Document ID: EPA-HQ-OPP-2008-0781-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-12-03T05:00Z

FILE NAME:   Valent.flumioxazin.tolpet.doc

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

<EPA Registration Division contact: Joanne Miller 703-305-6224>

 

<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:>

<[Valent U.S.A. Corporation]>

<[Insert petition number]>

<	EPA has received a pesticide petition ([insert petition number]) from
[Valent U.S.A. Corporation], [1600 Riviera Avenue, Suite 200, Walnut
Creek, CA 94596] 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, >

<(Options (pick one)>

<	1. by establishing a tolerance for residues of >

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

<	[the herbicide chemical flumioxazin,
2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazin-6-yl]-4,5
,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione and its metabolites APF
(3-oxo-4-prop-2-ynyl-6-amino-7-fluoro-3,4-dihydro-1,4-benzoxazin) and
482-HA
(N-(7-fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-1,4-benzoxazin-6-yl)cycl
ohex-1-ene-1-carboxamide-2-carboxylic acid)] in or on the raw commodity
[freshwater fish] at [1.5] 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. >[The metabolism of flumioxazin in crop plants has
been reported previously and is adequately understood. The OPP/HED
Chemistry Science Advisory Council determined at its May 30, 2007
meeting that the requirement for flumioxazin metabolism study in fish
may be waived provided the registrant provides residue data on magnitude
of the residues in fish of the metabolites APF and 482-HA in addition to
parent compound.  Such data have been submitted in support of this
petition.].  

<	2. Analytical method.  [An analytical method for detecting flumioxazin
and its metabolites in fish tissue has been submitted with this
petition.  The LOQ of flumioxazin and its metabolites in the analytical
method for fish tissue is 0.01 ppm, which will allow monitoring for
residues at the levels proposed for the tolerance.] 

>

<	3. Magnitude of residues. [A 28-day magnitude of the residue study was
conducted with bluegill sunfish (Lepomis macrochirus) and channel
catfish (Ictalurus punctatus). The study was performed at 2X the
proposed application rate for aquatic use to assess the potential
accumulation of flumioxazin and two metabolites, APF and 482-HA, in fish
tissue.  Maximum total flumioxazin plus metabolite residues were
measured at four hours after initiation of exposure, and residues in
both species declined significantly over the course of the 28-day study.
 Accounting for the 2X proposed application rate, adequate data exist to
support the proposed tolerance of flumioxazin parent and metabolites of
1.5 ppm.]  

>

<B. Toxicological Profile>

<	1. Acute toxicity.  [The toxicological profile for flumioxazin
supporting this petition for tolerances was published in the Federal
Register on March 31, 2004 (69 FR 16823)(FRL-7351-2).] 

>

<	2. Genotoxicity. [The toxicological profile for flumioxazin supporting
this petition for tolerances was published in the Federal Register on
March 31, 2004 (69 FR 16823)(FRL-7351-2).]  

>

<	3. Reproductive and developmental toxicity. [The toxicological profile
for flumioxazin supporting this petition for tolerances was published in
the Federal Register on March 31, 2004 (69 FR 16823)(FRL-7351-2).]  

>

<	4. Subchronic toxicity. [The toxicological profile for flumioxazin
supporting this petition for tolerances was published in the Federal
Register on March 31, 2004 (69 FR 16823)(FRL-7351-2).]  

>

<	5. Chronic toxicity. [The toxicological profile for flumioxazin
supporting this petition for tolerances was published in the Federal
Register on March 31, 2004 (69 FR 16823)(FRL-7351-2).]  

>

<	6. Animal metabolism. [The toxicological profile for flumioxazin
supporting this petition for tolerances was published in the Federal
Register on March 31, 2004 (69 FR 16823)(FRL-7351-2).]    

>

<	7. Metabolite toxicology. [The toxicological profile for flumioxazin
supporting this petition for tolerances was published in the Federal
Register on March 31, 2004 (69 FR 16823)(FRL-7351-2).]   

