 Page 1 of 55 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM August 15, 2006 SUBJECT: Propiconazole: FQPA Human Health Risk Assessment for New Uses on Various Crops. PP# 2F6371, 6E4788, 7E4860, and 8E4931. PC Code: 122101. DP Barcode D319598, 313963, 313965, 313967, 325817, 234716.

FROM: Yan Donovan, Chemist and Risk Assessor Reregistration Branch 4 Health Effects Division ( 7509C)

And Abdallah Khasawinah, Toxicologist James Miller, Environmental Scientist Reregistration Branch 4 Health Effects Division ( 7509C))

THROUGH: Susan Hummel, Senior Scientist, Reregistration Branch 4 Richard Loranger, Senior Scientist, Registration Branch 2 Health Effects Division ( 7509C)

TO: Mary Waller/ Cynthia Giles Parker Fungicide Branch Registration Division Attached is the Health Effect Division's ( HED's) human health risk assessment for propiconazole new and revised uses. Propiconazole is among the group of chemicals, which generate common metabolite, called 1,2,4 triazole and its conjugates triazole alanine and triazole acetic acid. A separate document is available to address the common metabolite risk issue ( HED memo of M. Doherty, 2/ 7/ 06, D322215). 1,2,4 triazole and its conjugates will not be further discussed in this document other than the data needs in Section 10. There are antimicrobial uses for propiconazole as well. Antimicrobial Division ( AD) has conducted a risk assessment for all existing and potential antimicrobial uses. The present aggregate risk assessment includes the Page 2 of 55 risks from antimicrobial uses in mushroom houses ( dietary) and in treated wood in play sets and residential decks ( residential post application exposure).

The Team Reviewers who contributed to the disciplinary chapters and the references are listed below.

1) Propiconazole: Phase 4, HED Chapter of the Re registration Eligibility Decision Document ( RED), Yan Donovan, 6/ 28/ 06, D329668;

2) Residue Chemistry Summary Document; Yan Donovan ( D238458, 7/ 31/ 2006);

3) Occupational and Residential Exposure Assessment; James Miller, Environmental Scientist ( D325817, 6/ 15/ 06);

4) Revised Occupational and Residential Exposure Assessment of the Antimicrobial Uses; Tim Leighton ( D324052, 02/ 01/ 06);

5) Amendment to the Propiconazole RED for Children's Post application Exposure from Treated Structures; Tim Leighton ( D330159, 06/ 20/ 06);

6) Dietary Exposure and Risk Assessment for New uses; Yan Donovan ( D312278, 8/ 15/ 06);

7) Drinking Water Assessment; James Lin from EFED ( D325821, 07 / 07/ 06). Page 3 of 55 TABLE OF CONTENTS 1.0 Executive Summary............................................................................................ 5 2.0 Ingredient Profile ................................................................................................ 8 2.1. Summary of Registered/ Proposed Uses ................................................................................................ 8 2.2 Structure and Nomenclature ............................................................................................................... 11 2.3 Physical and Chemical Properties....................................................................................................... 12 3.0 Metabolism Assessment .................................................................................. 13 3.1 Comparative Metabolic Profile........................................................................................................... 13 3.2 Nature of the Residue in Foods........................................................................................................... 14 3.2.1. Description of Primary Crop Metabolism .................................................................................. 14 3.2.2 Description of Livestock Metabolism.......................................................................................... 14 3.2.3 Description of Rotational Crop Metabolism, including identification of major metabolites and specific routes of biotransformation. ......................................................................................... 15 3.3 Environmental Degradation................................................................................................................ 15 3.4 Tabular Summary of Metabolites and Degradates ............................................................................... 15 3.5 Toxicity Profile of Major Metabolites and Degradates ........................................................................ 20 3.6 Summary of Residues for Tolerance Expression and Risk Assessment ................................................ 20 3.6.1 Tabular Summary ....................................................................................................................... 20 3.6.2 Rationale for Inclusion of Metabolites and Degradates.............................................................. 20 4.0 Hazard Characterization/ Assessment............................................................. 21 4.1 Hazard Characterization..................................................................................................................... 21 4.2 FQPA Hazard Considerations............................................................................................................. 22 4.3 Hazard Identification and Toxicity Endpoint Selection........................................................................ 22 4.4 Special FQPA Safety Factor ............................................................................................................... 25 4.5 Endocrine Disruption ......................................................................................................................... 25 5.0 PUBLIC HEALTH DATA.................................................................................... 26 5.1 Incident Reports................................................................................................................................. 26 6.0 Exposure Characterization/ Assessment ............................................................ 26 Page 4 of 55 6.1 Dietary Exposure/ Risk Pathway ......................................................................................................... 26 6.1.1 Residue Profile............................................................................................................................. 26 6.1.2 Acute and Chronic Dietary Exposure and Risk.......................................................................... 30 6.2 Water Exposure/ Risk Pathway ........................................................................................................... 31 6.3 Residential ( Non Occupational) Exposure/ Risk Pathway .................................................................... 32 7.0 Aggregate Risk Assessments and Risk Characterization............................. 34 7.1 Acute Aggregate Risk ........................................................................................................................ 35 7.2 Short Term Aggregate Risk................................................................................................................ 35 7.3 Intermediate Term Aggregate Risk..................................................................................................... 37 7.4 Long Term Aggregate Risk................................................................................................................ 38 7.5 Cancer Risk ....................................................................................................................................... 38 8.0 Cumulative Risk Characterization/ Assessment ............................................. 38 9.0 Occupational Exposure/ Risk Pathway............................................................ 39 9.1 Short/ Intermediate/ Long Term Handler Risk...................................................................................... 39 9.2 Short/ Intermediate/ Long Term Postapplication Risk........................................................................... 42 10.0 Data Needs and Label Requirements.............................................................. 44 10.1 Residue Chemistry Data Needs .......................................................................................................... 45 10.2 ORE Data Needs................................................................................................................................ 46 10.3 Toxicology Data Needs ..................................................................................................................... 46 Page 5 of 55 1.0 EXECUTIVE SUMMARY Syngenta Crop Protection ( Syngenta) and Interregional Research Project No. 4 ( IR 4) have submitted several petitions supporting new or amended uses on various crops for propiconazole, formulated as a 3.6 lb/ gal emulsifiable concentrate ( EC) or a 45% wettable powder ( WP). The proposed uses are for broadcast foliar applications using ground or aerial equipment at rates ranging from 0.11 to 0.28 lb ai/ A/ application. For tree nuts, the proposed use is for up to four foliar applications at 0.225 lb ai/ A, for a total of 0.90 lb ai/ A, with a 60 day preharvest interval ( PHI). For bush and cane berries and cranberries, the proposed uses are for 4 or 5 foliar applications at 0.17 lb ai/ A, for totals of 0.68 0.84 lb ai/ A, with PHIs of 30 or 45 days. For carrots, leaf petiole vegetables, dry peas and beans, sugar beets and strawberries, the proposed uses are for 3 or 4 broadcast foliar applications at 0.11 lb ai/ A, for totals of 0.34 or 0.45 lb ai/ A, with PHIs of 0 to 21 days. For mint, the proposed use is for two broadcast foliar applications at 0.113 lb ai/ A, for a total of 0.225 ai/ A, with a PHI of 30 days. For soybeans, the proposed use is for two broadcast foliar applications at 0.169 lb ai/ A at up to growth stage R6, for a total of 0.338 ai/ A, with a PHI of 30 days. For rice, the proposed use is for a single application or split applications at heading totaling ~ 0.30 lb ai/ A, with a PHI of 35 days. For other cereal grains, the proposed uses are for 2 to 4 broadcast foliar applications at 0.113 lb ai/ A up to heading or grain development, for totals of 0.22 or 0.45 ai/ A, with PHIs of 14 45 days. In conjunction with these uses, Syngenta and IR 4 are proposing permanent tolerances for propiconazole residues in/ on various plant commodities at levels ranging from 0.1 ppm on alfalfa to 32 ppm on soybean hay.

Propiconazole is a member of the class of the ergosterol biosynthesis inhibiting fungicides. The mode of antifungal action of propiconazole is attributed to the inhibition of CYP51 ( lanosterol 14 a demethylase). Propiconazole has low to moderate toxicity in experimental animals by the oral, dermal and inhalation routes, is moderately irritating to the eyes, and minimally irritating to the skin, and it is a dermal sensitizer. The primary target organ for propiconazole toxicity in animals is the liver. HED's Hazard Identification Assessment Review Committee ( HIARC) concluded that the toxicology database for propiconazole is complete for FQPA assessment. Endpoints and dose response have been selected for acute, chronic dietary, short and intermediate term dermal, inhalation, and incidental oral, and long term dermal and inhalation exposures. For the scenarios associated with the new uses, HED concludes that the endpoints selected by HIARC are still appropriate.

The HIARC also concluded that the database was adequate to characterize any potential for prenatal or postnatal risk for infants and children. There is low concern for pre and/ or postnatal toxicity resulting from exposure to propiconazole, and no residual uncertainties were identified. The exposure databases ( dietary food, drinking water, and residential) are complete and that the risk assessment for each potential exposure scenario includes all metabolites and/ or degradates of concern and does not underestimate the potential risk for infants and children. There fore, the FQPA factor is thus 1X. The HIARC had previously determined that an acute neurotoxicity ( ACN) study was required based on neurotoxic signs in pregnant rats administered high propiconazole doses ( 360 mg/ kg/ day) during gestation. HIARC had determined that for acute ( female age 13 49) and short term exposure scenarios, a 3X database uncertainty factor ( UFDB) was adequate to account for the lack of the ACN. In September 2005, the ACN was submitted to Page 6 of 55 the Agency and was reviewed. The study confirms that neurotoxic signs are observed at high doses, but without neuropathological or neurobehavioral effects. Accordingly, the propiconazole risk assessment team determined that a developmental neurotoxicity study was not necessary and the 3X database uncertainty factor for acute ( female 13 49) and short term scenarios was removed.

The HED Carcinogenicity Peer Review Committee ( CPRC) classified propiconazole as Group C  possible human carcinogen and recommended that for the purpose of risk characterization the reference Dose ( RfD) approach should be used and would be protective.

Tolerances are established for residues of propiconazole and its metabolites determined as 2,4 dichlorobenzoic acid, all expressed as parent compound in/ on various plant and animal commodities [ 40 CFR § 180.434]. The reassessed tolerances as recommended in the HED RED will be expressed as propiconazole per se. As a result, in some cases the tolerance levels will be over estimated, due to the fact that the analytical method for data collection is a comment moiety method that detects all residues convertible to 2,4 dichlorobenzoic acid ( DCBA), and the field data were reported as propiconazole and all its metabolites containing 2,4 DCBA. As a result, HED is unable to separate out the parent residue from the metabolites at this time. HED recommends that the registrant analyze parent and metabolites separately in all future field trials, so that more realistic tolerances can be set in the future.

Provided that minor changes are made to the proposed use directions, the available field trial data on almonds, bush and cane berries, carrots, celery, corn, cranberries, mint, onions, pecans, rice, sorghum, soybeans, strawberries and wheat are adequate and support the proposed use patterns for propiconazole ( EC or WP) on these crops. The number and geographic distribution of the field trials are adequate, and the appropriate samples were collected. Samples were analyzed using adequate analytical methods and the sample storage intervals are supported by the available storage stability data. Side by side field trials were conducted on almond, celery, field corn, and sugar beets to compare residues from the EC and WP formulation. These data show residues are comparable from the two products, with the exception of sugar beet tops at the requested PHI. A conditional registration can be established on sugar beet tops. For dry peas and beans, however, there are no sufficient field trial data to support the proposed use. HED recommends against the establishment of permanent tolerance on crop subgroup 6C until additional field trial data are submitted. The Agency's Guidance for Setting Pesticide Tolerances Based on Field Trial Data ( tolerance spread sheet) was utilized for determining appropriate tolerance levels on plant commodities.

The estimated drinking water concentrations from surface water sources were calculated using Tier II PRZM ( Pesticide Root Zone Model) and EXAMS ( Exposure Analysis Modeling System). For each specific use, the maximum allowable label rate was input to PE4V01. The output concentrations were without percent crop area ( PCA) consideration. The final estimated drinking water concentrations were then adjusted with the proper PCA. Except the uses of soybean ( 0.41) and wheat ( 0.56), other uses assume the default PCA of 0.87. Among these modeling results, turf use gives the highest acute concentration of 55.78 ug/ l. For the chronic exposure, turf use also gives the highest concentration of 21.61 ug/ L. Page 7 of 55 The estimated environmental concentrations in ground water were calculated using the Tier I SCI GROW ( Screening Concentration In Ground Water) model. SCI GROW is neither scenario nor crop specific. The only input requirements are application rate, number of applications, Koc, and aerobic soil metabolism half life. The higher estimated concentrations are associated with the higher rate. Turf use gives the highest concentration of 0.64 µ g/ L ( ppb).

Acute and chronic dietary analyses for propiconazole were conducted using tolerance levels and 100 % CT for all proposed new uses, revised uses, and existing uses. The results of the analyses indicate that acute and chronic risks from the dietary exposure ( food and water) to propiconazole do not exceed HED's level of concern for the United States population or any population subgroup.

Although no new residential use was requested associated with the subject petitions, there are existing residential uses for propiconazole. The registered residential use patterns result in post application dermal exposures to adults, and dermal and oral exposures to infants and children. These exposures are considered short term only and were previously assessed in HED's phase 4 RED. In addition to using HED's SOP for residential assessment, the turf transferable residue ( TTR) was used in the calculation. The dermal and incidental oral exposure to infants and children were combined, and all MOEs do not exceed HED's level of concern. Risk to children playing on propiconazole treated structures ( from antimicrobial use) was also assessed using a screening level assessment. This risk assessment, based on high end screening level assumptions, indicates no risk of concern. Confirmatory data for the surface residues are needed to verify this screening level assessment.

