**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS**

**PUBLISHED IN THE FEDERAL REGISTER**
**EPA Registration Division contact: [Mark Suarez, (703) 305**  **- 0120]** 

**INSTRUCTIONS: Please utilize this outline in**  **preparing the pesticide petition. In cases where the outline element does not apply, please insert “NA** **- Remove” and maintain the outline.**  **Please do not change the margins, font, or format in your pesticide petition. Simply replace the instructions that ap**  **pear in green**  **, i.e., “ [**  **insert company name ]**  **,” with the information specific to your action.** 

**TEMPLATE: [**  **BASF Corporation ]** 
**[Insert petition number]**
EPA has received a pesticide petition **( [**  **---------- ]**  **)** from **[ BASF Corporation**  **] ,**  **[ 26 Davis**  **Driv e,**  **P.O. Box 13528, Research Triangle Park, North Carolina 27709**  **- 3528**  **]** proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by amending the establish ed tolerance for residues of the fungicide **[ Fluxapyroxad**  **, (**  **BAS 700 F )**  **; 1**  **H -**  **Pyrazole -** **4 -** **carboxamide, 3**  **- (difluoromethyl)**  **- 1**  **- methyl**  **- N** **- (3',4',5'**  **- trifluoro[1,1'**  **- biphenyl]**  **- 2**  **- yl)**  **- , its**  **metabolites, and degradates**  **]** in or on the following raw agricultural commodit ies : **[ Fruit, stone** **, group 1 2**  **]** a t **[ 3.**  **0 ]**  parts per million ( ppm )
. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted d a ta at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.
A. Residue Chemistry2 1. Plant metabolism . **[ Nature of the residue studies were conducted in**  **wheat , soybean**  **and tomato as representative cro ps in order to characterize**  **the fate of fluxapyroxad**  **(BAS 700 F)**  **in all crop ma trices. Two radiocarbon labels w**  **ere studied in each crop, with 14 -**  **C labels positioned**  **i n**  **aniline and**  **pyrazole ring stru**  **ctures. Fluxapyroxad**  **was the predominant residue in most c**  **rops. In all crops the**  **fluxapyroxad Residues of Concern (ROC) were characterized as**  **parent fluxapyroxad**  **plus metabolites M700F048 and M700F002**  **. A conf ined rotational crop**  **study added metabolite M700F008 and confirmed that parent**  **fluxapyroxad plus metaboli** **tes M700F008** **, M700F048 and M700F002**  **w ere**  **the residue s**  **of concern in the representative rotational**  **crops of wheat, radish, and spinach**  **. ]** 

2. Analytical method. **[ Independently validated analytical methods have been**  **submitted for analyzing residues of parent fluxapyroxad (BAS 700 F)**  **plus metabolites M700F008** **, M700F048 and M700F002**  **with appropriate sensitivity in /on**  **stone fruits (group 12)**  **crops, represented by cherry, peach, and plum for which**  **tolerances have been**  **established .**  ]

3. Magnitude of residues. **[ Field trials were carried out to determine the magnitude of**  **the residue in/o n**  **Cherry, Peach, and Plums. The data wer e**  **used to establish a tolerance of 2 ppm for**  **fluxapyroxad ( BAS 700 F**  **) residues in/on the stonefruit crop group 12**  **commodities. For the Eu**  **ropean Union (EU) import MRL application for cherries, two (2) additional residue trials were conducted to complete the requirements. However, over** **- tolerance fluxapyroxad**  **residues were confirmed in some**  **cherry samples which require amendment of the establ ished**  **tolerance for the stonefruit crop group 12. The number**  **and locations of field trials are in accordance with OPPTS Guideline 860.1500. Field**  **trials were carried out using the maximum label rates, the maximum number of applications, and the minimum pre**  **- harvest interval (PHI)**  **for all the crops. Residues of M700F048 and M**  **700F002 were generally less than the limit of**  **quantitation and often less than the limit of detection**  **. Residues of M700F** **008 were significantly less than**  **residues of fluxapyroxad**  **. Detec** **te d residues of**  **fluxapyroxad in all crops**  **support the proposed tolerance based on parent**  **fluxapyroxad .**  **The impact of the amended**  **tolerance on the animal Maximum Reasonably Balanced Diets was**  **insignificant , and thus no**  **change s**  **in tol erances in animal commodit**  **ies are proposed.**  **]**

