[Federal Register Volume 80, Number 210 (Friday, October 30, 2015)]
[Rules and Regulations]
[Pages 66795-66801]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-27788]



40 CFR Part 180

[EPA-HQ-OPP-2014-0607; FRL-9934-88]

Metaflumizone; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.


SUMMARY: This regulation establishes a tolerance for the combined 
residues of the insecticide metaflumizone in or on the raw agricultural 
commodities citrus (crop group 10-10) at 0.04 parts per million (ppm); 
pome fruit (crop group 11-10) at 0.04 ppm; stone fruit (crop group 12-
12) at 0.04 ppm; and tree nut (crop group 14-12) at 0.04 ppm. BASF 
Corporation requested these tolerances under the Federal Food, Drug, 
and Cosmetic Act (FFDCA).

DATES: This regulation is effective October 30, 2015. Objections and 
requests for hearings must be received on or before December 29, 2015, 
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: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2014-0607, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 
1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public 
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through 
Friday, excluding legal holidays. The telephone number for the Public 
Reading Room is (202) 566-1744, and the telephone number for the OPP 
Docket is (703) 305-5805. Please review the visitor instructions and 
additional information about the docket available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Susan Lewis, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; main telephone 
number: (703) 305-7090; email 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. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111), e.g., agricultural 
workers; greenhouse, nursery, and floriculture workers; farmers.
     Animal production (NAICS code 112), e.g., cattle ranchers 
and farmers, dairy cattle farmers, livestock farmers.
     Food manufacturing (NAICS code 311), e.g., agricultural 
workers; farmers; greenhouse, nursery, and floriculture workers; 
ranchers; pesticide applicators.
     Pesticide manufacturing (NAICS code 32532), e.g., 
agricultural workers; commercial applicators; farmers; greenhouse, 
nursery, and floriculture workers; residential users.

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of 40 CFR 
part 180 through the Government Printing Office's e-CFR cite at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 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-2014-0607 in the subject line on the first 
page of your submission. All requests must be in writing, and must be 
received by the Hearing Clerk on or before December 29, 2015. Addresses 
for mail and hand delivery of objections and hearing requests are 
provided in 40 CFR 178.25(b).
    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 (excluding any Confidential Business Information (CBI)) for 
inclusion in the public docket. Information not marked confidential 
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without 
prior notice. Submit the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2014-0607, by one of 
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.html.
Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

II. Background and Statutory Findings

    In the Federal Register of December 17, 2014 (79 FR 75107) (FRL-
9918-90), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
#4F8286) by BASF Corporation, P.O. Box 13528, Research Triangle Park, 
NC 27709. The petition requested that 40 CFR 180.657 be amended by 
establishing a tolerance for the combined residues of the

[[Page 66796]]

insecticide metaflumizone (2-[2-(4-cyanophenyl)-1-[3-
hydrazinecarboxamide; E and Z isomers) and its metabolite 4-{2-oxo-2-
[3-(trifluoromethyl)phenyl]ethyl{time} -benzonitrile, in or on the raw 
agricultural commodities citrus (crop group 10-10) at 0.04 ppm; pome 
fruit (crop group 11-10) at 0.04 ppm; stone fruit (crop group 12-12) at 
0.04 ppm; and tree nut (crop group 14-12) at 0.04 ppm. In addition, 
that petition requested removal of the existing tolerances for 
metaflumizone in or on fruit, citrus group 10 at 0.04 ppm and nut, 
tree, group 14 at 0.04 ppm upon establishment of the petitioned-for 
tolerances. That document included a summary of the petition prepared 
by BASF Corporation, the registrant. There were no substantive comments 
received in response to the notice of filing.

