 

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

<EPA Registration Division contact: Mary Waller (703) 308-9354 >

 

<>

<Nichino America, Inc.>

<Pesticide Petition 0F6159>

<	EPA has received a pesticide petition (PP# 0F6159) from  Nichino
America, Inc., 4550 New Linden Hill Road Suite 501 Wilmington, DE 19808
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. 484
by establishing new or indirect new indirect or inadvertent residues for
the fungicide, flutolanil [N-(3-(1-methylethoxy) phenyl) -2-
(trifluoromethyl) benzamide] and its metabolite, M-4,
desisopropylflutolanil [N-(3-hydroxyphenyl)-2-(trifluromethyl)
benzamide], expressed as 2-trifluoromethyl benzoic acid and calculated
as flutolanil in or on the following raw agricultural commodities (RACs)
and feed commodities: soybean forage at 9.0 parts per million (ppm),
soybean hay at 2.0 parts per million (ppm), soybean seed 0.20 parts per
million (ppm); wheat bran at 0.30 parts per million (ppm), wheat forage
at 2.0 parts per million (ppm), wheat grain at 0.10 parts per million
(ppm), wheat hay at 1.0 parts per million (ppm), wheat straw at 0.30
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 metabolic profile of flutolanil is well
understood and has been elucidated in the three crops:  peanuts, rice,
and cucumber. The metabolic profile is similar in all crops.  The major
route of degradation is 4’-0-dealkylation to desisopropylflutolanil,
followed by conjugation.  Other metabolites may occur at very low levels
due hydroxylation and oxidation of the side chain, hydroxylation of the
aniline ring, and methylation of the hydroxyl groups.  These minor
metabolites were also subject to conjugation.  The residues of concern
are the parent, flutolanil, and M-4.

>

<2. Analytical method. A previously submitted analytical method
designated AU-95R-04 (MRID 45104001), a gas chromatography, mass
spectrometry detection method has been independently validated and is
adequate for enforcement purposes for flutolanil residue detection in
soybean and wheat raw agricultural commodities.  A multi-residue method
for flutolanil has been previously submitted.

>

<	3. Magnitude of residues. Ten rotational crop field residue trials
were conducted in 1994 in Texas, Georgia, Alabama, Florida, Virginia,
Oklahoma and North Carolina.  Flutolanil formulated as Moncut 70WP was
applied to bare soil at a total seasonal rate for peanuts (the highest
labeled rate for use on food crops) of 2.0 lb. a.i./acre, followed by
planting of the typical rotational crops wheat and soybeans at 30 days
after application.  The rotational crops were grown to maturity and
samples of relevant commodities collected at the appropriate
developmental stage.  These applications of flutolanil resulted in
residues that are within the proposed crop tolerances.  Processing
studies were conducted for soybeans and wheat using samples of wheat
grain and soybean seed collected from one of the trial sites above,
using normal agricultural practice.  Residues of concern were within the
proposed crop tolerances.>

<B. Toxicological Profile

<We have conducted an extensive battery of toxicology studies with
flutolanil.  EPA has evaluated the available toxicity data and
considered its validity, completeness, and reliability as well as the
relationship of the results of the studies to human risk.  The nature of
the toxic effects caused by flutolanil is discussed in Unit III.A. of
the Final Rule on Flutolanil Pesticide Tolerance published in the
Federal Register on February 20, 2001 (66 FR 10817) (FRL-6761-1).>   

1. Acute toxicity.  [N/A-Remove]

<	2. Genotoxicty. [N/A-Remove]>

<	3. Reproductive and developmental toxicity. [N/A-Remove]>

<	4. Subchronic toxicity. [N/A Remove]>

<	5. Chronic toxicity. [N/A- Remove]>

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>

<We have conducted an extensive battery of toxicology studies with
flutolanil.  EPA has evaluated the available toxicity data and
considered its validity, completeness, and reliability as well as the
relationship of the results of the studies to human risk.  The nature of
the toxic effects caused by flutolanil is discussed in Unit III.A. of
the Final Rule on Flutolanil Pesticide Tolerance published in the
Federal Register on February 20, 2001 (66 FR 10817) (FRL-6761-1).>   

