[Federal Register Volume 66, Number 100 (Wednesday, May 23, 2001)]
[Rules and Regulations]
[Pages 28386-28397]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-12899]


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

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301132; FRL-6784-7]
RIN 2070-AB78


Thiamethoxam; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: This regulation establishes tolerances for combined residues 
of thiamethoxam and its metabolite in or on tuberous and corm 
vegetables crop subgroup, fruiting vegetables crop group, tomato paste, 
cucurbit vegetables crop group, and pome fruits crop group. Syngenta 
Crop Protection, Inc. requested these tolerances under the Federal 
Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection 
Act of 1996.

DATES: This regulation is effective May 23, 2001. Objections and 
requests for hearings, identified by docket control number OPP-301132, 
must be received by EPA on or before July 23, 2001.

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 control number OPP-301132 in the 
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Dani Daniel, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW.,Washington, DC 20460; 
telephone number: (703) 305-5409; and e-mail address: 
<a href="/cdn-cgi/l/email-protection#d2b6b3bcbbb7befcb6b3bcbb92b7a2b3fcb5bda4"><span class="__cf_email__" data-cfemail="6e0a0f00070b02400a0f00072e0b1e0f40090118">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

[[Page 28387]]

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 Potentially
             Categories                 NAICS       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/. To access the OPPTS Harmonized 
Guidelines referenced in this document, go directly to the guidelines 
at http://www.epa.gov/opptsfrs/home/guidelin.htm. A frequently updated 
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_180/Title_40/40cfr180_00.html, a 
beta site currently under development.
    2. In person. The Agency has established an official record for 
this action under docket control number OPP-301132. 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 May 5, 1999 (64 FR 34153) (FRL-6072-7), 
EPA issued a notice pursuant to section 408 of the Federal Food, Drug, 
and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the Food Quality 
Protection Act of 1996 (FQPA) (Public Law 104-170) announcing the 
filing of a pesticide petition (9F5051) for tolerances by Syngenta Crop 
Protection, P.O. Box 18300 Greensboro, NC 27419-8300. This notice 
included a summary of the petition prepared by Syngenta Crop 
Protection, the registrant. There were no comments received in response 
to the notice of filing.
    The petition requested that 40 CFR 180.565 be amended by 
establishing tolerances for combined residues of the insecticide 
thiamethoxam, 3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-
nitro-4H-1,3,5-oxadiazin-4-imine and its metabolite (N-(2-chloro-
thiazol-5-ylmethyl)-N '-methyl-N ''-nitro-guanidine) in or on the raw 
agricultural commodities: tuberous and corm vegetables crop subgroup at 
0.02 ppm, cucurbit vegetables crop group at 0.20 ppm, pome fruit crop 
group at 0.20 ppm, fruiting vegetables crop group at 0.25 ppm and 
tomato paste at 0.80 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) defines ``safe'' to mean that`` there is a reasonable 
certainty that no harm will result from aggregate exposure to the 
pesticide chemical residue, including 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) 
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 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), 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), for a tolerance for combined residues of thiamethoxam and 
its metabolite in or on tuberous and corm vegetables crop subgroup at 
0.02 ppm, fruiting vegetables crop group at 0.25 ppm, tomato paste at 
0.80 ppm, cucurbit vegetables crop group at 0.20 ppm, and pome fruits 
crop group at 0.20 ppm. EPA's assessment of exposures and risks 
associated with establishing these tolerances 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 thiamethoxam are 
discussed in the following Table 1 as well as the no observed adverse 
effect level (NOAEL) and the lowest observed adverse effect level 
(LOAEL) from the toxicity studies reviewed.

[[Page 28388]]



