Penflufen; Pesticide Tolerances, 28276-28281 [2012-11629]
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Commodity
Parts per
million
Goat, meat ................................
Goat, meat byproducts .............
Grain, aspirated fractions .........
Grain, cereal, group 15, (except
corn, field, grain; except
corn, pop, grain; except corn,
kernels plus cobs with husks
removed; except wheat) .......
Grain, cereal, forage, fodder
and straw, group 16 ..............
Horse, fat ..................................
Horse, meat ..............................
Horse, meat byproducts ...........
Milk ...........................................
Oilseeds, group 20 ...................
Pea and bean, dried shelled
except soybean, subgroup
6C ..........................................
Pea and bean, succulent
shelled, subgroup 6B ............
Peanut ......................................
Peanut, refined oil ....................
Plum, prune ..............................
Potato, wet peel ........................
Rice, bran .................................
Rice, hulls .................................
Sheep, fat .................................
Sheep, meat .............................
Sheep, meat byproducts ..........
Soybean, hulls ..........................
Soybean, seed ..........................
Vegetable, foliage of legume,
group 7 ..................................
Vegetables, fruiting, group 8 ....
Vegetable, legume, edible podded, subgroup 6A .................
Vegetable, tuberous and corm,
subgroup 1C .........................
Wheat, bran ..............................
Wheat, grain .............................
0.01
0.03
20.0
This regulation is effective May
14, 2012. Objections and requests for
hearings must be received on or before
July 13, 2012, 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:
EPA has established a
docket for this action under docket
identification (ID) number EPA–HQ–
20
OPP–2010–0425. All documents in the
0.05
docket are listed in the docket index
0.01
available at https://www.regulations.gov.
0.03
0.005 Although listed in the index, some
0.9
information is not publicly available,
e.g., Confidential Business Information
(CBI) or other information whose
0.4
disclosure is restricted by statute.
Certain other material, such as
0.5
copyrighted material, is not placed on
0.01
the Internet and will be publicly
0.02
available only in hard copy form.
3.0
Publicly available docket materials are
0.1
4.5
available in the electronic docket at
8.0
https://www.regulations.gov, or, if only
0.05
available in hard copy, at the OPP
0.01
Regulatory Public Docket in Rm. S–
0.03
4400, One Potomac Yard (South Bldg.),
0.3
2777 S. Crystal Dr., Arlington, VA. The
0.15
Docket Facility is open from 8:30 a.m.
to 4 p.m., Monday through Friday,
30
excluding legal holidays. The Docket
0.7
Facility telephone number is (703) 305–
2.0
5805.
FOR FURTHER INFORMATION CONTACT:
0.02
Marianne Lewis, Registration Division
0.6
(7505P), Office of Pesticide Programs,
0.3
Environmental Protection Agency, 1200
(b) Section 18 emergency exemptions. Pennsylvania Ave. NW., Washington,
DC 20460–0001; telephone number:
[Reserved]
(703) 308–8043; email address:
(c) Tolerances with regional
lewis.marianne@epa.gov.
registrations. [Reserved]
(d) Indirect or inadvertent residues.
SUPPLEMENTARY INFORMATION:
[Reserved]
I. General Information
[FR Doc. 2012–11602 Filed 5–11–12; 8:45 am]
3.0
A. Does this action apply to me?
BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2010–0425; FRL–9341–8]
Penflufen; Pesticide Tolerances
Environmental Protection
Agency (EPA).
ACTION: Final rule.
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AGENCY:
This regulation establishes
tolerances for residues of penflufen in or
on multiple commodities which are
identified and discussed later in this
document. Bayer CropScience requested
these tolerances under the Federal Food,
Drug, and Cosmetic Act (FFDCA).
SUMMARY:
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ADDRESSES:
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You may be potentially affected by
this action if you are an agricultural
producer, food manufacturer, or
pesticide manufacturer. Potentially
affected entities may include, but are
not limited to those engaged in the
following activities:
• Crop production (NAICS code 111).
• Animal production (NAICS code
112).
• Food manufacturing (NAICS code
311).
• Pesticide manufacturing (NAICS
code 32532).
This listing is not intended to be
exhaustive, but rather to provide a guide
for readers regarding entities likely to be
affected by this action. Other types of
entities not listed in this unit could also
be affected. The North American
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Industrial Classification System
(NAICS) codes have been provided to
assist you and others in determining
whether this action might apply to
certain entities. If you have any
questions regarding the applicability of
this action to a particular entity, consult
the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How can I get electronic access to
other related information?
You may access a frequently updated
electronic version of EPA’s tolerance
regulations at 40 CFR part 180 through
the Government Printing Office’s e-CFR
site at https://ecfr.gpoaccess.gov/cgi/t/
text/text-idx?&c=ecfr&tpl=/ecfrbrowse/
Title40/40tab_02.tpl. To access the
OCSPP test guidelines referenced in this
document electronically, please go
https://www.epa.gov/ocspp and select
‘‘Test Methods and Guidelines.’’
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–2010–0425 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 July 13, 2012. 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 that does not
contain any 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 a copy of
your non-CBI objection or hearing
request, identified by docket ID number
EPA–HQ–OPP–2010–0425, by one of
the following methods:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the on-line
instructions for submitting comments.
• Mail: Office of Pesticide Programs
(OPP) Regulatory Public Docket (7502P),
Environmental Protection Agency, 1200
Pennsylvania Ave. NW., Washington,
DC 20460–0001.
• Delivery: OPP Regulatory Public
Docket (7502P), Environmental
Protection Agency, Rm. S–4400, One
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Potomac Yard (South Bldg.), 2777 S.
Crystal Dr. Arlington, VA. Deliveries are
only accepted during the Docket
Facility’s normal hours of operation
(8:30 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays).
Special arrangements should be made
for deliveries of boxed information. The
Docket Facility telephone number is
(703) 305–5805.
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II. Summary of Petitioned-For
Tolerance
In the Federal Register of September
8, 2010 (75 FR 54631) (FRL–8843–3),
EPA issued a notice pursuant to section
408(d)(3) of FFDCA, 21 U.S.C.
