Document ID: EPA-HQ-OPP-2008-0885-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-04-20T04:00Z

FILE NAME:   Valent.doc  (October 8, 2008)

EPA Registration Division contact: Laura Nollen  (703-305-7390)

Interregional Research Project Number 4 (IR-4)

PP# 8E7462

 Summary of Petitions

EPA has received a pesticide petition, PP 8E7462, from   SEQ CHAPTER \h
\r 1 IR-4, 500 College Road East, Suite 201 W, Princeton, NJ  08450,
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 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 commodities cucurbit vegetables, group 9 at 0.03 parts per
million (ppm), leaf petioles, subgroup 4B at 0.02 ppm, and hops, dried
cones at 0.07 ppm. The petitioner is also proposing revocation of the
existing tolerance for residues of flumioxazin in or on the raw
agricultural commodity almonds, because a tolerance on nut, tree, group
14 has been established and deletion of the existing tolerance for
melon, subgroup 9A since it will be superseded by the proposed tolerance
for cucurbit group 9.   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                                       

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

	2.  Analytical method.  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.

3. Magnitude of residues.  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

1. Dietary 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).  

i. Food.  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).

ii. Drinking water.   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.

2. Non-dietary exposure.  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  

1. U.S. population. 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.

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 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.