Aggregate risk assessments were conducted for acute, chronic, short and intermediate term exposure duration. The risks do not exceed HED's level of concern. Acute aggregate risk included food and water only; chronic aggregate risk also included food and water because no chronic exposure from residential uses is expected. Short term aggregate risk included food, water, and residential/ antimicrobial exposures. Intermediate term aggregate risk included food, water, and residential exposure to Children 1 2 years old from treated wood used in deck and play structures.

The short and intermediate term occupational handler non cancer risk assessment for propiconazole indicates that for all commercial/ agricultural handler scenarios, risks do not exceed HED's level of concern ( i. e., MOEs > 100) with use of chemical resistant gloves. For occupational post application exposures and risks, data from propiconazole specific studies were used along with crop specific transfer coefficients. The non cancer occupational postapplication worker risk assessment indicates that risks do not exceed HED's level of concern ( i. e., MOEs > 100) on the day of the treatment ( day after treatment ( DAT) = 0).

As a conazole pesticide, all propiconazole new registrations should be conditional until issues related to common metabolite risk are resolved. Pending the submission of label changes outlined in Section 10.1 under data gaps, HED recommends the establishment of permanent tolerances for propiconazole residues at the levels recommended in the Table 11. Registrations Page 8 of 55 should be granted on a conditional basis until the data outlined in Section 10.0 plus the sugar beet top data in Section 10.1 are submitted.

2.0 INGREDIENT PROFILE Propiconazole is a systemic broad spectrum fungicide registered for treatment of disease in a variety of crops. It is a member of the class of the ergosterol biosynthesis inhibiting fungicides. The mode of antifungal action of conazoles is attributed to the inhibition of CYP51 ( lanosterol 14 a demethylase). Propiconazole end use products are marketed in the United States under the trade names Tilt ® , Alamo ® , Banner ® , Orbit ® , and Quilt TM. The amount of active ingredients in the various formulations range from 11.4% to 45%. Recently, propiconazole is also registered for use on a variety of crops under the trade names of Stratego   Twin Pak   and Stratego   , which are end use products containing a mixture of trifloxystrobin and propiconazole. The propiconazole formulations registered for food/ feed uses include emulsifiable concentrate ( EC) and flowable concentrate ( FlC) formulations.

2.1. Summary of Registered/ Proposed Uses Table 2.1 summarized the new proposed agricultural uses. Uses are based on an example labels provided for the EC formulations ( 1/ 14/ 05) and the approved labels for the WP ( accepted 12/ 11/ 03) and EC MAI ( accepted 3/ 8/ 06).

Table 2.1. Summary of Directions for Proposed Uses of Propiconazole.

Application Timing, Type and Equipment Formulation [ EPA Reg. No.] Single rate ( Lb ai/ A) Max. # of Apps. per Season Max. Seasonal Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations 1 Almond Foliar applications beginning at bud break Ground or aerial equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.225 4 0.90 NS Apply in a minimum of 20 or 50 gal/ A using aerial and ground equipment, respectively. Minimum RTI is 7 days Do not graze livestock in treated areas or cut treated cover crop for feed Berries ( Bush and Cane berries) and Cranberry Foliar applications beginning at bud break or for cane berries beginning as a delayed dormant application Ground or aerial equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.169 5 0.84 30 Apply in a minimum of 5 10 or 20 50 gal/ A using aerial and ground equipment, respectively. The minimum RTI is 7 28 days depending on the disease.

Cranberry ( For use Only in Wisconsin and the Pacific Northwest) Broadcast foliar applications from bud break to fruit set 3.6 lb/ gal EC [ 100 702] 0.169 4 0.68 45 Minimum RTI is 10 days Carrots Broadcast foliar applications when conditions favor disease development Ground or aerial equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.113 4 0.45 14 Apply in a minimum of 5 or 15 gal/ A using aerial and ground equipment, respectively. Minimum RTI is 7 days Application may include spreader sticker Page 9 of 55 Table 2.1. Summary of Directions for Proposed Uses of Propiconazole.

Application Timing, Type and Equipment Formulation [ EPA Reg. No.] Single rate ( Lb ai/ A) Max. # of Apps. per Season Max. Seasonal Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations 1 Celery ( Leaf Petiole Vegetables, subgroup 4B) Broadcast foliar applications when conditions favor disease development Ground or aerial equipment 3.6 lb/ gal EC [ 100 617] 1.04 lb/ gal EC [ 100 1178] 45% WP [ 100 780] 0.113 4 0.45 14 Minimum RTI is 7 days Application may include spreader sticker Cereals ( wheat, barley, rye, triticale and oats) 3.6 lb/ gal EC [ 100 617] 0.113 2 0.225 30/ 35/ 45 Do not apply after Feekes Stage 10.5 Minimum RTI is 14 days. 30 and 45 day PHIs are specified for forage and hay, respectively, following an application at Feekes Stage 5. A general 35 day PHI is also specified for grazing or harvest of forage, hay and mature wheat. Broadcast foliar applications up to Flowering ( Feekes Stage 10.5) Aerial or ground equipment, including chemigation 1.04 lb/ gal EC [ 100 1178] 0.113 2 0.167 45 Do not harvest wheat for forage and do not graze or feed livestock treated forage or cut green crop of hay or silage Broadcast foliar applications up to Feekes Stage 8 Aerial or ground equipment, including chemigation 45% WP [ 100 780] 0.113 1 0.113 40 Do not apply after Feekes Stage 8 Do not apply to oats with 40 days of harvest. Except for oat forage and hay, do not graze or feed livestock treated forage or cut the green crop for hay or silage Corn ( field, seed, pop and sweet) Broadcast foliar applications when conditions favor disease development Aerial or ground equipment, including chemigation 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.113 4 0.45 14/ 30 Minimum RTI is 7 days. A 14 day PHI is specified for sweet corn forage and ears, and a 30 day PHI is specified for forage, grain and stover of field, pop, and seed corn.

Dry Beans and Peas Broadcast foliar applications when conditions favor disease development Aerial or ground equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.113 3 0.338 14 Do not apply to succulent bean varieties Apply in a minimum of 5 or 15 gal/ A using aerial and ground equipment, respectively. Minimum RTI is 14 days Filberts ( Hazelnuts) Foliar applications beginning at bud break Aerial or ground equipment 3.6 lb/ gal EC [ 100 617] 0.225 4 0.90 NS For aerial applications, minimum volumes of 5 10 or 20 gal/ A are recommended. For ground applications, minimum volumes of 10 50 or 100 gal/ A are recommended. Minimum RTI is 14 days Do not graze livestock in treated areas or cut treated cover crop for feed Onions ( green, dry bulb, or seed crop) 2 Broadcast foliar applications when conditions favor disease development Aerial or ground equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.225 2 0.45 0 3/ 14 Apply in a minimum of 5 or 15 gal/ A using aerial and ground equipment, respectively. Minimum RTI is 7 days Page 10 of 55 Table 2.1. Summary of Directions for Proposed Uses of Propiconazole.

Application Timing, Type and Equipment Formulation [ EPA Reg. No.] Single rate ( Lb ai/ A) Max. # of Apps. per Season Max. Seasonal Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations 1 PHIs are 0 for green onions and 14 days for dry bulb onions Peppermint and Spearmint Broadcast foliar applications beginning when plants are 2 4 inches in height Equipment not specified 3.6 lb/ gal EC [ 100 617] 0.113 2 0.225 30 Apply in a minimum of 20 gal/ A Minimum RTI is 10 days Pecans Foliar applications beginning at emergence of green leaves Aerial or ground equipment 3.6 lb/ gal EC [ 100 617] [ 100 702] 1.04 lb/ gal EC [ 100 1178] 45% WP [ 100 780] 0.225 4 0.90 NS Apply in a minimum of 20 gal/ A for aerial applications Minimum RTI is 14 days, Do not apply after shuck split The label for 100 1178 also specifies a 45 day PHI Do not graze livestock in treated areas or cut treated cover crop for feed Pistachios Foliar applications beginning at emergence of green leaves Aerial or ground equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.225 4 0.90 NS Apply in a minimum of 20 gal/ A for aerial applications and 50 100 gal/ A for ground applications Minimum RTI is 14 days Do not graze livestock in treated areas or cut treated cover crop for feed Rice ( Do not use in CA)

0.28 1 Broadcast foliar application( s) after tillering Ground or aerial equipment 3.6 lb/ gal EC [ 100 617] 1.04 lb/ gal EC [ 100 1178] 45% WP [ 100 780]

0.169 2 0.338 35 Apply aerially in a minimum of 5 20 gal/ A. Minimum RTI is 10 days The label for the 1.04 lb/ gal EC prohibits applications after head emergence. Do not apply to stubble or ratoon crop. Do not use in rice fields where crayfish farming will be practiced or drain water from treated fields into ponds used for crayfish farming. Do not use water drained from treated fields to irrigate other crops water Sorghum Broadcast foliar applications beginning at or just prior to flowering Aerial or ground equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.113 4 0.45 21/ 30 Apply in a minimum of 5 or 15 gal/ A using aerial and ground equipment, respectively. PHIs are 30 days for forage and 21 days for grain and stover Minimum RTI is 5 days Soybeans Broadcast foliar applications beginning at first appearance of disease until to pod fill ( Stage R5) Ground and aerial equipment 3.6 lb/ gal EC [ 100 617] 1.04 lb/ gal EC [ 100 1178] 45% WP [ 100 780] 0.169 2 0.338 30 Apply in a minimum of 5 and 15 gal/ A using aerial and ground equipment, respectively. Minimum RTI is 14 days Do not graze or feed soybean forage or hay Page 11 of 55 Table 2.1. Summary of Directions for Proposed Uses of Propiconazole.

Application Timing, Type and Equipment Formulation [ EPA Reg. No.] Single rate ( Lb ai/ A) Max. # of Apps. per Season Max. Seasonal Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations 1 Strawberries Broadcast foliar applications before disease levels reach 5% Aerial or ground equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.113 4 0.45 0 Apply in a minimum of 5 or 15 gal/ A using aerial and ground equipment, respectively. Minimum RTI is 7 days Sugar beets Broadcast foliar applications beginning at first appearance of disease Equipment not specified 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.113 3 0.338 21 Minimum RTI is 10 days Tree Nut Crops Foliar application at unspecified timing Ground and aerial equipment 3.6 lb/ gal EC [ 100 617] 45% WP [ 100 780] 0.225 4 0.90 60 Apply in a minimum of 20 for aerial applications, or 50 100 gal/ A for ground applications. Minimum RTI is not specified.

2.2 Structures and Nomenclature All pertinent product chemistry data requirements have been satisfied for the Novartis 95% T/ TGAI, except that additional data are required concerning stability and UV/ visible absorption ( OPPTS 830.6313 and 7050). Product chemistry refers to HED memo of Yan Donovan, 08/ 17/ 05, D318480. Page 12 of 55 TABLE 2.2. Test Compound Nomenclature Chemical Structure Cl Cl O O N N N CH 3 Empirical Formula C15H17Cl2N3O2 Common name Propiconazole Company experimental name CGA 64250 IUPAC name 1(( 2( 2,4 Dichlorophenyl) 4 propyl 1,3 dioxolan 2 yl) methyl) 1H 1,2,4 triazole CAS name 1H 1,2,4 Triazole, 1(( 2( 2,4 dichlorophenyl) 4 propyl 1,3 dioxolan 2 yl) methyl)

CAS Registry Number 60207 90 1 End use product/ EP Tilt ® , Alamo ® , Banner ® , and Orbit ® , Quilt, Stratego   Twin Pak   and Stratego   .

Chemical Class Triazole Known Impurities of Concern None 2.3 Physical and Chemical Properties Page 13 of 55 TABLE 2.3. Physicochemical Properties Parameter Value Reference Molecular Weight 342.23 MRID No.: 40583701 Boiling point/ range > 250 ° C at 101.325 kPa, 120 ° C at 1.9 Pa MRID No.: 43698701 pH 4.9 @ 25 ° C ( 1% aqueous dispersion) MRID No.: 43698701 Density 1.289 g/ cm3 typical @ 20 ° C MRID No.: 43698701 Water solubility ( 20 ° C) 0.10 g/ L at 20 ° C MRID No.: 41720301 Solvent solubility ( temperature not specified) Completely miscible in ethanol,

acetone, toluene and n octanol.

n hexane = 47 g/ L MRID No.: 42030201 Vapor pressure ( 25 ° C) 4.2 x 10 7 mmHg @ 25 ° C MRID No.: 41720301 Dissociation constant, pKa pKa 1.09 MRID No.: 43698701 Octanol/ water partition coefficient, Log ( KOW) ( 25 ° C) 3.72 @ pH 6.6 MRID No.: 43698701 UV/ visible absorption spectrum ( 8max, nm) Not available MRID No.: 40583703 3.0 METABOLISM ASSESSMENT 3.1 Rat Metabolic Profile The Rat metabolism study labeled with 14C at the triazole[ 3,5] position indicated that parent compound was extensively metabolized; a group of metabolites ( peak U8, 11%) appearing in the urine. Another study labeled with ( U 14C) Phenyl found several metabolites, including CGA 118245 ( 61.8% in males, 2.4% in females), CGA 217495 ( 8.9% in males, 58.3% in females), CGA 91304 ( 2.3% in males only), and CGA 118244 ( 3.6% in females only) after intravenous dosing. These metabolites were also detected to varying degrees in the urine of the orally dosed groups. In the feces, no parent material was detected in the iv group, but detected in the other groups ( 6.8 17.6% of the fecal radioactivity in males and females). Radiolabeled materials cochromatographing with standards CGA 91305, CGA 118245 and CGA 177291 were reported ranging from 0.5%  10.9% of the fecal radioactivity in males and females or in one sex alone. Most of the fecal radioactivity was not characterized. Metabolites CGA 217495 and CGA 177291 are not found in plant or livestock metabolism ( see Appendix for structures). In two other ( U 14C) phenyl and 14C triazole ring labeled propiconazole studies, the percentages of fecal metabolites extracted and distributed at various pH's were not substantially different between the triazole and phenyl labeled samples, which suggest that the bridge between the phenyl ring and the triazole ring remained intact. The proposed metabolic pathway appears to involve the cleavage of the dioxolane ring through the oxidation of the propyl side chain, with Page 14 of 55 subsequent dechlorination and conjugation. In a ( U 14C) phenyl labeled propiconazole metabolism study in mice, it was concluded that the major metabolic pathway in mice proceeds via elimination of the dioxolane ring leading to ketone formation ( CGA 91304) and reduction to yield the corresponding alcohol ( CGA 91305). Both CGA 91304 and CGA 91305 are found in plants and livestock.

