Clothianidin; Pesticide Tolerance, 6851-6856 [E8-1784]
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Federal Register / Vol. 73, No. 25 / Wednesday, February 6, 2008 / Rules and Regulations
that this regulation will not have a
significant economic impact on a
substantial number of small business
entities. This rule imposes no new costs
or burden on small entities. Rather, this
rule adds Spain to the list of nontraditional countries permitted to export
NRM to the United States, helping to
ensure that United States importers and
manufacturers will have access to, and
be able to procure, supplies of NRM to
meet legitimate United States medical,
scientific, research, and industrial
needs, to ensure maintenance of
adequate reserve stocks, and to meet
lawful export requirements.
Additionally, this rule provides DEA
registered importers with another source
from which to purchase NRM which are
utilized for the production of controlled
substances used in the United States for
medical purposes.
Executive Order 12866
The Deputy Assistant Administrator,
Office of Diversion Control, further
certifies that this rulemaking has been
drafted in accordance with the
principles in Executive Order 12866
Section 1(b). It has been determined that
this is a significant regulatory action.
Therefore, this action has been reviewed
by the Office of Management and
Budget.
Executive Order 12988
This rule meets the applicable
standards set forth in Sections 3(a) and
3(b)(2) of Executive Order 12988.
Executive Order 13132
This rule does not preempt or modify
any provision of State law; nor does it
impose enforcement responsibilities on
any State; nor does it diminish the
power of any State to enforce its own
laws. Accordingly, this rulemaking does
not have federalism implications
warranting the application of Executive
Order 13132.
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Unfunded Mandates Reform Act of 1995
This rule will not result in the
expenditure by State, local, and tribal
governments, in the aggregate, or by the
private sector, of $120,000,000 or more
(adjusted for inflation) in any one year,
and will not significantly or uniquely
affect small governments. Therefore, no
actions were deemed necessary under
the provisions of the Unfunded
Mandates Reform Act of 1995.
Congressional Review Act
This rule is not a major rule as
defined by Section 804 of the Small
Business Regulatory Enforcement
Fairness Act of 1996 (Congressional
Review Act). This rule will not result in
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an annual effect on the economy of
$100,000,000 or more; a major increase
in costs or prices; or significant adverse
effects on competition, employment,
investment, productivity, innovation, or
on the ability of United States-based
companies to compete with foreignbased companies in domestic and
export markets.
List of Subjects in 21 CFR Part 1312
Administrative practice and
procedure, Drug traffic control, Exports,
Imports, Reporting and recordkeeping
requirements.
For the reasons set out above, 21 CFR
part 1312 is amended as follows:
I
PART 1312—IMPORTATION AND
EXPORTATION OF CONTROLLED
SUBSTANCES
1. The authority citation for part 1312
continues to read as follows:
I
Authority: 21 U.S.C. 952, 953, 954, 957,
958.
2. Section 1312.13 is amended by
revising paragraphs (f) and (g) to read as
follows:
I
§ 1312.13
Issuance of import permit.
*
*
*
*
*
(f) Notwithstanding paragraphs (a)(1)
and (a)(2) of this section, the
Administrator shall permit, pursuant to
section 1002(a)(1) or 1002(a)(2)(A) of the
Act (21 U.S.C. 952(a)(1) or (a)(2)(A)), the
importation of approved narcotic raw
material (opium, poppy straw and
concentrate of poppy straw) having as
its source:
(1) Turkey,
(2) India,
(3) Spain,
(4) France,
(5) Poland,
(6) Hungary, and
(7) Australia.
(g) At least eighty (80) percent of the
narcotic raw material imported into the
United States shall have as its original
source Turkey and India. Except under
conditions of insufficient supplies of
narcotic raw materials, not more than
twenty (20) percent of the narcotic raw
material imported into the United States
annually shall have as its source Spain,
France, Poland, Hungary and Australia.
Dated: January 30, 2008.
Joseph T. Rannazzisi,
Deputy Assistant Administrator, Office of
Diversion Control.
[FR Doc. E8–2142 Filed 2–5–08; 8:45 am]
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ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2007–0280; FRL–8346–9]
Clothianidin; Pesticide Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes a
tolerance for residues of clothianidin in
or on sugar beet roots, tops and
molasses. Bayer CropScience requested
this tolerance under the Federal Food,
Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective
February 6, 2008. Objections and
requests for hearings must be received
on or before April 7, 2008, and must be
filed in accordance with the instructions
provided in 40 CFR part 178 (see also
Unit I.C. of the SUPPLEMENTARY
INFORMATION).
EPA has established a
docket for this action under docket
identification (ID) number EPA–HQ–
OPP–2007–0280. To access the
electronic docket, go to https://
www.regulations.gov, select ‘‘Advanced
Search,’’ then ‘‘Docket Search.’’ Insert
the docket ID number where indicated
and select the ‘‘Submit’’ button. Follow
the instructions on the regulations.gov
website to view the docket index or
access available documents. All
documents in the docket are listed in
the docket index available in
regulations.gov. Although listed in the
index, some information is not publicly
available, e.g., Confidential Business
Information (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 in the electronic docket at
https://www.regulations.gov, or, if only
available in hard copy, at the OPP
Regulatory Public Docket in Rm. S–
4400, One Potomac Yard (South Bldg.),
2777 S. Crystal Dr., Arlington, VA. The
Docket Facility is open from 8:30 a.m.
to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket
Facility telephone number is (703) 305–
5805.
FOR FURTHER INFORMATION CONTACT:
Kable Bo Davis, Registration Division
(7505P), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
ADDRESSES:
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(703) 306–0415; e-mail address:
davis.kable@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 those engaged in the
following activities:
• Crop production (NAICS code 111),
e.g., agricultural workers; greenhouse,
nursery, and floriculture workers;
farmers.
• Animal production (NAICS code
112), e.g., cattle ranchers and farmers,
dairy cattle farmers, livestock farmers.
• Food manufacturing (NAICS code
311), e.g., agricultural workers; farmers;
greenhouse, nursery, and floriculture
workers; ranchers; pesticide applicators.
• Pesticide manufacturing (NAICS
code 32532), e.g., agricultural workers;
commercial applicators; farmers;
greenhouse, nursery, and floriculture
workers; residential users.
This listing is not intended to be
exhaustive, but rather to provide a guide
for readers regarding entities likely to be
affected by this action. Other types of
entities not listed in this unit could also
be affected. The North American
Industrial Classification System
(NAICS) codes have been provided to
assist you and others in determining
whether this action might apply to
certain entities. If you have any
questions regarding the applicability of
this action to a particular entity, consult
the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies
of this Document?
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In addition to accessing an electronic
copy of this Federal Register document
through the electronic docket at https://
www.regulations.gov, you may access
this Federal Register document
electronically through the EPA Internet
under the ‘‘Federal Register’’ listings at
https://www.epa.gov/fedrgstr. You may
also access a frequently updated
electronic version of EPA’s tolerance
regulations at 40 CFR part 180 through
the Government Printing Office’s pilot
e-CFR site at https://www.gpoaccess.gov/
ecfr.