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 FFDCA section 408(b)(2)(D), EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with FFDCA 
section 408(b)(2), for a tolerance for metaflumizone, including 
exposure resulting from the tolerances established by this action. 
EPA's assessment of exposures and risks associated with establishing 
the tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
    Hematotoxicity (toxicity of the blood) was the primary toxic effect 
of concern following subchronic or chronic oral exposures to 
metaflumizone. Splenic extramedullary hematopoiesis, increased 
hemosiderin, and anemia were the most common hematotoxic effects 
reported after repeated oral dosing with metaflumizone. Chronic oral 
(gavage) exposures to dogs resulted in slight decreases in mean 
corpuscular hemoglobin concentration and total hemoglobin, leading to 
increased plasma bilirubin, increased urinary urobilinogen, and 
increased hemosiderin in the liver. In a chronic toxicity/
carcinogenicity study in mice, anemia was observed in the form of 
increased hemosiderin in the spleen, increased mean absolute 
reticulocyte count, decreased mean corpuscular volume, and mean 
corpuscular hemoglobin.
    The postulated pesticidal mode of action of metaflumizone involves 
inhibition of sodium channels in target insect species; however, in 
mammals (rats), there were only clinical signs of neurotoxicity (i.e., 
piloerection and body temperature variations) with no neuropathology in 
the presence of systemic toxicity (e.g., recumbency and poor general 
state) following acute or repeated exposures. Similarly, several immune 
system organs seem to be affected following metaflumizone 
administration via the oral, dermal, and inhalation routes (e.g., the 
presence of macrophages in the thymus, lymphocyte necrosis in the 
mesenteric lymph nodes, and diffuse atrophy of the mandibular); 
however, there was no evidence of any functional deficits at the 
highest dose tested in a recently submitted and reviewed guideline 
immunotoxicity study. Therefore, the clinical neurotoxicity signs and 
the effects on the immune system organs following metaflumizone 
administration are likely to be secondary to the hematotoxic effects.
    Metaflumizone induced an increased incidence of a missing 
subclavian artery at a relatively high dose that also caused severe 
maternal toxicity (e.g., late term abortions) in the developmental 
toxicity study in rabbits. There was no evidence (quantitative or 
qualitative) of increased susceptibility following in utero exposures 
to rats or rabbit and following pre- and post natal exposures. There 
was no evidence that metaflumizone is genotoxic and carcinogenicity 
studies with mice and rabbits were negative.
    Specific information on the studies received and the nature of the 
adverse effects caused by metaflumizone 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 entitled, ``Metaflumizone: Human 
Health Risk Assessment in Support of Section 3 Registrations for 
Application of Metaflumizone to Pome Fruit (crop group (CG) 11-10) and 
Stone Fruit (CG 12-12); Updating the CG Designation for Citrus to 10-10 
and Tree Nuts to 14-12; and Permitting Aerial Application to Citrus 
Fruits, Grapes, Tree Nuts, and Nurseries Containing Field-/Container-
Grown Nonbearing Stone and Pome Fruit Trees'' in docket ID number EPA-

B. Toxicological Endpoints of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern (LOCs) 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 the NOAEL and the LOAEL are identified. 
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 metaflumizone used for 
human risk assessment is provided below:

[[Page 66797]]

