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Tolylfluanid (Bayer). September 25, 2002. Classified as Likely to be carcinogenic to humans. EPA approves Pesticide Tolerances in or on imported apple, grape, hop, tomato. Federal Register. Final Rule.



http://www.epa.gov/fedrgstr/EPA-PEST/2002/September/Day-25/p24094.htm

[Federal Register: September 25, 2002 (Volume 67, Number 186)]
[Rules and Regulations]
[Page 60130-60142]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25se02-7]

=======================================================================
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2002-0216; FRL-7200-5]
 
Tolylfluanid; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation establishes an import tolerance for residues 
of tolylfluanid in or on imported apple, grape, hop, and tomato. Bayer 
Corporation requested this tolerance under the Federal Food, Drug, and 
Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act 
(FQPA) of 1996.

DATES: This regulation is effective September 25, 2002. Objections and 
requests for hearings, identified by docket ID number OPP-2002-0216, 
must be received on or before November 25, 2002.

ADDRESSES: Written objections and hearing requests may be submitted by 
mail, in person, or by courier. Please follow the detailed instructions 
for each method as provided in Unit VI. of the SUPPLEMENTARY 
INFORMATION. To ensure proper receipt by EPA, your objections and 
hearing requests must identify docket ID number OPP-2002-0216 in the 
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Mary Waller, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 308-9354; e-mail address: 
waller.mary@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer, or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                         Examples of
           Categories                NAICS codes         potentially
                                                      affected entities
------------------------------------------------------------------------
Industry                         111                 Crop production
                                 112...............  Animal production
                                 311...............  Food manufacturing
                                 32532.............  Pesticide
                                                      manufacturing
------------------------------------------------------------------------


    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet home page at http://www.epa.gov/. 
To access this document, on the home page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/. A frequently updated electronic 
version of 40 CFR part 180 is available at http://www.access.gpo.gov/
nara/cfr/cfrhtml_00/Title_40/40cfr180_00.html, Exit Disclaimer a beta site currently 
under development. To access the OPPTS Harmonized Guidelines referenced 
in this document, go directly to the guidelines at http://www.epa.gov/
opptsfrs/home/guidelin.htm.
    2. In person. The Agency has established an official record for 
this action under docket ID number OPP-2002-0216. The official record 
consists of the documents specifically referenced in this action, and 
other information related to this action, including any information 
claimed as Confidential Business Information (CBI). This official 
record includes the documents that are physically located in the 
docket, as well as the documents that are referenced in those 
documents. The public version of the official record does not include 
any information claimed as CBI. The public version of the official 
record, which includes printed, paper versions of any electronic 
comments submitted during an applicable comment period is available for 
inspection in the Public Information and Records Integrity Branch 
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy., 
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

II. Background and Statutory Findings

    In the Federal Register of August 11, 1997 (62 FR 42980) (FRL-5736-
1), EPA issued a notice pursuant to section 408 of the FFDCA, 21 U.S.C. 
346a, as amended by FQPA (Public Law 104-170), announcing the filing of 
a pesticide petition (PP 7E4825) by Bayer Corporation, 8400 Hawthorn 
Rd., Kansas City, MO 64120. This notice included a summary of the 
petition prepared by Bayer Corporation, the registrant. There were no 
comments received in response to the notice of filing.
    The petition requested that 40 CFR 180.584 be amended by 
establishing an import tolerance for residues of the fungicide 
tolylfluanid, (1,1-dichloro-N-[(dimethylamino)-sulfonyl]-1-fluoro-N-(4-
methylphenyl) methanesulfenamide), in or on apple at 5.0 parts per 
million (ppm), grape at 5.0 ppm, hop at 30 ppm, and tomato at 1.0 ppm.
    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of the FFDCA defines ``safe'' to mean that ``there is 
a reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including

[[Page 60131]]

all anticipated dietary exposures and all other exposures for which 
there is reliable information.'' This includes exposure through 
drinking water and in residential settings, but does not include 
occupational exposure. Section 408(b)(2)(C) of the FFDCA requires EPA 
to give special consideration to exposure of infants and children to 
the pesticide chemical residue in establishing a tolerance and to 
``ensure that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to the pesticide 
chemical residue....''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 of the FFDCA and a complete 
description of the risk assessment process, see the final rule on 
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-
5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed 
the available scientific data and other relevant information in support 
of this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2) of the FFDCA, for a tolerance for residues of tolylfluanid in 
or on apple at 5.0 ppm, grape at 11 ppm, hop at 30 ppm, and tomato at 
2.0 ppm.
    EPA's assessment of exposures and risks associated with 
establishing the tolerance follows.

A. Toxicological Profile

    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. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by tolylfluanid are 
discussed in Table 1 of this unit as well as the no-observed-adverse-
effect-level (NOAEL) and the lowest-observed-adverse-effect-level 
(LOAEL) from the toxicity studies reviewed.

            Table 1.--Subchronic, Chronic, and Other Toxicity
------------------------------------------------------------------------
         Guideline No.              Study Type            Results
------------------------------------------------------------------------
870.3100                        90-Day oral        NOAEL = 20.1
                                 toxicity rodents   milligram/kilogram/
                                 (rat)              day (mg/kg/day) male
                                                    (M)
                                                   LOAEL = 108 mg/kg/
                                                    day, based on
                                                    changes in clinical
                                                    blood chemistry
                                                    associated with the
                                                    liver and thyroid
                                                    (M)
                                                   NOAEL = 131 mg/kg/day
                                                    female (F)
                                                   LOAEL = 736.1 mg/kg/
                                                    day, based on
                                                    changes in clinical
                                                    blood chemistry
                                                    associated with the
                                                    liver and thyroid
                                                    and decreased body
                                                    weights (F)
                                                   Acceptable/guideline
-------------------------------
870.3150                        90-Day oral        NOAEL = 23.1/25 mg/kg/
                                 toxicity in        day (F/M)
                                 nonrodents (dog)  LOAEL = 67.2/69.4 (F/
                                                    M) mg/kg/day, based
                                                    on decreased body
                                                    weight gains and
                                                    changes in liver
                                                    structure and
                                                    function in both
                                                    sexes
                                                   Unacceptable/
                                                    guideline
-------------------------------
870.3700                        Prenatal           Maternal NOAEL = not
                                 developmental in   determined
                                 rodents (rat)     LOAEL = 100 mg/kg/
                                                    day, based on
                                                    decreased body
                                                    weight gains and
                                                    food consumption.
                                                   Developmental NOAEL =
                                                    1,000 mg/kg/day
                                                    highest dose tested
                                                    (HDT)
                                                   LOAEL > 1,000 mg/kg/
                                                    day
                                                   Acceptable/guideline
-------------------------------
870.3700                        Prenatal           Maternal NOAEL = 100
                                 developmental in   mg/kg/day
                                 rodents (rat)     LOAEL = 300 mg/kg/
                                                    day, based on dose-
                                                    related decreased
                                                    body weight gains
                                                    during the dosing
                                                    interval.
                                                   Developmental NOAEL >
                                                    1,000 mg/kg/day
                                                    (HDT)
                                                   LOAEL = not
                                                    identified
                                                   Acceptable/guideline
-------------------------------
870.3700                        Prenatal           Maternal NOAEL = 25
                                 developmental in   mg/kg/day
                                 nonrodents        LOAEL = 70 mg/kg/day,
                                 (rabbit)           based on evidence of
                                                    hepatotoxicity
                                                    (increased glutamate
                                                    dehydrogenase (GLDH)
                                                    and triglyceride
                                                    levels and gross and
                                                    microscopic liver
                                                    pathology) and
                                                    decreased food
                                                    consumption and
                                                    equivocal decreases
                                                    in body weight gain.
                                                   Developmental NOAEL =
                                                    25 mg/kg/day
                                                   LOAEL= 70 mg/kg/day,
                                                    based on increased
                                                    malformations
                                                    (arthrogryposis of
                                                    front extremities
                                                    and small orbital
                                                    cavity/folded
                                                    retina) and
                                                    variations (floating
                                                    rib and accelerated
                                                    ossification).
                                                   Acceptable/guideline
-------------------------------