C. Can I File an Objection or Hearing
Request?
Under section 408(g) of FFDCA, any
person may file an objection to any
aspect of this regulation and may also
request a hearing on those objections.
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You must file your objection or request
a hearing on this regulation in
accordance with the instructions
provided in 40 CFR part 178. To ensure
proper receipt by EPA, you must
identify docket ID number EPA–HQ–
OPP–2007–0280 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
as required by 40 CFR part 178 on or
before April 7, 2008.
In addition to filing an objection or
hearing request with the Hearing Clerk
as described in 40 CFR part 178, please
submit a copy of the filing that does not
contain any CBI for inclusion in the
public docket that is described in
ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2
may be disclosed publicly by EPA
without prior notice. Submit this copy,
identified by docket ID number EPA–
HQ–OPP–2007–0280, by one of the
following methods:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the on-line
instructions for submitting comments.
• Mail: Office of Pesticide Programs
(OPP) Regulatory Public Docket (7502P),
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001.
• Delivery: OPP Regulatory Public
Docket (7502P), Environmental
Protection Agency, Rm. S–4400, One
Potomac Yard (South Bldg.), 2777 S.
Crystal Dr., Arlington, VA. Deliveries
are only accepted during the Docket’s
normal hours of operation (8:30 a.m. to
4 p.m., Monday through Friday,
excluding legal holidays). Special
arrangements should be made for
deliveries of boxed information. The
Docket Facility telephone number is
(703) 305–5805.
II. Petition for Tolerance
In the Federal Register of April 30,
2007 (72 FR 21263) (FRL–8124–5), 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 6F7159) by Bayer
CropScience, 2 T.W. Alexander Drive,
Research Triangle Park, NC 27709. The
petition requested that 40 CFR 180.586
be amended by establishing a tolerance
for residues of the insecticide
clothianidin, (E)-1-(2-chloro-1,3-thiazol5-ylmethyl)-3-methyl-2-nitroguanidine,
in or on beet, sugar, root at 0.02 parts
per million (ppm); beet, sugar, tops at
0.04 ppm; and beet, sugar, molasses at
0.06 ppm. That notice referenced a
summary of the petition prepared by
Bayer CropScience, the registrant,
which is available to the public in the
docket, https://www.regulations.gov.
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There were no comments received in
response to the notice of filing.
Upon completing review of the
current clothianidin database, the
Agency concluded that the appropriate
tolerance levels for clothianidin
residues in or on pending crops should
be established as follows: Beet, sugar,
roots at 0.02 ppm, beet, sugar, molasses
at 0.05 ppm and beet, sugar, dried pulp
at 0.03 ppm. The Agency no longer
considers sugar beet tops to be a
significant livestock feedstuff; therefore,
a separate tolerance for tops is not
required.
III. Aggregate Risk Assessment and
Determination of Safety
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....’’ These provisions
were added to FFDCA by the Food
Quality Protection Act (FQPA) of 1996.
Consistent with FFDCA section
408(b)(2)(D), and the factors specified in
FFDCA section 408(b)(2)(D), 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 for the petitioned-for
tolerance for residues of clothianidin on
beet, sugar, roots at 0.02 ppm, beet,
sugar, molasses at 0.05 ppm and beet,
sugar, dried pulp at 0.03. 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
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concerning the variability of the
sensitivities of major identifiable
subgroups of consumers, including
infants and children. Specific
information on the studies received and
the nature of the adverse effects caused
by clothianidin as well as the noobserved-adverse-effect-level (NOAEL)
and the lowest-observed-adverse-effectlevel (LOAEL) from the toxicity studies
can be found at https://
www.regulations.gov. The risk
assessment is available in the docket
established by this action, which is
described under ADDRESSES, and is
identified as EPA–HQ–OPP–2007–0280
in that docket.
Clothianidin does not appear to
exhibit toxicity towards a consistent
specific target organ. Decreases in body
weight and body weight gain were
observed in rats, dogs, and mice. In
single-dose studies, mice (acute toxicity
category II) appear more sensitive than
rats (category IV). Clinical signs of
neurotoxicity were exhibited in both
mice (decreased motor activity, tremors,
and deep respirations at 50 milligram/
kilogram (mg/kg)) and rats (transient
signs of decreased arousal, motor
activity, and locomotor activity at 100
mg/kg) in acute neurotoxicity studies
following exposure by gavage; however,
no indications of neurotoxicity were
observed following dietary exposure in
the subchronic neurotoxicity study in
rats. In a developmental neurotoxicity
study in rats, decreased body weights,
body weight gains, motor activity, and
acoustic startle response amplitude
(females) were seen in offspring at doses
lower than those resulting in maternal
toxicity. Although the NOAELs were
similar for the subchronic and chronic
feeding studies in the rat, a greater
spectrum of effects was observed in the
chronic study (decreased body weight,
body weight gain, and food
consumption plus additional
observations in the liver, ovary, and
kidney) versus the subchronic study
(effects only on body weight and food
consumption). In the rat, administration
via the oral route appears to be more
toxic than via the dermal route. In
longer term studies, dogs exhibited
clinical signs of anemia. The only
observed effects in mice following
chronic dietary administration were
increases in vocalization and decreases
in body weight and body weight gain.
Clothianidin has been classified as not
likely to be carcinogenic to humans.
There was no evidence of increased
quantitative or qualitative susceptibility
of rat or rabbit offspring in
developmental studies; however,
increased quantitative susceptibility of
rat pups was seen in both the
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reproduction and developmental
neurotoxicity studies. The degree of
concern for both of these studies is low
because the observed effects are well
characterized, and there are clear
NOAELs and LOAELs. The NOAEL for
the effects of concern identified in the
reproduction study (decreased mean
body weight gain and absolute thymus
weights in pups, delayed sexual
maturation, and an increase in still
births) is the basis for the endpoint
selected for the chronic dietary and
short-term, intermediate-term and longterm non-dietary risk assessments.
In adult rats, a guideline
immunotoxicity study shows no
clothianidin-mediated immunotoxicity
at doses lower than those resulting in
generalized signs of toxicity (e.g.,
decreases in body weight); however, it
cannot be concluded that a similar lack
of effects will occur in offspring. Based
on evidence of decreased absolute and
adjusted organ weights of the thymus
and spleen in multiple studies in the
clothianidin data base and on evidence
of increased quantitative susceptibility
of juvenile rats, compared to adults, in
the 2–generation reproduction study to
these effects, a developmental
immunotoxicity (DIT) study has been
required.
B. Toxicological Endpoints
For hazards that have a threshold
below which there is no appreciable
risk, the toxicological level of concern
(LOC) is derived from the highest dose
at which the NOAEL in the toxicology
study identified as appropriate for use
in risk assessment. However, if a
NOAEL cannot be determined, the
LOAEL is sometimes used for risk
assessment. Uncertainty/safety factors
(UFs) are used in conjunction with the
LOC to take into account 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. Safety is
assessed for acute and chronic risks by
comparing aggregate exposure to the
pesticide to the acute population
adjusted dose (aPAD) and chronic
population adjusted dose (cPAD). The
aPAD and cPAD are calculated by
dividing the LOC by all applicable UFs.
