[Federal Register Volume 76, Number 86 (Wednesday, May 4, 2011)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-10706]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Clothianidin; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of
clothianidin in or on mustard, seed. Bayer CropScience requested these
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective May 4, 2011. Objections and
requests for hearings must be received on or before July 5, 2011, 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-2008-0771. All documents in the
docket are listed in the docket index available at http://www.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 http://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)
FOR FURTHER INFORMATION CONTACT: Marianne Lewis, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-8043; e-mail address: email@example.com.
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).
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 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
B. How can I access electronic copies of this document?
You may access a frequently updated electronic version of EPA's
tolerance regulations at 40 CFR part 180 through the Government
Printing Office's e-CFR cite at http://www.gpoaccess.gov/ecfr.
C. Can I file an objection or hearing request?
Under section 408(g) of FFDCA, 21 U.S.C. 346a, 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-2008-0771 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 July 5, 2011.
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
HQ-OPP-2008-0771, by one of the following methods:
Federal eRulemaking Portal: http://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 Facility'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. Summary of Petitioned-For Tolerance
In the Federal Register of June 23, 2010 (75 FR 35803) (FRL-8831-
3), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
0F7712) by Bayer CropScience, P.O. Box 12014, 2 T.W. Alexander Drive,
Research Triangle Park, NC 27709. The petition requested that 40 CFR
180.586 be amended by establishing tolerances for residues of the
insecticide clothianidin, (E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-
methyl-2-nitroguanidine, in or on mustard, seed at 0.01 parts per
million (ppm). That notice referenced a summary of the petition
prepared by Bayer CropScience, the registrant, which is available to
the public in the docket, http://www.regulations.gov. There were no
comments received in response to the notice of filing.
Bayer CropScience requested tolerances for residues of clothianidin
to support mustard, seed treatment uses.
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. * *
Consistent with section 408(b)(2)(D) of FFDCA, and the factors
specified in 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 for the petitioned-for
tolerances for clothianidin. EPA's assessment of exposures and risks
associated with clothianidin 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
EPA considered the toxicity of clothianidin as well as several
metabolites and degradates in conducting this risk assessment.
Metabolites/degradates of concern in plants include parent and TMG for
leafy and root and tuber vegetables; parent-only for other crops; and
parent, TZNG and MNG for rotational crops. For livestock commodities,
the metabolites/degradates of concern include: Parent and TZU, TZG,
TZNG and ATMG-pyruvate for ruminants; and parent and TZU, TZG, TZNG,
and ATG-acetate for poultry. Acute toxicity and genotoxicity data are
available for several metabolites/degradates of clothianidin. Given
that the points of departure (POD) used for risk assessment are well
below the LD50 levels observed in the acute toxicology
studies and that clothianidin and its metabolites/degradates of
toxicological concern are similar in structure, EPA is assuming that
these compounds are toxicologically equivalent to clothianidin with
respect to the endpoints being used for risk assessment.
Clothianidin and its metabolites and degradates have relatively low
acute toxicity via oral, dermal and inhalation routes of exposure;
however, acute oral administration of clothianidin in mouse and the TMG
metabolite in rat showed evidence of increased relative toxicity. There
is no evidence of dermal sensitization or eye irritation with the
exception of the clothianidin-triazan intermediate, which is a dermal
sensitizer. The available data indicate that there are no consistent
target organs in mammals; however, some effects noted in the liver,
hematopoietic system and kidney are similar to effects from other
In subchronic oral studies, the dog seemed to be more sensitive to
clothianidin than the rat. In addition to decreases in body weight and
body weight gains observed in both animals, dogs also displayed
decreased white blood cells, albumin and total protein, as well as some
anemia. Long-term dietary administration of clothianidin did not result
in a wider spectrum of effects in the dog; in contrast, the chronic
feeding studies in rats showed additional effects in the liver, ovaries
and kidneys. In the mouse chronic oral study, increases in vocalization
and decreases in body weight and body weight gain were noted.
Based on the lack of significant tumor increases in two adequate
rodent carcinogenicity studies, EPA has classified clothianidin as
``not likely to be carcinogenic to humans.'' A bone marrow micronucleus
assay in mice showed that clothianidin is neither clastogenic nor
aneugenic up to a toxic oral dose. Additionally, a study on the livers
of Wistar male mice showed no induction of unscheduled DNA sysnthesis
up to the limit dose; therefore, mutagenicity is not of concern.