            Table 1.--Subchronic, Chronic, and Other Toxicity
------------------------------------------------------------------------
         Guideline No.              Study Type            Results
------------------------------------------------------------------------
870.3100                        90-Day oral        NOAEL = 1.74 (males),
                                 toxicity - rat     92.5 (females) mg/kg/
                                                    day
                                                   LOAEL = 17.64
                                                    (males), 182.1
                                                    (females) mg/kg/day
                                                    based on increased
                                                    incidence of hyaline
                                                    change of renal
                                                    tubular epithelium
                                                    (males), fatty
                                                    change in adrenal
                                                    gland of females,
                                                    liver changes in
                                                    females, all at the
                                                    LOAEL.
------------------------------------------------------------------------
870.3100                        90-Day oral        NOAEL = 1.41 (males),
                                 toxicity - mouse   19.2 (females) mg/kg/
                                                    day
                                                   LOAEL = 14.3 (males),
                                                    231 (females) mg/kg/
                                                    day based on
                                                    increased incidence
                                                    of hepatocellular
                                                    hypertrophy. At
                                                    higher dose levels:
                                                    decrease in
                                                    bodyweight and
                                                    bodyweight gain,
                                                    necrosis of
                                                    individual
                                                    hepatocytes,
                                                    pigmentation of
                                                    Kupffer cells, and
                                                    lymphocytic
                                                    infiltration of the
                                                    liver in both sexes;
                                                    slight hematologic
                                                    effects and
                                                    decreased absolute
                                                    and relative kidney
                                                    weights in males;
                                                    and ovarian atrophy,
                                                    decreased ovary and
                                                    spleen weights and
                                                    increased liver
                                                    weights in females.
------------------------------------------------------------------------
870.3150                        90-Day oral        NOAEL = 8.23 (males),
                                 toxicity - dog     9.27 (females) mg/kg/
                                                    day
                                                   LOAEL = 32.0 (males),
                                                    33.9 (females) mg/kg/
                                                    day based on
                                                    slightly prolonged
                                                    prothrombin times
                                                    and decreased plasma
                                                    albumin and A/G
                                                    ratio (both sexes);
                                                    decreased calcium
                                                    levels and ovary
                                                    weights and delayed
                                                    maturation in the
                                                    ovaries (females);
                                                    decreased
                                                    cholesterol and
                                                    phospholipid levels,
                                                    testis weights,
                                                    spermatogenesis, and
                                                    spermatic giant
                                                    cells in testes
                                                    (males).
------------------------------------------------------------------------
870.3200                        28-Day dermal      NOAEL = 250 (males),
                                 toxicity - rat     60 (females) mg/kg/
                                                    day
                                                   LOAEL = 1000 (males),
                                                    250 (females) mg/kg/
                                                    day based on
                                                    increased plasma
                                                    glucose,
                                                    triglyceride levels,
                                                    and alkaline
                                                    phosphatase activity
                                                    and inflammatory
                                                    cell infiltration in
                                                    the liver and
                                                    necrosis of single
                                                    hepatocytes in
                                                    females and hyaline
                                                    change in renal
                                                    tubules and a very
                                                    slight reduction in
                                                    body weight in
                                                    males. At higher
                                                    dose levels in
                                                    females, chronic
                                                    tubular lesions in
                                                    the kidneys and
                                                    inflammatory cell
                                                    infiltration in the
                                                    adrenal cortex were
                                                    observed.
------------------------------------------------------------------------
870.3700a                       Prenatal           Maternal NOAEL = 30
                                 developmental -    mg/kg/day
                                 rat
                                                   LOAEL = 200 mg/kg/day
                                                    based on decreased
                                                    body weight, body
                                                    weight gain, and
                                                    food consumption.
                                                   Developmental NOAEL =
                                                    200 mg/kg/day
                                                   LOAEL = 750 mg/kg/day
                                                    based on decreased
                                                    fetal body weight
                                                    and anincreased
                                                    incidence of
                                                    skeletal anomalies.
------------------------------------------------------------------------
870.3700b                       Prenatal           Maternal NOAEL = 50
                                 developmental -    mg/kg/day
                                 rabbit
                                                   LOAEL = 150 mg/kg/day
                                                    based on maternal
                                                    deaths, hemorrhagic
                                                    uterine contents and
                                                    hemorrhagic
                                                    discharge, decreased
                                                    body weight and food
                                                    intake during the
                                                    dosing period.
                                                   Developmental NOAEL =
                                                    50 mg/kg/day
                                                   LOAEL = 150 mg/kg/day
                                                    based on decreased
                                                    fetal body weights,
                                                    increased incidence
                                                    of post-implantation
                                                    loss and a slight
                                                    increase in the
                                                    incidence of a few
                                                    skeletal anomalies/
                                                    variations.
------------------------------------------------------------------------
870.3800                        Reproduction and   Parental/Systemic
                                 fertility          NOAEL = 1.84
                                 effects - rat      (males), 202.06
                                                    (females)mg/kg/day
                                                   LOAEL = 61.25
                                                    (males), not
                                                    determined (females)
                                                    mg/kg/day based on
                                                    increased incidence
                                                    of hyaline change in
                                                    renal tubules in F0
                                                    and F1 males.
                                                   Reproductive NOAEL =
                                                    0.61 (males), 202.06
                                                    (females) mg/kg/day
                                                   LOAEL = 1.84 (males),
                                                    not determined
                                                    (females) mg/kg/day
                                                    based on increased
                                                    incidence and
                                                    severity of tubular
                                                    atrophy observed in
                                                    testes of the F1
                                                    generation males.
                                                   Offspring NOAEL =
                                                    61.25 (males), 79.20
                                                    (females) mg/kg/day
                                                   LOAEL = 158.32
                                                    (males), 202.06
                                                    (females) mg/kg/day
                                                    based on reduced
                                                    body weight gain
                                                    during the lactation
                                                    period in all
                                                    litters .
------------------------------------------------------------------------
870.4100                        Chronic toxicity - NOAEL = 4.05 (males),
                                  dog               4.49 (females) mg/kg/
                                                    day
                                                   LOAEL = 21.0 (males),
                                                    24.6 (females) mg/kg/
                                                    day based on
                                                    increase in
                                                    creatinine in both
                                                    sexes, transient
                                                    decrease in food
                                                    consumption in
                                                    females, and
                                                    occasional increase
                                                    in urea levels,
                                                    decrease in ALT, and
                                                    atrophy of
                                                    seminiferous tubules
                                                    in males.
------------------------------------------------------------------------
870.4200                        Carcinogenicity -  NOAEL = 2.63 (males),
                                 mouse              3.68 (females) mg/kg/
                                                    day

[[Page 28389]]

