### Page 2 of 32 Rachel Ricciardi, Chemical Review Manager Rose Kyprianou, Team Leader Lance Wormell, Branch Chief Risk Management Branch 2 (R M B 2 ) Antimicrobials Division (7510P)

Executive Summary

Following is the Health Effects Division’s (HED ’s ) and Antimicrobials Division’s (AD’s) human health scoping document for the triazole

- derived fungi cide tebu conazole to support Registration Review. To evaluate the scope of work necessary to support Registration Review, previous risk assessments for tebu conazole have been considered ; updates to its toxicity,

exposure
, and usage databases ; and the latest Agency science policy and risk assessment

method ologies. The most recent HED aggregate risk assessment for tebuc onazole was

co mpleted in 20 1 3 (D 4 1 2 600

, B. O’Keefe

, 1 2 / 3 1 /20 1 3 ). AD has not conducted a risk assessment for tebuconazole since the chemical was initially registered.

Tebuconazole is registe red for use in/on numerous agricultural field and orchard crops, as a post

harvest use on several fruits, on commercial ornamentals and golf course turf; and on residential

ornamentals and flowers. Additionally, there are registered uses of tebuconazole a s an antimicrobial pesticide , including the preservation of wood , and as a material preservative in adhesives, coatings, glues, plastics and metalworking fluids.

The toxicological database for tebuconazole is complete. The target organs in both rodents and

non

- rodents are the liver, adrenals, and hematopo i etic system

. In addition, ocular lesions are seen in dogs (including lenticular degeneration and increased cataract formation) following subchronic and chronic exposur e

. Some of th e 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 class of pesticides. The data

i ndicated that with in

- utero exposure to tebuconazole resulted in developmental effects in fetuses (rat, mouse and rabbit) and pups (rats). The point of departure for dietary ( acute and chronic )

and non

- dietary ( incidental oral, dermal and inhalation expo sures) is based on decreases in body weights, absolute brain weights, brain measurements and motor activity in offspring seen in the rat developmental neurotoxicity study at the lowest observed adverse effect level (LOAEL). A

no observed adverse effect le vel (NOAEL) was not seen in the study

. Th e Food Quality Protection Act ( FQPA ) Safety Factor is retained in the form of a LOAEL to NOAEL factor since

a LOAEL was used for overall risk assessment. A 3X as opposed to a 10X was deemed appropriate based on qu antifiable data and lack of residual uncertainties for pre and/or post

- natal toxicity. Tebuconazole i s classified as a Group C Chemical; “ P ossible H uman C arcinogen ”

. A human cancer risk assessment is not required since the chronic reference dose (cRfD) will be considered protective of all effects including cancer

.

For Tebuconazole Conventional Uses The residue chemistry database for tebuconazole is adequate to support current data requirements. Adequate metabolism studies (crop s, livestock, and rotational crops), storage

### Page 3 of 32

stability, magnitude of the residue, and processing data are available to support the registered uses. Adequate methods are available for enforcement of the currently established tolerances.

New dietary risk assessments are not anticipated during Registration Review, unless there are increases to the drinking water exposure estimates that need to be incorporated.

R esidential and occupational handler and post

- application exposure assessments are reflective of maximum application rates and current exposure policies and data, and did not identify risks of

concern. U pdated occupational and residential handler exposure assessments are not anticipated to be needed during Registration Review. Although existing occ upational and residential post

application assessments are reflective of current exposure policies and data, turf transferrable residue (TTR) and dislodgeable foliar residue (DFR) studies are not available and are required for tebuconazole during Registrat ion Review , because estimated post

- application exposures using default TTR and DFR values are not minimal in comparison to the level of concern

. Therefore, HED may need to reassess these exposures using the results of the required TTR and

DFR studies during Registration Review

.

HED will also examine the need for a volatilization assessment , as well as evaluate the potential for exposure from spray drift during Registration Review. However, for tebuconazole, several

end

- use products are labeled for us e on residential turf. Thus, the risk assessment for residential turf may potentially be considered protective of any type of exposure that would be associated with spray drift. Residential bystander exposures resulting from off

- site transport (i.e.,

vol atilization) may occur as a result of occupational applications of tebuconazole. The need for a bystander risk assessment for tebuconazole will be considered during Registration Review.

For Tebuconazole Antimicrobial Uses AD anticipates the need to condu ct new occupational risk assessments for all the antimicrobial uses of tebuconazole during R egistration R eview to ensure that the assessment is consistent with current AD policies and standards . In addition, AD will need to reassess residential exposures to treated wood products based on new wipe data that are anticipated as needed based on potential risks identified in the past residential risk assessment. Additional occupational and residential risk assessments will be conducted during R egistration R evi ew.

Exposure studies and use data will be needed for assessing the risk from the antimicrobial uses of

tebuconazole. AD anticipates the need to conduct new occupational exposure assessments for

R egistration R eview to support wood and material preservativ e uses and to conduct new residential applicator assessments to support the wood stain use. D ermal (Guideline 875.1200) and inhalation (Guideline 875. 1400) surrogate applicator data will be needed to assess human

health risks for occupational exposure for uses of tebuconazole as a wood preservati ve (s apstain and pressure treatment) and material preservatives (liquid pour). Occupational as well as residential surrogate data are also needed for the wood stain use (airless sprayer and paint

brush /roller). Product use data (Guideline 875. 17 00) are needed to clarify uses (particularly the

use in plastics), application rates (wood retentions), and application equipment.

AD anticipates the need to conduct a residential post

- application risk assessme nt based on potential risk concerns from the previous risk assessment (D346795 , B. O’Keefe, 11/26/2007 ;

### Page 4 of 32

updated in D397518, B. O’Keefe, 04/30/2012 ). A wipe stud y will be needed (Guideline

875

. 2300) to quantify residues from treated decks at the highest wo od retention rate for

tebuconazole. Product use data (Guideline 875.1700) will also be needed. The new residue data are needed to refine the p revious residential post

- application assessment, which was based on surrogate data.

Aggregate Aggregate exposur e to tebuconazole is currently not of concern to HED. However, t he short

term aggregate risk estimates will need reevaluation during Registration Review based on the submitted wood, TTR, and DFR studies.

I ntroduction

Tebu conazole is a t riazole fungicide active ingredient that act s by inhibiting C14

- demethylase, an enzyme which plays a role in sterol production in fungi. The most recent human health risk

assessment for tebu conazole was completed in 201 3 for tolerances on imported oranges and

orange commo dities (D4 12600 , B. O’Keefe, 12/ 31 /201 3 ).

For Tebuconazole Conventional Uses

Tebu conazole is currently registered for use in/ on the following use sites: 1) field and orchard/tree crops: almonds, apple, asparagus (domestic use and import), bananas, barle y (field and seed treatment), beans, Brassica leafy greens, bulb vegetables, cherries, corn (sweet corn, field corn, field corn grown for seed, and popcorn, plus seed treatment), cotton, cucurbits, fruiting vegetables, garden beets, grapes, grasses (grown for seed), hops, lychee, oats (seed treatment), okra, peaches, peanuts, pistachios, plantain, pome fruit, soybean, stone fruit, sunflower, tree nuts, triticale (seed treatment), turnips, watermelon, wheat (field and seed treatment) , and wine grapes ; 2) pos t

- harvest uses on cherry, mango and plum; 3) commercial ornamentals and golf course turf; and 4) residential ornamentals and flowe rs. There are existing tolerances with no US registration on coffee, garlic, onions, and oranges.

Tebu conazole end use products are formulated as liquids, flowable concentrates, granulars and ready

- to

- use solutions. Tebu conazole is also formulated into products with other fungicides. Applications can be made with ground, aerial, airblast, chemigation , ha nd held, or seed treatment equipment

, as well as postharvest sprays

.

Permanent tolerances are established for residues of tebuconazole in/on various plant commodities at levels ranging from 0.05 ppm in/on asparagus, bananas, field and popcorn grain,

pom e fruits, tree nuts, and sunflower seed to 55.0 ppm in/on grass seed screenings [40 CFR §180.474(a)(1)]. Permanent tolerances are also established for the combined residues of

tebuconazole and its metabolite 1

- (4

- chlorophenyl)

- 4,4

- dimethyl

- 3

- (1 H

- 1,2,4

- tri azole

- 1

- yl

methyl)

- pentane

- 3,5

- diol (HWG 2061) at 0.2 ppm in/on meat

- byproducts of cattle, goats, horses, and sheep, and at 0.1 ppm in milk [40 CFR §180.474(a)(2)]. Tolerances with regional registrations are established in 40 CFR §180.474(c) on turnip roo ts at 0.5 ppm and turnip tops at 7.0 ppm.

