[Federal Register Volume 74, Number 242 (Friday, December 18, 2009)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-30131]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Dinotefuran; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for combined residues
of dinotefuran in or on Brassica, leafy greens, subgroup 5B and turnip,
greens. The Interregional Research Project Number 4 (IR-4) requested
these tolerances under the Federal Food, Drug, and Cosmetic Act
DATES: This regulation is effective December 18, 2009. Objections and
requests for hearings must be received on or before February 16, 2010,
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-2009-0013. 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: Sidney Jackson, Registration Division,
Office of Pesticide Programs, Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number:
(703) 305-7610; e-mail address: [email protected].
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-
2009-0013 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 February 16,
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-2009-0013, 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. Petition for Tolerance
In the Federal Register of April 8, 2009 (74 FR 15971) (FRL-8407-
4), 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
8E7433) by IR-4, IR-4 Project Headquarters, 500 College Road East,
Suite 201 W, Princeton, NJ 08540. The petition requested that 40 CFR
180.603 be amended by establishing tolerances for combined residues of
the insecticide dinotefuran, (RS)-1-methyl-2-nitro-3-((tetrahydro-3-
furanyl)methyl)guanidine and its major metabolites DN, 1-methyl-3-
(tetrahydro-3-furylmethyl)guanidine, and UF, 1-methyl-3-(tetrahydro-3-
furylmethyl)-urea, expressed as dinotefuran in or on Brassica, leafy
greens, subgroup 5B at 17 parts per million (ppm) and turnip, greens at
17.0 ppm. That notice referenced a summary of the petition prepared by
Valent USA Corporation and Mitsui Chemical Inc., the registrants on
behalf of IR-4, 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.
Based upon review of the data supporting the petition, EPA has
revised the proposed tolerance of 17.0 ppm for both Brassica, leafy
greens, subgroup 5B, and turnip, greens to 15.0 ppm. The reason for
these changes are explained in Unit IV.C.
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 combined residues of dinotefuran in or on Brassica,
leafy greens, subgroup 5B at 15.0 ppm and turnip, greens at 15.0 ppm.
EPA's assessment of exposures and risks associated with establishing
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered their
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
Dinotefuran has low acute toxicity by oral, dermal, and inhalation
exposure routes. It is not a dermal sensitizer, but causes a low level
of skin irritation. The main target tissues are the nervous system and
the immune system, with effects seen in several species. Nervous system
toxicity is manifested as clinical signs and decreased motor activity
seen after acute dosing (in both rats and rabbits) and increased motor
activity seen after repeated dosing; these findings are consistent with
effects on the nicotinic cholinergic nervous system. Immune system
toxicity is manifested as decreases in spleen and thymus weights, seen
in multiple studies and species (including dogs, rats, and mice). There
are also indications of endocrine-related toxicity, manifested in the
reproductive toxicity study (in rats) as decreases in primordial
follicles and altered cyclicity in females, and abnormal sperm
parameters in males at the Limit Dose; changes in testes or ovary
weight were also seen in several species (mouse, dog, and rat).
No adverse effects in fetuses were seen in the developmental
toxicity studies in rats or rabbits, at maternally toxic doses, and
offspring effects in the reproduction study occurred at the same doses
causing parental effects. Acceptable oncogenicity and mutagenicity
studies provide no indication that dinotefuran is carcinogenic or
Review of available studies including developmental toxicity
studies in rats and rabbits, a reproductive toxicity study in rats, and
acute and subchronic neurotoxicity studies in rats led to the
conclusions that there is low concern for prenatal and/or postnatal
toxicity resulting from exposure to dinotefuran. However, there is a
concern for neurotoxicity and developmental neurotoxicity resulting
from exposure to dinotefuran. Considering the overall toxicity profile
and the doses and endpoints selected for risk assessment for
dinotefuran, the degree of concern for the effects observed in the rat
reproduction study is characterized as low, noting these effects
occurred in the presence of parental toxicity and only at the highest
dose tested. For all toxicity endpoints established for dinotefuran, a
NOAEL lower than this offspring NOAEL is used. No residual
uncertainties were identified.
