[Federal Register Volume 70, Number 55 (Wednesday, March 23, 2005)]
[Rules and Regulations]
[Pages 14535-14546]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-5620]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2005-0003; FRL-7695-5]


Dinotefuran; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for combined residues 
of dinotefuran, [N-methyl-N'-nitro-N''-((tetrahydro-3-
furanyl)methyl)guanidine] and its metabolites DN [1-methyl-3-
(tetrahydro-3-furylmethyl)guanidine] and UF [1-methyl-3-(tetrahydro-3-
furylmethyl)urea], expressed as dinotefuran in or on vegetable, 
fruiting, group 8; vegetable, cucurbit, group 9; brassica, head and 
stem, subgroup 5A; grape; grape, raisin; potato; potato, chips; potato, 
granules/flakes; tomato, paste; cotton, undelinted seed; cotton, gin 
byproducts; and for residues of dinotefuran, [N-methyl-N'-nitro-N''-
((tetrahydro-3-furanyl)methyl)guanidine] alone in or on cattle meat, 
fat, and meat byproducts (mbyp); goat meat, fat, and mbyp; hog meat, 
fat, and mbyp; horse meat, fat, and mbyp; sheep meat, fat, and mbyp; 
and milk. Mitsui Chemicals, Inc. requested these tolerances under the 
Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food 
Quality Protection Act of 1996 (FQPA).

DATES: This regulation is effective March 23, 2005. Objections and 
requests for hearings must be received on or before May 23, 2005.

ADDRESSES: To submit a written objection or hearing request follow the 
detailed instructions as provided in Unit VI. of the SUPPLEMENTARY 
INFORMATION. EPA has established a docket for this action under docket 
identification (ID) number OPP-2005-0003. All documents in the docket 
are listed in the EDOCKET index at http://www.epa.gov/edocket. Although 
listed in the index, some information is not publicly available, i.e., 
CBI or other information whose disclosure is restricted by statute. 
Certain other material, such as copyrighted material, is not placed on 
the Internet and will be publicly available only in hard copy form. 
Publicly available docket materials are available either electronically 
in EDOCKET or in hard copy at the Public Information and Records 
Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 1801 S. 
Bell St., Arlington, VA. This docket facility is open from 8:30 a.m. to 
4 p.m., Monday through Friday, excluding legal holidays. The docket 
telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: Rita Kumar, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8291; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS 111), e.g., agricultural workers; 
greenhouse, nursery, and floriculture workers; farmers.
     Animal production (NAICS 112), e.g., cattle ranchers and 
farmers, dairy cattle farmers, livestock farmers.
     Food manufacturing (NAICS 311), e.g., agricultural 
workers; farmers; greenhouse, nursery, and floriculture workers; 
ranchers; pesticide applicators.
     Pesticide manufacturing (NAICS 32532), e.g., agricultural 
workers; commercial applicators; farmers;

[[Page 14536]]

greenhouse, nursery, and floriculture workers; residential users.
    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 this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Access Electronic Copies of this Document and Other 
Related Information?

    In addition to using EDOCKET (http://www.epa.gov/edocket/), you may 
access this Federal Register document electronically through the EPA 
Internet under the ``Federal Register'' listings at http://www.epa.gov/fedrgstr/. A frequently updated electronic version of 40 CFR part 180 
is available at E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/. 
To access the OPPTS Harmonized Guidelines referenced in this document, 
go directly to the guidelines at http://www.epa.gov/opptsfrs/home/guidelin.htm/.

II. Background and Statutory Findings

    In the Federal Register of July 2, 2003 FR 39547-39554) (FRL-7312-
8), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 
U.S.C. 346a(d)(3), announcing the filing of two pesticide petitions (PP 
2F6427 and 3F6566) by Mitsui Chemicals, Inc., Chiyoda-ku, Tokyo, Japan. 
The petitions requested that 40 CFR 180.603 be amended by establishing 
tolerances for combined residues of the insecticide dinotefuran, [N-
methyl-N'-nitro-N''-((tetrahydro-3-furanyl)methyl)guanidine] and its 
metabolites DN [1-methyl-3-(tetrahydro-3-furylmethyl)guanidine] and UF 
[1-methyl-3-(tetrahydro-3-furylmethyl)urea], expressed as dinotefuran 
as follows: (PP 3F6566) in or on fruiting vegetables at 0.7 parts per 
million (ppm); tomato paste at 1.0 ppm; cucurbit at 0.5 ppm; head and 
stem brassica vegetables at 1.4 ppm; grape at 0.8 ppm; raisin at 2.5 
ppm; potato at 0.05 ppm; potato, chips at 0.10 ppm; granules at 0.15 
ppm; cattle, goat, hog, horse and sheep fat, meat, and byproducts, and 
milk at 0.05 ppm; and (PP 2F6427) in or on cotton seed undelinted at 
0.2 ppm; and cotton gin byproducts at 7.0 ppm. That notice included a 
summary of the petition prepared by Mitsui Chemicals Inc., the 
registrant. One comment was received from a private citizen, in support 
of this notice.
    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information''. This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue* * * 
.''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 of FFDCA and a complete 
description of the risk assessment process, see the final rule on 
Bifenthrin Pesticide Tolerances in the Federal Register of November 26, 
1997 (62 FR 62961) (FRL-5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2) of FFDCA, for tolerances for combined residues of 
dinotefuran, [N-methyl-N'-nitro-N''-((tetrahydro-3-
furanyl)methyl)guanidine] and its metabolites DN [1-methyl-3-
(tetrahydro-3-furylmethyl)guanidine] and UF [1-methyl-3-(tetrahydro-3-
furylmethyl)urea], expressed as dinotefuran on fruiting vegetables, 
group 8 at 0.7 ppm; tomato paste at 1.0 ppm; cucurbit at 0.5 ppm; head 
and stem brassica vegetables at 1.4 ppm; grape at 0.8 ppm, raisin at 
2.5 ppm, potato at 0.05 ppm, potato, chips at 0.10 ppm, potato, 
granules/flakes at 0.15 ppm; cotton seed undelinted at 0.4 ppm, cotton 
gin byproducts at 7.0 ppm; and for residues of dinotefuran, [N-methyl-
N'-nitro-N''-((tetrahydro-3-furanyl)methyl)guanidine] alone in or on 
cattle meat, fat, and meat byproducts (mbyp) at 0.05 ppm; goat meat, 
fat, and mbyp at 0.05 ppm; hog meat, fat, and mbyp at 0.05 ppm; horse 
meat, fat, and mbyp at 0.05 ppm; sheep meat, fat, and mbyp 0.05 ppm; 
and milk at 0.05 ppm. EPA's assessment of exposures and risks 
associated with establishing the tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by dinotefuran are 
discussed in Table 1 of this unit as well as the no observed adverse 
effect level (NOAEL) and the lowest observed adverse effect level 
(LOAEL) from the toxicity studies reviewed.

