[Federal Register Volume 69, Number 180 (Friday, September 17, 2004)]
[Rules and Regulations]
[Pages 55963-55975]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-20981]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2004-0155; FRL-7368-1]


Dinotefuran; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a tolerance for combined residues 
of dinotefuran N-methyl-N'-nitro-N'-[(tetrahydro-3-
furanyl)methyl)]guanidine and its metabolites DN [1-methy-3-
(tetrahydro-3-furylmethyl)]guanidine and UF [1-methyl-3-(tetrahydro-3-
furylmethyl)urea], expressed as dinotefuran in or on vegetable, leafy, 
except Brassica, group 4. Mitsui Chemicals, Inc. requested this 
tolerance 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 September 17, 2004. Objections and 
requests for hearings must be received on or before November 16, 2004.

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 
ID number OPP-2004-0155. 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 55964]]

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.gpo/opptsfrs/home/guidelin.htm/.

II. Background and Statutory Findings

    In the Federal Register of July 2, 2003 (FR 39547) (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 a pesticide petition (PP 2F6427) 
by Mitsui Chemicals, Inc., Chiyoda-ku, Tokyo, Japan. 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.
    The petition requested that 40 CFR 180.603 be amended by 
establishing a tolerance 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, in or on vegetable, leafy, 
except Brassica, group 4 at 5.0 parts per million (ppm).
    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 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 a tolerance 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 vegetable, leafy, except 
Brassica, group 4 at 5.0 ppm. EPA's assessment of exposures and risks 
associated with establishing the tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by 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 rats      NOAEL: 38/384 male and female (M/F)
                                                                             milligrams/kilogram/day (mg/kg/day)
                                                                            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
----------------------------------------------------------------------------------------------------------------
870.3100                                  90-Day oral toxicity in mice      NOAEL: 4,442/5,414 M/F mg/kg/day
                                                                            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 dogs      NOAEL: 307/not determined M/F mg/kg/
                                                                             day
                                                                            LOAEL: 862 M mg/kg/day, based on
                                                                             body weight gain, hemorrhagic lymph
                                                                             nodes; <59 F, based on decreased
                                                                             body weight, body weight gain
----------------------------------------------------------------------------------------------------------------

[[Page 55965]]

 
870.3200                                  28-Day dermal toxicity (rats)     Systemic
                                                                            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)
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870.3465                                  28-Day inhalation toxicity (rat)  NOAEL: < 0.22 M mg/L, 0.22 F mg/
                                                                            LOAEL: decreased body weight gain,
                                                                             food consumption M; increased
                                                                             clinical signs (protruding eyes) F
----------------------------------------------------------------------------------------------------------------
870.3700                                  Prenatal developmental toxicity   Maternal
                                           study (rats)                     NOAEL: 300 mg/kg/day
                                                                            LOAEL: 1,000 mg/kg/day based on body
                                                                             weight gain and food consumption
                                                                            Developmental
                                                                            NOAEL: 1,000 mg/kg/day
                                                                            LOAEL: not determined (no effects
                                                                             seen)
----------------------------------------------------------------------------------------------------------------
870.3700                                  Prenatal developmental toxicity   Maternal
                                           study (rabbits)                  NOAEL: 52 mg/kg/day
                                                                            LOAEL: 125 mg/kg/day based on 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 decreased spleen
                                                                             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 in sperm
                                                                             motility in F1 males
                                                                            Developmental
                                                                            NOAEL: 241/268 M/F mg/kg/day
                                                                            LOAEL: 822-935/907-1,005 M/F mg/kg/
                                                                             day based on decreased body
                                                                             weights, body weight gains, and
                                                                             spleen weights in F 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)
----------------------------------------------------------------------------------------------------------------

[[Page 55966]]

 
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
----------------------------------------------------------------------------------------------------------------
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 test   Negative,  S9 up to
                                                                             16,000 [mu]g/plate
----------------------------------------------------------------------------------------------------------------
870.5100                                  Bacterial reverse mutation test   Negative,  S9 up to
                                                                             limit dose of 5,000 [mu]g/plate
----------------------------------------------------------------------------------------------------------------
870.5300                                  In vitro mammalian cell gene      Negative,  S9 up to
                                           mutation test                     2,002 [mu]g/mL
                                                                            (Mouse lymphoma L5178Y cells)
----------------------------------------------------------------------------------------------------------------
870.5375                                  In vitro mammalian chromosome     Negative for clastogenic/aneugenic
                                           aberration test                   activity up to 2,000 [mu]g/mL
                                                                            (CHL/IU cells)
----------------------------------------------------------------------------------------------------------------
870.5395                                  In vivo mammalian cytogenics-     Negative at oral doses up to 1,080
                                           micronucleus assay                mg/kg/day for 2 days
----------------------------------------------------------------------------------------------------------------
870.6200                                  Acute neurotoxicity screening     NOAEL: 750 M, 325 F mg/kg/day
                                           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 pharmacokinetics   Absorption was > 90% regardless of
                                           (rats)                            dose. The 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-related or dose-
                                                                             related differences or label
                                                                             position effects were found.
----------------------------------------------------------------------------------------------------------------