3.2 Nature of the Residue in Foods 3.2.1. Description of Primary Crop Metabolism Available plant metabolism data ( primary and rotated crops) show that plants absorb, metabolize and translocate propiconazole throughout the plant. A major metabolic pathway in plants appears to be hydroxylation ( primarily of the beta carbon) of the n propyl group on the dioxolane ring of the cis/ trans isomers of propiconazole. These metabolites appear to readily form sugar conjugates. The majority of TRR was found in the stalks, such as peanut stalk, wheat forage and straw, grape leaves, and celery stalks ( See Table 3.4 for TRRs). A possible alternative pathway involves reductive deketalization of the dioxolane ring and sugar conjugation of the resulting metabolite. The alkyl bridge between the phenyl and triazole rings is metabolized and free triazole, as 1H 1,2,4 triazole, is released. The free triazole is readily conjugated with the amino acid, serine/ alanine, forming triazole alanine, which is further metabolized to triazole acetic acid possibly through the intermediate formation of triazole lactic acid. As mentioned earlier, the triazole issue will be addressed separately.

3.2.2 Description of Livestock Metabolism For one ruminant study, three lactating goats received [ phenyl 14C] propiconazole at 67 92 ppm for four consecutive days in feed. The parent ( 1.7 13.9% TRR), and metabolites CGA 118244 ( 9.4 34% TRR), and CGA 91305 ( 15.9 31.3% TRR) were identified in the organic extract of tissues; metabolites CGA 118244 ( 23% TRR) and CGA 91305 ( 24% TRR) were also identified in milk. In addition, an unknown was quantitated ( 6.2 31.1% TRR) in goat tissues. In a second ruminant study, a single goat was fed [ triazole 14C] propiconazole at 4.53 ppm ( 0.2x) for 10 days. The TRR in tissues and milk ranged from 0.01 ppm in muscle to 0.96 ppm in liver; TRR in milk were 0.015 ppm. On further analysis of subsamples of milk and liver, sulfate and glucuronide conjugates were found in milk, and conjugation with amino acids was suggested in liver; propiconazole per se was not identified in milk or liver.

For the poultry study, four laying hens received [ phenyl 14C] propiconazole at 67 ppm for eight consecutive days in feed. The dosing level corresponds to 560x the maximum theoretical dietary burden to poultry. The parent ( 1.4 39.0% TRR), and metabolites CGA 118244 ( 1.5 50.0% TRR), and CGA 91305 ( 17.7 78.6% TRR) were identified in the organic extracts of tissues and eggs. Page 15 of 55 3.2. Description of Rotational Crop Metabolism, including identification of major metabolites and specific routes of biotransformation.

The nature of the residue in confined rotational crops is understood, and no additional confined rotational crop data are required for the purpose of reregistration. Based on acceptable studies reviewed by EFED, the metabolism of propiconazole in rotational crops is similar to that in primary crops. In a rotational crop study, metabolites in peanut kernels were identified as triazole acetic acid ( 3.8% TRR) and triazole alanine ( 67.9% TRR). Metabolites identified in the rotational crop samples included triazole acetic acid ( 2.4% 68.7% TRR), triazole alanine ( 6.7% 79.4% TRR), triazole lactic acid ( 4.9% 35.8% TRR) and polar metabolites E, F, G, H ( 1.0% 7.0% TRR).

3.3 Environmental Degradation Acceptable and supplemental environmental fate data indicate that propiconazole is persistent in most soil and aqueous environments. Propiconazole is stable to hydrolysis and photodegradation in water. It has an aerobic soil metabolism half life of 69 days and is persistent in aquatic environments ( t ½ = 426 days). Aqueous photolysis may occur in the presence of sensitizers ( t ½ = < 1 day). Its principal route of dissipation in terrestrial environments appears to be adsorption to soil; adsorption increases with soil organic matter content ( Kd values= 1.2 on sand to 9.34 on silty clay loam soils). Terrestrial field dissipation half lives of about 100 days was reported in four soils. In supplemental aquatic dissipation studies in rice fields, propiconazole dissipated rapidly ( t ½ = < 5 days) although the route of dissipation was not apparent.

Propiconazole is moderately mobile to relatively immobile in most soil and aqueous environments. Propiconazole is not volatile ( vapor pressure is 1.3 x 10 6 Torr at 200 C). Propiconazole adsorbs to soil with adsorption increasing with soil organic matter content ( Kd values = 1.2 on sand to 9.34 on silty clay loam soils).

Propiconazole is broken down through hydroxylation of the propyl side chain and the dioxolane ring to give 1,2,4 triazole and other products, including particle bound material and carbon dioxide.

CGA 136735, CGA 118245 and CGA 71019 were identified as major degradates (> 10% of applied) in environmental fate studies.

Minor degradates include CGA 91304 and CGA 91305.

3.4 Tabular Summary of Metabolites and Degradates ( The highest % TRR is chosen when both [ 14C] triazole labeled propiconazole or [ 14C] phenyllabeled studies were conducted). Page 16 of 55 Table 3.4. Tabular Summary of Metabolites and Degradates Percent TRR ( PPM) 1 Chemical Name ( other names in parenthesis) Commodity Matrices  Major Residue (> 10% TRR) Matrices  Minor Residue (< 10% TRR) Structure Wheat grain ( 0.1 lbs ai/ A) 0.4 Wheat forage ( 0.1 lbs ai/ A) 7.3 Wheat straw ( 0.1 lbs ai/ A) 3.9 Wheat grain ( 0.5 lbs ai/ A) 0.8 Wheat forage ( 0.5 lbs ai/ A 17.2 Wheat straw ( 0.5 lbs ai/ A) 9.0 Celery, stalk 85.3 Grape, fruit 14.6 Grape, juice 2.0 Peanut, kernel ( field)

Peanut, stalk ( field) 54 Peanut, shell ( field)

Peanut, kernel ( green house) N/ A Peanut, stalk ( green house) 89 Peanut, shell ( green house) N/ A Rotational Crops Peanut, stalk 5 Peanut, shell

Peanut, kernel

Wheat, grain

Wheat, mature stalk

Wheat, immature stalk 0.7 Parent Lettuce, head  Cl Cl O O N N N CH 3 Page 17 of 55 Table 3.4. Tabular Summary of Metabolites and Degradates Percent TRR ( PPM) 1 Chemical Name ( other names in parenthesis) Commodity Matrices  Major Residue (> 10% TRR) Matrices  Minor Residue (< 10% TRR) Structure Carrot

Corn, kernel

Corn, cob

Corn, immature stalk

corn, mature stalk

Ruminant 1.7 13.9 Poultry 1.4 39 Rat

Water

Wheat grain ( 0.1 lbs ai/ A) 0.1 Wheat forage ( 0.1 lbs ai/ A) 0.3 Wheat straw ( 0.1 lbs ai/ A) 1.2 Wheat grain ( 0.5 lbs ai/ A) 0.3 Wheat forage ( 0.5 lbs ai/ A 0.3 Wheat straw ( 0.5 lbs ai/ A) 1.5 Celery, stalk 1.1 Grape, fruit 32.6 Grape, juice 31.4 Rotational Crops

Ruminant

Poultry

Rat 2  3.6 CGA 91304 Water < 10% Cl Cl O N N N Wheat grain ( 0.1 lbs ai/ A) 0.1 Wheat forage ( 0.1 lbs ai/ A) 0.3 CGA 91305 Wheat straw ( 0.1 lbs ai/ A) 0.1 Page 18 of 55 Table 3.4. Tabular Summary of Metabolites and Degradates Percent TRR ( PPM) 1 Chemical Name ( other names in parenthesis) Commodity Matrices  Major Residue (> 10% TRR) Matrices  Minor Residue (< 10% TRR) Structure Wheat grain ( 0.5 lbs ai/ A) 0.1 Wheat forage ( 0.5 lbs ai/ A 0.3 Wheat straw ( 0.5 lbs ai/ A) 0.1 Celery, stalk 1.9 Grape, fruit 4.9 Grape, juice 2.9 Peanut, kernel ( field)

Peanut, stalk ( field) 3 Peanut, shell ( field)

Peanut, kernel ( green house) 8 Peanut, stalk ( green house)

Peanut, shell ( green house)

Rotational Crops Peanut, stalk 2 Peanut, shell

Peanut, kernel

Wheat, grain

Wheat, mature stalk

Wheat, immature stalk 2.1 Lettuce, head

Carrot

Ruminant 15.9 31.3

Poultry 17.7 78.6

Rat  CGA 91305 Water < 10% Cl Cl OH N N N Page 19 of 55 Table 3.4. Tabular Summary of Metabolites and Degradates Percent TRR ( PPM) 1 Chemical Name ( other names in parenthesis) Commodity Matrices  Major Residue (> 10% TRR) Matrices  Minor Residue (< 10% TRR) Structure Wheat grain ( 0.1 lbs ai/ A) 0.4 Wheat forage ( 0.1 lbs ai/ A) 0.4 Wheat straw ( 0.1 lbs ai/ A) 1.0 Wheat grain ( 0.5 lbs ai/ A) 0.2 Wheat forage ( 0.5 lbs ai/ A 0.4 Wheat straw ( 0.5 lbs ai/ A) 1.1 Celery, stalk 1.4 Rotational Crops

Ruminant 9.4 34

Poultry 2 50

Rat 3.6 CGA 118244 Water  Cl Cl O O N N N CH 3 OH Wheat grain ( 0.1 lbs ai/ A) 0.4 Wheat forage ( 0.1 lbs ai/ A) 0.2 Wheat straw ( 0.1 lbs ai/ A) 0.4 Wheat grain ( 0.5 lbs ai/ A) 0.1 Wheat forage ( 0.5 lbs ai/ A 0.1 Wheat straw ( 0.5 lbs ai/ A) 0.3 Celery, stalk  CGA 118245 Rat 61.8 Cl Cl O O N N N OH Page 20 of 55 Wheat grain ( 0.1 lbs ai/ A)

Wheat forage ( 0.1 lbs ai/ A) ND Wheat straw ( 0.1 lbs ai/ A) 0.1 Wheat grain ( 0.5 lbs ai/ A) ND Wheat forage ( 0.5 lbs ai/ 0.1 Wheat straw ( 0.5 lbs ai/ A) 0.8 Celery, stalk  CGA 136735 Rat  Cl Cl O O N N N CH 3 O H 3.5 Toxicity Profile of Major Metabolites and Degradates See Section 3.6.2 3.6 Summary of Residues for Tolerance Expression and Risk Assessment 3.6.1 Tabular Summary Table 3.6. HED MARC Meeting Summary Chart : Propiconazole Date: 18 Dec 2001, and 08 Jan 2002 Residues of Concern Matrix For Risk Assessment i For Tolerance Expression Plants Parent plus all metabolites convertible to 2,4 DCBA Parent only Rotational crop Parent plus all metabolites convertible to 2,4 DCBA Parent only Livestock: Parent plus all metabolites convertible to 2,4 DCBA Parent only Water Parent only N/ A i Triazole is also a residue of concern, but it will be addressed separately.

3.6.2 Rationale for Inclusion of Metabolites and Degradates Page 21 of 55 Plant: The analytical method is a single moiety method, which detects all residues convertible to 2,4 dichlorobenzoic acid ( DCBA); therefore, MARC concluded that for risk assessment, parent and all metabolites convertible to 2,4 DCBA are residues of concern. The metabolites that have the basic structure of propiconazole ( e. g. alkanol, beta hydroxy and conjugates) would likely exhibit some of the same toxicity as the parent compound, but would not likely be more toxic than the parent compound. For the purposes of risk assessment HED would assume these metabolites would have equal toxicity as the parent compound. ( The conjugates are included because of the possibility they could be hydrolyzed in the stomach to the unconjugated form). For tolerance expression, MARC recommended parent only for the following reasons: 1) To harmonize with the Codex MRL which is parent only; 2) There are a number of pesticides that have 2,4 DCBA as common metabolite; and 3) FDA multiresidue method detects parent only, and that FDA monitoring pattern likely only detects parent.

Rotational crop: As with primary crops, parent and all metabolites convertible to 2,4 DCBA are residue of concern for risk assessment since the analytical method is a single moiety method which detects all residues convertible to 2,4 dichlorobenzoic acid ( DCBA). Although these metabolites are detected at very low levels, they are of toxicological concern and cannot be excluded from risk assessment. For tolerance expression, MARC recommended parent only. The most blatent misuse of propiconazole would be application to unlabeled crops. If rotational crop tolerances were expressed in terms of parent, then any residues of propiconazole on rotated crops would likely be due to direct application to these crops. While triazole acetic acid is the major metabolite in rotational crop study, triazole and its conjugates are common metabolites from a number of other pesticides and have been addressed separately.

Animals: MARC recommended that parent and all metabolites convertible to 2,4 DCBA are residues of concern for risk assessment since the analytical method detects all residues convertible to 2,4 dichlorobenzoic acid ( DCBA). Tolerance expression will be parent only. If only propiconazole per se is regulated, there will not likely be a need for meat and milk tolerances; only meat by products would likely require a tolerance. Should there be detectable residues of the parent compound in meat and milk, it would most certainly be as a result of a misuse.