[[Page 60132]]

870.3800                        2-Generation       Parental/systemic
                                 reproduction and   NOAEL = 7.9-10.5 mg/
                                 fertility          kg/day
                                 effects (rat)     LOAEL = 57.5-78.0 mg/
                                                    kg/day, based on
                                                    decreased body
                                                    weights, body weight
                                                    gains, and liver
                                                    weights in the P
                                                    females
                                                   Reproductive NOAEL =
                                                    7.9-10.5 mg/kg/day
                                                   LOAEL = 57.5-78.0 mg/
                                                    kg/day, based on
                                                    reduced litter size
                                                   Offspring NOAEL = 7.9-
                                                    10.5 mg/kg/day
                                                   LOAEL = 57.5-78.0 mg/
                                                    kg/day, based on
                                                    decreased pup
                                                    weights, increased
                                                    pup deaths and
                                                    related pup
                                                    viability indices
                                                   Acceptable/guideline
-------------------------------
870.3800                        2-Generation       Parental/systemic
                                 reproduction and   NOAEL not
                                 fertility          established
                                 effects (rat)     LOAEL = 15.9-21.5 mg/
                                                    kg/day, based on
                                                    hardened crania of P
                                                    generation animals
                                                   Reproductive NOAEL
                                                    not established
                                                   LOAEL = 15.9-21.5 mg/
                                                    kg/day, based on
                                                    increased clinical
                                                    signs of toxicity
                                                   Offspring NOAEL >
                                                    15.9-21.5 mg/kg/day
                                                    (HDT)
                                                   LOAEL not established
                                                   Unacceptable/
                                                    guideline
-------------------------------
870.3800                        2-Generation       Parental/Systemic
                                 reproduction and   NOAEL = 20.1-26.3 mg/
                                 fertility          kg/day
                                 effects (rat)     LOAEL = 83.4-109.5 mg/
                                                    kg/day, based on
                                                    decreased body
                                                    weights and body
                                                    weight gains
                                                   Reproductive NOAEL =
                                                    83.4 - 109.5 mg/kg/
                                                    day
                                                   LOAEL = 335.6-492.4
                                                    mg/kg/day, based on
                                                    decreased mean
                                                    litter size
                                                   Offspring NOAEL =
                                                    20.1-26.3 mg/kg/day
                                                   LOAEL = 83.4-109.5 mg/
                                                    kg/day, based on
                                                    decreased pup
                                                    weights
                                                   Acceptable/guideline
-------------------------------
870.3800                        2-Generation       Parental/Systemic
                                 reproduction and   NOAEL = 75 mg/kg/day
                                 fertility         LOAEL = 375 mg/kg/
                                 effects (rat)      day, based on
                                                    decreased body
                                                    weights and body
                                                    weight gains for
                                                    both generations
                                                   Reproductive NOAEL >
                                                    375 mg/kg/day (HDT)
                                                   LOAEL not established
                                                   Offspring NOAEL = 75
                                                    mg/kg/day
                                                   LOAEL = 375 mg/kg/
                                                    day, based on
                                                    decreased survival
                                                    and reduced body
                                                    weights during
                                                    lactation
                                                   Acceptable/guideline
-------------------------------
870.4300                        Combined chronic   NOAEL = 18.1/21.1 mg/
                                 toxicity/          kg/day (M/F)
                                 carcinogenicity   LOAEL = 90.1/105.2 mg/
                                 rodents (rat)      kg/day (M/F), based
                                                    on skeletal changes
                                                   Evidence of thyroid
                                                    follicular cell
                                                    adenomas and/or
                                                    carcinomas in high-
                                                    dose males and
                                                    females
                                                   Acceptable/guideline
-------------------------------
870.4300                        Combined chronic   NOAEL = 20/20 mg/kg/
                                 toxicity/          day (M/F)
                                 carcinogenicity   LOAEL = 80/110 mg/kg/
                                 rodents (rat)      day (M/F), based on
                                                    bone hyperostosis in
                                                    males and females
                                                   Evidence of thyroid
                                                    follicular cell
                                                    adenomas and/or
                                                    carcinomas in high-
                                                    dose males and
                                                    females
                                                   Acceptable/guideline
-------------------------------
870.4200                        Carcinogenicity    NOAEL = 76.3/123.9 mg/
                                 rodents (mouse)    kg/day (M/F)
                                                   LOAEL = 375.8/610.8
                                                    mg/kg/day (M/F),
                                                    based on skeletal,
                                                    liver, and kidney
                                                    changes
                                                   No evidence of
                                                    carcinogenicity
                                                   Acceptable/guideline
-------------------------------
870.4100                        Chronic toxicity   NOAEL = 12.5 mg/kg/
                                 (dog)              day
                                                   LOAEL = 62.5 mg/kg/
                                                    day (M), based on
                                                    decreased body
                                                    weight gains
                                                   Acceptable/guideline
-------------------------------
870.5100                        Bacterial gene     Tolylfluanid was
Technical.....................   mutation assay     cytotoxic to all
                                                    strains at = 8 [mu]g/plate +/
                                                    - S9 and
                                                    precipitated from
                                                    solutions in all
                                                    strains at 5,000
                                                    [mu]g/plate +/- S9.
                                                    There were no
                                                    reproducible, dose-
                                                    related differences
                                                    in the number of
                                                    revertant colonies
                                                    in any strain or
                                                    dose over the
                                                    background. Positive
                                                    controls induced
                                                    appropriate
                                                    response.
                                                   Acceptable/guideline
-------------------------------

[[Page 60133]]