Refer to Attachment 1 (Table 1) for the chemical identity of tebuconazole.

### Page 5 of 32

For Tebuconazole Antimicrobial Uses

Tebuconazole is re gistered for the preservation of wood intended for above

- ground and/or in

ground con tact, 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 fence posts, poles, decks, millwork, posts, etc. Wood treatment applications may include sa pstain and pressure

treatment. Tebuconazole is commonly used in combination with copper and propiconazole for different copper azole formulations. In addition to its major use as a wood preservative,

tebuconazole is also registered for use as a material preservative in adhesives, coatings, glues, plastics and metalworking fluids.

Hazard Identification/Toxicology

No new toxicity data ha ve been submitted since the la s t risk assessment (D412600, B. O’Keefe. 12/31/2013). The toxicological database for tebuconazole is complete for risk assessment

. Developmental toxicity studies are available in rats, rabbits, and mice; developmental toxicity

studies in rats and mice were administered via the oral and dermal routes. A developmental neurotoxicity in rats is also available and currently provides the most sensitive toxicity endpoints

and is used for establishing the point s of departure (POD) for risk assessment for all exposure scenarios (Attachment 3)

.

With repeated dosing, the common effects were seen in the liver, adrenals, and hematopoietic system 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.

Tebuconaz ole induced developmental effects in many oral developmental toxicity studies in rats, rabbits, and mice . In all three species the developmental effects mostly occurred at similar dose levels where maternal effects were found; however, the maternal effect s were minimal and did not increase substantially in severity at higher dose levels. The prominent developmental effect was on the developing nervous system manifested as increase d malformations of the nervous system and skull (including exencephaly and a crania, skull bone and vertebral anomalies). The developmental toxicity studies, including the developmental neurotoxicity study, demonstrate both quantitative and qualitative developmental susceptibility. Decreased absolute brain weight, morphometric me asurements, and decreased motor activity were seen in the offsprings of rats in the developmental neurotoxicity study. 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 pup deaths during the first week after birth), were seen in the developmental neurotoxicity study.

In contrast, tebuconazole did not produce any developmental effects in dermal developmental toxicity studies in rats and mice at dose levels up to the limit dose (1000 mg/kg /day). Furthermore, the 28

- day dermal toxicity study in rabbits found no effect at the limit dose (1000 mg/kg/day)

. However , none of these dermal development and dermal toxicity studies conducted measurements on brain morphometric measurements and absolute brain weight in the developing

animals.

### Page 6 of 32

Tebuconazole induced an increase in the incidence of hepatocellular adenomas, car cinomas and combined adenomas/carcinomas in male and female mice, but it showed no mutagenic potential.

Based on th ese finding s, t ebuconazole was classified as a Group C Chemical; “ P ossible H uman C arcinogen ”

. A human cancer risk assessment is not require d since the chronic reference dose

will be protective of all effects including cancer.

The target organs with 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 in this class . Tebuconazole also shares common metabolites with other chemicals in this group, including free triazole (1,2,4

- triazole) and triazole

- conjugated plant metabolites (such as triazole alanine ). These common metabolites were the subject of a recent aggregate risk assessment document ( D42 6493 , T. Morton, 04 / 09 /13 ) updated to incorporate new uses of triazole

- derivative fungicides.

The DNT was selected as the critical study for establishing the Point of Departure (POD) for overall risk assessment. The LOAEL of 8.8 mg/kg/day is based on decreased absolute brain weight, morphometric measurements, and decreased motor activity observed in the offsprings; a NOAEL was not established. Since a LOAEL wa s selected as the POD, the FQPA Safety Factor is retained in the form of a LOAEL to NOAEL uncertainty factor ((UF L 

### ). Typically, the default 10X will be retained. However, in the case of tebuconazole, the FQPA Safety Factor is reduced to 3 based on quantifi able data as discussed below:

A Bench Dose (BMD) analyses of the endpoints of concern in the DNT showed that all of the BMDLs (benchmark dose limit) to be 1

- 2x lower than the LOAEL. Therefore, an extrapolated NOAEL is not likely to be 10X lower than the LOAEL , therefore, a 3X uncertainty factor is adequate;

The use of a 3X UF to the POD results in an extrapolated NOAEL of 2.9 mg/kg/day (8.8 mg/kg/day÷ 3= 2.9 mg/kg/day) which is comparable to the developmental NOAEL (3 mg/kg/day) established in the pre

- n atal developmental toxicity study in rats;

The toxicology database is complete and there are no residual uncertainties for pre and/or

post

- natal toxicity.

Please r efer to Attachment 3 for a summary of the toxicity endpoints

, points of departure (PODs) and safety factors for tebuconazole, and to Attachment 4 for the complete toxicity profile tables

for tebuconazole

.

Conclusion : The toxicology database is adequate to support the existing registered uses and there

are no additional data requirements at t his time.

### Page 7 of 32

Residue Chemistry and Dietary Exposure

For Tebuco nazole Convention al Uses

The nature of the residue in primary / rotational crops and livestock has been adequately defined

. Tebu conazole (parent) is the residue of concern for risk assessment and for the tolerance expression for primary /

rotational crops . For poultry and ruminant livestock , tebuconazole and free and conjugated HWG

- 2061 are the residues of concern for risk assessment and for the tolerance expression

. For drinking water, the res idue of concern is tebu conazole ( parent only )

.

HED also has concern for residues of 1,2,4

- triazole, triazolylalanine ( TA ) , and triazolylacetic acid ( TAA ) in plants and livestock as a result of the use of tebu conazole. However, because separate endpoints for these compounds have been established, exposure and risk from free triazole and its conjugates will be addressed separately.

The existing residue chemistry database for tebu conazole is adequate to support current

R egistration Review data req uirements. Adequate metabolism

, enforcement methods, multiresidue methods, storage stability, field trials, p rocessing and rotational crop data are available to support the registered uses

.

Analytical reference standards for tebu conazole are currently available in the EPA National Pesticide Standards Repository with an expiration date of 4/26/2023 (personal communication

with Theresa Cole

, Analytical Chemistry Branch ( ACB )

, 10 / 1 5/ 2015 ). An analytical reference

standard for the t

- butylhydroxy metabolite is currentl y available at the Repository with an expiration date of 3/24/2016

.

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

were conducted in 201 3 (D416473, M. Negussie, 12/18/2013). The acute and chronic dietary

assessment s were somewhat refined. For the acute assessment, a nticipated residues for grapes, grape juice, and peaches were derived using the latest United States Department of Agriculture ( USDA ) Pesticide Data Program (PDP) monitoring data . Anticipated residues for all other registered and proposed food commodities were based on field trial data. Available processing data were used to refine anticipated residues for apples/pears (dried and juice), apricots (dried), cherry (juice), coffee (roasted bean), grapes (juice), orange (juice), plums (prunes/prune juice), peanut (oil), and tomatoes (paste and puree). For all other processed commodities, Dietary Exposure Evaluation Model ( DEEM ) (ver. 7.81) default processing factors were assumed.

A distribution o f estimated concentrations of tebuconazole in drinking water was provided by the

Environmental Fate and Effects Divis i on (EFED) and incorporated directly into the acute dietary

assessment (D412862, A. Shelby, 07/03/2013) . The acute assessment was conducte d using the

full 30

- year distribution of estimated residues in surface water generated by the Pesticide Root Zone Model/Exposure Analysis Modeling System ( PRZM

- EXAMS ) model. The highest exposure in surface water resulted from application of tebuconazole t o Florida turf. For the chronic dietary exposure, t he 1

- in

- 10 y ea r annual mean (chronic) concentration of 68.8 μg/L was used

. Due to the chemical properties of tebuconazole, surface water estimated drinking water

### Page 8 of 32

concentrations ( EDWCs ) are much larger th an ground water EDWCs, and therefore, PRZM

- GW estimates do not impact the findings.

The acute dietary exposure to tebu conazole is below HED’s level of concern for all population subgroups (<100% of the acute Population Adjusted Dose (aPAD) )

. Combined acute dietary exposure from food and drinking water at the 99.9 th 

### percentile of exposure utilized 45% of the aPAD for the general U.S. population and 84% of the aPAD for children 1 to 2 years old, the highest exposed population subgroup.

Chronic dietary e xposure estimates for food and drinking water are well below HED’s level of concern (<100% of the chronic Population Adjusted Dose (cPAD) ) for all population subgroups. The chronic dietary exposure from food and drinking water utilized 6.7% of the cPAD fo r the general U.S. population and 14% of the cPAD for all infants (<1 year old), the highest exposed population subgroup.

