1 of 52 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM DATE: 7/ 20/ 06 SUBJECT: Azoxystrobin. Human Health Risk Assessment for New Uses on Foliage of Legume Vegetables, Group 7; Fruiting Vegetables, Group 8 ( Except Tomato); Pea and Bean, Succulent and Dried Shelled ( Except Soybeans), Subgroups 6B and 6C; Nongrass Animal Feeds, Group 18; and Citrus; and Section 18 Requests for Groups 6 and 7 to Control Soybean Rust.

Petition # 5E6916 05FL11 05TN11 Chemical #: 128810 DP Num: 317291 317331 317333 Class: Fungicide 40 CFR: § 180.507 Trade Name: Amistar   , Quadris ® Flowable, Abound ® Fungicide, Heritage ® Fungicide, Quilt   Fungicide EPA Reg. #: 100 1164, 100 1098, 10182 415, 100 1093, 110 1178 FROM: W. Cutchin, Chemist Alternative Risk Integration Assessment Team ( ARIA) Registration Division ( 7505P)

THRU: B. O'Keefe, Branch Senior Scientist Registration Action Branch 3 Health Effects Division ( 7509P)

TO: D. Rosenblatt/ B. Madden PM 05 Registration Division ( 7505P) 2 of 52 1.0 EXECUTIVE SUMMARY................................................................................................. 3 2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION............................. 11 3.0 HAZARD CHARACTERIZATION ............................................................................... 13 3.1 Hazard Profile .............................................................................................................. 13 3.2 FQPA Considerations .................................................................................................. 13 3.3 Dose Response Assessment .......................................................................................... 14 3.4 Endocrine Disruption................................................................................................... 16 4.0 EXPOSURE ASSESSMENT........................................................................................... 16 4.1 Summary of Proposed Uses .......................................................................................... 16 4.2 Dietary Exposure/ Risk Pathway.................................................................................. 22 4.2.1 Residue Profile....................................................................................................... 22 4.2.2 Dietary Analysis..................................................................................................... 28 <IP_ADDRESS> Acute Dietary .................................................................................................. 28 <IP_ADDRESS> Chronic Dietary .............................................................................................. 30 <IP_ADDRESS> Cancer Dietary................................................................................................ 30 4.3 Water Exposure/ Risk Pathway.................................................................................... 30 4.4 Residential Exposure/ Risk Pathway............................................................................ 31 4.4.1 Home Uses.............................................................................................................. 32 4.4.2 Residential Handler Exposure and Risk............................................................... 32 4.4.3 Residential Postapplication Exposure and Risk................................................... 35 4.4.4 Recreational Postapplication Exposure and Risk ................................................ 39 4.4.5 Off Target Non Occupational Exposure............................................................... 39 5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION............. 39 5.1 Acute Aggregate Risk................................................................................................... 39 5.2 Short Term Aggregate Risk......................................................................................... 39 5.3 Intermediate Term Aggregate Risk............................................................................. 41 5.4 Chronic Aggregate Risk............................................................................................... 41 5.5 Cancer Aggregate Risk ................................................................................................ 42 6.0 CUMULATIVE RISK ..................................................................................................... 42 7.0 OCCUPATIONAL EXPOSURE..................................................................................... 42 7.1 Occupational Handler .................................................................................................. 42 7.2 Occupational Postapplication Exposure and Risk ..................................................... 51 8.0 DATA NEEDS.................................................................................................................. 51 8.1 Toxicology..................................................................................................................... 51 8.2 Residue Chemistry ....................................................................................................... 52 8.3 Occupational/ Residential................................................................................................ 52 References ................................................................................................................................ 52 3 of 52 1.0 EXECUTIVE SUMMARY Background In petition PP# 5E6916, the Interregional Research Project No. 4 ( IR 4) is proposing the use of azoxystrobin on citrus; foliage of legume vegetables, Group 7; vegetables, fruiting, Group 8 ( except tomato); pea and bean, succulent and dried ( except soybean), Subgroups 6B and 6C; and nongrass animal feeds, Group 18. In 05FL11 and 05TN11, the states of Florida and Tennessee are requesting quarantine exemption Section 18 registrations for the use of multiple formulations, one of which includes azoxystrobin, for the treatment of soybean rust on specialty legumes in Group 6 ( excluding soybeans) and Group 7. Assessments of human exposures and risks were conducted for acute and chronic dietary risk; exposure and risk to azoxystrobin residues in water; residential exposure and risk; aggregate risk; and exposure and risk to workers.

Azoxystrobin is a broad spectrum fungicide for control of many plant diseases. It has the same biochemical mode of action as the naturally occurring strobilurins and is structurally related to them. Azoxystrobin is a   methoxyacrylate. It is in the same chemical class as trifloxystrobin. Azoxystrobin acts by inhibiting electron transport. There are numerous tolerances established for azoxystrobin ranging from 0.02 ppm on cottonseed to the Herb Subgroup 19A, dried, except chive at 260 ppm.

Proposed Uses For petition PP# 5E6916, the proposed uses are for four applications of azoxystrobin at 0.1 0.25 lb ai/ A, up to 1.0 lb ai/ A/ season at 0 day preharvest interval ( PHI) on the foliage of legume vegetables, Group 7; vegetables, fruiting, Group 8 ( except tomato); pea and bean, succulent and dried ( except soybean), Subgroups 6B and 6C; and nongrass animal feeds, Group 18. The petitioner has also proposed a postharvest use on citrus for two applications using water, wax/ oil emulsion, or aqueous dilution of wax/ oil emulsion at 0.53 1.06 lb ai/ 250,000 lbs of fruit up to 1.5 lb ai/ 250,000 lbs of fruit following the previously established use for four applications at 0.20 0.25 lb ai/ A, up to 1 lb ai/ A/ season at 0 day PHI.

For 05FL11 and 05TN11, axozystrobin as formulated in Quilt   Fungicide ( EPA REG. No. 110 1178) will be applied twice at 0.014 lb ai/ A, up to 0.028 lb ai/ A/ season with a 0 day PHI on Group 6 ( except soybeans) and Group 7. The use is requested in response to the threat of soybean rust on specialty legumes.

Toxicology and Dose Response The toxicology database is complete and there are no data gaps. Endpoints were chosen for acute and chronic dietary, short and intermediate term incidental oral and inhalation but not for short, intermediate or long term dermal exposure assessment. No short, intermediate or long term dermal endpoints were chosen because no dermal or systemic toxicity was seen at the limit dose ( 1000 mg/ kg/ day) in a repeated dose 21 day dermal toxicity study in rats. 4 of 52 The acute dietary reference dose ( RfD) is based on the results of an acute neurotoxicity study in which rats had diarrhea at the lowest observed adverse effects level ( LOAEL) of 200 mg/ kg/ day. The acute RfD and the acute population adjusted dose ( aPAD) are 0.7 mg/ kg/ day ( uncertainty factor or UF= 300). The chronic dietary RfD is based on the results of a combined chronic toxicity/ carcinogenicity study in which male rats had reduced body weights, food consumption and food efficiency, and bile duct lesions at the LOAEL of 34 mg/ kg/ day and the LOAEL for females is 117 mg/ kg/ day based on reduced body weights. The no observed adverse effects level ( NOAEL) in males is 18.2 mg/ kg/ day and the NOAEL for females is 22.3 mg/ kg/ day. The chronic RfD and the chronic population adjusted dose ( cPAD) are 0.18 mg/ kg/ day ( UF= 100).

The short term incidental oral NOAEL is from a prenatal developmental oral study in rats, based on increased maternal diarrhea and other effects observed at the LOAEL of 100 mg/ kg/ day). The NOAEL is 25 mg/ kg/ day ( UF= 100). The intermediate term incidental oral NOAEL is from a 90 day feeding study in rats, based on decreased body weight gain and clinical signs observed at the LOAEL of 211/ 223 mg/ kg/ day for males and females, respectively. The NOAEL is 21 mg/ kg/ day ( UF= 100). No short, intermediate or long term dermal endpoints were chosen because no dermal or systemic toxicity was seen at the limit dose ( 1000 mg/ kg/ day) in a repeated dose 21 day dermal toxicity study in rats. The short term inhalation NOAEL is the same as that selected for short term incidental oral exposure. Similarly, the intermediate term inhalation NOAEL is the same as that selected for intermediate term incidental oral. A longterm inhalation endpoint was not chosen because the risk assessment is not applicable to the current use pattern for azoxystrobin.

The FQPA Safety Factor Committee recommended that the 10 fold safety factor for increased susceptibility of infants and children be removed ( i. e., reduced to 1x) in assessing the risk posed by this chemical.

There is no evidence for mutagenicity or carcinogenicity. Azoxystrobin has been classified as " not likely to be carcinogenic in humans" by Hazard Identification Assessment Review Committee ( HIARC, 11/ 7/ 96); therefore, no carcinogenic risk analyses were performed.

Dietary Risk from Drinking Water Sources Although moderately persistent in soils and stable to hydrolysis, the likelihood of azoxystrobin moving into ground and surface water is low due to high soil/ water partitioning coefficients and low single application rates. The HED Metabolism Assessment Review Committee ( MARC) determined that the residue of concern in water is azoxystrobin only, because the parent compound is the most likely residue to be found in surface water.

Monitoring data are not available to perform a quantitative drinking water risk assessment for azoxystrobin at this time. EFED provided estimated environmental concentrations ( EDWCs) for azoxystrobin based upon the crop with the highest application rate ( turf). Tier 1 surface and ground water EECs were generated using EFED's FIFRA Index Reservoir Screening Tool ( FIRST) and Screening Concentration in Ground Water ( SCI GROW) 5 of 52 models, respectively. As the use of azoxystrobin on turf has the highest yearly application rate ( 5 lb/ A/ year), this application rate was used in the FIRST and SCI GROW models to estimate the concentrations of this chemical in surface and ground water, respectively. Should the yearly application rate on non cropland change, or should a use of azoxystrobin with a higher use rate be added, EFED may have to revise the EDWCs accordingly.

Based on the SCI GROW screening model and the highest use rate ( turf use, 9 applications per year, 10 day interval, and 0.55 lb ai/ A/ application), the upper bound concentration of azoxystrobin in ground water was estimated at 3.1 ppb. This value can be used for both acute and chronic risk assessments. This value represents upper bound estimates of the concentrations that might be found in ground water which result from the use of azoxystrobin on turf. Based on the FIRST Tier 1 modeling results, azoxystrobin EECs in surface water are not likely to exceed 170 ppb for the acute ( peak) concentration or 33 ppb for the chronic ( annual average) concentration. These values represent upper bound estimates of the concentrations that might be found in surface water which result from the use of azoxystrobin on turf.

Dietary Risk Residue Chemistry Adequate plant metabolism studies on azoxystrobin have been previously conducted using grapes, peanuts, and wheat. Azoxystrobin undergoes photochemical isomerization to produce the Z isomer and is extensively metabolized in plants. Adequate livestock metabolism studies for azoxystrobin have also been submitted. The HED MARC has determined that the residues of concern in/ on plants for the tolerance expression and risk assessment are azoxystrobin [ methyl ( E) 2( 2( 6( 2 cyanophenoxy) pyrimidin 4 yloxy) phenyl) 3 methoxyacrylate] and the Z isomer of azoxystrobin, [ methyl ( Z) 2( 2( 6 ( 2 cyanophenoxy) pyrimidin 4 yloxy) phenyl) 3 methoxyacrylate]. The MARC also determined that the residue of concern in/ on livestock for the tolerance expression and risk assessment is azoxystrobin only.

Adequate methodology is available for enforcement of the established tolerances on plants. The gas chromatography with nitrogen phosphorus detector GC/ NPD method ( RAM 243/ 04) has undergone a method validation by the EPA analytical laboratory. EPA comments have been incorporated and the revised method ( designated RAM 243, dated 5/ 15/ 98; MRID 44595105) has been submitted to FDA for inclusion in the Pesticide Analytical Manual Volume II ( PAM II) as an enforcement method. Adequate methodology is available for enforcement of the established tolerances on livestock. The GC method 255/ 01 has been validated by the EPA analytical laboratory for the analysis of milk and livestock tissues. The EPA laboratory's written report with an EPA addendum to accompany the method, and the method, will be submitted to FDA for inclusion in PAM, Vol. II. Citrus samples were analyzed for residues of azoxystrobin and its Z isomer using Zeneca Report Number RAM 243/ 04, via GC/ NPD with minor modifications. Limit of detection ( LOD) for azoxystrobin and Z isomer were established at 0.0092 ppm and 0.0065 ppm in grapefruit, 0.011 ppm and 0.0074 ppm in orange, and 0.0077 ppm and 0.0056 ppm in lemon. Limit of quantitation ( LOQ) for azoxystrobin and Z isomer were established at 0.028 ppm and 0.020 ppm in grapefruit, 0.034 ppm and 0.022 ppm in orange, and 0.023 ppm and 0.017 ppm in lemon. Data pertaining to the multiresidue methods testing of azoxystrobin in conjunction with the grape tolerance petition have previously been submitted. 6 of 52 The data indicate that azoxystrobin could not be recovered through application of the multiresidue protocols. These data have been forwarded to FDA.

No new residue field trial data were submitted for the foliage of legume vegetables, Crop Group 7; vegetable, fruiting, Group 8 ( except tomato); pea and bean, succulent and dried, except soybean, Subgroups 6B and 6C; or nongrass animal feeds, Group 18. The representative commodities for Group 7 are foliar portions of any cultivar of bean, field pea, and soybean. RAB2 previously stated that as long as the use pattern is similar and the proposed field trial residue data supporting a tolerance for Group 4 are submitted and deemed adequate, it will be appropriate to request a tolerance for Group 7 at the same level as Group 4. The requirements set forth by RAB2 for the establishment of an azoxystrobin tolerance on the foliage of legume vegetables, Group 7 have been satisfied. TRB recommends for the establishment of a tolerance at 30.0 ppm for the residues of azoxystrobin on vegetables, foliage of legume, Group 7. Since the proposed tolerance on Group 7 will include a soybean hay and forage, the existing tolerances on those commodities should be removed.

