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 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 registered for food/ feed uses include emulsifiable concentrate ( EC) and flowable concentrate ( FlC) formulations. Except for pineapple and sugarcane ( seed pieces), all uses are pre harvest Page 58 of 112 foliar application, ground or air. Pineapple and sugarcane uses are post harvest uses. The application rates range from 0.081 lbs ai/ A/ season ( such as wheat) to 0.90 lbs ai/ A/ season ( grass grown for seed).

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. 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 aniline 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. 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, 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. For enforcement purpose, the Multiresidue Methods Section 302 ( Luke Method; Protocol D) picks up parent propiconazole.

Tolerances are established for residues of propiconazole and its metabolites determined as 2,4 dichlorobenzoic acid and expressed as parent compound in/ on various plant and animal commodities [ 40 CFR § 180.434]. The reassessed tolerances 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 data collection method is a moiety method that detects all residues convertible to 2,4 DCBA, and the field data were reported as propiconazole and all its metabolites containing the 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. With the exception of sunflower, the re registration requirements for magnitude of the residue in/ on all the raw agricultural commodities ( RACs), based on the currently registered use patterns, will be fulfilled pending label revisions and/ or tolerance adjustments: barley, rye, rice, wheat, sweet corn; field and pop corn, oat, peanut, pineapple, stone fruits, and aspirated grain fractions. As a result of this review, new tolerances are being proposed on several commodities. The re registration requirements for magnitude of the residue in the processed commodities have been fulfilled, except for pineapple ( juice). The re registration requirements for data depicting the magnitude of propiconazole residues of concern in meat, milk, poultry, and eggs have been fulfilled. The maximum theoretical dietary burden to livestock has been recalculated due to added new uses. Tolerances in ruminant commodities were reassessed at the existing level, while tolerances for poultry commodities are not required. Plantback restrictions have been established for propiconazole products registered for use on rotatable crops based on the confined rotational crop studies. Table 10 is the tolerance reassessment summary for propiconazole. Page 59 of 112 6.1.2 Acute and Chronic Dietary Exposure and Risk ( Food and Water) ( HED memo of 06/ 15/ 06, Yan Donovan, D329667)

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 for all population subgroups, including females 13 49 years is 0.3 mg/ kg/ day. The results of the analysis indicate that acute risk from dietary exposure 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 was 3% aPAD at the 95th percentile, the highest exposure was to all infants < 1 yrs old, at 8% aPAD. The exposure to females 13 49 yrs old is at 2 % aPAD.

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 indicated that chronic risk from the dietary exposure 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 was 3% cPAD and the most highly exposed subgroup, Children 1 2 yrs old, at 8% 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 concentrations ( EECs) of propiconazole for acute exposure is 86.4 parts per billion ( ppb) ( rice use), and for chronic exposure is 37.5 ppb ( turf use). For ground water, the highest EEC for acute and chronic exposure is 0.7 ppb. The highest estimates from surface water ( acute, 86.4 ppb and chronic, 37.5 ppb) were used in the DEEM analysis.

6.2 Water Exposure/ Risk Pathway Drinking water Assessment; James Lin ( D312353, 06/ 29/ 05) Revised Drinking Water Assessment; James Lin ( D323440, 06/ 07/ 06)

Based on U. S. Geological Survey National Water Assessment Data Warehouse ( link: Page 60 of 112 http:// infotrek. er. usgs. gov/ servlet/ page?_ pageid= 543&_ dad= portal30&_ schema= PORTAL30), there are not many samples analyzed for propiconazole. Among the samples analyzed, none of the samples exceed the detection limits ( from 0.001 to 0.021 µ g/ L).

Models, Scenarios, and Input Parameters Used To Estimate Concentrations of Propiconazole With the exception of rice use, estimated drinking water concentrations from surface water sources were calculated using Tier II PRZM ( Pesticide Root Zone Model) and EXAMS ( Exposure Analysis Modeling System). PRZM is used to simulate pesticide transport as a result of runoff, erosion, and off target spray drift from an agricultural field and EXAMS estimates environmental fate and transport of pesticides in surface water. These models are run using the linkage program shell, PE4V01, which incorporates the standard scenarios developed by EFED.

For use on rice, the Policy for Estimating Aqueous Concentrations from Pesticides Labeled for Use on Rice, dated October 29, 2002, was followed in estimating drinking water concentrations. Since propiconazole degrades quickly in the rice paddy environment with a half life of 5 days, which is equivalent to a first order degradation rate of 0. l39/ day, this degradation rate was used in simulating the continuing degradation in the rice paddy environment.

Several of EFED's standard scenarios were simulated for this drinking water assessment. For each specific use, drinking water concentrations were estimated assuming the maximum allowable label rate. The final estimated drinking water concentrations were then adjusted with the proper percent crop treated area ( PCA). The default PCA of 0.87 was used, except for the uses on sweet corn ( 0.46) and wheat ( 0.56). There is no PCA correction for rice use.

Drinking Water Estimates from Surface Water Sources The estimated drinking water concentrations of propiconazole in surface water were calculated. In general, the higher use rate produces the higher drinking water concentrations. Rice use results in the highest peak ( acute) drinking water concentration ( 86.49 ug/ L) among all scenarios assessed. The highest chronic values are 37.5 and 26.5 ug/ L, respectively for PA and FL turf scenarios. The high values are the results of high application rate ( up to 7.2 lb ai/ ac per year).

Drinking Water Estimates from Ground Water Sources Since the input value of 604 for soil adsorption Koc used in SCIGROW runs is outside the model development range of 32 to 180 mL/ g, the uncertainties of these estimated values are great. For these SCIGROW runs, all the fate input parameters are identical, except the propiconazole application information. The higher estimated drinking water concentrations are associated with the higher rate. Turf and ornamentals uses have the highest concentration of 0.72 µ g/ L ( ppb), whereas barley use has the lowest value of 0.01 µ g/ L.

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 86.5 0.7 Chronic ( non cancer) 37.5 0.7 Page 61 of 112 Table 6.2. Summary of Estimated Surface and Ground Water Concentrations for Chemical. Propiconazole parent compound Exposure Duration Surface water ( ppb) Ground water ( ppb) Chronic ( cancer) N/ A N/ A 6.3 Residential ( Non Occupational) Exposure/ Risk Pathway Propiconazole: Revised Occupational and Residential Exposure Assessment; James Miller, Environmental Scientist ( D329393, 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)

Residential Handler Exposure Assessment The anticipated use patterns and current labeling indicate three major residential exposure scenarios based on the types of equipment and techniques that can potentially be used to make propiconazole applications. The quantitative exposure/ risk assessment developed for residential handlers is based on these scenarios:

  Mixer/ Loader/ applying liquids and wettable powder in water soluble packets via 1) Low Pressure Handwand, and 2) Hose End Sprayer.   Applying treated paint using airless sprayer and Hose end spray.

Residential handler exposure scenarios are considered to be short term only due to the infrequent uses associated with homeowner products.

A series of assumptions and exposure factors served as the basis for completing the residential handler risk assessments. Each assumption and factor is detailed below. In addition to these factors, unit exposures were used to calculate risk estimates. Mostly, these unit exposures were taken from the Pesticide Handlers Exposure Database ( PHED) and the Outdoor Residential Exposure Task Force ( ORETF) studies.

HED believes that the scenarios assessed in this document represent worse case exposures and risks resulting from use of propiconazole in residential environments. It should also be noted that there were many other scenarios where medium to low quality PHED data were used to complete the assessment. Data quality should be considered in the interpretation of the uncertainties associated with each risk presented.

  Short term risks for residential handlers are presented below in Table 6.3a. All risks are below HED's level of concern ( i. e., MOEs are > 100) assuming handlers are wearing short sleeve shirt, short pants, shoes, and socks. Page 62 of 112 Table 6.3a: Summary of Residential Handler Exposure Estimates Max Appl. Rate ¹ Daily Area Treated ² Handler Scenario Short Term MOE Application. Equip. Crop( s)/ Site Lb ai/ Acre or % in paint* Acre/ day Or gal/ day* M/ L/ A Derml+ Inhln Baseline ( Liquids) 4400 Low Pressure Handwand 5*

( WP/ WSP) N/ A ( Liquids) 40,000 Hose end Sprayer Ornamentals ( woody and flowering plants), Shade Trees, Woody Shrubs and Vines 0.0024 5* ( WP/ WSP) N/ A ( Liquids) 1300 Low Pressure Handwand 0.023 ( WP/ WSP) N/ A ( Liquids) 530 Hose end Sprayer Turf ( Lawns) 1.8 0.5 ( WP/ WSP) N/ A Brush/ Roller3 0.35% 15* ( Paint) 330 Airless Sprayer3 Applying treated paint 2* ( Paint) 120 Notes: ¹ Application rates are the maximum rates provided for propiconazole in all cases. ² Amount handled per day values are HED estimates of area treated or gallons applied based on Exposure SAC SOP # 12 " Recommended Revisions to the Standard Operating Procedures for Residential Exposure Assessments," HED estimates and AD Standard Assumptions. 3 Paint exposure scenarios are from the AD Occupational and Residential Exposure Assessment ( T. Leighton, 2/ 1/ 2006, D326306). The density of paint is assumed to be 10 lb/ gal.

None of the residential handler exposure scenarios exceeded HED's level of concern. [ Note: Although the risk for mixing/ loading/ applying propiconazole with a low pressure handwand is not a concern, ( MOE = 1300) it is important to note that most labels identify a hose end sprayer as the method of application. Additionally, all risk calculations were conducted using the maximum turf application rate ( 1.8 lb ai/ acre). However, a turf application rate of 0.51 lb ai/ acre was identified on a residential use product label ( 100 773). This lower application rate may better represent homeowner use.

Residential Post application Exposures and Risks The 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 Page 63 of 112 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 6.3c), 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 6.3b: 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 6.3c: 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 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 210 170 Note: Combined MOE = NOAEL/( ADDhand to mouth + ADDobject to mouth + ADDincidental soil ingestion + ADDdermal) Level of Concern: MOE = 100 Page 64 of 112 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, are 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 6.3d 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 d. 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 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 order to determine if aggregate risks are of concern, HED then calculates 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 are then compared to the EDWCs provided by EFED; if model derived EDWCs exceed the Page 65 of 112 DWLOCs for surface or ground water, there may be a concern for dietary exposure to residues in drinking water, and monitoring data may be 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 chronic and cancer EDWCs can be used directly in chronic/ cancer 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 was also performed.

7.1 Acute Aggregate Risk Since the DEEM has included water exposure in the acute analysis, the result of acute aggregate is 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, post application exposure to propiconazole for 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 antimicrobials 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 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 is highly conservative because it is 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 short term 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 MOE 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 Page 66 of 112 Average Food and Water ( as background) N/ A Food and water 0.0078 30 3800 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 340, 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).

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 0.0031 30 9700 2 Residential Post application ( Residential Turf Gen. High Contact Activities)) 100 1 Dermal 0.085 30 350 3 340 Note: 1 Target MOE= 100, Developmental rat increase incidence of rudimentary. 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)].

Propiconazole also has homeowner uses. Homeowners can be exposed to propiconazole through dermal and inhalation routes while applying home use products. Table 7.2c aggregates the short Page 67 of 112 term risk for homeowner/ residential handlers from residential exposure and average food and water ( as a background). The highest residential handler exposure ( Hose end sprayer, MOE of 530) is used for the aggregate exposure assessment.