Clinical signs of neurotoxicity were exhibited in both rats
(decreased arousal, motor activity and locomotor activity) and mice
(decreased spontaneous motor activity, tremors and deep respirations)
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.
There was no evidence of increased quantitative or qualitative
susceptibility of rat or rabbit fetuses following in utero exposure to
clothianidin in developmental studies; however, increased quantitative
susceptibility of rat pups was seen in both the reproduction and
developmental neurotoxicity studies. In the rat reproduction study,
offspring toxicity (decreased body weight gains and absolute thymus
weights in pups, delayed sexual maturation and an increase in
stillbirths) was observed in the absence of maternal effects. In the
developmental neurotoxicity study in rats, offspring effects (decreased
weights, body weight gains, motor activity and acoustic startle
response amplitude) were noted at doses lower than those resulting in
Decreased absolute and relative thymus and spleen weights were
observed in multiple studies; these studies showed possible evidence of
effects on the immune system. In addition, juvenile rats in the rat
reproduction study appeared to be more susceptible to these effects.
However, a guideline immunotoxicity study showed no evidence of
clothianidin-mediated immunotoxicity in adult rats and a developmental
immunotoxicity study demonstrated no increased susceptibility for
offspring with regard to immunotoxicity.
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 http://www.regulations.gov in document ``Clothianidin: Human Health Risk
Assessment for Proposed Uses on Berries (Group 13-07H), Brassica
Vegetables (Group 5), Cotton, Cucurbit Vegetables (Group 9), Fig,
Fruiting Vegetables (Group 8), Leafy Green Vegetables (Group 4A),
Peach, Pomegranate, Soybean, Tree Nuts (Group 14), and Tuberous and
Corm Vegetables (Group 1C)'' in docket ID number EPA-HQ-OPP-2008-0945.
B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA
identifies toxicological POD and levels of concern to use in evaluating
the risk posed by human exposure to the pesticide. For hazards that
have a threshold below which there is no appreciable risk, the
toxicological POD is used as the basis for derivation of reference
values for risk assessment. PODs are developed based on a careful
analysis of the doses in each toxicological study to determine the dose
at which no adverse effects are observed (the NOAEL) and the lowest
dose at which adverse effects of concern are identified (the LOAEL).
Uncertainty/safety factors are used in conjunction with the POD to
calculate a safe exposure level--generally referred to as a population-
adjusted dose (PAD) or a reference dose (RfD)--and a safe margin of
exposure (MOE). For non-threshold risks, the Agency assumes that any
amount of exposure will lead to some degree of risk. Thus, the Agency
estimates risk in terms of the probability of an occurrence of the
adverse effect expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for clothianidin used for
human risk assessment is shown in the Table of this unit.
Table--Summary of Toxicological Doses and Endpoints for Clothianidin for Use in Human Health Risk Assessment
Point of departure and
Exposure/scenario uncertainty/safety RfD, PAD, LOC for risk Study and toxicological
factors assessment effects
Acute dietary (Females 13-49 years NOAEL = 25 milligrams/ Acute RfD = 0.25 mg/kg/ Rabbit developmental study.
of age). kilograms/day (mg/kg/ day. LOAEL = 75 mg/kg/day based
day). aPAD = 0.25mg/kg/day.. on increased litter
UFA = 10x............. incidence of a missing
UFH = 10x............. lobe of the lung.
FQPA SF = 1x..........
Acute dietary (General population). NOAEL = 25 mg/kg/day.. Acute RfD = 0.25 mg/kg/ Special neurotoxicity/
UFA = 10x............. day. pharmacological study in
UFH = 10x............. aPAD = 0.25 mg/kg/day. mice.
FQPA SF = 1x.......... LOAEL = 50 mg/kg/day based
on transient signs of
motor activity, tremors
and deep respirations.
Chronic dietary (All populations NOAEL= 9.8 mg/kg/day.. Chronic RfD = 0.098 mg/ 2-Generation reproduction
including infants and children). UFA = 10x............. kg/day. study.
UFH = 10x............. cPAD = 0.098 mg/kg/ LOAEL = 31.2 mg/kg/day
FQPA SF = 1x.......... day.. based on decreased body
weight gains and delayed
decreased absolute thymus
weights in F1 pups and
increased stillbirths in
Incidental oral (Short and NOAEL= 9.8 mg/kg/day.. LOC for MOE = 100..... 2-Generation reproduction
intermediate term). UFA = 10x............. study.