There are tolerances established for members of Group 8: peppers, okra, and eggplant at 2.0 ppm, and tomato at 0.2 ppm ( CFR § 180.507). Although all the existing residue data on the Group 8 representative commodities were determined to be sufficient to establish a crop group tolerance, risk cup issues at the time precluded increasing the tomato tolerance and separate tolerances were requested on okra and eggplant. Since the existing data were determined to be adequate for a crop group tolerance, there is sufficient data to support the petition for the requested subgroup. However, the commodity definition presented by the petitioner is incorrect. A new Section F should be submitted requesting a tolerance for the residues of azoxystrobin at 2.0 ppm on vegetables, fruiting, Group 8 ( except tomato). The existing separate tolerances on pepper, okra, and eggplant should be removed.

The existing tolerance commodity definitions are: pea and bean, dried shelled, except soybean, subgroup, except cowpea, and field pea; and pea and bean, succulent shelled, subgroup, except cowpea. The subgroup tolerances excluded cowpea and field pea because there was no residue field data for forage, hay, and/ or silage as livestock feeds. In order to satisfy the data requirements, RAB3 previously indicated that residue data on the representative crops of Group 7 were required. However, as stated above, the requirements set forth by RAB2 for the establishment of an azoxystrobin tolerance on vegetables, foliage of legume, Group 7 have been satisfied. Therefore, no further residue field trial data is required. TRB recommends for the establishment of tolerances at 0.5 ppm for the residues of azoxystrobin on pea and bean, succulent shelled, Subgroup 6B; and pea and bean, dried shelled, except soybean, Subgroup 6C.

IR 4 requested that the Agency use data supporting the tolerances for vegetable, leafy, except Brassica, Group 4 at 30.0 ppm, Brassica, leafy greens, Subgroup 5B at 25 ppm, and soybean, hay at 55.0 ppm to support the establishment of tolerances for animal feed, nongrass, Group 18, forage at 30.0 ppm and animal feed, nongrass, Group 18, hay at 55.0 ppm. ChemSAC has determined that the existing data cited by the petitioner is not sufficient to support the requested tolerance. TRB recommends against the proposed tolerances on animal feed, nongrass, Group 18, forage and hay. However, TRB concluded, based on the existing use on 7 of 52 soybeans, which has the same use pattern as that proposed for animal feed, nongrass, Group 18, a reduced number of residue field trials would be appropriate. Six residue field trials each with the appropriate geographic distribution on the two representative crops for animal feed, nongrass, Group 18, alfalfa and clover are required to support a proposed azoxystrobin tolerance.

There is an existing use for azoxystrobin on citrus fruit with an established tolerance of 2.0 ppm. The citrus field trials were conducted to demonstrate the residues of azoxystrobin in fruit which were treated by simulated postharvest applications following normal preharvest use. The petitioner first treated the fruit according to the existing preharvest use and showed that quantifiable residues were found similar to those previously found from the use. Those fruit were then treated with azoxystrobin using six different postharvest methods. The highest azoxystrobin residues were detected in grapefruit, orange and lemon samples that received preharvest as well as postharvest dip treatments ranging from 1.18 to 5.43 ppm, 1.213 4.00 ppm, and 1.47 to 9.18 ppm, respectively. The results of the residue chemistry field trials indicate that the residues of azoxystrobin following both preharvest and postharvest uses are not likely to exceed the proposed tolerance on citrus fruit.

Previous uses on legumes, except soybeans, included four applications of up to 0.25 lb ai/ A with a seasonal maximum of 1.0 lb ai/ A. Residues of azoxystrobin from the established use pattern did not exceed 0.5 ppm, which is the recommended tolerance on pea and bean, succulent shelled, Subgroup 6B; and pea and bean, dried shelled, except soybean, Subgroup 6C. The requested Section 18 uses will not exceed the established tolerances; therefore TRB recommends for the requested use.

There are no processed commodities associated with the uses of azoxystrobin on foliage of legume vegetables, Group 7; vegetables, fruiting, Group 8 ( except tomato); and pea and bean, succulent and dried shelled, except soybean, Subgroups 6B and 6C. The livestock feed items of regulatory interest for the current action are cowpea seed at 0.05 ppm, cowpea hay and forage at 30.0 ppm; and soybean, forage and hay, for which the tolerance will be raised to 30 ppm. Since the worst case cattle and swine diets using existing and proposed tolerances will not exceed the level of the ruminant feeding study used to establish the current tolerances, no increase in tolerances for ruminant and swine commodities are required. None of the commodities for which tolerances are proposed have poultry feed items of regulatory interest, therefore no change in azoxystrobin poultry tolerances is required.

No new processing studies were submitted for azoxystrobin on citrus fruit. Based on the Highest Average Field Trial ( HAFT) residue for citrus fruit of 8.7 ppm from the current field trials and the average concentration factors from the previously submitted processing studies of 2.1x for pulp, and 4.6x for oil, the petitioner's requests for proposed tolerances are adequate.

The proposed uses will have no impact on the established tolerances of animal commodities. The feed items associated with the proposed uses, citrus dried pulp and canola meal, have already been considered and found to have no effect on the maximum theoretical dietary burden ( MTDB) of azoxystrobin for livestock. The addition of the only other livestock 8 of 52 feed item associated with these actions, sunflower meal, will also have no effect on the MTDB to livestock. Accordingly, the current tolerances for animal commodities are adequate.

Adequate confined and field rotational crop studies are available to support rotational crop restrictions.

Dietary Exposure Analysis The acute dietary exposure analysis for azoxystrobin is a Tier 1 assessment because no additional data were used to refine the analysis. One hundred percent of proposed and registered crops are assumed treated with azoxystrobin ( 100% CT) and tolerancelevel residues were used in the analysis. The acute dietary endpoint applies to all population subgroups including infants and children. The highest estimate for acute drinking water exposure, 170 ppb, was used in the analysis. The dietary exposure estimates for the U. S. population at 27% of the aPAD and the most highly exposed subgroup, children 1 2 yrs old, at 74% of the aPAD, do not exceed HED's level of concern.

The chronic dietary exposure analysis for azoxystrobin is a Tier 2 assessment using some percent crop treated (% CT) information for selected crops. Tolerance level residues were used in the analysis. The chronic dietary endpoint applies to all population subgroups including infants and children. The highest estimate for chronic drinking water exposure, 33 ppb, was used in the analysis. The dietary exposure estimate for the U. S. population was 8% of the cPAD and the most highly exposed subgroup, children 1 2 yrs old, was 19% of the cPAD. Risk estimates for all population subgroups are below HED's level of concern ( 100% of the cPAD).

Residential Risk Azoxystrobin is currently registered for use on residential turfgrass and ornamentals, as well as indoor surfaces. Short term exposures may occur during adult residential handling activities. HED's Draft Standard Operating Procedures ( SOPs) for Residential Exposure Assessments, and Recommended Revisions ( ExpoSAC Policy Number 12, revised 2/ 22/ 01), were used as the basis for all residential handler exposure calculations. Some of the handler exposure data used in this assessment are from the Outdoor Residential Exposure Task Force ( ORETF; the risk manager is encouraged to pursue data compensation in the event the registrant is not a member of the task force). Non occupational handler inhalation margins of exposure ( MOE) were 1,700,000 for mixing, loading and applying the WDG formulation to indoor surfaces, and 2,700,000 and 230,000 for mixing, loading and applying liquid formulation to turf, for spot application with a low pressure handwand and for broadcasting with a garden hose end sprayer to turf, respectively. These MOEs are well above the level of concern ( LOC) for nonoccupational handler scenarios.

Short and intermediate term exposures may occur during postapplication activities for adults and children ( however, adult postapplication is not assessed because no dermal hazard was identified). Toddlers may experience short and intermediate term exposure to azoxystrobin via incidental ( non dietary) ingestion during postapplication activities on treated turf ( i. e., hand tomouth object to mouth [ turfgrass], and soil ingestion) and during postapplication activities on treated indoor surfaces ( i. e., hand to mouth). The postapplication risk assessment is based on 9 of 52 generic assumptions as specified by the Recommended Revisions to the Residential SOPs and recommended approaches by HED's ExpoSAC. Postapplication non dietary ingestion MOEs ranged from 280 to 530,000 for short term exposure from hand to mouth activities on treated indoor surfaces and soil ingestion on treated turf, respectively. All calculated non occupational postapplication MOEs are greater than 100 on the day of application, and do not exceed HED's level of concern.

Aggregate Risk Acute, short term, intermediate term, and chronic aggregate risk estimates resulting from aggregate exposure to azoxystrobin from food, drinking water, and residential uses are below HED's level of concern.

For the acute aggregate risk scenario, food and drinking water exposures were taken into account in the dietary exposure assessment. The estimated dietary exposures ( food and water) for the U. S. population at 27% of the aPAD and the most highly exposed subgroup, children 1 2 yrs old, at 74% of the aPAD does not exceed HED's level of concern.

For the short term aggregate risk scenario, food, drinking water and residential exposures are taken into account. No endpoint has been selected for short term dermal exposure to azoxystrobin; therefore, this assessment will combine dietary/ incidental oral exposure with inhalation exposure. The chronic dietary exposure estimate to the U. S. population was 8% of the cPAD and the most highly exposed subgroup, children 1 2 yrs old, was 19% of the cPAD. The aggregate short term MOEs, combining food, drinking water and residential exposures ranged from 200 for children 1 2 yrs old to 2150 for females 13 49 yrs old. Risk estimates for all population subgroups are below HED's level of concern ( MOEs of 100 or less).

For the intermediate term aggregate risk scenario, food, drinking water and residential exposures are taken into account. No endpoint has been selected for intermediate term dermal exposure to azoxystrobin; therefore, this assessment will combine dietary/ incidental oral exposure with inhalation exposure. An intermediate term risk assessment is not required for adults because intermediate term residential handler scenarios are not expected to occur. However, an intermediate term risk assessment is required for infants and children because there is a residential post application oral exposure scenario. The chronic dietary exposure estimate to the most highly exposed subgroup, children 1 2 yrs old, was 19% of the cPAD. The aggregate intermediate term MOE, combining food, drinking water and residential exposures for the most highly exposed subgroup was 260 for children 1 2 yrs old. Risk estimates for all population subgroups are below HED's level of concern ( MOEs of 100 or less).

For the chronic aggregate risk scenario, food, drinking water, and residential exposures were taken into account. In this case, chronic exposure in residential settings is not expected and the aggregate chronic assessment included food and drinking water only. Since the dietary exposure assessment already includes the highest chronic exposure from the drinking water modeling data, no further calculations are necessary. The dietary exposure estimate to the U. S. population was 8% of the cPAD and the most highly exposed subgroup, children 1 2 yrs old, was 10 of 52 19% of the cPAD. Risk estimates for all population subgroups are below HED's level of concern ( 100% of the cPAD). Therefore, chronic aggregate risk is below HED's level of concern.

Occupational Exposure and Risk No chemical specific handler exposure data were submitted in support of this Section 3 registration. It is the policy of the HED to use data from the Pesticide Handlers Exposure Database ( PHED) Version 1.1 as presented in PHED Surrogate Exposure Guide ( 8/ 98) to assess handler exposures for regulatory actions when chemical specific monitoring data are not available ( HED Science Advisory Council for Exposure [ ExpoSAC] Draft Policy # 7, dated 1/ 28/ 99).

Occupational handlers' inhalation margins of exposure ( MOEs) range from 17,000 for intermediate term exposure from mixing and loading liquid formulations for aerial application and chemigation to 6,300,000 for short term mixing, loading liquids for high pressure handwand application. These MOEs are well above the level of concern ( LOC) for occupational scenarios, which is an MOE of 100 or below.

Although occupational postapplication dermal exposure is possible following treatment of use sites with azoxystrobin, because no dermal endpoints were identified for this exposure potential ( and inhalation exposure is expected to be negligible for reentry activities) a postapplication risk assessment was not conducted. Nevertheless, per the Worker Protection Standard ( WPS), a 12 hour restricted entry interval ( REI) is required for chemicals classified under Toxicity Category III or IV, which are the Toxicity Categories azoxystrobin is classified under ( Toxicity Category III for acute dermal and primary eye irritation, and Toxicity Category IV for primary skin irritation). Even though a 12 hour REI is the shortest waiting period permitted under the WPS, REIs may be further reduced from 12 hours if certain criteria are met for both the technical material and the different end use products ( EUPs). Previously, HED determined that the criteria for the technical material had been met for azoxystrobin, and RD had determined the criteria for the EUPs Abound, Amistar and Heritage had been met for those formulations, and therefore, that a 4 hour REI is acceptable for those formulations. Azoxystrobin formulation A12910C contains cyproconazole as well, which does not meet all the criteria for a reduced REI.

Recommendation for Tolerances Provided a revised Section F is received, the Agency recommends establishing permanent tolerances for the combined residues of azoxystrobin, [ methyl( E) 2( 2( 6( 2 cyanophenoxy) pyrimidin 4 yloxy) phenyl)  3 methoxyacrylate] and the Z isomer of azoxystrobin, [ methyl( Z) 2( 2( 6( 2 cyanophenoxy) pyrimidin 4 yloxy) phenyl) 3 methoxyacrylate], in/ on the following commodities be established: 11 of 52 Commodity Tolerance ( ppm)

vegetables, foliage of legume, Group 7 30.0 vegetables, fruiting, Group 8 ( except tomato) 2.0 pea and bean, succulent shelled, Subgroup 6B 0.5 pea and bean, dried shelled, except soybean, Subgroup 6C 0.5 citrus, dried pulp 20.0 citrus, oil 40.0 fruit, citrus, Group 10 10.0 TRB recommends against the requested tolerance on animal feed, nongrass, Group 18 forage and hay. The residue chemistry database is not adequate to support the requested use, and additional residue field trial data is required.

The requested Section 18 uses on speciality legumes will not exceed the established azoxystrobin tolerances; therefore TRB recommends for the requested uses.

Note to PM: The existing tolerances on soybean hay and forage, pepper, okra, and eggplant should be removed.

The restricted entry interval ( REI) on the Quilt label is 24 hours, but the REI is not indicated on the Section 18 label addendum.

2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION Azoxystrobin is a broad spectrum fungicide for control of many plant diseases. It has the same biochemical mode of action as the naturally occurring strobilurins and is structurally related to them. Azoxystrobin is a   methoxyacrylate. It is in the same chemical class as trifloxystrobin. Azoxystrobin acts by inhibiting electron transport.