346a(d)(3), announcing the filing of a
pesticide petition (PP 0F7711) by Bayer
CropScience, 2 T.W. Alexander Drive
P.O. Box 12014, Research Triangle Park,
NC 27709. The petition requested that
40 CFR part 180 be amended by
establishing tolerances for residues of
the penflufen, N-[2-(1,3dimethylbutyl)phenyl]-5-fluoro-1,3dimethyl-1H-pyrazole-4-carboxamide,
in or on alfalfa, forage; alfalfa, hay;
vegetable, tuberous and corm, subgroup
1C; vegetable, legume, group 6;
vegetable, foliage of legume, group 7;
grain, cereal, group 15, grain, cereal,
forage, fodder and straw, group 16;
oilseed, group 19; cotton, gin byproducts at 0.01 parts per million
(ppm). That notice referenced a
summary of the petition prepared by
Bayer CropScience, 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 made
some minor modifications to some
commodity definitions for consistency
with EPA naming-conventions for those
commodities. The reason for these
changes is explained in Unit IV.D.
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
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give special consideration to exposure
of infants and children to the pesticide
chemical residue in establishing a
tolerance and to ‘‘ensure that there is a
reasonable certainty that no harm will
result to infants and children from
aggregate exposure to the pesticide
chemical residue * * *.’’
Consistent with section 408(b)(2)(D)
of FFDCA, and the factors specified in
section 408(b)(2)(D) of FFDCA, EPA has
reviewed the available scientific data
and other relevant information in
support of this action. EPA has
sufficient data to assess the hazards of
and to make a determination on
aggregate exposure for penflufen
including exposure resulting from the
tolerances established by this action.
EPA’s assessment of exposures and risks
associated with penflufen 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. Penflufen is an
alkylamide fungicide belonging to the
chemical class of carboxamides. The
reported pesticidal mode of action is as
an inhibitor of mitochondrial
respiration by inhibiting succinate
dehydrogenase, an enzyme in the
electron transport system.
The liver and thyroid are target organs
for penflufen. Increased liver weight,
alterations in clinical chemistry
parameters relevant to effects on the
liver, and an increase in the incidence
of hepatocellular hypertrophy were
consistent findings across species and
duration of exposure (28-day, 90-day,
and 1- to 2-year exposure periods). The
hepatic total cytochrome P–450 content,
and benzoxyresorufin (BROD) and
pentoxyresorufin (PROD) enzyme
activities, were shown to be increased in
rats of both sexes following subchronic
oral exposure. Additionally, increased
incidence of thyroid follicular cell
hypertrophy/hyperplasia was observed
across studies and species (no data
provided on thyroid hormone levels).
The liver and thyroid findings were
mostly reversible after a 3-month
recovery period in the rat. In the rat and
mouse, following 104 week/78 week
exposure periods at dose levels up to
and/or greater than the limit dose, there
was no increase in the incidence of liver
or thyroid tumors.
Reproductive toxicity was observed in
the 2-generation reproduction study in
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rats. Delayed sexual maturation was
observed in females in both generations,
and magnitude of the associated decline
in body weight was not considered to be
a factor in the delay in sexual
maturation. Developmental toxicity was
not observed in the rat or rabbit,
although the dose levels in both studies
were not considered adequate to assess
developmental toxicity potential of
penflufen. However, there is little
concern that new studies would identify
a developmental endpoint with a noobserved-adverse-effect-level (NOAEL)
lower than the NOAEL selected for risk
assessment.
Decreased motor/locomotor activity
was observed in both sexes of rats
following acute and in female rats
following subchronic oral exposure,
although neuropathological lesions were
not observed in either study.
There are no mutagenicity concerns.
Carcinogenicity studies with penflufen
found a statistically significant increase
in histiocytic sarcomas in male rats; a
marginal increase in brain astrocytomas,
a fatal tumor, in male rats at the high
dose; and ovarian adenomas in female
rats at the high dose. Although these
three tumors were considered treatmentrelated, they provided weak evidence of
carcinogenicity due to the marginal
nature of the tumor responses. There
was no evidence of carcinogenicity in
male or female mice. Given the weak
evidence indicating any potential for
carcinogenicity, EPA has determined
that quantification of risk using a nonlinear approach reference dose (i.e.,
RfD) will adequately account for all
chronic toxicity, including
carcinogenicity, which could result
from exposure to penflufen. The NOAEL
(38 milligram/kilogram/day (mg/kg/
day)) used for establishing the Chronic
RfD is approximately 10-fold lower than
the dose (approximately 300 mg/kg/day)
that induced a marginal tumor response.
The EPA has determined that the
chronic population adjusted dose is
protective of all long-term effects,
including potential carcinogenicity.
Specific information on the studies
received and the nature of the adverse
effects caused by penflufen as well as
the NOAEL and the lowest-observedadverse-effect-level (LOAEL) from the
toxicity studies can be found at https://
www.regulations.gov in document
‘‘Penflufen. Human Health Risk
Assessment to Support New Uses on
Potato (Crop Subgroup 1C), Legume
Vegetables (Crop Group 6 and Crop
Group 7), Cereal Grains (Crop Group 15
and Crop Group 16), Oilseeds (Crop
Group 20), and Alfalfa’’ in docket ID
number EPA–HQ–OPP–2010–0425.
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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 (LOC) 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
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 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 penflufen used for human
risk assessment is shown in the Table of
this unit.
TABLE—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR PENFLUFEN FOR USE IN HUMAN HEALTH RISK
ASSESSMENT
Point of departure
and uncertainty/
safety factors
Exposure/scenario
RfD, PAD, LOC for
risk assessment
Study and toxicological effects
Acute dietary (all populations, including
children and women 13–49 years of
age).
NOAEL = 50 mg/
kg/day.
UFA = 10x
UFH = 10x
FQPA SF = 1x
Acute RfD = 0.5
mg/kg/day.
aPAD = 0.5 mg/kg/
day
Acute neurotoxicity study in rats.
LOAEL = 100 mg/kg/day based on decreased motor and
locomotor activity (39–81% on day of treatment) in females.
Chronic dietary (All populations) ............
NOAEL= 38 mg/kg/
day.
UFA = 10x
UFH = 10x
FQPA SF = 1x
Chronic RfD = 0.38
mg/kg/day.
cPAD = 0.38 mg/
kg/day
Chronic toxicity study in dogs.
