Amicarbazone; Pesticide Tolerance, 55752-55761 [05-18951]
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Federal Register / Vol. 70, No. 184 / Friday, September 23, 2005 / Rules and Regulations
entitled Protection of Children from
Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
This action does not involve any
technical standards that would require
Agency consideration of voluntary
consensus standards pursuant to section
12(d) of the National Technology
Transfer and Advancement Act of 1995
(NTTAA), Public Law 104–113, section
12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are
established on the basis of a petition
under section 408(d) of FFDCA, such as
the tolerance in this final rule, do not
require the issuance of a proposed rule,
the requirements of the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. In addition, the
Agency has determined that this action
will not have a substantial direct effect
on States, on the relationship between
the national government and the States,
or on the distribution of power and
responsibilities among the various
levels of government, as specified in
Executive Order 13132, entitled
Federalism(64 FR 43255, August 10,
1999). Executive Order 13132 requires
EPA to develop an accountable process
to ensure ‘‘meaningful and timely input
by State and local officials in the
development of regulatory policies that
have federalism implications.’’ ‘‘Policies
that have federalism implications’’ is
defined in the Executive Order to
include regulations that have
‘‘substantial direct effects on the States,
on the relationship between the national
government and the States, or on the
distribution of power and
responsibilities among the various
levels of government.’’ This final rule
directly regulates growers, food
processors, food handlers and food
retailers, not States. This action does not
alter the relationships or distribution of
power and responsibilities established
by Congress in the preemption
provisions of section 408(n)(4) of
FFDCA. For these same reasons, the
Agency has determined that this rule
does not have any ‘‘tribal implications’’
as described in Executive Order 13175,
entitled Consultation and Coordination
with Indian Tribal Governments (65 FR
67249, November 6, 2000). Executive
Order 13175, requires EPA to develop
an accountable process to ensure
‘‘meaningful and timely input by tribal
officials in the development of
regulatory policies that have tribal
implications.’’ ‘‘Policies that have tribal
implications’’ is defined in the
Executive Order to include regulations
that have ‘‘substantial direct effects on
one or more Indian tribes, on the
relationship between the Federal
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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.
Commodity
Parts per million
Vegetable, fruiting group
81 .................................
0.04
1There
is no U.S. registration as of September 1, 2005.
(b) Section 18 emergency exemptions.
[Reserved]
(c) Tolerances with regional
registrations. [Reserved]
(d) Indirect or inadvertent residues.
[Reserved]
[FR Doc. 05–19061 Filed 9–22–05; 8:45 am]
BILLING CODE 6560–50–S
VIII. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801et seq., as added by the Small
Business Regulatory Enforcement
Fairness Act of 1996, generally provides
that before a rule may take effect, the
agency promulgating the rule must
submit a rule report, which includes a
copy of the rule, to each House of the
Congress and to the Comptroller General
of the United States. EPA will submit a
report containing this rule and other
required information to the U.S. Senate,
the U.S. House of Representatives, and
the Comptroller General of the United
States prior to publication of this final
rule in the Federal Register. This final
rule is not a ‘‘major rule’’ as defined by
5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection,
Administrative practice and procedure,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping
requirements.
Dated: September 15, 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 180.614 is added to read as
follows:
I
§ 180.614 Kasugamycin; tolerances for
residues.
(a) General. Tolerances are
established for residues of kasugamycin,
3-O-[2-amino-4[(carboxyiminomethyl)amino]-2,3,4,6tetradeoxy-a-D-arabino-hexopyranosyl]D-chiro-inositol in or on the following
raw agricultural commodity:
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ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[OPP–2005–0185; FRL–7736–3]
Amicarbazone; Pesticide Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes
tolerances for combined residues of
amicarbazone and its metabolites in or
on field corn and livestock commodities
and indirect or inadvertent residues of
amicarbazone and its metabolites in
alfalfa, cotton, soybean and wheat.
Arysta Lifescience North American
Corporation (perviously known as
Arvesta Corporation) requested this
tolerance under the Federal Food, Drug,
and Cosmetic Act (FFDCA), as amended
by the Food Quality Protection Act of
1996 (FQPA).
DATES: This regulation is effective
September 23, 2005. Objections and
requests for hearings must be received
on or before November 22, 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–
0185. 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.
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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:
Joanne I. Miller, Registration Division
(7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 305–6224; e-mail address:
miller.joanne@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
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 at E-CFR
Beta Site Two at https://
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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 January 22,
2004 (69 FR 3138) (FRL–7339–3), 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 0F6131) by Arysta
Lifescience North American
Corporation, 100 First Street, Suite
1700; San Francisco, CA 94105. The
petition requested that 40 CFR part 180
be amended by establishing tolerances
for combined residues of the herbicide
amicarbazone, 4-amino-4,5-dihydro-N(1,1-dimethylethyl)-3-(1-methylethyl)-5oxo-1H-1,2,4-triazole-1-carboxamide]
and its metabolities DA amicarbazone
(N-(1,1-dimethylethyl)-4,5-dihydro-3-(1methylethyl)-5-oxo-1H,2,4-triazole-1carboxamide) and iPr-2-OH DA
amicarbazone (N-(1,1-dimethylethyl)4,5-dihydro-3-(1-hydroxy-1methylethyl)-5-oxo-1H-1,2,4-triazole-1carboxamide), in or on the raw
agricultural commodities alfalfa forage
at 0.04 parts per million (ppm); alfalfa
hay at 0.06 ppm; corn forage at 0.8ppm;
corn grain, at 0.05 ppm; corn stover at
0.5 ppm; cotton gin by-product at 0.2
ppm; cottonseed hulls at 0.01 ppm;
cottonseed meal at 0.01 ppm; cottonseed
refined oil at 0.01 ppm; cotton
undelinted seed at 0.04 ppm; soybean
forage at 2.5 ppm; soybean hay at 7.0
ppm; soybean hulls at 0.2 ppm; soybean
meal at 0.25 ppm; soybean oil at 0.01
ppm; soybean seed at 0.6 ppm; wheat
bran at 0.08 ppm; wheat flour at 0.05
ppm; wheat forage at 0.6 ppm; wheat
germs at 0.05 ppm; wheat grain at 0.09
ppm; wheat hay at 0.9 ppm; wheat
middlings at 0.05 ppm; wheat shorts at
0.06 ppm; wheat straw at 0.4 ppm;
sugarcane at 0.15 ppm; sugarcane
molasses at 0.8 ppm; meat (cattle, goats,
hogs, horses, and sheep) at 0.01 ppm;
meat byproducts (cattle, goats, hogs,
horses,and sheep) at 0.2 ppm; and milk
at 0.01 ppm respectively.
Due to a lack of field trial data on
sugarcane, tolerances on sugarcane and
sugarcane molasses are not being
established at this time.
One comment was received in
response to the notice filing. B. Sachau
objected to the proposed tolerances
because of the amounts of pesticides
already consumed and carried by the
American population. She further
indicated that testing conducted on
animals have absolutely no validity and
are cruel to the test animals. EPA’s
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response to these comments is
contained in Unit IV.C.
