Isofetamid; Pesticide Tolerances, 45438-45443 [2015-18738]
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Federal Register / Vol. 80, No. 146 / Thursday, July 30, 2015 / Rules and Regulations
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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 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 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
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and pests, Reporting and recordkeeping
requirements.
Dated: July 22, 2015.
Susan Lewis,
Director, Registration Division, Office of
Pesticide Programs.
Therefore, 40 CFR chapter I is
amended as follows:
PART 180—[AMENDED]
1. The authority citation for part 180
continues to read as follows:
■
document. ISK Biosciences Corporation
requested these tolerances under the
Federal Food, Drug, and Cosmetic Act
(FFDCA).
This regulation is effective July
30, 2015. Objections and requests for
hearings must be received on or before
September 28, 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).
DATES:
The docket for this action,
identified by docket identification (ID)
■ 2. In § 180.418, revise the entries for
number EPA–HQ–OPP–2013–0138, is
‘‘corn, field, forage,’’ ‘‘corn, field,
available at https://www.regulations.gov
stover,’’ and ‘‘corn, pop, stover’’ in the
or at the Office of Pesticide Programs
table in paragraph (a)(2) to read as
Regulatory Public Docket (OPP Docket)
follows:
in the Environmental Protection Agency
Docket Center (EPA/DC), West William
§ 180.418 Cypermethrin and isomers
Jefferson Clinton Bldg., Rm. 3334, 1301
alpha-cypermethrin and zeta-cypermethrin;
Constitution Ave. NW., Washington, DC
tolerances for residues.
20460–0001. The Public Reading Room
(a) * * *
is open from 8:30 a.m. to 4:30 p.m.,
(2) * * *
Monday through Friday, excluding legal
holidays. The telephone number for the
Parts per
Commodity
million
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
Corn, field, forage .................
9.0 information about the docket available
at https://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT:
*
*
*
*
*
Susan Lewis, Registration Division
(7505P), Office of Pesticide Programs,
Corn, field, stover .................
30 Environmental Protection Agency, 1200
Pennsylvania Ave. NW., Washington,
DC 20460–0001; telephone number:
*
*
*
*
*
703–305–7090; email address:
Corn, pop, stover ..................
30 RDFRNotices@epa.gov.
SUPPLEMENTARY INFORMATION:
Authority: 21 U.S.C. 321(q), 346a and 371.
*
*
*
*
*
ADDRESSES:
I. General Information
A. Does this action apply to me?
*
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*
*
*
[FR Doc. 2015–18737 Filed 7–29–15; 8:45 am]
BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2013–0138; FRL–9923–86]
Isofetamid; Pesticide Tolerances
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
This regulation establishes
tolerances for residues of isofetamid in
or on multiple commodities that are
identified and discussed later in this
SUMMARY:
PO 00000
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).
• Animal production (NAICS code
112).
• Food manufacturing (NAICS code
311).
• Pesticide manufacturing (NAICS
code 32532).
B. How can I get electronic access to
other related information?
You may access a frequently updated
electronic version of EPA’s tolerance
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regulations at 40 CFR part 180 through
the Government Printing Office’s e-CFR
site at https://www.ecfr.gov/cgi-bin/textidx?&c=ecfr&tpl=/ecfrbrowse/Title40/
40tab_02.tpl.
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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–2013–0138 in the subject line on
the first page of your submission. All
objections and requests for a hearing
must be in writing, and must be
received by the Hearing Clerk on or
before September 28, 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–
2013–0138, by one of the following
methods:
• Federal eRulemaking Portal: https://
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 20460–0001.
• Hand Delivery: To make special
arrangements for hand delivery or
delivery of boxed information, please
follow the instructions at https://
www.epa.gov/dockets/contacts.html.
Additional instructions on commenting
or visiting the docket, along with more
information about dockets generally, is
available at https://www.epa.gov/
dockets.
II. Summary of Petitioned-For
Tolerance
In the Federal Register of June 5, 2013
(78 FR 33785) (FRL–9386–2), EPA
issued a document pursuant to FFDCA
section 408(d)(3), 21 U.S.C. 346a(d)(3),
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announcing the filing of a pesticide
petition (PP 3F8142) by ISK Biosciences
Corporation, 7470 Auburn Road, Suite
A, Concord, Ohio 44077. The petition
requested that 40 CFR part 180 be
amended by establishing tolerances for
residues of the fungicide isofetamid, N[1,1-dimethyl-2-[2-methyl-4-(1methylethoxy)phenyl]-2-oxoethyl]-3methyl-2-thiophenecarboxamide in or
on almond at 0.02 parts per million
(ppm); almond, hulls at 0.2 ppm;
lettuce, head at 6.0 ppm; lettuce, leaf at
7.0 ppm; low growing berry crop
subgroup 13–07G at 4.0 ppm; rapeseed,
crop subgroup 20A at 0.04 ppm; and
small fruit vine climbing crop subgroup
13–07F at 3.0 ppm. That document
referenced a summary of the petition
prepared by ISK Biosciences
Corporation, the registrant, which is
available in the docket, https://
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
determined that additional tolerances
are necessary; revised some of the
proposed tolerances; and corrected
some commodity definitions for the
tolerances. The reasons 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 FFDCA section
408(b)(2)(D), and the factors specified in
FFDCA section 408(b)(2)(D), EPA has
reviewed the available scientific data
and other relevant information in
support of this action. EPA has
sufficient data to assess the hazards of
and to make a determination on
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aggregate exposure for isofetamid
including exposure resulting from the
tolerances established by this action.
