Document ID: EPA-HQ-OPP-2007-0030-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-02-28T05:00Z

<COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE  (7/1/2006)>

<EPA Registration Division contact: [insert name and telephone number
with area code]>

 

<INSTRUCTIONS:  Please utilize this outline in preparing tolerance
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<TEMPLATE:>

<[Syngenta Crop Protection, Inc.]>

<[Insert petition number]>

	EPA has received a pesticide petition ([insert petition number]) from
[Syngenta Crop Protection, Inc.], [P.O. Box 18300, Greensboro, North
Carolina, 72409] 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 [mesotrione] in or
on the raw agricultural commodity [asparagus] at [0.01] parts per
million (ppm), [grass, seed screenings] at [0.10] ppm, [grass, straw] at
[0.10] ppm, [grass, forage] at [0.01] ppm, [grass, hay] at [0.01] ppm,
[oats, grain] at [0.01] ppm, [oats, straw] at [0.01] ppm, [oats, forage]
ppm, [oats, hay] at [0.01] ppm, [okra] at [0.01] ppm, [rhubarb] at
[0.01] ppm, [sorghum, forage] at [0.01] ppm, [sorghum, stover] at [0.01]
ppm, [sorghum, grain] at [0.01] ppm, [sorghum, sweet] at [0.01] ppm,
[sugarcane] at [0.01] ppm.  EPA has determined that the petition
contains data or information regarding the elements set forth in section
408 (d)(2) of the 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 nature of mesotrione residues is well
understood for corn, cranberries and peanuts. The metabolism in these
three diverse crops has been proven to be similar, and therefore the
metabolism of mesotrione is considered to be adequately understood for
all crops, per EPA Test Guideline 860.1300.  Mesotrione is rapidly and
completely metabolized in crops. The major crop metabolites,
2-amino-4-methylsulfonyl benzoic acid (AMBA) and its conjugates and
4-methylsulfonyl-2-nitrobenzoic acid  (MNBA), have been determined by
EPA to be not toxicologically significant and are not included in the
tolerance expression or in the mesotrione risk assessments.]>

<	2. Analytical method. [Practical and specific analytical method RAM
366/01 (MRID 45651803) is available for detecting and measuring the
level of mesotrione in or on various crop commodities.]>

<	3. Magnitude of residues. [The magnitude of the residue studies are
submitted with this petition for asparagus, grain sorghum, sweet
sorghum, grasses grown for seed, oats, okra, rhubarb, and sugarcane. 
All studies meet the  requirements per EPA Test Guideline 860.1000,
860.1500, and 860.1520.  No residues were detected above the analytical
method limit of quantitation of 0.01 ppm in any food commodity from any
of the crops proposed in this petition.  Residue between <0.01 and 0.09
ppm were detected in certain animal feed commodities of grasses grown
for seed.]>

<B. Toxicological Profile 

[EPA has evaluated the toxicology 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 the major
identifiable subgroups of consumers, including infants and children. 
The nature of the toxic effects caused by mesotrione, as well as the no
observable adverse effect levels (NOAEL) and the lowest observed adverse
effect levels (LOAEL) from the toxicity studies reviewed are discussed
in the Federal Register of June 21, 2001 (Federal Register Volume 66,
No. 120, June 21, 2001, pages 33187-33195).  A summary of the
toxicological endpoints for mesotrione used for human risk assessment is
discussed in the final rule published in the Federal Register of June
21, 2001.]>

<	1. Acute toxicity.  [NA-Remove]>

<	2. Genotoxicty. [NA-Remove]>

<	3. Reproductive and developmental toxicity. [NA-Remove]>

<	4. Subchronic toxicity. [NA-Remove]>

<	5. Chronic toxicity. [NA-Remove]>

<	6. Animal metabolism. [NA-Remove]>

<	7. Metabolite toxicology. [NA-Remove]>

<	8. Endocrine disruption. [NA-Remove]>

<C. Aggregate Exposure>

<	1. Dietary exposure. [A chronic dietary exposure evaluation was
completed by Syngenta for mesotrione using the Dietary Exposure
Evaluation Model (DEEM-FCIDTM), version 2.03 from Exponent.  In addition
to current tolerances for mesotrione on corn, this exposure assessment
included pending mesotrione uses on millet, flax and the berry Crop
Group (Crop Group 13), and proposed crop uses on asparagus, grasses
grown for seed, oats, okra, rhubarb, sorghum and sugarcane.  Percent of
crop treated values were conservatively estimated to be 100% for all
pending and proposed uses.  Drinking water estimates were incorporated
directly into the dietary exposure assessment using the higher of the
estimated drinking water concentrations (EDWCs) for surface and ground
water.  All consumption data for these assessments was taken from the
USDA’s Continuing Survey of Food Intake by individuals (CSFII) with
the 1994-96 consumption database and the Supplemental CSFII children’s
survey (1998) consumption database.]>

<	i. Food. [Mesotrione is not considered to be acutely toxic and an
acute toxicological endpoint was not selected by EPA.