[[Page 55967]]

 
Special study:                            Neonatal rat metabolism study     After a single oral 50 mg/kg dose of
                                           (12-day old rat pups)             G-14C MTI-446 to 12-day old rats,
                                                                             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 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 LOAELs of concern 
are identified 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 UFs may be used. ``Traditional 
UFs,'' the ``special FQPA safety factor,'' and the `` default FQPA 
safety factor.'' By the term ``traditional UF,'' EPA is referring to 
those additional UFs used prior to FQPA passage to account for data 
base deficiencies. These traditional UFs have been 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 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 
uncertainty factors 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, 
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 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                          NOAEL = 125 mg/kg/day    FQPA SF = 1              Developmental toxicity
(General population including infants  UF = 100...............  aPAD = acute RfD /.....   study in rabbits
 and children).                        Acute RfD = 1.25 mg/kg/  FQPA SF = 1.25 mg/kg/    LOAEL = 300 mg/kg/day
                                        day.                     day.                     based on clinical
                                                                                          signs in does (prone
                                                                                          position, panting,
                                                                                          tremor, erythema) seen
                                                                                          following a single
                                                                                          dose.
----------------------------------------------------------------------------------------------------------------

[[Page 55968]]

 
Chronic dietary                        LOAEL= 20 mg/kg/day      FQPA SF = 1              Chronic toxicity study
(All populations)....................  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                             NOAEL= 33 mg/kg/day      Residential LOC for MOE  Subchronic
Incidental oral (1 to 30 days).......                            = 100                    neurotoxicity study in
                                                                Occupational = NA......   rats
                                                                                         LOAEL = 327 mg/kg/day
                                                                                          based on increased
                                                                                          motor activity during
                                                                                          week 2
----------------------------------------------------------------------------------------------------------------
Intermediate-term                      NOAEL= 22 mg/kg/day      Residential LOC for MOE  Chronic toxicity study
Incidental oral (1 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 mg/ Residential LOC for MOE  Chronic toxicity study
                                        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
----------------------------------------------------------------------------------------------------------------
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                   = 1,000                  in dogs
                                       (inhalation absorption   Occupational LOC for     LOAEL = 20 mg/kg/day
                                        rate = 100%).            MOE = 1,000.             based on decreased
                                                                                          thymus weight in males
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)                                                        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. Currently there are no 
tolerances established for dinotefuran on any commodity. 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 
Dietary Exposure Evaluation Model software with the Food Commodity 
Intake Database (DEEM-FCIDTM), which incorporates food 
consumption data as reported by respondents in the United States 
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 leafy vegetables 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 DEEM 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 leafy vegetables had been treated with

[[Page 55969]]