Specific information on the studies received and the nature of the
adverse effects caused by dinotefuran 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 the document ``Dinotefuran: Human Health Risk
Assessment for Proposed Uses on Brassica Leafy Vegetables Subgroup 5B
and Turnip Greens,'' dated August 6, 2009, page 11 in docket ID number
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, a toxicological point of departure (POD) is
identified as the basis for derivation of reference values for risk
assessment. The POD may be defined as the highest dose at which no
adverse effects are observed (the NOAEL) in the toxicology study
identified as appropriate for use in risk assessment. However, if a
NOAEL cannot be determined, the lowest dose at which adverse effects of
concern are identified (the LOAEL) or a Benchmark Dose (BMD) approach
is sometimes used for risk assessment. Uncertainty/safety factors (UFs)
are used in conjunction with the POD 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
dietary risks by comparing aggregate food and water 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 POD by all applicable UFs. Aggregate short-, intermediate-
, and chronic-term risks are evaluated by comparing food, water, and
residential exposure to the POD to ensure that the margin of exposure
(MOE) called for by the product of all applicable UFs is not exceeded.
This latter value is referred to as the Level of Concern (LOC).
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
greater than that 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 dinotefuran used for
human risk assessment can be found at http://www.regulations.gov in
document ``Dinotefuran: Human Health Risk Assessment for Proposed Uses
on Brassica Leafy Vegetables Subgroup 5B and Turnip Greens,'' dated
August 6, 2009, page 14 in docket ID number EPA-HQ-OPP-2009-0013-0004.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to dinotefuran, EPA considered exposure under the petitioned-
for tolerances as well as all existing dinotefuran tolerances in 40 CFR
180.603. EPA assessed dietary exposures from dinotefuran in food as
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). As to residue levels in food, EPA assumed 100 percent crop
treated (PCT) and tolerance level residues of dinotefuran.
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 assumed 100 PCT and
tolerance level residues of dinotefuran in all registered raw
agricultural commodity uses.
iii. Cancer. Dinotefuran is classified as ``not likely to be a
carcinogen'' based on the absence of significant tumor increases in two
acceptable rodent carcinogenicity studies. Therefore, no exposure
assessment for quantifying cancer risk was performed.
iv. Anticipated residue and PCT information. EPA did not use
anticipated residue and/or PCT information in the dietary assessment
for dinotefuran. Tolerance level residues and/or 100 PCT were assumed
for all food commodities.
2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for dinotefuran in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of dinotefuran. 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.
The Agency has determined that it is appropriate to estimate for
parent dinotefuran and its metabolites/degradates MNG, DN, UF, and DN-
2-OH + DN-3-OH in drinking water.
Based on the Pesticide Root Zone Model/Exposure Analysis Modeling
System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-
GROW) models, the estimated drinking water concentrations (EDWCs) of
dinotefuran and its metabolites for acute exposures are estimated to be
75.78 parts per billion (ppb) for surface water and 2.75 ppb for ground
For chronic exposures, non-cancer assessments are estimated to be
20.97 ppb for surface water and 2.75 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 75.78 ppb was used to
assess the contribution to drinking water.
For chronic dietary risk assessment, the water concentration value
of 20.97 ppb was used to assess 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).
Dinotefuran is currently registered for the following uses that
could result in residential exposures: Professional turf management,
professional ornamental production, and residential lawns. The risk
assessment was conducted using the following residential exposure
assumptions: Outdoor uses for turf farms, golf courses, residential
lawns, and ornamentals.
There is a potential for short-term and intermediate-term exposures
to homeowners in residential settings during the application of
pesticide products containing dinotefuran. There is also a potential
for exposure from entering areas previously treated with dinotefuran
such as lawns where children might play, or golf courses and home
gardens that could lead to exposures for adults (gardens) or adults and
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA has not found dinotefuran to share a common mechanism of
toxicity with any other substances, and dinotefuran does not appear to
produce a toxic metabolite produced by other substances. For the
purposes of this
tolerance action, therefore, EPA has assumed that dinotefuran does not
have a common mechanism of toxicity with other substances. For
information regarding EPA's efforts to determine which chemicals have a
common mechanism of toxicity and to evaluate the cumulative effects of
such chemicals, see EPA's website 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 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 factor.