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 combined
residues of amicarbazone [4-amino-4, 5dihydro- N-(1,1-dimethylethyl)-3-(1methylethyl)-5-oxo-1H-1,2,4-triazole-1carboxamide] and its metabolites DA
amicarbazone [N-(1,1-dimethylethyl)4,5-dihydro-3-(1-methylethyl)-5-oxo-1H1,2,4-triazole-1-carboxamide] and iPr-2OH DA amicarbazone [N-(1,1dimethylethyl)-4,5-dihydro-3-(1hydroxy-1-methylethyl)-5-oxo-1H-1,2,4triazole-1-carboxamide], calculated as
parent equivalents, in or on corn, field,
forage at 0.80 ppm; corn, field, grain at
0.05 ppm; corn, field, stover at 1.0 ppm;
cattle, fat at 0.01 ppm; cattle, liver at 1.0
ppm; cattle, meat at 0.01 ppm; cattle,
meat byproducts, except liver at 0.10
ppm; goat, fat at 0.01 ppm; goat, liver at
1.0 ppm; goat, meat at 0.01 ppm; goat,
meat byproducts, except liver at 0.1
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ppm; hog, fat at 0.01 ppm; hog, liver at
0.1 ppm; hog, meat at 0.01 ppm; hog,
meat byproducts, except liver at 0.01
ppm; horse, fat at 0.01 ppm; horse, liver
at 1.0 ppm; horse, meat at 0.01 ppm;
horse, meat byproducts, except liver at
0.10 ppm; milk at 0.01 ppm; sheep, fat
at 0.01 ppm; sheep, liver at 1.0 ppm;
sheep, meat at 0.01 ppm; sheep, meat
byproducts, except liver at 0.10 ppm;
poultry, liver at 0.01 ppm. EPA can also
make a determination on aggregate
exposure for the establishment of
tolerances for the indirect or inadvertent
residues of amicarbazone and its
metabolites DA amicarbazone and iPr-2OH DA amicarbazone, calculated as
amicarbazone, in or on the following
raw agricultural commodities when
present therein as a result of the
application of amicarbazone to field
corn: Alfalfa, forage at 0.05 ppm; alfalfa,
hay at 0.10 ppm; cotton, undelinted
seed at 0.07 ppm; cotton, gin byproducts
at 0.30 ppm; soybean, forage at 1.50
ppm; soybean, hay at 5.0 ppm; soybean,
seed at 0.80 ppm; wheat, forage at 0.50
ppm; wheat, hay at 1.0 ppm; wheat,
grain at 0.10 ppm; wheat, straw at 0.50
ppm; wheat, grain, milled byproducts at
0.15 ppm.
EPA’s assessment of exposures and
risks associated with establishing the
tolerances follows.
A. Toxicological Profile
completeness, and reliability as well as
the relationship of the results of the
studies to human risk. EPA has also
considered available information
concerning the variability of the
sensitivities of major identifiable
subgroups of consumers, including
infants and children. Specific
information on the studies received and
the nature of the toxic effects caused by
amicarbazone 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.
EPA has evaluated the available
toxicity data and considered its validity,
TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY
Guideline No.
Study Type
Results
870.3100
90–Day oral toxicity - rodents (rats)
NOAEL = 33/38 milligram/kilogram/day (mg/kg/day)
LOAEL = 67/78 mg/kg/day based on decreased bodyweight (BW)
female and overall (weeks 1–13) bodyweight gain (BWG), decreased red cell indices, clinical chemistry (increased cholesterol,
T4 and T3 males, O-demethylase females, N-demethylase
males), increased relative liver weights females, and
histopathology effects in males (minimal hepatocytomegaly and
minimal pigmentation in the spleen)
870.3150
90–Day oral toxicity - nonrodents
(dogs)
NOAEL = 6.28 mg/kg/day
LOAEL = 24.99 mg/kg/day based on increased thyroid vacuolization
and decreased food consumption and glucose in females; increased platelets, phosphate, bile acids, absolute and relative
liver weights, and lymphoid hyperplasia of the gall bladder in
males; and decreased albumin and increased triglycerides, Ndemethylase, and O-demthylase in both sexes.
870.3200
21/28–Day dermal toxicity
NOAEL = 1,000 mg/kg/day
LOAEL = Not Observed
870.3700
Prenatal developmental in rats
Maternal NOAEL = 15 mg/kg/day
LOAEL = 100 mg/kg/day based on decreased BW/BWG and food
consumption, and increased incidences of hard stools.
Developmental NOAEL = 15 mg/kg/day
LOAEL = 100 mg/kg/day based on multiple skeletal development retardations (incomplete ossification/unossification was observed in
parietal bones, interparietal bones, supraoccipital bones,
squamosal bones, zygoma, pubis, xiphoid, and fontanelle
870.3700
Prenatal developmental in rabbits
Maternal NOAEL = 5 mg/kg/day
LOAEL = 20 mg/kg/day based on decreased BWG during treatment.
Developmental NOAEL = 20 mg/kg/day
LOAEL = 70 mg/kg/day based on decreased fetal BW, and increased incidences of incomplete ossification of the 5th medial
phalanx (bilateral) and the 13th caudal vertebra, and slightly thick
ribs.
870.3800
Reproduction and fertility effects
Parental/Systemic NOAEL = 6.4/7.3 mg/kg/day
LOAEL = 33.9/38.7 mg/kg/day based on decreased BW/BWG in
both sexes.
Reproductive NOAEL = 73.2/84.0 mg/kg/day
LOAEL = Not Observed
Offspring NOAEL = 6.4/7.3 mg/kg/day
LOAEL = 33.9/38.7 mg/kg/day based on decreased pup BW and
overall decreased BWG.
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TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.4100
Chronic toxicity in rodents (rats)
NOAEL = 2.3/2.7 mg/kg/day
LOAEL = 25.3/29.5 mg/kg/day based on decreased BW in females
and BWG in both sexes.
At the doses tested there was not a treatment related increase in
tumor incidence when compared to control. Dosing was considered adequate based on decreased BW in females and BWG in
both sexes.
870.4100
Chronic toxicity dogs (beagle)
NOAEL =2.5/2.3 mg/kg/day
LOAEL = 8.9/8.7 mg/kg/day based on effects on the liver, including
increased absolute and relative liver weights, and O-demethylase
in males; increased globulin and cytochrome P-450 in females;
and increased triglycerides and cholesterol in both sexes.
870.4300
Carcinogenicity-mice
NOAEL = 244.7/275.0 mg/kg/day
LOAEL = 709.0/806.3 mg/kg/day based on decreased BW and
BWG in both sexes, and subclinical anemia, and hemosiderin pigmentation of the spleen in males.
no evidence of carcinogenicity
At the doses tested there was not a treatment related increase in
tumor incidence when compared to control. Dosing was considered adequate based on decreased BW and BWG in both sexes,
and subclinical anemia, and hemosiderin pigmentation of the
spleen in males.
870.5100
Bacterial reverse mutation test
There was no evidence of induced mutant colonies over background.
870.5100
Bacterial reverse mutation test
There was no evidence of induced mutant colonies over background.
870.5100
Bacterial reverse mutation test
There was no evidence of induced mutant colonies over background.
870.5300
In vitro mammalian cell gene mutation test
There was no evidence that MKH3586 induced mutant colonies over
background in the presence or absence of S9-activation.
870.5375
In vitro mammalian chromosome aberration test
There was no evidence of chromosome aberration induced over
background in the presence or absence of S9-activation.
870.5395
Mammalian
erythrocyte
nucleus test
micro-
There was no significant increase in the frequency of
micronucleated polychromatic erythrocytes in bone marrow at any
treatment time.
870.6200
Acute neurotoxicity screening battery in rats (Fischer-344)
NOAEL = 10 mg/kg/day
LOAEL = 20 mg/kg/day based on eyelid ptosis, decreased approach
response (both sexes), and red nasal staining in males.
A series of acute neurotoxicity studies were performed, the NOAEL
for this study comes from 45121527.
870.6200
Subchronic neurotoxicity screening
battery in rats (Fischer-344)
Female: NOAEL = 7.8 mg/kg/day
LOAEL = 38.2 mg/kg/day based on decreased BW and overall BWG
in females.
Male: NOAEL = 66.5 mg/kd/day
LOAEL = was not observed for males.
870.6300
Developmental neurotoxicity in rats
Maternal NOAEL = 8 mg/kg/day
LOAEL = 39 mg/kg/day based primarily on decreased feed efficiency (combination of decreased BWG and increased food consumption) during lactation.