                                Table 1.--Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
             Guideline No.                       Study Type                            Results
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity in     NOAEL: 38/384 (M/F) mg/kg/day
                                          rats                       LOAEL: 384 (M) mg/kg/day based on adrenal
                                                                      histopathology; 1,871 (F) mg/kg/day based
                                                                      on decreased body weight/body weight gain,
                                                                      changes in hematology/clinical chemistry,
                                                                      changes in organ weights, and adrenal
                                                                      histopathology
----------------------------------------------------------------------------------------------------------------

[[Page 14537]]

 
870.3100                                 90-Day oral toxicity in     NOAEL: 4,442/5,414 (M/F) mg/kg/day
                                          mice                       LOAEL: 10,635/11,560 (M/F) mg/kg/day, based
                                                                      on decreased body weight, body weight gain
----------------------------------------------------------------------------------------------------------------
870.3150                                 90-Day oral toxicity in     NOAEL: 307/not determined (M/F) mg/kg/day
                                          dogs                       LOAEL: 862 (M) mg/kg/day, based on body
                                                                      weight gain, hemorrhagic lymph nodes; <59
                                                                      (F), based on decreased body weight, body
                                                                      weight gain
----------------------------------------------------------------------------------------------------------------
870.3200                                 28-Day dermal toxicity      Systemic
                                          (rats)                     NOAEL: 1,000 mg/kg/day
                                                                     LOAEL: not determined (no effects seen)
                                                                     Dermal:
                                                                     NOAEL: 1,000 (M), <=200 (F) mg/kg/day
                                                                     LOAEL: not determined/<=1,000 (M/F) mg/kg/
                                                                      day based on lack of effects in males,
                                                                      increase in acanthosis/hyperkeratosis in
                                                                      high dose females (lower doses not
                                                                      evaluated histopathologically)
----------------------------------------------------------------------------------------------------------------
870.3465                                 28-Day inhalation toxicity  NOAEL:<0.22 (M) mg/L, 0.22 (F) mg/L
                                          (rat)                      LOAEL: decreased body weight gain, food
                                                                      consumption (M); increased clinical signs
                                                                      (protruding eyes) (F)
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal developmental      Maternal
                                          toxicity study (rats)      NOAEL: 300 mg/kg/day
                                                                     LOAEL: 1,000 mg/kg/day based on decreased
                                                                      body weight gain and food consumption
                                                                     Developmental
                                                                     NOAEL: 1,000 mg/kg/day
                                                                     LOAEL: not determined (no effects seen)
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal developmental      Maternal
                                          toxicity study (rabbits)   NOAEL: 52 mg/kg/day
                                                                     LOAEL: 125 mg/kg/day based on decreased
                                                                      body weight gains, food consumption, and
                                                                      necropsy findings
                                                                     Developmental
                                                                     NOAEL: 300 mg/kg/day
                                                                     LOAEL: >300 mg/kg/day (no effects seen)
----------------------------------------------------------------------------------------------------------------
870.3800                                 Reproduction and fertility  Parental/systemic
                                          effects (rats)             NOAEL: 241/268 (M/F) mg/kg/day
                                                                     LOAEL: 822/907 (M/F) mg/kg/day, based on
                                                                      decreased food consumption, weight gain in
                                                                      males, soft feces in females, and
                                                                      decreasedspleen weights in both sexes
                                                                     Reproductive (tentative)
                                                                     NOAEL: 241/268 (M/F) mg/kg/day
                                                                     LOAEL: 822/907 (M/F) mg/kg/day, based on
                                                                      decreased uterine weights and microscopic
                                                                      alterations in the uterus and vagina of F0
                                                                      females, decreased numbers of primordial
                                                                      follicles in F1 females, altered estrous
                                                                      cyclicity in F0 and F1 females, increase
                                                                      in abnormal sperm morphology in F0 and F1
                                                                      males, decreased testicular sperm count in
                                                                      F0 males, and decreased sperm motility in
                                                                      F1 males
                                                                     Developmental
                                                                     NOAEL: 241/268 (M/F) mg/kg/day
                                                                     LOAEL: 822-935/907-1005 (M/F) mg/kg/day
                                                                      based on decreased body weights, body
                                                                      weight gains, and spleen weights in F1 and
                                                                      F2 males and females, decreased thymus
                                                                      weights in F2 males and females, and
                                                                      decreased forelimb grip strength (F1
                                                                      males) or hindlimb grip strength (F1
                                                                      females)
----------------------------------------------------------------------------------------------------------------
870.4100                                 Chronic toxicity (rats)     See 870.4300 combined chronic toxicity/
                                                                      carcinogenicity (rats)
----------------------------------------------------------------------------------------------------------------
870.4100                                 Chronic toxicity (dogs)     NOAEL: >20/22 (M/F) mg/kg/day
                                                                     LOAEL: 20/108 (M/F) mg/kg/day based on
                                                                      decreased thymus weight, decreased food
                                                                      efficiency, body weight, and body weight
                                                                      gain in females, decreased thymus weight
                                                                      in males
----------------------------------------------------------------------------------------------------------------
870.4200                                 Carcinogenicity (rats)      See 870.4300 combined chronic toxicity/
                                                                      carcinogenicity (rats)
----------------------------------------------------------------------------------------------------------------
870.4200                                 Carcinogenicity (mice)      NOAEL: <3 (M), <4 (F) mg/kg/day
                                                                     LOAEL: 3/4 (M/F) mg/kg/day based on
                                                                      decreased spleen weights at week 79
                                                                      terminal sacrifice in males and increased
                                                                      ovarian weights at week 53 in females
----------------------------------------------------------------------------------------------------------------

[[Page 14538]]