LOAEL = 357/425 mg/kg/day, based on decreased terminal body weight and body weight gain (females), increased prothrombin time (males), increased alkaline
phosphate activity, decreased cholesterol, increased
GGT levels, decreased albumin and albumin/globulin
ratio, decreased calcium and phosphorus, increased
liver weights, increased incidence of focal hepatocellular
brown pigment and hepatocellular hypertrophy, and an
increased incidence of thyroid follicular cell hypertrophy
in both sexes, and in increased incidence of zona glomerulosa vacuolation of the adrenal gland in females.
Cancer (Oral, dermal, inhalation) ...........
Quantification of risk using a non-linear approach (i.e., RfD) will adequately account for all chronic toxicity, including carcinogenicity that could result from exposure to penflufen.
UFA = extrapolation from animal to human (interspecies). 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. UFDB = to account for the absence of data or other data deficiency. FQPA SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose
(a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. Mg/kg/day = milligrams/kilograms/day.
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C. Exposure Assessment
1. Dietary exposure from food and
feed uses. In evaluating dietary
exposure to penflufen, EPA considered
exposure under the petitioned-for
tolerances. EPA assessed dietary
exposures from penflufen 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.
Such effects were identified for
penflufen. In estimating acute dietary
exposure, EPA used food consumption
information from the United States
Department of Agriculture (USDA)
1994–1996 and 1998 Nationwide
Continuing Surveys of Food Intake by
Individuals (CSFII). As to residue levels
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in food, EPA used tolerance-level
residues, default dietary exposure
evaluation model (DEEM) processing
factors for dried potatoes and assumed
100 percent crop treated (PCT) for all
commodities.
ii. Chronic exposure. In conducting
the chronic dietary exposure assessment
EP used the food consumption data
from the USDA 1994–1996 and 1998
CSFII. As to residue levels in food, EPA
used tolerance-level residues, default
DEEM processing factors for dried
potatoes and assumed 100 PCT for all
commodities.
ii. Chronic exposure. In conducting
the chronic dietary exposure assessment
EPA used the food consumption data
from the USDA 1994–1996 and 1998
CSFII. As to residue levels in food, EPA
used tolerance-level residues, default
DEEM processing factors for dried
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potatoes and assumed 100 PCT for all
commodities.
iii. Cancer. EPA determines whether
quantitative cancer exposure and risk
assessments are appropriate for a fooduse pesticide based on the weight of the
evidence from cancer studies and other
relevant data. Cancer risk is quantified
using a linear or non-linear approach. If
sufficient information on the
carcinogenic mode of action is available,
a threshold or non-linear approach is
used based on an earlier non-cancer key
event. If carcinogenic mode of action
data are not available, or if the mode of
action data determines a mutagenic
mode of action, a default linear cancer
slope factor approach is utilized. Based
on the data summarized in Unit III.A.,
EPA has concluded that a non-linear
RfD approach is appropriate for
assessing cancer risk to penflufen.
Cancer risk was assessed using the same
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exposure estimates as discussed in Unit
III.C.1.ii.
iv. Anticipated residue and PCT
information. EPA did not use
anticipated residue and/or PCT
information in the dietary assessment
for penflufen. Tolerance level residues
and/or 100 PCT were assumed for all
food commodities.
2. Dietary exposure from drinking
water. The Agency used screening level
water exposure models in the dietary
exposure analysis and risk assessment
for penflufen in drinking water. These
simulation models take into account
data on the physical, chemical, and fate/
transport characteristics of penflufen.
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 First Index Reservoir
Screening Tool (FIRST) and Screening
Concentration in Ground Water (SCI–
GROW) models, the estimated drinking
water concentrations (EDWCs) of
penflufen for acute exposures are
estimated to be 11.4 parts per billion
(ppb) for surface water and 16.6 ppb for
ground water. The EDWC of penflufen
for chronic exposures for non-cancer
assessments are estimated to be 1.8 ppb
for surface water and 16.6 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 16.6 ppb was
used to assess the contribution to
drinking water. For chronic dietary risk
assessment, the water concentration of
value 16.6 ppb was used to assess the
contribution to drinking water.
3. From non-dietary exposure. The
term ‘‘residential exposure’’ is used in
this document to refer to nonoccupational, non-dietary exposure
(e.g., for lawn and garden pest control,
indoor pest control, termiticides, and
flea and tick control on pets).
Penflufen is not registered for any
specific use patterns that would result
in residential exposure.
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 penflufen to share
a common mechanism of toxicity with
any other substances, and penflufen
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does not appear to produce a toxic
metabolite produced by other
substances. For the purposes of this
tolerance action, therefore, EPA has
assumed that penflufen 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.
In the rat multi-generation reproduction
study there was slight decrease in litter
size, delayed sexual maturation,
decreased body weight/gain, decreased
brain, spleen, and thymus weights were
noted in the offspring. At the same dose
level the adults exhibited decreased
body weight/gain, alteration in food
consumption, decreased thymus weight,
and decrease spleen weights. In the rat
developmental toxicity study, the
maternal findings (decreased body
weight gain) at the highest dose tested
(HDT) are considered minimal. No
adverse effects were observed on the
foetuses. In the rabbit developmental
toxicity study, the maternal findings
(decreased body weight gain) at the HDT
are considered minimal. No adverse
effects were observed at the HDT.
3. Conclusion. The Agency
recommends that the 10X FQPA safety
factor for the protection of infants and
children, be reduced to 1X. The risk
assessments conducted for penflufen
were based on the most sensitive
endpoints in the toxicity database, and
the NOAELs selected for risk assessment
are considered protective of potential
developmental, neurotoxic, and
immunotoxic effects for infants and
children. Highly conservative exposure
estimates were incorporated into the
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risk assessment for penflufen. There are
no residual uncertainties with regard to
pre- and/or postnatal toxicity or
neurotoxicity, and exposure; therefore,
reduction of the 10X FQPA safety factor
for penflufen to 1X is appropriate based
on the following findings:
i. The toxicity database for penflufen
is complete for consideration of
estimated risks for all populations of
concern.
ii. Although decreased motor activity
was observed following acute oral
exposure, no neuropathological lesions
were observed and there is little concern
for neurotoxicity. There is no need for
a developmental neurotoxicity study or
additional UFs to account for
neurotoxicity.
iii. Although there is some evidence
of qualitative sensitivity of the young
(delayed sexual maturation and
decreased litter size), the effects are well
characterized, and there is a clear
NOAEL. The dose level where offspring
effects were identified in the
reproduction study is comparable to the
high dose used in the rat developmental
toxicity study where no effects were
identified in either the maternal or fetal
rat. Since minimal/no effects were
observed in the developmental toxicity
studies following exposure of the
maternal animals to dose levels equal to
and greater than those tested in the
studies used for risk assessment, there is
little concern that new studies would
identify a developmental endpoint with
a NOAEL lower than the NOAELs
selected for risk assessment.
iv. There are no residual uncertainties
identified in the exposure databases.