For Tebuconazole Antimicrobial Registrations EPA has not established tolerances or tolerance exemptions for residues for the antimicr obial uses of tebuconazole. Tebuconazole has not been cleared as a food additive by the US Food and Drug Administration (US FDA) under the Federal Food, Drug, and Cosmetic Act (FFDCA) Section 409. Although there are registered antimicrobial uses that cou ld result in indirect food contact, these uses are expected to result in minimal dietary exposure compared to the conventional agricultural uses of tebuconazole (i.e., direct treatment to growing crops intended for human or animal consumption). Additional ly, the conventional agricultural uses of tebuconazole do not result in dietary risks of concern. Therefore, a dietary exposure assessment is not anticipated for the antimicrobial uses of tebuconazole.

Conclusions: At the time of the R egistration R eview risk assessment , HED will review updates to the PDP monitoring data, the percent crop treated information, and changes in drinking water exposure estimates, and will conduct a revised dietary assessment if there are likely to be increases to the dietary e xposure estimates.

Residential Exposure

For Tebuconazole Conventional Uses

T here are existing uses of tebu conazole on golf course turf , flower gardens, trees, and

ornamentals in residential settings that were previously assessed to reflect HED’s 2012

Residential SOPs 1 

### along with policy changes for body weight assumptions. Residential exposure is expected to be short

- term only; i ntermediate

- term exposures are not likely because of the intermittent nature of applications in residential settings

. Dermal and inhalation exposures for residential handlers were combined since the same endpoint and POD is used for both routes of exposure. All combined short

- term risk estimates for residential handlers are not of concern to HED with margins of exposure (MOEs) ranging from 2,800 to 91,000. Adults and children golfing and adults working in gardens may receive post

- application exposure to tebuconazole

residues. Residential dermal post

- application MOEs for all life stages range from 570 to 6,200.

1 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Page 9 of 32

Turf Transferable Residue (TTR): In accordance with the updated Part 158 data requirements (2007), a TTR study is required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses. As part of the recent revision to the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment

, HED analyzed all available data and selected new liquid and granular default values for the fraction of the ap plication rate available for transfer after a turf application (F AR 

### ). 2 

### These

defaults are 1% for formulations applied as liquids (i.e., emulsifiable concentrates, liquids, wettable powders, dry flowables, etc.) and 0.2% for granular formulations. Of the available TTR studies submitted to the Agency, the maximum F AR 

### value seen using a liquid product was 6.1% or 6.1 times higher than the default residue transfer value. The maximum F AR 

### value seen in a TTR study using a granular product was 0.69% or 3.5X the default residue transfer value. Therefore, for both liquid and granular formulations, a calculated MOE of approximately 10 times higher than the level of concern (e.g., an MOE >1,000 if the LOC = 100) using the default residue transfer values would provi de an adequate margin of safety for any potentially higher

residues seen in a chemical

- specific TTR study ( Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies . 6/7/2012, Exposure Science Advisory Co uncil). For tebuconazole, the LOC is 300, and therefore, an MOE >3,000 is needed to negate the requirement for a new TTR study. As a result, since the existing uses of tebuconazole result in post

- application risk estimates < 3,000 using default values fo r the fraction of application rate available for transfer after a turf application, a TTR (875.2100) study

is required for tebuconazole

.

Spray Drift and Volatilization : Residential bystander exposures resulting from off

- site transport (e.g., spray drift or volatilization) may occur as a result of applications of tebu conazole . The potential for spray drift will be quantitatively evaluated for each pesticide during the Reg istration Review process that ensures that all uses for that pesticide will be considered concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs)

– Residential Exposure Assessment S tandard Operating Procedures , draft Addenda 1: Consideration of Spray Drift. This document outlines the quantification of indirect

non

- occupational exposure to drift. In terms of volatilization, the agency has developed a Volatilization Screening Tool a nd a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219 ). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analyses are required for specific chemicals. However, for tebu conazole, several end

- use products are labeled for use on residential turf. Thus, the risk assessment for that use may be considered protective of any type of exposure that would be associated with spray drift.

For Tebuconazole Antimicrobial Uses AD anticipates the need to conduct a residential post

- application risk assessment during Registration Review to reevaluate or evaluate existing uses of tebuconazole in treated stains and wood products

, based on potential risk concerns from the last risk assessment (D346795, B. O’Keefe, 11/26/2007 ; updated in D397518, B. O’Keefe, 04/30/2 012 ). A p revious assessment was conducted for the residential use in order to assess aggregate exposure. AD anticipates the need to conduct residential handler dermal and inhalation risk assessments for the application of

2 http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Page 10 of 32

treated stains. The residential exposure scenarios applicable to this use include applicator brush/roller and airless sprayer . Wood products commercially treated with end use products containing tebuconazole may be used for decks and children’s play sets. Based on the p revious

risk as sessment (D346795 , B. O’Keefe, 11/26/2007 ; updated in D397518, B. O’Keefe,

04/30/2012 ), wipe studies ( Guideline § 875.2300) are needed to measure residues from treated decks at the highest wood retention rate for tebuconazole in order to refine the risk estimates

.

Because tebuconazole is also registered for use in plastics, t he A gency will also need product use

information ( Guideline § 875. 17 00) to clarify whether tebuconazole is used to manufacture toys; if tebuconazole may be used in toys, a post

- application incidental oral exposure assessment from use in/on plastics will be conducted during R egistration R eview.

Conclusions: Short

- term residential exposures are expected from existing uses on golf course turf, ornamental s, treated plastics, and treated wood products and the exposure and risk assessments may need to be updated during Registration R eview. The following studies will be needed to update the risk assessments: Guideline § 875.2100 Turf transferable residues;

G uideline § 875.1 7 00 Product Use Data on the use of tebuconazole in plastics and wood; and Guideline § 875.2300 Wipe Study from the use of tebuconazole on treated wood.

T he Agency will examine the need for a volatilization assessment , as well as evaluate th e potential for exposure from spray drift during Registration Review. However, for tebuconazole,

several end

- use products are labeled for use on residential turf. Thus, the risk assessment for residential turf may be considered protective of any type of exposure that would be associated with spray drift. Residential bystander exposures resulting from off

- site transport (i.e., volatilization) may occur as a result of occupational applications of tebu conazol e. The need for a bystander risk assessment for tebu conazole will be considered during Registration Review

.

Aggregate Risk Assessment

In accordance with the Food Quality Protection Act , HED must consider and aggregate pesticide exposures and risks from three major sources: food, drinking water, and re sidential exposures. The acute and chronic aggregate risk assessments included food and drinking water. The short

term aggregate risk assessment included food, drinking water, and residential exposures. No

intermediate

- term aggregate risk assessment was conducted since a ll residential/recreational exposures are anticipated to be short

- term in duration

.

Acute and Chronic Aggregate : The 201 3 acute and chronic aggregate risk assessments included

exposure to tebu conazole residues in food and drinking water. Acute and chronic dietary risk estimates for food and drinking water exposure are below HED’s level of concern (<100% of the aPAD and cPAD).

Short

- term Aggregate : In 201 3 , a short

- term aggregate risk assessment was completed for

tebu conazole . Fo r adults and children 6 to <11 years old , the short

- term aggregate assessment combined the average food and drinking water exposures with post

- application dermal exposures fr om garden ornamentals

. For youths 11 to <16 years old , the short

- term aggregate assessment combined the average food and drinking water exposures with post

- application dermal exposures

### Page 11 of 32

fr om golf course turf

. For small children (1 to <2 years old) , the short

- term aggregate assessment combined the average foo d and drinking water exposures with post

- application incidental oral (hand

- to

- mouth) exposures from contact with pressure treated wood surfaces

.

As noted in the Residential section above the residential exposure assessment will likely be

needed once the new studies have been received. The short

- term aggregate assessment will be

re

- evaluated when the residential assessment is updated.

Conclusions : Aggregate exposure to tebu conazole is currently not of concern to HED.
However, t he short

- term aggregate risk estimates will like ly need reevaluation during Registration Review based on the submitted wood, TTR, and DFR studies.

Occupational Exposure

Most occupational exposure scenarios for currently registered agricultural uses were previously

assessed using updated exposure assessment policies and body weight assumptions. However, occupational exposure scenarios for some antimicrobial uses have not been previously assessed. For conventional uses, o ccupational handler s and post

- application workers can become exposed

to tebuconazole over short

- or intermediate

- term durations. Additionally, for some antimicrobial

uses o ccupational handler s can become exposed to tebuconazole at short

- , intermediate

- , and long

- term durations.

