crops [38](#__RefHeading___Toc196283145)

5.1.3 Metabolism in Livestock [39](#__RefHeading___Toc196283146)

5.1.4 Analytical Methodology [40](#__RefHeading___Toc196283147)

5.1.5 Environmental Degradation [41](#__RefHeading___Toc196283148)

5.1.6 Comparative Metabolic Profile [42](#__RefHeading___Toc196283149)

5.1.7 Toxicity Profile of Major Metabolites and Degradates
[43](#__RefHeading___Toc196283150)

5.1.8 Pesticide Metabolites and Degradates of Concern
[45](#__RefHeading___Toc196283151)

5.1.9 Drinking Water Residue Profile [46](#__RefHeading___Toc196283152)

5.1.10 Food Residue Profile [47](#__RefHeading___Toc196283153)

5.1.11 International Residue Limits [49](#__RefHeading___Toc196283154)

5.2 Dietary Exposure and Risk [49](#__RefHeading___Toc196283155)

5.2.1 Acute Dietary Exposure/Risk [49](#__RefHeading___Toc196283156)

5.2.2 Chronic Dietary Exposure/Risk [49](#__RefHeading___Toc196283157)

5.2.3 Cancer Dietary Risk [49](#__RefHeading___Toc196283158)

5.3 Anticipated Residue and Percent Crop Treated (%CT) Information
[49](#__RefHeading___Toc196283159)

**6.0** **Residential (Non-Occupational) Exposure/Risk
Characterization** [49](#__RefHeading___Toc196283160)

6.1 Residential Handler Exposure [49](#__RefHeading___Toc196283161)

6.2 Residential Postapplication Exposure
[49](#__RefHeading___Toc196283162)

6.3 Other (Spray Drift, *etc.*) [49](#__RefHeading___Toc196283163)

**7.0** **Aggregate Risk Assessments and Risk Characterization**
[49](#__RefHeading___Toc196283164)

7.1 Acute Aggregate Risk [49](#__RefHeading___Toc196283165)

7.2 Short-/Intermediate-Term Aggregate Risk
[49](#__RefHeading___Toc196283166)

7.3 Long-Term Aggregate Risk [49](#__RefHeading___Toc196283167)

7.4 Cancer Risk [49](#__RefHeading___Toc196283168)

**8.0** **Cumulative Risk Characterization/Assessment**
[49](#__RefHeading___Toc196283169)

**9.0** **Occupational Exposure/Risk Pathway**
[49](#__RefHeading___Toc196283170)

9.1 Short-/Intermediate-Term Handler Risk
[49](#__RefHeading___Toc196283171)

9.2 Short-/Intermediate-Term Postapplication Risk
[49](#__RefHeading___Toc196283172)

**10.0** **Data Needs and Label Recommendations**
[49](#__RefHeading___Toc196283173)

10.1 Toxicology [49](#__RefHeading___Toc196283174)

10.2 Residue Chemistry [49](#__RefHeading___Toc196283175)

10.3 Occupational and Residential Exposure
[49](#__RefHeading___Toc196283176)

10.4 Triazole Data Requirements [49](#__RefHeading___Toc196283177)

**References:** [49](#__RefHeading___Toc196283178)

**Appendix A: Toxicology Assessment** [49](#__RefHeading___Toc196283179)

A.1 Toxicology Data Requirements [49](#__RefHeading___Toc196283180)

A.2 Toxicity Profiles [49](#__RefHeading___Toc196283181)

A.3 Executive Summaries [49](#__RefHeading___Toc196283182)

**Appendix B: Metabolism Assessment** [49](#__RefHeading___Toc196283183)

B.1 Metabolism Considerations [49](#__RefHeading___Toc196283184)

**Appendix C: Additional Information on Residential Assessment**
[49](#__RefHeading___Toc196283185)

**Appendix D: International Residue Limits**
[49](#__RefHeading___Toc196283186)

**Appendix E: EPA Review of Human Research**
[49](#__RefHeading___Toc196283187)

**1.0 Executive Summary**[]{#__RefHeading___Toc196283098 .anchor}

Tebuconazole
\[*alpha*-\[2-(4-chlorophenyl)ethyl\]-*alpha*-(1,1-dimethylethyl)-1*H*-1,2,4-triazole-1-ethanol\]
is a systemic fungicide registered for use in a wide variety of
agricultural and residential settings. Food/feed crops include peach,
nectarine, cherry, banana, plantain, grape, peanut, grasses, and seed
treatment use on barley, oats, wheat, and triticale. Non-agricultural
uses include ornamental plants, shrubs, vines, trees and flowers, plus
wood protection treatments, and other preservative/additive uses.

*Use Profile*

The proposed uses and imported commodities focused on in this document
are: 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 and are
summarized in Table 2.1. These proposed uses/tolerances result in new
dietary exposures and the proposed uses result in new occupational
exposures. Additionally, the proposed use on turf (residential golfer)
and currently registered residential uses \[ornamentals (residential
applicator) and treated wood surfaces (residential child)\] impact
residential/aggregate exposure and risk, and are therefore, addressed in
this document as well.

The formulations associated with the proposed uses are ELITE® 45 DF (a
45% ai dry flowable; EPA Reg. No. 264-749), FOLICUR® 3.6 F (a 3.76 lb
ai/gal flowable concentrate; EPA Reg. No. 264-752) and Lynx® 2 (another
liquid formulation with a concentration of 2 lb ai/gal; EPA Reg. No.
432-RUUU). Use rates on agricultural crops range from 0.084-0.57 lb ai/A
\[pre-harvest intervals (PHIs) range from 0-180 days\], and use rates on
turf and ornamentals range from 0.13 to 1.36 lb ai/A, with a minimum
re-treatment interval (RTI) of 7 days. The maximum number of
applications varies by crop, and is often not specified on the label --
although based on the single and seasonal application rates (and RTIs),
multiple applications are expected to growing crops (unless the use is
for post-harvest treatment, as is the case for cherries, plums and
mangos, for which a single application is expected; cherries and plums
may be treated as growing crops as well as post-harvest).

*Hazard Profile*

The toxicity database for tebuconazole is complete and adequate for
required endpoint selection for exposure scenarios, and for FQPA
evaluation. The database has been reviewed, considered for the overall
hazard profile, endpoint selection, and susceptibility of infants and
children as required by FQPA. In both rodent and non-rodent species, the
main target organs were the adrenal glands, liver, and hematopoetic and
nervous systems. There was evidence for neurotoxicity in both adults and
in the developing fetuses. In the developmental toxicity studies
conducted via the oral route, there was evidence of alterations to the
development of the fetal nervous system in mice, rats and rabbits.
However, in the developmental toxicity via the dermal route no
developmental toxicity was seen. For the overall risk assessments, the
point of departure (POD) used for all exposure scenarios was selected
from the developmental neurotoxicity (DNT) study. In addition to the
traditional uncertainty factors of 10x for interspecies extrapolation
and 10x for intraspecies variation, a 3x uncertainty factor is applied
to the POD to account for LOAEL to NOAEL extrapolation. Tebuconazole is
classified as a Group C Carcinogen-Possible Human Carcinogen based on
statistically significant increase in the incidence of liver tumors in
both sexes of mice.

*Dietary Exposure*

Acute and chronic aggregate dietary exposure and risk assessments were
conducted using the Dietary Exposure Evaluation Model (DEEM-FCID™),
Version 2.03, which uses food consumption data from the U.S. Department
of Agriculture's Continuing Surveys of Food Intakes by Individuals
(CSFII) from 1994-1996 and 1998.

Refined, acute probabilistic and chronic dietary exposure assessments
were conducted for all existing and proposed new food uses of
tebuconazole and drinking water. Anticipated residues for several
currently registered commodities (bananas, grapes, raisins, nectarines,
peaches, peanut butter and wheat) were derived using the latest USDA
Pesticide Data Program (PDP) monitoring data from 2002- 2006.
Anticipated residues for all other registered and proposed food
commodities were based on field trial data. Anticipated residues for all
current uses were further refined using percent crop treated (%CT) data.
Projected %CT data were used to refine anticipated residues for a few
proposed new uses that were determined in preliminary acute analyses to
contribute heavily to dietary exposure (apples, apricots, cherries,
hops, plums and sweet corn). For the remaining new uses, all of the
crops were assumed treated (100% crop treated). Available processing
data were used to refine anticipated residues for apples/pears (dried
and juice), apricots (dried), cherry (juice), coffee (roasted bean),
grapes (juice), plums (prunes/prune juice) and peanut (oil). For all
other processed commodities, default processing factors were assumed. A
distribution of estimated concentrations of tebuconazole in drinking
water was provided by the Environmental Fate and Effects Division (EFED)
and incorporated directly into the acute assessment. The assessment was
conducted using the full distribution of estimated residues in surface
water generated by the PRZM-EXAMS model. Because the highest
concentrations of total residues of tebuconazole in surface water
relevant to the acute dietary scenario resulted from the ground
application of tebuconazole to turf in Florida, it was used in the acute
dietary exposure assessment. For the chronic assessment, the highest
1-in-10 yr annual mean \[the relevant point estimate for the chronic
dietary scenario (44.9 µg/L)\] for surface water resulting from the
ground application of tebuconazole to turf in Pennsylvania was used in
the assessment.

Estimated acute dietary exposure to tebuconazole from food and drinking
water is below HED's level of concern for all population subgroups
(\<100% aPAD). Combined dietary exposure from food and drinking water at
the 99.9^th^ percentile of exposure is estimated to be 0.008171
mg/kg/day for the overall U.S. population, equivalent to 28% of the
acute Population Adjusted Dose (aPAD). The population subgroup with the
highest estimated acute dietary exposure to tebuconazole is infants \<1
year old, with an estimated exposure at the 99.9^th^ percentile of
0.015297 mg/kg/day, equivalent to 53% of the aPAD.

Chronic dietary exposure estimates for food and drinking water are well
below HED's level of concern (\<100% cPAD) for all population subgroups.
The dietary exposure is estimated at 0.001126 mg/kg/day for the general
U.S. population (4% of the chronic Population Adjusted Dose (cPAD)) and
0.003295 mg/kg/day (11% of the cPAD) for infants \<1 year old, the
population subgroup with the highest estimated chronic dietary exposure
to tebuconazole.

The chronic dietary risk assessment is considered to be protective of
any cancer effects; therefore, a separate quantitative cancer aggregate
risk assessment is not required.

Tebuconazole is among the group of pesticides which generate common
metabolites such as 1,2,4-triazole and conjugated triazole metabolites.
These triazole residues are evaluated for the entire class of
triazole-derivative compounds. HED has completed a comprehensive risk
assessment considering 1,2,4-triazole and conjugated triazole
metabolites based on established and proposed uses of
triazole-derivative fungicides as of September 2005 (D322215, Michael
Doherty, 2/7/06), and the cited risk assessment has been updated to
incorporate new uses of tebuconazole. The aggregate dietary exposure and
risk of the triazole metabolites associated with the new tebuconazole
(and other triazole-derivative fungicides) uses do not exceed HED's
level of concern (D350315, Michael Doherty, 3/27/08).

*Residential Exposure*

There is the potential for exposure in residential settings from the
existing uses of tebuconazole on residential ornamentals, in treated
wood products and in paints, and from the proposed use on golf course
turf. Because the Agency has received a voluntary intent to cancel
registrations for the paint uses, this use is not addressed in this
document. Therefore, risk assessments were conducted for residential
handlers treating ornamentals, and postapplication exposures that can
occur as a result of the treated wood products and golf course turf
uses:

-   Short-term dermal and inhalation exposures are expected for
    residential adult handlers mixing, loading, and applying
    tebuconazole products outdoors to ornamental plants (although
    postapplication exposure to treated ornamentals may occur, the
    scenario was not assessed as it is expected to be lower than handler
    exposure).

-   Short-term postapplication dermal exposure is expected for golfers,
    since residues may be contacted from treated golf course turf
    (analyses indicate the child golfer's exposure is likely to be
    similar to that of the adult golfer, therefore, the child is
    considered in the adult golfer scenario).

-   Short- and intermediate-term dermal and incidental oral exposures to
    children are expected from tebuconazole treated wood products at
    below ground treatment rates and above ground treatment rates
    (although short- and intermediate-term dermal postapplication
    exposures to adults are expected from tebuconazole treated wood
    products, adult exposure is expected to be lower than children's
    exposure).

Long-term residential exposure is not expected. Risk assessments have
been completed for high-end residential postapplication scenarios. Since
the POD and uncertainty factors (UFs) are the same for all endpoints,
all routes of exposure can be combined within a scenario and compared to
the same POD.

-   *Residential Handler Treating Ornamentals*

The MOEs for combined dermal and inhalation exposures range from 420 to
140,000 for the representative residential handler scenarios, which do
not exceed the level of concern (LOC) of an MOE of 300 or less.
Therefore, the estimated risks are not of concern.

-   *Adult Golfer (Postapplication)*

The duration of exposure is anticipated to be short-term. The estimated
MOE for the adult golfer is 2300, which does not exceed the LOC MOE of
300, and therefore is not of concern.

-   *Residential Treated-Wood Product Scenario (Children --
    Postapplication)*

HED used the same approach used by the Antimicrobial Division (AD) in
their recent assessment of identical exposures to propiconazole
(D330159, Timothy Leighton, 6/20/06), which was a modified algorithm
adapted from the probabilistic Stochastic Human Exposure and Dose
Simulation (SHEDS) model. However, the exposed child surface area inputs
to the equation were modified from the inputs used in the SHEDS report.
The calculated child surface area of the unclothed body areas of a child
from the SHEDS report can no longer be used, because parts of the data
are from human studies deemed not to pass ethics reviews. Therefore, a
new total surface area has been constructed from other data sources by
AD/HED staff and HED's Exposure Science Advisory Council (ExpoSAC)
concurred with these input values.

The existing labels indicate a maximum retention rate of 0.05 lbs ai/cu
ft of wood. However, the registrant (Lanxess Corporation in conjunction
with Bayer) has proposed reducing the amount or concentration of active
ingredient impregnated into wood solely intended for above ground uses,
resulting in a maximum retention rate of 0.02 lbs ai/cu ft of wood. The
amount of active ingredient impregnated into wood solely intended for
below ground uses remains at a maximum retention rate of 0.05 lbs ai/cu
ft of wood.

The combined \[dermal and incidental oral (*i.e.*, hand-to-mouth)\] MOEs
for below and above ground uses are 240 and 600, respectively. The
combined MOE for wood treated for below ground uses exceeds the LOC MOE
of 300, and therefore, indicates a potential risk of concern. However,
the combined MOE for wood treated for above ground uses does not exceed
the LOC of an MOE of 300 or less, and therefore, is not of concern.
Exposure over time to above ground wood is expected to more closely
represent actual exposures to children. The frequency of exposures to
above ground wood should greatly exceed any exposures to below ground
wood. Therefore, this assessment should be characterized as a
conservative screening-level assessment. However, since HED recognizes
that children may be exposed to some wood intended for below ground uses
(*e.g.*, deck pilings and playset support beams), the HED ExpoSAC
recommends that a wood wipe study on transferable residues from
tebuconazole-treated wood be submitted as confirmatory data to better
inform the exposure assessment.

*Aggregate Exposure*

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. When aggregating exposures and risks
from various sources, HED considers route and duration of exposure, as
well as the potential for concurrent exposure events.

The dietary route (food and water) alone is relevant for the acute and
long-term durations, therefore, the dietary exposure and risk assessment
described above consider aggregate exposure for these durations. On the
other hand, there are residential uses (also described above) that
result in short-/intermediate-term exposures that are considered with
background dietary exposure for short-/intermediate-term aggregate
assessments. The likelihood of the residential handler and adult golfer
scenarios co-occurring is considered low, therefore, each scenario is
considered separately with background dietary exposure.

-   *Residential Handler Treating Ornamentals*

The high-end residential handler scenario was an adult using a hose-end
sprayer (exposure via the dermal and inhalation routes); when considered
with background dietary exposure (oral route), the MOE is 400 and does
not exceed the level of concern (LOC) of an MOE of 300 or less.
Therefore, the estimated risks are not of concern.

-   *Adult Golfer (Postapplication)*

The adult golfer (exposure via the dermal route), when considered with
background dietary exposure (oral route) results in an MOE of 1800,
which does not exceed the LOC of an MOE of 300 or less, and therefore is
not of concern.

-   *Residential Treated-Wood Product Scenario (Children --
    Postapplication)*

For the toddler playing on treated wood surfaces (exposure via the
dermal and incidental oral routes), when considered with background
dietary exposure resulted in an MOE of 530 when considering the wood was
treated with an "above ground" application rate; and an MOE of 230 when
considering the wood was treated with a "below ground" application rate.
The aggregate MOEs for wood treated for below ground uses indicate a
potential risk of concern. However, the combined/aggregate MOEs for wood
treated for above ground uses do not pose a risk of concern, and
exposure to above ground wood is expected to more closely represent
actual exposures to children. Frequency of exposures to above ground
wood is expected to exceed exposures to below ground wood. Therefore,
this assessment should be characterized as a conservative
screening-level assessment.

Additionally, in connection with the pending new uses of tebuconazole,
the aggregate risk posed from the triazole-derivative fungicides remains
below HED's level of concern.

*Occupational Exposure*

This document addresses occupational exposure/risk for only wheat,
barley and tree nuts (Petition No. 7F4895). Other crop uses in the
additional petitions listed above (as well as the occupational
assessment of golf course maintenance workers) will be addressed in a
separate document (D315464). Occupational handlers may be exposed to
tebuconazole over the short-/intermediate-term duration while
mixing/loading and applying sprays to wheat, barley, pecans and tree
nuts. No chemical-specific handler exposure data were submitted in
support of this use pattern. It is the policy of the HED to use data
from the Pesticide Handlers Exposure Database (PHED) Version 1.1 when
compound specific data are not available. Since the dermal and
inhalation endpoints are the same, and since dermal and inhalation
exposures may occur simultaneously, these exposures can be combined to
determine a total combined margin of exposure (MOE). The MOEs for
combined dermal and inhalation exposures range from 410 to 8800 for the
representative occupational handler scenarios, with baseline clothing,
or in some cases, when gloves are used to mitigate exposure; the
estimated risk from these exposures is not of concern.

This document addresses foliar applications of tebuconazole to wheat,
barley and tree nuts. Therefore, there is a potential for dermal
postapplication exposure to workers and a risk assessment was conducted.
Postapplication inhalation exposure is expected to be negligible. The
postapplication exposure estimates are based on a surrogate approach due
to lack of chemical-specific data for tebuconazole. A day of treatment
(day 0) residue value was estimated; *i.e.*, after sprays have dried
(assumed to be approximately 12 hours). The estimated
short-/intermediate-term MOEs indicate that MOEs of 300 are achieved on
day 0 for wheat, barley and tree nut postapplication scenarios, and
therefore are not of concern.

The tebuconazole technical material has been classified in Toxicity
Category III for acute dermal and primary eye irritation, and shows no
evidence of skin irritation. Per the Worker Protection Standard (WPS), a
12-hr restricted entry interval (REI) is required for chemicals
classified under Toxicity Category III or IV. Therefore, HED concurs
with the proposed 12-hr REI on the labels on the basis of acute
toxicity.

*Conclusions*

There are no residue chemistry, toxicology, and/or exposure issues that
would preclude granting permanent tolerances and/or conditional
registrations for the requested uses of tebuconazole on the commodities,
crops, crop groups and/or use sites addressed in this document. However,
registrations should be made conditional pending adequate resolution of
issues associated with the 1,2,4-triazole and conjugated triazole
metabolites aggregate assessment (Section 10.4), the submission of a
revised Section B (label modifications -- see Section 10.2 and 10.3 of
this document), the submission of conditional data requirements
concerning the data on barley, field corn forage, pears, melons, turnip
tops and mustard greens (see Section 10.2), the submission of a revised
Section F (see Section 10.0), and resolution of the
recommendations/issues identified in D315464 by Barry O'Keefe (see
Section 10.0 for further details).

*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 exposures 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 USDA under the Continuing
Survey of Food Intake by Individuals (CSFII) 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, season 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, nondietary 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
postapplication are evaluated. Further considerations are currently in
development 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.

*EPA Review of Human Research*

This risk assessment relies in part on data from Pesticide Handlers
Exposure Database (PHED) and Outdoor Residential Exposure Task Force
(ORETF) studies in which adult human subjects were intentionally exposed
to a pesticide or other chemical. These studies have been determined to
require a review of their ethical conduct, have received that review,
and have been determined to be ethical (studies are listed in Appendix
E).

**2.0 Ingredient Profile**[]{#__RefHeading___Toc196283099 .anchor}

Tebuconazole is a triazole fungicide that is currently used to control a
wide variety of fungal diseases in a variety of agricultural fruit and
field crops, as well as in residential settings and industrial products.

**2.1 Summary of Registered/Proposed
Uses**[]{#__RefHeading___Toc196283100 .anchor}

Tebuconazole is currently registered for use in/on food/feed crops
\[bananas, barley (seed treatment), cherries, grapes, grasses (grown for
seed), nectarines, oats (seed treatment), peaches, peanuts, plantain,
triticale (seed treatment), wheat (seed treatment)\] and
non-agricultural uses \[adhesives, ornamentals (azalea, camellia,
crabapple, dogwood, elm, hawthorn, hibiscus, iris, oak, houseplants,
ground cover, flowering plants, trees, vines, woody shrubs,
rhododendron, roses), coatings, glues, lumber, metalwork cutting fluids,
as a paint preservative, paper/paperboard, particleboard, plastics,
plywood, polymers, polyurethane, styrene, vinyl, and wood\].
Furthermore, there have been Section 18 emergency exemptions for use of
tebuconazole on: asparagus, barley, garlic, irrigation supply systems,
leatherleaf fern, sunflowers and wheat.

The proposed tolerances, registrations and uses focused on in this
document are: 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 and are
summarized in Table 2.1 below. These proposed uses/tolerances result in
new dietary and/or occupational exposures. Additionally, the proposed
use on turf (residential golfer) and currently registered residential
uses \[ornamentals (residential applicator) and treated wood surfaces
(residential child)\] also impact the human health risk assessment, and
are therefore addressed in this document as well.

The formulations associated with the proposed uses are ELITE® 45 DF (a
45% ai dry flowable; EPA Reg. No. 264-749), FOLICUR® 3.6 F (a 3.76 lb
ai/gal flowable concentrate; EPA Reg. No. 264-752) and Lynx® 2 (another
liquid formulation with a concentration of 2 lb ai/gal; EPA Reg. No.
432-RUUU). Use rates on agricultural crops range from 0.084-0.57 lb ai/A
\[pre-harvest intervals (PHIs) range from 0-180 days\], and use rates on
turf and ornamentals range from 0.13 to 1.36 lb ai/A, with a minimum
re-treatment interval (RTI) of 7 days. The maximum number of
applications varies by crop, and is often not specified on the label --
although based on the single and seasonal application rates (and RTIs),
multiple applications are expected to growing crops (unless the use is
for post-harvest treatment, which is a single application).

**2.1.1 Residential Proposed/Registered
Uses**[]{#__RefHeading___Toc196283101 .anchor}

*Proposed Use: Golf Course Turf*

Bayer has proposed the use of tebuconazole on golf course turf by ground
application only at 0.2 to 1.36 lb ai/A (0.3 to 2.0 fl oz/1000 sq ft).
The maximum seasonal application rate is 4.4 lb ai/A/year (6.5 fl
oz/1000 sq ft). Concurrently, Bayer has requested the registration of a
Lynx^®^ 2 Turf and Ornamental Fungicide label (EPA Reg. No. 432-RUUU);
22% ai, 2 lbs ai/gallon, liquid. It is proposed as both a preventive,
and/or a curative treatment for differing fungal diseases.

*Registered Use: Residential Ornamentals*

There are currently several registered pesticide labels containing the
active ingredient tebuconazole that allow applications by homeowners to
ornamental plants, shrubs, vines, trees and flowers in a residential
setting to control against a wide variety of mold fungi. Applications
can be made by the following methods: 1) soil drench from a bucket or
watering can; 2) pump style sprayer; 3) dial style hose-end sprayer; 4)
concentrate plus water hose-end sprayer; and 5) ready-to-use trigger
sprayer. The use rates on the label range from 0.0012 to 0.0053 lb
ai/gal solution, and HED assumes 0.25 to 100 gallons of solution may be
applied to ornamentals per day in a residential scenario (the maximum
estimated amount ai handled is 0.028 lb ai/day).

*Registered Use: Impregnated Wood Products*

Tebuconazole is recommended for the preservation of wood intended for
above-ground and/or in-ground contact, such as Ponderosa pine, Scots
pine, Southern yellow pine, beech, oak, birch, and other wood species
susceptible to decay by rotting fungi. Such uses include railway
sleepers, fence posts, poles, horticultural posts, etc. Based upon the
"Preventol A8 Preservative" fungicide (EPA Reg. No. 39967-13) label
applications may be made by dip, double vacuum or pressure treatment
methods. On the currently approved labels application/retention rates
are not delineated by wood intended for above and below ground uses, and
only list a maximum retention rate of 0.05 lbs per cubic foot of wood.
However, the registrant has proposed reducing the amount or
concentration of active ingredient impregnated into wood solely intended
for above ground uses, resulting in a maximum retention rate of 0.02 lbs
ai/cu ft of wood (this label amendment is a condition of registration).
Wood for in-ground contact generally needs the highest treatment
retention. The residential exposure scenario with the highest potential
for exposure resulting from this use site, is toddlers playing on
treated wood surfaces.

**2.1.2 Occupational Proposed Uses**[]{#__RefHeading___Toc196283102
.anchor}

<table style="width:100%;">
<colgroup>
<col style="width: 26%" />
<col style="width: 0%" />
<col style="width: 13%" />
<col style="width: 0%" />
<col style="width: 13%" />
<col style="width: 0%" />
<col style="width: 6%" />
<col style="width: 0%" />
<col style="width: 11%" />
<col style="width: 0%" />
<col style="width: 10%" />
<col style="width: 0%" />
<col style="width: 19%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="13"><strong>Table 2.1.2. Summary of Directions for use of
Tebuconazole.</strong></th>
</tr>
<tr class="odd">
<th colspan="2"><strong>Application Timing, Type and
Equipment</strong></th>
<th colspan="2"><p><strong>Formulation</strong></p>
<p><strong>[EPA Reg. No.]</strong></p></th>
<th colspan="2"><strong>Single rates (lb ai/A)</strong></th>
<th colspan="2"><strong>Max. # of Appls</strong></th>
<th colspan="2"><p><strong>Max. Rate per Season</strong></p>
<p><strong>(lb ai/A)</strong></p></th>
<th colspan="2"><p><strong>PHI</strong></p>
<p><strong>(Days)</strong></p></th>
<th><strong>Use Directions and Limitations <sup>1</sup></strong></th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td colspan="13"><strong>Stone fruits (pre-harvest Cherry, Peach,
Nectarine, Plum, Plumcot, Prune (fresh), Cherry, Apricot)</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar applications beginning at bud swell through
flowering and fruit development</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>45% DF</p>
<p>[264-749]</p></td>
<td colspan="2">0.11-0.23</td>
<td colspan="2">NS</td>
<td colspan="2">1.4</td>
<td colspan="2">0</td>
<td>7- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Cherry (post-harvest)</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Post-harvest flood or spray application with water or
wax/emulsion</p>
<p>Packing line application</p></td>
<td colspan="2"><p>45% DF</p>
<p>[264-749]</p></td>
<td colspan="2">0.23-0.45 lb ai/ 25,000 lb of fruit</td>
<td colspan="2">1</td>
<td colspan="2">0.45</td>
<td colspan="2">NA</td>
<td><p>Maximum of 0.45 lb ai/ 25,000 lb of fruit</p>
<p>Apply only once post-harvest</p></td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Plums (post-harvest)</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Post-harvest spray application with or without
wax</p>
<p>Packing line application</p></td>
<td colspan="2"><p>45% DF</p>
<p>[264-749]</p></td>
<td colspan="2">0.23 lb ai/200,000 lb fruit</td>
<td colspan="2">1</td>
<td colspan="2">0.23</td>
<td colspan="2">NA</td>
<td><p>Maximum of 0.225 lb ai/ 200,000 lb of fruit</p>
<p>Apply only once post-harvest</p></td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Pome fruit</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar applications from green tip through second
cover spray</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>45% DF</p>
<p>[264-749]</p></td>
<td colspan="2">0.11-0.23</td>
<td colspan="2">NS</td>
<td colspan="2">1.4</td>
<td colspan="2">75</td>
<td>7- to 10- day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Tree Nuts – Pecans</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar applications</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.23</td>
<td colspan="2">NS</td>
<td colspan="2">0.90</td>
<td colspan="2">NS</td>
<td>Do not apply after shuck split. 10 to 14-day RTI.</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Tree Nuts – Almonds, Beechnut, Brazil nut,
Butternut, Cashew, Chestnut, Chinquapin, Filbert, Hickory nut, Macadamia
nut, Pistachios, Walnut</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar applications</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>45% DF</p>
<p>[264-749]</p></td>
<td colspan="2">0.23</td>
<td colspan="2">NS</td>
<td colspan="2">0.90</td>
<td colspan="2">35</td>
<td>7- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Cucurbits</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar applications</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.23</td>
<td colspan="2">NS</td>
<td colspan="2">0.68</td>
<td colspan="2">3</td>
<td>10- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Turnips</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar applications</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.20</td>
<td colspan="2">NS</td>
<td colspan="2">0.81</td>
<td colspan="2">7</td>
<td>12- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><p id="wheat-no-section-b-for-barley"
class="heading">Wheat (no section B for barley)</p></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar applications</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11</td>
<td colspan="2">1</td>
<td colspan="2">0.11</td>
<td colspan="2">30</td>
<td>Do not apply after heads have emerged on 50% of the plants.</td>
</tr>
<tr class="odd">
<td colspan="13"><h5
id="corn-field-sweet-pop-seed-and-field-corn-grown-for-seed">Corn
(field, sweet, pop, seed and field corn grown for seed)</h5></td>
</tr>
<tr class="even">
<td colspan="2"><p>Broadcast foliar</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2"><p>0.11-0.17</p>
<p>(0.002-0l5 lb ai/100 lbs seed)</p></td>
<td colspan="2">NS</td>
<td colspan="2">0.675</td>
<td colspan="2"><p>7 (ears and forage)</p>
<p>36 (grain and fodder)</p>
<p>49 (sweet corn fodder)</p></td>
<td>7- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Soybean</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Broadcast foliar</p>
<p>Ground or aerial equipment.</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.084-0.11</td>
<td colspan="2">3</td>
<td colspan="2">0.34</td>
<td colspan="2">21</td>
<td>10- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Cotton</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Broadcast foliar</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.17-0.23</td>
<td colspan="2">NS</td>
<td colspan="2">0.675</td>
<td colspan="2">30</td>
<td>7- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><h5 id="beans-fresh-2">Beans, fresh
<sup>2</sup></h5></td>
</tr>
<tr class="even">
<td colspan="2"><p>Broadcast foliar</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.17</td>
<td colspan="2">4</td>
<td colspan="2">0.675</td>
<td colspan="2">7</td>
<td>14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><h5 id="beans-dry">Beans, dry</h5></td>
</tr>
<tr class="even">
<td colspan="2"><p>Broadcast foliar</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.17</td>
<td colspan="2">2</td>
<td colspan="2">0.338</td>
<td colspan="2">14</td>
<td>14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Hops (Germany)</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar application</p>
<p>Ground equipment</p></td>
<td colspan="2"><p>250 g/L EW</p>
<p>[na]</p></td>
<td colspan="2">0.4 and 0.45</td>
<td colspan="2">2</td>
<td colspan="2">0.85</td>
<td colspan="2">21</td>
<td><p>10-day RTI</p>
<p>Apply in 1000-5000 L water/ha</p></td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Hops (U.S.) <sup>3</sup></strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar application</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.23</td>
<td colspan="2">NS</td>
<td colspan="2">0.9</td>
<td colspan="2">14</td>
<td>10- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Asparagus (imported)</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar application</p>
<p>Ground equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[na]</p></td>
<td colspan="2">0.11</td>
<td colspan="2">4</td>
<td colspan="2">0.45 lb ai/A</td>
<td colspan="2">30</td>
<td><p>21-day RTI</p>
<p>Apply in 21-64 GPA water</p></td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Asparagus (U.S.)</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar application</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.17</td>
<td colspan="2">3</td>
<td colspan="2">0.51</td>
<td colspan="2"><p>180</p>
<p>100 in CA</p></td>
<td>14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Coffee (imported)</strong></td>
</tr>
<tr class="even">
<td colspan="2"><p>Foliar application</p>
<p>Ground equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[na]</p></td>
<td colspan="2">0.22</td>
<td colspan="2">5</td>
<td colspan="2">1.12</td>
<td colspan="2">28</td>
<td><p>30-day RTI</p>
<p>Apply in &gt;53 GPA</p></td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Garlic (imported)</strong></td>
</tr>
<tr class="even">
<td colspan="2">Seed piece treatment (cloves)</td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[na]</p></td>
<td colspan="2">0.49 lb ai/2000 lb seed pieces</td>
<td colspan="2">1</td>
<td colspan="2">--</td>
<td colspan="2">--</td>
<td>--</td>
</tr>
<tr class="odd">
<td colspan="2">Soil drench</td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[na]</p></td>
<td colspan="2">0.45</td>
<td colspan="2">3</td>
<td colspan="2">1.34</td>
<td colspan="2">37</td>
<td><p>45 day RTI</p>
<p>Apply in &gt;52 GPA</p></td>
</tr>
<tr class="even">
<td colspan="13"><strong>Onion, dry bulb (imported)</strong></td>
</tr>
<tr class="odd">
<td colspan="2"><p>Foliar application</p>
<p>Ground equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[na]</p></td>
<td colspan="2">0.17</td>
<td colspan="2">4</td>
<td colspan="2">0.67</td>
<td colspan="2">7</td>
<td><p>12 day RTI</p>
<p>Apply in &gt;86 GPA</p></td>
</tr>
<tr class="even">
<td colspan="13"><strong>Mango (post-harvest treatment)</strong></td>
</tr>
<tr class="odd">
<td colspan="2">Apply by spraying dilute solution onto brushes in
commercial packing line</td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.21 lb ai/50,000 lb fruit</td>
<td colspan="2">NS</td>
<td colspan="2">--</td>
<td colspan="2">--</td>
<td>7.5 fl oz per 100 gal water/50,000 lb fruit</td>
</tr>
<tr class="even">
<td colspan="13"><strong>Okra</strong></td>
</tr>
<tr class="odd">
<td colspan="2"><p>Foliar application</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11 – 0.17</td>
<td colspan="2">NS</td>
<td colspan="2">0.675</td>
<td colspan="2">3</td>
<td>14-day RTI</td>
</tr>
<tr class="even">
<td colspan="13"><strong>Lychee</strong></td>
</tr>
<tr class="odd">
<td colspan="2"><p>Foliar application</p>
<p>Ground equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.17</td>
<td colspan="2">8</td>
<td colspan="2">1.4</td>
<td colspan="2">0</td>
<td><p>10-day RTI</p>
<p>Apply in 50-200 GPA</p></td>
</tr>
<tr class="even">
<td colspan="13"><p id="sunflower" class="heading">Sunflower</p></td>
</tr>
<tr class="odd">
<td colspan="2"><p>Foliar application</p>
<p>Ground or aerial equipment</p></td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.11-0.17</td>
<td colspan="2">NS</td>
<td colspan="2">0.45</td>
<td colspan="2">50</td>
<td>14 day RTI</td>
</tr>
<tr class="even">
<td colspan="13"><p><strong>Green onion, Leek, Spring onion, Scallion,
Japanese bunching onion,</strong></p>
<p><strong>Green shallots, Green eschalots</strong></p></td>
</tr>
<tr class="odd">
<td>Broadcast foliar applications under favorable disease conditions,
using ground or aerial equipment</td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.17</td>
<td colspan="2">NS</td>
<td colspan="2">0.67</td>
<td colspan="2">7</td>
<td colspan="2">Minimum retreatment intervals (RTIs) of 10-14 days.</td>
</tr>
<tr class="even">
<td colspan="13"><strong>Dry bulb onion, Garlic, Great-headed garlic,
Welch onion, Shallot</strong></td>
</tr>
<tr class="odd">
<td>Single In-furrow application at planting</td>
<td colspan="2" rowspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.57</td>
<td colspan="2">1</td>
<td colspan="2" rowspan="2"><p>0.34</p>
<p>(broadcast only)</p>
<p>0.91</p>
<p>(in-furrow + broadcast)</p></td>
<td colspan="2" rowspan="2">7</td>
<td colspan="2" rowspan="2"><p>Minimum RTIs of 10-14 days.</p>
<p>The in-furrow application may be made by chemigation.</p></td>
</tr>
<tr class="even">
<td>Broadcast foliar applications under favorable disease conditions,
ground or aerial equipment.</td>
<td colspan="2">0.11-0.17</td>
<td colspan="2">NS</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Leafy <em>Brassica</em> Greens</strong></td>
</tr>
<tr class="even">
<td>Broadcast foliar applications under favorable disease conditions,
using ground or aerial equipment</td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.084-0.11</td>
<td colspan="2">NS</td>
<td colspan="2">0.45</td>
<td colspan="2">7</td>
<td colspan="2">Minimum RTIs of 10-14 days.</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Garden Beets</strong></td>
</tr>
<tr class="even">
<td>Broadcast foliar applications under favorable disease conditions,
using ground or aerial equipment</td>
<td colspan="2"><p>3.6 lb/gal FlC</p>
<p>[264-752]</p></td>
<td colspan="2">0.20</td>
<td colspan="2">NS</td>
<td colspan="2">0.81</td>
<td colspan="2">7</td>
<td colspan="2">Minimum RTI of 14 days.</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Commercial Ornamentals</strong></td>
</tr>
<tr class="even">
<td colspan="2">Ground, aerial or chemigation application</td>
<td colspan="2"><p>Lynx<sup>®</sup> 2</p>
<p>2 lb ai/gal</p>
<p>[432-RUUU]</p></td>
<td colspan="2"><p>0.13 - 0.27</p>
<p>(0.06-0.13 lb ai/100 gal)</p></td>
<td colspan="2">NS</td>
<td colspan="2">NS</td>
<td colspan="2">NS</td>
<td>7- to 14-day RTI</td>
</tr>
<tr class="odd">
<td colspan="13"><strong>Turf (for use on golf courses only) and
Residential Ornamentals (for use by commercial applicators
only)</strong></td>
</tr>
<tr class="even">
<td colspan="2">Ground application only</td>
<td colspan="2"><p>Lynx<sup>®</sup> 2</p>
<p>2 lb ai/gal</p>
<p>[432-RUUU]</p></td>
<td colspan="2"><p>0.2 – 1.36</p>
<p>(0.3-2.0 fl oz/1000 ft<sup>2</sup>)</p>
<p>(turf)</p>
<p>0.13 - 0.27</p>
<p>(ornamentals)</p></td>
<td colspan="2">NS</td>
<td colspan="2"><p>4.4</p>
<p>(turf)</p>
<p>NS</p>
<p>(ornamentals)</p></td>
<td colspan="2">NA</td>
<td><p>14- to 30-day RTI (turf)</p>
<p>7- to 14-day RTI (ornamentals)</p></td>
</tr>
</tbody>
</table>

^1^ Both agricultural labels specify a restricted re-entry interval
(REI) of 12 hours, and the following rotational crop restriction: any
crop not specified on the label may be replanted into treated areas 120
days after the last application. Minimum application volumes for ground
and aerial application are respectively 50 and 15 gal/A on the 45% DF
label (tree/vineyard crops) and 10 and 5 gal/A on the 3.6 lb/gal FlC
label (field crops). Both labels prohibit applications through any type
of irrigation system.

^2^ The use directions for "fresh" beans do not indicate whether the use
is for podded succulent beans and/or succulent, shelled beans.

^3^ Use directions from pending Petition No. 9E6046.

RTI = retreatment interval; NA = not applicable; NS = not specified.

*Conclusions.* With the exceptions of the use directions for beans,
corn, soybeans and turnip tops, the proposed use directions adequately
reflect the use patterns used in the field trials. For beans, the use
directions include applications to "fresh" beans. However, residue data
were only provided for succulent, podded bean not succulent, shelled
beans. Therefore, the proposed label directions for bean should be
amended to exclude applications to beans grown for production of
succulent shelled beans. Alternatively, the registrant could provide
field trial data supporting the use of tebuconazole (FlC) on succulent,
shelled beans.

For corn, inadequate residue data were submitted for the 7 day PHI for
forage. A 21 day PHI could be supported.

In addition, the proposed use directions for soybeans specify a PHI of
21 days, which is adequate for seed. However, the available soybean
forage and hay data will support at 0-day PHI. Therefore, the label
could be amended to indicate a 0-day PHI for soybean forage and hay.

For turnip tops, the proposed label directions for turnips should be
amended to exclude applications to turnips west of the Rockies, because
no field trial data were submitted from Region 10.

A 120 day rotational crop interval is needed for all crops for which
there are no existing/proposed uses.

The personal protective equipment (PPE) gloves are required for
mixing/loading liquids and dry flowables intended for use on wheat,
barley and tree nuts.

