[Federal Register Volume 65, Number 246 (Thursday, December 21, 2000)]
[Rules and Regulations]
[Pages 80343-80353]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-32570]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301087; FRL-6758-1]
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 barley, canola, cotton, 
sorghum, wheat, milk, and the meat and meat byproducts of cattle, 
goats, hogs, horses, and sheep. Novartis Crop Protection, Inc. 
requested this tolerance under the Federal Food, Drug, and Cosmetic 
Act, as amended by the Food Quality Protection Act of 1996.

DATES: This regulation is effective December 21, 2000. Objections and 
requests hearings, identified by docket control number OPP-301087, must 
be received by EPA on or before February 20, 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-301087 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: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

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

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

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

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'', ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/. To access the OPPTS Harmonized 
Guidelines referenced in this document, go directly to the guidelines 
at http://www.epa.gov/opptsfrs/home/guidelin.htm.

[[Page 80344]]

    2. In person. The Agency has established an official record for 
this action under docket control number OPP-301087. 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 24153) (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 (9F5046 and 9F5051) for tolerance by 
Novartis Crop Protection, P. O. Box 18300 Greensboro, NC 27419-8300. 
This notice included a summary of the petition prepared by Novartis 
Crop Protection, the registrant. There were no comments received in 
response to the notice of filing.
    The petitions requested that 40 CFR part 180 be amended by 
establishing tolerances for the 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 CGA-322704 metabolite (N-(2-
chloro-thiazol-5-ylmethyl)--N'-methylN'-nitro-guanidine) in or on the 
raw agricultural commodity rapeseed (canola), tuberous and corm 
vegetables crop subgroup, barley grain, sorghum grain, sorghum forage, 
sorghum stover, wheat grain, wheat hay, wheat straw, and milk at 0.02 
ppm; barley straw at 0.03 ppm; barley hay at 0.05 ppm; undelinted 
cottonseed at 0.10 ppm; cucurbit vegetables crop group, and pome fruit 
crop group at 0.20 ppm; fruiting vegetables crop group at 0.25 ppm; 
wheat forage at 0.50 ppm; tomato paste at 0.80 ppm; head and stem 
Brassica vegetables crop subgroup at 1.00 ppm; cotton gin byproducts at 
1.50 ppm; leafy vegetables crop group, and leafy Brassica greens crop 
subgroup at 2.00 parts per million (ppm). In addition, meat of cattle, 
goats, hogs, horses, and sheep at 0.02 ppm and meat byproducts of 
cattle, goats, hogs, horses, and sheep at 0.02 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 tolerances for the combined residues of thiamethoxam and 
its metabolite in or on barley grain at 0.02 ppm; barley hay at 0.05 
ppm; barley straw at 0.03 ppm; undelinted cottonseed at 0.10 ppm; 
cotton gin byproducts at 1.5 ppm; sorghum forage at 0.02 ppm; sorghum 
grain at 0.02 ppm; sorghum stover at 0.02 ppm; wheat forage at 0.50 
ppm; wheat grain at 0.02 ppm; wheat hay at 0.02 ppm; wheat straw at 
0.02 ppm; milk at 0.02 ppm; meat of cattle, goats, hogs, horses, and 
sheep at 0.02 ppm; meat byproducts of cattle, goats, hogs, horses, and 
sheep at 0.02 ppm respectively. EPA's assessment of exposures and risks 
associated with establishing the tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by 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.

            Table 1.--Subchronic, Chronic and Other Toxicity
------------------------------------------------------------------------
         Guideline No.               Study Type            Results
------------------------------------------------------------------------
870.3100                         90-Day oral         NOAEL = 1.74
                                  toxicity - rat      (males), 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.
------------------------------------------------------------------------

[[Page 80345]]