For Tebuconazole Conventional Uses Occupational Handlers : Previous occupational handler exposure and risk assessments for

t ebu conazole were conducted at the maximum application rates and assumed the maximum area treated per day for all the registered use sites. Applications can be ma de with ground, aerial, airblast, chemigation, hand

- held, or seed treatment equipment

. Occupational exposure assessments have been updated in accordance with current HED policies and standard operating procedures. Risk estimates for all scenarios are not of concern, and t herefore, unless new data comes in, HED does not anticipate the need to reassess these exposures during Registration

Review

. MOEs ranged from 300 to 17,000 for conventional field and tree crops, 400 to 19,000 for seed treatments, 2,300 t o 18,000 for post

- harvest fruit treatments and 700 to 8,700 for golf

course turf.

Occupational Post

- Application : Based on the Agency's current practices, a quantitative occupational post

- application inhalation exposure assessment was not performed for

tebu conazole . If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for tebu conazole

.

Dermal post

- application exposures for occupational workers h ave been previously assessed for

all non

- antimicrobial uses of tebuconazole. Risk estimates for the day of application for all crops are not of concern to HED with MOEs ranging from 3 00 to 1 2 ,000.

Turf Transferable Residue (TTR): As detailed above in the Residential Exposure section, i n accordance with the updated Part 158 data requirements (2007), a TTR study is required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses.

### Page 12 of 32

For tebuconazole, the LOC is 300, and therefore, an MOE >3,000 is needed to negate the requirement for a new TTR study. As a result, since the existing uses of tebuconazole result in

post

- application risk estimates < 3,000 using default values for the fraction of application rate available for transfer after a turf application, a TTR study is required for tebuconazole

.

Note : In 1996, Bayer CropScience submitted a TTR study to EPA ( MRID 44108303 )

. The TTR data from this study were previously used as an estimate of day zero tebuconazole residues on treated turf (DP361303, B. O’Keefe, 12/28/09). However, based on a complete review of this study (D414822, B. O’Keefe, 10/31/2013) HED concluded that the study data should not be used as an estimate of day zero residues on turf.

Dislodegable Foliar Residue (DFR) : In accordance with 40 CFR § 158, DFR data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., orn amental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post

application exposure to foliage. In the absence of chemical

- specific DFR data, EPA uses default

values. The 2012 Standard Operating Procedures for Resid ential Pesticide Exposure

Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a revised default values for the fraction of the application rate available for transfer after a foliar application (F AR 

### ). This value is based on an analysis of 19 DFR studies. Since that time, the Agricultural Re

- entry Task Force has submitted information (MRID 49299201) that corrects an application rate error made in the original submission of “ARF039

– Determination of Dermal

and In halation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a result of this submission, the default value of 25% was not changed as it still reflects a high

- end, conservative value. However, it is importan t to note that the range of F AR 

### values was revised from 2%

- 89% to 2%

- 47%. In the data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field cond itions in the studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR 

### values is not expected when considering DFR data for a single

chemical. Because DFR d ata are not available for tebuconazole , EPA is using the default value

of 25%. Although there may be a small degree of uncertainty in the use of the default DFR value

for tebuconazole (i.e., there is a small chance that the F AR 

### value may exceed the applicable

default value ), it is likely that the health

- protective aspects of EPA’s occupational post

application assessment methodology will more than compensate for this potential uncertainty. For example, when assessing residentia l and occupational post

- application exposure to gardens and ornamentals, EPA assumes the following: exposures occur to zero

- day (i.e., day of application ) residues every day of the assessed exposure duration (i.e., EPA assumes that no dissipation or degr adation occurs, it doesn’t rain, etc); individuals perform the same post

application activities performed in the transfer coefficient study day after day (e.g., weeding, harvesting, pruning, etc.); and individuals engage in these post

- application activitie s for a high

end amount of time every day (represented by data reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is able to rely upon the calcula ted exposure estimates with confidence that exposure is not being underestimated.

### Page 13 of 32

Since the estimated post

- application exposure for occupational exposures for some crop use sites using default DFR values for tebuconazole is not minimal in comparison to t he level of concern (i.e., the calculated MOE is not greater than 2 times higher than the level of concern, MOE = 6 00 compared to the LOC of 300 ); future refinements of this post

- application exposure for

tebuconazole may be necessary due to increased use o f tebuconazole or advances in EPA risk

assessments. Therefore, EPA is requiring the 40 CFR DFR data requirement to facilitate any necessary exposure assessments refinements and to further EPA’s general understanding of the availability of dislodgeable fol iar pesticide residues.

For Tebuconazole Antimicrobial Uses

O ccupational exposure assessments for antimicrobial uses of tebuconazole have not been updated since the chemical was initially registered. As a result, AD will need to conduct new occupational risk assessments for all the specified antimicrobial uses in R egistration R eview in accordance with current policies

.

Occupational Handlers : EPA will need to conduct an occupational exposure assessme nt for

R egistration R eview to support wood and material preservation uses for tebuconazole. AD specific occupational exposure assessments will be needed to support current AD policies and standard operating procedures. O ccupational workers are anticipated to become exposed to tebuconazole wood preservatives during wood treatment activities such as sapstain, pressure treatment, and remedial uses such as applying wood stains using a brush/roller and/or airless sprayer on decks. In addition, occupational work ers could potentially become exposed through the dermal and inhalation routes from material preservatives from pouring liquids or from mists and vapors during metalworking operations (e.g., machinists). The agency anticipates the need to call in data (Guid elines §875.1200, §875.1400, and §875.1700) and use surrogate exposure to assess all of these handler exposures during R egistration R eview. The duration of exposure for the occupational uses for workers at wood treatment plants and for machinists at metal working fluids are considered to represent short (1 to 30 days), intermediate (30 days to 6 months), and long

- term (> 6 months) durations of exposure as workers in these settings. All other exposures from uses such as staining and pouring activities are m ore episodic and will be of short

- and

intermediate

- term durations.

Occupational Post

- application : AD does not anticipate the need to conduct a post

- application

exposure assessment. Any exposure for wood pressure treatment plants and machinists will

alre ady be captured in the occupational handler assessment. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for tebuconazole.

Conclusions : T he occupational handler and post

- application exposure assessments for

conventional uses are reflective of current exposure policies and data

. T here is sufficient

information available to assess these occupational handler exposures , and therefore, updated

o ccupational handle r exposure assessments for these uses are not anticipated to be needed during Registration Review. However , some antimicrobial use sites will need to be assessed for occupational handler exposures. P ost

- application exposure assessments may need to be updated

### Page 14 of 32

during Registration Review, since new TTR and DFR studies are needed

. T hese data may necessitate the need to update the post

- application exposure a ssessments for some use sites.

Public Health and Pesticide Epidemiology Data

In th e Main OPP Incident Data System (IDS) , from January 1, 20 10 to May 27 , 201 5 , there w ere eight (8) incidents reported for the single chemical tebu conazole only in the database. These incidents were classified as moderate severity

.

In the Aggregate IDS, from January 1, 20 10 to Ma y 27 , 201 5 , there were 444 incidents reported involving tebu conazole. These incidents were classified as minor severity.

A query of the Centers for Disease Control and Prevention/National Institute for Occupational Safety and He alth (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk

Pesticides (SENSOR)

- Pesticides database for 1998

- 201 1 identifies 16 cases involving

tebu conazole ; two of which involve a single a ctive i ngredient

. Both single active ingredient

case s were low in severity. One case was an agricultural worker who was exposed while conducting routine fieldwork. The case reported a skin rash, cough, nausea, vomiting, stomach pain, and headache. The second case was a homeowner who applied the product i n windy conditions and inhaled the product. This case reported dermal and ocular symptoms (skin pain and conjunctivitis).

The Agricultural Health Study (AHS) is a high quality

, prospective epidemiology study evaluating the link between pesticide use and various health outcomes

, including cancer. The AHS includes private and commercial pesticide applicators and their spouses

. Tebu conazole is not included in the AHS, and therefore, this study does not provide information for this report.

Conclusion: Alt hough there were a moderate number of tebuconazole incidents reported to Main and Aggregate IDS and SENSOR

- Pesticides, most of these incidents were classified as low severity. The effects experienced were generally minimally traumatic and resolv ed rapidly and usually involve d skin, eye or respiratory irritation. Based on the generally low severity of incidents reported to both IDS and SENSOR

- Pesticides, there does not appear to be a concern at

this time. The Agency will continue to monitor the incident d ata and if a concern is triggered, additional analysis will be conducted.