 
870.4300                                 Combined chronic toxicity/  NOAEL: 99.7/127.3 (M/F) mg/kg/day
                                          carcinogenicity (rats)     LOAEL: 991/1,332 (M/F) mg/kg/day based on
                                                                      decreased body weight gain, food
                                                                      efficiency in females, increased
                                                                      incidences of kidney pelvic mineralization
                                                                      and ulceration in males
----------------------------------------------------------------------------------------------------------------
870.5100                                 Bacterial reverse mutation  Negative.  S9 up to 16,000
                                          test                        [mu]g/plate
----------------------------------------------------------------------------------------------------------------
870.5100                                 Bacterial reverse mutation  Negative,  S9 up to limit dose
                                          test                        of 5,000 [mu]g/plate
----------------------------------------------------------------------------------------------------------------
870.5300                                 In vitro mammalian cell     Negative,  S9 up to 2002 [mu]g/
                                          gene mutation test          mL (mouse lymphoma L5178Y cells)
----------------------------------------------------------------------------------------------------------------
870.5375                                 In vitro mammalian          Negative for clastogenic/aneugenic activity
                                          chromosome aberration       up to 2000 [mu]g/mL (CHL/IU cells)
                                          test
----------------------------------------------------------------------------------------------------------------
870.5395                                 In vivo mammalian           Negative at oral doses up to 1,080 mg/kg/
                                          cytogenics -micronucleus    day for 2 days
                                          assay
----------------------------------------------------------------------------------------------------------------
870.6200                                 Acute neurotoxicity         NOAEL: 750 (M), 325 (F) mg/kg/day
                                          screening battery          LOAEL: 1,500 (M), 750 (F) mg/kg/day based
                                                                      on decreased motor activity on day 1
----------------------------------------------------------------------------------------------------------------
870.6200                                 Subchronic neurotoxicity    NOAEL: 33/40 (M/F) mg/kg/day
                                          screening battery          LOAEL: 327/400 (M/F) mg/kg/day based on
                                                                      increased motor activity during week 2
----------------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism and              Absorption was >90% regardless of dose. The
                                          pharmacokinetics (rats)     radiolabel was widely distributed through
                                                                      the body and was completely excreted
                                                                      within 168 hours of treatment. Urine was
                                                                      the primary elimination route, accounting
                                                                      for 88-99.8%. Excretion into the urine was
                                                                      rapid, being 84-99% complete within 24
                                                                      hours of treatment. Absorption of the
                                                                      radioactivity was linear within the dose
                                                                      range of 50 and 1,000 mg/kg. Elimination
                                                                      of radioactivity was fast for all groups
                                                                      with a T1/2 ranging from 3.64 to 15.2
                                                                      hours for the low and high doses,
                                                                      respectively. Radioactivity was rapidly
                                                                      transferred from maternal blood to milk
                                                                      and widely distributed in the fetal
                                                                      tissues. The Cmax for milk and fetal
                                                                      tissues was detected 0.5 hours after
                                                                      maternal treatment. The concentrations of
                                                                      radioactivity in fetal tissue and maternal
                                                                      milk declined quickly and were below
                                                                      detection limits 24 hours post-treatment.
                                                                      After IV or oral treatment, 75-93% of the
                                                                      administered radiolabeled test material,
                                                                      or nearly 93-97% of total urinary
                                                                      radiolabel, was excreted unchanged in the
                                                                      urine. The parent compound was also the
                                                                      primary component in the plasma, milk,
                                                                      bile, feces, and most tissues collected 4-
                                                                      8 hours after treatment and at both dose
                                                                      levels. Less than 10% of the parent
                                                                      compound was metabolized into numerous
                                                                      minor metabolites that were not well
                                                                      resolved by High Performance Liquid
                                                                      Chromotography (HPLC) or 2D-TLC. For all
                                                                      parameters measured in this study, no sex
                                                                       or dose-related differences or label
                                                                      position effects were found.
----------------------------------------------------------------------------------------------------------------
Special study                            Neonatal rat metabolism     After a single oral 50 mg/kg dose of (G-
                                          study (12-day old rat       14C) MTI-446 to 12-day old rats,
                                          pups)                       absorption was high (absorption could not
                                                                      be adequately determined but may have
                                                                      approached 80%) and the radiolabel was
                                                                      widely distributed within the body.
                                                                      Approximately 32-36% of the administered
                                                                      dose was excreted within 4 hours of
                                                                      treatment. Urine was the primary
                                                                      elimination route as indirectly evidenced
                                                                      by finding high radioactive areas in the
                                                                      kidneys and bladder by whole body
                                                                      autoradiography. No areas of tissue
                                                                      sequestration were found and no gender-
                                                                      related differences were identified. The
                                                                      test material was essentially not
                                                                      metabolized, the parent compound
                                                                      accounting for >97% of the radiolabel in
                                                                      the excreta, plasma, kidneys, and stomach,
                                                                      and nearly 61-83% in intestines (and
                                                                      contents), and liver.
----------------------------------------------------------------------------------------------------------------

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.
    Three other types of safety or uncertainty factors may be used: 
``Traditional uncertainty factors;'' the ``special FQPA safety 
factor;'' and the ``default FQPA safety factor''. By the term 
``traditional uncertainty factor,'' EPA is referring to those 
additional uncertainty factors used prior to FQPA passage to account 
for database deficiencies. These traditional uncertainty factors have 
been

[[Page 14539]]

incorporated by the FQPA into the additional safety factor for the 
protection of infants and children. The term ``special FQPA safety 
factor '' refers to those safety factors that are deemed necessary for 
the protection of infants and children primarily as a result of the 
FQPA. The ``default FQPA safety factor'' is the additional 10X safety 
factor that is mandated by the statute unless it is decided that there 
are reliable data to choose a different additional factor (potentially 
a traditional uncertainty factor (UF) or a special FQPA safety factor).
    For dietary risk assessment (other than cancer) the Agency uses the 
UF to calculate an acute or chronic reference dose (aRfD or cRfD) where 
the RfD is equal to the NOAEL divided by an UF of 100 to account for 
interspecies and intraspecies differences and any traditional UFs 
deemed appropriate (RfD = NOAEL/UF). Where a special FQPA safety factor 
or the default FQPA safety factor is used, 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 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). An example of how such a probability risk is expressed 
would be to describe the risk as one in one hundred thousand (1 x 
10-5), one in a million (1 x 10-6), or one in ten 
million (1 x 10-7). Under certain specific circumstances, 
margin of exposure (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 dinotefuran used for 
human risk assessment is shown in the following Table 2.

