Acetamiprid; Pesticide Tolerance, 19283-19293 [05-7225]
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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 the
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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X. 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: March 29, 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 180.1257 is added to subpart
D to read as follows:
I
§ 180.1257 Paecilomyces lilacinus strain
251; exemption from the requirement of a
tolerance.
An exemption from the requirement
of a tolerance is established for residues
of the microbial pesticide Paecilomyces
lilacinus strain 251 when used in or on
all agricultural commodities when
applied/used in accordance with label
directions.
19283
or on tuberous and corm vegetables.
Nippon Soda Company c/o Nisso
America Inc. requested this tolerance
under the Federal Food, Drug, and
Cosmetic Act (FFDCA), as amended by
the Food Quality Protection Act of 1996
(FQPA).
DATES: This regulation is effective April
13, 2005. Objections and requests for
hearings must be received on or before
June 13, 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–
0029. All documents in the docket are
listed in the EDOCKET index at http:/
/www.epa.gov/edocket. Although listed
in the index, some information is not
publicly available, i.e., CBI or other
information whose disclosure is
restricted by statute. Certain other
material, such as copyrighted material,
is not placed on the Internet and will be
publicly available only in hard copy
form. Publicly available docket
materials are available either
electronically in EDOCKET or in hard
copy at the Public Information and
Records Integrity Branch (PIRIB), Rm.
119, Crystal Mall #2, 1801 S. Bell St.,
Arlington, VA. This docket facility is
open from 8:30 a.m. to 4 p.m., Monday
through Friday, excluding legal
holidays. The docket telephone number
is (703) 305–5805.
FOR FURTHER INFORMATION CONTACT:
Akiva Abramovitch, Registration
Division (7505C), Office of Pesticide
Programs, Environmental Protection
Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460–0001; telephone
number: (703) 308–8328; e-mail address:
abramovitch.akiva@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
[FR Doc. 05–7226 Filed 4–12–05; 8:45 am]
A. Does this Action Apply to Me?
BILLING CODE 6560–50–S
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 code 111)
• Animal production (NAICS code
112)
• Food manufacturing (NAICS code
311)
• Pesticide manufacturing (NAICS
code 32532)
This listing is not intended to be
exhaustive, but rather provides a guide
for readers regarding entities likely to be
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[OPP–2005–0029; FRL–7705–7]
Acetamiprid; Pesticide Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes a
tolerance for residues of acetamiprid in
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Federal Register / Vol. 70, No. 70 / Wednesday, April 13, 2005 / Rules and Regulations
affected by this action. Other types of
entities not listed in this unit could also
be affected. The North American
Industrial Classification System
(NAICS) codes have been provided to
assist you and others in determining
whether this action might apply to
certain entities. If you have any
questions regarding the applicability of
this action to a particular entity, consult
the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies
of this Document and Other Related
Information?
In addition to using EDOCKET (http:/
/www.epa.gov/edocket/), you may
access this Federal Register document
electronically through the EPA Internet
under the ‘‘Federal Register’’ listings at
https://www.epa.gov/fedrgstr/. A
frequently updated electronic version of
40 CFR part 180 is available at E-CFR
Beta Site Two at https://
www.gpoaccess.gov/ecfr/. 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 August 4,
2004 (69 FR 47145) (FRL–7369–6), 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 3F6575) by
Nippon Soda Company c/o Nisso
America, 42 Broadway, Suite 2120, New
York, NY 10006. The petition requested
that 40 CFR 180.578 be amended by
establishing a tolerance for residues of
the insecticide acetamiprid, in or on
tuberous and corm vegetables at 0.01
parts per million (ppm). That notice
included a summary of the petition
prepared by Nisso America, Inc.. There
were two comments to the Acetamiprid
Notice of Filing and they are addressed
in Unit IV.D..
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 residues of
acetamiprid on tuberous and corm
vegetables at 0.01 ppm. EPA’s
assessment of exposures and risks
associated with establishing the
tolerance follows.
A. Toxicological Profile
EPA has evaluated the available
toxicity data and considered its validity,
completeness, and reliability as well as
the relationship of the results of the
studies to human risk. EPA has also
considered available information
concerning the variability of the
sensitivities of major identifiable
subgroups of consumers, including
infants and children. The nature of the
toxic effects caused by acetamiprid are
discussed in Table 1 of this unit as well
as the no-observed-adverse-effect-level
(NOAEL) and the lowest-observedadverse-effect-level (LOAEL) from the
toxicity studies reviewed.
TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY
Guideline No.
Study Type
Results
870.3100
90 days oral toxicity - rodents
NOAEL: 12.4/14.6 milligrams/kilograms (mg/kg)/day - Male/Female (M/F)
LOAEL: 50.8/56.0 mg/kg/day (M/F) based on decreased Body
Weight (BW), BW gain and food consumption.
870.3100
90 days oral toxicity - mouse
NOAEL: 106.1/129.4 mg/kg/day (M/F)
LOAEL: 211.1/249.1 mg/kg/day (M/F) based on reduced BW
and BW gain, decreased glucoseand cholesterol levels, reduced absolute organ weights.
870.3150
90–day oral toxicity in nonrodents
NOAEL: 13/14 mg/kg/day (M/F)
LOAEL: 32 mg/kg/day based on reduced BW gain in both
sexes.
870.3200
21–day dermal toxicity - rabbit
NOAEL: 1,000 mg/kg/day - Highest Dose Tested (HDT)
LOAEL: >1,000 mg/kg/day
870.3700
Prenatal developmental toxicity in
rodents
Maternal NOAEL: 16 mg/kg/day
Maternal LOAEL: 50 mg/kg/day based on reduced BW and BW
gain and food consumption, increased liver weights.
Developmental NOAEL: 16 mg/kg/day
Developmental LOAEL: 50 mg/kg/day based on increased incidence of shortening of the 13th rib.
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TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.3700
Prenatal developmental toxicity in
nonrodents
Maternal NOAEL: 15 mg/kg/day
Maternal LOAEL: 30mg/kg/day based on BW loss and decreased food consumption.
Developmental NOAEL: 30 mg/kg/day (HDT)
Developmental LOAEL: > 30 mg/kg/day
870.3800
Reproduction and fertility effects
Parental systemic NOAEL: 17.9/21.7 mg/kg/day (M/F)
Parental systemic LOAEL: 51.0/60.1 mg/kg/day (M/F) based on
decreased BW, BW gain and food consumption.
Offspring systemic NOAEL: 17.9/21.7 mg/kg/day (M/F)
Offspring systemic LOAEL: 51.0/60.1 mg/kg/day (M/F) based on
reductions in pup weight, litter size, viability and weaning indices; delay in age to attain preputial separation and vaginal
opening.
Reproductive NOAEL: 17.9/21.7 mg/kg/day (M/F)
Reproductive LOAEL: 51.0/60.1 mg/kg/day (M/F) based on reductions in litter weights and individual pup weights on day of
delivery.
870.4100
Chronic toxicity dogs
NOAEL: 20/21 mg/kg/day (M/F)
LOAEL: 55/61 mg/kg/day (M/F) based on initial BW loss and
overall reduction in BW gain.
870.4100/870.4200
Chronic
rats
870.4300
Carcinogenicity mice
NOAEL: 20.3/75.9 mg/kg/day (M/F)
LOAEL: 65.6/214.6 mg/kg/day (M/F) based on decreased BW
and BW gain and amyloidosis in numerous organs (M) and
decreased BW and BW gain (F). Not oncogenic under conditions of study.
870.5100
Reverse gene mutation assay
Salmonella typhimurium/E. coli - Not mutagenic under the conditions of the study.
870.5300
Mammalian cells in culture
Forward gene mutation assay CHO cells
Not mutagenic under the conditions of the study.
870.5375
In vitro mammalian chromosomal
aberrations - CHO cells
Acetamiprid is a clastogen under the conditions of the study.
870.5385
In vivo mammalian chromosome aberrations - rat bone marrow
Acetamiprid did not induce a significant increase in chromosome aberrations in bone marrow cells when compared to
the vehicle control group.
870.5395
In vivo mammalian cytogenetics micronucleus assay in mice
Acetamiprid is not a clastogen in the mouse bone marrow
micronucleus test.
870.5550
UDS
assay
in
primary
rat
hepatocytes/ mammalian cell culture
Acetamiprid tested negatively
hepatocytes in vivo.
870.6200
Acute neurotoxicity - rat
NOAEL: 10 mg/kg
LOAEL: 30 mg/kg based on reduction in locomotor activity.
870.6200
Subchronic neurotoxicity - rat
NOAEL: 14.8/16.3 mg/kg/day (M/F)
LOAEL: 59.7/67.6 mg/kg/day (M/F) based on reductions in BW,
BW gain, food consumption and food efficiency.
N/A
28–day feeding - dog
NOAEL: 16.7/19.1 mg/kg/day (M/F)
LOAEL: 28.0/35.8 mg/kg/day based on reduced BW gain.
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-
NOAEL: 7.1/8.8 mg/kg/day (M/F)
LOAEL: 17.5/22.6 mg/kg/day (M/F) based on decreases in
mean BW and BW gain (F) and hepatocellular vacuolation
(M)
Evidence of treatment-related increase in mammary tumors.
