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

**PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA Registration Division contact:**  **[ Shaja Joyner** **, (703) 308**  **- 3194**  **]**
**INSTRUCTIONS: Please utilize this outline i**  **n 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 a** **ppear 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 **( 5F**  **8344 )**  from **[ BASF Corporation**  **] ,**  **[ 26**  **Davis Drive, 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 b y establishing tolerances for residues of the fungici de **[ 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 commodities
. **[ C**  **itrus, dried pulp**  **]** at **[ 2.7**  **]** parts per million (ppm) ; **[ Citrus, oil** **]** at **[ 19**  **]** ppm ; **[ Fruit, citrus, group**  **10 -**  **10 ]**  at **[ 1.0**  **] ;**  ppmnd **[ Grass forage, fodder and hay, group 17**  **]** at **[ 30**  **]** ppm ; **[ Nong**  **rass animal feeds,**  **group 1 8**  **]** at **[ 30**  **]** ppm; **[ P**  **oultry, fat ]**  at **[ 0.005**  **]** ppm ; and to revise the established tolerance for [ **Egg]** from 0.002 ppm to **[ 0.01**  **]** ppm ; and revoke the established tolerance for inadvertent residues for nongrass animal feeds, group 18, at 0.3 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 data 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 Ch emistry 1. Plant metabolism
. **[ Nature of the residue studies were conducted in**  **wheat ,**  **soybean and tomato as representative crops 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 crops.**  **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 metabolites M700F008**  **, M700F048 and M700F002**  **w ere**  **the residue s**  **of concern in the representative**  **rotational crops of wheat, radish, and**  **spin ach**  **. ]** 2
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 plant/crop**  **raw agri**  **cultural commodities and processed fraction**  **s and in animal**  **meat, fat, liver and kidney matrices**  **, skin milk, cream,**  **poultry meat, fat, liver and eggs**  **for which tolerances**  **have been established or are being proposed**  **.** ] 3. Magnitude of residues. **[ Crop**  **f i**  **eld trials were conducted**  **using foliar treatment with a fluxapyroxad end**  **- use product on**  **the following crops: orange, lemon, and grapefruit representing the**  **citrus crop group 10**  **- 10;**  **alfalfa and**  **clover ,**  **representing the nongrass animal feeds; , and**  **Bermuda gr ass, bluegrass,**  **fescue, and**  **bromegrass representing Grass forage, fodder, and hay crop group 17. The studies**  **were conducted to determine the magnitude of the residue in/on the representative**  **raw agricultural commodities and processed fractions. The data ar e being**  **submitted to propose tolerances for the citrus group 10 -**  **10, grass forage, fodder and hay, group 17 and**  **nongrass animal feed**  **s , group 18. The petition does not seek**  **pasture use but proposes a use rate with a 14 day preharvest interval for group 17 a**  **nd group 18 commodities. 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). R esidues of M700F002 were generally less than the limit of**  **quantitation and often less than the limit of detection. Residues of M700F048 were generally less than the limit of quantitation and often less than the limit of detection**  **in citrus and significantl y less than residues of BAS 700 F in grass and nongrass**  **commodities. Residues of M700F008 were significantly less than residues of BAS 700 F. Detected residues of fluxapyroxad (BAS 700 F) in citrus**  **crops , grass**  **es and**  **nongrass animal feed**  **commodities suppo rt the proposed tolerances based on parent**  **fluxapyroxad (BAS 700 F). The impact of the new uses in animal feed items was evaluated, and an amended**  **tolerance in egg and a new tolerance in poultry fat are proposed due to the increase in the poultry feed bur**  **den. The feed burdens for ruminant or swine did not change significantly from the values determined in the prior EPA evaluation, so no**  **amended tolerances for ruminant or hog, meat, byproducts or new tolerances for hog commodities 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 irritating to the skin, and not a dermal sensitizer. The a**  **cute toxicity studies place technical**  **fluxapyroxad in toxicity category III for acute oral and**  **dermal and category IV for acute inhala tion, eye and skin irritation.**  **F luxapyroxad**  **i s not a dermal sensitizer.**  **]**3 2. Genotoxicty. **[ Fluxapyroxad**  **( BAS 700 F** **) was n**  **ot genotoxic in a battery of assays.**  **Fluxapyroxad was negative for inducing mutations in bacterial and**  **ma mmalian cell assays. No evidence of a clastogenic effect was observed in vitro or**  **in vivo, and fluxapyroxad**  **did not cause 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**  **toxici ty 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 decreased food consumption,**  **impaired bod y 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 develo**  **pm ental 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 obse rved 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 develo**  **pment. 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 ma**  **ternal and developmental NOAEL in ra bbits 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 consistent with liver enzyme ind**  **uction. 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 toxic ity studies was approximately**  **7.3 mg/kg bw/day**  **in the rat 90 -**  **day study. 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**  **fluxapyroxad (** **BAS 700 F )**  **was studi ed 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 increases of the landing foot** **- sp**  **lay in high dose males, reduction in the number of rearings in males, and impaired motor** 4