TABLE 2.0.1 Test Compound Nomenclature Compound Chemical Structure 12 of 52 Common name azoxystrobin Company experimental name ICIA5504 IUPAC name methyl ( E) 2{ 2[ 6( 2 cyanophenoxy) pyrimidin 4 yloxy] phenyl} 3 methoxyacrylate CAS name methyl ( E) 2[[ 6( 2 cyanophenoxy) 4 pyrimidinyl] oxy]    ( methoxymethylene) benzeneacetate CAS # 131860 33 8 End use product/ EP Amistar   ( EPA Reg. No.: 100 1164), Quadris ® Flowable ( EPA Reg. No.: 100 1098), Abound ® Fungicide ( EPA Reg. No.: 10182 415), Heritage ® Fungicide ( EPA Reg. No.: 100 1093), Quilt   Fungicide ( EPA Reg. No.: 110 1178)

TABLE 2.0.2 Physicochemical Properties Parameter Value Melting point/ range 114 116 ° C pH 6.4 Density 1.25 g/ cm3 Water solubility ( mg/ L at 20 ° C) solvent solubility water, pH 5.2 6.7 mg/ L water, pH 7 6.7 mg/ L water, pH 9.2 5.9 mg/ L Solvent solubility ( mg/ L at 20 ° C) solvent solubility n hexane 0.057 mg/ mL methanol 20 mg/ mL ethyl acetate 130 mg/ mL toluene 55 mg/ mL acetone 86 mg/ mL dichloromethane 400 mg/ mL Vapor pressure at 25 ° C 1.1 x 10 13 kPa = 8.2 x 10 13 mg Hg Dissociation constant ( pKa) Not dissociable Octanol/ water partition coefficient Log( KOW) log POW = 2.5 UV/ visible absorption spectrum Not available 13 of 52 3.0 HAZARD CHARACTERIZATION All toxicological data requirements for azoxystrobin technical have been satisfied. HED has a high degree of confidence in the toxicology database. Acute data requirements for all enduse products have been satisfied.

3.1 Hazard Profile The acute toxicity findings for azoxystrobin are presented below in Table 3. The scientific and regulatory quality of the azoxystrobin database is high, and so is the confidence in hazard assessments based on these data.

TABLE 3. 1 Acute Toxicity Data on Azoxystrobin Technical Guideline No. Study Type MRID # Results Toxicity Category 870.1100 Acute Oral  Rat 43678122 LD50 > 5000 mg/ kg ( Limit Test) in Males & Females IV 870.1200 Acute Dermal  Rat 43678124 LD50 > 2000 mg/ kg ( Limit Test) in Males & Females III 870.1300 Acute Inhalation  Rat 43678126 LC50 Males = 0.962 mg/ L ( 95% C. I. = 0.674) Females = 0.698 mg/ L ( 95% C. I. = 0.509, 2.425) The combined LC50 was not calculated due to mortality pattern. III 870.2400 Primary Eye Irritation  Rabbit 43678128 Slight to moderate erythema and slight chemosis in all rabbits within one hour, but effects resolved within 48 hours of treatment. III 870.2500 Primary Skin Irritation  Rabbit 43678130 Very slight erythema and edema that persisted for three days on one rabbit and for one hour on another. IV 870.2600 Dermal Sensitization  Guinea Pig 43678132 No erythema or edema were found 38 or 48 hrs after challenge with test material. Not a dermal sensitizer 3.2 FQPA Considerations On August 15, 2000, the HIARC reaffirmed the FQPA Safety Factor Committee's conclusions that the available studies indicated no increased susceptibility of rats or rabbits to in utero and/ or postnatal exposure to azoxystrobin ( HED Document No. 013102, dated 12/ 10/ 96). The FQPA Safety Factor Committee considered the available toxicology data base adequate for an FQPA assessment and recommended that the 10 fold safety factor for increased susceptibility of infants and children ( as required by Food Quality Protection Act of August 3, 1996) be 14 of 52 removed ( i. e., reduced to 1x). The azoxystrobin risk assessment team evaluated the quality of the exposure data and, based on these data, recommended that the special FQPA SF be reduced to 1x. The recommendation is based upon the following:

· The toxicology data base is complete; · The developmental and reproductive toxicity data did not indicate increased susceptibility of rats or rabbits to in utero and/ or postnatal exposure; · The acute and chronic dietary food exposure assessments utilize existing and proposed tolerance level residues and 100% crop treated information for all commodities ( NOTE: The chronic dietary exposure analysis for azoxystrobin is a Tier 2 assessment using some percent crop treated (% CT) information for selected crops). By using these screeninglevel assessments, actual exposures/ risks will not be underestimated; · The exposure assessments will not underestimate the potential dietary ( food and drinking water) or non dietary exposures for infants and children from the use of azoxystrobin; · The dietary drinking water assessment utilizes water concentration values generated by model and associated modeling parameters which are designed to provide conservative, health protective, high end estimates of water concentrations which are not likely to be exceeded; and · The residential postapplication assessment is based upon the residential SOPs. The assessment is based upon surrogate study data. These data are reliable and are not expected to underestimate risk to adults or children. The residential SOPs are based upon reasonable " worst case" assumptions and are not expected to underestimate risk.

3.3 Dose Response Assessment A summary of the dose levels and endpoints for use in risk assessment are presented in Table 4 below.

TABLE 3.3 Summary of Toxicological Doses and Endpoints for Azoxystrobin for Use in Human Risk Assessment Exposure Scenario Dose Used in Risk Assessment, UF FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary general population including infants and children NOAEL < 200 mg/ kg/ day UF = 300 Acute RfD = 0.67 mg/ kg/ day FQPA SF = 1X aPAD = acute RfD FQPA SF = 0.67 mg/ kg/ day Acute Neurotoxicity  Rat LOAEL = 200 mg/ kg based on diarrhea at two hours post dose at all dose levels up to and including the LOAEL.

Chronic Dietary all populations NOAEL= 18 mg/ kg/ day UF = 100 Chronic RfD = 0.18 mg/ kg/ day FQPA SF = 1X cPAD = chronic RfD FQPA SF = 0.18 mg/ kg/ day Combined Chronic Toxicity/ Carcinogenicity Feeding study  Rat LOAEL in males/ females = 34/ 117 mg/ kg/ day based on reduced body weights in both sexes and bile duct lesions in males. Page 15 of 52 TABLE 3.3 Summary of Toxicological Doses and Endpoints for Azoxystrobin for Use in Human Risk Assessment Exposure Scenario Dose Used in Risk Assessment, UF FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects Short Term ( 1 30 days) Incidental Oral ( Residential) NOAEL= 25 mg/ kg/ day UF = 100 FQPA SF = 1X Prenatal Developmental Oral Toxicity  Rat LOAEL = 100 mg/ kg/ day based on increased maternal diarrhea, urinary incontinence, and salivation.

Intermediate Term ( 1 week to 6months) Incidental Oral ( Residential) NOAEL= 20 mg/ kg/ day UF = 100 FQPA SF = 1X 90 Day Feeding  Rat LOAEL = 211/ 223 mg/ kg/ day in males/ females based on decreased body weight gain in both sexes and clinical signs indicative of reduced nutrition.

Short, Intermediate, and Long Term Dermal ( Occupational/ Residential) none No dermal or systemic toxicity was seen at the limit dose ( 1000 mg/ kg/ day). This risk assessment is not required. 21 Day Repeated Dose Dermal  Rat Short Term ( 1 30 days) Inhalation ( Occupational/ Residential) Oral NOAEL= 25 mg/ kg/ day Use route to route extrapolation ( inhalation absorption rate = 100%). LOC for MOE = 100 ( Occupational/ Residential) Prenatal Developmental Oral Toxicity  Rat LOAEL = 100 mg/ kg/ day based on increased maternal diarrhea, urinary incontinence, and salivation.

Intermediate Term ( 1 week to 6months) Inhalation ( Occupational/ Residential) Oral NOAEL= 20 mg/ kg/ day Use route to route extrapolation ( inhalation absorption rate = 100%). LOC for MOE = 100 ( Occupational/ Residential) 90 Day Feeding  Rat LOAEL = 211/ 223 mg/ kg/ day in males/ females based on decreased body weight gain in both sexes and clinical signs indicative of reduced nutrition.

Long Term (> 180 days) Inhalation NOAEL = N/ A This risk assessment is not applicable to the use scenario for azoxystrobin.

Cancer " Not Likely" NA HED RfD/ Peer Review Committee, 11/ 7/ 96 NOAEL = no observable adverse effect level; LOAEL = lowest observable adverse effect level; UF = uncertainty factor; MOE = margin of exposure; LOC = level of concern; PAD = population adjusted dose ( a = acute, c = chronic); RfD = reference dose; NA = not applicable.

The HED RfD/ Peer Review Committee, in its meeting of November 7, 1996, determined that azoxystrobin should be classified as " not likely to be a human carcinogen" according to the Page 16 of 52 revised Cancer Guidelines, based on lack of evidence of carcinogenicity in the long term rat and mouse feeding studies ( HED Document No. 012133, 1/ 14/ 97). Therefore, cancer risk assessments were not performed.

The HIARC recommended the following for aggregation of exposures from azoxystrobin:

° For acute aggregate exposure risk assessment, combine the high end exposure values from food + water and compare it to the acute RfD ( 0.67 mg/ kg) established for the general population. ° For chronic aggregate exposure risk assessment, combine the average exposure values from food + water and compare it to the chronic RfD ( 0.18 mg/ kg/ day). ° For short and intermediate term aggregate exposure risk assessment, the short term and intermediate term inhalation exposures should be converted to oral equivalent doses ( using 100% inhalation absorption rate), and should be added to the oral exposures ( from food + water) and compared to the respective oral NOAELs. ° No long term aggregate risk is required due to the lack of long term exposure.

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

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

4.0 EXPOSURE ASSESSMENT 4.1 Summary of Proposed Uses Details for the uses of azoxystrobin in PP# 5E6916, 05FL11, and 05TN11 are presented in Table 5. Page 17 of 52 Table 4. Summary of Directions for Use of Azoxystrobin.

Application Equipment Formul. tn [ EPA Reg. No.] Applic. Rate ( lb ai/ A) Max. #

Appl. per Season Max. Seasonal Appl. Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations Citrus Fruit ( Calamondin, Citron, Citrus hybrids, Grapefruit, Kumquat, Lemon, Lime, Mandarin, Orange [ sour and sweet], Pummelo, Salsuma mandarin, Tangerine,

including all cultivars and/ or hybrids of these)

Abound ®

Flowable Fungicide [ 100 1098] For high volume:

0.0052   0.042 lb ai/ gal solution For low volume:

0.021   0.15 lb ai/ gal soln For dip:

0.0052   0.010 lb ai/ gal soln Not specified For highvolume ( dilute) applications:

T Jet, Flooders or similar systems For low volume ( concentrate)

applications:

use a controlleddroplet type of applicator or similar system For dip applications:

use containers that hold 100 gal + Amistar ® Fungicide [ 100 1164] For high volume:

0.013   0.10 lb ai/ gal solution For low volume:

0.051   0.37 lb ai/ gal soln For dip:

0.013   0.026 lb ai/ gal soln 2 ( postharvest specificall y) Not specified 0   REI = 4 hours   Use as a dip, drench, flood or spray   For high volume applications: mix 32   64 fl oz of Abound/ Amistar in 25   100 gal of an appropriate water,

wax/ oil emulsion or aqueous dilution of a wax/ oil emulsion for crop being treated   For low volume applications: mix 32   64 fl oz of Abound/ Amistar in 7   25 gal of water, wax/ oil emulsion, or aqueous dilution of wax/ oil emulsion for the crop being treated; Apply to 250,000 lb of fruit   For dip applications: mix 32   64 fl oz of Abound/ Amistar in 100 gal of water, wax/ oil emulsion,

or aqueous dilution of wax/ oil emulsion; dip for approximately 30 sec and allow fruit to drain   For maximum decay control, treat citrus fruit once before storage and once after storage, just prior to marketing * For dip application the label instructs the user to use fl oz of Amistar   the label should be amended to refer to Amistar in oz, since it is a WDG formulation. Page 18 of 52 Table 4. Summary of Directions for Use of Azoxystrobin.

Application Equipment Formul. tn [ EPA Reg. No.] Applic. Rate ( lb ai/ A) Max. #

Appl. per Season Max. Seasonal Appl. Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations Peppers and other Fruiting Vegetables ( except cucurbits and tomatoes)

( Bell Pepper, Non Bell Pepper, Eggplant, Groundcherry, Okra, Pepino, Tomatillo)

Abound ®

Flowable Fungicide [ 100 1098] 0.10  0.25 ( 6.2   15.4 fl oz product/ A)

0.28   0.57 ( 0.4   0.8 fl oz product/ 1000 row feet   for soilborne diseases) 1.0 ( 1.92 quarts per acre per season)

Ground,

Aerial and Chemigation Equipment Amistar ® Fungicide 0.10   0.25 ( 2  5 oz product/ A)

0.27   0.54 ( 0.125   0.25 fl oz product/ 1000 row feet   for soilborne diseases) Not specified 1.0 ( 1.25 lbs product per acre per season) 0   REI = 4 hours   Abound/ Amistar should be integrated into an overall disease management strategy that includes selection of varieties with tolerance to disease and removal of plant debris in which inoculum overwinters   Do not make more than one application of Abound/ Amistar or any other strobilurin fungicide before alternating to a fungicide with a different mode of action   Abound/ Amistar applications should begin prior to disease development and continue throughout the season on a 7   14 day schedule, following the resistance management guidelines Page 19 of 52 Table 4. Summary of Directions for Use of Azoxystrobin.

Application Equipment Formul. tn [ EPA Reg. No.] Applic. Rate ( lb ai/ A) Max. #

Appl. per Season Max. Seasonal Appl. Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations Foliage of Legume Vegetables ( Any cultivar of bean [ Phaseolus spp.] and field pea [ Pisum spp])

Abound ®

Flowable Fungicide [ 100 1098] 0.10  0.25 ( 6.2   15.4 oz product/ A) 1.5 ( 2.88 quarts product/ A/ season)

Ground,

Aerial and Chemigation Equipment Amistar ® Fungicide [ 100 1164] 0.10  0.25 ( 6.2   15.4 oz product/ A) Not specified 1.5 ( 2.88 quarts product/ A/ season) 0   REI = 4 hours   Abound/ Amistar should be integrated into an overall disease management stragety that includes selection of varieties with disease tolerance, proper timing an dplacement of irrigation, crop rotation and crop residue management   Do not apply more than two sequential applications of Abound/ Amistar or other Group 11 fungicides before alternation with a fungicide that has a different mode of action   Abound/ Amistar applications should begin prior to disease development and continue throughout the season every 7 14 days following the resistance management guidelines   Use the higher rates under severe disease pressure * For the Amistar ® label, the application rate given in oz product/ A do not match lb ai/ A  the label should be amended, and read 2   5 oz product/ A; for the max appl rate, the oz/ product/ A should be amended to read 30 oz product/ A/ season Page 20 of 52 Table 4. Summary of Directions for Use of Azoxystrobin.