EPA’s assessment of exposures and risks
associated with isofetamid 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 children. The toxicology
database is complete for isofetamid. In
repeated dose studies, the liver was the
primary target organ in the rat, mouse,
and dog, as indicated by increased liver
weights, changes in the clinical
chemistry values, and liver
hypertrophy. A second target organ was
the thyroid in the rat and dog, as
indicated by changes in thyroid weights
and histopathology. Adrenal weight
changes were observed in the
subchronic rat and dog studies. In the
rat and dog, the dose levels where
toxicity was observed were similar or
higher in the chronic studies compared
with the respective subchronic studies,
showing an absence of progression of
liver toxicity with time. There was no
evidence of carcinogenicity in the rat or
mouse cancer studies; the mutagenicity
battery was negative. There are no
genotoxicity, neurotoxicity, or
immunotoxicity concerns observed in
the available toxicity studies.
Developmental toxicity was not
observed in the rat or rabbit, and
offspring effects such as decreased body
weight were seen only in the presence
of parental toxicity in the multigeneration rat study. Isofetamid is
classified as ‘‘Not Likely to be
Carcinogenic to Humans’’ based on the
absence of increased tumor incidence in
acceptable/guideline carcinogenicity
studies in rats and mice. Isofetamid is
not acutely toxic; it is classified as
Toxicity Category III for acute oral and
dermal exposure, and Toxicity Category
IV for inhalation exposure. Furthermore,
it is not irritating to the eye or skin, and
it is not a dermal sensitizer. Specific
information on the studies received and
the nature of the adverse effects caused
by isofetamid as well as the noobserved-adverse-effect-level (NOAEL)
and the lowest-observed-adverse-effectlevel (LOAEL) from the toxicity studies
can be found at https://
www.regulations.gov in document
Isofetamid. Aggregate Human Health
Risk Assessment for the Proposed New
Uses of the New Active Fungicide,
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including Agricultural Uses on
Almonds, Lettuce, Small Vine Climbing
Fruits (Crop Subgroup 13–07F), Low
Growing Berries (Crop Subgroup 13–
07G), and Rapeseed (Crop Subgroup
20A); and Uses on Turfgrass (including
Golf Courses, Sod Farms, Seed Farms,
Recreational Fields, and Commercial/
Residential Lawns) at pages 12–18 in
docket ID number EPA–HQ–OPP–2013–
0138.
B. Toxicological Points of Departure/
Levels of Concern
Once a pesticide’s toxicological
profile is determined, EPA identifies
toxicological points of departure (POD)
and levels of concern to use in
evaluating the risk posed by human
exposure to the pesticide. For hazards
that have a threshold below which there
is no appreciable risk, the toxicological
POD is used as the basis for derivation
of reference values for risk assessment.
PODs are developed based on a careful
analysis of the doses in each
toxicological study to determine the
dose at which no adverse effects are
observed (the NOAEL) and the lowest
dose at which adverse effects of concern
are identified (the LOAEL). Uncertainty/
safety factors are used in conjunction
with the POD to calculate a safe
exposure level—generally referred to as
a population-adjusted dose (PAD) or a
reference dose (RfD)—and a safe margin
of exposure (MOE). For non-threshold
risks, the Agency assumes that any
amount of exposure will lead to some
degree of risk. Thus, the Agency
estimates risk in terms of the probability
of an occurrence of the adverse effect
expected in a lifetime. For more
information on the general principles
EPA uses in risk characterization and a
complete description of the risk
assessment process, see https://
www.epa.gov/pesticides/factsheets/
riskassess.htm.
A summary of the toxicological
endpoints for isofetamid used for
human risk assessment is shown in
Table 1 of this unit.
TABLE 1—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR ISOFETAMID FOR USE IN HUMAN HEALTH RISK
ASSESSMENT
Exposure/scenario
Point of departure
and
uncertainty/safety
factors
RfD, PAD, LOC for
risk assessment
Study and toxicological effects
Acute Dietary (All Populations)
A toxicity endpoint was not identified.
Toxicological effects attributable to a single exposure (dose) were not observed in oral toxicity studies.
Chronic dietary (All populations)
NOAEL = 76.6 mg/
kg/day
UFA = 10X
UFH = 10X
FQPA SF = 1X
Chronic RfD = 0.77
mg/kg/day
cPAD = 0.77 mg/kg/
day
Reproduction and fertility effects (rat)
LOAEL = 679/775 mg/kg/day based on hepatocellular hypertrophy in the liver and follicular cell hypertrophy in the thyroid
in both sexes and generations, decreased spleen weights
and cytoplasmic eosinophilic inclusion bodies in the liver of
F1 males, and decreased pup body weight in both sexes and
generations.
Incidental oral short-term (1 to
30 days) and Incidental oral
intermediate-term (1 to 6
months)
NOAEL = 76.6 mg/
kg/day
UFA = 10X
UFH = 10X
FQPA SF = 1X
Residential LOC for
MOE = 100.
Reproduction and fertility effects (rat)
LOAEL = 679/775 mg/kg/day based on hepatocellular hypertrophy in the liver and follicular cell hypertrophy in the thyroid
in both sexes and generations, decreased spleen weights
and cytoplasmic eosinophilic inclusion bodies in the liver of
F1 males, and decreased pup body weight in both sexes and
generations
Dermal Short-Term (1–30 days)
A toxicity endpoint was not identified.
Systemic toxicity was not seen in 28-day dermal toxicity in rats up to the limit dose (1,000 mg/kg/day). There
are no concerns for developmental or reproductive toxicity or neurotoxicity in rat and rabbit studies.
