Spiromesifen; Pesticide Tolerance, 21631-21641 [05-8120]
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Federal Register / Vol. 70, No. 80 / Wednesday, April 27, 2005 / Rules and Regulations
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.
VII. 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: April 14, 2005.
Lois Rossi,
Director, Registration Division, Office of
Pesticide Programs.
Therefore, 40 CFR Chapter I is
amended as follows:
I
PART 180—[AMENDED]
1. The authority citation for part 180
continues to read as follows:
I
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.460 paragraph (a) is
revised to read as follows:
I
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§ 180.460 Benoxacor; tolerances for
residues.
(a) General. Tolerances are
established for residues of the inert
ingredient (safener) benoxacor (4(dichloroacetyl)-3,4-dihydro-3-methyl2H-1, 4-benzoxazine) at 0.01 parts per
million (ppm) when used in pesticide
formulations containing metolachlor or
S-metolachlor in or on raw agricultural
commodities for which tolerances have
been established for metolachlor or Smetolachlor.
*
*
*
*
*
[FR Doc. 05–8119 Filed 4–26–05; 8:45 am]
BILLING CODE 6560–50–S
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[OPP–2005–0046; FRL–7705–1]
Spiromesifen; Pesticide Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes a
tolerance for: Primary crops for the
combined residues of spiromesifen (2oxo-3-(2,4,6-trimethylphenyl)-1oxaspiro[4.4]non-3-en-4-yl 3,3dimethylbutanoate) and its enol
metabolite (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one), calculated as the parent
compound equivalents; rotational crops
for the inadvertent or indirect combined
residues of spiromesifen (2-oxo-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-4-yl 3,3-dimethylbutanoate), its enol
metabolite (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one), and its metabolites
containing the 4-hydroxymethyl moiety
(4-hydroxy-3-[4-(hydroxymethyl)-2,6dimethylphenyl]-1-oxaspiro[4.4]non-3en-2-one), calculated as the parent
compound equivalents; and livestock
commodities for the combined residues
of spiromesifen (2-oxo-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-4-yl 3,3-dimethylbutanoate), and its
metabolites containing the enol (4hydroxy-3-(2,4,6-trimethylphenyl)-1oxaspiro[4.4]non-3-en-2-one) and 4hydroxymethyl (4-hydroxy-3-[4(hydroxymethyl)-2,6-dimethylphenyl]1-oxaspiro[4.4]non-3-en-2-one) moieties,
calculated as the parent compound
equivalents. Bayer CropScience
requested these tolerances under the
Federal Food, Drug, and Cosmetic Act
(FFDCA), as amended by the Food
Quality Protection Act of 1996 (FQPA).
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21631
This regulation is effective April
27, 2005. Objections and requests for
hearings must be received on or before
June 27, 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–
0046. 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:
Thomas Harris, Registration Division
(7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 308–9423; e-mail address:
harris.thomas@epa.gov.
SUPPLEMENTARY INFORMATION:
DATES:
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;
greenhouse, nursery, and floriculture
workers; residential users.
This listing is not intended to be
exhaustive, but rather provides a guide
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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
https://www.epa.gov/fedrgstr/. A
frequently updated electronic version of
40 CFR part 180 is available on E-CFR
Beta Site Two athttps://
www.gpoaccess.gov/ecfr/. To access the
OPPTS Harmonized Guidelines
referenced in this document, go directly
to the guidelines at https://www.epa.gpo/
opptsfrs/home/guidelin.htm/.
II. Background and Statutory Findings
In the Federal Register of July 28,
2004 (69 FR 45047) (FRL–7366–2), 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 3F6537) by Bayer
CropScience, 2 T.W. Alexander Drive,
Research Triangle Park, NC 27709. The
petition requested that 40 CFR part 180
be amended by establishing a tolerance
for the combined residues of the
insecticide/miticide:
1. Spiromesifen; butanoic acid, 3,3dimethyl-, 2-oxo-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-4-yl ester [subsequently referred to as
(2-oxo-3-(2,4,6-trimethylphenyl)-1oxaspiro[4.4]non-3-en-4-yl 3,3dimethylbutanoate) and its enol
metabolite (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one)] in or on strawberry at 2.0
parts per million (ppm); vegetable,
tuberous and corm, crop subgroup 1C, at
0.01 ppm (subsequently revised to 0.02
ppm); vegetable, leafy greens (except
Brassica), crop subgroup 4A at 10 ppm
(subsequently revised to vegetable, leafy
greens, subgroup 4A at 12 ppm);
vegetable, Brassica, head and stem, crop
subgroup 5A, at 2.0 ppm; vegetable,
Brassica, leafy, crop subgroup 5B at 12
ppm; vegetable, fruiting, crop group 8,
at 0.30 ppm; tomato, paste at 0.60 ppm;
vegetable, cucurbit, crop group 9, at 0.10
ppm; corn, field, grain, at 0.01 ppm
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(subsequently revised to 0.02 ppm);
corn, field, forage, at 3.0 ppm; corn,
field, stover, at 5.0 ppm; cotton
(subsequently defined as cotton,
undelinted seed) at 0.50 ppm; and
cotton, gin byproducts, at 15 ppm.
2. Spiromesifen; butanoic acid, 3,3dimethyl-, 2-oxo-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-4-yl ester [subsequently referred to as
(2-oxo-3-(2,4,6-trimethylphenyl)-1oxaspiro[4.4]non-3-en-4-yl 3,3dimethylbutanoate), its enol metabolite
(4-hydroxy-3-(2,4,6-trimethylphenyl)-1oxaspiro[4.4]non-3-en-2-one), and its
metabolites containing the 4hydroxymethyl moiety (4-hydroxy-3-[4(hydroxymethyl)-2,6-dimethylphenyl]1-oxaspiro[4.4]non-3-en-2-one)] in or on
the rotational crop commodities alfalfa,
forage, at 1.5 ppm; alfalfa, hay, at 3.0
ppm; wheat, grain, at 0.01 ppm
(subsequently revised to 0.03 ppm);
wheat, forage, at 0.20 ppm; wheat, hay,
at 0.15 ppm; wheat, straw, at 0.25 ppm;
wheat, bran, at 0.05 ppm (subsequently
combined with wheat, shorts and
defined together as ‘‘wheat milled
byproducts’’ with no tolerance
required); wheat, shorts, at 0.03 ppm
(subsequently combined with wheat,
bran and defined together as ‘‘wheat
milled byproducts’’ with no tolerance
required); barley, grain, at 0.02 ppm
(subsequently revised to 0.03 ppm);
barley, hay, at 0.25 ppm; barley, straw,
at 0.25 ppm (subsequently revised to
0.15 ppm); beet, sugar, tops, at 0.20
ppm; beet, sugar, roots, at 0.02 ppm
(subsequently revised to 0.03 ppm); and
beet, sugar, molasses, at 0.05 ppm
(tolerance subsequently not required).
3. Spiromesifen; butanoic acid, 3,3dimethyl-, 2-oxo-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-4-yl ester [subsequently referred to as
2-oxo-3-(2,4,6-trimethylphenyl)-1oxaspiro[4.4]non-3-en-4-yl 3,3dimethylbutanoate), and its metabolites
containing the enol (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one) and 4-hydroxymethyl (4hydroxy-3-[4-(hydroxymethyl)-2,6dimethylphenyl]-1-oxaspiro[4.4]non-3en-2-one) moieties)] in or on the raw
agricultural commodities cattle, fat, at
0.05 ppm; cattle, meat byproducts, at
0.05 ppm; milk at 0.01 ppm (tolerance
subsequently not required); and milk,
fat, at 0.03 ppm (subsequently revised to
0.10 ppm).
Following the review of all data,
tolerances are also required for the
following commodities: Goat, fat at 0.05
ppm; goat meat byproducts at 0.05 ppm;
sheep, fat at 0.05 ppm; sheep, meat
byproducts at 0.05 ppm; horse, fat at
0.05 ppm; and horse, meat byproducts
at 0.05 ppm.
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That notice included a summary of
the petition prepared by Bayer
CropScience, the registrant. A comment
was received from a private citizen who
challenged the value of using animal
testing for evaluating pesticide toxicity
and questioned the data gaps related to
the tolerance proposal process. This
commenter’s objections have been
addressed in prior rulemaking
documents. See (69 FR 63083, 63096)
(October 29, 2004).
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 (62 FR
62961, November 26, 1997) (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 the combined
residues of spiromesifen on the crops
and animal commodities listed above.