**Note to AD**: Label revisions are needed to specify treatment rates to
wood for above and below ground use.

**2.2 Structure and Nomenclature**[]{#__RefHeading___Toc196283103
.anchor}

+-------------------+--------------------------------------------------+
| **Table 2.2.      |                                                  |
| Nomenclature of   |                                                  |
| Tebuconazole and  |                                                  |
| its Regulated     |                                                  |
| Metabolite**      |                                                  |
+===================+==================================================+
| Chemical          | ![                                               |
| Structure         | ](media/image2.wmf){width="2.2604166666666665in" |
|                   | height="1.2986111111111112in"}                   |
+-------------------+--------------------------------------------------+
| Empirical Formula | C~16~H~22~ClN~3~0                                |
+-------------------+--------------------------------------------------+
| Common name       | Tebuconazole                                     |
+-------------------+--------------------------------------------------+
| Company           | HWG 1608                                         |
| experimental name |                                                  |
+-------------------+--------------------------------------------------+
| IUPAC name        | (*RS*)-1-*p*-chlorophenyl-4,4-dimet              |
|                   | hyl-3-(1*H*-1,2,4-triazol-1-ylmethyl)pentan-3-ol |
+-------------------+--------------------------------------------------+
| CAS name          | α-\[2-(4-chlorophenyl)ethyl\]-α-(                |
|                   | 1,1-dimethylethyl)-1*H*-1,2,4-triazole-1-ethanol |
+-------------------+--------------------------------------------------+
| CAS registry      | 107534-96-3                                      |
| number            |                                                  |
+-------------------+--------------------------------------------------+
| Molecular weight  | 307.8                                            |
+-------------------+--------------------------------------------------+
| End-use product   | ELITE^®^ 45 DF (45% DF; EPA Reg. No. 264-749)    |
| (EP)              |                                                  |
|                   | FOLICUR^®^ 3.6 F (3.76 lb/gal FlC; EPA Reg. No.  |
|                   | 264-752)                                         |
|                   |                                                  |
|                   | Lynx^®^ 2 (2 lb ai/gal; EPA Reg. No. 432-RUUU)   |
+-------------------+--------------------------------------------------+
| Chemical Class    | Triazoles (and more specifically,                |
|                   | triazole-derivative fungicides)                  |
+-------------------+--------------------------------------------------+
| Known Impurities  | None                                             |
| of Concern        |                                                  |
+-------------------+--------------------------------------------------+
| Metabolite        | ![                                               |
|                   | ](media/image3.wmf){width="2.4583333333333335in" |
|                   | height="1.3020833333333333in"}                   |
+-------------------+--------------------------------------------------+
| Common name       | *t*-butylhydroxy-tebuconazole                    |
+-------------------+--------------------------------------------------+
| Company           | HWG 2061                                         |
| experimental name |                                                  |
+-------------------+--------------------------------------------------+
| IUPAC name        | Not available                                    |
+-------------------+--------------------------------------------------+
| CAS name          | 1-(4-chlorophenyl)-4,4-dimethyl-3-(1             |
|                   | *H*-1,2,4-triazole-1-yl-methyl)-pentane-3,5-diol |
+-------------------+--------------------------------------------------+
| CAS registry      | Not available                                    |
| number            |                                                  |
+-------------------+--------------------------------------------------+
| Molecular weight  | 323.8                                            |
+-------------------+--------------------------------------------------+

**2.3 Physical and Chemical Properties**[]{#__RefHeading___Toc196283104
.anchor}

+--------------------------+-------------------------+-----------------+
| **Table 2.3.             |                         |                 |
| Physicochemical          |                         |                 |
| Properties of            |                         |                 |
| Tebuconazole.**          |                         |                 |
+==========================+=========================+=================+
| Parameter                | Value                   | Reference       |
+--------------------------+-------------------------+-----------------+
| Molecular weight         | 307.8                   |                 |
+--------------------------+-------------------------+-----------------+
| Melting point/range      | 104.7°C                 | PP              |
|                          |                         | #9F374/9F03818, |
|                          |                         | G. Otakie,      |
|                          |                         | 5/9/91          |
+--------------------------+-------------------------+-----------------+
| pH                       | Not soluble enough      |                 |
+--------------------------+-------------------------+-----------------+
| Specific gravity (20ºC)  | 1.202 g/mL              |                 |
+--------------------------+-------------------------+-----------------+
| Water solubility (20°C)  | 32 mg/L                 |                 |
+--------------------------+-------------------------+-----------------+
| Solvent solubility (g/L  | n-hexane 2-5            |                 |
| at 20ºC)                 |                         |                 |
|                          | dichloromethane \>200   |                 |
|                          |                         |                 |
|                          | 2-propanol 100-200      |                 |
|                          |                         |                 |
|                          | toluene 50-100          |                 |
+--------------------------+-------------------------+-----------------+
| Vapor pressure           | 1.3 x 10^-3^ mPa (20ºC) |                 |
|                          |                         |                 |
|                          | 3.1 x 10^-3^ mPa (25ºC) |                 |
+--------------------------+-------------------------+-----------------+
| Dissociation constant,   | does not dissociate     |                 |
| pK~a~                    |                         |                 |
+--------------------------+-------------------------+-----------------+
| Octanol/water partition  | 3.7 at 20ºC             |                 |
| coefficient, Log(K~OW~)  |                         |                 |
+--------------------------+-------------------------+-----------------+
| UV/visible absorption    | Not available           |                 |
| spectrum                 |                         |                 |
+--------------------------+-------------------------+-----------------+

**3.0 Hazard
Characterization/Assessment**[]{#__RefHeading___Toc196283105 .anchor}

**3.1 Hazard and Dose-Response
Characterization**[]{#__RefHeading___Toc196283106 .anchor}

**3.1.1 Database Summary**[]{#__RefHeading___Toc196283107 .anchor}

The toxicology database for tebuconazole is complete. In addition to the
required toxicity studies, the registrant has submitted additional
developmental toxicity studies and has repeated some guideline studies
(*e.g.*, there are two chronic dog studies and multiple rabbit
developmental toxicity studies). The toxicity database for tebuconazole
has been reviewed by the Cancer Peer Review Committee (TXR# 0052724),
the Developmental and Reproductive Toxicity Peer Review Committee (TXR
\# 009794), the Toxicology Endpoint Selection Committee (TXR \# 013628),
the RfD Committee (TXR \# 011984), the HIARC (TXR \# 012516), and the
FQPA Safety Factor Committee (TXR \# 012534). Subsequently, the
registrant submitted an acute neurotoxicity study, a subchronic
neurotoxicity study and a developmental neurotoxicity study that were
required by the HIARC and several prenatal developmental toxicity
studies. In addition, a developmental neurotoxicity/ developmental
immunotoxicity study for tebuconazole has been published in the
peer-reviewed literature. These studies were reviewed and considered for
the overall hazard profile, endpoint selection, and susceptibility of
infants and children as required by FQPA.

1.  **Studies Available and Considered (animal, human, general
    literature)**

[]{#__RefHeading___Toc196283108 .anchor}

[Acute]{.underline}- oral, dermal, inhalation, eye irritation, skin
irritation, dermal sensitization;

[Subchronic]{.underline}- dermal 3-week rabbit, oral 28-day rat; oral
90-day rat, oral 8-week mouse, oral 30-day dog, oral 90-day dog;

[Chronic]{.underline}- oral rat and dog;

[Reproductive/developmental]{.underline}- oral developmental rabbit,
mouse, and rat; dermal mouse and rabbit, 2-generation reproductive rat,
developmental neurotoxicity rat, special mechanistic/maternal toxicity
studies in mouse and rabbit;

[Other]{.underline}- oral rat and mouse cancer studies, mutagenicity
screens, and metabolism studies; acute and subchronic neurotoxicity
studies; dermal penetration studies; literature study on developmental
neurotoxicity and immunotoxicity.

**3.1.1.2 Mode of Action, Metabolism, Toxicokinetic
Data**[]{#__RefHeading___Toc196283109 .anchor}

Tebuconazole is a systemic fungicide in the triazole class, and acts by
inhibiting fungal enzymes involved in sterol demethylation, thus
inhibiting production of ergosterol, a component of fungal cell walls.
Oral administration of tebuconazole to rats was rapidly and extensively
absorbed, metabolized, and excreted. Tebuconazole undergoes extensive
metabolism in rats. There were dose-dependent changes in metabolite
ratios of tebuconazole which was suggestive of changes in detoxication
patterns at the high dose; these may result from metabolic saturation.

**3.1.1.3 Sufficiency of Studies/Data**[]{#__RefHeading___Toc196283110
.anchor}

The toxicity database for tebuconazole is complete and adequate for
required endpoint selection for exposure risk assessment scenarios and
for FQPA evaluation.

In addition to the required prenatal developmental toxicity studies,
multiple studies on rabbit and mouse developmental toxicity, including
special mechanistic and maternal toxicity studies, have been submitted.
Although not all the studies are acceptable, they provide additional
useful information not available from other studies. The submitted
subchronic neurotoxicity study was classified as unacceptable due to
selection of inadequate high dose levels (no toxicity was detected at
any dose); this is not considered a data gap at this time, since
toxicity was seen in other studies at considerably lower doses than
those tested in the subchronic neurotoxicity study.

**3.1.2 Toxicological Effects**[]{#__RefHeading___Toc196283111 .anchor}

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. The main target organs 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 cataract formation) following subchronic or
chronic exposure.

Oral administration of tebuconazole caused developmental toxicity in all
species evaluated (rat, rabbit, and mouse), with the most prominent
effects seen 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. In the developmental neurotoxicity study in
rats, changes were seen in brain weight and brain measurements, as well
as in several behavioral parameters. A peer-reviewed developmental
neurotoxicity/immunotoxicity literature study (Moser *et al.*, 2001)
found impairment in acquisition of a learning task (Morris water maze)
in exposed offspring; alterations in some immunological parameters in
the same study were not considered adverse by study authors.

In the reproductive toxicity 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
first week after birth), were seen in the developmental neurotoxicity
study.

In the available toxicity studies on tebuconazole, there was no
toxicologically significant evidence of endocrine disruptor effects.

Tebuconazole was classified as a Group C - possible human carcinogen,
based on an increase in the incidence of hepatocellular adenomas,
carcinomas and combined adenomas/carcinomas in male and female mice.
Submitted mutagenicity studies did not demonstrate any evidence of
mutagenic potential for tebuconazole.

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 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 have been the subject of separate risk assessment
documents (D322215, Michael Doherty, 2/7/2006; updated in D350315 to
incorporate new uses of triazole-derivative fungicides on 3/27/08).

**3.1.3 Dose-Response**[]{#__RefHeading___Toc196283112 .anchor}

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, the NOAEL for maternal toxicity 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. For offspring
toxicity, the 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 not established. Benchmark Dose (BMD) analyses were
conducted using the critical datasets of the developmental neurotoxicity
(DNT) study with tebuconazole (TXR# 0054776). The analyses do not
provide a new point of departure (POD) for risk assessments. It does,
however, provide scientific support for reducing the default 10x
Uncertainty Factor applied to a LOAEL when a NOAEL is not identified in
the critical study used in risk assessments. All of the BMDLs modeled
successfully on statistically significant effects are 1-2x lower than
the established LOAEL. The results indicate that an extrapolated NOAEL
is not likely to be 10x lower than the LOAEL and that use of an
Uncertainty Factor of 3x would not underestimate risk. Using an UF~L~ of
3x would yield a POD of 2.9 mg/kg/day (8.8 mg/kg/day ÷ 3x = 2.9
mg/kg/day) which is further supported by the NOAELs established in other
studies in the tebuconazole toxicity database \[*i.e.*, 3 and 2.9
mg/kg/day, from a developmental toxicity study in mice and a chronic
toxicity study in dogs, respectively (respective LOAELs 10 and 4.5
mg/kg/day)\].

Tebuconazole is classified as a Group C Carcinogen-Possible Human
Carcinogen based on statistically significant increase in the incidence
of liver tumors in both sexes of mice. The chronic risk assessment is
considered to be protective of any cancer effects; therefore, a separate
quantitative cancer aggregate risk assessment is not required (TXR No.
0052724).

The uncertainty factors used in determining reference dose (RfD) and
population adjusted dose (PAD) exposure limits were 300 (10x for
intraspecies variation, 10x for interspecies extrapolation, and a 3x
FQPA SF retained, but reduced in the form of a LOAEL to NOAEL
extrapolation factor (UF~L~).

**3.2 Absorption, Distribution, Metabolism, Excretion
(ADME)**[]{#__RefHeading___Toc196283113 .anchor}

The metabolism of ^14^C-labeled tebuconazole technical after oral dosing
was studied in Wistar rats of both sexes (MRID Nos. 40995911 and
40995912). When \[phenyl-UL-^14^C\]-labeled tebuconazole was
administered as a single oral dose of 2 or 20 mg/kg to male and female
Wistar rats, the compound was rapidly and extensively absorbed,
extensively metabolized, and rapidly excreted. Over 98% of a single oral
dose of \[phenyl-UL-^14^C\]-labeled tebuconazole (2 mg/kg) was absorbed
from the GI tract, based on \[^14^C\] excretion in the urine (7.4% of
the dose) and in bile (90.68% of the dose), as determined in
bile-fistulated male rats. In intact rats, over 86-98% of the
administered radioactivity was excreted by 72 hours. About 14-16% and
72-82% of the dose appeared in urine and feces, respectively, in males
and about 28-32% and 62% of the dose appeared in urine and feces,
respectively, in females. Tissue concentrations were highest in liver at
sacrifice, 72 hours after dosing. Tebuconazole undergoes extensive
metabolism in rats. A total of 10 compounds were identified in excreta,
amounting to 51-58% of the dose in males and to 68-71% of the dose in
females. The untransformed parent compound amounted to 0.5-2.2% of the
dose. A large fraction of the identified metabolites corresponded to
successive stages in the oxidation of one of the methyl groups in the
t-butyl moiety of tebuconazole. Dose-dependent changes in metabolite
ratios of tebuconazole are suggestive of changes in detoxication
patterns at the high dose; these may result from metabolic saturation.

**3.3 FQPA Considerations**[]{#__RefHeading___Toc196283114 .anchor}

**3.3.1 Adequacy of the Toxicity
Database**[]{#__RefHeading___Toc196283115 .anchor}

The database for tebuconazole is adequate for FQPA consideration.

**3.3.2 Evidence of Neurotoxicity**[]{#__RefHeading___Toc196283116
.anchor}

Tebuconazole demonstrated neurotoxicity in the acute neurotoxicity study
in rats (the LOAEL of 100 mg/kg/day was based on increased motor
activity in male and female rats and decreased footsplay in female
rats), but not in the subchronic neurotoxicity (the subchronic study was
unacceptable due to inadequate dosing). 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 brain morphometric parameters, and
decreases in motor activity). In addition, malformations indicative of
disruption of nervous system development were seen in developmental
toxicity studies in three species (mice, rats, and rabbits).

**3.3.3 Developmental Toxicity Studies**[]{#__RefHeading___Toc196283117
.anchor}

Tebuconazole induced developmental toxicity in mice, rats, and rabbits
via the oral route of administration. In mice, the NOAEL for
developmental toxicity was lower than the NOAEL for maternal toxicity.
For rats and rabbits, although there was no increase in quantitative
sensitivity (maternal and developmental toxicity occurred at the same
dose), the qualitative toxicity in offspring was often more severe (for
example, malformations occurred at doses causing minor body weight
decrements or mild liver toxicity. Following dermal exposure,
developmental toxicity was not seen in mice or rats. The possible
kinetic differences between dermal and oral exposure were not considered
in the design of the available dermal developmental toxicity studies,
and may limit their utility.

**3.3.4 Reproductive Toxicity Study**[]{#__RefHeading___Toc196283118
.anchor}

In the two-generation reproduction study in rats, NOAELs/LOAELs were the
same for offspring and parental system toxicity. There was no evidence
of reproductive toxicity.

**3.3.5 Additional Information from Literature
Sources**[]{#__RefHeading___Toc196283119 .anchor}

In a published literature study (Moser *et al.*, 2001. Tox. Sci.
[62]{.underline}:339-352, MRID 45486901), neurological, immunological,
and reproductive functions were evaluated in adult Sprague-Dawley rats
following direct gavage exposure from GD14 to PND7 (to dams) and PND7-42
(to offspring) at doses of 0, 6, 20, or 60 mg/kg tebuconazole. Although
there were decreases in pup viability and body weight at the high dose,
no adverse impacts on reproductive function were detected. In the
immunotoxicity evaluations, high dose rats immunized with sheep red
blood cells (RBCs) had increased spleen weights and cellularity, and an
altered ratio of T and B cells. Study authors concluded that the
physiological relevance and immunological significance of these changes
were unclear, given the lack of changes in the immunological response to
sheep RBCs. Most measured neurological parameters were unaffected, but
there was a learning deficit identified in the Morris water maze at the
highest dose. Neuropathological effects identified in the original study
were later determined to be the result of fixation artifacts and were
retracted based on a pathology peer review (MRIDs 45591701, 46146701).

**3.3.6 Pre-and/or Postnatal Toxicity**[]{#__RefHeading___Toc196283120
.anchor}

**3.3.6.1 Determination of
Susceptibility**[]{#__RefHeading___Toc196283121 .anchor}

The data from prenatal developmental toxicity studies in mice and a
developmental neurotoxicity study in rats indicated an increased
quantitative and qualitative susceptibility following *in utero*
exposure to tebuconazole. The NOAELs/LOAELs for developmental toxicity
in these studies were found at dose levels less than those that induce
maternal toxicity or in the presence of slight maternal toxicity. There
was no indication of increased quantitative susceptibility in the rat
and rabbit developmental toxicity studies, the NOAELs for developmental
toxicity were comparable to or higher than the NOAELs for maternal
toxicity. In all three species, however, there was indication of
increased qualitative susceptibility. For most studies, minimal maternal
toxicity was seen at the LOAEL (consisting of increases in hematological
findings in mice, increased liver weights in rabbits and rats, and
decreased body weight gain/food consumption in rats) and did not
increase substantially in severity at higher doses; however, there was
more concern for the developmental effects at each LOAEL which included
increases in runts, increased fetal loss, and malformations in mice,
increased skeletal variations in rats, and increased fetal loss and
frank malformations in rabbits. Additionally, more severe developmental
effects (including frank malformations) were seen at higher doses in
mice, rats and rabbits. In the developmental neurotoxicity study,
maternal toxicity was seen only at the high dose (decreased body
weights, body weight gains, and food consumption, prolonged gestation
with mortality, and increased number of dead fetuses), while offspring
toxicity (including decreases in body weight, brain weight, brain
measurements and functional activities) was seen at all doses.

**3.3.6.2 Degree of Concern Analysis and Residual Uncertainties for Pre-
and/or Postnatal Susceptibility** []{#__RefHeading___Toc196283122
.anchor}

Since there was evidence of increased susceptibility of offspring
following exposure to tebuconazole in mice, rats and rabbits, a Degree
of Concern Analysis was performed to:

> i\. Determine the level of concern for the effects observed when
> considered in the context of all available toxicity data.
>
> ii\. Identify any residual uncertainties after establishing toxicity
> endpoints and traditional UFs to be used in the risk assessment for
> this chemical.

The toxicity database for tebuconazole is complete, and includes
prenatal developmental toxicity studies in three species (mouse, rat,
and rabbit), a reproductive toxicity study in rats, acute and subchronic
neurotoxicity studies in rats, and a developmental neurotoxicity study
in rats. Available data indicated greater sensitivity of the developing
organism to exposure to tebuconazole, as demonstrated by increases in
qualitative sensitivity in prenatal developmental toxicity studies in
rats, mice, and rabbits, and by increases in both qualitative and
quantitative sensitivity in the developmental neurotoxicity study in
rats with tebuconazole. However, the degree of concern is low because
the toxic endpoints in the prenatal developmental toxicity studies were
well characterized with clear NOAELs established and the most sensitive
endpoint from the developmental neurotoxicity is used for overall risk
assessments. Therefore, there are no residual uncertainties for pre- and
/or postnatal susceptibility.

**3.3.7 Recommendation for a Developmental Neurotoxicity
Study**[]{#__RefHeading___Toc196283123 .anchor}

A developmental neurotoxicity is already available for tebuconazole.

**3.4 Safety Factor for Infants and
Children**[]{#__RefHeading___Toc196283124 .anchor}

The tebuconazole risk assessment team has determined that reliable data
show that it would be safe for infants and children to reduce the FQPA
SF to 3x for all potential exposure scenarios. That decision is based on
the following findings:

i\. The toxicity database for tebuconazole is complete and includes an
acceptable rat developmental neurotoxicity study.

ii\. 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 the risk assessment of
tebuconazole. The degree of concern for residual uncertainties for
prenatal and/or postnatal toxicity is low.

iii\. The FQPA SF is retained as a UF~L~. Reduction of the UF~L~ from 10
to 3x is based on a Benchmark Dose (BMD) analyses of the datasets
relevant to the adverse offspring effects (decreased body weight and
brain weight) seen at the LOAEL in the DNT study. All of the BMDLs
modeled successfully on statistically significant effects are 1-2X lower
than the LOAEL. The results indicate that an extrapolated NOAEL is not
likely to be 10x lower than the LOAEL and that use of an UF~L~ of 3x
would not underestimate risk. Using an UF~L~ of 3x 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 \[with the lowest NOAELs
being 3 and 2.9 mg/kg/day, from a developmental toxicity study in mice
and a chronic toxicity study in dogs, respectively (respective LOAELs 10
and 4.5 mg/kg/day)\].

iv\. There are no residual uncertainties identified in the exposure
databases. Although the acute and chronic food exposure assessments are
refined, EPA believes that the assessments are based on reliable data
and will not underestimate exposure/risk. The drinking water estimates
were derived from conservative screening models. The residential
exposure assessment utilizes reasonable high-end variables set out in
EPA\'s Occupational/Residential Exposure SOPs (Standard Operating
Procedures). The aggregate assessment is based upon reasonable
worst-case residential assumptions, and is also not likely to
underestimate exposure/risk to any subpopulation, including those
comprised of infants and children.

**3.5 Hazard Identification and Toxicity Endpoint
Selection**[]{#__RefHeading___Toc196283125 .anchor}

**3.5.1 Acute Reference Dose (aRfD) - Females age 13-49 and General
Population including Infants and Children**
[]{#__RefHeading___Toc196283126 .anchor}

[Study Selected:]{.underline} Developmental Neurotoxicity Study-rats
870.6300/§83-6a

[MRID. Nos.]{.underline} 45074301

[Executive Summary]{.underline}: See Appendix A, Guideline 870.6300.

[Dose and Endpoint for Risk Assessment:]{.underline} Offspring Systemic
Toxicity LOAEL of 8.8 mg/kg/day based on decreases in body weights,
absolute brain weights, brain measurements and motor activity.

[Comments about Study and Endpoint:]{.underline} It is presumed that
changes in brain weight and morphometric parameters could result
following a single exposure during organogenesis. Also, since it cannot
be determined whether these effects occur after pre- and/or postnatal
exposure, these endpoints are considered to be relevant for the general
population, including infants and children. A BMD analysis showed that
the extrapolated NOAEL is not likely to be 10x lower than the LOAEL and
that the use of a UF~L~ of 3x would not underestimate risk.

[Uncertainty Factor (UF):]{.underline} 300 (10x for interspecies
extrapolation and 10x for intraspecies variability and 3x for
extrapolation from LOAEL to NOAEL).

**Acute RfD =** [8.8 mg/kg/day (LOAEL)]{.underline} = **0.029
mg/kg/day**

> 300 (UF)

**3.5.2 Chronic Reference Dose (cRfD)** []{#__RefHeading___Toc196283127
.anchor}

[Study Selected:]{.underline} Developmental Neurotoxicity Study-rats
870.6300/§83-6a

[MRID. Nos.]{.underline} 45074301

[Executive Summary:]{.underline} See acute dietary assessment above.

[Dose and Endpoint for Risk Assessment:]{.underline} Offspring Systemic
Toxicity LOAEL of 8.8 mg/kg/day based on decreases in body weights,
absolute brain weights, brain measurements and motor activity.

[Comments about Study and Endpoint:]{.underline} This study was selected
due to the higher degree of concern for the effects (alteration in the
brain in offspring) seen rather than the effects (adrenal gland lesions)
seen in the adult dog in the chronic study. Additionally, the
extrapolated NOAEL of 2.9 mg/kg/day (8.8 mg/kg/day ÷ 3 = 2.9 mg/kg/day),
is numerically similar to the NOAEL (2.96 mg/kg/day) in the dog and
would address the effects seen in the non-rodent species.

[Uncertainty Factor (UF):]{.underline} 300 (10x for interspecies
extrapolation and 10x for intraspecies variability and 3x for
extrapolation from LOAEL to NOAEL).

**Chronic RfD =** [8.8 mg/kg/day (LOAEL)]{.underline} = **0.029
mg/kg/day**

> 300 (UF)

**3.5.3 Incidental Oral Exposure (Short- and Intermediate-Term)**
[]{#__RefHeading___Toc196283128 .anchor}

[Study Selected:]{.underline} Developmental Neurotoxicity Study-rats
870.6300/§83-6a

[MRID. Nos.]{.underline} 45074301

[Executive Summary:]{.underline} See acute dietary assessment above.

[Dose and Endpoint for Risk Assessment:]{.underline} Offspring Systemic
Toxicity LOAEL of 8.8 mg/kg/day based on decreases in body weights,
absolute brain weights, brain measurements and motor activity.

[Comments about Study and Endpoint:]{.underline} Although the maternal
NOAEL (3.0 mg/kg/day) is numerically similar to the extrapolated NOAEL
of 2.9 mg/kg/day (8.8 mg/kg/day ÷ 3 = 2.9 mg/kg/day), the mouse study
was not selected since the endpoint observed in the offspring in the DNT
study are more relevant to the population (infants and children) than
the systemic toxicity seen in pregnant animals in the developmental
study.

[Uncertainty Factor (UF):]{.underline} 300 (10x for interspecies
extrapolation and 10x for intraspecies variability and 3x for
extrapolation from LOAEL to NOAEL).

**3.5.4 Dermal Absorption**[]{#__RefHeading___Toc196283129 .anchor}

In a 3 week dermal toxicity study in rabbits (MRID 40700937), no
systemic effects were seen up to the limit dose of 1000 mg/kg.
Similarly, no adverse effects were seen in dermal developmental toxicity
studies in rats and mice, up to the limit dose of 1000 mg/kg/day,
administered from days 6-15 of gestation. Changes in maternal liver
parameters in the mouse study (liver histopathology and increased liver
enzyme levels at 300 and 1000 mg/kg/day), were attributed to compound
exposure (indicating that tebuconazole was dermally absorbed), but were
not considered adverse.

Two dermal absorption studies are available for tebuconazole. In a
monkey dermal absorption study (MRID 46634901), the percent dermal
absorption for an 8 hour exposure to tebuconazole in Folicur EW 250, at
a dose of 132 micrograms/sq cm of skin, was 23.1% based on applied dose
minus TRR recovered in the skin wash (Memo R. Zendzian to P. Deschamp,
6/22/2005, see Appendix A.3.7 of this document). In a rat dermal
penetration study (MRID 40995913), the percent dermal absorption at a
dose of 0.604 micrograms/sq cm of skin was 52.5% at 24 h (including
27.8% absorbed and 24.7% remaining in skin).

Based on the above information, a 23.1% (at 8 hours) dermal absorption
factor was selected from the dermal absorption study in monkeys and
should be applied to dermal risk assessments.

**3.5.5 Dermal Exposure (Short- and Intermediate-Term)**
[]{#__RefHeading___Toc196283130 .anchor}

[Study Selected:]{.underline} Developmental Neurotoxicity Study-rats
870.6300/§83-6a

[MRID. No.]{.underline} 45074301

[Executive Summary:]{.underline} See acute dietary assessment above.

[Dose and Endpoint for Risk Assessment:]{.underline} Offspring Systemic
Toxicity LOAEL of 8.8 mg/kg/day based on decreases in body weights,
absolute brain weights, brain measurements and motor activity.

[Comments about Study and Endpoint:]{.underline} Although no maternal or
developmental toxicity was seen at the Limit Dose in the available
dermal developmental toxicity studies in mice and rats, those studies
did not assess the potential toxicity of tebuconazole on the fetal
nervous system which was demonstrated via the oral route in the DNT.
Therefore, the endpoints from an oral study were used for quantification
of dermal risk. A 23% dermal absorption factor should be used for
route-to-route extrapolation.

[MOE:]{.underline} 300 (10x for interspecies extrapolation and 10x for
intraspecies variability and 3x for extrapolation from LOAEL to NOAEL).

**3.5.6 Inhalation Exposure (Short- and Intermediate-Term)**
[]{#__RefHeading___Toc196283131 .anchor}

[Study Selected:]{.underline} Developmental Neurotoxicity Study-rats
870.6300/§83-6a

[MRID. No.]{.underline} 45074301

[Executive Summary:]{.underline} See acute dietary assessment above.

[Dose and Endpoint for Risk Assessment:]{.underline} Offspring Systemic
Toxicity LOAEL of 8.8 mg/kg/day based on decreases in body weights,
absolute brain weights, brain measurements and motor activity.

[Comments about Study and Endpoint:]{.underline} Although a 15-day
repeat inhalation study is available (the determined LOAEL of 155.8
mg/m^3^/day is based on clinical signs and induction of liver microsomal
enzymes), the study did not assess the potential toxicity of
tebuconazole on the fetal nervous system which was demonstrated via the
oral route in the DNT. Therefore, the endpoints from an oral study were
used for quantification of inhalation risk. Inhalation absorption was
assumed to be equivalent to oral absorption.

[MOE:]{.underline} 300 (10x for interspecies extrapolation and 10x for
intra-species variability and 3x for extrapolation from LOAEL to NOAEL).

**3.5.7 Level of Concern for Margin of
Exposure**[]{#__RefHeading___Toc196283132 .anchor}

+--------------------+----------------+--------------+----------------+
| **Table 3.5.7      |                |              |                |
| Summary of Levels  |                |              |                |
| of Concern for     |                |              |                |
| Risk Assessment.** |                |              |                |
+--------------------+----------------+--------------+----------------+
| **Route**          | **Short-Term** | **Interme    | **Long-Term**  |
|                    |                | diate-Term** |                |
|                    | **(1 - 30      |              | **(\> 6        |
|                    | Days)**        | **(1 - 6     | Months)**      |
|                    |                | Months)**    |                |
+--------------------+----------------+--------------+----------------+
| **Occupational     |                |              |                |
| (Worker)           |                |              |                |
| Exposure**         |                |              |                |
+--------------------+----------------+--------------+----------------+
| **Dermal**         | MOE \< 300     | MOE \< 300   | NA             |
+--------------------+----------------+--------------+----------------+
| **Inhalation**     | MOE \< 300     | MOE \< 300   | NA             |
+--------------------+----------------+--------------+----------------+
| **Residential      |                |              |                |
| Exposure**         |                |              |                |
+--------------------+----------------+--------------+----------------+
| **Dermal**         | MOE \< 300     | MOE \< 300   | NA             |
+--------------------+----------------+--------------+----------------+
| **Inhalation**     | MOE \< 300     | MOE \< 300   | NA             |
+--------------------+----------------+--------------+----------------+
| **Incidental       | MOE \< 300     | MOE \< 300   | NA             |
| Oral**             |                |              |                |
+--------------------+----------------+--------------+----------------+
| **Dietary (Food    | Exposure \>    | NA           | exposure \>    |
| and Water)**       | 100% aPAD      |              | 100% cPAD      |
|                    |                |              |                |
|                    | (acute, 1-day  |              | (chronic       |
|                    | exposure)      |              | exposure)      |
+--------------------+----------------+--------------+----------------+

The Levels of Concern (LOCs) for the dermal, inhalation and incidental
oral routes (MOEs) are based on the conventional interspecies
extrapolation (10x) and intraspecies variation (10x) uncertainty
factors. An additional uncertainty factor of 3x is applied to account
for LOAEL to NOAEL extrapolation (UF~L~). The LOCs for the dietary route
are expressed as a percentage of a maximum acceptable dose (*i.e.*, the
dose which HED has concluded will result in no unreasonable adverse
health effects). This dose is referred to as the population adjusted
dose (PAD). The PAD is equivalent to the RfD divided by the FQPA Safety
Factor (which has been retained as a UF~L~, and reduced to 3x in the
case of tebuconazole). For acute and non-cancer chronic exposures, HED
is concerned when estimated dietary risk exceeds 100% of the PAD.

**3.5.8 Recommendation for Aggregate Exposure Risk Assessments**
[]{#__RefHeading___Toc196283133 .anchor}

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 aggregate
risk assessments, the oral, dermal, and inhalation exposures can be
combined due to the presence of a common toxicity endpoint.

**3.5.9 Classification of Carcinogenic
Potential**[]{#__RefHeading___Toc196283134 .anchor}

The Carcinogenicity Peer Review Committee concluded that tebuconazole
should be classified as a Group C - possible human carcinogen (TXR No.
0052724). This conclusion was based on results in a 91-week
carcinogenicity study in NMRI mice (MRID 42175001, 42469301) in which
the following effects were observed : 1) a statistically significant
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 triazole 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 carcinogenic risk
assessment, the chronic risk assessment is considered to be protective
of any cancer effects; therefore, a separate quantitative cancer risk
assessment is not required.

**3.5.10 Summary of Toxicological Doses and Endpoints for Tebuconazole
for Use in Human Risk Assessments**[]{#__RefHeading___Toc196283135
.anchor}

+----------+--------+------------+----------+-------------------------+
| **Table  |        |            |          |                         |
| 3.5.1    |        |            |          |                         |
| Summary  |        |            |          |                         |
| of       |        |            |          |                         |
| Toxic    |        |            |          |                         |
| ological |        |            |          |                         |
| Doses    |        |            |          |                         |
| and      |        |            |          |                         |
| E        |        |            |          |                         |
| ndpoints |        |            |          |                         |
| for      |        |            |          |                         |
| Tebu     |        |            |          |                         |
| conazole |        |            |          |                         |
| for Use  |        |            |          |                         |
| in       |        |            |          |                         |
| Dietary  |        |            |          |                         |
| and      |        |            |          |                         |
| Non-Occu |        |            |          |                         |
| pational |        |            |          |                         |
| Human    |        |            |          |                         |
| Health   |        |            |          |                         |
| Risk     |        |            |          |                         |
| Asses    |        |            |          |                         |
| sments** |        |            |          |                         |
+==========+========+============+==========+=========================+
| E        | Point  | Uncert     | RfD,     | Study and Toxicological |
| xposure/ | of     | ainty/FQPA | PAD,     | Effects                 |
|          | Dep    | Safety     | Level of |                         |
| Scenario | arture | Factors    | Concern  |                         |
|          |        |            | for Risk |                         |
|          |        |            | As       |                         |
|          |        |            | sessment |                         |
+----------+--------+------------+----------+-------------------------+
| Acute    | LOAEL  | UF~A~= 10x | Acute    | Developmental           |
| Dietary  | = 8.8  |            | RfD =    | Neurotoxicity Study -   |
| (General | mg/    | UF~H~=10x  | 0.029    | Rat.                    |
| Pop      | kg/day |            | m        |                         |
| ulation, |        | FQ         | g/kg/day | LOAEL = 8.8 mg/kg/day   |
| i        | UF =   | PA(UF~L~)= |          | based on decreases in   |
| ncluding | 300    | 3x         | aPAD =   | body weights, absolute  |
| Infants  |        |            | 0.029    | brain weights, brain    |
| and      |        |            | m        | measurements and motor  |
| C        |        |            | g/kg/day | activity in offspring.  |
| hildren) |        |            |          |                         |
+----------+--------+------------+----------+-------------------------+
| Acute    | LOAEL  | UF~A~= 10x | Acute    | Developmental           |
| Dietary  | = 8.8  |            | RfD      | Neurotoxicity Study -   |
|          | mg/    | UF~H~=10x  | =0.029   | Rat.                    |
| (Females | kg/day |            | m        |                         |
| 13-49    |        | FQ         | g/kg/day | LOAEL = 8.8 mg/kg/day   |
| years of | UF =   | PA(UF~L~)= |          | based on decreases in   |
| age)     | 300    | 3x         | aPAD =   | body weights, absolute  |
|          |        |            | 0.029    | brain weights, brain    |
|          |        |            | m        | measurements and motor  |
|          |        |            | g/kg/day | activity in offspring.  |
+----------+--------+------------+----------+-------------------------+
| Chronic  | LOAEL  | UF~A~= 10x | Chronic  | Developmental           |
| Dietary  | = 8.8  |            | RfD =    | Neurotoxicity Study -   |
| (All     | mg/    | UF~H~=10x  | 0.029    | Rat.                    |
| Popu     | kg/day |            |          |                         |
| lations) |        | FQ         | m        | LOAEL = 8.8 mg/kg/day   |
|          | UF =   | PA(UF~L~)= | g/kg/day | based on decreases in   |
|          | 300    | 3x         |          | body weights, absolute  |
|          |        |            | cPAD     | brain weights, brain    |
|          |        |            | =0.029   | measurements and motor  |
|          |        |            | m        | activity in offspring.  |
|          |        |            | g/kg/day |                         |
+----------+--------+------------+----------+-------------------------+
| In       | LOAEL  | UF~A~= 10x | Res      | Developmental           |
| cidental | = 8.8  |            | idential | Neurotoxicity Study -   |
| Oral     | mg/    | UF~H~=10x  | LOC for  | Rat.                    |
| Short-/I | kg/day |            | MOE =    |                         |
| ntermedi |        | FQ         | 300      | LOAEL = 8.8 mg/kg/day   |
| ate-Term | UF =   | PA(UF~L~)= |          | based on decreases in   |
| (1-30    | 300    | 3x         |          | body weights, absolute  |
| days/1-6 |        |            |          | brain weights, brain    |
| months)  |        |            |          | measurements and motor  |
|          |        |            |          | activity in offspring.  |
+----------+--------+------------+----------+-------------------------+
| Dermal   | LOAEL  | UF~A~= 10x | Res      | Developmental           |
| Short-/I | = 8.8  |            | idential | Neurotoxicity Study -   |
| ntermedi | mg/    | UF~H~=10x  | LOC for  | Rat.                    |
| ate-Term | kg/day |            | MOE =    |                         |
| (1-30    |        | UF~L~= 3x  | 300      | LOAEL = 8.8 mg/kg/day   |
| days/1-6 | UF =   |            |          | based on decreases in   |
| months)  | 300    | DAF =      |          | body weights, absolute  |
|          |        | 23.1%      |          | brain weights, brain    |
|          |        |            |          | measurements and motor  |
|          |        |            |          | activity in offspring.  |
+----------+--------+------------+----------+-------------------------+
| In       | LOAEL  | UF~A~= 10x | Res      | Developmental           |
| halation | = 8.8  |            | idential | Neurotoxicity Study -   |
| Short-/I | mg/    | UF~H~=10x  | LOC for  | Rat.                    |
| ntermedi | kg/day |            | MOE =    |                         |
| ate-Term |        | UF~L~= 3x  | 300      | LOAEL = 8.8 mg/kg/day   |
| (1-30    | UF =   |            |          | based on decreases in   |
| days/1-6 | 300    | Inhalation |          | body weights, absolute  |
| months)  |        | and oral   |          | brain weights, brain    |
|          |        | toxicity   |          | measurements and motor  |
|          |        | are        |          | activity in offspring.  |
|          |        | assumed to |          |                         |
|          |        | be         |          |                         |
|          |        | equivalent |          |                         |
+----------+--------+------------+----------+-------------------------+
| Cancer   | Cla    |            |          |                         |
| (oral,   | ssific |            |          |                         |
| dermal,  | ation: |            |          |                         |
| inh      | Group  |            |          |                         |
| alation) | C-     |            |          |                         |
|          | po     |            |          |                         |
|          | ssible |            |          |                         |
|          | human  |            |          |                         |
|          | carc   |            |          |                         |
|          | inogen |            |          |                         |
|          | based  |            |          |                         |
|          | on     |            |          |                         |
|          | s      |            |          |                         |
|          | tatist |            |          |                         |
|          | ically |            |          |                         |
|          | signi  |            |          |                         |
|          | ficant |            |          |                         |
|          | in     |            |          |                         |
|          | crease |            |          |                         |
|          | in the |            |          |                         |
|          | inc    |            |          |                         |
|          | idence |            |          |                         |
|          | of     |            |          |                         |
|          | he     |            |          |                         |
|          | patoce |            |          |                         |
|          | llular |            |          |                         |
|          | ad     |            |          |                         |
|          | enoma, |            |          |                         |
|          | carc   |            |          |                         |
|          | inoma, |            |          |                         |
|          | and    |            |          |                         |
|          | co     |            |          |                         |
|          | mbined |            |          |                         |
|          | adenom |            |          |                         |
|          | a/carc |            |          |                         |
|          | inomas |            |          |                         |
|          | in     |            |          |                         |
|          | both   |            |          |                         |
|          | sexes  |            |          |                         |
|          | of     |            |          |                         |
|          | NMRI   |            |          |                         |
|          | mice.  |            |          |                         |
|          | The    |            |          |                         |
|          | c      |            |          |                         |
|          | hronic |            |          |                         |
|          | risk   |            |          |                         |
|          | asse   |            |          |                         |
|          | ssment |            |          |                         |
|          | is     |            |          |                         |
|          | cons   |            |          |                         |
|          | idered |            |          |                         |
|          | to be  |            |          |                         |
|          | prot   |            |          |                         |
|          | ective |            |          |                         |
|          | of any |            |          |                         |
|          | cancer |            |          |                         |
|          | ef     |            |          |                         |
|          | fects; |            |          |                         |
|          | ther   |            |          |                         |
|          | efore, |            |          |                         |
|          | a      |            |          |                         |
|          | se     |            |          |                         |
|          | parate |            |          |                         |
|          | quanti |            |          |                         |
|          | tative |            |          |                         |
|          | cancer |            |          |                         |
|          | risk   |            |          |                         |
|          | asse   |            |          |                         |
|          | ssment |            |          |                         |
|          | is not |            |          |                         |
|          | req    |            |          |                         |
|          | uired. |            |          |                         |
+----------+--------+------------+----------+-------------------------+

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

+---------+---------+---------+-----------+--------------------------+
| **Table |         |         |           |                          |
| 3.5.2   |         |         |           |                          |
| Summary |         |         |           |                          |
| of      |         |         |           |                          |
| Toxico  |         |         |           |                          |
| logical |         |         |           |                          |
| Doses   |         |         |           |                          |
| and     |         |         |           |                          |
| En      |         |         |           |                          |
| dpoints |         |         |           |                          |
| for     |         |         |           |                          |
| Tebuc   |         |         |           |                          |
| onazole |         |         |           |                          |
| for Use |         |         |           |                          |
| in      |         |         |           |                          |
| Occup   |         |         |           |                          |
| ational |         |         |           |                          |
| Human   |         |         |           |                          |
| Health  |         |         |           |                          |
| Risk    |         |         |           |                          |
| Assess  |         |         |           |                          |
| ments** |         |         |           |                          |
+=========+=========+=========+===========+==========================+
| Ex      | Point   | Unce    | Level of  | Study and Toxicological  |
| posure/ | of      | rtainty | Concern   | Effects                  |
|         | De      | Factors | for Risk  |                          |
| S       | parture |         | A         |                          |
| cenario |         |         | ssessment |                          |
+---------+---------+---------+-----------+--------------------------+
| Dermal  | LO      | UF      | Occ       | Developmental            |
| Sho     | AEL=8.8 | ~A~=10x | upational | Neurotoxicity Study -    |
| rt-/Int | mg      |         | LOC for   | Rat.                     |
| ermedia | /kg/day | UF      | MOE =300  |                          |
| te-Term |         | ~H~=10x |           | LOAEL = 8.8 mg/kg/day    |
| (1-30   |         |         |           | based on decreases in    |
| d       |         | U       |           | body weights, absolute   |
| ays/1-6 |         | F~L~=3x |           | brain weights, brain     |
| months) |         |         |           | measurements and motor   |
|         |         | DAF =   |           | activity in offspring.   |
|         |         | 23.1%   |           |                          |
+---------+---------+---------+-----------+--------------------------+
| Inh     | LO      | UF      | Occ       | Developmental            |
| alation | AEL=8.8 | ~A~=10x | upational | Neurotoxicity Study -    |
| Sho     | mg      |         | LOC for   | Rat.                     |
| rt-/Int | /kg/day | UF      | MOE =300  |                          |
| ermedia |         | ~H~=10x |           | LOAEL = 8.8 mg/kg/day    |
| te-Term |         |         |           | based on decreases in    |
| (1-30   |         | U       |           | body weights, absolute   |
| d       |         | F~L~=3x |           | brain weights, brain     |
| ays/1-6 |         |         |           | measurements and motor   |
| months) |         |         |           | activity in offspring.   |
+---------+---------+---------+-----------+--------------------------+
| Cancer  | C       |         |           |                          |
| (oral,  | lassifi |         |           |                          |
| dermal, | cation: |         |           |                          |
| inha    | Group   |         |           |                          |
| lation) | C-      |         |           |                          |
|         | p       |         |           |                          |
|         | ossible |         |           |                          |
|         | human   |         |           |                          |
|         | car     |         |           |                          |
|         | cinogen |         |           |                          |
|         | based   |         |           |                          |
|         | on      |         |           |                          |
|         | statis  |         |           |                          |
|         | tically |         |           |                          |
|         | sign    |         |           |                          |
|         | ificant |         |           |                          |
|         | i       |         |           |                          |
|         | ncrease |         |           |                          |
|         | in the  |         |           |                          |
|         | in      |         |           |                          |
|         | cidence |         |           |                          |
|         | of      |         |           |                          |
|         | hepatoc |         |           |                          |
|         | ellular |         |           |                          |
|         | a       |         |           |                          |
|         | denoma, |         |           |                          |
|         | car     |         |           |                          |
|         | cinoma, |         |           |                          |
|         | and     |         |           |                          |
|         | c       |         |           |                          |
|         | ombined |         |           |                          |
|         | aden    |         |           |                          |
|         | oma/car |         |           |                          |
|         | cinomas |         |           |                          |
|         | in both |         |           |                          |
|         | sexes   |         |           |                          |
|         | of NMRI |         |           |                          |
|         | mice.   |         |           |                          |
|         | The     |         |           |                          |
|         | chronic |         |           |                          |
|         | risk    |         |           |                          |
|         | ass     |         |           |                          |
|         | essment |         |           |                          |
|         | is      |         |           |                          |
|         | con     |         |           |                          |
|         | sidered |         |           |                          |
|         | to be   |         |           |                          |
|         | pro     |         |           |                          |
|         | tective |         |           |                          |
|         | of any  |         |           |                          |
|         | cancer  |         |           |                          |
|         | e       |         |           |                          |
|         | ffects; |         |           |                          |
|         | the     |         |           |                          |
|         | refore, |         |           |                          |
|         | a       |         |           |                          |
|         | s       |         |           |                          |
|         | eparate |         |           |                          |
|         | quant   |         |           |                          |
|         | itative |         |           |                          |
|         | cancer  |         |           |                          |
|         | risk    |         |           |                          |
|         | ass     |         |           |                          |
|         | essment |         |           |                          |
|         | is not  |         |           |                          |
|         | req     |         |           |                          |
|         | uired.. |         |           |                          |
+---------+---------+---------+-----------+--------------------------+

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 observed 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. UF~S\ =~
use of a short-term study for long-term risk assessment. UF~DB~ = to
account for the absence of key date (i.e., lack of a critical study).
MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
DAF = dermal absorption factor.