Water: MARC recommended that parent only is needed to be included in the risk assessment since the parent is persistent and immobile. There are several minor degradates (< 10% TRR) but none of them are expected to be significantly more toxic than the parent. Triazole is not a major degradate in water and therefore was not included in the water modeling; the potential for exposure to triazole in drinking water has been addressed in a separate document.

4.0 HAZARD CHARACTERIZATION/ ASSESSMENT 4.1 Hazard Characterization For detailed discussion on propiconazole toxicity profile, refer to HED's phase 4 reregistration eligibility document ( HED memo of 6/ 28/ 06, Yan Donovan, D329668). Page 22 of 55 Propiconazole has low to moderate toxicity in experimental animals by the oral ( Category III), dermal ( Category III) and inhalation routes ( Category IV). It is moderately irritating to the eyes ( Category III), and minimally irritating to the skin ( Category IV). It is a dermal sensitizer. Propiconazole is readily absorbed by the rat skin with a 40% absorption within 10 hours of dermal application.

Table 4.1a : Acute Toxicity Profile  Propiconazole Guideline No. Study Type MRID # Results Toxicity Category 870.1100 Acute Oral  rat 00058591 LD50 = 1517 mg/ kg III 870.1200 Acute Dermal rabbit 00058596 LD50 = > 4000 mg/ kg III 870.1300 Acute Inhalation  rat 41594801 LC50 = > 5.84 mg/ L IV 870.2400 Primary Eye Irritation 00058597 Corneal opacity reversed in 72 hours III 870.2500 Primary Skin Irritation 00058598 No irritation IV 870.2600 Dermal Sensitization 44949501 Sensitizer

4.2 FQPA Hazard Considerations HIARC ( February 13, 2003) concluded that the toxicology database for propiconazole is complete for FQPA assessment. The HIARC concluded that there is low concern for pre and/ or postnatal toxicity resulting from exposure to propiconazole. In the developmental toxicity study in rats, the HIARC considered the fetal effects observed in this study at a dose lower than that evoking maternal toxicity to be quantitative evidence of increased susceptibility of fetuses to in utero exposure to propiconazole. In the developmental toxicity study in rabbits, the HIARC determined that neither quantitative nor qualitative evidence of increased susceptibility of fetuses to in utero exposure to propiconazole was observed in this study. In the 2 generation reproduction study in rats, the HIARC determined that neither quantitative nor qualitative evidence of increased susceptibility of neonates ( as compared to adults) to pre and/ or postnatal exposure to propiconazole was observed in this study. Since there was quantitative evidence of increased susceptibility of the young following exposure to propiconazole in the developmental rat study, HIARC performed a Degree of Concern Analysis and concluded that the degree of concern for the effects observed in this study was low and no residual uncertainties were identified. The FQPA factor is thus 1X.

HIARC ( February 13, 2003) concluded that the toxicology database for propiconazole is complete for FQPA assessment. The database was adequate to characterize any potential for prenatal or postnatal risk for infants and children.

4.3 Hazard Identification and Toxicity Endpoint Selection Page 23 of 55 4.3.1 Margins of Exposure Summary of target Margins of Exposure ( MOEs) for risk assessment as recommended by HIARC.

Route Duration Short Term ( 1 30 Days) Intermediate Term ( 1  6 Months) Long Term (> 6 Months)

Occupational ( Worker) Exposure Dermal 100 100 100 Inhalation 100 100 100 Residential ( Non Dietary) Exposure Oral 100 100 NA Dermal 100 100 100 Inhalation 100 100 100 4.3.2 Recommendation for Aggregate Exposure Risk Assessments As per FQPA, 1996, when there are potential residential exposures to the pesticide, aggregate risk assessment must consider exposures from three major sources: oral, dermal and inhalation exposures. The toxicity endpoints selected for these routes of exposure may be aggregated as follows. ° For the General Population, including infants and children, the short term oral exposure can be aggregated with the short term dermal and inhalation due to a common toxicological endpoint ( clinical signs in the ACN study). ° A common toxicological endpoint was identified for intermediate and long term oral, dermal ( oral equivalent) and inhalation ( oral equivalent) routes. These routes can be aggregated for these scenarios for the appropriate population.

Table 4.3. Summary of Toxicological Doses and Endpoints for Propiconazole for Use in Human Risk Assessments Exposure Scenario Dose Used in Risk Assessment, UF FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( Females 13 49) Dev. NOAEL = 30 mg ai/ kg/ day UF = 100 Acute RfD = 0.3 mg/ kg/ day FQPA SF = 1X aPAD = acute RfD FQPA SF = 0.3 mg/ kg/ day Developmental Toxicity Study  Rats. Developmental toxicity: increased incidence of rudimentary ribs, cleft palate malformations ( 0.3%), unossified sternebrae, as well as increased incidence of shortened and absent renal papillae. Page 24 of 55 Table 4.3. Summary of Toxicological Doses and Endpoints for Propiconazole for Use in Human Risk Assessments Exposure Scenario Dose Used in Risk Assessment, UF FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( General Population including infants and children) NOAEL = 30 mg kg/ day UF = 100 Acute RfD = 0.3 mg/ kg/ day FQPA SF = 1X aPAD = acute RfD FQPA SF = 0.3 mg/ kg/ day Acute Neurotoxicity Study   Rats.

Clinical signs ( piloerection, diarrhea, tiptoe gait).

Chronic Dietary ( All populations) NOAEL = 10 mg ai/ kg/ day UF = 100 Chronic RfD = 0.1 mg/ kg/ day 1X cPAD = chronic RfD FQPA SF = 0.1 mg/ kg/ day 24 Month Oncogenicity Study  Mice. Liver toxicity ( increased liver weight in males and increase in liver lesions ( masses/ raised areas/ swellings/ nodular areas mainly)).

Short Term ( 1 30 days) Incidental Oral NOAEL = 30 mg kg/ day Residential MOE = 100 Occupational = NA Acute Neurotoxicity Study   Rats.

Clinical signs ( piloerection, diarrhea, tiptoe gait).

Intermediate Term ( 1  6 months) Incidental Oral NOAEL= 10 mg ai/ kg/ day Residential MOE = 100 Occupational = NA 24 Month Oncogenicity Study  Mice. Liver toxicity ( increased liver weight in males and increase in liver lesions ( masses/ raised areas/ swellings/ nodular areas mainly)).

Short Term ( 1  30 days) Dermal NOAEL= 30 mg ai/ kg/ day Dermal absorption rate = 40% Residential MOE = 100 Occupational MOE = 100 Acute Neurotoxicity Study   Rats.

Clinical signs ( piloerection, diarrhea, tiptoe gait). Page 25 of 55 Intermediate Term dermal ( 1  6 months) and Long Term dermal (> 6 months) Oral NOAEL= 10 mg ai/ kg/ day ( Dermal absorption rate = 40%) Residential MOE = 100 Occupational MOE = 100 24 Month Oncogenicity Study  Mice. Liver toxicity ( increased liver weight in males and increase in liver lesions) ( masses/ raised areas/ swellings/ nodular areas mainly)

Short Term ( 1  30 days) Inhalation NOAEL= 30 mg/ kg/ day ( Inhalation absorption rate = 100%) Residential MOE = 100 Occupational MOE = 100 Acute Neurotoxicity Study   Rats.

Clinical signs ( piloerection, diarrhea, tiptoe gait).

Intermediate Term ( 1  6 months) and Long Term Inhalation (> 6 months) Oral NOAEL= 10 mg/ kg/ day ( Inhalation absorption rate = 100%) Residential MOE = 100 Occupational MOE = 100 24 Month Oncogenicity Study  Mice. Liver toxicity ( increased liver weight in males and increase in liver lesions ( masses/ raised areas/ swellings/ nodular areas mainly)

Cancer ( Oral, dermal, inhalation) Group C, possible human carcinogen, and RfD approach for risk characterization.

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose ( a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure.

4.4 FQPA Safety Factor Based upon the above described data, no FQPA safety factor is needed ( i. e. 1X) since there are no residual uncertainties for pre and/ or post natal toxicity. The FQPA Safety Factor recommended by the HIARC assumes that the exposure databases ( dietary food, drinking water, and residential) are complete and that the risk assessment for each potential exposure scenario includes all metabolites and/ or degradates of concern and does not underestimate the potential risk for infants and children.

4.5 Endocrine Disruption 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 Page 26 of 55 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).

In the available toxicity studies on propiconazole, there was no estrogen, androgen, and/ or thyroid mediated toxicity.

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

5.0 Public Health Data 5.1 Incident Reports ( HED memo of J. Blondell, D319239, 07/ 26/ 05)

From the review of the Incident Data System, it appears that a majority of cases involved skin symptoms such as rash, itching, and skin irritation and respiratory effects such as difficulty breathing. Poison Control Center data would tend to support the Incident Data System results; dermal irritation, erythema, and difficulty breathing were among the most common effects reported.

Measures to limit skin and respiratory exposure are recommended for this pesticide. Appropriate personal protective equipment to protect the skin is also recommended for both handlers and field workers who are likely to have substantial contact with propiconazole.

6.0 EXPOSURE CHARACTERIZATION/ ASSESSMENT Residue Chemistry Summary Document; Yan Donovan ( D238458, 7/ 31/ 2006)

6.1 Dietary Exposure/ Risk Pathway 6.1.1 Residue Profile Propiconazole [ 1[[ 2( 2,4 dichlorophenyl) 4 propyl 1,3 dioxolan 2 yl] methyl] 1H 1,2,4 triazole] is a systemic broad spectrum fungicide registered for treatment of disease in/ on a variety of crops. Propiconazole end use products are marketed in the United States under the trade names Tilt ® , Alamo ® , Banner ® , and Orbit ® . Recently, propiconazole is also registered for use on a variety of crops under the trade names of Stratego   Twin Pak   and Stratego   , which are end use products containing a mixture of trifloxystrobin and propiconazole. The amount of active ingredient range from 11.4% to 45%. The propiconazole formulations Page 27 of 55 registered for food/ feed uses include emulsifiable concentrate ( EC) and flowable concentrate ( FlC) formulations.

Syngenta Crop Protection ( Syngenta) and Interregional Research Project No. 4 ( IR 4) have submitted several petitions supporting new or amended uses on various crops for propiconazole, formulated as a 3.6 lb/ gal emulsifiable concentrate ( EC) or a 45% wettable powder ( WP). The proposed uses are for broadcast foliar applications using ground or aerial equipment at rates ranging from 0.11 to 0.28 lb ai/ A/ application. For tree nuts, the proposed use is for up to four foliar applications at 0.225 lb ai/ A, for a total of 0.90 lb ai/ A, with a 60 day preharvest interval ( PHI). For bush and cane berries and cranberries, the proposed uses are for 4 or 5 foliar applications at 0.17 lb ai/ A, for totals of 0.68 0.84 lb ai/ A, with PHIs of 30 or 45 days. For carrots, leaf petiole vegetables, dry peas and beans, sugar beets and strawberries, the proposed uses are for 3 or 4 broadcast foliar applications at 0.11 lb ai/ A, for totals of 0.34 or 0.45 lb ai/ A, with PHIs of 0 to 21 days. For mint, the proposed use is for two broadcast foliar applications at 0.113 lb ai/ A, for a total of 0.225 ai/ A, with a PHI of 30 days. For soybeans, the proposed use is for two broadcast foliar applications at 0.169 lb ai/ A at up to growth stage R6, for a total of 0.338 ai/ A, with a PHI of 30 days. For rice, the proposed use is for a single application or split applications at heading totaling ~ 0.30 lb ai/ A, with a PHI of 35 days. For other cereal grains, the proposed uses are for 2 to 4 broadcast foliar applications at 0.113 lb ai/ A up to heading or grain development, for totals of 0.22 or 0.45 ai/ A, with PHIs of 14 45 days. In conjunction with these uses, Syngenta and IR 4 are proposing permanent tolerances for propiconazole residues in/ on various plant commodities at levels ranging from 0.1 ppm on alfalfa to 32 ppm on soybean hay.

The nature of propiconazole residues in plants and animals is adequately understood based on the available peanut, wheat, grape, rice, celery, carrot, goat, and poultry metabolism studies. A major metabolic pathway in plants appears to be hydroxylation ( primarily of the beta carbon) of the n propyl group on the dioxolane ring of the cis/ trans isomers of propiconazole. These metabolites appear to readily form sugar conjugates. The majority of TRR was found in the stalks, such as peanut stalk, wheat forage and straw, grape leaves, and celery stalks. The HED MARC concluded that for plants and animals, residues of propiconazole and all its metabolites containing the 2,4 dichlorophenyl moiety ( 2,4 DCBA), including conjugates, are of concern and should be included in the dietary ( food) risk assessments, and that propiconazole per se should be included in the dietary ( water) risk assessments. For tolerance expression, MARC concluded that the current tolerance expression for propiconazole should be amended to include residues of propiconazole per se only. This allows for harmonization with the residue definition for Codex.

The free triazole, triazole alanine, and triazole acetic acid are also residues of concern. Since these are common metabolites from several triazole containing pesticides, the risk from these metabolites has been assessed separately ( HED memo of 2/ 7/ 06, M. Doherty, D322215). The cited assessment included all the proposed propiconazole new uses in the subject petitions.

For enforcing the revised tolerances, a GC method using flame ionization detection ( Method AG 354) is also available for determining residues of propiconazole per se in/ on plant Page 28 of 55 commodities, and has an LOQ of 0.05 ppm. In addition, Multiresidue Methods Section 302 can also be used to determine parent propiconazole in both plant and animal matrices.

Samples from the various field trials and processing studies supporting the current petitions were analyzed for combined residues of propiconazole and its 2,4 DCBA containing metabolites using GC/ ECD Methods AG 454B and AG 626, which are more recent versions of AG 454A. With the exception of almond hulls, which had a LOQ of 0.1 ppm, the validated LOQ for combined residues was 0.05 ppm in all raw and processed commodities. Each of the methods was validated in conjunction with the field trials and processing studies. In addition, samples from one of the wheat field trials and processing studies were also analyzed for residues of propiconazole, per se, using a multiresidue method from the Pesticide Analytical Manual ( PAM, Vol. I, Section 302).