 
                                                   LOAEL = 63.8 (males),
                                                    87.6 (females) mg/kg/
                                                    day based on
                                                    hepatocyte
                                                    hypertrophy, single
                                                    cell necrosis,
                                                    inflammatory cell
                                                    infiltration,
                                                    pigment deposition,
                                                    foci of cellular
                                                    alteration,
                                                    hyperplasia of
                                                    Kupffer cells and
                                                    increased mitotic
                                                    activity; also, an
                                                    increase in the
                                                    incidence of
                                                    hepatocellular
                                                    adenoma (both
                                                    sexes). At higher
                                                    doses, there was an
                                                    increase in the
                                                    incidence of
                                                    hepatocellular
                                                    adenocarcinoma (both
                                                    sexes) and the
                                                    number of animals
                                                    with multiple
                                                    tumors. evidence of
                                                    carcinogenicity
------------------------------------------------------------------------
870.4300                        Combined chronic   NOAEL = 21.0 (males),
                                 carcinogenicity -  50.3 (females) mg/kg/
                                  rat               day
                                                   LOAEL = 63.0 (males),
                                                    155 (females) mg/kg/
                                                    day based on
                                                    increased incidence
                                                    of lymphocytic
                                                    infiltration of the
                                                    renal pelvis and
                                                    chronic nephropathy
                                                    in males and
                                                    decreased body
                                                    weight gain, slight
                                                    increase in the
                                                    severity of
                                                    hemosiderosis of the
                                                    spleen, foci of
                                                    cellular alteration
                                                    in liver and chronic
                                                    tubular lesions in
                                                    kidney in females.
                                                    no evidence of
                                                    carcinogenicity
------------------------------------------------------------------------
870.5100 and 870.5265           Gene mutation in   No evidence of gene
                                 S. typhimurium     mutation when tested
                                 and E. coli        up to 5,000 <greek-
                                                    m>g/plate. There was
                                                    no evidence of
                                                    cytotoxicity.
------------------------------------------------------------------------
870.5265                        Gene mutation in   No evidence of gene
                                 S. typhimurium     mutation when tested
                                                    up to 5,000 <greek-
                                                    m>g/plate.The S9
                                                    fraction was from
                                                    non-induced mouse
                                                    liver, Aroclor 1254
                                                    induced mouseliver,
                                                    or thiamethoxam
                                                    induced mouse liver,
                                                    following dietary
                                                    administration of
                                                    thiamethoxam for 14
                                                    days at
                                                    concentrations up to
                                                    2,500 ppm.
870.5300                        Gene mutation in   No evidence of gene
                                 chinese hamster    mutation when tested
                                 V79 cells at       up to solubility
                                 HGPRT locus        limit.
------------------------------------------------------------------------
870.5375                        CHO cell           No evidence of
                                 cytogenetics       chromosomal
                                                    aberrations when
                                                    tested up
                                                    tocytotoxic or
                                                    solubility limit
                                                    concentrations.
------------------------------------------------------------------------
870.5395                        In vivo mouse      Negative when tested
                                 bone marrow        up to levels of
                                 micronucleus       toxicity in whole
                                                    animals;however no
                                                    evidence of target
                                                    cell cytotoxicity.
------------------------------------------------------------------------
870.5550                        UDS assay          Negative when tested
                                                    up to precipitating
                                                    concentrations
------------------------------------------------------------------------
870.6200a                       Acute              NOAEL = 100 mg/kg/day
                                 neurotoxicity
                                 screening
                                 battery - rat
                                                   LOAEL = 500 mg/kg/day
                                                    based on drooped
                                                    palpebral closure,
                                                    decrease in rectal
                                                    temperature and
                                                    locomotor activity
                                                    and increase in
                                                    forelimb grip
                                                    strength (males
                                                    only). At higher
                                                    dose levels,
                                                    mortality, abnormal
                                                    body tone, ptosis,
                                                    impaired
                                                    respiration,
                                                    tremors, longer
                                                    latency to first
                                                    step in the open
                                                    field, crouched-over
                                                    posture, gait
                                                    impairment, hypo-
                                                    arousal, decreased
                                                    number of rears,
                                                    uncoordinated
                                                    landing during the
                                                    righting reflex
                                                    test, slight
                                                    lacrimation (females
                                                    only) and higher
                                                    mean average input
                                                    stimulus value in
                                                    the auditory startle
                                                    response test (males
                                                    only).
------------------------------------------------------------------------
870.6200b                       Subchronic         NOAEL = 95.4 (males),
                                 neurotoxicity      216.4 (females) mg/
                                 screening          kg/day, both
                                 battery - rat      highestdose tested.
                                                   LOAEL = not
                                                    determined. No
                                                    treatment-related
                                                    observations at any
                                                    dose level.
                                                   LOAEL was not
                                                    achieved. May not
                                                    have been tested at
                                                    sufficiently high
                                                    dose levels;
                                                    however, new study
                                                    not required because
                                                    the weight of the
                                                    evidence from the
                                                    other toxicity
                                                    studies indicates no
                                                    evidence of concern.
------------------------------------------------------------------------

[[Page 28390]]