Short-term, intermediate-term, and longterm risks are evaluated by comparing
aggregate exposure to the LOC to ensure
that the margin of exposure (MOE)
called for by the product of all
applicable UFs is not exceeded.
For non-threshold risks, the Agency
assumes that any amount of exposure
will lead to some degree of risk and
estimates risk in terms of the probability
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6853
of occurrence of additional adverse
cases. Generally, cancer risks are
considered non-threshold. For more
information on the general principles
EPA uses in risk characterization and a
complete description of the risk
assessment process, see https://
www.epa.gov/fedrgstr/EPA-PEST/1997/
November/Day–26/p30948.htm.
A summary of the toxicological
endpoints for clothianidin used for
human risk assessment can be found at
https://www.regulations.gov in document
‘‘Clothianidin: Human Health Risk
Assessment for Proposed Use on Sugar
Beet’’ at pages 18–20 in docket ID
number EPA–HQ–OPP–2007–0280.
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. In evaluating dietary
exposure to clothianidin, EPA
considered exposure under the
petitioned-for tolerances as well as all
existing clothianidin tolerances in (40
CFR 180.586). EPA assessed dietary
exposures from clothianidin in food as
follows:
i. Acute exposure. Quantitative acute
dietary exposure and risk assessments
are performed for a food-use pesticide,
if a toxicological study has indicated the
possibility of an effect of concern
occurring as a result of a 1–day or single
exposure.
In estimating acute dietary exposure,
EPA used food consumption
information from the U.S. Department of
Agriculture (USDA) 1994–1996 and
1998 Nationwide Continuing Surveys of
Food Intake by Individuals (CSFII). The
acute assessment is based on maximum
residues of clothianidin observed in
clothianidin and thiamethoxam field
trials and assumes 100 percent crop
treated (%CT).
ii. Chronic exposure. In conducting
the chronic dietary exposure assessment
EPA used the food consumption data
from the USDA 1994–1996 and 1998
CSFII. The chronic assessment is based
on average residues from clothianidin
and thiamethoxam field trials and
assumes 100% CT.
iii. Cancer. Because clothianidin is
not expected to pose a cancer risk, a
quantitative dietary exposure
assessment for the purposes of assessing
cancer risk was not conducted.
iv. Anticipated residue and percent
crop treated (PCT) information. Section
408(b)(2)(E) of FFDCA authorizes EPA
to use available data and information on
the anticipated residue levels of
pesticide residues in food and the actual
levels of pesticide residues that have
been measured in food. If EPA relies on
such information, EPA must pursuant to
FFDCA section 408(f)(1) require that
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data be provided 5 years after the
tolerance is established, modified, or
left in effect, demonstrating that the
levels in food are not above the levels
anticipated. For the present action, EPA
will issue such data call-ins as are
required by FFDCA section 408(b)(2)(E)
and authorized under FFDCA section
408(f)(1). Data will be required to be
submitted no later than 5 years from the
date of issuance of this tolerance.
The Agency used PCT information as
follows:
The acute assessment is based on
maximum residues of clothianidin
observed in clothianidin field trials and
assumes 100% crop treated. The chronic
assessment is based on average residues
from clothianidin field trials and also
assumes 100% CT.
The Agency believes that the three
conditions listed in Unit III. have been
met. With respect to Condition 1, PCT
estimates are derived from Federal and
private market survey data, which are
reliable and have a valid basis. The
Agency is reasonably certain that the
percentage of the food treated is not
likely to be an underestimation. As to
Conditions 2 and 3, regional
consumption information and
consumption information for significant
subpopulations is taken into account
through EPA’s computer-based model
for evaluating the exposure of
significant subpopulations including
several regional groups. Use of this
consumption information in EPA’s risk
assessment process ensures that EPA’s
exposure estimate does not understate
exposure for any significant
subpopulation group and allows the
Agency to be reasonably certain that no
regional population is exposed to
residue levels higher than those
estimated by the Agency. Other than the
data available through national food
consumption surveys, EPA does not
have available information on the
regional consumption of food to which
clothianidin may be applied in a
particular area.
2. Dietary exposure from drinking
water. The Agency lacks sufficient
monitoring data to complete a
comprehensive dietary exposure
analysis and risk assessment for
clothianidin 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 environmental fate characteristics of
clothianidin. Further information
regarding EPA drinking water models
used in pesticide exposure assessment
can be found at https://www.epa.gov/
oppefed1/models/water/index.htm.
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Based on the First Index Reservoir
Screening Tool (FIRST) and Screening
Concentration in Ground Water (SCIGROW) models, the estimated
environmental concentrations (EECs) of
clothianidin for acute exposures are
estimated to be 7.29 parts per billion
(ppb) for surface water and 5.84 ppb for
ground water. The EECs for chronic
exposures are estimated to be 1.35 ppb
for surface water and 5.84 ppb for
ground water.
Modeled estimates of drinking water
concentrations were directly entered
into the dietary exposure model. For
acute dietary risk assessment, the water
concentration value of 7.29 ppb was
used to access the contribution to
drinking water. For chronic dietary risk
assessment, the water concentration of
value 5.84 ppb was used to access the
contribution to drinking 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).
Clothianidin is currently registered
for the following residential non-dietary
sites: Turfgrass. EPA assessed
residential exposure using the following
assumptions: The following exposure
scenarios were assessed for residential
post-application risks: Toddlers playing
on treated turf, adults performing yard
work on treated turf, and adults and
youths playing golf on treated turf.
Additional information on residential
exposure assumptions can be found at
www.regulations.gov (Docket ID EPA–
HQ–OPP–2007–0280, pages 26 through
27).
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.’’
Clothianidin is a member of the
neonicotinoid class of pesticides and is
a metabolite of another neonicotinoid,
thiamethoxam. Structural similarities or
common effects do not constitute a
common mechanism of toxicity.
Evidence is needed to establish that the
chemicals operate by the same, or
essentially the same sequence of major
biochemical events (EPA, 2002).
Although clothianidin and
thiamethoxam bind selectively to insect
nicotinic acetylcholine receptors
(nAChR), the specific binding site(s)/
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receptor(s) for clothianidin,
thiamethoxam, and the other
neonicotinoids are unknown at this
time. Additionally, the commonality of
the binding activity itself is uncertain,
as preliminary evidence suggests that
clothianidin operates by direct
competitive inhibition, while
thiamethoxam is a non-competitive
inhibitor. Furthermore, even if future
research shows that neonicotinoids
share a common binding activity to a
specific site on insect nicotinic
acetylcholine receptors, there is not
necessarily a relationship between this
pesticidal action and a mechanism of
toxicity in mammals. Structural
variations between the insect and
mammalian nAChRs produce
quantitative differences in the binding
affinity of the neonicotinoids towards
these receptors, which, in turn, confers
the notably greater selective toxicity of
this class towards insects, including
aphids and leafhoppers, compared to
mammals. While the insecticidal action
of the neonicotinoids is neurotoxic, the
most sensitive regulatory endpoint for
clothianidin is based on unrelated
effects in mammals, including changes
in body and thymus weights, delays in
sexual maturation, and still births.