Adequate storage stability data are available indicating that residues of propiconazole are stable at   15 º C for up to 36 months in peaches, bananas, corn meal, wheat grain, celery, corn oil, and peanut nutmeat, hay, and hulls; 10 months in carrots; and 4 6 months in soybean seed and fodder. Weathered residues of propiconazole and its metabolites were also found to be stable under frozen storage conditions in grass forage, straw, and seed for up to 39 months at  20 º C; wild rice and stone fruits for up to 25 months; and peanut hulls and fodder for 25 months at  15 º C. These data support most of the samples storage intervals and conditions in the field trials and processing studies submitted with the current petitions. In cases where existing storage stability data are not available, concurrent storage stability data were submitted along with field trials.

Provided that minor changes are made to the proposed use directions, the available field trial data on almonds, bush and cane berries, carrots, celery, corn, cranberries, mint, onions, pecans, rice, sorghum, strawberries and wheat are adequate and support the proposed use patterns for propiconazole ( EC or WP) on these crops. The number and geographic distribution of the field trials are adequate, and the appropriate samples were collected. Samples were analyzed using adequate analytical methods and the sample storage intervals are supported by the available storage stability data. Side by side field trials were conducted on almond, celery, field corn, and sugar beets to compare residues from the EC and WP formulation. These data show residues are comparable from the two products, with the exception of sugar beet tops at the requested PHI.

Adequate field trial data are also available to support the use of the 45% WP formulation on sugar beets. However, based on the results of the side by side tests with the WP and EC formulations, residues in/ on tops at the proposed 21 day PHI are likely to be higher for the EC formulation than the WP formulation. Therefore, a complete set of field trial data is required for sugar beet tops reflecting the use of the EC formulation. A conditional registration can be established on sugar beet tops.

For soybeans, after considering all the available soybean field trial data, HED concluded that sufficient residue data are available to support tolerances on soybean forage and hay harvested 30 days following the second of two applications totaling 0.33 lb ai/ A ( 1x rate). Although the petitioner has requested tolerances for soybean forage and hay, the Agency notes that the Page 29 of 55 currently proposed use directions for soybean prohibit the feeding or grazing for forage or hay. HED also considers sufficient residue data are available to support tolerances on soybean seed, even though the PHIs of the soybean seed data vary from 30 to 90 days. Since soybean mature at different times depending on the growing regions, PHI in days can vary from region to region; therefore, provided the label has such language as " do not apply later than the R5 growth stage' or ` apply up to Stage R6", no additional field trials are required for soybean seeds.

For dry peas and beans, however, there are no sufficient field trial data to support the proposed use as only six dry bean field trials are available and no dry pea field trials were conducted. For a subgroup crop tolerance on 6C, a total of 12 dry bean field trials and 5 dry pea field trials are required. In addition, the available dry bean field trials support a PHI of 28 days rather than the 14 day PHI on the proposed label. HED recommends against the establishment of permanent tolerance on subgroup crop 6C until additional field trial data are submitted.

The Agency's Guidance for Setting Pesticide Tolerances Based on Field Trial Data ( tolerance spread sheet) was utilized for determining appropriate tolerance levels on plant commodities. While these tolerance/ residue levels are suitable for Tier I dietary risk assessment, they are considered conservative for tolerances in that the field trial data were reported as parent plus all metabolites containing 2,4 DCBA, while the tolerance expression is parent only. HED recommends that the registrant analyze parent and metabolites separately in all future field trials, so that more realistic tolerances can be set in the future.

Adequate processing studies are available for alfalfa ( rotational crop), field corn, mint, rice, sorghum, soybean, sugar beet, and wheat. These studies indicate that, with the exception of aspirated grain fractions ( AGF), combined propiconazole residues did not concentrate in processed commodities derived from alfalfa, field corn, mint, sorghum, and soybeans, or in polished rice, sugar beet refined sugar, or wheat germ, shorts, middlings and flour. However, combined residues were shown to concentrate in rice hulls ( 3.8x) and bran ( 2.9x), sugar beet molasses ( 7.4x) and dried pulp ( 4.9x), and wheat bran ( 3.2x). Considering the highest average field trial ( HAFT) residues in the various RACs and the above processing factors, appropriate tolerances for combined propiconazole residues are 20 and 15 ppm for rice hulls and bran, 1.5 and 1.0 ppm for sugar beet molasses and dried pulp, and 0.6 ppm for wheat bran. The recommended tolerance for wheat bran will be translated to bran of barley and rye. With regards to AGF, combined residues were also shown to concentrate by various degrees in AGF derived from field corn ( 12.8x), sorghum ( 5.2x), soybeans ( 32x), and wheat ( 13x) following late season applications. Considering these AGF concentration factors and the HAFT residues in the respective RACs, the maximum expected residues in AGF are 1.28 ppm for corn, 10.9 ppm for sorghum, 30 ppm for soybean, and 4.14 ppm for wheat. Therefore, the recommended tolerance for propiconazole residues in AGF is 30 ppm based on the soybean data.

The maximum theoretical dietary burdens ( MTDB) for combined propiconazole residues were calculated to be 28.0 ppm for beef and 18.5ppm for dairy cattle, 2.3 ppm for swine and 2.0 ppm for poultry. To estimate maximum combined residues in cattle and swine commodities, the residue levels for the 75 ppm feeding level at 21 days were selected, as these residue levels were the highest for the 75 ppm group. This feeding level represents a 2.7x the MTDBs for beef Page 30 of 55 cattle, 4.2x for dairy cattle, and a 32.6x for swine. Maximum combined residues were estimated by dividing the residue values for milk and tissues at the 75 ppm dose level by 2.7 for cattle, 4.2 for milk, and 32.6 for swine. For beef cattle, estimated combined residues at a 1x feeding level are 1.7 ppm for kidney, 1.6 ppm for liver, 0.03 ppm for muscle, 0.05 ppm for fat, and 0.03 pm for milk. For swine, estimated combined residues at a 1x feeding level are 0.14ppm for kidney, 0.13 ppm for liver and < 0.005 ppm for muscle and fat. HED recommends that the following tolerance levels be established: For cattle, goat, horses and sheep, kidney and liver at 2.0 ppm; meat and meat byproduct ( except kidney and liver) and fat at 0.05 ppm, milk at 0.05 ppm. For hog, kidney and liver at 0.20 ppm, no tolerances are needed for meat, fat, and meat byproduct.

For poultry tissues and eggs, estimated combined residues and parent residues were calculated in the same manner as for cattle and swine. The maximum combined residues in tissues and eggs from the 7.5 ppm dose group in the poultry feeding study were used to estimate residues at the 1x feeding level. The estimated combined residues at the 1x feeding level are all < LOQ. Therefore, tolerances for poultry tissues and eggs are not required as quantifiable levels of propiconazole are unlikely to occur in these commodities [ 40 CFR 180.6( a) ( 3)].

Adequate confined rotational crop studies are available indicating that the residues in rotational crops are similar to the primary crops. The confined studies also support the 105 day plant back interval ( PBI) currently listed on product labels for crops without direct uses. Under the current petition, Syngenta has submitted extensive rotational crop field trial data on alfalfa planted following propiconazole treated wheat and proposed a 0.1 ppm tolerance for inadvertent residues in/ on alfalfa. The available alfalfa rotational crop field trials are adequate and will support a 75 day PBI for alfalfa following propiconazole application( s) to primary crops at up to 0.22 lb ai/ A/ season.

6.1.2 Acute and Chronic Dietary Exposure and Risk ( Food and Water)

( HED memo of 08/ 15/ 06, Yan Donovan, D312278)

Acute and chronic dietary risk assessments were conducted using the Dietary Exposure Evaluation Model ( DEEM FCIDJ, Version 2.02) which uses food consumption data from the USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII) from 1994 1996 and 1998.

Acute Dietary Exposure Results and Characterization An acute dietary analysis for propiconazole was conducted using tolerance levels and 100 % CT for all existing and proposed uses. The acute PAD is 0.3 mg/ kg/ day for all population subgroups ( includes females 13 49 years). The results of the analysis indicate that acute risk from the dietary exposure ( food and water) to propiconazole from the requested uses did not exceed HED's level of concern for the U. S. population or any population subgroup. At the 95th percentile, the exposure to the U. S. population is at 6 % aPAD; the highest exposed subgroup ( all infants < 1 yrs old) is at 14% aPAD. Page 31 of 55 Chronic Dietary Exposure Results and Characterization A chronic dietary analysis for propiconazole was conducted using tolerance levels and 100 % CT for all existing and proposed uses. The results of the analysis indicate that chronic risk from the dietary exposure ( food and water) to propiconazole from the requested use did not exceed HED's level of concern for the U. S. population or any population subgroup. The exposure to the U. S. population is at 6 % cPAD, and the most highly exposed subgroup, Children 1 2 years old, is at 14 % cPAD.

Cancer Dietary Exposure Results and Characterization The HIARC classified propiconazole as a Group C  possible human carcinogen, nonquantifiable For the purpose of risk characterization the reference Dose ( RfD) approach should be used and would be protective.

Water Contribution The Agency used PRZM EXAMS and SCI GROW screening models to determine the EECs of propiconazole in surface and ground water, respectively. Based on the PRZM EXAMS and SCIGROW models, for surface water, the highest estimated environmental concentration ( EEC) of propiconazole for acute exposure is 55.8 parts per billion ( ppb) ( Turf use), and for chronic exposure is 21.6 ppb ( turf use). For ground water, the highest EEC for acute and chronic exposure is 0.64 ppb. The highest estimates from surface water ( acute, 55.8 ppb and chronic, 21.6 ppb) were used in the DEEM analysis.

6.2 Water Exposure/ Risk Pathway Drinking Water Assessment; James Lin ( D325821, 07/ 07/ 06)

Propiconazole appears to be persistent and moderately mobile to relative immobile in most soil environment. In the aquatic environment, propiconazole degradation appears to be dependent solely on aqueous photolysis in the presence of photo sensitizers. In soil environment, propiconazole dissipation appears to depend on incorporation or binding to soil organic matter content.

Laboratory and terrestrial field dissipation data indicate that propiconazole is stable in soil and aqueous environments. However, in supplemental aquatic dissipation data using basin irrigation and flow through irrigation systems in rice fields, propiconazole was found to be dissipated rapidly ( t ½ < 5 days). Aqueous photolysis studies using sensitizers indicated rapid degradation ( t ½ < 1 days) of propiconazole, which appears to be the case in rice fields. Furthermore, aquatic metabolism and dissipation studies indicate propiconazole dissipates by incorporation or binding into the organic matter content of soil/ sediment.

Propiconazole mobility in soil appears to be dependent on the soil's organic matter content. In general, propiconazole appears to be moderately mobile ( Kd < 5) in soils with a low organic Page 32 of 55 matter content (< 1%). However, in soils with higher organic matter content (> 1%), propiconazole appears to be relatively immobile ( Kd > 5). Therefore, propiconazole may reach ground water in soils with low organic contents. Propiconazole may also contaminate surface water through off site runoff and spray drift.

A registrant submitted drinking water monitoring study showed a very few detections among a total of thirty eight selected CWSs in twelve states. EFED concluded that the sampling scheduling of this monitoring study is not rigorous enough to be used for water assessment. Since the monitoring studies did not provide good quality data, this drinking water assessment is based on the model predicted drinking water concentrations Drinking Water Estimates from Surface Water Sources The estimated drinking water concentrations from surface water sources were calculated using Tier II PRZM ( Pesticide Root Zone Model) and EXAMS ( Exposure Analysis Modeling System). For each specific use, the maximum allowable label rate was input to PE4V01. The output concentrations were without PCA consideration. The final estimated drinking water concentrations were then adjusted with the proper PCA. Except the uses of soybean ( 0.41) and wheat ( 0.56), other uses assume the default PCA of 0.87. Among these modeling results, turf use gives the highest acute concentration of 55.78 ug/ l. For the chronic exposure, turf use has the highest concentration of 21.61 ug/ L,

Drinking Water Estimates from Ground Water Sources The estimated environmental concentrations in ground water were calculated using the Tier I SCI GROW ( Screening Concentration In Ground Water) model. SCI GROW is neither scenario nor crop specific. The only input requirements are application rate, number of applications, Koc, and aerobic soil metabolism half life. The higher estimated concentrations are associated with the higher rate. Turf use has the highest concentration of 0.64 µ g/ L ( ppb).

Table 6.2. Summary of Estimated Surface and Ground Water Concentrations for Chemical. Propiconazole parent compound Exposure Duration Surface water ( ppb) Ground water ( ppb) Acute 55.8 0.64 Chronic ( non cancer) 21.6 0.64 Chronic ( cancer) N/ A N/ A 6.3 Residential ( Non Occupational) Exposure/ Risk Pathway Propiconazole: Occupational and Residential Exposure Assessment; James Miller, Environmental Scientist ( D325817, 6/ 15/ 06) Propiconazole Occupational and Residential Exposure Assessment of the Antimicrobial Uses; Timothy Leighton ( D326306, 2/ 1/ 2006) Amendment to the Propiconazole RED for Children's Post application Exposure from Treated Structures; Tim Leighton ( D330159, 06/ 20/ 06) Page 33 of 55 Residential Post application Exposures and Risks The existing residential use patterns result in post application dermal exposures to adults, and dermal and oral exposures to infants and children. These exposures are considered short term only, due to the fact that: 1) Post application exposures were calculated using Propiconazole as the parent compound; 2) Compound specific TTR data indicates that at the Indiana, California, and Pennsylvania test sites, average total propiconazole residues declined to below the minimum quantifiable limit ( MQL) by DAT = 14, DAT = 10, and DAT = 8 respectively. These dissipation rates, combined with label specific use rates and frequency of use specifications, reinforce the hand to mouth short term exposure scenario; 3) For short term exposure to Children 1 2 years old, the driving factors for this risk assessment are hand to mouth, object to mouth, and dermal exposure. Soil ingestion is insignificant ( MOE> 300,000) compared to these factors, indicating that the post application scenario should be short term only In addition to using HED's SOP for residential assessment, the study specific turf transferable residue ( TTR) was used in the calculation. A summary of risk estimates for residential postapplication risks for adults and children is provided in the following tables. HED combines risk values resulting from separate post application exposure scenarios when it is likely they can occur simultaneously based on the use pattern and the behavior associated with the exposed population ( see Table 6.3b), and all MOEs are above 100, and not of concern. [ Note: Propiconazole is classified as a non volatile chemical; therefore a residential inhalation postapplication assessment is not required]. The assumptions used for each of the scenarios separately are already high ( i. e., time spent outdoors, dislodgeable residues). So, combining all these activities together is extra conservative.

