Document ID: EPA-HQ-OPP-2010-0426-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-06-09T04:00Z

<EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  (1/1/2010)>

<EPA Registration Division contact: Kathryn Montague Product Manager 23
(703) 305- 1243>

 

<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 and brackets, i.e., “[insert
company name],” with the information specific to your action.>

<TEMPLATE:>

<[Nichino America, Inc.]>

<[Pesticide Petition No. xxxxxx]>

<	EPA has received a pesticide petition (PP # xxxxxx) from Nichino
America, Inc. 4550 New Linden Hill Road Suite 501 Wilmington, DE 19808
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 180.585>

<>

<	1. by establishing a tolerance for residues of the herbicide,
pyraflufen-ethyl [ethyl
2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-1H-pyrazol-3-yl)-4-fluor
ophenoxyacetate] and its acid metabolite, E-1
[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-1H-pyrazol-3-yl)-4-fluo
rophenoxyacetic acid], expressed in terms of the parent, in or on the
following raw agricultural commodities: almond hulls at 0.02 parts per
million (ppm) and nuts, tree group 14 at 0.01 parts per million (ppm),
pistachio at 0.01  parts per million (ppm), fruit, pome fruit group 11
at 0.01 parts per million (ppm), fruit, stone fuit group 12 at 0.01
parts per million (ppm), pomegranates at 0.01 parts per million (ppm),
olives at 0.01 parts per million (ppm), grapes at 0.01 parts per million
(ppm), and hops at 0.05 parts per million (ppm).

>

<	2. to establish an exemption from the requirement of a tolerance for
“NA-Remove”>

<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. The qualitative nature of the residues of 

pyraflufen-ethyl (ET-751) in corn, soybeans, and wheat and pasture grass
is adequately understood. The metabolism of pyraflufen-ethyl has been
studied in cotton, wheat, and potato. Metabolism in the plant involves
ester hydrolysis, de-methylation on the pyrazole ring and further
degradation of the phenoyxyacetate moiety to bound polar metabolites.
The nature of the residue is adequately understood and the residues of
concern are the parent, pyraflufen-ethyl, and the acid metabolite, E-1,
only.

>

<2. Analytical method. Aqueous organic solvent extraction, column clean
up, and quantitation by gas chromatography is used to measure and
evaluate the chemical residues.

>

<	3. Magnitude of residues. Several residue trials were conducted in
almonds, pecans, apples, pears, grapes, and hops to satisfy the required
EPA region locations.   Based on these data, it is proposed that the
Agency establish new tolerances in  almond hulls at 0.02 ppm, nuts, tree
group 14 at 0.01 ppm, pistachio at 0.01 ppm, fruit, pome fruit group 11
at 0.01 ppm, fruit, stone fuit group 12 at 0.01 ppm, pomegranates at
0.01 ppm, olives at 0.01 ppm, grapes at 0.01 ppm, and hops at 0.05 ppm.

>

    	4. Magnitude of the residue in animals.--i. Ruminants. The results
of the meat and milk 28-day feeding study conclude that no finite
residues of the parent, ET-751 or the metabolites E-9, and E-15 can be
detected in milk at a dose level of 10 ppm, and that no residues of
either ET-751, E-5, or E-9, are detected in muscle, liver or fat
tissues, and low level residues of 0.0534 ppm in kidney tissues.  These
results concur with those of an earlier ruminant metabolism study (MRID
45283005) at a dose of 10 ppm. Although the results of this livestock
feeding study indicates that no finite residues could be detected in
meat and milk commodities from the anticipated dietary burdens, we are
using an anticipated residue value in milk calculated to be of 0.007
ppm.

    ii. Poultry. The maximum poultry dietary burden results from a diet 

comprised of cotton meal, corn grain, corn milled byproducts, soybean
seed, soybean meal, soybean hulls, wheat grain, and wheat milled
byproducts for a total dietary burden that is significantly lower than
the levels that would require the proposal of tolerances in poultry.
This conclusion is based on the exaggerated rate metabolism studies
carried out on pyraflufen-ethyl and its acid metabolite. Therefore, an
exemption from tolerances in poultry meat, meat byproducts, fat, and 

eggs under 40 CFR 180.6(a)(3) and (b) is proposed as it is not possible
to establish with certainty whether finite residues will be incurred,
but there is no reasonable expectation of finite residues.