870.5100                        Bacterial gene     There was no evidence
Metabolite--WAK 5815..........   mutation assay     of toxicity or
                                                    significant increase
                                                    in mutant colonies
                                                    over background in
                                                    any of strains
                                                    tested in either the
                                                    initial or repeat
                                                    mutagenicity assays.
                                                    Positive controls
                                                    induced appropriate
                                                    response.
                                                   Acceptable/guideline
-------------------------------
870.5100                        Bacterial gene     There were no
Metabolite--WAK 6550..........   mutation assay     reproducible, dose-
                                                    related differences
                                                    in the number of
                                                    revertant colonies
                                                    in any strain or
                                                    dose over the
                                                    background. Positive
                                                    controls induced
                                                    appropriate
                                                    response.
                                                   Acceptable/guideline
-------------------------------
870.5100                        Bacterial gene     There was no evidence
Metabolite--WAK 6676..........   mutation assay     of toxicity or
                                                    significant increase
                                                    in the mutant
                                                    colonies over
                                                    background in any
                                                    strain tested.
                                                    Positive controls
                                                    induced the
                                                    appropriate
                                                    responses in the
                                                    corresponding
                                                    strains and in the
                                                    solvent controls
                                                    were consistent with
                                                    the expected ranges
                                                    of revertant
                                                    colonies for the
                                                    strains used.
                                                   Acceptable/guideline
-------------------------------
870.5100                        Bacterial gene     Metabolite was
Metabolite--WAK 6698..........   mutation assay     cytotoxic at doses
                                                    =158
                                                    [mu]g/plate in the
                                                    initial assay and
                                                    1,581 [mu]g/plate in
                                                    the repeat assay.
                                                    There was no
                                                    evidence of a
                                                    significant increase
                                                    in mutant colonies
                                                    over background in
                                                    any strains tested
                                                    in the initial or
                                                    repeat mutagenicity
                                                    assays. Positive
                                                    controls induced
                                                    appropriate
                                                    response.
                                                   Acceptable/guideline
-------------------------------
870.5100                        Bacterial gene     Tolylfluanid was
Technical.....................   mutation assay     tested to cytotoxic
                                                    concentrations.
                                                    Tolylfluanid showed
                                                    no evidence of
                                                    inducing methionine
                                                    revertants in
                                                    Saccharomyces
                                                    cerevisiae strains +/
                                                    - S9. However, one
                                                    of the tests
                                                    (S211[
                                                    ]) was inadequate
                                                    or inconsistent.
                                                    Further, in the S9
                                                    activated assays,
                                                    the positive
                                                    controls did not
                                                    elicit an adequate
                                                    response, negating
                                                    the test with S9 for
                                                    both strains.
                                                   Unacceptable/
                                                    guideline
-------------------------------
870.5300                        In vitro           The compound was
Metabolite-- WAK 6698.........   mammalian cell     tested up to
                                 gene mutation      cytotoxic
                                 assay              concentrations in
                                                    two independent
                                                    assays (+/- S9). In
                                                    the initial test
                                                    concentrations
                                                    ranged from 50 to
                                                    1,000 [mu]g/mL +/-
                                                    S9. In the repeat
                                                    assay concentrations
                                                    ranged from 100 to
                                                    800 [mu]g/mL -S9 and
                                                    200 to 700 [mu]g/mL
                                                    + S9. Tolylfluanid
                                                    metabolite was
                                                    negative for
                                                    inducing forward
                                                    mutations at the TK
                                                    locus in mouse
                                                    L5178Y +/- S9.
                                                    Positive control
                                                    methyl
                                                    methanosulfonate and
                                                    3-methylcholanthrene
                                                    induced appropriate
                                                    responses.
                                                   Acceptable/guideline
-------------------------------
870.5300                        In vitro           These dose levels
Technical.....................   mammalian cell     were selected based
                                 gene mutation      on a preliminary
                                 assay              cytotoxicity study
                                                    conducted at 0.5 to
                                                    250 [mu]g/mL +/- S9.
                                                    Tolylfluanid has
                                                    been judged to be
                                                    non-mutagenic +/-
                                                    S9. Positive
                                                    controls induced
                                                    appropriate response
                                                    +/- S9.
                                                   Acceptable/guideline
-------------------------------
870.5300                        In vitro           Cultures were tested
Technical.....................   mammalian cell     to cytotoxic
                                 gene mutation      concentrations.
                                 assay              Tolylfluanid has
                                                    been judged to be
                                                    non-mutagenic +/-
                                                    S9. Positive
                                                    controls induced
                                                    appropriate response
                                                    +/- S9.
                                                   Acceptable/guideline
-------------------------------
870.5300                        In vitro           The compound was
Technical.....................   mammalian cell     tested up to
                                 gene mutation      cytotoxic
                                 assay              concentrations (+/-
                                                    S9). Tolylfluanid
                                                    was positive for
                                                    inducing forward
                                                    mutations at the TK
                                                    locus in mouse
                                                    L5178Y +/- S9.
                                                    Positive control
                                                    ethylmethane
                                                    sulfonate and 3-
                                                    methylcholanthrene
                                                    induced appropriate
                                                    responses. Colony
                                                    sizing was not
                                                    performed.
                                                   Acceptable/guideline
-------------------------------
Non-Guideline                   Mouse spot test    F1 pups from female
Technical.....................                      C57B1/6J mice
                                                    exposed by oral
                                                    gavage to
                                                    tolylfluanid (98.4%)
                                                    at concentration of
                                                    0; 1,750; 3,500; and
                                                    7,000 mg/kg did not
                                                    show difference in
                                                    incidence in
                                                    relative spots
                                                    between the treated
                                                    and controls.
                                                    Systemic toxicity
                                                    was observed in dams
                                                    at all doses.
                                                    Mortality was
                                                    observed at all
                                                    doses; however
                                                    treatment did not
                                                    affect reproductive
                                                    parameters nor there
                                                    was difference in
                                                    litter size.
                                                    Positive controls
                                                    showed a clear
                                                    increase in spots in
                                                    the progeny.
                                                   Acceptable/non-
                                                    guideline
-------------------------------

[[Page 60134]]

870.5375                        In vitro           The test was
Technical.....................   mammalian cell     conducted up to
                                 gene mutation      cytotoxic levels +/-
                                 assay              S9. Tolylfluanid was
                                                    weakly clastogenic
                                                    in Chinese hamster
                                                    V79 cells in the
                                                    presence of S9
                                                    activation. Positive
                                                    control mitomycin
                                                    and cyclophosphamide
                                                    induced appropriate
                                                    responses.
                                                   Acceptable/guideline
-------------------------------
870.5375                        In vitro           Cytotoxicity was
Technical.....................   mammalian cell     observed at
                                 gene mutation      concentrations 1 to
                                 assay              10 [mu]g/milliliter
                                                    (mL) -S9 and 5 to 10
                                                    [mu]g/mL +S9. Over
                                                    the ranges tested
                                                    clastogenic effects
                                                    included increased
                                                    incidences of
                                                    metaphases with
                                                    aberrations
                                                    including gaps,
                                                    metaphases excluding
                                                    gaps, metaphases
                                                    with exchanges, and
                                                    metaphases with
                                                    polyploidy were
                                                    observed.
                                                    Tolyfluanid is
                                                    clastogenic both in
                                                    the presence and in
                                                    the absence of S9
                                                    activation. Positive
                                                    control mitomycin
                                                    and endoxan induced
                                                    appropriate
                                                    responses.
                                                   Acceptable/guideline
-------------------------------
870.5380                        In vitro            No mortality or
Technical.....................   mammalian          clinical signs were
                                 spermatogonia      observed at either
                                 chromosomal        dose. No
                                 aberration test    statistically
                                                    significant
                                                    increases in the
                                                    frequency of
                                                    chromosomal
                                                    aberrations in
                                                    spermatogonia were
                                                    observed.
                                                   Unacceptable/
                                                    guideline
-------------------------------
870.5380                        In vitro           Clinical signs of
Technical.....................   mammalian          toxicity and
                                 spermatogonia      cytotoxicity to
                                 chromosomal        target cells were
                                 aberration test    seen at 5,000 mg/kg/
                                                    day. Tolylfluanid
                                                    did not induce
                                                    chromosomal
                                                    aberrations in
                                                    spermatogonia at any
                                                    dose. Positive
                                                    controls did not
                                                    produce strong
                                                    positive results.
                                                    Therefore,
                                                    sensitivity of assay
                                                    is questionable and
                                                    the findings of the
                                                    study are equivocal.
                                                   Unacceptable/
                                                    guideline
-------------------------------
870.5385                        Mammalian bone     3/10 animals died but
Technical.....................   marrow             exhibited no
                                 chromosomal        clinical signs. No
                                 aberration test    cytotoxicity was
                                                    observed at the dose
                                                    tested. Positive
                                                    controls induced
                                                    appropriate
                                                    response. Inadequate
                                                    sampling time and no
                                                    indication of test
                                                    material present at
                                                    target site;
                                                    therefore, data not
                                                    valid for regulatory
                                                    purposes.
                                                   Unacceptable/
                                                    guideline
-------------------------------
870.5385                        Mammalian bone     3/10 of 10 animals
Technical.....................   marrow             died but no clinical
                                 chromosomal        signs of toxicity
                                 aberration test    were observed at the
                                                    dose tested. Test
                                                    results were
                                                    erratic. Positive
                                                    controls induced
                                                    appropriate
                                                    response. Inadequate
                                                    study since test
                                                    samples were not
                                                    analyzed and doses
                                                    were not high enough
                                                    to produce toxicity.
                                                   Unacceptable/
                                                    guideline
-------------------------------
870.5395                        Mammalian          No clinical signs of
Technical.....................   erythrocyte        toxicity was
                                 micronucleus       observed and was not
                                 assay              toxic to the target
                                                    tissue. Treatment
                                                    with tolylfluanid
                                                    did not induce
                                                    micronucleated
                                                    polychromatic
                                                    erythrocytes.
                                                    Inadequate methods
                                                    and methodology.
                                                   Unacceptable/
                                                    guideline
-------------------------------
870.5450                        Dominant lethal    Did not induce
Technical.....................   assay (mice)       variations in any
                                                    dominant lethal
                                                    parameters nor any
                                                    reduced fertility.
                                                    Inadequate study.
                                                   No positive control
                                                    data
                                                   Unacceptable but
                                                    upgradable with
                                                    receipt of positive
                                                    control data
-------------------------------
870.5915                        In vivo sister     Mortality at 500 mg/
Technical.....................   chromatid          kg and above.
                                 exchange assay     Tolylfluanid did not
                                                    induce sister
                                                    chromatid exchange
                                                    at any dose level.
                                                    Positive control
                                                    cyclophosphamide
                                                    responded
                                                    appropriately.
                                                   Acceptable/guideline
-------------------------------
870.5500                        Other genotoxic    Tolylfluanid did not
Technical.....................   effects            induce UDS up to
                                 unscheduled DNA    15.0 [mu]g/mL. The
                                 synthesis (UDS)    17.5 and 20 [mu]g/mL
                                 in mammalian       doses were highly
                                 cells              toxic. The positive
                                                    control 2-
                                                    acetylaminofluorene
                                                    responded
                                                    appropriately.
                                                   Acceptable/guideline
-------------------------------
870.6200                        Acute              NOAEL = 50 mg/kg in
                                 neurotoxicity      females
                                 screening         LOAEL = 150 mg/kg/day
                                 battery (rat)      based on functional
                                                    observation battery
                                                    (FOB) effects and
                                                    decreased motor and
                                                    locomotor activity
                                                    in females
                                                   NOAEL = 2,000 mg/kg/
                                                    day (M)--limit dose
                                                   LOAEL = not
                                                    established (M)
                                                   Acceptable/guideline
-------------------------------

