Document ID: EPA-HQ-OPP-2006-0993-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-12-03T05:00Z

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

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

 

<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:>

<[Dow AgroSciences LLC]>

<[Insert petition number]>

<	EPA has received a pesticide petition ([insert petition number]) from
[Dow AgroSciences LLC], [9330 Zionsville Road, Indianapolis, IN  46268]
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>

<	[florasulam] in or on the raw agricultural commodity [turfgrass] at
[insert tolerance] 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  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 nature of the residue in plants and animals
is adequately understood for the purpose of this filing.  Based on the
findings from these studies, the residue of concern in plants and animal
commodities is the parent, florasulam.]>

<	2. Analytical method. [Adequate enforcement method for the combined
residues of florasulam is available to enforce the tolerance expression
in or on food. The analytical method uses capillary gas chromatography
and mass selective detection (GC-MSD).  The limits of quantitation (LOQ)
of the method is 0.01 ug/g for grain and 0.05 ug/g for forage, hay and
straw.  A suitable GC/MSD analytical method is available for measuring
florasulam in small grain commodities for enforcing the above
tolerances.]>

<	3. Magnitude of residues. [Geographically representative field trials
on wheat, barley, oat, rye using a soluble concentrate formulation of
florasulam were conducted according to proposed use patterns using
parameters that would likely result in the highest residues.  Tolerances
are established for residues of florasulam in or on barley, grain at
0.01 ppm, barley, hay at 0.05 ppm, barley straw at 0.05 ppm, oat, grain
at 0.01 ppm, oat, forage at 0.05 ppm, oat, hay at 0.05 ppm, oat, straw
at 0.05 ppm, rye, grain at 0.01 ppm, rye, forage at 0.05 ppm, rye, straw
at 0.05 ppm, wheat, grain at 0.01 ppm, wheat, forage at 0.05 ppm, wheat,
hay at 0.05 ppm, wheat, straw at 0.05 ppm.  Tolerances were based on
maximum field residue data, which were below the LOQ.]>

<B. Toxicological Profile>

<1. Acute toxicity. [Florasulam has low acute toxicity.  The rat acute
oral LD50 was greater than 6000 mg/kg, the rabbit acute dermal LD50 was
greater than 2000 mg/kg, and the rat acute inhalation LC50 was greater
than the highest attainable aerosol concentration, 5.0 mg/L (5,000
mg/cubic meter).  Only very slight dermal irritation was seen in
rabbits, and mild, transient eye irritation was noted in rabbits. 
Florasulam was negative for skin sensitization in guinea pigs.  No acute
toxicity endpoint has been identified.]>

<2. Genotoxicty. [Florasulam was negative for genotoxicity when tested
in in vitro and in vivo systems.  Short term assays for genotoxicity
consisting of a bacterial reverse mutation assay (Ames test), an in
vitro assay for cytogenetic damage using the Chinese hamster ovary
cells, an in vitro chromosomal aberration assay using rat lymphocytes,
and an in vivo cytogenetic assay in the mouse bone marrow (micronucleus
test) have been conducted with florasulam.  These studies show a lack
of> genotoxicity.]

<	3. Reproductive and developmental toxicity. [Developmental studies in
rats and rabbits were> conducted with florasulam.  Studies with
florasulam showed a maternal NOEL of 250 mg/kg/day and fetal NOEL of 750
mg/kg/day in the rat, and NOELs of 500 mg/kg/day for both maternal and
fetal in the rabbit.  Florasulam was not teratogenic in either species
nor was there any potential to interfere with in utero development.  A
two-generation reproduction study was conducted with florasulam in rats.
 This study in Sprague-Dawley rats showed a parental NOEL for systemic
effects of 100 mg/kg/day.  The NOEL for reproductive effects was 500
mg/kg/day (highest dose tested).  The NOEL for neonatal effects was 100
mg/kg/day based on transient decreases in pup weights at 500 mg/kg/day.]