Table 7.2c : Short term Aggregate Risk Estimates to Propiconazole for Adult Residential Handlers 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 0.0031 30 9700 2 Residential handler ( Hoseend sprayer) 100 Dermal & Inhalation 0.057 30 530 3 500 Note: 1 Target MOE= 100, Developmental rat increase incidence of rudimentary. NOAEL = 30 2 MOE food and water = [( short term oral NOAEL)/( chronic dietary exposure)] 3 MOE dermal /( inhalation) = [( short  term dermal/ inhalation NOAEL)/( high end dermal/ inhalation residential exposure)] 4 Aggregate Combined MOE ( food, water, and residential) = 1 ÷ [( 1 ÷ MOE food and water) + ( 1 ÷ MOE handler dermal)].

Table 7.2d aggregates the short term risk from residential handlers of paint ( antimicrobial) use and average food and water ( as a background). The highest residential handler exposure ( Painting airless spray, MOE of 120) is used for the aggregate exposure assessment.

Table 7.2d : Short term Aggregate Risk Estimates to Propiconazole for Adult Residential Handlers of Paint ( antimicrobial use)

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 0.0031 30 9700 2 Residential Handler ( Painting airless spray) 100 Dermal & Inhalation 0.25 30 120 3 120 Note: 1 Target MOE= 100, Developmental rat increase incidence of rudimentary. NOAEL = 30 2 MOE food and water = [( short term oral NOAEL)/( chronic dietary exposure)] 3 MOE dermal /( inhalation) = [( short  term dermal / inhalation NOAEL)/( high end dermal/ inhalation residential exposure)] 4 Aggregate Combined MOE ( food, water, and residential) = 1 ÷ [( 1 ÷ MOE food and water) + ( 1 ÷ MOE handler dermal + inhalation)].

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). Page 68 of 112 Table 7.3 shows the aggregate risk for intermediate term exposure to Children 1 2 years old. The aggregate MOE is 130, 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 0.0078 10 1300 2 Incidental oral 100 1 Oral 0.0056 10 18003 Dermal Contact Activities 100 1 Dermal 0.068 10 150 4 130 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) ].

7.4 Long Term Aggregate Risk Since there are no residential uses that will likely to 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 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 0.009650 3.2 0.003113 3.1 All Infants (< 1 year old) 0.02352 7.8 0.006597 6.6 Children 1 2 years old 0.01843 6.1 0.007753 7.8 Children 3 5 years old 0.01556 5.2 0.006464 6.5 Children 6 12 years old 0.01074 3.6 0.004314 4.3 Youth 13 19 years old 0.00700 2.3 0.002627 2.6 Adults 20 49 years old 0.00730 2.4 0.002510 2.5 N/ A Page 69 of 112 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 Adults 50+ years old 0.00700 2.3 0.002490 2.5 Females 13 49 years old 0.00725 2.4 0.002434 2.4 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 Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to propiconazole and any other substances. Propiconazole is among the group of chemicals which generates a common metabolite called 1,2,4 Triazole and conjugates. A separate document will be available to address this common metabolite issue. For the purposes of this tolerance action, therefore, EPA has not assumed that propiconazole has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http:// www. epa. gov/ pesticides/ cumulative/.

9.0 OCCUPATIONAL EXPOSURE/ RISK PATHWAY Revised Occupational and Residential Exposure Assessment; James Miller, ( D329393, 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 Page 70 of 112 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 occupational 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.

In order to refine this occupational risk assessment, exposure studies for many equipment types that lack data or that are not well represented in PHED ( e. g., because of low replicate numbers or data quality) should be considered based on the data gaps identified in Section 10.2. A summary of the combined, dermal plus inhalation short, and intermediate term risks for each exposure scenario are presented in Table 9.1. Page 71 of 112 Table 9.1: Summary of Short and Intermediate Term Propiconazole Occupational Handler Non cancer Risk Estimates 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 2 gal/ day) Baseline Baseline + Gloves Baseline Baseline + Gloves Mixer/ Loader  Liquid Barley, Rye, Oats, Wheat ( Past Feekes 8), Corn, Sunflower 0.1125 1200 13 1500 4.5 500 Celery, Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum), Mint, Triticale 0.1125 350 46 5100 15 1700 Non bearing Citrus, Pecans, Non bearing Hazelnuts, Peanuts 0.225 350 23 2600 7.7 850 Grasses grown for seed ( forage and fodder grasses), Wild Rice 0.225 350 23 2600 7.7 850 Sod farm turf 1.8 350 2.9 320 1.0 110 Wheat 0.08 1200 19 2100 6.3 700 Aerial Rice 0.28 1200 5.4 600 1.8 200 Barley, Rye, Oats, Wheat ( Past Feekes 8), Corn, Sunflower 0.1125 200 80 9000 27 3000 Celery, Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum), Mint, Triticale 0.1125 80 200 22000 67 7500 Non bearing Citrus, Nonbearing Hazelnuts, Pecans, Peanuts 0.225 80 100 11000 33 3700 Grasses grown for seed ( forage and fodder grasses) 0.225 80 100 11000 33 3700 Sod farm turf 80 13 1400 4.2 470 Golf Course turf 1.8 40 25 2800 8.4 930 Groundboom Wheat 0.08 200 110 13000 38 4200 Pecans, Non bearing Citrus 0.225 40 200 22000 67 7500 Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum) 0.1125 40 400 45000 130 15000 Ornamental ( Flowering and Woody plants) 0.37 40 120 14000 41 4500 Airblast Bananas and Plantains 0.084 40 540 60000 180 20000 Barley, Rye, Oats, Wheat ( Past Feekes 8), Corn, Sunflower, Celery 0.1125 350 46 5100 15 1700 Grasses grown for seed ( forage and fodder grasses), Non bearing citrus, Peanut 0.225 350 23 2600 7.7 850 Wheat 0.08 350 65 7200 22 2400 Chemigation Rice 0.28 350 18 2100 6.2 690 Page 72 of 112 Table 9.1: Summary of Short and Intermediate Term Propiconazole Occupational Handler Non cancer Risk Estimates 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 2 gal/ day) Baseline Baseline + Gloves Baseline Baseline + Gloves Handgun Sprayer Turf 1.8 100 10 1100 3.3 370 Mixer/ Loader  Wettable Powder in Water Soluble Packets Barley, Rye, Oats, Wheat ( Past Feekes 8), Corn, Sunflower 0.1125 1200 1800 3700 600 1200 Celery, Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum), Mint, Triticale 0.1125 350 6200 13000 2100 4300 Non bearing Citrus, Pecans, Non bearing Hazelnuts, Peanuts 0.225 350 3100 6400 100 2100 Grasses grown for seed ( forage and fodder grasses), Wild rice 0.225 350 3100 6400 100 2100 Sod farm turf 1.8 350 390 800 130 270 Wheat 0.08 1200 2500 5300 840 1800 Aerial Rice 0.28 1200 720 1500 240 500 Barley, Rye, Oats, Wheat ( Past Feekes 8), Corn, Sunflower 0.1125 200 11000 22000 3600 7500 Celery, Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum), Mint, Triticale 0.1125 80 27000 56000 9000 19000 Non bearing Citrus, Nonbearing Hazelnuts, Pecans, Peanuts 0.225 80 14000 28000 4500 9300 Grasses grown for seed ( forage and fodder grasses) 0.225 80 14000 28000 4500 9300 Sod Farm turf 80 1700 3500 560 1200 Golf Course turf 1.8 40 3400 7000 110 2300 Groundboom Wheat 0.08 200 15000 32000 5100 11000 Pecans, Non bearing Citrus 0.225 40 27000 56000 9000 19000 Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum) 0.1125 40 54000 110000 18000 37000 Ornamental ( Flowering and Woody plants) 0.37 40 16000 34000 5500 11000 Airblast Bananas and Plantains 0.084 40 72000 150000 24000 50000 Chemigation Barley, Rye, Oats, Wheat 0.1125 350 6200 13000 2100 4300 Page 73 of 112 Table 9.1: Summary of Short and Intermediate Term Propiconazole Occupational Handler Non cancer Risk Estimates 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 2 gal/ day) Baseline Baseline + Gloves Baseline Baseline + Gloves ( Past Feekes 8), Corn, Sunflower, Celery Grasses grown for seed ( forage and fodder grasses), Non bearing citrus, Peanut 0.225 350 3100 6400 1000 2100 Wheat 0.08 200 8700 18000 2900 6000 Rice 0.28 350 2500 5200 830 1700 Handgun Sprayers Turf 1.8 100 1400 2800 450 930 Applicator Barley, Rye, Oats, Wheat ( Past Feekes 8), Corn, Sunflower 0.1125 1200 7500 16000 2500 5500 Celery, Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum), Mint, Triticale 0.1125 350 26000 56000 8600 19000 Non bearing Citrus, Pecans, Non bearing Hazelnuts, Peanuts 0.225 350 31000 28000 4300 9400 Grasses grown for seed ( forage and fodder grasses), Wild rice 0.225 350 31000 28000 4300 9400 Sod farm turf 1.8 350 1600 3500 540 1200 Wheat 0.08 1200 11000 23000 3500 7700 1 Aerial Rice 0.28 1200 3000 6600 1000 2200 Barley, Rye, Oats, Wheat ( Past Feekes 8), Corn, Sunflower 0.1125 200 15000 15000 4900 4900 Celery, Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum), Mint, Triticale 0.1125 80 37000 37000 12000 12000 Non bearing Citrus, Nonbearing Hazelnuts, Pecans, Peanuts 0.225 80 18000 18000 6100 6100 Grasses grown for seed ( forage and fodder grasses) 0.225 80 18000 18000 6100 6100 Sod Farm turf 1.8 80 2300 2300 770 770 Groundboom ( Open Cab)

Wheat 0.08 200 21000 21000 6900 6900 Pecans, Non bearing Citrus 0.225 40 1600 2300 520 770 Airblast Stone Fruits ( Apricots, Cherry, Nectarine, Peach, 0.1125 40 3100 4600 1000 1500 Page 74 of 112 Table 9.1: Summary of Short and Intermediate Term Propiconazole Occupational Handler Non cancer Risk Estimates 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 2 gal/ day) Baseline Baseline + Gloves Baseline Baseline + Gloves Plum)

Ornamental ( Flowering and Woody plants) 0.37 40 960 1400 320 470 Bananas and Plantains 0.084 40 4200 6200 1400 2100 Flagger Barley, Rye, Oats, Wheat ( Past Feekes 8), Corn, Sunflower Celery, Stone Fruits ( Apricots, Cherry, Nectarine, Peach, Plum), Mint, Triticale 0.1125 350 11000 10000 3700 3500 Non bearing Citrus, Pecans, Non bearing Hazelnuts, Peanuts Grasses grown for seed ( forage and fodder grasses), Wild rice 0.225 350 5600 5200 1900 1700 Sod farm turf 1.8 350 700 650 230 220 Wheat 0.08 350 16000 15000 5300 4900 1 Aerial applications Rice 0.28 350 4500 4200 1500 1400 Mixer/ Loader/ Applicator ( Liquid formulations)

High Pressure Handwand Non bearing Fruits and Nuts, Ornamental Woody and Flowering plants 2 1000 NA 780 NA 260 Low Pressure Handwand Non bearing Fruits and Nuts, Ornamental Woody and Flowering plants 0.0024 2 40 550 110000 180 36000 Handgun Sprayer Turf 1.8 5 NA 12000 NA 390 Seed piece Dip Sugarcane ( HI only) .00021 21000 8600 960000 2900 320000 Notes: 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 Application and Flagging for Aerial scenarios are accessed without gloves; therefore data is ( N/ A). 2 Area treated: ( gal/ day) Page 75 of 112 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. Propiconazole use is varied as it can be used on a wide variety of agricultural crops ( food, feed, ornamentals, and turf). As a result, a wide array of individuals can potentially be exposed by working in areas that have been previously treated. 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 six residue dissipation studies are available. These studies described residue dissipation and exposure for corn, peaches, rice, pecans, ornamentals and turf. 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 peach data have been used to complete all assessments for the following agronomic crop groups: Tree fruit, stone fruit, bunch/ bundle, and ornamentals. The rice data have been used to complete all assessments for field/ row crops, low/ medium: peanuts, wheat, barley, mint, rice. The pecan data have been used to complete all assessments for tree nuts. The turf TTR data have been used to complete all assessments for turf: sod farm, recreational areas and golf courses. 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 are shown in Table 9.2. All short term occupational risks are below HED's level of concern ( i. e., MOEs > 100) at day 0. The occupational post application risks that exceed HED's level of concern ( i. e., MOE's < 100 at Day = 0) are as follows:

  Intermediate Term post application hand harvesting ( cut flowers), risks are of concern on the day of application ( DAT = 0) and do not reach the target MOE of 100 until 1day after treatment ( DAT = 1)

o Day 0 ( MOE = 97) o Day 1 ( MOE = 104)

[ Note: The day 0 intermediate term MOE of concern ( 97) for hand harvesting cut flowers were calculated using the average of day 0 residues and represents a conservative estimate].