EPA’s assessment of exposures and
risks associated with establishing the
tolerances follows.
A. Toxicological Profile
EPA has evaluated the available
toxicity data and considered its validity,
completeness, and reliability as well as
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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 spiromesifen are
discussed in Table 1 of this unit as well
as the no observed adverse effect level
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(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
870.3050
28–Day oral toxicity
(mouse)
NOAEL was not established
LOAEL (M/F) = 202.6/269.6 mg/kg/day based on decreased body weight gain
870.3050
28–Day oral toxicity
(mouse)
NOAEL was not established
LOAEL (M/F) = 444.3 mg/kg/day based on decreased body weight gain and increase in alkaline phosphatase
870.3100
28–Day oral toxicity (rat)
NOAEL = 53.4 mg/kg/day
LOAEL = 536.3 mg/kg/day based on clinical signs (piloerection, reduced motility,
spastic gait, discolored feces and increased reactivity when touched), decrease in
body weight gain, and food consumption, hematology (thromboplastin time increase), clinical chemistry (increased aspartateaminotransferase and alanine
aminotransferase), liver enzyme (increased aldrin expoxidase and epoxide hydrolase), increased spleen and lymph node cell proliferation, organ-weights (increase
brain, heartand kidneys, decrease in weights in the ovaries, spleen and thymus),
gross pathology (thin appearance, discolored adrenal glands and white mucous in
the duodenum and jejunum), and microscopic findings (vacuolation of the superficial mucosal cells in the jejunum and duodenum, increased follicular cell hypertrophy in the thyroid, indistinct corticomedullary junction in the thymus and
cytoplasmic changes in the adrenal glands)
870.3150
90–Day oral toxicity (nonrodent)
NOAEL = 9.2 mg/kg/day
LOAEL = 71 mg/kg/day (HDT) based on clinical chemistry(increased ALP) and liver
histopathology
870.3150
90–Day oral toxicity (nonrodent)
NOAEL was not established
LOAEL = 98.4 mg/kg/day (HDT) based on increase in alkalinephosphatase and liver
histopathology (cytoplasmic changes)
870.3150
90–Day oral toxicity (rat)
NOAEL (M/F) = 31.7/7.7 mg/kg/day.
LOAEL (F) = 36.6 mg/kg/day based on thyroid effects (increased thyroid stimulating
hormone, thyroxine binding capacity and thyroid follicular cell hypertrophy), kidney
effects (mineralization), and liver effect (increased ALP)
LOAEL (M) = 204.0 mg/kg/day based on thyroid effect (colloidal alteration, follicular
cell hypertrophy, decreased T3 and T4 and increased TBC and TSH), kidney effects (Hyalin droplets), and liver effects (increase in ALP and ALAT)
870.3200
21/28–Day dermal toxicity
(rat)
NOAEL = 1,000 mg/kg/day (HDT)
LOAEL was not established
870.3465
5–Day inhalation toxicity
(rat)
NOAEL = 20.7 mg/kg/day
LOAEL = 134.2 mg/kg/day based onthe clinical signs (tremors, clonic-tonic convulsions, reduced activity,bradypnea, labored breathing,vocalization, avoidance reaction,giddiness, piloerection, limp,emaciation, cyanosis, squattedposture, apathy,
and salivation), andgross pathology (dark red areas orfoci in the lungs, bloated
stomachsand pale liver)
870.3465
30–Day inhalation toxicity
(rat)
NOAEL >21.1 mg/kg/day
LOAEL was not established
870.3700
Prenatal developmental
(rat)
Maternal NOAEL = 10 mg/kg/day
Maternal LOAEL = 70 mg/kg/daybased on decreased body weight gainand reduced
food consumption.
Developmental NOAEL ≥ 500mg/kg/day (HDT)
Developmental LOAEL > 500 mg/kg day
870.3700
Prenatal developmental
(nonrodent)
Maternal NOAEL = 5 mg/kg/day
Maternal LOAEL = 35 mg/kg/day based on body weight loss and reduced food consumption
Developmental NOAEL ≥ 250 mg/kg/day
Developmental LOAEL > 250 mg/kg/day
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TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.3800
Reproduction and fertility
effects (rat)
Parental/Systemic NOAEL (M/F) = 2.2/3.8 mg/kg/day
Parental/Systemic LOAEL (M/F) = 8.8/13.2 mg/kg/day based on significantly decreased spleen weight (absolute and relative in parental females and F1 males)
and significantly decreased growing ovarian follicles in females
Reproductive NOAEL (M/F) = 37/64 mg/kg/day (HDT)
Reproductive LOAEL = Not established
Offspring NOAEL = 2.2 mg/kg/day
Offspring LOAEL = 8.8 mg/kg/day based on pup body weight decrements during lactation
870.4100
Chronic toxicity (rat)
NOAEL (M/F) = 15.9/19.3 mg/kg/day
LOAEL (M/F) = 42.4/51.7 mg/kg/day based on increase in T3 hormone in males,
gross pathology (enlarged liver in males, dilated uterus and discolored adrenal
gland in females) and histopathology (adrenal cytoplasmic eosinophilia, metritise,
thyroid colloidal alteration in female and thyroid follicular cell hypertrophy in both
males and females)
870.4100
Chronic toxicity (nonrodent)
NOAEL (M/F) = 11.5/10.8 mg/kg/day
LOAEL (M/F) = 109/117 mg/kg/day based on increase in alkaline phosphatase and
liver histopathology (cytoplasmic changes, inclusions and vacuoles)
870.4200
Carcinogenicity (rat)
NOAEL (M/F) = 14.8/19.5 mg/kg/day
LOAEL (M/F) = 40.0/53.5 mg/kg/day based on clinical signs (palpable masses, vaginal bleeding and pallor), gross necropsy (discolored area in the lungs, nodules/dilation of uterus) and hispathology (osseus metaplasia and granulomatous inflammation of the lungs in the males, liver necrosis; endometritis/metritis, endometrial
hyperplasia of the cervix uteria and colloidal alteration of the thyroid gland in females) and increased TSH in females.
No evidence of carcinogenicity
870.4200
Carcinogenicity (mouse)
NOAEL (M/F) = 3.3/3.8 mg/kg/day
LOAEL (M/F) = 22/30 mg/kg/day based on gross (enlarged adrenal gland in males)
and microscopic changes (cytoplamic eosinophilia, ceroid deposits, and diffuse
fatty changes of the adrenal cortex and pancreatic amyloidosis in both sexes)
No evidence of carcinogenicity
870.5100
Gene mutation--In Vitro
bacteria
Negative
870.5300
Cytogenetics In Vitro
Mammalian Gene Mutation
Negative
870.5375
Cytogenetics--In Vitro
Mammalian
Negative
870.5395
Cytogenetics In Vivo
Mammalian Micronucleus (mouse)
Negative
870.6200
Acute neurotoxicity
screening battery
NOAEL = 2,000 mg/kg/day
LOAEL = Not established
870.6200
Subchronic neurotoxicity
screening battery
NOAEL (M/F) = 31.8/38.3 mg/kg/day.
LOAEL (M/F) = 122.7/149.3 mg/kg/day based on decreased body weight gain and
food consumption.
870.7485
Metabolism and pharmacokinetics (rat)
Spiromesifen exhibits moderate absorption (approximately 43%), relatively rapid excretion primarily via the urine and feces. Approximately 39% of the administered
dose was excreted in the urine and 55 to 57% in the feces with 88 to 90% of the
dose being eliminated within the first 24 hours. Maximum concentration in the
blood achieved within 1 to 6 hours post- dose depending upon the dose. Concentrations of residual radioactivity in the tissues were quite low at 72 hours postdose. The test material was initially metabolized to the keto-enol by loss of the
dimethylbutyric acid moiety. Both the phenyl and cyclopentyl rings were
hydoxylated and the methyl groups on the phenyl ring were ultimately oxidized to
a carboxylic acid. These metabolites were largely recovered in the bile and urine.
The predominate moiety recovered in the feces was the unmetabolized test material.
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TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.7600
Dermal penetration (nonrodent)
Intravenous injection resulted in excretion of the radiolabel mainly via urine: Urine
(54.32%), feces (13.08%), and cage debris/rinse (26.57%). Excretion was rapid in
that 70% of the dose was excreted within 24 hours. Dermal application of
spiromesifen resulted in limited absorption after 8–hour exposure (3.3%), which a
large portion was recovered from urine and cage debris/rinse showing that it is
poorly absorbed through the skin layers.