UFH = 10x............. LOAEL = 31.2 mg/kg/day
FQPA SF = 1x.......... based on decreased body
weight gains and delayed
decreased absolute thymus
weights in F1 pups and
increased stillbirths in
Dermal (All durations)............. Oral study NOAEL = 9.8 LOC for MOE = 100..... 2-Generation reproduction
mg/kg/day (dermal study.
absorption rate = 1%. LOAEL = 31.2 mg/kg/day
UFA = 10x............. based on decreased body
UFH = 10x............. weight gains and delayed
FQPA SF = 1x.......... sexual maturation,
decreased absolute thymus
weights in F1 pups and
increased stillbirths in
Inhalation (All durations)......... Oral study NOAEL= 9.8 LOC for MOE = 100..... 2-Generation reproduction
mg/kg/day (inhalation study.
absorption rate = LOAEL = 31.2 mg/kg/day
100%). based on decreased body
UFA = 10x............. weight gains and delayed
UFH = 10x............. sexual maturation,
FQPA SF = 1x.......... decreased absolute thymus
weights in F1 pups and
increased stillbirths in
Cancer (Oral, dermal, inhalation).. ``Not likely to be Carcinogenic to Humans''
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
of the human population (intraspecies). FQPA SF = Food Quality Protection Act Safety Factor. PAD = population
adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to clothianidin, EPA considered exposure from the petitioned-
for tolerances as well as all existing clothianidin tolerances in 40
CFR 180.586. EPA assessed dietary exposures from clothianidin in food
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.
Such effects were identified for clothianidin. In estimating acute
dietary exposure, EPA used food consumption information from the United
States Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide
Continuing Surveys of Food Intake by Individuals (CSFII). As to residue
levels in food from use of clothianidin, EPA used maximum field trial
values, empirical processing factors and assumed 100 percent crop
treated (PCT) for all commodities. Clothianidin is a major metabolite
of thiamethoxam, and there are a number of crops for which uses of both
clothianidin and thiamethoxam have been registered. The labels for the
various end-use products containing these active ingredients prohibit
the application of both active ingredients to the same crop during a
growing cycle. Due to that restriction and the assumption of 100 PCT, a
single value reflecting the greatest clothianidin residue from either
active ingredient has been used for crops listed for use with both
active ingredients (versus combined estimates from clothianidin and
from thiamethoxam). Generally, this assessment uses the established or
recommended clothianidin tolerance for crops having tolerances for both
compounds (the exception being low-growing berry, subgroup 13-07G,
which is based on observed clothianidin residues in thiamethoxam
strawberry field trials). For foods with thiamethoxam tolerances but
without clothianidin tolerances, maximum residues of clothianidin
observed in thiamethoxam field trials have been used in these
assessments. These include meats, meat by-products, artichoke, tropical
fruits, coffee, hop, mint, rice, and strawberry. The metabolism of
clothianidin is complex, with a few major (> 10% of the total
radioactive residues) and numerous minor metabolites. Metabolites/
degradates of concern in plants include clothianidin and TMG for leafy
and root and tuber vegetables; parent-only for other crops; and parent,
TZNG and MNG for rotational crops. For livestock commodities, the
metabolites of concern include: Parent and TZU, TZG, TZNG, and ATMG-
pyruvate for ruminants; and parent and TZU, TZG, TZNG, and ATG-acetate
for poultry. For leafy vegetables the EPA required analysis for
residues of TMG along with parent in field trial samples. Residues of
TMG were shown to occur in leafy vegetables at levels approximately 10-
fold below those of clothianidin. EPA has not included these
metabolites in the tolerance expression for plant or animal commodities
because the metabolites are only found in certain commodities,
including the metabolites would create tolerance harmonization issues
with Canada, and monitoring residues of clothianidin based on parent
only would be representative of total clothianidin residues and thus
adequate for enforcement. Because the metabolites are not included in
the tolerance expressions, an adjustment factor of 1.1 has been
incorporated into the assessment for leafy vegetables to account for
the presence of the metabolite TMG, and an adjustment factor of 1.5 has
been incorporated for livestock-derived commodities (milk) to account
for the presence of metabolites TZU, TZG, TZNG, ATMG-pyruvate and ATG-
acetate. The 1.1 adjustment factor is based on field trial data showing
TMG does not exceed 10% of the parent compound residue level in leafy
vegetables and the 1.5 factor was based on metabolism data.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA 1994-1996
and 1998 CSFII. As to residue levels in food, EPA assessed chronic
dietary exposure using the same residue information and assumptions
regarding metabolites/degradates as in the acute exposure analysis.