Offspring NOAEL = 39 mg/kg/day
LOAEL = 91 mg/kg/day based on decreased BWG.
870.7485
Metabolism and pharmacokinetics
95% of the radioactive dose was recovered within 72 hours following dosing. The majority of the dose was recovered from the
urine within 24 hours (64%), indicating substantial absorption.
Fecal excretion accounted for 27% of the dose within 24 hours.
Major metabolites were DA MKH, N-methyl DA MKH, and
decarboxamide.
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TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.7485
Metabolism and pharmacokinetics
91% of the radioactive dose was recovered within 96 hours. Urinary
excretion accounted for 70% of the radioactive dose within 12
hours, showing substantial absorption. Only 8% of the radioactive
dose was excreted via the feces within 24 hours.
Non-guideline
Subchronic mechanistic feeding in
rats
Thyroid hormones were increased in the >19.4 mg/kg/day females
and 40.0 mg/kg/day males. However, thyroid to blood ratios of
125I in treated groups were comparable to negative controls, indicating there was no impairment of thyroid hormone synthesis.
Thus, the differences in thyroid hormones is probably due to metabolism at an extra-thyroidal site. The liver was implicated as this
site because liver weights and UDP-glucuronosyltransferase activity were increased.
Non-guideline
In vitro studies on enzymes of thyroid hormone regulation
MKH 3586 does not affect the iodide organification step of thyroid
hormone synthesis or the peripheral metabolism of thyroid hormones via Type I or Type II deiodinases in vivo. These findings
support the subchronic mechanistic studies in rats which indicate
that upregulation of UDP-glucuronosyl transferase in the liver may
account for alterations in thyroid hormone profile.
Non-guideline
Behavioral study in rats
The following clinical signs were observed: Sedation, ptosis, salivation. Additionally at the HDT, piloerection, Straub phenomenon,
and prone position were observed. The effects were observed at
30 minutes post dose, and no effect was observed at 150 minutes
post dose, with the higher dose groups showing greater persistence of effects. A dose- and time-dependent effect was demonstrated on motor activity - decreased travel distance, increased
resting time, and decreased rearing.
Non-guideline
Study of central nervous system
safety pharmacology in mice
The data indicate that a single dose of MKH 3586 at 100 mg/kg
causes minimal CNS functional impairment, characterized by increased reaction times to nociceptive stimuli, reduced traction
force, impaired motor coordination, sedation, partial ptosis, and a
mild anticonvulsive effect.
B. Toxicological Endpoints
For hazards that have a threshold
below which there is no appreciable
risk, 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 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.
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
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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 = NOAE/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
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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 nonthreshold hazards such as cancer. The
Q* approach assumes that any amount
of exposure will lead to some degree of
cancer risk, estimates risk in terms of
the probability of occurrence of
additional cancer cases. 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), one in a 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
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derived from the dose response curve.
To estimate risk, a ratio of the point of
departure to exposure (MOE cancer =
point of departure/exposures) is
calculated.
A summary of the toxicological
endpoints for amicarbazone used for
55757
human risk assessment is shown in
Table 2 of this unit:
TABLE 2.—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR AMICARBAZONE FOR USE IN HUMAN RISK
ASSESSMENTS
Dose Used in Risk Assessment UF
Exposure Scenario
Special FQPA SF* and
LOC for Risk Assessment
Study and Toxicological Effects
Acute dietary
(females 13–49 years of age)
NOAEL = 10 mg/kg/day
UF = 100X
Acute RfD = 0.10 mg/kg/
day
Special FQPA SF = 1X
aPAD = 0.10 mg/kg/day
Acute neurotoxicity screening battery
LOAEL = 20 mg/kg/day, based on eyelid ptosis, decreased approach response, red nasal
staining in male rats.
Acute dietary
(general population)
NOAEL = 10 mg/kg/day
UF = 100X
Acute RfD = 0.10 mg/kg/
day
Special FQPA SF = 1X
aPAD = 0.10 mg/kg/day
Acute neurotoxicity screening battery
LOAEL = 20 mg/kg/day, based on eyelid ptosis, decreased approach response, red nasal
staining in male rats.
Chronic dietary
(all populations)
NOAEL = 2.3 mg/kg/day
UF = 100X
Chronic RfD = .023 mg/kg/
day
Special FQPA SF = 1X
cPAD = 0.023 mg/kg/day
Chronic rat and chronic dog
LOAEL = 25.3 and 8.7, respectively, based on
rat - decreased BW and BWG dog - liver effects, including increased absolute and relative liver weights, and O-demethylase in
male
dogs;
increased
globulin
and
cytochrome p450 in female dogs; and increased triglycerides and cholesterol in both
sexes
Dermal (all durations)
Not required: No systemic toxicity by dermal route was seen at the limit dose. Evidence of low dermal absorption.
Inhalation short-term
(1 - 30 days)
NOAEL = 6.28 mg/kg/day
LOC for MOE = 100
90–Day oral toxicity in dogs
LOAEL = 24.99 mg/kg/day, based on increased
thyroid vacuolization and decreased food
consumption and glucose in females; increased platelets, phosphate, bile acids, absolute and relative liver weights, and lymphoid hyperplasia of the gall bladder in males;
and decreased albumin and increased
triglycerides,
N-demethylase,
and
Odemethylase in both sexes
Inhalation intermediate-term
(1-6 months)
NOAEL = 6.28 mg/kg/day
LOC for MOE = 100
90–Day oral toxicity in dogs
LOAEL = 24.99 mg/kg/day, based on increased
thyroid vacuolization and decreased food
consumption and glucose in females; increased platelets, phosphate, bile acids, absolute and relative liver weights, and lymphoid hyperplasia of the gall bladder in males;
and decreased albumin and increased
triglycerides,
N-demethylase,
and
Odemethylase in both sexes
Cancer (oral, dermal, inhalation)
Classification: There was no treatment related increase in tumor incidence when compared to control. Dosing was considered adequate. This chemical is not likely to be a carcinogen.
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. No tolerances have been
established in 40 CFR part 180
previously for the combined residues of
amicarbazone, in or on a variety of raw
agricultural commodities. Risk
assessments were conducted by EPA to
assess dietary exposures from
amicarbazone in food as follows:
i. Acute exposure. Quantitative acute
dietary exposure and risk assessments
are performed for a food-use pesticide,
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if a toxicological study has indicated the
possibility of an effect of concern
occurring as a result of a 1–day or single
exposure.
The Dietary Exposure Evaluation
Model (DEEMTM) analysis evaluated the
individual food consumption 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. The following assumptions
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were made for the acute exposure
assessments: For the acute analyses,
tolerance-level residues were assumed
for all food commodities with proposed
amicarbazone tolerances, and it was
assumed that 100% of all of the crops
included in the analysis were treated.
The DEEMTM analyses included
drinking water in addition to the food
sources of residues.
ii. Chronic exposure. In conducting
the chronic dietary exposure assessment
EPA used the DEEM software with the
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Food Commodity Intake Database
(DEEM-FCIDTM), which incorporates
food consumption data as reported by
respondents in the USDA 1994–1996
and 1998 Nationwide CSFII, and
accumulated exposure to the chemical
for each commodity. The following
assumptions were made for the chronic
exposure assessments: For the chronic
analyses tolerance-level residues were
assumed for all food commodities with
proposed amicarbazone tolerances, and
it was assumed that 100% of all of the
crops included in the analysis were
treated. As with the acute analyses,
drinking water was included in the
assessment.
2. Dietary exposure from drinking
water. The Agency lacks sufficient
monitoring exposure data to complete a
comprehensive dietary exposure
analysis and risk assessment for
amicarbazone 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
amicarbazone.
Based on the FIRST and SCI-GROW
models, the estimated environmental
concentrations (EECs) of amicarbazone
for acute exposures are estimated to be
21.4 parts per billion (ppb) for surface
water and 102.9 ppb for ground water.