Inhalation short-term (1 to 30
days)
NOAEL = 76.6 mg/
kg/day
UFA = 10X
UFH = 10X
FQPA SF = 1X
Cancer (Oral, dermal, inhalation)
Classification: ‘‘Not likely to be Carcinogenic to Humans’’ based on the absence of significant tumor increases
in two adequate rodent carcinogenicity studies.
Residential LOC for
MOE = 100
Reproduction and fertility effects (rat)
LOAEL = 679/775 mg/kg/day based on hepatocellular hypertrophy in the liver and follicular cell hypertrophy in the thyroid
in both sexes and generations, decreased spleen weights
and cytoplasmic eosinophilic inclusion bodies in the liver of
F1 males, and decreased pup body weight in both sexes and
generations.
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FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level of concern. mg/kg/day =
milligram/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-level. PAD = population adjusted dose (a = acute, c =
chronic). RfD = reference dose. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFDB = to account for the absence of data or other data deficiency. UFH = potential variation in sensitivity among members of the human population (intraspecies). UFL = use
of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk assessment.
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. EPA assessed dietary
exposures from isofetamid in food as
follows:
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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
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exposure. No such effects were
identified in the toxicological studies
for isofetamid; therefore, a quantitative
acute dietary exposure assessment is
unnecessary.
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ii. Chronic exposure. In conducting
the chronic dietary exposure
assessment, EPA used the 2003–2008
food consumption data from the USDA’s
National Health and Nutrition
Examination Survey, What We Eat in
America (NHANES/WWEIA). A
partially refined chronic (food and
drinking water) dietary assessment was
conducted assuming mean field trial
residues of the combined residues of
parent and GPTC for all proposed crops
and 100% CT. Empirical and default
processing factors were used as
available.
iii. Cancer. Based on the data
summarized in Unit III.A., EPA has
concluded that isofetamid 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 PCT information in the dietary
assessment for isofetamid. Mean field
trial residues of the combined residues
of parent and GPTC were used.
2. Dietary exposure from drinking
water. The Agency used screening level
water exposure models in the dietary
exposure analysis and risk assessment
for isofetamid in drinking water. These
simulation models take into account
data on the physical, chemical, and fate/
transport characteristics of isofetamid.
Further information regarding EPA
drinking water models used in pesticide
exposure assessment can be found at
https://www.epa.gov/oppefed1/models/
water/index.htm.
Based on the Pesticide Flooded
Application Model and the Pesticide
Root Zone Model Ground Water (PRZM
GW) the estimated drinking water
concentrations (EDWCs) of isofetamid
for chronic exposures for non-cancer
assessments are estimated to be 110 ppb
for surface water and 43 ppb for ground
water.
Modeled estimates of drinking water
concentrations were directly entered
into the dietary exposure model. For
chronic dietary risk assessment, the
water concentration value of 110 ppb
was used to assess the contribution from
drinking water.
3. From non-dietary exposure. The
term ‘‘residential exposure’’ is used in
this document to refer to nonoccupational, non-dietary exposure
(e.g., for lawn and garden pest control,
indoor pest control, termiticides, and
flea and tick control on pets).
Isofetamid is currently under review
for registering the following uses that
could result in residential exposures:
Foliar and systemic fungicide for
control in turfgrass including golf
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courses, residential lawns, and
recreational turfgrass. Since there may
be residential use sites, residential
handler exposure and risk estimates
were calculated for all possible
residential exposure scenarios.
Including all possible residential
exposure scenarios provides a
conservative and health protective
assessment for the potential for
homeowners to use the professionally
labeled products on residential use
sites. Since there is no dermal toxicity
endpoint, the residential handler
assessment only includes the inhalation
route of exposure. Residential handler
exposure is expected to be short-term in
duration as a maximum of eight
applications are allowed per year. Thus,
intermediate-term exposures are not
likely because of the intermittent nature
of applications by homeowners. Unit
exposure values and estimates for area
treated or amount handled were taken
from the Agency’s 2012 Residential
SOPs 1 (Lawns/Turf). The algorithms
used to estimate exposure and dose for
residential handlers can be found in the
2012 Residential SOPs 2 (Lawns/Turf).
Risk estimates of all possible scenarios
are not of concern. Short-term
inhalation MOEs range from 850,000 to
18,000,000. Further information
regarding EPA standard assumptions
and generic inputs for residential
exposures may be found at https://
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.’’
EPA has not found isofetamid to share
a common mechanism of toxicity with
any other substances, and isofetamid
does not appear to produce a toxic
metabolite produced by other
substances. For the purposes of this
tolerance action, therefore, EPA has
assumed that isofetamid 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 Web site at https://
www.epa.gov/pesticides/cumulative.
1 Available: https://www.epa.gov/pesticides/
science/residential-exposure-sop.html.
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D. Safety Factor for Infants and
Children
1. In general. Section 408(b)(2)(C) of
FFDCA provides that EPA shall apply
an additional tenfold (10X) margin of
safety for infants and children in the
case of threshold effects to account for
prenatal and postnatal toxicity and the
completeness of the database on toxicity
and exposure unless EPA determines
based on reliable data that a different
margin of safety will be safe for infants
and children. This additional margin of
safety is commonly referred to as the
FQPA Safety Factor (SF). In applying
this provision, EPA either retains the
default value of 10X, or uses a different
additional safety factor when reliable
data available to EPA support the choice
of a different factor.
2. Prenatal and postnatal sensitivity.
There is no evidence of developmental
toxicity or reproductive susceptibility,
and there are no residual uncertainties
concerning pre- or post-natal toxicity or
exposure.