    i. Acute Dietary Endpoint (General population including infants and 
children). An acute dietary endpoint was not established for this 
population group since an endpoint of concern (effect) attributable to 
a single dose was not identified in the database. Studies considered 
for this endpoint included the acute neurotoxicity study for which a 
LOAEL was not observed.
    ii. Acute Dietary Endpoint (Females 13-49 years old). This endpoint 
was established based on a developmental effect observed in the rabbit 
developmental toxicity study that can be potentially due to a single 
dose of metaflumizone. This effect consisted of an increased incidence 
of an absent subclavian artery in the offspring at the LOAEL of 300 
milligram/kilogram (mg/kg) body weight/day (bw/day) metaflumizone 
(NOAEL = 100 mg/kg bw/day). The rat developmental toxicity study was 
also considered for this endpoint; however, no developmental effects 
were observed in this study at the highest dose tested of 120 mg/kg bw/
day metaflumizone. A combined uncertainty factor (UF) of 300 was 
applied to account for interspecies (10x) and intraspecies (10x) 
extrapolation. A Food Quality Protection Act (FQPA) safety factor (SF) 
of 3x was retained because the rabbit developmental toxicity study was 
performed via oral gavage dosing. In an absorption study submitted by 
the petitioner, dietary exposures (which are more relevant for human 
exposures) exhibited an approximately 2-fold greater absorption into 
the systemic circulation than oral gavage dosing and, thus, can 
potentially lead to toxicity at 2-fold lower levels of exposure. Thus, 
aPAD for females 13-49 years old is estimated to be 0.33 mg/kg bw/day.
    iii. Chronic Dietary Endpoint. This endpoint was established based 
on results of a chronic toxicity study with dogs via capsule 
administration. The effects at the LOAEL of 30 mg/kg bw/day (NOAEL = 12 
mg/kg bw/day), consisted of reduced general health condition, slight to 
severe ataxia, recumbency, and severe salivation, decreases in mean 
cell hemoglobin concentration (MCHC) and total hemoglobin (Hb) and 
increased bilirubin, increased urobilinogen, and increased hemosiderin 
in the liver. A combined UF of 300 was applied to account for 
interspecies (10x) and intraspecies (10x) extrapolation and an FQPA SF 
of 3x was retained for the higher absorption observed in dietary 
exposures to metaflumizone (see above). Thus, the chronic population 
adjusted dose (cPAD) is estimated to be 0.040 mg/kg bw/day.
    iv. Incidental Oral (Short- and Intermediate-Term). This endpoint 
was selected on the basis of the maternal effects observed in the rat 
two-generation reproductive toxicity study at the LOAEL of 50 mg/kg bw/
day metaflumizone (NOAEL = 20 mg/kg bw/day). Maternal toxicity 
consisted of poor general health and body weight deficits which were 
also associated with improper nursing behavior. Similar effects were 
also noted in a developmental neurotoxicity study (gavage, range 
finding) also considered for this endpoint. In this study, poor 
maternal health was also observed at the LOAEL of 120 mg/kg bw/day 
metaflumizone (NOAEL = 80 mg/kg bw/day). Both studies considered for 
this endpoint achieved a clear maternal NOAEL for the offspring 
effects, but the NOAEL of 20 mg/kg bw/day for the 2-generation 
reproductive toxicity study is considered more protective. A combined 
UF of 300 was applied to account for interspecies (10x) and 
intraspecies (10x) extrapolation, and an FQPA SF of 3x to account for 
the 2-fold greater absorption observed in dietary versus oral gavage 