The EECs for chronic exposures are
estimated to be 13.4 ppb for surface
water and 102.9 ppb for ground water.
The ground water EEC was used in both
the acute and chronic DEEM analyses
described earlier in this section.
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).
Amicarbazone 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
amicarbazone and any other substances
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and amicarbazone 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 amicarbazone 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 is no evidence of increased
susceptibility of rat or rabbit fetuses
following in utero exposure in the
developmental studies with
amicarbazone. There is no evidence of
increased susceptibility of rats in the
reproduction study with amicarbazone.
EPA concluded that there are no
residual uncertainties for prenatal and/
or postnatal exposure.
3. Conclusion. There is a complete
toxicity data base for amicarbazone and
exposure data are complete or are
estimated based on data that reasonably
accounts for potential exposures. The
Agency concluded that there was
reliable data to remove the 10X
children’s safety factor based upon the
following: The toxicity database showed
no increase in susceptibility in fetuses
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and pups with in utero and post-natal
exposure; the dietary exposure
assessment is based on HEDrecommended tolerance-level residues,
assumes 100% crop treated for all
commodities, and utilizes high-end
estimates of concentrations in water;
and there are no residential uses
proposed for this chemical at this time.
E. Aggregate Risks and Determination of
Safety
1. Acute risk. Using the exposure
assumptions discussed in this unit for
acute exposure, the acute dietary
exposure from food and drinking water
to amicarbazone will occupy 7% of the
aPAD for the U.S. population, 6% of the
aPAD for females 13 years and older,
23% of the aPAD for the all infant
subpopulation, which is the
subpopulation with the greatest
exposure, and 12% of the aPAD for
children 1–2 years old. Therefore, EPA
does not expect the acute aggregate risk
exposure to exceed 100% of the aPAD.
2. Chronic risk. Using the exposure
assumptions described in this unit for
chronic exposure, EPA has concluded
that exposure to amicarbazone from
food and drinking water will utilize
14% of the cPAD for the U.S.
population, 39% of the cPAD for for the
all infant subpopulation, which is the
subpopulation with the greatest
exposure, and 26% of the cPAD for
children 1–2 years old. There are no
residential uses for amicarbazone that
result in chronic residential exposure to
amicarbazone. Therefore, the aggregate
risk is the sum of the risk from food and
water, which do not exceed the
Agency’s LOC.
3. Short-term risk. Short-term
aggregate exposure takes into account
residential exposure plus chronic
exposure to food and water (considered
to be a background exposure level).
Amicarbazone is not registered for use
on any sites that would result in
residential exposure. Therefore, the
chronic aggregate risk is the sum of the
risk from food and water, which do not
exceed the Agency’s LOC.
4. Intermediate-term risk.
Intermediate-term aggregate exposure
takes into account residential exposure
plus chronic exposure to food and water
(considered to be a background
exposure level). Amicarbazone 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
does not exceed the Agency’s LOC.
5. Aggregate cancer risk for U.S.
population. A cancer dietary exposure
analysis was not performed because the
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Agency determined that amicarbazone
was not likely to cause cancer.
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
amicarbazone residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology
(liquid chromatography/mass
spectrometry/mass spectrometry) is
available to enforce the tolerance
expression. The methods for both plant
and livestock commodities may be
requested from: Chief, Analytical
Chemistry Branch, Environmental
Science Center, 701 Mapes Rd., Ft.
Meade, MD 20755–5350; telephone
number: (410) 305–2905; e-mail address:
residuemethods@epa.gov.
B. International Residue Limits
There are currently no established
Codex, Canadian or Mexican residue
limits for amicarbazone.
C. Response to Comments
Ms. Sachau’s comments regarding
general exposure to pesticides contained
no scientific data or evidence to rebut
the Agency’s conclusion that there is a
reasonable certainty that no harm will
result from aggregate exposure to
amicarbazone, including all anticipated
dietary exposures and all other
exposures for which there is reliable
information. This comment as well as
her comments regarding animal testing
have been responded to by EPA on
several occasions. 70 FR 1349 (January
7, 2005)(FRL–7691–4); 69 FR 63083,
(October 29, 2004)(FRL–7681–9).
V. Conclusion
Therefore, tolerances are established
for combined residues of amicarbazone
[4-amino-N-(1,1-dimethyl)-4,5-dihydro3-(1-methylethyl)-5-oxo-1H-1,2,4triazole-1-carboxamide] and its
metabolites DA amicarbazone [N-(1,1dimethylethyl)-4,5-dihydro-3-(1methylethyl)-5-oxo-1H-1,2,4-triazole-1carboxamide] and iPr-2-OH DA
amicarbazone [N-(1,1-dimethylethyl)4,5-dihydro-3-(1-hydroxy-1methylethyl)-5-oxo-1H-1,2,4-triazole-1carboxamide], calculated as parent
equivalents, in or on corn, field, grain at
0.05 ppm; corn, field, forage at 0.80
ppm; corn, field, stover at 1.0 ppm;
cattle, fat at 0.01 ppm; cattle, liver at 1.0
ppm; cattle, meat at 0.01 ppm; cattle,
meat byproducts, except liver at 0.10
ppm; goat, fat at 0.01 ppm; goat, liver at
1.0 ppm; goat, meat at 0.01 ppm; goat,
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meat byproducts, except liver at 0.1
ppm; hog, fat at 0.01 ppm; hog, liver at
0.1 ppm; hog, meat at 0.01 ppm; hog,
meat byproducts, except liver at 0.01
ppm; horse, fat at 0.01 ppm; horse, liver
at 1.0 ppm; horse, meat at 0.01 ppm;
horse, meat byproducts, except liver at
0.10 ppm; milk at 0.01 ppm; sheep, fat
at 0.01 ppm; sheep, liver at 1.0 ppm;
sheep, meat at 0.01 ppm; sheep, meat
byproducts, except liver at 0.10 ppm;
poultry, liver at 0.01 ppm.
Tolerances are also established for the
indirect or inadvertent residues of
amicarbazone and its metabolites DA
amicarbazone and iPr-2-OH DA
amicarbazone, calculated as
amicarbazone, in or on the following
raw agricultural commodities when
present therein as a result of the
application of amicarbazone to field
corn: Alfalfa, forage at 0.05 ppm;
Alfalfa, hay at 0.10 ppm; Cotton,
undelinted seed at 0.07 ppm; Cotton,
gin byproducts at 0.30 ppm; Soybean,
forage at 1.50 ppm; Soybean, hay at 5.0
ppm; Soybean, seed at 0.80 ppm; Wheat,
forage at 0.50 ppm; Wheat, hay at 1.0
ppm; Wheat, grain at 0.10 ppm; Wheat,
straw at 0.50 ppm; Wheat, grain, milled
byproducts at 0.15 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–2005–0185 in the subject line on
the first page of your submission. All
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55759
requests must be in writing, and must be
mailed or delivered to the Hearing Clerk
on or before November 22, 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 issue(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 VIA, 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–2005–0185, 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 email 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.
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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
issue(s) in the manner sought by the
requestor would be adequate to justify
the action requested (40 CFR 178.32).
