Document ID: EPA-HQ-OPP-2016-0380-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2016-08-29T04:00Z

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

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

 

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 appear 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 (5E8366) 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 by  establishing  tolerances for residues of the fungicide
[Fluxapyroxad, (BAS 700 F);
1H-Pyrazole-4-carboxamide,3-(difluoromethyl)-1-methyl-N-(3',4',5'-triflu
oro[1,1'-biphenyl]-2-yl)-, its metabolites, and degradates] in or on the
following raw agricultural commodities [Banana] at [3.0] parts per
million (ppm); [Coffee, green bean] at [0.2] ppm; [Mango] at [0.7] ppm;
and [Papaya] at [0.6] 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  plant/crop raw agricultural commodities and processed
fractions 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 field trials were conducted using
foliar treatment with a fluxapyroxad end-use product on the following
crops: banana, mango, papaya and coffee. The studies were conducted 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 banana, mango, papaya and coffee,
green bean. The number of field trials is in accordance with the EPA
guidance document, “NAFTA Guidance Document on Data Requirements for
Tolerances on Imported Commodities in the United States and Canada”,
December 2005. For bananas twelve trials are submitted, three trials
each in Costa Rica and Ecuador, two trials in Columbia and four trials
from Brazil. The trials in Brazil are considered to also support exports
from Honduras and Mexico due to a similar climate. Four trials each in
mango and papaya, all trials performed in Brazil, the only country with
a registered use in that commodity, are submitted. For coffee twelve
trials are submitted from Brazil, the only country planning to register
fluxapyroxad products with uses in coffee. Field trials were carried out
using the maximum label rates, the maximum number of applications and
the minimum pre-harvest interval (PHI). Residues did not concentrate in
the coffee process fractions of coffee, bean, roasted or coffee, bean
roasted; instant. For bananas, trials were performed with applications
to bagged and unbagged fruit, and whole fruit, pulp and peel were
analyzed. Residues of metabolites M700F002 and M700F048 were less than
the limit of detection; residues of M700F008 were generally less than
the limit of quantitation and often less than the limit of detection.
Detected residues of fluxapyroxad (BAS 700 F) in banana, coffee, mango
and papaya support the proposed import tolerances based on parent
fluxapyroxad (BAS 700 F).

The new uses have no impact on animal feed items, and no changes to
tolerances for animal 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 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.

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 uses for all current
established tolerances (40 CFR 180.666), the pending increased tolerance
for foliar treatment of cotton, the pending tolerances in citrus, oil, 
fruit, citrus, group 10-10,  and poultry fat, the pending increased
tolerance for egg  and the proposed uses in banana, mango, papaya and
coffee. 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.]

	i. Food. [Acute Dietary Exposure Assessment

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 conducted 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 the EPA analysis performed in July 3013) c) for the proposed foliar
use in cotton (submitted in January 2014) and the proposed use in citrus
(submitted in January 2015), 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 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. For the newly proposed import tolerances in
banana, coffee, mango and papaya, the MRL was used with no adjustment
for metabolite since the level of M700F008 was generally less than the
limit of detection of 0.002 ppm. 

EPA default processing factors were applied to dried banana and papaya,
and the default processing factor for dried papaya was applied to dried
mango. Study derived processing factors were used for citrus, coffee,
cottonseed, grape, peanut, rice, brown, rice flour, rice, white 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 feed burdens
calculated in the January 2015 submission. 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
of 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.  The highest acute Estimated Drinking Water
Concentrations (EDWC) was estimated to be 203 µg/L (ppb) for use in
turf.   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 10.8 % 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 Current and Proposed Tolerances using
DEEM-FCID (v. 4.02) at the 95th Percentile

Population	Exposure Estimate	% aPAD

Subgroups	(mg/kg b.w./day)

	U.S. Population	0.074905	6.0

All Infants (< 1 year old)	0.111265	8.9

Children (1-2 years old)	0.135601	10.8

Children (3-5 years old)	0.112723	9.0

Children (6-12 years old)	0.070500	5.6

Youth (13-19 years old)	0.056323	4.5

Adults (20-49 years old)	0.068608	5.5

Adults (50+ years old)	0.069467	5.6

Females (13-49 years old)	0.070819	5.7

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 set as follows: (a) for
crops approved as of May 14, 2012, the combined highest average field
trial values for parent plus metabolite M700F008 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 treatment in cotton and citrus, 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. For banana the average field residue measured for banana
pulp for treated unbagged banana was used. For the newly proposed import
tolerances in coffee, mango and papaya, the field trial average residue
value was used. The metabolite M700F008 levels were <LOD and were not
considered.  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. EPA default
processing factors were applied to dried banana and papaya, and the
default processing factor for dried papaya was applied to dried mango
Study derived processing factors were used for citrus, coffee,
cottonseed, grape, peanut, rice and sugarcane process commodities. The
analysis assumed 100% of all crops were treated.  The residue levels
used for ruminant and poultry commodities were those used in the
submission of January 2015 and were derived by extrapolation from
residue levels of parent and M700F008 measured in the feeding studies
based on the calculated feed burdens (January 2015 submission). 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
Concentrations (EDWC) was estimated to be 184 µg/L (ppb).   The
drinking water exposure was included in the dietary analysis in Table 2.

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 89.8% cPAD.  The results of the chronic dietary
assessment are presented in Table 2.

Table 2.  Results for fluxapyroxad (BAS 700 F) Chronic Dietary Exposure
(Food and Water) Considering All  Commodities using DEEM-FCID

Population	Exposure Estimate	% cPAD

Subgroups	(mg/kg b.w./day)

	U.S. Population	0.007111	33.9

All Infants (< 1 year old)	0.018859	89.8

Children (1-2 years old)	0.015045	71.6

Children (3-5 years old)	0.011638	55.4

Children (6-12 years old)	0.007308	34.8

Youth (13-19 years old)	0.005012	23.9

Adults (20-49 years old)	0.006492	30.9

Adults (50+ years old)	0.006648	31.7

Females (13-49 years old)	0.006446	30.7

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 µg/L (ppb).  The    
highest chronic EDWC’s for fluxapyroxad (BAS 700 F) were estimated to
be 184 µg/L (ppb).  

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

Short- and intermediate-term aggregate risk assessments include 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. 

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-Populations	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	0.007111	0.022000	0.029111	309

Children 1-2 years old	0.015045	0.003500	0.018545	485

The aggregate MOEs 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 risk 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 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.]

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 (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
the aggregate exposure to fluxapyroxad (BAS 700 F) 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 (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 Journal 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 (including 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 Residues (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

Some commodities might not be covered due to differences in crop groups
and extrapolations.

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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

	

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