B. Toxicological Profile

1. Acute toxicity. **[ Fluxapyroxad**  **( BAS 700 F**  **) displayed low acute toxicity via the oral,**  **dermal and inhalation routes of exposure. It was not irritating to the eyes, only slightly**3

**irritating to the skin, and not a dermal sensitizer. The acute toxicity studies place technical**  **fluxapyroxad in toxicity category III for acute oral and dermal and category IV for acute**  **inhalation, eye and skin irritation. F**  **luxapyroxad i**  **s not a dermal sensitizer. ]** 

2. Genotoxicty. **[ Fluxapyroxad**  **( BAS 700 F**  **) was not genotoxic in a battery of assays.**  **Fluxapyroxad was negative for inducing mutations in bacterial and mammalian cell assays. No**  **evidence of a clastogenic effect was observed in vitro or in vivo, and fluxapyroxad**  **did not cau**  **se unscheduled DNA synthesis in hepatocytes of treated rats. ]** 

3. Reproductive and developmental toxicity. **[ The reproductive and developmental**  **toxicity of fluxapyroxad**  **( BAS 700 F**  **) was investigated in a 2**  **- generation rat reproduction study**  **as well as in rat and rabbit developmental toxicity studies. In the reproduction study, there**  **were no effects on fertility, up to the highest dose tested of 300 mg/kg bw/d. At the high -**  **and mid**  **- (50 mg/kg bw/d) doses tested,**  **fluxapyroxad administration resulted in decrease**  **d food consumption, impaired body weight development, clinical chemistry and select organ weight**  **changes and histopathology. Impairment of pup body weight development was also seen at these doses. The NOAEL for systemic and developmental toxicity was 10 mg** **/kg bw/day. In the rat developmental toxicity study, slight maternal toxicity was observed at the high dose**  **level of 1000 mg/kg bw/d, in the form of limited clinical chemistry, liver and thyroid weight effects, and thyroid histopathology. No evidence of**  **developmental toxicity was observed in the rat up to the highest dose tested of 1000 mg/kg bw/d.**  **At the highest dose tested in the rabbit teratology study (60 mg/kg bw/d), maternal toxicity consisted of clinical signs, abortion, reduced food consumption,**  **and impaired body weight development. The only developmental effect at the high dose, which caused substantial**  **maternal toxicity, consisted of a commonly observed, reversible external variation, paw hyperflexion. Based on the effects described, the materna**  **l and developmental NOAEL in rabbits was 25 mg/kg bw/d.**  **]**

4. Subchronic toxicity. **[ The principal target organ in all studies in rats, mice and dogs**  **was the liver, as indicated by organ weight changes and altered clinical chemistry parameters, which were c**  **onsistent with liver enzyme induction. Histopathological changes in the liver were only evident in rats. The thyroid was also identified as a target organ in rats, as indicated**  **by organ weight changes, histopathology and thyroid hormone changes. The lowest NOAEL in**  **subchronic oral toxicity studies was approximately 7.3**  **mg/kg bw/day in the rat 90**  **- day study.** 4

**No systemic toxicity was observed in a 28 -**  **day repeat dose dermal toxicity study at doses as high as 1000 mg/kg bw/day.** 
**The neurotoxic potential of flu**  **xapyroxad (**  **BAS 700 F )**  **was studied following both acute and subchronic oral administration in the rat. In the acute study, treatment** **- related**  **neurobehavioral effects were noted in mid and high dose animals on the day of treatment. These consisted of slight i**  **ncreases of the landing foot -**  **splay in high dose males, reduction in the number of rearings in males, and impaired motor activity in high and mid dose males and**  **females. No effects on these parameters were observed on study days 7 and 14. Additionally, no t**  **reatment -**  **related neuropathological findings (brain weight changes, neurohistopathological findings) were observed. Therefore, the affected parameters indicated**  **a neuropharmacological effect rather than neuronal damage. Based on the results of this study th**  **e NOAEL for acute neurotoxicity was 125 mg/kg bw/d in male and female rats.**
**There was no indication of clinical (general clinical observation, FOB and motor activity) or neurohistopathological neurotoxicity in a subchronic neurotoxicity study. Systemic si** **gns of toxicity were consistent with those seen in repeated dose studies with**  **fluxapyroxad . Under**  **the conditions of the present study the no observed adverse effect level (NOAEL) for neurotoxicity was 5000 ppm (approximately 320 mg/kg bw/d), the highest do**  **se tested. ]** 