VII. Statutory and Executive Order
Reviews
This final rule establishes a tolerance
under section 408(d) of FFDCA in
response to a petition submitted to the
Agency. The Office of Management and
Budget (OMB) has exempted these types
of actions from review under Executive
Order 12866, entitled Regulatory
Planning and Review (58 FR 51735,
October 4, 1993). Because this rule has
been exempted from review under
Executive Order 12866 due to its lack of
significance, this rule is not subject to
Executive Order 13211, Actions
Concerning Regulations That
Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May
22, 2001). This final rule does not
contain any information collections
subject to OMB approval under the
Paperwork Reduction Act (PRA), 44
U.S.C. 3501 et seq., or impose any
enforceable duty or contain any
unfunded mandate as described under
Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Public
Law 104–4). Nor does it require any
special considerations under Executive
Order 12898, entitled Federal Actions to
Address Environmental Justice in
Minority Populations and Low-Income
Populations (59 FR 7629, February 16,
1994); or OMB review or any Agency
action under Executive Order 13045,
entitled Protection of Children from
Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
This action does not involve any
technical standards that would require
Agency consideration of voluntary
consensus standards pursuant to section
12(d) of the National Technology
Transfer and Advancement Act of 1995
(NTTAA), Public Law 104–113, section
12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are
established on the basis of a petition
under section 408(d) of FFDCA, such as
the tolerance in this final rule, do not
require the issuance of a proposed rule,
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the requirements of the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. In addition, the
Agency has determined that this action
will not have a substantial direct effect
on States, on the relationship between
the national government and the States,
or on the distribution of power and
responsibilities among the various
levels of government, as specified in
Executive Order 13132, entitled
Federalism (64 FR 43255, August 10,
1999). Executive Order 13132 requires
EPA to develop an accountable process
to ensure ‘‘meaningful and timely input
by State and local officials in the
development of regulatory policies that
have federalism implications.’’ ‘‘Policies
that have federalism implications’’ is
defined in the Executive order to
include regulations that have
‘‘substantial direct effects on the States,
on the relationship between the national
government and the States, or on the
distribution of power and
responsibilities among the various
levels of government.’’ This final rule
directly regulates growers, food
processors, food handlers and food
retailers, not States. This action does not
alter the relationships or distribution of
power and responsibilities established
by Congress in the preemption
provisions of section 408(n)(4) of
FFDCA. For these same reasons, the
Agency has determined that this rule
does not have any ‘‘tribal implications’’
as described in Executive Order 13175,
entitled Consultation and Coordination
with Indian Tribal Governments (65 FR
67249, November 6, 2000). Executive
Order 13175, requires EPA to develop
an accountable process to ensure
‘‘meaningful and timely input by tribal
officials in the development of
regulatory policies that have tribal
implications.’’ ‘‘Policies that have tribal
implications’’ is defined in the
Executive order to include regulations
that have ‘‘substantial direct effects on
one or more Indian tribes, on the
relationship between the Federal
Government and the Indian tribes, or on
the distribution of power and
responsibilities between the Federal
Government and Indian tribes.’’ This
rule will not have substantial direct
effects on tribal governments, on the
relationship between the Federal
Government and Indian tribes, or on the
distribution of power and
responsibilities between the Federal
Government and Indian tribes, as
specified in Executive Order 13175.
Thus, Executive Order 13175 does not
apply to this rule.
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VIII. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801 et seq., as added by the Small
Business Regulatory Enforcement
Fairness Act of 1996, generally provides
that before a rule may take effect, the
agency promulgating the rule must
submit a rule report, which includes a
copy of the rule, to each House of the
Congress and to the Comptroller General
of the United States. EPA will submit a
report containing this rule and other
required information to the U.S. Senate,
the U.S. House of Representatives, and
the Comptroller General of the United
States prior to publication of this final
rule in the Federal Register. This final
rule is not a ‘‘major rule’’ as defined by
5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection,
Administrative practice and procedure,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping
requirements.
Dated: September 12, 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 180.615 is added to subpart
C to read as follows:
I
§ 180.615
residues
Amicarbazone; tolerances for
(a) General. Tolerances are
established for combined residues of the
herbicide, amicarbazone [4-amino-4, 5dihydro- N-(1,1-dimethylethyl)-3-(1methylethyl)-5-oxo-1H-1,2,4-triazole-1carboxamide] and its metabolites DA
amicarbazone [N-(1,1-dimethylethyl)4,5-dihydro-3-(1-methylethyl)-5-oxo-1H1,2,4-triazole-1-carboxamide] and iPr-2OH DA amicarbazone [N-(1,1dimethylethyl)-4,5-dihydro-3-(1hydroxy-1-methylethyl)-5-oxo-1H-1,2,4triazole-1-carboxamide], calculated as
parent equivalents, in or on the
following commodities:
Commodity
Cattle, fat ........................
Cattle, liver ......................
Cattle, meat ....................
Cattle, meat byproducts,
except liver ..................
Corn, field, forage ...........
Corn, field, grain .............
Corn, field, stover ...........
Goat, fat ..........................
E:\FR\FM\23SER1.SGM
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Parts per million
0.01
1.0
0.01
0.10
0.80
0.05
1.0
0.01
Federal Register / Vol. 70, No. 184 / Friday, September 23, 2005 / Rules and Regulations
Commodity
Parts per million
Goat, liver .......................
Goat, meat ......................
Goat, meat byproducts,
except liver ..................
Hog, fat ...........................
Hog, liver ........................
Hog, meat .......................
Hog, meat byproducts,
except liver ..................
Horse, fat ........................
Horse, liver .....................
Horse, meat ....................
Horse, meat byproducts,
except liver ..................
Milk .................................
Sheep, fat .......................
Sheep, liver .....................
Sheep, meat ...................
Sheep, meat byproducts,
except liver ..................
Poultry, liver ....................
1.0
0.01
0.10
0.01
0.10
0.01
0.01
0.01
1.0
0.01
0.10
0.01
0.01
1.0
0.01
0.10
0.10
(b) Section 18 emergency exemptions.
[Reserved]
(c) Tolerances with regional
registrations. [Reserved]
(d) Indirect or inadvertent residues.
Tolerances are established for the
indirect or inadvertent residues of
amicarbazone [4-amino-4, 5-dihydro-N(1,1-dimethylethyl)-3-(1-methylethyl)-5oxo-1H-1,2,4-triazole-1-carboxamide]
and its metabolites DA amicarbazone
[N-(1,1-dimethylethyl)-4,5-dihydro-3-(1methylethyl)-5-oxo-1H-1,2,4-triazole-1carboxamide] and iPr-2-OH DA
amicarbazone [N-(1,1-dimethylethyl)4,5-dihydro-3-(1-hydroxy-1methylethyl)-5-oxo-1H-1,2,4-triazole-1carboxamide], calculated as parent
equivalents, in or on the following
commodities when present therein as a
result of application of amicarbazone to
the growing crops in paragraph (a) of
this section:
Commodity
Parts per million
Alfalfa, forage .................
Alfalfa, hay ......................
Cotton, gin byproducts ...
Cotton, undelinted seed
Soybean, forage .............
Soybean, hay ..................
Soybean, seed ................
Wheat, forage .................
Wheat, grain ...................
Wheat, grain, milled byproducts ......................
Wheat, hay .....................
Wheat, straw ...................
0.05
0.10
0.30
0.07
1.50
5.0
0.80
0.50
0.10
0.15
1.0
0.50
[FR Doc. 05–18951 Filed 9–22–05; 8:45 am]
BILLING CODE 6560–50–S
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[OPP–2005–0267; FRL–7738–6]
Pyridaben; Pesticide Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes
tolerances for residues of pyridaben in
or on hop, dried cones; papaya; star
apple; sapote, black; mango; sapodilla;
sapote, mamey; canistel, fruit, stone,
group 12; strawberry; and tomato.
Interregional Research Project Number 4
(IR-4) requested these tolerances under
the Federal Food, Drug, and Cosmetic
Act (FFDCA), as amended by the Food
Quality Protection Act of 1996 (FQPA).
EPA is also deleting certain pyridaben
tolerances that are no longer needed as
result of this action.
DATES: This regulation is effective
September 23, 2005. Objections and
requests for hearings must be received
on or before November 22, 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–
0267. 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:
Barbara Madden, Registration Division
(7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 305–6463; e-mail address:
madden.barbara@epa.gov.