[[Page 60135]]

870.6200                        Subchronic         NOAEL = 25 mg/kg (F)
                                 neurotoxicity     LOAEL = 134 mg/kg
                                 screening          based on decreased
                                 battery (rat)      mean body weights in
                                                    females.
                                                   No treatment-related
                                                    neurotoxicological
                                                    effects were
                                                    observed at any
                                                    treatment level.
                                                   Acceptable/guideline
-------------------------------
870.7485                        Metabolism and     In a metabolism study
                                 pharmacokinetics   in rats,
                                 (rat)              tolylfluanid was
                                                    administered in
                                                    single doses of 2 or
                                                    100 mg/kg of body
                                                    weight, was readily
                                                    absorbed and rapidly
                                                    hydrolyzed within 48
                                                    hours. Absorption
                                                    and excretion were
                                                    independent of dose,
                                                    sex, and
                                                    pretreatment. About
                                                    86-100% of the dose
                                                    was recovered in 48
                                                    hours, with 56-80%
                                                    of the dose being
                                                    excreted in urine,
                                                    12-36% in the feces,
                                                    and <= 0.48% found
                                                    in the carcass.
                                                    Urinary metabolite
                                                    common to both sexes
                                                    were
                                                    dimethylaminosulfony
                                                    lamino-benzoic acid
                                                    (RNH 0166; 46-78%),
                                                    and 4-methylamino-
                                                    benzoic acid (RNH
                                                    0416; 3-6%). Fecal
                                                    compounds identified
                                                    were unchanged
                                                    tolylfluanid (1-
                                                    19%),
                                                    dimethylaminosulfoto
                                                    luidid (DMST; 5-8%),
                                                    RNH 0166 (3-12%),
                                                    and RNH 0416 (< 1%).
                                                    The data indicate
                                                    that tolylfluanid
                                                    hydrolyzed to DMST,
                                                    which is then
                                                    transformed to the
                                                    major metabolite RNH
                                                    0166, which can be
                                                    further demethylated
                                                    to the minor
                                                    metabolite, RNH 0416
                                                    (MRID No. 44285805).
                                                   Acceptable/guideline
-------------------------------
870.7485                        Metabolism and     Series of metabolism
                                 pharmacokinetics   studies showed that
                                 (rat)              metabolic profile
                                                    dependent upon label
                                                    position. With
                                                    [dichlorofluoromethy
                                                    l-\14\C]-
                                                    tolylfluanid
                                                    labeling major
                                                    urinary metabolite
                                                    was thiazolidine-2-
                                                    thione-4carbonic
                                                    acid resulting from
                                                    cleavage of the side
                                                    chain and accounted
                                                    for 73-74% and 50-
                                                    63%, respectively by
                                                    IV and oral routes.
                                                    Benzene ring label
                                                    resulted in
                                                    metabolite 4-
                                                    (dimethylamino-
                                                    sulfonylamino)
                                                    benzoic acid which
                                                    accounted for 90% of
                                                    urinary metabolic
                                                    activity and 70% of
                                                    fecal radioactivity.
                                                    The study with
                                                    single oral dose of
                                                    2 or 20 mg/kg/day
                                                    also supported the
                                                    results of the main
                                                    study (MRID No.
                                                    44285805).
-------------------------------
Non-guideline                   Non-guideline      Thyroid-stimulating
                                 (rat) thyroid      hormone levels
                                 function           significantly
                                                    increased (168-425%)
                                                    in high-dose males
                                                    and females.
                                                    Slightly increased
                                                    T3 levels in males
                                                    rats above 119.3 mg/
                                                    kg/day
                                                   Acceptable/
                                                    nonguideline
-------------------------------
Metabolite                      Non-guideline      Tolylfluanid's
                                 (mice)In vitro     metabolite TTCA was
                                 investigation of   shown to reversibly
                                 TTCA goitrogenic   inhibit thyroid
                                 properties         peroxidase (TPO)-
                                                    mediated reactions
                                                    involved with the
                                                    initial stages of
                                                    thyroid hormone
                                                    synthesis. This was
                                                    shown by the dose-
                                                    dependent decrease
                                                    in formation of
                                                    reactive iodine; the
                                                    interference of the
                                                    nonenzymatic and TPO-
                                                    mediated iodination
                                                    of L-tyrosine, and
                                                    by TPO-mediated
                                                    metabolism of TTCA.
                                                    In the latter
                                                    reaction, TTCA did
                                                    not interfere with
                                                    tyrosine iodination
                                                    when the
                                                    concentration in the
                                                    reaction mixture
                                                    fell below a certain
                                                    concentration.
                                                    Therefore, TTCA,
                                                    unlike tolylfluanid,
                                                    behaves as a
                                                    goitrogenic compound
                                                    with a potency
                                                    approximately equal
                                                    to propylthiouracil
                                                    (PTU), a known
                                                    thionamide inhibitor
                                                    of initial thyroid
                                                    hormone synthesis.
                                                   Acceptable/
                                                    nonguideline
-------------------------------
Non-guideline                   Non-guideline      In a \32\P--post-
                                 (rat)              labelling assay for
                                \32\P--post-        detection of adduct
                                 labelling assay.   formation in lung,
                                                    thyroid, and liver
                                                    DNA in rats revealed
                                                    that there was no
                                                    evidence of DNA
                                                    adduct formation in
                                                    the liver, lung, or
                                                    thyroid of rats
                                                    exposed to
                                                    tolylfluanid.
                                                    Positive control 2-
                                                    acetylaminofluorene
                                                    (2-AAF) (liver,
                                                    lung, and thyroid
                                                    DNA adducts),
                                                    benzidine (lung DNA
                                                    adducts), 2-Thiourea
                                                    (lung and thyroid
                                                    DNA adducts), and
                                                    dibenz[a,h]anthracen
                                                    e (DBA) (DNA adducts
                                                    in the lungs)
                                                    produced appropriate
                                                    results.
                                                   Acceptable/
                                                    nonguideline
------------------------------------------------------------------------

