Document ID: EPA-HQ-OPP-2022-0258-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2022-07-20T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: Shaja Joyner, (703) 308-3194

TEMPLATE:

BASF Corporation

PP#1F8974

	EPA has received a pesticide petition (#1F8974) from BASF Corporation, 26 Davis Drive, P.O. Box 13528, Research Triangle Park, North Carolina 27709-3528 requesting, 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 establishing a tolerance for residues of Fluxapyroxad, (BAS 700 F); 1H-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 raw agricultural commodity Avocado at 0.6 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 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 Chemistry

	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 matrices. Two radiocarbon labels were studied in each crop, with 14-C labels positioned in aniline and pyrazole ring structures. 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 confined rotational crop study added metabolite M700F008 and confirmed that parent fluxapyroxad plus metabolites M700F008, M700F048 and M700F002 were the residues 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 avocado.

	3. Magnitude of residues. Field trials using foliar treatment with a fluxapyroxad end-use product on avocado were performed to determine the magnitude of the residue in/on the representative raw agricultural commodities and processed fractions. The data are being submitted to propose tolerances for the avocado group 24B. The petition proposes a use rate with a 0-day preharvest interval for group 24B 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). Residues of M700F002 were generally less than the limit of quantitation and often less than the limit of detection. Detected residues of fluxapyroxad (BAS 700 F) in the commodities support the proposed tolerances based on parent BAS 700 F.

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 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. Fluxapyroxad is 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 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 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 decreased 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 maternal 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 consistent 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.

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 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 increases 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 treatment-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 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 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 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 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 response in the liver, and indicates 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 to determine the nature of the fluxapyroxad (BAS 700 F) residues in animals. Studies 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 either excreted rapidly in urine and feces or transformed to a number of metabolites after administration to animals. All relevant metabolites were identified. Unchanged 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 produce metabolites that are rapidly excreted, along with parent, and do not readily accumulate in tissues or milk. Residues in milk 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 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 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 fluxapyroxad.  Rat, goat and hen metabolism studies 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 metabolism study, a justification 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 not 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 range 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 studies 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 metabolism 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 vitro 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 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 commodities except milk, for which M700F010 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 all current established tolerances (40 CFR 180.666) and the use in avocado, proposed in this petition. The acute and chronic dietary exposure estimates were conducted using DEEM, version 4.02 which includes the consumption data from the NHANES 2-day food consumption data for 2005 to 2010.

 Food. 
      Acute Dietary Exposure Assessment

The acute dietary exposure values are shown in Table 1. A conservative acute dietary analysis was performed utilizing DEEM input values from the US EPA's 2016 dietary and risk assessment evaluation, in addition to the newly proposed tolerances for avocado. Tolerance level residues were adjusted to account for the metabolites of concern (M700F008). Established and newly proposed tolerances (avocado) were multiplied by a factor or 1.5x to account for the M700F008 metabolite for plant commodities. This factor was inserted into Adjustment Factor 2 for the acute analysis. Processing factors including DEEM default and empirical processing factors used in the dietary assessment conducted as part of the evaluation by EPA in March of 2021. Study derived processing factors were used for citrus, grape, cottonseed, rice and sugarcane process commodities. The analysis assumed 100% of all crops were treated.  The residue levels used for ruminant and poultry commodities were derived from the EPA tolerances approved in 2016. Anticipated residues accounting for parent and the metabolites of concern (M700F008 and/or M700F010) were used.

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.  The highest acute Estimated Drinking Water Concentrations (EDWC) was estimated to be 203 ug/L (ppb). The drinking water exposure was included in the dietary analysis in Table 1.

The resulting 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 1.25 mg/kg/day with an FQPA safety factor of 1.  The most highly exposed sub-population was children 1-2 years old with 14.1 % utilization of the aPAD (Table 1; DEEM, version 4.02) (Table 2; CARES NG[(R)], version 1.2.1).

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

                                  Population
                               Exposure Estimate
                                    % aPAD
                                   Subgroups
                               (mg/kg b.w./day)
                                       
                                U.S. Population
                                   0.103199
                                      8.3
                         All Infants (< 1 year old)
                                   0.148390
                                     11.9
                           Children (1-2 years old)
                                   0.176300
                                     14.1
                           Children (3-5 years old)
                                   0.154535
                                     12.4
                           Children (6-12 years old)
                                   0.099210
                                      7.9
                            Youth (13-19 years old)
                                   0.080612
                                      6.4
                           Adults (20-49 years old)
                                   0.096840
                                      7.7
                            Adults (50+ years old)
                                   0.098169
                                      7.9
                           Females (13-49 years old)
                                   0.101148
                                      8.1

Table 2. Results for fluxapyroxad (BAS 700 F) Acute Dietary Exposure (Food and Water) Considering all Current and Proposed Tolerances using CARES NG(R) at the 95th Percentile