There was an absence of a dose - response and a lack of
statistically significant increase in the mammary adenocarcinoma incidence by pair with comparison of the mid- and the
high-dose groups with the controls. Although the incidence
exceeded the historical control data from the same laboratory, it was within the range of values from the supplier.
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for
UDS
in
mammalian
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TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.7485(SS)
Metabolism - mouse, rat, rabbit Special Study (SS)
Male mice, rats or rabbits were administered single doses of
acetamiprid by gavage, intraperitoneal injection (i.p.) or intravenous injection (i.v.) up to 60 mg/kg. The animals were assessed for a variety of neurobehavioral parameters. In vitro
experiments were also done using isolated ileum sections
from guinea pigs to assess contractile responses in the absence and presence of agonists (acetylcholine, histamine
diphosphate, barium chloride and nicotine tartrate).
Acetamiprid was also assessed via i.v. in rabbits for effects
on respiratory rate, heart rate and blood pressure; via gavage
in mice for effects on gastrointestinal motility; and via i.p. in
rats for effects on water and electrolyte balance in urine, and
blood coagulation, hemolytic potential and plasma cholinesterase activity. Based on a number of neuromuscular, behavioral and physiological effects of acetamiprid in male
mice, under the conditions of this study, a overall NOAEL of
10 mg/kg (threshold) and LOAEL of 20 mg/kg could be estimated for a single dose by various exposure routes.
870.7485
Metabolism and pharmaco-kinetics rat
Extensively and rapidly metabolized. Metabolites 79–86% of administered dose. Profiles similar for males and females for
both oral and intravenous dosing. Three to seven percent of
dose recovered in urine and feces as unchanged test article.
Urinary and fecal metabolites from 15–day repeat dose experiment only showed minor differences from single-dose
test. Initial Phase I biotransformation: demethylation of parent. 6-chloronicotinic acid most prevalent metabolite. Phase II
metabolism shown by increase in glycine conjugate.
870.7600
Dermal absorption
The majority of the dose was washed off with the percent increasing with dose. Skin residue was the next largest portion
of the dose with the percent decreasing with dose. In neither
case was there evidence of an exposure related pattern. Absorption was small and increased with duration of exposure.
Since there are no data to demonstrate that the residues remaining on the skin do not enter the animal, then as a conservative estimate of dermal absorption, residues remaining
on the skin will be added to the highest dermal absorption
value. The potential total absorption at 24 hours could be approximately 30%.
B. Toxicological Endpoints
The dose at which no adverse effects
are observed (the NOAEL) from the
toxicology study identified as
appropriate for use in risk assessment is
used to estimate the toxicological level
of concern (LOC). However, the lowest
dose at which adverse effects of concern
are identified (the LOAEL) is sometimes
used for risk assessment if no NOAEL
was achieved in the toxicology study
selected. An uncertainty factor (UF) is
applied to reflect uncertainties inherent
in the extrapolation from laboratory
animal data to humans and in the
variations in sensitivity among members
of the human population as well as
other unknowns. An UF of 100 is
routinely used, 10X to account for
interspecies differences and 10X for
intraspecies differences.
Three other types of safety or
uncertainty factors may be used:
‘‘Traditional uncertainty factors;’’ the ‘‘
special FQPA safety factor;’’ and the
‘‘default FQPA safety factor.’’ By the
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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
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interspecies and intraspecies differences
and any traditional uncertainty factors
deemed appropriate (RfD = NOAEL/UF).
Where a special FQPA safety factor or
the default FQPA safety factor is used,
this additional factor is applied to the
RfD by dividing the RfD by such
additional factor. The acute or chronic
Population Adjusted Dose (aPAD or
cPAD) is a modification of the RfD to
accommodate this type of safety factor.
For non-dietary risk assessments
(other than cancer) the UF is used to
determine the LOC. For example, when
100 is the appropriate UF (10X to
account for interspecies differences and
10X for intraspecies differences) the
LOC is 100. To estimate risk, a ratio of
the NOAEL to exposures (margin of
exposure (MOE) = NOAEL/exposure) is
calculated and compared to the LOC.
The linear default risk methodology
(Q*) is the primary method currently
used by the Agency to quantify
carcinogenic risk. The Q* approach
assumes that any amount of exposure
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will lead to some degree of cancer risk.
A Q* is calculated and used to estimate
risk which represents a probability of
occurrence of additional cancer cases
(e.g., risk). An example of how such a
probability risk is expressed would be to
describe the risk as one in one hundred
thousand (1 X 10-5), one in a million (1
X 10-6), or one in ten million (1 X 10-7).
Under certain specific circumstances,
MOE calculations will be used for the
carcinogenic risk assessment. In this
non-linear approach, a ‘‘point of
departure’’ is identified below which
carcinogenic effects are not expected.
The point of departure is typically a
NOAEL based on an endpoint related to
cancer effects though it may be a
19287
different value derived from the dose
response curve. To estimate risk, a ratio
of the point of departure to exposure
(MOEcancer = point of departure/
exposures) is calculated.
A summary of the toxicological
endpoints for acetamiprid used for
human risk assessment is shown in
Table 2 of this unit:
TABLE 2.—SUMMARY OF TOXICOLOGICAL DOSE AND ENDPOINTS FOR ACETAMIPRID FOR USE IN HUMAN RISK
ASSESSMENT.
FQPA SF1 and Endpoint for Risk
Assessment
Dose Used in Risk Assessment, UF
Exposure/Scenario
Study and Toxicological Effects
Acute dietary
General population including infants and children
NOAEL = 10 mg/kg
UF = 100
Acute RfD = 0.10 mg/kg/day
FQPA SF = 1
aPAD = 0.10 mg/kg/day
Acute mammalian neurotoxicity
study in the rat
LOAEL = 30 mg/kg based on reduction in locomotor activity in
males.
Chronic dietary
All populations
NOAEL= 7.1 mg/kg/day
UF = 100
Chronic RfD = 0.071 mg/kg/day
FQPA SF = 1
cPAD = 0.071 mg/kg/day
Chronic/oncogenicity study in the
rat
LOAEL = 17.5 mg/kg/day based on
reduced body weight and body
weight
gain
(females)
and
hepatocellular
vacuolation
(males).
Short- and Intermediate-Term
Incidental oral (1 to 30 days
and 1 month to 6 months)
(Residential)
NOAEL = 15 mg/kg/day
LOC for MOE =
100 (Residential)
Co-critical studies: subchronic oral
(rat); subchronic neurotoxicity
(rat) developmental toxicity (rat);
LOAEL = 50 mg/kg/day based on
reductions in body weight, body
weight gain and food consumption.
Short- and Intermediate-Term
Dermal (1 to 30 days; and 1
month to 6 months)
(Residential)
Oral study NOAEL= 17.9 mg/
kg/day
(dermal absorption rate = 30%)
LOC for MOE =
100 (Occupational)
100 (Residential)
2-generation reproduction study
(rat)
LOAEL = 51.0 mg/kg/day based on
reductions in pup weights in both
generations, reductions in litter
size and viability and weaning indices among F2 offspring, significant delays in age to attain vaginal opening and preputial separation.
Long-Term Dermal (6 months
to lifetime)
(Residential)
Oral study NOAEL= 7.1 mg/kg/
day
(dermal absorption rate = 30%)
LOC for MOE =
100 (Occupational)
100 (Residential)
Chronic/oncogenicity study in the
rat
LOAEL = 17.5 mg/kg/day based on
reduced body weight and body
weight
gain
(females)
and
hepatocellular
vacuolation
(males).
Short- and Intermediate-Term
Inhalation (1 to 30 days and 1
month to 6 months)
(Residential)
Oral study NOAEL= 17.9 mg/
kg/day
(inhalation absorption rate =
100%)
LOC for MOE =
100 (Occupational)
100 (Residential)
2-generation reproduction study
(rat)
LOAEL = 51.0 mg/kg/day based on
reductions in pup weights in both
generations, reductions in litter
size and viability and weaning indices among F2 offspring, significant delays in age to attain vaginal opening and preputial separation.
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TABLE 2.—SUMMARY OF TOXICOLOGICAL DOSE AND ENDPOINTS FOR ACETAMIPRID FOR USE IN HUMAN RISK
ASSESSMENT.—Continued
Exposure/Scenario
Long-Term Inhalation (6
months to lifetime)
(Residential)
FQPA SF1 and Endpoint for Risk
Assessment
Dose Used in Risk Assessment, UF
Oral study NOAEL = 7.1 mg/
kg/day
(inhalation absorption rate =
100%)
LOC for MOE =
100 (Occupational)
100 (Residential)
Cancer (oral, dermal, inhalation)
Study and Toxicological Effects
Chronic/oncogenicity study in the
rat
LOAEL = 17.5 mg/kg/day based on
reduced body weight and body
weight
gain
(females)
and
hepatocellular
vacuolation
(males).
Not likely to be carcinogenic.
1
The reference to the FQPA Safety Factor refers to any additional safety factor that is retained due to concerns unique to the FQPA. The
PAD (Population-adjusted Dose) incorporates the FQPA Safety Factor into the dose for use in risk assessment: PAD = RfD/FQPA SF.
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. Tolerances have been
established (40 CFR 180.578) for the
residues of acetamiprid, in or on a
variety of raw agricultural commodities.