SUPPLEMENTARY INFORMATION:
VerDate Aug<31>2005
14:48 Sep 22, 2005
Jkt 205001
PO 00000
Frm 00057
Fmt 4700
Sfmt 4700
55761
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
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 at E-CFR
Beta Site Two at https://
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 3, 2003
(68 FR 39942) (FRL–7315–4), EPA
issued a notice pursuant to section
408(d)(3) of FFDCA, 21 U.S.C.
346a(d)(3), announcing the filing of
pesticide petitions (0E6068, 1E6226,
1E6303, 2E6457, and 2E6460) from IR4, 681 U.S. Highway #1 South, North
Brunswick, NJ 08902–3390. The
E:\FR\FM\23SER1.SGM
23SER1
]]>Agencies
[Federal Register Volume 70, Number 184 (Friday, September 23, 2005)]
[Rules and Regulations]
[Pages 55752-55761]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-18951]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2005-0185; FRL-7736-3]
Amicarbazone; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes tolerances for combined residues
of amicarbazone and its metabolites in or on field corn and livestock
commodities and indirect or inadvertent residues of amicarbazone and
its metabolites in alfalfa, cotton, soybean and wheat. Arysta
Lifescience North American Corporation (perviously known as Arvesta
Corporation) requested this tolerance under the Federal Food, Drug, and
Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of
1996 (FQPA).
DATES: This regulation is effective September 23, 2005. Objections and
requests for hearings must be received on or before November 22, 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-2005-0185. 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.
[[Page 55753]]
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: Joanne I. Miller, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-6224; e-mail address:
miller.joanne@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 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 at E-CFR Beta Site Two at https://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 January 22, 2004 (69 FR 3138) (FRL-7339-
3), 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
0F6131) by Arysta Lifescience North American Corporation, 100 First
Street, Suite 1700; San Francisco, CA 94105. The petition requested
that 40 CFR part 180 be amended by establishing tolerances for combined
residues of the herbicide amicarbazone, 4-amino-4,5-dihydro-N-(1,1-
dimethylethyl)-3-(1-methylethyl)-5-oxo-1H-1,2,4-triazole-1-carboxamide]
and its metabolities DA amicarbazone (N-(1,1-dimethylethyl)-4,5-
dihydro-3-(1-methylethyl)-5-oxo-1H,2,4-triazole-1-carboxamide) and iPr-
2-OH DA amicarbazone (N-(1,1-dimethylethyl)-4,5-dihydro-3-(1-hydroxy-1-
methylethyl)-5-oxo-1H-1,2,4-triazole-1-carboxamide), in or on the raw
agricultural commodities alfalfa forage at 0.04 parts per million
(ppm); alfalfa hay at 0.06 ppm; corn forage at 0.8ppm; corn grain, at
0.05 ppm; corn stover at 0.5 ppm; cotton gin by-product at 0.2 ppm;
cottonseed hulls at 0.01 ppm; cottonseed meal at 0.01 ppm; cottonseed
refined oil at 0.01 ppm; cotton undelinted seed at 0.04 ppm; soybean
forage at 2.5 ppm; soybean hay at 7.0 ppm; soybean hulls at 0.2 ppm;
soybean meal at 0.25 ppm; soybean oil at 0.01 ppm; soybean seed at 0.6
ppm; wheat bran at 0.08 ppm; wheat flour at 0.05 ppm; wheat forage at
0.6 ppm; wheat germs at 0.05 ppm; wheat grain at 0.09 ppm; wheat hay at
0.9 ppm; wheat middlings at 0.05 ppm; wheat shorts at 0.06 ppm; wheat
straw at 0.4 ppm; sugarcane at 0.15 ppm; sugarcane molasses at 0.8 ppm;
meat (cattle, goats, hogs, horses, and sheep) at 0.01 ppm; meat
byproducts (cattle, goats, hogs, horses,and sheep) at 0.2 ppm; and milk
at 0.01 ppm respectively.
Due to a lack of field trial data on sugarcane, tolerances on
sugarcane and sugarcane molasses are not being established at this
time.
One comment was received in response to the notice filing. B.
Sachau objected to the proposed tolerances because of the amounts of
pesticides already consumed and carried by the American population. She
further indicated that testing conducted on animals have absolutely no
validity and are cruel to the test animals. EPA's response to these
comments is contained in Unit IV.C.
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 combined residues of
amicarbazone [4-amino-4, 5-dihydro- N-(1,1-dimethylethyl)-3-(1-
methylethyl)-5-oxo-1H-1,2,4-triazole-1-carboxamide] and its metabolites
DA amicarbazone [N-(1,1-dimethylethyl)-4,5-dihydro-3-(1-methylethyl)-5-
oxo-1H-1,2,4-triazole-1-carboxamide] and iPr-2-OH DA amicarbazone [N-
(1,1-dimethylethyl)-4,5-dihydro-3-(1-hydroxy-1-methylethyl)-5-oxo-1H-
1,2,4-triazole-1-carboxamide], calculated as parent equivalents, in or
on corn, field, forage at 0.80 ppm; corn, field, grain at 0.05 ppm;
corn, field, stover at 1.0 ppm; cattle, fat at 0.01 ppm; cattle, liver
at 1.0 ppm; cattle, meat at 0.01 ppm; cattle, meat byproducts, except
liver at 0.10 ppm; goat, fat at 0.01 ppm; goat, liver at 1.0 ppm; goat,
meat at 0.01 ppm; goat, meat byproducts, except liver at 0.1
[[Page 55754]]
ppm; hog, fat at 0.01 ppm; hog, liver at 0.1 ppm; hog, meat at 0.01
ppm; hog, meat byproducts, except liver at 0.01 ppm; horse, fat at 0.01
ppm; horse, liver at 1.0 ppm; horse, meat at 0.01 ppm; horse, meat
byproducts, except liver at 0.10 ppm; milk at 0.01 ppm; sheep, fat at
0.01 ppm; sheep, liver at 1.0 ppm; sheep, meat at 0.01 ppm; sheep, meat
byproducts, except liver at 0.10 ppm; poultry, liver at 0.01 ppm. EPA
can also make a determination on aggregate exposure for the
establishment of tolerances for the indirect or inadvertent residues of
amicarbazone and its metabolites DA amicarbazone and iPr-2-OH DA
amicarbazone, calculated as amicarbazone, in or on the following raw
agricultural commodities when present therein as a result of the
application of amicarbazone to field corn: Alfalfa, forage at 0.05 ppm;
alfalfa, hay at 0.10 ppm; cotton, undelinted seed at 0.07 ppm; cotton,
gin byproducts at 0.30 ppm; soybean, forage at 1.50 ppm; soybean, hay
at 5.0 ppm; soybean, seed at 0.80 ppm; wheat, forage at 0.50 ppm;
wheat, hay at 1.0 ppm; wheat, grain at 0.10 ppm; wheat, straw at 0.50
ppm; wheat, grain, milled byproducts at 0.15 ppm.
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 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. Specific information on the studies received and the nature
of the toxic effects caused by amicarbazone are discussed in Table 1 of
this unit as well as the no observed adverse effect level (NOAEL) and
the lowest observed adverse effect level (LOAEL) from the toxicity
studies reviewed.
Table 1.--Subchronic, Chronic, and Other Toxicity
------------------------------------------------------------------------
Guideline No. Study Type Results
------------------------------------------------------------------------
870.3100 90-Day oral NOAEL = 33/38
toxicity - milligram/
rodents (rats) kilogram/day (mg/
kg/day)
LOAEL = 67/78 mg/
kg/day based on
decreased
bodyweight (BW)
female and
overall (weeks 1-
13) bodyweight
gain (BWG),
decreased red
cell indices,
clinical
chemistry
(increased
cholesterol, T4
and T3 males, O-
demethylase
females, N-
demethylase
males), increased
relative liver
weights females,
and
histopathology
effects in males
(minimal
hepatocytomegaly
and minimal
pigmentation in
the spleen)
------------------------------------------------------
870.3150 90-Day oral NOAEL = 6.28 mg/kg/
toxicity - day
nonrodents (dogs) LOAEL = 24.99 mg/
kg/day based on
increased thyroid
vacuolization and
decreased food
consumption and
glucose in
females;
increased
platelets,
phosphate, bile
acids, absolute
and relative
liver weights,
and lymphoid
hyperplasia of
the gall bladder
in males; and
decreased albumin
and increased
triglycerides, N-
demethylase, and
O-demthylase in
both sexes.