870.7800
4–Week immunotoxicity
(rat)
NOAEL (M/F) = 52.8/45.7 mg/kg/day
LOAEL (M/F) = 291.6/288.6 mg/kg/day based on mortality, clinical signs and decreased body weights, body weight gains and food consumption.
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
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 (acute RfD or chronic RfD) 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 spiromesifen used for
human risk assessment is shown in
Table 2 of this unit:
TABLE 2.— SUMMARY OF TOXICOLOGICAL DOSE AND ENDPOINTS FOR SPIROMESIFEN FOR USE IN HUMAN RISK
ASSESSMENT
1Exposure Scenario
Acute dietary (females 13-49
years of age)
Dose Used in Risk Assessment, Interspecies and
Intraspecies and any Traditional UF
Not applicable
Special FQPA SF and
Level of Concern for Risk
Assessment
None
Study and Toxicological Effect
An endpoint of concern attributable to a single
dose was not identified. An aRfD was not
established.
Acute dietary (general population)
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TABLE 2.— SUMMARY OF TOXICOLOGICAL DOSE AND ENDPOINTS FOR SPIROMESIFEN FOR USE IN HUMAN RISK
ASSESSMENT—Continued
Dose Used in Risk Assessment, Interspecies and
Intraspecies and any Traditional UF
1Exposure Scenario
Chronic dietary (all populations)
NOAEL= 2.2 mg/kg/day
UF = 100X
Chronic RfD = 0.022 mg/kg/
day
Cancer (oral, dermal, inhalation)
17:56 Apr 26, 2005
Special FQPA SF = 1X
Study and Toxicological Effect
2–generation reproduction study in rats.
The parental systemic
LOAEL:
13.2 mg/kg/day based on significantly decreased spleen weight (absolute and relative
in parental females and F1 males) and significantly decreased growing ovarian follicles
in females.
Classification: ‘‘Not likely to be carcinogenic to humans.’’
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. No tolerances have previously
been established for spiromesifen. Risk
assessments were conducted by EPA to
assess dietary exposures from
spiromesifen in food as follows:
i. Acute exposure. Acute dietary risk
assessments are performed for a fooduse 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. Acute dietary
exposure limits for all populations,
including infants and children, were not
performed because an endpoint of
concern attributable to a single exposure
(dose) was not identified from the oral
toxicity studies.
ii. Chronic exposure. In conducting
the chronic dietary risk assessment EPA
used the Dietary Exposure Evaluation
Model software with the Food
Commodity Intake Database (DEEMFCIDTM) and the LifelineTM model
version 2.0, which incorporates food
consumption data as reported by
respondents in the USDA 1994–1996
and 1998 Nationwide Continuing
Surveys of Food Intake by Individuals
(CSFII), and accumulated exposure to
the chemical for each commodity.
Percent crop treated and anticipated
residues were not used.
An unrefined, Tier 1 chronic dietary
exposure assessment was conducted
using the following:
a. Recommended tolerances for all
plant and livestock except the leafygreen and leafy-Brassica vegetable
subgroups;
b. EPA calculated residues of concern
(parent and metabolites) for the leafygreen and leafy-Brassica vegetable
subgroups;
c. 100% crop treated (CT) information
for all proposed uses; and
d. Default processing factors for all
commodities.
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Level of Concern for Risk
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The metabolism studies show that the
hydroxymethyl metabolite is formed
along with the enol metabolite in the
leafy-green and leafy-Brassica vegetable
subgroups. EPA determined that these
two metabolites along with the
spiromesifen should be included in the
chronic dietary risk assessment for these
crops. Residue data are unavailable for
the 4-hydroxymethyl metabolite; to
account for this metabolite in the risk
assessment, the recommended tolerance
levels for these crops was multiplied by
a correction factor of 1.3x, where:
1.3 = Metabolites in Risk Assessment
(ppm)/Metabolites in Tolerance
Expression (ppm).
The dietary-exposure assessment was
conducted for the general U.S.
population and various population
subgroups. This assessment concludes
that the chronic dietary exposure
estimates are below EPA’s level of
concern (<100% cPAD) for the general
U.S. population (27% cPAD and 29%
cPAD, based on the LifelineTM and
DEEM-FCIDTM analyses, respectively)
and all population subgroups. Both
LifelineTM and DEEM-FCIDTM estimate
that children 3 to 5 years old are the
most highly-exposed subpopulation
with risks of 30% cPAD and 37% cPAD,
respectively.
iii. Cancer. A cancer exposure
assessment was not performed because
spiromesifen is classified as ‘‘not likely
to be carcinogenic to humans.’’
2. Dietary exposure from drinking
water. The Agency lacks sufficient
monitoring exposure data to complete a
comprehensive dietary exposure
analysis and risk assessment for
spiromesifen 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
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the physical characteristics of
spiromesifen.
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 Concentrations
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
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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 spiromesifen
they are further discussed in the
aggregate risk sections in Unit E.
Based on the PRZM/EXAMS and SCIGROW models, the EECs of
spiromesifen for acute exposures are
estimated to be 7.1 parts per billion
(ppb) for surface water and 0.005 ppb
for ground water. The EECs for chronic
exposures are estimated to be 0.70 ppb
for surface water and 0.005 ppb for
ground water.
EECs of spiromesifen and its
metabolites for acute exposures are
estimated to be 26 ppb for surface water
and 28 ppb for ground water. The EECs
for chronic exposures are estimated to
be 11 ppb for surface water and 28 ppb
for ground water.
3. From non-dietary exposure. The
term ‘‘residential exposure’’ is used in
this document to refer to nonoccupational, non-dietary exposure
(e.g., for lawn and garden pest control,
indoor pest control, termiticides, and
flea and tick control on pets).
Spiromesifen is not registered for use
on any sites that would result in
residential exposure.
4. Cumulative effects from substances
with a common mechanism of toxicity.
Section 408(b)(2)(D)(v) of the 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
spiromesifen and any other substances
and spiromesifen 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 spiromesifen 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 Office of Pesticide
Programs concerning common
mechanism determinations and
procedures for cumulating effects from
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substances found to have a common
mechanism on EPA’s website at https://
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
uncertainty (safety) factors 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 uncertainty factors and/or
special FQPA safety factors, as
appropriate.
2. Prenatal and postnatal sensitivity.
There was no evidence of increased
susceptibility of rats or rabbits to in
utero and/or postnatal exposure to
spiromesifen. In a rat developmental
toxicity study, no developmental
toxicity was observed at doses up to 500
mg/kg/day (the highest dose tested) in
the presence of maternal toxicity. The
rat maternal LOAEL was determined to
be 70 mg/kg/day based on decreased
body-weight gain and reduced food
consumption. In the rabbit
developmental toxicity study, there was
no developmental toxicity observed at
doses up to 250 mg/kg/day (the highest
dose tested), but the maternal LOAEL
was determined to be 35 mg/kg/day
based on body weight loss and reduced
food consumption. There is no
qualitative and/or quantitative evidence
of increased susceptibility to
spiromesifen following pre/postnatal
exposure in a 2–generation reproduction
study in rats.
There is no concern for
developmental neurotoxicity resulting
from exposure to spiromesifen.
Neurotoxic effects such as reduced
motility, spastic gait, increased
reactivity, tremors, clonic-tonic
convulsions, reduced activity, labored
breathing, vocalization, avoidance
reaction, piloerection, limp, cyanosis,
squatted posture, and salivation were
observed in two studies (5–day
inhalation and subchronic oral rat).
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However, these effects were considered
as secondary, not neurotoxic, effects due
to the high dosage. There was no
evidence of neurotoxicity in the acute or
subchronic neurotoxicity or any other
studies.
3. Conclusion. For spiromesifen, EPA
determined that the 10X safety factor to
protect infants and children should be
removed. A 1X safety factor is
appropriate because:
• There is a complete toxicity data
base for spiromesifen.
• There is no evidence of increased
susceptibility of rats or rabbits to in
utero and/or postnatal exposure to
spiromesifen. In the prenatal
developmental toxicity studies in rats
and rabbits and in the 2–generation
reproduction study in rats,
developmental toxicity to the offspring
occurred at equivalent or higher doses
than maternal toxicity.
• There are no neurotoxicity concerns
based on acute and subchronic
neurotoxicity studies.
• The dietary food exposure
assessment uses proposed tolerance
levels or higher residues and assumed
100% crop-treated (CT) information for
all commodities. By using these
screening-level assessments, chronic
exposures and risks will not be
underestimated. The ‘‘higher residues’’
are those that were calculated using a
modifying factor to account for the lack
of spiromesifen-4-hydroxymethyl
residue data.