Application Equipment Formul. tn [ EPA Reg. No.] Applic. Rate ( lb ai/ A) Max. #

Appl. per Season Max. Seasonal Appl. Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations Legume Vegetables, dry and succulent ( grain, sweet, white and white sweet lupin; adzuki, asparagus, broad ( fava), field, kidney, lablab ( hyacinth), lima, moth, mung, navy, pinto, rice, runner, snap,

sword, tepary, urd, wax and yardlong beans; blackeyed, cow, catjang, Crowder, dwarf, edible pod, English, garden, green, field, pigeon, snow, sugar snap,

southern peas; Chinise longbean; chickpea ( garbanzo bean); guar; jackbean; and lentils)

Abound ®

Flowable Fungicide [ 100 1098] 0.10   0.25 ( 6.2   15.4 fl oz/ product/ A)

0.28   0.57 ( 0.40   0.80 fl oz product/ 1000 row feet   for soilborne diseases) 1.5 ( 2.88 quarts product/ A/ season)

Ground,

Aerial and Chemigation Equipment Amistar ® Fungicide [ 100 1164] 0.10   0.25 ( 2   5 oz product/ A)

0.27   0.54 ( 0.125   0.25 fl oz product/ 1000 row feet   for soilborne/ seedling disease control) Not specified 1.5 ( 1.88 lbs product/ A/ season) 0   REI = 4 hours   Abound/ Amistar should be integrated into an overall disease management strategy that includes selection of varieties with disease tolerance, proper timing and placement of irrigation, crop rotation and crop residue management   Do not apply more than two sequential applications of Abound/ Amistar or other Group 11 fungicides before alternation with a fungicide that has a different mode of action   Abound/ Amistar applications should begin prior to disease development and continue throughout the season every 7   14 days following the resistance management guidelines   Use the higher rates under severe disease pressure Page 21 of 52 Table 4. Summary of Directions for Use of Azoxystrobin.

Application Equipment Formul. tn [ EPA Reg. No.] Applic. Rate ( lb ai/ A) Max. #

Appl. per Season Max. Seasonal Appl. Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations Forage, Fodder, Straw and Hay Grass and Nongrass ( alfafa, bean, velvet, clover, kudzu, lespedeza, lupin, sainfoin, trefoil, vetch, and crown and milk vetch)

Abound ®

Flowable Fungicide [ 100 1098] 0.10  0.25 ( 6.2   15.4 oz product/ A) For pure stands of nongrass forage: 1.5 ( 2.88 quarts product/ A/ season)

For mixed grass and nongrass stands:

0.75 ( 1.44 quarts product/ A/ season)

Ground,

Aerial and Chemigation Equipment Amistar ® Fungicide [ 100 1164] 0.10  0.25 ( 2  5 oz product/ A) Not specified For pure stands of nongrass forage: 1.5 ( 1.88 lbs product/ A/ season)

For mixed grass and nongrass stands:

0.75 ( 0.93 lbs product/ A/ season) For pure stands of nongrass forage:

0 For mixed grass and nongrass stands:

8   REI = 4 hours   Abound/ Amistar should be integrated into an overall disease management strategy that includes selection of varieties with disease tolerance, proper timing and placement of irrigation, crop rotation and crop residue management   Do not apply more than two sequential applications of Abound/ Amistar or other Group 11 fungicides before alternation with a fungicide that has a different mode of action   For management of Asian soybean/ bean rust,

Abound/ Amistar applications should begin prior to disease developmentand continue throughout the season every 7   14 days following the resistance management guidelines   Use the higher rates under severe disease pressure   For management of outbreaks of Asian rust on alternate host species such as kudzu, llespedeza, trefoil and vetch, apply Abound/ Amistar to forages grown in the vicinity of soybeans and other legume crops ( beans and peas) as part of an Asian rust disease management strategy   Not for use on rangeland Page 22 of 52 Residential uses are not proposed in this petition. However, azoxystrobin is currently registered for use on residential turfgrass and ornamentals, as well as indoor surfaces. Other proposed uses of azoxystrobin also include applications to tobacco, greenhouse roses, and indoor carpets/ other surfaces. Short term exposures may occur during adult residential handling activities. Non occupational handler exposure may occur from mixing, loading and applying to turf, for spot application with a low pressure handwand, for broadcasting with a garden hose end sprayer to turf, and to indoor surfaces. Short and intermediate term exposures may occur during postapplication activities for adults and children ( however, adult postapplication exposure was not assessed because no dermal hazard endpoint was identified). Toddlers may experience shortand intermediate term exposure to azoxystrobin via incidental oral ( non dietary) ingestion during postapplication activities on treated turf ( i. e., hand to mouth, object to mouth [ turfgrass], and soil ingestion) and during postapplication activities on treated indoor surfaces ( i. e., hand tomouth Details of residential use and resulting exposure estimates are presented later in this document.

4.2 Dietary Exposure/ Risk Pathway 4.2.1 Residue Profile Metabolism in Plants and Livestock Adequate metabolism studies on grapes, peanuts, and wheat were submitted in conjunction with earlier petitions. Azoxystrobin ( methyl ( E) 2( 2( 6( 2 cyanophenoxy) pyrimidin 4 yloxy) phenyl) 3 methoxyacrylate) undergoes photochemical isomerization to produce the Z isomer ( methyl ( Z) 2( 2( 6( 2 cyanophenoxy) pyrimidin 4 yloxy) phenyl) 3 methoxyacrylate) and is extensively metabolized in plants. The parent compound undergoes cleavage of the ether linkages between the phenylacrylate and pyrimidinyl rings and the cyanophenyl and pyrimidinyl rings, with subsequent oxidation, hydrolysis, and/ or reduction of the primary metabolites to form numerous secondary metabolites. Azoxystrobin was found to be systemic. The HED MARC has determined that the residues of concern in/ on plants for the tolerance expression and risk assessment purposes are azoxystrobin and its Z isomer.

Adequate ruminant and poultry metabolism studies were submitted in conjunction with earlier petitions. The HED MARC has determined that the residue of concern in livestock is parent azoxystrobin only.

Analytical Method for Plants and Livestock Method RAM 243/ 04 has undergone method validation by the Analytical Chemistry Branch ( ACB), BEAD. BEAD comments have been incorporated and the revised method designated RAM 243, " Residue Analytical Method for the Analysis of ICIA5504 and R230310 in Grain and Grapes for EPA Confirmation," dated 5/ 15/ 98; MRID 44595105, has been submitted to FDA for inclusion in PAM II. Adequate methodology is available for enforcement Page 23 of 52 of the established tolerances on livestock. The GC method 255/ 01 has been validated by the EPA analytical laboratory for the analysis of milk and livestock tissues. The EPA laboratory's written report with an EPA addendum to accompany the method, and the method, will be submitted to FDA for inclusion in PAM, Vol. II.

Citrus samples were analyzed for residues of azoxystrobin and its Z isomer using Zeneca Report Number RAM 243/ 04, via GC/ NPD with minor modifications. LOD for azoxystrobin and Z isomer were established at 0.0092 ppm and 0.0065 ppm in grapefruit, 0.011 ppm and 0.0074 ppm in orange, and 0.0077 ppm and 0.0056 ppm in lemon. LOQ for azoxystrobin and Zisomer were established at 0.028 ppm and 0.020 ppm in grapefruit, 0.034 ppm and 0.022 ppm in orange, and 0.023 ppm and 0.017 ppm in lemon.

Multiresidue Methods Data have previously been submitted pertaining to the multiresidue methods testing of azoxystrobin in conjunction with the grape tolerance petition. The data indicate that azoxystrobin could not be recovered through application of the multiresidue protocols. These data have been forwarded to FDA.

Storage Stability Data Previously submitted storage stability data indicate that residues of azoxystrobin and the Z isomer are stable in oil seed rape, soybean meal, corn grits, carrot root, leaf lettuce, and wheat forage for at least two years under frozen storage. The information is adequate for the purpose of supporting the proposed tolerances.

Citrus samples were stored frozen for up to 411 days between sampling and extraction. Previously submitted storage stability data indicates that residues of azoxystrobin and the Zisomer are stable in orange oil, orange juice, and orange pulp for at least two years under frozen storage. The information is adequate for the purpose of supporting the azoxystrobin and the Zisomer residue data on citrus.

Magnitude of the Residue Foliage of Legume Vegetables, Group 7 No new residue field trial data were submitted for the foliage of legume vegetables, Group 7. The representative commodities for Group 7 are foliar portions of any cultivar of bean, field pea, and soybean. RAB2 previously stated that as long as the use pattern is similar and the proposed field trial residue data supporting a tolerance for Group 4 are submitted and deemed adequate, it will be appropriate to request a tolerance for Group 7 at the same level as Group 4. The requirements set forth by RAB2 for the establishment of an azoxystrobin tolerance on the foliage of legume vegetables, Group 7 have been satisfied. TRB recommends for the establishment of a tolerance at 30.0 ppm for the residues of azoxystrobin on vegetables, foliage of legume, Group 7. Since the proposed tolerance on Group 7 will include a soybean hay and forage, the existing tolerances on those commodities should be removed. Page 24 of 52 Fruiting Vegetables, Group 8 ( Except Tomato)

No new residue field trial data were submitted for the vegetable, fruiting, Group 8 ( except tomato). There are tolerances established for members of Group 8: peppers, okra, and eggplant at 2.0 ppm, and tomato at 0.2 ppm ( CFR § 180.507). Although all the existing residue data on the Group 8 representative commodities were determined to be sufficient to establish a crop group tolerance, risk cup issues at the time precluded increasing the tomato tolerance and separate tolerances were requested on okra and eggplant. Since the existing data were determined to be adequate for a crop group tolerance, there is sufficient data to support the petition for the requested subgroup. However, the commodity definition presented by the petitioner is incorrect. A new Section F should be submitted requesting a tolerance for the residues of azoxystrobin at 2.0 ppm on vegetables, fruiting, Group 8 ( except tomato). The existing separate tolerances on pepper, okra, and eggplant should be removed.

Pea and Bean, Succulent and Dried Shelled ( Except Soybeans), Subgroups 6B and 6C No new residue field trial data were submitted for the pea and bean, succulent shelled, Subgroup 6B; and pea and bean, dried shelled, except soybean, Subgroup 6C. The existing tolerance commodity definitions are: pea and bean, dried shelled, except soybean, subgroup, except cowpea, and field pea; and pea and bean, succulent shelled, subgroup, except cowpea. The subgroup tolerances excluded cowpea and field pea because there was no residue field data for forage, hay, and/ or silage as livestock feeds. In order to satisfy the data requirements, RAB3 previously indicated that residue data on the representative crops of Group 7 were required. However, as stated above, the requirements set forth by RAB2 for the establishment of an azoxystrobin tolerance on vegetables, foliage of legume, Group 7 have been satisfied. Therefore, no further residue field trial data is required. TRB recommends for the establishment of tolerances at 0.5 ppm for the residues of azoxystrobin on pea and bean, succulent shelled, Subgroup 6B; and pea and bean, dried shelled, except soybean, Subgroup 6C.

Nongrass Animal Feeds, Group 18 No new residue field trial data were submitted for the animal feed, nongrass, Group 18. IR 4 requested that the Agency use data supporting the tolerances for vegetable, leafy, except Brassica, Group 4 at 30.0 ppm, Brassica, leafy greens, Subgroup 5B at 25 ppm, and soybean, hay at 55.0 ppm to support the establishment of tolerances for animal feed, nongrass, Group 18, forage at 30.0 ppm and animal feed, nongrass, Group 18, hay at 55.0 ppm. ChemSAC has determined that the existing data cited by the petitioner is not sufficient to support the requested tolerance. TRB recommends against the proposed tolerances on animal feed, nongrass, Group 18, forage and hay. However, TRB concluded, based on the existing use on soybeans, which has the same use pattern as that proposed for animal feed, nongrass, Group 18, a reduced number of residue field trials would be appropriate. Six residue field trials each with the appropriate geographic distribution on the two representative crops for animal feed, nongrass, Group 18, alfalfa and clover are required to support a proposed azoxystrobin tolerance. Page 25 of 52 Citrus IR 4 has submitted residue data for azoxystrobin and its Z isomer on citrus treated with both preharvest and postharvest applications. The submitted data were obtained from trials conducted in Florida ( 1 trial), Texas ( 1 trial), and California ( 4 trials) ( EPA Region III, VI, and X, respectively). Each of the field site consisted of one untreated control plot and one treated plot. The total numbers of citrus trials, as well as the number of trials per site, are not in compliance with the recommended numbers in the EPA Residue Chemistry Test Guidelines, OPPTS 860.1500 Crop Field Trials. However, since the study was conducted to obtain data for the post harvest use, only, the number and location of the trials are adequate.

At each test location, azoxystrobin was applied as Azoxystrobin 80WG, which is a water dispersible granule formulation containing 80% azoxystrobin. Each treated plot received two foliar applications at the single application rate of ~ 0.25 lb ai/ A with 6 to 8 days between applications. Mature citrus fruits were collected on the day of the final application. Adequate amounts of treated fruit were collected from each site for separate post harvest treatments. Additional oranges from a California trial were collected to generate control peel and flesh samples as well as post harvest dip without storage wax treatment samples.

Six different types of post harvest treatment were tested in the study: 1) dip with Decco 202 storage wax; 2) packing line spray with storage wax; 3) dip without wax; 4) packing line spray without wax followed by application of Decco 400 shipping wax; 5) dip with storage wax followed by dip without storage wax; and, 6) packing line spray with storage wax, followed by wash with Decco cleaner, followed by packing line spray without storage wax, followed by application of shipping wax. All post harvest test solutions contained Azoxystrobin 80WG and were applied at 1.0 lb ai/ 100 gal water ( dip) and 1.0 lb ai/ 250,000 lb fruits ( packing line spray).