Tolerance Assessment and International Harmonization

Tolerances are established for plant commodities under 40 CFR §180. 474 (a)(1) for residues of

tebu conazole. Compliance with the tolerance levels is to be determined by measuring only

tebu conazole [α

- [2

- (4

- chlorophenyl) ethyl]

- α

- (1,1

- dimethylethyl)

- 1 H

- 1,2,4

- triazole

- 1

- ethanol]

.

Tolerances are established for livestock commodities under 40 CFR §180. 474 (a)(2) for residues

of teb u conazole. Compliance with the tolerance levels is to be determined by measuring the sum

of tebu conazole [α

- [2

- (4

- chlorophenyl) ethyl]

- α

- (1,1

- dimethylethyl)

- 1 H

- 1,2,4

- triazole

- 1

- ethanol]

and its diol metabolite (1

- (4

- chlorophenyl)

- 4,4

- dimethyl

- 3

- (1 H

- 1,2,4

- triazole

- 1

- yl

- methyl)

- pentane

- 3,5

- diol), calculated as the stoichiometric equivalent of tebuconazole.

### Page 15 of 32

Tolerances with regional registrations are established for residues of tebuconazole in/on turnip roots at 0.5 ppm and turnip tops at 7.0 ppm 40 CFR §180. 474 (c)

.

The tolerance expression under 40 CFR §180.474 is correct and reflects both the measurement and compliance statements addressing tebuconazole residues. Compliance with the tolerance levels is to be determined by measuring only tebuconazole in p lants and the sum of tebuconazole

and its diol metabolite in livestock commodities.

T he US and Canadian tolerance expressions for plants and livestock are harmon i z ed ; w hereas

, the US and Codex tolerance expre ssions are harmon ized for plants only. The Codex tolerance expression for livestock commodities includes parent only. Residue definition in the US includes parent and the metabolite

. Th ere are Codex and Canadian maximum residue limits ( MRLs ) established for residues of tebuconazole. The US a nd Codex MRLs are in harmony only on banana, cotton undelinted seed, plum (except prunes), tree nuts, and wheat grain. The US livestock tolerances are not harmonized with Codex except for byproducts of sheep and hogs.

T he US and Canadian tolerances are h armonized for several plant and livestock commodities.

Please r efer to Attachment 6

.

Note s to C

RM : The existing US tolerances for pistachio (0.05 ppm) need to be removed from 40 CFR §180.4 74 (a) since this commodit y is included in crop group tree nuts (0.05 ppm).

T he established tolerances (listed below) need to be revised to include an additional significant figure ( 1. 0 ppm rather than 1 ppm). This is in order to avoid the situation where rounding of a

residue result to the level of precision of the tolerance expression would be considered non

violative (such as 1 .4 ppm being rounded to 1 ppm).

Note to C RM : The existing regional registration for turnip tops (7.0 ppm) and roots (0.05 ppm) need to be removed from 40 CFR §180.4 74 ( c ) to 40 CFR §180.4 74 ( a) (1) since the required additional data was submitted (D403309, 12/06/12).

Table 1. Tolerance Recommendations for Tebuconazole.
Commodity Established

Tolerance (ppm) Recommended

Tolerance (ppm) Comments

Pistachio 0.05 None Remove
Nut, tr ee, group 14 (0.05 ppm)

Peach 1.0 None Remove Fruit, stone, group 12, except cherry (1.0 ppm) Plum 1.0

Tole rance Revisions for Correct Commodity Definition

Brassica, leafy greens, subgroup 5B 2.5 2.5 Brassica, leafy greens, subgroup 5B, except turnip greens

Cherry, sweet, pre

- and post

- harvest 5.0 5.0 Cherry

Cherry, tart, pre

- and post

- harvest 5.0 5.0

Grain aspirated fractions 16.0 16 Grain, aspirated grain fractions

### Page 16 of 32

Table 1. Tolerance Recommendations for Tebuconazole.
Commodity Established

Tolerance (ppm) Recommended

Tolerance (ppm) Comments

Mango, postharvest 0.15 0.15 Mango

Tolerance Revisions for Significant Figure (a)General (1)

Apple, wet pomace 0.1 0.1 0

Barley, grain 0.3 0.3 0

Bean, dry seed 0.1 0.1 0

Bean, succulent 0.1 0.1 0

Coffee, roasted bean 1 0.3 0.3 0

Cotton, gin byproducts 25.0 25

Grass, hay 25.0 25

Grass, seed screenings 55.0 55

Grass, straw 30.0 30

Hop, dried cones 35.0 35

Onion, bulb, subgroup 3

- 07A 0.2 0.2 0

Peanut 0.1 0.1 0

Sunflower, meal 0.2 0.2 0

Sunflower, refined oil 0.2 0.2 0

Vegetable, cucurbit, group 9 0.4 0.4 0

Tolerance Revisions for Significant Figure (a)General (2)

Cattle, meat byproducts 0.2 0.20

Goat, meat byproducts 0.2 0.20

Horse, meat byproducts 0.2 0.20

Milk 0.1 0.10

Sheep, meat byproducts 0.2 0.20



### Cumulative

Tebu c on azole is a member of the triazole

- containing class of pesticides. Although conazoles act similarly in plants (fungi) by inhibiting ergosterol biosynthesis, there is not necessarily a relationship between their pesticidal activity and their mechanism of to xicity 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 conazoles, however, a variable pattern of toxicological responses is found; some are hepatotoxic and hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some induce developmental, reproductive, and neurological effects in rodents. Furthermore, the conazoles produ ce 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,

ther e is currently no evidence to indicate that conazoles share common mechanisms of toxicity and EPA is not following a cumulative risk approach based on a common mechanism of toxicity for the conazoles. For information regarding EPA’s procedures for cumulat ing effects from substances found to have a common mechanism of toxicity, see EPA’s website at

### Page 17 of 32

http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/cumulative

- assessment

risk

- pesticides

.

Human Studies

The risk assessment s which have been previously conducted for tebu conazole rel ied in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many

differe nt pesticides, comprise generic pesticide exposure databases such as the Pesticide

Ha ndlers Exposure Database (PHED)

, the Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF)

, the Agricultural Reent ry Task Force (ARTF) Database and the Antimicrobial Exposure Assessment Task Force II (AEATF II)

. EPA has reviewed all the studies supporting these multi

- pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at

the time the research was conducted. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research ( 40 CFR Part 26) have been satisfied , and t here is no regulatory barrier to continued reliance on these studies

.

Data Defic i e ncies

O ccupational and residential exposure data are needed to support the registered uses of

tebu conazole are listed in Table 2.

Table 2. Exposure Studies Needed for Tebuconazole

. Study Needed Guideline Applicator or Post

- application Exposure Scenario
Foliar Dislodgeable Residue Dissipation Data 875.2100 Post

- application worker or residential exposure

Turf Transferrable Residue Dissipation Data 875.2100 Post

- application worker or residential exposure

Dermal Applicator Data 875.1200*

- Worker exposure to sapstain and pressure treatment

- Open pour liquid preservatives

- Applying wood s tains using a brush/roller and/or airless spray er on decks

. Inhalation Applicator Data 875.1400*

- Worker exposure to sapstain and pressure treatment

- Open pour liquid preservatives

- Applying wood stains using a brush/roller and/or airless sprayer on decks

. Product Use Data 875.1700 All Antimicrobial Uses Product use data is needed to clarify uses (particularly the use of plastics in toys), application rates and wood retentions, and application equipment.

Indoor Residue Data (wipe study) 875.2300 Dermal and Incidental Oral Exposures to Children playing on pressure treated decks and playground equipment ( children aged 1 to 2)

. * For products with both indoor and outdoor uses, and similar conditions of use, data are generally required for the indoor a pplications only.

### Page 18 of 32

References

Recent Memoran da Relevant to Registration Review of Tebu conazole

Author DP/TXR # Date Title

Human Health Risk Assessment s B. O’Keefe DP 412600 12 / 31/13 Tebuconazole: Human Health Risk Assessment for Tolerance on Imported Oranges.

T. Morton DP414592 10/24/13 Common Triazole Metabolites: Updated Aggregate Human Health Risk

Assessment to Address The New Section 3 Registrations For Use of Propiconazole on Rapeseed Crop Subgroup 20A; Use of Difenoconazole on Rapeseed Crop Subgroup 20A; and Use of Tebuconazole on Importe d Oranges

. B. O’Keefe DP 402457 01 / 31/13 Tebuconazole: Human Health Risk Assessment for Tolerance Increases Based on Submission of Condition of Registration Requirements for Barley and Cantaloupe; and Crop Group Expansion for Fruiting Vegetable Crop Group 8

- 10.