<6. Animal metabolism.	  The metabolism of flutolanil has been
extensively studied in various species of mammals. Studies in rats,
ruminants and poultry suggest that flutolanil is not well absorbed
following oral administration.  Once absorbed, however, it is rapidly
metabolized, primarily to desisopropylflutolanil and its conjugates, and
rapidly excreted via urine and feces.  

 

7. Metabolite toxicology. [N/A-Remove]

>

<8. Endocrine disruption. No special studies have been conducted to
investigate the potential of flutolanil to induce estrogenic or other
endocrine effects. No evidence of such effects has been observed in the
subchronic, chronic or reproductive studies previously discussed.  Thus,
the potential for flutolanil to cause endocrine effects is considered to
be not relevant.

 

9.Toxicity  endpoint selection.   Flutolanil is of low acute toxicity
via all

routes of administration and did not induce significant maternal or
developmental toxicity in either rats or rabbits, even at the limit dose
of 1000 mg/kg/day.  Furthermore, no evidence of toxicity was noted
following repeated dosing at 1000 mg/kg/day in a 21-day dermal toxicity
study.  Thus acute dietary, occupational and residential risk
assessments are not considered necessary.  The Agency has concluded that
the cPAD (chronic population adjusted dose) for flutolanil should be
0.87 mg/kg/day, based on the NOAEL of 87 mg/kg/day from the rat 2-year
chronic/oncogenicity study and a 100-fold uncertainty factor.  The
Agency has also determined that the cancer classification for flutolanil
should be “Group E – Evidence of Non-Carcinogenicity for Humans.”

	>

<C. Aggregate Exposure>

<	1. Dietary exposure. Chronic dietary risk analyses were conducted to
estimate the potential flutolanil residues in/on the following crops: 
rice, peanuts, potato, wheat, and soybeans.    Meat, milk, poultry, and
egg residues were included.  Analyses were performed using the Lifeline
TM Version 3.0 which incorporates data as reported by respondents in the
USDA 1994-1996 and 1998 Nationwide Continuing Surveys of Food Intake by
Individuals (CSFII) and accumulated exposure to the chemical for each
commodity.  Chronic exposure estimates to food were based on tolerance
levels and assumed 100% crop treatment, yielding the worst case chronic
dietary exposure estimates.>

<	i. Food.  An acute dietary assessment is not required as there is no
acute toxicity associated with flutolanil exposure.  The chronic dietary
exposure estimated food exposure to be 0.0027 mg/kg/day for the U.S.
population, based on the Lifeline TM Version 3.0.  The number of
individuals simulated was 3000.  The highest exposure group was
children, age 1-2, with exposures of 0.0069 mg/kg/day. These are
considered conservative values as all exposure was based on tolerance
levels and assumed all crops were treated with flutolanil. 

>

<	ii. Drinking water. The potential for flutolanil to leach into
groundwater has been assessed in two terrestrial field dissipation
studies, a long-term terrestrial field dissipation study, and an aquatic
field dissipation study.  Under field conditions, the half-life of
flutolanil varied from 101 to 123 days in the long-term study, which was
consistent with the other field studies, and was approximately 180 days
in the aquatic environment.  Flutolanil strongly adsorbs to soil
following application and did not exhibit mobility under either
terrestrial or aquatic conditions.  Based on these observations, the
Agency concluded that the most important means of dissipation in surface
water and also in ground water will most likely be dilution.  Due to the
lack sufficient monitoring exposure data to complete a dietary risk
assessment for flutolanil in drinking water, models that best accounted
for the application of flutolanil to rice paddies were used to simulate
exposure to flutolanil in drinking water.  Based on the First
Approximation Rice Model and Screening Concentrations in Ground Water
(SCI-GROW) model, the estimated environmental concentrations (EECs) of
flutolanil for acute exposures are 3.8 parts per billion (ppb) for
surface water and 0.34 ppb for ground water.  The EECs for chronic
exposures are 3.8 ppb for surface water and 0.34 ppb for ground water. 
>