     Table 2.--Summary of Toxicological Dose and Endpoints for Dinotefuran for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                  Special FQPA SF and
          Exposure/Scenario               Dose Used in Risk       Level of Concern for   Study and Toxicological
                                            Assessment, UF          Risk Assessment              Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (General population      NOAEL = 125 mg/kg/day    FQPA SF = 1              Developmental toxicity
 including infants and children)       UF = 100...............  aPAD = acute RfD / FQPA   study in rabbits
                                       Acute RfD = 1.25 mg/kg/   SF = 1.25 mg/kg/day.    LOAEL = 300 mg/kg/day
                                        day.                                              based on clinical
                                                                                          signs in does (prone
                                                                                          position, panting,
                                                                                          tremor, erythema) seen
                                                                                          following a single
                                                                                          dose.
----------------------------------------------------------------------------------------------------------------
Chronic dietary (All populations)      LOAEL= 20 mg/kg/day      FQPA SF = 1              Chronic toxicity study
                                       UF = 1,000.............  cPAD = chronic RfD /      in dogs
                                       Chronic RfD = 0.02 mg/    FQPA SF = 0.02 mg/kg/   LOAEL = 20 mg/kg/day
                                        kg/day.                  day.                     based on decreased
                                                                                          thymus weight in males
----------------------------------------------------------------------------------------------------------------
Short-term incidental oral (1 to 30    NOAEL= 33 mg/kg/day      Residential LOC for MOE  Subchronic
 days)                                                           = 100                    neurotoxicity study in
                                                                Occupational = NA......   rats
                                                                                         LOAEL = 327 mg/kg/day
                                                                                          based on increased
                                                                                          motor activity during
                                                                                          week 2
----------------------------------------------------------------------------------------------------------------
Intermediate-term incidental oral (1   NOAEL= 22 mg/kg/day      Residential LOC for MOE  Chronic toxicity study
 to 6 months)                                                    =100                     in dogs
                                                                Occupational = NA......  LOAEL = 108 mg/kg/day
                                                                                          based on decreased
                                                                                          body weight and body
                                                                                          weight gain in females
----------------------------------------------------------------------------------------------------------------
Short-term dermal (1 to 30 days)       No quantitation          Residential LOC for MOE  No quantitation
                                        required.                = NA                     required. No systemic
                                                                Occupational LOC for      toxicity was seen at
                                                                 MOE = NA.                the limit dose in a 28-
                                                                                          day dermal toxicity
                                                                                          study in which
                                                                                          neurotoxicity was
                                                                                          evaluated. No
                                                                                          developmental toxicity
                                                                                          concerns.
----------------------------------------------------------------------------------------------------------------
Intermediate-term dermal (1 to 6       Oral study NOAEL = 22    Residential LOC for MOE  Chronic toxicity study
 months)                                mg/kg/day (dermal        = 100                    in dogs
                                        absorption rate = 30%)  Occupational LOC for     LOAEL = 108 mg/kg/day
                                                                 MOE =100.                based on decreased
                                                                                          body weight and body
                                                                                          weight gain in females
----------------------------------------------------------------------------------------------------------------
Long-term dermal (>6 months)           Oral study LOAEL = 20    Residential LOC for MOE  Chronic toxicity study
                                        mg/kg/day (dermal        = 1,000                  in dogs
                                        absorption rate = 30%)  Occupational LOC for     LOAEL = 20 mg/kg/day
                                                                 MOE = 1,000.             based on decreased
                                                                                          thymus weight in males
----------------------------------------------------------------------------------------------------------------
Short-term inhalation (1 to 30 days)   Inhalation study LOAEL=  Residential LOC for MOE  28-day Inhalation
                                        60 mg/kg/day             = 1,000                  toxicity study in rats
                                                                Occupational LOC for     LOAEL = 60 mg/kg/day
                                                                 MOE = 1,000.             based on decreased
                                                                                          body weight gain in
                                                                                          males
----------------------------------------------------------------------------------------------------------------

[[Page 14540]]

 
Intermediate-term inhalation (1 to 6   Inhalation study LOAEL   Residential LOC for MOE  28-day Inhalation
 months)                                = 60 mg/kg/day           =1,000                   toxicity study in rats
                                                                Occupational LOC for     LOAEL = 60 mg/kg/day
                                                                 MOE = 1,000.             based on decreased
                                                                                          body weight gain in
                                                                                          males
----------------------------------------------------------------------------------------------------------------
Long-term inhalation (>6 months)       Oral study LOAEL= 20 mg/ Residential LOC for MOE  Chronic toxicity study
                                        kg/day (inhalation       = 1,000                  in dogs
                                        absorption rate =       Occupational LOC for     LOAEL = 20 mg/kg/day
                                        100%)                    MOE = 1,000.             based on decreased
                                                                                          thymus weight in males
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)      NA                       NA                       Not required; no
                                                                                          evidence of
                                                                                          carcinogenicity.
----------------------------------------------------------------------------------------------------------------
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL =
  lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference
  dose, MOE = margin of exposure, LOC = level of concern, NA = Not applicable.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Tolerances have been 
established (40 CFR 180.603) for the combined residues of dinotefuran 
and its metabolites, in or on a variety of raw agricultural 
commodities. Risk assessments were conducted by EPA to assess dietary 
exposures from dinotefuran 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 1-day or 
single exposure.
    In conducting the acute dietary risk assessment EPA used the 
DEEMTM software with the FCID, which incorporates food 
consumption data as reported by respondents in the U.S. Department of 
Agriculture (USDA) 1994-1996 and 1998 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: The dietary risk analyses incorporated 
tolerance level residues and assumed 100% of the crops had been treated 
with dinotefuran. The acute risk estimates are below the Agency's level 
of concern (< 100% aPAD) for the general U.S. population and all 
population subgroups.
    ii. Chronic exposure. In conducting the chronic dietary risk 
assessment EPA used the DEEMTM software with the FCID, which 
incorporates food consumption data as reported by respondents in the 
USDA 1994-1996 and 1998 CSFII, and accumulated exposure to the chemical 
for each commodity. The following assumptions were made for the chronic 
exposure assessments: The dietary risk analyses incorporated tolerance 
level residues and assumed 100% of the crops had been treated with 
dinotefuran. The chronic risk estimates are below the Agency's level of 
concern (<100% cPAD) for the general U.S. population and all population 
subgroups.
    iii. Cancer. Dinotefuran is classified as ``not likely to be a 
carcinogen,'' therefore, an exposure assessment for quantifying cancer 
risk was not conducted.
    2. Dietary exposure from drinking water. The Agency lacks 
sufficient monitoring exposure data to complete a comprehensive dietary 
exposure analysis and risk assessment for dinotefuran 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 dinotefuran.
    The Agency uses the FQPA Index Reservoir Screening Tool (FIRST) or 
the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/
EXAMS), to produce estimates of pesticide concentrations in an index 
reservoir. The SCI-GROW model is used to predict pesticide 
concentrations in shallow ground water. For a screening-level 
assessment for surface water EPA will use FIRST (a Tier 1 model) before 
using PRZM/EXAMS (a Tier 2 model). The FIRST model is a subset of the 
PRZM/EXAMS model that uses a specific high-end runoff scenario for 
pesticides. Both FIRST and PRZM/EXAMS incorporate an index reservoir 
environment, and both models include a percent crop treated (PCT) area 
factor as an adjustment to account for the maximum PC 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 screen for sorting out pesticides for which it is 
unlikely that drinking water concentrations would 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), which are the model estimates of a 
pesticide's concentration in water. EECs derived from these models are 
used 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 dinotefuran they are 
further discussed in the aggregate risk sections below.
    Based on the FIRST and SCI-GROW models, the EECs of dinotefuran for 
acute exposures are estimated to be 76 parts per billion (ppb) for 
surface water and 5.1 ppb for ground water. The EECs for chronic 
exposures are estimated to be 21 ppb for surface water and 5.1 ppb for 
ground water.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in