**3.6 Endocrine Disruption**[]{#__RefHeading___Toc196283136 .anchor}

EPA is required under the FFDCA, as amended by FQPA, to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) "may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other such endocrine effects as the Administrator may designate."
Following recommendations of its Endocrine Disruptor and Testing
Advisory Committee (EDSTAC), EPA determined that there was a scientific
basis for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system. EPA also
adopted EDSTAC's recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA authority to
require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

When additional appropriate screening and/or testing protocols being
considered under the Agency's EDSP have been developed, tebuconazole may
be subjected to further screening and/or testing to better characterize
effects related to endocrine disruption.

**4.0 Public Health and Pesticide Epidemiology
Data**[]{#__RefHeading___Toc196283137 .anchor}

**Reference:** D325383, Monica S. Hawkins and Hans Allender 9/19/06.

The public health incident data listed below are limited and indicate
non-specific responses to reported tebuconazole exposure; the data do
not provide information that would influence/alter the outcome/findings
of this HED human health risk assessment.

**4.1 Incident Reports**[]{#__RefHeading___Toc196283138 .anchor}

The following databases have been consulted for the poisoning incident
data on the active ingredient tebuconazole:

1\) OPP Incident Data System (IDS)

Three incidents: reported effects: malaise (1994 after applied to field
across the street), nausea, vomiting, fever (2005, after loading treated
grain on a truck), and tachycardia (2005 after planting treated seed)

2\) Poison Control Centers (1993 through 2003)

12 cases reported, 2 cases followed, of which one was presented symptoms
classified as moderate (superficial burns to the skin). The data suggest
exposure to tebuconazole is unlikely to result in serious health
effects.

3\) California Department of Pesticide Regulation - (suspected pesticide
poisonings since 1982 to 2003)

One case - a worker who reported headache, nausea, vomiting, and
abdominal discomfort after seeing the product being applied and the mist
from the spray drifted onto the right side of his body as he drove a
tractor by an orchard.

4\) National Pesticide Information Center (NPIC) -- (1984-1991)

On the list of the top 200 chemicals for which NPIC received calls from
1984-1991 inclusively, tebuconazole was not reported to be involved in
human incidents.

5\) National Institute of Occupational Safety and Health's Sentinel
Event Notification System for Occupational Risks (NIOSH SENSOR) (1998
through 2003)

One case - 1999 CA a 37 year old male farm worker exposed to Elite
Fungicide, the individual reported anxiety/hyperactivity and abdominal
pain/cramping.

There were almost no reports of ill effects from exposure to
tebuconazole in the available databases. No recommendations are made
based on the limited information available.

**4.2 National Health and Nutritional Examination Survey (NHANES)**
[]{#__RefHeading___Toc196283139 .anchor}

Although tebuconazole made the list of candidate chemicals to be
included in NHANES
(<http://www.cdc.gov/exposurereport/pdf/fr_093003.pdf> \[group 4\]), it
did not make the final list
(<http://www.cdc.gov/exposurereport/results.htm>), and therefore, there
is no information re: tebuconazole from NHANES.

**4.3 Agricultural Health Study (AHS)** []{#__RefHeading___Toc196283140
.anchor}

The AHS also has not reported out on tebuconazole
(<http://www.aghealth.org/cgi-bin/texis/webinator/search/?db=ahs&query=tebuconazole>).

**4.4 Other Pesticide Epidemiology Published
Literature**[]{#__RefHeading___Toc196283141 .anchor}

No scientific literature was found concerning human poisoning or other
adverse effects from exposure to tebuconazole.

**5.0 Dietary Exposure/Risk
Characterization**[]{#__RefHeading___Toc196283142 .anchor}

> **Reference:** D287292, Susan Hummel, 11/27/06
>
> D338564, Susan Hummel, 4/10/08

**5.1 Pesticide Metabolism and Environmental
Degradation**[]{#__RefHeading___Toc196283143 .anchor}

**5.1.1 Metabolism in Primary Crops**[]{#__RefHeading___Toc196283144
.anchor}

Adequate plant metabolism studies are available reflecting the
application of \[^14^C\] tebuconazole in grapes and \[U-^14^C-triazole\]
tebuconazole in wheat and peanuts. The residue of concern in plants for
tolerance and risk assessment is tebuconazole *per se*.

In the grape metabolism study (PP#9G3817, C. Olinger, 6/8/90, DEB No.
6022) , a single application of ^14^C- tebuconazole was made to grape
vines at 0.25 lbs ai/A. Grapes were harvested 0, 3, 7, 14, 21 and 28
days following application. In the 14, 21 and 28 day PHI samples,
approximately 92 to 95% of the total radioactive residue (TRR) was
identified as tebuconazole. A majority of the parent residues (85 to 89%
of the TRR) were identified as surface residues with a small portion
identified in a methanol extract of the homogenized fruit. Metabolite
residues at significant quantities (\>10% TRR) were not identified in
these samples.

Two tebuconazole metabolism studies in peanuts were submitted. The first
peanut metabolism study was conducted using with
\[U-^14^C-chlorophenyl\] tebuconazole. Similar amounts of radioactivity
were found as those reported in the triazole metabolism study discussed
below. The study was required to be repeated with a higher seasonal
application rate (PP#9G3817, C. Olinger, 6/8/1990).

The second peanut metabolism study was conducted using with
\[U-^14^C-triazole\] tebuconazole. Most of the residue was found in the
foliage and was comprised primarily of tebuconazole and the t-butyl
hydroxy metabolite (HWG 2061). Triazole, triazolyl alanine, and
triazolyl alanine acid were found in the peanut meats. A considerable
amount of residue was unidentified. Almost 20% of the radioactivity in
the hulls was identified as tebuconazole and the hydroxy metabolite.
Even after refluxing with 6 N HCl, a considerable amount of activity was
unextractable (PP#9G3817, C. Olinger, 6/8/1990).

In a wheat metabolism study, using \[U-^14^C-triazole\] tebuconazole,
most of the residue on the forage appeared to be tebuconazole. No
attempt was made to characterize the bound residue, which was the
primary residue in wheat chaff. In wheat grain, the primary residues
were triazolyl alanine (80%) and triazolyl acetic acid (13%), with a
smaller amount of tebuconazole (6%).

The metabolism of tebuconazole in peanuts was considered at a Metabolism
Committee meeting on 12/15/92 (Issue Paper, G. Otakie, 12/10/92;
Toxicity of HWG-2061 metabolite, A. Protzel, 12/9/92; Decision Document,
G. Otakie, 12/17/92). The question to the committee was whether the
t-butyl hydroxyl metabolite of tebuconazole (HWG-2061) should be
included in the tolerance expression for plants. The Metabolism
Committee recommended that the tolerance expression in plants include
only the parent tebuconazole. However, if higher residues of HWG-2061
are found in other commodities, then that metabolite will have to be
either included in the tolerance expression or the risk assessment.

The presence of triazole metabolites in tebuconazole treated plants are
assessed independently as part of the triazole aggregate risk assessment
(D322215, Michael Doherty, 2/7/2006; updated in D350315, Michael
Doherty, 3/27/08 to incorporate new uses of triazole-derivative
fungicides).

**5.1.2 Metabolism in Rotational Crops**[]{#__RefHeading___Toc196283145
.anchor}

An acceptable confined rotational crop study was previously reviewed by
EFED (E.B. Conerly, 4/16/1992), and HED has determined that the residues
of concern in rotated crops consist only of parent. Based on the results
from the confined study, crops not listed on tebuconazole labels may be
planted in treated areas 120 days after the last tebuconazole
application.

To support an earlier 30-day plant back interval (PBI) for soybeans
following tebuconazole-treated wheat, the registrant Bayer conducted
extensive rotational field crop trials (MRID 45094501) on soybeans
planted \~30 days following an application of tebuconazole (FlC) to
wheat at \~0.113 lb ai/A. Subsequently, Bayer proposed tolerances for
inadvertent residues in/on soybean commodities. However, Bayer has since
proposed direct use of tebuconazole (FlC) on soybeans, along with
tolerances on soybean commodities (Petition No. 4F6854).

**5.1.3 Metabolism in Livestock**[]{#__RefHeading___Toc196283146
.anchor}

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 conjugated
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 degradates 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.

In conjunction with a concurrent petition for use on wheat (Petition No.
7F4895), Bayer has also submitted additional livestock metabolism
studies reflecting oral dosing of goats and poultry with
\[triazole-3,5-^14^C\] tebuconazole. Results from these studies are
summarized below.

**Goats:** In a ruminant metabolism study, two dairy goats were dosed
orally via capsules once a day for 3 consecutive days with
\[triazole-3,5-^14^C~2~\] tebuconazole (100% radiochemical purity) at a
dose of 3.0 mg/kg body weight/day. Based on actual feed consumption,
this dose was equivalent to 39 ppm in the diet. The dose is at least 3x
higher than what is expected, as estimated dietary burdens ranged from
0.044 ppm in poultry to 10.9 ppm in dairy cattle.

The overall recovery of the dosed ^14^C-material could not be determined
as radioactivity in urine and feces, and was not reported. However, a
total of 10.32% of the administered dose was recovered in the tissues
and milk, with the majority being recovered in kidney (5% dose) and
liver (5% dose). Radioactivity in muscle, fat and milk accounted for
0.07%, 0.2% and 0.05% of the dose, respectively. Concentrations of total
radioactive residues (TRR) were 0.011 and 0.009 ppm in milk on Study
Days 1 and 2, and 2.007 ppm in kidney, 1.895 ppm in liver, 0.095 ppm in
fat, and 0.027 ppm in muscle collected at sacrifice.

A total of 53% of the TRR in milk and 81-93% of the TRR in tissues was
identified. In both milk and tissues, the major metabolite was
hydroxy-tebuconazole glucuronide (ECW-4393), accounting for 46% of the
TRR in milk and 54-77% of the TRR in tissues. Substantial amounts of
tebuconazole glucuronide were also identified in kidney (36% TRR) and
liver (17% TRR), and parent compound (tebuconazole, HWG-1608) was also
detected at lower levels in milk (7% TRR) and all tissues (3-18% TRR).
The metabolite 1,2,4-triazole was not detected in any tissues, but was
tentatively detected in milk at 12% of the TRR (0.001 ppm). Minor
unknowns were also detected in milk and tissues, with each unknown
accounting for ≤9% of the TRR.

[]{.mark}

Based on the observed metabolite profile, the metabolism of tebuconazole
in goats primarily involves either the direct conjugation of parent
tebuconazole with glucuronic acid or oxidation of tebuconazole to
hydroxy tebuconazole followed by conjugation with glucuronic acid. The
cleavage of tebuconazole to yield free 1,2,4-triazole was not a
significant metabolic pathway in goats.

[]{.mark}

**Poultry:** In a poultry metabolism study, ten laying hens were dosed
orally via capsules once a day for three days with \[triazole-^14^C\]
tebuconazole at a dose of 2.0 mg/kg body weight/day. Based on actual
feed consumption, the average dose was equivalent to 30 ppm of \[^14^C\]
tebuconazole in the diet. The dose is exaggerated, as the estimated
dietary burden for poultry is 0.044 ppm (\~ 680x lower).

The overall recovery of the dosed ^14^C-material could not be determined
as radioactivity in excreta was not reported. However, 15.1% of the
administered ^14^C-dose was recovered in poultry tissues and eggs, with
the majority of the dose being recovered in the liver (12.4% dose). Fat
and muscle accounted for 0.98% and 0.60% of the dose, respectively, and
1.16% of the dose was excreted in the eggs. Levels of TRR plateaued in
eggs on Day 2 at 0.162 ppm, and TRR levels in tissues were highest in
liver (3.722 ppm) and considerably lower in both muscle (0.179 ppm) and
fat (0.295 ppm).

A total of 72-94% of the TRR was identified in eggs and tissues.
Tebuconazole and hydroxyl tebuconazole (HWG-2061) were major
^14^C-residues in eggs and all tissues, with tebuconazole accounting for
16% of the TRR in liver and 31-65% of the TRR in fat, muscle, and eggs,
and hydroxy tebuconazole accounting for 19-33% of the TRR in tissues and
eggs. In liver, hydroxy tebuconazole sulfate (ECW-4390, 26% TRR) and
tebuconazole acid (HWG-2443, 22% TRR) were also major metabolites, along
with minor amounts of tebuconazole acid glucuronide (7% TRR) and hydroxy
tebuconazole glucuronide (ECW-4393, 4% TRR). In muscle and eggs,
1,2,4-triazole was also a major residue accounting for 11-14% of the
TRR. Minor unknowns detected in eggs and tissues each accounted for ≤11%
of the TRR in eggs or ≤4% of the TRR in tissues.

Based on the observed metabolite profile, the metabolism of tebuconazole
in poultry involves oxidation of tebuconazole to hydroxy tebuconazole
followed either by conjugation with sulfate or glucuronic acid or
further oxidation of the t-butyl group to yield tebuconazole acid, which
is also conjugated with glucuronic acid. Limited cleavage of the parent
molecule to yield 1,2,4-triazole was also observed in muscle and eggs,
but not in fat or liver.

**5.1.4 Analytical Methodology**[]{#__RefHeading___Toc196283147 .anchor}

Adequate GC/NPD and LC/MS/MS methods are available for collecting
residue data for tebuconazole and its metabolites in plant commodities,
livestock matrices and processing studies. The GC/NPD method has been
adequately validated by an independent laboratory in conjunction with a
previous petition and is available in PAM II as an enforcement method.

In the GC/NPD enforcement method (Report No. 101341), for plant
commodities, residues of tebuconazole are extracted with acetone:water
(3:1, v/v) and filtered. The resulting extract is saturated with sodium
chloride, and residues are partitioned into dichloromethane and
concentrated. For oily matrices, residues are redissolved in ACN and
partitioned against hexane to remove oils. Residues are then cleaned up
using gel permeation and silica gel columns, and if necessary a C~18~
column. Residues are determined by GC/NPD, using external standards. The
validated LOQ for residues in most plant matrices is 0.05 ppm.

In the GC/NPD enforcement method (Report No. 101316) for livestock
commodities, residues of tebuconazole and free and conjugated HWG 2061
are extracted from fat and skin with hexane, and residues are then
partitioned into ACN. The residual solids are re-extracted with
methanol, and the resulting extract is combined with the ACN fraction
and concentrated. For milk, eggs, liver, kidney and meat, residues are
extracted with methanol and filtered. The filtrate is partitioned
against hexane and reserved, and the hexane fraction is partitioned with
ACN. The resulting ACN fraction is combined with the partitioned aqueous
methanol fraction and concentrated. Extracted residues from all matrices
are then acid hydrolyzed by refluxing in 2N HCl for 16 hours. The
hydrolysate is adjusted to pH 5, and residues are partitioned into
acetone/chloroform, and depending on the matrix, cleaned up using gel
permeation chromatography, hexane/ACN partitioning, and/or preparative
HPLC analysis. Residues of HWG 2061 are derivatized with
N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA), and
residues of tebuconazole and the derivatized HWG 2061 are then
determined by GC/NPD, using external standards. The reported LOQ for
both analytes is 0.1 ppm in tissues and eggs and 0.05 ppm in milk.

Adequate multiresidue method testing for tebuconazole and its metabolite
HWG 2061 have been submitted (DP Barcode D170444, G. Otakie, 2/9/93) and
forwarded to FDA. The FDA PESTDATA database dated 06/05 (PAM Vol. I,
Appendix I), indicate that tebuconazole is completely recovered using
Multiresidue Method Section 302 (Protocol D) without cleanup, but
information was not listed for Methods 303 and 304. The metabolite HWG
2061 is not recovered using multiresidue methods.

**5.1.5 Environmental Degradation**[]{#__RefHeading___Toc196283148
.anchor}

> **Reference:** D311610, I. Maher, 2/7/07

Triazole degradates may occur in drinking water from the use of
tebuconazole and other triazole pesticides; however, exposure to these
degradates was assessed independently as part of the triazole aggregate
risk assessment (personal communication; James Hetrick, EFED,
10/03/2006).

Tebuconazole is persistent in soil (aerobic metabolism T~1/2~ = 796
days) and moderately mobile to relatively immobile (adsorption K~D~s
range from 7.69 to 16.39, adsorption K~OC~s range from 906 to 1251
ml/g). Tebuconazole has little potential to reach groundwater, except in
soils of high sand and low organic matter content. However, during a
runoff event, tebuconazole adsorbed onto the soil particles could enter
adjacent bodies of surface water via runoff.

Tebuconazole is resistant to hydrolysis (T~1/2~ \>\> 28 days or stable
at pH 5, 7, and 9), aqueous and soil photodegradation \[T~1/2~= stable
(extrapolated T~1/2~ = 590 days and 192.5 days, respectively)\], and
soil metabolism (aerobic metabolism T~1/2~ = 796 days).

Terrestrial field dissipation half-lives varied from about 1.6 to 4
months and beyond (*i.e.*, 10 months). A supplemental study on bare
ground in Florida showed leaching of tebuconazole into a lower soil
horizon. In sand soil of Vero Beach, FL (sand = 92%, silt = 0.4%, clay =
7.6%, and organic matter = 1%) tebuconazole was detected up to 0.12 ppm
in the depth of 6 to 12 inches 30 days after surface application of 1.5
lb. ai/acre (lower depths were not sampled, MRID 40700963). In addition,
tebuconazole has a low potential for bioaccumulation in fish tissues
(BCFs = 25X, 228X, and 99X for edible, nonedible, and whole fish
tissues).

Based on registrant-submitted tebuconazole field residue studies,
tebuconazole foliar dissipation half-lives ranged from 1.2 days in wheat
forage to 8.4 days in soybean forage.

**5.1.6 Comparative Metabolic Profile**[]{#__RefHeading___Toc196283149
.anchor}

Tebuconazole is readily absorbed through the rat gastrointestinal tract
(at least 98.1% of a 2 mg/kg single dose), and after 72 hours, 14-33% of
the dose is excreted as urine, and 61-82% is excreted in feces. No major
gender differences were identified. Three compounds were definitively
identified: parent (HWG-1608), HWG-2443 and HWG-2061 (reference
standards were available). And eight additional compounds were
tentatively identified (based on GC/MS and NMR patterns): ECW-4393,
ECW-4390, ECW-4873, ECW-4908, ECW-4886, ECW-4882, HWG-2251 and ECW-4895
(triazole). These metabolites include parent, hydroxylated parent,
sulfate and glucuronide conjugates, acids and triazole. Although a
metabolic pathway is not postulated in the rat, similar compounds are
identified in the postulated livestock metabolic cascades (with
exceptions pointed out in Section 5.1.7, and structures in Appendix
B.1).

Based on the observed metabolite profile, the metabolism of tebuconazole
in goats primarily involves either the direct conjugation of parent
tebuconazole with glucuronic acid or oxidation of tebuconazole to
hydroxy tebuconazole followed by conjugation with glucuronic acid. The
cleavage of tebuconazole to yield free 1,2,4-triazole was not a
significant metabolic pathway in goats. Similarly, (although direct
conjugation of parent with glucuronic acid is not postulated), poultry
metabolism involves oxidation of tebuconazole to hydroxy tebuconazole
followed either by conjugation with sulfate or glucuronic acid or
further oxidation of the t-butyl group to yield tebuconazole acid, which
is also conjugated with glucuronic acid. Similar to goats, there was
limited cleavage of the parent molecule to yield 1,2,4-triazole in
muscle and eggs, and no cleavage in fat or liver.

In environmental matrices, tebuconazole mainly persists, and degradation
into other compounds (other than the common triazole
metabolites/degradates) is not significant. This is similar to
metabolism findings in grapes and wheat. In grapes, a majority of the
parent residue (85 to 89% of the TRR) was identified as surface residue
with a small portion identified in a methanol extract of the homogenized
fruit. Metabolite residues at significant quantities (\>10% TRR) were
not identified in these samples. In wheat, most of the residue on the
forage appeared to be tebuconazole, whereas in the grain, the primary
residues were triazolyl alanine (80%) and triazolyl acetic acid (13%),
with a smaller amount of tebuconazole (6%).

On the other hand, in peanuts, most of the residue was found in the
foliage and was comprised of tebuconazole and the t-butyl hydroxy
metabolite (HWG 2061 -- the main metabolite identified in the poultry
metabolism study). Also, in peanut meat, triazole, triazolyl alanine,
and triazolyl alanine acid were found, as well as a considerable amount
of unidentified residue. In the hulls about 20% of the radioactivity was
identified as tebuconazole and the hydroxy metabolite, yet much of the
TRR was unextractable.

**5.1.7 Toxicity Profile of Major Metabolites and
Degradates**[]{#__RefHeading___Toc196283150 .anchor}

Little information is available on the toxicity of the major
tebuconazole metabolites. However, most of the significant metabolites
were also identified in the rat metabolism study, and are therefore part
of the total toxic exposure identified in the mammalian toxicology
database.

In plants, the significant metabolites are tebuconazole (in grapes and
peanuts and wheat forage), the triazole metabolites (in wheat), and
HWG-2061 (in peanuts).

In the goat metabolism study, significant amounts of tebuconazole,
(HWG-1608, 15% and 18% TRR in the liver and fat, respectively),
tebuconazole glucuronide (36% and 17% TRR in kidney and liver,
respectively) and hydroxy tebuconazole glucuronide (ECW-4393, 54% TRR in
kidney, 55% TRR in liver, 63% TRR in fat, 77% TRR in muscle and 46% TRR
in milk) were identified. Out of these significant metabolites
identified, only tebuconazole is included as a residue of concern for
risk assessment and tolerance expression. Out of the three compounds,
tebuconazole and ECW-4393 were identified in the rat metabolism study,
whereas only tebuconazole glucuronide was not identified.

In the poultry metabolism study, significant amounts of hydroxy
tebuconazole sulfate (ECW-4390, 26% TRR) and tebuconazole acid
(HWG-2443, 22% TRR) were identified in the liver. Although they were not
identified as residues of concern for risk assessment, they are
compounds identified in the rat metabolism study. On the other hand,
both tebuconazole (HWG-1608) and hydroxy tebuconazole (HWG-2061) were
identified in significant amounts in all poultry matrices (liver,
muscle, fat and eggs) and both compounds are identified in the rat
metabolism study and included as residues of concern for risk assessment
and tolerance expression.

Tebuconazole glucuronide, hydroxy tebuconazole glucuronide (ECW-4393),
hydroxy tebuconazole sulfate (ECW-4390) and tebuconazole acid (HWG-2443)
are major metabolites identified in the two livestock metabolism studies
not explicitly included in the residues of concern for risk assessment.
However, because the livestock analytical method includes a hydrolysis
step, it is likely that the method would measure the additional
livestock metabolites (tebuconazole glucuronide, hydroxy tebuconazole
glucuronide, tebuconazole acid and hydroxy tebuconazole sulfate).
Therefore, all of these metabolites are likely included in the dietary
exposure and risk assessment (and are likely measured via the
enforcement method as well). Also, these compounds (except for
tebuconazole glucuronide) are identified in the rat metabolism study,
and are therefore, part of the total toxic exposure in the mammalian
toxicology database (on which the hazard assessment is based).
Additionally, even though tebuconazole glucuronide is not identified in
the rat metabolism study, the formation of conjugates is part of the
body's detoxifying mechanism, so the compound is expected to be less
toxic than the parent.

+------------+-----------------+--------------------------+-----------+
| **Table    |                 |                          |           |
| 5.1.7.     |                 |                          |           |
| Iden       |                 |                          |           |
| tification |                 |                          |           |
| of         |                 |                          |           |
| Compounds  |                 |                          |           |
| from the   |                 |                          |           |
| Goat and   |                 |                          |           |
| Poultry    |                 |                          |           |
| Metabolism |                 |                          |           |
| Studies**  |                 |                          |           |
+============+=================+==========================+===========+
| **Common   | **Chemical      | **Chemical structure**   | **M       |
| name**     | name**          |                          | atrices** |
+------------+-----------------+--------------------------+-----------+
| Te         | α-\[2-          | ![                       | Goat --   |
| buconazole | (4-chlorophenyl | ](media/image4.wmf){widt | all       |
|            | )ethyl\]-α-(1,1 | h="1.9194444444444445in" | tissues   |
| (HWG-1608) | -dimethylethyl) | height                   | and milk  |
|            | -1*H*-1,2,4-tri | ="1.0979166666666667in"} |           |
|            | azole-1-ethanol |                          | Poultry   |
|            |                 |                          | -- all    |
|            |                 |                          | tissues   |
|            |                 |                          | and eggs  |
|            |                 |                          |           |
|            |                 |                          | Rat       |
+------------+-----------------+--------------------------+-----------+
| t-Bu       | 5-(4-           | !                        | Poultry   |
| tylhydroxy | chlorophenyl)-2 | [](media/image5.wmf){wid | -- all    |
| Te         | ,2-dimethyl-3-( | th="2.079861111111111in" | tissues   |
| buconazole | 1*H*-1,2,4-tria | heigh                    | and eggs  |
| (or        | zol-1-ylmethyl) | t="1.101388888888889in"} |           |
| hydroxyl   | pentan-1,3-diol |                          | Rat       |
| teb        |                 |                          |           |
| uconazole) |                 |                          |           |
|            |                 |                          |           |
| (HWG-2061) |                 |                          |           |
+------------+-----------------+--------------------------+-----------+
| Te         | 5-(4-chlorophe  | ![                       | Poultry   |
| buconazole | nyl)-2,2-dimeth | ](media/image6.wmf){widt | -- liver  |
| Acid       | yl-3-(1*H*-1,2, | h="1.9902777777777778in" |           |
|            | 4-triazol-1-ylm | height                   | Rat       |
| (HWG-2443) | ethyl)pentanoic | ="1.1006944444444444in"} |           |
|            | acid            |                          |           |
+------------+-----------------+--------------------------+-----------+
| Hydroxy    | Not reported    | ![                       | Goat --   |
| te         |                 | ](media/image7.wmf){widt | all       |
| buconazole |                 | h="2.4694444444444446in" | tissues   |
| g          |                 | height                   | and milk  |
| lucuronide |                 | ="0.9486111111111111in"} |           |
|            |                 |                          | Poultry   |
| (ECW-4393) |                 |                          | -- liver  |
|            |                 |                          |           |
|            |                 |                          | Rat       |
+------------+-----------------+--------------------------+-----------+
| Te         | Not reported    | ![                       | Goat --   |
| buconazole |                 | ](media/image8.wmf){widt | liver and |
| g          |                 | h="2.0194444444444444in" | kidney    |
| lucuronide |                 | height                   |           |
|            |                 | ="1.2006944444444445in"} |           |
+------------+-----------------+--------------------------+-----------+
| Hydroxy    | Not reported    | !                        | Poultry   |
| te         |                 | [](media/image9.wmf){wid | -- liver  |
| buconazole |                 | th="2.328472222222222in" |           |
| Sulfate    |                 | height                   | Rat       |
|            |                 | ="1.0979166666666667in"} |           |
| (ECW-4390) |                 |                          |           |
+------------+-----------------+--------------------------+-----------+
| Te         | Not reported    | ![]                      | Poultry   |
| buconazole |                 | (media/image10.wmf){widt | -- liver  |
| acid       |                 | h="1.8395833333333333in" | (minor)   |
| g          |                 | height                   |           |
| lucuronide |                 | ="0.9972222222222222in"} |           |
|            |                 |                          |           |
|            |                 | R~1~ = H or glucuronic   |           |
|            |                 | acid                     |           |
|            |                 |                          |           |
|            |                 | R~2~ = H or glucuronic   |           |
|            |                 | acid                     |           |
+------------+-----------------+--------------------------+-----------+
| 1,2,       | 1,2,4-triazole  | ![]                      | Goat --   |
| 4-triazole |                 | (media/image11.wmf){widt | milk      |
|            |                 | h="0.4791666666666667in" |           |
| (ECW-4895) |                 | height                   | Poultry   |
|            |                 | ="0.6965277777777777in"} | -- muscle |
|            |                 |                          | and eggs  |
|            |                 |                          |           |
|            |                 |                          | Rat       |
+------------+-----------------+--------------------------+-----------+

The metabolism cascades/inventories included in the rat, goat and
poultry metabolism studies are in Appendix B.

**5.1.8 Pesticide Metabolites and Degradates of
Concern**[]{#__RefHeading___Toc196283151 .anchor}

+---------+------------+----------------------+----------------------+
| **Table |            |                      |                      |
| 5       |            |                      |                      |
| .1.8.** |            |                      |                      |
| **      |            |                      |                      |
| Summary |            |                      |                      |
| of      |            |                      |                      |
| Meta    |            |                      |                      |
| bolites |            |                      |                      |
| and     |            |                      |                      |
| Deg     |            |                      |                      |
| radates |            |                      |                      |
| i       |            |                      |                      |
| ncluded |            |                      |                      |
| in the  |            |                      |                      |
| Tebuc   |            |                      |                      |
| onazole |            |                      |                      |
| Risk    |            |                      |                      |
| Ass     |            |                      |                      |
| essment |            |                      |                      |
| and     |            |                      |                      |
| To      |            |                      |                      |
| lerance |            |                      |                      |
| Expre   |            |                      |                      |
| ssion** |            |                      |                      |
+=========+============+======================+======================+
| **M     |            | **Residues included  | **Residues included  |
| atrix** |            | in**                 | in**                 |
|         |            |                      |                      |
|         |            | **Risk               | **Tolerance          |
|         |            | Assessment**^1^      | Expression**         |
+---------+------------+----------------------+----------------------+
| Plants  | Primary    | Tebuconazole         | Tebuconazole         |
|         | Crop       |                      |                      |
+---------+------------+----------------------+----------------------+
|         | Rotational | Tebuconazole         | Tebuconazole         |
|         | Crop       |                      |                      |
+---------+------------+----------------------+----------------------+
| Li      | Ruminant   | Tebuconazole and     | Tebuconazole and     |
| vestock |            | Free and Conjugated  | Free and Conjugated  |
|         |            | HWG-2061             | HWG-2061^2^          |
+---------+------------+----------------------+----------------------+
|         | Poultry    | Tebuconazole and     | Tebuconazole and     |
|         |            | Free and Conjugated  | Free and Conjugated  |
|         |            | HWG-2061             | HWG-2061             |
+---------+------------+----------------------+----------------------+
| D       |            | Tebuconazole         | Not Applicable       |
| rinking |            |                      |                      |
| Water   |            |                      |                      |
+---------+------------+----------------------+----------------------+

^1^ HED has determined that 1,2,4-triazole, triazole alanine (TA) and
triazole acetic acid (TAA) are potential residues of concern for all
triazole fungicides. Therefore, they are considered in the triazole risk
assessment (D322215, M. Doherty *et al.*, 2/7/06, which is being updated
in D349934).

^2^ Although the tolerance expression for livestock commodities does not
reference conjugated residues, the conjugated residues are converted to
free HWG-2061 by the data collection method; HWG-2061 is t-butylhydroxy
tebuconazole or
5-(4-chlorophenyl)-2,2-dimethyl-3-(1*H*-1,2,4-triazol-1-ylmethyl)pentan-1,3-diol.

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
(D186731; G. Otakie; 2/19/93). The residues of concern in animal
commodities include tebuconazole and free and conjugated t-butylhydroxy
tebuconazole, HWG-2061 (D170444; G. Otakie;.2/19/93).

The tebuconazole risk assessment team determined that the residue of
concern in drinking water for this single chemical risk assessment is
tebuconazole *per se*. Triazole degradates may occur in drinking water
from the use of tebuconazole and other triazole pesticides; however,
exposure to these degradates was assessed independently as part of the
triazole aggregate risk assessment.

**5.1.9 Drinking Water Residue Profile**[]{#__RefHeading___Toc196283152
.anchor}

Tebuconazole trade name, Lynx 2 (formulation targeted for turf and
ornamental use) label has been changed by the registrant, Bayer
CropScience (via email 15-OCT-2007, to M. Waller, EPA from Mike Gorrell
of Bayer) to revise the following for the turf and ornamental uses: (1)
limit use on turf to golf courses, (2) give up use on residential turf
and sod farms, (3) give up aerial and chemigation use on turf, (4) limit
the use on golf courses to Lynx 2 (liquid), and (5) withdraw the new
product application for Lynx 45 WDG.

The estimated drinking water concentrations (EDWCs) for tebuconazole
were calculated for surface water using the Tier II (PRZM/EXAMS) surface
water modeling. The assessment was based on the proposed maximum use
rates of tebuconazole on turf, ornamentals, corn, peaches, and apples,
and minimum application rate on turf. The turf scenarios (ground
applications in FL and PA) result in the highest EDWCs of all the
scenarios modeled that are relevant to the currently proposed labels/use
profile. The Pennsylvania and Florida turf scenarios were modeled with
three preventive maximum applications of 1.47 lbs ai/acre (1.65 kg
ai/ha) made at 14-day intervals, three preventive minimum applications
of 0.37 lbs ai/acre (0.41 kg ai/ha) made at 14-day intervals, and with
one curative application of 2.94 lbs ai/acre (3.30 kg ai/ha). The turf
scenarios were assessed with a percent cropped area (PCA) of 1 (which
assumes all of the watershed are treated), as well as with Golf Course
Adjustment Factor (GCAF) of 0.05 and 0.34. The GCAFs are used to model
EDWCs as if tebuconazole turf uses were limited to the golf course use
on tees and greens or the golf course use on tees, greens, and fairways,
respectively.

There is an uncertainty associated with the selection of the partition
coefficient input parameter. For the modeling purpose, the lowest
non-sand K~D~ was used for sandy loam since, statistically, there is no
significant relationship between K~D~ values and the organic carbon
content. Therefore, the input parameter of the average K~oc~ value was
used in the second round of the model simulations to account for the
uncertainty in the selection of the lowest non-sand K~D~ as the
partition coefficient. For the human health risk assessment, the highest
relevant EDWCs are recommended.

+------------------+-------------------+-----------------+------------+
| **Table 5.1.9    |                   |                 |            |
| Summary of       |                   |                 |            |
| Estimated        |                   |                 |            |
| Surface Water    |                   |                 |            |
| and Groundwater  |                   |                 |            |
| Concentrations   |                   |                 |            |
| for              |                   |                 |            |
| Tebuconazole.**  |                   |                 |            |
+==================+===================+=================+============+
|                  | **Surface Water   |                 | **G        |
|                  | Conc., ppb**      |                 | roundwater |
|                  |                   |                 | Conc., ppb |
|                  |                   |                 | ^c^**      |
+------------------+-------------------+-----------------+------------+
|                  | Lowest non-sand   | Average K~oc~   | 1.56       |
|                  | K~d~ as the       | value as the    |            |
|                  | partition         | partition       |            |
|                  | coefficient input | coefficient     |            |
|                  | parameter ^a^     | input parameter |            |
|                  |                   | ^b^             |            |
+------------------+-------------------+-----------------+------------+
| Acute (1 in 10   | **78.5**          | 57.3            |            |
| year annual      |                   |                 |            |
| peak)            |                   |                 |            |
+------------------+-------------------+-----------------+------------+
| Chronic,         | 41.3              | **44.9**        |            |
| non-cancer (1 in |                   |                 |            |
| 10 year annual   |                   |                 |            |
| mean)            |                   |                 |            |
+------------------+-------------------+-----------------+------------+
| Chronic, cancer  | 23.3              | 32.3            |            |
| (36 year annual  |                   |                 |            |
| mean)            |                   |                 |            |
+------------------+-------------------+-----------------+------------+
| ^a^ From the     |                   |                 |            |
| Tier II          |                   |                 |            |
| PRZM-EXAMS -     |                   |                 |            |
| Index Reservoir  |                   |                 |            |
| model. Input     |                   |                 |            |
| parameters are   |                   |                 |            |
| based on FL Turf |                   |                 |            |
| -- ground        |                   |                 |            |
| applied, PCA     |                   |                 |            |
| = 1. application |                   |                 |            |
| rate 1.65 kg     |                   |                 |            |
| ai/ha x 3 = 4.95 |                   |                 |            |
| kg ai/ha/year    |                   |                 |            |
|                  |                   |                 |            |
| ^b^ From the     |                   |                 |            |
| Tier II          |                   |                 |            |
| PRZM-EXAMS -     |                   |                 |            |
| Index Reservoir  |                   |                 |            |
| model. Input     |                   |                 |            |
| parameters are   |                   |                 |            |
| based on PA Turf |                   |                 |            |
| -- ground        |                   |                 |            |
| applied, PCA =   |                   |                 |            |
| 1, application   |                   |                 |            |
| rate 1.65 kg     |                   |                 |            |
| ai/ha x 3 = 4.95 |                   |                 |            |
| kg ai/ha/year    |                   |                 |            |
|                  |                   |                 |            |
| ^c^ From the     |                   |                 |            |
| SCI-GROW model   |                   |                 |            |
| assuming a       |                   |                 |            |
| maximum seasonal |                   |                 |            |
| use rate of 1.47 |                   |                 |            |
| lb ai/A, a K~oc~ |                   |                 |            |
| of 968 ml/g, and |                   |                 |            |
| a half-life of   |                   |                 |            |
| 800 days.        |                   |                 |            |
+------------------+-------------------+-----------------+------------+

**5.1.10 Food Residue Profile**[]{#__RefHeading___Toc196283153 .anchor}

With the exceptions of the field trial data on turnip tops, pears,
cucurbits, barley, field corn forage and mustard greens, the available
field trial and post-harvest application data are adequate and support
the proposed use patterns for tebuconazole on turnip roots, beans
(succulent podded and dried), soybeans, pome fruits, stone fruits, tree
nuts and almond hulls, wheat, corn (field, pop and sweet), asparagus
(both imported and domestic), imported coffee, cotton, imported garlic,
hops (both imported and domestic), lychee, mango (post-harvest use),
okra, imported onions, sunflower, green and bulb onions (subgroups), and
garden beets.

*[Turnip]{.underline}*: The available field trial data on turnips
support the use of tebuconazole (FlC) at up to four applications at 0.20
lb ai/A to turnips east of the Rockies (Revised Section B needed), at 14
day intervals, for a seasonal maximum of 0.81 lb ai/A, and a PHI of 7
days. A revised Section B is needed to limit use to east of the Rockies,
because no field trial data were submitted for turnip tops from Region
10.

*[Pome Fruit]{.underline}*: The previously reviewed field trial data on
apples and pears conditionally support the use of up to six applications
of tebuconazole (DF) to pome fruits at 0.225 lb ai/A/application, at a
minimum RTI of 7 days, for a total of 1.35 lb ai/A/season, with a PHI of
75 days. Two additional pear field trials (in regions 10 and 11)
conducted at 1x are required. In the interim, the available data will
support a conditional registration on pome fruits.

*[Stone Fruit (pre-and post-harvest)]{.underline}*: Together with the
original field trial data (D210244, G. Otakie, 3/14/95) on cherries and
peaches, the new field trial data on plums and the post-harvest residue
data on cherries and plums adequately support separate tolerances on
cherry and stone fruits crop group (except cherry). The field trial data
support the use on stone fruits of up to 6 applications of tebuconazole
(DF) at 0.225 lb ai/A/application, at a minimum RTI of 7 days, for a
total of 1.35 lb ai/A/season, with a 0-day PHI.

[*Cucurbits*:]{.underline} The available field trial data on cucumber,
summer squash, and cantaloupe will tentatively support the use of
tebuconazole (FlC) on cucurbits as a foliar spray, applied at 0.169 lb
ai/A at 14 day intervals for a maximum of 0.675 lb ai/season, with a PHI
of 7 days. A revised Section B is needed to change the proposed PHI from
3 days to 7 days, because insufficient field trial data were submitted
to support the proposed PHI of 3 days. Additional data are required for
all three representative commodities. A 7 day PHI could be supported for
a conditional registration, with submission of 2 additional field trials
on melons in California.

*[Barley]{.underline}*: Tolerances were proposed for barley commodities,
but no field trial data were submitted. Field trial data for wheat can
be translated; however, there are no field trial data for regions 9 and
10; these data are required. A conditional registration could be
supported.

*[Beans]{.underline}*: Although adequate field trial data are available
on succulent, podded beans and dry beans, no field trial data were
submitted using varieties of succulent, shelled beans. Therefore, the
proposed label directions for "fresh" should exclude applications to
varieties of succulent, shelled beans. In addition, the label specified
PHI for soybean is 21 days, which is adequate for seed. However, the
available soybean forage and hay data will support a 0-day PHI.
Therefore, the label could be amended to indicate a 0-day PHI for
soybean forage and hay.

*[Corn]{.underline}*: The petitioner was to have submitted data or
calculations showing that the proposed corn seed treatment would not add
to the residues from foliar treatments (G. Herndon, 7/10/1997). This use
is on some labels, but was not included in Section B of Petition No.
0F6129. HED has not received this information. Provided the corn seed
treatment results in non-quantifiable residues, the available field
trial data support the use of up to four applications of tebuconazole
(FlC) to sweet corn at 0.169 lb ai/A/application, at minimum RTIs of 7
days, for a total of 0.68 lb ai/A/season. The data support PHIs of 7
days for sweet corn ears and forage and 49 days for sweet corn stover.
The available field corn grain and stover data are adequate and support
the use of up to four applications of tebuconazole (FlC) to field and
pop corn at 0.169 lb ai/A/application, at a minimum RTI of 7 days, for a
total of 0.68 lb ai/A/season. These data support the proposed 36-day PHI
for field and pop corn grain and stover. However, the field corn forage
data are inadequate. As forage samples were harvested over a wide
variety of post-treatment intervals, an insufficient number of forage
samples are available at any one interval to support a specific PHI or
tolerance for forage. To support a tolerance on field corn forage, new
field trials are required in which forage samples are collected from
each test at a uniform PHI. None of the requested tests need to include
residue decline data, as decline data are available on sweet corn
forage. Alternatively, sufficient field trial data are available to
support a PHI for corn forage of 21 days. If a shorter PHI is desired,
additional data are required.

*[Mustard Greens]{.underline}*: The available mustard greens data
support the use of four broadcast foliar applications of tebuconazole to
mustard greens during vegetative development at 0.11-0.12 lb
ai/A/application and RTIs of 12-16 days, for a total of 0.45-0.47 lb
ai/A/season (1x rate). To support uses only on mustard greens, a total
of 5 field trials are required; however, when mustard greens are being
used to support uses on all *Brassica* leafy greens, a total of 8 field
trials are required.