 
870.3100                         90-Day oral         NOAEL = 1.41
                                  toxicity - mouse    (males), 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 body weight and
                                                      body weight 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
                                  toxicity - dog      (males), 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 occurrence of
                                                      spermatic giant
                                                      cells in testes
                                                      (males).
------------------------------------------------------------------------
870.3200                         28-Day dermal       NOAEL = 250
                                  toxicity - rat      (males), 60
                                                      (females) mg/kg/
                                                      day LOAEL = 1,000
                                                      (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 LOAEL =
                                  rat                 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 an
                                                      increased
                                                      incidence of
                                                      skeletal
                                                      anomalies.
------------------------------------------------------------------------
870.3700b                        Prenatal            Maternal NOAEL = 50
                                  developmental -     mg/kg/day LOAEL =
                                  rabbit              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 effects   NOAEL = 1.84
                                  - 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
                                  dog                 (males), 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
                                  mouse               (males), 3.68
                                                      (females) mg/kg/
                                                      day 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.
------------------------------------------------------------------------

[[Page 80346]]

 
870.4300                         Combined chronic    NOAEL = 21.0
                                  carcinogenicity -   (males), 50.3
                                  rat                 (females) mg/kg/
                                                      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 870.5265                Gene mutation in    No evidence of gene
                                  S. typhimurium      mutation when
                                  and E. coli         tested up to 5,000
                                                      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
                                                      g/plate.
                                                      The S9 fraction
                                                      was from non-
                                                      induced mouse
                                                      liver, Aroclor
                                                      1,254 induced
                                                      mouse liver, 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
                                  V79 cells at        tested up to
                                  HGPRT locus         solubility limit.
------------------------------------------------------------------------
870.5375                         CHO cell            No evidence of
                                  cytogenetics        chromosomal
                                                      aberrations when
                                                      tested up to
                                                      cytotoxic or
                                                      solubility limit
                                                      concentrations.
------------------------------------------------------------------------
870.5395                         In vivo mouse bone  Negative when
                                  marrow              tested up to
                                  micronucleus        levels of 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/
                                  neurotoxicity       day LOAEL = 500 mg/
                                  screening battery   kg/day based on
                                  - rat               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
                                  neurotoxicity       (males), 216.4
                                  screening battery   (females) mg/kg/
                                  - rat               day, both highest
                                                      dose 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.
------------------------------------------------------------------------
870.7485                         Metabolism and      Absorbed rapidly
                                  pharmacokinetics -  and extensively,
                                   rat                widely
                                                      distributed,
                                                      followed by very
                                                      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.
                                                      <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.
------------------------------------------------------------------------

[[Page 80347]]

 
870.7485                         Metabolism and      Approximately 72%
                                  pharmacokinetics -  of administered
                                   mouse              dose 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 penetration  Estimates of dermal
                                  - rat               absorption were
                                                      based on the sum
                                                      of radioactivity
                                                      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        NOAEL = 16 (males),
                                  proliferation       20 (females) mg/kg/
                                  study - mouse       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     NOAEL = 711 mg/kg/
                                  synthesis in 28-    day (highest dose
                                  day feeding study   tested) LOAEL =
                                  - male rat          not established.
                                                      Immunohistochemica
                                                      l staining o 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    NOAEL = 17 (males),
                                  assess liver        20 (females) mg/kg/
                                  biochemistry in     day LOAEL = 74
                                  mouse               (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 Beta-
                                                      oxidation.
------------------------------------------------------------------------

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 intraspecies 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 10-6 or one in a million). 
Under certain specific circumstances, MOE calculations will be used for 
the carcinogenic risk assessment. In this non-linear approach, a 
``point of departure'' is identified below which carcinogenic effects 
are not expected. The point of departure is typically a NOAEL based on 
an endpoint related to cancer effects though it may be a different 
value derived from the dose response curve. To estimate risk, a ratio 
of the point of departure to exposure (MOEcancer = point of 
departure/exposures) is calculated. A summary of the toxicological 
endpoints for thiamethoxam used for human risk

[[Page 80348]]

assessment is shown in the following Table 2:

    Table 2.--Summary of Toxicological Doses and Endpoints for Thiamethoxam for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                 FQPA SF* and Level of
          Exposure Scenario               Dose Used in Risk         Concern for Risk     Study and Toxicological
                                            Assessment, UF             Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary general population       NOAEL = 100 mg/kg/day    FQPA SF = 10 aPAD =      Acute mammalian
 including infants and children         UF = 100 Acute RfD = 1   acute RfD FQPA SF =      neurotoxicity study in
                                        mg/kg/day                0.1 mg/kg/day            the rat LOAEL = 500 mg/
                                                                                          kg/day based on
                                                                                          treatment-related
                                                                                          neurobehavioral
                                                                                          effects observed in
                                                                                          the FOB and LMA
                                                                                          testing (drooped
                                                                                          palpebral closure,
                                                                                          decreased rectal
                                                                                          temperature and
                                                                                          locomotor activity,
                                                                                          increased forelimb
                                                                                          grip strength)
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations        NOAEL= 0.6 mg/kg/day UF  FQPASF = 10 cPAD =       2-Generation
                                        = 100 Chronic RfD =      chronic RfD FQPA SF =    reproduction study
                                        0.006 mg/kg/day          0.0006 mg/kg/day         LOAEL = 1.8 mg/kg/day
                                                                                          based on increased
                                                                                          incidence and severity
                                                                                          of tubular atrophy in
                                                                                          testes of F1
                                                                                          generation males.
----------------------------------------------------------------------------------------------------------------
Oral Nondietary (all durations)        NOAEL= 0.6 mg/kg/day     LOC for MOE = 1,000      2-Generation
                                                                 (Residential)            reproduction study
                                                                                          LOAEL = 1.8 mg/kg/day
                                                                                          based on increased
                                                                                          incidence and severity
                                                                                          of tubular atrophy in
                                                                                          testes of F1
                                                                                          generation males.
----------------------------------------------------------------------------------------------------------------
Dermal (all durations) (Residential)   Oral study NOAEL= 0.6    LOC for MOE = 1,000      2-Generation
                                        mg/kg/day (dermal        (Residential) LOC for    reproduction study
                                        absorption rate = 27%)   MOE = 100                LOAEL = 1.8 mg/kg/day
                                                                 (Occupational)           based on increased
                                                                                          incidence and severity
                                                                                          of tubular atrophy in
                                                                                          testes of F1
                                                                                          generation males.
----------------------------------------------------------------------------------------------------------------
Inhalation (all durations)             Oralstudy NOAEL= 0.6 mg/ LOC for MOE = 1,000      2-Generation
 (Residential)                          kg/day                   (Residential) LOC for    reproduction study
                                        (inhalationabsorption    MOE = 100                LOAEL = 1.8 mg/kg/day
                                        rate = 100%)             (Occupational)           based on increased
                                                                                          incidence and severity
                                                                                          of tubular atrophy in
                                                                                          testes of F1
                                                                                          generation males.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)       Q1* (mg/kg/day)-1 is    greater than 1 x 10-6    Likely carcinogen for
                                        3.77 x 10-2                                       humans based on
                                                                                          increased incidence of
                                                                                          hepatocellular
                                                                                          adenomas and
                                                                                          carcinomas in male and
                                                                                          female mice.
                                                                                          Quantification of risk
                                                                                          based on most potent
                                                                                          unit risk: male mouse
                                                                                          liver adenoma and/or
                                                                                          carcinoma combined
                                                                                          tumor rate. The upper
                                                                                          bound estimate of unit
                                                                                          risk, Q1* (mg/kg/day)-
                                                                                          1 is 3.77 x 10-2 in
                                                                                          human equivalents.
----------------------------------------------------------------------------------------------------------------
*The reference to the FQPA Safety Factor re fers to any additional safety factor retained due to concerns unique
  to the FQPA.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. The dietary exposure 
is based on the combined residues of thiamethoxam and its metabolite in 
or on the following raw agricultural commodities: barley, canola, 
cotton, sorghum, wheat, milk, and the meat and meat byproducts of 
cattle, goats, hogs, horses, and sheep. Risk assessments were conducted 
by EPA to assess dietary exposures from thiamethoxam and its metabolite 
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)

[[Page 80349]]

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 Dietary Exposure Evaluation Model (DEEM) 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 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
------------------------------------------------------------------------
                                                          Percent Crop
                         Crop                               Treated
------------------------------------------------------------------------
Barley...............................................                1.0
Wheat................................................                  2
Canola...............................................                 55
Sorghum..............................................                  9
Cotton...............................................                 20
------------------------------------------------------------------------

    The Agency used information provided by the registrant and Agency 
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 
5.0 ppb for ground water. The EECs for chronic exposures are estimated 
to be 0.6 ppb for surface water and 5.0 ppb for ground water. These 
levels are extremely conservative, because they are based on foliar and 
seed treatment uses. These levels are anticipated to be much lower 
based on the seed treatment use alone.
    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).