• The dietary drinking water
assessment (Tier 2 estimates) uses
values generated by model and
associated modeling parameters which
are designed to provide conservative,
health protective, and high-end
estimates of water concentrations.
• Residential exposure is not
expected--spiromesifen will be
registered for agricultural and
greenhouse/ornamental uses only.
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
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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
chronic exposure and the EECs from
DEEM-FCIDTM as these were slightly
higher, and thus are more conservative,
than the LifelineTM estimates, EPA has
concluded that exposure to
spiromesifen from food will utilize 29%
of the cPAD for the U.S. population,
15% of the cPAD for all infants less than
1 year old, and 37% of the cPAD for
children 3-5 years old. There are no
residential uses for spiromesifen that
result in chronic residential exposure to
spiromesifen. There is no concern
regarding spiromesifen in ground water
and surface 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 Table 3 of this
unit:
calculated DWLOCs, OPP concludes
with reasonable certainty that exposures
to the pesticide in drinking water (when
considered along with other sources of
exposure for which OPP has reliable
data) would not result in unacceptable
levels of aggregate human health risk at
this time. Because OPP considers the
aggregate risk resulting from multiple
exposure pathways associated with a
pesticide’s uses, levels of comparison in
drinking water may vary as those uses
change. If new uses are added in the
future, OPP will reassess the potential
impacts of residues of the pesticide in
drinking water as a part of the aggregate
risk assessment process.
1. Acute risk. Spiromesifen is not
expected to pose an acute risk because
an endpoint of concern attributable to a
single exposure (dose) was not
identified from the oral toxicity studies.
2. Chronic risk. Using the exposure
assumptions described in this unit for
TABLE 3.—AGGREGATE RISK ASSESSMENT FOR CHRONIC (NON-CANCER) EXPOSURE TO SPIROMESIFEN + METABOLITES
cPAD mg/
kg/day
Population Subgroup
Surface
Water EEC
(ppb)
% cPAD
(Food)1
Ground
Water EEC
(ppb)
Chronic
DWLOC
(ppb)
U.S. population
0.022
29
11
28
545
All Infants (<1 year old)
0.022
15
11
28
187
Children (1-2 years old)
0.022
35
11
28
142
Children (3-5 years old)
0.002
37
11
28
138
Children (6-12 years old)
0.022
30
11
28
155
Youth (13-19 years old)
0.022
25
11
28
492
Adults (20-49 years old)
0.022
29
11
28
544
Adults (50 + years old)
0.022
29
11
28
470
Females (13-49 years old)
0.022
30
11
28
539
1Based
on exposure estimates from DEEM-FCID
3. Spiromesifen is not registered for
use on any sites that would result in
residential exposure. Therefore, the
aggregate risk is the sum of the risk from
food and water, which do not exceed
the Agency’s level of concern.
4. Spiromesifen is not registered for
use on any sites that would result in
residential exposure. Therefore, the
aggregate risk is the sum of the risk from
food and water, which do not exceed
the Agency’s level of concern.
5. Aggregate cancer risk for U.S.
population. Spiromesifen 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
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from aggregate exposure to spiromesifen
residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate analytical enforcement
methodologies, liquid chromatography
LC)/mass spectrometry (MS)/MS, exist
and have been successfully validated by
independent laboratories.
B. International Residue Limits
There are no international residue
limits for spiromesifen listed in CODEX.
V. Conclusion
Therefore, the tolerance is established
for:
1. Primary crops for the combined
residues of spiromesifen (2-oxo-3-(2,4,6-
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trimethylphenyl)-1-oxaspiro[4.4]non-3en-4-yl 3,3-dimethylbutanoate) and its
enol metabolite (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one), calculated as the parent
compound equivalents in or on
strawberries at 2.0 parts per million
(ppm); vegetable, tuberous and corm,
subgroup 1C at 0.02 ppm; vegetable,
leafy greens, subgroup 4A at 12 ppm;
vegetable, Brassica, head and stem,
subgroup 5A at 2.0 ppm; vegetable,
Brassica, leafy greens, subgroup 5B at 12
ppm; vegetable, fruiting, group 8 at 0.30
ppm; tomato, paste at 0.60 ppm;
vegetable, cucurbit, group 9 at 0.10
ppm; corn, field, grain at 0.02 ppm;
corn, field, forage at 3.0 ppm; corn,
field, stover at 5.0 ppm; cotton,
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undelinted seed at 0.50 ppm; and
cotton, gin byproducts at 15 ppm.
2. Rotational crops for the inadvertent
or indirect combined residues of
spiromesifen (2-oxo-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-4-yl 3,3-dimethylbutanoate), its enol
metabolite (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one), and its metabolites
containing the 4-hydroxymethyl moiety
(4-hydroxy-3-[4-(hydroxymethyl)-2,6dimethylphenyl]-1-oxaspiro[4.4]non-3en-2-one), calculated as the parent
compound equivalents in or on alfalfa,
forage at 1.5 ppm; alfalfa, hay at 3.0
ppm; wheat, grain at 0.03 ppm; wheat,
forage at 0.20 ppm; wheat, hay at 0.15
ppm; wheat, straw at 0.25 ppm; barley,
grain at 0.03 ppm; barley, hay at 0.25
ppm; barley, straw at 0.15 ppm; beet,
sugar, tops at 0.20 ppm; and beet, sugar,
roots at 0.03 ppm.
3. Livestock commodities for the
combined residues of spiromesifen (2oxo-3-(2,4,6-trimethylphenyl)-1oxaspiro[4.4]non-3-en-4-yl 3,3dimethylbutanoate), and its metabolites
containing the enol (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one) and 4-hydroxymethyl (4hydroxy-3-[4-(hydroxymethyl)-2,6dimethylphenyl]-1-oxaspiro[4.4]non-3en-2-one) moieties, calculated as the
parent compound equivalents in or on
cattle, fat at 0.05 ppm; cattle, meat
byproducts at 0.05 ppm; milk, fat at 0.10
ppm; goat, fat at 0.05 ppm; goat, meat
byproducts at 0.05 ppm; sheep, fat at
0.05 ppm; sheep, meat byproducts at
0.05 ppm; horse, fat at 0.05 ppm; and
horse, meat byproducts at 0.05 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.
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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–2005–0046 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 June 27, 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–2005–0046, 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-
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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
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Federal Register / Vol. 70, No. 80 / Wednesday, April 27, 2005 / Rules and Regulations
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
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17:56 Apr 26, 2005
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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: April 14, 2005.
James Jones,
Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is
amended as follows:
I
PART 180—AMENDED
1. The authority citation for part 180
continues to read as follows:
I
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.607 is added to read as
follows:
I
§ 180.607 Spiromesifen; tolerances for
residues.
(a) General. (1) Tolerances are
established for the combined residues of
spiromesifen (2-oxo-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-4-yl 3,3-dimethylbutanoate) and its
enol metabolite (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one), calculated as the parent
compound equivalents in or on the
following primary crop commodities:
Parts per
million
Commodity
Corn, field, forage .....................
Corn, field, grain .......................
Corn, field, stover .....................
PO 00000
Frm 00028
Fmt 4700
Sfmt 4700
0.02
3.0
5.0
Commodity
Cotton, gin byproducts .............
Cotton, undelinted seed ...........
Strawberry ................................
Tomato, paste ...........................
Vegetable, brassica, head and
stem, subgroup 5A ................
Vegetable, brassica, leafy
greens, subgroup 5B ............
Vegetable, cucurbit, group 9 ....
Vegetable, fruiting, group 8 ......
Vegetable, leafy greens, subgroup 4A ...............................
Vegetable, tuberous and corm,
subgroup 1C .........................
Parts per
million
15
0.50
2.0
0.60
2.0
12
0.10
0.30
12
0.02
(2) Tolerances are established for the
inadvertent or indirect combined
residues of spiromesifen (2-oxo-3-(2,4,6trimethylphenyl)-1- oxaspiro[4.4]non-3en-4-yl 3,3-dimethylbutanoate), its enol
metabolite (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one), and its metabolites
containing the 4-hydroxymethyl moiety
(4-hydroxy-3-[4-(hydroxymethyl)-2,6dimethylphenyl]-1-oxaspiro[4.4]non-3en-2-one), calculated as the parent
compound equivalents in the following
rotational crop commodities:
Commodity
Alfalfa, forage ...........................