**activity in high and mid dose males and females. No effects on these parameters were observed on study days 7 and 14. Additionally, no treatment** **- related**  **neuropathologi cal 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 the 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 signs 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 dose tested.**  **]** 5. Chronic toxici ty. **[ 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 indic ated 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 carcinogenic 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 males at dose levels ≥**  **250 ppm an d 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 response in the liver** **, and indic ates there is a threshold for tumor development and a margin of**  **exposure cancer risk assessment is appropriate. In the rat chronic/oncogenicity study, the NOAEL in males and females was 50 ppm**  **(2.1 and 2.7 mg/kg bw/day, respectively). 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 metabolism studies were**  **conducted t o 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 ring label only)**  **. BAS 700 F**  **was e ither 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 met**  **abolism of fluxapyroxad**  **in the animals is well understood.**  **Degradation proceeds via N -**  **demethylation of the pyrazole ring**5

**and/or hyroxylation of the biphenyl ring followed by subsequent O -**  **and N****** **conjugation reactions to produce 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 consistent**  **metabolic pathway for fluxa** **pyroxad 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 metabolism 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 pathway in all animals like that for**  **f luxapyroxad**  **. 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 at levels >10 TRR in soybean seed**  **in the plant metabolism and was present only at low levels in the rat urine.**  **In lieu of a fish metaboli**  **sm study, a justi** **fication was submitted to waive the data requirement for a metabolism study in fish.**  **The justification was based on the relatively low BCF of 25 in edible tissues of**  **bluegill sunfish and the negligible BCF of <1 in the crayfish field accumulation study. This was sufficient information to fulfill the requirements for the use in rice,**  **including in paddy rice, an aquatic system. BASF does no t believe that an additional**  **metabolism study in a bottom feeder (catfish) or predator (bass) fish will provide any new information that would add value to the existing Fluxapyroxad data**  **package. 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 ra nge of common and structurally related**  **compounds. Due to the similar structural nature of most metabolites, the toxicity of most plant metabolites is adequately estimated from the results of studies 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 he n,**  **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 conjugat**  **e since the plant metabolite would not be formed in animal metabolism. In animal**  **metabolism studies, M700F048 was rapidly hydrolyzed to metabolite M700F008, a**6

**key metabolite in the metabolic pathway of fluxapyroxad**  **. Unchanged M700F048**  **was not detected in e dible animal commodities.**  **Toxicology studies (Acute oral toxicity, Ames test, in vitro mutagenicity test in ma**  **mmalian 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 acute**  **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. However, 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 commoditie s except**  **milk ,**  **for which M700F01 0**  **is also included. Exposure assessments were conducted**  **to evaluate the potential risk due to acute and chronic dietary exposure of the U.S. population**  **and all sub -** **populations. The assessments included**  **uses for all current**  **established tolerances (40 CFR 180.666),**  **the pending increase**  **d tolerance for**  **foliar treatment of**  **cotton and the proposed uses in citrus, animal feed, nongrass and**  **grass, forage, fodder and hay which have an impact on the animal feed burden and expected**  **res idues in animal commodities**  **. The a**  **cute and chronic**  **dietary exposure estimates were**  **conducted using DEEM, version 3.18 which includes t he**  **consumption data from the**  **NHANES 2 -**  **day food consumption data for 2003 to 2008**  **. ]**  i. Food. **[ Acute Dietary Exposure Ass**  **essment For plant commodities, the residue levels were set as follows: (a) for crops approved**  **as of May 14, 2012, tolerance values adjusted with a factor of 1.5 to account for metabolite M700F008 were used as was done in the acute dietary assessment**  **condu cted as part of the evaluation by EPA (a few input values were changed as**  **discussed below); (b) for crops approved as of February 26, 2014, tolerance values plus the HAFT for any level of M700F008 greater than the LOQ were used**  **(this is different from th**  **e EPA analysis performed in July 3013) c) for the proposed foliar**  **use in cotton (submitted in January 2014) and the use in citrus, tolerance values plus the HAFT for any level of M700F008 greater than the LOQ were used. A 1.5 factor**  **was not used to adjust the tolerances for the**  **commodities evaluated in 2013 or for**7

