Document ID: EPA-HQ-OPP-2011-1002-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-03-15T04:00Z

<EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  (11/11/2011)>

<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-fluor
ophenoxyacetic acid, expressed in terms of the parent, in or on the
following raw agricultural commodities: hop, dried cone at 0.01 parts
per million (ppm), peanut at 0.01 parts per million (ppm), peanut, hay
at 0.07 parts per million (ppm), peanut, meal at 0.01 parts per million
(ppm), and peanut, refined oil at 0.01 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 hops, peanuts, peanut hay, peanut meal, and
peanut refined oil are adequately understood.  The metabolism of
pyraflufen-ethyl has been studied in cotton, wheat, potato, and oranges.
 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 with mass spectrometry is
used to measure and evaluate the chemical residues.

>

<	3. Magnitude of residues. Residue trials were conducted in hops and
peanuts to satisfy the required EPA region locations.  Other than peanut
hay, there were no residues found in any hop, peanut, or peanut
processed samples above the limit of quantitation for the analytical
method established at 0.005 ppm.  Based on these data, it is proposed
that the Agency establish new tolerances in hop, dried cone at 0.01 ppm,
peanut at 0.01 ppm, peanut hay at 0.07 ppm, peanut meal at 0.01 ppm, and
peanut refined oil at 0.01 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 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 were detected 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 indicate that no finite residues are 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 from a diet
comprised of cotton meal, corn grain, corn milled byproducts, soybean
seed, soybean meal, soybean hulls, wheat grain, and wheat milled
byproducts results in a total dietary burden that is significantly lower
than the levels that would require tolerances in poultry and poultry
byproducts.

<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 on pyraflufen-ethyl 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.  Specific information on the nature of the adverse
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 can be found at   HYPERLINK "http://www.regulations.gov" 
http://www.regulations.gov  in the document “Pyraflufen-ethyl: Human
Health Risk Assessment for a Section 3 Registration of New Food Uses on
Tree Nuts (Crop Group 14), Pistachios, Pome Fruit (Crop Group 11-10),
and Stone Fruit (Crop Group 12), Hops, Grapes, Olives, and
Pomegranates,” at page 17 in docket ID number EPA-HQ-OPP-2010-0426.

>

<	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 animal metabolism studies or plant metabolism studies
on cotton, potatoes, and mandarin 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. Quantitative acute dietary exposure and risk
assessments are performed for a food-use pesticide if a toxicological
study has indicated the possibility of an effect of concern occurring as
a result of a 1-day or single exposure.  No such effects attributable to
a single exposure (dose) were observed in oral toxicity studies,
including the developmental toxicity studies in rats and rabbits
conducted with pyraflufen-ethyl; therefore, a quantitative acute dietary
exposure assessment is not necessary.  Chronic dietary risk analyses
were conducted using Dietary Exposure Evaluation Model Software with the
Food Commodity Intake Database (DEEM-FCID).  These dietary exposure
assessments used the following assumptions:  100 percent crop treated
(PCT) and tolerance-level residues for pyraflufen-ethyl on all treated
crops except corn, cottonseed, potato, soybean, wheat, pome fruit, stone
fruit, pomegranate, olive, grape, tree nuts, pistachio, hops, and
peanuts for which one half of the combined Levels of Quantification
(LOQs) for the parent and the metabolite were used since all field trial
residue levels were less than the LOQ.  Exposure estimates to water were
based on modeling with FIRST, PRZM/EXAMS, and SCI-GROW.

>

<	i. Food. Using the exposure assumptions listed above, chronic exposure
to pyraflufen-ethyl from food including the proposed new uses on hops
and peanuts will incrementally utilize <1% of the cPAD of 0.172
mg/kg/day for all population groups.

>

<	ii. Drinking water. The residue of concern in drinking water was
determined to be pyraflufen-ethyl.  Based on the First Index Reservoir
Screening Tool (FIRST), Pesticide Root Zone Model/Exposure Analysis
Modeling System (PRZM/EXAMS), and Screening Concentration in Ground
Water (SCI-GROW) models, the estimated drinking water concentrations
(EDWCs) of pyraflufen-ethyl for acute exposures are estimated to be
1,247 parts per trillion (ppt) for surface water and 1.8 ppt for ground
water.  For chronic exposures for non-cancer and cancer assessments, the
EDWCs are estimated to be 281 ppt for surface water and 1.8 ppt for
ground water.

	2. Non-dietary exposure. EPA calculated non-dietary exposure scenarios
as listed 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. 
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. 
Current available data and information does not indicate or suggest that
pyraflufen-ethyl has a common mechanism of toxicity with other
substances.  Therefore, for the purposes of this Food Quality Protection
Act (FQPA) document, assessment of cumulative risk is not required.

>

<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.  A worse case estimate,
using proposed tolerance values, of chronic dietary exposure of
pyraflufen-ethyl from hops and peanuts 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 toxicity data set
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.  There is essentially no incremental cancer risk
associated with pyraflufen-ethyl treated hops and peanuts.  Cancer risk
was calculated by EPA as listed 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 hops and peanuts 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 EDWCs for surface and
ground water, it is not expected the aggregate exposure to children will
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 in the reproduction study with pyraflufen-ethyl.  There are
no residual uncertainties for pre- and/or post-natal exposure.

<F. International Tolerances>

<	There are no Codex maximum residue levels (MRLs) established for
residues of pyraflufen-ethyl and the acid metabolite, E-1, expressed in
terms of parent on any crop.  Canada has not established MRLs for
pyraflufen-ethyl.

>

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