Risk assessments were conducted by
EPA to assess dietary exposures from
acetamiprid in food as follows:
i. Acute exposure. Acute dietary risk
assessments are performed for a fooduse pesticide, if a toxicological study
has indicated the possibility of an effect
of concern occurring as a result of a 1–
day or single exposure.
In conducting the acute dietary risk
assessment EPA used the Dietary
Exposure Evaluation Model software
with the Food Commodity Intake
Database (DEEM-FCIDTM version 1.3),
which incorporates food consumption
data as reported by respondents in the
USDA 1994–1996 and 1998 Nationwide
Continuing Surveys of Food Intake by
Individuals (CSFII), and accumulated
exposure to the chemical for each
commodity. The assumptions made for
the acute exposure assessments are
discussed in Unit III.C.1.ii.
ii. Chronic exposure. In conducting
the chronic dietary risk assessment EPA
used the DEEM-FCIDTM, which
incorporates food consumption data as
reported by respondents in the USDA
1994–1996 and 1998 CSFII, and
accumulated exposure to the chemical
for each commodity. The following
assumptions were made for the chronic
exposure assessments:
For both the acute and chronic
analyses, tolerance-level residues were
assumed for all food commodities with
current and proposed acetamiprid
tolerances, and it was assumed that all
of the crops included in the analysis
were treated (i.e., 100% crop treated).
These assumptions result in highly
conservative estimates of dietary
exposure and risk. In calculating dietary
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risk estimates, the Agency has compared
the acute and chronic populationadjusted doses (aPAD, cPAD) to the
estimated dietary exposures from the
models. Typically, the Agency has
concerns regarding dietary risk when
the exposure estimates exceed 100% of
the aPAD and/or cPAD. Even with the
conservative assumptions noted above,
risk estimates associated with dietary
exposure to acetamiprid are below the
Agency’s LOC.
iii. Cancer. Acetamiprid has been
classified as not likely to be
carcinogenic to humans; therefore, a
dietary assessment for cancer risk was
not conducted. This classification is
based on the absence of a dose-response
and a lack of a statistically significant
increase in the mammary
adenocarcinoma incidence by pair-wise
comparison of the mid- and high-dose
groups with the controls. Although the
incidence exceeded the historical
control data from the same lab, it was
within the range of values from the
supplier.
2. Dietary exposure from drinking
water. The Agency lacks sufficient
monitoring exposure data to complete a
comprehensive dietary exposure
analysis and risk assessment for
acetamiprid 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
acetamiprid.
Tier 1 simulated estimated drinking
water concentrations (EDWCs) for
acetamiprid in surface water using the
FQPA Index Resevoir Screening Test
(FIRST) to calculate surface water
concentrations and screening
concentration in ground water (SCIGROW) to calculate ground water
concentrations.
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For the surface water assessment, the
application rate for citrus was used,
which represents the highest label rate
for a single application of any crop (0.55
lb a.i./A/season). However, it is
important to note that due to limitations
imposed by the use of two applications
at the highest single application rate
(0.25 lb a.i./A), the modeled application
rate was equal to only 0.50 lb a.i./A.
The proposed applications of
acetamiprid on tuberous and corm
vegetables would result in lower EDWCs
than citrus, and thus has little effect on
the drinking water assessment for this
chemical. By using the application rate
for citrus crops, the surface and ground
water estimated concentrations are
conservative estimates for the proposed
new use scenarios (tuberous and corm
vegetables) because of the higher
application rate.
The primary use of these models by
the Agency at this stage is to provide a
screen for sorting out pesticides for
which it is unlikely that drinking water
concentrations would exceed human
health levels of concern.
Since the models used are considered
to be screening tools in the risk
assessment process, the Agency does
not use estimated environmental
concentrations (EECs), which are the
model estimates of a pesticide’s
concentration in water. EECs derived
from these models are used to quantify
drinking water exposure and risk as a
%RfD or %PAD. Instead drinking water
levels of comparison (DWLOCs) are
calculated and used as a point of
comparison against the model estimates
of a pesticide’s concentration in water.
DWLOCs are theoretical upper limits on
a pesticide’s concentration in drinking
water in light of total aggregate exposure
to a pesticide in food, and from
residential uses. Since DWLOCs address
total aggregate exposure to acetamiprid
they are further discussed in the
aggregate risk sections.
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Based on the FIRST and SCI-GROW
models, the EECs of acetamiprid for
acute exposures are estimated to be 17
parts per billion (ppb) for surface water
and 0.0008 ppb for ground water. The
EECs for chronic exposures are
estimated to be 4 ppb for surface water
and 0.0008 ppb for ground water.
3. From non-dietary exposure. The
term ‘‘residential exposure’’ is used in
this document to refer to nonoccupational, non-dietary exposure
(e.g., for lawn and garden pest control,
indoor pest control, termiticides, and
flea and tick control on pets).
Acetamiprid is currently registered for
use on the following residential nondietary sites: Ornamentals and flowers.
The risk assessment was conducted
using the following residential exposure
assumptions:
Acetamiprid is currently registered for
use on the following residential nondietary sites: Ornamentals and flowers.
No chemical specific data were
available to estimate exposure and risk
for homeowners applying acetamiprid
to ornamentals and flowers. The risk
assessment was conducted using the
following conservative residential
exposure assumptions: Little use of any
protective equipment by residential
applicators, the use of agricultural
transfer coefficients which incorporate
larger acreage and greater foliar contact
for dermal exposure, and
postapplication exposure to the
maximum levels of residues on the day
of application. Using such assumptions
for residential applicators, total MOEs
for short- and intermediate-term
residential dermal and inhalation
exposures range from 1.2 X 105 to 6 X
105. For post-application activities,
short- and intermediate-term MOEs
range from 1.8 X 104 to 1.8 X 105 for
adults and from 2.3 X 104 to 2.2 X 105
for youth ages 10–12 years. The
residential uses for acetamiprid are not
expected to result in long-term
exposures.
4. Cumulative effects from substances
with a common mechanism of toxicity.
Section 408(b)(2)(D)(v) of FFDCA
requires that, when considering whether
to establish, modify, or revoke a
tolerance, the Agency consider
‘‘available information’’ concerning the
cumulative effects of a particular
pesticide’s residues and ‘‘other
substances that have a common
mechanism of toxicity.’’
EPA does not have, at this time,
available data to determine whether
acetamiprid has a common mechanism
of toxicity with other substances. Unlike
other pesticides for which EPA has
followed a cumulative risk approach
based on a common mechanism of
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toxicity, EPA has not made a common
mechanism of toxicity finding as to
acetamiprid and any other substances
and acetamiprid 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 acetamiprid 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 web site at http:/
/www.epa.gov/pesticides/cumulative/.
D. Safety Factor for Infants and
Children
1. In general. Section 408 of FFDCA
provides that EPA shall apply an
additional tenfold margin of safety for
infants and children in the case of
threshold effects to account for prenatal
and postnatal toxicity and the
completeness of the data base on
toxicity and exposure unless EPA
determines based on reliable data that a
different margin of safety will be safe for
infants and children. Margins of safety
are incorporated into EPA risk
assessments either directly through use
of a MOE analysis or through using
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 safety factor value
based on the use of traditional
uncertainty factors and/or special FQPA
safety factors, as appropriate.
2. Prenatal and postnatal sensitivity.
In the developmental toxicity studies in
rats and rabbits, the Agency determined
that neither quantitative nor qualitative
evidence of increased susceptibility of
fetuses to in utero exposure to
acetamiprid were observed. However, in
the multigeneration reproduction study,
qualitative evidence of increased
susceptibility of rat pups is observed.
Considering the overall toxicity profile
and the doses and endpoints selected
for risk assessment for acetamiprid, the
Agency characterized the degree of
concern for the effects observed in this
study as low, noting that:
i. There is a clear NOAEL for the
offspring, and;
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19289
ii. These effects occurred in the
presence of parental toxicity and only at
the highest dose tested. No residual
uncertainties were identified.
The NOAEL for offspring effects is
used for short- and intermediate-term
dermal and inhalation exposure
scenarios. All other toxicology
endpoints established for acetamiprid
are based on a lower NOAEL than this,
and are thus protective of offspring
effects.
3. Conclusion. The Agency concluded
that there is concern for neurotoxicity
resulting from exposure to acetamiprid
because:
i. Clinical signs of neurotoxicity were
observed in the acute neurotoxicity
study on the day of dosing, and;
ii. Studies in literature with
structurally similar chemicals from the
same chemical class (neonicotinoids)
suggest that nicotine, when
administered to humans and/or animals
in utero causes developmental toxicity,
including functional deficits.
The Agency concluded that the
toxicology database for acetamiprid is
not complete for FQPA assessment,
since a developmental neurotoxicity
(DNT) study in rats is currently under
review and has not yet been finalized
and is part of a comprehensive
evaluation of many DNT studies of
various pesticides, some of which have
not yet been submitted. The preliminary
review of the study indicates the results
are not likely to have a significant
impact on risks for the currently
proposed use, or on existing uses of
acetamiprid. Based on weight of the
evidence, an uncertainty factor UFDB is
not needed (1X) since developmental
neurotoxicity data received and
reviewed for other compounds in this
chemical class indicate that the results
of the required DNT will not likely
impact the regulatory doses selected for
the proposed uses of acetamiprid.