HED has used the latest information to complete this post application risk assessment for propiconazole. Several data gaps exist such as a lack of post application studies in different crop groupings and lack of exposure data on mechanized or partially mechanized cultural practices where there is a potential for exposure. Page 76 of 112 Table 9.2: Summary of Propiconazole Non cancer Post application Worker Risk Estimates Crop Activity TC cm2/ hr Max. App. Rate ( lb ai/ A) DAT ( days) DFR ug/ cm2 ( adjusted) Short Term MOE 1Int Term MOE irrigating, scouting, handweeding 100 0 0.184 36000 12000 irrigating, scouting 1500 0 0.184 2400 800 Celery, Mint, Wild rice, ( MN only), Barley, Oats, Rye, Wheat, Rice, Peanuts hand harvesting 2500 0.28 0 0.184 1400 500 hand weeding 100 0 0.059 110000 37000 irrigating, scouting 1000 0 0.059 1100 3700 Corn ( field, pop, sweet), Sunflower detasseling, handharvesting 17000 0.1125 0 0.059 700 220 irrigating, scouting 1000 0 0.254 2600 860 hand weeding, hand harvesting, hand pruning, 1500 0 0.254 1700 570 Stone Fruits, Peaches, Nonbearing Apples,

thinning 3000 0.1125 0 0.254 860 290 irrigation, scouting, handweeding 1000 0 0.508 1300 430 Non bearing Citrus hand pruning, thinning 3000 0.225 0 0.508 430 140 irrigation, hand weeding 100 0 0.190 35000 12000 scouting, irrigation 1300 0 0.190 2700 900 Bananas, Plantains hand harvesting,, thinning, hand weeding/ pruning 2000 0.084 0 0.190 1700 600 scouting, hand weeding/ pruning, irrigation, thinning 400 0 0.382 4300 1400 Non bearing Blueberries hand pruning 1500 0.169 0 0.382 1200 380 pruning, tying 110 0 0.835 7100 2040 Ornamentals ( Woody and Herbaceous) plants transporting, moving potted plants 400 0 0.835 2000 560 0 0.835 150 97 Cut Flowers hand harvesting S Term 5100 I term 2700 0.37 1 .778 165 104 hand weeding, thinning, irrigating, scouting 500 0 0.255 5200 1700 Pecans, Nonbearing Hazelnuts hand pruning, thinning 2500 0.225 0 0.255 1000 340 Page 77 of 112 Table 9.2: Summary of Propiconazole Non cancer Post application Worker Risk Estimates Crop Activity TC cm2/ hr Max. App. Rate ( lb ai/ A) DAT ( days) DFR ug/ cm2 ( adjusted) Short Term MOE 1Int Term MOE Turf maintenance 3400 1.8 0 0.0106 1800 600 Turf ( grasses grown for seed, golf courses, sod farms) hand weeding/ harvesting transplanting, handharvest mech harvesting 6800 1.8 0 0.0106 900 300 10.0 DATA NEEDS AND LABEL REQUIREMENTS 10.1 Residue Chemistry Data Needs   Amend the product labels for the 41.8% EC formulations to indicate the propiconazole concentration in terms of lb ai/ gal. In addition, the following products have label restrictions prohibiting the feeding of treated forage and/ or hay of cereals and corn to livestock: the 41.8% EC ( 100 617 and 100 737) and the 45% WP ( 100 780) formulations. Such restrictions are no longer permitted and must be removed.

  The maximum number of applications for peanuts on the Stratego   label is not very clear. After discussing with RD and the registrant, it is understood that the maximum number of six applications is intended only for the 7.0 oz ai/ A rate, while the restricted number of application at 14 oz ai/ A is only two. HED recommends that the registrant to amend the Stratego   label to specify these instructions.

  HED is translating the wheat grain, wheat straw, wheat hay and forage data to barley and rye grain, straw, hay and forage. The product labels for the 41.8% EC ( EPA Reg. Nos. 100 617 and 100 737) and the 45% WP ( EPA Reg. No. 100 780) formulations must be modified to make the use patterns for barley and rye identical to wheat.

  The use directions for rice on all labels should be amended to specify a 45 day PHI .

  HED recommends increasing the wheat grain tolerance to 0.3 ppm, wheat straw to 15.0 ppm, and to propose new tolerances on wheat hay and forage at 2.0 ppm, and on wheat bran at 1.0 ppm.

  HED recommends the registrant to cancel all 24C uses while revising the Section 3 label to cover these 24C uses.

  A more appropriate level for the oat hay tolerance of 2.0 ppm should be established using data translated from wheat. The reassessed tolerances for barley grain and rye Page 78 of 112 grain should be 0.3 ppm, for barley and rye straw should be 15.0 ppm. New tolerances for barley hay and rye forage should be established at 2.0 ppm.

  The available rice residue data support the established 3.0 ppm tolerance for propiconazole residues in/ on rice straw; however, the data also indicate that the registrant should propose increasing the tolerance for residues in/ on rice grain. An appropriate level for residues in/ on rice grain would be 0.3 ppm. The registrant needs to propose new tolerances on rice grain at 0.3 ppm. Based on the Agency's review of the rice processing study, the registrant needs to propose new tolerances on rice bran at 1.0 ppm, and rice hulls at 1.2 ppm.

  HED recommends a 5.0 ppm tolerance on aspirated grain fractions for propiconazole.

  The use on sunflower for seeds can not be considered a non food use, because the seed is a food. No tolerance can be established on sunflower until a petition and field trial data are submitted.

  A pineapple processing study is required to determine the potential for concentration in pineapple juice, unless a field trial study conducted at 5x the maximum application rate indicates that all residue levels in/ on pineapples are less than LOD.

  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.

10.2 ORE Data Needs Occupational handler data gaps identified for this assessment include:

  Seed piece dip treatments ( pineapples and sugarcane); Note: Labels call for chemical resistant gloves, apron and protective eyewear.

  Tree injections; Note: Labels call for chemical resistant gloves, protective eyewear/ face shield.

  Mixing/ Loading/ Applying wettable powders in water soluble packets for handheld equipment. Note: Although there are no data to assess this scenario, it is reasonable to assume that M/ L/ A exposures associated with this formulation are lower than M/ L/ A exposures with liquid formulations. This rationale is based on the assumption that the " application" component of the exposure will not be significantly different for the same application method ( both will be applied as a spray); however, as seen in scenarios where the activities are separate, the " mixing/ loading" exposure component is greater for liquid formulations. Page 79 of 112 10.3 Toxicology Data Needs None. Page 80 of 112 Table 10: Tolerance Reassessment Summary for Propiconazole.

Commodity Current Tolerance, ppm Reassessed Tolerance, ppm Comment [ Correct Commodity Definition]

Tolerances Established Under 40 CFR § 180.434( a)

Bananas 0.2 0.2 [ Banana]

Barley, grain 0.1 0.3 Translated from wheat data. Memo of 02/ 02/ 05, Y. Donovan, D271790.

Barley, straw 1.5 15.0 Translated from wheat data. Memo of 02/ 02/ 05, Y. Donovan, D271790.

Cattle, fat 0.1 0.1 0.08 ppm combined residues in fat were expected from MTDB.

Cattle, kidney 2.0 2.0 1.01 ppm combined residues in kidney were expected from MTDB. However, several new uses are pending which may increase the MTDB.

Cattle, liver 2.0 2.0 1.33 ppm combined residues in liver were expected from MTDB. However, several new uses are pending which may increase the MTDB.

Cattle, meat byproducts, except kidney and liver 0.1 0.1 ( see comments above in fat)

Cattle, meat 0.1 0.1 0.04 ppm combined residues in meat were expected from MTDB. However, several new uses are pending which may increase the MTDB.

Celery 5.0 5.0 Corn, field, stover 12 12 Expiration date 11/ 30/ 08 [ Corn, field, stover]

Corn, field, forage 12 12 Expiration date 11/ 30/ 08 [ Corn, field, forage]

Corn, field, grain 0.1 0.1 Expiration date 11/ 30/ 08 [ Corn, field, grain]

Corn, sweet, kernels plus cobs with husks removed 0.1 0.1 Expiration date 11/ 30/ 08 [ Corn, sweet, kernels plus cobs with husks removed] Page 81 of 112 Table 10: Tolerance Reassessment Summary for Propiconazole.

Commodity Current Tolerance, ppm Reassessed Tolerance, ppm Comment [ Correct Commodity Definition]

Eggs 0.1 Revoke Feeding study data indicate that tolerances for poultry commodities are not necessary.

Fruit, Stone, group 12 1.0 1.0 [ Fruit, stone, group 12]

Goat, fat 0.1 0.1 ( see comments in cattle)

Goat, kidney 2.0 2.0 ( see comments in cattle)

Goat, liver 2.0 2.0 ( see comments in cattle)

Goat, meat byproducts, except kidney and liver 0.1 0.1 ( see comments in cattle)

Goat, meat 0.1 0.1 ( see comments in cattle)

Grass, forage 0.5 0.5 Grass, hay ( straw) 40 40 [ Grass, hay]

Grass, straw 40 40 [ Grass, straw]

Hog, fat 0.1 0.1 ( see comments in cattle)

Hog, kidney 2.0 2.0 ( see comments in cattle)

Hog, liver 2.0 2.0 ( see comments in cattle)

Hog, meat byproducts, except kidney and liver 0.1 0.1 ( see comments in cattle)

Hog, meat 0.1 0.1 ( see comments in cattle)

Horse, fat 0.1 0.1 ( see comments in cattle)

Horse, kidney 2.0 2.0 ( see comments in cattle)

Horse, liver 2.0 2.0 ( see comments in cattle)

Horse, mbyp ( except kidney and liver) 0.1 0.1 [ Horse, meat byproducts, except kidney and liver]( see comments in cattle)

Horse, meat 0.1 0.1 ( see comments in cattle)

Milk 0.05 0.05 0.03 ppm combined residues in milk were expected from 26.5ppm MTDB. Page 82 of 112 Table 10: Tolerance Reassessment Summary for Propiconazole.