exposures (see above). The LOC is 300.
    v. Dermal (Short- and Intermediate-Term). This endpoint was based 
on a rat 90-day dermal toxicity study in which deficits in body weight, 
body-weight gain, and food consumption (in males and females); 
anogenital smearing; increased macrophages in the thymus; lymphocyte 
necrosis in the mesenteric lymph nodes; diffuse atrophy of the 
mandibular lymph node; and increased hemosiderin in the liver (females 
only) were observed at the LOAEL of 300 mg/kg bw/day (NOAEL = 100 mg/kg 
bw/day). The LOC, for both occupational and residential exposure is 
100, based on a combined UF of 100 for interspecies (10x) and in 
intraspecies (10x) extrapolation. The FQPA SF is reduced to 1x for this 
exposure scenario because there is no residual uncertainty concerning 
potential effects on infants and children.
    vi. Inhalation (Short- and Intermediate-Term). There is a 28-day 
inhalation study that is adequate for both exposure durations. There 
was no NOAEL identified for female rats. At the LOAEL of 0.10 
milligrams per Liter (mg/L) metaflumizone (NOAEL = 0.03 mg/L), 
histopathology of the nasal tissues, lungs, thymus, prostate, and 
adrenal cortex was observed in males. The LOAEL of 0.03 mg/L identified 
in females resulted in lymphocyte necrosis in the mesenteric lymph 
    The methods and dosimetry equations described in EPA's reference 
concentration (RfC) guidance (1994) are suited for calculating human-
equivalent concentrations (HECs) based on the inhalation toxicity point 
of departure (NOAEL, LOAEL, or Benchmark Dose Lower Confidence Limit 
(BMDL)) for use in MOE calculations. The regional-deposited-dose ratio 
(RDDR), which accounts for the particulate diameter (mass median 
aerodynamic diameter (MMAD) and geometric standard deviation ([sigma]g) 
of aerosols), can be used to estimate the different dose fractions 
deposited along the respiratory tract. The RDDR accounts for 
interspecies differences in ventilation and respiratory-tract surface 
areas. Thus, the RDDR can be used to adjust an observed inhalation 
particulate exposure of an animal to the predicted inhalation exposure 
for a human. For the subchronic inhalation toxicity study with 
metaflumizone, an RDDR was estimated at 2.81 based on systemic effects 
(lymphocyte necrosis in the mesenteric lymph node) in females at the 
LOAEL of 0.03 mg/L (no NOAEL established), and a MMAD of 1.7 micrometer 
([mu]m) and [sigma]g of 2.7.
    For this action with metaflumizone, residential and occupational 
handler scenarios are being assessed. For residential handler 
scenarios, 2-hr/day inhalation exposures are assumed. Adjustment to 
shorter exposure scenarios relative to the animal toxicity study 
duration (e.g., 2 hr. residential exposures) should only be made if 
there is time-course information that would support a shorter time-
frame. Since there is no such information available for metaflumizone, 
the unadjusted animal POD was used to assess the shorter duration 
residential handler exposures. Thus, the HEC equals the LOAEL from the 
study, and was calculated to be 0.084 mg/L. The FQPA SF of 10x is being 
retained for lack of a NOAEL for females in the study. The standard 
interspecies extrapolation UF can be reduced from 10x to 3x due to the 
HEC calculation accounting for pharmacokinetic (not pharmacodynamic) 
interspecies differences. The intraspecies UF remains at 10x. 
Therefore, the LOC for this scenario is 300, which includes the FQPA SF 
of 10x, interspecies (3x), and intraspecies (10x) extrapolation.