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 to 1X. That decision is
based on the following findings:
i. The toxicity database for isofetamid
is complete.
ii. There is no indication that
isofetamid is a neurotoxic chemical and
there is no need for a developmental
neurotoxicity study or additional UFs to
account for neurotoxicity.
iii. There is no evidence that
isofetamid results in increased
susceptibility in in utero rats or rabbits
in the prenatal developmental studies or
in young rats in the 2-generation
reproduction study.
iv. There are no residual uncertainties
identified in the exposure databases.
The dietary food exposure assessments
were performed based on 100 PCT and
average (mean) field trial residues. EPA
made conservative (protective)
assumptions in the ground and surface
water modeling used to assess exposure
to isofetamid 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 isofetamid.
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 acute PAD (aPAD) and
chronic PAD (cPAD). For linear cancer
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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.
1. Acute risk. An acute aggregate risk
assessment takes into account acute
exposure estimates from dietary
consumption of food and drinking
water. No adverse effect resulting from
a single oral exposure was identified
and no acute dietary endpoint was
selected. Therefore, isofetamid is not
expected to pose an acute risk.
2. Chronic risk. Using the exposure
assumptions described in this unit for
chronic exposure, EPA has concluded
that chronic exposure to isofetamid
from food and water will utilize <1% of
the cPAD for children (1–2 years old),
the population group receiving the
greatest exposure. Based on the
explanation in Unit III.C.3., regarding
residential use patterns, chronic
residential exposure to residues of
isofetamid 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). Isofetamid 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
isofetamid.
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
MOEs of 24,000 and 3,900 for adults
and children (1–2 years old)
respectively. Because EPA’s level of
concern for isofetamid is a MOE of 100
or below, these MOEs 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). An
intermediate-term adverse effect was
identified; however, isofetamid is not
registered for any use patterns that
would result in intermediate-term
residential exposure. Intermediate-term
risk is assessed based on intermediateterm residential exposure plus chronic
dietary exposure. Because there is no
intermediate-term residential exposure
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and chronic dietary exposure has
already been assessed under the
appropriately protective cPAD (which is
at least as protective as the POD used to
assess intermediate-term risk), no
further assessment of intermediate-term
risk is necessary, and EPA relies on the
chronic dietary risk assessment for
evaluating intermediate-term risk for
isofetamid.
5. Aggregate cancer risk for U.S.
population. Based on the lack of
evidence of carcinogenicity in two
adequate rodent carcinogenicity studies,
isofetamid 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 isofetamid
residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology
liquid chromatography with tandem
mass spectrometry (LC–MS/MS) method
(Document Number JSM0119; MRID
49011967) is available to enforce the
tolerance expression.
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.
The Codex has not established any
MRLs for isofetamid. Canada is
concurrently establishing tolerances for
all of the same commodities identified
in this document except almond hulls
because Canada does not set tolerances
on livestock feed commodities. Canada’s
recommended tolerance levels for these
commodities are the same as the U.S.
established tolerance levels. The
tolerance expression for the U.S. and
PO 00000
Frm 00048
Fmt 4700
Sfmt 4700
Canada is the same, with isofetamid as
the residue of concern for primary
crops.
C. Revisions to Petitioned-For
Tolerances
The Agency has made revisions to
some of the petitioned-for tolerance
levels based on the following reasons:
1. Organization for Economic
Cooperation and Development (OECD)
tolerance calculation procedures;
2. The parent only is the residue of
concern for primary crop tolerances
rather than parent and the metabolite
GPTC; and
3. The concentration of residues in
two processed commodities.
Since all residues of isofetamid
(parent) were nondetectable (<0.01
ppm) in almond nutmeat and hulls, the
proposed tolerances of 0.02 ppm for
almond (nutmeat) and 0.2 ppm for
almond hulls will both be reduced to
0.01 ppm, the limit of quantitation of
the analytical method.
Based on the OECD tolerance
calculation procedures, the proposed
tolerance for head lettuce of 6.0 ppm
will be reduced to 5.0 ppm. Based on
the OECD tolerance calculation
procedures, the proposed tolerance for
the rapeseed subgroup 20A of 0.04 ppm
will be reduced to 0.015 ppm.
The petitioner did not propose
tolerances for the processed
commodities, canola oil and raisins.
Since residues concentrate significantly
in canola oil and raisins, tolerances will
be established at 0.03 ppm for canola,
refined oil, and 5.0 ppm for grape,
raisin. These Agency recommendations
are based on the highest average field
trial (HAFT) residues for canola seed
and grape and the processing factors for
canola oil and raisins. The petitioner
did not propose tolerances for flaxseed
oil, mustard seed oil, or sesame oil.
However, flaxseed, mustard seed, and
sesame are members of the rapeseed
subgroup 20A, with canola as the
representative crop, and treated
commodities could be processed to
produce sesame oil, mustard seed oil
and flaxseed oil. Therefore, the Agency
is also establishing tolerances for
residues in flaxseed oil, mustard seed
oil, and sesame oil. Tolerances are being
established at 0.03 ppm, the same level
as for refined canola oil.
Additionally, some of the requested
tolerances have been corrected. Almond
has been revised from 0.02 ppm to 0.01
ppm; almond, hulls from 0.2 ppm to
0.01 ppm; lettuce, head from 6.0 ppm to
5.0 ppm; and rapeseed, subgroup 20A
from 0.04 ppm to 0.015 ppm. The
Agency is setting tolerances on some
processed commodities that were not
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Federal Register / Vol. 80, No. 146 / Thursday, July 30, 2015 / Rules and Regulations
proposed by the petitioner including
canola, refined oil at 0.03 ppm; flax,
seed, oil at 0.03 ppm; grape, raisin at 5.0
ppm; mustard, seed, oil at 0.03 ppm and
sesame, oil at 0.03 ppm.