**the new commodities used in the assessment since the levels of metabolite M700F008**  **were generally**  **much less than 50% of the tolerance. The**  **Values changed from the EPA dietary analysis of February**  **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**  **commodities to reflect the proposed rice use .**  **Processing factors including DEEM default and empirical processing factors used in**  **the dietary assessment conducted as part of the evaluation by EPA in May 2012 were included. Study derived processing**  **factors were used for citrus, grape, cottonseed, rice and sugarcane process commodities (see Part A). The analysis assumed 100% of all cro**  **ps were treated. The residue levels used for**  **ruminant and poultry commodities were derived**  **by extrapolation**  **from residue levels of parent and M700F008 measured in the feeding studies**  **based on the newly calculated feed burdens (see part A). The metabolite M700F010 was considered to be equal to fluxapyroxad levels in milk.**  **The tolerances of 0.01 mg/kg were used for**  **freshwater finfish,**  **shellfish, crustacean and hog, meat,**  **byproducts .**  **The total exposure estimates are lower than those in the EPA evaluation o f July 25,**  **2013 since for commodities registered in 2014 and for newly proposed commodities, the calculation of the total residue is based on tolerance plus the actual measured**  **HAFT for M700F008 levels rather than the tolerance multiplied by a factor, such as**  **1.5, to set the metabolite levels in plant commodities. For drinking water all**  **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.**  **T he**  **highest acute Estimated Drinking Water Concentrations (EDWC) w**  **as estimated to**  **be 2**  **03 μ**  **g/L (ppb)**  **for use in turf .**  **The drinking water exposure was**  **included in the dietary**  **analysis in Table 1**  **. The result** **ing exposur**  **e 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 1**  **. 25 mg/kg/day with an FQPA**  **safety factor of 1. The most highly expos**  **ed sub**  **- population was**  **children 1**  **- 2**  **years old**  **with 10.0**  **% utilization of the aPAD. The results of the acute dietary assessment are presented in Table**  **1. Table**  **1 .**  **Results for**  **fluxapyroxad (** **BAS 700**  **F )**  **Acute Dietary**  **Exposure (Food**  **and Water)**  **Considering all**  **Curr ent**  **and Proposed**  **Toler ances**  **using DEEM -**  **FCID at**  **the 95**  **th Percentile** 

**Population Exposure Estimate**  **% a PAD**  **Subgroups (mg/kg b.w./day)**  **U.S. Population 0.070893**  **5.7 All Infants (< 1 year old)**  **0.096648 7.7**  **Children (1 -** **2 years old) 0.125256**  **1 0.0** 8 **Children (3 -**  **5 years old) 0.110571**  **8.9 Children (6**  **- 12 years old)**  **0.065201 5.2**  **Youth (13 -**  **19 years old) 0.053369**  **4.3 Adults (20**  **- 49 years old)**  **0.067673 5.4**  **Adults (50+ years old) 0.066053**  **5.3 Females (13**  **- 49 years old)**  **0.070237 5.6**  **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 reduc**  **e the estimated exposure values. Chronic Dietary Exposure Assessment**  **For plant commodities, the residue levels were set as follows: (a) for crops approved as of May 14, 2012, the combined highest average field trial values for parent plus**  **metabolite M700 F008 were used as was done in the acute dietary assessment**  **conducted as part of the February 2012 evaluation by EPA (a few input values were changed as discussed below); (b) for crops approved as of February 26, 2014 and**  **the pending use in foliar treatmen t in cotton and the newly proposed uses, the field**  **trial average residue values for parent plus the HAFT for the metabolite M700F008 (when greater than the LOQ) were used, similar to the EPA evaluation performed**  **in July 3013. Processing factors including DEEM default and empirical processing**  **factors used in the dietary assessment conducted as part of the evaluation by EPA in February 2012 were included. Study derived processing factors were used for citrus,**  **grape, cottonseed, rice and sugarcane process com modities (see Part A). The**  **analysis assumed 100% of all crops were treated. The residue levels used for ruminant and poultry commodities were derived by extrapolation from residue**  **levels of parent and M700F008 measured in the feeding studies based on the newly**  **calculated feed burdens (see part A). The metabolite M700F010 was considered to be equal to fluxapyroxad levels in milk. The tolerances of 0.01 mg/kg were used for**  **freshwater finfish, shellfish, crustacean and hog, meat, byproducts. For drinking w**  **ater all 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 Estimated Drinking**  **Water Concentrations (EDWC) was estimated to be 184 μg/L (ppb). The drinking water exposure was included in the dietary**  **analysis in Table 2 .**  **The consumption data was from the NHANES 2 -**  **day food consumption data for 2003 to 2008**  **and the assessment was pe rformed using the Dietary Exposure**  **Evaluation Module (DEEM -** **FCID) software , version 3.18**  **. 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** 9

