[Federal Register: March 23, 2005 (Volume 70, Number 55)]
[Rules and Regulations]
[Page 14535-14546]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23mr05-6]
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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: kumar.rita@epa.gov.
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
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Guideline No. Study Type Results
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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
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[[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
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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
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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)
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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)
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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)
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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)
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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)
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870.4100 Chronic toxicity (rats) See 870.4300 combined chronic toxicity/
carcinogenicity (rats)
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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
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870.4200 Carcinogenicity (rats) See 870.4300 combined chronic toxicity/
carcinogenicity (rats)
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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
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[[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
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870.5100 Bacterial reverse mutation Negative. S9 up to 16,000
test [mu]g/plate
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870.5100 Bacterial reverse mutation Negative, S9 up to limit dose
test of 5,000 [mu]g/plate
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870.5300 In vitro mammalian cell Negative, S9 up to 2002 [mu]g/
gene mutation test mL (mouse lymphoma L5178Y cells)
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870.5375 In vitro mammalian Negative for clastogenic/aneugenic activity
chromosome aberration up to 2000 [mu]g/mL (CHL/IU cells)
test
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870.5395 In vivo mammalian Negative at oral doses up to 1,080 mg/kg/
cytogenics -micronucleus day for 2 days
assay
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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
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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
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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.
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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.
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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
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Special FQPA SF and
Exposure/Scenario Dose Used in Risk Level of Concern for Study and Toxicological
Assessment, UF Risk Assessment Effects
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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.
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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
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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
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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.
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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:
residuemethods@epa.gov.
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: opp-docket@epa.gov. Please use an ASCII
file format and avoid the use of special characters and any form of
encryption. Copies of electronic objections and hearing requests will
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format.
Do not include any CBI in your electronic copy. You may also submit an
electronic copy of your request at many Federal Depository Libraries.
B. When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
genuine and substantial issue of fact; there is a reasonable
possibility that available evidence identified by the requestor would,
if established resolve one or more of such issues in favor of the
requestor, taking into account uncontested claims or facts to the
contrary; and resolution of the factual issues(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).
VII. 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