[[Page 14541]]

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).
    Dinotefuran is currently registered for use on the following 
residential non-dietary sites: Professional turf management, 
professional ornamental production, residential indoor, and lawn. The 
risk assessment was conducted using the following residential exposure 
assumptions: Outdoor uses for turf farms, golf courses, residential 
lawns, and ornamentals.
    There is a potential for exposure to homeowners in residential 
settings during the application of products containing dinotefuran. 
There is also a potential for exposure from entering areas previously 
treated with dinotefuran such as lawns where children might play, or 
golf courses and home gardens that could lead to exposures for adults. 
As a result, risk assessments were previously discussed for both 
residential handler and postapplication scenarios in the final rule for 
setting tolerance on leafy vegetables in the Federal Register of 
September 17, 2004 (69 FR 55963) (FRL-7368-1). The proposed new 
agricultural uses of dinotefuran do not add any additional residential 
exposures or risks.
    The risks from the combined exposures of adults applying 
dinotefuran to residential lawns and then being dermally exposed from 
postapplication activities on the treated lawn do not exceed the 
Agency's level of concern. Children's combined risks from activities on 
treated lawns do not exceed the Agency's level of concern.
    4. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    Unlike other pesticides for which EPA has followed a cumulative 
risk approach based on a common mechanism of toxicity, EPA has not made 
a common mechanism of toxicity finding as to dinotefuran and any other 
substances and dinotefuran 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 dinotefuran has a 
common mechanism of toxicity with other substances. For information 
regarding EPA's efforts to determine which chemicals have a common 
mechanism of toxicity and to evaluate the cumulative effects of such 
chemicals, see the policy statements released by EPA concerning common 
mechanism determinations and procedures for cumulating effects from 
substances found to have a common mechanism on EPA's web site at http://www.epa.gov/pesticides/cumulative/.

D. Safety Factor for Infants and Children

    1. In general. Section 408 of FFDCA provides that EPA shall apply 
an additional tenfold margin of safety for infants and children in the 
case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the database on toxicity and exposure 
unless EPA determines based on reliable data that a different margin of 
safety will be safe for infants and children. Margins of safety are 
incorporated into EPA risk assessments either directly through use of a 
MOE analysis or through using uncertainty (safety) factors (UFs) in 
calculating a dose level that poses no appreciable risk to humans. In 
applying this provision, EPA either retains the default value of 10X 
when reliable data do not support the choice of a different factor, or, 
if reliable data are available, EPA uses a different additional safety 
factor value based on the use of traditional UFs and/or special FQPA 
safety factors, as appropriate.
    2. Prenatal and postnatal sensitivity. Prenatal developmental 
toxicity studies in rats and rabbits provided no indication of 
increased susceptibility (qualitative or quantitative) of rat or rabbit 
fetuses to in utero exposure to dinotefuran. There was no indication of 
increased (quantitative) susceptibility in the fetuses as compared to 
parental animals in the two generation reproduction study. Qualitative 
susceptibility was observed in the reproduction study; however, the 
degree of concern is low because the observed effects are well 
characterized (decreased body weight, decreased thymus weight, and 
decreased grip strength) and there are clear NOAELs/LOAELs.
    3. Conclusion. Although there is generally low concern and no 
residual uncertainties for prenatal and/or postnatal toxicity resulting 
from exposure to dinotefuran, some uncertainty is raised by a 
deficiency in the data (a lack of a NOAEL in the chronic dog study) and 
the need for a developmental immunotoxicity study (DIT).
    The absence of a NOAEL for the chronic dog study and the need for a 
DIT study generate some uncertainty regarding the protectiveness of 
chronic regulatory endpoints and long-term levels of concern. 
Accordingly, EPA does not have reliable data supporting adoption of a 
safety factor other than the default additional 10X factor as specified 
in FFDCA section 408(b)(2)(C). The chronic endpoint and long-term level 
of concern have therefore, been generated using an overall safety/UF of 
1,000 (representing 100X for interspecies and intraspecies variation 
and an additional 10X pursuant to FFDCA section 408(b)(2)(C).
    The Agency does not have similar concerns regarding acute, short-
term, and intermediate-term risk assessments for several reason. First, 
the absence of a NOAEL only occurred in a chronic study. Second, 
reliable data show that the DIT is unlikely to result in a NOAEL for 
acute, short-term, or intermediate-term effects that is lower than the 
NOAELs currently being used to assess the risk from such effects. EPA 
has required a DlT study with dinotefuran based on the changes in the 
thymus weight in offspring in the reproduction study and in adult rats 
and dogs. There is, however, little evidence to support a direct effect 
of dinotefuran on immune function. This is because lymphoid organ 
weight changes can be secondary to generalized toxicity (e.g., 
reductions in body weight, body weight gain, and/or food efficiency). 
In the reproduction study, decreased thymus weights were seen in 
offspring in the presence of decreased body weight only at the Limit 
Dose (10,000 ppm). In the 1-year dog study, decrease in thymus weight 
was seen in the absence of other toxicity, however, no decrease in 
thymus weight was seen in the subchronic study in dogs which was 
conducted at higher doses (i.e., the results of the 1-year study was 
not supported by the results of the 90-day study).
    Further, the only evidence on dinotefuran's potential immunological 
effect is found in studies with prolonged exposure. In the reproduction 
study, the effect of concern i.e, decrease in thymus weight in only 1-
generation (F2) was seen only following approximately 13-weeks of 
exposure to the parental animals at close to the limit dose (1,000 mg/
kg). Similarly, thymus effects in the chronic dog study were only 
observable after long-term exposures, but were not seen in the 90-day 
dog study.
    Finally, it is clear that the DIT study, which is performed in the 
rat, will have to be conducted at high doses (close to the limit dose) 
to elicit a potential single dose effect and this will result in a 
potential NOAEL higher than that currently used for various risk