 
870.7485                        Metabolism and     Absorbed rapidly and
                                 pharmacokinetics   extensively, widely
                                 - rat              distributed,
                                                    followed byvery
                                                    rapid elimination,
                                                    mostly in urine.
                                                    Highest tissue
                                                    concentrations in
                                                    skeletal muscle: 10-
                                                    15% of administered
                                                    dose. Half life
                                                    times from tissues
                                                    ranged from 2-6
                                                    hours. Tissue
                                                    residues after 7
                                                    days extremely low.
                                                    Approximately 84-95%
                                                    of administered dose
                                                    excreted in urine
                                                    and 2.5-6% excreted
                                                    in feces within 24
                                                    hours. Greater than
                                                    0.2% detected in
                                                    expired air. Most
                                                    excreted as
                                                    unchanged parent: 70-
                                                    80% of dose. The
                                                    major
                                                    biotransformation
                                                    reaction is cleavage
                                                    of oxadiazine ring
                                                    to corresponding
                                                    nitroguanidine
                                                    compound. Minor
                                                    pathways: (1)
                                                    cleavage of
                                                    nitroguanidine group
                                                    yielding guanidine
                                                    derivative, (2)
                                                    hydrolysis of
                                                    guanidine group to
                                                    corresponding urea,
                                                    (3) demethylation of
                                                    guanidine group, and
                                                    (4) substitution of
                                                    the chlorine of the
                                                    thiazole ring by
                                                    glutathione.
                                                    Cleavage between
                                                    thiazole- and
                                                    oxadiazine ring
                                                    occurs to a small
                                                    extent. Glutathione
                                                    derivatives prone to
                                                    further degradation
                                                    of the glutathione
                                                    moiety resulting in
                                                    various sulfur-
                                                    containing
                                                    metabolites (e.g.
                                                    mercapturates,
                                                    sulfides, and
                                                    sulfoxides). Both
                                                    the thiazole and
                                                    oxadiazine moiety
                                                    susceptible to
                                                    oxidative attack.
                                                    Small but measurable
                                                    amounts exhaled,
                                                    most probably as
                                                    CO2. Metabolites
                                                    eliminated very
                                                    rapidly.
                                                    Enterohepatic
                                                    circulation
                                                    negligible.
------------------------------------------------------------------------
870.7485                        Metabolism and     Approximately 72% of
                                 pharmacokinetics   administered dose
                                 - mouse            excreted in the
                                                    urine;19% excreted
                                                    in feces. Small but
                                                    measurable amount
                                                    detected in expired
                                                    air(approximately
                                                    0.2% of dose).
                                                   Predominant
                                                    metabolites:
                                                    unchanged parent (33-
                                                    41% of administered
                                                    dose; 2 other
                                                    metabolites: 8-12%
                                                    and 9-18% of
                                                    administered dose.
                                                    These are the same
                                                    structures that were
                                                    most commonly
                                                    observed in rat
                                                    excreta, however the
                                                    proportions are
                                                    quite different in
                                                    mouse excreta. One
                                                    additional
                                                    significant
                                                    metabolite (mouse
                                                    R6) was isolated
                                                    from feces samples.
                                                    Between 30-60% of
                                                    the administered
                                                    dose was excreted as
                                                    metabolites.
------------------------------------------------------------------------
870.7600                        Dermal             Estimates of dermal
                                 penetration -      absorption were
                                 rat                based on the sum
                                                    ofradioactivity in
                                                    skin test site,
                                                    urine, feces, blood,
                                                    and carcass.
                                                    Percentage dermal
                                                    absorption is 27.0,
                                                    highest mean dermal
                                                    absorption value
                                                    across all groups.
                                                    This value is
                                                    considered to
                                                    represent the
                                                    potential cumulative
                                                    dermal absorption of
                                                    test material that
                                                    might occur after a
                                                    10 hour dermal
                                                    exposure. As the
                                                    study design did not
                                                    permit analysis of
                                                    the fate of skin
                                                    bound residues,
                                                    residues at skin
                                                    site were included
                                                    in determination of
                                                    dermal absorption.
------------------------------------------------------------------------
Hepatic cell                    proliferation      NOAEL = 16 (males),
                                 study - mouse      20 (females) mg/kg/
                                                    day
                                                   LOAEL = 72 (males),
                                                    87 (females) mg/kg/
                                                    day based on
                                                    proliferative
                                                    activity of
                                                    hepatocytes. At
                                                    higher dose levels,
                                                    increases in
                                                    absolute and
                                                    relative liver wts,
                                                    speckled liver,
                                                    hepatocellular
                                                    glycogenesis/fatty
                                                    change,
                                                    hepatocellular
                                                    necrosis, apoptosis
                                                    and pigmentation
                                                    were observed.
------------------------------------------------------------------------
Replicative DNA synthesis       28-day feeding     NOAEL = 711 mg/kg/day
                                 study - male rat   (highest dose
                                                    tested)
                                                   LOAEL = not
                                                    established.
                                                    Immunohistochemical
                                                    staining of liver
                                                    sections from
                                                    control and high-
                                                    dose animals for
                                                    proliferating cell
                                                    nuclear antigen gave
                                                    no indication for a
                                                    treatment-related
                                                    increase in the
                                                    fraction of DNA
                                                    synthesizing
                                                    hepatocytes in S-
                                                    phase. CGA 293343
                                                    did not stimulate
                                                    hepatocyte cell
                                                    proliferation in
                                                    male rats.
------------------------------------------------------------------------
Special study to assess liver                      NOAEL = 17 (males),
 biochemistry in mouse                              20 (females) mg/kg/
                                                    day
                                                   LOAEL = 74 (males),
                                                    92 (females) mg/kg/
                                                    day based on
                                                    marginal to slight
                                                    increases in
                                                    absolute and
                                                    relative liver
                                                    weights, a slight
                                                    increase in the
                                                    microsomal protein
                                                    content of the
                                                    livers, moderate
                                                    increases in the
                                                    cytochrome P450
                                                    content, slight to
                                                    moderate increases
                                                    in the activity of
                                                    several microsomal
                                                    enzymes, slight to
                                                    moderate induction
                                                    of cytosolic
                                                    glutathione S-
                                                    transferase
                                                    activity. Treatment
                                                    did not affect
                                                    peroxisomal fatty
                                                    acid <greek-b>-
                                                    oxidation.
------------------------------------------------------------------------


[[Page 28391]]

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 
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 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 Safety Factor.
    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.
    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<SUP>-</SUP>\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 (MOE<INF>cancer</INF> = point of 
departure/exposures) is calculated. A summary of the toxicological 
endpoints for thiamethoxam used for human risk assessment is shown in 
the following Table 2:

     Table 2.--Summary of Toxicological Dose and Endpoints for Thiamethoxam for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                            FQPA SF\*\ and
        Exposure Scenario            Dose Used in Risk     Level of Concern     Study and Toxicological Effects
                                      Assessment, UF     for Risk Assessment
----------------------------------------------------------------------------------------------------------------
Acute Dietary general population   NOAEL = 100 mg/kg/    FQPA SF = 10; aPAD   Acute mammalian neurotoxicity
 including infantsand children      day; UF = 100;        = acute RfD/FQPA     study in the rat
                                    Acute RfD = 1 mg/kg/  SF = 0.1 mg/kg/day
                                    day
                                                                              LOAEL = 500 mg/kg/day based on
                                                                               treatment-related
                                                                               neurobehavioraleffects observed
                                                                               in the FOB and LMA testing
                                                                               (drooped palpebral
                                                                               closure,decreased rectal
                                                                               temperature and locomotor
                                                                               activity, increased forelimbgrip
                                                                               strength)
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations    NOAEL = 0.6 mg/kg/    FQPA SF = 10; cPAD   2-Generation reproduction study
                                    day; UF = 100;        = chronic RfD/FQPA
                                    Chronic RfD = 0.006   SF = 0.0006 mg/kg/
                                    mg/kg/day             day
                                                                              LOAEL = 1.8 mg/kg/day based on
                                                                               increased incidence and severity
                                                                               oftubular atrophy in testes of F1
                                                                               generation males.
----------------------------------------------------------------------------------------------------------------
Oral Nondietary (all durations)    NOAEL = 0.6 mg/kg/    LOC for MOE = 1,000  2-Generation reproduction study
                                    day                   (Residential)
                                                                              LOAEL = 1.8 mg/kg/day based on
                                                                               increased incidence and severity
                                                                               of tubular atrophy in testes of
                                                                               F1 generation males.
----------------------------------------------------------------------------------------------------------------
Dermal (all durations)             Oral study NOAEL=     LOC for MOE = 1,000  2-Generation reproduction study
 (Residential)                      0.6 mg/kg/day         (Residential)
                                    (dermal
                                    absorptionrate =
                                    27%)
                                                         LOC for MOE = 100    LOAEL = 1.8 mg/kg/day based on
                                                          (Occupational)       increased incidence and severity
                                                                               of tubular atrophy in testes of
                                                                               F1 generation males.
----------------------------------------------------------------------------------------------------------------
Inhalation (all durations)         Oral study NOAEL =    LOC for MOE = 1,000  2-Generation reproduction study
 (Residential)                      0.6 mg/kg/day         (Residential)
                                    (inhalation
                                    absorption rate
                                    =100%)
                                                         LOC for MOE = 100    LOAEL = 1.8 mg/kg/day based on
                                                          (Occupational)       increased incidence and severity
                                                                               oftubular atrophy in testes of F1
                                                                               generation males.
----------------------------------------------------------------------------------------------------------------