Commodity Current Tolerance, ppm Reassessed Tolerance, ppm Comment [ Correct Commodity Definition]

Mushroom 0.1 0.1 Use of propiconazole on mushrooms is being supported by IR 4. Currently there are no registered uses of propiconazole on mushrooms. [ Mushroom]

Oat, forage 10.0 10.0 [ Oat, forage]

Oat, grain 0.1 0.1 [ Oat, grain]

Oat, hay 30.0 2.0 Translated from wheat hay. [ Oat, hay]

Oat, straw 1.0 1.0 [ Oat, straw]

Peanut 0.2 0.2 Expiration date 11/ 30/ 08 [ Peanut]. Parent accounted 30% of the TRR based on peanut metabolism ( MARC memo of 4/ 4/ 02, D279299).

Peanut, hay 20.0 20.0 Expiration date 11/ 30/ 08 [ Peanut, hay]

Pecans 0.1 0.1 Syngenta has proposed removal of the established tolerance for pecans on establishment of the proposed tree nut crop group tolerance ( pending tolerance petition PP# 9F3470).

Pineapple 0.1 0.1 Expiration date 11/ 30/ 08 Pineapple, fodder 0.1 Revoke Expiration date 11/ 30/ 08; no longer considered a significant livestock feed item.

Plum, prune, fresh 1.0 Revoke This tolerance has been replaced by the stone fruits group tolerance.

Rice, grain 0.1 0.3 The available data, reflecting the maximum registered use pattern, indicate that the maximum combined residues of propiconazole and its metabolites determined as 2,4 DCBA were 0.28 ppm in/ on rice grain. ( HED memo of 02/ 23/ 05, T. Morton, D240856). Page 83 of 112 Table 10: Tolerance Reassessment Summary for Propiconazole.

Commodity Current Tolerance, ppm Reassessed Tolerance, ppm Comment [ Correct Commodity Definition]

Rice, straw 3.0 3.0 ( HED memo of 02/ 23/ 05, T. Morton, D240856).

Rye, grain 0.1 0.3 Translated from wheat data. Memo of 02/ 02/ 05, Y. Donovan, D271790.

Rye, straw 1.5 15.0 Translated from data for wheat straw.

Sheep, fat 0.1 0.1 ( see comments in cattle)

Sheep, kidney 2.0 2.0 ( see comments in cattle)

Sheep, liver 2.0 2.0 ( see comments in cattle)

Sheep, meat byproducts, except kidney and liver 0.1 0.1 ( see comments in cattle)

Sheep, meat 0.1 0.1 ( see comments in cattle)

Wheat, grain 0.1 0.30 Memo of 02/ 02/ 05, Y. Donovan, D271790.

Wheat, straw 1.5 15.0 Memo of 02/ 02/ 05, Y. Donovan, D271790.

Tolerances To Be Proposed Under 40 CFR § 180.434( a)

Grain, aspirated fractions 20 ( sorghum) 1 5.0 Memo of 02/ 02/ 05, Y. Donovan, D271790. [ Grain, aspirated fraction]

Barley, hay None established 2.0 Translate from wheat hay Corn, pop, grain None established 0.1 Translate from field corn Corn, pop, stover None established 12 Translate from field corn Corn, sweet, forage None established 12 Translate from field corn Corn, sweet, stover None established 12 Translate from field corn Rice, bran None established 1.0 Concentration factor for rice bran is 2.9x. ( MRID45080811. DER2)

Rice, hulls None established 1.2 Concentration factor for rice hulls is 3.8x. ( MRID45080811. DER2)

Rye, forage None established 2.0 Memo of 02/ 02/ 05, Y. Donovan, D271790.

Wheat forage None established 2.0 Memo of 02/ 02/ 05, Y. Donovan, D271790. [ wheat, forage] Page 84 of 112 Table 10: Tolerance Reassessment Summary for Propiconazole.

Commodity Current Tolerance, ppm Reassessed Tolerance, ppm Comment [ Correct Commodity Definition]

Wheat hay None established 2.0 Memo of 02/ 02/ 05, Y. Donovan, D271790. [ Wheat, hay]

Wheat Bran None established 1.0 Memo of 02/ 02/ 05, Y. Donovan, D271790. [ Wheat, bran]

Tolerances Established Under 40 CFR § 180.434( b)

Blueberry 1.0 N/ A Expiration date 11/ 31/ 07. Recommended in Agency memo of 02/ 22/ 05, D. Rate, D313289. [ Blueberry]

Cranberry 1.0 N/ A Expiration date 12/ 31/ 05 [ Cranberry]

Dry bean forage 8.0 N/ A Expiration date 12/ 31/ 05 [ Bean, dry, forage]

Dry bean hay 8.0 N/ A Expiration date 12/ 31/ 05 [ Bean, dry, hay]

Dry bean 0.5 N/ A Expiration date 12/ 31/ 05 [ Bean, dry]

Sorghum, aspirated grain fractions 20 N/ A Expiration date 06/ 30/ 05 Sorghum, grain, grain 0.2 N/ A Expiration date 06/ 30/ 05 [ Sorghum, , grain, grain]

Sorghum, grain, stover 1.5 N/ A Expiration date 06/ 30/ 05 Soybean, bean 0.5 ( pending) N/ A Agency memo of 04/ 14/ 04, J. R. Tomerlin, D262299.

Soybean, forage 8.0 ( pending) N/ A Agency memo of 04/ 14/ 04, J. R. Tomerlin, D262299.

Soybean, hay 25.0 ( pending) N/ A Agency memo of 04/ 14/ 04, J. R. Tomerlin, D262299. Page 85 of 112 Commodity Current Tolerance, ppm Reassessed Tolerance, ppm Comment [ Correct Commodity Definition]

Tolerances Established Under 40 CFR § 180.434( c)

Sunflower None established TBD 2 Peppermint, tops; [ Spearmint, tops 0.3 0.3 Regional registration for use west of the Cascade Mountains only. [ Peppermint, tops] [ Spearmint, tops]

Rice, wild 0.5 0.5 MN [ Rice, wild] Note: 1 The 20 ppm tolerance for sorghum aspirated grain fractions is a time limited tolerance to support a Section 18 Exemption. 2 Tolerance can not be established until field data are submitted. Page 86 of 112 CODEX HARMONIZATION 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 in harmonized with the US tolerance expression. HED has harmonized tolerance levels on most commodities that have Codex MRLs to the extend possible. A numerical comparison of the Codex MRLs and the corresponding reassessed U. S. tolerances is presented in Table 11.

Table 11: Codex MRLs for Propiconazole and applicable U. S. tolerances.

Codex Commodity ( As Defined) MRL 1 ( mg/ kg) Step Reassessed U. S. Tolerance ( ppm) Recommendation and Comments Almonds 0.05 CXL  No U. S. registration.

Banana 0.1 CXL TBD Barley 0.05 CXL 0.3 Coffee beans 0.1 CXL  No U. S. registration.

Edible offal ( mammalian) 0.05 CXL  No U. S. registration.

Eggs 0.05 (*) CXL  No U. S. registration.

Grapes 0.5 CXL  No U. S. registration Mango 0.05 CXL  No U. S. registration.

Meat ( from mammals other than marine) 0.05 (*) CXL 0.1 Milks 0.01 (*) CXL 0.05 Unable to harmonize 2 Oats 0.05 (*) CXL 0.1 Peanut 0.05 CXL 0.1 Unable to harmonize 2 Peanut, whole 0.1 CXL   Not currently regulated by U. S. EPA.

Pecan 0.05 CXL 0.1 Unable to harmonize 2 Poultry meat 0.05 (*) CXL  No U. S. registration.

Rape seed 0.05 CXL  No U. S. registration.

Rye 0.05 (*) CXL 0.3 Unable to harmonize 2 Stone fruits 1 CXL 1.0 Sugar beet 0.05 CXL  No U. S. registration. Page 87 of 112 Table 11: Codex MRLs for Propiconazole and applicable U. S. tolerances.

Codex Commodity ( As Defined) MRL 1 ( mg/ kg) Step Reassessed U. S. Tolerance ( ppm) Recommendation and Comments Sugar beet leaves or tops 0.5 CXL  No U. S. registration.

Sugar cane 0.05 CXL  Use in the U. S. is considered a non food use.

Wheat 0.05 (*) CXL 0.30 Unable to harmonize due to higher use rate Note: 1 Asterisk designates MRL set at the limit of quantization. 2 Can not harmonize because current use patterns in the United States supports the higher value. Page 88 of 112 APPENDICES TOXICOLOGY STUDIES The executive summaries of toxicity studies not discussed in previous sections are provided below.

Chronic Oral Toxicity  Dogs: 870.4100b Chronic Toxicity   Dog In a chronic toxicity study ( MRID 00151515), propiconazole was fed as CGA 64250 technical ( 90.2% purity, batch # FL 831527) to beagle dogs ( 7/ sex/ dose ( control and high dose) and 5/ sex/ group ( low and mid dose groups) at dietary dose levels of 0, 5, 50 or 250 ppm ( time weighted average dietary concentrations based on mean food consumption are: 0.2, 1.9, 8.4 mg/ kg/ day for males and 0.2, 1.9 , 8.9 mg/ kg/ day for females, respectively) for a period of 52 weeks. These doses were based on a 3 month study in dogs fed 50, 250 or 1,250 ppm where a LOAEL of 250 ppm was set based on changes in the pyloric region of the stomach. All animals were sacrificed after 52 weeks except for two males and two females of the control and 250 ppm were sacrificed after a four week recovery period during of which these dogs were fed diets free of CGA 64250.

All dogs survived the 12 month treatment. No treatment related effects were noted in mean body weights, body weight gains, mean food consumption, hematologic and clinical chemistry, opthalmological findings, electrocardiograms, organ weights and gross pathological findings.

Histopathologic examinations revealed hypermia of the mucosa of the stomach in 3/ 5 of the 250 ppm males, and no comparable findings were seen in the control males. Functional hypertrophy of the mammary gland was reported in 1/ 5 control females, 2/ 5 receiving 50 ppm, and 3/ 5 receiving 250 ppm of the test material. All other findings including the necropsy and histopathological examination of the dogs in the recovery period were unremarkable.

Deficiencies in the study conduct included non homogeneous distribution of the test material in the mid and high dose groups during weeks 14 21. Analytical results showed the mean propiconazole concentrations for the 50 ppm diet ranged from 38 to 47 ppm and for the 250 ppm diet ranged from 161 to 518 ppm during this period. According to study authors this was due to mixing problems and crystallization of the test material during refrigeration storage. The test material was reported to be stable at room temperature, however, it was stored at room temperature only during the later half of the study and heated to 50 98o C prior to feed preparation. Nevertheless, the diet analysis data indicated the test material was stable throughout the study. Page 89 of 112 The LOAEL is 250 ppm ( 8.4 mg/ kg/ day), based on hypermia of the stomach in males ( indicating mild irritation of the mucosa). The NOAEL is 50 ppm ( 1.9 mg/ kg/ day). However an OHEA and OPP work group ( May 25, 1987) noted a mistake in the estimation of NOAEL dose and recommended instead the usual dose conversion factor for dogs of 1 ppm = 0.025 mg/ kg/ day. This revision results in slightly lower NOAEL of 1.25 mg/ kg/ day. Accordingly the LOAEL is revised to 6.25 mg/ kg/ day. ( Acceptable/ Guideline)

SUBCHRONIC  RAT: 870.3100 90 Day Oral Toxicity  Rat In a subcronic toxicity study ( MRID 00058606 & 93194032), CGA 64250 ( 90.0% purity) was administered to Tif ( RAIF) SPF rats, approximately four weeks of age ( 20/ sex/ dose) at dietary concentrations of 0, 240, 1200, or 6000 ppm ( 0, 15.85, 76.08 and 461.73 mg/ kg bw/ day in males and 0, 16.82, 77.59 and 400.90 mg/ kg bw/ day in females, respectively) for 13 weeks.