B. Toxicological Endpoints

    The dose at which no adverse effects are observed (the NOAEL) from 
the toxicology study identified as appropriate for use in risk 
assessment is used to estimate the toxicological level of concern 
(LOC). However, the lowest dose at which adverse effects of concern are 
identified (the LOAEL) is sometimes used for risk assessment if no 
NOAEL was achieved in the toxicology study selected. An uncertainty 
factor (UF) is applied to reflect uncertainties inherent in the 
extrapolation from laboratory animal data to humans and in the

[[Page 60136]]

variations in sensitivity among members of the human population as well 
as other unknowns. An UF of 100 is routinely used, 10X to account for 
interspecies differences and 10X for intra species differences.
    For dietary risk assessment (other than cancer) the Agency uses the 
UF to calculate an acute or chronic reference dose (acute RfD or 
chronic RfD) where the RfD is equal to the NOAEL divided by the 
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor (SF) 
is retained due to concerns unique to the FQPA, this additional factor 
is applied to the RfD by dividing the RfD by such additional factor. 
The acute or chronic Population Adjusted Dose (aPAD or cPAD) is a 
modification of the RfD to accommodate this type of FQPA SF.
    For non-dietary risk assessments (other than cancer) the UF is used 
to determine the LOC. For example, when 100 is the appropriate UF (10X 
to account for interspecies differences and 10X for intraspecies 
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to 
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and 
compared to the LOC. In this case because it is an import tolerance 
only, there is only dietary risk.
    The linear default risk methodology (Q*) is the primary method 
currently used by the Agency to quantify carcinogenic risk. The Q* 
approach assumes that any amount of exposure will lead to some degree 
of cancer risk. A Q* is calculated and used to estimate risk which 
represents a probability of occurrence of additional cancer cases 
(e.g., risk is expressed as 1 x 10-\6\ or one in a million). 
Under certain specific circumstances, MOE calculations will be used for 
the carcinogenic risk assessment. In this non-linear approach, a 
``point of departure'' is identified below which carcinogenic effects 
are not expected. The point of departure is typically a NOAEL based on 
an endpoint related to cancer effects though it may be a different 
value derived from the dose-response curve. To estimate risk, a ratio 
of the point of departure to exposure (MOEcancer = point of 
departure/exposures) is calculated. A summary of the toxicological 
endpoints for tolylfluanid used for human risk assessment is shown in 
Table 2 of this unit:

     Table 2.--Summary of Toxicological Dose and Endpoints for Tolylfluanid for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                              FQPA SF* and Level of
         Exposure Scenario              Dose Used in Risk       Concern for Risk       Study and Toxicological
                                         Assessment, UF            Assessment                  Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary                        NOAEL = 25              1x                      Prenatal developmental
females 13-50 years of age.........  UF\1\ = 300...........                           toxicity/rabbit
                                     Acute RfD = aPAD =                              LOAEL = 70 mg/kg/day based
                                      0.083 mg/kg/day.                                on increased malformations
                                                                                      (arthrogryposis of front
                                                                                      extremities and small
                                                                                      orbital cavity/folded
                                                                                      retina) and variations
                                                                                      (floating ribs and
                                                                                      accelerated ossification).
------------------------------------
Acute dietary                        NOAEL = 50              1x                      Acute oral neurotoxicity/
general population including         UF\1\ = 300...........                           rat
 infants and children.               Acute RfD = aPAD =                              LOAEL = 150 mg/kg/day based
                                      0.17 mg/kg/day.                                 on FOB effects
                                                                                      (pilorection, decreased
                                                                                      activity, gait
                                                                                      abnormalities, decreased
                                                                                      body temperature, and/or
                                                                                      decreased rearing).
------------------------------------
Chronic dietary                      NOAEL= 7.9              1x                      2-Generation reproduction/
all populations....................  UF\1\ = 300...........                           rat
                                     Chronic RfD = cPAD =                            LOAEL = 57.5 mg/kg/day
                                      0.026 mg/kg/day.                                based on decreased body
                                                                                      weights, body weight
                                                                                      gains, and liver weights.
------------------------------------
Cancer                                Classification: ``Likely to be carcinogenic to humans'' by the oral route,
                                        based on thyroid tumors in high-dose male and female rats. The FQPA SF
                                      Committee further recommended a linear low-dose extrapolation approach for
                                        the quantification of human cancer risk based on the thyroid tumors in
                                         rats. Q1* = 1.59 x 10-\3\ based upon male rat thyroid adenomas and/or
                                                                 carcinomas combined.
----------------------------------------------------------------------------------------------------------------
\1\ UF (uncertainty factor), FQPA Safety Factor (SF), no-observed-adverse-effect-level (NOAEL), lowest-observed-
  adverse-effect-level (LOAEL), acute Population Adjusted Dose (aPAD), chronic Population Adjusted Dose (cPAD),
  reference dose (RfD).
* The reference to the FQPA SF refers to any additional SF retained due to concerns unique to the FQPA.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. This activity reflects 
the establishment of the first U.S. import tolerance for tolylfluanid 
on apple, grape, hop, and tomato without a U.S. registration. Since 
there are no other food or feed uses in the United States, the only 
exposure to occur is dietary.
    Risk assessments were conducted by EPA to assess dietary exposures 
from tolylfluanid in food as follows:
    i. Acute exposure. Acute dietary risk assessments are performed for 
a food-use pesticide if a toxicological study has indicated the 
possibility of an effect of concern occurring as a result of a one day 
or single exposure. The Dietary Exposure Evaluation Model 
(DEEM\TM\7.76) analysis evaluated the individual food consumption as 
reported by respondents in the United States Department of Agriculture 
(USDA) 1989-1992 nationwide Continuing Surveys of Food Intake by 
Individuals (CSFII) and accumulated exposure to the chemical for each 
commodity. The following assumptions were made for the acute Tier 2 
(partially refined analysis) exposure assessments: An aPAD of 0.083 mg/
kg/day was used for females between 13 and 50 years of age based on 
developmental toxicity in rabbits. An aPAD of 0.17 was used for the 
general U.S. population (including infants and children) based on acute 
neurotoxicity in rats. Anticipated residues were calculated based upon 
submitted field trial and livestock metabolism data for all proposed 
uses of tolylfluanid.
    The resulting acute dietary exposure estimates do not exceed EPA's 
level of concern (<100% aPAD) at the 95\th\ exposure percentile for 
females 13-50 years old (42% aPAD), the general U.S. population (31% of 
the aPAD) and all other population subgroups. The most

[[Page 60137]]

highly exposed population subgroup is infants (<1 year old, at 100% of 
the aPAD).

            Table 3.--Acute Dietary Exposure to Tolylfluanid
------------------------------------------------------------------------
                                             Acute Dietary\1\
                                 ---------------------------------------
       Population Subgroup         Dietary Exposure
                                      (mg/kg/day)           % aPAD
------------------------------------------------------------------------
U.S. Population (total)           0.051973            31
---------------------------------
All Infants                       0.169772            100
(< 1 year old)..................
---------------------------------
Children                          0.159553            94
1-6 years old...................
---------------------------------
Children                          0.063237            37
7-12 years old..................
---------------------------------
Females                           0.034529            20
13-50 years old.................
---------------------------------
Males                             0.023476            14
13-19 years old.................
---------------------------------
Males                             0.030744            18
20+ years old...................
---------------------------------
Seniors                           0.033375            20
55+ years old...................
------------------------------------------------------------------------
\1\Acute dietary endpoint of 0.083 mg/kg/day applies to females 13-50
  years old only; acute dietary endpoint of 0.17 mg/kg/day applies to
  the general U.S. population (including infants and children).