Chronic Exposure.  The mesotrione chronic dietary (food only) risk
assessment was performed for all population subgroups with a chronic
reference dose of 0.0007 mg/kg-bw/day based on a mouse reproduction
study with a Lowest Observable Adverse Effect Level (LOAEL) of 2.1
mg/kg-bw/day and an uncertainty factor of 3,000X, which is currently
being used by EPA.  For the purpose of the aggregate risk assessment,
exposure values were expressed in terms of margin of exposure (MOE),
which was calculated by dividing the LOAEL by the exposure for each
population subgroup.  In addition, exposure was also expressed as a
percent of the reference dose (%RfD).  Chronic (food only) exposure to
the U.S. population resulted in a MOE of 404,706 (0.7% of the chronic
RfD of 0.0007 mg/kg-bw/day).  The most sensitive sub-population was
children (3-5 years old) with a MOE of 152,081 (2.0% of the chronic
RfD). 

Cancer.  Mesotrione is considered “not likely to be a human
carcinogen”.  Therefore, no cancer risk assessment was performed for
mesotrione.]>

<	ii. Drinking Food. [To determine the Estimated Drinking Water
Concentrations (EDWCs) for mesotrione, the Pesticide Root Zone Model-
Exposure Analysis Modeling Systems (PRZM- EXAMS) and the Screening
Concentration in Ground Water (SCI-GROW) models were used for estimation
of surface and ground water EDWCs, respectively.  Using the EPA's PRZM
standard crop scenario for Louisiana sugarcane, the highest chronic
surface water EDWC was conservatively estimated to be 0.8815 ppb.  Based
on SCI-GROW modeling, the ground water EDWC for mesotrione was
conservatively estimated to be 0.117 ppb.  Since the modeled surface
water EDWC exceeds the modeled ground water EDWC, the surface water
value of 0.8815 ppb considered to be protective for any ground water
concentration concerns.

The modeled chronic surface value of 0.8815 ppb was input directly into
the DEEM-FCID™ software as water, direct and indirect, all sources to
model the chronic drinking water exposure.  Chronic drinking water
exposure to the U.S. population resulted in a MOE of 112,962 (2.7% of
the chronic RfD of 0.0007 mg/kg-bw/day).  The most sensitive
sub-population was infants (< 1 year old) with a MOE of 34,455 (8.7% of
the chronic RfD).]>

<	2. Non-dietary exposure. [There are no current approved residential
uses for mesotrione and therefore no sources on non-dietary exposures
were included in this assessment.]>

<D. Cumulative Effects>

<	[A highly conservative cumulative risk assessment was published by EPA
in the Federal Register Notice of Pesticide Tolerance for topramezone
(Federal Register: August 10, 2005, Volume 70, Number 153, Page
46410-46419).  Though exposure was highly overestimated (EPA assumed
100% of corn crops had tolerance level residues of topramezone,
isoxaflutole and mesotrione), EPA concluded that “because the use
patterns, exposure assumptions, and  risk characterizations for the
three pesticides do not suggest that any potential cumulative effect
would be at a level of concern, EPA concludes it has adequately
considered the potential cumulative effects of topramezone and the
pesticides for which it may possibly share a common mechanism of
toxicity.”   Since the new proposed mesotrione uses do not result in
any quantifiable residues in food commodities and the conservative
estimated EDWCs are very minor, the exposures from the registered and
proposed uses for mesotrione fall well below the conservative
assumptions made by EPA in this cumulative risk assessment.  The new
uses proposed in this petition therefore would not change the
conclusions made by EPA in the cumulative risk assessment conducted for
mesotrione.]>

<E. Safety Determination>

<	1. U.S. population. [The chronic dietary exposure analysis (food plus
water) showed that exposure from all established, pending and proposed
mesotrione crop uses would result in a MOE of 88,312 (3.4% of the
chronic RfD) for the general U.S. population.]>

<	2. Infants and children. [The chronic dietary exposure analysis (food
plus water) showed that exposure from all established and proposed
mesotrione tolerances would result in a MOE of 30,653 (9.8% of the
chronic RfD) for infants less than one year old (the most sensitive
population subgroup).]>

<F. International Tolerances>

<	[There are currently no Codex maximum residue levels established for
mesotrione]>