5. Chronic toxicity. **[ Systemic toxicity in long term oral exposure studies in dogs, mice**  **and rats included effects on food consumption, body weight development and clinical chemistry changes. The liver was identified as the main target organ**  **in all species tested, as indicated by liver weight changes and non**  **- neoplastic lesions. Additional target organs in the**  **rat included the thyroid and bones. The spleen, gall bladder and prostate were affected in dogs.** 
**Fluxapyroxad (**  **BAS 700 F )**  **was not carci nogenic in C57BL mice following continuous dietary**  **administration for 18 months at dietary concentrations up to 6000 ppm (approximately 1000 mg/kg bw/d).**  **Treatment of fluxapyroxad**  **for 2 years in rats resulted in the induction of hepatocellular tumors in ma**  **les at dose levels ≥ 250 ppm and in females at ≥ 1500 ppm. A**  **mitogenic, Phenobarbital -**  **like mechanism is proposed as the probable mode of action for liver tumor development**  **in rats. This was supported by mechanistic studies on enzyme induction**  **and S -**  **Phase r esponse in the liver** **, and indicates there is a threshold for tumor development and a margin of exposure cancer risk assessment is appropriate.** 5

**In the rat chronic/oncogenicity study, the NOAEL in males and females was 50 ppm (2.1 and 2.7 mg/kg bw/day, resp**  **ectively). NOAEL’s in the mouse oncogenicity study were 150 ppm in males (21 mg/kg bw/day) and in females (33 mg/kg bw/day). In a chronic dog study, the**  **NOAEL was 300 ppm (approximately 8 mg/kg bw/day). ]** 

6. Animal metabolism. **[ The rat, goat and hen meta**  **bolism studies were conducted to det**  **ermine the nature of the fluxapyroxad (**  **BAS 700 F )**  **residues in animals. S** **tudies were conducted with radiolabeled**  **fluxapyroxad with 14** **- C labels positioned in**  **aniline and**  **pyrazole ring structures**  **(hen metabolism, aniline ri ng label only)**  **. BAS 700 F**  **was either excreted rapidly in urine and feces or transformed to a number of metabolites after administration to**  **animals. All relevant metabolites were identified. U**  **nchanged parent compound was found as the predominant component**  **in most animal matrices. The metabolism of fluxapyroxad**  **in the animals is well understood.**  **Degradation proceeds via N**  **- demethylation of the pyrazole ring**  **and/or hyroxylation of the biphenyl ring followed by subsequent O -**  **and N -**  **conjugation reactions**  **to produ ce metabolites that are rapidly excreted, along with parent, and do not**  **readily accumulate in tissues or milk. Residues in m**  **ilk and most edible tissues are low.**  **The same**  **metabolic reactions were observed in each of the animals studied, so there is a consis** **tent metabolic pathway for**  **fluxapyroxad in animals.**  **Rat, goat**  **and hen metabolism studies were also conducted with**  **radiolabeled M700F048, a N**  **- glucoside of N**  **- desmethyl BAS**  **700F, a plant metabolite, seen at levels >10 TRR in soybean seed in the plant metabol ism**  **study . In all animals, the glucoside**  **was readily hydrolyzed to generate M700F008, a key intermediate in the metabolism of**  **fluxapyroxad in animals. The radiolabeled residue was**  **rapidly excreted with little uptake in tissue, following a metabolic pathwa y in all animals like**  **that for fluxapyroxad**  **. Rat ,**  **goat and hen metabolism stu dies were also conducted with**  **radiolabeled M700F002, a carboxylic acid attached to the pyrazole**  **- ring formed by cleavage of**  **the fluxapyroxad**  **carboxamide bond. M700F002 was seen a t levels >10 TRR in soybean seed**  **in the plant metabolism and was present only at low levels in the rat urine. In all animal studies, M700F002 was not metabolized and was almost completely and rapidly excreted**  **unchanged ,**  **with no uptake in tissue. ]** 

7. Metabolite toxicology . **[ The metabolism of**  **fluxapyroxad (**  **BAS 700 F )**  **is similar in plants and mammals. The metabolism of**  **fluxapyroxad , both in plants and animals, is largely**  **based on two key transformation reactions, N -**  **demethylation of the pyrazole moiety and hydroxylation of the biphenyl moiety. Both reactions, combinations thereof, and subsequent**  **conjugation reactions (e.g. glucose, glucuronic acid, cysteine) result in a range of common and structurally related compounds. Due to the similar structural natur** **e of most metabolites, the toxicity of most plant metabolites is adequately estimated from the results of studies** 6