C. Exposure Assessment

    1. Dietary Exposure from Food and Feed Uses. Tolerances have been 
established in (40 CFR 180.657) for the residues of metaflumizone, in 
or on a variety of raw agricultural commodities. Risk assessments were 
conducted by EPA to assess dietary exposures from metaflumizone in food 
as follows:

[[Page 66798]]

    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 metaflumizone. In estimating acute dietary exposure, EPA used food 
consumption information from the United States Department of 
Agriculture (USDA) National Health and Nutrition Examination Survey, 
What We Eat in America (NHANES/WWEIA). This dietary survey was 
conducted from 2003 to 2008. As to residue levels in food, EPA assumed 
tolerance-level residues. It was further assumed that 100% of crops 
with the requested uses of metaflumizone were treated.
    ii. Chronic Exposure. In conducting the chronic dietary exposure 
assessment, EPA used the food consumption data from the USDA NHANES/
WWEIA. As to residue levels in food, EPA assumed tolerance-level 
residues. It was further assumed that 100% of crops with the requested 
uses of metaflumizone were treated.
    iii. Cancer. EPA has concluded that metaflumizone does not pose a 
cancer risk to humans; therefore, a dietary exposure assessment for the 
purpose of assessing cancer risk is unnecessary.
    iv. Anticipated Residue and Percent Crop Treated (PCT) Information. 
EPA did not use anticipated residue or PCT information in the dietary 
assessment for metaflumizone. Tolerance-level residues and 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 metaflumizone in drinking water. These simulation models 
take into account data on the physical, chemical, and fate/transport 
characteristics of metaflumizone. 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 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 
metaflumizone for acute exposures are estimated to be 1.03 parts per 
billion (ppb) for surface water and 1.09 x 10-\12\ ppb for 
ground water. The EDWCs of metaflumizone for chronic exposures for non-
cancer chronic assessments are estimated to be 0.487 ppb for surface 
water and 1.09 x 10-\12\ 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 1.03 ppb was used to 
assess the contribution of drinking water. For chronic dietary risk 
assessment, the water concentration value of 0.487 ppb was used to 
assess the contribution of 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). Metaflumizone is 
currently registered for the following uses that could result in 
residential exposures: As a fire ant bait for application to lawns, 
landscapes, golf courses, and other non-cropland area; and as a fly 
bait for use around industrial buildings, commercial facilities, 
agricultural structures/premises, and recreational facilities/areas.
    EPA assessed residential exposure using the following assumptions: 
Fire ant bait applications to home lawns are expected to result in 
short-term, residential handler exposure to adults. Fire ant bait 
applications to lawns and golf-courses are expected to result in short-
term, post-application dermal exposure to adults, children 11 to <16 
years old, and children 1 to <2 years old, and incident oral exposure 
for children 1 to <2 years old. For the fly bait product, residential 
handler exposure is not expected, because the product is applied by 
commercial handlers. The fly bait product is expected to result in 
short-term, post-application dermal exposure to adults, children 11 to 
<16 years old, and children 1 to <2 years old, and incident oral 
exposure for children 1 to <2 years old.
    For residential handlers, dermal and inhalation exposures are 
combined since the endpoints are similar for these routes. For children 
(1- to <2-year-olds), post-application hand-to-mouth and dermal 
exposures are combined. Since the LOCs for the dermal, inhalation and 
incidental oral routes are not the same (dermal LOC = 100, inhalation 
LOC = 300, and incidental oral LOC = 300), these routes were combined 
using the aggregate risk index approach. Further information regarding 
EPA standard assumptions and generic inputs for residential exposures 
may be found at http://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
    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.''
    Unlike other pesticides for which EPA has followed a cumulative 
risk approach based on a common mechanism of toxicity, EPA has not made 
a common mechanism of toxicity finding as to metaflumizone and any 
other substances and metaflumizone does not appear to produce a toxic 
metabolite produced by other substances. For the purposes of this 
tolerance action; therefore, EPA has not assumed that metaflumizone has 
a common mechanism of toxicity with other substances. For information 
regarding EPA's efforts to determine which chemicals have a common 
mechanism of toxicity and to evaluate the cumulative effects of such 
chemicals, see the policy statements released by EPA's Office of 
Pesticide Programs concerning common mechanism determinations and 
procedures for cumulating effects from substances found to have a 
common mechanism on EPA's Web site at http://www.epa.gov/pesticides/cumulative.

D. Safety Factor for Infants and Children

    1. In general. Section 408 of FFDCA provides that EPA shall apply 
an additional ten-fold margin of safety for infants and children in the 
case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the data base on toxicity and exposure 
unless EPA determines based on reliable data that a different margin of 
safety will be safe for infants and children. Margins of safety are 
incorporated into EPA risk assessments either directly through use of a 
MOE analysis or through using uncertainty (safety) factors in 
calculating a dose level that poses no appreciable risk to humans. In 
applying this provision, EPA either retains the default value of 10X 
when reliable data do not support the choice of a different factor, or, 
if reliable data are available, EPA uses a different additional safety 
factor value based on the use of traditional uncertainty factors and/or 
special FQPA SFs, as appropriate.
    2. Prenatal and Postnatal Sensitivity. There is no evidence for 
increased qualitative or quantitative sensitivity/susceptibility 
resulting from pre- and/or postnatal exposures. In the rat prenatal 
development toxicity study, there was no offspring toxicity reported at 