Lhorne on DSK7TPTVN1PROD with RULES
V. Conclusion
Therefore, tolerances are established
for residues of isofetamid, in or on
almond at 0.01 ppm; almond, hulls at
0.01 ppm; canola, refined oil at 0.03
ppm; flax, seed, oil at 0.03 ppm; grape,
raisin at 5.0 ppm; lettuce, head at 5.0
ppm; lettuce, leaf at 7.0 ppm; berry, low
growing, subgroup 13–07G at 4.0 ppm;
mustard, seed, oil at 0.03 ppm; rapeseed
subgroup 20A at 0.015 ppm; sesame, oil
at 0.03 ppm; and fruit, small vine
climbing, except fuzzy kiwifruit,
subgroup 13–07F at 3.0 ppm.
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 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 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
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13:32 Jul 29, 2015
Jkt 235001
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: July 21, 2015.
Jack Housenger,
Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is
amended as follows:
PART 180—[AMENDED]
1. The authority citation for part 180
continues to read as follows:
■
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Add § 180.681 to subpart C to read
as follows:
■
§ 180.681
residues.
Isofetamid; tolerances for
(a) General. Tolerances are
established for residues of the fungicide
isofetamid, including its metabolites
PO 00000
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Fmt 4700
Sfmt 4700
45443
and degradates, in or on the
commodities in the table below.
Compliance with the tolerance levels
specified below is to be determined by
measuring only isofetamid, N-[1,1dimethyl-2-[2-methyl-4-(1methylethoxy)phenyl]-2-oxoethyl]-3methyl-2-thiophenecarboxamide, in or
on the following commodities:
Commodity
Parts per
million
Almond ..................................
Almond, hulls ........................
Berry, low growing, subgroup
13–07G .............................
Canola, refined oil ................
Flax, seed, oil .......................
Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13–07F ....................
Grape, raisin .........................
Lettuce, head ........................
Lettuce, leaf ..........................
Mustard, seed, oil .................
Rapeseed subgroup 20A ......
Sesame, oil ...........................
0.01
0.01
4.0
0.03
0.03
3.0
5.0
5.0
7.0
0.03
0.015
0.03
(b) Section 18 emergency exemptions.
[Reserved]
(c) Tolerances with regional
registrations. [Reserved]
(d) Indirect or inadvertent residues.
[Reserved]
[FR Doc. 2015–18738 Filed 7–29–15; 8:45 am]
BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2013–0714; FRL–9927–63]
Benalaxyl-M; Pesticide Tolerances
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
This regulation establishes
tolerances for residues of benalaxyl-M
in or on grape and tomato. Since there
are currently no U.S. registrations of
benalaxyl-M for use on grape and
tomato, this tolerance will allow the
import of grape and tomato containing
residues of benalaxyl-M. Technology
Sciences Group, on behalf of Isagro
S.p.A, requested these tolerances under
the Federal Food, Drug, and Cosmetic
Act (FFDCA).
DATES: This regulation is effective July
30, 2015. Objections and requests for
hearings must be received on or before
September 28, 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).
SUMMARY:
E:\FR\FM\30JYR1.SGM
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Agencies
[Federal Register Volume 80, Number 146 (Thursday, July 30, 2015)]
[Rules and Regulations]
[Pages 45438-45443]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-18738]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2013-0138; FRL-9923-86]
Isofetamid; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes tolerances for residues of
isofetamid in or on multiple commodities that are identified and
discussed later in this document. ISK Biosciences Corporation requested
these tolerances under the Federal Food, Drug, and Cosmetic Act
(FFDCA).
DATES: This regulation is effective July 30, 2015. Objections and
requests for hearings must be received on or before September 28, 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-2013-0138, is available at https://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 https://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; telephone
number: 703-305-7090; email address: RDFRNotices@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.
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).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
B. How can I get electronic access to other related information?
You may access a frequently updated electronic version of EPA's
tolerance
[[Page 45439]]
regulations at 40 CFR part 180 through the Government Printing Office's
e-CFR site at https://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-2013-0138 in the subject line on the first
page of your submission. All objections and requests for a hearing must
be in writing, and must be received by the Hearing Clerk on or before
September 28, 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-2013-0138, by one of
the following methods:
Federal eRulemaking Portal: https://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
20460-0001.
Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at https://www.epa.gov/dockets/contacts.html. Additional
instructions on commenting or visiting the docket, along with more
information about dockets generally, is available at https://www.epa.gov/dockets.