<B. Toxicological Profile>

<	1. Acute toxicity.  [Insert text.] “NA-Remove”>

<	2. Genotoxicty. [Insert text.] “NA-Remove”>

<	3. Reproductive and developmental toxicity. [Insert text.]
“NA-Remove”>

<	4. Subchronic toxicity. [Insert text.] “NA-Remove”

>

<	5. Chronic toxicity. [Insert text.] “NA-Remove”

	EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities of
major identifiable subgroups of consumers,

including infants and children. The nature of the toxic effects caused
by pyraflufen-ethyl as well as the no observed adverse effect level
(NOAEL) and the lowest 

observed adverse effect level (LOAEL) from the toxicity studies reviewed
are discussed in the Federal Register of April 30, 2003 (  HYPERLINK
"http://www.epa.gov/EPA-PEST/2003/April/Day-30/p10264.htm"  68 FR 23046
) (FRL-7300-9).

>

<	6. Animal metabolism.  The qualitative nature of the residues of
pyraflufen-ethyl and its acid metabolite, E-1, in animals is adequately
understood. Pyraflufen-ethyl is rapidly absorbed, metabolized, and
excreted to feces and urine, with greater than 90% of the administered
dose excreted within 24 hours in rats. Based on metabolism studies with
goats, hens, and rats, there is no reasonable expectation that
measurable pyraflufen-ethyl-related residues will occur in meat, milk,
poultry, or eggs from the proposed use.

>

<	7. Metabolite toxicology. No toxicologically significant metabolites
were detected in plant or animal metabolism studies for cotton,
potatoes, or mandarine oranges.

>

<	8. Endocrine disruption. Chronic, lifespan, and multigenerational 

bioassays in mammals and acute and subchronic studies on aquatic
organisms and wildlife did not reveal any endocrine effects for
pyraflufen-ethyl. Any endocrine related effects would have been detected
in this comprehensive series of required tests. The probability of any
such effect due to agricultural uses of pyraflufen-

ethyl is negligible.

>

<C. Aggregate Exposure>

<	1. Dietary exposure. Acute dietary risk assessments are performed for
a food-use pesticide, if toxicological study has indicated the
possibility of an effect of concern occurring as a result of a one-day
or single exposure.  No adverse effect attributable to a single exposure
(dose) was observed in oral toxicity studies, including the
developmental toxicity studies in rats and rabbits.  Therefore, EPA did
not identify an acute dietary endpoint and an acute dietary assessment
was not performed.  Chronic dietary risk analyses was conducted to
estimate potential pyraflufen-ethyl residues in/on the following crops: 
almond, beechnut, Brazil nut, butternut, cashew, chestnut, chinquapin,
filbert, hickory nut, macadamia nut, pecans, walnuts, pistachio, apple,
crabapple, loquat, mayhaw, pear, oriental pear, quince, apricot, sweet
cherry, tart cherry, nectarine, plum, Chickasaw, Damson plum, Japanese
plum, plumcot, fresh prune, pomegranates, olives, grapes and hops and
anticipated residues in milk of 0.007 ppm, using Dietary Exposure
Evaluation Model Software with the Food Commodity Intake Database
(DEEM-FCID).  These estimates assuming tolerance level residues in the
established and proposed commodities except corn, cottonseed, potato,
soybean seeds, and wheat grains had nondetectable residues.  Exposure
estimates to water were based on modeling with FIRST and SCI-GROW.

>

<	i. Food. The chronic population adjusted dose (cPAD) for the 

general population, based on residues at the tolerance levels and ½ of
the combined LOQs for  the parent and metabolites for corn, soybeans,
potato, wheat, and cotton. A default processing factor of 6.5 X for dry
potato, 1.5x for corn syrup, an experimental processing factor of 0.6x
for cotton seed oil and calculated milk value of 0.007 ppm.  One hundred
percent crop treated (%CT) was assumed for all crop commodities.  The
new crops will incrementally utilize <1% of the cPAD of 0.2 mg/kg/day
for the U.S. population and <1% of cPAD for children (1-6 years).   

>

<	ii. Drinking water. The residue of concern in drinking water was
determined to be pyraflufen-ethyl.  Based on the FIRST and SCI-GROW
models, the EECs of pyraflufen-ethyl for acute exposures are estimated
to be 1247 parts per trillion (ppt) for surface water and 1.8 ppt for
ground water. The EECs for chronic exposures are estimated to be 281 ppt
for surface water and 1.8 ppt for ground water.