    The assessment of acute dietary exposure used the following 
conservative assumptions likely to generate upper-end estimates of the 
quantity of tolylfluanid and tolylfluanid residues ingested:
    [sbull]
No import consumption data were used in the assessment 
(i.e., the assessment assumes that all acute dietary exposure from the 
proposed commodities is from imported commodities).
    [sbull]
100% crop treated (CT) was assumed for these imported 
commodities: All imported grape, apple, hop, and tomato were assumed to 
have been treated with tolylfluanid and to have tolylfluanid residues 
at the level of the tolerance.
    Inclusion of additional data, such as %CT/import consumption data 
and/or monitoring data (including metabolites of concern), could be 
made in order to refine the acute dietary exposure assessment.
    ii. Chronic exposure. In conducting this chronic dietary risk 
assessment the DEEM\TM\ analysis evaluated the individual food 
consumption as reported by respondents in the USDA 1989-1992 nationwide 
CSFII and accumulated exposure to the chemical for each commodity. The 
following assumptions were made for the chronic exposure assessments:
    A cPAD of 0.026 mg/kg/day was used based on the 2-generation rat 
reproduction study. All dietary exposure from the proposed commodities 
is from imported commodities. Import share data generated within the 
Agency were used in the assessment to estimate what proportion of the 
grape, apple, hop, and tomato consumed in the United States are 
imported. Modified DEEM\TM\ processing factors based on the results of 
processing studies were used for raisins and apple and grape juice/
juice concentrates. Default DEEM\TM\ processing factors were used for 
all other processed commodities. Anticipated residues calculations were 
used based upon submitted field trial and livestock metabolism data.

               Table 4.--Chronic Exposure to Tolylfluanid
------------------------------------------------------------------------
                                            Chronic Dietary\1\
                                 ---------------------------------------
       Population Subgroup         Dietary Exposure
                                      (mg/kg/day)           % aPAD
------------------------------------------------------------------------
U.S. Population (total)           0.000780            3
---------------------------------
All Infants                       0.003397            13
(< 1 year old)..................
---------------------------------
Children                          0.003638            14
1-6 years old...................
---------------------------------
Children                          0.001029            4
7-12 years old..................
---------------------------------
Females                           0.000399            2
13-50 years old.................
---------------------------------
Males                             0.000342            1
13-19 years old.................
---------------------------------
Males                             0.000340            1
20+ years old...................
---------------------------------
Seniors                           0.000333            1
55+ years old...................
------------------------------------------------------------------------
\1\Chronic dietary endpoint of 0.026 mg/kg/day applies to general U.S.
  population and all population subgroups.

    The assessment of chronic dietary exposure for the general U.S. 
population and all population subgroups (including infants and 
children) used the following conservative assumptions to generate 
upper-end estimates of the quantity of tolylfluanid and tolylfluanid 
residues ingested:

100% CT was assumed for these imported commodities: All 
imported grape, apple, hop, and tomato were assumed to have been 
treated with tolylfluanid and to have tolylfluanid residues at the 
level of the tolerance.

The calculated ARs (parent and additional metabolites of 
concern not in tolerance expression) are based on field trial data, 
submitted by the registrant to support tolerances. Field trial residue 
data are generally considered by the Agency as an upper-end or a worst 
case scenario of possible residues and are more suited to the 
requirements of tolerance setting, because it requires highest rates of 
application and shortest PHI, than to the requirements of dietary 
exposure assessment (when a more realistic estimate is desired).
    The chronic dietary exposure estimates do not exceed EPA's level of 
concern (<100% cPAD) for the general U.S. population (3% cPAD) and all 
population subgroups. The most highly exposed population subgroup is 
children 1-6 years old at 14% of the cPAD.
    iii. Cancer. A partially refined, cancer dietary exposure 
assessment was conducted for the general U.S. population using the same 
assumptions as were used in the chronic risk assessment (listed in the 
preceding section). Import share data generated within the Agency were 
used in the assessment to estimate what proportion of the grape, apple, 
hop, and tomato consumed in the United States are imported. Modified 
DEEM\TM\ processing factors based on the results of processing studies 
were used for raisins and apple and grape juice/juice concentrates. 
Default DEEM\TM\ processing factors were used for all other processed 
commodities The cancer risk estimate is 1.2 x 10-\6\ for the 
general U.S. population.
    For cancer dietary risk estimates, the Agency is generally 
concerned with cancer risks that exceed the range of 1 x 
10-\6\. The following conservative assumptions were used in 
the cancer dietary exposure assessment:

The percent import consumption information used for apple, 
grape and tomato commodities assume that 100% of these imported 
commodities are treated with tolylfluanid.

The calculated ARs are based on field trial data, submitted 
by the registrant to support tolerances. Field trial residue data are 
generally considered by the Agency as providing an upper-end scenario 
of possible residues and are more suited to the requirements of 
tolerance setting, because it requires highest rates of application and 
shortest PHI, than to the requirements of dietary exposure

[[Page 60138]]

assessment (when a more realistic estimate is desired).
    With additional refinements to the dietary exposure assessment 
(i.e., country-specific percent import consumption data and/or 
monitoring data (including metabolites of concern) the Agency expects 
the estimated cancer risk to be significantly lower.
    iv. Anticipated residue and %CT.
    Section 408(b)(2)(E) of the FFDCA authorizes EPA to use available 
data and information on the anticipated residue levels of pesticide 
residues in food and the actual levels of pesticide chemicals that have 
been measured in food. Adequate reliable information was not available 
on the fraction of imported grape, apple, hop, and tomato which were 
treated with tolylfluanid, therefore the Agency assumed that all these 
commodities were treated (100% CT). In addition, the Agency must 
provide for periodic evaluation of any estimates used. As required by 
section 408(b)(2)(E) of the FFDCA, EPA will issue a data call-in for 
information relating to anticipated residues to be submitted no later 
than 5 years from the date of issuance of this tolerance.
    Section 408(b)(2)(F) of the FFDCA states that the Agency may use 
data on the actual percent of food treated for assessing chronic 
dietary risk only if the Agency can make the following findings: 
Condition 1, that the data used are reliable and provide a valid basis 
to show what percentage of the food derived from such crop is likely to 
contain such pesticide residue; Condition 2, that the exposure estimate 
does not underestimate exposure for any significant subpopulation 
group; and Condition 3, if data are available on pesticide use and food 
consumption in a particular area, the exposure estimate does not 
understate exposure for the population in such area. In addition, the 
Agency must provide for periodic evaluation of any estimates used. To 
provide for the periodic evaluation of the estimate of %CT as required 
by section 408(b)(2)(F) of the FFDCA, EPA may require registrants to 
submit data on %CT. The Agency used %CT information as follows:
    Since the tolerances being established are for imported commodities 
only and a petition for domestic use of tolyfluanid is not currently 
pending with EPA, the Agency analyzed the amount of imported apple, 
grape, hop, and tomato, relative to domestic production, and derived a 
``percent crop imported'' figure for each commodity. The Agency based 
this analysis on import and domestic production data available from the 
USDA for the years 1995 through 1999. The proportion of imports 
relative to domestic production for each of the commodities are as 
follows: Fresh apple--5.6%; apple juice--56.4%; canned apple--0.1%; 
fresh grape--0.2%, grape juice--43.4%; fresh tomato--16.4%; and 
processed tomato--4.1%. The Agency's analysis assumed 100% for hop. 
Tolylfluanid is currently only registered for use in a small number of 
European countries, however, the estimates stated in this unit reflect 
total imports of these commodities into the United States, not just 
imports from Europe. Therefore, the values used in the Agency's risk 
assessment assume that all imported commodities contain residues of 
tolyfluanid. These assumptions fulfill Condition 1 by overestimating 
the portion of imported apple, grape, hop, and tomato with tolylfluanid 
residues. As to Conditions 2 and 3, regional consumption information 
and consumption information for significant subpopulations is taken 
into account through EPA's computer-based model for evaluating the 
exposure of significant subpopulations including several regional 
groups. Use of this consumption information in EPA's risk assessment 
process ensures that EPA's exposure estimate does not understate 
exposure for any significant subpopulation group and allows the Agency 
to be reasonably certain that no regional population is exposed to 
residue levels higher than those estimated by the Agency.
    2. Dietary exposure from drinking water. Residues in drinking water 
are not expected to result as a consequence of establishing an import 
tolerance for tolylfluanid residues in or on apple, grape, hop, and 
tomato. Tolylfluanid is not registered for use in the United States. 
Therefore, exposure through drinking water is unlikely.
    3. From 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 pets). Tolylfluanid is not 
registered for use on any sites that would result in residential 
exposure.
    4. Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of the 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.''
    EPA does not have, at this time, available data to determine 
whether tolylfluanid has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment. Unlike other pesticides for which EPA has followed a 
cumulative risk approach based on a common mechanism of toxicity, 
tolylfluanid 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 tolylfluanid 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 final rule 
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).