[[Page 28392]]

 
Cancer (oral, dermal, inhalation)  Q1* (mg/kg/day)<SUP>-</SUP>\1\   Greater than 1 x 10<SUP>-</SUP> Likely carcinogen for humans based
                                    is 3.77 x 10<SUP>-</SUP>\2\      \6\                  on increased incidenceof
                                                                               hepatocellular adenomas and
                                                                               carcinomas in male and female
                                                                               mice.Quantification of risk based
                                                                               on most potent unit risk: male
                                                                               mouse liveradenoma and/or
                                                                               carcinoma combined tumor rate.
                                                                               The upper bound estimateof unit
                                                                               risk, Q1* (mg/kg/day)<SUP>-</SUP>\1\ is 3.77
                                                                               x 10<SUP>-</SUP>\2\ in human equivalents.
----------------------------------------------------------------------------------------------------------------
\*\ The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns
  unique to the FQPA.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Tolerances have been 
established (40 CFR 180.565) for the combined residues of thiamethoxam 
and its metabolite, in or on a variety of raw agricultural commodities. 
The following raw agricultural commodities have established tolerances: 
barley, canola, cotton, sorghum, wheat, milk, and the meat and meat 
byproducts of cattle, goats, horses, and sheep. Risk assessments were 
conducted by EPA to assess dietary exposures from thiamethoxam 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<Register>) analysis evaluated the individual food consumption as 
reported by respondents in the 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 exposure assessments: tolerence level residues and 100% 
crop treated.
    ii. Chronic exposure.In conducting this chronic dietary risk 
assessment the DEEM<Register> 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: 
percent crop treated (based on projected market shares) and anticipated 
residues (Tier 3).
    iii. Cancer. The dietary exposure for determining cancer risk is 
based on the chronic exposure explained in the previous paragraph using 
the same assumptions.
    Section 408(b)(2)(E) 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. If EPA relies on such information, EPA must require 
that data be provided 5 years after the tolerance is established, 
modified, or left in effect, demonstrating that the levels in food are 
not above the levels anticipated. Following the initial data 
submission, EPA is authorized to require similar data on a time frame 
it deems appropriate. As required by section 408(b)(2)(E), 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) 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 percent crop 
treated (PCT) as required by section 408(b)(2)(F), EPA may require 
registrants to submit data on PCT.
    The Agency used percent crop treated (PCT information as follows in 
Table 3:

    Table 3.--Thiamethoxam Uses and Estimates of Percent Crop Treated
------------------------------------------------------------------------
                      Crop                         Percent Crop Treated
------------------------------------------------------------------------
Tuberous and Corm Vegetables - Crop Subgroup 1                         9
 C.............................................
Fruiting Vegetables (Except Cucurbits - Crop                          15
 Group 8.......................................
Cucumbers......................................                        5
Melons.........................................                       13
Casabas........................................                       44
Crenshaws......................................                       44
Squash.........................................                       44
Pumpkin........................................                       44
Apples.........................................                    15-20
Crabapples.....................................                       53
Pears..........................................                        9
Quinces........................................                       53
Loquats........................................                       53
------------------------------------------------------------------------


[[Page 28393]]