**2.1 mg/kg bw/day**  **using a FQPA safety factor of 1. The most highly expos ed**  **population sub -**  **group was all infan**  **ts (< 1 year old) which utilized**  **71.8 % c** **PAD. The results of the chronic dietary ass**  **e ssment are presented in Table**  **2 .**  **Table 2 . Results for**  **fluxapyrox ad (** **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**  **0.007134 34.0**  **All Infants (< 1 year old) 0.015081**  **71.8 Children (1**  **- 2 y**  **ears old) 0.014897**  **70.9 Children (3**  **- 5 years old)**  **0.011889 56**  **.6 Children (6**  **- 12 years old)**  **0.007493 35.7**  **Youth (13 -**  **19 years old) 0.005143**  **24.5 Adults (20**  **- 49 years old)**  **0.006554 31.2**  **Adults (50+ years old) 0.006742**  **32.1 Females (13**  **- 49 years old)**  **0.00655 9**  **31.2 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 valu**  **es) 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 assessments above.**  **Fo r 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 highest acute Estimated Drinking**  **Water Concentrations (EDWC) was estimated to be 203 μg/ L (ppb).**  **The highest**  **chronic EDWC’s for fluxapyroxad**  **( BAS 700**  **F )**  **were estimated to be 184**  **μ g/L**  **(ppb). Short** **- and Intermediate** **- Term Aggregate Exposure and Risk (food, water, and**  **residential) Short** **- and intermediate** **- term aggregate risk assessments in**  **clude exposure from food, water, and residential uses. Fluxapyroxad (BAS 700 F) is registered for use on**  **residential turf. The residential uses of Fluxapyroxad will result is short -** **term exposure. The residential uses will not result in intermediate and**  **therefore, an intermediate**  **- term aggregate risk assessment is not required. Because no dermal**  **hazard of concern was identified for fluxapyroxad only inhalation exposure was assessed for residential handlers, and incidental oral exposure (hand to mouth) was**  **assessed for activities of children on treated turf.**10

**The short -** **term oral NOAEL is 9.0 mg/kg bw/day. The short -** **term aggregate risk assessment is presented in Table 3**  **. Table 3: Short** **- Term Aggregate Exposure and Risk for fluxapyroxad (BAS 700 F)**  **Sub -**  **P opulations**  **Short -** **term Aggregate Food + water**  **exp. (mg/kg bw/day)**  **Residential**