D. Safety Factor for Infants and Children

    1. In general. Section 408 of the FFDCA provides that EPA shall 
apply an additional 10-fold margin of safety for infants and children 
in the case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the data base on toxicity and exposure 
unless EPA determines that a different margin of safety will be safe 
for infants and children. Margins of safety are incorporated into EPA 
risk assessments either directly through use of a MOE analysis or 
through using uncertainty (safety) factors in calculating a dose level 
that poses no appreciable risk to humans.
    2. Prenatal and postnatal sensitivity. There is no quantitative or 
qualitative evidence of increased susceptibility following in utero 
exposure in the prenatal developmental study in rats. Although there is 
qualitative evidence of increased susceptibility in the prenatal 
developmental study in rabbits and in the 2-generation reproduction 
study in rats, the Agency did not identify any residual uncertainties 
after establishing toxicity endpoints and traditional UFs to be used in 
the risk assessment of tolylfluanid.
    3. Conclusion. There is a complete toxicity data base for 
tolylfluanid and exposure data are complete or are estimated based on 
data that reasonably accounts for potential exposures. The RfDs 
established are protective of pre-/post-natal toxicity following acute 
and chronic exposures. The Agency therefore concluded that no Special 
FQPA FS is necessary to protect the safety of infants and children in 
assessing tolylfluanid exposure and

[[Page 60139]]

risks. However, a FQPA factor in the form of data base UF 
(UFDB) of 3x was applied to the acute RfDs and chronic RfDs 
to account for the comparative thyroid assay (adult versus young 
animals) data requirement. 3X is adequate in this case since the 
observed thyroid hormone changes that necessitated the additional study 
occurred at a dose level more than three-fold higher than the dose 
levels (based on developmental and reproductive toxicity) used as the 
basis for endpoints for risk assessment. Thus, use of an additional 3X 
FQPA SF will provide at least a 10X margin of safety regarding the 
effects for which there is some uncertainty and for which additional 
data is required.

                                     Table 5.--Additional FQPA Safety Factor
----------------------------------------------------------------------------------------------------------------
                                                                                                 Special FQPA
                                    LOAEL to NOAEL       Subchronic to      Incomplete Data      Safety Factor
                                         (UFL)           Chronic (UFS)        base (UFDB)         (Hazard and
                                                                                                   Exposure)
----------------------------------------------------------------------------------------------------------------
Magnitude of factor               1X                  1X                  3X                  1X
---------------------------------
Rationale for the factor          No LOAEL to NOAEL   No subchronic to    Lack of             No residual
                                   extrapolations      chronic             comparative         uncertainties
                                   performed           extrapolations      thyroid assay       regarding pre- or
                                                       performed          (adult versus        post-natal
                                                                           young animals).     toxicity or
                                                                                               completeness of
                                                                                               the toxicity or
                                                                                               exposure data
                                                                                               bases
---------------------------------
Endpoints to which the factor is  Not applicable      NA                  All dietary         NA
 applied                           (NA)                                    exposure
                                                                           scenarios
----------------------------------------------------------------------------------------------------------------

E. Aggregate Risks and Determination of Safety

    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food to 
tolylfluanid will occupy 31% of the aPAD for the U.S. population, 20% 
of the aPAD for females 13 years and older, 100% of the aPAD for 
infants < 1year old, and 94% of the aPAD for children between 7 and 12 
years old. In addition, there is no potential for acute dietary 
exposure to tolylfluanid in drinking water. Although this risk 
assessment projects that infants under 1 year of age will receive the 
maximum safe exposure, for the reasons detailed in this unit, this 
assessment is likely to substantially overstate risk.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
tolylfluanid from food will utilize 3% of the cPAD for the U.S. 
population, 13% of the cPAD for infants < 1 year old, and 14% of the 
cPAD for children between 1 and 6 years old. There are no residential 
uses for tolylfluanid that result in chronic residential exposure to 
tolylfluanid.
    3. Short-term risk. Short-term aggregate exposure takes into 
account residential exposure plus chronic exposure to food and water 
(considered to be a background exposure level). Tolylfluanid is not 
registered for use on any sites that would result in residential 
exposure. Therefore, a short-term aggregate risk was not performed.
    4. Intermediate-term risk. Tolylfluanid is not registered for use 
on any sites that would result in residential exposure. Therefore, an 
intermediate-term aggregate risk was not performed.
    5. Aggregate cancer risk for U.S. population. The cancer risk 
estimate for the general U.S. population from tolylfluanid is 1.2 x 
10-\6\. In general, the Agency's level of concern for cancer 
exposure is for risks in the range of 1 x 10-\6\ and this 
risk estimate is comfortably with this range. Moreover, several 
conservative assumptions were included in the assessment (enumerated in 
Unit III.C.1., Dietary exposure from food and feed uses). With 
additional refinements to the dietary exposure assessment (i.e., 
country-specific percent import consumption data and/or monitoring data 
(including metabolites of concern), the Agency expects the cancer risk 
to be substantially lower.
    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, and to infants and children from aggregate 
exposure to tolylfluanid residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    For tolylfluanid in/on apple, grape, hop, and tomato, the submitted 
independent laboratory validation (ILV) using a gas chromatograph (GC)/
thermal ionization detector (TID) procedure designated as Method 00441 
and entitled Determination of Tolylfluanid in/on Various Raw 
Agricultural and Processed Commodities has been received and the method 
has been forwarded to the Agency's laboratory for validation. The 
petitioner will be required to make any modifications or revisions to 
the proposed method resulting from EPA's validation.
    The petitioners submitted the multiresidue data concerning the 
recovery of tolylfluanid residues using the Food and Drug 
Administration (FDA) MRM protocols (PAM Vol. I) and following modified 
cleanup procedures. These results indicate that tolylfluanid is likely 
to be recovered through FDA MRM Protocols D and E. The results have 
been forwarded to the FDA for inclusion in the Pesticide Analytical 
Method Volume I.
    Prior to publication and upon request, the method will be available 
from the Analytical Chemistry Branch (ACB), BEAD (75053), Environmental 
Science Center, 701 Mapes Rd., Ft. George C. Meade, MD 20755-5350. 
Contact Francis D. Griffith, Jr., telephone number: (410) 305-2905; e-
mail address: griffith.francis@epa.gov. The analytical standards are 
also available from the EPA National Standard Repository at the same 
location.
    Based on the proposed uses, a residue enforcement method for 
livestock commodities is not necessary at this time.