    The Agency used information provided by the registrant to determine 
percent crop treated based on projected percent market share 
information. The Agency believes that the procedures used were the best 
available, because thiamethoxam is a new chemical and has never been 
used. 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 regional populations.
    2. Dietary exposure from drinking water. The Agency lacks 
sufficient monitoring exposure data to complete a comprehensive dietary 
exposure analysis and risk assessment for thiamethoxam in drinking 
water. Because the Agency does not have comprehensive monitoring data, 
drinking water concentration estimates are made by reliance on 
simulation or modeling taking into account data on the physical 
characteristics of thiamethoxam.
    The Agency uses the Generic Estimated Environmental Concentration 
(GENEEC) or the Pesticide Root Zone/Exposure Analysis Modeling System 
(PRZM/EXAMS) to estimate pesticide concentrations in surface water and 
SCI-GROW, which predicts pesticide concentrations in groundwater. In 
general, EPA will use GENEEC (a tier 1 model) before using PRZM/EXAMS 
(a tier 2 model) for a screening-level assessment for surface water. 
The GENEEC model is a subset of the PRZM/EXAMS model that uses a 
specific high-end runoff scenario for pesticides. GENEEC incorporates a 
farm pond scenario, while PRZM/EXAMS incorporate an index reservoir 
environment in place of the previous pond scenario. The PRZM/EXAMS 
model includes a percent crop area factor as an adjustment to account 
for the maximum percent crop coverage within a watershed or drainage 
basin.
    None of these models include consideration of the impact processing 
(mixing, dilution, or treatment) of raw water for distribution as 
drinking water would likely have on the removal of pesticides from the 
source water. The primary use of these models by the Agency at this 
stage is to provide a coarse screen for sorting out pesticides for 
which it is highly unlikely that drinking water concentrations would 
ever exceed human health levels of concern.
    Since the models used are considered to be screening tools in the 
risk assessment process, the Agency does not use estimated 
environmental concentrations (EECs) from these models to quantify 
drinking water exposure and risk as a %RfD or %PAD. Instead, drinking 
water levels of comparison (DWLOCs) are calculated and used as a point 
of comparison against the model estimates of a pesticide's 
concentration in water. DWLOCs are theoretical upper limits on a 
pesticide's concentration in drinking water in light of total aggregate 
exposure to a pesticide in food, and from residential uses. Since 
DWLOCs address total aggregate exposure to thiamethoxam they are 
further discussed in the aggregate risk sections below.
    Based on the PRZM/EXAMS and SCI-GROW models the estimated 
environmental concentrations (EECs) of thiamethoxam for acute exposures 
are estimated to be 8.0 parts per billion (ppb) for surface water and 
1.94 ppb for ground water. The EECs for chronic exposures are estimated 
to be 0.6 ppb for surface water, and 1.94 ppb for ground water.
    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).
    Thiamethoxam is not registered for use on any sites that would 
result in residential exposure. Although such uses have been requested, 
they are not being assessed at this time.
    4. Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) 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 thiamethoxam 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, 
thiamethoxam 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 thiamethoxam 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. Safety factor for infants and children--i. In general. FFDCA 
section 408 provides that EPA shall apply an additional tenfold 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 
database 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 margin of exposure (MOE) analysis or through 
using uncertainty (safety) factors in calculating a dose level that 
poses no appreciable risk to humans.
    ii. Prenatal and postnatal sensitivity. The developmental toxicity 
studies indicated no quantitative or qualitative evidence of increased 
susceptibility of rat or rabbit fetus to in utero exposure based on the 
fact that the developmental NOAELs are either higher than or equal to 
the maternal NOAELs. However, the reproductive studies indicate effects 
in male rats in the form of increased incidence and severity of 
testicular tubular atrophy. These data are considered to be evidence of 
increased quantitative susceptibility for male pups when compared to 
the parents.
    iii. Conclusion. Based on: (a) effects on endocrine organs observed 
across species; (b) the significant decrease in alanine amino 
transferase levels in the companion animal studies and in the dog 
studies; (c) the mode of action of this chemical in insects (interferes 
with the nicotinic acetyl choline receptors of the insect's nervous 
system) thus a developmental neurotoxicity study is required; (d) the 
transient clinical signs of neurotoxicity in several studies across 
species; and (e) the suggestive evidence of increased quantitative 
susceptibility in the rat reproduction study, the Agency is retaining 
the FQPA factor which is l0X.

E. Aggregate Risks and Determination of Safety

    To estimate total aggregate exposure to a pesticide from food, 
drinking water, and residential uses, the Agency

[[Page 28394]]

calculates DWLOCs which are used as a point of comparison against the 
model estimates of a pesticide's concentration in water (EECs). DWLOC 
values are not regulatory standards for drinking water. DWLOCs are 
theoretical upper limits on a pesticide's concentration in drinking 
water in light of total aggregate exposure to a pesticide in food and 
residential uses. In calculating a DWLOC, the Agency determines how 
much of the acceptable exposure (i.e., the PAD) is available for 
exposure through drinking water e.g., allowable chronic water exposure 
(mg/kg/day) = cPAD - (average food + residential exposure). This 
allowable exposure through drinking water is used to calculate a DWLOC.
    A DWLOC will vary depending on the toxic endpoint, drinking water 
consumption, and body weights. Default body weights and consumption 
values as used by the USEPA Office of Water are used to calculate 
DWLOCs: 2L/70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg 
(child). Default body weights and drinking water consumption values 
vary on an individual basis. This variation will be taken into account 
in more refined screening-level and quantitative drinking water 
exposure assessments. Different populations will have different DWLOCs. 
Generally, a DWLOC is calculated for each type of risk assessment used: 
acute, short-term, intermediate-term, chronic, and cancer.
    When EECs for surface water and groundwater are less than the 
calculated DWLOCs, the Office of Pesticide Programs (OPP) concludes 
with reasonable certainty that exposures to the pesticide in drinking 
water (when considered along with other sources of exposure for which 
OPP has reliable data) would not result in unacceptable levels of 
aggregate human health risk at this time. Because OPP considers the 
aggregate risk resulting from multiple exposure pathways associated 
with a pesticide's uses, levels of comparison in drinking water may 
vary as those uses change. If new uses are added in the future, OPP 
will reassess the potential impacts of residues of the pesticide in 
drinking water as a part of the aggregate risk assessment process.
    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food to 
thiamethoxam will occupy 3% of the aPAD for the U.S. population, 2% of 
the aPAD for females 13-50 years old, 8% of the aPAD for all infants 
less than 1 year old and 7% of the aPAD for children 1-6 years old. In 
addition, there is potential for acute dietary exposure to thiamethoxam 
in drinking water. The surface water EEC is 8.0 <greek-m>g/L and the 
ground water EEC is 1.94 <greek-m>g/L. Since the surface water value is 
greater than the ground water value, the surface water value will be 
used for comparison purposes and will protect for any concerns for 
ground water concentrations. After calculating DWLOCs and comparing 
them to the EECs for surface water, EPA does not expect the aggregate 
exposure to exceed 100% of the aPAD.