E. Aggregate Risks and Determination of
Safety
To estimate total aggregate exposure
to a pesticide from food, drinking water,
and residential uses, the Agency
calculates DWLOCs which are used as a
point of comparison against EECs.
DWLOC values are not regulatory
standards for drinking water. DWLOCs
are theoretical upper limits on a
pesticide’s concentration in drinking
water in light of total aggregate exposure
to a pesticide in food and residential
uses. In calculating a DWLOC, the
Agency determines how much of the
acceptable exposure (i.e., the PAD) is
available for exposure through drinking
water (e.g., allowable chronic water
exposure (mg/kg/day) = cPAD - (average
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food + residential exposure)). This
allowable exposure through drinking
water is used to calculate a DWLOC.
A DWLOC will vary depending on the
toxic endpoint, drinking water
consumption, and body weights. Default
body weights and consumption values
as used by the EPA’s Office of Water are
used to calculate DWLOCs: 2 liter (L)/
70 kg (adult male), 2L/60 kg (adult
female), and 1L/10 kg (child). Default
body weights and drinking water
consumption values vary on an
individual basis. This variation will be
taken into account in more refined
screening-level and quantitative
drinking water exposure assessments.
Different populations will have different
DWLOCs. Generally, a DWLOC is
calculated for each type of risk
drinking water as a part of the aggregate
risk assessment process.
1. Acute risk. Using the exposure
assumptions discussed in this unit for
acute exposure, the acute dietary
exposure from food to acetamiprid will
occupy 18 % of the aPAD for the U.S.
population, 12 % of the aPAD for
females 13 years and older, 44 % of the
aPAD for all infants less than one year
old, and 61 % of the aPAD for 1–2 years
old children. In addition, there is
potential for acute dietary exposure to
acetamiprid in drinking water. After
calculating DWLOCs and comparing
them to the EECs for surface and ground
water, EPA does not expect the
aggregate exposure to exceed 100% of
the aPAD, as shown in Table 3 of this
unit:
assessment used: Acute, short-term,
intermediate-term, chronic, and cancer.
When EECs for surface water and
ground water are less than the
calculated DWLOCs, EPA concludes
with reasonable certainty that exposures
to the pesticide in drinking water (when
considered along with other sources of
exposure for which EPA has reliable
data) would not result in unacceptable
levels of aggregate human health risk at
this time. Because EPA considers the
aggregate risk resulting from multiple
exposure pathways associated with a
pesticide’s uses, levels of comparison in
drinking water may vary as those uses
change. If new uses are added in the
future, EPA will reassess the potential
impacts of residues of the pesticide in
TABLE 3.—AGGREGATE RISK ASSESSMENT FOR ACUTE EXPOSURE TO ACETAMIPRID
aPAD (mg/
kg)
Population/Subgroup
Surface
Water EEC/
(ppb)
% aPAD/
(Food)
Ground
Water EEC/
(ppb)
Acute
DWLOC/
(ppb)
US Population
0.10
18
17
0.0008
2,900
All Infants < 1 year
0.10
44
17
0.0008
540
Children 1–2 years
0.10
61
17
0.0008
370
Children 3–5 years
0.10
42
17
0.0008
560
Children 6–12 years
0.10
22
17
0.0008
790
Youth 13–19 years
0.10
14
17
0.0008
2,600
Adults 20–49 years
0.10
11
17
0.0008
3,100
Adults 50+ years
0.10
10
17
0.0008
3,100
Females 13–49 years
0.10
12
17
0.0008
2,600
2. Chronic risk. Using the exposure
assumptions described in this unit for
chronic exposure, EPA has concluded
that exposure to acetamiprid from food
will utilize 8% of the cPAD for the U.S.
population, 16% of the cPAD for all
infants <1 year old, and 31% of the
them to the EECs for surface water and
ground water, EPA does not expect the
aggregate exposure to exceed 100% of
the cPAD, as shown in Table 4 of this
unit:
cPAD for children 1–2 year old. Based
the use pattern, chronic residential
exposure to residues of acetamiprid is
not expected. In addition, there is
potential for chronic dietary exposure to
acetamiprid in drinking water. After
calculating DWLOCs and comparing
TABLE 4.—AGGREGATE RISK ASSESSMENT FOR CHRONIC (NON-CANCER) EXPOSURE TO ACETAMIPRID
cPAD/mg/
kg/day
Population/Subgroup
Surface
Water EEC/
(ppb)
%/cPAD/
(Food)
Ground/
Water EEC/
(ppb)
Chronic/
DWLOC
(ppb)
US Population
0.071
8
4
0.0008
2,300
All Infants < 1 year
0.071
16
4
0.0008
600
Children 1–2 years
0.071
31
4
0.0008
490
Children 3–5 years
0.071
21
4
0.0008
560
Children 6–12 years
0.071
11
4
0.0008
630
Youth 13–19 years
0.071
6
4
0.0008
2,000
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19291
TABLE 4.—AGGREGATE RISK ASSESSMENT FOR CHRONIC (NON-CANCER) EXPOSURE TO ACETAMIPRID—Continued
cPAD/mg/
kg/day
Population/Subgroup
Surface
Water EEC/
(ppb)
%/cPAD/
(Food)
Ground/
Water EEC/
(ppb)
Chronic/
DWLOC
(ppb)
Adults 20–49 years
0.071
5
4
0.0008
2,400
Adults 50+ years
0.071
5
4
0.0008
2,000
Females 13–49 years
0.071
5
4
0.0008
2,400
3. Short and intermediate-term risk.
Short and intermediate-term aggregate
exposure takes into account residential
exposure plus chronic exposure to food
and water (considered to be a
background exposure level).
Acetamiprid is currently registered for
use that could result in short-term
residential exposure and the Agency has
determined that it is appropriate to
addition, short-term DWLOCs were
calculated and compared to the EECs for
chronic exposure of acetamiprid in
ground water and surface water. After
calculating DWLOCs and comparing
them to- the EECs for surface water and
ground water, EPA does not expect
short-term aggregate exposure to exceed
the Agency’s level of concern, as shown
in Table 5 of this unit:
aggregate chronic food and water and
short-term exposures for acetamiprid.
Using the exposure assumptions
described in this unit for short and
intermediate-term exposures, EPA has
concluded that food and residential
exposures aggregated result in aggregate
MOEs of 810–820 for adults male and
female. These aggregate MOEs do not
exceed the Agency’s LOC for aggregate
exposure to food and residential uses. In
TABLE 5.—AGGREGATE RISK ASSESSMENT FOR SHORT-TERM AND INTERMEDIATE TERM EXPOSURE TO ACETAMIPRID
Aggregate/
MOE/(Food
+ Residential)
Population/Subgroup
Aggregate
Level of
Concern/
(LOC)
Surface
Water EEC/
(ppb)
Ground/
Water EEC/
(ppb)
Short-Term
DWLOC
(ppb)
Adult male
820
100
4
0.0008
5,500
Adult female
810
100
4
0.0008
4,700
Adult 50+
810
100
4
0.0008
4,700
4. Aggregate cancer risk for U.S.
population. Acetamiprid is not likely to
be carcinogenic to humans.
5. 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 acetamiprid
residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate analytical methods are
available for enforcement of tolerances
for plant commodities (GC/ECD and
HPLC/UV) and animal comodities
(HPLC/UV). However, the registrant also
proposed that an HPLC/MS method be
used for enforcement of plant
commodities tolerances. The proposed
HPLC/MS/MS enforcement method for
plant commodities should undergo
independent laboratory validation (ILV)
as a condition of registration, and
possibly Agency method validation.
B. International Residue Limits
There are no CODEX, or Canadian
Maximum Residue Limits for
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acetamiprid on tuberous and corm
vegetables.
C. Conditions
A Developmental Neurotoxicity study
(DNT) study is currently under review.
The proposed HPLC/MS/MS
enforcement method for plant
commodities should undergo
independent laboratory validation (ILV)
as a condition of registration, and
possibly Agency method validation.
D. Response to Comments
One commenter expressed a general
objection to the approval of pesticide
tolerances and also criticized the use of
animal testing to determine the safety of
pesticides. This commenter’s concerns
have been addressed in previous
tolerance documents. See the Federal
Register of October 29, 2004, (69 FR
63083) (FRL–7681–9). The other
comment was from the WTO (World
Trade Organization) Enquiry Point in
China and asked for extra time to
translate the document and prepare
comments. This comment was received
after the close of the comment period on
Sepember 7, 2004 via e-mail. On
February 28, 2005 EPA contacted the
commenter and requested that if it had
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any comments to submit them by March
15, 2005. No further response was
received by EPA.
V. Conclusion
Therefore, the tolerance is established
for residues of acetamiprid, in or on
tuberous and corm vegetables at 0.01
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
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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–2005–0029 in the subject line on
the first page of your submission. All
requests must be in writing, and must be
mailed or delivered to the Hearing Clerk
on or before June 13, 2005.