Additionally, the most sensitive
toxicological effect in mammals differs
across the neonicotinoids (e.g.,
testicular tubular atrophy with
thiamethoxam; mineralized particles in
thyroid colloid with imidaclopid). Thus,
there is currently no evidence to
indicate that neonicotinoids share
common mechanisms of toxicity, and
EPA is not following a cumulative risk
approach based on a common
mechanism of toxicity for the
neonicotinoids. 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
concerning common mechanism
determinations and procedures for
cumulating effects from substances
found to have a common mechanism
released by EPA’s Office of Pesticide
Programs on EPA’s website at https://
www.epa.gov/pesticides/cumulative/.
Note that because clothianidin is a
major metabolite of thiamethoxam, EPA
has combined exposure to clothianidin
resulting both from thiamethoxam use
and from use of clothianidin as an
active ingredient and has compared this
aggregate exposure estimate to relevant
endpoints for clothianidin. EPA has
taken the further conservative step of
assuming that, in instances where both
thiamethoxam and clothianidin are
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yshivers on PROD1PC62 with RULES
registered for use on a crop, both
pesticides will, in fact, be used on that
crop.
D. Safety Factor for Infants and
Children
1. In general. Section 408 of FFDCA
provides that EPA shall apply an
additional (‘‘10X’’) tenfold margin of
safety for infants and children in the
case of threshold effects to account for
prenatal and postnatal toxicity and the
completeness of the database on toxicity
and exposure unless EPA determines
based on reliable data that a different
margin of safety will be safe for infants
and children. This additional margin of
safety is commonly referred to as the
FQPA safety factor. In applying this
provision, EPA either retains the default
value of 10X when reliable data do not
support the choice of a different factor,
or, if reliable data are available, EPA
uses a different additional FQPA safety
factor value based on the use of
traditional UFs and/or special FQPA
safety factors, as appropriate.
2. Prenatal and postnatal sensitivity.
In the developmental neurotoxicity
study, toxicity in the offspring was
observed at a lower dose level than the
dose that caused toxicity in the maternal
animals. Maternal effects included
decreased body weights, body weight
gains, and food consumption. Effects
seen in the offspring included decreased
body weights, body weight gains, motor
activity, and acoustic startle response in
the females. However, EPA determined
that the degree of concern for the
developmental neurotoxicity study is
low and there are no residual
uncertainties for prenatal and/or
postnatal toxicity due to the results of
the developmental neurotoxicity study
because the observed effects are well
characterized and there are clear
NOAELs/LOAELs.
In the 2–generation reproduction
study, offspring toxicity (decreased
body weight gains, delayed sexual
maturation in males, decreased absolute
thymus weights in F1 pups of both
sexes, and an increase in stillbirths in
both generations) was seen at a lower
dose than the dose that caused parental
toxicity. Based on evidence of decreased
absolute and adjusted organ weights of
the thymus and spleen in multiple
studies in the clothianidin data base and
on evidence of increased quantitative
susceptibility of juvenile rats, compared
to adults, in the 2–generation
reproduction study to these effects. EPA
has required that testing be conducted
to assess immune system function in
adults and in young animals following
exposure during the period of
organogenesis. No quantitative or
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qualitative susceptibility was observed
in either of the developmental rat or
rabbit studies. In the rat, no
developmental toxicity was observed at
the highest dose tested, although this
dose level induced decreases in body
weight gain and food consumption in
the dams. In the rabbit, premature
deliveries, decreased gravid uterine
weights, an increase in litter incidence
of a missing lobe of the lung, and a
decrease in the litter average for ossified
sternal centra per fetus were noted at a
dose level in which maternal death, a
decrease in food consumption, and
clinical signs (scant feces and orange
urine) were observed. Since the
developmental effects observed in the
rabbit study were seen in the presence
of maternal toxicity, they are not
considered to be qualitatively more
severe than the maternal effects.
3. Conclusion. The exposure data for
clothianidin are complete or are
estimated based on data that reasonably
accounts for potential exposures. The
acute dietary exposure assessment is
based on maximum residues of
clothianidin observed in clothianidin
and thiamethoxam field trials and
assumes 100% CT. The chronic
assessment is based on average residues
from clothianidin and thiamethoxam
field trials and also assumes 100% CT.
For water, the highest acute estimate
from conservative models was used for
both the acute and the chronic dietary
exposure analyses. By using these
conservative assessments, acute and
chronic exposures/risks will not be
underestimated. The residential
exposure assessment utilizes residential
standard operation procedures (SOPs) to
assess post-application exposure to
children as well as incidental oral
ingestion by toddlers. The residential
SOPs are based on reasonable worstcase assumptions and will not likely
underestimate exposure/risk. These
assessments are unlikely to
underestimate the potential exposure to
74,800 infants and children resulting
from the use of clothianidin.
The toxicology data base for
clothianidin, however, is not complete
for FQPA purposes. A complete
complement of acceptable
developmental, reproduction,
developmental neurotoxicity,
mammalian neurotoxicity and special
neurotoxicity studies are available;
however, due to evidence of decreased
absolute and adjusted organ weights of
the thymus and spleen in multiple
studies in the clothianidin database, and
because juvenile rats in the two–
generation reproduction study appear to
be more susceptible to these effects,
EPA has determined that testing should
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Fmt 4700
Sfmt 4700
6855
be conducted to assess immune system
function in adults and in young animals
following developmental exposures.
Given the levels at which this testing
should be conducted it could result in
selection of a more protective (i.e.,
lower) regulatory endpoint.
Due to the uncertainty with regard to
potential effects on immune system
function in young animals, EPA cannot
conclude that there are reliable data
supporting selection of a children’s
safety factor different from the
presumptive 10X factor. Therefore, the
10X FQPA children’s safety factor will
be retained. This safety factor will be in
the form of a database uncertainty factor
to account for the lack of the testing
with regard to immune system function
with clothianidin.
E. Aggregate Risks and Determination of
Safety
Safety is assessed for acute and
chronic risks by comparing aggregate
exposure to the pesticide to the aPAD
and cPAD. The aPAD and cPAD are
calculated by dividing the LOC by all
applicable UFs. For linear cancer risks,
EPA calculates the probability of
additional cancer cases given aggregate
exposure. Short-term, intermediateterm, and long-term risks are evaluated
by comparing aggregate exposure to the
LOC to ensure that the MOE called for
by the product of all applicable UFs is
not exceeded.
1. Acute risk. Using the exposure
assumptions discussed in this unit for
acute exposure, the acute dietary
exposure from food and water to
clothianidin will occupy 45% of the
aPAD for the population group (children
1–2 years old) receiving the greatest
exposure.
2. Chronic risk. Using the exposure
assumptions described in this unit for
chronic exposure, EPA has concluded
that exposure to clothianidin from food
and water will utilize 16% of the cPAD
for the population group (children 1–2
years old). Based on the use pattern,
chronic residential exposure to residues
of clothianidin is not expected.