[[Page 14542]]

assessments. As noted, in the rat reproduction study, effects only 
occurred at doses close to the limit dose (1,000 mg/kg/day). The limit 
dose is the maximum dose recommended for testing in the Series 870 
Health Effects Harmonized Test Guidelines; toxic effects occurring only 
at or near the limit dose are of less concern for human health since 
they may be specifically related to the high dose exposure and may not 
occur at the much lower doses to which humans are exposed. 
Additionally, in the acute neurotoxicity study in the rat, the LOAEL 
was 750 mg/kg/day in females and 1,500 mg/kg/day in males based on 
reductions in motor activity indicating that high doses are required to 
elicit dinotefuran-induced toxicity in rats.
    The NOAELs in the critical studies selected for acute dietary (125 
mg/kg/day), short-term incidental oral (33 mg/kg/day), and 
intermediate-term incidental oral and dermal (22 mg/kg/day) exposure 
scenarios are lower than the offspring NOAEL (241 mg/kg/day) in the 
reproduction study. Therefore, EPA is confident that the doses selected 
for these risk assessments will address the concerns for the thymus 
weight changes seen in the offspring in the reproduction study and will 
not underestimate the potential risk from exposure to dinotefuran.
    The Agency believes there are reliable data showing that the 
regulatory endpoints are protective of children despite the need for a 
development neuorotoxicity (DNT) study. DNT data received and reviewed 
for other compounds in this chemical class (neonicotinoids) including 
thiacloprid, clothianidin, and imidacloprid, indicate that the results 
of the required DNT study will not likely impact the regulatory doses 
selected for dinotefuran.
    In addition, the acute and chronic dietary food exposure assessment 
utilized proposed tolerance level residues and 100% crop treated 
information for all commodities. By using these screening-level 
assessments, acute and chronic exposure/risks will not be 
underestimated. Furthermore, the dietary drinking water assessment 
(Tier 1 estimates) uses values generated by models and associated 
modeling parameters which are designed to provide conservative, health 
protective, high-end estimates of water concentrations. Finally, the 
residential assessment for children's postapplication exposures is 
based upon maximum application rates in conjunction with chemical-
specific study data and are not expected to underestimate risk.

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 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 EPA's Office of Water are used to calculate 
DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (youth and 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 ground water are less than the 
calculated DWLOCs, EPA concludes with reasonable certainty that 
exposures to the pesticide in drinking water (when considered along 
with other sources of exposure for which EPA has reliable data) would 
not result in unacceptable levels of aggregate human health risk at 
this time. Because EPA 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, EPA 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 
dinotefuran will occupy 1.2% of the aPAD for the U.S. population, 1.2% 
of the aPAD for females 13 to 49 years old, 1.3% of the aPAD for 
infants <1 year old, and 2.9% of the aPAD for children 1 to 2 years 
old. In addition, there is potential for acute dietary exposure to 
dinotefuran in drinking water. After calculating DWLOCs and comparing 
them to the EECs for surface water, and ground water, EPA does not 
expect the aggregate exposure to exceed 100% of the aPAD, as shown in 
the following Table 3.

                      Table 3.--Aggregate Risk Assessment for Acute Exposure to Dinotefuran
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population/Subgroup                 aPAD /(mg/     %aPAD/     Water EEC/   Water EEC/  Acute DWLOC
                                                   kg/day)       (Food)       (ppb)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                         1.25          1.2           76          5.1       43,000
----------------------------------------------------------------------------------------
All infants (<1 year old)                               1.25          1.3           76          5.1       12,000
----------------------------------------------------------------------------------------------------------------
Children (1-2 years old)                                1.25          2.9           76          5.1       12,000
----------------------------------------------------------------------------------------
Females (13-49 years old)                               1.25          1.2           76          5.1       37,000
----------------------------------------------------------------------------------------------------------------

    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
dinotefuran from food will utilize 21% of the cPAD for the U.S. 
population, 18% of the cPAD for infants <1 year old, and 54% of the 
cPAD for children 1 to 2 years old, and 20% of the cPAD for females 13 
to 49 years old. Based on the use pattern, chronic residential exposure 
to residues of dinotefuran does not exceed the

[[Page 14543]]

Agency's level of concern, as discussed in Unit III.E.3. below. In 
addition, there is potential for chronic dietary exposure to 
dinotefuran in drinking water. After calculating DWLOCs and comparing 
them to the EECs for surface water, and ground water, EPA does not 
expect the aggregate exposure to exceed 100% of the cPAD, as shown in 
the following Table 4.

              Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Dinotefuran
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
        Population Subgroup           cPAD (mg/kg/day)     %cPAD (FOOD)     Water EEC    Water EEC     Chronic
                                                                              (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                   0.02                 21           21          5.1          550
----------------------------------------------------------------------------------------------------------------
All infants (<1 year old)                         0.02                 18           21          5.1          160
----------------------------------------------------------------------------------------------------------------
Children (1-2 years old)                          0.02                 54           21          5.1           90
----------------------------------------------------------------------------------------------------------------
Females (13-49 years old)                         0.02                 19           21          5.1          490
----------------------------------------------------------------------------------------------------------------

    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).
    Dinotefuran is currently registered for uses that could result in 
short-term residential exposure. Short-term and intermediate-term 
aggregate risk assessments based on exposure from oral, inhalation, and 
dermal routes were considered. However, the toxicological effects for 
oral and inhalation routes of exposure are different (i.e., 
neurotoxicity for oral and decrease in body weight for inhalation); and 
therefore, these exposure scenarios have not been combined. Also, 
because no systemic toxicity was seen at the limit dose in a 28-day 
dermal toxicity study, no quantification of short-term dermal risk is 
required. Therefore, a short-term aggregate risk assessment was not 
performed for dinotefuran. An intermediate-term aggregate risk 
assessment was performed as a screening level assessment, which will 
apply to short-term aggregate risk.
    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).
    Dinotefuran is currently registered for use(s) that could result in 
intermediate-term residential exposure and the Agency has determined 
that it is appropriate to aggregate chronic food and water and 
intermediate-term exposures for dinotefuran. An intermediate-term 
aggregate risk assessment was performed as a screening level assessment 
for adults and children.
    For children, the children's subgroup with the highest estimated 
chronic dietary exposure (children 1-2 years old) was aggregated with 
residential exposures to children playing on treated lawns (dermal and 
oral hand-to-mouth exposures) in order to calculate the worst case 
intermediate-term aggregate risk to children. The reciprocal MOE method 
was used to conduct the intermediate-term aggregate risk assessment for 
children, since the level of concern MOEs are identical for all MOEs in 
the calculation.For adults, the aggregate risk index method was used, 
since level of concern MOEs are not identical for all types of exposure 
in the calculation.
    i. Intermediate-term aggregate risk for children. The child 
subgroup with the highest estimated chronic dietary exposure (children 
1-2 years old) was used to calculate the intermediate-term aggregate 
risk, including chronic dietary (food and drinking water) and 
residential and oral exposures. Based on the toxicity endpoint 
information, all acceptable MOEs are 100, and an intermediate-term oral 
endpoint for incidental ingestion residential exposure was identified. 
Therefore, the intermediate-term incidental oral endpoint (NOAEL) was 
used to incorporate dietary (food and water), and residential 
incidental ingestion exposures in the aggregate risk assessment. An 
intermediate-term residential exposure scenario was identified and 
includes dermal and incidental oral exposure routes. To complete the 
aggregate intermediate-term exposure and risk assessment, chronic 
dietary (food and drinking water) and residential dermal and oral 
exposures must be included.
    For children's combined exposure on turf, the total MOE was 
estimated to be 590. The average (chronic) dietary exposure for the 
highest exposed child subgroup (children 1-2 years old) was estimated 
to be 0.011 mg/kg/day. The reciprocal MOE equation is solved for MOE 
water to determine the DWLOCIntermediate-term for 
children. Compared with the Estimated Drinking Water Concentrations 
(EDWCs), EPA's calculated aggregate intermediate-term DWLOC does not 
exceed the Agency's level of concern for the subgroup population of 
children 1 to 2 years old. The aggregate risk assessment for 
intermediate-term exposure to children is summarized in the following 
Table 5.