<	4. Subchronic toxicity. [Following subchronic exposure of florasulam,
(13-weeks), effects on the kidneys were seen in rats, mice and dogs at
high dose levels.  Hypertrophy of renal collecting duct epithelial cells
was the most sensitive morphologic change noted, and was observed in
dogs at 50 mg/kg/day, and rodents at 500 mg/kg/day.  In addition,
increased serum AP was seen in dogs at 50 mg/kg/day, and liver weights
were increased in dogs at 100 mg/kg/day.  With higher dose levels, other
effects such as decreases in body weight gains and changes in red cell
indices were noted.  The NOAELs following subchronic exposure were 5
mg/kg/day in dogs, and 100 mg/kg/day in rats and mice.]>

<	5. Chronic toxicity. [NOAELs found in the chronic dietary studies are
as follows: 5 mg/kg/day (dog), 10 mg/kg/day (male and female rat). 
There was no increase in tumor incidence in either rats or mice with
florasulam.  Based on the chronic study on dog, EPA has determined a
chronic reference dose (cRFD) of 0.05 mg/kg/day, using an uncertainty
factor of 100 (10 for intraspecies variation X 10 for interspecies
variation).  No additional FQPA factor is needed.]>

<	6. Animal metabolism. [Based on the ruminant and poultry nature of
residue (NOR) studies, the residue definition for livestock is
florasulam, the parent compound alone. NOR studies in ruminants and
poultry showed that florasulam was rapidly absorbed and excreted by the
test animals and demonstrated that the residues of florasulam in animal
feedstuffs would not be readily transferred into milk or eggs and edible
tissues of ruminants and poultry.  As such, residue levels in edible
tissues, milk and eggs are predicted to be below detectable levels. 
Based on the results of the magnitude of residue studies in wheat,
barley, oat and rye, and NOR studies in ruminants and poultry, livestock
feeding studies were not undertaken, and tolerances were not considered
necessary.  Dow AgroSciences has requested a waiver for these studies.]>

<	7. Metabolite toxicology. [A metabolism study with florasulam in wheat
revealed the presence of florasulam and only low levels of a glucose
conjugate of the 4-OH-florasulam.  Inasmuch as 4-OH-florasulam is only
detected in animal feed products (forage and hay) and is not present in
grain, the Residue of Concern (ROC) in plant and animal products is the
parent compound, florasulam.  No significant mammalian metabolites of
florasulam have been identified in the rat metabolism study.]>

<	8. Endocrine disruption. [Florasulam did not have any primary effects
on endocrine organs or tissues in mice, rats or dogs in any of the
studies conducted.  There were no indications of effects on fetal
development in either rats or rabbits, or on reproductive performance in
rats.  Based on the lack of any effects on the endocrine system,
florasulam is not considered an endocrine disrupter.]>

<C. Aggregate Exposure>

<Dietary exposure. >

<	i. Food. [Tolerances have been established for the residues of
florasulam in or on wheat, barley, oat, and rye raw agricultural
commodities (0.01 ppm for grain and 0.05 ppm for forage, hay, and
straw). These proposed tolerances are adequate to cover the highest
expected field residues from the labeled use of florasulam.

An acute dietary exposure is not required because no adverse effect
attributable to a single exposure of florasulam was observed in the
available toxicity studies.  Therefore, Dow AgroSciences did not
identify an acute dietary endpoint and no acute risk is expected.

In conducting the chronic dietary assessment, Dow AgroSciences used the
Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database (DEEM-FCID, Version 2.14) which incorporates food
consumption data as reported in the CSFII Survey 1994-1996 and 1998.  A
conservative analysis (Tier 1) was performed with the assumptions that
100% of crops with approved and proposed uses of florasulam would be
treated with the pesticide and that the residues would be present at the
tolerance levels, which represent the levels of quantitation in the
residue studies for florasulam.  Based on these conservative assumptions
and using a cRfD of 0.05 mg/kg/day, for the U.S. general population, the
Tier I chronic, dietary exposure was estimated to be 0.000019 mg/kg/day,
less than 0.1% of the cRfD.  The chronic Tier I dietary assessments for
the population sub-groups predicted to be potentially most exposed are
children (1-2 years).  Tier I risk assessments for this population
subgroup indicate a TMRC of 0.000047 mg/kg/day, which represents 0.1% of
the cRfD.  Adverse effects are not expected for exposures utilizing less
than 100% of the RfD, therefore, chronic dietary exposure and risk for
the general U.S. population and children are well within the acceptable
levels.]>

<	ii. Drinking water. [Since the Agency lacks sufficient monitoring data
to complete a comprehensive exposure and risk assessment for florasulam
in drinking water, drinking water concentration estimates are made on
simulation taking into account data on the physical characteristics of
florasulam.  