Table 6.3a: Adult Residential Risk Estimates for Post application Exposure to Propiconazole Exposure Scenario TC cm ² / hr Route of Exposure Application Rate MOE at Day 0 Outdoors Residential Turf ( Gen. High Contact Activities) 70000 Dermal 1.8 lb ai/ acre 350 Residential Turf ( Mowing) 500 Dermal 1.8 lb ai/ acre 50,000 Level of Concern: MOE = 100 Table 6.3b: Toddler Residential Risk Estimates for Post application Exposure to Propiconazole Exposure Scenario TC cm ² / hr Route of Exposure Application Rate MOE at Day 0 Combined MOE Outdoors Hand to Mouth Activity on Turf N/ A Oral 1.8 lb ai/ acre 1100 170 Page 34 of 55 Object to Mouth Activity on Turf N/ A Oral 1.8 lb ai/ acre 4500 Soil Ingestion N/ A Oral 1.8 lb ai/ acre 330,000 Turf   General High Contact Activities 25000 Dermal 1.8 lb ai/ acre 210 Note: Combined MOE = NOAEL/( ADDhand to mouth + ADDobject to mouth + ADDincidental soil ingestion + ADDdermal) Level of Concern: MOE = 100 Residential post application scenarios from antimicrobial uses were also assessed. No postapplication exposure to adult is expected because of propiconazole's low vapor pressure ( therefore, no inhalation exposure) and the registrants' deletion of the only other use ( i. e., materials preservative in fabrics, textiles, area carpet fibers). Propiconazole is used on many different types of wood including 1) green or fresh cut lumber, poles, posts, and timbers; 2) manufactured wood products such as logs ( including for log home construction), wood chips/ sawdust, plywood veneer, and particle board; 3) dry lumber; and 4) finished wood products such as millwork, shingles, shakes, siding, plywood, and structural lumber and composites. Except " dry lumber" uses, the other 3 groupings would result in minimal dermal and/ or incidental oral exposure. Inhalation exposure ( e. g., in log homes treated with propiconazole) is also expected to be negligible based on the low vapor pressure. For " dry lumber" uses, if propiconazole treated lumber is used to build residential decks and/ or play sets, then there is the potential for dermal and incidental oral exposures to treated lumber used in decks and or play sets. AD assessed the risk to children playing on propiconazole treated structures using screening level assessment. Table 6.3c shows the result of aggregate risk from incidental oral and dermal exposure from propiconazole treated wood. This risk assessment, based on high end screening level assumptions, indicates no risk of concern. Confirmatory data for the surface residues are needed to verify this screening level assessment.

Table 6.3 c. Propiconazole Assessment of Children Playing on Treated Structures. MOEs ( Target = 100) b Exposure Dose ( mg/ kg/ day) a Short term Intermediate Dermal Contact 0.0675 450 150 Incidental Oral 0.00563 5,300 1,800 Aggregate 0.0731 410 140 a Aggregate dose = dermal dose + oral dose. b MOEs = ST and IT NOAELs ( mg/ kg/ day) / Dose ( mg/ kg/ day). Where ST NOAEL = 30 mg/ kg/ day and IT NOAEL = 10 mg/ kg/ day. Target MOE = 100.

7.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION In accordance with the FQPA, HED must consider and aggregate ( add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative Page 35 of 55 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.

For most pesticide active ingredients, water monitoring data are considered inadequate to determine surface and ground water drinking water exposure estimates, so model estimates have been used to estimate residues in drinking water ( EDWCs). In the past, in order to determine if aggregate risks are of concern, HED calculated drinking water levels of comparison, or DWLOCs. The DWLOC is the maximum amount of a pesticide in drinking water that would be acceptable in light of combined exposure from food and residential pathways. The calculated DWLOCs were then compared to the EDWCs provided by EFED; if model derived EDWCs exceed the DWLOCs for surface or ground water, there may have been a concern for dietary exposure to residues in drinking water, and monitoring data may have been required.

In order to fully implement the requirements of FQPA, HED and EFED have been working toward refining the screening level DWLOC approach to conducting aggregate risk assessments that combine exposures across all pathways. As part of this process, EFED and HED have agreed that acute, chronic and cancer EDWCs can be used directly in dietary exposure assessments, to calculate aggregate dietary ( food + water) risk. This is done by using the relevant PRZM EXAMS value as a residue for water ( all sources) in the dietary exposure assessment. The principal advantage of this approach is that the actual individual body weight and water consumption data from the CSFII are used, rather than assumed weights and consumption for broad age groups. This refinement has been used for propiconazole acute and chronic aggregate risk assessments.

Aggregate exposure risk assessments were performed for the following: acute aggregate exposure ( food + drinking water) and chronic aggregate exposure ( food + drinking water). Short term aggregate ( food + water+ residential exposure) risk assessments were also performed.

7.1 Acute Aggregate Risk Since the DEEM has included water exposure in the acute analysis, the acute aggregate risks are as shown in Table 7.4 in Section 7.4 below.

7.2 Short Term Aggregate Risk Short intermediate term aggregate exposure takes into account residential exposure plus average exposure levels to food and water ( considered to be a background exposure level). Based on the residential use pattern, propiconazole post application exposures to adults are from dermal exposure only, for infants and children are from dermal and oral routes. Table 7.2a aggregates the short term risk for Toddlers from incidental oral, dermal, and food and water ( as a background). Although both residential and antimicrobial uses result in incidental oral and dermal exposure to children, the highest incidental oral and dermal exposure scenarios are from residential use on turf, which were used in the short term aggregate risk assessment. The short Page 36 of 55 term aggregate risk does not exceed HED's level of concern. This assessment is considered very conservative in that the residential incidental oral post application exposure was calculated by combining three screening level assessments ( which by themselves already have conservative estimates). HED also did a back calculation to estimate room available in the risk cup for shortterm aggregate risk. In order to obtain a short term aggregate MOE   100, the MOE resulting from additional short term exposures to Children 1 2 ( from possible dermal and incidental oral exposure from treated wood or other sources) needs to be   270. As stated above in Section 6.3, the combined short term MOE ( dermal and incidental oral) from antimicrobial use of propiconazole in treated wood for Toddler is 410, which is greater than 270.

Table 7.2a: Short term Aggregate Risk Estimates to Propiconazole for Toddler ( Children 1 2years)

Exposure Scenario Target MOE Route of Exposure Exposure NOAELs MOE at Day 0 Combined MOE5 Average Food and Water ( As background) N/ A Food and water 0.014 30 2100 2 Hand to Mouth Activity on Turf 100 1 Oral 0.0269 30 1100 3 Object to Mouth Activity on Turf 100 1 Oral 0.0067 30 4500 3 Soil Ingestion 100 1 Oral 0.00009 30 330,000 3 Turf   General High Contact Activities 100 1 Dermal 0.1410 30 210 4 160 Note: 1 Target MOE= 100, Developmental rat severe maternal clinical toxicity. NOAEL= 30 2 MOE food = [( short term oral NOAEL)/( chronic dietary exposure)] 3 MOE oral = [( short  term oral NOAEL)/( hand to mouth residential exposure)] 4 MOE dermal = [( short  term dermal NOAEL)/( high end dermal residential exposure)] 5 Aggregate Combined MOE ( food, water, and residential) = 1 ÷ [( 1 ÷ MOE food and water) + ( 1 ÷ MOE oral) + ( 1 ÷ MOE dermal)].

Table 7.2b aggregates the short term risk fro adults from residential post application, and average food and water ( as a background). Based on the low vapor pressure of propiconazole, no post application inhalation exposure is anticipated to occur. No post application exposures are expected to occur with antimicrobial uses. The highest post application exposure from residential use on turf was used in the short term aggregate. The aggregate MOE is 330, which is greater than the target MOE of 100. This aggregate exposure assessment is considered very conservative because the assumptions used for each of the scenarios separately are already high end ( i. e., time spent outdoors, dislodgeable residues). Page 37 of 55 Table 7.2b: Short term Aggregate Risk Estimates to Propiconazole for Adults from Post Application Activities Exposure Scenario Target MOE Route of Exposure Exposure Or Daily dose NOAELs MOE at Day 0 Combined MOE4 Average Food and Water ( As background) N/ A Food and water 0.0060 30 5100 2 Residential Post application ( Residential Turf Gen. High Contact Activities)) 100 1 Dermal 0.085 30 350 3 330 Note: 1 Target MOE= 100, Developmental rat increased incidence of rudimentary risks. NOAEL = 30 2 MOE food and water = [( short term oral NOAEL)/( chronic dietary exposure)] 3 MOE dermal = [( short  term dermal NOAEL)/( high end dermal residential exposure)] 4 Aggregate Combined MOE ( food, water, and residential) = 1 ÷ [( 1 ÷ MOE food and water) + ( 1 ÷ MOE post appl. dermal)].

7.3 Intermediate Term Aggregate Risk The only residential use scenario that will result in potential intermediate term exposure to propiconazole is post application exposure to Children from wood treatment ( antimicrobial use). Table 7.3 shows the aggregate risk for intermediate term exposure to Children 1 2 years old. The aggregate MOE is 120, which is greater than the target MOE of 100.

Table 7.3: Intermediate  term Aggregate Risk Estimates to Propiconazole for Toddler ( Children 1 2years)

Exposure Scenario Target MOE Route of Exposure Exposure NOAELs MOE at Day 0 Combined MOE5 Average Food and Water ( As background) N/ A Food and water 0.014 10 710 2 Incidental oral 100 1 Oral 0.0056 10 18003 Dermal Contact Activities 100 1 Dermal 0.068 10 150 4 120 Note: 1 Target MOE= 100, 24 Month oncogenicity study. NOAEL= 10 2 MOE food = [( intermediate term oral NOAEL)/( chronic dietary exposure)] 3 MOE oral = [( intermediate  term oral NOAEL)/( hand to mouth residential exposure)] 4 MOE dermal = [( intermediate  term dermal NOAEL)/( high end dermal residential exposure)] 5 Aggregate Combined MOE ( food, water, and residential) = 1 ÷ [( 1 ÷ MOE food and water) + ( 1 ÷ MOE oral) + ( 1 ÷ MOE dermal)]. Page 38 of 55 7.4 Long Term Aggregate Risk Since there are no residential uses that will likely result in chronic exposure to propiconazole, chronic aggregate includes food and water only. Water exposure has been included in the DEEM analysis; therefore, the result of chronic aggregate risk assessment is as shown in Table 7.4 below. Propiconazole does not possess a separate cancer dietary endpoint  the RfD approach is considered protective; therefore, the results of only the acute and chronic analyses are given.

Table 7.4. Summary of Dietary Exposure and Risk for Propiconazole FOOD PLUS WATER.

Acute Dietary ( 95th Percentile) Chronic Dietary Cancer Population Subgroup* Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % cPAD Dietary Exposure ( mg/ kg/ day) Risk General U. S. Population 0.018998 6 0.006020 6 All Infants (< 1 year old) 0.042618 14 0.014109 14 Children 1 2 years old 0.039530 13 0.014440 14 Children 3 5 years old 0.032646 11 0.012419 12 Children 6 12 years old 0.023610 8 0.008441 8 Youth 13 19 years old 0.016052 5 0.005401 5 Adults 20 49 years old 0.015817 5 0.005132 5 Adults 50+ years old 0.012248 4 0.004164 4 Females 13 49 years old 0.014334 5 0.004718 5 N/ A 7.5 Cancer Risk The HIARC classified propiconazole as a Group C  possible human carcinogen. RfD approach will be protective.

8.0 CUMULATIVE RISK CHARACTERIZATION/ ASSESSMENT Propiconazole 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 this pesticidal activity and their mechanism of toxicity in mammals. Page 39 of 55 Structural similarities do not constitute a common mechanism of toxicity. Evidence is needed to establish that the chemicals operate by the same, or essentially the same sequence of major biochemical events ( EPA, 2002). A variable pattern of toxicological responses are found for conazoles. 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 have 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 the toxicological outcomes. Thus, there is currently no evidence to indicate that conazoles share common mechanisms of toxicity and EPA is not following a cumulative risk approach based on a common mechanism of toxicity for the conazoles. For information regarding EPA's procedures for cumulating effects from substances found to have a common mechanism of toxicity, see EPA's website at http:// www. epa. gov/ pesticides/ cumulative 9.0 OCCUPATIONAL EXPOSURE/ RISK PATHWAY Occupational and Residential Exposure Assessment; James Miller, ( D325817, 6/ 15/ 06)

9.1 Short/ Intermediate Term Handler Risk There is potential for exposure to propiconazole in occupational scenarios from handling propiconazole products during the application process ( i. e., mixer/ loaders, applicators, flaggers, and mixer/ loader/ applicators) and a potential for post application worker exposure from entering into areas previously treated with propiconazole. As a result, risk assessments have been completed for occupational handler scenarios. HED uses the term " handlers" to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and that exposures can vary depending on the specifics of each task. Job requirements ( e. g., amount of chemical to be used in an application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event. Occupational handler exposure assessments are completed by HED using different levels of personal protection. A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. No chemical specific information was available for propiconazole handler exposure assessments; all analyses were completed using acceptable surrogate exposure data for the scenario in question.