B. O’Keefe DP 387596 11 / 30/11 Tebuconazole: Human Health Risk Assessment for Proposed Use on Almond, Apple, Cherry, Peanut, Pecan, Pistachio, Tree Nuts, Watermelon, and Wine Grapes.

B. O’Keefe DP 384949 02 / 14/11 Tebuconazole: Human Health Risk Assessment to Harmonize Tolerances

of Tebuconazole in/on Oats and Wheat with Canada

B. O’Keefe DP 373948 02 / 19/10 Tebuconazole: Amended Human Health Risk Assessment to Clarify Anticipated Residue and Percent Crop Treated Information.

B. O’Keefe DP 3613058 12 / 28 /0 9 Tebuconazole: Human Health Risk Assessment for Proposed Use on

Ornamentals and Golf Course Turf.

B. O’Keefe DP 362718 12 / 28 /0 9 Tebuconazole: Human Health Risk Assessment for Proposed Uses on Fruiting Vegetables (Crop Group 8).

S. Winfield DP 354807 07 / 22 /08 Tebuconazole: Amendment to D258383 Human Health Risk assessment for Tebuconazole; Proposed Tolerances for Cherry, Plum, and Commodity Definition for Hops.

S. Winfield DP 353954 06 / 30 /08 Tebuconazole: Amendment to D258383 Human Health Risk a ssessment for Tebuconazole; Proposed Tolerances for Tree Nut Group 14 and

Pistachios

S. Winfield DP 25 2188 0 4/ 30 /08 Tebuconazole: Amendment to D258383 Human Health Risk assessment for Tebuconazole; Proposed Tolerances for Tree Nut Group 14 and

Pistachios

S. Winfield DP 25 2188 0 4/ 30 /08 Tebuconazole: Addendum to Human Health Risk Assessment

S. Winfield DP 256074/

DP276447 0 4/18/08 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. Residue Chemistry M. Negussie DP416474 12/18/13 Tebuconazole. Request to Establish a Tolerance for Imported Oranges. Summary of Analytical Chemistry and Residue Data. Dietary Exposure Assessment M. Negussie DP416473 12/18/13 Tebuconazole: Acute and Chronic Aggregate Dietary Exposure and Risk Assessments for Establishment of a Tolerance for Imported Oranges. Occupational and Residential Exposure Assessments

B. O’Keefe DP408080 10/31/13 Tebuconazole. Occupational and Residential Exposure Assessment for a New Use on Home Lawns, Athletic Fields, and Sod.

### Page 19 of 32

Recent Memoran da Relevant to Registration Review of Tebu conazole

Author DP/TXR # Date Title

B. O’Keefe DP405729 06/06/13 Tebuconazole. Occupational and Residential Exposure Assessment for a

New Granular Formulation for Use on Golf Course Turf and Residential

Ornamentals.

B. O’Keefe DP397518 04/30/12 Tebuconazole: Occupational Exposure and Risk Assessment for Proposed Increase in Application Rate for Golf Course Turf.

B. O’Keefe DP389289 08/05/11 Tebucon azole: Occupational Exposure and Risk Assessment for Proposed Increase in Application Rate for Golf Course Turf.

B. O’Keefe DP376329 04/09/10 Amendment: Tebuconazole: Occupational and Residential Exposure Assessment for Proposed Uses on Ornamentals and Golf Course Turf

B. O’Keefe DP375909 03/29/10 Tebuconazole: Occupational and Residential Exposure Assessment for Proposed Uses on Barley, Pecan, Soybean, and Wheat on the Absolute 500 SC Fungicide Label

B. O’Keefe DP361303 12/28/09 Tebuconazole: Occupati onal and Residential Exposure Assessment for Proposed Uses on Ornamentals and Golf Course Turf

B. O’Keefe DP362766 12/28/09 Tebuconazole: Occupational and Residential Exposure Assessment for Proposed Uses on Fruiting Vegetables (crop group 8)

B. O’Keefe DP315464 04/16/08 Tebuconazole: Occupational Exposure and Risk Assessment to Support Requests for Proposed Uses on Asparagus, Beans (Fresh & Dry), Bulb Vegetables, Corn, Cotton, Cucurbits, Garden Beet, Hops, Leafy Brassica Greens, Lychee, Okra, Pome Fruit, Soybean, Stone Fruit, Sunflower, Turnips, Golf Course Turf, Ornamentals, plus Post

- Harvest Use on Cherry, Plum & Mango, & Seed Treatment of Corn Seed.

B. O’Keefe DP349913 03/13/08 Tebuconazole: Occupational Exposure and Risk Assessment of Proposed

Uses o n Wheat, Barley, and Tree Nuts.

B. O’Keefe DP349926 03/13/08 Tebuconazole: Residential Exposure and Risk Assessment of Proposed Use on Golf Course Turf and Existing Uses on Residential Ornamentals.

B. O’Keefe DP346795 11/26/07 Tebuconazole: Residential Exposure and Risk Assessment of Existing

Antimicrobial Uses on Wood Products and in Paints. Incident Report

S. Recore D 429846 10 / 28 /15 Tebu conazole: Tier I Review of Human Incidents



### Attachment s 1. Chemical Identity Table

2. Physicochemical Properties of Technical Grade Tebu conazole Table

3. Endpoint Selection Table

4 . Toxicity Profile Tables 5. Toxicology Data Requirements Table

6. Tolerance/MRL Table

### Page 20 of 32

Attachment 1 Chemical Identity Table

Table A

. 1 . Nomenclature of Tebuconazole and its Regulated Metabolite.
Compound

Common name Tebuconazole Company experimental name HWG 1608

IUPAC name ( RS )

- 1

- p

- chlorophenyl

- 4,4

- dimethyl

- 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 number 107534

- 96

- 3 Molecular weight 307.8

End

- use products (EP) FOLICUR ® 25EW (25% w/v 250 g/L ; EPA Reg. No. 264

- 748)

Metabolite

Common name t

- butylhydroxy

- tebuconazole Company experimental name HWG 2061

IUPAC name Not available

CAS name 1

- (4

- chlorophenyl)

- 4,4

- dimethyl

- 3

- (1 H

- 1,2,4

- triazole

- 1

- ylmethyl)

- pe n tane

- 3,5

- diol CAS registry number Not available Molecular weight 323.8

### Page 21 of 32

Attachment 2

Table A.2 . Physicochemical Properties of Tebuconazole.

Parameter Value Reference

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

G. Otakie pH Not soluble enough

Specific gravity (20 oC) 1.202 g/mL

Water solubility (20 °C) 32 mg/L

Solvent solubility (g/L at 20oC) n

- hexane 2

- 5

dichloromethane >200

2

- propanol 100

- 200

toluene 50

- 100

Vapor pressure 1.3 x 10

- 3 mPa (20 oC)

3.1 x 10

- 3 mPa (25 oC)

Dissociation constant, pK

a does not dissociate

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

UV/visible absorption spectrum Not available

### Page 22 of 32

Attachment 3

Summary of Toxicity Endpoints and Points of Departure of Tebuco nazole

Table A.3 . Summary of Toxicological Doses and Endpoints for Tebuconazole for Use in Dietary and Non

Occupational Human Health Risk Assessments.
Exposure/

Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD, PAD, Level of

Concern for Risk

Assessment Study and Toxicological Effects

Acute Dietary (General Population, including Infants

and Children) LOAEL = 8.8

mg/kg/day UF A = 10x

UF H =10x (UF L )= 3x FQPA=1X Acute RfD = 0.029

mg/kg/day

aPAD = 0.029 mg/kg/day Developmental Neurotoxicity Study

- Rat.

LOAEL = 8.8 mg/kg/day based on decreases in body weights, absolute brain weights, brain measurements and motor activity in offspring. Chronic Dietary (All Populations) LOAEL = 8.8

mg/kg/day UF A = 10x

UF H =10x (UF L )= 3x FQPA=1X Chronic RfD = 0.029

mg/kg/day

cPAD =0.029 mg/kg/day Developmental Neurotoxicity Study

- Rat.

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

Incidental Oral

Short

- Term (1

- 30 days) and

Intermediate

- term (30 days

– 6 months) LOAEL = 8.8

mg/kg/day UF A = 10x

UF H =10x (UF L )= 3x FQPA=1X Residential LOC for

MOE = 300 Developmental Neurotoxicity Study

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

Dermal ( All

durations ) LOAEL = 8.8

mg/kg/day UF A = 10x

UF H =10x

UF L = 3x

DAF = 13% Residential LOC for

MOE = 300 Developmental Neurotoxicity Study

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

Inhalation ( All

durations ) LOAEL = 8.8

mg/kg/day UF A = 10x

UF H =10x

UF L = 3x Residential LOC for

MOE = 300 Developmental Neurotoxicity Study

- Rat. LOAEL = 8.8 mg/kg/day based on decreases in body weights, absolute brain weights, brain measurements and motor activity in offspring. Cancer (oral, dermal, inhalation) Classification: Group C

- possible human with no quantification. The chronic risk assessment is considered

to be protective of any cancer effects; therefore, a separate quantitative cancer risk assessment is not required. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant hu man 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 huma n 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 applic able. DAF = dermal absorption factor.