1. Filing the request. Your objection
must specify the specific provisions in
the regulation that you object to, and the
grounds for the objections (40 CFR
178.25). If a hearing is requested, the
objections must include a statement of
the factual issues(s) on which a hearing
is requested, the requestor’s contentions
on such issues, and a summary of any
evidence relied upon by the objector (40
CFR 178.27). Information submitted in
connection with an objection or hearing
request may be claimed confidential by
marking any part or all of that
information as CBI. Information so
marked will not be disclosed except in
accordance with procedures set forth in
40 CFR part 2. A copy of the
information that does not contain CBI
must be submitted for inclusion in the
public record. Information not marked
confidential may be disclosed publicly
by EPA without prior notice.
Mail your written request to: Office of
the Hearing Clerk (1900L),
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001. You may also deliver
your request to the Office of the Hearing
Clerk in Suite 350, 1099 14th St., NW.,
Washington, DC 20005. The Office of
the Hearing Clerk is open from 8 a.m.
to 4 p.m., Monday through Friday,
excluding legal holidays. The telephone
number for the Office of the Hearing
Clerk is (202) 564–6255.
2. Copies for the Docket. In addition
to filing an objection or hearing request
with the Hearing Clerk as described in
Unit VI.A., you should also send a copy
of your request to the PIRIB for its
inclusion in the official record that is
described in ADDRESSES. Mail your
copies, identified by docket ID number
OPP–2005–0029, 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
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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.
B. When Will the Agency Grant a
Request for a Hearing?
A request for a hearing will be granted
if the Administrator determines that the
material submitted shows the following:
There is a genuine and substantial issue
of fact; there is a reasonable possibility
that available evidence identified by the
requestor would, if established resolve
one or more of such issues in favor of
the requestor, taking into account
uncontested claims or facts to the
contrary; and resolution of the factual
issues(s) in the manner sought by the
requestor would be adequate to justify
the action requested (40 CFR 178.32).
VII. Statutory and Executive Order
Reviews
This final rule establishes a tolerance
under section 408(d) of FFDCA in
response to a petition submitted to the
Agency. The Office of Management and
Budget (OMB) has exempted these types
of actions from review under Executive
Order 12866, entitled Regulatory
Planning and Review (58 FR 51735,
October 4, 1993). Because this rule has
been exempted from review under
Executive Order 12866 due to its lack of
significance, this rule is not subject to
Executive Order 13211, Actions
Concerning Regulations That
Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May
22, 2001). This final rule does not
contain any information collections
subject to OMB approval under the
Paperwork Reduction Act (PRA), 44
U.S.C. 3501 et seq., or impose any
enforceable duty or contain any
unfunded mandate as described under
Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Public
Law 104–4). Nor does it require any
special considerations under Executive
Order 12898, entitled Federal Actions to
Address Environmental Justice in
Minority Populations and Low-Income
Populations (59 FR 7629, February 16,
1994); or OMB review or any Agency
action under Executive Order 13045,
entitled Protection of Children from
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Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
This action does not involve any
technical standards that would require
Agency consideration of voluntary
consensus standards pursuant to section
12(d) of the National Technology
Transfer and Advancement Act of 1995
(NTTAA), Public Law 104–113, section
12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are
established on the basis of a petition
under section 408(d) of FFDCA, such as
the tolerance in this final rule, do not
require the issuance of a proposed rule,
the requirements of the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. In addition, the
Agency has determined that this action
will not have a substantial direct effect
on States, on the relationship between
the national government and the States,
or on the distribution of power and
responsibilities among the various
levels of government, as specified in
Executive Order 13132, entitled
Federalism (64 FR 43255, August 10,
1999). Executive Order 13132 requires
EPA to develop an accountable process
to ensure ‘‘meaningful and timely input
by State and local officials in the
development of regulatory policies that
have federalism implications.’’ ‘‘Policies
that have federalism implications’’ is
defined in the Executive order to
include regulations that have
‘‘substantial direct effects on the States,
on the relationship between the national
government and the States, or on the
distribution of power and
responsibilities among the various
levels of government.’’ This final rule
directly regulates growers, food
processors, food handlers and food
retailers, not States. This action does not
alter the relationships or distribution of
power and responsibilities established
by Congress in the preemption
provisions of section 408(n)(4) of
FFDCA. For these same reasons, the
Agency has determined that this rule
does not have any ‘‘tribal implications’’
as described in Executive Order 13175,
entitled Consultation and Coordination
with Indian Tribal Governments (65 FR
67249, November 6, 2000). Executive
Order 13175, requires EPA to develop
an accountable process to ensure
‘‘meaningful and timely input by tribal
officials in the development of
regulatory policies that have tribal
implications.’’ ‘‘Policies that have tribal
implications’’ is defined in the
Executive Order to include regulations
that have ‘‘substantial direct effects on
one or more Indian tribes, on the
relationship between the Federal
Government and the Indian tribes, or on
E:\FR\FM\13APR1.SGM
13APR1
Federal Register / Vol. 70, No. 70 / Wednesday, April 13, 2005 / Rules and Regulations
the distribution of power and
responsibilities between the Federal
Government and Indian tribes.’’ This
rule will not have substantial direct
effects on tribal governments, on the
relationship between the Federal
Government and Indian tribes, or on the
distribution of power and
responsibilities between the Federal
Government and Indian tribes, as
specified in Executive Order 13175.
Thus, Executive Order 13175 does not
apply to this rule.
VIII. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement
Fairness Act of 1996, generally provides
that before a rule may take effect, the
agency promulgating the rule must
submit a rule report, which includes a
copy of the rule, to each House of the
Congress and to the Comptroller General
of the United States. EPA will submit a
report containing this rule and other
required information to the U.S. Senate,
the U.S. House of Representatives, and
the Comptroller General of the United
States prior to publication of this final
rule in the Federal Register. This final
rule is not a ‘‘major rule’’ as defined by
5 U.S.C. 804(2).
*
*
*
*
*
[FR Doc. 05–7225 Filed 4–12–05; 8:45 am]
BILLING CODE 6560–50–S
FEDERAL COMMUNICATIONS
COMMISSION
47 CFR Parts 1, 22, and 90
[WT Docket Nos. 03–103, 05–42; FCC 04–
287]
Air-Ground Telecommunications
Services
Federal Communications
Commission.
ACTION: Final rule.
AGENCY:
SUMMARY: In this document, the Federal
Communications Commission
(‘‘Commission’’) revises rules governing
the four megahertz of dedicated
spectrum in the 800 MHz commercial
Air-Ground Radiotelephone Service
band. The Commission adopts a flexible
regulatory approach to determine the
configuration of the band; adopts rules
that enable interested parties to bid on
spectrum licenses according to the band
configuration that they believe will best
meet their needs for the provision of airground services; makes available
nationwide air-ground licenses in three
List of Subjects in 40 CFR Part 180
configurations: band plan 1, comprised
of two overlapping, shared, crossEnvironmental protection,
polarized 3 MHz licenses (licenses A
Administrative practice and procedure,
and B, respectively), band plan 2,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping comprised of an exclusive 3 MHz
license and an exclusive 1 MHz license
requirements.
(licenses C and D, respectively), and
band plan 3, comprised of an exclusive
Dated: April 1, 2005.
1 MHz license and an exclusive 3 MHz
Lois Rossi,
license (licenses E and F, respectively),
Director, Registration Division, Office of
with the blocks at opposite ends of the
Pesticide Programs.
band from the second configuration; and
I Therefore, 40 CFR chapter I is
finally, the Commission revises and
amended as follows:
eliminates certain Public Mobile
Services (PMS) rules that are no longer
PART 180—[AMENDED]
warranted as a result of technological
change, increased competition in
I 1. The authority citation for part 180
Commercial Mobile Radio Services
continues to read as follows:
(CMRS), supervening changes to related
Authority: 21 U.S.C. 321(q), 346a and 371.
Commission rules, or a combination of
I 2. Section 180.578 is amended by
these factors.
alphabetically adding the following
DATES: Effective May 13, 2005.
commodity to the table in paragraph
FOR FURTHER INFORMATION CONTACT:
(a)(1) to read as follows:
Richard Arsenault, Chief Counsel,
Mobility Division, Wireless
§ 180.578 Acetamiprid; tolerances for
Telecommunications Bureau, at 202–
residues.
418–0920 or via e-mail at
(a) General. (1) * * *
Richard.Arsenault@fcc.gov.
Commodity
Parts per million
SUPPLEMENTARY INFORMATION: This is a
summary of the Commission’s Report
*
*
*
*
*
and Order portion (Report and Order) of
Tuberous and Corm
the Commission’s Report and Order and
Vegetables ..................
0.01
Notice of Proposed Rulemaking, FCC
*
*
*
*
*
04–287, in WT Docket Nos. 03–103 and
VerDate jul<14>2003
16:30 Apr 12, 2005
Jkt 205001
PO 00000
Frm 00041
Fmt 4700
Sfmt 4700
19293
05–42, adopted December 15, 2004, and
released February 22, 2005.
Contemporaneous with this document,
the Commission publishes a Notice of
Proposed Rulemaking (Notice)
(summarized elsewhere in this
publication). The full text of this
document is available for public
inspection and copying during regular
business hours at the FCC Reference
Information Center, 445 12th St., SW.,
Room CY–A257, Washington, DC 20554.
The complete text may be purchased
from the Commission’s duplicating
contractor: Best Copy & Printing, Inc.,
445 12th Street, SW., Room CY–B402,
Washington, DC 20554, telephone 800–
378–3160, facsimile 202–488–5563, or
via e-mail at fcc@bcpiweb.com. The full
text may also be downloaded at:
https://www.fcc.gov. Alternative formats
are available to persons with disabilities
by contacting Brian Millin at (202) 418–
7426 or TTY (202) 418–7365 or at
Brian.Millin@fcc.gov.