3. Short-term / Intermediate-term risk.
Short-term aggregate and intermediateterm aggregate exposures take into
account residential exposure plus
chronic exposure to food and water
(considered to be a background
exposure level).
Clothianidin is currently registered
for use(s) that could result in short-term
residential exposure and the Agency has
determined that it is appropriate to
aggregate chronic food and water and
short-term exposures for clothianidin.
EPA has determined that, for
clothianidin, the toxicological effects
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are the same across oral, dermal, and
inhalation routes of exposure and has
selected the same endpoint and dose for
short-term and intermediate-term
exposure scenarios. Therefore, the
exposures are simply summed
(combined/aggregated) for use in risk
calculations. Short- and intermediate
aggregate risk estimates range from an
MOE of 1,100 for toddlers (food + water
+ treated turf + treated soil + dermal) to
22,000 for youth golfers (food + water +
post-application treated turf). The shortterm and intermediate-term aggregate
risks associated with the registered and
proposed uses of clothianidin do not
exceed the Agency’s LOC for the general
U.S. population or any population
subgroup.
4. Aggregate cancer risk for U.S.
population. Clothianidin has been
classified as a ‘‘not likely human
carcinogen.’’ It is not expected to pose
a cancer risk.
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, or to infants and children
from aggregate exposure to clothianidin
residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate liquid chromotography/
mass spectrometry/mass spectrometry
(LC/MS/MS) methods are available for
both collecting data and enforcing
tolerances for clothianidin residues in
plant (Bayer Methods 00552 and
109240–1) and animal (Bayer Method
00624) commodities. The validated
limit of quantitation (LOQ) for
clothianidin in plant commodities is
0.010 ppm, except for wheat straw
(0.020 ppm), and the validated LOQs are
0.010 ppm in milk and 0.020 ppm in
animal tissues. All three of these
methods have been reviewed by EPA’s
Analytical Chemistry Laboratory (ACL),
approved for tolerance enforcement, and
forwarded to FDA for inclusion in PAM
Volume II.
B. International Residue Limits
There are no established or proposed
Canadian, Mexican, or Codex maximum
residue limits (MRLs) for clothianidin
residues on sugar beet commodities.
yshivers on PROD1PC62 with RULES
V. Conclusion
Therefore, the tolerance is established
for residues of (E)-1-(2-chloro-1,3thiazol-5-ylmethyl)-3-methyl-2nitroguanidine, in or on beet, sugar,
roots at 0.02 ppm, beet, sugar, molasses
at 0.05 ppm and beet, sugar, dried pulp
at 0.03.
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15:18 Feb 05, 2008
Jkt 214001
VI. 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, 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) or Executive Order 13045,
entitled Protection of Children from
Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
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., 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).
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.
This final rule directly regulates
growers, food processors, food handlers,
and food retailers, not States or tribes,
nor does this action alter the
relationships or distribution of power
and responsibilities established by
Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such,
the Agency has determined that this
action will not have a substantial direct
effect on States or tribal governments,
on the relationship between the national
government and the States or tribal
governments, or on the distribution of
power and responsibilities among the
various levels of government or between
the Federal Government and Indian
tribes. Thus, the Agency has determined
that Executive Order 13132, entitled
Federalism (64 FR 43255, August 10,
1999) and Executive Order 13175,
entitled Consultation and Coordination
with Indian Tribal Governments (65 FR
67249, November 6, 2000) do not apply
to this rule. In addition, This rule does
not impose any enforceable duty or
contain any unfunded mandate as
described under Title II of the Unfunded
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Frm 00024
Fmt 4700
Sfmt 4700
Mandates Reform Act of 1995 (UMRA)
(Public Law 104–4).
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).
VII. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801 et seq., generally provides
that before a rule may take effect, the
agency promulgating the rule must
submit a rule report 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: January 22, 2008.
Lois Rossi,
Director, Registration Division, Office of
Pesticide Programs.
Therefore, 40 CFR chapter I is
amended as follows:
I
PART 180—[AMENDED]
1. The authority citation for part 180
continues to read as follows:
I
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.586 is amended by
alphabetically adding the following
commodities to the table in paragraph
(a) to read as follows:
I
§ 180.586
residues.
Clothianidin; tolerances for
(a) * * *
Commodity
Parts per million
Beet, sugar, dried pulp ...
Beet, sugar, molasses ....
Beet, sugar, roots ...........
*
*
*
*
*
*
*
0.03
0.05
0.02
*
*
*
[FR Doc. E8–1784 Filed 2–5–08; 8:45 am]
BILLING CODE 6560–50–S
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Agencies
[Federal Register Volume 73, Number 25 (Wednesday, February 6, 2008)]
[Rules and Regulations]
[Pages 6851-6856]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-1784]
=======================================================================
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2007-0280; FRL-8346-9]
Clothianidin; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a tolerance for residues of
clothianidin in or on sugar beet roots, tops and molasses. Bayer
CropScience requested this tolerance under the Federal Food, Drug, and
Cosmetic Act (FFDCA).
DATES: This regulation is effective February 6, 2008. Objections and
requests for hearings must be received on or before April 7, 2008, and
must be filed in accordance with the instructions provided in 40 CFR
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2007-0280. To access the
electronic docket, go to https://www.regulations.gov, select ``Advanced
Search,'' then ``Docket Search.'' Insert the docket ID number where
indicated and select the ``Submit'' button. Follow the instructions on
the regulations.gov website to view the docket index or access
available documents. All documents in the docket are listed in the
docket index available in regulations.gov. Although listed in the
index, some information is not publicly available, e.g., Confidential
Business Information (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 in the electronic docket at https://www.regulations.gov, or,
if only available in hard copy, at the OPP Regulatory Public Docket in
Rm. S-4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr.,
Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The Docket Facility
telephone number is (703) 305-5805.
FOR FURTHER INFORMATION CONTACT: Kable Bo Davis, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number:
[[Page 6852]]
(703) 306-0415; e-mail address: davis.kable@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 those
engaged in the following activities:
Crop production (NAICS code 111), e.g., agricultural
workers; greenhouse, nursery, and floriculture workers; farmers.
Animal production (NAICS code 112), e.g., cattle ranchers
and farmers, dairy cattle farmers, livestock farmers.
Food manufacturing (NAICS code 311), e.g., agricultural
workers; farmers; greenhouse, nursery, and floriculture workers;
ranchers; pesticide applicators.
Pesticide manufacturing (NAICS code 32532), e.g.,
agricultural workers; commercial applicators; farmers; greenhouse,
nursery, and floriculture workers; residential users.
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at https://
www.regulations.gov, you may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at https://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of EPA's tolerance regulations at
40 CFR part 180 through the Government Printing Office's pilot e-CFR
site at https://www.gpoaccess.gov/ecfr.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of FFDCA, any person may file an objection to
any aspect of this regulation and may also request a hearing on those
objections. You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in 40 CFR part
178. To ensure proper receipt by EPA, you must identify docket ID
number EPA-HQ-OPP-2007-0280 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 as required by 40 CFR part 178 on or
before April 7, 2008.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit this copy, identified by docket ID number
EPA-HQ-OPP-2007-0280, by one of the following methods:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket Facility telephone number is (703) 305-5805.