B. International Residue Limits

    There are no Canadian or Mexican MRLs established for tolylfluanid 
residues in/on crop commodities. The Codex Alimentarius Commission has 
established MRLs for tolylfluanid residues in/on various commodities, 
including currant at 5 ppm, gherkin at 2 ppm, lettuce head at 1 ppm, 
pome

[[Page 60140]]

fruits at 5 ppm, strawberry at 3 ppm, and tomato at 2 ppm. The Codex 
MRLs are expressed in terms of tolylfluanid per se. Although the 
submitted residue data support the proposed tolerance of 1.0 ppm on 
tomato, the Agency is establishing this tolerance at 2.0 ppm in order 
to harmonize with the current Codex MRL.

V. Conclusion

    Therefore, the tolerance is established for residues of 
tolylfluanid, (1,1-dichloro-N-[(dimethylamino)-sulfonyl]-1-fluoro-N-(4-
methylphenyl)methanesulfenamide), in or on apple at 5 ppm, grape at 11 
ppm, hop at 30 ppm, and tomato at 2 ppm.

VI. Objections and Hearing Requests

    Under section 408(g) of the FFDCA, as amended by the FQPA, any 
person may file an objection to any aspect of this regulation and may 
also request a hearing on those objections. The EPA procedural 
regulations which govern the submission of objections and requests for 
hearings appear in 40 CFR part 178. Although the procedures in those 
regulations require some modification to reflect the amendments made to 
the FFDCA by the FQPA, EPA will continue to use those procedures, with 
appropriate adjustments, until the necessary modifications can be made. 
The new section 408(g) of the FFDCA provides essentially the same 
process for persons to ``object'' to a regulation for an exemption from 
the requirement of a tolerance issued by EPA under new section 408(d) 
of the FFDCA, as was provided in the old sections 408 and 409 of the 
FFDCA. However, the period for filing objections is now 60 days, rather 
than 30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number OPP-2002-0216 in the subject line on the 
first page of your submission. All requests must be in writing, and 
must be mailed or delivered to the Hearing Clerk on or before November 
25, 2002.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900C), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Rm.104, Crystal Mall 
i
2, 1921 Jefferson Davis Hwy., Arlington, VA. The Office of the Hearing Clerk is open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Office of the Hearing Clerk is (703) 603-0061. 2. Tolerance fee payment. If you file an objection or request a hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or request a waiver of that fee pursuant to 40 CFR 180.33(m). You must mail the fee to: EPA Headquarters Accounting Operations Branch, Office of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please identify the fee submission by labeling it ``Tolerance Petition Fees.'' EPA is authorized to waive any fee requirement ``when in the judgement of the Administrator such a waiver or refund is equitable and not contrary to the purpose of this subsection.'' For additional information regarding the waiver of these fees, you may contact James Tompkins by phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov, or by mailing a request for information to Mr. Tompkins at Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460- 0001. If you would like to request a waiver of the tolerance objection fees, you must mail your request for such a waiver to: James Hollins, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001. 3. Copies for the Docket. In addition to filing an objection or hearing request with the Hearing Clerk as described in Unit VI.A., you should also send a copy of your request to the PIRIB for its inclusion in the official record that is described in Unit I.B.2. Mail your copies, identified by docket ID number OPP-2002-0216, to: Public Information and Records Integrity Branch, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460- 0001. In person or by courier, bring a copy to the location of the PIRIB described in Unit I.B.2. You may also send an electronic copy of your request via e-mail to: opp-docket@epa.gov. Please use an ASCII file format and avoid the use of special characters and any form of encryption. Copies of electronic objections and hearing requests will also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format. Do not include any CBI in your electronic copy. You may also submit an electronic copy of your request at many Federal Depository Libraries. B. When Will the Agency Grant a Request for a Hearing? A request for a hearing will be granted if the Administrator determines that the material submitted shows the following: There is a genuine and substantial issue of fact; there is a reasonable possibility that available evidence identified by the requestor would, if established resolve one or more of such issues in favor of the requestor, taking into account uncontested claims or facts to the contrary; and resolution of the factual issues(s) in the manner sought by the requestor would be adequate to justify the action requested (40 CFR 178.32). VII. Regulatory Assessment Requirements This final rule establishes a tolerance under section 408(d) of the FFDCA in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993). Because this rule has been exempted from review under Executive Order 12866 due to its lack of significance, this rule is not subject to Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001). This final rule does not contain any information collections subject to OMB approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or contain any unfunded mandate as described under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor does it require any [[Page 60141]] special considerations under Executive Order 12898, entitled Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations (59 FR 7629, February 16, 1994); or OMB review or any Agency action under Executive Order 13045, entitled Protection of Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does not involve any technical standards that would require Agency consideration of voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since tolerances and exemptions that are established on the basis of a petition under section 408(d) of the FFDCA, such as the tolerance in this final rule, do not require the issuance of a proposed rule, the requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply. In addition, the Agency has determined that this action will not have a substantial direct effect on States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government, as specified in Executive Order 13132, entitled Federalism (64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to develop an accountable process to ensure ``meaningful and timely input by State and local officials in the development of regulatory policies that have federalism implications.'' ``Policies that have federalism implications'' is defined in the Executive order to include regulations that have ``substantial direct effects on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government.'' This final rule directly regulates growers, food processors, food handlers, and food retailers, not States. This action does not alter the relationships or distribution of power and responsibilities established by Congress in the preemption provisions of section 408(n)(4) of the FFDCA. For these same reasons, the Agency has determined that this rule does not have any ``tribal implications'' as described in Executive Order 13175, entitled Consultation and Coordination with Indian Tribal Governments (59 FR 22951, November 6, 2000). Executive Order 13175, requires EPA to develop an accountable process to ensure ``meaningful and timely input by tribal officials in the development of regulatory policies that have tribal implications.'' ``Policies that have tribal implications'' is defined in the Executive order to include regulations that have ``substantial direct effects on one or more Indian tribes, on the relationship between the Federal Government and the Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes.'' This rule will not have substantial direct effects on tribal governments, on the relationship between the Federal Government and Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes, as specified in Executive Order 13175. Thus, Executive Order 13175 does not apply to this rule. VIII. Submission to Congress and the Comptroller General The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the Small Business Regulatory Enforcement Fairness Act of 1996, generally provides that before a rule may take effect, the agency promulgating the rule must submit a rule report, which includes a copy of the rule, to each House of the Congress and to the Comptroller General of the United States. EPA will submit a report containing this rule and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of this final rule in the Federal Register. This final rule is not a ``major rule'' as defined by 5 U.S.C. 804(2). List of Subjects in 40 CFR Part 180 Environmental protection, Administrative practice and procedure, Agricultural commodities, Pesticides and pests, Reporting and recordkeeping requirements. Dated: September 13, 2002. James Jones, Acting Director, Office of Pesticide Programs. Therefore, 40 CFR chapter I is amended as follows: PART 180--[AMENDED] 1. The authority citation for part 180 continues to read as follows: Authority: 21 U.S.C. 321(q), 346(a) and 371. 2. Section 180.584 is added to subpart C to read as follows: Sec. 180.584 Tolylfluanid, tolerances for residues. (a) General. Tolerances are established for residues of tolylfluanid, 1,1-dichloro-N-[(dimethylamino)-sulfonyl]-1-fluoro-N-(4- methylphenyl)methanesulfenamide in or on the following commodities. ---------------------------------------------------------------------------------------------------------------- Commodity Parts per million ---------------------------------------------------------------------------------------------------------------- Apple\1\............................................. 5.0 Grape\1\.............................................. 11 Hop\1\................................................ 30 Tomato\1\............................................. 2.0 ---------------------------------------------------------------------------------------------------------------- \1\ No U.S. registration as of August 31, 2002. [[Page 60142]] (b) Section 18 emergency exemptions. [Reserved] (c) Tolerances with regional registrations. [Reserved] (d) Indirect or inadvertent residues. [Reserved] [FR Doc. 02-24094 Filed 9-24-02; 8:45 am] BILLING CODE 6560-50-S