
[Federal Register: December 18, 2009 (Volume 74, Number 242)]
[Rules and Regulations]               
[Page 67098-67104]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18de09-10]                         

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2009-0013; FRL-8803-1]

 
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 
(FFDCA).

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) 
305-5805.

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: jackson.sidney@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).
     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 
INFORMATION CONTACT.

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

[[Page 67099]]

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, 
2010.
    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 
tolerances follows.

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 
children.
    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 
mutagenic.
    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

[[Page 67100]]

Assessment for Proposed Uses on Brassica Leafy Vegetables Subgroup 5B 
and Turnip Greens,'' dated August 6, 2009, page 11 in docket ID number 
EPA-HQ-OPP-2009-0013-0004.

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 
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). 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 
water.
    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 
youth (golf).
    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

[[Page 67101]]

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 
parental toxicity.
    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/

[[Page 67102]]

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

[[Page 67103]]

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 
purposes.
    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: residuemethods@epa.gov.

B. International Residue Limits

    There are currently no established Codex, Canadian, or Mexican 
maximum residue limits for residues of dinotefuran in or on plant 
commodities.

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.

V. Conclusion

    Therefore, 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 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 
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.

[[Page 67104]]

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: December 10, 2009.
G. Jeffrey Herndon,
Acting 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 180.603 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 
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 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