Synopsis of the Report and Order
A. 800 MHz Air-Ground Radiotelephone
Service
1. The Commission initiated this
proceeding, inter alia, to reexamine the
800 MHz Air-Ground Radiotelephone
Service band plan and service rules.
Although the Commission initially
licensed six 800 MHz air-ground
nationwide licensees, only one licensee
(Verizon Airfone) continues to provide
service in the band, and our current
technical rules allow it to provide only
a limited range of narrowband voice and
data services. This circumstance led us
to question in the Notice of Proposed
Rulemaking in this proceeding, 68 FR
44003, July 25, 2003, whether our
existing rules were impeding the
provision of telecommunications
services desired by the public onboard
aircraft. Nearly all parties commenting
on these issues agree that our existing
band plan and rules have hindered the
efficient, competitive provision of airground services desired by the public.
Based on our review of the record in
this proceeding, we find that the public
interest will be served by adopting
flexible rules that will enable interested
parties to bid on licenses in three
possible band configurations. Each of
the three band configurations includes
at least one spectrum block that will
permit the provision of high-speed
telecommunications services to the
public onboard aircraft.
2. In reexamining the current band
plan and service rules, we must address
both competitive issues (i.e., how many
competitors can the spectrum and the
market support) and technical
E:\FR\FM\13APR1.SGM
13APR1
]]>Agencies
[Federal Register Volume 70, Number 70 (Wednesday, April 13, 2005)]
[Rules and Regulations]
[Pages 19283-19293]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-7225]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2005-0029; FRL-7705-7]
Acetamiprid; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a tolerance for residues of
acetamiprid in or on tuberous and corm vegetables. Nippon Soda Company
c/o Nisso America Inc. requested this tolerance under the Federal Food,
Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality
Protection Act of 1996 (FQPA).
DATES: This regulation is effective April 13, 2005. Objections and
requests for hearings must be received on or before June 13, 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-2005-0029. 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: Akiva Abramovitch, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 308-8328; e-mail address:
abramovitch.akiva@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 code 111)
Animal production (NAICS code 112)
Food manufacturing (NAICS code 311)
Pesticide manufacturing (NAICS code 32532)
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be
[[Page 19284]]
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 August 4, 2004 (69 FR 47145) (FRL-7369-
6), 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
3F6575) by Nippon Soda Company c/o Nisso America, 42 Broadway, Suite
2120, New York, NY 10006. The petition requested that 40 CFR 180.578 be
amended by establishing a tolerance for residues of the insecticide
acetamiprid, in or on tuberous and corm vegetables at 0.01 parts per
million (ppm). That notice included a summary of the petition prepared
by Nisso America, Inc.. There were two comments to the Acetamiprid
Notice of Filing and they are addressed in Unit IV.D..
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 residues of acetamiprid on
tuberous and corm vegetables at 0.01 ppm. EPA's assessment of exposures
and risks associated with establishing the tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by acetamiprid 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 days oral NOAEL: 12.4/14.6
toxicity - milligrams/
rodents kilograms (mg/kg)/
day - Male/Female
(M/F)
LOAEL: 50.8/56.0
mg/kg/day (M/F)
based on
decreased Body
Weight (BW), BW
gain and food
consumption.
------------------------------------------------------
870.3100 90 days oral NOAEL: 106.1/129.4
toxicity - mouse mg/kg/day (M/F)
LOAEL: 211.1/249.1
mg/kg/day (M/F)
based on reduced
BW and BW gain,
decreased
glucoseand
cholesterol
levels, reduced
absolute organ
weights.
------------------------------------------------------
870.3150 90-day oral NOAEL: 13/14 mg/kg/
toxicity in day (M/F)
nonrodents LOAEL: 32 mg/kg/
day based on
reduced BW gain
in both sexes.
------------------------------------------------------
870.3200 21-day dermal NOAEL: 1,000 mg/kg/
toxicity - rabbit day - Highest
Dose Tested (HDT)
LOAEL: >1,000 mg/
kg/day
------------------------------------------------------
870.3700 Prenatal Maternal NOAEL: 16
developmental mg/kg/day
toxicity in Maternal LOAEL: 50
rodents mg/kg/day based
on reduced BW and
BW gain and food
consumption,
increased liver
weights.
Developmental
NOAEL: 16 mg/kg/
day
Developmental
LOAEL: 50 mg/kg/
day based on
increased
incidence of
shortening of the
13th rib.
------------------------------------------------------
[[Page 19285]]
870.3700 Prenatal Maternal NOAEL: 15
developmental mg/kg/day
toxicity in Maternal LOAEL:
nonrodents 30mg/kg/day based
on BW loss and
decreased food
consumption.
Developmental
NOAEL: 30 mg/kg/
day (HDT)
Developmental
LOAEL: > 30 mg/kg/
day
------------------------------------------------------
870.3800 Reproduction and Parental systemic
fertility effects NOAEL: 17.9/21.7
mg/kg/day (M/F)
Parental systemic
LOAEL: 51.0/60.1
mg/kg/day (M/F)
based on
decreased BW, BW
gain and food
consumption.
Offspring systemic
NOAEL: 17.9/21.7
mg/kg/day (M/F)
Offspring systemic
LOAEL: 51.0/60.1
mg/kg/day (M/F)
based on
reductions in pup
weight, litter
size, viability
and weaning
indices; delay in
age to attain
preputial
separation and
vaginal opening.
Reproductive
NOAEL: 17.9/21.7
mg/kg/day (M/F)
Reproductive
LOAEL: 51.0/60.1
mg/kg/day (M/F)
based on
reductions in
litter weights
and individual
pup weights on
day of delivery.
------------------------------------------------------
870.4100 Chronic toxicity NOAEL: 20/21 mg/kg/
dogs day (M/F)
LOAEL: 55/61 mg/kg/
day (M/F) based
on initial BW
loss and overall
reduction in BW
gain.
------------------------------------------------------
870.4100/870.4200 Chronic toxicity/ NOAEL: 7.1/8.8 mg/
Carcinogenicity - kg/day (M/F)
rats LOAEL: 17.5/22.6
mg/kg/day (M/F)
based on
decreases in mean
BW and BW gain
(F) and
hepatocellular
vacuolation (M)
Evidence of
treatment-related
increase in
mammary tumors.
There was an
absence of a dose
- response and a
lack of
statistically
significant
increase in the
mammary
adenocarcinoma
incidence by pair
with comparison
of the mid- and
the high-dose
groups with the
controls.
Although the
incidence
exceeded the
historical
control data from
the same
laboratory, it
was within the
range of values
from the
supplier.
------------------------------------------------------
870.4300 Carcinogenicity NOAEL: 20.3/75.9
mice mg/kg/day (M/F)
LOAEL: 65.6/214.6
mg/kg/day (M/F)
based on
decreased BW and
BW gain and
amyloidosis in
numerous organs
(M) and decreased
BW and BW gain
(F). Not
oncogenic under
conditions of
study.
------------------------------------------------------
870.5100 Reverse gene Salmonella
mutation assay typhimurium/E.
coli - Not
mutagenic under
the conditions of
the study.
------------------------------------------------------
870.5300 Mammalian cells in Not mutagenic
culture under the
Forward gene conditions of the
mutation assay - study.
CHO cells.
------------------------------------------------------
870.5375 In vitro mammalian Acetamiprid is a
chromosomal clastogen under
aberrations - CHO the conditions of
cells the study.
------------------------------------------------------
870.5385 In vivo mammalian Acetamiprid did
chromosome not induce a
aberrations - rat significant
bone marrow increase in
chromosome
aberrations in
bone marrow cells
when compared to
the vehicle
control group.
------------------------------------------------------
870.5395 In vivo mammalian Acetamiprid is not
cytogenetics - a clastogen in
micronucleus the mouse bone
assay in mice marrow
micronucleus
test.
------------------------------------------------------
870.5550 UDS assay in Acetamiprid tested
primary rat negatively for
hepatocytes/ UDS in mammalian
mammalian cell hepatocytes in
culture vivo.
------------------------------------------------------
870.6200 Acute NOAEL: 10 mg/kg
neurotoxicity - LOAEL: 30 mg/kg
rat based on
reduction in
locomotor
activity.
------------------------------------------------------
870.6200 Subchronic NOAEL: 14.8/16.3
neurotoxicity - mg/kg/day (M/F)
rat LOAEL: 59.7/67.6
mg/kg/day (M/F)
based on
reductions in BW,
BW gain, food
consumption and
food efficiency.
------------------------------------------------------
N/A 28-day feeding - NOAEL: 16.7/19.1
dog mg/kg/day (M/F)
LOAEL: 28.0/35.8
mg/kg/day based
on reduced BW
gain.
------------------------------------------------------
[[Page 19286]]
870.7485(SS) Metabolism - Male mice, rats or
mouse, rat, rabbits were
rabbit Special administered
Study (SS) single doses of
acetamiprid by
gavage,
intraperitoneal
injection (i.p.)
or intravenous
injection (i.v.)
up to 60 mg/kg.