<table style="width:100%;">
<colgroup>
<col style="width: 13%" />
<col style="width: 16%" />
<col style="width: 10%" />
<col style="width: 7%" />
<col style="width: 4%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 9%" />
<col style="width: 7%" />
<col style="width: 7%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="11"><strong>Table 5.1.10a Summary of Residue Data from
Field Trials with Tebuconazole (FIC)</strong></th>
</tr>
<tr class="odd">
<th rowspan="2">Commodity</th>
<th rowspan="2">Application Method</th>
<th rowspan="2"><p>Total Rate</p>
<p>(lb ai/A)</p></th>
<th rowspan="2">PHI (days)</th>
<th colspan="7">Residue Levels (ppm)<sup>1</sup></th>
</tr>
<tr class="header">
<th>n</th>
<th>Min.</th>
<th>Max.</th>
<th>HAFT <sup>2</sup></th>
<th><p>Median</p>
<p>(STMdR)<sup>3</sup></p></th>
<th><p>Mean</p>
<p>(STMR)<sup>3</sup></p></th>
<th>Std. Dev.</th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td colspan="11"><strong>Bean</strong></td>
</tr>
<tr class="even">
<td>Beans, succulent, podded</td>
<td>Broadcast foliar</td>
<td>0.68</td>
<td>12-14</td>
<td>15</td>
<td>&lt;0.05</td>
<td>0.06</td>
<td>0.06</td>
<td>0.025</td>
<td>0.030</td>
<td>0.012</td>
</tr>
<tr class="odd">
<td>Beans, dry</td>
<td>Broadcast foliar</td>
<td>0.34</td>
<td>8-15</td>
<td>19</td>
<td>&lt;0.05</td>
<td>0.08</td>
<td>0.08</td>
<td>0.025</td>
<td>0.030</td>
<td>0.016</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Soybean</strong></td>
</tr>
<tr class="odd">
<td>Forage</td>
<td rowspan="3">Broadcast foliar</td>
<td rowspan="2">0.336-0.345</td>
<td>0</td>
<td>40</td>
<td>2.99</td>
<td>18.2</td>
<td>14.5</td>
<td>8.29</td>
<td>8.76</td>
<td>3.80</td>
</tr>
<tr class="even">
<td>Hay</td>
<td>0</td>
<td>40</td>
<td>6.33</td>
<td>44.7</td>
<td>42.1</td>
<td>19.75</td>
<td>20.29</td>
<td>8.50</td>
</tr>
<tr class="odd">
<td>Seed</td>
<td>0.330-0.345</td>
<td>18-24</td>
<td>40</td>
<td>&lt;0.01</td>
<td>0.07</td>
<td>0.06</td>
<td>0.01</td>
<td>0.02</td>
<td>0.02</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Plum (field use)</strong></td>
</tr>
<tr class="odd">
<td>Plum</td>
<td>Foliar</td>
<td>1.35</td>
<td>0</td>
<td>12</td>
<td>0.02</td>
<td>0.47</td>
<td>0.41</td>
<td>0.11</td>
<td>0.17</td>
<td>0.16</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Plum (post-harvest use)</strong></td>
</tr>
<tr class="odd">
<td rowspan="3">Plum</td>
<td>Foliar only</td>
<td>1.35</td>
<td>0</td>
<td>4</td>
<td>0.01</td>
<td>0.02</td>
<td>0.02</td>
<td>0.01</td>
<td>0.01</td>
<td>0.005</td>
</tr>
<tr class="even">
<td>Foliar only</td>
<td>1.35 + COC<sup>9</sup></td>
<td>0</td>
<td>4</td>
<td>0.05</td>
<td>0.11</td>
<td>0.08</td>
<td>0.06</td>
<td>0.06</td>
<td>0.026</td>
</tr>
<tr class="odd">
<td>Foliar + 1-3x post-harvest</td>
<td>1.35 + 0.225 to 0.675 lb ai/200K lb</td>
<td>0</td>
<td>24</td>
<td>0.09</td>
<td>0.44</td>
<td>0.36</td>
<td>0.20</td>
<td>0.22.</td>
<td>0.086</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Cherry (post-harvest use)
<sup>4</sup></strong></td>
</tr>
<tr class="odd">
<td rowspan="6">Cherry</td>
<td>Foliar only (Trt#2)</td>
<td>1.35</td>
<td rowspan="6">0</td>
<td>14</td>
<td>0.49</td>
<td>1.05</td>
<td>0.99</td>
<td>0.75</td>
<td>0.78</td>
<td>0.18</td>
</tr>
<tr class="even">
<td>Foliar + low rate post-harvest (Trt#3)</td>
<td>1.58</td>
<td>6</td>
<td>0.57</td>
<td>2.02</td>
<td>1.89</td>
<td>0.87</td>
<td>1.12</td>
<td>0.61</td>
</tr>
<tr class="odd">
<td>Foliar + medium rate post-harvest (Trt#4)</td>
<td>1.69</td>
<td>6</td>
<td>0.76</td>
<td>2.37</td>
<td>2.25</td>
<td>1.14</td>
<td>1.40</td>
<td>0.68</td>
</tr>
<tr class="even">
<td>Foliar + high rate post-harvest (Trt#5)</td>
<td>1.80</td>
<td>14</td>
<td>0.50</td>
<td>3.55</td>
<td>2.17</td>
<td>1.08</td>
<td>1.26</td>
<td>0.79</td>
</tr>
<tr class="odd">
<td>Foliar + high rate post-harvest w/ wax (Trt#6)</td>
<td>1.80</td>
<td>12</td>
<td>0.33</td>
<td>2.60</td>
<td>2.33</td>
<td>0.88</td>
<td>1.22</td>
<td>0.85</td>
</tr>
<tr class="even">
<td>High rate post-harvest only (Trt#7)</td>
<td>0.450</td>
<td>6</td>
<td>0.33</td>
<td>1.10</td>
<td>0.96</td>
<td>0.79</td>
<td>0.75</td>
<td>0.30</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Turnip</strong></td>
</tr>
<tr class="even">
<td>Turnip, roots</td>
<td>Foliar</td>
<td>0.76-0.83</td>
<td>6-8</td>
<td>10</td>
<td>&lt;0.05</td>
<td>0.23</td>
<td>0.19</td>
<td>0.14</td>
<td>0.13</td>
<td>0.06</td>
</tr>
<tr class="odd">
<td><p>Turnip, tops</p>
<p>1<sup>st</sup> harvest</p>
<p>2d harvest</p></td>
<td>Foliar</td>
<td><p>0.56-063</p>
<p>0.20-0.21</p></td>
<td>6-8</td>
<td>20</td>
<td>0.75</td>
<td>5.62</td>
<td>5.22</td>
<td>1.10</td>
<td>1.76</td>
<td>1.37</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Cucurbits</strong></td>
</tr>
<tr class="odd">
<td>Summer squash</td>
<td>Foliar</td>
<td>0.45-0.691</td>
<td>2-3</td>
<td>4</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>NA</td>
</tr>
<tr class="even">
<td></td>
<td></td>
<td></td>
<td>6-7</td>
<td>10</td>
<td>&lt;0.05</td>
<td>0.07</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Cucumber</td>
<td>Foliar</td>
<td>0.425-0.629</td>
<td>2</td>
<td>12</td>
<td>0.01</td>
<td>0.06</td>
<td>0.06</td>
<td>0.03</td>
<td>0.03</td>
<td>0.016</td>
</tr>
<tr class="even">
<td>Cantaloupe</td>
<td>Foliar</td>
<td>0.732-1.09</td>
<td>3</td>
<td>4</td>
<td>0.028</td>
<td>0.076</td>
<td>0.066</td>
<td>0.050</td>
<td>0.051</td>
<td>0.020</td>
</tr>
<tr class="odd">
<td></td>
<td></td>
<td></td>
<td>6-8</td>
<td>8</td>
<td>0.013</td>
<td>0.052</td>
<td>0.039</td>
<td>0.024</td>
<td>0.026</td>
<td>0.017</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Sweet Corn</strong></td>
</tr>
<tr class="odd">
<td>Forage</td>
<td rowspan="3">Broadcast Foliar</td>
<td rowspan="3">0.67-0.68</td>
<td>7</td>
<td>24</td>
<td>0.22</td>
<td>6.60</td>
<td>5.85</td>
<td>1.03</td>
<td>1.41</td>
<td>1.49</td>
</tr>
<tr class="even">
<td>Ears</td>
<td>7</td>
<td>24</td>
<td>&lt;0.01</td>
<td>0.44</td>
<td>0.37</td>
<td>0.05</td>
<td>0.10</td>
<td>0.12</td>
</tr>
<tr class="odd">
<td>Stover</td>
<td>27-59</td>
<td>22</td>
<td>0.07</td>
<td>5.70</td>
<td>4.65</td>
<td>0.57</td>
<td>0.92</td>
<td>1.30</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Field Corn</strong></td>
</tr>
<tr class="odd">
<td>Forage</td>
<td rowspan="3">Broadcast Foliar</td>
<td rowspan="3">0.67-0.70</td>
<td>1-29 <sup>5</sup></td>
<td>40</td>
<td>0.07</td>
<td>3.82</td>
<td>2.90</td>
<td>0.40</td>
<td>0.63</td>
<td>0.83</td>
</tr>
<tr class="even">
<td>Grain</td>
<td>36-71</td>
<td>40</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Stover</td>
<td>36-71</td>
<td>40</td>
<td>&lt;0.02</td>
<td>2.40</td>
<td>2.35</td>
<td>0.22</td>
<td>0.42</td>
<td>0.51</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Wheat</strong></td>
</tr>
<tr class="odd">
<td rowspan="3">Forage</td>
<td rowspan="3">Broadcast Foliar</td>
<td rowspan="3">1.8-2.1 oz ai/A</td>
<td>6-8</td>
<td>32</td>
<td>0.20</td>
<td>2.67</td>
<td>2.51</td>
<td>0.71</td>
<td>0.91</td>
<td>0.50</td>
</tr>
<tr class="even">
<td>0</td>
<td>2</td>
<td>5.60</td>
<td>8.63</td>
<td>8.63</td>
<td>7.11</td>
<td>7.11</td>
<td>2.14</td>
</tr>
<tr class="odd">
<td>14-22</td>
<td>4</td>
<td>&lt;0.10</td>
<td>0.43</td>
<td>0.43</td>
<td>0.13</td>
<td>0.18</td>
<td>0.17</td>
</tr>
<tr class="even">
<td rowspan="3">Hay</td>
<td rowspan="3">Broadcast Foliar</td>
<td rowspan="3">1.8-2.1 oz ai/A</td>
<td>6-8</td>
<td>34</td>
<td>0.19</td>
<td>5.65</td>
<td>5.31</td>
<td>5.31</td>
<td>1.76</td>
<td>1.12</td>
</tr>
<tr class="odd">
<td>0</td>
<td>2</td>
<td>9.60</td>
<td>13.2</td>
<td>13.2</td>
<td>11.4</td>
<td>11.4</td>
<td>2.54</td>
</tr>
<tr class="even">
<td>10-15</td>
<td>4</td>
<td>0.27</td>
<td>1.99</td>
<td>1.99</td>
<td>1.24</td>
<td>1.19</td>
<td>0.84</td>
</tr>
<tr class="odd">
<td>Straw</td>
<td>Broadcast Foliar</td>
<td>1.8-2.1 oz ai/A</td>
<td>32-69</td>
<td>34</td>
<td>0.09</td>
<td>1.32</td>
<td>1.27</td>
<td>0.14</td>
<td>0.32</td>
<td>0.44</td>
</tr>
<tr class="even">
<td>Grain</td>
<td>Broadcast Foliar</td>
<td>1.8-2.1 oz ai/A</td>
<td>32-69</td>
<td>34</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>NA</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Pecans</strong></td>
</tr>
<tr class="even">
<td>Nutmeat</td>
<td>Foliar</td>
<td>0.9</td>
<td>12-50</td>
<td>10</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>NA</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Almonds</strong></td>
</tr>
<tr class="even">
<td>Nutmeat</td>
<td>Foliar</td>
<td>0.9</td>
<td>25-49</td>
<td>18</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>&lt;0.05</td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Almond Hulls</td>
<td>Foliar</td>
<td>0.9</td>
<td>25-49</td>
<td>18</td>
<td>1.00</td>
<td>4.13</td>
<td>4.13</td>
<td>2.01</td>
<td>2.23</td>
<td>1.38</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Domestic Hops</strong></td>
</tr>
<tr class="odd">
<td>Hop cones, dried</td>
<td>Foliar</td>
<td>0.913-0.916</td>
<td>13-15</td>
<td>6</td>
<td>0.58</td>
<td>3.42</td>
<td>3.17</td>
<td>1.06</td>
<td>1.65</td>
<td>1.20</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Imported Hops</strong></td>
</tr>
<tr class="odd">
<td rowspan="3">Dried Cones</td>
<td rowspan="3">Foliar applications</td>
<td rowspan="3">0.95-1.05</td>
<td>14</td>
<td>8</td>
<td>7.00</td>
<td>26.0</td>
<td>26.0</td>
<td>10.10</td>
<td>11.98</td>
<td>6.35</td>
</tr>
<tr class="even">
<td>21</td>
<td>8</td>
<td>5.80</td>
<td>21.0</td>
<td>21.0</td>
<td>9.65</td>
<td>11.05</td>
<td>5.75</td>
</tr>
<tr class="odd">
<td>28</td>
<td>8</td>
<td>3.00</td>
<td>18.0</td>
<td>18.0</td>
<td>4.80</td>
<td>6.69</td>
<td>4.90</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Cotton <sup>6</sup></strong></td>
</tr>
<tr class="odd">
<td rowspan="5">Undelinted Seed</td>
<td rowspan="7">Broadcast Foliar</td>
<td rowspan="5">0.66-0.69</td>
<td>22-25</td>
<td>11</td>
<td>&lt;0.05</td>
<td>0.17</td>
<td>0.17</td>
<td>0.03</td>
<td>0.04</td>
<td>0.04</td>
</tr>
<tr class="even">
<td>28-32</td>
<td>11</td>
<td>&lt;0.05</td>
<td>0.22</td>
<td>0.22</td>
<td>0.03</td>
<td>0.04</td>
<td>0.06</td>
</tr>
<tr class="odd">
<td>35-39</td>
<td>11</td>
<td>&lt;0.05</td>
<td>0.12</td>
<td>0.12</td>
<td>0.03</td>
<td>0.04</td>
<td>0.04</td>
</tr>
<tr class="even">
<td>29-32</td>
<td>6 <sup>7</sup></td>
<td>0.09</td>
<td>0.78</td>
<td>0.70</td>
<td>0.43</td>
<td>0.41</td>
<td>0.27</td>
</tr>
<tr class="odd">
<td>29-32</td>
<td>6 <sup>8</sup></td>
<td>0.09</td>
<td>1.89</td>
<td>1.66</td>
<td>0.42</td>
<td>0.73</td>
<td>0.75</td>
</tr>
<tr class="even">
<td rowspan="2">Gin Byproducts</td>
<td rowspan="2">0.66-0.69</td>
<td rowspan="2">29-32</td>
<td>6 <sup>7</sup></td>
<td>0.20</td>
<td>4.20</td>
<td>4.10</td>
<td>1.47</td>
<td>1.92</td>
<td>1.79</td>
</tr>
<tr class="odd">
<td>6 <sup>8</sup></td>
<td>6.23</td>
<td>15.20</td>
<td>13.45</td>
<td>11.00</td>
<td>10.74</td>
<td>3.31</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Asparagus, domestic</strong></td>
</tr>
<tr class="odd">
<td>Ferns</td>
<td>Foliar applications</td>
<td>0.512-0.541</td>
<td>100-199</td>
<td>16</td>
<td>&lt;0.02</td>
<td>&lt;0.02</td>
<td>&lt;0.02</td>
<td>&lt;0.02</td>
<td>&lt;0.02</td>
<td>NA</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Asparagus, imported</strong></td>
</tr>
<tr class="odd">
<td>Ferns</td>
<td>Foliar applications</td>
<td>0.45</td>
<td>29-30</td>
<td>6</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>NA</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Coffee Beans, imported</strong></td>
</tr>
<tr class="odd">
<td>Mature bean</td>
<td>Foliar applications</td>
<td>1.12</td>
<td>28-30</td>
<td>8</td>
<td>&lt;0.01</td>
<td>0.066</td>
<td>0.063</td>
<td>&lt;0.01</td>
<td>0.02</td>
<td>0.027</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Garlic, imported</strong></td>
</tr>
<tr class="odd">
<td>Heads</td>
<td>Seed piece + 3 drench</td>
<td>0.49 lb ai/2000 lb + 1.34</td>
<td>37</td>
<td>4</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>&lt;0.01</td>
<td>NA</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Onion, dry bulb, imported</strong></td>
</tr>
<tr class="odd">
<td>Bulb</td>
<td>Foliar applications</td>
<td>0.67</td>
<td>7</td>
<td>4</td>
<td>&lt;0.1</td>
<td>&lt;0.1</td>
<td>&lt;0.1</td>
<td>&lt;0.1</td>
<td>&lt;0.1</td>
<td>NA</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Mango, post-harvest</strong></td>
</tr>
<tr class="odd">
<td rowspan="3">Whole fruit</td>
<td rowspan="3">Post-harvest</td>
<td>0.00176 lb ai/1000 lb</td>
<td>0</td>
<td>4</td>
<td>0.0554</td>
<td>0.0737</td>
<td>0.0646</td>
<td>0.060</td>
<td>0.060</td>
<td>0.0089</td>
</tr>
<tr class="even">
<td>0.00275 lb ai/1000 lb</td>
<td>0</td>
<td>2</td>
<td>0.0746</td>
<td>0.100</td>
<td>0.087</td>
<td>0.087</td>
<td>0.087.</td>
<td>0.018</td>
</tr>
<tr class="odd">
<td>0.004 lb ai/1000 lb</td>
<td>0</td>
<td>2</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>NA</td>
</tr>
<tr class="even">
<td rowspan="3">Peel only</td>
<td rowspan="3">Post-harvest</td>
<td>0.00176 lb ai/1000 lb</td>
<td>0</td>
<td>5</td>
<td>0.219</td>
<td>0.252</td>
<td>0.242</td>
<td>0.228</td>
<td>0.23</td>
<td>0.012</td>
</tr>
<tr class="odd">
<td>0.00275 lb ai/1000 lb</td>
<td>0</td>
<td>2</td>
<td>0.686</td>
<td>0.739</td>
<td>0.71</td>
<td>0.71</td>
<td>0.71</td>
<td>0.037</td>
</tr>
<tr class="even">
<td>0.004 lb ai/1000 lb</td>
<td>0</td>
<td>2</td>
<td>0.409</td>
<td>0.341</td>
<td>0.375</td>
<td>0.375</td>
<td>0.375</td>
<td>0.048</td>
</tr>
<tr class="odd">
<td rowspan="3">Pulp only</td>
<td rowspan="3">Post harvest</td>
<td>0.00176 lb ai/1000 lb</td>
<td>0</td>
<td>4</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>NA</td>
</tr>
<tr class="even">
<td>0.00275 lb ai/1000 lb</td>
<td>0</td>
<td>2</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>NA</td>
</tr>
<tr class="odd">
<td>0.004 lb ai/1000 lb</td>
<td>0</td>
<td>2</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>NA</td>
</tr>
<tr class="even">
<td colspan="11"><strong>Okra</strong></td>
</tr>
<tr class="odd">
<td>Whole</td>
<td>Foliar applications</td>
<td>0.887-0.944</td>
<td>3-4</td>
<td>12</td>
<td>&lt;0.050</td>
<td>0.59</td>
<td>0.40</td>
<td>0.22</td>
<td>0.22</td>
<td>0.17</td>
</tr>
<tr class="even">
<td></td>
<td></td>
<td>0.902</td>
<td>4-8</td>
<td>4</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>&lt;0.050</td>
<td>NA</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Lychee</strong></td>
</tr>
<tr class="even">
<td>Whole</td>
<td>Foliar applications</td>
<td>1.34-1.38</td>
<td>0</td>
<td>6</td>
<td>0.12</td>
<td>0.98</td>
<td>0.84</td>
<td>0.75</td>
<td>0.71</td>
<td>0.25</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Sunflower</strong></td>
</tr>
<tr class="even">
<td rowspan="2">Seed</td>
<td rowspan="2">Foliar applications</td>
<td>0.450-0.465</td>
<td>48-58</td>
<td>14</td>
<td>&lt;0.040</td>
<td>&lt;0.040</td>
<td>&lt;0.040</td>
<td>&lt;0.040</td>
<td>&lt;0.040</td>
<td>NA</td>
</tr>
<tr class="odd">
<td>2.25-2.33</td>
<td>48-58</td>
<td>14</td>
<td>&lt;0.040</td>
<td>0.128</td>
<td>0.126</td>
<td>0.062</td>
<td>0.050</td>
<td>0.033</td>
</tr>
</tbody>
</table>

^1^ The Method LOQ for tebuconazole is 0.01 ppm in plums, soybean forage
and seeds, sweet corn ears, forage, and stover, field corn grain and
forage, 0.02 ppm in field corn stover, 0.05 ppm in cotton seed,
cherries, and soybean hay, and dried hops, and 0.20 ppm in cotton gin
byproducts. For calculation of the median, mean, and standard deviation,
½LOQ was used for samples with residues \<LOQ.

^2^ HAFT = Highest Average Field Trial.

^3^ STMdR = Supervised Trial Median Residue; STMR = Supervised Trial
Mean Residue.

^4^ The post-harvest trials for cherries included a prior treatment at
the 1x field rate except in one treatment

^5^ The forage from field corn was collected at variable intervals with
no particular post-treatment interval accounting for the majority of
samples.

^6^ The cotton was harvested by hand unless otherwise indicated.

^7^ The cotton was harvested using a mechanical stripper.

^8^ The cotton was harvested using a mechanical picker.

^9^ COC = 1% v/v crop oil concentrate

<table style="width:100%;">
<colgroup>
<col style="width: 14%" />
<col style="width: 17%" />
<col style="width: 7%" />
<col style="width: 0%" />
<col style="width: 6%" />
<col style="width: 8%" />
<col style="width: 8%" />
<col style="width: 8%" />
<col style="width: 8%" />
<col style="width: 8%" />
<col style="width: 9%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="11"><strong>Table 5.10.1b. Cont. Summary of Residue Data
from Field Trials with Tebuconazole (FlC)</strong></th>
</tr>
<tr class="odd">
<th rowspan="2">Crop matrix</th>
<th rowspan="2">Total Applic. Rate (lb ai/A)</th>
<th colspan="2" rowspan="2">PHI (days)</th>
<th colspan="7">Residue Levels (ppm) <sup>1</sup></th>
</tr>
<tr class="header">
<th>n</th>
<th>Min.</th>
<th>Max.</th>
<th>HAFT <sup>2</sup></th>
<th>Median</th>
<th>Mean</th>
<th>Std. Dev.</th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td colspan="11"><strong>Green Onions (proposed use = 0.672 lb ai/A
total application rate, 7-day PHI)</strong></td>
</tr>
<tr class="even">
<td>Green onions</td>
<td>0.67-0.72</td>
<td>7-8</td>
<td colspan="2">6</td>
<td>0.06</td>
<td>0.80</td>
<td>0.80</td>
<td>0.11</td>
<td>0.32</td>
<td>0.37</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Bulb Onions (proposed use = 0.336 lb ai/A total
application rate, 7-day PHI)</strong></td>
</tr>
<tr class="even">
<td>Bulb onions <sup>3</sup></td>
<td>0.65-0.69</td>
<td>6-7</td>
<td colspan="2">16</td>
<td>&lt;0.05</td>
<td>0.09</td>
<td>0.09</td>
<td>0.05</td>
<td>0.06</td>
<td>0.01</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Bulb Onions (proposed use = 0.91 lb ai/A total
application rate, 7-day PHI)</strong></td>
</tr>
<tr class="even">
<td>Bulb onions <sup>4</sup></td>
<td><p>0.89-1.04</p>
<p>(2.26) <sup>5</sup></p></td>
<td>5-7</td>
<td colspan="2">18</td>
<td>&lt;0.020</td>
<td>0.101</td>
<td>0.061</td>
<td>0.025</td>
<td>0.031</td>
<td>0.020</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Mustard Greens (proposed use = 0.45 lb ai/A,
7-day PHI)</strong></td>
</tr>
<tr class="even">
<td>Mustard greens</td>
<td>0.45-0.47</td>
<td>6-7</td>
<td colspan="2">14</td>
<td>0.073</td>
<td>1.40</td>
<td>1.23</td>
<td>0.90</td>
<td>0.75</td>
<td>0.44</td>
</tr>
<tr class="odd">
<td colspan="11"><strong>Garden Beets (proposed use = 0.81 lb ai/A,
7-day PHI)</strong></td>
</tr>
<tr class="even">
<td>Roots</td>
<td>0.79-0.92</td>
<td>6-8</td>
<td colspan="2">14</td>
<td>&lt;0.03</td>
<td>0.47</td>
<td>0.45</td>
<td>0.09</td>
<td>0.17</td>
<td>0.16</td>
</tr>
<tr class="odd">
<td rowspan="2">Tops (leaves)</td>
<td>0.60-0.62 <sup>6</sup></td>
<td>6-8</td>
<td colspan="2">14</td>
<td>0.12</td>
<td>2.02</td>
<td>1.91</td>
<td>0.67</td>
<td>0.76</td>
<td>0.60</td>
</tr>
<tr class="even">
<td>0.79-0.93 <sup>7</sup></td>
<td>6-7</td>
<td colspan="2">14</td>
<td>0.21</td>
<td>3.76</td>
<td>3.52</td>
<td>0.97</td>
<td>1.22</td>
<td>1.10</td>
</tr>
</tbody>
</table>

^1^ The LOQ for tebuconazole was 0.03 ppm for green onions, mustard
greens, and beet roots, 0.02 or 0.045 ppm for bulb onion, and 0.05 ppm
for beet tops. For calculating the median, mean and standard deviation,
the LOQ was used for residue values at \<LOQ.

^2^ HAFT = Highest average field trial residues.

^3^ Bulb onions received four broadcast foliar applications.

^4^ Bulb onions received an in-furrow application at planting followed
by two broadcast foliar applications.

^5^ In one bulb onion field trial, the in-furrow application was made at
3.3x the target rate. However, by normal crop maturity, exaggerated
in-furrow application rate did not result in higher residue levels than
from the 1x in-furrow rate. Therefore, the residue data from this test
were included with the data from the 1x tests.

^6^ Beet tops harvested following three broadcast foliar applications.

^7^ Beet tops harvested following four broadcast foliar applications.

[*Processing Studie*s]{.underline}: Adequate processing studies on
apple, coffee, corn, cotton, plum, and soybean were submitted. The field
corn and cotton processing studies indicate that tebuconazole residues
do not concentrate in field corn and cotton processed fractions.
Residues were also reduced (≤0.3x) in apple juice and applesauce, but
concentrated in wet apple pomace by 3.3x. Based on the highest average
field trial (HAFT) residues of 0.02 ppm for apples and the 3.3x
processing factor, the maximum expected residues in wet apple pomace
would be 0.066 ppm, which exceeds the proposed 0.05 ppm tolerance for
pome fruits. A separate tolerance should be proposed at 0.1 ppm for
residues in wet apple pomace. In the coffee processing study, residues
concentrated 2x in roasted coffee beans, and were reduced in instant
coffee. In the plum processing study, residues also concentrated
slightly (1.2x) in prunes. Based on HAFT residues of 0.41 ppm for plums
and the 1.2x processing factor, the maximum expected residues in prunes
would be 0.49 ppm, which is well below the proposed 1.0 ppm tolerance
for stone fruits. Therefore a separate tolerance for prunes is not
required. Separate tolerances are also not required for processed
soybean commodities as residues were either reduced (≤0.4x) in meal and
oil or concentrated only slightly (1.1x) in hulls. However, the soybean
data indicate that a separate tolerance will be necessary for aspirated
grain fractions (AGF). Based on the 276x processing factor observed for
soybean AGF and HAFT residues of 0.055 ppm in/on soybean seed, the
maximum expected residues in soybean AGF would be 16 ppm. AGF of corn
and wheat were not analyzed, as the residues in the grain were
non-quantifiable (\<0.05 ppm).

*[Livestock]{.underline}*: Tolerances for tebuconazole residues in
livestock commodities were recently reassessed in conjunction with
petitions for use on pome fruits, stone fruits and various commodities
mentioned above (D287292, S. Hummel, 27-Nov-07). The current tolerances
for meat byproducts (0.2 ppm) of cattle, goats, horses, and sheep could
be reduced to 0.1 ppm. The current tolerance for milk (0.1 ppm) could be
revoked, as it is not needed. The data also indicate that the
time-limited tolerance for residues in meat byproducts of hogs (0.1 ppm)
should be revoked. Tolerances are not required for meat and fat of
cattle, goats, hogs, horses or sheep, or for eggs and poultry
commodities.

Although these changes to the livestock tolerances could be made, since
they are currently harmonized with Canada, HED recommends retaining the
current tolerances (and tolerance expression), and in discussion with
Canada, consider these changes in the future.

**5.1.11 International Residue Limits**[]{#__RefHeading___Toc196283154
.anchor}

There are currently Codex, Canadian and Mexican maximum residue limits
(MRLs) for residues of tebuconazole in/on a variety of plant and
livestock commodities (See Appendix D). The tolerance definition for
residues in plants is tebuconazole, *per se*, for Codex, Canada, and
Mexico. For livestock commodities, the tolerance expression is for the
combined residues of tebuconazole and HWG 2061 in the U.S. and Canada,
and tebuconazole, *per se*, for Codex. Where possible, the proposed
tolerances levels have been harmonized with the MRLs from Canada,
Mexico, and Codex.

**5.2 Dietary Exposure and Risk**[]{#__RefHeading___Toc196283155
.anchor}

> **Reference:** D349724, Sheila Piper, 3/3/08

Acute and chronic aggregate dietary exposure and risk assessments were
conducted using the Dietary Exposure Evaluation Model (DEEM-FCID™),
Version 2.03, which uses food consumption data from the U.S. Department
of Agriculture's Continuing Surveys of Food Intakes by Individuals
(CSFII) from 1994-1996 and 1998. The analyses were performed as part of
a registration action; (1) to support the proposed FIFRA sec. 3
registration (or amended registration or FFDCA/import) of the fungicide,
tebuconazole, on asparagus, barley, beans, coffee (import), corn,
cotton, cucurbits, garlic (import), hops, lychee, mango, okra, onions
(import), pome fruit, soybean, stone fruit, sunflower, tree nuts, turf,
turnips and wheat; as well as a previously proposed Section 18 emergency
exemption for the use of tebuconazole to control soybean rust on
specialty legumes; (2) to support a petition for tolerances in
conjunction with an Interregional Research Project No. 4 (IR-4) petition
for new uses of the fungicide, tebuconazole, on bulb vegetables,
*Brassica* and garden beet roots and leaves; (3) to include drinking
water estimates reflecting Bayer's proposal for changes to the label on
turf and ornamental uses; and (4) to incorporate the new evaluation of
the acute and chronic toxicological endpoints into the dietary risk
assessment.

Refined, acute probabilistic and chronic dietary exposure assessments
were conducted for all existing and proposed new food uses of
tebuconazole and drinking water. Anticipated residues for a few
currently registered commodities (bananas, grapes, raisins, nectarines,
peaches, peanut butter and wheat) were derived using the latest USDA
Pesticide Data Program (PDP) monitoring data from 2002- 2006.
Anticipated residues for all other registered and proposed food
commodities were based on field trial data. Projected percent crop
treated (%CT) data were used to refine anticipated residues for a few
proposed new uses that were determined in preliminary acute analyses to
contribute heavily to dietary exposure (apples, apricots, cherries,
hops, plums and sweet corn). For the remaining new uses, all of the
crops were assumed treated. Available processing data were used to
refine anticipated residues for apple juice (translated to cherry and
pear juice), plums (translated to apricots dried), coffee (roasted
bean), grapes (juice), plums (prunes/prune juice) and peanut (oil). For
all other processed commodities, DEEM (ver. 7.81) default processing
factors were assumed.

A distribution of estimated concentrations of tebuconazole in drinking
water was provided by EFED and incorporated directly into the acute
assessment. The acute assessment was conducted using the full
distribution of estimated residues in surface water generated by the
PRZM-EXAMS model, which was based on the ground application of
tebuconazole to turf in Florida, as that provided the distribution with
the highest concentrations of total residues of tebuconazole in surface
water. For the chronic assessment, the highest relevant concentration
was used, which was the 1-in-10 yr annual mean (44.9 µg/L) for surface
water, resulting from the ground application of tebuconazole to turf in
Pennsylvania.

Estimated acute dietary exposure to tebuconazole from food and drinking
water is below HED's level of concern for all population subgroups
(\<100% aPAD) using the FL turf scenario for drinking water. Combined
dietary exposure from food and drinking water at the 99.9^th^ percentile
of exposure is estimated to be 0.008171 mg/kg/day for the overall U.S.
population, equivalent to 28% of the acute Population Adjusted Dose
(aPAD). The population subgroup with the highest estimated acute dietary
exposure to tebuconazole is infants \<1 year old, with an estimated
exposure at the 99.9^th^ percentile of 0.015297 mg/kg/day, equivalent to
53% of the aPAD.

Chronic dietary exposure estimates for food and using the PA turf
drinking water scenario are well below HED's level of concern (\<100%
cPAD) for all population subgroups. The dietary exposure is estimated at
0.001126 mg/kg/day for the general U.S. population (4% of the chronic
Population Adjusted Dose (cPAD)) and 0.003295 mg/kg/day (11% of the
cPAD) for infants \<1 year old, the population subgroup with the highest
estimated chronic dietary exposure to tebuconazole.

**5.2.1 Acute Dietary Exposure/Risk**[]{#__RefHeading___Toc196283156
.anchor}

+----------------+--------+-------+-----+-------+-----+-------+------+
| **Table 5.2.1. |        |       |     |       |     |       |      |
| Results of     |        |       |     |       |     |       |      |
| Acute Dietary  |        |       |     |       |     |       |      |
| (Food +        |        |       |     |       |     |       |      |
| Drinking       |        |       |     |       |     |       |      |
| Water)         |        |       |     |       |     |       |      |
| Exposure and   |        |       |     |       |     |       |      |
| Risk for       |        |       |     |       |     |       |      |
| Tebuconazole** |        |       |     |       |     |       |      |
+================+========+=======+=====+=======+=====+=======+======+
| Population     | aPAD   | 9     |     | 99th  |     | 99.   |      |
| Subgroup       | (mg/k  | 5^th^ |     | Perce |     | 9^th^ |      |
|                | g/day) | Perce |     | ntile |     | Perce |      |
|                |        | ntile |     |       |     | ntile |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
|                |        | Exp   | \%  | Exp   | \%  | Exp   | \%   |
|                |        | osure | a   | osure | a   | osure | aPAD |
|                |        | (     | PAD | (     | PAD | (     |      |
|                |        | mg/kg |     | mg/kg |     | mg/kg |      |
|                |        | /day) |     | /day) |     | /day) |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| General U.S.   | 0.029  | 0.0   | 7   | 0.0   | 13  | 0.0   | 28   |
| Population     |        | 02088 |     | 03913 |     | 08171 |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| **All          |        | **    | **2 | **    | **3 | **    | **   |
| Infants**      |        | 0.005 | 0** | 0.009 | 1** | 0.015 | 53** |
|                |        | 841** |     | 105** |     | 297** |      |
| **(\< 1 year   |        |       |     |       |     |       |      |
| old)**         |        |       |     |       |     |       |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| Children 1-2   |        | 0.0   | 11  | 0.0   | 19  | 0.0   | 47   |
| years old      |        | 03065 |     | 05452 |     | 13514 |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| Children 3-5   |        | 0.0   | 10  | 0.0   | 18  | 0.0   | 53   |
| years old      |        | 02746 |     | 05283 |     | 15286 |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| Children 6-12  |        | 0.0   | 7   | 0.0   | 12  | 0.0   | 26   |
| years old      |        | 01940 |     | 03546 |     | 07633 |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| Youth 13-19    |        | 0.0   | 5   | 0.0   | 12  | 0.0   | 27   |
| years old      |        | 01579 |     | 03500 |     | 07873 |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| Adults 20-49   |        | 0.0   | 7   | 0.0   | 12  | 0.0   | 23   |
| years old      |        | 01986 |     | 03473 |     | 06785 |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| Adults 50+     |        | 0.0   | 6   | 0.0   | 11  | 0.0   | 25   |
| years old      |        | 01789 |     | 03293 |     | 07332 |      |
+----------------+--------+-------+-----+-------+-----+-------+------+
| Females 13-49  |        | 0.0   | 6   | 0.0   | 11  | 0.0   | 21   |
| years old      |        | 01773 |     | 03125 |     | 06092 |      |
+----------------+--------+-------+-----+-------+-----+-------+------+

**5.2.2 Chronic Dietary Exposure/Risk**[]{#__RefHeading___Toc196283157
.anchor}

+--------------------+------------+----------+-----------+-------------+
| **Table 5.2.2.     |            |          |           |             |
| Results of Chronic |            |          |           |             |
| Dietary Exposure   |            |          |           |             |
| and Risk for       |            |          |           |             |
| Tebuconazole**     |            |          |           |             |
+====================+============+==========+===========+=============+
|                    | Food Only  |          | Food and  |             |
|                    |            |          | Drinking  |             |
|                    |            |          | Water     |             |
+--------------------+------------+----------+-----------+-------------+
| Population         | Exposure   | \% cPAD  | Exposure  | \% cPAD     |
| Subgroup           |            |          |           |             |
|                    | (          |          | (m        |             |
|                    | mg/kg/day) |          | g/kg/day) |             |
+--------------------+------------+----------+-----------+-------------+
| General U.S.       | 0.000180   | \<1      | 0.001126  | 4           |
| Population         |            |          |           |             |
+--------------------+------------+----------+-----------+-------------+
| **All Infants (\<  | **         | \<1      | **0       | **11**      |
| 1 year old)**      | 0.000192** |          | .003295** |             |
+--------------------+------------+----------+-----------+-------------+
| Children 1-2 years | 0.000294   | 1        | 0.001699  | 6           |
| old                |            |          |           |             |
+--------------------+------------+----------+-----------+-------------+
| Children 3-5 years | 0.000265   | \<1      | 0.001581  | 6           |
| old                |            |          |           |             |
+--------------------+------------+----------+-----------+-------------+
| Children 6-12      | 0.000168   | \<1      | 0.001075  | 4           |
| years old          |            |          |           |             |
+--------------------+------------+----------+-----------+-------------+
| Youth 13-19 years  | 0.000129   | \<1      | 0.000814  | 3           |
| old                |            |          |           |             |
+--------------------+------------+----------+-----------+-------------+
| Adults 20-49 years | 0.000187   | \<1      | 0.001071  | 4           |
| old                |            |          |           |             |
+--------------------+------------+----------+-----------+-------------+
| Adults 50+ years   | 0.000160   | \<1      | 0.001090  | 4           |
| old                |            |          |           |             |
+--------------------+------------+----------+-----------+-------------+
| Females 13-49      | 0.000128   | \<1      | 0.001008  | 4           |
| years old          |            |          |           |             |
+--------------------+------------+----------+-----------+-------------+

**5.2.3 Cancer Dietary Risk**[]{#__RefHeading___Toc196283158 .anchor}

Tebuconazole is classified as a Group C Carcinogen-Possible Human
Carcinogen based on statistically significant increase in the incidence
of liver tumors in both sexes of mice (TXR# 0052724). The chronic risk
assessment is considered to be protective of any cancer effects;
therefore, a separate quantitative cancer dietary risk assessment is not
required.

**5.3 Anticipated Residue and Percent Crop Treated (%CT)
Information**[]{#__RefHeading___Toc196283159 .anchor}

**Reference:** D331887, Alan Halvorson and Tara Chandgoyal, 11/30/2006.

Anticipated residues for bananas, grapes, raisins, nectarines, peaches,
peanut butter and wheat were derived using the latest USDA Pesticide
Data Program (PDP) monitoring data from 2002-2006. Anticipated residues
for all other registered and proposed food commodities were based on
field trial data. Anticipated residues for all current uses were further
refined using percent crop treated (%CT) data, following the guidance
provided in HED SOP 99.6 (*Classification of Food Forms with Respect to
level of Blending*; 8/20/99). Projected %CT data were used to refine
anticipated residues for a few proposed new uses that were determined in
preliminary acute analyses to contribute heavily to dietary exposure
(apples, apricots, cherries, hops, plums and sweet corn). See Table 5.3
below for details. For the remaining new uses, all of the crops were
assumed treated.

  ----------------------------------- -----------------------------------
  **Table 5.3 Percent Crop Treated    
  Summary Table**                     

  **Projected % Crop Treated**        

  Crop                                Projected % Treated

  Apple                               44

  Apricot                             56

  Cherry, Preharvest only             42

  Corn, sweet                         22

  Hop                                 64

  Plum                                26

  Turnip                              68

  **% Crop Treated**                  

  Crop                                \% Treated

  Grape                               25

  Grape, raisin                       25

  Nectarine                           25

  Oats                                2.5

  Peach                               20

  Peanut                              45
  ----------------------------------- -----------------------------------

**6.0 Residential (Non-Occupational) Exposure/Risk
Characterization**[]{#__RefHeading___Toc196283160 .anchor}

**References:** D346795, Barry O'Keefe, 11/26/07.

> D349926, Barry O'Keefe, 3/13/08.

There is the potential for handler and postapplication exposure in
residential settings from existing and/or proposed uses of tebuconazole.
Therefore, risk assessments were conducted for residential handlers as
well as for residential postapplication exposures that can occur as a
result of these tebuconazole uses.

Short-term dermal and inhalation exposures are possible for residential
adult handlers mixing, loading, and applying tebuconazole products
outdoors to ornamental plants. Short- and intermediate-term dermal
postapplication exposures to adults and children are also possible
during golfing and/or playing on treated wood structures. Children may
also be exposed via the incidental oral route when playing on treated
wood structures. Long-term exposure is not expected. As a result, risk
assessments have been completed for residential handler scenarios as
well as residential postapplication scenarios.

**6.1 Residential Handler Exposure**[]{#__RefHeading___Toc196283161
.anchor}

Several currently registered products containing tebuconazole can be
applied to residential ornamentals. Applications can be made by
homeowners by the following methods:

1\) soil drench from a bucket or watering can;

2\) pump style sprayer;

3\) dial style hose-end sprayer;

4\) concentrate plus water hose-end sprayer; and

5\) ready-to-use trigger sprayer.

To assess the watering can handler exposure a conservative assessment
approach was used, *i.e.*, using the highest application rate on roses
of 0.0053 lb ai/gal of solution and a hose-end sprayer. It is
anticipated that the following scenarios should conservatively cover the
most highly exposed residential pesticide handler
mixer/loader/applicator exposures:

-   mixing/loading/applying liquids with a hand held pump sprayer
    (residential ORETF data --ornamentals; MRID 44518501, OMA005);

-   mixing/loading/applying liquids with hose-end sprayer (residential
    ORETF data --ornamentals; MRID 44518501, OMA005);

-   mixing/loading/applying liquids with backpack sprayer (PHED); and

-   mixing/loading/applying liquids with a ready-to-use (RTU) trigger
    sprayer (residential ORETF data -- home gardens; MRID 44459801,
    OMA006).

The factors used for this tebuconazole assessment were those presented
in the Exposure Science Advisory Committee's Policy No. 12: *Recommended
Revisions To The Standard Operating Procedures For Residential Exposure
Assessment* which was completed on February 22, 2001. HED assumes
residential handlers wear shorts and short-sleeved shirts with no
gloves. Additionally, HED believes these residential handler exposures
are mostly of short-term duration. However, some intermediate-term
exposures may occur since multiple applications (3 to 4) are allowed by
the labels. Nevertheless, since the endpoint and point of departure is
the same for all short- and intermediate-term dermal and inhalation
exposures the risk estimates are the same. Table 6.1 presents the
exposure/risk estimates for these exposure scenarios at baseline for
residential handlers. The MOEs for combined dermal and inhalation
exposures range from 420 to 140,000 for the representative residential
handler scenarios, which do not exceed the level of concern (LOC) of an
MOE of 300 or less. Therefore, the estimated risks are not of concern.