The dietary food exposure assessments
were performed based on 100 PCT and
tolerance-level residues. EPA made
conservative (protective) assumptions in
the ground and surface water modeling
used to assess exposure to penflufen in
drinking water. These assessments will
not underestimate the exposure and
risks posed by penflufen.
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
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.
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Federal Register / Vol. 77, No. 93 / Monday, May 14, 2012 / Rules and Regulations
1. Acute risk. An acute aggregate risk
assessment takes into account acute
exposure estimates from dietary
consumption of food and drinking
water. A highly conservative acute
dietary exposure assessment
demonstrated that penflufen does not
pose an unacceptable aggregate risk.
2. Chronic risk. There are no
residential uses for penflufen; therefore,
the chronic aggregate risk assessment
includes exposures from dietary
consumption of food and water only. A
highly conservative chronic aggregate
dietary exposure assessment
demonstrated that penflufen does not
pose an unacceptable aggregate chronic
risk.
3. Short-term risk. There are no
residential uses of penflufen; therefore a
short-term aggregate risk assessment
was not conducted for this chemical.
4. Intermediate-term risk. There are
no residential uses of penflufen;
therefore an intermediate-term aggregate
risk assessment was not conducted for
this chemical.
5. Aggregate cancer risk for U.S.
population. In a rat carcinogenicity
study with penflufen a statistically
significant increase in histiocytic
sarcomas with a positive trend in male
rats only (but in the absence of a dose
response and lack of pre-neoplastic
lesions) were seen. A marginal increase
in brain astrocytomas was also observed
in males at the high dose; however, this
effect was not dose-related, did not
reach statistical significance, and there
was no overall trend. In addition, there
were no pre-neoplastic lesions, such as
glial proliferations, which are a good
indicator of chemical tumor induction
(i.e., there will be changes in the cells
prior to transformation to a neoplasm).
The ovarian adenomas observed at the
high dose also showed no dose
response, no pair-wise significance, no
decrease in latency, and there were no
pre-neoplastic lesions such as
hyperplasia of the epithelial cells of the
endometrium. Additionally, there was
no evidence of carcinogenicity in male
or female mice (at doses that were
judged to be adequate to assess the
carcinogenic potential), no concern for
mutagenicity (in vivo or in vitro) for the
parent molecule or the two metabolites,
and there were no other lines of
evidence (such as structure-activity
relationship). Although these three
tumors were considered treatmentrelated, they provided weak evidence of
carcinogenicity due to the marginal
nature of the tumor responses and the
other factors mentioned in this unit.
Given the weak evidence indicating any
potential for carcinogenicity, EPA has
determined that quantification of risk
VerDate Mar<15>2010
14:45 May 11, 2012
Jkt 226001
using a non-linear approach (i.e., RfD)
will adequately account for all chronic
toxicity, including carcinogenicity,
which could result from exposure to
penflufen. The NOAEL (38 mg/kg/day)
used for establishing the chronic RfD is
approximately 10-fold lower than the
dose (approximately 300 mg/kg/day)
that induced a marginal tumor response.
The EPA has determined that the
chronic population adjusted dose is
protective of all long-term effects,
including potential carcinogenicity.
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 penflufen
residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology
is available to enforce the tolerance
expression. The method involves
extraction of samples with acetonitrile/
water, cleanup using solid phase
extraction, and analysis of penflufen by
liquid chromatography/mass
spectrometry (LC/MS/MS) (EL–002–
P09–03).
B. International Residue Limits
In making its tolerance decisions, EPA
seeks to harmonize U.S. tolerances with
international standards whenever
possible, consistent with U.S. food
safety standards and agricultural
practices. EPA considers the
international maximum residue limits
(MRLs) established by the Codex
Alimentarius Commission (Codex), as
required by FFDCA section 408(b)(4).
The Codex Alimentarius is a joint U.N.
Food and Agriculture Organization/
World Health Organization food
standards program, and it is recognized
as an international food safety
standards-setting organization in trade
agreements to which the United States
is a party. EPA may establish a tolerance
that is different from a Codex MRL;
however, FFDCA section 408(b)(4)
requires that EPA explain the reasons
for departing from the Codex level.
The Codex has not established a MRL
for penflufen.
C. Revisions to Petitioned-For
Tolerances
Some minor modifications to
commodity definitions initially
submitted were made to be consistent
with the updated EPA namingconventions for commodities.
PO 00000
Frm 00044
Fmt 4700
Sfmt 4700
V. Conclusion
Therefore, tolerances are established
for residues of penflufen, in or on
alfalfa, forage; alfalfa, hay; vegetable,
tuberous and corm, subgroup 1C;
vegetable, legume, group 6; vegetable,
foliage of legume, group 7; grain, cereal,
group 15, grain, cereal, forage, fodder
and straw, group 16; oilseed, group 19;
cotton, gin by-products at 0.01 ppm.
VI. Statutory and Executive Order
Reviews
This final rule establishes tolerances
under section 408(d) of FFDCA in
response to a petition submitted to the
Agency. The Office of Management and
Budget (OMB) has exempted these types
of actions from review under Executive
Order 12866, entitled Regulatory
Planning and Review (58 FR 51735,
October 4, 1993). Because this final rule
has been exempted from review under
Executive Order 12866, this final rule is
not subject to Executive Order 13211,
entitled Actions Concerning Regulations
That Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May
22, 2001) or Executive Order 13045,
entitled Protection of Children from
Environmental Health Risks and Safety
Risks (62 FR 19885, April 23, 1997).
This final rule does not contain any
information collections subject to OMB
approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et
seq., nor does it require any special
considerations under Executive Order
12898, entitled Federal Actions to
Address Environmental Justice in
Minority Populations and Low-Income
Populations (59 FR 7629, February 16,
1994).