 >

<	8. Endocrine disruption. [The toxicological profile for flumioxazin
supporting this petition for tolerances was published in the Federal
Register on March 31, 2004 (69 FR 16823)(FRL-7351-2).]

>

<C. Aggregate Exposure>

<	1. Dietary exposure. [Acute and chronic dietary analyses were
conducted to estimate exposure to potential flumioxazin residues in/on
the currently registered crops (see CFR 180.568 for details), freshwater
fish, and drinking water.  DEEM-FCID version 2.16 was used to conduct
these assessments.  This Tier I assessment assumed tolerance level
residues in all commodities and 100% crop treated.  No adjustments were
made for common washing, cooking or preparation practices.  Exposure
estimates for drinking water were made based upon the drinking water
EECs given below, and explained in detail in a report submitted with
this petition.]>

<	i. Food. [a. Acute - The aPAD was defined using the NOAEL from an oral
developmental study in rats and an uncertainty factor of 100 to account
for intra- and inter-species variation (NOAEL = 3 mg/kg bw/day, aPAD =
0.03 mg/kg/day). Thus, females of child-bearing age is the only
population subgroup with an identified flumioxazin acute toxicity
endpoint.  The estimated acute dietary exposure, including food and
drinking water, for females 13-49 years of age is 0.020054 mg/kg/d (67%
aRfD) at the 95th percentile.  The 95th percentile is the appropriate
level for a conservative tolerance-level exposure assessment that
assumes 100% crop treated.  b. Chronic - The cPAD was defined using the
NOAEL from a rat two-year chronic/oncogenicity study and an uncertainty
factor of 100 to account for intra- and inter-species variation  (NOAEL
= 2 mg/kg bw/day, cPAD = 0.02 mg/kg/day).  Chronic dietary exposures,
including food and drinking water,  to flumioxazin range from 0.000974
mg/kg/d (4.9% cPAD) for youth aged 13-19 years old to 0.003749 mg/kg/d
(18.7% cPAD) for all infants.  Chronic dietary exposure for the general
U.S. population is 0.001298 mg/kg/d (6.5% cPAD).]  

 >

rn modeled, acute drinking water EECs range from 21.3 μg/L (ppb) to 397
ppb for a single applications and from 21.8 ppb to 407 ppb for four
applications.  Depending on the depth and use pattern modeled, chronic
drinking water EECs range from less than 0.5 ppb to 8.3 ppb for a single
applications and from less than 2 ppb to approximately 33.2 ppb for four
applications.]

>

<	2. Non-dietary exposure. [Flumioxazin is proposed for aquatic use in
water bodies that may be used for swimming and other recreational
activities.  Flumioxazin will be applied directly to water bodies at
concentrations of up to 400 ppb for control of aquatic weeds.  Exposures
for recreational swimming have been estimated using SWIMODEL.  Total
daily exposure on the day of application of flumioxazin to water bodies
was estimated to be 0.00288 mg/kg/d for adult females and 0.00730
mg/kg/d for children.  Assessed against the short- and intermediate-term
incidental oral endpoint of 6.3 mg/kg/d, MOEs are calculated to be 2,190
and 863 for adult females and children, respectively.]  

  >

<D. Cumulative Effects>

<	[Section 408(b)(2)(D)(v) requires that the Agency must consider
“available information” concerning the cumulative effects of a
particular pesticide's residues and for “other substances that have a
common mechanism of toxicity.” Available information in this context
include not only toxicity, chemistry, and exposure data, but also
scientific policies and methodologies for understanding common
mechanisms of toxicity and conducting cumulative risk assessments.
Although the Agency has some information in its files that may turn out
to be helpful in eventually determining whether a pesticide shares a
common mechanism of toxicity with any other substances, EPA does not at
this time have the methodologies to resolve the complex scientific
issues concerning common mechanism of toxicity in a meaningful way for
most registered pesticides.]