Samples were analyzed for residues of azoxystrobin and its Z isomer via GC/ NPD. Extraction and analysis of all samples for azoxystrobin and Z isomer were conducted using Zeneca Report Number RAM 243/ 04, with minor modifications. LOD for azoxystrobin and Zisomer were established at 0.0092 ppm and 0.0065 ppm in grapefruit, 0.011 ppm and 0.0074 ppm in orange, and 0.0077 ppm and 0.0056 ppm in lemon. LOQ for azoxystrobin and Z isomer were established at 0.028 ppm and 0.020 ppm in grapefruit, 0.034 ppm and 0.022 ppm in orange, and 0.023 ppm and 0.017 ppm in lemon. Azoxystrobin residues found in grapefruit, orange, and lemon samples that were only treated in the field ranged from 0.098 to 0.29 ppm, 0.075 to 1.98 ppm, and 0.29 to 0.69 ppm, respectively. Azoxystrobin residues detected in grapefruit, orange and lemon samples that received preharvest as well as postharvest dip treatments ranged from 1.19 to 5.43 ppm, 1.21 to 3.99 ppm, and 1.47 to 9.18 ppm, respectively. Azoxystrobin residues detected in grapefruit, orange, and lemon samples that received preharvest as well as packingline spray postharvest treatments ranged from 0.41 to 0.92 ppm, 0.37 to 1.08 ppm, and 0.72 to 1.57 ppm. Finally, residues in the orange peel and flesh samples ranged from 4.69 to 5.52 ppm and 0.53 to 0.75 ppm, respectively. No Z isomer residues above the lower limit of method validation ( LLMV) of 0.02 ppm were observed in any sample. Page 26 of 52 TABLE 4.2.1 Summary of Residue Data from Citrus Field Trials with Azoxystrobin.

Total Application Rate 1 Residue Levels ( ppm) Analyte Preharvest Rate ( lb ai/ A) Post harvest dip ( lb ai/ 100 gal.) Post harvest spray ( lb ai/ 250,000 lbs. fruit) PHI ( days)

n Min. Max. HAFT 2 Median ( STMdR) Mean ( STMR) Std. Dev.

1 0 36 1.19 9.18 8.67 2.09 2.87 1.95 Azoxystrobin 0.500  0.503 1 0 18 0.37 1.57 1.37 0.79 0.79 0.30 1 0 36 < 0.02 < 0.02 < 0.02 N/ A3 N/ A N/ A Z isomer 0.500  0.503 1 0 18 < 0.02 < 0.02 < 0.02 N/ A N/ A N/ A 1  Total Application Rate for Azoxystrobin and Z isomer together. 2  HAFT = Highest Average Field Trial. 3  N/ A  Not applicable The study was conducted to demonstrate the residues of azoxystrobin in fruit, which were treated by simulated post harvest applications following normal pre harvest use. For this purpose, the number and location of the trials are adequate. There is an existing use for azoxystrobin on citrus fruit with an established tolerance of 2.0 ppm. The petitioner first treated the fruit according to the existing preharvest use and showed that quantifiable residues were found similar to those previously found from the use. Those fruit were then treated with azoxystrobin using six different postharvest methods. The highest azoxystrobin residues were detected in grapefruit, orange and lemon samples that received preharvest as well as postharvest dip treatments ranging from 1.19 to 5.43 ppm, 1.21 to 3.99 ppm, and 1.47 to 9.18 ppm, respectively. The results of the residue chemistry field trials indicate that the residues of azoxystrobin following both preharvest and postharvest uses are not likely to exceed the proposed tolerance on citrus fruit. Therefore, TRB recommends for the increase in the tolerance on Citrus Fruit to 10.0 ppm, in order to cover both pre and postharvest uses.

Section 18s  Specialty Legumes For 05FL11 and 05TN11, axozystrobin as formulated in Quilt   Fungicide ( EPA REG. No. 110 1178) will be applied twice at 0.014 lb ai/ A, up to 0.028 lb ai/ A/ season with a 0 day PHI on Group 6 ( except soybeans) and Group 7. The use is requested in response to the threat of soybean rust on specialty legumes. The use will entail applications to 86,502 acres with 18922.4 gal of formulation ( 1173.2 lb ai azoxystrobin). Previous uses on legumes, except soybeans, included four applications of up to 0.25 lb ai/ A with a seasonal maximum of 1.0 lb ai/ A. Residues of azoxystrobin from the established use pattern did not exceed 0.5 ppm. The requested the Section 18 uses will not exceed the established azoxystrobin tolerances; therefore TRB recommends for the requested use. The product, Quilt   Fungicide ( EPA REG. No. 110 1178), also contains propiconazole ( PC Code: 122101). The use of this chemical on Group 6 ( except soybeans) and Group 7 commodities is not under review here. Page 27 of 52 Processed Food and Feed There are no processed commodities associated with the uses of azoxystrobin on foliage of legume vegetables, Group 7; vegetables, fruiting, Group 8 ( except tomato); and pea and bean, succulent and dried shelled, except soybean, Subgroups 6B and 6C.

Citrus No new citrus processing study was submitted with this action. A citrus processing study has been previously reviewed. Total residues of azoxystrobin and its Z isomer did not concentrate in juice processed from oranges bearing detectable residues. Total residues of azoxystrobin and its Z isomer may concentrate 1.9 2.3x in dried pulp ( avg. 2.1x) and 4.4 4.7x in oil ( avg. 4.6x) processed from oranges bearing detectable residues.

The HAFT residue for citrus fruit ( grapefruit, lemons, and oranges) treated at 1x the maximum seasonal rate from the submitted citrus field trials was 8.67 ppm ( total residues of azoxystrobin and its Z isomer). Based on the HAFT and an average concentration factor of 2.1x, the highest expected residues in dried citrus pulp would be 18.2 ppm and based on an average concentration factor of 4.6x, the highest expected residues in citrus oil would be 39.9 ppm.

Based on the HAFT residue for citrus fruit of 8.7 ppm ( total residues of azoxystrobin and its Z isomer) and the average concentration factors from the previously submitted processing studies of 2.1x for pulp and 4.6x for oil, the petitioner's requests for proposed tolerances are adequate. Therefore, TRB recommends for azoxystrobin tolerances of 20.0 ppm for citrus, dried pulp and 40.0 ppm for citrus, oil.

Meat, Milk, Poultry and Eggs The livestock feed items of regulatory interest for foliage of legume vegetables, Group 7; vegetables, fruiting, Group 8 ( except tomato); and pea and bean, succulent and dried shelled, except soybean, Subgroups 6B and 6C are cowpea seed at 0.05 ppm, cowpea hay and forage at 30.0 ppm; and soybean, forage and hay, for which the tolerance will be raised to 30 ppm. Since the worst case cattle and swine diets using existing and proposed tolerances will not exceed the level of the ruminant feeding study used to establish the current tolerances, no increase in tolerances for ruminant and swine commodities are required. None of the commodities for which tolerances are proposed have poultry feed items of regulatory interest, therefore no change in azoxystrobin poultry tolerances is required.

The citrus feed item, citrus dried pulp, has already been considered and found to have no effect on the MTDB of azoxystrobin for livestock. Therefore, the currently established tolerances for secondary residues of azoxystrobin remain adequate.

Confined/ Field Accumulation in Rotational Crops Adequate confined studies have previously been reviewed. Several conjugated metabolites of primary crop metabolites were identified, indicating that azoxystrobin is more Page 28 of 52 extensively metabolized in rotational crops than in primary crops. The residues of concern in rotational crops are parent and the Z isomer.

Limited field rotational crop studies were previously reviewed. The limited field accumulation study is adequate to indicate that residues of azoxystrobin and Z isomer will not occur in mustard greens, turnip roots, turnip tops, and wheat grain planted 36 days after application of azoxystrobin. This study also indicates that small residues of azoxystrobin per se may occur in wheat matrices other than grain at a plantback interval of approximately 60 days after treatment. No residues of Z isomer were found in any matrix at any plantback interval. The label indicates that only crops with registered uses may be planted within 12 months of application. This plantback interval is adequate.

4.2.2 Dietary Analysis Acute and chronic dietary exposure assessments were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEMFCID   , Version 2.03), which incorporates consumption data from USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII), 1994 1996 and 1998. The 1994 96, and 98 data are based on the reported consumption of more than 20,000 individuals over two non consecutive survey days. Foods " as consumed" ( e. g., apple pie) are linked to EPA defined food commodities ( e. g. apples, peeled fruit  cooked; fresh or N/ S; baked; or wheat flour  cooked; fresh or N/ S, baked) using publicly available recipe translation files developed jointly by USDA/ ARS and EPA. For chronic exposure assessment, consumption data are averaged for the entire U. S. population and within population subgroups, but for acute exposure assessment are retained as individual consumption events. Based on analysis of the 1994 96, and 98 CSFII consumption data, which took into account dietary patterns and survey respondents, HED concluded that it is most appropriate to report risk for the following population subgroups: the general U. S. population, all infants (< 1 year old), children 1 2, children 3 5, children 6 12, youth 13 19, adults 20 49, females 13 49, and adults 50+ years old.

Established and recommended tolerances were used in acute and chronic dietary assessments. Percent crop treated data were not applied. DEEM   default concentration factors were used except for tomato juice, puree, paste and catsup. Processing data show no concentration in these fractions; the values were set at one.

<IP_ADDRESS> Acute Dietary The acute dietary exposure analysis for azoxystrobin is a Tier 1 assessment because no additional data were used to refine the analysis. One hundred percent of proposed and registered crops are assumed treated with azoxystrobin ( 100% CT) and tolerance level residues were used in the analysis. The acute dietary endpoint applies to all population subgroups including infants and children. The highest estimate for acute drinking water exposure, 170 ppb, was used in the analysis ( see Section 4.3, below). The dietary exposure estimates for the U. S. population at 27% of the aPAD and the most highly exposed subgroup, children 1 2 yrs old, at 74% of the aPAD, do not exceed HED's level of concern. Page 29 of 52 TABLE <IP_ADDRESS> Results of Acute Dietary Exposure Analysis 95th Percentile Population Subgroup aPAD ( mg/ kg/ day) Exposure ( mg/ kg/ day) % aPAD General U. S. Population 0.67 0.183066 27 All Infants (< 1 year old) 0.67 0.157206 24 Children 1 2 years old 0.67 0.496490 74 Children 3 5 years old 0.67 0.373851 56 Children 6 12 years old 0.67 0.241694 36 Youth 13 19 years old 0.67 0.185218 28 Adults 20 49 years old 0.67 0.151215 23 Adults 50+ years old 0.67 0.138010 21 Females 13 49 years old 0.67 0.159688 24 Page 30 of 52 <IP_ADDRESS> Chronic Dietary The chronic dietary exposure analysis for azoxystrobin is a Tier 2 analysis: tolerancelevel residues and some % CT were used in the analysis. The chronic dietary endpoint applies to all population subgroups including infants and children. The highest estimate for chronic drinking water exposure, 33 ppb, was used in the analysis ( see Section 4.3, below).

The dietary exposure estimate for the U. S. population was 8% of the cPAD and the most highly exposed subgroup, children 1 2 yrs old, was 21% of the cPAD. Risk estimates for all population subgroups are below HED's level of concern ( 100% of the cPAD).

Table <IP_ADDRESS> Results of Chronic Dietary Exposure Analysis Population Subgroup cPAD ( mg/ kg/ day) Exposure ( mg/ kg/ day) % cPAD General U. S. Population 0.18 0.013570 8 All Infants (< 1 year old) 0.18 0.010552 6 Children 1 2 years old 0.18 0.034658 19 Children 3 5 years old 0.18 0.027564 15 Children 6 12 years old 0.18 0.017825 10 Youth 13 19 years old 0.18 0.011536 6 Adults 20 49 years old 0.18 0.011228 6 Adults 50+ years old 0.18 0.011754 7 Females 13 49 years old 0.18 0.011497 6 <IP_ADDRESS> Cancer Dietary The HED RfD/ Peer Review Committee, in its meeting of November 7, 1996, determined that azoxystrobin should be classified as " not likely to be a human carcinogen." Due to the classification, no cancer risk assessment was performed.

4.3 Water Exposure/ Risk Pathway Although moderately persistent in soils and stable to hydrolysis, the likelihood of azoxystrobin moving into ground and surface water is low due to high soil/ water partitioning coefficients and low single application rates. The HED MARC determined that the residue of Page 31 of 52 concern in water is azoxystrobin only because the parent compound is the most likely residue to be found in surface water.

Monitoring data are not available to perform a quantitative drinking water risk assessment for azoxystrobin at this time. EFED provided EECs for azoxystrobin based upon the crop with the highest application rate ( turf). Tier 1 surface and ground water EECs were generated using EFED's FIRST and SCI GROW models, respectively. As the use of azoxystrobin on turf has the highest single and yearly application rate at 0.55 lb ai/ A and 5 lb ai / A/ year, respectively, this application rate was used in the FIRST and SCI GROW models to estimate the concentrations of this chemical in surface and ground water, respectively. Should the yearly application rate on non cropland change, or should a use of azoxystrobin with a higher use rate be added, EFED may have to revise the EECs accordingly.

Ground Water The SCI GROW screening model developed in EFED estimates potential ground water concentrations under hydrologically vulnerable conditions. Based on the highest use rate ( turf use, 9 applications per year, 10 day interval, and 0.55 lb ai/ A/ application), the upper bound concentration of azoxystrobin was estimated at 3.1 ppb. This value can be used for both acute and chronic risk assessments. This value represents upper bound estimates of the concentrations that might be found in ground water which result from the use of azoxystrobin on turf.

Surface Water Based on the Tier I modeling results, azoxystrobin EECs in surface water are not likely to exceed 170 ppb for the acute ( peak) concentration or 33 ppb for the chronic ( annual average) concentration. These values represent upper bound estimates of the concentrations that might be found in surface water which result from the use of azoxystrobin on turf.