2. Prenatal and postnatal sensitivity. Prenatal developmental
toxicity studies in rats and rabbits provided no indication of
increased susceptibility (qualitative or quantitative) following in
utero exposure to dinotefuran. In the 2-generation reproduction study
in the rat there was evidence of increased qualitative susceptibility
in the offspring. However, the level of concern for the observed
susceptibility (decreased body weight, decreased thymus weight, and
decreased grip strength) is low because:
i. Clear NOAELs and LOAELS are established for the endpoints of
concern for parental and offspring toxicity.
ii. The effects in the offspring were seen in the presence of
iii. The effects were seen only at the highest dose tested (Limit
Dose of 1,000 milligrams/kilograms/day (mg/kg/day).
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF was reduced to 1X for acute exposure, however, a safety factor
of 10X has been retained for assessing chronic dietary and short- and
intermediate-term inhalation exposure due to a lack of a NOAEL in the
chronic dietary (dog) and 28-day inhalation toxicity studies. That
decision is based on the following findings:
i. The toxicity database for dinotefuran is complete except for
developmental neurotoxicity testing. The Agency has available a newly
submitted dose-range finding developmental neurotoxicity and
immunotoxicity study on dinotefuran in rats. Under the conditions of
the study, dinotefuran did not affect the distribution of splenocyte
subpopulations (total B cell, total T cells, helper/DTH T cells,
cytotoxic T cells, and natural killer cells) in the weanlings of
F1 generation. It did not affect the anti-SRBC antibody
forming cell response (humoral immunity) and NK cell activity (innate
immunity). Therefore, it was concluded that dinotefuran showed no
evidence of an effect on the functionality of the immune system in rats
that were exposed to dinotefuran during the prenatal, postnatal, and
post-weaning periods. Although, this study was a dose-range-finding
study for a developmental immunotoxicity study, it examined all the
parameters which would have been required in a regular developmental
immunotoxicity study and the highest tested dose (1,035 mg/kg) was
slightly greater than the limit dose (1,000 mg/kg). Considering the
results and conduct of the study, EPA believes that this range-finding
study provides sufficient data for understanding the immunotoxic
potential of dinotefuran in young animals and satisfies the data
requirement for a developmental immunotoxicity study. With respect to
the requirement for an adult immunotoxicity study, the Agency has
analyzed the entire data base of dinotefuran and that of a structurally
related chemical, clothianidin. Clothianidin was found to produce
similar effects on the thymus and spleen as dinotefuran in the repeated
dosing studies, and an immunotoxicity study was conducted in both adult
and the offspring animals. No immunotoxicity was found in either the
adults or the offspring treated with clothianidin. Based on the
available information, EPA believes that conducting an immunotoxicity
study in adult rats would probably not provide additional information
on the immunotoxicity of dinotefuran and certainly would not impact the
risk assessment of this pesticide.
ii. There is concern for developmental neurotoxicity following
exposure to dinotefuran, and a developmental neurotoxicity (DNT) study
in rats is required. Evidence of neurotoxicity in the dinotefuran data
base includes changes in motor activity observed in acute and
subchronic neurotoxicity studies, decreased grip strength in adult
offspring in the 2-generation rat study and maternal clinical signs
(prone position and tremor) in the rabbit developmental study. These
effects occurred at doses ranging from approximately 300 to 1,500 mg/
kg/day. Because of a concern for these neurotoxic effects, EPA required
a DNT study to determine possible effects on the nervous system in the
developing young. However, the Agency determined that a database
uncertainty factor (UFDB) is not needed to account for the
lack of the DNT study based on the following:
The developmental neurotoxicity data for other
neonicotinoid compounds (thiacloprid, imidacloprid and clothainadin)
where neurotoxicity (in the presence of decreased pup body weight) was
seen in only one compound (imidacloprid). Based on these data EPA
concluded that the results of the required dinotefuran DNT study would
not likely impact the regulatory doses selected for dinotefuran.