### Page 23 of 32

Attachment 4

Toxicity Profile for Tebu conazole

Table A.4.1. Acute Toxicity Profile for Tebuconazole

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

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

870.1200 Acute dermal [rat] 40700917

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

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

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

870.2400 Acute eye irritation [rabbit] 40700925

40700917 Slight to Mild irritant III

870.2500 Acute dermal irritation

[rabbit] 40700917

40995910 Non

- irritant IV

870.2600 Skin sensitization

[guinea pig] 40700928

41290802 No evidence of skin sensitization

using the Buehler test NA

Table A. 4.2. Subchronic, Chronic and Other Toxicity Profile for Tebu conazole Technical

. Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.3100

90

- Day oral toxicity

- rat 40700930 (1986) (0, 100, 400, 1600 ppm in diet); 0, 8.6, 34.8, 171.7 mg/kg/d (m); 0, 10.8, 46.5, 235.2 mg/kg/d (f) Acceptable/guideline Male: NOAEL = 34.8 mg/kg/d; LOAEL= 171.7 mg/kg/d based on decreased body wt., body wt. gain, and histopathology findings.

Femal e: NOAEL=10.8 mg/kg/d, LOAEL= 46.5 mg/kg/d based on histopathological changes in the adrenal gland.

870.3150

90

- Day oral toxicity

- dog 40700934 (1987) (0, 200, 1000, 5000 ppm in diet); 0, 73.7, 368.3, 1749.1 mg/kg/d (m); 0, 73.4, 351.8, 1724.8 mg/kg/d (f) Acceptable/guideline NOAEL = 73.4/73.7 mg/kg/d (m/f) LOAEL = 368.3/ 351.8 mg/kg/d (m/f) based on decreased body wt. gain, food consumption and increased liver enzyme activities.

870.3200

21/28

- Day dermal toxicity

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

870.3465

21

- Day inhalation toxicity

- rat 40700938 (1985) 0, 1.2, 10. 6, 155.8 mg/m 3 Acceptable/ non

- guide line NOAEL = 10.6 mg/m 3 /d ay (≈2.0 mg/kg/day)

LOA EL = 155.8 mg/m 3 /d ( ≈28 mg/ kg /day) based on clinical signs (bristling coat).

870.3700a Prenatal developmental

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

- 15 Acceptable/guideline Maternal NOAEL = 30 mg/kg/day LOAEL=60 mg/kg/d based on increased liver

w iegh t and liver/body weight ratios. 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.

### Page 24 of 32

Table A. 4.2. Subchronic, Chronic and Other Toxicity Profile for Tebu conazole Technical

. Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.3700a Prenatal developmental

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

6

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

seen via dermal route.

870.3700a Prenatal developmental

- mouse 40821 501 (1988) 0, 10, 30, 100 mg/kg/d, GD 6

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

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

of runts.

870.3700a Prenatal developmental

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

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

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

liver cells. Developmental : NOAEL= 3 mg/kg/d LOAEL=10 mg/kg/d based on increased external, visceral, and skeletal malformation/variation in the

head and skull.

870.3700a Prenatal developmental

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

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

seen via dermal route.

870.3700b Prenatal developmental

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

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

- implantation losses, decreased live fetuses/doe, and external and skeletal

abnormalities.

870.3700b

Pre natal developmental

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

- 18 Acceptable/guideline Maternal NOAEL = Not established (<10 mg/kg/d) LOAEL = 10 mg/kg/d based on increased incidence of single cell necrosis in liver cells. Developmental NOAEL = 10 mg/kg/d LOAEL = 30 mg/kg/d based on increased external

and visceral malformation/variations.

870.3800 Reproduction and fertility effects

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

LOAEL = not determined

Off spring NOAEL = 15 mg/kg/day LOAEL = 50 mg/kg/day based on decreased pup body wt.

### Page 25 of 32

Table A. 4.2. Subchronic, Chronic and Other Toxicity Profile for Tebu conazole Technical

. Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.4300

Chronic/ carcinogenicity

- rat 40700939, 40816401 (1988) 0, 100, 300, 1000 ppm in diet; M: 0, 5.2, 15.9, 55 mg/kg/d; F: 0, 7.4, 22.8, 86.3 mg/kg/d Acceptable/guideline Males: NOAEL = 15.9 mg/kg/d; LOAEL=55 mg/kg/day based on decreased testes weight. Females: NOAEL= 7.4 mg/kg/d; LOAEL=22.8 mg/kg/day based on decreased body wt. & wt. gain, decreased erythrocyte parameters and increased incidence of sp lenic hemosiderosis (increased erythrocyte clearance). No evidence of carcinogenicity at the doses tested.

870.4100b Chronic toxicity

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

870.4100b Chronic toxicity

- dog 42030601 (main) (1989) & 42537201 (suppl.) (1992); 0, 100, 150 ppm; M: 0, 2.96, 4.39 mg/kg/d F: 0, 2.94, 4.4 5 mg/kg/d Acceptable/guideline together

with 40700940 NOAEL = 2.96 mg/kg/day (m), 2.94 mg/kg/d (f) LOAEL = 4.39 mg/kg/day (m), 4.45 mg/kg/d (f) based on lesions in the adrenal gland.

870.4200b Carcinogenicity

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

42175001 0, 500, 1500 ppm M: 0, 84.9, 279 mg/kg/day F: 0, 103.1, 365.5 mg/kg/day Acceptable/guideline 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% c ontrols), hepatocellular carcinomas (21% vs. 0% controls) and combined adenomas and/or carcinomas (47% vs. 5% controls).

870.5100 Salmonella point

mutation 40700947 & 40700948 (1988) Acceptable/guideline Negative with or without activation at doses rangi ng from 39.5 to 450 μg/plate

870.5300

CHO

- HGPRT forward

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

- 200 and 80

- 100 μg/mL, respectively; highest concentration tested

did not produce high level of cytotoxicity.

870.5375 In vitro Cytogenetics (human lymphocytes) 40700953 (1988) Acceptable with activation; Unacceptable without activation Negative for chromosome aberrations with activation (30

- 300 μg/mL) and without activation ( 10

- 300 μg/mL); highest dose not cytotoxic

without activation.

870.5395 Mammalian erythrocyte

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

870.5450

Mouse dominant lethality 40700950 (1986) Unacceptable/guideline Negative at 2000 mg/kg bw (only dose tested) during 12 serial mating periods; positive control

was not included

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

co ncentrations ranging from 625

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

### Page 26 of 32

Table A. 4.2. Subchronic, Chronic and Other Toxicity Profile for Tebu conazole Technical

. Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.5550

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

- 25.2 μg/mL

870.5900

Sister chromatid exchange (CHO cells in

vitro ) 40700952 (1987) Acceptable/guideline Negative with and without activation with S9 at concentrations ranging from 4

- 30 μg/mL and 15

- 120 μg/mL, respectively.

870.6200a

Acute neurotoxicity screening battery

- rat 44449301, 44545701 (1997)

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

Unacceptable/Guideline (Upgradeable) NOAEL = 50 mg/kg/day LOAEL = 100 mg/kg/day based on increased motor activity in males and females and decreased footsp lay in females.

870.6200b

Subchronic neurotoxicity screening battery

- rat 44588001 (1998) 0, 100, 400, or 1600 ppm M: 0.00, 7.57, 29.2, 107 mg/kg/day F: 0.00, 8.81, 34.0,

122 mg/kg/day Unacceptable/Guideline (Not upgradeable) NOAEL = 107 mg/kg/day LOAEL = Not determined [>107 mg/kg/day]

870.6300

Developmental neurotoxicity

- rat 45074301 (2000)

0, 100, 300, 1000 ppm

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

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

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

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

870.7485

Metabolism

- rat 40995911, 40995912 (1987)

Acceptable/guideline 98.1% of oral dose is absorbed. Over 87% of dose

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

870.7600 Dermal penetration

- monkey 46634901 (2003)

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

administration

Acceptable/nonguideline Estimated dermal absorption 23.1%. (including the

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

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

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

GD14

- PND7 to dams, PND7

- 42 to offspring Study evaluated reproductive, immuno

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

- review.