Alfalfa, hay ................................
Barley, grain .............................
Barley, hay ................................
Barley, straw .............................
Beet, sugar, roots .....................
Beet, sugar, tops ......................
Wheat, forage ...........................
Wheat, grain .............................
Wheat, hay ...............................
Wheat, straw .............................
Parts per
million
1.5
3.0
0.03
0.25
0.15
0.20
0.03
0.03
0.20
0.15
0.25
(3) Tolerances are established for the
combined residues of spiromesifen (2oxo-3-(2,4,6-trimethylphenyl)-1oxaspiro[4.4]non-3-en-4-yl 3,3dimethylbutanoate), and its metabolites
containing the enol (4-hydroxy-3-(2,4,6trimethylphenyl)-1-oxaspiro[4.4]non-3en-2-one) and 4-hydroxymethyl (4hydroxy-3-[4-(hydroxymethyl)-2,6dimethylphenyl]-1-oxaspiro[4.4]non-3en-2-one) moieties, calculated as the
parent compound equivalents in the
following livestock commodities:
Commodity
Cattle, fat ..................................
Cattle, meat byproducts ...........
Goat, fat ....................................
Goat, meat byproducts .............
Horse, fat ..................................
Horse, meat byproducts ...........
Milk, fat .....................................
Sheep, fat .................................
E:\FR\FM\27APR1.SGM
27APR1
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million
0.05
0.05
0.05
0.05
0.05
0.05
0.10
0.05
Federal Register / Vol. 70, No. 80 / Wednesday, April 27, 2005 / Rules and Regulations
Parts per
million
Commodity
Sheep, meat byproducts ..........
0.05
(b) Section 18 emergency exemptions.
[Reserved]
(c) Tolerances with regional
registrations. [Reserved]
(d) Indirect or inadvertent residues.
[Reserved]
[FR Doc. 05–8120 Filed 4–26–05; 8:45 am]
BILLING CODE 6560–50–S
through Friday, excluding legal
holidays. The docket telephone number
is (703) 305–5805.
John
W. Pates, Jr., Special Review and
Reregistration Division (7508C), Office
of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460–
0001; telephone number: 703–308–8195;
e-mail address: pates.john@epa.gov.
FOR FURTHER INFORMATION CONTACT:
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[OPP–2004–0142; FRL–7710–9]
Trifluralin; Pesticide Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes a
tolerance for residues of trifluralin in
spearmint and peppermint oil under the
Federal Food, Drug, and Cosmetic Act
(FFDCA), as amended by the Food
Quality Protection Act of 1996 (FQPA).
The FQPA substantially rewrote section
408 of FFDCA. As a result, the revisions
made it necessary, once again, to
establish tolerances for mint oils that
had previously been deemed
unnecessary.
This regulation is effective April
27, 2005. Objections and requests for
hearings must be received on or before
June 27, 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–2004–
0142. 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
DATES:
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17:56 Apr 26, 2005
Jkt 205001
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;
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
https://www.epa.gov/fedrgstr/. A
frequently updated electronic version of
40 CFR part 180 is available at E-CFR
Beta Site Two at https://
www.gpoaccess.gov/ecfr/.
PO 00000
Frm 00029
Fmt 4700
Sfmt 4700
21641
II. Background
In the Federal Register of November
24, 2004 (69 FR 68287) (FRL–7686–4),
EPA on its own initiative, under section
408(e) of FFDCA, 21 U.S.C. 346a(e),
announced a proposal to establish a
permanent tolerance for residues of the
herbicide trifluralin in spearmint and
peppermint oil at 2.0 parts per million
(ppm). The proposal included a
summary of the exposure assessment
prepared by the Agency. The Agency
received three submissions for
comment; two from private citizens and
one from Dow AgroSciences, the
registrant.
III. Response to Comments
Comments received from the
registrant address the following areas:
evidence of errors and inconsistencies/
miscalculations, belief that potential
risks are significantly overstated, belief
that unrealistic assumptions have been
made, and the position that relevant
information has been omitted and not
incorporated into the Agency’s
decision(s). Additionally, the registrant
has asked for clarification on labeling
requirements. However, in general, the
registrant does agree with the
assessments that have been conducted
for the human health and residue
chemistry risk studies available for
trifluralin. Furthermore, the registrant
does not state any objections to the
establishment of a permanent tolerance
for residues of the herbicide trifluralin
in peppermint and spearmint oil at 2.0
ppm.
One of the private citizen’s comments
raised objections to any establishment of
a tolerance for trifluralin. The citizen’s
comments and EPA’s response to those
comments follow:
1. Comment. Both 28–day dermal and
developmental toxicity tests on rabbits
as well as a 1–year oral capsule study
on dogs have no validity and are
abusive to the test animals.
EPA response. This commenter’s
objections to animal testing have been
addressed in prior rulemaking
documents. See 69 FR 63083, 63096
(October 29, 2004).
2. Comment. 1994 surveys of food
intake are out of date.
EPA response. Consumption survey
data is used in part to determine acute
and chronic exposure. In assessing
exposure to trifluralin, EPA relied on
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). These surveys are
generally updated every 10 years or so.
E:\FR\FM\27APR1.SGM
27APR1
]]>Agencies
[Federal Register Volume 70, Number 80 (Wednesday, April 27, 2005)]
[Rules and Regulations]
[Pages 21631-21641]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-8120]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2005-0046; FRL-7705-1]
Spiromesifen; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a tolerance for: Primary crops for
the combined residues of spiromesifen (2-oxo-3-(2,4,6-trimethylphenyl)-
1-oxaspiro[4.4]non-3-en-4-yl 3,3-dimethylbutanoate) and its enol
metabolite (4-hydroxy-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-
en-2-one), calculated as the parent compound equivalents; rotational
crops for the inadvertent or indirect combined residues of spiromesifen
(2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl 3,3-
dimethylbutanoate), its enol metabolite (4-hydroxy-3-(2,4,6-
trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one), and its metabolites
containing the 4-hydroxymethyl moiety (4-hydroxy-3-[4-(hydroxymethyl)-
2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one), calculated as the
parent compound equivalents; and livestock commodities for the combined
residues of spiromesifen (2-oxo-3-(2,4,6-trimethylphenyl)-1-
oxaspiro[4.4]non-3-en-4-yl 3,3-dimethylbutanoate), and its metabolites
containing the enol (4-hydroxy-3-(2,4,6-trimethylphenyl)-1-
oxaspiro[4.4]non-3-en-2-one) and 4-hydroxymethyl (4-hydroxy-3-[4-
(hydroxymethyl)-2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one)
moieties, calculated as the parent compound equivalents. Bayer
CropScience 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 April 27, 2005. Objections and
requests for hearings must be received on or before June 27, 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-2005-0046. All documents in the docket
are listed in the EDOCKET index at https://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: Thomas Harris, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-9423; e-mail address: harris.thomas@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; greenhouse, nursery, and
floriculture workers; residential users.
This listing is not intended to be exhaustive, but rather provides
a guide
[[Page 21632]]
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 (https://www.epa.gov/edocket/), you may
access this Federal Register document electronically through the EPA
Internet under the ``Federal Register'' listings at https://www.epa.gov/
fedrgstr/. A frequently updated electronic version of 40 CFR part 180
is available on E-CFR Beta Site Two athttps://www.gpoaccess.gov/ecfr/.
To access the OPPTS Harmonized Guidelines referenced in this document,
go directly to the guidelines at https://www.epa.gpo/opptsfrs/home/
guidelin.htm/.
II. Background and Statutory Findings
In the Federal Register of July 28, 2004 (69 FR 45047) (FRL-7366-
2), 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
3F6537) by Bayer CropScience, 2 T.W. Alexander Drive, Research Triangle
Park, NC 27709. The petition requested that 40 CFR part 180 be amended
by establishing a tolerance for the combined residues of the
insecticide/miticide:
1. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6-
trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester [subsequently
referred to as (2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-
en-4-yl 3,3-dimethylbutanoate) and its enol metabolite (4-hydroxy-3-
(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one)] in or on
strawberry at 2.0 parts per million (ppm); vegetable, tuberous and
corm, crop subgroup 1C, at 0.01 ppm (subsequently revised to 0.02 ppm);
vegetable, leafy greens (except Brassica), crop subgroup 4A at 10 ppm
(subsequently revised to vegetable, leafy greens, subgroup 4A at 12
ppm); vegetable, Brassica, head and stem, crop subgroup 5A, at 2.0 ppm;
vegetable, Brassica, leafy, crop subgroup 5B at 12 ppm; vegetable,
fruiting, crop group 8, at 0.30 ppm; tomato, paste at 0.60 ppm;
vegetable, cucurbit, crop group 9, at 0.10 ppm; corn, field, grain, at
0.01 ppm (subsequently revised to 0.02 ppm); corn, field, forage, at
3.0 ppm; corn, field, stover, at 5.0 ppm; cotton (subsequently defined
as cotton, undelinted seed) at 0.50 ppm; and cotton, gin byproducts, at
15 ppm.
2. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6-
trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester [subsequently
referred to as (2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-
en-4-yl 3,3-dimethylbutanoate), its enol metabolite (4-hydroxy-3-
(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one), and its
metabolites containing the 4-hydroxymethyl moiety (4-hydroxy-3-[4-
(hydroxymethyl)-2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one)] in
or on the rotational crop commodities alfalfa, forage, at 1.5 ppm;
alfalfa, hay, at 3.0 ppm; wheat, grain, at 0.01 ppm (subsequently
revised to 0.03 ppm); wheat, forage, at 0.20 ppm; wheat, hay, at 0.15
ppm; wheat, straw, at 0.25 ppm; wheat, bran, at 0.05 ppm (subsequently
combined with wheat, shorts and defined together as ``wheat milled
byproducts'' with no tolerance required); wheat, shorts, at 0.03 ppm
(subsequently combined with wheat, bran and defined together as ``wheat
milled byproducts'' with no tolerance required); barley, grain, at 0.02
ppm (subsequently revised to 0.03 ppm); barley, hay, at 0.25 ppm;
barley, straw, at 0.25 ppm (subsequently revised to 0.15 ppm); beet,
sugar, tops, at 0.20 ppm; beet, sugar, roots, at 0.02 ppm (subsequently
revised to 0.03 ppm); and beet, sugar, molasses, at 0.05 ppm (tolerance
subsequently not required).
3. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6-
trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester [subsequently
referred to as 2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-
4-yl 3,3-dimethylbutanoate), and its metabolites containing the enol
(4-hydroxy-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one) and
4-hydroxymethyl (4-hydroxy-3-[4-(hydroxymethyl)-2,6-dimethylphenyl]-1-
oxaspiro[4.4]non-3-en-2-one) moieties)] in or on the raw agricultural
commodities cattle, fat, at 0.05 ppm; cattle, meat byproducts, at 0.05
ppm; milk at 0.01 ppm (tolerance subsequently not required); and milk,
fat, at 0.03 ppm (subsequently revised to 0.10 ppm).
Following the review of all data, tolerances are also required for
the following commodities: Goat, fat at 0.05 ppm; goat meat byproducts
at 0.05 ppm; sheep, fat at 0.05 ppm; sheep, meat byproducts at 0.05
ppm; horse, fat at 0.05 ppm; and horse, meat byproducts at 0.05 ppm.
That notice included a summary of the petition prepared by Bayer
CropScience, the registrant. A comment was received from a private
citizen who challenged the value of using animal testing for evaluating
pesticide toxicity and questioned the data gaps related to the
tolerance proposal process. This commenter's objections have been
addressed in prior rulemaking documents. See (69 FR 63083, 63096)
(October 29, 2004).
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 (62 FR 62961, November 26, 1997) (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 the combined residues of
spiromesifen on the crops and animal commodities listed above.
EPA's assessment of exposures and risks associated with
establishing the tolerances follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as
[[Page 21633]]
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
spiromesifen 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
----------------------------------------------------------------------------------------------------------------
870.3050 28-Day oral toxicity NOAEL was not established
(mouse) LOAEL (M/F) = 202.6/269.6 mg/kg/day based
on decreased body weight gain
----------------------------------------
870.3050 28-Day oral toxicity NOAEL was not established
(mouse) LOAEL (M/F) = 444.3 mg/kg/day based on
decreased body weight gain and increase in
alkaline phosphatase
...........................................
----------------------------------------
870.3100 28-Day oral toxicity (rat) NOAEL = 53.4 mg/kg/day
LOAEL = 536.3 mg/kg/day based on clinical
signs (piloerection, reduced motility,
spastic gait, discolored feces and
increased reactivity when touched),
decrease in body weight gain, and food
consumption, hematology (thromboplastin
time increase), clinical chemistry
(increased aspartateaminotransferase and
alanine aminotransferase), liver enzyme
(increased aldrin expoxidase and epoxide
hydrolase), increased spleen and lymph
node cell proliferation, organ-weights
(increase brain, heartand kidneys,
decrease in weights in the ovaries, spleen
and thymus), gross pathology (thin
appearance, discolored adrenal glands and
white mucous in the duodenum and jejunum),
and microscopic findings (vacuolation of
the superficial mucosal cells in the
jejunum and duodenum, increased follicular
cell hypertrophy in the thyroid,
indistinct corticomedullary junction in
the thymus and cytoplasmic changes in the
adrenal glands)
----------------------------------------
870.3150 90-Day oral toxicity NOAEL = 9.2 mg/kg/day
(nonrodent) LOAEL = 71 mg/kg/day (HDT) based on
clinical chemistry(increased ALP) and
liver histopathology
----------------------------------------
870.3150 90-Day oral toxicity NOAEL was not established
(nonrodent) LOAEL = 98.4 mg/kg/day (HDT) based on
increase in alkalinephosphatase and liver
histopathology (cytoplasmic changes)
----------------------------------------
870.3150 90-Day oral toxicity (rat) NOAEL (M/F) = 31.7/7.7 mg/kg/day.
LOAEL (F) = 36.6 mg/kg/day based on thyroid
effects (increased thyroid stimulating
hormone, thyroxine binding capacity and
thyroid follicular cell hypertrophy),
kidney effects (mineralization), and liver
effect (increased ALP)
LOAEL (M) = 204.0 mg/kg/day based on
thyroid effect (colloidal alteration,
follicular cell hypertrophy, decreased T3
and T4 and increased TBC and TSH), kidney
effects (Hyalin droplets), and liver
effects (increase in ALP and ALAT)
----------------------------------------
870.3200 21/28-Day dermal toxicity NOAEL = 1,000 mg/kg/day (HDT)
(rat) LOAEL was not established
----------------------------------------
870.3465 5-Day inhalation toxicity NOAEL = 20.7 mg/kg/day
(rat) LOAEL = 134.2 mg/kg/day based onthe
clinical signs (tremors, clonic-tonic
convulsions, reduced activity,bradypnea,
labored breathing,vocalization, avoidance
reaction,giddiness, piloerection,
limp,emaciation, cyanosis,
squattedposture, apathy, and salivation),
andgross pathology (dark red areas orfoci
in the lungs, bloated stomachsand pale
liver)
----------------------------------------
870.3465 30-Day inhalation toxicity NOAEL >21.1 mg/kg/day
(rat) LOAEL was not established
----------------------------------------
870.3700 Prenatal developmental Maternal NOAEL = 10 mg/kg/day
(rat) Maternal LOAEL = 70 mg/kg/daybased on
decreased body weight gainand reduced food
consumption.
Developmental NOAEL >= 500mg/kg/day (HDT)
Developmental LOAEL > 500 mg/kg day
----------------------------------------
870.3700 Prenatal developmental Maternal NOAEL = 5 mg/kg/day
(nonrodent) Maternal LOAEL = 35 mg/kg/day based on body
weight loss and reduced food consumption
Developmental NOAEL >= 250 mg/kg/day
Developmental LOAEL > 250 mg/kg/day
----------------------------------------
[[Page 21634]]
870.3800 Reproduction and fertility Parental/Systemic NOAEL (M/F) = 2.2/3.8 mg/
effects (rat) kg/day
Parental/Systemic LOAEL (M/F) = 8.8/13.2 mg/
kg/day based on significantly decreased
spleen weight (absolute and relative in
parental females and F1 males) and
significantly decreased growing ovarian
follicles in females
Reproductive NOAEL (M/F) = 37/64 mg/kg/day
(HDT)
Reproductive LOAEL = Not established
Offspring NOAEL = 2.2 mg/kg/day
Offspring LOAEL = 8.8 mg/kg/day based on
pup body weight decrements during
lactation
----------------------------------------
870.4100 Chronic toxicity (rat) NOAEL (M/F) = 15.9/19.3 mg/kg/day
LOAEL (M/F) = 42.4/51.7 mg/kg/day based on
increase in T3 hormone in males, gross
pathology (enlarged liver in males,
dilated uterus and discolored adrenal
gland in females) and histopathology
(adrenal cytoplasmic eosinophilia,
metritise, thyroid colloidal alteration in
female and thyroid follicular cell
hypertrophy in both males and females)
----------------------------------------
870.4100 Chronic toxicity NOAEL (M/F) = 11.5/10.8 mg/kg/day
(nonrodent) LOAEL (M/F) = 109/117 mg/kg/day based on
increase in alkaline phosphatase and liver
histopathology (cytoplasmic changes,
inclusions and vacuoles)
----------------------------------------
870.4200 Carcinogenicity (rat) NOAEL (M/F) = 14.8/19.5 mg/kg/day
LOAEL (M/F) = 40.0/53.5 mg/kg/day based on
clinical signs (palpable masses, vaginal
bleeding and pallor), gross necropsy
(discolored area in the lungs, nodules/
dilation of uterus) and hispathology
(osseus metaplasia and granulomatous
inflammation of the lungs in the males,
liver necrosis; endometritis/metritis,
endometrial hyperplasia of the cervix
uteria and colloidal alteration of the
thyroid gland in females) and increased
TSH in females.