II. Petition for Tolerance
In the Federal Register of April 30, 2007 (72 FR 21263) (FRL-8124-
5), 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
6F7159) by Bayer CropScience, 2 T.W. Alexander Drive, Research Triangle
Park, NC 27709. The petition requested that 40 CFR 180.586 be amended
by establishing a tolerance for residues of the insecticide
clothianidin, (E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-
nitroguanidine, in or on beet, sugar, root at 0.02 parts per million
(ppm); beet, sugar, tops at 0.04 ppm; and beet, sugar, molasses at 0.06
ppm. That notice referenced a summary of the petition prepared by Bayer
CropScience, the registrant, which is available to the public in the
docket, https://www.regulations.gov. There were no comments received in
response to the notice of filing.
Upon completing review of the current clothianidin database, the
Agency concluded that the appropriate tolerance levels for clothianidin
residues in or on pending crops should be established as follows: Beet,
sugar, roots at 0.02 ppm, beet, sugar, molasses at 0.05 ppm and beet,
sugar, dried pulp at 0.03 ppm. The Agency no longer considers sugar
beet tops to be a significant livestock feedstuff; therefore, a
separate tolerance for tops is not required.
III. Aggregate Risk Assessment and Determination of Safety
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....'' These provisions were added to FFDCA by the Food Quality
Protection Act (FQPA) of 1996.
Consistent with FFDCA section 408(b)(2)(D), and the factors
specified in FFDCA section 408(b)(2)(D), 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 for the petitioned-for tolerance
for residues of clothianidin on beet, sugar, roots at 0.02 ppm, beet,
sugar, molasses at 0.05 ppm and beet, sugar, dried pulp at 0.03. 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
[[Page 6853]]
concerning the variability of the sensitivities of major identifiable
subgroups of consumers, including infants and children. Specific
information on the studies received and the nature of the adverse
effects caused by clothianidin as well as the no-observed-adverse-
effect-level (NOAEL) and the lowest-observed-adverse-effect-level
(LOAEL) from the toxicity studies can be found at https://
www.regulations.gov. The risk assessment is available in the docket
established by this action, which is described under ADDRESSES, and is
identified as EPA-HQ-OPP-2007-0280 in that docket.
Clothianidin does not appear to exhibit toxicity towards a
consistent specific target organ. Decreases in body weight and body
weight gain were observed in rats, dogs, and mice. In single-dose
studies, mice (acute toxicity category II) appear more sensitive than
rats (category IV). Clinical signs of neurotoxicity were exhibited in
both mice (decreased motor activity, tremors, and deep respirations at
50 milligram/kilogram (mg/kg)) and rats (transient signs of decreased
arousal, motor activity, and locomotor activity at 100 mg/kg) in acute
neurotoxicity studies following exposure by gavage; however, no
indications of neurotoxicity were observed following dietary exposure
in the subchronic neurotoxicity study in rats. In a developmental
neurotoxicity study in rats, decreased body weights, body weight gains,
motor activity, and acoustic startle response amplitude (females) were
seen in offspring at doses lower than those resulting in maternal
toxicity. Although the NOAELs were similar for the subchronic and
chronic feeding studies in the rat, a greater spectrum of effects was
observed in the chronic study (decreased body weight, body weight gain,
and food consumption plus additional observations in the liver, ovary,
and kidney) versus the subchronic study (effects only on body weight
and food consumption). In the rat, administration via the oral route
appears to be more toxic than via the dermal route. In longer term
studies, dogs exhibited clinical signs of anemia. The only observed
effects in mice following chronic dietary administration were increases
in vocalization and decreases in body weight and body weight gain.
Clothianidin has been classified as not likely to be carcinogenic to
humans.
There was no evidence of increased quantitative or qualitative
susceptibility of rat or rabbit offspring in developmental studies;
however, increased quantitative susceptibility of rat pups was seen in
both the reproduction and developmental neurotoxicity studies. The
degree of concern for both of these studies is low because the observed
effects are well characterized, and there are clear NOAELs and LOAELs.
The NOAEL for the effects of concern identified in the reproduction
study (decreased mean body weight gain and absolute thymus weights in
pups, delayed sexual maturation, and an increase in still births) is
the basis for the endpoint selected for the chronic dietary and short-
term, intermediate-term and long-term non-dietary risk assessments.
In adult rats, a guideline immunotoxicity study shows no
clothianidin-mediated immunotoxicity at doses lower than those
resulting in generalized signs of toxicity (e.g., decreases in body
weight); however, it cannot be concluded that a similar lack of effects
will occur in offspring. Based on evidence of decreased absolute and
adjusted organ weights of the thymus and spleen in multiple studies in
the clothianidin data base and on evidence of increased quantitative
susceptibility of juvenile rats, compared to adults, in the 2-
generation reproduction study to these effects, a developmental
immunotoxicity (DIT) study has been required.
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, the toxicological level of concern (LOC) is derived
from the highest dose at which the NOAEL in the toxicology study
identified as appropriate for use in risk assessment. However, if a
NOAEL cannot be determined, the LOAEL is sometimes used for risk
assessment. Uncertainty/safety factors (UFs) are used in conjunction
with the LOC to take into account 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. Safety is assessed for acute and chronic risks by
comparing aggregate exposure to the pesticide to the acute population
adjusted dose (aPAD) and chronic population adjusted dose (cPAD). The
aPAD and cPAD are calculated by dividing the LOC by all applicable UFs.
Short-term, intermediate-term, and long-term risks are evaluated by
comparing aggregate exposure to the LOC to ensure that the margin of
exposure (MOE) called for by the product of all applicable UFs is not
exceeded.
For non-threshold risks, the Agency assumes that any amount of
exposure will lead to some degree of risk and estimates risk in terms
of the probability of occurrence of additional adverse cases.
Generally, cancer risks are considered non-threshold. For more
information on the general principles EPA uses in risk characterization
and a complete description of the risk assessment process, see https://
www.epa.gov/fedrgstr/EPA-PEST/1997/November/Day-26/p30948.htm.
A summary of the toxicological endpoints for clothianidin used for
human risk assessment can be found at https://www.regulations.gov in
document ``Clothianidin: Human Health Risk Assessment for Proposed Use
on Sugar Beet'' at pages 18-20 in docket ID number EPA-HQ-OPP-2007-
0280.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to clothianidin, EPA considered exposure under the petitioned-
for tolerances as well as all existing clothianidin tolerances in (40
CFR 180.586). EPA assessed dietary exposures from clothianidin in food
as follows:
i. Acute exposure. Quantitative acute dietary exposure and risk
assessments are performed for a food-use pesticide, if a toxicological
study has indicated the possibility of an effect of concern occurring
as a result of a 1-day or single exposure.
In estimating acute dietary exposure, EPA used food consumption
information from the U.S. Department of Agriculture (USDA) 1994-1996
and 1998 Nationwide Continuing Surveys of Food Intake by Individuals
(CSFII). The acute assessment is based on maximum residues of
clothianidin observed in clothianidin and thiamethoxam field trials and
assumes 100 percent crop treated (%CT).