>

<E. Safety Determination>

<	1. U.S. population. [i. Acute Risk.  Aggregate flumioxazin exposures
from all sources (i.e., dietary and swimming) have been estimated for
adult females and children.  Adult males are not included in the
aggregate assessment because exposures to adult females represent the
worst case for adults, and toddlers/infants are not included in the
aggregate assessment because swimming exposures are not estimated for
these subpopulations.  For the aggregate assessment, average daily
dietary exposures (i.e., estimates of chronic dietary exposure) are
aggregated with swimming exposures from the day of exposure (i.e.,
assuming 400 ppb flumioxazin applied to the water).  Residential dietary
and postapplication recreational swimming exposures were aggregated and
assessed against the short- and intermediate-term oral endpoint of 6.3
mg/kg/d. Total estimated aggregate exposures are 0.00404 mg/kg/d for
adult females and 0.00872 mg/kg/d for children.  Corresponding MOEs are
1,560 for adult females and 722 for children.  Because these MOE are
greater than 100, it can be concluded that there is a reasonable
certainty that no harm will result to the overall U.S. Population and
its subpopulations from aggregate acute exposure to flumioxazin
residues. ii.  Chronic Risk.  See Above for chronic dietary risk (food
plus drinking water).  Chronic risk due to swimming is not relevant due
to the seasonal, short-term nature of exposure.  Chronic dietary
exposures for all subpopulations are well below the cPAD, indicating
reasonable certainty that no harm will result to the overall U.S.
Population from aggregate chronic exposure to flumioxazin residues.]

>

<	2. Infants and children. [i. Safety Factor for Infants and Children. 
EPA has determined that the special 10X SF to protect infants and
children should be removed [Federal Register of March 31, 2004 (69 FR
16823) (FRL-7351-2)].  The FQPA factor has been removed because
developmental toxicity and offspring toxicity NOAELs/LOAELs are well
characterized; there is a well-defined dose-response curve for the
cardiovascular effects; and the endpoints of concern used for overall
risk assessments are appropriate for the route of exposure and
population subgroups.

ii. Acute Risk.  No acute endpoint has been identified for infants and
children.  Therefore, no assessment of acute exposure from food to this
subgroup is required.

iii.  Chronic Risk.  The potential chronic exposure from all registered
and proposed food uses, and drinking water to all infants <1 year old
(the most highly exposed child/infant subgroup) will utilize at most
18.7% of the cPAD.  Therefore, it can be concluded that there is a
reasonable certainty that no harm will result to infants and children
from aggregate chronic exposure to flumioxazin residues.]

>

<F. International Tolerances>

<	[Flumioxazin has not been evaluated by the JMPR and there are no Codex
Maximum Residue Limits (MRL) for flumioxazin. MRL values have been
established to allow the following uses of flumioxazin in the following
countries: 

Argentina; soybean, 0.015 ppm; sunflower, 0.02 ppm

Brazil; Cotton, 0.05 ppm

	 Garlic, 0.05 ppm

	 Potato, 0.05 ppm

	 Coffee, 0.05 ppm

	 Sugarcane, 0.05 ppm

	 Onion, 0.05 ppm

	 Citrus, 0.05 ppm

	 Bean, dry, 0.05 ppm

	 Soybean, 0.1 ppm

South Africa; soybean, 0.02 ppm; groundnut, 0.02 ppm

In addition, the following flumioxazin MRLs have been promulgated in the
EU:

	Bulb, root and tuber vegetables, 0.050 ppm

	Dry beans, peas, other pulse crops, 0.050 ppm

	Oilseeds, 0.10 ppm

	Olives, 0.050 ppm

	Cereal grains, 0.05 ppm

	Coffee, tea, cocoa, 0.1 ppm

	Hops, 0.1 ppm]

>

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