**performed with fluxapyroxad**  **in animals. In addition, the metabolism of metabolites M700F002, and M700F048 were each investigated in rat, goat**  **and hen. Animal metabolism studie**  **s were performed with M700F002 since the plant metabolite was seen in the rat**  **metabolism only at low levels in urine. In rat, goat and hen, M700F002 is rapidly and almost completely excreted unchanged with almost no uptake**  **in tissue, milk or eggs. M700F002 is not metabolized in animal to any significant extent.** 
**Animal metabolism studies were performed with M700F048, a glucoside conjugate since the plant metabolite would not be formed in animal metabolism. In animal metab**  **olism studies, M700F048 was rapidly hydrolyzed to metabolite M700F008, a key metabolite in the metabolic**  **pathway of fluxapyroxad**  **. Unchanged M700F048 was not detected in edible animal**  **commodities.**
**Toxicology studies (Acute oral toxicity, Ames test, in vitr o mutagenicity test in mammalian**  **cells, in vitro chromosome aberration test, in vivo mouse micronucleus, 28/90 -** **day rat feeding and developmental toxicity in rabbits) were conducted on**  **three metabolites .**  **Overall, M700F001, M700F002 and M700F048 are of low a**  **cute and subchronic toxicity in rats. The metabolites showed no genotoxic potential in a battery of genotoxicity studies. In addition, no**  **adverse effects were observed up to the highest doses tested in developmental toxicity study with rabbits.**  **]**

8. Endocrine disruption . **[ No specific tests have been conducted with**  **fluxapyroxad (**  **BAS 700 F**  **) to determine whether the chemical may have an effect in humans that is similar to an**  **effect produced by a naturally occurring estrogen or other endocrine effects. Howeve r, there**  **were no significant findings in other relevant toxicity studies (e.g., sub -**  **chronic and chronic toxicity, developmental toxicity and multi**  **- generation reproductive studies) which would**  **suggest that fluxapyroxad**  **produces any endocrine disruption. ]** 

C . Aggregate Exposure

1. Dietary exposure. **[ The tolerance expression**  **for dietary risk**  **assessment is**  **fluxapyroxad (**  **BAS 700 F )**  **and M700F008 in plant and animal commodities except milk ,**  **for which M700F01**  **0 is also included.**  **Exposure assessments were conduct ed to evaluate the**  **potential risk due to acute and chronic dietary exposure of the U.S. population and all sub**  **** **populations. The assessments included**  **all current established tolerances , pending tolerances,** 7

**the crop**  **commodities proposed for tolerances ,**  **and a nimal matrices including egg, milk and**  **cream .**  **]** i. Food. **[ Acute Dietary Exposure Assessment**  **Acute dietary exposure estimates were based on (**  **a) tolerance v** **alues on crops approved as of May 14, 2012 with the factor of 1.5 that was used in the acute dietary a**  **ssessment conducted as part of the evaluation by EPA (a few input values were changed as discussed below)**  **; (**  **b) proposed tolerance values**  **for crops for which tolerances are pending, and crops included in**  **this submission. A**  **1.5 factor was not used to adjust the tolerances**  **for the new commodities used in the assessment since the levels of metabolite M700F008 were**  **always much less than 5**  **0% of the tolerance .**  **The analysis assumed 100% of all crops treated.**  **Values changed from the EPA**  **dietary analysis of Februa**  **ry 2012 are soybean seed commodities changed from 0.75 mg/kg to 0.15**  **mg/ kg** **, sweet corn changed from 0.015 to 0.15 mg/kg and rice comm odities to**  **reflect new pending**  **rice use. The impact of the new commodities on the animal Maximum Reasonably Balanced Diets**  **was minimal and thus no change s**  **in tol erances in animal**  **commodities are proposed.** 
**For drinking water a ll**  **fluxapyroxad (**  **BAS 700 F )**  **uses were examined at maximum use rates, maximum number of applications, and all proposed application methods to determine**  **which use would result in the highest water concentrations. The highes** **t acute**  **water concentration occurred from the**  **rice use**  **scenario. T**  **he highest acute Estimated Drinking Water Concentrations (EDWC) for BAS 700 F were**  **estimated to be 26.1**  **μ g/L**  **(ppb) in s urface water**  **. The consumption of water was included in the analysis, and the residue concentration in**  **water was set at 0.0 261**  **mg/L based on the surface water concentration determined for the pending**  **use in rice**  **. The consumption data was from the**  **NHANES 2**  **- day food consumption data for 2003 to**  **2008 and**  **the assessment was performed using the Dietary Exposure Evaluation Module (DEEM**  **** **FCID) software.**