                                  Population
                               Exposure Estimate
                                    % aPAD
                                   Subgroups
                               (mg/kg b.w./day)
                                       
                                U.S. Population
                                   0.103236
                                      8.3
                         All Infants (< 1 year old)
                                   0.148651
                                     11.9
                           Children (1-2 years old)
                                   0.176407
                                     14.1
                           Children (3-5 years old)
                                   0.154658
                                     12.4
                           Children (6-12 years old)
                                   0.098765
                                      7.9
                            Youth (13-19 years old)
                                   0.080505
                                      6.4
                           Adults (20-49 years old)
                                   0.096870
                                      7.7
                            Adults (50+ years old)
                                   0.098410
                                      7.9
                           Females (13-49 years old)
                                   0.101001
                                      8.1

The 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 
For plant commodities, the residue levels were done according to the 2021 US EPA acute and chronic risk assessment evaluation. This petition includes the newly proposed avocado tolerance. The combined average field trial residues for parent plus the maximum M700F008 metabolite residue was used; this first-tier analysis was conducted by the US EPA to save resources instead of adding individual residues of parent and M700F008 from individual trials and then calculating the average. Processing factors including DEEM default and empirical processing factors used in the dietary assessment conducted as part of the evaluation by EPA in March 2021 were included. Study derived processing factors were used for citrus, grape, cottonseed, rice and sugarcane process commodities. 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. 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 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.  The highest chronic Estimated Drinking Water Concentration (EDWC) was estimated to be 188 ug/L (ppb). The drinking water exposure was included in the dietary analysis in Table 3.

The consumption data was from the NHANES 2-day food consumption data for 2005 to 2010 and the assessment was performed using the Dietary Exposure Evaluation Module (DEEM-FCID) software, version 4.02. A side-by-side comparison using Cumulative and Aggregate Risk Evaluation System-New Generation (CARES NG[(R)]), version 1.2.1 was also provided. 

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 value of 2.1 mg/kg bw/day using a FQPA safety factor of 1.  The most highly exposed population sub-group was all infants (< 1 year old) which utilized 91.4% cPAD using DEEM and 92.9% using CARES NG[(R)].  The results of the chronic dietary assessment are presented in Table 3 and Table 4.

Table 3.  Results for fluxapyroxad (BAS 700 F) Chronic Dietary Exposure (Food and Water) Considering All Current and Proposed Tolerances using DEEM-FCID
                                  Population
                               Exposure Estimate
                                    % cPAD
                                   Subgroups
                               (mg/kg b.w./day)
                                       
                                U.S. Population
                                   0.006956
                                     33.1
                         All Infants (< 1 year old)
                                   0.019197
                                     91.4
                           Children (1-2 years old)
                                   0.014496
                                     69.0
                           Children (3-5 years old)
                                   0.010981
                                     52.3
                           Children (6-12 years old)
                                   0.006919
                                     32.9
                            Youth (13-19 years old)
                                   0.004814
                                     22.9
                           Adults (20-49 years old)
                                   0.006449
                                     30.7
                            Adults (50+ years old)
                                   0.006503
                                     31.0
                           Females (13-49 years old)
                                   0.006365
                                     30.3

Table 4.  Results for fluxapyroxad (BAS 700 F) Chronic Dietary Exposure (Food and Water) Considering All Current and Proposed Tolerances using CARES NG[(R)]

                                  Population
                               Exposure Estimate
                                    % cPAD
                                   Subgroups
                               (mg/kg b.w./day)
                                       
                                U.S. Population
                                   0.007081
                                     33.7
                         All Infants (< 1 year old)
                                   0.019512
                                     92.9
                           Children (1-2 years old)
                                   0.014795
                                     70.5
                           Children (3-5 years old)
                                   0.011308
                                     53.8
                           Children (6-12 years old)
                                   0.007159
                                     34.1
                            Youth (13-19 years old)
                                   0.004939
                                     23.5
                           Adults (20-49 years old)
                                   0.006542
                                     31.2
                            Adults (50+ years old)
                                   0.006583
                                     31.3
                           Females (13-49 years old)
                                   0.006365
                                     30.3

The results of the risk assessment show that for all populations 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 assessments above. For drinking water all 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 ug/L (ppb).  The highest chronic EDWC's for fluxapyroxad (BAS 700 F) were estimated to be 188 ug/L (ppb).

	2. Non-dietary exposure. EPA conducted a residential exposure and risk assessment for the residential use of fluxapyroxad products for disease control in turf (April 8, 2021, DP Barcode D457531). 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.

Short-Term Aggregate Exposure and Risk (food, water, and residential)
Short-term aggregate risk assessment includes exposure from food, water, and residential uses.  The residential uses of fluxapyroxad may result in short-term exposure, which is aggregated with the chronic dietary (food and water) exposure.  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. 