4.4 Residential Exposure/ Risk Pathway Azoxystrobin is currently registered for use on residential turfgrass and ornamentals, as well as indoor surfaces. Short term exposures may occur during adult residential handling activities. HED's Draft Standard Operating Procedures ( SOPs) for Residential Exposure Assessments, and Recommended Revisions ( ExpoSAC Policy Number 12, revised 2/ 22/ 01), were used as the basis for all residential handler exposure calculations. Some of the handler exposure data used in this assessment are from the Outdoor Residential Exposure Task Force ( ORETF; the risk manager is encouraged to pursue data compensation in the event the registrant is not a member of the task force). Non occupational handler inhalation MOEs were 1,700,000 for mixing, loading and applying WDG formulation to indoor surfaces, and 2,700,000 and 230,000 for mixing, loading and applying liquid formulation to turf, for spot application with a low pressure handwand and for broadcasting with a garden hose end sprayer to turf, respectively. These MOEs are well above the LOC for non occupational handler scenarios, and therefore, are not of concern. Page 32 of 52 4.4.1 Home Uses Products containing azoxystrobin are registered for application to turf, ornamentals, and indoor carpets/ other surfaces. These products may be applied to turf at rates up to 0.95 lb ai per acre, 5 times per year ( not to exceed 5 lb ai/ A/ yr), to ornamentals at rates up to 0.75 lb ai per acre, every 7 to 14 days ( not to exceed 5 lb ai/ A/ yr), and indoors to carpets/ other surfaces at rates up to 3.3E 5 lb ai/ ft2, every 3 months as needed ( not to exceed 4 times per year).

Residential handlers may receive short term dermal and inhalation exposure to azoxystrobin when mixing, loading and applying the formulations. Adults and children may be exposed to azoxystrobin residues from dermal contact with foliage/ surfaces during postapplication activities. Toddlers may receive short and intermediate term oral exposure from incidental ingestion during postapplication activities.

As no dermal endpoint was selected by the HIARC, a dermal exposure and risk assessment was not conducted for residential handlers or postapplication activities. NOAELs of 25 mg/ kg/ day and 20 mg/ kg/ day from oral toxicity studies were selected by the HIARC for assessing the risk from short and intermediate term incidental oral exposures, respectively. These same NOAELs were selected by the HIARC for assessing the risks from short and intermediate term inhalation exposures, assuming a 100% absorption factor. The HED FQPA Safety Factor Committee met on August 24, 1998, and decided to reduce the 10X safety factor to 1X for the U. S. population and all population subgroups and for all exposure scenarios. Thus, the LOC for risk assessment purposes are MOEs of 100 or less.

No chemical specific exposure or residue dissipation data for handler or postapplication activities were submitted to HED in support of the registered lawn uses or indoor carpet/ other surfaces uses. HED's Draft Standard Operating Procedures ( SOPs) for Residential Exposure Assessments, and Recommended Revisions ( HED Policy Number 12, revised 2/ 22/ 01), were used as the basis for all residential handler exposure calculations. Some of the handler exposure data used in this assessment are from the ORETF ( the risk manager is encouraged to pursue data compensation in the event the registrant is not a member of the task force). The ORETF data were designed to replace the present PHED data with higher confidence, higher quality data that contain more replicates than the PHED data for those scenarios.

4.4.2 Residential Handler Exposure and Risk Indoor Carpet and Other Surfaces Although the currently registered label for use on indoor carpets/ other surfaces prohibits non commercial applicators from mixing, loading and applying azoxystrobin, the label amendment for the Heritage ® Fungicide label does not. Furthermore, the currently registered label for use on indoor carpets/ other surfaces specifies use restrictions, whereas the Heritage ® Fungicide label does not. Therefore, inhalation daily doses for residential handlers were calculated for the WDG formulation using data for mixing, loading and applying a liquid. Based Page 33 of 52 on PHED unit exposure values from other handler scenarios with these formulation types, the exposure from a WDG is expected to be less than that of handling a liquid. The open mixing, loading, and applying liquid using a low pressure handwand ( PHED) handler scenario was evaluated.

The following assumptions ( which include HED standard values) were used to calculate inhalation exposures:

* The maximum application rate from Heritage ® Fungicide ( EPA Reg No 100 1093) of 3.4E 5 lb ai/ ft2:

0.5 lb ai x 8.34 lb product x 1 gal product x 0.26 fl. oz x 1 gal tank mix lb product gal product 128 fl. oz. product gal tank mix 250 ft2 [ assume density of water]

* Handlers were assumed to be using a low pressure handwand for spot or broadcast treatments to 1,000 ft2 areas indoors, once per day. * The inhalation unit exposure for the low pressure handwand is 30

g/ lb ai handled ( from Appendix B of the 1997 Draft SOPs for Residential Exposure Assessments). * Residential handler body weight is 70 kg. * The overall estimate of inhalation exposure represents a central to high end value.

As shown in Table 4.4.2, the inhalation MOE for residential handlers applying azoxystrobin indoors is well above the LOC of an MOE of 100 or less.

TABLE 4.4.2. a Handler Exposure and Risk Estimates for Residential Indoor Surface Applicators Handler Scenario Rate ( lb ai/ ft2) Area Treated ( ft2/ day) PHED Unit Exposure1 ( mg/ lb ai) Short term Daily Inh. Dose 2 ( mg/ kg/ day) Short term Inhalation MOE 3 Open Mixing, Loading, and Applying Liquid using a Low Pressure Handwand 3.4E 5 1000 0.03 1.5E 5 1,700,000 1 Data Confidence for inhalation unit exposures: low pressure handwand: 80 replicates, ABC grade, medium confidence 2 Daily Dose = [ Rate ( lb ai/ ft2) x Area Treated ( ft2/ day) x Unit Exposure# ( mg/ lb ai handled)] / Body Weight ( 70 Kg) 3 MOE = NOAEL ( 25 mg/ kg/ day) / Daily Inhalation Dose ( mg/ kg/ day)

Although there is a potential for residential bystander exposure, the exposure scenario is not assessed for the following reasons: the label specifically restricts humans ( other than the applicator) and domestic animals from being present while applications are being made, until after the application has dried; and bystander exposure is expected to be less than applicator exposure, and the MOEs for the applicator exposure scenario are high, indicating bystanders would be subject to even less exposure and risk. Page 34 of 52 Turf and Ornamentals The currently registered labels for turf and ornamentals do not prohibit non commercial applicators from mixing, loading and applying either the liquid or the WDG formulations. The residential exposure and risk assessment for turf and ornamentals was conducted using the application rate for turf because it is the highest use rate. Inhalation daily doses for residential handlers were calculated for the flowable concentrate formulation using data for mixing, loading and applying a liquid. Appropriate data are not available for handling the WDG formulation for this use, however, based on PHED unit exposure values from other handler scenarios with these formulation types, the exposure is expected to be less than that of handling a liquid. The following handler scenarios were evaluated:

1. mix, load and spot application of liquid formulation ( low pressure hand sprayer), and 2. mix, load and broadcast application of liquid formulation ( garden hose end sprayer)

The following assumptions ( which include HED standard values) were used to calculate inhalation exposures:

* The maximum application rate from Abound ® Flowable ( EPA Reg No. 10182 415) of 1.35 fluid ounces of product (@ 2.08 lb ai/ Gal) per 1,000 square feet or 0.95 lb ai per acre was assumed. * Handlers were assumed to be using a low pressure hand sprayer for spot treatments to 1,000 ft2 areas, or a garden hose end sprayer for broadcast to a 0.5 acre lawn. * The inhalation unit exposure for the low pressure hand sprayer is 30 Fg/ lb ai handled ( from Appendix B of the 1997 Draft SOPs for Residential Exposure Assessments), and for and garden hose end sprayer is 16 Fg/ lb ai handled ( from ORETF data). * Residential handler body weight is 70 kg. * The overall estimate of inhalation exposure represents a central to high end value.

As shown in Table 4.2.2. b, the inhalation MOEs for residential handlers are well above the LOC of an MOE of 100 or below.

TABLE 4.4.2. b Handler Exposure and Risk Estimates for Residential Lawn Applicators Handler Scenario Rate ( lb ai/ acre) Acres Treated ( acres/ day) PHED/ ORETF Unit Exposure1 ( mg/ lb ai) Short term Daily Inh. Dose 2 ( mg/ kg/ day) Short term Inhalation MOE 3 1. mix/ load and spot application of liquid formulation ( low pressure hand sprayer) 0.95 0.023 0.030 9.4E 06 2,700,000 2. mix/ load and broadcast application of liquid formulation ( garden hose end sprayer) 0.95 0.5 0.016 1.1E 04 230,000 Page 35 of 52 1 Data Confidence for inhalation unit exposures: low pressure hand sprayer: 80 replicates, ABC grade, medium confidence garden hose end sprayer: 30 replicates, A grade, high confidence 2 Daily Dose = [ Rate ( lb ai/ A) x Acres Treated ( A/ day) x Unit Exposure# ( mg/ lb ai handled)] / Body Weight ( 70 kg) 3 MOE = NOAEL ( 25 mg/ kg/ day) / Daily Inhalation Dose ( mg/ kg/ day)

4.4.3 Residential Postapplication Exposure and Risk Indoor Carpet and Other Surfaces Commercial and residential applicators ( when formulation and application rates are the same) deposit the same amount of residue on the treated site. The residential postapplication scenario for use of azoxystrobin on indoor carpets and other surfaces has been recently assessed in an Antimicrobial Division ( AD) memorandum ( DP Num: 299065, D. Aviado, 7/ 2/ 04). Both the Heritage ® Fungicide label and the formulation assessed in the AD memorandum ( 2.08 SC) call for a liquid spray to indoor surfaces, and both have similar application rates ( 2.08 SC: 3.3E 5 lb ai/ ft2; Heritage ® : 3.4E 5 lb ai/ ft2). Considered together, the potential for postapplication exposure following application of Heritage is expected to be quantitatively and qualitatively similar to postapplication exposure following application of the 2.08 SC formulation. However, because the restrictions on the labels differ, and because AD and HED sometimes employ different assumptions in their exposure algorithms, the residential postapplication exposure scenario assessment is being conducted again in this document.

The following postapplication exposure scenarios resulting from indoor surface treatment were assessed:

( 1) toddlers' incidental ingestion of pesticide residues on hard indoor surfaces from hand to mouth transfer, and ( 2) toddlers' incidental ingestion of pesticide residues on carpet/ textile indoor surfaces from hand to mouth transfer.

The exposure and risk estimates for the residential exposure scenarios are assessed for the day of application ( day " 0") because it is assumed that toddlers could contact the indoor surface immediately after the application has dried. Both short and intermediate term exposure is expected. The equation used for the exposure calculations are presented below and the results are presented in Table 4.4.3. a.

PDRt for hand to mouth = ISR * SA * EX * FQ * ET Where:

PDRt = potential dose rate on day " t" ( mg/ day) ISR = AR * F * ( 1 D) t * CF1 * CF2 ( mg/ cm2)

and: AR = application rate ( lb ai/ ft2); 3.4E 5 lb ai/ ft2 Page 36 of 52 F = fraction of ai available on vinyl/ hard surfaces or carpet/ textile surfaces ( unitless); 10% and 5%, respectively D = fraction of residue that dissipates daily ( unitless)  not employed in this assessment t = postapplication day on which exposure is being assessed  assumed to be day " 0" in this assessment CF1 = conversion factor ( 4.54E+ 5 mg/ lb) CF2 = conversion factor ( 1.08E 3 ft2/ cm2 )

SA = surface area of the hands ( cm2/ event); use palmar surface area of 3 fingers; 20 cm2 EX = extraction from the hand by saliva = 50% FQ = frequency of hand to mouth activity ( events/ hr); 20 events/ hr for short term, 9.5 events/ hr for intermediate term ET = exposure time ( hr/ day); 4 hrs/ day for vinyl/ hard surfaces; 8 hrs/ day for carpet/ textile surfaces and: PDRt norm = PDRt / BW ( 15 kg); potential dose rate, normalized to body weight, on day " t" ( mg/ kg/ day) MOE = NOAEL / PDRt norm; ( NOAELoral = 25 mg/ kg/ day ( short term), 20 mg/ kg/ day ( intermediate term)

TABLE 4.4.3. a Short and Intermediate Term Incidental Ingestion Exposure and Risk from Treated Indoor Surfaces Scenarios ISR ( mg/ cm2) Short Term PDR0 norm ( mg/ kg/ day) Int Term PDR0 norm ( mg/ kg/ day) Short Term MOE Int term MOE*

( 1) Hand to Mouth ( vinyl/ hard surfaces) 1.7E 3 0.089 0.042 280 480 ( 2) Hand to Mouth ( carpet/ textile surfaces) 8.34E 4 0.089 0.042 280 480 * Although the intermediate term MOEs are higher than the short term MOEs, one should not assume that it is safer to be exposed for a longer duration. It is an artifact of dose spacing in toxicity studies, and conservative exposure assumptions.

These exposure and risk estimates are considered conservative because they are based on the residue available on day " 0", upper percentile values ( exposure duration, S T hand to mouth events/ hr) and conservative assumptions ( total replenishment after each hand to mouth event, surface area mouthed, and % application rate available as residue). Although the turf postapplication scenario ( assessed previously and reported below) involves three exposure pathways, even when they are combined, they pose less risk than via the indoor surfaces Page 37 of 52 postapplication pathway. Outdoor and indoor postapplication exposure estimates are not combined, because co occurrence is considered unlikely, and would compound already conservative assumptions.

Turf and Ornamentals The following postapplication exposure scenarios resulting from lawn treatment were assessed:

( 1) toddlers' incidental ingestion of pesticide residues on lawns from hand to mouth transfer, ( 2) object to mouth transfer from mouthing of pesticide treated turfgrass, and ( 3) incidental ingestion of soil from pesticide treated residential areas.

Postapplication exposures from various activities following lawn treatment are considered to be the most common and significant in residential settings. The exposure via incidental ingestion of other plant material may occur but is considered negligible. The exposure and risk estimates for the residential exposure scenarios are assessed for the day of application ( day " 0") because it is assumed that toddlers could contact the lawn immediately after application. The equations used for the exposure calculations are presented below and the results are presented in Table 4.3.3. b.