**The result ing**  **exposure estimates were compared against the fluxapyroxad**  **( BAS**  **700 F )**  **acute Population Adjusted**  **Dose (aPAD) of 1.25**  **mg/kg b.w./day for all populations.**  **The endpoint is**  **based on the NOAEL of 12**  **5 mg/kg/day with an FQPA safety factor of 1. The most highly**  **expos ed**  **sub -**  **population was children 1**  **- 2 years old**  **with 8.9**  **% utilization of the aPAD. The results**  **of the acute dietary assessment are presented in Table 1.** 8

**Table 1 . Results**  **for fluxapyroxad**  **( BAS 700 F**  **) Acute Dietary Exposure**  **(Food and Water) Considering**  **all Current and**  **Proposed Toler ances**  **using DEEM -**  **FCID at the 95 th**  **Percentile**

**Population Exposu**  **re Estimate % a**  **PAD Subgroups**  **(mg/kg b.w./day) U.S. Population**  **0.047194 3.8**  **All Infants (< 1 year old) 0.090603**  **7.2 Children (1**  **- 2 years old)**  **0.111309 8.9**  **Children (3 -**  **5 years old) 0.090178**  **7.2 Children (6**  **- 12 years old)**  **0.047793 3.8**  **Youth (13 -**  **19 years old)**  **0.031709 2.5**  **Adults (20 -** **49 years old) 0.039777**  **3.2 Adults (50+ years old)**  **0.03779 3.0**  **Females (13 -** **49 years old) 0.039958**  **3.2**

**Th e**  **results of the analysis show that for all populations, the estimated exposures are well below the Agency's level of**  **concern (< 100% aPAD). Additional refinements in the dietary risk assessment (i.e. utilizing anticipated residue values, percent crop treated values) would**  **further reduce the estimated exposure values.**
**Chronic Dietary Exposure Assessment The**  **c hronic diet**  **ary e xposure estimates were based on**  **combined residues of the highest average field trial (HAFT) values for parent and HAFT**  **values for residues of**  **M700F008 for all**  **registered raw agricultural commodities and all newly proposed raw agricultural commodities**9

**except for the use of the mean residue values of fluxapyroxad (**  **BAS 700 F )**  **and HAFT values for**  **residues of M700F008**  **for the commodities of barley** **, buckwheat, millet, oat, and rice.**  **Processing factors for appl e juice (0.2), apple sauce (0.25**  **) , potato dry gr** **anules (1.17) ,**  **sugarcane refined sugar (0.04) and molasses (0.16) as**  **determined in processing studies were**  **used. Some other changes were made to values used in the EPA evaluation of February 2012**  **in that apricot and nectarine residues were set equal to pe ach**  **residues , rye and triticale**  **residues were set equal to wheat residues and sweet corn was set to 0.15 mg/kg rather than**  **0.01 mg/kg.**
**For drinking water a ll**  **fluxapyroxad (**  **BAS 700 F )**  **uses were examined at maximum use rates, maximum number of applications,**  **and all proposed application methods to determine which use would result in the highest water concentrations. The highest**  **chronic water concentration occurred from the**  **use in paddy rice scenario**  **. T**  **he highest chronic EDWC’s for BAS 700F were estimated to**  **be 23.623**  **μ g/L in surface water**  **. The consumption of water was included in the**  **analysis, and the residue concentration in water was set at 0.0236 mg/L based on the surface water concentration determined for the use in paddy rice.**  **The consumption data was fr om the**  **NHANES 2 -**  **day food consumption data for 2003 to 2008**  **and the assessment was performed using the**  **Dietary Exposure Evaluation Module (DEEM**   ** FCID) software.**
**The chronic Population Adjusted Dose (cPAD) used for U.S. population and all sub**  **- populations**  **is 0.021**  **mg/kg bw/day. This endpoint is based on the NOAEL valu e of 2.1**  **mg/kg bw/day using**  **a FQPA safety factor of 1. The most highly expos ed**  **population sub -** **group was children 1 -**  **2 years of age which utilized**  **70.3 % c**  **PAD. The results of the chronic dietary a ss**  **e ssment are**  **presented in Table 2**  **.**
**Table 2 . Results for**  **fluxapyroxad (**  **BAS 700 F )**  **Chronic Dietary Exp osure**  **(Food and Water) Considering All**  **Commodities using DEEM**  **- FCID** 