The short-term oral NOAEL is 7.3 mg/kg bw/day.  The short-term aggregate risk assessment is presented in Table 5 using dietary exposures estimated with DEEM-FCID, and in Table 6 using dietary exposures estimated with CARES NG[(R)].

 Table 5:  Short-Term Aggregate Exposure and Risk for Fluxapyroxad 
                                Sub-Populations
                             Short-term Aggregate

                     Food + water exposure*
(mg/kg bw/day)
                      Residential exposure (mg/kg bw/day)
                         Total exposure (mg/kg bw/day)
                                 Aggregate MOE
                                 US Population
                                   0.006956
                                   0.000044
                                   0.0070000
                                     1043
                            Children 1-2 years old
                                   0.014496
                                    0.0035
                                   0.0179960
                                      406
* Dietary exposure calculated using DEEM-FCID ver. 4.02

 Table 6:  Short-Term Aggregate Exposure and Risk for Fluxapyroxad 
                                Sub-Populations
                             Short-term Aggregate

                    Food + water exposure**
(mg/kg bw/day)
                      Residential exposure (mg/kg bw/day)
                         Total exposure (mg/kg bw/day)
                                 Aggregate MOE
                                 US Population
                                   0.007081
                                   0.000044
                                   0.0071250
                                     1025
                            Children 1-2 years old
                                   0.014795
                                    0.0035
                                   0.0182950
                                      399
** Dietary exposure calculated using CARES NG[(R)] ver. 1.2.1

The aggregate MOEs for dietary (food + water) and residential exposures are 399 to 406 for children and 1025 to 1043 for adults.  These MOEs indicate that aggregate risk from the use of fluxapyroxad is not a concern.

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 fluxapyroxad. 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 the aggregate exposure to fluxapyroxad from the current tolerances and proposed new tolerances does not result in an unacceptable risk.

	2. Infants and children. Based on this risk assessment, BASF concludes that the aggregate exposure to fluxapyroxad 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:
- March 2016 [Commission Regulation (EU) No 2016/486 of 29 March 2016; MRLs for fluxapyroxad (BAS 700 F) in various commodities of plant and animal origin. EFSA Journal 2015; 13(9):4223 [25 pp.]
- October 2016 [Commission Regulation (EU) No 2016/1902 of 27 October 2016; MRLs for fluxapyroxad (BAS 700 F) in various commodities of plant and animal origin. EFSA Journal 2016; 14(3):4004 [28 pp.]
- March 2017 [Commission Regulation (EU) No 2017/626 of 31 March 2017; MRLs for fluxapyroxad (BAS 700 F) in various commodities of plant and animal origin. EFSA Journal 2015;13(7):4208 [178 pp.] and 2016;14(8):4571 [166 pp.].
- May 2018 [Commission Regulation (EU) No 2018/685 of 3 May 2018; MRLs for fluxapyroxad (BAS 700 F) in various commodities of plant and animal origin. EFSA Journal 2017; 15(9):4975 [30 pp.]

      CODEX maximum residue levels were proposed for residues of fluxapyroxad (BAS 700 F) in/on raw agricultural commodities and processed fractions by the 2016 and 2019 Joint Meeting on Pesticide Residues (JMPR) and approved by the Codex Committee on Pesticide Residues (CCPR 48 and 51) in May 2016 (Summary Report from the 2016 Joint FAO/WHO Meeting on Pesticide Residues (JMPR), July 2016) and May 2019 (Summary Report from the 2019 Joint FAO/WHO Meeting on Pesticide Residues (JMPR), July 2019.)  The following CODEX MRLs have been established, but do not have a corresponding EPA tolerance:  
      
  Crop
  Codex MRL (ppm)
   Bayberry
   7
   Bean, dwarf
   2
   Bean, flageolet
   2
   Bean, French
   2
   Bean, haricot
   2
   Bilberry, Bog
   7
   Buffaloberry
   7
   Cabbage, savoy
   2
   Chokecherry
   3
   Hemp seed
   0.8
   Mulberry
   7
   Persimmon, Japanese
   0.9
   Riberry
   7
   Serviceberry
   7
   Strawberries, Wild
   7
   Wasabi, leaves
   4
      

      Health Canada Pest Management Regulatory Agency (PMRA) has published Maximum Residue Limits (MRL) for fluxapyroxad residues on multiple crop commodities at February 02, 2016 and June 01, 2017. 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) has published Maximum Residue Limits (MRL) for fluxapyroxad residues on multiple crop commodities at May 4, 2018 in Australia. The Food Standards Australia New Zealand also proposed Maximum residue limits on multiple crop commodities at March 13, 2018.