No clinical symptoms nor any signs of local and/ or systemic toxicity were observed. The survival and mean food consumption of animals was unaffected by the treatment. The body weight and body weight gain of all male and females at 6000 ppm was significantly decreased from weeks 2 13 ( 79% and 80% of controls body weight and 75% and 73% of controls body weight gain at week 13 for males and females, respectively). The body weight and body weight gain of the females of the 1200 ppm group was significantly decreased from weeks 9 13 when compared to the control ( 92% of controls body weight and 89% of the controls body weight gain at week 13). Although there was some statistically significant reduction ( 2 5%) in body weight gain during the same weeks of the study in the low dose females, the slight decrease in body weight gain in this group is not considered biologically significant. For all animals in the 6000 ppm groups, absolute organ weights ( heart, kidney, and adrenal glands in males; kidneys and heart in females) were decreased and relative organ weights to body weight increased and to brain weight mostly decreased.

Ophthalmic, auditory and hematological findings showed no evidence of treatment related effects.

Erythrocyte count, hematocrit and hemoglobin concentration were found to be significantly lower in the female rats of the high dose group at week 13.

The only clinical chemistry findings noted consisted of an increase in alkaline phosphatase activity in the high dose female rats at week 13 and an increase in the   glutamyl transpeptidase activity in male and female rats of the high dose groups at weeks 4, 8, and 13.

Histopathology examination of the spleen of all female rats from the 6000 ppm group showed an increase in hemosiderosis.

The NOAEL for the study is considered 1200 ppm in males ( 76 mg/ kg bw/ day) and 240 ppm in females ( 16.82 mg/ kg bw/ day). The LOAEL is 6000 ppm in males ( 462 mg/ kg bw / day) and 1200 ppm in females ( 77.59 mg/ kg bw/ day) based on reduced body weight gain. ( Acceptable/ Guideline) Page 90 of 112 SUBCHRONIC  MOUSE: 870.3100 90 Day Oral Toxicity  Mouse In a subcronic toxicity study ( MRID 42050501), propiconazole was administered as CGA 64250 ( 92.0% purity, batch number FL 850083) to 7 week old Crl: CD 1 ( ICR) BR ( Swiss) mice ( 20/ sex/ dose) at dietary concentrations of 0, 20, 500, or 2500 ppm ( 0, 2.7, 65, 352 mg/ kg/ day in males and 0, 3.4, 85, 434 mg/ kg/ day in females, respectively) for 17 weeks. Two additional groups of male mice ( 20/ group) were administered the test material at 850 or 1450 ppm ( 112, 194 mg/ kg/ day, respectively).

Twice daily inspections of the animals revealed no clinical signs and mortality attributable to the administration of the test article.

There were no treatment related effects on the body weight, body weight gain and food consumption in treated mice.

Ophthalmological examinations of all animals at the termination of the study revealed no treatment related eye lesions.

Statistically significant increases ( p < 0.01) in liver weights ( absolute: 115% 192% of control, and relative to body weight: 113% 204% or relative to brain weight: 116% 194%) were found in the male animals at $ 500 ppm and in the female mice at the 2500 ppm ( 179% of control, 184% relative to body weight and 189% relative to brain weight).

Gross pathological examination of the livers from the male mice revealed a significant increase in liver enlargement ($ 1450 ppm) and focal discoloration ($ 850 ppm). The female mice showed a significant increase in liver enlargement at 2500 ppm; focal discoloration was present at 2500 ppm. The increase in absolute and relative liver weights also correlated well with histopathological ( hypertrophy and necrosis) and clinical chemistry ( increases in both ALT and AST) findings. Males showed significant decreases ( p< 0.01) in serum cholesterol at $ 1450 ppm after 13 weeks and at $ 850 ppm. Significant increase ( p< 0.01) in alanine aminotransferase occurred after 17 weeks in males at $ 1450 ppm and in females at 13 and 17 weeks at 2500 ppm. Aspartate aminotransferase increased significantly ( p< 0.01) in females at the 17 week interval at 2500 ppm. Clinical chemistry analysis was limited to liver only. Hematology was not performed.

Male mice showed a dose related increase in both the incidence and severity of histopathological lesions of the liver, while the females showed significant increases only at 2500 ppm. At 500 and 850 ppm dose levels, all diagnosed hypertrophy in the males was mild; moderate hypertrophy was present in 9/ 20 and 18/ 20 for animals in the 1450 and 2500 ppm groups, respectively. In females at the 2500 ppm dose, 14/ 20 showed minimal to mild hypertrophy, while 3/ 20 was classified as moderate. Necrosis occurred both as scattered individual cell foci and multicellular areas. Necrosis was present in males at 500 ppm with significant increases found at $ 850 ppm. The severity and incidence of the necrosis for males in the 1450 ppm group Page 91 of 112 was minimal for 2/ 20, mild for 5/ 20 and moderate for 1/ 20. At 2500 ppm 7/ 20 and 5/ 20 male mice showed minimal and mild necrosis, respectively. For females at 2500 ppm 6/ 20 showed mild necrosis. Cellular necrosis in males was minimal for 2/ 20 at 1450 ppm and 7/ 20 at 2500 ppm and mild for 5/ 20 at 2500 ppm.

Vacuolation also occurred as scattered individual foci and multicellular areas. Significant vacuolation was present only in the 2500 ppm group where 2/ 20, 7/ 20 and 1/ 20 showed minimal, mild and moderate vacuolation, respectively. No compound related effect was found when sections of male livers were stained using Oil Red 0, since nearly all of the sections ( including the controls) were stained for microvesicular lipid. Males appeared to be more sensitive to the test article than females.

The LOAEL based on increase in absolute and relative liver weights and histopathological changes is 500 ppm ( 65 mg/ kg/ day) in males and 2500 ppm ( 434 mg/ kg/ day) in females. The NOAEL is 20 ppm in males ( 2.7 mg/ kg/ day) and 500 ppm in females ( 85 mg/ kg/ day). ( Acceptable/ Guideline)

In a subcronic toxicity study ( MRID 42050502) propiconazole administered as CGA 64250 ( 92.0% purity, batch number FL 850083) was administered to 37 days old Crl: CD 1 ( ICR) BR Swiss male mice ( 40/ dose) at dietary concentrations of 0, 20, 500, 850, 1450 or 2500 ppm ( 0, 2.7, 65, 112, 194, 352 mg/ kg/ day, respectively) for 13 weeks. One group of 10 males/ dose was sacrificed after 4 weeks, a second group of 10 males/ dose after 8 weeks and the third group of 20 males/ dose was sacrificed after 13 weeks. This study was conducted to determine the maximum tolerated dose ( MTD).

Twice daily inspections of the animals revealed no clinical signs and mortality attributable to the administration of the test article.

Significant differences in weekly body weights between the control and treated mean body weights were limited to animals in the 2500 ppm group during the first 8 weeks of the study. A significant difference was also observed in the 1450 ppm group after 4 weeks. The mean cumulative body weight gains showed significant decreases ( p < 0.01) for animals in the 2500 ppm during weeks 1, 2, and 4( 36%, 70%, 70% of the body weight gain of the controls, respectively); by week 8 the decrease in body weight gain was 11%. Although the food consumption at 2500 ppm was comparable to controls, the males at 2500 ppm had lower food efficiency ( 0.7% vs. 1.4% in controls).

There were no treatment related eye lesions noted.

Statistically significant (< 0.01) increases in liver weights ( absolute: 116% 182% of controls, and relative to body weight: 118 194% of controls, and relative to brain weight: 119 192% of control) were found in the male animals at $ 500 ppm at the end of the treatment period. Gross pathology examinations revealed generalized enlargement and focal discoloration of the livers. Page 92 of 112 Hepatocellular hypertrophy, necrosis and vacuolation of the liver significantly increased at $ 500 ppm at all sacrifice times. In general, the severity of the histopathological lesions was dose related with the highest incidence of mild to moderate lesions occurring in the highest dose groups. None of the lesions were classified as either marked or severe.

Serum cholesterol significantly decreased ( p< 0.01) at $ 850 ppm and serum alanine aminotransferase ( aserum enzyme associated with hepatic necrosis) and sorbitol dehydrogenate increased at $ 1450 ppm and $ 850 ppm, respectively. Only liver enzymes were measured.

Hematology was not performed.

The LOAEL is 500 ppm ( 65 mg/ kg/ day), based on increase in absolute and relative liver weights and histopathological liver lesions. The NOAEL is 20 ppm ( 2.7 mg/ kg/ day). ( Acceptable/ Guideline)

SUBCHRONIC  DOG: 870.3150 90 Day Oral Toxicity  Dog In a sub chronic toxicity study ( MRID 00058607, 93194033), CGA 64250 technical( 88.0% purity, batch number 35/ 5) was administered to pure bred Beagle dogs ( 4/ sex/ dose) at dietary concentrations of 0, 50, 250, or 1250 ppm ( 0, 1.5, 7.3, 36.0 mg/ kg/ day, respectively) for 13 weeks. The initial age of the dogs was 19 28 weeks and body weights ranged from 7.9 13.0 kg for males and 6.0 11.6 kg for females. The dogs were housed in kennels equipped with underfloor heating.

Some animals of all groups including controls showed slight to moderate diarrhea during the whole study. Survival, body weight gain, food consumption, clinical chemistry, urinalysis, ophthalmic and auditory examinations and organ weights revealed no treatment related effects.

Necropsy showed that in 3/ 4 of male dogs from the highest dosage group ( 1250 ppm), slightly granular surface in the pyloric and propyloric part of the stomach was noted. Apart from this finding no gross anatomical changes were seen neither in treated nor in control dogs. Microscopically, in 3 out of 4 male dogs from the highest dose group and 1 out of 4 female dogs from the 250 ppm group slightly increased amount of lymphoid follicles in the mucous membrane of the pyloric part of the stomach was seen. However, this was not seen in the high dose females. These histological findings are considered compound related.

The LOAEL is 250 ppm ( 7.3 mg/ kg/ day) based on the finding of lymphoid follicles in the mucous membrane of the pyloric part of the stomach. The NOAEL is 50 ppm ( 1.5 mg/ kg/ day). ( Acceptable/ Guideline)

METABOLISM: In a metabolism study [ MRID 42403901], the metabolism and excretion of propiconazole labeled with 14C at the triazole[ 3,5] position was investigated in TIF: RIA f ( SPF) male rats ( number and age of animals not given) orally gavaged a single dose of 31.4 mg/ kg, Page 93 of 112 dissolved in water/ ethanol/ propylene glycol 200 ( 50/ 30/ 20 v/ v/ v). Animals were house individually in metabolism cages.

This study focused on the identification of the urinary and fecal metabolites. Several analytical techniques were used to separate the various metabolites including high performance liquid chromatography, thin layer chromatography, methylation, acetylation, sylation and other derivitization techniques.

The test compound was rapidly metabolized with 81, 94 and 96% of the radioactivity appearing in the urine and feces 1,2, and 3 days, respectively after dosing. The ratio of the urine to feces radioactivity was approximately 5: 4. The parent compound is extensively metabolized; only a small percentage remained unabsorbed and appeared in the feces. The n propyl side chain is first metabolized to  ,   and   hydroxy derivatives and then to  ,   and  ,   diols. The  ,   diol is further metabolized to   hydroxy carboxylic derivative, a major metabolite ( metabolite U8, 11%) appearing in the urine. The side chain is sequentially decarboxylated to yield acetic and formic acid derivatives. Once the dioxolane derivative ring is cleaved, a wide variety of metabolic reactions occurs, leading, in general, to the hydroxylation of the dichlorophenyl and triazole rings. Sulfation appeared to be the preferential route of secondary metabolism and accounted for 5.5% of the dose. ( Acceptable/ Guideline). It partially satisfies the guideline requirement for a metabolism study ( 870.7485, § 85 1) because absorption and tissue distribution of radioactivity were not determined in this study.