There are short and intermediate term non cancer commercial/ agricultural handler scenarios for propiconazole that have risks of concern; however, these risks are at baseline PPE, whereas all labels call for baseline plus glove levels of PPE.

A summary of the combined, dermal plus inhalation short, and intermediate term risks for each exposure scenario are presented in Table 9.1. Page 40 of 55 Table 9.1: Summary of Short and Intermediate Term Propiconazole Occupational Handler Non cancer Risks S Term MOE ( Dermal+ Inhalation) I Term MOE ( Dermal+ Inhalation) Exposure Scenario Crops Appl. Rate ( lb ai/ acre or lb ai/ gallon) Area Treated ( acre/ day or ¹ gal/ day) Baselin e Baseline + Gloves Baseline Baseline + Gloves Mixer/ Loader   Emulsifiable Concentrate Cereals ( Barley, Oats, Rye, Triticale) Alfalfa, Sorghum, Corn 0.1125 1200 13 1500 4.5 500 Celery, Mint, Carrots, Legume ( Vegetables), Peanuts, Strawberries, Sugar beets 0.1125 350 46 5100 15 1700 Almonds, Tree Nuts, Filberts, Onions 0.225 350 23 2600 7.7 850 Soybean 0.169 1200 8.9 1000 3 330 Cranberries 0.169 350 31 3400 10 1100 Wheat 0.08 1200 19 2100 6.3 700 Aerial Rice 0.28 1200 5.4 600 1.8 200 Cereals ( Barley, Oats, Rye, Triticale) Alfalfa, Sorghum, Corn 0.1125 200 80 9000 27 3000 Celery, Mint, Carrots, Legume ( Vegetables), Peanuts, Strawberries, Sugar beets 0.1125 80 200 22000 67 7500 Almonds, Tree Nuts, Filberts, Onions 0.225 80 100 11000 33 3700 Soybean 0.169 200 54 6000 18 2000 Cranberries 0.169 80 130 15000 45 5000 Wheat 0.08 200 110 13000 38 4200 Groundboom Rice 0.28 200 32 3600 11 1200 Airblast Almonds, Tree Nuts, Filberts 0.1125 40 400 45000 130 15000 Cereals ( Barley, Rye, Oats, Trticale), Corn, Legume ( vegetables), Peanuts, Sorghum, Sugar beets 0.1125 350 46 5100 15 1700 Wheat 0.08 350 65 7200 22 2400 Chemigation Rice 0.28 350 18 2100 6.2 690 Seed Piece Dip Pineapple ( HI) 0.00021 1000 ¹ 8600 960000 2900 320000 Applicator  Emulsifiable Concentrate Page 41 of 55 Cereals ( Barley, Oats, Rye, Triticale) Alfalfa, Sorghum, Corn 0.1125 1200 7500 16000 2500 5500 Celery, Mint, Carrots, Legume ( Vegetables), Peanuts, Strawberries, Sugar beets 0.1125 350 26000 56000 8600 19000 Almonds, Tree Nuts, Filberts, Onions 0.225 350 13000 28000 4300 9400 Soybean 0.169 1200 5000 11000 1700 3600 Cranberries 0.169 350 17000 37000 5700 12000 Wheat 0.08 1200 11000 23000 3500 7700 Aerial Aerial Rice 0.28 1200 3000 6600 1000 2200 Cereals ( Barley, Oats, Rye, Triticale) Alfalfa, Sorghum, Corn 0.1125 200 15000 15000 4900 4900 Celery, Mint, Carrots, Legume ( Vegetables), Peanuts, Strawberries, Sugar beets 0.1125 80 37000 37000 12000 12000 Almonds, Tree Nuts, Filberts, Onions 0.225 80 18000 18000 6100 6100 Soybean 0.169 200 9800 9800 3300 3300 Cranberries 0.169 80 24000 24000 8200 8200 Wheat 0.08 200 2100 2100 6900 6900 Groundboom ( Open Cab)

Rice 0.28 200 37000 37000 12000 12000 Air blast ( open cab) Almonds, Tree Nuts, Filberts 0.1125 40 3100 4600 1000 1500 Seed Piece dipping Pineapple No data Flagger  Emulsifiable Concentrate Cereals ( Barley, Oats, Rye, Triticale) Alfalfa, Sorghum, Corn Celery, Mint, Carrots, Legume ( Vegetables), Peanuts, Strawberries, Sugar beets 0.1125 350 11000 10000 3700 3500 Almonds, Tree Nuts, Filberts, Onions 0.225 350 5600 5200 1900 1700 Aerial Soybean Cranberries 0.169 350 7500 6900 2500 2300 Page 42 of 55 Wheat 0.08 350 16000 15000 5300 4900 Rice 0.28 350 4500 4200 1500 1400 Note:  Baseline PPE = ( long sleeve shirt, long pants, no gloves, and no respirator)  MOE = NOAEL/ Daily Dose where the NOAEL for both dermal and inhalation is 30.0 mg/ kg/ day for Short term and 10.0 mg/ kg/ day for Intermediate/ Long term exposures.  The target MOE is 100 for Short and Intermediate term Dermal/ Inhalation exposure. ¹ Area treated: ( gal/ day)

9.2 Short/ Intermediate Term Post application Risk HED uses the term " post application" to describe exposures to individuals that occur as a result of being in an environment that has been previously treated with a pesticide ( also referred to as re entry exposure). HED believes that there are distinct job functions or activities that occur in previously treated areas. These job functions ( e. g., the kinds of jobs to cultivate a crop), the nature of the crop or target that was treated, and the how chemical residues degrade in the environment can cause exposure levels to differ over time. A series of assumptions and exposure factors served as the basis for completing the occupational post application worker risk assessments for agricultural scenarios. A total of three residue dissipation studies were used. These studies described residue dissipation and exposure for corn, rice, and pecans. The corn data have been used to complete all assessments for the following agronomic crop groups: Tall field/ row crop: corn ( field/ pop/ sweet), sunflowers breeder's seed. The rice data have been used to complete all assessments for field/ row crops, low/ medium: wheat, barley, mint, and rice. The pecan data have been used to complete all assessments for tree nuts. 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).

All agricultural scenarios were evaluated using propiconazole specific DFR/ TTR dissipation data. A summary of the post application risks for each crop/ activity combination is shown in Table 9.2. Table 9.2: Summary of Propiconazole Non cancer Post application Worker Risk Estimates Crop Activity TC cm2/ hr Max. App. Rate ( lb ai/ A or Gal/ day) DFR ug/ cm 2 ( adjusted) Short Term MOE Int Term MOE irrigating, scouting, hand weeding 100 0.184 36000 12000 irrigating, scouting 1500 0.184 2400 800 Alfalfa, Celery, Mint, Barley, Legume, Oats, Peanuts, Rice, Rye, Soybean, Sugar beets, Triticale, Wheat, hand harvesting 2500 0.28 0.184 1400 500 scouting , weeding 100 0.059 110000 37000 scouting , weeding ( more mature foliaged plants) 400 0.059 28100 9000 scouting, weeding, irrigation 1000 0.059 11000 3700 Corn ( field, pop, sweet), Sorghum detasseling, handharvesting 17000 0.1125 0.059 660 220 scouting, handweeding irrigation, thinning 300 0.505 4000 1400 irrigating, scouting 1500 0.505 870 290 Carrots, Onions irrigating, scouting 2500 0.225 0.505 520 170 hand weeding, thinning, pruning, irrigating, scouting 400 0.379 4300 400 Cranberries, Strawberries, hand pruning, harvest, pinch, train 1500 0.169 0.379 1200 390 hand weeding, thinning, irrigating, scouting 500 0.255 5200 1700 Almonds, Tree Nuts, Filberts hand pruning, thinning 2500 0.225 0.255 1000 340 Note: All DFR and Margin of Exposure data are measured at DAT = 0.

Most occupational post application short, intermediate and long term risks do not exceed HED's level of concern ( i. e., MOEs > 100) at day 0. The occupational post application short and intermediate and long term risks that exceed HED's level of concern ( i. e., MOE's < 100) at Day = 0 are as follows: Page 44 of 55 Short Term: All short term occupational risks are below HED's level of concern ( i. e., MOEs > 100) at day 0.

Intermediate Term: All intermediate term occupational risks are below HED's level of concern ( i. e., MOEs > 100) at day 0.

10.0 DATA NEEDS AND LABEL REQUIREMENTS Since propiconazole is a triazole generating pesticide, as specified in HED's February 7, 2006 risk assessment ( M. Doherty et al, DP# 322215) 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 uses of propiconazole be conditioned upon resolution of the following issues:

  Chemistry:  Final two year storage stability study with 1,2,4 triazole;  Resolution of concerns regarding the prevalence of conjugated residues of TA and the ability of the analytical method to quantify them.   Toxicology:  Free triazole:

  Developmental neurotoxicity study in rats;

  Chronic toxicity   1 year chronic rat study in males and females   Acute neurotoxicity study in rats [ This study, included in the original data requirements, was placed in reserve pending the results of the combined subchronic/ neurotoxicity study, in response to a previous waiver request. A new waiver request for this study was submitted in August 2005, and is under review.];  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.

In addition to the above data requirements, the following data requirements are also needed for this particular registration action. Page 45 of 55 10.1 Residue Chemistry Data Needs   HED recommends that the registrant analyze parent and metabolites separately in all future field trials, so that more realistic tolerances can be set in the future.

  Label directions for the EC and WP formulations must be amended to include the recommended changes listed under the ` Directions for use' section in the Residue Chemistry Summary Chapter.

  To support the use of the EC formulation on sugar beets, an additional 8 sugar beet field trials are required using a representative EC formulation. As the available data indicate that residues in/ on roots are similar for the WP and EC formulations, only residue data on sugar beet tops are required from these trials. HED recommends that registration of the EC on sugar beets be conditional upon the data on tops.

  A total of 12 dry bean field trials and 5 dry pea field trials are required to support the proposed tolerance on the dry pea and bean subgroup 6C. Only five dry bean field trials are available, and they support a 28 day PHI rather than the proposed 14 day PHI. Additional 7 trials on dry beans and 5 trials on dry peas at the proposed rates are needed.

  Since data are available supporting tolerances on soybean forage and hay, the petitioner may delete the " prohibit animal grazing" or " prohibit feeding hay to livestock" on the label.

  The available wheat field trial will only support a maximum use rate of 0.11 lb ai/ A prior to the harvest of forage or hay. Label must be revised to specify that no more than 0.11 lbs ai/ A be applied before the harvest of forage and hay. If the petitioner intends to support the use of two applications totaling 0.22 lb ai/ A prior to harvest of forage and hay, then an additional 8 field trials are required on forage and a complete set of 20 field trials are required for hay.

  The available field corn and sorghum field trial data will only support applications totaling 0.22 lb ai/ A prior to the harvest of forage. If the petitioner intends to support total application rate up to 0.44 lb ai/ A prior to the harvest of forage, than additional field corn and sorghum forage data will be required to support the higher use rate.

  As propiconazole is one of the triazole producing pesticides, any requests for new uses submitted after September 1, 2005 will require data related to assessing the common metabolites. For detailed information, please refer to HED memo of 4/ 25/ 06, M. Doherty, D327788, " Guidance on Residue Chemistry Data Submission". Page 46 of 55 10.2 ORE Data Needs   None.

10.3 Toxicology Data Needs None.

11.0 RECOMMENDED TOLERANCES Table 11 lists the Agency's recommended tolerances. The Agency notes that these recommended tolerance levels are relatively conservative, as they are based on data for combined residues instead of propiconazole, per se.

The Codex Alimentarius Commission has established several maximum residue limits ( MRLs) for propiconazole in/ on various raw agricultural commodities. The Codex MRLs are expressed in terms of propiconazole per se, which is the same as the US tolerance expression, recommended by the RED for existing tolerances and for the new uses in the present action. In addition, both Canada and Mexico have established MRLs/ tolerances on several commodities which also have U. S. tolerances. To the extent possible, U. S. tolerances have been harmonized with Codex, Canadian, and Mexican MRLs; however, differences in use patterns and the supporting residue data have precluded reducing many tolerances. A comparison of Codex MRLs, Canadian MRLs, and Mexican tolerances and the corresponding U. S. tolerances is presented in Appendix I. Page 47 of 55 Table 11. Tolerance Summary for Propiconazole Crop Commodity Proposed or ( Established) Tolerance ( ppm) 6 HED Recommend ed Tolerance ( ppm) Comments ( Correct Commodity Definition) Tolerances under § 180.434( a)

AGF 17 30 Based on the maximum expected residues in AGF from corn ( 1.28 ppm), sorghum ( 10.9 ppm), soybeans ( 44.8 ppm), and wheat ( 4.14 ppm), the tolerance for AGF should be based on the available soybean data. Grain, aspirated fractions Alfalfa 0.1 None As the tolerance is for rotated alfalfa, it should be established under § 180.434( d) for inadvertent residues Almond, hulls 8.0 7.0 1 Adequate data are available. Almond, hulls Banana ( 0.2) 0.2 The existing tolerance is adequate Barley, grain 0.5 0.3 Barley, hay 2.0 1.4 Barley, straw 13 10 Barley, bran 2.5 0.6 Tolerances for barley commodities are based on residue data translated from wheat.

Cattle, fat ( 0.1) 0.05 Cattle, kidney ( 2.0) 2.0 Cattle, liver ( 2.0) 2.0 Cattle, meat ( 0.1) 0.05 Cattle, meat byproducts, except liver and kidney ( 0.1) 0.05 The recalculated MTDB for beef cattle ( 28 ppm). Estimated combined residues are: 1.7 ppm in kidney, 1.6 ppm in liver, 0.03 ppm in muscle, 0.05 ppm in fat.