                     Table 4.--Aggregate Risk Assessment for Acute Exposure to Thiamethoxam
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
             Population Subgroup\a\              aPAD(mg/kg)     %aPAD      Water DWEC     Water     Acute DWLOC
                                                                 (Food)       (ppb)      DWEC(ppb)     (ppb)\b\
----------------------------------------------------------------------------------------------------------------
U.S. General Population                                  0.1            3            8         1.94        3,400
All infants (< 1 year)                                   0.1            8            8         1.94          920
Children (1-6 years)                                     0.1            7            8         1.94          930
Children (7-12 years)                                    0.1            4            8         1.94          960
Females (13-50 years)                                    0.1            2            8         1.94        2,900
----------------------------------------------------------------------------------------------------------------
\a\Population subgroups shown include the U.S. general population and the maximally exposed subpopulation of
  adults, infants and children, and women of child-bearing age for each exposure scenario.
\b\DWLOC = Maximum Water Exposure (mg/kg/day) -- 1,000 <greek-m>g/mg -- body weight (70 kg general population/
  males 13+, 60 kg females 13+, 10 kg infants and children) <divide> Water Consumption (2 L/day adults, 1 L/day
  infants and children). Maximum water exposure = aPAD - dietary exposure (mg/kg/day)

    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
thiamethoxam from food will utilize 5% of the cPAD for the U.S. 
population, 13% of the cPAD for all infants < 1 year old and 13% of the 
cPAD for children 1-6 years old. Proposed residential uses are not 
being addressed in this risk assessment. In addition to chronic dietary 
exposure, there is potential for chronic dietary exposure to 
thiamethoxam in drinking water. The surface water EEC is 0.6 
<greek-m>g/L and the groundwater EEC is 1.94 <greek-m>g/L. Since the 
groundwater value is greater than the surface water value, the 
groundwater value will be used for comparison purposes and will protect 
for any concerns for surface water concentrations. After calculating 
the DWLOCs and comparing them to the EECs for groundwater, EPA does not 
expect the aggregate exposure to exceed 100% of the cPAD.

              Table 5.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Thiamethoxam
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                cPAD mg/kg/  cPAD (Food)   Water DWEC   Water DWEC  DWLOC (ppb)
                                                     day                      (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population                                       0.0006            5          0.6         1.94           20
All infants (< 1 year)                                0.0006           13          0.6         1.94          5.2
Children (1-6 years)                                  0.0006           13          0.6         1.94          5.2
Children (7-12 years)                                 0.0006            7          0.6         1.94          5.6
Females (13-50 years)                                 0.0006            3          0.6         1.94           17
----------------------------------------------------------------------------------------------------------------


[[Page 28395]]

    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). Thiamethoxam is not 
registered for use on any sites that would result in residential 
exposure. Therefore, the aggregate risk is the sum of the risk from 
food and water, which does not exceed the Agency's level of concern.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level). Thiamethoxam 
is not registered for use on any sites that would result in residential 
exposure. Therefore, the aggregate risk is the sum of the risk from 
food and water, which does not exceed the Agency's level of concern.
    5. Aggregate cancer risk for U.S. population. The cancer aggregate 
dietary risk estimate was calculated in two ways, one using the 
Agency's 20% estimated market share for apples and the other using a 5% 
estimated market share for apples (as indicated by the registrant). The 
dietary (food only) cancer risk is either 1.0 x 10<SUP>-</SUP>\6\ or 
0.70 x 10<SUP>-</SUP>\6\ with the 20% or 5% estimated market share for 
apples, respectively. With the 20% market share, it is not possible to 
estimate a DWLOC for cancer based on an assumed negligible risk value 
of 1.0 x 10<SUP>-</SUP>\6\. Using the latter with 5% market share for 
apples, the DWLOC is extremely low (0.23 ppb). Therefore, for risk 
management purposes, an assumed negligible risk value of 3.0 x 
10<SUP>-</SUP>\6\ will be used to estimate the DWLOC for cancer. The 
DWLOC for cancer aggregate risk (no residential uses) is calculated 
using the following equations:
    DWLOC<INF>cancer</INF>(<greek-m>g/L) = chronic water 
exposure(mg/kg/day) x (body weight (kg))/consumption (L) x 
10<SUP>-</SUP>\3\ mg/<greek-m>g

    chronic water exposure (mg/kg/day)=negligible risk/Q* - chronic 
food exposure(mg/kg/day)

    Assuming a risk value of 3 x 10<SUP>-</SUP>\6\, (which is generally 
considered to be within the range of 10<SUP>-</SUP>\6\, the risk value 
considered to represent a negligible cancer risk), for the 20% market 
share for apples, the chronic water exposure value is estimated to be:
    3 x 10<SUP>-</SUP>\6\/3.77 x 10<SUP>-</SUP>\2\ - 0.000027 = 
0.0000525 mg/kg/day

    The DWLOC<INF>cancer</INF> = 0.0000525 mg/kg/day x 70 kg/2L x 
10<SUP>-</SUP>\3\ mg/<greek-m>g = 1.8 <greek-m>g/L