------------------------------------------------------
870.3200 21/28-Day dermal NOAEL = 1,000 mg/
toxicity kg/day
LOAEL = Not
Observed
------------------------------------------------------
870.3700 Prenatal Maternal NOAEL =
developmental in 15 mg/kg/day
rats LOAEL = 100 mg/kg/
day based on
decreased BW/BWG
and food
consumption, and
increased
incidences of
hard stools.
Developmental
NOAEL = 15 mg/kg/
day
LOAEL = 100 mg/kg/
day based on
multiple skeletal
development
retardations
(incomplete
ossification/
unossification
was observed in
parietal bones,
interparietal
bones,
supraoccipital
bones, squamosal
bones, zygoma,
pubis, xiphoid,
and fontanelle
------------------------------------------------------
870.3700 Prenatal Maternal NOAEL = 5
developmental in mg/kg/day
rabbits LOAEL = 20 mg/kg/
day based on
decreased BWG
during treatment.
Developmental
NOAEL = 20 mg/kg/
day
LOAEL = 70 mg/kg/
day based on
decreased fetal
BW, and increased
incidences of
incomplete
ossification of
the 5th medial
phalanx
(bilateral) and
the 13th caudal
vertebra, and
slightly thick
ribs.
------------------------------------------------------
870.3800 Reproduction and Parental/Systemic
fertility effects NOAEL = 6.4/7.3
mg/kg/day
LOAEL = 33.9/38.7
mg/kg/day based
on decreased BW/
BWG in both
sexes.
Reproductive NOAEL
= 73.2/84.0 mg/kg/
day
LOAEL = Not
Observed
Offspring NOAEL =
6.4/7.3 mg/kg/day
LOAEL = 33.9/38.7
mg/kg/day based
on decreased pup
BW and overall
decreased BWG.
------------------------------------------------------
[[Page 55755]]
870.4100 Chronic toxicity NOAEL = 2.3/2.7 mg/
in rodents (rats) kg/day
LOAEL = 25.3/29.5
mg/kg/day based
on decreased BW
in females and
BWG in both
sexes.
At the doses
tested there was
not a treatment
related increase
in tumor
incidence when
compared to
control. Dosing
was considered
adequate based on
decreased BW in
females and BWG
in both sexes.
------------------------------------------------------
870.4100 Chronic toxicity NOAEL =2.5/2.3 mg/
dogs (beagle) kg/day
LOAEL = 8.9/8.7 mg/
kg/day based on
effects on the
liver, including
increased
absolute and
relative liver
weights, and O-
demethylase in
males; increased
globulin and
cytochrome P-450
in females; and
increased
triglycerides and
cholesterol in
both sexes.
------------------------------------------------------
870.4300 Carcinogenicity- NOAEL = 244.7/
mice 275.0 mg/kg/day
LOAEL = 709.0/
806.3 mg/kg/day
based on
decreased BW and
BWG in both
sexes, and
subclinical
anemia, and
hemosiderin
pigmentation of
the spleen in
males.
no evidence of
carcinogenicity
At the doses
tested there was
not a treatment
related increase
in tumor
incidence when
compared to
control. Dosing
was considered
adequate based on
decreased BW and
BWG in both
sexes, and
subclinical
anemia, and
hemosiderin
pigmentation of
the spleen in
males.
------------------------------------------------------
870.5100 Bacterial reverse There was no
mutation test evidence of
induced mutant
colonies over
background.
------------------------------------------------------
870.5100 Bacterial reverse There was no
mutation test evidence of
induced mutant
colonies over
background.
------------------------------------------------------
870.5100 Bacterial reverse There was no
mutation test evidence of
induced mutant
colonies over
background.
------------------------------------------------------
870.5300 In vitro mammalian There was no
cell gene evidence that
mutation test MKH3586 induced
mutant colonies
over background
in the presence
or absence of S9-
activation.
------------------------------------------------------
870.5375 In vitro mammalian There was no
chromosome evidence of
aberration test chromosome
aberration
induced over
background in the
presence or
absence of S9-
activation.
------------------------------------------------------
870.5395 Mammalian There was no
erythrocyte significant
micronucleus test increase in the
frequency of
micronucleated
polychromatic
erythrocytes in
bone marrow at
any treatment
time.
------------------------------------------------------
870.6200 Acute NOAEL = 10 mg/kg/
neurotoxicity day
screening battery LOAEL = 20 mg/kg/
in rats (Fischer- day based on
344) eyelid ptosis,
decreased
approach response
(both sexes), and
red nasal
staining in
males.
A series of acute
neurotoxicity
studies were
performed, the
NOAEL for this
study comes from
45121527.
------------------------------------------------------
870.6200 Subchronic Female: NOAEL =
neurotoxicity 7.8 mg/kg/day
screening battery LOAEL = 38.2 mg/kg/
in rats (Fischer- day based on
344) decreased BW and
overall BWG in
females.
Male: NOAEL = 66.5
mg/kd/day
LOAEL = was not
observed for
males.
------------------------------------------------------
870.6300 Developmental Maternal NOAEL = 8
neurotoxicity in mg/kg/day
rats LOAEL = 39 mg/kg/
day based
primarily on
decreased feed
efficiency
(combination of
decreased BWG and
increased food
consumption)
during lactation.
Offspring NOAEL =
39 mg/kg/day
LOAEL = 91 mg/kg/
day based on
decreased BWG.
------------------------------------------------------
870.7485 Metabolism and 95% of the
pharmacokinetics radioactive dose
was recovered
within 72 hours
following dosing.
The majority of
the dose was
recovered from
the urine within
24 hours (64%),
indicating
substantial
absorption. Fecal
excretion
accounted for 27%
of the dose
within 24 hours.
Major metabolites
were DA MKH, N-
methyl DA MKH,
and
decarboxamide.
------------------------------------------------------
[[Page 55756]]
870.7485 Metabolism and 91% of the
pharmacokinetics radioactive dose
was recovered
within 96 hours.
Urinary excretion
accounted for 70%
of the
radioactive dose
within 12 hours,
showing
substantial
absorption. Only
8% of the
radioactive dose
was excreted via
the feces within
24 hours.
------------------------------------------------------
Non-guideline Subchronic Thyroid hormones
mechanistic were increased in
feeding in rats the >19.4 mg/kg/
day females and
40.0 mg/kg/day
males. However,
thyroid to blood
ratios of \125\I
in treated groups
were comparable
to negative
controls,
indicating there
was no impairment
of thyroid
hormone
synthesis. Thus,
the differences
in thyroid
hormones is
probably due to
metabolism at an
extra-thyroidal
site. The liver
was implicated as
this site because
liver weights and
UDP-
glucuronosyltrans
ferase activity
were increased.
------------------------------------------------------
Non-guideline In vitro studies MKH 3586 does not
on enzymes of affect the iodide
thyroid hormone organification
regulation step of thyroid
hormone synthesis
or the peripheral
metabolism of
thyroid hormones
via Type I or
Type II
deiodinases in
vivo. These
findings support
the subchronic
mechanistic
studies in rats
which indicate
that upregulation
of UDP-
glucuronosyl
transferase in
the liver may
account for
alterations in
thyroid hormone
profile.
------------------------------------------------------
Non-guideline Behavioral study The following
in rats clinical signs
were observed:
Sedation, ptosis,
salivation.