### Page 27 of 32

Table A. 4.2. Subchronic, Chronic and Other Toxicity Profile for Tebu conazole Technical

. Guideline No. Study Type MRID No. (year)

Doses/ Classification Results

870.7800 Immunotoxicity 48769501 (2012) Acceptable/Guideline Doses: 0, 100, 300, 1000 ppm 0, 8.1, 24.3, 78.4 mg/kg/day Systemic: NOAEL = 78.4 mg/kg/day LOAEL > 78.4 mg/kg/day

Immunotoxicity: NOAEL = 78.4 mg/kg/day

LOAEL = 78.4 mg/kg/day

### Page 28 of 32

Attachment 5 Toxicology Data Requirements

The requirements (40 CFR § 158.340) for food and non

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

were used.

Table A. 5 .1 Toxicology Data Requirements for Tebuconazole

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity

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

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

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

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

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

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

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

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

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

- Day Dermal

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

- Day Dermal

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

- Day Inhalation

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

yes

yes CR

yes yes

yes

yes

no
yes+

870.3700a Developmental Toxicity (rodent)

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

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

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

yes

yes yes

yes

yes

870.4100a Chronic Toxicity (rodent)

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

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

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

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

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

yes

no

yes

yes no

yes

— yes

yes

870.5100 Mutagenicity

— Gene Mutation

- bacterial

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

— Gene Mutation

- mammalian

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

— Structural Chromosomal Aberrations

... 870.5xxx Mutagenicity

— Other Genotoxic Effects

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

yes

yes yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen)

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

- Day Neurotoxicity (hen)

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

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

- Day Neuro. Screening Battery (rat)

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

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

no

yes

yes

yes —

— yes

yes

yes

870.7485 General Metabolism

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

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

no

yes yes

yes

yes

Special Studies for Ocular Effects

Acute Oral (rat)

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

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

- month Oral (dog)

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

no

no no

no

no

+ : 21

- day inhalation toxicity study is available

.

### Page 29 of 32

Attachment 6

Tolerance/MRL Tabl e



## International Residue Limits

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 

### Codex 2

40 CFR § 180

. 474 (a) General. (1) Compliance with the tolerance levels specified below is to be determined by measuring only tebuconazole [α

- [2

- (4

- chlorophenyl)ethyl]

- α

- (1,1

- dimethylethyl)

- 1H

- 1,2,4

- triazole

- 1

- ethanol] α

- [2

- (4

- chlorophenyl)ethyl]

-

α

- (1,1

- dimethylethyl)

- 1 H

1,2,4

- triazole

- 1

- ethanol Tebuconazole

The residue is fat

- soluble.



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

US Canada Mexico 1 

### Codex 2

Almond, hulls 6.0 Apple, wet pomace 0.1 Asparagus 0.05

Banana 0.05 0.03 0.05 Barley, grain 0.3 0.3 2 Barley, hay 7.0 Barley, straw 3.5 40 Bean, dry seed 0.1 0.3
Bean, succulent 0.1 Beet, garden, roots 0.70 Beet, garden, tops 7.0 Brassica, leafy greens, subgroup 5B 2.5

Cherry, sweet, pre

- and post

harvest 5.0 3 cherry 4 cherries

Cherry, tart, pre

- and post

harvest 5.0

Coffee, green bean 1 0.15 0.1 coffee beans
Coffee, roasted bean 1 0.3 Corn, field, forage 4.0 Corn, field, grain 0.05 0.05
Corn, field, stover 3.5 Corn, pop, grain 0.05 Corn, pop, stover 3.5 Corn, sweet, forage 7.0 Corn, sweet, kernel plus cob

with husks removed 0.5 0.5 0.6

Corn, sweet, stover 6.0 Cotton, gin byproducts 25.0
Cotton, undelinted seed 2.0 2 Fruit, pome, group 11 0.05 1 apple, pear,
Fruit, stone, group 12, except cherry 1.0 1 nectarines, peaches 2 apricot, nectarine, peach, 1 plums (except prunes) 3 prunes

### Page 30 of 32

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 

### Codex 2

Grain, aspirated fractions 16.0 Grape 5.0 5 6 7 dried grapes (=currants, raisins and sultanas) Grass, forage 8.0 Grass, hay 25.0 Grass, seed screenings 55.0
Grass, straw 30.0 Hop, dried cones 35.0 40 Lychee 1.6 Mango, postharvest 0.15 0.05 mango Nut, tree, group 14 0.05 0.05 0.05 (*) Oat, forage 0.10 Oat, grain 0.15 0.15 2 Oat, hay 0.10
Oat, straw 0.10 Onion, bulb, subgroup 3

- 07A 0.2 0.1 garlic, onion bulb Onion, green, subgroup 3

- 07B 1.3 0.7 leek

Orange 1 1.0 Orange, oil 1 10

Peach 1.0 1 2

Peanut 0.1 0.15 40 peanut fodder

Pistachio 0.05 0.05 0.05 (*) tree nuts
Plum, pre

- and post

- harvest 1.0 1 (except prunes) Soybean, forage 25 Soybean, hay 50 Soybean, seed 0.08 0.08 0.15
Sunflower, seed 0.05
Sunflower, meal 0.2
Sunflower, refined oil 0.2 Vegetable, cucurbit, group 9 0.4 0.4 0.15 cucumber, melons (except watermelon), 0.2 squash summer 0.1 watermelon (proposed) Vegetable, fruiting, group 8

- 10 1.3 0.1 Eggplant 10 peppers, chili, dried 1 peppers sweet (including pimento or pimiento)

0.7 tomato Wheat, forage 3.0 Wheat, germ 0.20 Wheat, grain 0.15 0.15 0.15 wheat, triticale Wheat, hay 7.0
Wheat, shorts 0.20
Wheat, straw 1.5 40 MRLs with NO US Equivalent

Artichoke 0.6

Broccoli 0.2

### Page 31 of 32

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 

### Codex 2

Brussels sprouts 0.3 Cabbages, head 1

Carrot 0.4

Cauliflower 0.05 (*) Common bean (pods and/or immature seeds) (proposed) 2 (proposed)

Elderberries 1.5
Lettuce, head 5

Olives 0.05 (*) Papaya 2

Passion fruit 0.1 Rapeseed 0.3

Rice 1.5 Rye 0.15 Rye straw and fodder, dry 40

(2) Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of tebuconazole (alpha

- [2

- (4

- chlorophenyl)ethyl]

- alpha

- (1,1

- dimethylethyl)

- 1 H

- 1,2,4

- triazole

- 1

- ethanol) and its diol metabolite (1

- (4

- chlorophenyl)

- 4,4

- dimethyl

- 3

- (1 H

- 1,2,4

- triazole

- 1

- yl

- methyl)

- pentane

- 3,5

- diol),

calculated as the stoichiometric equivalent of tebucon a zole α

- [2

- (4

- chlorophenyl)ethyl]

-

α

- (1,1

- dimethylethyl)

- 1 H

1,2,4

- triazole

- 1

- ethanol, including the

metabolite 5

- (4

-

c hlorophenyl)

- 2,2

- dimethyl

- 3

- (1 H

1,2,4

- triazol

- 1

- ylmethyl)

- 1,3

- pentanediol Tebuconazole

The residue is fat

- soluble.



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

US Canada Mexico 1 

### Codex 2

Cattle, meat byproducts 0.2 0.2 0.05 (*)
Goat, meat byproducts 0.2 0.2 0.05 (*) Horse, meat byproducts 0.2 0.2 0.05 (*)

Milk 0.1 0.1 0.01 (*) Sheep, meat byproducts 0.2 0.2 0.2 MRLs with NO US Equivalent Eggs 0.1 0.05 (*) Meat byproducts of hogs 0.2 0.2 Meat byproducts of poultry 0.1 0.05 (*) Meat of (cattle, goats, hogs, horses, sheep) 0.2 0.05 (*)

Meat of poultry 0.1 0.05 (*) M. Negussie; 10/08/15

1 There are no U.S. registrations.

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

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

(c) Tolerances with regional registrations. Tolerances are established for residues of the fungicide tebuconazole, including its metabolites and degradates, in or on the commodities in the following table. C ompliance with the

### Page 32 of 32

tolerance levels specified below is to be determined by measuring only tebuconazole, alpha

- [2

- (4

- chlorophenyl)ethyl]

- alpha

- (1,1

- dimethylethyl)

- 1 H

- 1,2,4

- triazole

- 1

- ethanol, in or on the commodity.

Commodity Parts per million

Turnip, roots 0.5

Turnip, tops 7.0