                                                  Table 5.--Aggregate Risk Assessment for Intermediate-Term Exposure of Children to Dinotefuran
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                        Average                                                Ground    Surface
                                                                NOAEL/mg/kg/    Target        Max         Food    Residential   Aggregate MOE    Max Water     Water      Water    Intermediate-
                          Population                                day         MOE\1\    Exposure\2\   Exposure  Exposure\3\      (food &      Exposure\5\    EEC\6\     EEC\6\   Term DWLOC\7\
                                                                                           mg/kg/day   mg/kg/day   mg/kg/day   residential)\4\   mg/kg/day    [mu]g/L    [mu]g/L      [mu]g/L
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Children (3-5 years old)                                                 22          100        0.22       0.011       0.037            460           0.17         5.1         21        1,700
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ The target MOE of 100 is based on the standard inter- and intra-species safety factors, 10x for intra-species variability and 10x for inter-species extrapolation.
\2\ Maximum exposure (mg/kg/day) = NOAEL/Target MOE

[[Page 14544]]

 
\3\ Residential exposure to children playing on treated lawns (combined dermal + oral hand-to-mouth + oral object-to-mouth + oral soil ingestion)
\4\ Aggregate MOE = [NOAEL/(Avg. Food Exposure + Residential Exposure)]
\5\ Maximum Water Exposure (mg/kg/day) = Target Maximum Exposure - (Food Exposure + Residential Exposure)
\6\ The use site producing the highest level was used; i.e., turf.
\7\ DWLOC ([mu]g/L) = [Maximum water exposure (mg/kg/day) x body weight (10 kg)]/[Water exposure (1L) x 10-3 mg/[mu]g]

    ii. Intermediate term aggregate risk for adults. For adults, the 
worst case intermediate-term aggregate risk assessment includes the 
following scenarios: (1) Dermal and inhalation exposures to residential 
handlers (i.e. M/L/A of liquids to lawns by hose-end sprayers); (2) 
dermal postapplication exposures on treated lawns;, and (3) oral 
dietary exposures (i.e. food + drinking water). Based on the toxicity 
endpoint information, the acceptable MOEs are not all identical. The 
intermediate-term inhalation endpoint has a UF/MOE of 1,000, because a 
NOAEL was not reached and a LOAEL was used instead, while the 
assessments for incorporating food, water and dermal exposures have 
UFs/MOEs of 100. In this case, the aggregate risk index (ARI) method 
was used to calculate DWLOC values for the adult aggregate 
intermediate-term risk assessment.
    The highest estimated average (chronic) dietary exposure for adults 
occurred with the general U.S. population (i.e. 0.0042 mg/kg/day). The 
adult residential combined risks from dermal (ARI = 17) and inhalation 
(ARI = 970) exposures to residential handlers and dermal 
postapplication exposures (ARI = 12) on treated lawns were combined.
    The intermediate-term aggregate risk including drinking water 
exposure can be calculated using the ARI method for aggregating 
exposure. The equations are solved for MOEwater to determine 
the DWLOC Intermediate-term for adults. Compared with the 
EDWCs, EPA's calculated aggregate intermediate-term DWLOC does not 
exceed Agency's level of concern for the general U.S. population. The 
aggregate risk assessment for intermediate-term exposure to adults is 
summarized in the following Table 6.

                              Table 6.--Aggregate Risk Assessment for Intermediate-Term Exposure of Adults to Dinotefuran.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                           Residential ARIs\3\
                                                                  ------------------------------------               Ground
                                             Target        ARI           Applicators       Postapplic   Max Water     Water      Surface   Intermediate-
                Population                   ARI\1\      Food\2\  ------------------------    ation     Exposure     EDWC\5\   Water EDWC  Term DWLOC\6\
                                                                     Dermal    Inhalation    Dermal      ARI\4\      [mu]/L      [mu]/L        [mu]/L
                                                                    Exposure    Exposure    Exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females (14-49 years old)                          1         116          17         970          12        1.18         5.1          21         5,600
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ ARI (Aggregate Risk Index) = MOE Calculated/MOEAceeptable
\2\ 2 ARIFood = [22 / 0.0019] / 100 = 116
\3\ ARIdermal = MOEcalculated/100 and, ARIinhal = MOE inhal/1,000
\4\ ARIWater = 1/[1/1- (1/ARIResidential aplicator dermal) + (1/ARIResidential applicator inhalation) + (1/ARIPostapplication dermal)]
\5\ The use site producing the highest level was used; i.e. turf.
\6\ DWLOC ([mu]/L) = [Maximum water exposure (mg/kg/day) x body weight (60 kg)]/[Water exposure (2 L) x 10-3 mg/[mu]g] where Maximum water exposure =
  NOAEL (22) / [ARIWater (1.18) x 100] = 0.1866 mg/kg/day

    5. Aggregate cancer risk for U.S. population. Dinotefuran is not 
expected to pose a cancer risk.
    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 dinotefuran residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology for plant commodities (High 
Performance Liquid Chromatography (HPLC)/Mass Spectrometry (MS); HPLC/
Ultraviolet (UV); and HPLC/MS/MS) is available to enforce the tolerance 
expression. The methods may be requested from: Chief, Analytical 
Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. 
Meade, MD 20755-5350; telephone number: (410) 305-2905; e-mail address: 
[email protected].
    A livestock enforcement method is needed to enforce the proposed 
tolerances of dinotefuran on milk, meat, and meat byproducts. The 
Liquid Chromatography (LC)/MS/MS method, which was used for the 
analysis of samples collected from the cow feeding study, may be used 
for tolerance enforcement. The independent laboratory validation and 
radiovalidation data are currently under review by the Agency.

B. International Residue Limits

    There are currently no established Codex, Canadian, or Mexican 
maximum residue limits for residues of dinotefuran in/on plant or 
livestock commodities.