In another metabolism study [ MRID 41326701], the absorption, distribution, metabolism and excretion of propiconazole labeled with ( U 14C) Phenyl was investigated in groups of ( 5/ sex/ group) Sprague Dawley rats ( Crl: CD( SD) BR strain) following oral or intravenous ( iv) administration at dose levels of 0.5 mg/ kg. Additionally, one group was administered daily single oral dose of 0.5 mg/ kg of the non radiolabeled compound for 14 days followed with a single oral dose of 0.5 mg/ kg of the radiolabeled material 24 hours after the last dose. Another group was administered a single oral dose of 50 mg/ kg of the radiolabeled compound. Animals were housed individually in metabolism cages. Urine and feces were collected at regular intervals and analyzed by two dimensional thin layer chromatography and autoradiography. Tissues were collected at sacrifice time ( 168 hours) and radio assayed.

Administration of 0.5 mg/ kg of radiolabeled CGA 64250 to rats by oral or iv routes resulted in similar patterns of elimination, possibly as a result of biliary excretion. Renal elimination data suggest that 35 50% of the oral dose was absorbed. More than 90% of the administered radioactivity was eliminated in the urine and feces ( including cage washes) after 168 hours of dosing. Most of the excreted radioactivity occurred within the first 48 hours of treatment. Traces or non detectable levels were seen in the tissues and expired air. Female rats appeared to eliminate more of the radioactivity in the urine than in the feces( 46.3% vs 39.0% in the orally dosed; 43.8% vs 37.0% in the iv dosed). While male rats eliminated more radioactivity in the urine than in the feces in most of the groups except for the iv group where urine and fecal elimination were about equal. No significant differences in the excretion pattern were seen between the low and high oral dose groups or the repeated dosing group. The distribution of radioactivity in tissues was similar in low and high dose groups. Page 94 of 112 Examination of the pooled urine and fecal samples indicated that ( U 14C) Phenyl labeled CGA 64250 was extensively metabolized into 24 and 47 different radiolabeled components, respectively. The latter may reflect a difference in assay sensitivity as well as a dose level effect. Within each sample type, the pattern of metabolites varied according to sex and dose group. The radiolabled parent compound was only detected in the urine of the iv group males and females ( 27.1 and 29.9% of the urine radioactivity in males and females, respectively). In the iv urine radiolableled material co chromatographing with standards CGA 188245 ( 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), CGA 118244 ( 3.6% in females only). 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). Radiolabeld materials co chromatographing with standards CGA 91305, CGA 188245 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.

( U 14C) Phenyl radiolabeled is extensively metabolized in male and female rats following oral or iv administration. The proposed metabolic pathway involves initial side chain oxidation giving the hydroxylated propel derivative or replacement of the propyl group by carboxylic acid. The alkyl side chain attached to the dioxolane ring in CGA 64250 is probably attacked with the possible loss of the dioxolane ring itself. ( Acceptable/ Guideline). However, it partially satisfies the guideline requirement for a metabolism study ( 85 1) because most of the metabolites were not identified.

In another metabolism study [ MRID 00074506 & 00074507], urinary and fecal metabolites of ( U 14C) phenyl or 14C triazole ring labeled propiconazole administered to Tif: RAI F ( SPF) male rats were investigated. The triazole[ 3,5 14C] CGA 64250 ( specific activity 23.1 uCi/ mg) was given to 20 male rats at an average single oral dose of 31.4 mg/ kg. The phenyl[ U 14C] CGA 64250 ( specific activity 38.9 uCi/ mg) was given to 3 male rats at an average single oral dose of 32.5 mg/ kg. Animals were kept in individual metabolism cages. Urine and feces were collected and pooled for an unspecified period of time and analyzed for radioactivity.

The study mainly focused on the analysis of urinary and fecal metabolites. Within 3 days > 95% of the administered triazole labeled dose was excreted in urine ( 52%) and feces ( 43%). Animals treated with the phenyl label showed a similar pattern of excretion in urine ( 51%) and feces ( 48%).

Examination of the 0 24 hour urine by two dimensional TLC revealed 12 metabolites in both the triazole and phenyl labeled and a 13th metabolite in the triazole labeled compound. No parent material was detected. When the urine was incubated with    glucurodinase or with   glucurodinase/ aryl sulfatase certain metabolite fractions disappeared suggesting the presence of glucuronic acid and sulfuric acid conjugates. Two other fractions co chromatographed with CGA 77502 and CGA 58533. High voltage electrophoresis showed 80% of the urinary metabolites to be acidic and fecal metabolites were some what polar. Page 95 of 112 The percentages of fecal metabolites extracted and distributed at various pH's were not substantially different between the triazole and phenyl labeld CGA 64250. TLC of the fecal extracts revealed at least 8 metabolites, which were less polar than the urinary metabolites. TLC also indicated the presence of metabolites CGA 77502 and CGA 58533 in addition to unchanged parent material ( 5% of fecal radioactivity).

The similarities in the excretion pattern and metabolite distribution from the two different labels suggest that the bridge between the phenyl ring and the triazole ring remained intact.

The proposed major metabolic pathway appears to involve the cleavage of the dioxalone ring with subsequent dechlorination and conjugation and through the oxidation of the propel side chain. The metabolic profile of both urine and feces appear to be similar except for the presence of parent material in the feces while the urine had conjugated phenolic metabolites. ( Acceptable/ Guideline). However, it partially satisfies the guideline requirement for a metabolism study ( 870.7485, § 85 1) because it did not provide absorption and pharmacokinetic data.

870.7485 Metabolism  Mouse In a metabolism study [ MRID 00164795], the absorption, distribution, metabolism and excretion of ( U 14C) phenyl labeled propiconazole was investigated in CD 1 mice and Tif: RAI F ( SPF) rats. Male and female mice ( 5/ dose level) were fed ad libitum unlabeled CGA 64250 ( Batch No. OP 412127, 91.1% purity) in the diet for 21 days at levels of 5, 100 or 2500 ppm followed by a single oral dose of the radiolabeled CGA 64250 ( Batch No. GAN VA 43) at the corresponding levels ( equivalent to 0.81, 16.8 and 434 mg/ kg for males and 1.02, 21.5 and 475 mg/ kg for the females). Three female mice were given a bolus dose of 600 mg/ kg 14C CGA 64250 without pretreatment of unlabeled compound ( these mice showed severe signs of toxicity and two died 48 72 hours post dosing). Two male rats were given 9.4 mg/ kg single oral dose of the 14C CGA 64250 without pretreatment of unlabeled compound. After 14C CGA 64250 dosing, animals were kept in glass metabolism cages. Urine and feces were collected at 24 hour intervals. Animals were killed 4 days post 14C dosing. Blood, liver, kidneys, lungs and remaining carcass were taken for analysis.

Excretion: Mice pre treated with the unlabeled CGA 64250 excreted 83 103% of the administered 14C radioactivity within 96 hours ( mostly within the first 24 48 hours) in the urine and feces. More radioactivity ( particularly at the higher doses of 100 and 2500 ppm) was excreted in the urine than in the feces ( 1.5 3.7x) in males and females. The high dose females excreted the least amount ( 83% of the administered dose ( AD)). Total recovered radioactivity ranged from 88 106% of the AD. The male rats excreted nearly equal amounts of the radioactivity in urine ( 48%) and feces ( 54%).

Tissue Disribution: Tissues and carcass residues were less than 0.55% of the AD in treated rats and mice. Four days post dosing with 14C CGA 64250, residues were detected in the liver in rats and liver, kidneys and carcass in mice. Page 96 of 112 Urinary Metabolites: Two dimensional TLC revealed 15 30 metabolites in the 0 24 urine samples ( identified in the report by their TLC code). Metabolites U1, U2, U9, U12, U17, U18 representing 5 19%, 6 73%, 2 8%, 2 22%, 2 3% and 1 16% of the urine radioactivity, respectively were the most predominant in the two species. Metabolite U2 was highest in the male mice urine ( 61 73%). Female mice urine contained 29 36% while the male rat had the least ( 6%) of the U2 metabolite. The U12 fraction was another example of species and sex difference in metabolic products. At 5 and 100 ppm female mice ( and the male rats) excreted more of the U12 metabolite than in the other groups ( 18 and 21% in female mice, respectively and 22% in male rats). In an earlier study this metabolite was identified as   hydroxy carboxyacid ( metabolite CU).

When mouse urine was incubated with   glucuronidase then 75 85% of the U2 fraction disappears giving rise to a more unpolar U18 fraction. In rat urine, however, the most polar fraction U1 completely disappears after   glucuronidase incubation and forms several unpolar fractions while the U2 fraction of the rat urine is not significantly affected. The U18 fraction consisted of at least two compounds, one is the alcohol CGA 91305 and the other is the analogus ketone CGA 91304. The major urinary metabolite isolated from the U2 fraction was determined to be Met IU, the glucuronic acid conjugate of metabolite CGA 91305.

Metabolic Pathway: It was concluded that the major metabolic pathway in mice proceeds via elimination of the dioxolane ring leading via ketone formation ( CGA 91304) to the corresponding acid to yield metabolite CGA 91305. In males this represents 30% of the Ad whereas in the females it represents 15% of the AD. In rats, the unpolar metabolite fractions U15 through U18 represent metabolites where the dioxolane ring has been cleared. In conclusion mice cleaved the dioxolane ring to a greater extent ( 70% and 40% for males and females, respectively) than do male rats ( 30%)."( Acceptable/ Non Guideline). Page 97 of 112 N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 CH3 CH2 N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 CH3 CH2 * * *

N HC =

= CH N N CH2 C Cl Cl O N HC =

= CH N N CH2 CH Cl Cl OH CGA 64250, triazole label CGA 64250, phenyl label CGA 77502 CGA 58533 APPENDIX 1: REFERENCE COMPOUNDS Page 98 of 112 N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 CH3 CH2 N HC =

= CH N N CH2 C Cl Cl O N HC =

= CH N N CH2 CH Cl Cl OH N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH CH2 OH COOH N HC =

= CH N N CH2 C Cl Cl O CH2 CH CH2 COOH CH2 N HC =

= CH N N CH2 CH Cl Cl OH OH N HC =

= CH N N CH2 C Cl OH OH N HC =

= CH N N CH2 C Cl OH OH Glucuronic acid Sulfuric acid Conjugates CGA 64250 Appendix 2: Proposed major metabolic pathways of CGA 64250*

* Chart from page 11 of MRID 00074507: 14C triazole or phenyl labeled propiconazole in the Rat Page 99 of 112 N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 CH3 CH2 N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 CH2 CH2 N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 CH3 CH OH OH N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 COOH CH2 N HC =

= CH N N CH2 C Cl Cl O O CH2 CH C COOH CH2 N HC =

= CH N N CH2 C Cl Cl O O CH2 CH COOH OH N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH CH3 CH2 OH N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH CH3 CH OH OH N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH CH2 CH2 OH CH2 C Cl Cl O O CH2 CH COOH CH2 OH N HC =

= CH N N Met. H F (< 1%)

Met. W F , X F , Y F ( 1%)

Met. Z F7 ( 1%) Met. U F (< 1%)

Met. Eu 2 , Ku, Z F , Z F1 ( 3%) Met. Cu, Du, Xu, Wu, TF ( 14%)

Met. Eu3 ( 2%)

Met. Eu 1 ( 2%) 2) Appendix 1: Proposed Metabolic Pathway of 14C Triazole Propiconazole in the Rat ( taken from of study MRID 42403901 ( Fig 16): values represent percent of dose) 1) Page 100 of 112 N HC =