Since tolerances and exemptions that
are established on the basis of a petition
under section 408(d) of FFDCA, such as
the tolerance in this final rule, do not
require the issuance of a proposed rule,
the requirements of the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates
growers, food processors, food handlers,
and food retailers, not States or tribes,
nor does this action alter the
relationships or distribution of power
and responsibilities established by
Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such,
the Agency has determined that this
action will not have a substantial direct
effect on States or tribal governments,
on the relationship between the national
government and the States or tribal
governments, or on the distribution of
power and responsibilities among the
various levels of government or between
the Federal Government and Indian
E:\FR\FM\14MYR1.SGM
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Federal Register / Vol. 77, No. 93 / Monday, May 14, 2012 / Rules and Regulations
tribes. Thus, the Agency has determined
that Executive Order 13132, entitled
Federalism (64 FR 43255, August 10,
1999) and Executive Order 13175,
entitled Consultation and Coordination
with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply
to this final rule. In addition, this final
rule does not impose any enforceable
duty or contain any unfunded mandate
as described under Title II of the
Unfunded Mandates Reform Act of 1995
(UMRA) (Pub. L. 104–4).
This action does not involve any
technical standards that would require
Agency consideration of voluntary
consensus standards pursuant to section
12(d) of the National Technology
Transfer and Advancement Act of 1995
(NTTAA), Public Law 104–113, section
12(d) (15 U.S.C. 272 note).
specified in the table is to be
determined by measuring only
penflufen N-[2-(1,3dimethylbutyl)phenyl]-5-fluoro-1,3dimethyl-1H-pyrazole-4-carboxamide,
in or on the following commodities.
VII. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801 et seq., generally provides
that before a rule may take effect, the
agency promulgating the rule must
submit a rule report to each House of
the Congress and to the Comptroller
General of the United States. EPA will
submit a report containing this rule and
other required information to the U.S.
Senate, the U.S. House of
Representatives, and the Comptroller
General of the United States prior to
publication of this final rule in the
Federal Register. This final rule is not
a ‘‘major rule’’ as defined by 5 U.S.C.
804(2).
(b) Section 18 emergency exemptions.
[Reserved]
(c) Tolerances with regional
registrations. [Reserved]
(d) Indirect or inadvertent residues.
[Reserved]
List of Subjects in 40 CFR Part 180
Environmental protection,
Administrative practice and procedure,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping
requirements.
Withdrawal of Revocation of TSCA
Section 4 Testing Requirements for
One High Production Volume Chemical
Substance
Dated: May 3, 2012.
Steven Bradbury,
Director, Office of Pesticide Programs.
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. Section 180.664 is added to subpart
C to read as follows:
emcdonald on DSK29S0YB1PROD with RULES
■
§ 180.664 Penflufen; tolerances for
residues.
(a) General. Tolerances are
established for residues of the fungicide
penflufen, including its metabolites and
degradates, in or on the following
commodities listed in the table.
Compliance with the tolerance levels
18:07 May 11, 2012
Jkt 226001
Alfalfa, forage .............................
Alfalfa, hay ..................................
Cotton, gin by-products ..............
Grain cereal, forage, fodder and
straw, group 16 .......................
Grain, cereal, group 15 ..............
Oilseed, group 20 .......................
Vegetable, foliage of legume,
group 7 ....................................
Vegetable, legume, group 6 .......
Vegetable, tuberous and corm
subgroup 1C ...........................
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
[FR Doc. 2012–11629 Filed 5–11–12; 8:45 am]
BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 799
[EPA–HQ–OPPT–2005–0033; FRL–9350–2]
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
In the Federal Register issue
of March 16, 2012, EPA published a
direct final rule revoking certain testing
requirements promulgated under the
Toxic Substances Control Act (TSCA)
for 10 chemical substances, including
benzenesulfonic acid, [[4-[[4(phenylamino)phenyl][4-(phenylimino)2,5-cyclohexadien-1ylidene]methyl]phenyl]amino]- (CAS
No. 1324–76–1), also known as C.I.
Pigment Blue 61. EPA received an
adverse comment regarding C.I. Pigment
Blue 61. This document withdraws the
revocation of testing requirements for
C.I. Pigment Blue 61 as described in the
March 16, 2012 direct final rule. In
withdrawing the revocation, this
document also restores the original
testing requirements as currently shown
in the Code of Federal Regulations
PO 00000
Frm 00045
Fmt 4700
(CFR). Elsewhere in today’s Federal
Register, EPA is publishing a proposed
rule revoking the same testing
requirements for C.I. Pigment Blue 61
that were published in the March 16,
2012 direct final rule.
This final rule is effective May
15, 2012.
DATES:
For
technical information contact: Catherine
Roman, Chemical Control Division
(7405M), Office of Pollution Prevention
and Toxics, Environmental Protection
Agency, 1200 Pennsylvania Ave. NW.,
Washington, DC 20460–0001; telephone
number: (202) 564–8157; email address:
roman.catherine@epa.gov.
For general information contact: The
TSCA-Hotline, ABVI–Goodwill, 422
South Clinton Ave., Rochester, NY
14620; telephone number: (202) 554–
1404; email address: TSCAHotline@epa.gov.
FOR FURTHER INFORMATION CONTACT:
SUPPLEMENTARY INFORMATION:
I. Does this action apply to me?
A list of potentially affected entities is
provided in the Federal Register issue
of March 16, 2012 (77 FR 15609) (FRL–
9335–6). If you have questions regarding
the applicability of this action to a
particular entity, consult the technical
person listed under FOR FURTHER
INFORMATION CONTACT.
II. What rule is being withdrawn?
RIN 2070–AD16
SUMMARY:
Therefore, 40 CFR chapter I is
amended as follows:
VerDate Mar<15>2010
Parts per
million
Commodity
28281
Sfmt 4700
In the March 16, 2012 Federal
Register, EPA issued a revocation of
some or all of the TSCA section 4 testing
requirements for 10 chemical substances
by direct final rule. In accordance with
the procedures described in the March
16, 2012 Federal Register document,
EPA is withdrawing the revocation of
certain testing requirements for C.I.
Pigment Blue 61 and also restoring the
original testing requirements found in
the CFR, because the Agency received
an adverse comment concerning this
chemical substance. The final rule
revoking testing requirements for the
other 9 chemical substances described
in the March 16, 2012 Federal Register
document is otherwise unaffected by the
withdrawal of the revocation for C.I.
Pigment Blue 61. Elsewhere in today’s
Federal Register, EPA is proposing a
rule to revoke certain test rule
requirements for C.I. Pigment Blue 61.