PDRt for hand to mouth = TTRt * SA * EX * FQ * ET * CF1 PDRt for object to mouth ( turfgrass) = GRt * IgR1 * CF1 PDRt for soil ingestion = SRt * IgR2 * CF1 Where: PDRt = potential dose rate on day " t" ( mg/ day) TTRt = AR * F * ( 1 D) t * CF2 * CF3 GRt = AR * F * ( 1 D) t * CF2 * CF3 SRt = AR * F * ( 1 D) t * CF2 * CF3 * CF4 Where: TTRt = turf transferrable residue on day " t" ( µ g / cm2 turf) SA = surface area of the hands ( cm2/ event); use palmar surface area of 3 fingers; 20 cm2 EX = extraction from the hand by saliva = 50% FQ = frequency of hand to mouth activity ( events/ hr); 20 events/ hr for shortterm 9.5 events/ hr for intermediate term ET = exposure time ( hr/ day); 2 hrs/ day CF1 = conversion factor ( 0.001 mg/ µ g for the TTR or GR equation, or 1E 6 g/ µ g in the SR equation) GRt = grass ( and plant matter) residue on day " t" ( µ g / cm2) IgR1 = mouthing rate of grass ( cm2/ day); 25 cm2/ day SRt = soil residue on day " t" ( µ g / g) Page 38 of 52 IgR2 = ingestion rate of soil ( mg/ day); 100 mg/ day AR = application rate ( lb ai/ acre); 0.95 lb ai/ acre F = fraction of ai available on turf/ grass or in uppermost cm of soil ( unitless); 5% and 20% on turf/ grass for hand to mouth and object to mouth, respectively, and 100% in uppermost 1 cm of soil D = fraction of residue that dissipates daily ( unitless); 10% t = postapplication day on which exposure is being assessed CF2 = conversion factor ( 4.54E+ 8 µ g / lb) CF3 = conversion factor ( 2.47E 8 acre/ cm2 ) CF4 = conversion factor ( 0.67 cm3/ g soil) and PDRt norm = PDRt / BW MOE = NOAEL / PDRt norm Where: PDRt norm = potential dose rate, normalized to body weight, on day " t" ( mg/ kg/ day) BW = body weight ( kg); 15 kg NOAELoral = 25 mg/ kg/ day ( short term), 20 mg/ kg/ day ( intermediate term)

TABLE 4.4.3. b. Short and Intermediate Term Incidental Ingestion Exposure and Risk from Treated Turf Scenarios TTR/ GR/ SR0 ( µ g / cm2 or g) Short Term PDR0 norm ( mg/ kg/ day) Int Term PDR0 norm ( mg/ kg/ day) Short Term MOE Int term MOE*

( 1) Hand to Mouth 0.53 0.014 0.0067 1,800 3,000 ( 2) Mouthing Grass 2.13 0.0035 0.0035 7,000 5,600 ( 3) Soil Ingestion 7.1 0.000048 0.000048 530,000 420,000 Combined N/ A 0.018 0.010 1,400 1,900 * Although the intermediate term MOEs are higher than the short term MOEs, one should not assume that it is safer to be exposed for a longer duration. It is an artifact of dose spacing in toxicity studies, and conservative exposure assumptions.

Both short term and intermediate term MOEs for each scenario, and the combined MOE resulting from all three exposures, are above the LOC.

The exposure estimates generated above are based on some upper percentile ( i. e., maximum application rate, initial amount of transferrable residue and duration of exposure) and some central tendency ( i. e., surface area, hand to mouth activity, and body weight) assumptions and are considered to be representative of high end exposures. The uncertainties associated with this assessment stem from the use of an assumed amount of pesticide available from turf, and assumptions regarding transfer of chemical residues and hand to mouth activity. The estimated exposures are believed to be reasonable high end estimates based on observations from chemical specific field studies and professional judgement. Page 39 of 52 4.4.4 Recreational Postapplication Exposure and Risk Recreational exposures to turf and indoor surfaces are expected to be similar to, or in many cases less than, those evaluated in section 4.4.3 Residential Postapplication Exposure and Risk; therefore, a separate recreational exposure assessment was not included. Although azoxystrobin may be applied to golf courses, a risk assessment for the golfing scenario is not required because no dermal endpoint was selected by the HIARC.

4.4.5 Off Target Non Occupational Exposure Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for azoxystrobin. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/ labeling. The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U. S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off target drift and risks associated with aerial as well as other application types where appropriate.

Please note that as indicated in this assessment, azoxystrobin is directly applied to residential turf and does not result in exposures of concern. It is unlikely that the potential for risk of exposure to spray drift from agricultural uses would be higher than that estimated for the turf use of this chemical.

5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION 5.1 Acute Aggregate Risk ( food + drinking water)

The aggregate acute risk estimates include exposure to residues of azoxystrobin in food and water, and does not include dermal, inhalation or incidental oral exposure. Since the dietary exposure assessment already includes the highest acute exposure from the drinking water modeling data, no further calculations are necessary. The acute risk estimate for the U. S. population and all other population subgroups, resulting from aggregate exposure to azoxystrobin in food and drinking water is below HED's level of concern. The food and water exposure estimates for the U. S. population is 27% of the aPAD and the most highly exposed subgroup, children 1 2 yrs old, is 74% of the aPAD.

5.2 Short Term Aggregate Risk ( food + drinking water + residential) Page 40 of 52 The short term aggregate risk assessment estimates risks likely to result from 1 to 30 day exposure to azoxystrobin residues from food, drinking water, and residential pesticide uses. High end estimates of residential exposure are used in the short term assessment, while average values are used for food and drinking water exposure ( i. e. chronic exposures).

No endpoint has been selected for short term dermal exposure to azoxystrobin; therefore it will not be included in this assessment. The same endpoints were identified by HIARC for short term incidental oral and inhalation risk assessment ( based on increased maternal diarrhea, urinary incontinence, and salivation). Therefore, this assessment will combine dietary/ incidental oral exposure with inhalation exposure.

A short term risk assessment is required for adults because there is a residential handler inhalation exposure scenario. In addition, a short term risk assessment is required for infants and children because there is a residential post application oral exposure scenario. Average food and drinking water exposures are already included in the chronic dietary exposure assessment in Table <IP_ADDRESS>, above. Adult inhalation risks are summarized for indoor and outdoor uses in Tables 4.3.3. a and 4.3.3. b, above. Toddlers' incidental oral exposure is assumed to include hand to mouth exposure, object to mouth exposure and exposure through incidental ingestion of soil. Incidental oral risks for children are summarized for indoor and outdoor uses in Tables 4.4.3. a and 4.4.3. b, above.

TABLE 5.2. Short Term Aggregate Risk ( Food, Water and Incidental Oral Exposure)

Short Term Scenario Population NOAEL mg/ kg/ day LOC MOE1 Average Food + Water Exposure mg/ kg/ day Residential Exposure2 mg/ kg/ day Aggregate MOE ( food and residential) 3 US Population 0.013570 0.00011 1800 Youth ( 13 19 years) 0.011536 0.00011 2150 All Infants (< 1 year) 0.010552 0.089 250 Children ( 1 2 years) 0.034658 0.089 200 Females ( 13 49 years old) 25 100 0.011497 0.00011 2150 1 The level of concern ( LOC) MOE is 100, based on inter and intra species safety factors totaling 100. 2 Residential Exposure = [ Incidental Oral exposure from all possible sources or Inhalation exposure]. No residential oral exposure is expected for adults. 3 Aggregate MOE = [ NOAEL ( 25 mg/ kg/ day) ÷ ( Avg Food Exposure + Residential Exposure)]. Page 41 of 52 As shown above in Table 5.2, the aggregate short term MOEs for the US population at 1800 and children 1 2 years old at 250 do not exceed HED's level of concern, a MOE of 100. TRB does not consider short term aggregate risk for adults and children to be a concern.

5.3 Intermediate Term Aggregate Risk The intermediate term aggregate risk assessment estimates risks likely to result from one to six months of exposure to azoxystrobin residues from food, drinking water, and residential pesticide uses. High end estimates of residential exposure are used in the intermediate term assessment, while average values are used for food and drinking water exposure ( i. e. chronic exposures).

No endpoint has been selected for intermediate term dermal exposure to azoxystrobin; therefore it will not be included in this assessment. The same endpoints were identified by HIARC for intermediate term incidental oral and inhalation risk assessment ( based on decreased body weight gain in both sexes and clinical signs indicative of reduced nutrition. the basis for the oral endpoint is increased maternal diarrhea, urinary incontinence, and salivation). Therefore, this assessment will combine dietary/ incidental oral exposure with inhalation exposure.

An intermediate term risk assessment is not required for adults because intermediate term residential handler scenarios are not expected to occur. However, an intermediate term risk assessment is required for infants and children because there is a residential post application oral exposure scenario.

TABLE 5.3 Intermediate Term Aggregate Risk ( Food, Water and Incidental Oral Exposure)

Intermediate Term Scenario Population NOAEL mg/ kg/ day LOC MOE1 Average Food + Water Exposure mg/ kg/ day Residential Exposure2 mg/ kg/ day Aggregate MOE ( food and residential) 3 Children ( 1 2 years) 20 100 0.034658 0.042 260 1 The level of concern ( LOC) MOE is 100, based on inter and intra species safety factors totaling 100. 2 Residential Exposure = [ Incidental Oral exposure from all possible sources + Inhalation exposure]. No residential oral exposure is expected for adults. 3 Aggregate MOE = [ NOAEL ( 20 mg/ kg/ day) ÷ ( Avg Food Exposure + Residential Exposure)].

As shown above in Table 5.3, the aggregate intermediate term MOEs for children 1 2 years old, which is the population subgroup with the highest exposure, at 260 do not exceed HED's level of concern, a MOE of 100. TRB does not consider intermediate term aggregate risk for adults and children to be a concern.

5.4 Chronic Aggregate Risk The aggregate chronic risk assessment takes into account average exposure estimates from dietary consumption of azoxystrobin ( food and drinking water) and residential uses. Since the exposure from all the residential uses is considered short term, the aggregate chronic assessment included food Page 42 of 52 and drinking water only. Since the dietary exposure assessment already includes the highest chronic exposure from the drinking water modeling data, no further calculations are necessary. The general U. S. population and all population subgroups have exposure and risk estimates which are below HED's level of concern ( i. e., the percentages of the chronic population adjusted doses ( cPADs) are all below 100%). The exposure to the U. S. population was 8% of the cPAD and the most highly exposed subgroup, children 1 2 yrs old, at 19% of the cPAD. Therefore, chronic risk estimates resulting from aggregate exposure to azoxystrobin in food and drinking water are below HED's level of concern from all population subgroups.

5.5 Cancer Aggregate Risk The HED RfD/ Peer Review Committee, in its meeting of November 7, 1996, determined that azoxystrobin should be classified as " not likely to be a human carcinogen." Due to the classification, no cancer risk assessment was performed.

6.0 CUMULATIVE RISK The Food Quality Protection Act ( 1996) stipulates that when determining the safety of a pesticide chemical, EPA shall base its assessment of the risk posed by the chemical on, among other things, available information concerning the cumulative effects to human health that may result from dietary, residential, or other non occupational exposure to other substances that have a common mechanism of toxicity. The reason for consideration of other substances is due to the possibility that low level exposures to multiple chemical substances that cause a common toxic effect by a common mechanism could lead to the same adverse health effect as would a higher level of exposure to any of the other substances individually. A person exposed to a pesticide at a level that is considered safe may in fact experience harm if that person is also exposed to other substances that cause a common toxic effect by a mechanism common with that of the subject pesticide, even if the individual exposure levels to the other substances are also considered safe.

HED did not perform a cumulative risk assessment as part of this tolerance action for azoxystrobin, because HED has not yet initiated a review to determine if there are any other chemical substances that have a mechanism of toxicity common with that of azoxystrobin. For purposes of this tolerance action, EPA has assumed that azoxystrobin does not have a common mechanism of toxicity with other substances.

7.0 OCCUPATIONAL EXPOSURE Workers may be exposed to azoxystrobin during mixing, loading, application, and postapplication activities. Based on the proposed use pattern, short, and intermediate term exposures may occur. Chronic exposures ( more than 6 months of continuous exposure) are not expected.

7.1 Occupational Handler Handlers are assumed to have potential short ( 1 30 consecutive days) and intermediate term ( 31 180 consecutive days) dermal and inhalation exposure to azoxystrobin. However, potential Page 43 of 52 intermediate term exposure is less likely due to the use directions for azoxystrobin formulations ( which involve restrictions on sequential azoxystrobin/ strobilurin fungicide formulation applications, specific inter application intervals, and number of applications per season). Long term handler exposure is not expected via any route.

As previously stated, there is no hazard via the dermal route, therefore, only risk via the inhalation route is considered in this document. The short term inhalation toxicity endpoint is based on increased maternal diarrhea, urinary incontinence, and salivation seen in the rat prenatal developmental oral toxicity study at the LOAEL of 100 mg/ kg/ day ( NOAEL = 25 mg/ kg/ day). The intermediate term inhalation toxicity endpoint is based on decreased body weight gain in both sexes and clinical signs indicative of reduced nutrition in the rat 90 day feeding study at the LOAEL of 211/ 223 mg/ kg/ day in males/ females ( LOAEL = 20 mg/ kg/ day). Daily doses were calculated assuming a 70 kg body weight for adults ( because the toxicity endpoints are not gender specific) and a 100% inhalation absorption factor.

No chemical specific handler exposure data were submitted in support of this action to inform daily dose calculations. It is the policy of HED to use data from PHED Version 1.1 as presented in the PHED Surrogate Exposure Guide ( 8/ 98) to assess handler exposures for regulatory actions when chemical specific monitoring data are not available ( HED Science Advisory Council for Exposure [ ExpoSAC] Draft Policy # 7, dated 1/ 28/ 99). Proprietary data from the Outdoor Residential Exposure Task Force ( ORETF) have also been used in this assessment. The ORETF data were designed to replace the present PHED data with higher confidence, higher quality data that contain more replicates than the PHED data for particular scenarios ( the risk manager is encouraged to pursue data compensation in the event the registrant is not a member of the task force). Additionally, typical HED standard values were used for the amount treated per day ( ExpoSAC Policy # 9, dated 7/ 5/ 00).

The daily doses presented in this assessment are characterized as mid to high end exposure estimates because both conservative and average values were used in the calculations: the unit exposure values from PHED are considered to be central tendency; the areas treated per day values are considered typical to high end; the application rates and other treatment variables used in this assessment are upper percentile values; and the inhalation absorption factor and body weight values are considered conservative.