iii. Cancer. Based on the lack of evidence of carcinogenicity in
two adequate rodent carcinogenicity studies, EPA has classified
clothianidin as ``not likely to be carcinogenic to humans.'' Therefore,
a quantitative exposure assessment to evaluate cancer risk is
iv. Anticipated residue and PCT information. For food with
thiamethoxam tolerances but without colothianidin tolerances, maximum
residues of clothianidin observed in thiamethoxam field trials have
been used in these assessments. For all commodities, 100 PCT was
2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for clothianidin in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of clothianidin. Further information regarding EPA
drinking water models used in pesticide exposure assessment can be
found at http://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 drinking water concentrations (EDWCs) of clothianidin for
surface water are estimated to be 7.29 parts per billion (ppb) for
acute exposures and 1.35 ppb for chronic exposures. For ground water,
the EDWC is estimated to be 5.88 ppb.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. The water concentration value
of 7.29 ppb was used to assess the contribution to drinking water for
the acute dietary assessment. For chronic dietary risk assessment, the
water concentration value of 5.88 ppb was used.
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 use on turf. Residential
handler exposure is not expected from the currently registered or
proposed uses of clothianidin since these products are to be applied by
commercial applicators. Adult short- and intermediate-term
postapplication exposures were assessed for dermal exposures from
commercial applications (via granular push-type spreaders), dermal
post-application contact and golfer postapplication contact. For
toddlers, short- and intermediate-term postapplication incidental oral
(hand-to-mouth and soil ingestion) and dermal risks were assessed for
exposure to treated turf.
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
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 nAChRs, 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 (such as testicular tubular atrophy with thiamethoxam,
and 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 OPP on EPA's Web site at http://www.epa.gov/pesticides/cumulative/.
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(c) of FFDCA provides that EPA
shall apply an additional tenfold (10X) 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 (SF). In applying this provision, EPA either retains the default
value of 10X, or uses a different additional safety factor when
reliable data available to EPA support the choice of a different
2. Prenatal and postnatal sensitivity. There is no indication of
increased quantitative or qualitative susceptibility, as compared to
adults, of rat and rabbit fetuses following in utero exposure to
clothianidin in developmental studies. However, increased quantitative
susceptibility was observed in both the developmental neurotoxicity and
rat multi-generation reproduction studies. In the developmental
neurotoxicity study, offspring toxicity (decreased body weight gains,
motor activity and acoustic startle response) was seen at a lower dose
than that which caused maternal toxicity. In the 2-generation rat
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 dose lower than that which caused parental
3. Conclusion. In the final rule published in the Federal Register
of February 6, 2008 (73 FR 6851) (FRL-8346-9), EPA had previously
determined that the FQPA SF for clothianidin should be retained at 10X
because EPA had required the submission of a developmental
immunotoxicity study to address the combination of evidence of
decreased absolute and adjusted organ weights of the thymus and spleen
in multiple studies in the clothianidin data base, and evidence showing
that juvenile rats in the 2-generation reproduction study appear to be
more susceptible to these potential immunotoxic effects. In the absence
of a developmental immunotoxicity study EPA concluded that there was
sufficient uncertainty regarding immunotoxic effects in the young that
the 10X FQPA factor should be retained as a database uncertainty
factor. Since that determination, EPA has received and reviewed an
acceptable/guideline developmental immunotoxicity study, which
demonstrated no treatment-related effects. Taking the results of this
study into account as well as the rest of the data on clothianidin, EPA
has determined that reliable data show the safety of infants and
children would be adequately protected if the FQPA SF for clothianidin
were reduced to 1X. That decision is based on the following findings:
i. The toxicity database for clothianidin is complete. As noted,
the prior data gap concerning developmental immunotoxicity has been
addressed by the submission of an acceptable developmental
ii. A rat developmental neurotoxicity study is available and shows
evidence of increased quantitative susceptibility of offspring.