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

**(mg/kg bw/day)**  **Aggregate**

**MOE US Population**  **0.007134 0.022000**  **0.029134 309**  **Children 1 -** **2 years old 0.014897**  **0.003500 0.018397**  **489 The aggregate M**  **OEs for dietary (food + water) and residential exposures are 489 for children and 309 for adults. 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 ri**  **sk assessment was conducted for the proposed residential use of fluxapyroxad (BAS 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 handle**  **rs, 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 conc**  **ern. ]**  D. Cumulative Effects **[ "Section 408(b)(2)(D)(v) requires that, when considering**  **whether 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 for which EPA has followed a cumulative risk approach based on a**  **common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to**  **fluxapyrox ad**  **( 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 conc** **ludes that the aggregate exposure to fluxapyroxad (BAS 700 F) from the current tolerances and**  **proposed new tolerances does not result in an unacceptable risk.]**11 2. Infants and children
. **[ Based on this risk assessment, BASF concludes that**  **the aggregate exp osure to fluxapyroxad (BAS 700 F) from the current tolerances**  **and proposed new tolerances does not result in an unacceptable risk.]** F. International Tolerances **[ European Maximum Residue Limits (MRL) were established for**  **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 J** **ournal 2011; 9(6):2196 [68 pp.] Health Canada Pest Management 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 section 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 (i**  **ncluding prunes)] for the purpose of harmonizing MRLs with the U.S.**  **CODEX maximum**  **residue levels**  **were proposed**  **for residues**  **of fluxapyroxad**  **(BAS 700 F) in/on**  **raw agricultural commodities and processed fractions by**  **the 2012 Joint Meeting**  **on Pesticide**  **Resid ues**  **(JMPR) and**  **approved by**  **the Codex**  **Committee on**  **Pesticide Residues**  **(CCPR) in**  **May 2013**  **( Summary**  **Report from**  **the 2012**  **Joint FAO/WHO Meeting on Pesticide Residues (JMPR), Oct 2012**  **) .**  **Summary of International MRLs (ppm ) as of December, 2014**  **Som e commodities**  **might not be covered due to differences in crop groups and extrapolations. Parentheses indicate that the U. S. MRL is m** **ore critical than the country MRL. Comm** **odity US**  **Codex EU**  **Australia Brazil**  **Canada Japan**  **Korea** Apple 0.8 0.9 0.9 0.8 {0.5} 0.8 0.9 0.8 Apricot 3 {2} {1} {2} {2} {2} {2} Barley, grain 3 {2} {2} {0.2} {0.3} 3 3 {2} Bean, broad (fava), succulent 0.5
--- {0.09} {0.1}
--- 0.5 7 Bean, snap, succulent (w

pods) 2 2 2 2 Bean, snap, succulent, shelled 0.5 {0.09} {0.09} {0.1} {0.03} Be an, dry 0.4 0.3 0.4 Beet, sugar, root 0.1 0.15 0.15 0.1 0.15 0.1 0.2 0.1 Blackberry 5
--- {0.01} {0.1}
--- --- --- Blueberry, highbush 7
--- {0.01} {0.1}
--- --- --- Broccoli 4
--- {0.07} {0.1}
--- --- ---12