Agricultural Crops For the proposed uses on agricultural crops, the scenarios assessed in this document are the following ( the source of the unit exposure values used for each scenario is in parenthesis):

( 1) Open Mixing/ Loading Liquids for Aerial Application and Chemigation ( PHED) ( 2) Open Mixing/ Loading Liquids for Groundboom ( PHED) ( 3) Open Mixing/ Loading Dry Flowable for Aerial Application and Chemigation ( PHED) ( 4) Open Mixing/ Loading Dry Flowable for Groundboom ( PHED) ( 5) Application of Liquid using Aerial Fixed Wing, Enclosed Cockpit ( PHED) ( 6) Flagging for Aerial Liquid Application ( PHED) Page 44 of 52 ( 7) Application of Liquid using Groundboom ( PHED) dd Greenhouse Roses For greenhouse roses, the scenarios assessed in this document are the following ( the source of the unit exposure values used for each scenario is in parenthesis): ( 1) Open Mixing/ Loading Liquid for a High Pressure Handwand ( PHED) ( 2) Application of Liquid using a High Pressure Handwand ( PHED) ( 3) Open Mixing/ Loading Liquid for, and Applying Liquid using, a Backpack Sprayer ( PHED) ( 4) Open Mixing/ Loading Liquid for, and Applying Liquid using, a Low Pressure Handwand ( PHED) ( 5) Open Mixing/ Loading Liquid for, and Applying Liquid using, a High Pressure Handwand ( PHED) ( 6) Open Mixing/ Loading Emulsifiable Concentrate for, and Applying Liquid using, a Low Pressure Handwand ( ORETF, HO, garden/ ornamental, MRID 445185 01, ExpoSAC Memorandum, dated 3/ 5/ 03)

The azoxystrobin formulation proposed for use on greenhouse roses also contains the ai cyproconazole. Exposure to cyproconazole resulting from use of A12910C on greenhouse roses was assessed in an HED memorandum ( DP Num: 313833, M. Dow, 8/ 25/ 05), in which scenarios 1 through 4 listed above were used to assess handler exposure. This document focuses on azoxystrobin. Scenarios 5 and 6 were included in this document to further characterize the greenhouse roses use, and to provide more refined exposure estimates, using data of higher quality.

The A12910C Fungicide label indicates " all types of spray equipment [ can be] used for making greenhouse applications." When handlers are using low pressure handwands and backpack sprayers, HED typically assumes 40 gal/ day are used; and when handlers are using high pressure handwands, HED typically assumes 1000 gal/ day are used. However, the A12910C label does not specify the desired concentration of the tank mix, which makes it difficult to employ the gal/ day standard values. For handgun sprayers, HED typically assumes five acres [ A]/ day are treated, a value more easily employed with the fl oz./ A application rate provided in the A12910C Fungicide label. Therefore, all greenhouse roses handler scenarios ( using different spray equipment) assume five A/ day are treated.

It should be noted that the cyproconazole HED memorandum assumed two A/ day were treated in the assessment of A12910C Fungicide on greenhouse roses. The memorandum cited a journal article ( J. Stamper et al., ( 1989) Pesticide Exposure to Greenhouse Handgunners. Arch. Environm. Contam. Toxicol. 18: 515 529) that found occupational pesticide handlers can treat up to approximately two acres of greenhouse area, and the reviewer noted that even if greenhouses are larger than two acres, it is unlikely that all acres in a greenhouse operation would require any given pesticide treatment at the same time due to different " crops" and " cultivars" requiring different treatments at different times in the greenhouse.

In this assessment five A/ day is employed in calculating daily doses because ExpoSAC Policy # 9, dated 7/ 5/ 00 assumes five A/ day for handgun sprayers ( which the reviewer believes is an adequate proxy for other handheld spray equipment), and the 9/ 15/ 05 ExpoSAC Meeting Minutes state that the Page 45 of 52 ExpoSAC recommends a value of five A/ day for short term exposure scenarios for nursery crops. This is be a conservative assumption.

Unlike for agricultural crops, HED believes only short term exposure ( 1  30 days) would be experienced by occupational handlers for the greenhouse roses scenarios related to the use of A12910C because of label restrictions: only one application may be made without " rotating" to another class of fungicide. That restriction, coupled with azoxystrobin's low vapor pressure, makes it unlikely that intermediate term duration ( 1  6 months) exposures could occur ( even if pesticide treatments are made in different parts of the operation at different times depending on disease pressure/ outbreak).

Indoor Carpet and Other Surfaces The Heritage ® Fungicide label amendment submitted by Syngenta requests an indoor use on carpets by commercial applicators and/ or residential applicators ( communication between M. Schulz [ Syngenta] and B. O'Keefe/ J. Bazuin [ EPA] 10/ 10/ 05). The commercial applicator scenario has been recently assessed for Azoxystrobin Mold Retardant 2.08 SC in the AD memorandum: Proposed Registration for AZOXYSTROBIN MOLD RETARDANT 2.08 SC End Use Product as a New Indoor, Non Agricultural Use Pattern for the Azoxystrobin Active Ingredient: Non Dietary Occupational/ Residential Exposure Considerations ( DP Num: 299065, D. Aviado, 7/ 2/ 04).

The AD memorandum considers a liquid formulation, whereas this document considers a WDG formulation. Appropriate data are not available for handling the WDG formulation for this use ( mixing, loading and applying handheld spray equipment), however, based on PHED unit exposure values from other handler scenarios with these formulation types, the exposure is expected to be less than that of handling a liquid. Other parameters that factor into the daily dose calculation, such as use patterns ( equipment types, area treated, etc.) and application rates ( 2.08 SC: 3.3E 5 lb ai/ ft2; Heritage ® : 3.4E 5 lb ai/ ft2) for the two products are similar. Considered together, in addition to the conservative nature of the AD assessment, estimated daily doses for commercial applicators using Heritage are expected to be quantitatively and qualitatively similar to daily doses for commercial applicators using the 2.08 SC formulation, and therefore the AD commercial applicator assessment serves as a surrogate/ proxy assessment for this label amendment ( the result of the worst case scenario is reported in Table 20).

Section 18 Uses The states of Florida and Tennessee have requested an emergency exemption for the use of azoxystrobin ( formulated with propiconazole in the emulsifiable concentrate [ EC, liquid] formulation QUILT ® ) on Crop Group 6 ( legume vegetables, excluding soybeans) and Crop Group 7 ( foliage of legume vegetables) to control Phakospora pachyrizi ( more commonly known as Asian Soybean Rust or Australasian Soybean Rust). This action is part of a larger action involving 9 end use products and 5 active ingredients ( ai) aimed to provide protection to legume vegetables in the event of a soybean rust outbreak. The fungicides proposed for use on legumes in the event of a soybean rust outbreak are tebuconazole, myclobutanil, propiconazole, trifloxystrobin, and azoxystrobin. Although the states of Florida and Tennessee are the only applicants in this Section 18 request, they expect other states will apply to obtain exemptions, citing their application. Page 46 of 52 Directions provided as part of the larger Section 18 action, propose a maximum of three collective applications of approved Section 18 fungicides, and no more than two applications are proposed for any one given ai. The total acreage of Crop Group 6 ( excluding soybeans) and 7 is 60,002 acres in Florida, 26,500 acres in Tennessee, and 6,026,018 acres in the United States ( based on 45 states that responded to the applicant's survey). It is unlikely that the total acreage of these crops would have to be treated, and therefore, these are maximum estimates of potential acreage treated.

For azoxystrobin in particular, the applicants submitted a label that proposed a maximum application rate of 14 fluid ounces ( fl oz) of QUILT ® ( 0.182 lbs. ai [ azoxystrobin and propiconazole], 0.0678 lbs. azoxystrobin) per acre ( A), applied at a maximum of 3 times per season, with interapplication intervals ranging from 14 to 21 days depending on disease pressure ( maximum seasonal application rate 42 fl oz. QUILT ® ) . Note that this conflicts with the general use directions provided for the entire Section 18 application, which indicated a maximum of 2 applications would be permitted with any one active ingredient. The applicants estimated, based on the use of up to two applications of QUILT ® , that 362,500 lbs of propiconazole and azoxystrobin would be used per 1 million acres treated. Note again that the estimated use of up to 2 applications of Quilt ® conflicts with the proposed 3 applications ( on the specific Section 18 label addendum), and maximum seasonal application rate of 42 fl oz/ A; which is equivalent to 3 applications at the maximum application rate of 14 fl oz./ A ( however, it corresponds with the general use directions for the entire Section 18). This Section 18 addresses the active ingredient azoxystrobin only, propiconazole ( and the other active ingredients) will be considered in separate documents.

Summary Handlers are assumed to have potential short ( 1 30 consecutive days) and intermediate term ( 31 180 consecutive days) dermal and inhalation exposure to azoxystrobin. However, potential intermediateterm exposure is less likely due to the use directions for azoxystrobin formulations ( which involve restrictions on sequential azoxystrobin/ strobilurin fungicide formulation applications and specific interapplication intervals). Long term handler exposure is not expected via any route.

As previously stated, there is no hazard via the dermal route, therefore, only risk via the inhalation route is considered in this document. The short term inhalation toxicity endpoint is based on increased maternal diarrhea, urinary incontinence, and salivation seen in the rat prenatal developmental oral toxicity study at the LOAEL of 100 mg/ kg/ day ( NOAEL = 25 mg/ kg/ day). The intermediate term inhalation toxicity endpoint is based on decreased body weight gain in both sexes and clinical signs indicative of reduced nutrition in the rat 90 day feeding study at the LOAEL of 211/ 223 mg/ kg/ day in males/ females ( NOAEL = 20 mg/ kg/ day). Daily doses were calculated assuming a 70 kg body weight for adults ( because the toxicity endpoints are not gender specific) and a 100% inhalation absorption factor.

No chemical specific handler exposure data were submitted in support of this action to inform daily dose calculations. It is the policy of HED to use data from PHED Version 1.1 as presented in the PHED Surrogate Exposure Guide ( 8/ 98) to assess handler exposures for regulatory actions when chemicalspecific monitoring data are not available ( HED Science Advisory Council for Exposure [ ExpoSAC] Page 47 of 52 Draft Policy # 7, dated 1/ 28/ 99). Additionally, typical HED standard values were used for the amount treated per day ( ExpoSAC Policy # 9, dated 7/ 5/ 00).

The daily doses presented in this assessment are characterized as mid to high end exposure estimates because both conservative and average values were used in the calculations: the unit exposure values from PHED are considered to be central tendency; the areas treated per day values are considered typical to high end; the application rates and other treatment variables used in this assessment are upper percentile values; and the inhalation absorption factor and body weight values are considered conservative.

For the proposed uses on agricultural crops, the scenarios assessed in this document are the following ( the source of the unit exposure values used for each scenario is in parenthesis):

Typical Agricultural Handler Scenarios: 1. Open Mixing/ Loading Liquids for Aerial Application and Chemigation ( PHED) 2. Open Mixing/ Loading Liquids for Groundboom ( PHED) 3. Open Mixing/ Loading Dry Flowable for Aerial Application and Chemigation ( PHED) 4. Open Mixing/ Loading Dry Flowable for Groundboom ( PHED) 5. Application of Liquid using Aerial Fixed Wing, Enclosed Cockpit ( PHED) 6. Flagging for Aerial Liquid Application ( PHED) 7. Application of Liquid using Groundboom ( PHED)

Post harvest Handler Scenarios: 8. Open Mixing/ Loading Liquids for post harvest Commodity Treatment ( PHED) a. High volume ( dilute) applications b. Low volume ( concentrated) applications c. Dip applications 9. Open Mixing/ Loading Dry Flowable for post harvest Commodity Treatment ( PHED) a. High volume ( dilute) applications b. Low volume ( concentrated) applications c. Dip applications The following lays out the methodology employed by HED to assess exposure resulting from the postharvest citrus handler scenario. HED determined that during citrus waxing and packing operations, the amount handled per day can be calculated as follows: a large operation can process up to 2,000 boxes per hour, each weighing 90 lbs; while there are some differences between products, a typical product is applied at a rate of 212 grams of a 98.5 percent product in 192.5 gal of waxing solution (~ 0.0024 lb ai/ gal of soln [ in this assessment, label specific solution concentrations are used in the calculations]); the material is then applied at a rate of 1 gallon per 8,000 10,000 pounds of fruit ( this assumption, as well as label specific information is used in the calculations). If fresh solution is used without recycling, the amount of material handled at a facility would be:

Amount mixed ( lb ai/ hr) = 2,000 ( boxes/ hr) x 90 ( lbs/ box) x 1/ 8,000 ( gal/ lbs fruit) x soln conc ( lb ai/ gal)   Solution concentrations are label specific in this assessment ( labels indicate concentrations ranging from 0.0052   0.149 lb ai/ gal [ Abound] and 0.013   0.37 lb ai/ gal [ Amistar])   The number of gallons of solution used per amount fruit treated ( gal/ lbs fruit) are both label specific ( when available, i. e., for the low volume [ concentrated] applications, which Page 48 of 52 specifies 250,000 lbs of fruit can be treated per batch of 7 to 25 gallons of solution [ 1 gal soln/ 36,000 lbs fruit was used in the exposure estimate calculations for this exposure scenario]); for the other scenarios ( high volume [ dilute] applications and dipping applications, 1 gal/ 8,000 lbs of fruit is assumed.

Other assumptions are as follows:   A work shift is assumed to be 8 hours/ day   An average worker weighs 70 kg   The respiration rate during these activities is 1.0 m ³ per hour ( light activity, NAFTA Recommendations). Under these conditions respiratory exposure can usually be considered negligible ( although are calculated here to ensure HED is protective).   Dermal exposure is not considered because there is no hazard via the dermal route. Respiratory exposures were obtained from the PHED Surrogate Guide. The inhalation unit exposure estimates for mixer/ loaders wearing a single layer of clothing with no gloves are 0.0012 mg/ lb ai ( liquid) and 0.00077 mg/ lb ai ( flowable) for the respiratory routes.

Respiratory Exposure ( mg/ kg/ day) = unit exposure ( mg/ lb ai) x amount mixed ( lb ai/ hr) x 8 ( hrs/ day)/ 70 kg The estimates of exposure resulting from these calculations should be considered to be conservative for the following reasons; ( 1) workers are not assumed to wear any protective clothing while mixing/ loading the material for post harvest treatments ( e. g., respirators); ( 2) the material is not assumed to be recycled, in practice some chemicals are recycled 3 5 times before new formulation is mixed; ( 3) the estimates are derived from citrus data, other commodities may not have the throughput associated with a large citrus packing plant.

It should be noted that this methodology was not derived for dip application, a scenario for which HED has no data; however, because there is no dermal hazard, the post harvest treatment scenario is considered an adequate surrogate to assess inhalation exposure for the dip application scenario.