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA 1994-1996
and 1998 CSFII. The chronic assessment is based on average residues
from clothianidin and thiamethoxam field trials and assumes 100% CT.
iii. Cancer. Because clothianidin is not expected to pose a cancer
risk, a quantitative dietary exposure assessment for the purposes of
assessing cancer risk was not conducted.
iv. Anticipated residue and percent crop treated (PCT) information.
Section 408(b)(2)(E) of FFDCA authorizes EPA to use available data and
information on the anticipated residue levels of pesticide residues in
food and the actual levels of pesticide residues that have been
measured in food. If EPA relies on such information, EPA must pursuant
to FFDCA section 408(f)(1) require that
[[Page 6854]]
data be provided 5 years after the tolerance is established, modified,
or left in effect, demonstrating that the levels in food are not above
the levels anticipated. For the present action, EPA will issue such
data call-ins as are required by FFDCA section 408(b)(2)(E) and
authorized under FFDCA section 408(f)(1). Data will be required to be
submitted no later than 5 years from the date of issuance of this
tolerance.
The Agency used PCT information as follows:
The acute assessment is based on maximum residues of clothianidin
observed in clothianidin field trials and assumes 100% crop treated.
The chronic assessment is based on average residues from clothianidin
field trials and also assumes 100% CT.
The Agency believes that the three conditions listed in Unit III.
have been met. With respect to Condition 1, PCT estimates are derived
from Federal and private market survey data, which are reliable and
have a valid basis. The Agency is reasonably certain that the
percentage of the food treated is not likely to be an underestimation.
As to Conditions 2 and 3, regional consumption information and
consumption information for significant subpopulations is taken into
account through EPA's computer-based model for evaluating the exposure
of significant subpopulations including several regional groups. Use of
this consumption information in EPA's risk assessment process ensures
that EPA's exposure estimate does not understate exposure for any
significant subpopulation group and allows the Agency to be reasonably
certain that no regional population is exposed to residue levels higher
than those estimated by the Agency. Other than the data available
through national food consumption surveys, EPA does not have available
information on the regional consumption of food to which clothianidin
may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring data to complete a comprehensive dietary exposure
analysis and risk assessment for clothianidin 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 environmental
fate characteristics of clothianidin. Further information regarding EPA
drinking water models used in pesticide exposure assessment can be
found at https://www.epa.gov/oppefed1/models/water/index.htm.
Based on the First Index Reservoir Screening Tool (FIRST) and
Screening Concentration in Ground Water (SCI-GROW) models, the
estimated environmental concentrations (EECs) of clothianidin for acute
exposures are estimated to be 7.29 parts per billion (ppb) for surface
water and 5.84 ppb for ground water. The EECs for chronic exposures are
estimated to be 1.35 ppb for surface water and 5.84 ppb for ground
water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For acute dietary risk
assessment, the water concentration value of 7.29 ppb was used to
access the contribution to drinking water. For chronic dietary risk
assessment, the water concentration of value 5.84 ppb was used to
access the contribution to drinking 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).
Clothianidin is currently registered for the following residential
non-dietary sites: Turfgrass. EPA assessed residential exposure using
the following assumptions: The following exposure scenarios were
assessed for residential post-application risks: Toddlers playing on
treated turf, adults performing yard work on treated turf, and adults
and youths playing golf on treated turf.
Additional information on residential exposure assumptions can be
found at www.regulations.gov (Docket ID EPA-HQ-OPP-2007-0280, pages 26
through 27).
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.''
Clothianidin is a member of the neonicotinoid class of pesticides
and is a metabolite of another neonicotinoid, thiamethoxam. Structural
similarities or common effects do not constitute a common mechanism of
toxicity. Evidence is needed to establish that the chemicals operate by
the same, or essentially the same sequence of major biochemical events
(EPA, 2002). Although clothianidin and thiamethoxam bind selectively to
insect nicotinic acetylcholine receptors (nAChR), the specific binding
site(s)/receptor(s) for clothianidin, thiamethoxam, and the other
neonicotinoids are unknown at this time. Additionally, the commonality
of the binding activity itself is uncertain, as preliminary evidence
suggests that clothianidin operates by direct competitive inhibition,
while thiamethoxam is a non-competitive inhibitor. Furthermore, even if
future research shows that neonicotinoids share a common binding
activity to a specific site on insect nicotinic acetylcholine
receptors, there is not necessarily a relationship between this
pesticidal action and a mechanism of toxicity in mammals. Structural
variations between the insect and mammalian nAChRs produce quantitative
differences in the binding affinity of the neonicotinoids towards these
receptors, which, in turn, confers the notably greater selective
toxicity of this class towards insects, including aphids and
leafhoppers, compared to mammals. While the insecticidal action of the
neonicotinoids is neurotoxic, the most sensitive regulatory endpoint
for clothianidin is based on unrelated effects in mammals, including
changes in body and thymus weights, delays in sexual maturation, and
still births. Additionally, the most sensitive toxicological effect in
mammals differs across the neonicotinoids (e.g., testicular tubular
atrophy with thiamethoxam; mineralized particles in thyroid colloid
with imidaclopid). Thus, there is currently no evidence to indicate
that neonicotinoids share common mechanisms of toxicity, and EPA is not
following a cumulative risk approach based on a common mechanism of
toxicity for the neonicotinoids. 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 concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a
common mechanism released by EPA's Office of Pesticide Programs on
EPA's website at https://www.epa.gov/pesticides/cumulative/.
Note that because clothianidin is a major metabolite of
thiamethoxam, EPA has combined exposure to clothianidin resulting both
from thiamethoxam use and from use of clothianidin as an active
ingredient and has compared this aggregate exposure estimate to
relevant endpoints for clothianidin. EPA has taken the further
conservative step of assuming that, in instances where both
thiamethoxam and clothianidin are
[[Page 6855]]
registered for use on a crop, both pesticides will, in fact, be used on
that crop.
D. Safety Factor for Infants and Children
1. In general. Section 408 of FFDCA provides that EPA shall apply
an additional (``10X'') tenfold margin of safety for infants and
children in the case of threshold effects to account for prenatal and
postnatal toxicity and the completeness of the database on toxicity and
exposure unless EPA determines based on reliable data that a different
margin of safety will be safe for infants and children. This additional
margin of safety is commonly referred to as the FQPA safety factor. In
applying this provision, EPA either retains the default value of 10X
when reliable data do not support the choice of a different factor, or,
if reliable data are available, EPA uses a different additional FQPA
safety factor value based on the use of traditional UFs and/or special
FQPA safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. In the developmental
neurotoxicity study, toxicity in the offspring was observed at a lower
dose level than the dose that caused toxicity in the maternal animals.
Maternal effects included decreased body weights, body weight gains,
and food consumption. Effects seen in the offspring included decreased
body weights, body weight gains, motor activity, and acoustic startle
response in the females. However, EPA determined that the degree of
concern for the developmental neurotoxicity study is low and there are
no residual uncertainties for prenatal and/or postnatal toxicity due to
the results of the developmental neurotoxicity study because the
observed effects are well characterized and there are clear NOAELs/
LOAELs.