	2. Non-dietary exposure. EPA calculated the non-dietary exposure
scenarios in the Federal Register May 12, 2004 (69 FR 26305)
(FRL-7358-2). Pyraflufen-ethyl is registered in several non-food sites,
including airports, commercial plants, nurseries and ornamental
plantings; established ornamental turf; railroad, roadside, and utility
rights-of-ways, and other similar non-crop areas. 

>

<>

<D. Cumulative Effects>

<Pyraflufen-ethyl belongs to the protox inhibitor class of compounds,
and chemically is a 3-phenylpyrazole. The herbicidal activity of protox
inhibitors is due to the inhibition of protoporphyrinogen IX oxidase.
All relevant toxicological data has been provided to EPA. Chemicals with
a similar mode of action, i.e., the protox inhibitors, have different
chemical structures compared to pyraflufen-ethyl. Although other protox
inhibitors have a similar herbicidal mode of action, there is no
information available to suggest that these compounds exhibit a similar
toxicity profile in the mammalian system. We are aware of no information
to indicate or suggest that pyraflufen-ethyl has any toxic effects on
mammals that would be cumulative with those of any other chemical. Since
pyraflufen-ethyl is relatively non-toxic, cumulative effects of residues
and other compounds are not anticipated. Therefore, for the purposes of
this Food Quality Protection Act (FQPA) document, there should be no
consideration of cumulative risk that would require assessment.

>

<E. Safety Determination>

<U.S. population. 

i.  Acute risk. No adverse effect attributable to a single exposure
(dose) of pyraflufen-ethyl was observed in the oral toxicity studies,
including the developmental toxicity studies in rats and rabbits.
Therefore, an acute reference dose was not established and no acute risk
is expected.

ii. Chronic Risk.  Based on the chronic toxicity data, the cPAD for
pyraflufen-ethyl is considered to be 0.172 mg/kg/day. This value is
based on the NOAEL of 17.2 mg/kg/day observed in the chronic rat feeding
study and a safety (uncertainty) factor of 100, the worse case estimate
of chronic dietary exposure of pyraflufen-ethyl from cotton, potatoes,
corn, soybean, and wheat, almond, beechnut, Brazil nut, butternut,
cashew, chestnut, chinquapin, filbert, hickory nut, macadamia nut,
pecans, walnuts, pistachio, apple, crabapple, loquat, mayhaw, pear,
oriental pear, quince, apricot, sweet cherry, tart cherry, nectarine,
plum, Chickasaw, Damson plum, Japanese plum, plumcot, fresh prune,
pomegranates, olives, grapes and hops and calculated value of 0.007 ppm
in milk will utilize less than 1% of the cPAD for the general U.S.
population. EPA generally has no concern for exposures below 100% of the
RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. The complete and reliable toxicity data and the
conservative chronic exposure assumptions support the conclusion that
there is a reasonable certainty of no harm from dietary (food) exposure
to pyraflufen-ethyl and the acid metabolite residues. Moreover, as
exposure to residues of pyraflufen-ethyl and the acid metabolite via
water is negligible, there is a reasonable certainty of no harm from
aggregate exposure to pyraflufen-ethyl and the acid metabolite residues.

iii.  Cancer Risk.  Cancer risk was calculated by the EPA in the Federal
Register May 12, 2004 (69 FR 26305) (FRL-7358-2) for both food and
water.  This assessment substantially overstates risk because it is
based on the assumption that all commodities covered by pyraflufen-ethyl
tolerances contain tolerance level residues.  The cancer risk estimate
was in the range of 1 in 1 million and does not exceed the Agency’s
level of concern for exposure from either food or water sources.  

>

<	2. Infants and children. The chronic dietary exposure of
pyraflufen-ethyl and the acid metabolite from corn, soybeans, and wheat
and calculated value in milk will utilize < 1% of the cPAD for children
(1-6 years). Exposure to potential residues in drinking water is
expected to be negligible.  In the Federal Register May 12, 2004 (69 FR
26305) (FRL-7358-2) after calculating DWLOCs and comparing them to the
EECs for surface and ground water, EPA does not expect the aggregate
exposure to children to exceed the Agency’s level of concern.>

There is no evidence of increased susceptibility of rat or rabbit
fetuses following in utero exposure in the developmental studies with
pyraflufen-ethyl.  There is no evidence of increased susceptibility of
young rats n the reproduction study with Pyraflufen-ethyl.  EPA
concluded there are no residual uncertainties for pre- and/or post-natal
exposure.

<F. International Tolerances>

<	There are no Codex maximum residue level established for residues of
pyraflufen-ethyl and the acid metabolite, E-1, expressed in terms of
parent on any crops.

>

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