Additionally at
the HDT,
piloerection,
Straub
phenomenon, and
prone position
were observed.
The effects were
observed at 30
minutes post
dose, and no
effect was
observed at 150
minutes post
dose, with the
higher dose
groups showing
greater
persistence of
effects. A dose-
and time-
dependent effect
was demonstrated
on motor activity
- decreased
travel distance,
increased resting
time, and
decreased
rearing.
------------------------------------------------------
Non-guideline Study of central The data indicate
nervous system that a single
safety dose of MKH 3586
pharmacology in at 100 mg/kg
mice causes minimal
CNS functional
impairment,
characterized by
increased
reaction times to
nociceptive
stimuli, reduced
traction force,
impaired motor
coordination,
sedation, partial
ptosis, and a
mild
anticonvulsive
effect.
------------------------------------------------------------------------
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, 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 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.
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 = NOAE/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 non-threshold hazards such as
cancer. The Q* approach assumes that any amount of exposure will lead
to some degree of cancer risk, estimates risk in terms of the
probability of occurrence of additional cancer cases. 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), one in a 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
[[Page 55757]]
derived from the dose response curve. To estimate risk, a ratio of the
point of departure to exposure (MOE cancer = point of departure/
exposures) is calculated.
A summary of the toxicological endpoints for amicarbazone used for
human risk assessment is shown in Table 2 of this unit:
Table 2.--Summary of Toxicological Doses and Endpoints for Amicarbazone for Use in Human Risk Assessments
----------------------------------------------------------------------------------------------------------------
Dose Used in Risk Special FQPA SF* and Study and Toxicological
Exposure Scenario Assessment UF LOC for Risk Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary NOAEL = 10 mg/kg/day Special FQPA SF = 1X Acute neurotoxicity
(females 13-49 years of age)......... UF = 100X.............. aPAD = 0.10 mg/kg/day.. screening battery
Acute RfD = 0.10 mg/kg/ LOAEL = 20 mg/kg/day,
day. based on eyelid
ptosis, decreased
approach response, red
nasal staining in male
rats.
----------------------------------------------------------------
Acute dietary NOAEL = 10 mg/kg/day Special FQPA SF = 1X Acute neurotoxicity
(general population)................. UF = 100X.............. aPAD = 0.10 mg/kg/day.. screening battery
Acute RfD = 0.10 mg/kg/ LOAEL = 20 mg/kg/day,
day. based on eyelid
ptosis, decreased
approach response, red
nasal staining in male
rats.
----------------------------------------------------------------
Chronic dietary NOAEL = 2.3 mg/kg/day Special FQPA SF = 1X Chronic rat and chronic
(all populations).................... UF = 100X.............. cPAD = 0.023 mg/kg/day. dog
Chronic RfD = .023 mg/ LOAEL = 25.3 and 8.7,
kg/day. respectively, based on
rat - decreased BW and
BWG dog - liver
effects, including
increased absolute and
relative liver
weights, and O-
demethylase in male
dogs; increased
globulin and
cytochrome p450 in
female dogs; and
increased
triglycerides and
cholesterol in both
sexes
----------------------------------------------------------------
Dermal (all durations) Not required: No systemic toxicity by dermal route was seen at the limit
dose. Evidence of low dermal absorption.
----------------------------------------------------------------
Inhalation short-term NOAEL = 6.28 mg/kg/day LOC for MOE = 100 90-Day oral toxicity in
(1 - 30 days)........................ dogs
LOAEL = 24.99 mg/kg/
day, based on
increased thyroid
vacuolization and
decreased food
consumption and
glucose in females;
increased platelets,
phosphate, bile acids,
absolute and relative
liver weights, and
lymphoid hyperplasia
of the gall bladder in
males; and decreased
albumin and increased
triglycerides, N-
demethylase, and O-
demethylase in both
sexes
----------------------------------------------------------------
Inhalation intermediate-term NOAEL = 6.28 mg/kg/day LOC for MOE = 100 90-Day oral toxicity in
(1-6 months)......................... dogs
LOAEL = 24.99 mg/kg/
day, based on
increased thyroid
vacuolization and
decreased food
consumption and
glucose in females;
increased platelets,
phosphate, bile acids,
absolute and relative
liver weights, and
lymphoid hyperplasia
of the gall bladder in
males; and decreased
albumin and increased
triglycerides, N-
demethylase, and O-
demethylase in both
sexes
----------------------------------------------------------------
Cancer (oral, dermal, inhalation) Classification: There was no treatment related increase in tumor
incidence when compared to control. Dosing was considered adequate. This
chemical is not likely to be a carcinogen.
----------------------------------------------------------------------------------------------------------------
C. Exposure Assessment
1. Dietary exposure from food and feed uses. No tolerances have
been established in 40 CFR part 180 previously for the combined
residues of amicarbazone, in or on a variety of raw agricultural
commodities. Risk assessments were conducted by EPA to assess dietary
exposures from amicarbazone in food as follows:
i. Acute exposure. Quantitative acute dietary exposure and 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.
The Dietary Exposure Evaluation Model (DEEM\TM\) analysis evaluated
the individual food consumption 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. The following assumptions were made for the acute exposure
assessments: For the acute analyses, tolerance-level residues were
assumed for all food commodities with proposed amicarbazone tolerances,
and it was assumed that 100% of all of the crops included in the
analysis were treated. The DEEM\TM\ analyses included drinking water in
addition to the food sources of residues.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the DEEM software with the
[[Page 55758]]
Food Commodity Intake Database (DEEM-FCID\TM\), which incorporates food
consumption data as reported by respondents in the USDA 1994-1996 and
1998 Nationwide CSFII, and accumulated exposure to the chemical for
each commodity. The following assumptions were made for the chronic
exposure assessments: For the chronic analyses tolerance-level residues
were assumed for all food commodities with proposed amicarbazone
tolerances, and it was assumed that 100% of all of the crops included
in the analysis were treated. As with the acute analyses, drinking
water was included in the assessment.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for amicarbazone 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 amicarbazone.
Based on the FIRST and SCI-GROW models, the estimated environmental
concentrations (EECs) of amicarbazone for acute exposures are estimated
to be 21.4 parts per billion (ppb) for surface water and 102.9 ppb for
ground water. The EECs for chronic exposures are estimated to be 13.4
ppb for surface water and 102.9 ppb for ground water. The ground water
EEC was used in both the acute and chronic DEEM analyses described
earlier in this section.
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).
Amicarbazone 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 amicarbazone and any other
substances and amicarbazone 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 amicarbazone 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 is no evidence of
increased susceptibility of rat or rabbit fetuses following in utero
exposure in the developmental studies with amicarbazone. There is no
evidence of increased susceptibility of rats in the reproduction study
with amicarbazone. EPA concluded that there are no residual
uncertainties for prenatal and/or postnatal exposure.
3. Conclusion. There is a complete toxicity data base for
amicarbazone and exposure data are complete or are estimated based on
data that reasonably accounts for potential exposures. The Agency
concluded that there was reliable data to remove the 10X children's
safety factor based upon the following: The toxicity database showed no
increase in susceptibility in fetuses and pups with in utero and post-
natal exposure; the dietary exposure assessment is based on HED-
recommended tolerance-level residues, assumes 100% crop treated for all
commodities, and utilizes high-end estimates of concentrations in
water; and there are no residential uses proposed for this chemical at
this time.
E. Aggregate Risks and Determination of Safety
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food and
drinking water to amicarbazone will occupy 7% of the aPAD for the U.S.
population, 6% of the aPAD for females 13 years and older, 23% of the
aPAD for the all infant subpopulation, which is the subpopulation with
the greatest exposure, and 12% of the aPAD for children 1-2 years old.
Therefore, EPA does not expect the acute aggregate risk exposure to