No evidence of carcinogenicity
----------------------------------------
870.4200 Carcinogenicity (mouse) NOAEL (M/F) = 3.3/3.8 mg/kg/day
LOAEL (M/F) = 22/30 mg/kg/day based on
gross (enlarged adrenal gland in males)
and microscopic changes (cytoplamic
eosinophilia, ceroid deposits, and diffuse
fatty changes of the adrenal cortex and
pancreatic amyloidosis in both sexes)
No evidence of carcinogenicity
----------------------------------------
870.5100 Gene mutation--In Vitro Negative
bacteria
----------------------------------------
870.5300 Cytogenetics In Vitro Negative
Mammalian Gene Mutation
----------------------------------------
870.5375 Cytogenetics--In Vitro Negative
Mammalian
----------------------------------------
870.5395 Cytogenetics In Vivo Negative
Mammalian Micronucleus
(mouse)
----------------------------------------
870.6200 Acute neurotoxicity NOAEL = 2,000 mg/kg/day
screening battery LOAEL = Not established
----------------------------------------
870.6200 Subchronic neurotoxicity NOAEL (M/F) = 31.8/38.3 mg/kg/day.
screening battery LOAEL (M/F) = 122.7/149.3 mg/kg/day based
on decreased body weight gain and food
consumption.
----------------------------------------
870.7485 Metabolism and Spiromesifen exhibits moderate absorption
pharmacokinetics (rat) (approximately 43%), relatively rapid
excretion primarily via the urine and
feces. Approximately 39% of the
administered dose was excreted in the
urine and 55 to 57% in the feces with 88
to 90% of the dose being eliminated within
the first 24 hours. Maximum concentration
in the blood achieved within 1 to 6 hours
post- dose depending upon the dose.
Concentrations of residual radioactivity
in the tissues were quite low at 72 hours
post-dose. The test material was initially
metabolized to the keto-enol by loss of
the dimethylbutyric acid moiety. Both the
phenyl and cyclopentyl rings were
hydoxylated and the methyl groups on the
phenyl ring were ultimately oxidized to a
carboxylic acid. These metabolites were
largely recovered in the bile and urine.
The predominate moiety recovered in the
feces was the unmetabolized test material.
----------------------------------------
[[Page 21635]]
870.7600 Dermal penetration Intravenous injection resulted in excretion
(nonrodent) of the radiolabel mainly via urine: Urine
(54.32%), feces (13.08%), and cage debris/
rinse (26.57%). Excretion was rapid in
that 70% of the dose was excreted within
24 hours. Dermal application of
spiromesifen resulted in limited
absorption after 8-hour exposure (3.3%),
which a large portion was recovered from
urine and cage debris/rinse showing that
it is poorly absorbed through the skin
layers.
----------------------------------------
870.7800 4-Week immunotoxicity NOAEL (M/F) = 52.8/45.7 mg/kg/day
(rat) LOAEL (M/F) = 291.6/288.6 mg/kg/day based
on mortality, clinical signs and decreased
body weights, body weight gains and food
consumption.
----------------------------------------------------------------------------------------------------------------
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 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 (acute RfD or
chronic RfD) 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 spiromesifen used for
human risk assessment is shown in Table 2 of this unit:
Table 2.-- Summary of Toxicological Dose and Endpoints for Spiromesifen for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
Dose Used in Risk
Assessment, Special FQPA SF and
1Exposure Scenario Interspecies and Level of Concern for Study and Toxicological
Intraspecies and any Risk Assessment Effect
Traditional UF
----------------------------------------------------------------------------------------------------------------
Acute dietary (females 13-49 years of Not applicable None An endpoint of concern
age) attributable to a
single dose was not
identified. An aRfD
was not established.
--------------------------------------
Acute dietary (general population)
--------------------------------------
[[Page 21636]]
Chronic dietary (all populations) NOAEL= 2.2 mg/kg/day Special FQPA SF = 1X 2-generation
UF = 100X.............. ....................... reproduction study in
Chronic RfD = 0.022 mg/ ....................... rats.
kg/day. ....................... The parental systemic
LOAEL:
13.2 mg/kg/day based on
significantly
decreased spleen
weight (absolute and
relative in parental
females and F1 males)
and significantly
decreased growing
ovarian follicles in
females.
--------------------------------------
Cancer (oral, dermal, inhalation) Classification: ``Not likely to be carcinogenic to humans.''
----------------------------------------------------------------------------------------------------------------
C. Exposure Assessment
1. Dietary exposure from food and feed uses. No tolerances have
previously been established for spiromesifen. Risk assessments were
conducted by EPA to assess dietary exposures from spiromesifen 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. Acute dietary exposure limits for all populations,
including infants and children, were not performed because an endpoint
of concern attributable to a single exposure (dose) was not identified
from the oral toxicity studies.
ii. Chronic exposure. In conducting the chronic dietary risk
assessment EPA used the Dietary Exposure Evaluation Model software with
the Food Commodity Intake Database (DEEM-FCID\TM\) and the Lifeline\TM\
model version 2.0, which incorporates food consumption data as reported
by respondents in the USDA 1994-1996 and 1998 Nationwide Continuing
Surveys of Food Intake by Individuals (CSFII), and accumulated exposure
to the chemical for each commodity. Percent crop treated and
anticipated residues were not used.
An unrefined, Tier 1 chronic dietary exposure assessment was
conducted using the following:
a. Recommended tolerances for all plant and livestock except the
leafy-green and leafy-Brassica vegetable subgroups;
b. EPA calculated residues of concern (parent and metabolites) for
the leafy-green and leafy-Brassica vegetable subgroups;
c. 100% crop treated (CT) information for all proposed uses; and
d. Default processing factors for all commodities.
The metabolism studies show that the hydroxymethyl metabolite is formed
along with the enol metabolite in the leafy-green and leafy-Brassica
vegetable subgroups. EPA determined that these two metabolites along
with the spiromesifen should be included in the chronic dietary risk
assessment for these crops. Residue data are unavailable for the 4-
hydroxymethyl metabolite; to account for this metabolite in the risk
assessment, the recommended tolerance levels for these crops was
multiplied by a correction factor of 1.3x, where:
1.3 = Metabolites in Risk Assessment (ppm)/Metabolites in Tolerance
Expression (ppm).
The dietary-exposure assessment was conducted for the general U.S.
population and various population subgroups. This assessment concludes
that the chronic dietary exposure estimates are below EPA's level of
concern (<100% cPAD) for the general U.S. population (27% cPAD and 29%
cPAD, based on the Lifeline\TM\ and DEEM-FCID\TM\ analyses,
respectively) and all population subgroups. Both Lifeline\TM\ and DEEM-
FCID\TM\ estimate that children 3 to 5 years old are the most highly-
exposed subpopulation with risks of 30% cPAD and 37% cPAD,
respectively.
iii. Cancer. A cancer exposure assessment was not performed because
spiromesifen is classified as ``not likely to be carcinogenic to
humans.''
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for spiromesifen 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 spiromesifen.
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 Concentrations 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
[[Page 21637]]
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 spiromesifen they are further discussed in
the aggregate risk sections in Unit E.
Based on the PRZM/EXAMS and SCI-GROW models, the EECs of
spiromesifen for acute exposures are estimated to be 7.1 parts per
billion (ppb) for surface water and 0.005 ppb for ground water. The
EECs for chronic exposures are estimated to be 0.70 ppb for surface
water and 0.005 ppb for ground water.