= CH N N CH2 C N HC =

= CH N NH Cl Cl Cl Cl HOOC O N HC =

= CH N N CH2 C Cl Cl O N HC =

= CH N N CH2 C Cl N HC =

= CH N N CH2 C Cl N HC =

= CH N N CH 2 Cl Cl N HC =

= C N N CH2 CH Cl Cl OH N HC =

= CH N N CH2 C N HC =

= CH N N CH2 Cl Cl N HC =

= N N CH2 Cl Cl OH OH OH OH OH OH OH OH OH OH C OH OH CH CH CH OH Cl OH SCH3 SCH3 SCH3 SCH3 Met. Zu16, Zu36 ( 2%)

Met. LF (< 1%) Met. Hu, Zu18, Zu23, Zu32, CF ( 3%) 5)

Met. Lu, Ru, Zu7, Zu11, Zu20, Zu22 SF ( 6%) 5)

Met. Tu ( 1%)

Met. Zu9 (< 1%) Met. Zu3, Zu14, Zu15 (< 1%) 5) Met. KF, Zu13, Zu4 Zu17 ( 3%) 5)

Met. Pu, Zu, Zu2 ( 1%) Met. Zu19, Zu27, DF ( 3%) 5)

Met. Z29a (< 1%) Met. Zu6, Zu10, Zu12, Zu24 Zu25, Zu33, Zu34, Zu 29b ( 4%) 5) 4) 4)

1) These figures are based on the amounts of metabolites actually isolated 2) Hypothetical intermediate 3) Metabolite Zu16 might be metabolically formed from all metabolites above 4) Artifacts 5) Metabolites partially excreted as sulfuric and/ or glucuronic acid conjugate 3) 3) 3) 3)

N HC =

= CH N N CH2 CH Cl Cl OH OH N HC =

= C N N CH2 CH Cl Cl OH OH , N HC =

= CH N N CH 2 CH Cl Cl OH Page 101 of 112 * N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH CH3 CH2 OH N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 CH2 OH N HC =

= CH N N CH2 C Cl Cl O O CH2 CH COOH CH2 C Cl Cl O O CH2 CH COOH CH2 N HC =

= CH N N N HC =

= CH N N CH2 C Cl Cl O N HC =

= CH N N CH2 CH Cl Cl OH Cl Cl HOOC N HC =

= CH N N CH2 C Cl Cl O O CH2 CH CH2 CH3 CH2 CGA 64250 CGA 118244 CGA 118245 CGA 217495 CGA 217496 CGA 91304 CGA 91305 CGA 177291 APPENDIX: REFERENCE COMPOUNDS Page 102 of 112 Page 103 of 112 Page 104 of 112 REFERENCES 00058591 Bathe, R. ( 1978) Report on Acute Oral LD50 in the Rat of Technical CGA 64250: Project No. 785244. Unpublished. Ciba Geigy Corp., Greensboro, N. C.

00058596 Bathe, R. ( 1979) Report on Acute Dermal LD50 in the Rat of Technical CGA 64250: Project No. 785245. Unpublished. Ciba Geigy Corp., Greensboro, N. C.; CDL: 244271 G)

00058597 Sachsse, K.; Ullmann, L. ( 1978) Eye Irritation in the Rabbit after Single Application of Technical CGA 64250: Project No. 785248. Unpublished. Ciba Geigy Corp., Greensboro, N. C.

00058598 Sachsse, K.; Ullmann, L. ( 1978) Skin Irritation in the Rabbit after Single Application of Technical CGA 64250: Project No. 785249. Unpublished. Ciba Geigy Corp., Greensboro, N. C.; CDL: 244271 I)

00058599 Ullmann, L. ( 1979) Report on Acute Aerosol Inhalation Toxicity in the Rat of CGA 64250 EC 250 ( A 6099 B): Project No. 790741. Unpublished. Ciba Geigy Corp., Greensboro, N. C.

00058600 Ullmann, L. ( 1979) Report on Skin Sensitizing ( Contact Allergenic) Effect in Guinea Pigs of Technical CGA 64250: Project No. 785250. Unpublished. Ciba Geigy Corp., Greensboro, N. C.

00058601 Arni, P.; Muller, D. ( 1979) Salmonella/ Mammalian Microsome Mutagenicity Test with CGA 64250: No. of Experiment: 78/ 2577. ( Unpublished study received Jan 28, 1981 under 100 618; prepared by Ciba Geigy Ltd., Switzerland, submitted by Ciba Geigy Corp., Greensboro, N. C.; CDL: 244271 L)

00058602 Hool, G. ( 1979) Dominant Lethal Study: CGA 64250: Mouse: No. of Experiment: 790034. ( Unpublished study received Jan 28, 1981 under 100 618; prepared by Ciba Geigy Ltd., Switzerland, submitted by Ciba Geigy Corp., Greensboro, N. C.; CDL: 244271 M)

00058603 Hool, G.; Langauer, M. ( 1979) Nucleus Anomaly Test in Somatic Interphase Nuclei: CGA 64250: Chinese Hamster: No. of Experiment: 79 0805. ( Unpublished study received Jan 28, 1981 under 100 618; prepared by Ciba Geigy Ltd., Switzerland, submitted by Ciba Geigy Corp., Greensboro, N. C.; CDL: 244271 N) Page 106 of 112 00058604 Fritz, H.; Becker, H. ( 1979) Report on CGA 64250 Tech.: Teratology Study ( Seg. II) in Rats: Project No. 790011. Unpublished. Ciba Geigy Corp., Greensboro, NC 00058605 Fritz, H.; Becker, H. ( 1979) Report on CGA 64250 Tech.: Teratology Study ( Seg. II) in Rabbits: Project No. 790009. Unpublished. Ciba Geigy Corp., Greensboro, N. C.

00058606 Sachsse, K.; Suter, P.; Luetkemeier, H.; et al. ( 1979) CGA 64250 Techn. Three Months Toxicity Study on Rats: Project No. 790014. Final rept. Unpublished. Ciba Geigy Corp., Greensboro, N. C.

00058607 Sachsse, K.; Bathe, R.; Luetkemeier, H.; et al. ( 1979) CGA 64250 3 Month Toxicity Study on Dogs. Final rept. Unpublished. Ciba Geigy Corp., Greensboro, N. C.; CDL: 244271 R)

00074505 Hambock, H. ( 1979) Distribution, Degradation and Excretion of CGA 64250 in the Rat: Project Report 24/ 79. ( Unpublished study received Jun 8, 1981 under 100 EX 69; prepared by Ciba Geigy Ltd., Switzerland, submitted by Ciba Geigy Corp., Greensboro, N. C.; CDL: 070164 K)

00074506 Muecke, W. ( 1979) Characterization of Urinary and Faecal Metabolites of Rats after Oral Application of CGA 64250: Project Report 35/ 79. ( Unpublished study received Jun 8, 1981 under 100 EX 69; prepared by Ciba Geigy Ltd., Switzerland, submitted by Ciba Geigy Corp., Greensboro, N. C.; CDL: 070164 L)

00074507 Mucke, W. ( 1981) The Major Metabolic Pathways of CGA 64250 in the Rat: Project Report 9/ 81. ( Unpublished study received Jun 8, 1981 under 100 EX 69; prepared by Ciba Geigy Ltd., Switzerland, submitted by Ciba Geigy Corp., Greensboro, N. C.; CDL: 070164 M)

00116591 Larson, E.; Matthews, R.; Naismith, R.; et al. ( 1982) 21 Day Dermal Toxicity Study in Rabbits: [ CGA 64250 Technical]: PH 430 CG 001 82. Pharmakon Research International, Inc., Unpublished. Ciba Geigy Corp., Greensboro, NC;.

00129570 Hunter, B.; Scholey, D.; Haywood, R.; et al. ( 1982) CGA 64250: Long term Feeding Study in Mice: CBG/ 196/ 81827. Final rept. Unpublished. Huntingdon Research Centre, Eng., Ciba Geigy Corp., Greensboro, NC.

00129906 Simoneaux, B. ( 1983) Dermal Absorption of Triazole 14C CGA 64250 by Rats: Report No. ABR 82068. ( Unpublished study received Jul 21, 1983 under 100 641; submitted by Ciba Geigy Corp., Greensboro, NC; CDL: 250782 G) Page 107 of 112 00129918 Hunter, B.; Slater, N.; Heywood, R.; et al. ( 1982) CGA 64250: Potential Tumorigenic and Toxic Effects in Prolonged Dietary Administration to Rats: CBG 193/ 8284 ( Test No. 789023). Final rept. Huntingdon Research Centre, Eng., Unpublished. Ciba Geigy Corp., Greensboro, NC.

00131098 Simoneaux, B. ( 1983) Dermal Absorption of Triazole 14C CGA 64250 by Rats: Report No. ABR 82068. ( Unpublished study received Sep 8, 1983 under 100 617; submitted by Ciba Geigy Corp., Greensboro, NC; CDL: 251239 I)

00132946 Simoneaux, B. ( 1983) Dermal Absorption of Triazole 14C CGA 64250 by Rats: M5 62 2A: Report No. ABR 82068. ( Unpublished. Ciba Geigy Corp., Greensboro, NC; CDL: 072224 V.

00133343 Arni, P. ( 1982) Saccharomyces cerevisiae D7/ Mammalian microsome Mutagenicity Test in vitro with CGA 64250 ( Test for Mutagenic Properties in Yeast Cells): Experiment No. 811558. ( Unpublished study received Dec 12, 1983 under 100 617; prepared by Ciba Geigy Ltd., Switz., submitted by Ciba Geigy Corp., Greensboro, NC; CDL: 072206 C)

00133347 Puri, E. ( 1982) Autoradiographic DNA Repair Test on Human Fibroblasts: CGA 64250 ( in vitro Test for DNA damaging Properties): Experiment No. 811655. ( Unpublished study received Dec 12, 1983 under 100 617; prepared by Ciba Geigy Ltd., Switz., submitted by Ciba Geigy Corp., Greensboro, NC; CDL: 072206 G)

00133348 Puri, E. ( 1982) Autoradiographic DNA Repair Test on Rat Hepatocytes: CGA 64250 ( in vitro Test for DNA damaging Properties): Experiment No. 811514. ( Unpublished study received Dec 12, 1983 under 100 617; prepared by Ciba Geigy Ltd., Switz., submitted by Ciba Geigy Corp., Greensboro, NC; CDL: 072206 H)

00133350 Fritz, H.; Giese, K.; Zak, F. ( 1981) Report on CGA 64250 Tech.: 2 Generation Study in Rats: Test No. 79 0010. ( Unpublished study received Dec 12, 1983 under 100 617; prepared by Ciba Geigy Ltd., Switz., submitted by Ciba Geigy Corp., Greensboro, NC; CDL: 072206 K)

00143454 Ciba Geigy Corp. ( 1984) Response by Ciba Geigy to the April 12, 1984 Letter Regarding Rat and Rabbit Teratology Studies with CGA 64250 Technical. Unpublished. 467 p. 00151502 Ciba Geigy Corp. ( 1985) Response to EPA Review of the Two Year Dietary Oncogenicity and Chronic Toxicity Study with CGA 64250 Technical: Historical Control Data and an Addendum to the HRC Report No. CBG 193/ 8284. Unpublished. 373 p. Page 108 of 112 00151502 Ciba Geigy Corp. ( 1985) Response to EPA Review of the Two Year Dietary Oncogenicity and Chronic Toxicity Study with CGA 64250 Technical: Includes Historical Control Data and an Addendum to the HRC Report No. CBG 193/ 8284. Unpublished. 373 p.