However, EPA considers the degree of concern for the developmental
neurotoxicity study to be low for pre- and postnatal toxicity because
the NOAEL and LOAEL were well characterized, and the doses and
endpoints selected for risk assessment are protective of the observed
susceptibility; therefore, there are no residual concerns regarding
effects in the young.
iii. While the rat multi-generation reproduction study showed
evidence of increased quantitative susceptibility of offspring compared
to adults, the degree of concern is low because the study NOAEL and
LOAEL have been selected for risk assessment purposes for relevant
exposure routes and durations. In addition, the potential immunotoxic
effects observed in the study have been further characterized with the
submission of a developmental immunotoxicity study that showed no
evidence of susceptibility. As a result, there are no concerns or
residual uncertainties for pre- and postnatal toxicity after
establishing toxicity endpoints and traditional UFs to be used in the
risk assessment for clothianidin.
iv. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed based
on assumptions that were judged to be highly conservative and health-
protective for all durations and population subgroups, including
maximum field trial residues, adjustment factors from metabolite data,
empirical processing factors, and 100 PCT for all commodities.
Additionally, EPA made conservative (protective) assumptions in the
ground and surface water modeling used to assess exposure to
clothianidin in drinking water. EPA
used similarly conservative assumptions to assess postapplication
exposure of children and adults as well as incidental oral exposure of
toddlers. These assessments will not underestimate the exposure and
risks posed by clothianidin.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic dietary pesticide
exposures are safe by comparing aggregate exposure estimates to the
aPAD and cPAD. For linear cancer risks, EPA calculates the probability
of additional cancer cases given the estimated aggregate exposure.
Short-, intermediate-, and chronic-term risks are evaluated by
comparing the estimated aggregate food, water, and residential exposure
to the appropriate POD to ensure that an adequate MOE exists.
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 23% of the aPAD for children 1-2 years old,
the population group receiving the greatest exposure.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
clothianidin from food and water will utilize 19% of the cPAD for
children 1-2 years old, the population group receiving the greatest
exposure. Based on the explanation in Unit III.C.3., regarding
residential use patterns, chronic residential exposure to residues of
clothianidin is not expected.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account short- and intermediate-term
residential exposure plus chronic exposure to food and water
(considered to be a background exposure level).
Clothianidin is currently registered for use on turf that could
result in short- and intermediate-term residential exposure and the
Agency has determined that it is appropriate to aggregate chronic
exposure through food and water with short- and intermediate-term
residential exposures to clothianidin. Using the exposure assumptions
described in this unit for short- and intermediate-term exposures, EPA
has concluded the combined short- and intermediate-term food, water,
and residential exposures result in aggregate MOEs of greater than 380
for all population subgroups. As the aggregate MOEs are greater than
100 (the LOC) for all population subgroups, including infants and
children, short- and intermediate-term aggregate exposures to
clothianidin are not of concern to EPA.
4. Aggregate cancer risk for U.S. population. Based on the lack of
evidence of carcinogenicity in mice and rats at doses that were judged
to be adequate to assess the carcinogenic potential, clothianidin was
classified as ``not likely to be carcinogenic to humans,'' and is not
expected to pose a cancer risk 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, or to infants and children from aggregate
exposure to clothianidin residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology is available to enforce the
tolerance expression. This method involves extraction of residues with
acetonitrile/water, cleanup using solid phase extraction (SPE)
cartridges, and analysis of clothianidin by liquid chromatography/mass
spectrometry/mass spectrometry (LC/MS/MS). The method may be requested
from: Chief, Analytical Chemistry Branch, Environmental Science Center,
701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-
2905; e-mail address: firstname.lastname@example.org.
B. International Residue Limits
In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and
Agriculture Organization/World Health Organization food standards
program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
The Codex has not established a MRL for clothianidin in/on mustard,
C. Revisions to Petitioned-For Tolerances
The tolerance is considered appropriate as proposed; therefore, no
revisions were needed.
Therefore, tolerances are established for residues of clothianidin,
or on mustard, seed at 0.01 ppm.
VI. Statutory and Executive Order Reviews
This final rule establishes tolerances 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 final rule has been
exempted from review under Executive Order 12866, this final rule is
not subject to Executive Order 13211, entitled 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 9, 2000) do not apply to this final
rule. In addition, this final 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) (Pub. L. 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
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
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: April 26, 2011.
G. Jeffrey Herndon,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.586 is amended by alphabetically adding ``Mustard,
seed'' to the table in paragraph (a)(1) to read as follows:
Sec. 180.586 Clothianidin; tolerances for residues.
(a) * * *
(1) * * *
* * * * *
Mustard, seed.............................................. 0.01
* * * * *
* * * * *
[FR Doc. 2011-10706 Filed 5-3-11; 8:45 am]
BILLING CODE 6560-50-P