**Population Exposure Estimate**  **% cPAD Subgroups**  **(mg/kg b.w./day) U.S. Population**  **0.0 05725**  **27.3 All Infants (< 1 year old)**  **0.009033 43.0** 10 **Children (1 -**  **2 years old) 0.014769**  **70.3 Children (3**  **- 5 years old)**  **0.011421 54.4**  **Children (6 -**  **12 years old) 0.006514**  **31.0 Youth (13**  **- 19 years old)**  **0.003794 18.1**  **Adults (20 -** **49 years old) 0.004983**  **23.7 Ad**  **ults (50+ years old) 0.005376**  **25.6 Females (13**  **- 49 years old)**  **0.005047 24.0** 

**The results of the**  **risk assessment show that for all pop**  **ulations the exposures are**  **below a level of concern (< 100% cPAD).**  **Additional refinements in the dietary risk assessment ( i.e.**  **utilizing anticipated residue values, percent crop treated values) would further reduce the estimated exposure values.**  **]**

ii. Drinking water. **[ The consumption of**  **fluxapyroxad (**  **BAS 700 F )**  **residues in drinking water was included in the dietary assessmen**  **ts above. For drinking water a**  **ll fluxapyroxad**  **uses were examined at maximum use rates, maximum number of applications, and all proposed**  **application methods to determine which use would result in the highest water concentrations. The highes** **t acute and chron**  **ic water concentration**  **occurred from the rice**  **use scenario. T**  **he highest acute Estimated Drinking Water Concentrations (EDWC) for fluxapyroxad**  **were estimated to be 26.1**  **μ g/L**  **(ppb) in surface water .**  **The consumption of water was included in the analysis, an**  **d the residue concentration in water was set at 0.0**  **261 mg/L based on the surface water concentration determined for the use in**  **rice.**
**The highest chronic water concentration**  **occurred from the use in paddy rice**  **. The highest**  **chronic EDWC’s for fluxapyrox** **ad (**  **BAS 700 F**  **) were estimated to be**  **23.623 μ** **g/L in surface water**  **. The consumption of water was included in the analysis, and the residu**  **e c**  **oncentration in water was set at 0.0236 mg/L based on the surface water concentration determined for the**  **use in paddy rice.** 

**Short -**  **and Intermediate -** **Term Aggregate Exposure and Risk (food, water, and residential)**11

**Short -**  **and intermediate -** **term aggregate risk assessments include exposure from food, water,**  **and residential uses. Fluxapyroxad**  **( BAS**  **700 F )**  **i \**  **hs s**  **been proposed fo r**  **regist ration**  **for use on residential turf.**  **Because no dermal hazard of concern was identified for fluxapyroxad**  **only inhalation exposure was assessed for residential handlers, and incidental ingestion was**  **assessed for activities of children on treated tur f.** 

**The short**  **- term oral NOAEL is 9.0 mg/kg bw/day and the**  **intermediate -** **term NOAEL is 7.3**  **mg/kg bw/day. The short -** **term aggregate risk assessment is**  **presented in Table 3 and the intermediate**  **- term aggregate risk assessment is presented in Table 4.** 

**Table 3: Short**  **- Term Aggregate Exposure and Risk for**  **fluxapyroxad ( BAS 700 F**  **)**

**Sub -**  **Populations Short**  **- term Aggregate**  **Food + water exp. (mg/kg**  **bw/day) Residential** 

**exp (mg/kg bw/day)**  **Total exp**

**(mg/kg bw/day)**  **MOE**
**US Population 0.005725**  **0.000000 0.005725**  **1572 C**  **hildren 1 -**  **2 years old 0.014769**  **0.021385 0.036154**  **249**