II. Summary of Petitioned-For Tolerance
In the Federal Register of June 5, 2013 (78 FR 33785) (FRL-9386-2),
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 3F8142)
by ISK Biosciences Corporation, 7470 Auburn Road, Suite A, Concord,
Ohio 44077. The petition requested that 40 CFR part 180 be amended by
establishing tolerances for residues of the fungicide isofetamid, N-
[1,1-dimethyl-2-[2-methyl-4-(1-methylethoxy)phenyl]-2-oxoethyl]-3-
methyl-2-thiophenecarboxamide in or on almond at 0.02 parts per million
(ppm); almond, hulls at 0.2 ppm; lettuce, head at 6.0 ppm; lettuce,
leaf at 7.0 ppm; low growing berry crop subgroup 13-07G at 4.0 ppm;
rapeseed, crop subgroup 20A at 0.04 ppm; and small fruit vine climbing
crop subgroup 13-07F at 3.0 ppm. That document referenced a summary of
the petition prepared by ISK Biosciences Corporation, the registrant,
which is available in the docket, https://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
determined that additional tolerances are necessary; revised some of
the proposed tolerances; and corrected some commodity definitions for
the tolerances. The reasons 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 FFDCA section 408(b)(2)(D), and the factors
specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for isofetamid including exposure
resulting from the tolerances established by this action. EPA's
assessment of exposures and risks associated with isofetamid 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
children. The toxicology database is complete for isofetamid. In
repeated dose studies, the liver was the primary target organ in the
rat, mouse, and dog, as indicated by increased liver weights, changes
in the clinical chemistry values, and liver hypertrophy. A second
target organ was the thyroid in the rat and dog, as indicated by
changes in thyroid weights and histopathology. Adrenal weight changes
were observed in the subchronic rat and dog studies. In the rat and
dog, the dose levels where toxicity was observed were similar or higher
in the chronic studies compared with the respective subchronic studies,
showing an absence of progression of liver toxicity with time. There
was no evidence of carcinogenicity in the rat or mouse cancer studies;
the mutagenicity battery was negative. There are no genotoxicity,
neurotoxicity, or immunotoxicity concerns observed in the available
toxicity studies. Developmental toxicity was not observed in the rat or
rabbit, and offspring effects such as decreased body weight were seen
only in the presence of parental toxicity in the multi-generation rat
study. Isofetamid is classified as ``Not Likely to be Carcinogenic to
Humans'' based on the absence of increased tumor incidence in
acceptable/guideline carcinogenicity studies in rats and mice.
Isofetamid is not acutely toxic; it is classified as Toxicity Category
III for acute oral and dermal exposure, and Toxicity Category IV for
inhalation exposure. Furthermore, it is not irritating to the eye or
skin, and it is not a dermal sensitizer. Specific information on the
studies received and the nature of the adverse effects caused by
isofetamid as well as the no-observed-adverse-effect-level (NOAEL) and
the lowest-observed-adverse-effect-level (LOAEL) from the toxicity
studies can be found at https://www.regulations.gov in document
Isofetamid. Aggregate Human Health Risk Assessment for the Proposed New
Uses of the New Active Fungicide,
[[Page 45440]]
including Agricultural Uses on Almonds, Lettuce, Small Vine Climbing
Fruits (Crop Subgroup 13-07F), Low Growing Berries (Crop Subgroup 13-
07G), and Rapeseed (Crop Subgroup 20A); and Uses on Turfgrass
(including Golf Courses, Sod Farms, Seed Farms, Recreational Fields,
and Commercial/Residential Lawns) at pages 12-18 in docket ID number
EPA-HQ-OPP-2013-0138.
B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA
identifies toxicological points of departure (POD) and levels of
concern to use in evaluating the risk posed by human exposure to the
pesticide. For hazards that have a threshold below which there is no
appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which no adverse effects are observed (the NOAEL)
and the lowest dose at which adverse effects of concern are identified
(the LOAEL). Uncertainty/safety factors are used in conjunction with
the POD to calculate a safe exposure level--generally referred to as a
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe
margin of exposure (MOE). For non-threshold risks, the Agency assumes
that any amount of exposure will lead to some degree of risk. Thus, the
Agency estimates risk in terms of the probability of an occurrence of
the adverse effect expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see https://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for isofetamid used for
human risk assessment is shown in Table 1 of this unit.
Table 1--Summary of Toxicological Doses and Endpoints for Isofetamid for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
Point of departure
Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effects
safety factors risk assessment
----------------------------------------------------------------------------------------------------------------
Acute Dietary (All Populations) A toxicity endpoint was not identified.
Toxicological effects attributable to a single exposure (dose) were not
observed in oral toxicity studies.
----------------------------------------------------------------------------------------------------------------
Chronic dietary (All populations) NOAEL = 76.6 mg/kg/ Chronic RfD = 0.77 Reproduction and fertility effects
day mg/kg/day (rat)
UFA = 10X........... cPAD = 0.77 mg/kg/ LOAEL = 679/775 mg/kg/day based on
UFH = 10X........... day. hepatocellular hypertrophy in the
FQPA SF = 1X........ liver and follicular cell
hypertrophy in the thyroid in
both sexes and generations,
decreased spleen weights and
cytoplasmic eosinophilic
inclusion bodies in the liver of
F1 males, and decreased pup body
weight in both sexes and
generations.
----------------------------------------------------------------------------------------------------------------
Incidental oral short-term (1 to NOAEL = 76.6 mg/kg/ Residential LOC for Reproduction and fertility effects
30 days) and Incidental oral day MOE = 100. (rat)
intermediate-term (1 to 6 UFA = 10X........... LOAEL = 679/775 mg/kg/day based on
months) UFH = 10X........... hepatocellular hypertrophy in the
FQPA SF = 1X........ liver and follicular cell
hypertrophy in the thyroid in
both sexes and generations,
decreased spleen weights and
cytoplasmic eosinophilic
inclusion bodies in the liver of
F1 males, and decreased pup body
weight in both sexes and
generations
----------------------------------------------------------------------------------------------------------------
Dermal Short-Term (1-30 days) A toxicity endpoint was not identified.
Systemic toxicity was not seen in 28-day dermal toxicity in rats up to the
limit dose (1,000 mg/kg/day). There are no concerns for developmental or
reproductive toxicity or neurotoxicity in rat and rabbit studies.
----------------------------------------------------------------------------------------------------------------
Inhalation short-term (1 to 30 NOAEL = 76.6 mg/kg/ Residential LOC for Reproduction and fertility effects
days) day MOE = 100 (rat)
UFA = 10X........... LOAEL = 679/775 mg/kg/day based on
UFH = 10X........... hepatocellular hypertrophy in the
FQPA SF = 1X........ liver and follicular cell
hypertrophy in the thyroid in
both sexes and generations,
decreased spleen weights and
cytoplasmic eosinophilic
inclusion bodies in the liver of
F1 males, and decreased pup body
weight in both sexes and
generations.