    Using the same equation, for the 5% estimated market share for 
apples, the DWLOC<INF>cancer</INF> = 2.1 <greek-m>g/L.
    The surface water EEC is 0.6 <greek-m>g/L and the ground water EEC 
is 1.94 <greek-m>g/L. Since the ground water value is greater than the 
surface water value it will be used for comparison purposes and will 
protect for any concerns for surface water concentrations. The 
estimated chronic ground water value for thiamethoxam (1.94 <greek-m>g/
L) is greater than the DWLOC<INF>cancer</INF> for the general 
population using the 20% market share for apples. Using the 5% market 
share, the DWLOC<INF>cancer</INF> is less than the Agency's level of 
concern.
    The Agency used a screening level model designed to estimate 
pesticide concentrations in shallow groundwater. Although the 20% 
market share for apples results in EECs that are marginally above the 
DWLOC<INF>cancer</INF>, a number of factors lead EPA to believe that 
the actual lifetime exposure through drinking water will be less than 
the DWLOC<INF>cancer</INF>. These reasons are as follows:
    i. Thiamethoxam is systemic. EPA's Tier 1 groundwater model assumes 
that all of the product that is applied to the crop is available for 
runoff. The registrant has submitted data to show that a percentage 
(15-25%) of the product is absorbed by the plant, resulting in that 
much less product available to leach into groundwater. Although the 
registrant has submitted data on only 2 crops, beans and cucumbers, it 
is likely that the total amount of thiamethoxam that is available to 
leach into groundwater is less than the amount EPA uses as an input 
into its model. Due to a limited data on the amount absorbed, EPA is 
unable to quantify this.
    ii. Although the Agency model is based on aerobic soil half lives, 
EPA's risk assessment for cancer estimate is for lifetime exposure. 
Data indicate the anaerobic aquatic half life for thiamethoxam is 
shorter than the aerobic soil half life and longer than the aerobic 
aquatic half life. Although EPA is unable to predict with a high degree 
of certainty about what happens to thiamethoxam over time in 
groundwater, this does provide some support for an expectation that 
concentrations in groundwater will decline between annual applications.
    iii. Shallow groundwater modeling is not the perfect model for 
representing all drinking water from ground water sources. It is likely 
to be an overestimate of most drinking water, which tends to originate 
from deeper sources. EPA's experience is that the model is reasonably 
accurate for shallow drinking water, but the Agency believes that it is 
less accurate for drinking water from deeper sources.
    iv. Currently there is no exposure to thiamethoxam through drinking 
water. The Agency is establishing conditions of registration for the 
subject uses of this document which will include two prospective ground 
water studies and a retrospective monitoring study, so that the 
reasonable certainty of no harm finding will be sustained.
    v. The cancer risk from the food uses alone is 1.0 x 
10<SUP>-</SUP>\6\. The dietary risk is based on residue data derived 
from the average of field trials, which were performed at a higher 
applied on rate than were accepted by the EPA. It is not unusual in the 
Agency's experience for field trial data to be an order of magnitude 
above actual monitoring. Since thiamethoxam is not registered (for uses 
other than very recently registered seed treatments), actual monitoring 
data is not available. It is likely that the actual risk contribution 
from food will be much lower than current data indicate, which would 
result in a larger DWLOC<INF>cancer</INF>. EPA expects that this 
refined DWLOC<INF>cancer</INF> would be larger than the EECs for the 
proposed uses.
    Thus, EPA does not expect that the general population would be 
exposed to levels exceeding the DWLOC<INF>cancer</INF> over a lifetime.
    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 thiamethoxam residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (HPLC/UV or MS) is available to 
enforce the tolerance expression. The method may be requested from: 
Calvin Furlow, PIRIB, IRSD (7502C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW, 
Washington, DC 20460; telephone number: (703) 305-5229; e-mail address: 
<a href="/cdn-cgi/l/email-protection#cfa9babda3a0b8e1acaea3b9a6a18faabfaee1a8a0b9"><span class="__cf_email__" data-cfemail="660013140a09114805070a100f082603160748010910">[email protected]</span></a>.

B. International Residue Limits

    There are no international residue limits for thiamethoxam.

C. Conditions

    Registration of the proposed uses will include the requirement for 
two prospective groundwater studies, as well as monitoring of drinking 
water in a number of states selected for high cropping density and 
vulnerable soils.

V. Conclusion

    Therefore, the tolerances are established for combined residues of

[[Page 28396]]

 thiamethoxam, 3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-
nitro-4H-1,3,5-oxadiazin-4-imine) and its metabolite (N-(2-chloro-
thiazol-5-ylmethyl)-N 'methyl-N ''-nitro-guanidine, in or on tuberous 
and corm vegetables crop subgroup at 0.02 ppm, fruiting vegetables crop 
group at 0.25 ppm, tomato paste at 0.80 ppm, cucurbit vegetables crop 
group at 0.20 ppm, and pome fruits crop group at 0.20 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 of 1996, EPA will continue to use those 
procedures, with appropriate adjustments, until the necessary 
modifications can be made. The new section 408(g) 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), as was provided in the old FFDCA sections 408 and 409. 
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 control number OPP-301132 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 July 23, 
2001.
    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 (1900), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460. You may also deliver your request to the Office 
of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St., SW., 
Washington, DC 20460. 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 (202) 260-4865.
    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 <a href="/cdn-cgi/l/email-protection#a9ddc6c4d9c2c0c7da87c3c0c4e9ccd9c887cec6df"><span class="__cf_email__" data-cfemail="f3879c9e83989a9d80dd999a9eb3968392dd949c85">[email protected]</span></a>, 
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.
    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.
    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 control number OPP-301132, 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. 
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: <a href="/cdn-cgi/l/email-protection#721d02025f161d11191706321702135c151d04"><span class="__cf_email__" data-cfemail="7a150a0a571e1519111f0e3a1f0a1b541d150c">[email protected]</span></a>. 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 FFDCA section 408(d) 
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). 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 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 other 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

[[Page 28397]]

tolerances and exemptions that are established on the basis of a 
petition under FFDCA section 408(d), 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 FFDCA section 408(n)(4). 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 (65 FR 67249, 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 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:May 14, 2001.
James Jones,
Director, Registration Division, 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 180.565 is amended by alphabetically adding commodities 
to the table in paragraph (a) to read as follows:


Sec. 180.565  Thiamethoxam; tolerances for resdues.

    (a) General. * * *

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
                   *      *      *      *      *
Cucurbit Vegetables Crop Group.............................          0.2
Fruiting Vegetables Crop Group.............................         0.25
                   *      *      *      *      *
Pome Fruit Crop Group......................................          0.2
                   *      *      *      *      *
Tomato Paste...............................................         0.80
Tuberous and Corm Vegetables Crop Subgroup.................         0.02
                   *      *      *      *      *
------------------------------------------------------------------------

* * * * *
[FR Doc. 01-12899 Filed 5-22-01; 8:45 am]
BILLING CODE 6560-50-S


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