**Table 4: Intermediate -** **Term Aggregate Exposure and Risk for BAS 700 F**

**Sub -**  **Populations Intermediate**  **- Term Aggregate**  **Food + water Exp. (mg/kg**  **bw/day) Residential** 

**Exp. (mg/kg bw/day)**  **Total Exp.**

**(mg/kg bw/day)**  **MOE**
**US Population 0.005725**  **0.000000 0.005725**  **1275 Children 1**  **- 2 years old**  **0.014769 0.021385**  **0.036154 202** 12

**The aggregate MOEs for dietary (food + water) and residential exposures are 202 and 24** **9 for**  **children 1 -**  **2 years old and 1275 and 15**  **72 for the**  **general US population. These MOE values indicate that aggregate risk from the use of BAS 700 F is not a concern.**  **]**

2. Non - dietary exposure . **[ A residential exposure and risk assessment was conducted for the proposed residential use of**  **fluxapyroxad (B** **AS 700 F) products for disease control in turf. Because no dermal hazard of**  **concern was identified for fluxapyroxad, only inhalation exposure was assessed for residential handlers, and incidental ingestion was assessed for activities of children on treated**  **turf. In all exposure scenarios, the MOEs for residential use of fluxapyroxad were well above EPA’s level**  **of concern (MOE < 100) indicating that these exposures are not of concern.**
**The combined post -**  **application exposure for children 1 to <2 years old was estimated using**  **highly conservative assumptions including: a) basing the transferable residue on the seasonal maximum application rate; b) combining all sources of incidental exposure; c) using EPA**  **default values for children’s activities. With these high ly conservative assumptions the**  **incidental exposure was calculated to be 0.021385 mg/kg/day, resulting in short -**  **and intermediate**  **- term MOEs of 420 and 341, respectively.**  **]**
D. Cumulative Effects **[ "Section 408(b)(2)(D)(v) requires that, when considering whet**  **her to establish, modify, or revoke a tolerance, the Agency consider “available information''**  **concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity." Unlike other pesticides fo**  **r which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not**  **made a common mechanism of toxicity finding as to fluxapyroxad**  **( BAS**  **700 F )**  **. For the**  **purposes of this tolerance action, therefore, BASF has not assumed that**  **fluxapyroxad has a**  **common mechanism of toxicity with other substances. ]** 
E. Safety Determination

1. U.S. population. **[ Based on this risk assessment, BASF concludes that there is a**  **reasonable certainty that no harm will result to the general populati on from the ag** **gregate exposure to**  **fluxapyroxad ( BAS 7**  **00 F**  **) from the proposed**  **increase in tolerance for the stonefruit crops, group 12**  **. ]** 13

2. Infants and children
. **[ Based on this risk assessment, BASF concludes that there is a**  **reasonable certainty that no h arm will result to infants or children from**  **the aggregate exposure to**  **fluxapyroxad ( BAS 7**  **00 F**  **) from the proposed**  **increase in tolerance for stonefruit crops, group 12**  **. ]** 

F. International Tolerances
**[ European Maximum Residue Limits (MRL) were established f** **or fluxapyroxad on multiple crops in October 2011**  **[ Commission Regulation (EU) No**  **978/2011 of 3 October**  **2011 ;**  **MRLs for fluxapyroxad (BAS 700 F) in various commodities of plant and animal origin. EFSA Journal 2011; 9(6):2196 [68 pp.].**  **]**

**Health Canada Pest Ma nagement Regulatory Agency (PMRA) has published Maximum Residue**  **Limits (MRL) for fluxapyroxad residues on multiple crop commodities. A complete list can be found on the Maximum Residue Limits for Pesticides webpage in the Pesticides and Pest**  **Management sec tion of Health Canada’s website.**  

### The **Australian Pesticides and Veterinary Medicines Authority (APVMA) established an**  **MRL of 0.1 ppm on barley and all other crops grown in Australia.**  **The Food Standards Australia New Zealand also proposed**  **an MRL of 2 mg/kg (** **ppm) on stone fruits [except plums**  **(including prunes)] for the purpose of harmonizing MRLs with the U.S.**  **There are no CODEX maximum residue levels established for residues of fluxapyroxad (BAS**  **700 F) in**  **/on stone fruits (group 12)**  **. Several crops, including stonefruits, were**  **nominated for**  **inclusion on the 201 1**  **tentative CODEX**  **evaluation schedule and the Data Directory for fluxapyroxad was submitted for the 2012 Joint Meeting on Pesticide Residues (JMPR).**