The animals were
assessed for a
variety of
neurobehavioral
parameters. In
vitro experiments
were also done
using isolated
ileum sections
from guinea pigs
to assess
contractile
responses in the
absence and
presence of
agonists
(acetylcholine,
histamine
diphosphate,
barium chloride
and nicotine
tartrate).
Acetamiprid was
also assessed via
i.v. in rabbits
for effects on
respiratory rate,
heart rate and
blood pressure;
via gavage in
mice for effects
on
gastrointestinal
motility; and via
i.p. in rats for
effects on water
and electrolyte
balance in urine,
and blood
coagulation,
hemolytic
potential and
plasma
cholinesterase
activity. Based
on a number of
neuromuscular,
behavioral and
physiological
effects of
acetamiprid in
male mice, under
the conditions of
this study, a
overall NOAEL of
10 mg/kg
(threshold) and
LOAEL of 20 mg/kg
could be
estimated for a
single dose by
various exposure
routes.
------------------------------------------------------
870.7485 Metabolism and Extensively and
pharmaco-kinetics rapidly
- rat metabolized.
Metabolites 79-
86% of
administered
dose. Profiles
similar for males
and females for
both oral and
intravenous
dosing. Three to
seven percent of
dose recovered in
urine and feces
as unchanged test
article. Urinary
and fecal
metabolites from
15-day repeat
dose experiment
only showed minor
differences from
single-dose test.
Initial Phase I
biotransformation
: demethylation
of parent. 6-
chloronicotinic
acid most
prevalent
metabolite. Phase
II metabolism
shown by increase
in glycine
conjugate.
------------------------------------------------------
870.7600 Dermal absorption The majority of
the dose was
washed off with
the percent
increasing with
dose. Skin
residue was the
next largest
portion of the
dose with the
percent
decreasing with
dose. In neither
case was there
evidence of an
exposure related
pattern.
Absorption was
small and
increased with
duration of
exposure. Since
there are no data
to demonstrate
that the residues
remaining on the
skin do not enter
the animal, then
as a conservative
estimate of
dermal
absorption,
residues
remaining on the
skin will be
added to the
highest dermal
absorption value.
The potential
total absorption
at 24 hours could
be approximately
30%.
------------------------------------------------------------------------
B. Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological level of concern
(LOC). However, the lowest dose at which adverse effects of concern are
identified (the LOAEL) is sometimes used for risk assessment if no
NOAEL was achieved in the toxicology study selected. An uncertainty
factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10X to account for
interspecies differences and 10X for intraspecies differences.
Three other types of safety or uncertainty factors may be used:
``Traditional uncertainty factors;'' the `` special FQPA safety
factor;'' and the ``default FQPA safety factor.'' By the term
``traditional uncertainty factor,'' EPA is referring to those
additional uncertainty factors used prior to FQPA passage to account
for database deficiencies. These traditional uncertainty factors have
been incorporated by the FQPA into the additional safety factor for the
protection of infants and children. The term ``special FQPA safety
factor'' refers to those safety factors that are deemed necessary for
the protection of infants and children primarily as a result of the
FQPA. The ``default FQPA safety factor'' is the additional 10X safety
factor that is mandated by the statute unless it is decided that there
are reliable data to choose a different additional factor (potentially
a traditional uncertainty factor or a special FQPA safety factor).
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by an UF of
100 to account for interspecies and intraspecies differences and any
traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF).
Where a special FQPA safety factor or the default FQPA safety factor is
used, this additional factor is applied to the RfD by dividing the RfD
by such additional factor. The acute or chronic Population Adjusted
Dose (aPAD or cPAD) is a modification of the RfD to accommodate this
type of safety factor.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10X
to account for interspecies differences and 10X for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure
[[Page 19287]]
will lead to some degree of cancer risk. A Q* is calculated and used to
estimate risk which represents a probability of occurrence of
additional cancer cases (e.g., risk). An example of how such a
probability risk is expressed would be to describe the risk as one in
one hundred thousand (1 X 10-\5\), one in a million (1 X
10-\6\), or one in ten million (1 X 10-\7\).
Under certain specific circumstances, MOE calculations will be used for
the carcinogenic risk assessment. In this non-linear approach, a
``point of departure'' is identified below which carcinogenic effects
are not expected. The point of departure is typically a NOAEL based on
an endpoint related to cancer effects though it may be a different
value derived from the dose response curve. To estimate risk, a ratio
of the point of departure to exposure (MOEcancer = point of
departure/exposures) is calculated.
A summary of the toxicological endpoints for acetamiprid used for
human risk assessment is shown in Table 2 of this unit:
Table 2.--Summary of Toxicological Dose and Endpoints for Acetamiprid for Use in Human Risk Assessment.
----------------------------------------------------------------------------------------------------------------
Dose Used in Risk FQPA SF\1\ and Endpoint Study and Toxicological
Exposure/Scenario Assessment, UF for Risk Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary NOAEL = 10 mg/kg FQPA SF = 1 Acute mammalian
General population including infants UF = 100............... aPAD = 0.10 mg/kg/day.. neurotoxicity study in
and children. Acute RfD = 0.10 mg/kg/ the rat
day. LOAEL = 30 mg/kg based
on reduction in
locomotor activity in
males.
----------------------------------------------------------------
Chronic dietary NOAEL= 7.1 mg/kg/day FQPA SF = 1 Chronic/oncogenicity
All populations...................... UF = 100............... cPAD = 0.071 mg/kg/day. study in the rat
Chronic RfD = 0.071 mg/ LOAEL = 17.5 mg/kg/day
kg/day. based on reduced body
weight and body weight
gain (females) and
hepatocellular
vacuolation (males).
----------------------------------------------------------------
Short- and Intermediate-Term NOAEL = 15 mg/kg/day LOC for MOE = Co-critical studies:
Incidental oral (1 to 30 days and 1 100 (Residential)...... subchronic oral (rat);
month to 6 months). subchronic
(Residential)........................ neurotoxicity (rat)
developmental toxicity
(rat);
LOAEL = 50 mg/kg/day
based on reductions in
body weight, body
weight gain and food
consumption.
----------------------------------------------------------------
Short- and Intermediate-Term Oral study NOAEL= 17.9 LOC for MOE = 2-generation
Dermal (1 to 30 days; and 1 month to mg/kg/day 100 (Occupational)..... reproduction study
6 months). (dermal absorption rate 100 (Residential)...... (rat)
(Residential)........................ = 30%). LOAEL = 51.0 mg/kg/day
based on reductions in
pup weights in both
generations,
reductions in litter
size and viability and
weaning indices among
F2 offspring,
significant delays in
age to attain vaginal
opening and preputial
separation.
----------------------------------------------------------------
Long-Term Dermal (6 months to Oral study NOAEL= 7.1 LOC for MOE = Chronic/oncogenicity
lifetime) mg/kg/day 100 (Occupational)..... study in the rat
(Residential)........................ (dermal absorption rate 100 (Residential)...... LOAEL = 17.5 mg/kg/day
= 30%). based on reduced body
weight and body weight
gain (females) and
hepatocellular
vacuolation (males).
----------------------------------------------------------------
Short- and Intermediate-Term Oral study NOAEL= 17.9 LOC for MOE = 2-generation
Inhalation (1 to 30 days and 1 month mg/kg/day 100 (Occupational)..... reproduction study
to 6 months). (inhalation absorption 100 (Residential)...... (rat)
(Residential)........................ rate = 100%). LOAEL = 51.0 mg/kg/day
based on reductions in
pup weights in both
generations,
reductions in litter
size and viability and
weaning indices among
F2 offspring,
significant delays in
age to attain vaginal
opening and preputial
separation.
----------------------------------------------------------------
[[Page 19288]]
Long-Term Inhalation (6 months to Oral study NOAEL = 7.1 LOC for MOE = Chronic/oncogenicity
lifetime) mg/kg/day 100 (Occupational)..... study in the rat
(Residential)........................ (inhalation absorption 100 (Residential)...... LOAEL = 17.5 mg/kg/day
rate = 100%). based on reduced body
weight and body weight
gain (females) and
hepatocellular
vacuolation (males).
----------------------------------------------------------------
Cancer (oral, dermal, inhalation) Not likely to be carcinogenic.
----------------------------------------------------------------------------------------------------------------
\1\ The reference to the FQPA Safety Factor refers to any additional safety factor that is retained due to
concerns unique to the FQPA. The PAD (Population-adjusted Dose) incorporates the FQPA Safety Factor into the
dose for use in risk assessment: PAD = RfD/FQPA SF.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.578) for the residues of acetamiprid, in or on
a variety of raw agricultural commodities. Risk assessments were
conducted by EPA to assess dietary exposures from acetamiprid in food
as follows:
i. Acute exposure. Acute dietary risk assessments are performed for
a food-use pesticide, if a toxicological study has indicated the
possibility of an effect of concern occurring as a result of a 1-day or
single exposure.
In conducting the acute dietary risk assessment EPA used the
Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database (DEEM-FCID\TM\ version 1.3), which incorporates food
consumption data as reported by respondents in the USDA 1994-1996 and
1998 Nationwide Continuing Surveys of Food Intake by Individuals
(CSFII), and accumulated exposure to the chemical for each commodity.