<	2. Non-dietary exposure. The term “residential exposure” is used
in this document to refer to non-occupational, non-dietary exposure
(e.g. for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pests).  Flutolanil is
currently registered for use on the following residential non-dietary
sites:  Turf grass.  The risk assessment was conducted using the
following residential exposure assumptions:  There are non-occupational
uses associated with flutolanil.  Non-occupational handlers may mix,
load and apply flutolanil products on turf grass.  These exposures were
assessed for inhalation risk.  Post-application inhalation exposure
following turfgrass treatment is considered negligible and was not
assessed.  Because certain flutolanil products are registered for use on
residential lawns, postapplication exposure to infants may result in
their hand-to-mouth activities on treated turf.  The MOE’s for these
scenarios ranged from 6.7 x 102 to 1.4 x 103.  These MOEs are greater
than the LOC of 100 and lie above the Agency’s level of concern.  

>

<D. Cumulative Effects>

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether
to establish, modify, or revoke a tolerance, the Agency consider
``available information'' concerning the cumulative effects of a
particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.'' Unlike other pesticides for which EPA
has followed a cumulative risk approach based on a common mechanism of
toxicity, EPA has not made a common mechanism of toxicity finding as to
flutolanil and any other substances and flutolanil does not appear to
produce a toxic metabolite produced by other substances. For the
purposes of this tolerance action, therefore, EPA has not assumed that
flutolanil has a common mechanism of toxicity with other substances. For
information regarding EPA's efforts to determine which chemicals have a
common mechanism of toxicity and to evaluate the cumulative effects of
such chemicals, see the policy statements released by EPA's OPP
concerning common mechanism determinations and procedures for cumulating
effects from substances found to have a common mechanism on EPA's
website at     

    HYPERLINK "http://www.epa.gov/pesticides/cumulative/"    ADVANCE \d
4 http://www.epa.gov/ pesticides/cumulative/ 

Flutolanil has demonstrated only minimal toxicity in animal studies. 
The mechanism of this toxicity is not known.  Furthermore, there are no
available data to indicate that flutolanil has a common mechanism of
toxicity with other substances.  Thus, only the potential risks from
flutolanil are being considered in this document.

<E. Safety Determination>

<	1. U.S. population. The (cPAD) was determined to be 0.87 mg/kg/day
based on an oral NOAEL of 87 mg/kg/day in the rat chronic oncogenicity
study and an uncertainty factor of 100X for inter- and intra-species
variations and an FQPA children’s safety factor of 1X.  Based on the
existing tolerances in rice, peanuts and secondary commodities plus the
proposed tolerances in soybean, and wheat commodities, the chronic food
exposure is estimated to be 0.0027 mg/kg/day for the U.S. population in
general.  There is generally no concern for exposures below 100% of the
cPAD since the cPAD represents the exposure level at or below which
daily exposure over a lifetime will not pose any appreciable risks to
human health.  Therefore, there is a reasonable certainty that no harm
will result to the U.S. population in general from aggregate exposure to
flutolanil.

 >

<	2. Infants and children. Data from reproductive and developmental
toxicity studies are generally used to assess the potential for
increased sensitivity of infants and children.  No evidence of
developmental toxicity was evident.  Therefore, there is no reason to
believe there is an increased sensitivity in infants and children. The
FQPA safety factor was determined to be 1x. >

<F. International Tolerances>

		Canada, Codex, and Mexico do not have maximum residue limits (MRLs)
for residues of flutolanil or desisopropylflutolanil residues on the
proposed crops.  Therefore, harmonization is not an issue.  

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