**Table 6.1. Residential Handler Exposure and Risk Estimates from
Treating Ornamentals**

<table>
<colgroup>
<col style="width: 9%" />
<col style="width: 25%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 6%" />
</colgroup>
<tbody>
<tr class="odd">
<td><strong>Exposure Scenarios for M/L/A with Liquids</strong></td>
<td><strong>Unit Exposure Data Source</strong></td>
<td><strong>Baseline Dermal Unit Exposure (mg/lb ai)</strong></td>
<td><strong>Baseline Inhal. Unit Exposure (µg/lb ai)</strong></td>
<td><p><strong>Max. Applic. Rate<sup>1</sup></strong></p>
<p><strong>(lb ai/gal soln)</strong></p></td>
<td><strong>Amount Handled Daily (gal/day)</strong></td>
<td><p><strong>Daily Dermal Exposure<sup>2</sup></strong></p>
<p><strong>(mg/kg/day)</strong></p></td>
<td><p><strong>Daily Inhal.</strong></p>
<p><strong>Exposure<sup>2</sup></strong></p>
<p><strong>(mg/kg/day)</strong></p></td>
<td><strong>Daily Total Exposure (mg/kg/day)</strong></td>
<td><strong>Total MOE<sup>3</sup></strong></td>
</tr>
<tr class="even">
<td>Hand Held Pump Sprayer</td>
<td>ORETF (3.5.03, G. Bangs); MRID 44518501, OMA005: Resident M/L/A –
handheld pump sprayer: fruit trees and ornamentals</td>
<td>56</td>
<td>2.6</td>
<td>0.0053</td>
<td>5</td>
<td>5.71E-3</td>
<td>1.15E-6</td>
<td>5.71E-3</td>
<td>1,500</td>
</tr>
<tr class="odd">
<td>Hose-end sprayer</td>
<td>ORETF (3.5.03, G. Bangs); MRID 44518501, OMA005: Resident M/L/A -
hose-end sprayer: fruit trees and ornamentals</td>
<td>39</td>
<td>1.6</td>
<td>0.0014</td>
<td>100</td>
<td>2.10E-2</td>
<td>3.73E-6</td>
<td>2.10E-2</td>
<td>420</td>
</tr>
<tr class="even">
<td>Backpack sprayer</td>
<td>Surrogate PHED V1.1 Appendix B; Backpack/Liquid/Open Pour (MLAP) Low
confidence, both dermal and inhalation unit exposure</td>
<td>5.1</td>
<td>30</td>
<td>0.0014</td>
<td>5</td>
<td>1.37E-4</td>
<td>3.50E-6</td>
<td>1.41E-4</td>
<td>63,000</td>
</tr>
<tr class="odd">
<td>RTU Trigger Sprayer</td>
<td>ORETF (3.5.03, G. Bangs); MRID 44459801, OMA006: Resident M/L/A –
ready-to-use sprayer: home garden</td>
<td>54</td>
<td>19</td>
<td>0.0012</td>
<td>0.25</td>
<td>6.24E-5</td>
<td>9.50E-8</td>
<td>6.25E-5</td>
<td>140,000</td>
</tr>
</tbody>
</table>

^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 60-kg; where
dermal absorption is 23.1%. 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 Postapplication
Exposure**[]{#__RefHeading___Toc196283162 .anchor}

The term "postapplication" describes exposures to individuals that occur
as a result of being in an environment that has been previously treated
with a pesticide. Since tebuconazole can be used on ornamentals, shrubs,
trees, and flowers in many residential areas that can be entered by the
general population, as well as on golf courses, individuals can be
exposed via the dermal route by entering these treated areas.
Additionally tebuconazole is impregnated in wood, and children playing
on tebuconazole-treated wood structures can be exposed via the dermal
and/or incidental oral route. Inhalation exposures are thought to be
negligible in outdoor postapplication scenarios, since tebuconazole has
low vapor pressure and the dilution factor outdoors is considered
infinite.

*Ornamentals*

Although tebuconazole is applied to ornamental plants, postapplication
exposure is expected to be minimal compared to handler exposure.
Therefore, the residential handler exposure and risk assessment for the
ornamental use (Section 6.1) is considered protective of any
postapplication exposure to ornamental plants.

*Golf Courses*

Golfers have the potential for dermal exposure to tebuconazole, since
residues may be contacted from treated golf course turf. Based on the
discussion presented in the Exposure SAC document (Child Golfer Exposure
Characterization 9/29/03) the child golfer's exposure is likely to be
similar to that of the adult golfer. Hence, there is only one potential
non-occupational postapplication scenario associated with tebuconazole
use on golf course turf, *i.e.*, adults golfing. The duration of
exposure is anticipated to be short-term.

Adult exposure during golfing activities was estimated using a dermal
transfer coefficient from the Science Advisory Council For Exposure
Policy Number 3.1: Agricultural Transfer Coefficients, August 2000. In
1996, the registrant submitted a turf transferable residue (TTR) study
(MRID 44108303) in which turf was treated with tebuconazole (LYNX). The
TTR data from this study was generated using rollers that are relevant
to HED transfer coefficients, and therefore, these data can be used as
reliable estimates of day zero tebuconazole residues on treated turf.
The study was conducted in three locations (Florida, New Jersey and
Kansas) representing the geographically distinct southeastern,
northeastern and midwestern regions of the United States. At each site,
LYNX was applied at a rate of 1.36 lb ai/acre. The turf dislodgeable
residue samples were collected by the PUF roller method, designed by
Hsu, *et. al.*, 1990, with modifications as described by Ross *et. al.*,
1991. The day zero, tebuconazole transferable residue levels were 0.028,
0.43, and 0.50 µg/cm^2^ (*i.e.*, 0.3%, 3.8% & 3.9% transferability) for
the FL, NJ, and KS sites, respectively. The highest transferable residue
value of 0.50 µg/cm^2^was used to compute an estimated daily dose and
MOE, as follows:

Daily Dose = (Turf Transferable Residue x 1E-3 mg/µg x Dermal Transfer
Coefficient x Dermal Absorption Factor x Exposure Time) / Body weight

Daily Dose = 0.50 µg/cm^2^ x 1E-3 mg/µg x 500 cm^2^/hr x 23.1% x 4 hrs
per day / 60 kg = 0.00384 mg/kg/day

ST Dermal MOE = LOAEL (8.8 mg/kg/day) /Daily Dose (0.00246 mg/kg/day) =
2300

The MOE for the adult golfer is 2300, which does not exceed the LOC MOE
of 300, and therefore is not of concern.

*Treated Wood Surfaces*

The residential exposure scenario assessed for tebuconazole-treated wood
is children playing on tebuconazole-treated wood structures, since the
labels do not preclude wood being used for structures such as decks and
children's playsets. A screening level residential exposure assessment
of toddlers/children has been conducted to assess risk resulting from
this use site (exposure is expected via the dermal and incidental oral
routes). These postapplication exposures are assessed for the day after
application (day "1") because it is assumed that toddlers could contact
the treated wood immediately after the application has dried (which
takes 24 hours, based on the product data sheets). Although adults may
also experience postapplication exposure, it is expected to be less than
the postapplication exposure of children, since adults are only exposed
via the dermal route and their surface area to body mass is more
protective than that of children. Therefore, adult postapplication
exposure was not assessed.

At this time there are no chemical-specific surface wipe residue data
available to assess the dermal and incidental oral exposure for children
playing on treated wood structures. Therefore, HED chose to use the same
approach used by the Antimicrobial Division (AD) in their recent
assessment of exposures to propiconazole treated wood surfaces (D330159,
Timothy Leighton, 6/20/06). A deterministic screening-level assessment
was developed by AD using exposure algorithms and parameters from the
probabilistic Stochastic Human Exposure and Dose Simulation (SHEDS)
model (SHEDS-Wood Final Report. February, 2005) to assess children's
exposure to propiconazole treated wood products. Several tebuconazole
wood preservative labels contain equivalent concentrations of
propiconazole and tebuconazole (see Appendix C for more detailed
information).

The deterministic algorithm/model requires the user to input the wood
surface residue available for transfer to a human contacting the treated
wood (*i.e.*, a "transferable residue"). Until the propiconazole
assessment, wood transferable residue data had not been estimated
without a wood wipe study. Subsequently, AD determined a high-end,
conservative transferable residue value of 1 µg/cm^2^ by selecting a
value higher than the maximum residue seen for chromium and
non-chromium-based wood preservatives (products for which AD had wood
wipe studies). The transferable residue value of 1 µg/cm^2^ accounts for
the skin reduction factor, or "transfer efficiency" from a cloth wipe
(*i.e.*, cloth wipe surface residues are higher than that available to
the skin) and represents a bounding estimate of the steady state amount
of residue on a hand wiping the surface of treated wood (this value also
makes sense based on the application rates for tebuconazole on wood).
However, the registrant has proposed reducing the amount/concentration
of tebuconazole impregnated into wood solely intended for above ground
uses, resulting in a maximum retention rate of 0.02 lbs ai/cu ft of
wood. This scaled down retention rate results in a surface residue
concentration of 0.4 µg/cm^2^ (assuming a linear relationship between
retention rate and resulting wood transferable residues). This surface
residue concentration was used to estimate exposure and MOEs for wood
intended for above ground uses (see Table 6.2) in addition to the
surface residue concentration of 1.0 µg/cm^2^, which was used to
estimate exposure and MOEs for wood intended for below ground uses.

The frequency of exposure is believed to be best represented by the
short-term duration; *i.e.*, 1 to 30 days of continuous exposure.
Intermediate-term exposures are also possible; *i.e.*, a small portion
of the population of children may play continuously on treated
structures up to 6 months at a time. However, for tebuconazole, the
short- and intermediate-term endpoints are identical, and therefore,
result in the same risk estimate.

The potential daily dose (PDD) from a short-/intermediate-term exposure
event for the dermal route of exposure is estimated using the following
modified equation from the SHEDS report (*i.e.*, SHEDS Appendix 2 page
A2-5):

PDD = [SR x SA x DA x CF1]{.underline}

BW

where:

PDD = Potential daily dose (mg/kg/day);

SR = 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 - see Appendix C for more detailed information);

SA = Total surface area, assuming 100% contacts the treated area, of
unclothed body areas (1,710 cm^2^ warm weather), plus 10% of clothed
body areas (352.5 cm^2^ warm weather - see Appendix C for more detailed
information);

DA = Dermal absorption (23%, from a dermal absorption study in the
monkey);

CF1 = Unit conversion factor (0.001 mg/µg); and

BW = Body weight (15 kg).

The results of the **dermal exposure** assessment indicate an absorbed
dose of 0.032 and 0.013 mg/kg/day for below and above ground treatment
rates, respectively. The margin of exposures (MOEs) are 280 and 690 for
below and above ground treatment rates, respectively, with a level of
concern (LOC) MOE of 300 (see Table 6.2). Therefore, this risk estimate
is somewhat below the protective value of 300 for the below ground
treatment rate.

The potential daily dose (PDD) from a short-/intermediate-term exposure
event via the incidental oral route of exposure is estimated using the
following modified equation from the SHEDS report (*i.e.*, SHEDS
Appendix 2 page A2-8):

PDD = [SR x SA x FQ x ET x SE x CF1]{.underline}

BW

where:

PDD = Potential daily dose (mg/kg/day);

SR = Wood surface residue adjusted for dermal transfer or "transfer
efficiency" (EPA high end assumption of 1 μg/cm^2^ see dermal exposure
section above for more information on this value) (D330159, Timothy
Leighton, 6/20/06);

SA = Surface area of the hands that contact both the treated area, and
the individuals mouth (20 cm^2^/event) (Exposure SAC SOP Policy No. 12,
Revised February 22, 2001);

FQ = Frequency of hand-to-mouth events (mean 8.45 events/hr) (SHEDS-Wood
Final Report. February, 2005);

SE = Saliva extraction efficiency (50% unitless fraction) (Exposure SAC
SOP Policy No. 12, Revised February 22, 2001);

ET = Exposure Time (mean 1 hr/day) (SHEDS-Wood Final Report. February,
2005);

CF1 = Unit conversion factor (0.001 mg/µg); and

BW = Body weight (15 kg) (Exposure SAC SOP Policy No. 12, Revised
February 22, 2001).

The results of the incidental oral exposure assessment indicate a dose
of 0.0045 and 0.0018 mg/kg/day, which result in MOEs of 1900 and 4,900
for below and above ground treatment rates, respectively. Since the LOC
is an MOE of 300 or less, this screening-level assessment indicates no
risk of concern alone via the incidental oral route of exposure (see
Table 6.2 for details).

Since the dermal and incidental oral endpoints are the same, and since
dermal and incidental oral exposures may occur simultaneously, these
exposures can be combined to determine a total MOE. Table 6.2 presents
the combined risk via these two routes for wood treated for below and
above ground uses. The combined or total MOEs for below and above ground
uses are 240 and 600, respectively. The combined MOE for wood treated
for below ground uses exceeds HED's LOC, and therefore indicates a
potential risk of concern. However, the combined MOE for wood treated
for above ground uses does not exceed the LOC, and therefore is not of
concern. Exposure to above ground wood is expected to more closely
represent actual exposures to children. Frequency of exposures to above
ground wood should greatly exceed any exposures to below ground wood.
Therefore, this assessment should be characterized as a conservative
screening-level assessment. However, HED recognizes children may be
exposed to some wood intended for below ground uses (*e.g.*, deck
pilings and playset support beams). Subsequently, the HED Exposure SAC
recommends that a wood wipe study on transferable residues from
tebuconazole-treated wood be submitted as confirmatory data to better
inform the exposure assessment.

+-------------+------------+-------------+-------------+-------------+
| **Table     |            |             |             |             |
| 6.2.        |            |             |             |             |
| Assessment  |            |             |             |             |
| of Children |            |             |             |             |
| Playing on  |            |             |             |             |
| Wood        |            |             |             |             |
| Structures  |            |             |             |             |
| Treated     |            |             |             |             |
| with        |            |             |             |             |
| Tebu        |            |             |             |             |
| conazole**. |            |             |             |             |
+-------------+------------+-------------+-------------+-------------+
| Exposure    | Exposure   |             | Short-/I    |             |
|             | (mg/       |             | ntermediate |             |
|             | kg/day)^a^ |             | --Term MOEs |             |
|             |            |             |             |             |
|             |            |             | (LOC        |             |
|             |            |             | =300)^b^    |             |
+-------------+------------+-------------+-------------+-------------+
| Assumed     | 1.0        | 0.4         | 1.0         | 0.4         |
| T           | µg/cm^2^   | µg/cm^2^    | µg/cm^2^    | µg/cm^2^    |
| ransferable | Below      | Above       | Below       | Above       |
| Residue     | Ground     | Ground Wood | Ground Wood | Ground Wood |
|             | Wood       |             |             |             |
+-------------+------------+-------------+-------------+-------------+
| Dermal      | 0.032      | 0.013       | 280         | 690         |
| Contact     |            |             |             |             |
+-------------+------------+-------------+-------------+-------------+
| Incidental  | 0.0045     | 0.0018      | 1,900       | 4,900       |
| Oral        |            |             |             |             |
+-------------+------------+-------------+-------------+-------------+
| Combined    | 0.037      | 0.015       | 240         | 600         |
+-------------+------------+-------------+-------------+-------------+

a Dose (mg/kg/day) = See above equations for dermal and oral exposure.
Aggregate dose = dermal dose + oral dose.

b MOEs = ST/IT NOAEL (mg/kg/day) / Dose (mg/kg/day). Where ST/IT NOAEL =
8.8 mg/kg/day. LOC MOE = 300.

**6.3 Other (Spray Drift, *etc.*)**[]{#__RefHeading___Toc196283163
.anchor}

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 ground application method employed for
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. On a chemical by chemical basis, 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 database submitted by the Spray Drift Task 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 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 with specific products with significant risks
associated with drift.

It is noted that there are a number of residential exposure scenarios
assessed in this document. In particular, a residential golfer dermal
exposure and risk assessment based on a 1.36 lb ai/A application rate
for turf (which is about 3-6x higher than most agricultural use rates),
as well as a postapplication residential exposure (via the dermal and
incidental oral routes) and risk assessment of toddlers playing on
treated wood surfaces. As the scenarios assessed deal with direct
treatment, sometimes at higher treatment rates than agricultural
application rates, these scenario are likely protective of any exposure
of farm children via spray drift from agricultural tebuconazole
applications.

**7.0 Aggregate Risk Assessments and Risk
Characterization**[]{#__RefHeading___Toc196283164 .anchor}

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 Aggregate Risk**[]{#__RefHeading___Toc196283165 .anchor}

Refer to Section 5.2, which discusses acute dietary exposure (food and
water) 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.

**7.2 Short-/Intermediate-Term Aggregate
Risk**[]{#__RefHeading___Toc196283166 .anchor}

The short-/intermediate-term aggregate 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 \[dietary exposure estimates use point estimates for
food and drinking water residues (anticipated residues based on field
trial and PDP data, and tolerance level residues) and the residential
scenarios also employ point estimates (central to high-end values
considered protective)\]. Exposures 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-term exposures (1 to 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, the
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 aggregate risk assessments
are considered protective.

+--------+----------+--------+----+--------+--------+--------+--------+
| *      |          |        |    |        |        |        |        |
| *Table |          |        |    |        |        |        |        |
| 7.2.   |          |        |    |        |        |        |        |
| Shor   |          |        |    |        |        |        |        |
| t-Term |          |        |    |        |        |        |        |
| and    |          |        |    |        |        |        |        |
| Inter  |          |        |    |        |        |        |        |
| mediat |          |        |    |        |        |        |        |
| e-Term |          |        |    |        |        |        |        |
| Agg    |          |        |    |        |        |        |        |
| regate |          |        |    |        |        |        |        |
| Risk   |          |        |    |        |        |        |        |
| Ca     |          |        |    |        |        |        |        |
| lculat |          |        |    |        |        |        |        |
| ions** |          |        |    |        |        |        |        |
+========+==========+========+====+========+========+========+========+
| **     | **Res    | ***S   |    |        |        |        |        |
| Popula | idential | hort-/ |    |        |        |        |        |
| tion** | Sc       | Interm |    |        |        |        |        |
|        | enario** | ediate |    |        |        |        |        |
|        |          | *-Term |    |        |        |        |        |
|        |          | Scena  |    |        |        |        |        |
|        |          | rios** |    |        |        |        |        |
+--------+----------+--------+----+--------+--------+--------+--------+
|        |          | **L    | ** | **Max  | **Ave  | *      | **Agg  |
|        |          | OAEL** | LO | Allow  | rage** | *Resid | regate |
|        |          |        | C^ | able** |        | ential | MOE**  |
|        |          | *      | 1^ |        | **Food | E      |        |
|        |          | *mg/kg | ** | **E    | &      | xposur | *      |
|        |          | /day** |    | xposur | W      | e^3^** | *(food |
|        |          |        |    | e^2^** | ater** |        | and**  |
|        |          |        |    |        |        | *      |        |
|        |          |        |    | *      | **Expo | *mg/kg | *      |
|        |          |        |    | *mg/kg | sure** | /day** | *resid |
|        |          |        |    | /day** |        |        | ential |
|        |          |        |    |        | *      |        | )^4^** |
|        |          |        |    |        | *mg/kg |        |        |
|        |          |        |    |        | /day** |        |        |
+--------+----------+--------+----+--------+--------+--------+--------+
| G      | Handler  | 8.8    | 3  | 0.029  | 0.     | 0.021  | 400    |
| eneral | using    |        | 00 |        | 001126 |        |        |
| U.S.   | Hose-end |        |    |        |        | (      |        |
| Popu   | sprayer, |        |    |        |        | dermal |        |
| lation | orn      |        |    |        |        | and    |        |
|        | amentals |        |    |        |        | inhal  |        |
|        |          |        |    |        |        | ation) |        |
+--------+----------+--------+----+--------+--------+--------+--------+
|        | Golfer,  | 8.8    | 3  | 0.029  | 0.     | 0      | 1800   |
|        | turf     |        | 00 |        | 001126 | .00384 |        |
|        |          |        |    |        |        |        |        |
|        |          |        |    |        |        | (d     |        |
|        |          |        |    |        |        | ermal) |        |
+--------+----------+--------+----+--------+--------+--------+--------+
| F      | Handler  | 8.8    | 3  | 0.029  | 0.     | 0.021  | 400    |
| emales | using    |        | 00 |        | 001008 |        |        |
| 13-49  | Hose-end |        |    |        |        | (      |        |
|        | sprayer, |        |    |        |        | dermal |        |
|        | orn      |        |    |        |        | and    |        |
|        | amentals |        |    |        |        | inhal  |        |
|        |          |        |    |        |        | ation) |        |
+--------+----------+--------+----+--------+--------+--------+--------+
|        | Golfer,  | 8.8    | 3  | 0.029  | 0.     | 0      | 1800   |
|        | turf     |        | 00 |        | 001008 | .00384 |        |
|        |          |        |    |        |        |        |        |
|        |          |        |    |        |        | (d     |        |
|        |          |        |    |        |        | ermal) |        |
+--------+----------+--------+----+--------+--------+--------+--------+
| Ch     | Toddler, | 8.8    | 3  | 0.029  | 0.     | 0.015  | 530    |
| ildren | above    |        | 00 |        | 001581 |        |        |
| 3-5    | ground   |        |    |        |        | (inci  |        |
|        | wood     |        |    |        |        | dental |        |
|        | surfaces |        |    |        |        | oral   |        |
|        |          |        |    |        |        | and    |        |
|        |          |        |    |        |        | d      |        |
|        |          |        |    |        |        | ermal) |        |
+--------+----------+--------+----+--------+--------+--------+--------+
|        | Toddler, | 8.8    | 3  | 0.029  | 0.     | 0.037  | 230    |
|        | below    |        | 00 |        | 001581 |        |        |
|        | ground   |        |    |        |        | (inci  |        |
|        | wood     |        |    |        |        | dental |        |
|        | surfaces |        |    |        |        | oral   |        |
|        |          |        |    |        |        | and    |        |
|        |          |        |    |        |        | d      |        |
|        |          |        |    |        |        | ermal) |        |
+--------+----------+--------+----+--------+--------+--------+--------+

*^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 estimates.*

*^4^ Aggregate MOE = \[LOAEL / (Avg Food & Water Exposure + Residential
Exposure)\]*

Note: The aggregate MOE for a child's exposure to wood treated at the
below ground rate is 230, this is very similar to the combined dermal
and incidental oral MOE of 240 (which does not consider background
dietary exposure). This indicates background dietary exposure does not
significantly contribute to this aggregate exposure scenario (children
being exposed to tebuconazole-treated wood surfaces treated at the below
ground application rate). The combined and aggregate MOEs for wood
treated for below ground uses exceed HED's LOC, and indicate a potential
risk of concern. However, the combined/aggregate MOEs for wood treated
for above ground uses does not exceed the LOC, and exposure to above
ground wood is expected to more closely represent actual exposures to
children. Frequency of exposures to above ground wood is expected to
exceed exposures to below ground wood. Therefore, this assessment should
be characterized as a conservative screening-level assessment.

**7.3 Long-Term Aggregate Risk**[]{#__RefHeading___Toc196283167 .anchor}

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

**7.4 Cancer Risk**[]{#__RefHeading___Toc196283168 .anchor}

Tebuconazole is classified as a Group C Carcinogen-Possible Human
Carcinogen based on statistically significant increase in the incidence
of liver tumors in both sexes of mice (TXR No. 0052724). The chronic
risk assessment is considered to be protective of any cancer effects;
therefore, a separate quantitative cancer aggregate risk assessment is
not required (*i.e.*, the chronic risk assessment is considered to be
protective of any cancer effects).

**8.0 Cumulative Risk
Characterization/Assessment**[]{#__RefHeading___Toc196283169 .anchor}

Tebuconazole is a member of the triazoles (and more specifically,
triazole-derivative fungicides). Although triazoles act similarly in
plants (fungi) by inhibiting ergosterol biosynthesis, there is not
necessarily a relationship between their pesticidal activity and their
mechanism of toxicity in mammals. 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. In triazole-derivative
fungicides, however, a variable pattern of toxicological responses is
found: some are hepatotoxic and hepatocarcinogenic in mice; some induce
thyroid tumors in rats; and some induce developmental, reproductive, and
neurological effects in rodents. Furthermore, the triazoles produce a
diverse range of biochemical events including altered 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 triazole-derivative fungicides share common mechanisms of
toxicity and EPA is not following a cumulative risk approach based on a
common mechanism of toxicity for the triazole-derivative fungicides. For
information regarding EPA's procedures for cumulating effects from
substances found to have a common mechanism of toxicity, see EPA's
website at http://www.epa.gov/pesticides/cumulative.

However, the triazole-derivative fungicides can form the common
metabolites 1,2,4-triazole and conjugated triazole metabolites. To
support existing tolerances and to establish new tolerances for
triazole-derivative fungicides, including tebuconazole, U.S. EPA
conducted a human health risk assessment for exposure to 1,2,4-triazole,
triazolylalanine, and triazolylacetic acid resulting from the use of all
current and pending uses of any triazole-derivative fungicide. The risk
assessment is a highly conservative, screening-level evaluation in terms
of hazards associated 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
10X 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 reregistration docket at
http://www.regulations.gov, Docket Identification (ID) Number
EPA-HQ-OPP-2005-0497.

In connection with the pending new uses of tebuconazole (and other
triazole-derivative fungicides), HED has revised the triazole dietary
assessment to include the new uses of tebuconazole and has determined
that aggregate risk (food, water and residential) remains below HED's
level of concern (D350315, Michael Doherty, 3/27/08).

**9.0 Occupational Exposure/Risk
Pathway**[]{#__RefHeading___Toc196283170 .anchor}

**Reference:** D349913, Barry O'Keefe, 3/5/08.

This document addresses aggregate risk for all currently proposed
tolerances and existing and proposed non-food residential uses; however,
it only supports new registrations for wheat, barley, and tree nuts.
Occupational risk assessments for all other use sites (including
occupational exposure to golf course maintenance workers) will be
provided in a separate document (D315464).

**9.1 Short-/Intermediate -Term Handler
Risk**[]{#__RefHeading___Toc196283171 .anchor}

Occupational handlers may experience short-/intermediate-term exposure
to tebuconazole while mixing/loading and applying sprays to wheat and
barley. No chemical-specific handler exposure data were submitted in
support of this use pattern. It is the policy of the HED to use data
from the Pesticide Handlers Exposure Database (PHED) Version 1.1 as
presented in PHED Surrogate Exposure Guide (8/98) to assess handler
exposures when chemical-specific monitoring data are not available ( HED
Science Advisory Council for Exposure Draft Policy \# 7, dated 1/28/99).

Exposure assumptions and MOE estimates are summarized in Table 9.1.
Since the dermal and inhalation endpoints are the same, and since dermal
and inhalation exposures may occur simultaneously, these exposures can
be combined to determine a total margin of exposure (MOE); *i.e.* dermal
and inhalation exposures are summed. The MOEs for combined dermal and
inhalation exposures range from 410 to 8800 for the representative
occupational handler scenarios, indicating risks do not exceed the level
of concern (LOC) of an MOE of 300 or less, and therefore are not of
concern with baseline clothing, or in some cases, when gloves are used
to mitigate exposure.

The minimum level of PPE for handlers is based on acute toxicity for the
end-use product. The Registration Division (RD) is responsible for
ensuring that PPE listed on the label is in compliance with the Worker
Protection Standard (WPS).

+------------------------+----+------+-------+-------+------+-------+
| **Table 9.1.           |    |      |       |       |      |       |
| Sh                     |    |      |       |       |      |       |
| ort-/Intermediate-Term |    |      |       |       |      |       |
| Occupational Risk      |    |      |       |       |      |       |
| Estimates for          |    |      |       |       |      |       |
| Tebuconazole use on    |    |      |       |       |      |       |
| Wheat, Barley and Tree |    |      |       |       |      |       |
| nuts.** All estimates  |    |      |       |       |      |       |
| are at baseline        |    |      |       |       |      |       |
| mitigation (except for |    |      |       |       |      |       |
| mixing/loading which   |    |      |       |       |      |       |
| requires the PPE       |    |      |       |       |      |       |
| gloves to reach the    |    |      |       |       |      |       |
| LOC). The dermal and   |    |      |       |       |      |       |
| inhalation LOAEL (POD) |    |      |       |       |      |       |
| is 8.8 mg/kg/day.      |    |      |       |       |      |       |
+========================+====+======+=======+=======+======+=======+
| **Exposure Scenario**  | *  | **De | **    | **Ma  | **Am | **Sho |
|                        | *C | rmal | Inhal | ximum | ount | rt-/I |
|                        | ro | Unit | ation | A     | T    | nt-** |
|                        | ps | Expo | Unit  | pplic | reat |       |
|                        | ** | sure | Exp   | ation | ed** | **t   |
|                        |    | (m   | osure | R     |      | erm** |
|                        |    | g/lb | (     | ate** | *    |       |
|                        |    | ai)  | mg/lb |       | *(A/ | **Com |
|                        |    | ^    | ai)   | **(lb | day) | bined |
|                        |    | 1^** | ^2^** | ai/A) | ^    | MOE   |
|                        |    |      |       | ^3^** | 4^** | ^5^** |
+------------------------+----+------+-------+-------+------+-------+
| Mixer/Loader           |    |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Mixing/Loading Liquid  | Wh | 0    | 0     | 0.11  | 200  | 3700  |
| (open pour) for        | ea | .023 | .0012 |       |      |       |
| Groundboom application | t, | (w   |       |       |      |       |
|                        | Ba | /glo |       |       |      |       |
|                        | rl | ves) |       |       |      |       |
|                        | ey |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
|                        | P  | 0    | 0     | 0.23  | 80   | 1200  |
|                        | ec | .023 | .0012 |       |      |       |
|                        | an | (w   |       |       |      |       |
|                        |    | /glo |       |       |      |       |
|                        |    | ves) |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Mixing/Loading Liquid  | Wh | 0    | 0     | 0.11  | 1200 | 620   |
| (open pour) for Aerial | ea | .023 | .0012 |       |      |       |
| application            | t, | (w   |       |       |      |       |
|                        | Ba | /glo |       |       |      |       |
|                        | rl | ves) |       |       |      |       |
|                        | ey |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
|                        | P  | 0    | 0     | 0.23  | 350  | 1000  |
|                        | ec | .023 | .0012 |       |      |       |
|                        | an | (w   |       |       |      |       |
|                        |    | /glo |       |       |      |       |
|                        |    | ves) |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Mixing/Loading Liquid  | P  | 0    | 0     | 0.23  | 40   | 8800  |
| (open pour) for        | ec | .023 | .0012 |       |      |       |
| Airblast application   | an | (w   |       |       |      |       |
|                        |    | /glo |       |       |      |       |
|                        |    | ves) |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Mixing/Loading Dry     | Tr | 0    | 0.    | 0.23  | 350  | 410   |
| Flowable (open pour)   | ee | .066 | 00077 |       |      |       |
| for Aerial application | Nu | (w   |       |       |      |       |
|                        | ts | /glo |       |       |      |       |
|                        |    | ves) |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Mixing/Loading Dry     | Tr | 0    | 0.    | 0.23  | 40   | 3600  |
| Flowable (open pour)   | ee | .066 | 00077 |       |      |       |
| for Airblast           | Nu | (w   |       |       |      |       |
| application            | ts | /glo |       |       |      |       |
|                        |    | ves) |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Applicator             |    |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Groundboom application | Wh | 0    | 0.    | 0.11  | 200  | 6000  |
|                        | ea | .014 | 00074 |       |      |       |
|                        | t, |      |       |       |      |       |
|                        | Ba |      |       |       |      |       |
|                        | rl |      |       |       |      |       |
|                        | ey |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Aerial application     | Wh | 0.   | 0.0   | 0.11  | 1200 | 3300  |
| (Enclosed Cockpit)     | ea | 0050 | 00068 |       |      |       |
|                        | t, |      |       |       |      |       |
|                        | Ba |      |       |       |      |       |
|                        | rl |      |       |       |      |       |
|                        | ey |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
|                        | Pe | 0    | 0.0   | 0.23  | 350  | 5300  |
|                        | ca | .005 | 00068 |       |      |       |
|                        | n, |      |       |       |      |       |
|                        | Tr |      |       |       |      |       |
|                        | ee |      |       |       |      |       |
|                        | Nu |      |       |       |      |       |
|                        | ts |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Airblast application   | Pe | 0.36 | 0     | 0.23  | 40   | 660   |
| (Open Cab)             | ca |      | .0045 |       |      |       |
|                        | n, |      |       |       |      |       |
|                        | Tr |      |       |       |      |       |
|                        | ee |      |       |       |      |       |
|                        | Nu |      |       |       |      |       |
|                        | ts |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Flagger                |    |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
| Flagging for Aerial    | Wh | 0    | 0.    | 0.11  | 350  | 4800  |
| application            | ea | .011 | 00035 |       |      |       |
|                        | t, |      |       |       |      |       |
|                        | Ba |      |       |       |      |       |
|                        | rl |      |       |       |      |       |
|                        | ey |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+
|                        | Pe | 0    | 0.    | 0.23  | 350  | 2300  |
|                        | ca | .011 | 00035 |       |      |       |
|                        | n, |      |       |       |      |       |
|                        | Tr |      |       |       |      |       |
|                        | ee |      |       |       |      |       |
|                        | Nu |      |       |       |      |       |
|                        | ts |      |       |       |      |       |
+------------------------+----+------+-------+-------+------+-------+

^1^ Dermal unit exposure values represent baseline clothing (long pants,
long sleeved shirts, shoes, and socks), except where the addition of
gloves is indicated.

^2^ Inhalation unit exposure values represent exposure without use of a
respirator.

^3^ Application rates are based on maximum proposed values.

^4^ Amount treated is the area that can be reasonably applied in a
single day for each exposure scenario of concern, based on the
application method and formulation/packaging type. (Standard EPA/OPP/HED
values).

^5^ Short-/Intermediate-Term Combined MOE = LOAEL (8.8 mg/kg/day) /
\[Daily Absorbed Short-/Intermediate-Term Dermal +
Short-/Intermediate-Term Inhalation Dose\]. The LOC is 300. Daily
Absorbed Dermal Dose (mg/kg/day) = \[Dermal unit exposure \* 23.1%
(Dermal absorption) \* Application rate \* Area treated\] / 60-kg Body
weight. Daily Absorbed Inhalation Dose (mg/kg/day) = \[Inhalation unit
exposure \* 100% (Inhalation absorption) \* Application rate \* Area
treated\] / 60-kg Body weight.

**9.2 Short-/Intermediate-Term Postapplication
Risk**[]{#__RefHeading___Toc196283172 .anchor}

Foliar applications of tebuconazole to wheat, barley, and tree nuts
result in the potential for dermal postapplication exposure.
Postapplication inhalation exposure is expected to be negligible during
outdoor postapplication scenarios, since tebuconazole has a relatively
low vapor pressure and the dilution factor outdoors is considered
infinite. HED's dermal postapplication exposure estimates are based on a
surrogate approach due to lack of chemical-specific data for
tebuconazole. The maximum application rate is used in this assessment,
while assumptions regarding dislodgeable foliar residues (DFR) and
workday duration are believed to be average values. Twenty percent of
the residues are assumed available for transfer. A day of treatment
residue value was estimated; *i.e.* after sprays have dried (assumed to
be approximately 12 hours). Dissipation of foliar residues is assumed to
occur at the rate of 10% of the application rate per day. The workday
duration is assumed to be 8 hours. These risk estimates are
characterized as central to high-end. In addition to these residue data,
transfer coefficients (TC) are used to relate the foliage residue values
to activity patterns (*e.g.*, irrigating and scouting) to estimate
potential human exposure. The transfer coefficients used in this
assessment are from an interim transfer coefficient policy developed by
HED's Science Advisory Council for Exposure using proprietary data from
the Agricultural Re-entry Task Force (ARTF) database (policy \# 3.1).
The estimated short-/intermediate-term MOEs are presented in Table 9.2.
For wheat and barley, the results of the postapplication exposure and
risk assessment indicate that MOEs of 300 are achieved on Day 0 for both
scenarios, and therefore are not of concern. For tree nuts, the
activities of irrigating, scouting, and hand weeding also indicate that
an MOE of 300 is achieved on Day 0, and therefore are not of concern.
Although thinning, hand harvest and hand pruning are sometimes
considered in postapplication assessments for tree nuts, the proposed
labels indicate that applications to tree nuts will be made beginning at
early bud break, continuing through pollination and flowering stages,
and ending not too long after petal fall. Also, for pecans, no
applications are allowed after shucks begin to split. Given these
proposed use patterns and the expected cultural practices for tree nuts,
the activities of thinning, hand harvesting, and hand pruning are either
not expected to occur, or should not occur close to the times when
applications are made; and therefore, such activities are not assessed.

The tebuconazole technical material has been classified in Toxicity
Category III for acute dermal and primary eye irritation, and shows no
evidence of skin irritation. Per the Worker Protection Standard (WPS), a
12-hr restricted entry interval (REI) is required for chemicals
classified under Toxicity Category III or IV. Therefore, HED concurs
with the proposed 12-hr REI on the label on the basis of acute toxicity.

<table style="width:100%;">
<colgroup>
<col style="width: 20%" />
<col style="width: 0%" />
<col style="width: 12%" />
<col style="width: 0%" />
<col style="width: 10%" />
<col style="width: 0%" />
<col style="width: 10%" />
<col style="width: 0%" />
<col style="width: 26%" />
<col style="width: 0%" />
<col style="width: 18%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="11"><strong>Table 9.2. Summary of Occupational
Postapplication Risks for Tebuconazole used on Wheat, Barley &amp; Tree
nuts</strong></th>
</tr>
<tr class="odd">
<th><strong>Crops</strong></th>
<th colspan="2"><p><strong>Application Rate</strong></p>
<p><strong>(lb ai/A)</strong></p></th>
<th colspan="2"><strong>DFR <sup>1</sup>
(μg/cm<sup>2</sup>)</strong></th>
<th colspan="2"><strong>TC <sup>2</sup>
(cm<sup>2</sup>/hr)</strong></th>
<th colspan="2"><strong>Activity</strong></th>
<th colspan="2"><strong>Short-/Int-Term MOE <sup>2</sup></strong></th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td colspan="2" rowspan="2">Wheat &amp; Barley</td>
<td colspan="2" rowspan="2">0.11</td>
<td colspan="2" rowspan="2">0.2467</td>
<td colspan="2">100</td>
<td colspan="2">Irrigating &amp; Scouting (minimum foliage
development)</td>
<td>12,000</td>
</tr>
<tr class="even">
<td colspan="2">1500</td>
<td colspan="2">Irrigating &amp; Scouting (full foliage
development)</td>
<td>780</td>
</tr>
<tr class="odd">
<td colspan="2">Tree Nuts, including Pecan</td>
<td colspan="2">0.23</td>
<td colspan="2">0.5046</td>
<td colspan="2">500</td>
<td colspan="2">Irrigating, Scouting, Hand Weeding</td>
<td>1100</td>
</tr>
</tbody>
</table>

^1^ DFR = Application Rate (lb ai/A) x 4.54E+8 µg/lb x 2.47E-8 A/cm^2^ x
Percent Residue Available Day 0 (20%)

^2^ MOE = LOAEL/Daily Dose. Short-/Intermediate-Term LOAEL = 8.8
mg/kg/day. Where Daily Dose = \[DFR x (0.001 mg/µg) x Dermal Transfer
Coefficient x Dermal Absorption Factor (23.1%) x Exposure Time (8 hr)\]
/ \[Body weight (60 kg)\], DAT = days after treatment

**10.0 Data Needs and Label
Recommendations**[]{#__RefHeading___Toc196283173 .anchor}

**10.1 Toxicology**[]{#__RefHeading___Toc196283174 .anchor}

There are no data gaps in the toxicology database.

**10.2 Residue Chemistry**[]{#__RefHeading___Toc196283175 .anchor}

-   The label directions for the use on beans allows applications to
    "fresh" or "dry" beans; however, residue data are only available
    supporting uses on either succulent, podded beans or dry beans. No
    residue data are available on succulent, shelled beans. The
    petitioner must amend the proposed label directions to exclude
    applications to beans grown for production of succulent shelled
    beans. Alternatively, the registrant could provide data from 6 field
    trials supporting the use of tebuconazole (FlC) on succulent,
    shelled beans.

-   The proposed use directions for soybeans should be amended to
    specify a 0-day PHI for soybean forage and hay.

-   A 21 day PHI is needed for field corn forage. If a shorter PHI is
    desired, additional data are required.

-   Data or calculations are needed, showing that the proposed seed
    treatment on corn will result in non-quantifiable residues on corn
    (requested in a 5/6/97 meeting between Gustafson and EPA).

-   Insufficient residue data are available for turnip tops. Two
    additional field trials are needed from Region 10. Alternatively, a
    revised Section B is needed, restricting use to east of the Rockies.

-   Residue data are available on only four pear samples from four field
    trials conducted at the 1x rate. Two additional pear field trials
    should be conducted for pome fruits, one each in Regions 10 and 11.

-   Insufficient residue data are available for melons. The crop group
    tolerance for the Cucurbits, Crop group 9 could be established,
    provided the PHI for cucurbits is changed to 7 days. Four additional
    field trials are needed on melons, two in Region 10, one in Region 2
    and one in Region 5, with a PHI of 3 days, or two additional field
    trials in Region 10, with a revised Section B, specifying a PHI of 6
    days. It appears that residues in melons are higher than residues in
    cucumbers or squash, so these data are critical to support the crop
    group tolerance.

-   Insufficient residue data are available for cucumbers and summer
    squash at the proposed PHI of 3 days. A 7 day PHI is needed. For
    cucumbers, all the field trials had application rates below the 1x
    rate. For summer squash, only 2 field trials are available at the
    proposed PHI of 3 days or less.

-   No residue data are available for barley. Field trial data can be
    translated from wheat, but field trials are still needed from
    regions 9 and 10.

-   Only 7 of the required 8 field trials were conducted on mustard
    greens, which is the representative crop for Brassica leafy greens.
    An additional mustard greens field trial should be conducted in Zone
    3 and submitted for evaluation prior to removing the conditions of
    registration.

-   Due to the substantial difference in residues in/on green and bulb
    onions (\>5x), separate tolerances of 1.3 and 0.2 ppm should be
    established for the bulb onion subgroup (3A) and the green onion
    subgroup (3B) as follows:

    -   Onion, bulb, subgroup 3-07A 0.2 ppm

    -   Onion, green subgroup 3-07B 1.3 ppm

-   A detailed summary of the recommended revisions to petitioned for
    tolerances, (revised Section F) recommended label modifications
    (revised Section B), and data requirements to meet conditions of
    registration is presented in Table 10.2.