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation) Classification: ``Not likely to be Carcinogenic to Humans'' based on the
absence of significant tumor increases in two adequate rodent
carcinogenicity studies.
----------------------------------------------------------------------------------------------------------------
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
of concern. mg/kg/day = milligram/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
level. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. UF = uncertainty factor.
UFA = extrapolation from animal to human (interspecies). UFDB = to account for the absence of data or other
data deficiency. UFH = potential variation in sensitivity among members of the human population
(intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term
risk assessment.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. EPA assessed dietary
exposures from isofetamid 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. No such effects were
identified in the toxicological studies for isofetamid; therefore, a
quantitative acute dietary exposure assessment is unnecessary.
[[Page 45441]]
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment, EPA used the 2003-2008 food consumption data from the
USDA's National Health and Nutrition Examination Survey, What We Eat in
America (NHANES/WWEIA). A partially refined chronic (food and drinking
water) dietary assessment was conducted assuming mean field trial
residues of the combined residues of parent and GPTC for all proposed
crops and 100% CT. Empirical and default processing factors were used
as available.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has
concluded that isofetamid 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 PCT information in the dietary assessment for
isofetamid. Mean field trial residues of the combined residues of
parent and GPTC were used.
2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for isofetamid in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of isofetamid. Further information regarding EPA
drinking water models used in pesticide exposure assessment can be
found at https://www.epa.gov/oppefed1/models/water/index.htm.
Based on the Pesticide Flooded Application Model and the Pesticide
Root Zone Model Ground Water (PRZM GW) the estimated drinking water
concentrations (EDWCs) of isofetamid for chronic exposures for non-
cancer assessments are estimated to be 110 ppb for surface water and 43
ppb for ground water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For chronic dietary risk
assessment, the water concentration value of 110 ppb was used to assess
the contribution from 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).
Isofetamid is currently under review for registering the following
uses that could result in residential exposures: Foliar and systemic
fungicide for control in turfgrass including golf courses, residential
lawns, and recreational turfgrass. Since there may be residential use
sites, residential handler exposure and risk estimates were calculated
for all possible residential exposure scenarios. Including all possible
residential exposure scenarios provides a conservative and health
protective assessment for the potential for homeowners to use the
professionally labeled products on residential use sites. Since there
is no dermal toxicity endpoint, the residential handler assessment only
includes the inhalation route of exposure. Residential handler exposure
is expected to be short-term in duration as a maximum of eight
applications are allowed per year. Thus, intermediate-term exposures
are not likely because of the intermittent nature of applications by
homeowners. Unit exposure values and estimates for area treated or
amount handled were taken from the Agency's 2012 Residential SOPs \1\
(Lawns/Turf). The algorithms used to estimate exposure and dose for
residential handlers can be found in the 2012 Residential SOPs \2\
(Lawns/Turf). Risk estimates of all possible scenarios are not of
concern. Short-term inhalation MOEs range from 850,000 to 18,000,000.
Further information regarding EPA standard assumptions and generic
inputs for residential exposures may be found at https://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
---------------------------------------------------------------------------
\1\ Available: https://www.epa.gov/pesticides/science/residential-exposure-sop.html.
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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 isofetamid to share a common mechanism of
toxicity with any other substances, and isofetamid does not appear to
produce a toxic metabolite produced by other substances. For the
purposes of this tolerance action, therefore, EPA has assumed that
isofetamid 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 Web site at https://www.epa.gov/pesticides/cumulative.
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA Safety
Factor (SF). In applying this provision, EPA either retains the default
value of 10X, or uses a different additional safety factor when
reliable data available to EPA support the choice of a different
factor.
2. Prenatal and postnatal sensitivity. There is no evidence of
developmental toxicity or reproductive susceptibility, and there are no
residual uncertainties concerning pre- or post-natal toxicity or
exposure.
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 to 1X. That decision is based on the following
findings:
i. The toxicity database for isofetamid is complete.
ii. There is no indication that isofetamid is a neurotoxic chemical
and there is no need for a developmental neurotoxicity study or
additional UFs to account for neurotoxicity.
iii. There is no evidence that isofetamid results in increased
susceptibility in in utero rats or rabbits in the prenatal
developmental studies or in young rats in the 2-generation reproduction
study.
iv. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed based
on 100 PCT and average (mean) field trial residues. EPA made
conservative (protective) assumptions in the ground and surface water
modeling used to assess exposure to isofetamid 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 isofetamid.
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
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer
[[Page 45442]]
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.
1. Acute risk. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. No adverse effect resulting from a single oral exposure
was identified and no acute dietary endpoint was selected. Therefore,
isofetamid is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
isofetamid from food and water will utilize <1% of the cPAD for
children (1-2 years old), the population group receiving the greatest
exposure. Based on the explanation in Unit III.C.3., regarding
residential use patterns, chronic residential exposure to residues of
isofetamid 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). Isofetamid 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 isofetamid.
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 MOEs of 24,000 and 3,900
for adults and children (1-2 years old) respectively. Because EPA's
level of concern for isofetamid is a MOE of 100 or below, these MOEs
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). An intermediate-term adverse effect was identified; however,
isofetamid is not registered for any use patterns that would result in
intermediate-term residential exposure. Intermediate-term risk is
assessed based on intermediate-term residential exposure plus chronic
dietary exposure. Because there is no intermediate-term residential
exposure and chronic dietary exposure has already been assessed under
the appropriately protective cPAD (which is at least as protective as
the POD used to assess intermediate-term risk), no further assessment
of intermediate-term risk is necessary, and EPA relies on the chronic
dietary risk assessment for evaluating intermediate-term risk for
isofetamid.