            Guidance from EPA has indicated that Tier 1 screening level
models, such as FIRST (FQPA Index Reservoir Screening Tool), and
SCI-GROW, maybe used to estimate upper-bound pesticide residues in
surface water and ground water when assessing potential exposure through
drinking water.  Florasulam is not expected to contribute to drinking
water exposure, based on conservative Tier 1 assessments.  Tier 1
estimated environmental concentrations (EEC) of florasulam (0.000057
ppm) have been calculated for surface water screen using FIRST the
screening level model for FQPA pesticide exposure assessments.  FIRST is
an extremely conservative estimate for predicting surface water
concentrations, and considers adsorption of the pesticide to soil or
sediment, incorporation of the pesticide at application, direct
deposition of spray drift into the water body, and degradation of the
pesticide in soil before runoff and within the water body.  The
assumptions used with FIRST included a Koc of 28.75 days (Average of 4
soils for reported Koc adsorption); a soil metabolic half-life of 9 days
(reported value for Naicam-Hoodoo soil DT50 at 20C); an aquatic
metabolic half-life of 18 days (In aquatic systems, florasulam degrades
with half-lives of 3-18 days in aerobic systems and half-lives of 2-13
days in anaerobic systems); and a photolysis half-life value of 80 days
(longest value, spring at latitude 40 deg). 

               Estimated environmental concentrations (EEC) of pesticide
in surface water were then inputted into DEEM model for estimation of
dietary exposure from water both direct and indirect sources.  The input
of water residues along with food into the DEEM model provides a
conservative estimate of the total exposure from food and water sources.
 The chronic dietary exposure, including water, represents ≤ 0.1 % of
the cRfD.  

Therefore, aggregate exposure to florasulam in drinking water would not
result in unacceptable levels of human health risk.]

>

<	2. Non-dietary exposure. [The proposed use on turf presents
opportunity for residential exposure or non-occupational exposure to
florasulam.  Residential assessments were conducted for florasulam use
on turf, in order to estimate potential exposure to adults (during and
post-application) and children (post application).  Conservative Tier I
exposure assessments for florasulam resulted in MOEs >48,000.  This is
significantly greater than the MOE target of >100.]>

<D. Cumulative Effects>

<	[Currently, no methodologies are available to resolve the complex
scientific issues concerning common mechanism of toxicity and cumulative
exposure and risk.  The U.S. EPA has begun a pilot process to study this
issue further through the examination of particular classes of
pesticides.  There is no reliable information to indicate that toxic
effects produced by florasulam would be cumulative with those of any
other pesticide chemical.  Thus, Dow AgroSciences believes it is
appropriate to consider only the potential risks of florasulam in this
exposure assessment.]>

<E. Safety Determination>

<	1. U.S. population. [Using the conservative exposure assumptions
described above, and based on the completeness and reliability of the
toxicity data, the aggregate exposure (food and water only) to
florasulam, as determined under the guidance of the FQPA, will utilize
no more than 0.1% of the RfD from the dietary exposure for children aged
1-6 years and 7-12 years, the largest exposed subgroups of the U.S.
population.  The calculated exposure was greatest from water as
estimated by FIRST surface water modeling.  Generally, and under the
FQPA, the U.S. EPA has no concern for exposures below 100% of the RfD
because the RfD represents the level at or below which daily dietary
exposure over a lifetime will not pose appreciable risks to human
health.  Therefore, there is a reasonable certainty that no harm will
result to the general U.S. population from aggregate exposure to
florasulam residues from proposed use.] >

<	2. Infants and children. [In assessing the potential for additional
sensitivity of infants and children to residues of florasulam, data from
developmental toxicity studies in rats and rabbits and a
multi-generation reproduction study in the rat are considered.  The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism resulting from pesticide exposure during
prenatal development.  Reproduction studies provide information relating
to effects from exposure of both parents to the pesticide on the
reproductive capability and potential systemic toxicity of mating
animals and on various parameters associated with the well being of
offspring.

FFDCA section 408 provides that the U.S. EPA may apply an additional
safety factor for infants and children in the case of threshold effects
to account for pre- and post-natal toxicity and the completeness of the
database.  Based on the current toxicological data requirements, the
database for florasulam relative to pre- and post-natal effects for
children is complete. 

It is concluded that there is no indication of increased sensitivity of
infants and children relative to adults and that an additional FQPA
safety factor is not required. 

Thus, based on the completeness and reliability of the toxicity data and
the conservative exposure assessment, it is concluded that there is a
reasonable certainty that no harm will result to infants and children
from chronic, short- and intermediate-term aggregate exposures to
florasulam residues from current and proposed uses.]>

<F. International Tolerances>

<	[There are no Codex maximum residue levels established for residues of
florasulam on any food or feed crop.]>

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