+---------------+----------+----------+------------------------------+
| **Table 10.2  |          |          |                              |
| Tolerance     |          |          |                              |
| Summary for   |          |          |                              |
| T             |          |          |                              |
| ebuconazole** |          |          |                              |
+===============+==========+==========+==============================+
| **Crop        | **       | **Rec    | **Comments re: Labels        |
| Commodity**   | Proposed | ommended | (Section B),**               |
|               | or       | T        |                              |
|               | Est      | olerance | **Tolerances (Section F),    |
|               | ablished | (ppm)**  | and/or**                     |
|               | T        |          |                              |
|               | olerance |          | **Condition of Registration  |
|               | (p       |          | (COR) data.**                |
|               | pm)^1^** |          |                              |
+---------------+----------+----------+------------------------------+
| Almond, hulls | 5.0      | 6.0^2^   | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2  |
|               |          |          |                              |
|               |          |          | *COR*^5^*:* None             |
+---------------+----------+----------+------------------------------+
| Apple, wet    | \--      | 0.1      | *Section B:* None            |
| pomace        |          |          |                              |
|               |          |          | *Section F:* Based on HAFT   |
|               |          |          | residues of 0.02 ppm for     |
|               |          |          | apples and the 3.3x          |
|               |          |          | processing factor, the       |
|               |          |          | maximum expected residues in |
|               |          |          | wet apple pomace would be    |
|               |          |          | 0.066 ppm. Therefore, a      |
|               |          |          | separate tolerance is        |
|               |          |          | required for apple, wet      |
|               |          |          | pomace.                      |
|               |          |          |                              |
|               |          |          | *COR:* None                  |
+---------------+----------+----------+------------------------------+
| Asparagus     | 0.01     | 0.05^4^  | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 4. |
|               |          |          | Adequate residue data are    |
|               |          |          | available for both U. S.     |
|               |          |          | grown and foreign grown      |
|               |          |          | asparagus.                   |
|               |          |          |                              |
|               |          |          | *COR:* None                  |
+---------------+----------+----------+------------------------------+
| Barley, grain | \--      | 0.05     | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* No data were    |
|               |          |          | provided. Data can be        |
|               |          |          | translated from wheat, but   |
|               |          |          | field trials are still       |
|               |          |          | needed from regions 9 and    |
|               |          |          | 10. See Footnote 2 in        |
|               |          |          | regards to the recommended   |
|               |          |          | tolerances for Barley, hay   |
|               |          |          | and Barley, straw.           |
|               |          |          |                              |
|               |          |          | *COR:* Field trials are      |
|               |          |          | still needed from regions 9  |
|               |          |          | and 10.                      |
+---------------+----------+----------+------------------------------+
| Barley, hay   | 6.0      | 7.0^2^   |                              |
+---------------+----------+----------+------------------------------+
| Barley, straw | 1.4      | 1.5^2^   |                              |
+---------------+----------+----------+------------------------------+
| Bean,         | 0.1      | 0.1      | *Section B:* The proposed    |
| succulent     |          |          | label directions for bean    |
|               |          |          | should be amended to exclude |
|               |          |          | applications to beans grown  |
|               |          |          | for production of succulent  |
|               |          |          | shelled beans.               |
|               |          |          |                              |
|               |          |          | *Section F:* Adequate        |
|               |          |          | residue data are available   |
|               |          |          | on podded succulent beans    |
|               |          |          | and on dry beans.            |
|               |          |          |                              |
|               |          |          | *COR:* None for Bean,        |
|               |          |          | succulent and Bean, dry.     |
|               |          |          | However, the registrant      |
|               |          |          | could provide field trial    |
|               |          |          | data to support the use of   |
|               |          |          | tebuconazole on succulent,   |
|               |          |          | shelled beans.               |
+---------------+----------+----------+------------------------------+
| Bean, dry     | 0.1      | 0.1      |                              |
+---------------+----------+----------+------------------------------+
| Beet, garden, | 0.70     | 0.70^2^  | *Section B:* None            |
| root          |          |          |                              |
|               |          |          | *Section F:* None            |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Beet, garden, | 5.0      | 7.0^2^   | *Section B:* None            |
| leaves        |          |          |                              |
|               |          |          | *Section F:* In regards to   |
|               |          |          | the recommended tolerance,   |
|               |          |          | only residue data from       |
|               |          |          | samples which received four  |
|               |          |          | applications at a 1x maximum |
|               |          |          | single application rate      |
|               |          |          | (versus 3 applications, at a |
|               |          |          | less than maximum            |
|               |          |          | application rate), were used |
|               |          |          | to calculate the tolerance   |
|               |          |          | level. See Footnote 2.       |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| *Brassica*,   | 2.5      | 2.5^2^   | *Section B:* None            |
| leafy greens, |          |          |                              |
| subgroup 5B   |          |          | *Section F:* None.           |
|               |          |          |                              |
|               |          |          | *COR:* Only 7 of the         |
|               |          |          | required 8 field trials are  |
|               |          |          | available for mustard        |
|               |          |          | greens, an additional field  |
|               |          |          | trial should be conducted in |
|               |          |          | Zone 3.                      |
+---------------+----------+----------+------------------------------+
| Cherry        | 4.0      | 5.0      | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* Using the       |
|               |          |          | available residue data and   |
|               |          |          | the tolerance spreadsheet,   |
|               |          |          | the recommended tolerance    |
|               |          |          | for cherry is 4.5 ppm;       |
|               |          |          | however, HED is recommending |
|               |          |          | a 5.0 ppm tolerance to       |
|               |          |          | harmonize with the current   |
|               |          |          | Codex MRL for cherry.        |
|               |          |          |                              |
|               |          |          | *COR:* None                  |
+---------------+----------+----------+------------------------------+
| Coffee, bean, | 0.1      | 0.1      | *Section B:* NA, no U.S.     |
| green         |          | 5^2,\ 3^ | registration is being        |
|               |          |          | proposed.                    |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2  |
|               |          |          | and 3.                       |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Coffee, bean, | 0.2      | 0.       |                              |
| roasted       |          | 3^2,\ 3^ |                              |
+---------------+----------+----------+------------------------------+
| Corn, field,  | 0.01     | 0.05^4^  | *Section B:* None            |
| grain         |          |          |                              |
|               |          |          | *Section F:* See Footnote 4  |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Corn, field,  | 3.0      | 4.0^2^   | *Section B:* HED recommends  |
| forage        |          |          | the label specify a 21 day   |
|               |          |          | PHI, as the proposed 7 day   |
|               |          |          | PHI is not supported by the  |
|               |          |          | submitted data.              |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2  |
|               |          |          |                              |
|               |          |          | *COR:* The registrant could  |
|               |          |          | provide field trial data to  |
|               |          |          | support their proposed 7 day |
|               |          |          | PHI on field corn forage.    |
+---------------+----------+----------+------------------------------+
| Corn, field,  | 3.0      | 3.5^2^   | *Section B:* None            |
| stover        |          |          |                              |
|               |          |          | *Section F:* See Footnote 2  |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Corn, pop,    | 0.01     | 0.05^4^  | *Section B:* None            |
| grain         |          |          |                              |
|               |          |          | *Section F:* See Footnote 4  |
|               |          |          |                              |
|               |          |          | *COR:* None, based on field  |
|               |          |          | corn residue data.           |
+---------------+----------+----------+------------------------------+
| Corn, pop,    | 3.0      | 3.5^2^   | *Section B:* None            |
| stover        |          |          |                              |
|               |          |          | *Section F:* See Footnote 2  |
|               |          |          |                              |
|               |          |          | *COR:* None, based on field  |
|               |          |          | corn residue data.           |
+---------------+----------+----------+------------------------------+
| Corn, sweet,  | 0.5      | 0.5      | *Section B:* None            |
| kernel plus   |          |          |                              |
| cob with      |          |          | *Section F:* None            |
| husks removed |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Corn, sweet,  | 6.0      | 7.0^2^   | *Section B:* None            |
| forage        |          |          |                              |
|               |          |          | *Section F:* See Footnote 2  |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Corn, sweet,  | 5.0      | 6.0^2^   |                              |
| stover        |          |          |                              |
+---------------+----------+----------+------------------------------+
| Cotton,       | 2.0      | 2.0      | *Section B:* None            |
| undelinted    |          |          |                              |
| seed          |          |          | *Section F:* None            |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Cotton, gin   | 16.0     | 25.0^2^  | *Section B:* None            |
| byproducts    |          |          |                              |
|               |          |          | *Section F:* Adequate        |
|               |          |          | residue data are available   |
|               |          |          | on cotton gin trash derived  |
|               |          |          | from cotton harvested using  |
|               |          |          | a mechanical stripper or     |
|               |          |          | picker. Residue data from    |
|               |          |          | picker-harvested cotton were |
|               |          |          | used to calculate the        |
|               |          |          | tolerance, as residues in    |
|               |          |          | picker-harvested cotton were |
|               |          |          | consistently higher than in  |
|               |          |          | stripper-harvested cotton.   |
|               |          |          | See Footnote 2.              |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Fruit, pome,  | 0.05     | 0.05     | *Section B:* None            |
| group 11      |          |          |                              |
|               |          |          | *Section F:* None            |
|               |          |          |                              |
|               |          |          | *COR:* Two additional        |
|               |          |          | residue data are required    |
|               |          |          | for pears, one each in       |
|               |          |          | Region 10 and 11.            |
+---------------+----------+----------+------------------------------+
| Fruit, stone, | 1.0      | 1.0      | *Section B:* None            |
| group 12,     |          |          |                              |
| except cherry |          |          | *Section F:* None            |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available   |
|               |          |          |                              |
|               |          |          | Note: the needed tolerance   |
|               |          |          | for cherry is 5x the needed  |
|               |          |          | tolerance for stone fruit.   |
+---------------+----------+----------+------------------------------+
| Garlic, bulb  | 0.1^3^   | \--      | *Section B:* NA              |
|               |          |          |                              |
|               |          |          | *Section F:* Superseded by   |
|               |          |          | crop group tolerance         |
|               |          |          | petition. See onion, bulb,   |
|               |          |          | subgroup 3-07A *COR:* None   |
+---------------+----------+----------+------------------------------+
| Grain,        | 15.0     | 16.0     | *Section B:* None            |
| aspirated     |          |          |                              |
| fractions     |          |          | *Section F:* Based on the    |
|               |          |          | processing factor of 276x    |
|               |          |          | for soybean AGF and HAFT     |
|               |          |          | residues of 0.055 ppm, the   |
|               |          |          | maximum expected residues in |
|               |          |          | soybean AGF would be 15.2    |
|               |          |          | ppm.                         |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available   |
+---------------+----------+----------+------------------------------+
| Hop, dry cone | 30^3^    | 35^2^    | *Section B:* NA              |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available   |
|               |          |          | on dried hops from eight     |
|               |          |          | German field trials.         |
+---------------+----------+----------+------------------------------+
| Hops          | 5.0      | \--      | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* The tolerance   |
|               |          |          | needed to cover foreign use  |
|               |          |          | is higher. Tolerances are no |
|               |          |          | longer established for fresh |
|               |          |          | hops.                        |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available   |
|               |          |          | from U. S. trials.           |
+---------------+----------+----------+------------------------------+
| Lychee        | 1.5      | 1.6^2^   | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Mango         | 0.2      | 0.15^2^  | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available   |
|               |          |          | from post-harvest treatment. |
+---------------+----------+----------+------------------------------+
| Nut, tree,    | 0.05     | 0.05     | *Section B:* None            |
| group 14      |          |          |                              |
|               |          |          | *Section F:* None            |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Okra          | 1.0      | 1.2^2^   | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2  |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Onion, bulb   | 0.1^3^   | \--      | *Section B:* NA              |
|               |          |          |                              |
|               |          |          | *Section F:* Superseded by   |
|               |          |          | subsequently proposed        |
|               |          |          | domestic use, see below.     |
|               |          |          |                              |
|               |          |          | *COR:* None                  |
+---------------+----------+----------+------------------------------+
| Onion, bulb,  | \--      | 0.2^2^   | *Section B:* None            |
| subgroup      |          |          |                              |
| 3-07A         |          |          | *Section F:* A 0.1 ppm       |
|               |          |          | tolerance was previously     |
|               |          |          | recommended for imported     |
|               |          |          | bulb onions, which is lower  |
|               |          |          | than the 0.2 ppm tolerance   |
|               |          |          | recommended based on the     |
|               |          |          | U.S. data submitted as part  |
|               |          |          | of the proposal for a        |
|               |          |          | Vegetable, bulb, group 03    |
|               |          |          | tolerance (see below). See   |
|               |          |          | Footnote 2.                  |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Onion ,       | \--      | 1.3^2^   | *Section B:* None            |
| green,        |          |          |                              |
| subgroup      |          |          | *Section F:* None, however,  |
| 3-07B         |          |          | this is the same tolerance   |
|               |          |          | as was proposed for the      |
|               |          |          | Vegetable, bulb, group 03    |
|               |          |          | tolerance (see below). See   |
|               |          |          | Footnote 2.                  |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Plum          | 1.0      | \--      | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* No separate     |
|               |          |          | tolerance is needed, as      |
|               |          |          | there is a stone fruit crop  |
|               |          |          | group tolerance considered   |
|               |          |          | in this document.            |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Soybean,      | 17.0     | 25.0^2^  | *Section B:* None            |
| forage        |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Soybean, hay  | 45.0     | 50.0^2^  | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Soybean, seed | 0.06     | 0.08     | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* Based on the    |
|               |          |          | maximum residues observed in |
|               |          |          | the field trials, as the     |
|               |          |          | residue data included a      |
|               |          |          | substantial number (\>20%)   |
|               |          |          | of values \<LOQ              |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Soybean,      | 0.06     | \--      | *Section B:* None            |
| hulls         |          |          |                              |
|               |          |          | *Section F:* As soybean      |
|               |          |          | hulls are only utilized as a |
|               |          |          | livestock feedstuff and the  |
|               |          |          | concentration factor for     |
|               |          |          | residues in hulls is slight  |
|               |          |          | (1.1x), a separate tolerance |
|               |          |          | for hulls is not required.   |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Sunflower,    | 0.05     | 0.05     | *Section B:* None            |
| seed          |          |          |                              |
|               |          |          | *Section F:* None            |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Sunflower,    | 0.2      | 0.2      |                              |
| meal          |          |          |                              |
+---------------+----------+----------+------------------------------+
| Sunflower,    | 0.2      | 0.2      |                              |
| refined oil   |          |          |                              |
+---------------+----------+----------+------------------------------+
| Turnip, tops  | 8        | 7.0^2^   | *Section B:* The proposed    |
|               |          |          | label directions for turnips |
|               |          |          | should be amended to exclude |
|               |          |          | applications to turnips west |
|               |          |          | of the Rockies.              |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* Adequate residue data |
|               |          |          | are available for a regional |
|               |          |          | registration east of the     |
|               |          |          | Rockies, if a U.S.           |
|               |          |          | registration is desired,     |
|               |          |          | additional field trials need |
|               |          |          | to be submitted.             |
+---------------+----------+----------+------------------------------+
| Turnip, roots | 0.4      | 0.5^2^   | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Vegetable,    | 1.3      | \--      | *Section B:* None            |
| bulb, group   |          |          |                              |
| 03            |          |          | *Section F:* The available   |
|               |          |          | green and bulb onion field   |
|               |          |          | trials are adequate, but the |
|               |          |          | residue data indicate that   |
|               |          |          | separate tolerances would be |
|               |          |          | more appropriate for the     |
|               |          |          | bulb onion and green onion   |
|               |          |          | subgroups (3A and 3B).       |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Vegetable,    | 0.1      | 0.09^2^  | *Section B:* HED recommends  |
| cucurbit,     |          |          | the label specify a 7 day    |
| group 09      |          |          | PHI, as the proposed 3 day   |
|               |          |          | PHI is not supported by the  |
|               |          |          | submitted data.              |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* Inadequate residue    |
|               |          |          | data were submitted for      |
|               |          |          | cantaloupe; additional data  |
|               |          |          | are required for all three   |
|               |          |          | representative commodities.  |
+---------------+----------+----------+------------------------------+
| Wheat, forage | 3.0      | 3.0^2^   | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* None            |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Wheat, grain  | \--      | 0.05     | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* Tolerances are  |
|               |          |          | needed even when the         |
|               |          |          | residues are non-detectable. |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Wheat, hay    | 6.0      | 7.0^2^   | *Section B:* None            |
|               |          |          |                              |
|               |          |          | *Section F:* See Footnote 2. |
|               |          |          |                              |
|               |          |          | *COR:* None, adequate        |
|               |          |          | residue data are available.  |
+---------------+----------+----------+------------------------------+
| Wheat, straw  | 1.4      | 1.5^2^   |                              |
+---------------+----------+----------+------------------------------+

^1^ Established tolerances listed in table are the tolerances in wheat
and barley commodities, and in cherry.

^2^ Tolerance level was calculated using the tolerance spreadsheet and
the relevant Agency guidance.

^3^ Proposed or recommended tolerance for imported commodities.

^4^ Tolerances cannot be set at a level lower than the enforcement
analytical method can detect. The tolerance can be set at the lower
level if the LC/MS/MS method is proposed as the enforcement method.

^5^ COR = conditions of registration

**10.3 Occupational and Residential
Exposure**[]{#__RefHeading___Toc196283176 .anchor}

-   The registrant has proposed reducing the amount or concentration of
    active ingredient impregnated into wood solely intended for above
    ground uses, resulting in a maximum retention rate of 0.02 lbs ai/cu
    ft of wood; HED recommends this label amendment be a condition of
    registration, however, HED acknowledges this is at the discretion of
    the Antimicrobial Division (AD).

-   The actual retention rate in treated wood products for tebuconazole
    is unknown. Therefore, a wood wipe study on transferable residues
    from tebuconazole-treated wood is recommended as confirmatory data
    to better inform the exposure assessment.

-   Although the Lynx 2 label does not indicate that the product is
    applied by licensed or commercial applicators, it is acknowledged
    that the homeowner will not be applying the product to golf courses,
    and therefore, a risk assessment for residential handler exposure
    was not conducted.

-   The Lynx 2 label has a typo: under the use directions for "Zoysia
    patch, Large patch of zoysia (*Rhizoctonia solani*)" the label
    indicates use rates of 1.0 to 12.0 fl oz/1000 sq ft. The rate of 12
    fl oz. exceeds the maximum seasonal rate of 6.5 fl oz/1000 sq
    ft/year, and therefore should be amended to 2 fl oz/1000 sq ft. This
    document does not address a use rate of 12 fl oz/1000 sq ft on golf
    course turf grass.

-   Note: For the Lynx 2 proposed label (EPA Reg. No. 432-RUUU), the
    Non-Ag Use Requirements reentry statement is wrong. It should be as
    follows:

    -   **Entry Restriction for Non-WPS uses**: "Do not enter or allow
        others to enter the treated area until sprays have dried. If
        watering in is required after the application, do not enter or
        allow others to enter the treated areas (except those involved
        in the watering) until the watering-in is complete and the
        surface is dry."

**10.4 Triazole Data Requirements**[]{#__RefHeading___Toc196283177
.anchor}

As specified in HED's February 7, 2006 risk assessment (M. Doherty *et
al*, D322215) for 1,2,4-triazole and its metabolites triazole alanine
and triazole acetic acid, HED recommended that resolution of various
issues be a condition of registration for new uses of
triazole-derivative fungicides and for new active ingredients which
contain the 1,2,4-triazole ring. The requirement for a chronic
toxicity/oncogenicity study in male rats and female mice in the 2/7/2006
memo was later modified by HED to a 1-year chronic study in male and
female rats (Kit Farwell, DP# 321328, 5/10/2006). Therefore, HED
recommends that the registration of the proposed new
tolerances/registrations/uses of tebuconazole be conditioned upon
resolution of the following issues:

-   Chemistry:

    -   Final two-year storage stability study with 1,2,4-triazole.

-   Toxicology:

    -   Free triazole:

        -   Developmental neurotoxicity study in rats;

        -   Chronic toxicity -- 1 year chronic rat study in males and
            females.

    -   Triazole alanine:

        -   Developmental toxicity study in rabbits;

        -   Chronic toxicity study in rats, conducted according to
            current guidelines that include neurobehavioral assessments,
            with additional neuropathology evaluations conducted
            according to the neurotoxicity guidelines;

    -   Triazole acetic acid:

        -   Developmental toxicity study in rabbits;

        -   Combined 90-day feeding/neurotoxicity study in rats

**References:**[]{#__RefHeading___Toc196283178 .anchor}

*Amended Tebuconazole (Parent Only)Drinking Water Assessment in Support
of Registration Actions for Uses on Turf, Ornamentals, Almonds,
Asparagus, Barley, Beans, Corn (foliar and seed treatment), Cotton,
Cucurbits, Bulb Vegetables, Leafy Brassica Greens, Garden Beets, Hops,
Lychee, Okra, Pecan, Pistachio, Pome Fruit, Soybean, Stone Fruit (except
cherries), Sunflower, Turnip, and Wheat,* D311610, D311622, D313985,
D319241, D319245, D332177 and D332261, I. Maher, 2/7/07.

*Review of Tebuconazole Incident Reports* Chemical #325383, D325383,
Monica S. Hawkins and Hans Allender, 9/19/06.

*Tebuconazole: Benchmark Dose Analysis of the Developmental
Neurotoxicity Study -- Report of the Developmental Neurotoxicity
Workgroup* TXR No. 0054776, D340033, Jess Rowland, 11/8/07.

*Tebuconazole: Residential Exposure and Risk Assessment of Existing
Antimicrobial Uses on Wood Products and in Paints* PC Code: 128997,
D346795, Barry O'Keefe, 11/26/07.

*Tebuconazole: Residential Exposure and Risk Assessment of Proposed Use
on Golf Course Turf and Existing Uses on Residential Ornamentals* PC
Code: 128997, D349926, Barry O'Keefe, 3/13/08.

*Tebuconazole: Occupational Exposure and Risk Assessment of Proposed
Uses on Wheat, Barley, and Tree Nuts* PC Code 128997, D349913, Barry
O'Keefe, 3/13/08.

*Tebuconazole. Petitions for Tolerances on Pome Fruits (PP#6F4668),
Stone Fruits except Cherry and Cherry from post-harvest treatment
(PP#1F6289), Corn and Soybeans as rotational crops (PP# 0F6129), Cotton
and Beans (PP#0F6086), Soybeans (PP#4F6854), Asparagus (domestic)
(PP#6E7036) and Imported Hops (PP# 4E6842). Summary of Analytical
Chemistry and Residue Data; Incorporating conclusions for Petitions
PP#7F4895 on Wheat and Tree Nuts (and revised Section F), PP#0E6091 on
Imported Asparagus, Coffee, Garlic and Onion (and revised Section F),
PP#0E6158 on Okra, PP#0E6103 on Mango, PP#0E6212 on Lychee, PP#0E6153 on
Sunflower, PP#0E6117 on Plum from post-harvest treatment, PP#9E6046 on
Domestic Hops, PP#9E6048 on Cucurbits, PP#9E6045 on Turnips (tops and
roots)*, D287292, D312029, D315463, D315469, D315474, D315476, D315476,
D315479, D315867, D316409, D316410, D318838, D318511, D322912, D324776,
D324883, Susan Hummel, 11/27/06.

*Tebuconazole. Petition for Tolerance on Bulb Vegetables, Brassica and
Garden Beet Roots and Leaves. Summary of Analytical Chemistry and
Residue Data. Petition Number 6E7097*, D338564, Susan Hummel, 4/10/08

*Tebuconazole: Acute and Chronic Aggregate Dietary Exposure and Risk
Assessments for the Proposed Section 3 Registration on Asparagus,
Barley, Beans, Coffee (Import), Corn, Cotton, Cucurbits, Garlic
(Import), Hops, Lychee, Mango, Okra, Onions (Import), Pome Fruit,
Soybean, Stone Fruit, Sunflower, Tree Nuts, Turf, and Wheat (Foliar
Use); and Proposed Section 18 Emergency Exemption on Specialty Legumes*,
D333449, Susan L. Stanton, 1/18/07.

*Tebuconazole: Acute and Chronic Aggregate Dietary Exposure and Risk
Assessments for an IR-4 Section 3 Registration Action on Bulb Vegetables
(Crop Group 3), Brassica (Subgroup 5B) and Garden Beet Roots and
Leaves*, D349724, Sheila Piper, 3/3/08.

*Dietary Exposure Assessments for the Common Triazole Metabolites
1,2,4-Triazole, Triazolylalanine, Triazolylacetic Acid, and
Triazolylypyruvic Acid; Updated to Include New Uses of Fenbuconazole,
Ipconazole, Metconazole, Tebuconazole, and Uniconazole; and a Change in
Plant-back Restriction for Tetraconazole*, D350315, D350315, D350322,
D350323, D350738, D350992, Michael A. Doherty, 3/27/08.

*Projected Percent Crop Treated for Fungicide Tebuconazole on Seven
Crops PC 128997*, D331887, Alan Halvorson and Tara Chandgoyal,
11/30/2006.

**Appendix A: Toxicology Assessment**[]{#__RefHeading___Toc196283179
.anchor}

**A.1 Toxicology Data Requirements**[]{#__RefHeading___Toc196283180
.anchor}

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 protocols were used.

+-----------------------------------------+-------------+-------------+
| **Test**                                | **          |             |
|                                         | Technical** |             |
+=========================================+=============+=============+
|                                         | *           | **          |
|                                         | *Required** | Satisfied** |
+-----------------------------------------+-------------+-------------+
| 870.1100 Acute Oral Toxicity            | yes         | yes         |
|                                         |             |             |
| 870.1200 Acute Dermal Toxicity          | yes         | yes         |
|                                         |             |             |
| 870.1300 Acute Inhalation Toxicity      | yes         | yes         |
|                                         |             |             |
| 870.2400 Primary Eye Irritation         | yes         | yes         |
|                                         |             |             |
| 870.2500 Primary Dermal Irritation      | yes         | yes         |
|                                         |             |             |
| 870.2600 Dermal Sensitization           | yes         | yes         |
+-----------------------------------------+-------------+-------------+
| 870.3100 Oral Subchronic (rodent)       | yes         | yes         |
|                                         |             |             |
| 870.3150 Oral Subchronic (nonrodent)    | yes         | yes         |
|                                         |             |             |
| 870.3200 21-Day Dermal                  | yes         | yes         |
|                                         |             |             |
| 870.3250 90-Day Dermal                  | no          | no          |
|                                         |             |             |
| 870.3465 90-Day Inhalation              | no          | no          |
+-----------------------------------------+-------------+-------------+
| 870.3700a Developmental Toxicity        | yes         | yes         |
| (rodent)                                |             |             |
|                                         | yes         | yes         |
| 870.3700b Developmental Toxicity        |             |             |
| (nonrodent)                             | yes         | yes         |
|                                         |             |             |
| 870.3800 Reproduction                   |             |             |
+-----------------------------------------+-------------+-------------+
| 870.4100a Chronic Toxicity (rodent)     | no          | no          |
|                                         |             |             |
| 870.4100b Chronic Toxicity (nonrodent)  | yes         | yes         |
|                                         |             |             |
| 870.4200a Oncogenicity (rat)            | yes         | yes         |
|                                         |             |             |
| 870.4200b Oncogenicity (mouse)          | yes         | yes         |
|                                         |             |             |
| 870.4300 Chronic/Oncogenicity           | yes         | yes         |
+-----------------------------------------+-------------+-------------+
| 870.5100 Mutagenicity---Gene Mutation - | yes         | yes         |
| bacterial                               |             |             |
|                                         | yes         | yes         |
| 870.5300 Mutagenicity---Gene Mutation - |             |             |
| mammalian                               | yes         | yes         |
|                                         |             |             |
| 870.5xxx Mutagenicity---Structural      |             |             |
| Chromosomal Aberrations                 |             |             |
|                                         |             |             |
| 870.5xxx Mutagenicity---Other Genotoxic |             |             |
| Effects                                 |             |             |
+-----------------------------------------+-------------+-------------+
| 870.6100a Acute Delayed Neurotox. (hen) | no          | \-          |
|                                         |             |             |
| 870.6100b 90-Day Neurotoxicity (hen)    | no          | \-          |
|                                         |             |             |
| 870.6200a Acute Neurotox. Screening     | yes         | yes         |
| Battery (rat)                           |             |             |
|                                         | yes         | yes         |
| 870.6200b 90-Day Neuro. Screening       |             |             |
| Battery (rat)                           | yes         | yes         |
|                                         |             |             |
| 870.6300 Develop. Neuro                 |             |             |
+-----------------------------------------+-------------+-------------+
| 870.7485 General Metabolism             | yes         | yes         |
|                                         |             |             |
| 870.7600 Dermal Penetration             | no          | yes         |
+-----------------------------------------+-------------+-------------+
| Special Studies for Ocular Effects      | no          | no          |
|                                         |             |             |
| > Acute Oral (rat)                      | no          | no          |
| >                                       |             |             |
| > Subchronic Oral (rat)                 | no          | no          |
| >                                       |             |             |
| > Six-month Oral (dog)                  |             |             |
+-----------------------------------------+-------------+-------------+

**A.2 Toxicity Profiles**[]{#__RefHeading___Toc196283181 .anchor}

+----------+------------------+--------+----------------------+-------+
| **Table  |                  |        |                      |       |
| A.2.1    |                  |        |                      |       |
| Acute    |                  |        |                      |       |
| Toxicity |                  |        |                      |       |
| P        |                  |        |                      |       |
| rofile - |                  |        |                      |       |
| Tebuco   |                  |        |                      |       |
| nazole** |                  |        |                      |       |
+----------+------------------+--------+----------------------+-------+
| **G      | **Study Type**   | **MRI  | **Results**          | **Tox |
| uideline |                  | D(s)** |                      | icity |
| No.**    |                  |        |                      | Categ |
|          |                  |        |                      | ory** |
+----------+------------------+--------+----------------------+-------+
| 870.1100 | Acute oral       | 40     | LD~50~ (fasted) = \> | III   |
|          | \[rat\]          | 700917 | 5000 mg/kg (M); 3933 |       |
|          |                  |        | mg/kg (F);           |       |
|          |                  |        |                      |       |
|          |                  |        | (unfasted)=4264      |       |
|          |                  |        | mg/kg (M); 3352      |       |
|          |                  |        | mg/kg (F)            |       |
+----------+------------------+--------+----------------------+-------+
| 870.1200 | Acute dermal     | 40     | LD~50~ = \>5000      | III   |
|          | \[rat\]          | 700917 | mg/kg (M & F)        |       |
|          |                  |        |                      |       |
|          |                  | 41     |                      |       |
|          |                  | 290801 |                      |       |
+----------+------------------+--------+----------------------+-------+
| 870.1300 | Acute inhalation | 40     | LC~50~ (4 h,         | II    |
|          | \[rat\]          | 700922 | aerosol)= \>371      |       |
|          |                  |        | mg/m^3^              |       |
|          |                  |        |                      |       |
|          |                  |        | LC~50~ (4 h, dust)=  |       |
|          |                  |        | \>5093 mg/ m^3^      |       |
+----------+------------------+--------+----------------------+-------+
| 870.2400 | Acute eye        | 40     | Slight to Mild       | III   |
|          | irritation       | 700925 | irritant             |       |
|          | \[rabbit\]       |        |                      |       |
|          |                  | 40     |                      |       |
|          |                  | 700917 |                      |       |
+----------+------------------+--------+----------------------+-------+
| 870.2500 | Acute dermal     | 40     | Non-irritant         | IV    |
|          | irritation       | 700917 |                      |       |
|          | \[rabbit\]       |        |                      |       |
|          |                  | 40     |                      |       |
|          |                  | 995910 |                      |       |
+----------+------------------+--------+----------------------+-------+
| 870.2600 | Skin             | 40     | No evidence of skin  | NA    |
|          | sensitization    | 700928 | sensitization using  |       |
|          |                  |        | the Buehler test     |       |
|          | \[guinea pig\]   | 41     |                      |       |
|          |                  | 290802 |                      |       |
+----------+------------------+--------+----------------------+-------+

+---------------+---------------------+--------------------------------+
| **TABLE A.2.2 |                     |                                |
| Subchronic,   |                     |                                |
| Chronic and   |                     |                                |
| Other         |                     |                                |
| Toxicity      |                     |                                |
| Profile**     |                     |                                |
+===============+=====================+================================+
| **Guideline   | **MRID No. (year)** | **Results**                    |
| No.**         |                     |                                |
|               | **Doses/            |                                |
| **Study       | Classification**    |                                |
| Type**        |                     |                                |
+---------------+---------------------+--------------------------------+
| 870.3100      | 40700930 (1986)     | Male: NOAEL = 34.8 mg/kg/d;    |
|               |                     | LOAEL= 171.7 mg/kg/d based on  |
| 90-Day oral   | (0, 100, 400, 1600  | decreased body wt., body wt.   |
| toxicity      | ppm in diet);       | gain, and histopathology       |
|               |                     | findings.                      |
| \- rat        | 0, 8.6, 34.8, 171.7 |                                |
|               | mg/kg/d (m);        | Female: NOAEL=10.8 mg/kg/d,    |
|               |                     | LOAEL= 46.5 mg/kg/d based on   |
|               | 0, 10.8, 46.5,      | histopathological changes in   |
|               | 235.2 mg/kg/d (f)   | the adrenal gland.             |
|               |                     |                                |
|               | A                   |                                |
|               | cceptable/guideline |                                |
+---------------+---------------------+--------------------------------+
| 870.3150      | 40700934 (1987)     | NOAEL = 73.4/73.7 mg/kg/d      |
|               |                     | (m/f)                          |
| 90-Day oral   | (0, 200, 1000, 5000 |                                |
| toxicity      | ppm in diet);       | LOAEL = 368.3/ 351.8 mg/kg/d   |
|               |                     | (m/f) based on decreased body  |
| \- dog        | 0, 73.7, 368.3,     | wt. gain, food consumption and |
|               | 1749.1 mg/kg/d (m); | increased liver enzyme         |
|               |                     | activities.                    |
|               | 0, 73.4, 351.8,     |                                |
|               | 1724.8 mg/kg/d (f)  |                                |
|               |                     |                                |
|               | A                   |                                |
|               | cceptable/guideline |                                |
+---------------+---------------------+--------------------------------+
| 870.3200      | 40700937 (1984)     | NOAEL = 1000 mg/kg/day.        |
|               |                     |                                |
| 21/28-Day     | 0, 50, 250, 1000    | No dermal or systemic toxicity |
| dermal        | mg/kg/day           | was seen.                      |
| toxicity -    |                     |                                |
| rabbit        | A                   |                                |
|               | cceptable/guideline |                                |
+---------------+---------------------+--------------------------------+
| 870.3465      | 40700938 (1985)     | NOAEL =10.6 mg/m^3^/d (0.0106  |
|               |                     | mg/L/day)                      |
| 15-Day        | 0, 1.2, 10. 6,      |                                |
| inhalation    | 155.8 mg/m^3^       | LOAEL = 155.8 mg/m^3^/d        |
| toxicity      |                     | (0.1558 mg/L/day) based on     |
|               | A                   | clinical signs and induction   |
| \- rat        | cceptable/guideline | of liver microsomal enzymes.   |
+---------------+---------------------+--------------------------------+
| 870.3700a     | 40700943 (1988)     | **Maternal** NOAEL = 30        |
|               |                     | mg/kg/day                      |
| Prenatal      | 0, 30, 60 , 120     |                                |
| developmental | mg/kg/d, GD 6-15    | LOAEL=60 mg/kg/d based on      |
|               |                     | increased liver wt and         |
| \- rat        | A                   | liver/body weight ratios.      |
|               | cceptable/guideline |                                |
|               |                     | **Developmental** NOAEL=30     |
|               |                     | 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     | 41450801 (1988)     | **Maternal** NOAEL= 1000       |
|               |                     | mg/kg/d                        |
| Prenatal      | 0, 100, 300, 1000   |                                |
| developmental | mg/kg/d, GD 6-15    | **Developmental** NOAEL= 1000  |
|               |                     | mg/kg/d                        |
| \- rat        | A                   |                                |
| (Dermal)      | cceptable/guideline | No evidence of maternal or     |
|               |                     | developmental toxicity seen    |
|               |                     | via dermal route.              |
+---------------+---------------------+--------------------------------+
| 870.3700a     | 40821501 (1988)     | **Maternal** NOAEL = 30        |
|               |                     | mg/kg/d                        |
| Prenatal      | 0, 10, 30, 100      |                                |
| developmental | mg/kg/d, GD 6-15    | LOAEL = 100 mg/kg/d based on   |
|               |                     | increased hepatic              |
| \- mouse      | 40821500 (1988)     | triglycerides, pale lobular    |
|               |                     | liver, increased severity of   |
|               | Supplementary study | hepatic vacuoles and           |
|               |                     | lipidosis.                     |
|               | 0, 10, 20, 30, 100  |                                |
|               | mg/kg/d GD 6-15     | **Developmental** NOAEL = 10   |
|               |                     | mg/kg/d                        |
|               | A                   |                                |
|               | cceptable/guideline | LOAEL = 30 mg/kg/d based on    |
|               |                     | increased number of runts.     |
+---------------+---------------------+--------------------------------+
| 870.3700a     | 43776201,           | **Maternal:** NOAEL = 3        |
|               | 43776202(1995)      | mg/kg/d                        |
| Prenatal      |                     |                                |
| developmental | 0, 10, 30, 100      | LOAEL = 10 mg/kg/d based on    |
|               | mg/kg/d, GD 6-15    | increased hepatic enzyme       |
| \- mouse      |                     | induction and severity of      |
|               | Supplementary group | vacuolization in liver cells.  |
|               |                     |                                |
|               | 0, 1, 3 mg/kg/d GD  | **Developmental**: NOAEL= 3    |
|               | 6-15                | mg/kg/d                        |
|               |                     |                                |
|               | A                   | LOAEL=10 mg/kg/d based on      |
|               | cceptable/guideline | increased external, visceral,  |
|               |                     | and skeletal                   |
|               |                     | malformation/variation in the  |
|               |                     | head and skull.                |
+---------------+---------------------+--------------------------------+
| 870.3700a     | 42010301 (1990)     | **Maternal** NOAEL= 1000       |
|               |                     | mg/kg/d                        |
| Prenatal      | 0,100,300,1000      |                                |
| developmental | mg/kg/d GD 6-15     | **Developmental** NOAEL= 1000  |
|               |                     | mg/kg/d                        |
| \- mouse      | A                   |                                |
| (Dermal)      | cceptable/guideline | No evidence of maternal or     |
|               |                     | developmental toxicity seen    |
|               |                     | via dermal route.              |
+---------------+---------------------+--------------------------------+
| 870.3700b     | 40700945 (1987)     | **Maternal** NOAEL = 30        |
|               |                     | mg/kg/d                        |
| Prenatal      | 0, 10,30,100        |                                |
| developmental | mg/kg/d, GD 6-18    | LOAEL = 100 mg/kg/d based on   |
|               |                     | decreased body weight gain and |
| \- rabbit     | A                   | food consumption.              |
|               | cceptable/guideline |                                |
|               |                     | **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     | 43776201 (1995)     | **Maternal** NOAEL = Not       |
|               |                     | established (\<10 mg/kg/d)     |
| Prenatal      | 0, 10, 30, 100      |                                |
| developmental | mg/kg/day GD 6-18   | LOAEL = 10 mg/kg/d based on    |
|               |                     | increased incidence of single  |
| \- rabbit     | A                   | cell necrosis in liver cells.  |
|               | cceptable/guideline |                                |
|               |                     | **Developmental** NOAEL = 10   |
|               |                     | mg/kg/d                        |
|               |                     |                                |
|               |                     | LOAEL = 30 mg/kg/d based on    |
|               |                     | increased external and         |
|               |                     | visceral                       |
|               |                     | malformation/variations.       |
+---------------+---------------------+--------------------------------+
| 870.3800      | 40700946 (1987)     | **Parental/Systemic** NOAEL =  |
|               |                     | 15 mg/kg/day (m&f)             |
| Reproduction  | 0, 100, 300, 1000   |                                |
| and fertility | ppm in diet         | LOAEL = 50 mg/kg/day based on  |
| effects       | (equivalent to 0,   | increased severity of splenic  |
|               | 5, 15, 50           | hemosiderosis (m&f), increased |
| \- rat        | mg/kg/day)          | incidence of splenic           |
|               |                     | hematopoiesis (m), and         |
|               | A                   | decreased weight gain during   |
|               | cceptable/guideline | 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      | 40700939, 40816401  | Males: NOAEL = 15.9 mg/kg/d;   |
|               | (1988)              | LOAEL=55 mg/kg/day based on    |
| Chronic/      |                     | decreased testes weight.       |
| ca            | 0, 100, 300, 1000   |                                |
| rcinogenicity | ppm in diet;        | Females: NOAEL= 7.4 mg/kg/d;   |
|               |                     | LOAEL=22.8 mg/kg/day based on  |
| \- rat        | M: 0, 5.2, 15.9, 55 | decreased body wt. & wt. gain, |
|               | mg/kg/d;            | decreased erythrocyte          |
|               |                     | parameters and increased       |
|               | F: 0, 7.4, 22.8,    | incidence of splenic           |
|               | 86.3 mg/kg/d        | hemosiderosis (increased       |
|               |                     | erythrocyte clearance).        |
|               | A                   |                                |
|               | cceptable/guideline | No evidence of carcinogenicity |
|               |                     | at the doses tested.           |
+---------------+---------------------+--------------------------------+
| 870.4100b     | 40700940 (1987)     | NOAEL = 15.5 mg/kg/day         |
|               |                     |                                |
| Chronic       | 0, 40, 200,         | LOAEL = 77.3 mg/kg/day based   |
| toxicity      | 1000/2000 ppm in    | on ocular lesions and changes  |
|               | diet;               | in erythrocyte morphology      |
| \- dog        |                     | (anisocytosis)                 |
|               | 0, 15.5, 77.3, 483  |                                |
|               | mg/kg/d             |                                |
|               |                     |                                |
|               | A                   |                                |
|               | cceptable/guideline |                                |
+---------------+---------------------+--------------------------------+
| 870.4100b     | 42030601 (main)     | NOAEL = 2.96 mg/kg/day (m),    |
|               | (1989) & 42537201   | 2.94 mg/kg/d (f)               |
| Chronic       | (suppl.) (1992);    |                                |
| toxicity      |                     | LOAEL = 4.39 mg/kg/day (m),    |
|               | 0, 100, 150 ppm;    | 4.45 mg/kg/d (f) based on      |
| \- dog        |                     | lesions in the adrenal gland.  |
|               | M: 0, 2.96, 4.39    |                                |
|               | mg/kg/d             |                                |
|               |                     |                                |
|               | F: 0, 2.94, 4.45    |                                |
|               | mg/kg/d             |                                |
|               |                     |                                |
|               | A                   |                                |
|               | cceptable/guideline |                                |
|               | together with       |                                |
|               | 40700940            |                                |
+---------------+---------------------+--------------------------------+
| 870.4200b     | 40700941 (1988)     | Male mice had statistically    |
|               |                     | significant, dose-related      |
| Ca            | 0, 20, 60, 180 ppm  | increasing trends in           |
| rcinogenicity | in diet;            | hepatocellular adenomas,       |
|               |                     | carcinomas and combined        |
| \- mouse      | M: 0, 5.9, 18.2,    | adenomas and/or carcinomas.    |
|               | 53.1 mg/kg/d        | There were also statistically  |
|               |                     | significant differences in the |
|               | F: 0, 9.0, 26.1,    | pair-wise comparisons of the   |
|               | 80.5 mg/kg/d        | controls with the 1500 ppm     |
|               |                     | dose group for hepatocellular  |
|               | 42175001            | adenomas (29% vs. 5%           |
|               |                     | controls), hepatocellular      |
|               | 0, 500, 1500 ppm    | carcinomas (21% vs. 0%         |
|               |                     | controls) and combined         |
|               | M: 0, 84.9, 279     | adenomas and/or carcinomas     |
|               | mg/kg/day           | (47% vs. 5% controls).         |
|               |                     |                                |
|               | F: 0, 103.1, 365.5  |                                |
|               | mg/kg/day           |                                |
|               |                     |                                |
|               | A                   |                                |
|               | cceptable/guideline |                                |
+---------------+---------------------+--------------------------------+
| 870.5100      | 40700947 & 40700948 | Negative with or without       |
|               | (1988)              | activation at doses ranging    |
| Salmonella    |                     | from 39.5 to 450 μg/plate      |
| point         | A                   |                                |
| mutation      | cceptable/guideline |                                |
+---------------+---------------------+--------------------------------+
| 870.5300      | 40700949 (1988)     | Negative with or without       |
|               |                     | activation at concentrations   |
| CHO-HGPRT     | Una                 | ranging from 12.5-200 and      |
| forward       | cceptable/guideline | 80-100 μg/mL, respectively;    |
| mutation      |                     | highest concentration tested   |
|               |                     | did not produce high level of  |
|               |                     | cytotoxicity.                  |
+---------------+---------------------+--------------------------------+
| 870.5375      | 40700953 (1988)     | Negative for chromosome        |
|               |                     | aberrations with activation    |
| In vitro      | Acceptable with     | (30-300 μg/mL) and without     |
| Cytogenetics  | activation;         | activation (10-300 μg/mL);     |
| (human        | Unacceptable        | highest dose not cytotoxic     |
| lymphocytes)  | without activation  | without activation             |
+---------------+---------------------+--------------------------------+
| 870.5395      | 40700951 (1985)     | Negative at all doses up to    |
|               |                     | 2000 mg/kg bw                  |
| Mammalian     | A                   |                                |
| erythrocyte   | cceptable/guideline |                                |
| micronucleus  |                     |                                |
+---------------+---------------------+--------------------------------+
| 870.5450      | 40700950 (1986)     | Negative at 2000 mg/kg bw      |
|               |                     | (only dose tested) during 12   |
| Mouse         | Una                 | serial mating periods;         |
| dominant      | cceptable/guideline | positive control was not       |
| lethality     |                     | included                       |
+---------------+---------------------+--------------------------------+
| 870.5500      | 40700955 (1983)     | Negative with or without       |
|               |                     | activation at concentrations   |
| DNA damage    | Una                 | ranging from 625-10,000        |
| and repair    | cceptable/guideline | μg/plate); no growth           |
| (*E.coli)*    |                     | inhibition zone detected       |
+---------------+---------------------+--------------------------------+
| 870.5550      | 40816402 (1988)     | No evidence of an increase in  |
|               |                     | unscheduled DNA synthesis at   |
| Unscheduled   | A                   | 0.504-25.2 μg/mL               |
| DNA synthesis | cceptable/guideline |                                |
| (rat          |                     |                                |
| hepatocytes)  |                     |                                |
+---------------+---------------------+--------------------------------+
| 870.5900      | 40700952 (1987)     | Negative with and without      |
|               |                     | activation with S9 at          |
| Sister        | A                   | concentrations ranging from    |
| chromatid     | cceptable/guideline | 4-30 μg/mL and 15-120 μg/mL,   |
| exchange (CHO |                     | respectively.                  |
| cells *in     |                     |                                |
| vitro*)       |                     |                                |
+---------------+---------------------+--------------------------------+
| 870.6200a     | 44449301, 44545701  | NOAEL = 50 mg/kg/day           |
|               | (1997)              |                                |
| Acute         |                     | LOAEL = 100 mg/kg/day based on |
| neurotoxicity | 0, 21, 50, 103,     | increased motor activity in    |
| screening     | 497, 950 mg/kg      | males and females and          |
| battery       |                     | decreased footsplay in         |
|               | Una                 | females.                       |
| -rat          | cceptable/Guideline |                                |
|               |                     |                                |
|               | (Upgradeable)       |                                |
+---------------+---------------------+--------------------------------+
| 870.6200b     | 44588001 (1998)     | NOAEL = 107 mg/kg/day          |
|               |                     |                                |
| Subchronic    | 0, 100, 400, or     | LOAEL = Not determined \[\>107 |
| neurotoxicity | 1600 ppm            | mg/kg/day\]                    |
| screening     |                     |                                |
| battery       | M: 0.00, 7.57,      |                                |
|               | 29.2, 107 mg/kg/day |                                |
| -rat          | F: 0.00, 8.81,      |                                |
|               | 34.0, 122 mg/kg/day |                                |
|               |                     |                                |
|               | Una                 |                                |
|               | cceptable/Guideline |                                |
|               |                     |                                |
|               | (Not upgradeable)   |                                |
+---------------+---------------------+--------------------------------+
| 870.6300      | 45074301 (2000)     | **Maternal** NOAEL = 22        |
|               |                     | mg/kg/day                      |
| Developmental | 0, 100, 300, 1000   |                                |
| neurotoxicity | ppm                 | LOAEL = 65 mg/kg/day based on  |
|               |                     | decreased body weight, body    |
| -rat          | \[GD/LD 0/0,        | weight gain, and food          |
|               | 8.8/16.3, 22/41.3,  | consumption; prolonged         |
|               | 65/125.4 to dams\], | gestation with mortality,      |
|               | GD6 to LD11         | increased number of dead       |
|               |                     | fetuses.                       |
|               | A                   |                                |
|               | cceptable/Guideline | **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      | 40995911, 40995912  | 98.1% of oral dose is          |
|               | (1987)              | absorbed. Over 87% of dose     |
| Metabolism    |                     | excreted in urine & feces      |
|               | A                   | within 72 hours after dosing.  |
| \- rat        | cceptable/guideline | 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 metabolic          |
|               |                     | saturation.                    |
+---------------+---------------------+--------------------------------+
| 870.7600      | 46634901 (2003)     | Estimated dermal absorption    |
|               |                     | 23.1%. (including the fraction |
| Dermal        | 132 µg/cm^2^        | of the dose absorbed and the   |
| penetration   | tebuconazole in     | amount of dose remaining in    |
|               | Folicur EW250,      | the skin after washing).       |
| \- monkey     | single 8 hr         |                                |
|               | administration      |                                |
|               |                     |                                |
|               | Acce                |                                |
|               | ptable/nonguideline |                                |
+---------------+---------------------+--------------------------------+
| Literature    | 45486901 (2001),    | Study evaluated reproductive,  |
| study:        | 45591701 (2002),    | immuno-, and neurotoxicity in  |
| Developmental | 46146701 (2003)     | offspring. Identified one      |
| neurotoxicity |                     | effect of concern: learning    |
| /i            | 0, 6, 20, 60 mg/kg  | deficits in high dose          |
| mmunotoxicity | (gavage) GD14-PND7  | offspring, evaluated starting  |
|               | to dams, PND7-42 to | on PND74. Neuropathological    |
|               | offspring           | effects identified in the      |
|               |                     | original study were retracted  |
|               |                     | based on a pathology           |
|               |                     | peer-review.                   |
+---------------+---------------------+--------------------------------+

**A.3 Executive Summaries**[]{#__RefHeading___Toc196283182 .anchor}

**A.3.1 Subchronic Toxicity**

**870.3100 90-Day Oral Toxicity in Rats**

In a subchronic oral study (MRID 40700930), tebuconazole (HWG 1608,
93.4% ai, Batch No. 16007/83) was fed to Wistar rats (10/sex/group) at
concentrations of 0, 100, 400, or 1600 ppm (equivalent to 0, 8.6, 34.8,
or 171.7 mg/kg bw/day for males and 0, 10.8, 46.5, or 235.2 mg/kg bw/day
for females, respectively) for 13 weeks.