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 Screening Concentration in Groundwater (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 
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 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 Index Reservoir Screening Tool (FIRST) and SCI-GROW 
models, the EECs of dinotefuran for acute exposures are estimated to be 
75.78 parts per billion (ppb) for surface water and 5.06 ppb for ground 
water. The EECs for chronic exposures are estimated to be 20.97 ppb for 
surface water and 5.06 ppb for ground water.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets).
    Dinotefuran is proposed to be registered for use on the following 
residential non-dietary sites: Professional turf management, 
professional ornamental production, residential indoor, lawn and 
garden. The risk assessment was conducted using the following 
residential exposure assumptions: Outdoor uses for turf farms, golf 
courses and residential lawns, ornamentals and vegetable gardens.
    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, home gardens that could lead to exposures for adults. As 
a result, risk assessments have been completed for both residential 
handler and post-application scenarios.
    Residential handlers may be exposed dermally and by inhalation 
during mixing, loading and application of dinotefuran for short-term 
durations. However, a short-term dermal endpoint was not identified. 
For this reason, and because the short-term and intermediate-term 
inhalation endpoints are the same, intermediate-term risks are assessed 
for residential handlers as a screen for their potential short-term 
exposures. Because common toxicity endpoints were identified for both 
dermal and inhalation routes, a combined risk from both routes of 
exposure is assessed. Combined risk was estimated by calculating an 
aggregate risk index (ARI). All residential handler estimated exposures 
meet or exceed the Agency's target ARI of 1, and are therefore, not of 
concern.
    Residential post-application exposures are assumed to be mostly of 
short-term duration (1 to 30 days); although intermediate-term (1 to 6 
months) exposures are possible. Because there are numerous dinotefuran 
use products and scenarios, those scenarios assessed were chosen to 
cover the major residential use sites (i.e. turf, home garden etc.) and 
highest use rates and exposures. The margins of exposure (MOEs) for 
post-application exposure to dinotefuran are above the target MOE of 
100, and therefore, do not exceed Agency's level of concern for the 
following scenarios: (1) Exposure to adults and children from turf 
products; and (2) exposure to adults in vegetable gardens.
    The Agency combines risks resulting from exposures to individual 
chemicals when it is likely they can occur simultaneously based on the 
use pattern and the behavior associated with the exposed population. 
For this assessment, the Agency has added together risk values for 
adults applying dinotefuran to residential lawns and then being exposed 
to the treated lawn. For children, dermal and incidental oral exposures 
from activities on treated lawn were combined. These are considered to 
represent worst case scenarios for co-occurring residential exposures.
    The risks from the combined exposures of adults applying 
dinotefuran to residential lawns and then being dermally exposed from 
post-application 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

[[Page 55970]]

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's OPP 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 data base 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 UF (safety) 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 pre- and/or postnatal toxicity resulting 
from exposure to dinotefuran, some uncertainty is raised by a 
deficiency in the data (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 endpoint and long-term level 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 a overall safety/
uncertainty factor of 1,000 (representing 100X for inter-and intra-
species 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. 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 
Developmental Immunotoxicity Study (DIT) 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 
one 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 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 
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 
developmental neuorotoxicity study. Developmental neurotoxicity 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

[[Page 55971]]

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 (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 0.68% of the aPAD for the U.S. population, 
0.76% of the aPAD for females 13 years and older, 0.21% of the aPAD for 
infants <1 year old, and 0.76% of the aPAD for children 3 to 5 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/kg/    % aPAD     Water EEC    Water EEC   Acute DWLOC
                                                     day)        (Food)       (ppb)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                         1.25         0.68        75.78         5.06       43,000
----------------------------------------------------------------------------------------------------------------
All infants (< 1 year old)                              1.25         0.21        75.78         5.06       12,000
----------------------------------------------------------------------------------------------------------------
Children (3-5 years old)                                1.25         0.76        75.78         5.06       12,000
----------------------------------------------------------------------------------------------------------------
Females (13-49 years old)                               1.25         0.76        75.78         5.06       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 8.6% of the cPAD for the U.S. 
population, 4.4% of the cPAD for infants <1 year old, 8.6% of the cPAD 
for children 3-5 years old and 9.4% of the cPAD for females 13-49 years 
old. 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/    %cPAD      Water EEC    Water EEC     Chronic
                                                     day)        (FOOD)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                         0.02          8.6        20.97         5.06          640
----------------------------------------------------------------------------------------------------------------
All infants (< 1 year old)                              0.02          4.4        20.97         5.06          190
----------------------------------------------------------------------------------------------------------------
Children (3-5 years old)                                0.02          8.6        20.97         5.06          180
----------------------------------------------------------------------------------------------------------------
Females (13-49 years old)                               0.02          9.4        20.97         5.06          550
----------------------------------------------------------------------------------------------------------------

    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 proposed for uses that could result in short-term 
residential exposure, and the Agency has determined that it is 
appropriate to aggregate chronic food and water and short-term 
exposures. For dinotefuran, short-term and intermediate-term aggregate 
risk assessments based on exposure from oral, inhalation, and dermal 
routes were considered.

[[Page 55972]]