Celery ( 5.0) Delete Once the tolerance of the leaf petioles subgroup is established the separate tolerance on celery should be deleted Crop Subgroup 4 B, leaf petioles 5.0 5.0 1 The available residue data on celery will support the 5 ppm tolerance on Vegetable, leaf petioles, subgroup 4B Crop Subgroup 6 C, Dried shelled peas and bean ( except soybean) 0.5 None 5 Insufficient residue data to support a tolerance on the Pea and bean, dried shelled, except soybean, subgroup 6C Crop Group 13 Berries Group 1.0 1.0 1 Adequate residue data are available on blueberries, black berries, and raspberries to support a tolerance for Berry, group 13 Carrot 0.2 0.25 1 Adequate residue data are available. Carrot, root Corn, field, forage 4.0 12 Adequate residue data are available supporting a 30 day PHI for field corn forage following applications totaling 0.44 lb ai/ A. Corn, field, forage Page 48 of 55 Table 11. Tolerance Summary for Propiconazole Crop Commodity Proposed or ( Established) Tolerance ( ppm) 6 HED Recommend ed Tolerance ( ppm) Comments ( Correct Commodity Definition)

Corn, sweet, forage None 6.0 3 A separate tolerance should be established for sweet corn forage. Based on the available sweet corn field trials, in which maximum residues were 5.0 ppm in/ on forage from a test conducted at a 0.9x rate, a 6.0 ppm tolerance should be established for residues in/ on Corn, sweet, forage.

Corn, field, grain 0.3 0.2 2 Adequate residue data are available supporting the reduced 30 day PHI.

Corn, pop, grain None 0.22 Adequate residue data are available supporting the reduced 30 day PHI.

Corn, sweet, K+ CWHR ( 0.1) 0.1 Adequate residue data are available supporting the existing tolerance. Corn, sweet, K+ CWHR Corn, stover 25 30 1 Adequate residue data are available supporting the reduced 30 day PHI.

Corn, pop, stover None 30 1 Based on the field corn stover data.

Corn, sweet, stover None 30 1 Based on the field corn stover data.

Corn, oil 0.5 None Processing factors for corn oil were 0.6x 1.6x and averaged 1x; therefore, a separate tolerance is not required for corn oil Fruit, stone, group 12 None 1.0 Tolerance was reassessed by the Agency ( HED memo of propiconazole RED, 6/ 28/ 06, Y. Donovan, D329668). Goat, fat ( 0.1) 0.05 Goat, kidney ( 2.0) 2.0 Goat, liver ( 2.0) 2.0 Goat, meat ( 0.1) 0.05 Goat, meat byproducts, except liver and kidney ( 0.1) 0.05 See comments under cattle.

Grass, forage ( 0.5) 0.5 Grass, hay ( 0.5) 0.5 Grass, straw ( 40) 40 The existing tolerances are adequate. ( HED memo of propiconazole RED, 6/ 28/ 06, Y. Donovan, D329668). Hog, fat ( 0.1) Delete Hog, kidney ( 2.0) 0.2 Hog, liver ( 2.0) 0.2 Hog, meat ( 0.1) Delete Hog, meat byproducts, except liver and kidney ( 0.1) Delete The recalculated MTDB for swine ( 2.3 ppm) and estimated residues in liver ( 0.13 ppm), kidney ( 0.14 ppm), muscle (< 0.005 ppm) and fat ( 0.005 ppm) at a 1x feeding level.

Horse, fat ( 0.1) 0.05 See comments under cattle. Page 49 of 55 Table 11. Tolerance Summary for Propiconazole Crop Commodity Proposed or ( Established) Tolerance ( ppm) 6 HED Recommend ed Tolerance ( ppm) Comments ( Correct Commodity Definition) Horse, kidney ( 2.0) 2.0 Horse, liver ( 2.0) 2.0 Horse, meat ( 0.1) 0.05 Horse, meat byproducts, except liver and kidney ( 0.1) 0.05 Mint, spearmint, tops 3.0 3.5 1 Adequate data are available. Mint, peppermint, tops 3.0 3.5 1 Adequate data are available.

Milk ( 0.05) 0.05 MTDB for dairy cattle is 18.5 ppm. The estimated combined residue on milk at 1x MTDB based on feeding study is 0.03 ppm. Mushroom ( 0.1) 0.1 The existing tolerance is adequate. Oats, forage 10.0 1.7 Oats, grain 0.1 0.32 Oats, hay 30.0 1.4 Oats, straw 1.0 10 As the proposed changes to the label directions will also cover oats in addition to wheat, the wheat residue data will also be translated to oats to reassess the existing tolerances.

Onion, bulb 0.3 0.2 2 Adequate residue data are available. Maximum combined residues were 0.18 ppm in/ on dry bulb onions. Onion, dry bulb Onion, green 8.0 9.0 1 Adequate residue data are available. Onion, green Peanut, nut meat ( 0.2) 0.2 Peanut, hay ( 20) 20 The existing tolerances are adequate.

Pecans ( 0.1) Delete Once the tree nut crop group tolerance is established, the separate tolerance for pecans should be deleted Pineapple ( 0.1) 0.1 The existing tolerance is adequate.

Pistachio 0.2 0.1 Tolerance is based on residue data from almonds and pecans Rice, bran 28 15 Based on HAFT residues of 5.05 ppm for rice grain and an average processing factor of 2.9x for bran, the maximum expected residues in bran would be 14.6 ppm. Rice, bran Rice, grain 7.0 7.0 4 Adequate field trial data are available. Rice, grain Rice, hulls 28 20 Based on HAFT residues of 5.05 ppm for rice grain and an average processing factor of 3.8x for hulls, the maximum expected residues in hulls would be 19.2 ppm. Rice, hulls Rice, straw 18 18 1 Adequate field trial data are available. Page 50 of 55 Table 11. Tolerance Summary for Propiconazole Crop Commodity Proposed or ( Established) Tolerance ( ppm) 6 HED Recommend ed Tolerance ( ppm) Comments ( Correct Commodity Definition) Rice, straw Rye, grain 0.5 0.3 Rye, forage 3.0 1.7 Rye, straw 13 10 Rye, bran 2.5 0.6 Tolerances for rye commodities are based on residue data translated from wheat.

Grain sorghum, forage 10 12 1 Grain sorghum, grain 2.5 3.5 1 Grain sorghum, ( stover) 15 15 1 Adequate field trial data are available for sorghum. Sorghum, grain, forage; Sorghum, grain; and Sorghum, grain, stover Sheep, fat ( 0.1) 0.05 Sheep, kidney ( 2.0) 2.0 Sheep, liver ( 2.0) 2.0 Sheep, meat ( 0.1) 0.05 Sheep, meat byproducts, except liver and kidney ( 0.1) 0.05 See comments under cattle.

Soybean, forage 8.0 11 1 Soybean, hay 32 30 1 Adequate field trial data are available at the 1x rate to support a 30 day PHI for Soybean, forage and Soybean, hay Soybean, seed 2.0 2.0 Field trial data are available to support Soybean seed following applications up to Stage R6.

Strawberry 1.5 1.3 1 Adequate residue data are available. Strawberry Sugar beet, dried pulp 2.0 1.0 Based on HAFT residues of 0.18 ppm for roots and a 4.9x processing factor for dried pulp, maximum expected residues in dried pulp would be 0.88 ppm. Beet, sugar, dried pulp Sugar beet, roots 0.3 0.3 2 Adequate residue data are available and indicate that there is no difference in residue levels in/ on roots between the WP and EC formulations. Tolerance in based on maximum residues of 0.23 ppm in/ on roots Beet, sugar, roots Page 51 of 55 Table 11. Tolerance Summary for Propiconazole Crop Commodity Proposed or ( Established) Tolerance ( ppm) 6 HED Recommend ed Tolerance ( ppm) Comments ( Correct Commodity Definition)

Sugar beet, tops 10 10 5 Adequate residue data are available for the WP formulation and suggest a tolerance level of 4.5 ppm. However, the limited field trial data for the EC formulation indicate that a higher tolerance is required. A tolerance should be set at 10 ppm, with the registration conditioned upon the submission of additional residue data on tops for the EC formulation. Beet, sugar, tops Sugar beet, molasses 3.0 1.5 Based on HAFT residues of 0.18 ppm for roots and a 7.4x processing factor for molasses, maximum expected residues in molasses would be 1.33 ppm. Beet, sugar, molasses Tree nuts crop group 0.2 0.12 Adequate residue data are available on pecans and almonds. Tolerance is based on maximum residues of 0.09 ppm for almonds and < 0.1 ppm for pecans. Nut, tree, group 14 Wheat, bran 2.5 0.6 Based on HAFT combined residues of 0.18 ppm for wheat grain and an average 3.2x processing factor for wheat bran, maximum expected residues in bran would be 0.58 ppm. Wheat, bran Wheat, forage 3.0 1.71 Adequate residue data are available to support only a single application prior to the harvest of Wheat, forage.

Wheat, grain 0.5 0.3 2 Tolerance is based on maximum values of 0.20 ppm for combined residues or 0.05 ppm for parent residues. Wheat, grain Wheat, hay 2.0 1.41 Adequate residue data are available reflecting only a single application prior to harvest of Wheat, hay.

Wheat, straw 13 101 Adequate residue data are available. Wheat, straw Tolerances under § 180.434( c)

Cranberry 1.0 1.0 Adequate residue data are available. Although the tolerance spreadsheet recommends a 0.9 ppm tolerance, a slightly higher 1.0 ppm tolerance was selected to harmonize with the berries crop group. Cranberry Page 52 of 55 Table 11. Tolerance Summary for Propiconazole Crop Commodity Proposed or ( Established) Tolerance ( ppm) 6 HED Recommend ed Tolerance ( ppm) Comments ( Correct Commodity Definition)

Mint, tops ( leaves and stems) 0.3 Delete Adequate data are available for all major mint growing regions. The tolerance under 180.434( c) should be deleted once the new tolerance on mint is established under 180.434( a) Tolerances under § 180.434( d)

Alfalfa 0.1 0.1 2 Adequate residue data are available to support a 75 day PBI for alfalfa. Separate tolerances should be established for inadvertent residues in/ on alfalfa, forage and alfalfa, hay, each at 0.1 ppm 1 Tolerance level was calculated using the tolerance spreadsheet and the relevant Agency guidance. 2 Recommended tolerance is based on maximum residue levels due to the large portion (> 15%) of samples having residues < LOQ. 3 The residue data on sweet corn were reviewed under PP# 8F3674 ( C. Deyrup, 12/ 14/ 88). 4 The tolerance spreadsheet recommended a tolerance of 16 ppm for rice grain assuming that the data are distributed lognormally. However, an examination of the plot suggests that the data are not log normal; therefore, a tolerance of 7 ppm was selected using the California Method ( µ + 3 ). Combined residues in/ on rice grain were < 0.05 5.20 ppm and averaged 1.49 ppm. 5 Additional residue data are required. Therefore only a conditional, time limited tolerance is being recommended. 6 Tolerances in parenthesis are currently established under 40 CFR § 180.434. Page 53 of 55 Appendix I   International Residue Limits INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: 1[[ 2 ( 2,4 dichlorophenyl) 4 propyl 1,3 dioxolan 2 yl] methyl] 1H 1,2,4 triazole Common Name: Propiconazole X Proposed tolerances 9 Reevaluated tolerance 9 Other Date: 7/ 14 / 06 Codex Status ( Maximum Residue Limits) U. S. Tolerances X No Codex proposal step 6 or above 9 No Codex proposal step 6 or above for the crops requested Petition Number: 2F6371, 6E4788, 7E4860, and 8E4931 DP Barcode: D238458 Other Identifier:

Reviewer/ Branch: Y. Donovan/ RAB4 Residue definition ( step 8/ CXL): Propiconazole Residue definition: Tolerances are currently expressed as the combined residues of propiconazole and its metabolites determined as 2,4 DCBA and expressed as parent. However, HED has recommended that the tolerance expression be changed to include only parent.

Crop ( s) 1 MRL ( mg/ kg) Crop( s) Proposed or Established Tolerance ( ppm)

Almonds 0.05 Tree nuts 0.10 Banana 0.1 Banana 0.2 Barley 0.05 Barley, grain 0.3 Coffee beans 0.1 Not registered use Liver and Kidneys of cattle, goats, horses, hogs, and sheep 2.0 Edible offal ( mammalian) 0.05 Meat byproducts, except liver and kidney 0.1 Eggs 0.05 Tolerance not required Grapes 0.5 No registered uses Mango 0.05 No registered uses Meat ( from mammals other than marine 0.05 Meat and fat of cattle, goats, horses, hogs, and 0.1 Page 54 of 55 mammals) sheep Milks 0.01 Tolerance not required Oats 0.05 Oats, grain 0.3 Peanut 0.05 Peanut, whole 0.1 Peanut 0.2 Pecan 0.05 Tree Nuts 0.10 Poultry meat 0.05 Tolerance not required Rape seed 0.05 No registered uses Rye 0.05 Rye, grain 0.3 Stone fruits 1.0 Fruit, Stone, group 12 1.0 Sugar beet 0.05 Beet, sugar, roots Sugar beet leaves or tops 0.5 Beet, sugar, tops 10 Sugar cane 0.05 No registered uses Wheat 0.05 Wheat Grain 0.3 Limits for Canada Limits for Mexico 9 No Limits 9 No Limits for the crops requested 9 No Limits 9 No Limits for the crops requested Residue definition: Propiconazole and its metabolites including the 2,4 DCBA moiety Residue definition: Propiconazole Crop( s) MRL ( mg/ kg) Crop( s) MRL ( ppm) Liver and kidney of cattle 2 Barley 0.1 Apricots, cherries, peaches/ nectarines, plums 1 Beans 0.5 Dried blueberries 0.15 Walnut 0.1 Asparagus 0.1 Banana 0.2 Barley, oats, wheat 0.05 Wheat 0.1 Blueberries 0.02 blackberries, loganberries and raspberries 0.7 proposed Notes/ Special Instructions: Page 55 of 55 CC: Yan Donovan