The docket identification (ID) number
for the test rule concerning this
chemical substance was established at
EPA–HQ–OPPT–2005–0033. That
docket includes information considered
by the Agency in developing those rules
and the adverse comment.
E:\FR\FM\14MYR1.SGM
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Agencies
[Federal Register Volume 77, Number 93 (Monday, May 14, 2012)]
[Rules and Regulations]
[Pages 28276-28281]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-11629]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2010-0425; FRL-9341-8]
Penflufen; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes tolerances for residues of
penflufen in or on multiple commodities which are identified and
discussed later in this document. Bayer CropScience requested these
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective May 14, 2012. Objections and
requests for hearings must be received on or before July 13, 2012, and
must be filed in accordance with the instructions provided in 40 CFR
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2010-0425. All documents in the
docket are listed in the docket index available at https://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at https://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Marianne Lewis, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone
number: (703) 308-8043; email address: lewis.marianne@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this action apply to me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to those
engaged in the following activities:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How can I get electronic access to other related information?
You may access a frequently updated electronic version of EPA's
tolerance regulations at 40 CFR part 180 through the Government
Printing Office's e-CFR site at https://ecfr.gpoaccess.gov/cgi/t/text/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl. To access the
OCSPP test guidelines referenced in this document electronically,
please go https://www.epa.gov/ocspp and select ``Test Methods and
Guidelines.''
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-2010-0425 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
July 13, 2012. 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 that does not contain any 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 a copy of
your non-CBI objection or hearing request, identified by docket ID
number EPA-HQ-OPP-2010-0425, by one of the following methods:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania Ave.
NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One
[[Page 28277]]
Potomac Yard (South Bldg.), 2777 S. Crystal Dr. Arlington, VA.
Deliveries are only accepted during the Docket Facility's normal hours
of operation (8:30 a.m. to 4 p.m., Monday through Friday, excluding
legal holidays). Special arrangements should be made for deliveries of
boxed information. The Docket Facility telephone number is (703) 305-
5805.
II. Summary of Petitioned-For Tolerance
In the Federal Register of September 8, 2010 (75 FR 54631) (FRL-
8843-3), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
0F7711) by Bayer CropScience, 2 T.W. Alexander Drive P.O. Box 12014,
Research Triangle Park, NC 27709. The petition requested that 40 CFR
part 180 be amended by establishing tolerances for residues of the
penflufen, N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-
pyrazole-4-carboxamide, in or on alfalfa, forage; alfalfa, hay;
vegetable, tuberous and corm, subgroup 1C; vegetable, legume, group 6;
vegetable, foliage of legume, group 7; grain, cereal, group 15, grain,
cereal, forage, fodder and straw, group 16; oilseed, group 19; cotton,
gin by-products at 0.01 parts per million (ppm). That notice referenced
a summary of the petition prepared by Bayer CropScience, 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 made
some minor modifications to some commodity definitions for consistency
with EPA naming-conventions for those commodities. The reason for these
changes is explained in Unit IV.D.
III. Aggregate Risk Assessment and Determination of Safety
Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical residue * *
*.''
Consistent with section 408(b)(2)(D) of FFDCA, and the factors
specified in section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure for penflufen including
exposure resulting from the tolerances established by this action.
EPA's assessment of exposures and risks associated with penflufen
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. Penflufen is an alkylamide fungicide belonging to the
chemical class of carboxamides. The reported pesticidal mode of action
is as an inhibitor of mitochondrial respiration by inhibiting succinate
dehydrogenase, an enzyme in the electron transport system.
The liver and thyroid are target organs for penflufen. Increased
liver weight, alterations in clinical chemistry parameters relevant to
effects on the liver, and an increase in the incidence of
hepatocellular hypertrophy were consistent findings across species and
duration of exposure (28-day, 90-day, and 1- to 2-year exposure
periods). The hepatic total cytochrome P-450 content, and
benzoxyresorufin (BROD) and pentoxyresorufin (PROD) enzyme activities,
were shown to be increased in rats of both sexes following subchronic
oral exposure. Additionally, increased incidence of thyroid follicular
cell hypertrophy/hyperplasia was observed across studies and species
(no data provided on thyroid hormone levels). The liver and thyroid
findings were mostly reversible after a 3-month recovery period in the
rat. In the rat and mouse, following 104 week/78 week exposure periods
at dose levels up to and/or greater than the limit dose, there was no
increase in the incidence of liver or thyroid tumors.
Reproductive toxicity was observed in the 2-generation reproduction
study in rats. Delayed sexual maturation was observed in females in
both generations, and magnitude of the associated decline in body
weight was not considered to be a factor in the delay in sexual
maturation. Developmental toxicity was not observed in the rat or
rabbit, although the dose levels in both studies were not considered
adequate to assess developmental toxicity potential of penflufen.
However, there is little concern that new studies would identify a
developmental endpoint with a no-observed-adverse-effect-level (NOAEL)
lower than the NOAEL selected for risk assessment.
Decreased motor/locomotor activity was observed in both sexes of
rats following acute and in female rats following subchronic oral
exposure, although neuropathological lesions were not observed in
either study.
There are no mutagenicity concerns. Carcinogenicity studies with
penflufen found a statistically significant increase in histiocytic
sarcomas in male rats; a marginal increase in brain astrocytomas, a
fatal tumor, in male rats at the high dose; and ovarian adenomas in
female rats at the high dose. Although these three tumors were
considered treatment-related, they provided weak evidence of
carcinogenicity due to the marginal nature of the tumor responses.
There was no evidence of carcinogenicity in male or female mice. Given
the weak evidence indicating any potential for carcinogenicity, EPA has
determined that quantification of risk using a non-linear approach
reference dose (i.e., RfD) will adequately account for all chronic
toxicity, including carcinogenicity, which could result from exposure
to penflufen. The NOAEL (38 milligram/kilogram/day (mg/kg/day)) used
for establishing the Chronic RfD is approximately 10-fold lower than
the dose (approximately 300 mg/kg/day) that induced a marginal tumor
response. The EPA has determined that the chronic population adjusted
dose is protective of all long-term effects, including potential
carcinogenicity.
Specific information on the studies received and the nature of the
adverse effects caused by penflufen as well as the NOAEL and the
lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies
can be found at https://www.regulations.gov in document ``Penflufen.