[[Page 80350]]

    Thiamethoxam is not registered for use on any sites that would 
result in residential exposure.
    4. Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) 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 
data base on toxicity and exposure unless EPA determines that a 
different margin of safety will be safe for infants and children. 
Margins of safety are incorporated into EPA risk assessments either 
directly through use of a 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. There is not 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. The 
reproductive studies indicate effects in males 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. Base on: (1) Effects endocrine organs observed 
across species (2) the significant decrease in alanine amino 
transferadse levels in the companion animal studies and in the dog 
studies (3) 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); (4) the 
transient clinical signs of neurotoxicity in several studies across the 
species; and (5) the suggestive evidence of increased quantitative 
susceptibility in the rat reproduction study, the Agency is retaining 
the FQPA factor which is 10X.

E. Aggregate Risks and Determination of Safety

    To estimate total aggregate exposure to a pesticide from food, 
drinking water, and residential uses, the Agency 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, 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 1% of the aPAD for the U.S. population, <1 of 
the aPAD for females 13 years and older, 1% of the aPAD for all infants 
<1 year and 2% of the aPAD for children 1-6 years. In addition, there 
is potential for acute dietary exposure to thiamethoxam in drinking 
water. The surface water EEC is 8.0 g/L and the ground water 
EEC is 5.0 g/L. The estimated EEC levels are very 
conservative, because they are based on both foliar uses and seed 
treatment applications. 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, as shown in the following Table 4.

                     Table 4.--Aggregate Risk Assessment for Acute Exposure to Thiamethoxam
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroupa                aPAD (mg/      %aPAD      Water DWEC   Water DWEC  Acute DWLOC
                                                     kg)         (Food)       (ppb)        (ppb)        (ppb)b
----------------------------------------------------------------------------------------------------------------
U.S. General Population                                  0.1            1            8            5         3500
----------------------------------------------------------------------------------------------------------------

[[Page 80351]]

 
All infants (<1 year)                                    0.1            1            8            5          990
----------------------------------------------------------------------------------------------------------------
 Children (1-6 years)                                    0.1            2            8            5          980
----------------------------------------------------------------------------------------------------------------
Children (7-12 years)                                    0.1            1            8            5          990
----------------------------------------------------------------------------------------------------------------
Females (13-50 years)                                    0.1           <1            8            5         3000
----------------------------------------------------------------------------------------------------------------

    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 <1% of the cPAD for the U.S. 
population, <1% of the cPAD for all infants <1 year and 1% of the cPAD 
for children 1-6 years. 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 
g/L and the ground water EEC is 5.0 g/L. The 
estimated EEC levels are very conservative, because they are based on 
both foliar uses and seed treatment applications. Since the ground 
water value is greater than the surface water value, the ground water 
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 ground water, EPA does not expect 
the aggregate exposure to exceed 100% of the cPAD as shown in the 
following Table 5.

              Table 5.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Thiamethoxam
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
           Population Subgroup               cPAD mg/kg/day      %cPAD      Water DWEC   Water DWEC    Chronic
                                                                 (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population                                       0.0006            5          0.6            5           21
----------------------------------------------------------------------------------------------------------------
All infants (<1 year)                                 0.0006           13          0.6            5            6
----------------------------------------------------------------------------------------------------------------
Children (1-6 years)                                  0.0006           13          0.6            5            6
----------------------------------------------------------------------------------------------------------------
Children (7-12 years)                                 0.0006            7          0.6            5            6
----------------------------------------------------------------------------------------------------------------
Females (13-50 years)                                 0.0006            3          0.6            5           18
----------------------------------------------------------------------------------------------------------------

    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 do 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 do not exceed the Agency's level of concern.
    5. Aggregate cancer risk for U.S. population. The cancer risk 
estimate associated with the use of thiamethoxam as a seed treatment on 
barley, canola, cotton, sorghum and wheat is 4.1  x  10-8 
for the U.S. population based on an exposure estimate of 0.000001 mg/
kg/day. The above cancer risk estimates show that the cancer risk is 
negiligible. Based on modeling estimates, exposure through drinking 
water will not significantly increase the dietary risk in food.
    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, PRRIB, IRSD (7502C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW, 
Washington, DC 20460; telephone number: (703) 305-5229; e-mail address: 
[email protected].