No concerns for developmental neurotoxicity were seen in
the range-finding DNT study for dinotefuran where the offspring LOAEL
was the Limit Dose (1,035 mg/kg/day) based on decreased body weight and
the offspring NOAEL was 317 mg/kg/day. Establishment of such a high
LOAEL in the range-finding study clearly indicates that in order to
elicit toxicity, dose selection for the definitive DNT study will
likely result in a point of departure much higher than those currently
used for overall risk assessment (range from 2.0 to 125 mg/kg/day).
In the current risk assessment, a point of departure for
neurotoxicity was used in two risk assessment scenarios: (1) A NOAEL of
125 mg/kg/day was used for general population acute dietary risk based
on transient clinical signs (prone position, tremor, erythema) seen at
300 mg/kg/day (LOAEL) following a single dose and no longer apparent
after 24 hours; (2) a NOAEL of 33 mg/kg/day was used for short-term
incidential oral risk based on increased motor activity seen at 327 mg/
kg/day following multiple doses. Similar or lower points of departure
for other systemic toxicities were used for the other risk assessment
scenarios: The NOAEL of 33 mg/kg/day, which was used for assessment of
short-term incidental oral risk, the chronic RfD is based on an
extrapolated NOAEL of 2.0 mg/kg/day based on decreased thymus weight,
the intermediate term incidental oral exposure is based on a NOAEL of
22 mg/kg/day based on changes in body weight/body weight gain, and the
short and the intermediate inhalation exposure endpoints are based on
an extrapolated NOAEL of 6.0 mg/
kg/day based on decreased body weight and food consumption.
Therefore, the Agency believes there are reliable toxicity data
showing that the points of departures used for the overall risk
assessment of dinotefuran are protective of infants and children.
iii. There is no evidence that dinotefuran results in increased
susceptibility in in utero rats or rabbits in the prenatal
developmental studies. Although there is evidence of increased
qualitative susceptibility in the two generation reproduction study in
the rat, the degree of concern is low and the Agency did not identify
any residual uncertainties after establishing toxicity endpoints and
traditional UFs to be used in the risk assessment of dinotefuran.
iv. A safety factor of 10X has been retained for chronic dietary
and short- and intermediate-term inhalation exposure due to a lack of a
NOAEL in the chronic dietary (dog) and 28-day inhalation toxicity
studies. For the chronic Reference Dose (RfD) the default 10X UF was
deemed to be adequate based on the magnitude and the nature of response
at the LOAEL in the study: (1) At the LOAEL, the decreased thymus
weight was limited to one sex (males) with no corroborative
histopathological lesions in the thymus glands; (2) this appears to be
a species specific effect since no treatment-related effects on the
thymus (weight or histopathology) was seen following chronic exposures
to mice or rats; and (3) there is high confidence that the extrapolated
NOAEL of 2.0 mg/kg/day (LOAEL = 20 / 10; UF = 2.0) will be protective
of the systemic toxicity seen at higher doses in mice (LOAEL = 34 mg/
kg/day) and rats (LOAEL = 991 mg/kg/day) following chronic exposures.
For the short- and intermediate-term inhalation exposures, the
default 10X UF is deemed to be adequate since following exposures for
28-days, no toxicity to the target organ (respiratory system) was seen
at any concentration; and the endpoint of concern was generalized
systemic toxicity characterized by decreased body weight gain and food
consumption in one sex (males).
v. There are no residual uncertainties identified in the exposure
databases. The acute and chronic dietary food exposure assessment
utilized proposed and registered tolerance level residues and 100% crop
treated information for all commodities. By using these screening-level
assessments, acute and chronic exposure/risks will not be
underestimated. Furthermore, EPA made conservative (protective)
assumptions in the ground and surface water modeling used to assess
exposure to dinotefuran in drinking water. EPA used similarly
conservative assumptions to assess postapplication exposure of children
as well as incidental oral exposure of toddlers. These assessments will
not underestimate the exposure and risks posed by dinotefuran.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic pesticide exposures are
safe by comparing aggregate exposure estimates to the aPAD and cPAD.