**Summary of International MRLs (ppm ) as of December, 2014**  **Som e commodities**  **might not be covered due to differences in crop groups and extrapolations. Parentheses indicate that the U. S. MRL is m** **ore critical than the country MRL. Comm** **odity US**  **Codex EU**  **Australia Brazil**  **Canada Japan**  **Korea** Brussels sprouts 4
--- {0.07} {0.1}
--- --- --- Buckwheat, grain 3 3 3 Cabbage 4
--- {0.07} {0.1}
--- --- --- Cantaloupe 0.5
--- {0.01} {0.1} {0.05}
--- --- Cardoon 30
--- {0.01} {0.1}
--- --- --- --- Carrot 0.9
--- {0.1} {0.1} {0.02}
--- --- Celery 30
--- {0.01} {0.1}
--- --- --- Cherry, sweet 3 {2} {0.01} {2} {2} {2} {2} {2} Chickpea, dry 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 Corn, grain 0.01 0.01 0.01 0.1 0.05 0.01 0.2 0.15 Corn, sweet 0.15 0.15 0.15 {0.1} 0.15 0.15 0.2 0.15 Cottonseed 0.01 0.01 0.01 0.1 0.5 0.01 0.01 Cow p ea, dry 0.4
--- {0.3} 0.4
--- 0.4 0.4 Cucumber 0.5
--- {0.01} {0.1} {0.05}
--- {0.02} Eggplant 0.7 {0.6} {0.6} {0.1} {0.6} 0.7 0.7 Endive (escarole) 30
--- {0.03} {0.1}
--- --- --- Fennel, bulb 30
--- {0.01} {0.1}
--- --- {2} Flaxseed/Linseed 0.9 {0.8} 0.9 {0.1} {0.8} 0.9 0.9 Garlic, bulb 1.5
--- {0.1} {0.1}
--- --- --- Ginseng, root, fresh 0.9
--- {0.01} {0.1}
--- --- 7 Gold of pleasure 0.9
--- 0.9 {0.1}
--- 0.9
--- --- Grape, table 2
--- {0.01} {0.1}
--- --- --- Jujube, Chinese 3 {2} {1 .5} {0.1} {2} {2} {0.8} Lentil, dry 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 Loquat 0.8 0.9 0.9 0.8 0.9 0.8
--- --- Lupin, dry 0.4
--- {0.3} 0.4
--- 0.4 0.4
--- May haw 0.8 0.9 0.9 {0.1} 0.9 0.8
--- --- Melon, casaba 0.5
--- {0.01} {0.1} {0.05}
--- --- 0.5 Muskmelon 0.5
--- {0.01} {0.1} {0.05}
--- --- 0.5 Nectarine 3 {2} {1} {2} {2} {2} {2} Nut, cashew 0.06
--- {0.01} 0.1
--- --- 0.8 Oat, grain 3 {2} {2} {0.1} {0.3} 3 3 Onion, bulb 1.5
--- {0.1} {0.1} {0.01}
--- --- Pea, dry (field) 0.4 0.4 0.4 0.4 0. 4 0.4 0.4 0.4 Peach 3 {2} {1} {2} {2} {2}
--- {0.3} Peanut 0.01 0.01 0.01 0.1 0.01 0.01 0.01 0.01 Pear 0.8 0.9 0.9 0.8 0.9 0.8 0.9 0.8 Pepino 0.7 {0.6} {0.6} {0.1} {0.6} 0.7
--- Pepper, bell 0.7 {0.6} {0.6} {0.1} {0.05} 0.7 0.7 {0.3} Pepper, non
-bel l 0.7 {0.6} {0.6} {0.1} {0.6} 0.7 0.7 {0.3} Plum 3 {2} {1.5} {0.1} {2} {2} {2}
--- Plumcot 3 {2} {1.5} {0.1} {2} {2} {2}
--- Poppy, seed 0.9 {0.8} 0.9 {0.1} {0.8} 0.9 {0.9}
--- Potato 0.02 0.03 0.03 0.1 {0.01} 0.02 0.03 0.02 Pum pkin 0.5
--- {0.01} {0. 1}
--- --- ---13

**Summary of International MRLs (ppm ) as of December, 2014**  **Som e commodities**  **might not be covered due to differences in crop groups and extrapolations. Parentheses indicate that the U. S. MRL is m** **ore critical than the country MRL. Comm** **odity US**  **Codex EU**  **Australia Brazil**  **Canada Japan**  **Korea** Purslane, garden 30
--- {0.03} {0.1}
--- --- {7} Quince 0.8 0.9 0.9 0.8 0.9 0.8 0.9 Rape seed (canola) 0.9 {0.8} 0.9 {0.1} {0.8} 0.9 0.9 {0.4} Raspberry, black/red 5
--- {0.01} {0.1}
--- --- --- Rhubarb 30
--- {0.01} {0.1}
--- --- { 0.6}
--- Rye, grain 3 {0.3} {0.4} {0.1} {0.3} 3 3 Safflower, seed 0.9 {0.8} 0.9 {0.1} {0.8} 0.9 0.9 Sesame, seed 0.9 {0.8} 0.9 {0.1} {0.8} 0.9 0.9 Sorghum, grain 3
--- {0.7} {0.1} {2} 3 3 {0.8} Soy bean 0.15 0.15 0.15 0.3 {0.05} 0.15 0.3 0.15 Straw berry 4
--- {0.01} {0.1}
--- --- --- Sugar cane 3
--- {0.01} {0.1} {0.03}
--- --- --- Sunflower, seed 0.9 {0.8} {0.8} {0.1} {0.2} 0.9 0.9 {0.2} Sweet potato 0.02
--- {0.01} 0.1
--- 0.02 0.02 Swiss chard 30
--- {0.03} {0.1}
--- --- {7} Tomato 0.7 {0 .6} {0.6} {0.1} {0.2} 0.7 0.7 {0.3} Triticale, grain 0.3 0.3 0.4 {0.1} 0.3 3 3 Watermelon 0.5
--- {0.01} {0.1}
--- --- --- {0.1} Wheat, grain 0.3 0.3 0.4 {0.1} 0.5 0.3 0.3 0.3 Yam, true, tuber 0.02
--- {0.01} 0.1
--- 0.02 0.02