Human Health Risk Assessment to Support New Uses on Potato (Crop
Subgroup 1C), Legume Vegetables (Crop Group 6 and Crop Group 7), Cereal
Grains (Crop Group 15 and Crop Group 16), Oilseeds (Crop Group 20), and
Alfalfa'' in docket ID number EPA-HQ-OPP-2010-0425.
[[Page 28278]]
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 (LOC) 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 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 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 penflufen used for
human risk assessment is shown in the Table of this unit.
Table--Summary of Toxicological Doses and Endpoints for Penflufen 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, NOAEL = 50 mg/kg/day Acute RfD = 0.5 mg/ Acute neurotoxicity study in rats.
including children and women 13- UFA = 10x........... kg/day. LOAEL = 100 mg/kg/day based on
49 years of age). UFH = 10x........... aPAD = 0.5 mg/kg/ decreased motor and locomotor
FQPA SF = 1x........ day. activity (39-81% on day of
treatment) in females.
----------------------------------------------------------------------------------------------------------------
Chronic dietary (All populations) NOAEL= 38 mg/kg/day. Chronic RfD = 0.38 Chronic toxicity study in dogs.
UFA = 10x........... mg/kg/day. LOAEL = 357/425 mg/kg/day, based
UFH = 10x........... cPAD = 0.38 mg/kg/ on decreased terminal body weight
FQPA SF = 1x........ day. and body weight gain (females),
increased prothrombin time
(males), increased alkaline
phosphate activity, decreased
cholesterol, increased GGT
levels, decreased albumin and
albumin/globulin ratio, decreased
calcium and phosphorus, increased
liver weights, increased
incidence of focal hepatocellular
brown pigment and hepatocellular
hypertrophy, and an increased
incidence of thyroid follicular
cell hypertrophy in both sexes,
and in increased incidence of
zona glomerulosa vacuolation of
the adrenal gland in females.
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation) Quantification of risk using a non-linear approach (i.e., RfD) will
adequately account for all chronic toxicity, including carcinogenicity that
could result from exposure to penflufen.
----------------------------------------------------------------------------------------------------------------
UFA = extrapolation from animal to human (interspecies). 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. UFDB = to account for the absence of data or other data deficiency. FQPA
SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD =
reference dose. MOE = margin of exposure. LOC = level of concern. Mg/kg/day = milligrams/kilograms/day.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to penflufen, EPA considered exposure under the petitioned-for
tolerances. EPA assessed dietary exposures from penflufen 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.
Such effects were identified for penflufen. In estimating acute
dietary exposure, EPA used food consumption information from the United
States Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide
Continuing Surveys of Food Intake by Individuals (CSFII). As to residue
levels in food, EPA used tolerance-level residues, default dietary
exposure evaluation model (DEEM) processing factors for dried potatoes
and assumed 100 percent crop treated (PCT) for all commodities.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EP used the food consumption data from the USDA 1994-1996
and 1998 CSFII. As to residue levels in food, EPA used tolerance-level
residues, default DEEM processing factors for dried potatoes and
assumed 100 PCT for all commodities.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA 1994-1996
and 1998 CSFII. As to residue levels in food, EPA used tolerance-level
residues, default DEEM processing factors for dried potatoes and
assumed 100 PCT for all commodities.
iii. Cancer. EPA determines whether quantitative cancer exposure
and risk assessments are appropriate for a food-use pesticide based on
the weight of the evidence from cancer studies and other relevant data.
Cancer risk is quantified using a linear or non-linear approach. If
sufficient information on the carcinogenic mode of action is available,
a threshold or non-linear approach is used based on an earlier non-
cancer key event. If carcinogenic mode of action data are not
available, or if the mode of action data determines a mutagenic mode of
action, a default linear cancer slope factor approach is utilized.
Based on the data summarized in Unit III.A., EPA has concluded that a
non-linear RfD approach is appropriate for assessing cancer risk to
penflufen. Cancer risk was assessed using the same
[[Page 28279]]
exposure estimates as discussed in Unit III.C.1.ii.
iv. Anticipated residue and PCT information. EPA did not use
anticipated residue and/or PCT information in the dietary assessment
for penflufen. Tolerance level residues and/or 100 PCT were assumed for
all food commodities.
2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for penflufen in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of penflufen. 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 First Index Reservoir Screening Tool (FIRST) and
Screening Concentration in Ground Water (SCI-GROW) models, the
estimated drinking water concentrations (EDWCs) of penflufen for acute
exposures are estimated to be 11.4 parts per billion (ppb) for surface
water and 16.6 ppb for ground water. The EDWC of penflufen for chronic
exposures for non-cancer assessments are estimated to be 1.8 ppb for
surface water and 16.6 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 16.6 ppb was used to
assess the contribution to drinking water. For chronic dietary risk
assessment, the water concentration of value 16.6 ppb was used to
assess the contribution to drinking water.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
Penflufen is not registered for any specific use patterns that
would result in residential exposure.
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 penflufen to share a common mechanism of toxicity
with any other substances, and penflufen does not appear to produce a
toxic metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has assumed that penflufen 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. In the rat multi-generation
reproduction study there was slight decrease in litter size, delayed
sexual maturation, decreased body weight/gain, decreased brain, spleen,
and thymus weights were noted in the offspring. At the same dose level
the adults exhibited decreased body weight/gain, alteration in food
consumption, decreased thymus weight, and decrease spleen weights. In
the rat developmental toxicity study, the maternal findings (decreased
body weight gain) at the highest dose tested (HDT) are considered
minimal. No adverse effects were observed on the foetuses. In the
rabbit developmental toxicity study, the maternal findings (decreased
body weight gain) at the HDT are considered minimal. No adverse effects
were observed at the HDT.
3. Conclusion. The Agency recommends that the 10X FQPA safety
factor for the protection of infants and children, be reduced to 1X.