No treatment-related deaths, clinical signs were observed. One high-dose
male died during week 1 and one high-dose female died during week 4 due
to hemorrhagic diathesis and two control males died due to blood
sampling. Mean body weights were significantly decreased by 8-12% and
overall body weight gain was significantly decreased by 12% in high-dose
male and female rats. Food consumption was markedly increased in
high-dose male and female rats and transiently increased in mid-dose
females. Ophthalmoscopic examination showed corneal erosion and a right
corneal lens cataract in one high-dose male and one female rat,
respectively. An increased incidence of vacuole formation in zona
fasciculate cells in the adrenals was seen in high dose animals of both
sexes (males: 6/10 vs. 4/10 in control, females: 9/10 vs. 0/10 in
control animals), and in mid-dose females (4/10 vs. 0/10 in control). In
addition, high dose males and females had increased incidence of splenic
hemosiderosis. Adverse effects appeared to be more intense in females
than in males and maybe attributed to increased females food
consumption.

**For males, the LOAEL is 1600 ppm (171.7 mg/kg bw/day) based on
decreased body weight, weight gain and histpathological changes in
adrenal, the NOAEL is 400 ppm (34.8 mg/kg bw/day). For females, the
LOAEL is 400 ppm (46.5 mg/kg/day) based on histopathological findings in
the adrenal gland (vacuole formation in the zona fasciculata), the NOAEL
is 100 ppm (10.8 mg/kg bw/day).**

This subchronic toxicity study is **acceptable/guideline** and satisfies
the guideline requirement for a subchronic oral study (OPPTS 870.3100)
in rats.

**870.3100 90-Day Oral Toxicity in Dogs**

In a subchronic toxicity study (MRID 40700934), beagle dogs
(4/sex/group) were fed tebuconazole (HG 1608, 93.4% ai, Batch No.
16007/83) in diet at concentrations of 0, 200, 1000, or 5000 ppm
(equivalent to 0, 73.7, 368.3, or 1749.1 mg/kg bw/day for males and 0,
73.4, 351.8, or 1724.8 mg/kg bw/day for females, respectively) for 13
week.

One high-dose female that died on day 2 of the study was replaced with
another animal. A few mid- and high-dose males and high-dose females
appeared thin after week 7 of the study. Mean body weight was decreased
in both sexes at the high-dose level (up to -11% in males and up to -17%
in females), and overall body weight gain was decreased in both sexes by
19-25% at the mid-dose level and by 46-48% at the high-dose levels. Food
consumption was slightly decreased in high-dose males and mid- and
high-dose females. The ophthalmoscopic examination showed lens opacity
in one high-dose male and two high-dose females at week 7 and in all
high-dose dogs at week 10. Hematologic changes included severe
anisocytosis in 6/8 high-dose animals of both sexes and increased
platelet count in high-dose females. Effects on the liver included
increased alkaline phosphatase, decreased albumin, increased liver
enzymes, cytochrome p-450 at the high-dose and a dose-related increase
in N-demethylase activity. Microscopic examination of the eyes showed
lens degeneration in all high-dose males and one high-dose female and
cataracts in three high-dose females, splenic hemosiderosis in five
high-dose animals (vs. one control), hemosiderosis in the liver Kupffer
cells of five high-dose animals (vs. one control) and increased
vacuolation in the adrenals of high-dose females.

**The LOAEL is 1000 ppm (368.3 and 351.8 mg/kg bw/day for males and
females, respectively) based on decreased body weight gain and food
consumption and increased liver enzyme activities. The NOAEL is 200 ppm
(73.4 and 73.7 mg/kg bw/day for males and females, respectively).**

This 90-day oral toxicity study in the dog is **acceptable/guideline**
and satisfies the requirement for a subchronic study (OPPTS 870.3150) in
dogs.

**870.3200 21-Day Dermal Toxicity Study in Rabbits**

In a 21-day dermal toxicity study (MRID 40700937), tebuconazole (97.2%
ai) was administered dermally to New Zealand White rabbits at 0, 50,
250, or 1000 mg/kg/day, 6 hours/day, 5 days/week over a three week
period. No dermal or systemic toxicity was seen.

**For dermal and systemic toxicity, the NOAEL is 1000 mg/kg/day.**

This study is classified as **acceptable/guideline** and satisfied
guideline requirement for a 21-day dermal toxicity study (OPPTS
870.3200).

**870.3465 15-Day Inhalation Toxicity Study in Rats**

In a subchronic inhalation toxicity study (MRID 40700938), groups of ten
male and ten female Wistar rats were exposed head/nose only to
tebuconazole (HWG 1608, 96.2% ai, Batch No. 16001/83) (in
lutrol-ethanol) aerosol at concentrations of 0 (control air), 0 (vehicle
control), 5, 50, or 500 mg/m^3^ (analytical concentrations: 0 (vehicle),
1.2, 10.6, and 155.8 mg/m^3^, respectively), 6 hours/day, 5 days/week
for a total of 15 exposures. The animals were exposed in a 20-L chamber
that had a 20-L antechamber. The MMAD was 2.0, 2.1, 2.0, and 2.1 μm,
respectively.

No treatment-related effects were observed on survival, body weight or
body weight gain, hematology parameters, or urinalysis parameters.
Exposure at 155.8 mg/m^3^ caused piloerection. At the highest exposure
level, there was also a moderate induction of liver O-demethylase and a
statistically significant induction of liver N-demethylase in both
sexes. There were no other significantly toxicological effects on
clinical laboratory parameters or organ weights nor was there an
increase in histological lesions.

**The LOAEL is 155.8 mg/m^3^/day based on clinical signs and induction
of liver microsomal enzymes. The NOAEL is 10.6 mg/m^3^/day.**

This inhalation toxicity study is **acceptable/guideline** and satisfies
guideline requirement for a subchronic inhalation study in rats (OPPTS
870.3465).

**A.3.2 Developmental and Reproduction Toxicity**

**870.3700a Developmental Toxicity Study in Rats**

In a developmental toxicity study (MRID 40700943), tebuconazole (HWG
1608, 98.3% ai, Lot No. 16002/85) was administered to groups of 25
pregnant Wistar/NAN (Kfm:WIST, Outbred, SPF) rats by gavage at dose
levels of 0, 30, 60, or 120 mg/kg bw/day from gestation day (GD) 6 to
15. The dams were sacrificed on GD 21 followed by gross examination of
all internal organs with a focus on the uterus, uterine contents,
position of fetuses in the uterus, and number of corpora lutea. The
uteri plus contents were weighed; uteri in non-pregnant females were
stained with ammonium sulfide solution to identify implantation sites.
Fetuses were sexed, individually weighed, and examined for gross
abnormalities. One-half of the fetuses in each litter were processed for
examination of visceral and brain abnormalities using Wilson's technique
and remaining one-half was cleared and stained for skeletal examination.

No compound-related mortality or clinical signs of toxicity were
reported at any dose level. Although body weight gains for days 6-21 of
gestation were slightly decreased (85% of controls) at the high-dose,
corrected or uncorrected body weight gains were not significantly
different from controls at any dose level. Mean daily food consumption
during days 6-16 was significantly decreased with respect to controls at
the mid-dose (-7%) and at the high-dose (-15%). There was a slight
increase in daily food consumption (about 5%) during the post-dosing
period. A significant decrease in absolute body weight was reported for
the high-dose and a dose-dependent and statistically significant
increase in liver weight/body weight was reported at the high- and
mid-dose.

**The maternal toxicity LOAEL is 60 mg/kg/day based on increased
absolute liver weights and relative liver/body weight ratios. The NOAEL
is 30 mg/kg/day.**

An increase in the numbers of early and late resorptions and a decrease
in mean fetal weights (-10.6%) and in total live fetuses (19.4% below
controls) was observed at the high-dose. This latter value was reflected
in the decreased number of live fetuses/dam (9.7 high-dose vs. 12.0
controls) and is consistent with the increased resorptions and %
postimplantation loss observed at the high-dose. The mean fetal weight
depression may be treatment-related since the decrease in mean fetal
weight was observed despite a reduction in litter size in the high-dose.
External examination of fetuses revealed a missing tail in one high-dose
fetus, and agnathia (lower jaw), microstomia and anophthalmia in another
fetus of a different HDT litter. Historical control data for missing
tail for 1985-1988 indicate a low frequency for this effect.

Visceral examination of fetuses revealed findings of excess fluid in the
thoracic cavity at the high-dose (3 pups in 1 litter, 1 pup in another
litter) and at the low-dose (1 pup). Skeletal examination revealed
dose-dependent, statistically significant increases in several fetal
frequencies and some litter frequencies of skeletal variations. Skeletal
variations observed to have increased fetal frequencies in both the
mid-dose and the high-dose were nonossified cervical vertebra 2,
vertebral arch 6 (right), digit 1 distal phalanx (left), digit 3
proximal phalanx (left and right), digit 2 proximal phalanx (right),
digit 4 proximal phalanx (right) and toe 5 distal phalanx (right).

There was a dose-dependent increase in the litter and fetal incidences
of non-ossified sacral vertebral arch 6 (R), which is statistically
significant vs. controls at the mid-dose and the high-dose \[i.e. litter
incidences: 2/24, 8.3% (low-dose), 6/22, 27.2% (mid-dose) and 8/24,
33.3% (high-dose) vs. 0/24 controls\]. Historical control data indicate
that the effect is very infrequent: it was observed once in 1 of 31
studies (at a litter incidence of 4% for the study) at an overall litter
incidence for the 31 studies of 1/763 (0.13%). There was a
dose-dependent increase in the fetal incidences of non-ossification of
the digit 4 proximal phalanxes (R) with statistically significant litter
and fetal incidences at the mid-dose and high-dose \[i.e. litter
incidences: 6/24, 25% (mid-dose and high-dose) vs. 1/24, 4%
(controls)\]. Historical control data indicate that litter frequencies
for this effect are in the range of 4.2-47.8%. Coupled to the marked
increase in fetal incidence of non-ossification of cervical vertebra 2
(41.4% at the high-dose vs. 20.1% in controls) there is an increased
litter incidence 20/24 (83.3%) at the high-dose vs. 14/24 (58.3%) in
controls. It is noted, however, that the historical control range for
litter frequencies is 36-80%.

These effects on litter/fetal incidences appear to be consistent with a
treatment-related developmental effect of tebuconazole at the mid-dose
and high-dose. In addition, the fetal and litter incidences of dumbbell
shaped centrum in thoracic vertebrae are increased at the high-dose (5.1
% fetuses, 16.6% litters) vs. controls (1.4% fetuses, 8.3% litters).
These values, although not statistically significantly different from
concurrent controls, exceed values for historical controls for 1988,
1986 and 1985 (0-13.6%). Values for 1987 should not be included since
they include other related effects.

There was also an increase in the litter incidence of supernumerary ribs
at the mid-dose and the high-dose \[13/22 (55%) litters at the mid-dose
and 12/24 (50%) at the high-dose vs. 9/24 (37.5%) in controls\] coupled
to statistically significant increases in their fetal incidence at the
high-dose. These litter incidences for supernumerary ribs, however, are
within historical control ranges which showed litter incidences of up to
56.0-70.8% for supernumerary ribs.

**The developmental toxicity LOAEL is 60 mg/kg bw/day based on delayed
ossification of several bones and increased numbers of fetuses with
supernumerary ribs. The developmental toxicity NOAEL is 30 mg/kg
bw/day.**

This prenatal developmental toxicity study in rats is
**acceptable/guideline** and satisfies the requirement (OPPTS 870.3700)
for a prenatal developmental toxicity study in the rat.

**870.3700a Developmental Toxicity Study in Rats**

In a **dermal** developmental toxicity study (MRID 41450801),
Tebuconazole (Technical) in aqueous 1 % Cremophor EL was administered
dermally to pregnant Bor:WISW (SPE Cpb) rats on days 6-15 of gestation
at nominal levels of 0, 100, 300 and 1000 mg/kg/day. The test material
was applied to a 25 cm2 area of shaved skin (nominal doses of 0, 0.87,
2.6, and 8.7 mg/cm2/day) for 6 hours, then removed followed by washing
of the application site with lukewarm water. Dams were sacrificed on day
20 of gestation and gross macroscopic observation of all organs was
performed. At C-section the uteri and their contents were weighed to
obtain corrected maternal bodyweight gains and were examined to
determine the number of implantations. The fetuses were sexed, weighed
and examined for external malformations. Approximately 50% of the
fetuses were examined for visceral malformations by Wilson's technique,
and the rest were cleared in potassium hydroxide and stained with
alizarin S for evaluation of skeletal malformations by Dawson's method.

No evidence of maternal toxicity (changes in body weights, corrected
body weights, food consumption, clinical signs, pathology, deaths,
abortions, premature deliveries) were noted at any dose level, No
developmental toxicity was noted at any dose level based upon indices of
mean corpora lutealdam, implantations/dam, live or dead fetuses/dam,
resorptions/dam (early and late), mean fetal weights, sex ratios (%
male), mean crown-rump length (cm), mean runts/dam, variations or
malformations.

**For maternal and developmental toxicity by dermal route, the NOEL is
1000 mg/kg/day (HDT). The LOEL was [\>]{.underline}1000 mg/kg/day**.

This study is classified as **acceptable/guideline** and satisfies the
guideline requirements for a developmental toxicity study (OPPTS
870.3700a) in rats.

This study had been reviewed by the HED Peer Review Committee (PRC) and
it had noted that higher dose levels may have been used as indicated by
the absence of maternal toxicity. In addition, the slow absorption of
this chemical by the dermal route suggests that plasma levels may not
have plateaued until late in the period of organogenesis. The PRC noted
that knowledge of a compound's pharmacokinetics was essential in the
design of studies such as this and it recommended that additional
information concerning pharmacokinetics following dermal administration
in the rat be submitted.

**870.3700a Developmental Toxicity Study in Mice**

In a developmental toxicity study (MRID 40821501), tebuconazole (HWG
1608, 93.6% ai, Lot No. 161002/84) was administered to groups of 25
presumed pregnant NMRI/ORIG Kisslegg mice by gavage at dose levels of 0,
10, 30, or 100 mg/kg bw/day from gestation day (GD) 6 to 15. The dams
were sacrificed on GD 18 followed by gross examination of all internal
organs. The uteri and contents were examined, the number of
implantations and live and dead fetuses were recorded, and the sex of
all live fetuses was determined. The placenta was weighed; each fetus
was weighed individually. Fetuses were examined for external and
visceral abnormalities using a modified Wilson's technique and skeletal
abnormalities after clearing and staining. In a supplementary study to
examine maternal toxicity (MRID 40821500), groups of 10 mated and
presumed pregnant mice were administered tebuconazole (HWG 1608, 97.4%,
ai, Lot No. 16012/86) by gavage at doses of 0, 10, 20, 30, or 100
mg/kg/day from GD 6-15 and sacrificed on GD 16. The animals were
observed for mortality and clinical signs, and one-half of the mice were
subjected to gross examination. The liver, kidneys, spleen, and adrenal
glands were weighed, and the livers were processed for microscopic
examination. Blood was drawn from five anesthetized mice/group for
hematology and clinical chemistry evaluation.

No maternal deaths or treatment-related clinical signs or body weight
gains were observed in the main or supplemental study. Food consumption
was not measured. In the supplemental study, hematocrit was
significantly decreased at 30 and 100 mg/kg/day and mean corpuscular
volume (MCV) was significantly decreased at 20, 30 and 100 mg/kg/day; no
clear dose-related trend was observed for either parameter. Serum enzyme
activities \[aspartate aminotransferase (AST), alanine aminotransferase
(ALT), and alkaline phosphatase\] were increased at most doses, but no
clear dose-related trend was observed for these parameters. Liver
triglycerides were elevated at 100 mg/kg/day. No clear trend was
observed for the increase in absolute liver weight, but relative
liver/body weight was increased at all doses, particularly at 100
mg/kg/day. Gross examination showed pale lobular livers in 100 mg/kg/day
mice compared with 0/5 in controls. Microscopically, mild to severe
liver cell vacuolation and moderate to severe lipidosis (ORO stain) were
observed in 5/5 mice at 100 mg/kg/day (2/5 in control mice).

**The maternal toxicity LOAEL is 100 mg/kg/day based on increased
hepatic triglycerides, pale lobular liver, and increased severity of
hepatic vacuoles and lipidosis. The NOAEL is 30 mg/kg/day**.

No treatment-related effect was observed on the number of live
fetuses/dam, mean fetal weight, resorptions/dam, percent
post-implantation loss, or sex ratio. The total number of resorptions
was marginally increased at 100 mg/kg/day. There was a dose-dependent
and significantly significant increase in the number of runts per litter
(fetuses weighing less than 1.3 g) at the 30 mg/kg/day (0.91) and the
100 mg/kg/day (1.20) compared to the control (0.21). At 100 mg/kg/day,
seven fetuses in six litters had skull abnormalities (cleft palate,
micrognathia, partial dysplasia of the parietal bone) and five fetuses
in four litters had neural tube abnormalities (brain ventricle
enlargement, asymmetrical vertebral bodies, spinal column dysplasia, and
abnormal flexion of spinal column) compared with none in the control
group. At 100 mg/kg/day, five fetuses in four litters had rudimentary
ossification centers in the cranium compared with one fetus in the
control group.

**The developmental toxicity LOAEL is 30 mg/kg/day based on an increased
number of runts. The NOAEL is 10 mg/kg/day.**

This prenatal developmental toxicity study is **acceptable/guideline**
and satisfies the requirement (OPPTS 870.3700a) for assessing prenatal
developmental toxicity in mice.

**870.3700a Developmental Toxicity Study in Mice**

In a developmental toxicity study (MRID 43776202), 35 presumed pregnant
NMRI KFM-HAN mice were administered tebuconazole (HWG 1608, 95.8-96.8%
ai, Batch No. 816196048) in 0.5 % Cremophor EL by gavage at doses of 0,
10, 30, or 100 mg/kg/day on gestation days (GD) 6-15, inclusive. On GD
18, dams were sacrificed, subjected to gross necropsy, and all fetuses
examined externally. One-half of the fetuses were examined viscerally,
and the remaining fetuses were examined for skeletal
malformations/variations. An additional ten mated dams/group were
included in a satellite study to assess the effects on hematology and
clinical biochemistry parameters and pathological changes of target
organs. In the satellite study, blood was collected on GD 16, and the
dams were then euthanized and subjected to gross necropsy. Liver tissue
samples were collected to determine cytochrome P450 content and N-- and
O-demethylase activities or triglyceride content. The spleens, kidneys,
adrenals, and livers from all females (both main and satellite groups)
were weighed and examined histologically. Because of equivocal
developmental effects observed at all dose levels, a supplemental study
was conducted in which 30 mated dams/group received nominal doses of
tebuconazole at 0, 1, or 3 mg/kg/day orally by gavage on GD 6-15,
inclusive. The evaluations of the groups were the same as those in the
main study except that only liver and adrenals were weighed and examined
histologically. A satellite study was also again conducted: an
additional 7 mated dams/group were added to assess the effects of
tebuconazole on target organs. Satellite group animals were sacrificed
on GD 16, and the liver and adrenals were weighed and examined
histologically.

No treatment-related mortalities, clinical signs of toxicity, or
differences in maternal body weights, body weight changes, or food
consumption were observed in the study.

Based on the results from all three studies, there were dose-dependent
increases in hepatic cytochrome P450 content, N-demethylase activity,
and O-demethylase activity and vacuoliza­tion. There was a statistically
significant increases (p\<0.01) in relative liver weights of main and
satellite group dams (+20% and +29%, respectively) and absolute liver
weights of satellite group dams (+37%).

**The maternal toxicity LOAEL is 10 mg/kg/day based on increased hepatic
enzyme induction (increased cytochrome P450 content and N-demethylase
activity) and severity of vacuolization in liver cells. The maternal
toxicity NOAEL is 3 mg/kg/day.**

Treatment with 100 mg/kg/day resulted in statistically significant
increases (p\<0.05; 0.01) in postimplantation loss (35.3% vs. 8.4%
control) and the number of resorptions/dam (4.3 vs.1.0 control)
including early resorptions (3.5 vs. 0.8 control) and late resorptions
(0.8 vs. 0.2 control), and statistically significant decreases in mean
fetal weights (1.1 g vs. 1.2 g control) and the number of live
fetuses/litter (8.1 vs. 10.9 control). The combined incidence rate of
litters containing fetuses with external, visceral, and skeletal
malformations was 1/21, 6/20, and 3/18 for the 0, 1, and 3 mg/kg/day
groups, respectively, and 3/29, 7/28, 6/24, and 15/26 (p\<0.01) for the
0, 10, 30, and 100 mg/kg/day groups, respectively. The incidences of
exencephaly (partial acrania), cleft palate, open eyes, fused/bifurcated
ribs, vertebral defects (includes dysplastic vertebral bodies and
missing cervical and lumbar vertebral bodies, sacral vertebrae, and
coc­cygeal vertebrae), and retarded ossification of individual phalanges
of the fore- and hindlimbs were statistically significantly increased
(p\<0.05, 0.01) in litters in the 100 mg/kg/day group. Increases in
incidence of exencephaly, acrania, and skull malformations were also
seen in the 10 and 30 mg/kg groups. There was also an apparently
dose-related increase in incidence of 'growth on forepaw/toe, seen in 1
(1) control, 2 (2) 10 mg/kg/day, 5(4) 30 mg/kg/day, and 7(4) 100
mg/kg/day fetuses (litters), but no litters in the supplementary study
at 0, 1, or 3 mg/kg/day. Other malformations/variations were either not
statistically significant or not treatment-related at the lower doses;
no increase in incidence of malformations was seen in the supplemental
study at 1 or 3 mg/kg/day.

**The developmental toxicity LOAEL is 10 mg/kg/day based on increased
external, visceral, and skeletal malformations/variations in the head
and skull. The developmental toxicity NOAEL is 3 mg/kg/day.**

This study is classified as **acceptable/guideline** and satisfies the
guideline requirements for a developmental toxicity study (OPPTS
870.3700a) in mice.

**870.3700a Developmental Toxicity Study in Mice**

In a **dermal** developmental toxicity study (MRID 42010301), pregnant
NMRI mice received repeated dermal applications of tebuconazole in
aqueous 4% carboxymethylcellulose (CMC) at dose levels of 0, 100, 300,
or 1000 mg/kg/day during gestations days 6 through 15, inclusive. The
test material was applied to shaved skin for 6 hours/day. Dams were
sacrificed on day 18 of gestation. Since no overt maternal toxicity was
observed in this study, an additional study, employing the same
treatment regimen was conducted to assess further the maternal toxicity
of the compound. In the second study, liver microsomal enzyme activities
were increased, the incidence and severity of fatty changes in the liver
were increased, and increases were observed in the activities of AST
(GOT) and ALT (GPT) in plasma. Nevertheless, the maternal toxicity
observed in this study was considered to be equivocal. No
treatment-related developmental toxicity was observed in this study.

**For maternal and developmental toxicity by dermal route, the NOEL is
1000 mg/kg/day (HDT). The LOEL was [\>]{.underline}1000 mg/kg/day**.

This study is classified as **acceptable/guideline** and satisfies the
guideline requirements for a developmental toxicity study (OPPTS
870.3700a) in mice.

**870.3700b Developmental Toxicity Study in Rabbits**

In a developmental toxicity study (MRID 40700945), tebuconazole (HWG
1608, 98.2% ai, Lot No. 16002/85) was administered to groups of 16
presumed pregnant Chinchilla rabbits by gavage at dose levels of 0, 10,
30, or 100 mg/kg bw/day from gestation day (GD) 6 to 18. The dams were
sacrificed on GD 28 followed by gross examination of all internal organs
with a focus on the uterus, uterine contents, position of fetuses in the
uterus, and number of corpora lutea. The uteri and contents were
weighed; uteri in non-pregnant females were stained with ammonium
sulfide solution to identify implantation sites. The livers were
weighed. Fetuses were sexed, individually weighed, and examined for
gross abnormalities. The internal examination included the thorax,
abdomen, and pelvis and sex determination. The crania were examined for
ossification and the heads were fixed, serially section, and examined.
The carcasses were cleared and stained for skeletal examination.

In the high-dose group, maternal weight gain was decreased by 38% during
the dosing period, 29% during post-dosing period and 27% from GD 6-28.
After correcting for gravid uterus weight, the high-dose group had a
small weight loss (-0.3 g vs. 1.4 g weight gain for controls), whereas
the controls had a small weight gain. Food consumption was decreased by
12% in high-dose does during dosing, but was similar to or slightly
greater than that of controls during the post-dosing period. Absolute
and relative liver weights were not affected by treatment and no
treatment related gross lesions were observed in maternal animals.

**The maternal toxicity LOAEL is 100 mg/kg bw/day based on decreased
body weight gains and decreased food consumption during dosing. The
NOAEL is 30 mg/kg bw/day.**

A statistically significant increase in post-implantation loss was
observed at the 100 mg/kg/day as evidenced by increased fetal
resorptions and decreased numbers of live fetuses/dam. External
examination revealed frank malformations (peromelia, palatoschisis,
malrotation of hindlimb, agenesis of claws of the hindpaw) in the high
dose group. Examination of the fetal heads by the Wilson technique
revealed one fetus with hydrocephalus internus in the high dose.
Skeletal examination of fetuses revealed abnormalities and delayed
ossification in the high dose group only.

**The developmental toxicity LOAEL is 100 mg/kg bw/day based on
increased post-implantation loss, frank malformations, hydrocephalus and
increased external and skeletal abnormalities. The NOAEL is 30 mg/kg
bw/day.**

This developmental toxicity study is classified as
**acceptable/guideline** and satisfies the requirement (OPPTS 870.3700b)
for a prenatal developmental toxicity study in rabbits.

**870.3700b Developmental Toxicity Study in Rabbits**

In a developmental toxicity study (MRID 43776201), 16 pregnant
Chinchilla rabbits per group were administered Tebuconazole (HWG 1608
Technical) (96.3-96.8% ai; Batch No.: 816196048) by gavage at nominal
doses of 0, 10, 30, or 100 mg/kg/day on gestation days (GD) 6-18,
inclusive. On GD 28, all surviving does were sacrificed and all fetuses
were weighed and examined for external malformation/variations. Each
fetus was examined viscerally by dissection and the sex determined.
After the skin was removed, the cranium was examined for the degree of
ossification. One-half of the fetuses were decapitated, the heads fixed
in a solution of trichloroacetic acid and formaldehyde, and serially
sectioned and examined. All carcasses were processed for skeletal
examination. In the supplementary study, blood was collected from 5
does/group on GD 6, 12, and 19 for hematology and clinical chemistry. On
GD 19, these animals were necropsied following blood collection. The
adrenals, kidneys, liver, and spleen were weighed and examined
histologically. Liver samples were analyzed for cytochrome P-450
content, *N*- and *O*-demethylase activity, and triglyceride content.

No treatment-related mortalities or clinical signs of toxicity were
observed in any doe in any treated group. Decreased body weights and
decreased food consumption for gestation days 6-11 were noted in does at
the high-dose (100 mg/kg/day). In the supplementary study, with an
identical treatment regimen, single cell necrosis of the liver was seen
in 5/5 does examined in all treatment groups, compared with 1/5 in the
control animals. In addition, focal necrosis in the liver was noted in
one dam at the mid-dose.

**The maternal toxicity LOAEL is 10 mg/kg/day, based on increased
incidence of single cell necrosis (minimal severity) in liver cells; the
maternal toxicity NOAEL is not identified.**

No treatment-related differences were observed between the treated and
control groups for number of corpora lutea/doe, implantations/doe, pre-
or postimplantation loss, resorptions/doe, fetal body weights, or fetal
sex ratios. The number of fetuses (litters) examined in the 0, 10, 30,
and 100 mg/kg/day groups was 141(16), 142(15), 109(14), and 119(14),
respectively. No treatment-related skeletal malformations/variations
were observed in any fetuses. The combined incidence rate of litters
containing fetuses with external and visceral malformations was 0/16,
2/15, 5/14 (p less than 0.05), and 5/14 (p less than 0.05),
respectively.

**The developmental toxicity LOAEL is 30 mg/kg/day based on external and
visceral malformations/variations and the developmental toxicity NOAEL
is 10 mg/kg/day.**

This study is classified as **acceptable/guideline** and satisfies the
guideline requirements for a developmental toxicity study (OPPTS
870.3700b) in rabbits.

**870.3800 Reproduction Toxicity Study in Rats**

In a two-generation reproduction study (MRID 40700946), tebuconazole
(HWG 1608, 95.2% ai, Batch No. Fl No. 132) was administered in the diet
to groups of 25 male and 25 female SPF-bred Wistar \[Bor: WISW (SPF
Cpb)\] rats at concentrations of 0, 100, 300, or 1000 ppm (equivalent to
0, 5, 15, or 50 mg/kg/day). The premating period was 120 days for the
F~0~ generation and about 70 days for the F~1~ generation. The F~1~
parents were selected from the F~1b~ litters. F~0~ and F~1~ males
received the test material throughout the study until sacrifice after
mating to produce the F~1b~ and F~2b~ litters, respectively. F~0~ and
F~1~ females received the test material during the premating, mating,
gestation, and lactation periods for two litters each until sacrifice
after weaning their second litters.

Five females (three controls and two high-dose rats) died due to causes
unrelated to administration of test material. High-dose F~0~ males and
mid- and high-dose F~1~ adult females had an increased incidence of hair
loss. High-dose males and females in both generations weighed
significantly less than controls throughout the study, including the
gestation and lactation periods for all four litters. However, the
overall decrease in weight gain for F~0~ and F~1~ adult males was within
6% of the control value, and weight gain for females was within 9% of
the control value except for the gestation periods of high-dose F~0~
females, which gained 14-15% less weight than controls. Food consumption
was not significantly affected by treatment, but the overall mean food
consumption was slightly decreased at the high-dose level for F~0~ males
and F~1~ adult males and females. Absolute liver, kidney, and adrenal
weights were significantly reduced by 10-12% in high-dose F~1~ adult
male rats, and absolute kidney weight was significantly reduced by 7% in
high-dose F~1b~ female rats; relative weights were not significantly
reduced in either sex. The relative testes weight was significantly
increased by 8% in high-dose F~1~ adult males. There were no
treatment-related lesions in the liver or kidneys in either generation.
The severity but not the incidence of splenic hemosiderosis was
increased in high-dose F~0~ male and female rats and the incidence of
hemosiderosis was significantly increased in high-dose F~1~ adult female
rats. Hemosiderosis was more severe in females than in males. The
incidence of hematopoiesis in the spleen also was significantly
increased in high-dose F~0~ males. The effect of treatment on splenic
hemosiderosis and hematopoiesis is suggestive of increased erythrocyte
turnover.

**The parental toxicity LOAEL is 1000 ppm (50 mg/kg/day) based on
decreased weight gain during gestation in females and increased severity
of splenic hemosiderosis in both sexes and increased incidence of
hematopoiesis in the spleen in males. The NOAEL is 300 ppm (15
mg/kg/day).**

There was no treatment-related effect on reproductive indices
(insemination or mating, fertility, gestation) in either the F~0~ or
F~1~ generations. The length of gestation also was similar in all
treated groups in both generation and the controls.

**The reproductive toxicity NOAEL is 1000 ppm (50 mg/kg/day), the
highest concentration tested.**

The viability index for the low- and high-dose F~1a~ pups and the
lactation index for the low- and high-dose F~1b~ pups were significantly
reduced compared with that of controls; these data show no dose-response
relationship. Viability and lactation indices were not affected in F~2a~
and F~2b~ pups. The number of F~1a~ and F~1b~ pups/litter was reduced at
birth and throughout lactation; statistical significance was reached
only for F~1b~ pups. High-dose F~1a~, F~2a~, F~2b~ pup body weights were
significantly reduced at birth and throughout lactation; high-dose F~1b~
pup body weight was significantly decreased at week 4 (weaning). The
bone (femur) length and diameter in F~1b~ pups was similar to that of
controls.

**The offspring LOAEL is 1000 ppm (50 mg/kg/day) based on decreased pup
weight. The NOAEL is 300 ppm (15 mg/kg/day).**

This two-generation reproduction study in rats is classified as
**acceptable/guideline** and satisfies the guideline requirement (OPPTS
870.3800) for a reproduction and fertility study.

**A.3.3 Chronic Toxicity and Carcinogenicity**

**870.4300 Combined Chronic/Carcinogenicity Study in Rats**

In a chronic toxicity/carcinogenicity study (MRID 40700939),
tebuconazole (HWG 1608, 95% ai, Batch No. Fl. No. 132) was administered
to Wistar \[Bor: WISW (SPF Cpb)\] (50/sex/group) rats at dietary
concentrations of 0, 100, 300, or 1000 ppm (equivalent to 0, 5.2, 15.9,
or 55.0 mg/kg bw/day for males and 0, 7.4, 22.8, or 86.3 mg/kg bw/day
for females, respectively) for 2 years. Groups of 10 male and 10 female
rats receiving the same diets were sacrificed at 12 months for interim
evaluation.

No adverse clinical signs or decreased mortality was observed in treated
rats. Mean body weight and weight gain in males were not affected by
treatment with the test material, but high-dose females weighed 7-10%
less than controls throughout the study and gained 12% less weight than
controls during the first year and gained 11% less weight overall.
Weight gain during the second year was not different from that of
controls. A compound --related decrease in food efficiency was seen in
mid- and high-dose females. Treatment-related hematologic changes
included significantly decreased hemoglobin, hematocrit, mean
corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in mid-
and high-dose females at week 79. MCV and MCH were significantly
decreased in high-dose females at week 27, hematocrit and MCV were
significantly decreased at week 52, and MCH was significantly decreased
at week 104. No treatment-related hematological effects were apparent in
males. Clinical chemistry changes were inconsistent, sporadic, and were
not dose or sex related.

Gross pathology observation of animals dead or sacrificed moribund
revealed an increase in the incidences of cysts/cystic kidneys (4/50
high-dose males vs. 0/49 in control) and of reddened lymph nodes (6/50
high-dose males vs. 1/49 in control). Significant decreases of absolute
and relative adrenal weight were noted in all female treatment groups at
terminal sacrifice. A dose-related significant decrease in relative
testes weights was also reported in the high-dose males at the final
sacrifice. The incidences of shrunken testes were increased at the mid
(7/50) and high-doses (6/50) vs. controls (3/49).

Non-neoplastic histopathology indicated a statistically significant
increase in hemosiderin deposition in the spleen of high dose females
(19/50) vs. controls (2/50); these changes were consistent with the
hematological findings and indicated increased clearance of RBC's in the
spleen. Increased incidence of thyroid C-cell hyperplasia was observed
in the mid- and high-dose males (7/50 and 6/50, respectively) vs. 1/50
in controls.

**The chronic toxicity LOAEL for males is 1000 ppm (55 mg/kg/day) based
on decreased testes weight, the NOAEL is 300 ppm (15.9 mg/kg/day). The
LOAEL for females is 300 ppm (22.8 mg/kg/day) based on decreased body
weight and weight gain and evidence of increased erythrocyte clearance
(decreases in erythrocyte parameters and an increase in the incidence of
splenic hemosiderosis), the NOAEL is 100 ppm (7.4 mg/kg bw/day).**

There was no evidence of a treatment-related increase in the incidence
of neoplastic lesions in male or female rats. Thyroid c-cell hyperplasia
was significantly increased in mid-dose females and marginally increased
in high-dose females compared with the incidence in the control group.
The doses used in this study were considered adequate based on decreased
body weight and weight gain in females and decreased testes weight in
males at the high dose.

This chronic toxicity/carcinogenicity study is **acceptable/guideline**
and satisfies the guideline requirement for a chronic
toxicity/carcinogenicity study (OPPTS 870.4300).

**870.4100b Chronic Toxicity Study in Dogs**

In a chronic oral toxicity study (MRID 40700940), four male and four
female beagle dogs were fed tebuconazole (HWG 1608, 96.9% ai, Batch No.
Fl.132) at dietary concentrations of 0, 40, 200, or 1000/2000 ppm
(equivalent to 0, 15.5, 77.3, or 483 mg/kg/day, respectively) for 12
months. The high dose group was fed the diet containing 1000 ppm for the
first 39 weeks and 2000 ppm from week 40 to termination at 52 weeks.

All animals survived to study termination, and no treatment-related
clinical signs or effects on body weight, weight gain, or food
consumption were observed. Ophthalmoscopic examination showed corneal
opacity in all groups, but it was more severe in the three mid- and
three high-dose dogs than in the two controls examined. Moderate
anisocytosis was observed in two mid-dose and five high-dose dogs
compared with none of the controls, splenic hemosiderosis was observed
in five high-dose, three mid-dose, and three low-dose dogs compared with
two controls, and hemosiderin phagocytosis was observed in two low-dose,
three mid-dose, and three high-dose dogs compared with two controls.
Splenic and liver hemosiderin is likely related to the increased
anisocytosis. No clear treatment-related effect was observed on clinical
chemistry parameters. Liver triglycerides were increased by 20% and 61%
in high-dose male and female dogs, respectively, at study termination.
Gross changes were observed in the liver (lobulation) of two mid- and
five high-dose dogs, but microscopic changes (ORO-positive lipids) were
observed in the liver of only one mid- and one high-dose male dog
compared with none of the male controls. The lobulation may have been
due to the increase in N-demethylase activity in the liver of male and
female dogs in the high-dose group, which is likely an adaptive
response. No dose-related changes in liver, kidney, or adrenal weights
were observed. Cytoplasmic vacuoles were observed in the zona
fasciculata cells of the adrenal gland in two mid- and two high-dose
females.