00151503 Ciba Geigy Corp. ( 1985) Response to the EPA Review of the Long Term Feeding Study in Mice with CGA 64250 Technical: Chemistry Data of Test Material, Details of Diet Preparation, Summary of Incidence of Clinical Signs, and Addendum to Report CBG 196/ 81827. Unpublished. 214 p.

00151514 Borders, C.; Salamon, C. ( 1985) Two Generation Reproduction Study in Albino Rats with CGA 64250 Technical: Toxigenics Study 450 1202. Unpublished study prepared by Toxigenics, Inc. 1886 p.

00151515 Johnson, W.; Thompson, S. ( 1985) One year Subchronic Oral Toxicity Study in Beagle Dogs with CGA 64250 Technical: ( Final Report): FDRL Study No. 7737. Unpublished. Food and Drug Research Laboratories, Inc. 570 p.

00151516 Waechter, F.; Bentley, P.; Staeubli, W. ( 1984) The Effect of Propiconazole on Drug Metabolizing Enzymes in the Liver of Male Rats and Mice. Unpublished. Ciba Geigy Ltd. 22 p.

00151517 Froehlich, E.; Bentley, P.; Staeubli, W.; et al. ( 1984) Promotion Study with CGA 64250: Study on the Influence of CGA 64250 in the Formation of Focal Proliferative Changes in the Rat Liver: GU Exploratory Research Project No. 834015. Unpublished. Ciba Geigy Ltd. 553 p.

00163164 Salamon, C. ( 1983) Two generation Reproduction Study in Albino Rats Using CGA 64250 Technical: Study No. 450 1202. Unpublished study prepared by ToxiGenics, Inc. 20 p.

00164469 Murphy, T.; Brown, K.; Doornheim, D.; et al. ( 1986) Dermal Absorption of Carbon 14 Propiconazole in Rats after a Ten hour Exposure Period: Report No. ABR 86053. Unpublished. Ciba Geigy Corp. 76 p.

00164794 Ballantine, L. ( 1986) Propiconazole Animal Metabolism Update: Metabolism in Mice: Dermal Absorption in the Rat: Report No. ABR 86071. Unpublished. Ciba Geigy Corp. 10 p.

00164794 Ballantine, L. ( 1986) Propiconazole Animal Metabolism Update: Metabolism in Mice: Dermal Absorption in the Rat: Report No. ABR 86071. Unpublished compilation prepared by Ciba Geigy Corp. 10 p.

00164795 Bissig, R. ( 1986) The Metabolism of C14 phenyl CGA 64250 in Mice after Pretreatment with Unlabelled CGA 64 250: Project Report 6/ 86. Unpublished. Ciba Geigy Limited. 52 p. Page 109 of 112 00164796 Hamboeck, H. ( 1979) Distribution, Degradation and Excretion of CGA 64250 in the Rat: Project Report 24/ 79. Unpublished. Ciba Geigy Limited. 19 p.

00164797 Muecke, W. ( 1981) The Major Metabolic Pathways of CGA 64250 in the Rat: Project Report 9/ 81. Unpublished study prepared by Ciba Geigy Limited. 13 p.

00164798 Muecke, W. ( 1983) The Metabolism of CGA 64250 in the Rats: Project Report 24/ 83. Unpublished. Ciba Geigy Limited. 145 p.

00164800 Raab, D.; Youreneff, M.; Giknis, L.; et al. ( 1986) CGA 64250 Technical: A Teratology Study in New Zealand White Rabbits: Toxicology/ Pathology Report 86043 ( MIN 852172). Unpublished. Ciba Geigy Corp. 437 p.

40425001 Giknis, M. ( 1987) CGA Technical: Teratology ( Segment II) Study in Rats: Laboratory Project ID 86004. Unpublished. Ciba Geigy Corporation. 425 p.

40425002 Mallows, S.; Levy, E.; Goknis, M.; et al. ( 1987) CGA 64250: A Modified Teratology ( Segment II) Study in Albino Rats Laboratory Project ID 86189. Unpublished. Ciba Geigy Corporation. 408 p.

40425004 Raab, D.; Youreneff, M.; Giknis, M.; et al. ( 1987) Propiconazole: A Teratology Study in New Zealand Rabbits: Final Report Amendment No. 1: Laboratory Project ID 86043. Unpublished. Ciba Geigy Corporation. 125 p.

41178301 Stevens, J. ( 1989) Propiconazole Technical: Perspective: Liver Tumor Response Noted in Male Mice After the Administration of an Excessive Level of Propiconazole. Unpublished. Ciba Geigy Corp. 23 p.

41326701 Cresswell, D. ( 1989) C14 Phenyl CGA 64250: Absorption, Distribution, Metabolism and Excretion in the Rat: Lab Project Number: 380/ 105. Unpublished. Hazleton UK. 520 p.

41594801 Hartmann, H. ( 1988) CGA 64250 Technical: Acute Aerosol Inhalation Toxicity Study in Rats: Lab Project Number: 871471. Unpublished. Ciba Geigy Ltd. 22 p.

41594802 Deparade, E. ( 1983) CGA 64250 Technical: Salmonella/ Mammalian Microsome Mutagenicity Test: Lab Project Number: 830121. Unpublished study prepared by Ciba Geigy Ltd. 31 p.

41594803 Strasser, F. ( 1987) CGA 64250 Technical: Micronucleus Test ( Chinese Hamster): Lab Project Number: 860359. Unpublished study. Ciba Geigy Ltd. 28 p. Page 110 of 112 41594804 Cresswell, D. ( 1989) C14 phenyl CGA 64250: Absorption, Distribution, Metabolism and Excretion in the Rat: Lab Project No. 380/ 105. Unpublished. Hazleton UK. 520 p.

42050501 Potrepka, R.; Turnier, J. ( 1991) Subchronic Dietary Toxicity Study with CGA 64250 in Mice: Lab Project Number: F 00098. Unpublished. Ciba Geigy Corp. 302 p.

42050502 Potrepka, R.; Turnier, J. ( 1991) 13 Week Dietary Toxicity Study with CGA 64250 in Male Mice: Lab Project Number: F 00107. Unpublished. Ciba Geigy Corp. 226 p.

42050504 Ogorek, B. ( 1983) Intrasanguine Host Mediated Assay with S. typhimurium: CGA 64250: Lab Project Number: 830120. Unpublished. Ciba Geigy Ltd. 21 p.

42050505 Strasser, F. ( 1984) Chromosome Studies on Human Lymphocytes in vitro: CGA 64 250: Lab Project Number: 840025. Unpublished. Ciba Geigy Ltd. 19 p.

42403901 Mucke, W. ( 1983) The Metabolism of CGA 64250 in the Rat: Lab Project Number: 24/ 83. Unpublished. Ciba Geigy Ltd. 148 p.

42415701 Murphy, T. ( 1986) Dermal Absorption of C14 Propiconazole: Addendum to ABR 86053: Lab Project Number: ABR 86064. Unpublished. Ciba Geigy Corp. 85 p.

44381401 Gerspach, R. ( 1997) CGA 64250 Technical: 18 Month Oncogenicity Study in Mice: Lab Project Number: 943126. Unpublished. Novartis Crop Protection Ag. 453 p. 93194026 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00058591. Acute Oral Toxicity in the Rat: Study # 785244. Unpublished. CIBA GEIGY Limited. 10 p.

93194027 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00058596. Acute Dermal Toxicity in the Rat: Propiconazole: Study # 785245. Unpublished. CIBA CEIGY Limited. 10 p.

93194029 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00058597. Primary Eye Irritation in the Rabbit: Study 785248. Unpublished. CIBA CEIGY Limited. 10 p.

93194030 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00058598. Primary Dermal Irritation in the Rabbit: Propiconazole: Study # 785249. Unpublished. CIBA CEIGY Limited. 10 p. Page 111 of 112 93194031 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00058600. Skin Sensitization in the Guinea Pig: Propiconazole: Study # 785250. Unpublished. CIBA CEIGY Limited. 10 p.

93194032 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00058606. 90 Day Toxicity Study in Rats: Propiconazole: Study # 790014. Unpublished. CIBA CEIGY Limited. 13 p.

93194033 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00058607. 90 Day Toxicity Study in Dogs: Study # 785751. Unpublished. CIBA GEIGY Limited. 12 p.

93194034 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00116591. 21 Day Dermal Study in Rabbit: Study # 430 CG 001 82. Unpublished. Pharmakon Research International. 12 p.

93194035 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00129918 and Related MRIDs 00074494, 00151502. Combined Chronic Oncongenicity/ Toxicity Study in Rats: Study # 193/ 8284. 15 p.

93194036 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00151515. One Year Oral Toxicity Study in the Dog: Study # 7737. 13 p.

93194037 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00129570 and Related MRIDs 00084153, 00151503, 00130844. Long Term Feeding Study in Mice: Propiconazole: Study # 196/ 81827. 14 p.

93194038 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID Unpublished. CIBA GEIGY Corp. 12 p.

93194039 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 40425002. Modified Teratology Study in Rats: Propiconazole: Study # MIN 862244. Prepared by CIBA GEIGY Corp. 12 p.

93194040 Gillis, J.; Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00164800 and Related MRIDs 40425004. Teratology Study in Rabbits: Propiconazole: Study # MIN 852172. Prepared by CIBA GEIGY Corp. 12 p.

93194041 Tisdel, M. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00138167 and Related MRIDs 00151514, 00163164. Two Generation Reproduction Study in Rats: Study # 450 1202. Prepared by Toxigenics, Inc. 12 p.

93194042 Breckenridge, C. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 41594802. Salmonella/ Mammalian Microsome Mutagenicity Test: Propiconazole: Study No. 830121. Unpublished. Ciba Geigy Limited. 12 p. Page 112 of 112 93194043 Breckenridge, C. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 41594803. Micronucleus Test  Chinese Hamster: Propiconazole: Study No. 860359. Unpublished. Ciba Geigy Limited. 12 p.

93194044 Breckenridge, C. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 00133348 and Related MRIDs 00151509. DNA Repair Test, Rat Hepatocytes: Propiconazole: Study # 811514. Unpublished. CIBA GEIGY Limited. 12 p.

93194045 Hochman, J. ( 1990) Ciba Geigy Corp. Phase 3 Summary of MRID 41326701. Propiconazole  Rat Metabolism: Project 380/ 150. Hazleton UK. 17 p.

93194083 Sachsse, K.; Suter, P.; Luetkemeier, H. et al. ( 1990) Ciba Geigy Corp. Phase 3 Reformat of MRID 00058606. Three Months Toxicity Study on Rats: Propiconazole: Study # 790014. Unpublished. CBIA GEIGY Limited. 195 p.

93194084 Sachsse, K.; Bathe, R.; Luetkemeier, H. et al. ( 1990) Ciba Geigy Corp. Phase 3 Reformat of MRID 00058607. Three Month Toxicity Study on Dogs: Propiconazole: Study # 785751. Prepared by Ciba Geigy Limited. 204 p.

46604601 Milburn, G. M. ( 2005). CGA 64250: Acute neurotoxicity study in rats. Central Toxicology Laboratory: Alderly Park Macclesfield, Cheshire, UK. CTL # AR7501, June 29, 2005. MRID 46604601. Unpublished, 648 p.

46604602 Barnes, E. 2004. CGA 64250: Preliminary acute neurotoxicity study in rats. Central Toxicology Laboratory: Alderly Park Macclesfield, Cheshire, UK. CTL # AR7500, November 19, 2004. MRID 46604602. Unpublished, 9 p.

CC: Yan Donovan