B. International Residue Limits

    There are no international residue limits for thiamethoxam.

C. Conditions

    Developmental neurotoxicity (Guideline #870.6300) and soil residue 
dissipation (Guideline #875.2200) studies are required as conditions of 
registration.

V. Conclusion

    Therefore, the tolerance is established for combined residues of 
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 barley grain 
at 0.02 ppm; barley hay at 0.05 ppm; barley straw at 0.03 ppm; 
undelinted cottonseed at 0.10

[[Page 80352]]

ppm; cotton gin byproducts at 1.5 ppm; sorghum forage at 0.02 ppm; 
sorghum grain at 0.02 ppm; sorghum stover at 0.02 ppm; wheat forage at 
0.50 ppm; wheat grain at 0.02 ppm; wheat hay at 0.02 ppm; wheat straw 
at 0.02 ppm; milk at 0.02 ppm; meat of cattle, goats, hogs, horses, and 
sheep at 0.02 ppm; meat byproducts of cattle, goats, hogs, horses, and 
sheep at 0.02 ppm respectively.

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-301087 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 February 
20, 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 [email protected], 
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-301087, 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: [email protected]. 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 file format 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 prior consultation as specified by Executive Order 
13084, entitled Consultation and Coordination with Indian Tribal 
Governments (63 FR 27655, May 19, 1998); special considerations as 
required by Executive Order 12898, entitled Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations (59 FR 7629, February 16, 1994); or require OMB review or 
any Agency action under Executive Order 13045, entitled Protection of 
Children from Environmental Health Risks and Safety Risks (62 FR 19885, 
April 23, 1997). This action does not involve any technical standards 
that would require Agency consideration of voluntary

[[Page 80353]]

consensus standards pursuant to section 12(d) of the National 
Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law 
104-113, section 12(d) (15 U.S.C. 272 note). Since tolerances and 
exemptions that are established on the basis of a petition under 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).

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: December 1, 2000.

Joseph J. Merenda,

Acting Director, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180-- [AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:

    Authority: 21 U.S.C. 321(q), (346a) and 371.


    2. Section 180.565 is amended by adding text to paragraph (a) to 
read as follows:


Sec. 180.565  Thiamethoxam; tolerance for residues.

    (a) General. A tolerance is established for the combined residues 
of the insecticide thiamethoxam [3-[(2-chloro-5-
thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-
imine] (CAS Reg. No. 153719-23-4) and its metabolite [N-(2-chloro-
thiazol-5-ylmethyl)-N'-methyl-N'-nitro-guanidine] in or on the 
following raw agricultural commodities:

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
Barley, grain........................................               0.02
Barley, hay..........................................               0.05
Barley, straw........................................               0.03
Canola, seed.........................................               0.02
Cattle, mbyp.........................................               0.02
Cattle, meat.........................................               0.02
Cotton, gin byproducts...............................                1.5
Cotton, undelinted seed..............................               0.10
Goat, mbyp...........................................               0.02
Goat, meat...........................................               0.02
Hog, mbyp............................................               0.02
Hog meat.............................................               0.02
Horse, mbyp..........................................               0.02
Horse, meat..........................................               0.02
Milk.................................................               0.02
Sheep, mbyp..........................................               0.02
Sheep, meat..........................................               0.02
Sorghum, forage......................................               0.02
Sorghum, grain.......................................               0.02
Sorghum, stover......................................               0.02
Wheat, forage........................................               0.50
Wheat, grain.........................................               0.02
Wheat, hay...........................................               0.02
Wheat, straw.........................................               0.02
------------------------------------------------------------------------

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[FR Doc. 00-32570 Filed 12-20-00; 8:45 am]
BILLING CODE 6560-50-S