Document ID: EPA-HQ-OPP-2007-0871-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-09-28T04:00Z

FILE NAME:   Valent.wpd July 6, 2007)

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

[Insert Petition Number]

 Summary of Petitions

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, by establishing a tolerance for residues of 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, in or on the raw
agricultural commodity corn, field grain at 0.02 parts per million
(ppm); corn, field forage at 0.02 ppm; and corn, field stover at 0.02
ppm.  EPA has determined that the petition contains data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
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                                       

. The metabolism of flumioxazin is adequately understood for the purpose
of granting the proposed tolerances.

.  Practical analytical methods for detecting and measuring levels of
flumioxazin have been developed and validated in/on all appropriate
agricultural commodities and respective processing fractions.  The LOQ
of flumioxazin in the methods is 0.02 ppm which will allow monitoring of
food with residues at the levels proposed for the tolerances.

.  Residue data has been submitted which adequately support the
requested tolerances. 

B. Toxicological Profile

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

C. Aggregate Exposure

.  Acute and chronic dietary analyses were conducted to estimate
exposure to potential flumioxazin residues in/on the following crops and
food items: peanuts; soybeans; cottonseed oil; grapes; sugarcane;
vegetable, tuberous and corm (Subgroup 1C); mint; strawberry; pistachio;
fruit, pome (Group 11); and fruit, stone (Group 12); asparagus,
vegetable, bulb (Group 3); dried shelled peas and beans (Subgroup 6C);
vegetables, fruiting (Group 8); vegetables, cucurbit (Group 9); bush
berries (Subgroup 13B); nut, tree (Group 14), meat, poultry, and dairy
products.  The Cumulative and Aggregate Risk Evaluation System (CARES)
Version 2.2 was used to conduct these assessments.  This Tier III
assessment used actual residue data, experimentally obtained processing
factors, and an estimation of percent crop treated.  No adjustments were
made for common washing, cooking or preparation practices. Exposure
estimates for water were made based upon a Tier II modeling program
(PRZM-EXAMS).  

.  a. Acute- The acute dietary exposure estimate of flumioxazin residues
in food at the 99.9th percentile for females 13-49 years old was
calculated to be, at most, 0.70% of the acute Population Adjusted Dose
(a-PAD) with a Margin of Exposure (MOE) of 14,284.  This is the only
population subgroup with an identified acute toxicity endpoint. The
a-PAD was defined as the NOEL from an oral developmental study in rats
and includes an uncertainty factor of 100 to account for intra- and
inter-species variation (NOEL = 3 mg/kg bw/day, a-PAD = 0.03 mg/kg/day).

b.  Chronic-The chronic dietary exposure estimate of flumioxazin
residues in food was calculated to be, at most, 1.19% of the chronic
Population Adjusted Dose (c-PAD) with a MOE of 8,662.  The population
subgroup with the highest exposure was children 1-2 years old.  The
c-PAD was defined as the NOEL from a rat two-year chronic/oncogenicity
study and includes an uncertainty factor of 100 to account for intra-
and inter-species variation  (NOEL = 2 mg/kg bw/day, c-PAD = 0.02
mg/kg/day).

.   Tier II PRZM-EXAMS modeling was used to quantify potential exposure
from drinking water. This modeling was conducted using the EPA Platform
Pe4(v02) and 28 EPA EFED standard scenarios for the Standard Index
Reservoir.  The Index reservoir scenario with the highest predicted
water concentration was used to obtain a daily concentration time series
for the simulated years.  The scenario with the highest predicted water
concentrations was PA apples (26 years of weather data).  The 26-year
daily time series was imported to the CARES water module to conduct the
drinking water exposure analysis.

.  Flumioxazin is proposed only for agricultural uses and no  homeowner
or turf uses. Thus, no non-dietary risk assessment is needed. 

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 "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  

i.  Acute Risk.  The potential acute exposure from food to females 13-49
years old will utilize at most 0.70% of the a-PAD.  This is the only
population subgroup with an identified acute toxicity endpoint. 
Addition of dietary exposure from water increases this exposure at the
99.9th percentile to 0.74% of the a-PAD.  The Agency has no cause for
concern if total acute residue contribution is less than 100% of the
a-PAD, because the PAD represents the level at or below which daily
aggregate exposure over a lifetime will not pose appreciable risk to
human health.  Therefore, it can be concluded that there is a reasonable
certainty that no harm will result to the overall U.S. Population from
aggregate, acute exposure to flumioxazin residues.

ii.  Chronic Risk.  The potential chronic exposure from food to the U.S.
Population and various non-child/infant population subgroups will
utilize at most 0.21% of the c-PAD.  Addition of dietary exposure from
water has no effect on this exposure.  The Agency has no cause for
concern if total chronic residue contribution is less than 100% of the
c-PAD, because the PAD represents the level at or below which daily
aggregate exposure over a lifetime will not pose appreciable risk to
human health.  Therefore, it can be concluded that there is a reasonable
certainty that no harm will result to the overall U.S. Population from
aggregate, chronic exposure to flumioxazin residues.

.  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 food to
children 1-2 years old (the most highly exposed child/infant subgroup)
will utilize at most 1.19% of the c-PAD.  Addition of dietary exposure
from water increases this exposure to 1.2% of the c-PAD.  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. 

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