EECs of spiromesifen and its metabolites for acute exposures are
estimated to be 26 ppb for surface water and 28 ppb for ground water.
The EECs for chronic exposures are estimated to be 11 ppb for surface
water and 28 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).
Spiromesifen is not registered for use on any sites that would
result in residential exposure.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of the 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 spiromesifen and any other
substances and spiromesifen 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 spiromesifen 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 Office of
Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a
common mechanism on EPA's website at https://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 uncertainty (safety) factors 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 uncertainty factors and/or
special FQPA safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. There was no evidence of
increased susceptibility of rats or rabbits to in utero and/or
postnatal exposure to spiromesifen. In a rat developmental toxicity
study, no developmental toxicity was observed at doses up to 500 mg/kg/
day (the highest dose tested) in the presence of maternal toxicity. The
rat maternal LOAEL was determined to be 70 mg/kg/day based on decreased
body-weight gain and reduced food consumption. In the rabbit
developmental toxicity study, there was no developmental toxicity
observed at doses up to 250 mg/kg/day (the highest dose tested), but
the maternal LOAEL was determined to be 35 mg/kg/day based on body
weight loss and reduced food consumption. There is no qualitative and/
or quantitative evidence of increased susceptibility to spiromesifen
following pre/postnatal exposure in a 2-generation reproduction study
in rats.
There is no concern for developmental neurotoxicity resulting from
exposure to spiromesifen. Neurotoxic effects such as reduced motility,
spastic gait, increased reactivity, tremors, clonic-tonic convulsions,
reduced activity, labored breathing, vocalization, avoidance reaction,
piloerection, limp, cyanosis, squatted posture, and salivation were
observed in two studies (5-day inhalation and subchronic oral rat).
However, these effects were considered as secondary, not neurotoxic,
effects due to the high dosage. There was no evidence of neurotoxicity
in the acute or subchronic neurotoxicity or any other studies.
3. Conclusion. For spiromesifen, EPA determined that the 10X safety
factor to protect infants and children should be removed. A 1X safety
factor is appropriate because:
There is a complete toxicity data base for spiromesifen.
There is no evidence of increased susceptibility of rats
or rabbits to in utero and/or postnatal exposure to spiromesifen. In
the prenatal developmental toxicity studies in rats and rabbits and in
the 2-generation reproduction study in rats, developmental toxicity to
the offspring occurred at equivalent or higher doses than maternal
toxicity.
There are no neurotoxicity concerns based on acute and
subchronic neurotoxicity studies.
The dietary food exposure assessment uses proposed
tolerance levels or higher residues and assumed 100% crop-treated (CT)
information for all commodities. By using these screening-level
assessments, chronic exposures and risks will not be underestimated.
The ``higher residues'' are those that were calculated using a
modifying factor to account for the lack of spiromesifen-4-
hydroxymethyl residue data.
The dietary drinking water assessment (Tier 2 estimates)
uses values generated by model and associated modeling parameters which
are designed to provide conservative, health protective, and high-end
estimates of water concentrations.
Residential exposure is not expected--spiromesifen will be
registered for agricultural and greenhouse/ornamental uses only.
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
[[Page 21638]]
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, OPP concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which OPP has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because OPP considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, OPP will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
1. Acute risk. Spiromesifen is not expected to pose an acute risk
because an endpoint of concern attributable to a single exposure (dose)
was not identified from the oral toxicity studies.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure and the EECs from DEEM-FCID\TM\ as these were
slightly higher, and thus are more conservative, than the Lifeline\TM\
estimates, EPA has concluded that exposure to spiromesifen from food
will utilize 29% of the cPAD for the U.S. population, 15% of the cPAD
for all infants less than 1 year old, and 37% of the cPAD for children
3-5 years old. There are no residential uses for spiromesifen that
result in chronic residential exposure to spiromesifen. There is no
concern regarding spiromesifen in ground water and surface 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 Table 3 of this unit:
Table 3.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Spiromesifen + Metabolites
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup cPAD mg/kg/ % cPAD Water EEC Water EEC Chronic
day (Food)\1\ (ppb) (ppb) DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population 0.022 29 11 28 545
------------------------------------------------
All Infants (<1 year old) 0.022 15 11 28 187
------------------------------------------------
Children (1-2 years old) 0.022 35 11 28 142
------------------------------------------------
Children (3-5 years old) 0.002 37 11 28 138
------------------------------------------------
Children (6-12 years old) 0.022 30 11 28 155
------------------------------------------------
Youth (13-19 years old) 0.022 25 11 28 492
------------------------------------------------
Adults (20-49 years old) 0.022 29 11 28 544
------------------------------------------------
Adults (50 + years old) 0.022 29 11 28 470
------------------------------------------------
Females (13-49 years old) 0.022 30 11 28 539
----------------------------------------------------------------------------------------------------------------
1Based on exposure estimates from DEEM-FCID
3. Spiromesifen is not registered for use on any sites that would
result in residential exposure. Therefore, the aggregate risk is the
sum of the risk from food and water, which do not exceed the Agency's
level of concern.
4. Spiromesifen is not registered for use on any sites that would
result in residential exposure. Therefore, the aggregate risk is the
sum of the risk from food and water, which do not exceed the Agency's
level of concern.
5. Aggregate cancer risk for U.S. population. Spiromesifen 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 spiromesifen residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate analytical enforcement methodologies, liquid
chromatography LC)/mass spectrometry (MS)/MS, exist and have been
successfully validated by independent laboratories.
B. International Residue Limits
There are no international residue limits for spiromesifen listed
in CODEX.
V. Conclusion
Therefore, the tolerance is established for:
1. Primary crops for the combined residues of spiromesifen (2-oxo-
3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl 3,3-
dimethylbutanoate) and its enol metabolite (4-hydroxy-3-(2,4,6-
trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one), calculated as the
parent compound equivalents in or on strawberries at 2.0 parts per
million (ppm); vegetable, tuberous and corm, subgroup 1C at 0.02 ppm;
vegetable, leafy greens, subgroup 4A at 12 ppm; vegetable, Brassica,
head and stem, subgroup 5A at 2.0 ppm; vegetable, Brassica, leafy
greens, subgroup 5B at 12 ppm; vegetable, fruiting, group 8 at 0.30
ppm; tomato, paste at 0.60 ppm; vegetable, cucurbit, group 9 at 0.10
ppm; corn, field, grain at 0.02 ppm; corn, field, forage at 3.0 ppm;
corn, field, stover at 5.0 ppm; cotton,
[[Page 21639]]
undelinted seed at 0.50 ppm; and cotton, gin byproducts at 15 ppm.
2. Rotational crops for the inadvertent or indirect combined
residues of spiromesifen (2-oxo-3-(2,4,6-trimethylphenyl)-1-
oxaspiro[4.4]non-3-en-4-yl 3,3-dimethylbutanoate), its enol metabolite
(4-hydroxy-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one),
and its metabolites containing the 4-hydroxymethyl moiety (4-hydroxy-3-
[4-(hydroxymethyl)-2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one),
calculated as the parent compound equivalents in or on alfalfa, forage
at 1.5 ppm; alfalfa, hay at 3.0 ppm; wheat, grain at 0.03 ppm; wheat,
forage at 0.20 ppm; wheat, hay at 0.15 ppm; wheat, straw at 0.25 ppm;
barley, grain at 0.03 ppm; barley, hay at 0.25 ppm; barley, straw at
0.15 ppm; beet, sugar, tops at 0.20 ppm; and beet, sugar, roots at 0.03
ppm.
3. Livestock commodities for the combined residues of spiromesifen
(2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl 3,3-
dimethylbutanoate), and its metabolites containing the enol (4-hydroxy-
3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one) and 4-
hydroxymethyl (4-hydroxy-3-[4-(hydroxymethyl)-2,6-dimethylphenyl]-1-
oxaspiro[4.4]non-3-en-2-one) moieties, calculated as the parent
compound equivalents in or on cattle, fat at 0.05 ppm; cattle, meat
byproducts at 0.05 ppm; milk, fat at 0.10 ppm; goat, fat at 0.05 ppm;
goat, meat byproducts at 0.05 ppm; sheep, fat at 0.05 ppm; sheep, meat
byproducts at 0.05 ppm; horse, fat at 0.05 ppm; and horse, meat
byproducts at 0.05 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-2005-0046 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 June 27,
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 14\th\ 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-2005-0046, 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