**The chronic toxicity LOAEL is 200 ppm (77.3 mg/kg/day) based on ocular
lesions and changes in erythrocyte morphology (anisocytosis) in both
sexes and adrenal gland lesions in females. The NOAEL is 40 ppm (15.5
mg/kg/day).**

This chronic toxicity study is **acceptable/guideline** and satisfies
the requirement for a chronic oral toxicity study (OPPTS 870.4100b) in
dogs.

**870.4100b Chronic Toxicity in Dogs**

In a chronic toxicity study (MRID 42030601 and 42537201), tebuconazole
(HWG 1608, 96% ai, Batch No. 16013/86) was administered in the diet to
groups of four male and four female pure-bred beagle dogs at
concentrations of 0, 100, or 150 ppm (equivalent to 0, 2.96, or 4.39
mg/kg bw/day for males and 0, 2.94, or 4.45 mg/kg bw/day for females,
respectively) for 1 year. One female dog in the control group sacrificed
on day 70 because of deteriorating physical condition was replaced by
another female from the same shipment. This study was conducted as a
follow up to the initial dog study (MRID 40700940) to further define the
NOAEL for HWG 1608 in dogs.

No treatment-related effects on mortality, clinical signs, body weight,
weight gain, food consumption, hematologic parameters, clinical
chemistry parameters, urinalysis parameters, eyes (ophthalmoscopic),
organ weights, or gross lesions were observed in this study. Hepatic
N-demethylase showed a dose-related decrease in both sexes and hepatic
triglycerides showed a dose-related increased in female dogs. Hepatic
O-demethylase activity showed a dose-related increase in males.
Histopathologic examination indicated the adrenal gland as a target of
the test material in both sexes. In males, hypertrophy of the zona
fasciculata cells in the adrenal gland was observed in 4/4 dogs at 150
ppm compared with none at 100 ppm or the control group; lipid
hyperplasia in the adrenal cortex was observed in 2/4 dogs at 150 ppm
compared with 1/4 at 100 ppm and 1/4 controls; fatty change in the zona
glomerulosa was observed in 3/4 dogs at 150 ppm compared with 14 in the
100-ppm and the control groups. In females, hypertrophy of the zona
fasciculata was observed in 4/4 at 150 ppm compared with 0/4 at 100 ppm
and 1/4 controls; fatty change in the zona glomerulosa was observed in
2/4 dogs at 150 ppm compared with 1/4 in the 100-ppm and control groups.

**The chronic toxicity study LOAEL is 150 ppm (4.39 and 4.45 mg/kg/day,
respectively) based on lesions in the adrenal gland of both sexes. The
NOAEL is 100 ppm (2.96 and 2.94 mg/kg/day, respectively).**

This chronic toxicity study taken together with the initial study (MRID
40700940) is **acceptable/guideline** and satisfies the guideline
requirement for a chronic oral study (OPPTS 870.4100b) in a non-rodent
species.

**870.4200b Carcinogenicity Study in Mice**

In a carcinogenicity study (MRID 40700941), HWG 1608 was administered in
the diet to groups of 50 male and 50 female Bor:NMRI (SPF Han) mice at
concentrations of 0, 20, 60, or 180 ppm (equivalent to 0, 5.9, 18.2, or
53.1 mg/kg bw/day for males and 0, 9.0, 26.1, or 80.5 mg/kg bw/day for
females, respectively) for 21 months. Additional groups of 10 male and
10 female mice were administered the same dietary concentrations for 12
months for interim evaluation.

Statistical analysis of mortality data indicated no significant trends
in mortality with increasing doses in either sex. However, pair-wise
comparisons indicated a significant total higher mortality (p \< 0.05)
in high-dose males (24/52) vs. controls (13/51)

Body weight and body weight gain were slightly but significantly
decreased 4.9% and 7% from control, respectively, in males at the
highest dose tested (HDT). No alteration in female body weight was
noted.

There were no consistent, compound-related changes in hematology.
Clihical chemistry values were altered in females but not in males.
Bilirubin values were statistically significantly elevated in a
dose-related fashion at all doses relative to controls, and cholesterol
levels were decreased in 180 ppm females at 53 weeks and in 60 ppm
females at termination.

At termination of the study there was a consistent elevation in absolute
and relative liver weight at the HDT for both sexes, but statistical
significance was reached only for relative weights in the HDT males.
Terminal sacrifice histopathology also indicated the liver as the major
target for toxicity, although minimal effects were noted in some other
organs. In males, the most frequent hepatic alterations (in 50
mice/dose) were minimal to marked centrilobular fine vacuolation
(0/control vs. 1/LDT, 4/MDT, 13/HDT); minimal focal periportal
vacuolation (0/control vs. 0/LDT, l/MDT, and 8/HDT); various degrees of
centrilobular and periportal lipid deposition (3/controls vs. 1/LDT,
4/MDT, and 19/HDT); minimal focal centrilobular fine vacuolation
(0/controls vs. 2/LDT, 5/MDT, and 2/HDT).

In females, the most frequent hepatic alterations (in 50 mice/dose) were
moderate centrilobular vacuolation (0/control vs. 2/MDT, 2/HDT); minimal
diffuse vacuolation (0/control vs. 7/HDT); minimal extramedullary
hemopoiesis (2/control vs. 5/LDT, 6 for MDT and HDT); increased
sinusoidal cellularity (1/control vs. 5/HDT); various degrees of lipid,
deposition (3/control vs. 6/MDT, 12/HDT).

Statistical analysis of tumor data indicated no significant
compound-related hepatocellular tumor rates in either males or females.
The combined incidences of adenornas/carcinomas in either males or
females (up to 12%) were within the historical control range (6-18%)
reported by the Registrant for combined benign plus malignant liver
tumors from 6 studies with NNRI mice performed from 1980 to 1984.
Pulmonary adenomas and adenocarcinomas were observed, but the effect was
not dose-related.

The HED Carcinogenicity Peer review Committee (CPRC) reviewed the study
and concluded that the high-dose treatment (180 ppm) was not high enough
to assess the carcinogenic potential of the chemical and classified this
study as Supplementary. Following this, the registrant submitted a
second carcinogenicity study in mice at high doses. The study is
summarized as follows.

In a carcinogenicity study (MRID 42175001), groups of Bor:NbI(SPF Han)
mice (60/sex/dose) received tebuconazole (HWG 1608, 96.2% ai) in the
diet at dose levels of 0, 500, or 1500 ppm (equivalent to 0, 84.9 or 279
mg/kg/day for males and 0, 103.1 or 365.5 mg/kg/day for females,
respectively) for up to 91 weeks. A group consisting of 10 mice/sex/dose
was interim-sacrificed at 52 weeks, the remaining animals were
terminally sacrificed, at 91 weeks. Doses were selected based on the
first mouse carcinogenicity study and in two prior 4- and 8- week pilot
feeding studies conducted in mice of the same strain.

Statistical analysis of mortality data indicated no significant trends
in mortality with increasing doses in either sex. Body weight in both
sexes was depressed in a dose-related fashion; effects were seen at 500
ppm in the first half of the study (-6.3% in males, sporadic in females)
and 1500 ppm throughout the study in both males (-9% to -11%) and
females (-7.6% to -8.5%) . Body weight gain was decreased in a dose-
related fashion in both sexes. For weeks 0-24, body weight gain averaged
8% and 10.4% below control levels in both sexes of the 500 and 1500 ppm
groups, respectively. Statistically significantly increased food
consumption at 500 ppm in males and at 1500 ppm in both sexes was
reported, consistent with decreased food efficiency in these groups.

Statistically significant changes in blood parameters were observed at
the high dose in both sexes, mainly in males. At sacrifice, the
statistically significant changes included leucocytosis, and changes
consistent with anemia (decreased erythrocytes, hemoglobin, MCHC, and
hematocrit values). In addition, high-dose males had statistically
significantly increased platelet counts and decreased throroboplastin
times. In the case of high-dose females, a reduced hematocrit and
leucocytosis were observed at 51 weeks, and only an increased platelet
count at terminal sacrifice.

Clinical chemistry data revealed dose-dependent and statistically
significant increases in alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) for both sexes in the interim and final
sacrifices. Alkaline phosphatase (AP) increased with dose in both sexes
and reached statistical significance at 1500 ppm. These changes
correlated with dose- dependent and statistically significant
histopathological findings in liver. Cholesterol was statistically
significantly decreased vs. controls in both sexes at 500 and 1500 ppm
for the interim sacrifice, and at 500 ppm for the final sacrifice.

Non-neoplastic histopathology at interim sacrifice (52 weeks) revealed
hepatocellular abnormalities in both sexes. In males, "dose-dependent
increases in individual hepatocyte necrosis, panacinar fatty
vacuolation, pigment laden Kupfer cells and CRC stained panacinar fat
which were statistically significant (p c 0.05-0.001) at 500 and 1500
ppm. Incidences of these effects at 1500 ppm ranged from 5/10
(periportal fibrosis) to 10/10 (panacinar fine fatty vacuolation) vs.
0/10 in controls. In addition, the incidence of bile duct hyperplasia at
the HDT (8/10) was statistically significantly elevated vs. controls

(0/10).

In females, panacinar fine fatty vacuolation was seen in 100% of both
500 and 1500 ppm females and was statistically significantly elevated (p
c 0.001) vs. controls which had no incidence of this effect. There were
also dose-related increases in individual hepatocyte necrosis, bile duct
hyperplasia, chronic inflammatory cells in the portal area,
extramedullary hemopoiesis, all of which reached statistical
significance at the high-dose (p \< 0.05-0.001). Incidences of these
effects at 1500 ppm ranged from 6/10 (extramedulary hemopoiesis) to 9/10
(hepatocyte necrosis) vs. 0/10 in controls.

Non-neoplastic histopathology at terminal sacrifice (91 weeks) revealed
hepatocellular abnormalities in both sexes (Table 10). In males,
dose-related and statistically significant increases in hepatic
panacinar fine fatty vacuolation at 500 (14/48) and 1500 (25/48) ppm vs.
0/47 in controls and statistically significant increases in focal
hyperplasia of hepatocytes (23/48) and oval cell proliferation (23/48)
at 1500 ppm vs. 0/47 in controls.

In females, dose-related increases in hepatic panacinar fine fatty
vacuolation (19/46) which was statistically significant at 1500 ppm. In
addition, at 1500 ppm there were increases in periacinar hepatocyte
hypertrophy (13/46), oval cell proliferation (17/46), and eosinophilic
foci of hepatocyte alteration (7/46) which were statistically
significant vs. controls (0/47).

Statistical analysis of tumor data indicated that male mice had
statistically significant, dose-related increasing trends in
hepatocellular adenomas, carcinomas and combined 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% controls) and combined adenomas and/or carcinomas (47% vs.
5% controls). No statistically significant differences were found in
paired comparisons for the 500 ppm group vs. controls.

The combined carcinogenicity study is considered acceptable/guideline
and satisfies guideline requirement for a carcinogenicity study in mice
(OPPTS 870.4200b).

**A.3.4 Mutagenicity**

**Gene Mutation**

+-----------------------+----------------------------------------------+
| Guideline 870.5100    | Mutagenicity was tested at seven             |
|                       | concentrations ranging from 39.5-450 μ/plate |
| Salmonella point      | in the presence and absence of rat liver S9  |
| mutation              | fraction.                                    |
|                       |                                              |
| MRID 40700947 &       | The test was negative at all doses in the    |
| 40700948              | presence and absence of S9                   |
|                       |                                              |
| Acceptable/guideline  | A ranging-finding test showed strong         |
|                       | cytotoxicity at 600 μg/plate and above       |
| Guideline 870.5300    |                                              |
|                       | Mutagenicity was tested at six               |
| CHO-HGPRT in vitro    | concentrations in the absence of metabolic   |
| forward mutation      | activation ranging from 80-100 μg/mL and at  |
|                       | six concentrations in the presence of rat    |
| MRID 40700949         | liver S9 ranging from 12.5-200 μg/mL.        |
|                       |                                              |
| U                     | Both tests were negative in the presence and |
| nacceptable/guideline | absence of S9. The required level of         |
|                       | cytotoxicity was not reached in the presence |
|                       | or absence of S9.                            |
+-----------------------+----------------------------------------------+

**Cytogenetics**

+-----------------------+----------------------------------------------+
| Guideline 870.5375    | Mutagenicity was tested on primary human     |
|                       | lymphocyte cultures at three concentrations  |
| In vitro cytogenetic  | ranging from 3.0-30.0 μg/mL in the absence   |
| (human lymphocytes)   | of rat liver S9 and at three concentrations  |
|                       | ranging from 30.0-300.0 μg/mL in the         |
| MRID 40700953         | presence of rat liver S9.                    |
|                       |                                              |
| Ac                    | The test was negative at all doses in the    |
| ceptable/guideline, + | presence and absence of S9. The required     |
| S9                    | level of cytotoxicity was not reached in the |
|                       | absence of S9.                               |
| Un                    |                                              |
| acceptable/guideline, | The induction of micronuclei was tested on   |
| -S9                   | bone marrow erythrocytes taken from mice     |
|                       | injected i.p. with 200, 500, or 1000 mg/kg   |
| Guideline 870.5395    | bw and sacrificed 24, 48, or 72 hours after  |
|                       | injection.                                   |
| Mammalian erythrocyte |                                              |
| micronucleus test     | The test was negative at all doses           |
|                       |                                              |
| MRID 40700951         | Dominant lethality was tested in male mice   |
|                       | administered a single oral dose of HWG 1608  |
| Acceptable/guideline  | at 0 or 2000 mg/kg bw followed by serial     |
|                       | mating of each male with untreated virgin    |
| Guideline 870.5450    | females for 12 periods.                      |
|                       |                                              |
| Mouse dominant        | Dominant lethality was not induced. A        |
| lethality test        | positive control was not used and only one   |
|                       | dose was tested                              |
| MRID 40700950         |                                              |
|                       |                                              |
| U                     |                                              |
| nacceptable/guideline |                                              |
+-----------------------+----------------------------------------------+

**Other Genotoxicity**

+-----------------------+----------------------------------------------+
| Guideline 870.5500    | The test was conducted on two strains of E.  |
|                       | coli (repair deficient and repair            |
| DNA damage and repair | proficient) at five different doses ranging  |
| (E.coli)              | from 625-10,000 μg/plate in the presence and |
|                       | absence of rat S9.                           |
| MRID 40700955         |                                              |
|                       | No DNA damage or repair was detected in the  |
| U                     | presence or absence of S9.                   |
| nacceptable/guideline |                                              |
|                       | No growth inhibition zone detected.          |
| Guideline 870.5550    |                                              |
|                       | Unscheduled DNA synthesis was tested on      |
| Unscheduled DNA       | primary rat hepacytes incubated with six     |
| synthesis (rat        | concentrations ranging from 0.504-25.2       |
| primary hepatocyte    | μg/mL.                                       |
| cultures)             |                                              |
|                       | The test was negative at all doses tested.   |
| MRID 40816402         |                                              |
|                       | CHO cells were incubated at four             |
| Acceptable/guideline  | concentration ranging from 4-30 μg/mL in the |
|                       | absence of rat liver S9 and four             |
| Guideline 870.5900    | concentrations ranging from 15-120 μg/mL in  |
|                       | the presence of S9                           |
| Sister chromatid      |                                              |
| exchange (CHO cell in | The test was negative in the presence and    |
| vitro)                | absence of S(                                |
|                       |                                              |
| MRID 40700952         |                                              |
|                       |                                              |
| Acceptable/guideline  |                                              |
+-----------------------+----------------------------------------------+

**A.3.5 Neurotoxicity**

**870.6200 Acute Neurotoxicity in Rats**

In an acute oral neurotoxicity study (MRID 44449301), technical grade
tebuconazole (Batch \# 603-0013, 96.5% purity) was administered by
gavage to 12 male Fischer 344 rats at doses of 0, 100, 500, or 1000
mg/kg and to 12 female Fischer 344 rats at doses of 0, 100, 250, or 500
mg/kg. Because a NOAEL did not appear to be attained in this study, a
second (supplemental) acute oral neurotoxicity study (MRID 44545701)
using the same batch and doses of 0, 20, or 50 mg/kg to 12 Fischer 344
rats/sex/group was performed. Based on analytical results, actual doses
were 0, 0, 21, 50, 103, 497, and 950 mg/kg for male rats and 0, 0, 21,
50, 103, 239, and 497 mg/kg for female rats. In the main study,
functional observational battery (FOB) and motor activity tests were
performed pretreatment, on the day of test material administration (day
0), and on days 7 and 14 posttreatment; in the supplemental study, an
abbreviated FOB and motor activity tests were performed on day 0 only.
At the completion of the main study (day 14), 6 rats/sex in the control
and high-dose groups were subjected to perfusion, and brain and nervous
tissues were examined microscopically. No histopathological evaluations
were performed in the supplemental study.

The high dose of 1000 mg/kg resulted in mortality of 6/12 male rats
within two days of treat­ment. One male rat in the 500 mg/kg dose group
also died. There was no treatment-related mortality in females of any
dose group. Clinical signs of incoordination, decreased activity, and
nasal and perianal stains were observed on day 0, primarily in the two
highest dose groups (males, 500 and 1000 mg/kg; females, 250 and 500
mg/kg). Effects on body weight were minimal; weights were 96-101% of
control weights on day 14. There was no effect of treatment on brain
weight and there were no histopathological findings in the brain or
tissues of the nervous system that could be attributed to treatment.

FOB tests on the day of treatment showed treatment-related effects on
gait (incoordination, ataxia); activity, arousal, and response to
stimuli (all decreased); hindlimb grip strength (decreased); footsplay
(decreased in females only); and body temperature (decreased) in one or
both sexes in the two highest dose groups (males, 500 and 1000 mg/kg and
females, 250 and 500 mg/kg). Most of these parameters were statistically
significantly different from control values (p\<0.05). Increased arousal
in the open field and decreased footsplay were also noted in females at
100 mg/kg. All effects except decreased footsplay in 250 and 500 mg/kg
females were resolved by post-test day 7. No changes in FOB parameters
were observed in males in the 100 mg/kg dose group. No treatment-related
FOB effects were observed in either sex in the 20 and 50 mg/kg dose
groups.

Relative to concurrent controls, motor and locomotor activity were
increased on day 0 in males and females in the 100 mg/kg dose group and
decreased in the higher dose groups (males, 500 and 1000 mg/kg and
females, 500 mg/kg; all p\<0.05). There was no statistically significant
change in 250 mg/kg females. No adverse effect of treatment on motor
activity was observed in either sex in the 20 and 50 mg/kg dose groups,
although there was a slight (non-statistically significant) increase in
50 mg/kg males that was considered compound-related. No effect of
treatment was observed on motor or locomotor activity on days 7 and 14.

**The LOAEL is 100 mg/kg based on increased motor activity in male and
female rats and decreased footsplay in female rats. The NOAEL for both
male and female rats is 50 mg/kg.**

This study is classified as **Unacceptable/Guideline/(upgradeable)** as
an acute oral neurotoxicity study and does not fulfill FIFRA guideline
requirements for an acute oral neurotoxicity study in rats \[OPPTS
870.6200 (§81-8)\]. This study can be upgraded by submission of (1) a
report from the range-finding study, so that time of peak effect can be
verified; (2) additional information regarding the test substance
preparation and analysis.

**870.6200b Subchronic Neurotoxicity in Rats**

In a 90-day dietary neurotoxicity study (MRID 44588001), tebucona­zole
(Batch No.: 603-0013, 96.7%-98.2% purity) was administered to 12 Fischer
344 rats/sex/dose at dietary levels of 0, 100, 400, or 1600 ppm. Based
on analytical measurements, doses were 0.00, 7.57, 29.2, and 107
mg/kg/day for males and 0.00, 8.81, 34.0, and 122 mg/kg/day for females.
Functional observational battery (FOB) and motor activity tests were
performed pretreatment and during weeks 4, 8, and 13. At the completion
of the study, 6 rats/sex/dose group were subjected to perfusion; brain
and nervous tissues were examined microscopically in high dose and
control groups only.

No deaths occurred and there were no clinical signs attributable to
treatment. Relative to con­trols, body weights of male and female rats in
the group receiving 1600 ppm in the diet were statistically
significantly reduced after one week, by 7% in males and 5% in females
(both p\<0.05). Lower body weights continued throughout the remainder of
the study with reductions of 8% for males and 7% for females at study
termination (both p\<0.05). Food consumption was reduced throughout the
study in this group, with average daily food consumption for males and
females of 94% and 92% relative to respective controls. Food efficiency
was reduced by 11% and 13% in high-dose males and high-dose females,
respectively. Relative to controls, there were no treatment-related
effects on body weight or food consumption or efficiency in the other
dietary groups.

No treatment-related effects were observed on FOB tests or motor
activity tests. There were no gross or histopathological findings that
could be attributed to treatment with tebuconazole.

**The NOAEL is 1600 ppm in the diet (107 mg/kg/day in male rats and 122
mg/kg/day in female rats). A LOAEL was not achieved in this study.**

This study is classified as **Unacceptable/Guideline** and does not
fulfill FIFRA guideline requirements for a subchronic neurotoxicity
(90-day) study in rats \[870.6200(§82-1b)\] because the study was not
tested at adequate doses based on observations of treatment-related but
toxicologically insignificant reductions in body weight, food intake,
and food efficiency; the absence of effects in the FOB and motor
activity tests; and the absence of histopathological lesions in the
brain and nervous system..

**870.6300 Developmental Neurotoxicity in Rats**

In a developmental neurotoxicity study (MRID 45074301), tebuconazole
(96-96.9% ai; Lot/Batch #603-0013) in corn oil was administered via the
diet to pregnant Crl:CD^®^BR VAF/Plus^®^ (Sprague Dawley) rats (25/dose)
from gestation day (GD) 6 to lactation day (LD) 11 at doses of 0, 100,
300 or 1000 ppm (equivalent to \[GD/LD\] 0/0, 8.8/16.3, 22.0/41.3, and
65.0/125.4 mg/kg/day). No analytical data were provided. P dams were
allowed to deliver naturally. On day 5 postpartum, litters were
standardized to a maximum of 10 pups/litter. Pups were assigned to one
of 5 Subsets (20 pups/sex/dose in each subset). Physical development
landmarks were evaluated for all subsets (including surface righting,
eye opening, pinna unfolding, acoustic startle response, and pupil
constriction); sexual maturation was evaluated in subsets 2-4. Subset 1
pups were sacrificed on postnatal day 12; brains were weighed for all
Subset 1 pups, and histopathological evaluations were performed on 6/sex
in control and high dose groups (morphometric analysis was performed on
6/sex in control, mid-dose, and high dose groups). Subset 2 pups were
evaluated for learning and memory on day 23-25 (passive avoidance) and
on day 59-63 (Water M-maze). Subset 3 pups were evaluated for motor
activity (days 14, 18, 22, and 62) and for auditory startle habituation
(days 23 and 63). Subset 4 pups received detailed weekly clinical
evaluations. In addition, 6 animals/sex/group in Subset 4 were selected
for neuropathological evaluations; brains were weighed and the high dose
and control animals were evaluated histopathologically on day 83
(morphometric analysis was performed on 6/sex in control, mid dose, and
high dose groups). Subset 5 pups were sacrificed and necropsied on day
22.

At 1000 ppm, two P females died as a result of prolonged gestation. Body
weights were slightly decreased (p0.01) in the P females during
gestation (4-8%) and early lactation (6-12%). Body weight gains were
decreased (p0.01 or 0.05) during GDs 6-9 (400%) and 6-21 (22%), and
during LDs 1-12 (55-164%). When compared to concurrent controls,
absolute (g/animal/day) food consumption was reduced (p0.05 or 0.01) in
the dams throughout gestation (9-23%) except during the GD 0-6 interval,
and during the LD intervals 4-7 (20%) and 7-12 (18%). Relative
(g/kg/day) food consumption was reduced (p0.05 or 0.01) starting on GD 6
(6-20%) and during early lactation (up to day 12, (8-12%). There was
also an increase in alopecia in high dose dams. The number of live
fetuses/dam was decreased relative to concurrent controls (6%, p0.01);
while the number of dead fetuses/dam was increased relative to
concurrent controls (200%, p0.01).

No treatment-related findings were observed in dams at 300 or 100 ppm.

**The LOAEL for maternal toxicity is 1000 ppm (equivalent to \[GD/LD\]
65.0/125.4 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. The NOAEL is 300 ppm (equivalent to
\[GD/LD\] 22.0/41.3 mg/kg/day).**

At 1000 ppm, the stillborn index was increased (200%, p0.01) and the
number of pup deaths (calculated by reviewers) was increased during days
1-5 (229%). Body weights were decreased (p0.01) in the males from PND 5
to 86 (7-23%) and in the females from PND 5 to 72 (5-24%). Pinna
unfolding was delayed (19%, p0.01) relative to concurrent controls.
There were decreases in several morphometric measurements of the brain,
including decreased (p0.01) thickness of the cerebellum in the males and
females on day 12 (10-14%) and on day 83 (7-9%), and an increased
thickness of the germinal layer of the cerebellar cortex in the Day 12
males (23%, p0.01). Absolute brain weights were decreased in the Day 12
and Day 83 animals (10-16%, p0.01 or 0.05). Relative (to body) brain
weights were increased (p0.01 or 0.05) in the day 12 males and females
(10-15%). There were also statistically significant changes in motor
activity on days 14 (43% decrease in males \[p\<0.01\], 24% decrease in
females \[n.s.\]) and 22 (39% increase in males \[p\<.05\], 19% increase
in females \[n.s.\]), and changes in auditory startle amplitude at both
time points (decreased in both sexes on day 23 \[14-33%\], decreased in
females \[20%\] and increased in males \[71%\] on day 63).

At 300 ppm, there were also decreases in body weight (3-7%) and body
weight gain (4-16%, PND5-23 and 72-86 in males, PND5-51 in females).
Pinna unfolding was delayed (16%). There were changes in auditory
startle amplitude in both sexes: a dose-related decrease in females on
day 23 (decreased 26%), and a dose-related increase in males on day 63
(increased 18%). In addition, there was a decrease in absolute brain
weight in both sexes (3-4%) on day 12 (statistically significant for
females only), and in brain measurements (anterior/posterior cerebrum).

At 100 ppm, there were decreases in body weight (3-7%) and body weight
gain (5-13%) (PND 5-37 in males, PND 5-51 in females). There were
decreases in motor activity (on days 14 and 18 in males \[28-35%\]) and
changes in auditory startle amplitude (decreased 9% in day 14 females,
increased 16% in day 63 males, n.s.). There was also a decrease in
absolute brain weight in both sexes on day 12 (4%, statistically
significant for both sexes), and in brain measurements
(anterior/posterior cerebrum).

**The LOAEL for offspring toxicity is 100 ppm (8.8 mg/kg/day for males
and 16.3 mg/kg/day for females)** **based on** **decreases in body
weights, absolute brain weights, brain measurements, and motor activity.
The NOAEL is not determined.**

This study is classified as **Acceptable/Guideline** and satisfies the
guideline requirement for a developmental neurotoxicity study in rats
(OPPTS 870.6300).

**A.3.6 Metabolism**

In a metabolism study (MRID 40995911 and 40995912), labeled
tebuconazole, (phenyl-UL-14CJ- and triazole-3,5-14C) was administered to
male and females Wistar rats as a single oral dose of 2 or 20 mg/kg or
as a single oral dose of 2 mg/kg following oral administration of
unlabeled tebuconazole at 2 mg/kg/day for 14 days. The triazole-labeled
compound was administered as a single oral dose of 20 mg/kg.

When \[phenyl-UL-14C\]-labeled tebuconazole was administered as a single
oral dose of 2 or 20 mg/kg to male and female Wistar rats, the compound
was rapidly and extensively absorbed, extensively metabolized, and
rapidly excreted. Over 98% of a single oral dose of
\[phenyl-UL-'4C\]-labeled tebuconazole (2mg/kg) was absorbed from the GI
tract, based on \[14C\] excretion in urine (7.4% of the dose) and in
bile (90.68% of the dose), as determined in bile-fistulated male rats.
In intact rats, over 86-98% of the administered radioactivity was
excreted by 72 hours. About 14-16% and 72-82% of the dose appeared in
urine and feces, respectively, in males and about 28-32% and 62% of the
dose appeared in urine and feces, respectively, in females. Tissue
concentrations were highest in liver at sacrifice, 72 hours after
dosing. Tebuconazole undergoes extensive metabolism in rats. A total of
10 compounds were identified in excreta, amounting to 51-58% of the dose
in males and to 68-71 % of the dose in females. The untransformed parent
compound amounted to 0.5- 2.2% of the dose. A large fraction of the
identified metabolites corresponded to successive stages in the
oxidation of one of the methyl groups in the t-butyl moiety of
tebuconazole. Dose- dependent changes in metabolite ratios of
tebuconazole are suggestive of changes in detoxication patterns at the
high dose; these may result from metabolic saturation.

**A.3.7 Dermal Absorption**

Two dermal absorption studies are available for Tebuconazole. In a
monkey dermal absorption study (MRID 46634901), the percent dermal
absorption for an 8 hour exposure to tebuconazole in Folicur EW 250, at
a dose of 132 micrograms/sq cm of skin, was 23.1% (Memo R. Zendzian to
P. Deschamp, 6/22/2005). This includes the fraction of the dose absorbed
(11.5%) and the amount of the dose remaining in the skin after washing
(estimated as 11.6%, based on the proportion of the dose not recovered
via excretion or washing). In a rat dermal penetration study (MRID
40995913), the percent dermal absorption at a dose of 0.604
micrograms/sq cm of skin was 52.5% at 24 h (including 27.8% absorbed and
24.7% remaining in skin).

Based on the above information, a 23.1% (at 8 hours) dermal absorption
factor was selected from the dermal absorption study in monkeys and
should be applied to dermal risk assessments.

![](media/image12.wmf){width="6.489583333333333in"
height="8.408333333333333in"}

![](media/image13.wmf){width="6.489583333333333in"
height="8.408333333333333in"}

![](media/image14.wmf){width="6.489583333333333in"
height="8.408333333333333in"}

**Appendix B: Metabolism Assessment**[]{#__RefHeading___Toc196283183
.anchor}

**B.1 Metabolism Considerations**[]{#__RefHeading___Toc196283184
.anchor}

***Proposed Goat Metabolism:***

![](media/image15.png){width="4.134027777777778in" height="3.375in"}

![](media/image16.wmf){width="5.95625in" height="3.9763888888888888in"}

***Proposed Poultry Metabolism:***

![](media/image17.png){width="4.385416666666667in"
height="3.9069444444444446in"}

![](media/image18.wmf){width="5.779166666666667in"
height="4.5256944444444445in"}

***Rat Metabolism:***

Note -- HWG-2685 is depicted in the figure, but was not identified in
the rat metabolism study

![](media/image19.png){width="6.995138888888889in"
height="6.7965277777777775in"}

**Appendix C: Additional Information on Residential
Assessment**[]{#__RefHeading___Toc196283185 .anchor}

SHEDS was developed by EPA to assess exposure to children contacting
CCA-treated structures (*i.e.*, decks and play sets). Although the SHEDS
model was not developed to provide a deterministic assessment, EPA
believes that a high end screening-level estimate is appropriate to
determine "reasonable certainty of no harm". EPA believes the SHEDS
model is the best model available at this time. It was vetted at the
EPA's Science Advisory Panel (SAP) for use in the CCA assessment. Input
parameters, such as the transferable residue and the child surface area,
as well as algorithms have been modified from those presented in the
SHEDS documents. The SHEDS report along with EPA's response to the
Science Advisory Panel's (SAP) review comments is located at
http://www.epa.gov/heasd/sheds/cca_treated.htm. The SHEDS model includes
the following exposure scenarios for children playing on treated
structures:

• Dermal exposure to wood transferable residues;

• Incidental ingestion from hand-to-mouth activities (wood residues);

• Incidental ingestion from soil; and

• Dermal exposure to soil.

Based on the results of the CCA assessment and calculations for
propiconazole, direct contact with the treated wood exhibits the highest
potential for exposure. The leaching of wood preservative into the soil
and subsequent exposure is much less than that attributed to direct
contact with the treated wood itself by more than a factor of ten. As a
conservative screening-level assessment, AD assumes that only a very
small percentage of the assumed available residue from wood can leach
into the soil. Such an assessment may result in an overestimation of
residues in soil, since the wood transferable residue is the day 1
residue, while the residue leached into the soil occurs over a period of
time. Additionally, children may be exposed to only a fraction of the
residues that are leached into the soil, since residues are mixed into
and leached through the soil, and AD only assesses oral exposures from
such affected soil. Therefore, the exposure from soil is expected to be
of minimal additional contribution compared to the exposure from contact
with the treated wood; and therefore, only contact to treated wood is
quantified in this assessment.

*Surface Residue*

Residue transfer (*i.e.*, the transferable residue of 1 µg/cm^2^ used in
this assessment) to exposed body SA for wood assessments is based on
wipe studies reaching \"steady state\" by using 20 hand passes. This is
a conservative assumption because it is doubtful that the arms and legs
would receive this much contact with the treated wood. This conservatism
can be refined by designing studies to mimic children\'s exposure. The
conservatism is some what off set by assuming only exposure to palms for
hands, bottom of feet, and no exposure to the head.

*Surface Area*

The surface area inputs into the potential daily dose (PDD) equation
have been modified from the inputs used in the SHEDS report. The
calculated surface area of the unclothed body areas of a child from the
SHEDS report can no longer be used, because parts of the data are from
studies deemed not to pass ethics reviews. Therefore, a new total
surface area has been constructed by AD/HED staff using the 1997
exposure factors handbook (EFH) as cited in the NAFTA Recommendations
which are identical to Child EFH 2002. The average surface area of the
median aged (3 to 4 year old) male and female child surface areas is
6565 cm^2^ \[median SA values are used to be consistent with the median
BW of a 3 year old (15.1 kg) to represent 1 to 6 year olds\]. This new
total exposed surface area estimate accounts for all unclothed body
areas of a child, plus penetration through clothed body parts. This
value is further modified to determine the surface area likely to come
into contact with wood on a deck or playset, assuming children are
exposed to wood in warm weather. This represents the high-end season
(*i.e.*, warm) and assumes (professional judgment) that children on
decks/play sets wear short pants, short sleeved shirts, and no shoes. It
is assumed that just the palms and the bottom of the bare feet are
exposed to the wood (assumes 50% SA for these body parts). HED's
Exposure SAC concurred with these input values.

**Appendix D: International Residue Limits**
[]{#__RefHeading___Toc196283186 .anchor}

+-----------------+-----------------+-------------------+--------------+
| INTERNATIONAL   |                 |                   |              |
| RESIDUE LIMIT   |                 |                   |              |
| STATUS          |                 |                   |              |
+=================+=================+===================+==============+
| Chemical Name:  | Common Name:    | X Proposed        | Date:        |
|                 | Tebuconazole    | tolerance         | 5/08/2006    |
| α-\[2-          |                 |                   |              |
| (4-chlorophenyl |                 | Reevaluated       |              |
| )ethyl\]-α-(1,1 |                 | tolerance         |              |
| -dimethylethyl) |                 |                   |              |
| -1*H*-1,2,4-tri |                 | Other             |              |
| azole-1-ethanol |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
| **Codex Status  |                 | **U. S.           |              |
| (Maximum        |                 | Tolerances**      |              |
| Residue         |                 |                   |              |
| Limits)**       |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
| No Codex        |                 | Petition Numbers: |              |
| proposal step 6 |                 | 6F4668, 1F6289,   |              |
| or above        |                 | 0F6129, 0F6086,   |              |
|                 |                 | 4F6854, and       |              |
| No Codex        |                 | 4E6842            |              |
| proposal step 6 |                 |                   |              |
| or above for    |                 | DP Barcodes:      |              |
| the crops       |                 | D318338, D311602, |              |
| requested       |                 | D315479, D316409, |              |
|                 |                 | D316410, D308836, |              |
|                 |                 | D311619, D315474, |              |
|                 |                 | D315867, D287292, |              |
|                 |                 | D311592, D315477, |              |
|                 |                 | D318511, D322912  |              |
|                 |                 |                   |              |
|                 |                 | Other Identifier: |              |
+-----------------+-----------------+-------------------+--------------+
| Residue         |                 | Reviewer/Branch:  |              |
| definition      |                 | Susan Hummel/ RRB |              |
| (step 8/CXL):   |                 | 4                 |              |
| Tebuconazole    |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
|                 |                 | Residue           |              |
|                 |                 | definition:       |              |
|                 |                 | Parent only       |              |
+-----------------+-----------------+-------------------+--------------+
| Crop (s)        | MRL (mg/kg)     | Crop(s)           | Tolerance    |
|                 |                 |                   | (ppm)        |
+-----------------+-----------------+-------------------+--------------+
| Banana          | 0.05            | Bean, succulent   | 0.1          |
+-----------------+-----------------+-------------------+--------------+
| Barley          | 0.2             | Bean , dry        | 0.1          |
+-----------------+-----------------+-------------------+--------------+
| Barley straw    | 10              | Cotton,           | 2.0          |
| and fodder, dry |                 | undelinted seed   |              |
+-----------------+-----------------+-------------------+--------------+
| Cattle meat     | 0.05            | Cotton, gin       | 25           |
|                 |                 | byproducts        |              |
+-----------------+-----------------+-------------------+--------------+
| Cattle milk     | 0.01            | Corn pop, grain   | 0.01         |
+-----------------+-----------------+-------------------+--------------+
| Cattle, edible  | 0.05            | Corn pop, stover  | 3.5          |
| offal of        |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Cherries        | 5               | Cherry            | 5.0          |
+-----------------+-----------------+-------------------+--------------+
| Chicken eggs    | 0.05            | Corn, field,      | 0.01         |
|                 |                 | grain             |              |
+-----------------+-----------------+-------------------+--------------+
| Chicken meat    | 0.05            | Corn, field,      | 4.0 ^1^      |
|                 |                 | forage            |              |
+-----------------+-----------------+-------------------+--------------+
| Chicken, edible | 0.05            | Corn, field,      | 3.5          |
| offal of        |                 | stover            |              |
+-----------------+-----------------+-------------------+--------------+
| Cucumber        | 0.2             | Soybean, seed     | 0.08         |
+-----------------+-----------------+-------------------+--------------+
| Dried grapes    | 3               | Soybean, hay      | 50           |
| (raisins)       |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Grapes          | 2               | Soybean, forage   | 25           |
+-----------------+-----------------+-------------------+--------------+
| Oats            | 0.05            | Grain, aspirated  | 15           |
|                 |                 | fractions         |              |
+-----------------+-----------------+-------------------+--------------+
| Peach           | 1               | Fruit, stone,     | 1.0          |
|                 |                 | group 12, except  |              |
|                 |                 | cherries          |              |
+-----------------+-----------------+-------------------+--------------+
| Peanut          | 0.05            | Corn Sweet,       | 0.5          |
|                 |                 | kernel plus cob   |              |
|                 |                 | with husks        |              |
|                 |                 | removed           |              |
+-----------------+-----------------+-------------------+--------------+
| Peanut fodder   | 30              | Corn, Sweet,      | 7.0          |
|                 |                 | Forage            |              |
+-----------------+-----------------+-------------------+--------------+
| Peppers, sweet  | 0.5             | Corn, Sweet,      | 6.0          |
|                 |                 | Stover (fodder)   |              |
+-----------------+-----------------+-------------------+--------------+
| Pome fruits     | 0.5             | Fruit, pome       | 0.05 ^1^     |
+-----------------+-----------------+-------------------+--------------+
|                 |                 | Wet apple pomace  | 0.2          |
+-----------------+-----------------+-------------------+--------------+
| Rape seed       | 0.05            | Onion, bulb,      | 0.1          |
| (canola)        |                 | subgroup 3A       |              |
+-----------------+-----------------+-------------------+--------------+
| Rye             | 0.05            | Onion, green,     | 1.3          |
|                 |                 | subgroup 3B       |              |
+-----------------+-----------------+-------------------+--------------+
| Rye straw and   | 5               | Brassica, leafy   | 2.5          |
| fodder, dry     |                 | greens, subgroup  |              |
|                 |                 | 5B                |              |
+-----------------+-----------------+-------------------+--------------+
| Squash, summer  | 0.02            | Beet, garden,     | 0.70         |
|                 |                 | root              |              |
+-----------------+-----------------+-------------------+--------------+
| Tomato          | 0.2             | Beet, garden,     | 7.0          |
|                 |                 | leaves            |              |
+-----------------+-----------------+-------------------+--------------+
| Wheat           | 0.05            |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Wheat straw and | 10              |                   |              |
| fodder, dry     |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
| **Limits for    |                 | **Limits for      |              |
| Canada**        |                 | Mexico**          |              |
+-----------------+-----------------+-------------------+--------------+
| No Limits       |                 | No Limits         |              |
|                 |                 |                   |              |
| No Limits for   |                 | X No Limits for   |              |
| the crops       |                 | the crops         |              |
| requested       |                 | requested         |              |
+-----------------+-----------------+-------------------+--------------+
| Residue         |                 | Residue           |              |
| definition:     |                 | definition:       |              |
| tebuconazole    |                 | tebuconazole      |              |
+-----------------+-----------------+-------------------+--------------+
| Crop(s)         | MRL (mg/kg)     | Crop(s)           | MRL (mg/kg)  |
+-----------------+-----------------+-------------------+--------------+
| Grapes          | 5               | Barley            | 0.05         |
+-----------------+-----------------+-------------------+--------------+
| Cherries        | 3               | Wheat             | 0.05         |
+-----------------+-----------------+-------------------+--------------+
| Pea             | 1               | Grapes            | 5.0          |
| ches/nectarines |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Peanuts         | 0.1             | Banana            | 0.05         |
+-----------------+-----------------+-------------------+--------------+
| Wheat           | 0.05            |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Bananas         | 0.03            |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Barley          | 0.01            |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Oats            | 0.01            |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Milk            | 0.1             |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Meat and meat   | 0.2             |                   |              |
| by-products of  |                 |                   |              |
| cattle, goats,  |                 |                   |              |
| hogs, horses,   |                 |                   |              |
| and sheep       |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Eggs            | 0.1             |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Meat and meat   | 0.1             |                   |              |
| by-products of  |                 |                   |              |
| poultry         |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+
| Notes/Special   |                 |                   |              |
| Instructions:   |                 |                   |              |
|                 |                 |                   |              |
| ^1^             |                 |                   |              |
| Time-limited    |                 |                   |              |
| tolerance,      |                 |                   |              |
| based on        |                 |                   |              |
| available       |                 |                   |              |
| residue data.   |                 |                   |              |
+-----------------+-----------------+-------------------+--------------+

**Appendix E: EPA Review of Human
Research**[]{#__RefHeading___Toc196283187 .anchor}

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 have been determined to require a review of
their ethical conduct, and have received that review. The studies were
considered appropriate (or ethically conducted) for use in risk
assessments.

**Studies reviewed for ethical conduct:**

*The PHED Task Force, 1995. The Pesticide Handlers Exposure Database,
Version 1.1. Task Force members Health Canada, U.S. Environmental
Protection Agency, and the National Agricultural Chemicals Association,
released February, 1995.*

*MRID 44518501, OMA005*

*Merricks, D. (1998) Carbaryl Mixer/Loader/Applicator Exposure Study
During Application of RP-2 Liquid (21%) to Fruit Trees and Ornamental
Plants: Lab Project Number: 1518. Unpublished study prepared by
Agrisearch Inc., Rhone-Poulenc Ag Co., and Morse Laboratories, Inc. 320
p.*

*MRID 44459801, OMA006*

*Merricks, D. (1997) Carbaryl Mixer/Loader/Applicator Exposure Study
During Application of RP-2 Liquid (21%), Sevin Ready to Use Insect Spray
or Sevin 10 Dust to Home Garden Vegetables: Lab Project Number: 1519:
10564: ML97-0676-RHP. Unpublished study prepared by Agrisearch Inc.,
Rhone-Poulenc Ag Co. and Morse Labs., Inc. 358 p.*