[[Page 66799]]

dose tested whereas in the rabbit study a maltransformation based on an 
absent subclavian artery was noted to occur only in the presence of 
severe maternal toxicity. Similarly, offspring mortality in the 2-
generation reproductive toxicity occurred only in the presence of a 
poor maternal health state. Thus, there is no evidence for increased 
    3. Conclusion. EPA has determined that reliable data show the 
safety of infants and children would be adequately protected if the 
FQPA SF were reduced from 10x to 3x for all oral exposure scenarios; 
retained at 10x for inhalation exposure scenarios; and reduced to 1x 
for dermal exposures. That decision is based on the following findings:
    i. The toxicological database for metaflumizone is adequate for 
risk assessment and FQPA SF evaluation. Several studies are available 
for evaluating the safety of metaflumizone, although differences in 
dose administration and a missing NOAEL warrant retention of various 
FQPA safety factors in this instance.
    Dietary exposures exhibited an approximately 2-fold greater 
absorption into the systemic circulation as compared to oral gavage 
and, thus, can potentially lead to toxicity at 2-fold lower levels of 
exposure. Applying an FQPA SF of 3x for all oral exposure scenarios is 
adequate to protect against any greater toxicity that might occur in 
dietary exposures (absorption was noted to be 2-fold greater in dietary 
versus oral gavage studies).
    The FQPA SF of 10x is being retained for inhalation exposure 
scenarios for the use of a LOAEL instead of a NOAEL (no NOAEL achieved) 
for histopathological lesions consisting of lymphocyte necrosis in the 
mesenteric lymph node. The FQPA SF of 10x is adequate because the 
effect (lymphocyte necrosis) is considered minimal to slight and does 
not exhibit a strong dose dependence.
    The FQPA SF for dermal exposure scenarios is being reduced from 10x 
to 1x since there is a route-specific study with a clear NOAEL.
    ii. There is no indication that metaflumizone directly affects the 
nervous system. Clinical signs indicative of neurotoxicity were 
observed in several studies; however, these signs were generally 
observed in the presence of poor animal health (e.g., reduced general 
health condition, loss of body weight, or death). In addition, no 
neuropathology was observed in any study with metaflumizone. There is 
no need for a developmental neurotoxicity study or additional 
uncertainty factors to account for neurotoxicity.
    iii. There are no residual concerns or uncertainties for increased 
sensitivity/susceptibility in developing animals resulting from pre- 
and/or postnatal exposure.
    iv. There are no residual uncertainties identified in the exposure 

The dietary analyses assumed tolerance-level residues, 100 PCT, and 
modeled drinking water estimates. EPA made conservative (protective) 
assumptions in the ground and surface water modeling used to assess 
exposure to metaflumizone in drinking water. EPA used similarly 
conservative assumptions to assess post-application exposure of 
children as well as incidental oral exposure of toddlers. These 
assessments will not underestimate the exposure and risks posed by 

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 lifetime 
probability of acquiring cancer 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 PODs to ensure that an adequate MOE exists. Based on 
the proposed/registered uses and since inhalation, dermal, and 
incidental oral exposures can be combined, aggregate acute (dietary), 
short-term (dietary, incidental oral, and/or dermal), and chronic 
(dietary) assessments were conducted.
    1. Acute Risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute aggregate exposure assessment 
consists of exposure from only food and water. The acute dietary 
exposure assessment for females 13-49 years old was 1.6% of the aPAD 
and therefore, does not exceed EPA's LOC.
    2. Chronic Risk. Since there are no registered/proposed uses that 
result in chronic residential exposure, the chronic aggregate exposure 
assessment consists of exposure from only food and water. The chronic 
dietary exposure estimate was <=7.2% the cPAD and therefore, does not 
exceed EPA's LOC.
    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). Metaflumizone 
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 metaflumizone. Since the LOC and 
toxicological points of departure for the short-term dermal and oral 
routes of exposure differ, the aggregate risk index method was used to 
determine aggregate risk (aggregate risk indices >1 are not a risk of 
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water, 
and residential exposures result in aggregate risk indices of 42 for 
the general population, and 22 for children 1-2 years old. Because 
EPA's LOC for metaflumizone is an aggregate risk index less than 1, the 
aggregate risks are not of concern.
    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). Metaflumizone is not currently registered for uses that could 
result in intermediate-term residential exposure; however, since the 
PODs for the short- and intermediate-term durations are the same for 
metaflumizone, the short-term aggregate assessment is protective of 
intermediate-term exposures.
    5. Aggregate Cancer Risk for U.S. Population. As discussed in Unit 
III.A., EPA does not expect metaflumizone to pose a cancer risk to 
    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, and to infants and children from aggregate 
exposure to metaflumizone residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    EPA previously reviewed method validation and independent 
laboratory validation (ILV) studies for the BASF high-performance 
liquid chromatography (HPLC)/mass spectrometry (MS)/MS analytical 
method 531/0 and forwarded the method to FDA for tolerance enforcement 
(46264221.der; D308394, T. Bloem, 30-Nov-2005; D328915, T. Bloem, 17-
May-2006). It is noted that following method validation, BASF 
incorporated several minor modifications to method 531/0 with this 
revised method specified as 531/1 (method 531/1 is the current 
enforcement method). Based on the similarities of the proposed crops to 
that currently registered and since the grape, citrus, and tree nut 
residue samples