 However, for short-term aggregate exposure assessment, oral and 
inhalation risk estimates cannot be combined due to the different bases 
of their endpoints; i.e., neurotoxicity for oral and decrease in body 
weight for inhalation. 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 cannot be performed for dinotefuran. However, 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 proposed for uses 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.
    The child subgroup with the highest estimated chronic dietary 
exposure (children 3-5 years old) was used to calculate the 
intermediate-term aggregate risk, including chronic dietary (food and 
drinking water) and residential dermal and oral exposures. All 
acceptable MOEs must be identical for all MOEs to be included in the 
intermediate-term risk assessment. Based on the toxicity endpoint 
information, all acceptable MOEs are 100, and an oral endpoint for 
hand-to-mouth residential exposure was identified. In this case, the 
chronic dietary endpoint (NOAEL) was used to incorporate dietary (food 
and water), and residential exposures in the aggregate risk assessment. 
An intermediate-term residential exposure scenario was identified and 
includes dermal and 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 residential MOE 
was estimated to be 590. The average (chronic) dietary exposure for the 
highest exposed child subgroup (children 3-5 years old) was estimated 
to be 0.0017 mg/kg/day. 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                                                           Surface
                                                                   NOAEL/mg/    Target       Max         Food     Residential  Aggregate MOE   Max Water      Ground      Water    Intermediate-
                            Population                               kg/day      MOE1    Exposure2/  Exposure mg/  Exposure3     (food and     Exposure5    Water EEC6     EEC6     Term DWLOC7
                                                                                          mg/kg/day     kg/day     mg/kg/day   residential)4   mg/kg/day     [mu]g/L     [mu]g/L      [mu]g/L
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 yrs old                                                      22        100        0.22       0.0017     0.037227           565         0.181        20.97       5.06        1,810
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
1 The target MOE of 100 is based on the standard inter-species 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.
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 103 mg/[mu]g.

    Compared with the EECs, the aggregate intermediate-term DWLOC does 
not exceed Agency's level of concern for the subgroup population of 
children 3-5 years old.
    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 post-application 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 occurred 
with females 13-49 years old (i.e. 0.0019 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 assessed and combined. The 
aggregate risk assessment for intermediate-term exposure to adults is 
summarized in following Table 6.

[[Page 55973]]



                              Table 6.--Aggregate Risk Assessment for Intermediate-Term Exposure of Adults to Dinotefuran.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                       Residential ARIs3
                                                            ---------------------------------------
                                                                    Applicators           Post-      Max Water      Ground      Surface    Intermediate-
            Polulation             Target ARI1   ARI Food2  -------------------------- application    Exposure    Water EEC5   Water EEC5   Term DWLOC6
                                                                Dermal     Inhalation     Dermal        ARI4       [mu]g/L      [mu]g/L       [mu]g/L
                                                               Exposure     Exposure     Exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females 14-49 years old                      1          116           17          970           12         1.18        20.97         5.06         5,600
--------------------------------------------------------------------------------------------------------------------------------------------------------
1 ARI (Aggregate Risk Index) = MOEcalculated/MOEacceptable
2 ARIFood = 22 / 0.0019 / 100 = 116
3. ARIdermal = MOEcalculated/100 and, ARIinhal = MOEinhal/1,000
4. ARI Water = 1/1/1- (1/ARIResidential aplicator dermal) + (1/ARIResidential applicator inhalation) + (1/ARI Post-application dermal)
5. The use site producing the highest level was used; i.e. turf.
6. DWLOC ([mu]g/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) / ARI Water (1.18) x 100 = 0.1866 mg/kg/day.

    Compared with the EEC, the aggregate intermediate-term DWLOC does 
not exceed Agency's level of concern for the subgroup population of 
females 13-49 years old.
    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 (High Performance Liquid 
Chromatography/Ultraviolet for the determination of residues of 
dinotefuran per se in lettuce, and High Performance Liquid 
Chromatography/Mass Spectrometry and High Performance Liquid 
Chromatography/Mass Spectrometry/Mass Spectrometry method for the 
determination of dinotefuran metabolites DN [1-methyl-3-(tetrahydro-3-
furylmethyl)guanidine] and UF [1-methyl-3-(tetrahydro-3-
furylmethyl)urea] in lettuce) is available to enforce the tolerance 
expression. The method 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].

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, leafy, except Brassica, group 4 at 5.0 
ppm.

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-2004-0155 in the subject line on the 
first page of your submission. All requests must be in writing, and 
must be mailed or delivered to the Hearing Clerk on or before November 
16, 2004.
    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, Environmental Protection Agency, 1099 14th 
Street NW., Suite 350, Washington DC 20005, (telephone number (202) 
564-6255). The Office of the Hearing Clerk is open from 8 a.m. to 4 
p.m., Monday through Friday, excluding legal holidays. The telephone 
number for the Office of the Hearing Clerk is (703) 603-0061.
    2. 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-2004-0155, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide

[[Page 55974]]

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 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: September 9, 2004.
James Jones,
Director, 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 added to subpart C to read as follows:


Sec.  180.603  Dinotefuran; tolerances for residues.

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

[[Page 55975]]



------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Vegetable, leafy, except Brassica, group 4                           5.0
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 04-20981 Filed 9-16-04; 8:45 am]
BILLING CODE 6560-50-S?>