The aPAD and cPAD represent the highest safe exposures, taking into
account all appropriate SFs. EPA calculates the aPAD and cPAD by
dividing the POD by all applicable UFs. 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 POD to ensure that the MOE called for
by the product of all applicable UFs is not exceeded.
1. Acute risk. An acute aggregate risk assessment takes into
account exposure estimates from acute dietary consumption of food and
drinking water. Using the exposure assumptions discussed in this unit
for acute exposure, the acute dietary exposure from food and water to
dinotefuran will occupy 3.5% of the aPAD for children 1 to 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
dinotefuran from food and water will utilize 68% of the cPAD for
children 1 to 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
dinotefuran is not expected.
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).
Dinotefuran is currently registered for uses that could result in
short-term residential exposure and the Agency has determined that it
is appropriate to aggregate chronic exposure through food and water
with short-term residential exposures to dinotefuran. Because there are
existing residential uses of dinotefuran, short- and intermediate-term
aggregate risk assessments based on exposure from oral, inhalation, and
dermal routes were considered. However, the toxicological effects for
oral and inhalation routes of exposure are different (i.e.,
neurotoxicity for oral and decrease in body weight for inhalation); and
therefore, these exposure scenarios have not been combined. Also,
because no systemic toxicity was seen at the limit dose in a 28-day
dermal toxicity study, no quantification of short-term dermal risk is
required. Therefore, only short-term oral residential hand-to-mouth
exposures for toddlers need to be aggregated with chronic food and
drinking water exposures. However, these exposures were not aggregated,
and instead as a worst-case estimate of risk, intermediate-term dermal
and oral residential hand-to-mouth exposures for toddlers were
aggregated with chronic food and drinking water exposures. The point of
departure for intermediate-term dermal and oral exposures is a NOAEL of
22 mg/kg/day versus the point of departure for short-term oral
exposures which is 33 mg/kg/day.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level). An intermediate-term aggregate risk assessment was performed as
a screening level assessment. Intermediate-term aggregate risk
assessments were performed for adults and children. For children, the
subgroup with the highest estimated chronic dietary exposure (children
1 to 2 years old) was aggregated with residential exposures to children
playing on treated lawns (dermal and oral hand-to-mouth exposures) in
order to calculate the worst case intermediate-term aggregate risk to
children. Intermediate term is a worst case because the short- and
intermediate-term incidental oral exposures are the same and the POD
for intermediate-term risk is lower than the POD for short term risk.
Further, intermediate dermal plus incidental oral exposures are
combined (same toxic effect), thus the total intermediate-term exposure
is higher than short term exposure.The reciprocal MOE method was used
to conduct the intermediate-term aggregate risk assessment for
children, since the levels of concern are identical for all MOEs in the
calculation. For adults, the aggregate risk index (ARI) method was
used, since levels of concern are not identical for all types of
exposure in the calculation. For children, the aggregate MOE is 430.
Because the level of concern is for
exposures with a MOE of less than 100, this MOE does not raise a safety
concern. For adults, the total aggregate ARI is 5.9. Because the level
of concern using the ARI approach is with an ARI of less than 1, the
total aggregate ARI for dinotefuran does not raise a safety concern.
5. Aggregate cancer risk for U.S. population. Based on the lack of
evidence of carcinogenic effects in two acceptable carcinogenicity
studies, dinotefuran was classified as ``not likely to be carcinogenic
to humans'' and is not expected to pose a cancer risk to humans.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, or to infants and children from aggregate
exposure to dinotefuran residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Three methods for plants have been available for enforcement of
tolerances: A high performnce liquid chromatography mass spectrometry
(HPLC/MS/MS) method for the determination of residues of dinotefuran,
DN, and UF; a HPLC/UV method for the determination of dinotefuran; and
a HPLC/MS and HPLC/MS/MS method for the determination of DN and UF. An
additional LC/MS/MS method was developed by Wildlife International,
Ltd. (Project No. 236C-113), entitled ``Laboratory Validation of
Method(s) for the Analysis of MTI-446 and its metabolites DN and UF in
Multiple Crop Substrates,'' to quantitate residues in mustard greens.