5. Aggregate cancer risk for U.S. population. Based on the lack of
evidence of carcinogenicity in two adequate rodent carcinogenicity
studies, isofetamid 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 isofetamid residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology liquid chromatography with tandem
mass spectrometry (LC-MS/MS) method (Document Number JSM0119; MRID
49011967) is available to enforce the tolerance expression.
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.
The Codex has not established any MRLs for isofetamid. Canada is
concurrently establishing tolerances for all of the same commodities
identified in this document except almond hulls because Canada does not
set tolerances on livestock feed commodities. Canada's recommended
tolerance levels for these commodities are the same as the U.S.
established tolerance levels. The tolerance expression for the U.S. and
Canada is the same, with isofetamid as the residue of concern for
primary crops.
C. Revisions to Petitioned-For Tolerances
The Agency has made revisions to some of the petitioned-for
tolerance levels based on the following reasons:
1. Organization for Economic Cooperation and Development (OECD)
tolerance calculation procedures;
2. The parent only is the residue of concern for primary crop
tolerances rather than parent and the metabolite GPTC; and
3. The concentration of residues in two processed commodities.
Since all residues of isofetamid (parent) were nondetectable (<0.01
ppm) in almond nutmeat and hulls, the proposed tolerances of 0.02 ppm
for almond (nutmeat) and 0.2 ppm for almond hulls will both be reduced
to 0.01 ppm, the limit of quantitation of the analytical method.
Based on the OECD tolerance calculation procedures, the proposed
tolerance for head lettuce of 6.0 ppm will be reduced to 5.0 ppm. Based
on the OECD tolerance calculation procedures, the proposed tolerance
for the rapeseed subgroup 20A of 0.04 ppm will be reduced to 0.015 ppm.
The petitioner did not propose tolerances for the processed
commodities, canola oil and raisins. Since residues concentrate
significantly in canola oil and raisins, tolerances will be established
at 0.03 ppm for canola, refined oil, and 5.0 ppm for grape, raisin.
These Agency recommendations are based on the highest average field
trial (HAFT) residues for canola seed and grape and the processing
factors for canola oil and raisins. The petitioner did not propose
tolerances for flaxseed oil, mustard seed oil, or sesame oil. However,
flaxseed, mustard seed, and sesame are members of the rapeseed subgroup
20A, with canola as the representative crop, and treated commodities
could be processed to produce sesame oil, mustard seed oil and flaxseed
oil. Therefore, the Agency is also establishing tolerances for residues
in flaxseed oil, mustard seed oil, and sesame oil. Tolerances are being
established at 0.03 ppm, the same level as for refined canola oil.
Additionally, some of the requested tolerances have been corrected.
Almond has been revised from 0.02 ppm to 0.01 ppm; almond, hulls from
0.2 ppm to 0.01 ppm; lettuce, head from 6.0 ppm to 5.0 ppm; and
rapeseed, subgroup 20A from 0.04 ppm to 0.015 ppm. The Agency is
setting tolerances on some processed commodities that were not
[[Page 45443]]
proposed by the petitioner including canola, refined oil at 0.03 ppm;
flax, seed, oil at 0.03 ppm; grape, raisin at 5.0 ppm; mustard, seed,
oil at 0.03 ppm and sesame, oil at 0.03 ppm.
V. Conclusion
Therefore, tolerances are established for residues of isofetamid,
in or on almond at 0.01 ppm; almond, hulls at 0.01 ppm; canola, refined
oil at 0.03 ppm; flax, seed, oil at 0.03 ppm; grape, raisin at 5.0 ppm;
lettuce, head at 5.0 ppm; lettuce, leaf at 7.0 ppm; berry, low growing,
subgroup 13-07G at 4.0 ppm; mustard, seed, oil at 0.03 ppm; rapeseed
subgroup 20A at 0.015 ppm; sesame, oil at 0.03 ppm; and fruit, small
vine climbing, except fuzzy kiwifruit, subgroup 13-07F at 3.0 ppm.
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 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 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: July 21, 2015.
Jack Housenger,
Director, Office of Pesticide Programs.
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. Add Sec. 180.681 to subpart C to read as follows:
Sec. [emsp14]180.681 Isofetamid; tolerances for residues.
(a) General. Tolerances are established for residues of the
fungicide isofetamid, including its metabolites and degradates, in or
on the commodities in the table below. Compliance with the tolerance
levels specified below is to be determined by measuring only
isofetamid, N-[1,1-dimethyl-2-[2-methyl-4-(1-methylethoxy)phenyl]-2-
oxoethyl]-3-methyl-2-thiophenecarboxamide, in or on the following
commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Almond.................................................. 0.01
Almond, hulls........................................... 0.01
Berry, low growing, subgroup 13-07G..................... 4.0
Canola, refined oil..................................... 0.03
Flax, seed, oil......................................... 0.03
Fruit, small vine climbing, except fuzzy kiwifruit, 3.0
subgroup 13-07F........................................
Grape, raisin........................................... 5.0
Lettuce, head........................................... 5.0
Lettuce, leaf........................................... 7.0
Mustard, seed, oil...................................... 0.03
Rapeseed subgroup 20A................................... 0.015
Sesame, oil............................................. 0.03
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 2015-18738 Filed 7-29-15; 8:45 am]
BILLING CODE 6560-50-P