The risk assessments conducted for penflufen were based on the most
sensitive endpoints in the toxicity database, and the NOAELs selected
for risk assessment are considered protective of potential
developmental, neurotoxic, and immunotoxic effects for infants and
children. Highly conservative exposure estimates were incorporated into
the risk assessment for penflufen. There are no residual uncertainties
with regard to pre- and/or postnatal toxicity or neurotoxicity, and
exposure; therefore, reduction of the 10X FQPA safety factor for
penflufen to 1X is appropriate based on the following findings:
i. The toxicity database for penflufen is complete for
consideration of estimated risks for all populations of concern.
ii. Although decreased motor activity was observed following acute
oral exposure, no neuropathological lesions were observed and there is
little concern for neurotoxicity. There is no need for a developmental
neurotoxicity study or additional UFs to account for neurotoxicity.
iii. Although there is some evidence of qualitative sensitivity of
the young (delayed sexual maturation and decreased litter size), the
effects are well characterized, and there is a clear NOAEL. The dose
level where offspring effects were identified in the reproduction study
is comparable to the high dose used in the rat developmental toxicity
study where no effects were identified in either the maternal or fetal
rat. Since minimal/no effects were observed in the developmental
toxicity studies following exposure of the maternal animals to dose
levels equal to and greater than those tested in the studies used for
risk assessment, there is little concern that new studies would
identify a developmental endpoint with a NOAEL lower than the NOAELs
selected for risk assessment.
iv. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed based
on 100 PCT and tolerance-level residues. EPA made conservative
(protective) assumptions in the ground and surface water modeling used
to assess exposure to penflufen in drinking water. These assessments
will not underestimate the exposure and risks posed by penflufen.
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 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.
[[Page 28280]]
1. Acute risk. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. A highly conservative acute dietary exposure assessment
demonstrated that penflufen does not pose an unacceptable aggregate
risk.
2. Chronic risk. There are no residential uses for penflufen;
therefore, the chronic aggregate risk assessment includes exposures
from dietary consumption of food and water only. A highly conservative
chronic aggregate dietary exposure assessment demonstrated that
penflufen does not pose an unacceptable aggregate chronic risk.
3. Short-term risk. There are no residential uses of penflufen;
therefore a short-term aggregate risk assessment was not conducted for
this chemical.
4. Intermediate-term risk. There are no residential uses of
penflufen; therefore an intermediate-term aggregate risk assessment was
not conducted for this chemical.
5. Aggregate cancer risk for U.S. population. In a rat
carcinogenicity study with penflufen a statistically significant
increase in histiocytic sarcomas with a positive trend in male rats
only (but in the absence of a dose response and lack of pre-neoplastic
lesions) were seen. A marginal increase in brain astrocytomas was also
observed in males at the high dose; however, this effect was not dose-
related, did not reach statistical significance, and there was no
overall trend. In addition, there were no pre-neoplastic lesions, such
as glial proliferations, which are a good indicator of chemical tumor
induction (i.e., there will be changes in the cells prior to
transformation to a neoplasm). The ovarian adenomas observed at the
high dose also showed no dose response, no pair-wise significance, no
decrease in latency, and there were no pre-neoplastic lesions such as
hyperplasia of the epithelial cells of the endometrium. Additionally,
there was no evidence of carcinogenicity in male or female mice (at
doses that were judged to be adequate to assess the carcinogenic
potential), no concern for mutagenicity (in vivo or in vitro) for the
parent molecule or the two metabolites, and there were no other lines
of evidence (such as structure-activity relationship). Although these
three tumors were considered treatment-related, they provided weak
evidence of carcinogenicity due to the marginal nature of the tumor
responses and the other factors mentioned in this unit. Given the weak
evidence indicating any potential for carcinogenicity, EPA has
determined that quantification of risk using a non-linear approach
(i.e., RfD) will adequately account for all chronic toxicity, including
carcinogenicity, which could result from exposure to penflufen. The
NOAEL (38 mg/kg/day) used for establishing the chronic RfD is
approximately 10-fold lower than the dose (approximately 300 mg/kg/day)
that induced a marginal tumor response. The EPA has determined that the
chronic population adjusted dose is protective of all long-term
effects, including potential carcinogenicity.
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 penflufen residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology is available to enforce the
tolerance expression. The method involves extraction of samples with
acetonitrile/water, cleanup using solid phase extraction, and analysis
of penflufen by liquid chromatography/mass spectrometry (LC/MS/MS) (EL-
002-P09-03).
B. International Residue Limits
In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and
Agriculture Organization/World Health Organization food standards
program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
The Codex has not established a MRL for penflufen.
C. Revisions to Petitioned-For Tolerances
Some minor modifications to commodity definitions initially
submitted were made to be consistent with the updated EPA naming-
conventions for commodities.
V. Conclusion
Therefore, tolerances are established for residues of penflufen, in
or on alfalfa, forage; alfalfa, hay; vegetable, tuberous and corm,
subgroup 1C; vegetable, legume, group 6; vegetable, foliage of legume,
group 7; grain, cereal, group 15, grain, cereal, forage, fodder and
straw, group 16; oilseed, group 19; cotton, gin by-products at 0.01
ppm.
VI. Statutory and Executive Order Reviews
This final rule establishes tolerances under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this final rule has been
exempted from review under Executive Order 12866, this final rule is
not subject to Executive Order 13211, entitled Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
Protection of Children from Environmental Health Risks and Safety Risks
(62 FR 19885, April 23, 1997). This final rule does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any
special considerations under Executive Order 12898, entitled Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian
[[Page 28281]]
tribes. Thus, the Agency has determined that Executive Order 13132,
entitled Federalism (64 FR 43255, August 10, 1999) and Executive Order
13175, entitled Consultation and Coordination with Indian Tribal
Governments (65 FR 67249, November 9, 2000) do not apply to this final
rule. In addition, this final rule does not impose any enforceable duty
or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4).
This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
note).
VII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: May 3, 2012.
Steven Bradbury,
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. Section 180.664 is added to subpart C to read as follows:
Sec. 180.664 Penflufen; tolerances for residues.
(a) General. Tolerances are established for residues of the
fungicide penflufen, including its metabolites and degradates, in or on
the following commodities listed in the table. Compliance with the
tolerance levels specified in the table is to be determined by
measuring only penflufen N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-
dimethyl-1H-pyrazole-4-carboxamide, in or on the following commodities.
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Alfalfa, forage............................................. 0.01
Alfalfa, hay................................................ 0.01
Cotton, gin by-products..................................... 0.01
Grain cereal, forage, fodder and straw, group 16............ 0.01
Grain, cereal, group 15..................................... 0.01
Oilseed, group 20........................................... 0.01
Vegetable, foliage of legume, group 7....................... 0.01
Vegetable, legume, group 6.................................. 0.01
Vegetable, tuberous and corm subgroup 1C.................... 0.01
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 2012-11629 Filed 5-11-12; 8:45 am]
BILLING CODE 6560-50-P