V. Conclusion

    Therefore, the tolerance is established for combined residues of 
dinotefuran, [N-methyl-N'-nitro-N''-((tetrahydro-3-
furanyl)methyl)guanidine] and its metabolites DN [1-methyl-3-
(tetrahydro-3-furylmethyl)guanidine] and UF [1-methyl-3-(tetrahydro-3-
furylmethyl)urea], expressed as dinotefuran, in or on vegetable, 
fruiting, group 8 at 0.7 ppm; vegetable, cucurbit, group 9 at 0.5 ppm; 
Brassica, head and stem, subgroup 5A at 1.4 ppm; grape at 0.9 ppm; 
grape, raisin at 2.5 ppm; potato at 0.05 ppm; potato, chips at 0.1 ppm; 
potato, granules/flakes at 0.15 ppm; tomato, paste at 1.0 ppm; cotton, 
undelinted seed at 0.4 ppm; cotton, gin byproducts at 8.0 ppm; and for 
residues of dinotefuran alone in or on cattle, meat at 0.5 ppm; cattle, 
fat at 0.05 ppm; cattle meat byproducts (mbyp) at 0.05 ppm; goat, meat 
at 0.05 ppm; goat, fat at 0.05 ppm; goat mbyp at 0.05 ppm; hog, meat at 
0.05 ppm; hog, fat at 0.05 ppm; hog mbyp at 0.05 ppm; horse, meat at 
0.05 ppm; horse, fat at 0.05 ppm; horse, mbyp at 0.05 ppm; milk at 0.05 
ppm; sheep, meat at 0.05 ppm; sheep, fat at 0.05 ppm; and sheep, mbyp 
at 0.05 ppm.

[[Page 14545]]

VI. Objections and Hearing Requests

    Under section 408(g) of FFDCA, as amended by 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 FFDCA by FQPA, EPA 
will continue to use those procedures, with appropriate adjustments, 
until the necessary modifications can be made. The new section 408(g) 
of FFDCA provides essentially the same process for persons to 
``object'' to a regulation for an exemption from the requirement of a 
tolerance issued by EPA under new section 408(d) of FFDCA, as was 
provided in the old sections 408 and 409 of FFDCA. However, the period 
for filing objections is now 60 days, rather than 30 days.

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

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number OPP-2005-0003 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 May 23, 
2005.
    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 (1900L), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Suite 350, 1099 14th St., NW., 
Washington, DC 20005. 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) 564-6255.
    2. 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 ADDRESSES. Mail your 
copies, identified by docket ID number OPP-2005-0003, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the 
PIRIB described in ADDRESSES. 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 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. Statutory and Executive Order Reviews

    This final rule establishes a tolerance under section 408(d) of 
FFDCA in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this rule has been 
exempted from review under Executive Order 12866 due to its lack of 
significance, this rule is not subject to Executive Order 13211, 
Actions Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001). This final rule does 
not contain any information collections subject to OMB approval under 
the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose 
any enforceable duty or contain any unfunded mandate as described under 
Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 
104-4). Nor does it require any special considerations under Executive 
Order 12898, entitled Federal Actions to Address Environmental Justice 
in Minority Populations and Low-Income Populations (59 FR 7629, 
February 16, 1994); or OMB review or any Agency action under Executive 
Order 13045, entitled Protection of Children from Environmental Health 
Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does 
not involve any technical standards that would require Agency 
consideration of voluntary consensus standards pursuant to section 
12(d) of the National Technology Transfer and Advancement Act of 1995 
(NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since 
tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of FFDCA, such as the tolerance in this 
final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply. In addition, the Agency has determined that this 
action will not have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132, entitled Federalism 
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to 
develop an accountable process to ensure ``meaningful and timely input 
by State and local officials in the development of regulatory policies 
that have federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive Order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This final rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not

[[Page 14546]]

alter the relationships or distribution of power and responsibilities 
established by Congress in the preemption provisions of section 
408(n)(4) of FFDCA. For these same reasons, the Agency has determined 
that this rule does not have any ``tribal implications'' as described 
in Executive Order 13175, entitled Consultation and Coordination with 
Indian Tribal Governments (65 FR 67249, November 6, 2000). Executive 
Order 13175, requires EPA to develop an accountable process to ensure 
``meaningful and timely input by tribal officials in the development of 
regulatory policies that have tribal implications.'' ``Policies that 
have tribal implications'' is defined in the Executive Order to include 
regulations that have ``substantial direct effects on one or more 
Indian tribes, on the relationship between the Federal Government and 
the Indian tribes, or on the distribution of power and responsibilities 
between the Federal Government and Indian tribes.'' This rule will not 
have substantial direct effects on tribal governments, on the 
relationship between the Federal Government and Indian tribes, or on 
the distribution of power and responsibilities between the Federal 
Government and Indian tribes, as specified in Executive Order 13175. 
Thus, Executive Order 13175 does not apply to this rule.

VIII. Congressional Review Act

    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: February 25, 2005.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

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

0
2. Section 180.603 is revised to read as follows:


Sec.  180.603  Dinotefuran; tolerances for residues.

    (a) General. (1) Tolerances are established for the combined 
residues of Dinotefuran, [N-methyl-N'-nitro-N''-((tetrahydro-3-
furanyl)methyl)guanidine] and its metabolites DN [1-methyl-3-
(tetrahydro-3-furylmethyl)guanidine] and UF [1-methyl-3-(tetrahydro-3-
furylmethyl)urea], expressed as dinotefuran.

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Brassica, head and stem, subgroup 5A.......................          1.4
Cotton, undelinted seed....................................          0.4
Cotton, gin byproducts.....................................          8.0
Grape......................................................          0.9
Grape, raisin..............................................          2.5
Potato.....................................................         0.05
Potato, chips..............................................          0.1
Potato, granules/flakes....................................         0.15
Tomato, paste..............................................          1.0
Vegetable, fruiting, group 8...............................          0.7
Vegetable, cucubit, group 9................................          0.5
Vegetable, leafy, except Brassica, group 4.................          5.0
------------------------------------------------------------------------

    (2) Tolerances are established for residues of dinotefuran N-
methyl-N'-nitro-N''-tetrahydro-3-furanyl)methyl)guanidine in/on the 
following commodities:

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Cattle, fat................................................         0.05
Cattle, mbyp...............................................         0.05
Cattle, meat...............................................         0.05
Goat, fat..................................................         0.05
Goat, mbyp.................................................         0.05
Goat, meat.................................................         0.05
Hog, fat...................................................         0.05
Hog, mbyp..................................................         0.05
Hog, meat..................................................         0.05
Horse, fat.................................................         0.05
Horse, mbyp................................................         0.05
Horse, meat................................................         0.05
Milk.......................................................         0.05
Sheep, fat.................................................         0.05
Sheep, mbyp................................................         0.05
Sheep, meat................................................         0.05
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 05-5620 Filed 3-22-05; 8:45 am]
BILLING CODE 6560-50-S