The method was validated using untreated mustard greens fortified
separately with dinotefuran, DN and UF at 0.01 for each analyte.
Adequate recovery data were provided. Based on the method validation
data and concurrent recovery data, the submitted LC/MS/MS method for
leafy Brassica greens is adequate for enforcement and data collection
Adequate enforcement methodologies as described above are available
to enforce the tolerance expression. The methods 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: [email protected].
B. International Residue Limits
There are currently no established Codex, Canadian, or Mexican
maximum residue limits for residues of dinotefuran in or on plant
C. Revisions to Petitioned-For Tolerances
EPA has revised the tolerance levels for residues of dinotefuran
from the, proposed 17 ppm for both Brassica, leafy greens, subgroup 5B
and turnip greens to 15 ppm each based on analysis of field trial data
and the North American Free Trade Agreement (NAFTA) MRL Spreadsheet.
Additionally, EPA has revised the tolerance expression to clarify,
(1) that, as provided in section 408(a)(3) of FFDCA, the tolerance
covers metabolites and degradates of dinotefuran not specifically
mentioned; and (2) that compliance with the specified tolerance levels
is to be determined by measuring only the specific compounds mentioned
in the tolerance expression. These changes were made to both the
tolerance expressions for plant commodities and animal commodities.
They result in no substantive change to the meaning of the tolerance
but clarify the existing language.
Therefore, tolerances are established for residues of dinotefuran,
including its metabolites and degradates, in or on the commodities
listed below in Sec. 180.603. Compliance with the tolerance levels
specified is to be determined by measuring only the sum of dinotefuran
and its metabolites DN, 1-methyl-3-(tetrahydro-3-furylmethyl)guanidine,
and UF, 1-methyl-3-(tetrahydro-3-furylmethyl)urea, calculated as the
stoichiometric equivalent of dinotefuran, in or on Brassica, leafy
greens, subgroup 5B at 15.0 ppm and turnip, greens at 15.0 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 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
Dated: December 10, 2009.
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 180.603 is amended by revising the introductory text in
paragraphs (a)(1) and (2); and alphabetically adding ``Brassica, leafy
greens subgroup 5B'' and ``Turnip, greens'' to the table in paragraph
(a)(1) to read as follows:
Sec. 180.603 Dinotefuran; tolerances for residues.
(a) * * * (1) Tolerances are established for residues of
furanyl)methyl)guanidine, including its metabolites and degradates, in
or on the commodities listed in the following table. Compliance with
the tolerance levels specified below is to be determined by measuring
only the sum of dinotefuran and its metabolites DN, 1-methyl-3-
(tetrahydro-3-furylmethyl)guanidine, and UF, 1-methyl-3-(tetrahydro-3-
furylmethyl)urea, calculated as the stoichiometric equivalent of
dinotefuran, in or on the commodities listed in the table below:
Commodity Parts per million
* * * * *
Brassica, leafy greens, subgroup 5B.................. 15.0
* * * * *
Turnip, greens....................................... 15.0
* * * * *
(2) Tolerances are established for residues of dinotefuran, (RS)-1-
methyl-2-nitro-3-((tetrahydro-3-furanyl)methyl)guanidine, including its
metabolites and degradates, in or on the commodities listed in the
following table. Compliance with the tolerance levels specified below
is to be determined by measuring only the sum of dinotefuran, (RS)-1-
methyl-2-nitro-3-((tetrahydro-3-furanyl)methyl)guanidine in or on the
commodities listed in the table below:
* * * * *
[FR Doc. E9-30131 Filed 12-17-09; 8:45 am]
BILLING CODE 6560-50-S