[[Page 66800]]

were analyzed using a method very similar to the current enforcement 
method and since adequate validation data were submitted, EPA concludes 
that the current enforcement method is suitable for enforcement of the 
tolerances recommended herein. The limit of quantitation (LOQ) is 0.01 
ppm for metaflumizone (E and Z isomers) and 0.018 ppm for M320I04 
(expressed in parent equivalents).
    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; email address: 
[email protected].

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 United Nations 
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.
    Codex MRLs are not established in/on the relevant crops for 
metaflumizone; therefore, harmonization is not an issue for this 

V. Conclusion

    Therefore, the tolerance is established for the combined residues 
of the insecticide metaflumizone (2-[2-(4-cyanophenyl)-1-[3-
hydrazinecarboxamide; E and Z isomers), in or on the following raw 
agricultural commodities: Fruit, citrus, group 10-10 at 0.04 ppm; 
fruit, pome, group 11-10 at 0.04 ppm; fruit, stone, group 12-12 at 0.04 
ppm; and nut, tree, group 14-12 at 0.04 ppm. The existing tolerances 
for fruit, citrus, group 10 at 0.04 ppm and for nut, tree, group 14 at 
0.04 ppm are removed because they are superseded by the tolerances 
being established in this action.

VI. Statutory and Executive Order Reviews

    This action establishes tolerances under FFDCA section 408(d) 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 action has been 
exempted from review under Executive Order 12866, this action 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 action 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 FFDCA section 408(d), such as the tolerances 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 action 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 FFDCA section 408(n)(4). 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 action. In addition, this 
action does not impose any enforceable duty or contain any unfunded 
mandate as described under Title II of the Unfunded Mandates Reform Act 
(UMRA) (2 U.S.C. 1501 et seq.).
    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 (NTTAA) (15 U.S.C. 272 note).

VII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
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 
the rule in the Federal Register. This action 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: October 21, 2015.
G. Jeffrey Herndon,
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 180.657 is amended as follows:
a. Remove the entries for ``Fruit, citrus, group 10'' and ``Nut, tree, 
group 14'' from the table in paragraph (a).
b. Add alphabetically the following list of commodities to the table in 
paragraph (a).
    The additions read as follows:

Sec.  [emsp14]180.657  Metaflumizone; tolerances for residues.

    (a) * * *

                                                              Parts per
                         Commodity                             million
                                * * * * *
Fruit, citrus, group 10-10.................................         0.04
Fruit, pome, group 11-10...................................         0.04
Fruit, stone, group 12-12..................................         0.04
                                * * * * *
Nut, tree, group 14-12.....................................         0.04
                                * * * * *

[[Page 66801]]

* * * * *
[FR Doc. 2015-27788 Filed 10-29-15; 8:45 am]