The assumptions made for the acute exposure assessments are discussed
in Unit III.C.1.ii.
ii. Chronic exposure. In conducting the chronic dietary risk
assessment EPA used the DEEM-FCID\TM\, which incorporates food
consumption data as reported by respondents in the USDA 1994-1996 and
1998 CSFII, and accumulated exposure to the chemical for each
commodity. The following assumptions were made for the chronic exposure
assessments:
For both the acute and chronic analyses, tolerance-level residues
were assumed for all food commodities with current and proposed
acetamiprid tolerances, and it was assumed that all of the crops
included in the analysis were treated (i.e., 100% crop treated). These
assumptions result in highly conservative estimates of dietary exposure
and risk. In calculating dietary risk estimates, the Agency has
compared the acute and chronic population-adjusted doses (aPAD, cPAD)
to the estimated dietary exposures from the models. Typically, the
Agency has concerns regarding dietary risk when the exposure estimates
exceed 100% of the aPAD and/or cPAD. Even with the conservative
assumptions noted above, risk estimates associated with dietary
exposure to acetamiprid are below the Agency's LOC.
iii. Cancer. Acetamiprid has been classified as not likely to be
carcinogenic to humans; therefore, a dietary assessment for cancer risk
was not conducted. This classification is based on the absence of a
dose-response and a lack of a statistically significant increase in the
mammary adenocarcinoma incidence by pair-wise comparison of the mid-
and high-dose groups with the controls. Although the incidence exceeded
the historical control data from the same lab, it was within the range
of values from the supplier.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for acetamiprid 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 acetamiprid.
Tier 1 simulated estimated drinking water concentrations (EDWCs)
for acetamiprid in surface water using the FQPA Index Resevoir
Screening Test (FIRST) to calculate surface water concentrations and
screening concentration in ground water (SCI-GROW) to calculate ground
water concentrations.
For the surface water assessment, the application rate for citrus
was used, which represents the highest label rate for a single
application of any crop (0.55 lb a.i./A/season). However, it is
important to note that due to limitations imposed by the use of two
applications at the highest single application rate (0.25 lb a.i./A),
the modeled application rate was equal to only 0.50 lb a.i./A.
The proposed applications of acetamiprid on tuberous and corm
vegetables would result in lower EDWCs than citrus, and thus has little
effect on the drinking water assessment for this chemical. By using the
application rate for citrus crops, the surface and ground water
estimated concentrations are conservative estimates for the proposed
new use scenarios (tuberous and corm vegetables) because of the higher
application rate.
The primary use of these models by the Agency at this stage is to
provide a screen for sorting out pesticides for which it is unlikely
that drinking water concentrations would exceed human health levels of
concern.
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs), which are the model estimates of a
pesticide's concentration in water. EECs derived from these models are
used to quantify drinking water exposure and risk as a %RfD or %PAD.
Instead drinking water levels of comparison (DWLOCs) are calculated and
used as a point of comparison against the model estimates of a
pesticide's concentration in water. DWLOCs are theoretical upper limits
on a pesticide's concentration in drinking water in light of total
aggregate exposure to a pesticide in food, and from residential uses.
Since DWLOCs address total aggregate exposure to acetamiprid they are
further discussed in the aggregate risk sections.
[[Page 19289]]
Based on the FIRST and SCI-GROW models, the EECs of acetamiprid for
acute exposures are estimated to be 17 parts per billion (ppb) for
surface water and 0.0008 ppb for ground water. The EECs for chronic
exposures are estimated to be 4 ppb for surface water and 0.0008 ppb
for ground water.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
Acetamiprid is currently registered for use on the following
residential non-dietary sites: Ornamentals and flowers. The risk
assessment was conducted using the following residential exposure
assumptions:
Acetamiprid is currently registered for use on the following
residential non-dietary sites: Ornamentals and flowers. No chemical
specific data were available to estimate exposure and risk for
homeowners applying acetamiprid to ornamentals and flowers. The risk
assessment was conducted using the following conservative residential
exposure assumptions: Little use of any protective equipment by
residential applicators, the use of agricultural transfer coefficients
which incorporate larger acreage and greater foliar contact for dermal
exposure, and postapplication exposure to the maximum levels of
residues on the day of application. Using such assumptions for
residential applicators, total MOEs for short- and intermediate-term
residential dermal and inhalation exposures range from 1.2 X
105 to 6 X 105. For post-application activities,
short- and intermediate-term MOEs range from 1.8 X 104 to
1.8 X 105 for adults and from 2.3 X 104 to 2.2 X
105 for youth ages 10-12 years. The residential uses for
acetamiprid are not expected to result in long-term exposures.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA does not have, at this time, available data to determine
whether acetamiprid has a common mechanism of toxicity with other
substances. 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 acetamiprid
and any other substances and acetamiprid 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 acetamiprid 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 web site 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 safety factor
value based on the use of traditional uncertainty factors and/or
special FQPA safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. In the developmental
toxicity studies in rats and rabbits, the Agency determined that
neither quantitative nor qualitative evidence of increased
susceptibility of fetuses to in utero exposure to acetamiprid were
observed. However, in the multigeneration reproduction study,
qualitative evidence of increased susceptibility of rat pups is
observed. Considering the overall toxicity profile and the doses and
endpoints selected for risk assessment for acetamiprid, the Agency
characterized the degree of concern for the effects observed in this
study as low, noting that:
i. There is a clear NOAEL for the offspring, and;
ii. These effects occurred in the presence of parental toxicity and
only at the highest dose tested. No residual uncertainties were
identified.
The NOAEL for offspring effects is used for short- and
intermediate-term dermal and inhalation exposure scenarios. All other
toxicology endpoints established for acetamiprid are based on a lower
NOAEL than this, and are thus protective of offspring effects.
3. Conclusion. The Agency concluded that there is concern for
neurotoxicity resulting from exposure to acetamiprid because:
i. Clinical signs of neurotoxicity were observed in the acute
neurotoxicity study on the day of dosing, and;
ii. Studies in literature with structurally similar chemicals from
the same chemical class (neonicotinoids) suggest that nicotine, when
administered to humans and/or animals in utero causes developmental
toxicity, including functional deficits.
The Agency concluded that the toxicology database for acetamiprid
is not complete for FQPA assessment, since a developmental
neurotoxicity (DNT) study in rats is currently under review and has not
yet been finalized and is part of a comprehensive evaluation of many
DNT studies of various pesticides, some of which have not yet been
submitted. The preliminary review of the study indicates the results
are not likely to have a significant impact on risks for the currently
proposed use, or on existing uses of acetamiprid. Based on weight of
the evidence, an uncertainty factor UFDB is not needed (1X) since
developmental neurotoxicity data received and reviewed for other
compounds in this chemical class indicate that the results of the
required DNT will not likely impact the regulatory doses selected for
the proposed uses of acetamiprid.
E. Aggregate Risks and Determination of Safety
To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates DWLOCs
which are used as a point of comparison against EECs. DWLOC values are
not regulatory standards for drinking water. DWLOCs are theoretical
upper limits on a pesticide's concentration in drinking water in light
of total aggregate exposure to a pesticide in food and residential
uses. In calculating a DWLOC, the Agency determines how much of the
acceptable exposure (i.e., the PAD) is available for exposure through
drinking water (e.g., allowable chronic water exposure (mg/kg/day) =
cPAD - (average
[[Page 19290]]
food + residential exposure)). This allowable exposure through drinking
water is used to calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the EPA's Office of Water are used to calculate
DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult female), and
1L/10 kg (child). Default body weights and drinking water consumption
values vary on an individual basis. This variation will be taken into
account in more refined screening-level and quantitative drinking water
exposure assessments. Different populations will have different DWLOCs.
Generally, a DWLOC is calculated for each type of risk assessment used:
Acute, short-term, intermediate-term, chronic, and cancer.
When EECs for surface water and ground water are less than the
calculated DWLOCs, EPA concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which EPA has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because EPA considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, EPA will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food to
acetamiprid will occupy 18 % of the aPAD for the U.S. population, 12 %
of the aPAD for females 13 years and older, 44 % of the aPAD for all
infants less than one year old, and 61 % of the aPAD for 1-2 years old
children. In addition, there is potential for acute dietary exposure to
acetamiprid in drinking water. After calculating DWLOCs and comparing
them to the EECs for surface and ground water, EPA does not expect the
aggregate exposure to exceed 100% of the aPAD, as shown in Table 3 of
this unit:
Table 3.--Aggregate Risk Assessment for Acute Exposure to acetamiprid
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population/Subgroup aPAD (mg/ % aPAD/ Water EEC/ Water EEC/ Acute DWLOC/
kg) (Food) (ppb) (ppb) (ppb)
----------------------------------------------------------------------------------------------------------------
US Population 0.10 18 17 0.0008 2,900
--------------------------------------------------------------
All Infants < 1 year 0.10 44 17 0.0008 540
--------------------------------------------------------------
Children 1-2 years 0.10 61 17 0.0008 370
--------------------------------------------------------------
Children 3-5 years 0.10 42 17 0.0008 560
--------------------------------------------------------------
Children 6-12 years 0.10 22 17 0.0008 790
--------------------------------------------------------------
Youth 13-19 years 0.10 14 17 0.0008 2,600
--------------------------------------------------------------
Adults 20-49 years 0.10 11 17 0.