In the 2-generation reproduction study, offspring toxicity
(decreased body weight gains, delayed sexual maturation in males,
decreased absolute thymus weights in F1 pups of both sexes, and an
increase in stillbirths in both generations) was seen at a lower dose
than the dose that caused parental toxicity. Based on evidence of
decreased absolute and adjusted organ weights of the thymus and spleen
in multiple studies in the clothianidin data base and on evidence of
increased quantitative susceptibility of juvenile rats, compared to
adults, in the 2-generation reproduction study to these effects. EPA
has required that testing be conducted to assess immune system function
in adults and in young animals following exposure during the period of
organogenesis. No quantitative or qualitative susceptibility was
observed in either of the developmental rat or rabbit studies. In the
rat, no developmental toxicity was observed at the highest dose tested,
although this dose level induced decreases in body weight gain and food
consumption in the dams. In the rabbit, premature deliveries, decreased
gravid uterine weights, an increase in litter incidence of a missing
lobe of the lung, and a decrease in the litter average for ossified
sternal centra per fetus were noted at a dose level in which maternal
death, a decrease in food consumption, and clinical signs (scant feces
and orange urine) were observed. Since the developmental effects
observed in the rabbit study were seen in the presence of maternal
toxicity, they are not considered to be qualitatively more severe than
the maternal effects.
3. Conclusion. The exposure data for clothianidin are complete or
are estimated based on data that reasonably accounts for potential
exposures. The acute dietary exposure assessment is based on maximum
residues of clothianidin observed in clothianidin and thiamethoxam
field trials and assumes 100% CT. The chronic assessment is based on
average residues from clothianidin and thiamethoxam field trials and
also assumes 100% CT. For water, the highest acute estimate from
conservative models was used for both the acute and the chronic dietary
exposure analyses. By using these conservative assessments, acute and
chronic exposures/risks will not be underestimated. The residential
exposure assessment utilizes residential standard operation procedures
(SOPs) to assess post-application exposure to children as well as
incidental oral ingestion by toddlers. The residential SOPs are based
on reasonable worst-case assumptions and will not likely underestimate
exposure/risk. These assessments are unlikely to underestimate the
potential exposure to 74,800 infants and children resulting from the
use of clothianidin.
The toxicology data base for clothianidin, however, is not complete
for FQPA purposes. A complete complement of acceptable developmental,
reproduction, developmental neurotoxicity, mammalian neurotoxicity and
special neurotoxicity studies are available; however, due to evidence
of decreased absolute and adjusted organ weights of the thymus and
spleen in multiple studies in the clothianidin database, and because
juvenile rats in the two-generation reproduction study appear to be
more susceptible to these effects, EPA has determined that testing
should be conducted to assess immune system function in adults and in
young animals following developmental exposures. Given the levels at
which this testing should be conducted it could result in selection of
a more protective (i.e., lower) regulatory endpoint.
Due to the uncertainty with regard to potential effects on immune
system function in young animals, EPA cannot conclude that there are
reliable data supporting selection of a children's safety factor
different from the presumptive 10X factor. Therefore, the 10X FQPA
children's safety factor will be retained. This safety factor will be
in the form of a database uncertainty factor to account for the lack of
the testing with regard to immune system function with clothianidin.
E. Aggregate Risks and Determination of Safety
Safety is assessed for acute and chronic risks by comparing
aggregate exposure to the pesticide to the aPAD and cPAD. The aPAD and
cPAD are calculated by dividing the LOC by all applicable UFs. For
linear cancer risks, EPA calculates the probability of additional
cancer cases given aggregate exposure. Short-term, intermediate-term,
and long-term risks are evaluated by comparing aggregate exposure to
the LOC to ensure that the MOE called for by the product of all
applicable UFs is not exceeded.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food and water
to clothianidin will occupy 45% of the aPAD for the population group
(children 1-2 years old) receiving the greatest exposure.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
clothianidin from food and water will utilize 16% of the cPAD for the
population group (children 1-2 years old). Based on the use pattern,
chronic residential exposure to residues of clothianidin is not
expected.
3. Short-term / Intermediate-term risk. Short-term aggregate and
intermediate-term aggregate exposures take into account residential
exposure plus chronic exposure to food and water (considered to be a
background exposure level).
Clothianidin is currently registered for use(s) that could result
in short-term residential exposure and the Agency has determined that
it is appropriate to aggregate chronic food and water and short-term
exposures for clothianidin.
EPA has determined that, for clothianidin, the toxicological
effects
[[Page 6856]]
are the same across oral, dermal, and inhalation routes of exposure and
has selected the same endpoint and dose for short-term and
intermediate-term exposure scenarios. Therefore, the exposures are
simply summed (combined/aggregated) for use in risk calculations.
Short- and intermediate aggregate risk estimates range from an MOE of
1,100 for toddlers (food + water + treated turf + treated soil +
dermal) to 22,000 for youth golfers (food + water + post-application
treated turf). The short-term and intermediate-term aggregate risks
associated with the registered and proposed uses of clothianidin do not
exceed the Agency's LOC for the general U.S. population or any
population subgroup.
4. Aggregate cancer risk for U.S. population. Clothianidin has been
classified as a ``not likely human carcinogen.'' It is not expected to
pose a cancer risk.
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, or to infants and children from aggregate
exposure to clothianidin residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate liquid chromotography/mass spectrometry/mass spectrometry
(LC/MS/MS) methods are available for both collecting data and enforcing
tolerances for clothianidin residues in plant (Bayer Methods 00552 and
109240-1) and animal (Bayer Method 00624) commodities. The validated
limit of quantitation (LOQ) for clothianidin in plant commodities is
0.010 ppm, except for wheat straw (0.020 ppm), and the validated LOQs
are 0.010 ppm in milk and 0.020 ppm in animal tissues. All three of
these methods have been reviewed by EPA's Analytical Chemistry
Laboratory (ACL), approved for tolerance enforcement, and forwarded to
FDA for inclusion in PAM Volume II.
B. International Residue Limits
There are no established or proposed Canadian, Mexican, or Codex
maximum residue limits (MRLs) for clothianidin residues on sugar beet
commodities.
V. Conclusion
Therefore, the tolerance is established for residues of (E)-1-(2-
chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine, in or on
beet, sugar, roots at 0.02 ppm, beet, sugar, molasses at 0.05 ppm and
beet, sugar, dried pulp at 0.03.
VI. 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, 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) or Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997). 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., 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).
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.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 6, 2000) do not apply to this rule. In addition, This
rule does not 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).
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).
VII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report 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: January 22, 2008.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. Section 180.586 is amended by alphabetically adding the following
commodities to the table in paragraph (a) to read as follows:
Sec. 180.586 Clothianidin; tolerances for residues.
(a) * * *
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
Beet, sugar, dried pulp.............................. 0.03
Beet, sugar, molasses................................ 0.05
Beet, sugar, roots................................... 0.02
* * * * *
------------------------------------------------------------------------
* * * * *
[FR Doc. E8-1784 Filed 2-5-08; 8:45 am]
BILLING CODE 6560-50-S