Topramezone; Pesticide Tolerances, 35115-35120 [2017-15744]
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Federal Register / Vol. 82, No. 144 / Friday, July 28, 2017 / Rules and Regulations
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BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2015–0825; FRL–9960–37]
Topramezone; Pesticide Tolerances
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
This regulation establishes a
tolerance for residues of topramezone in
or on sugarcane, cane. BASF
Corporation requested this tolerance
under the Federal Food, Drug, and
Cosmetic Act (FFDCA).
DATES: This regulation is effective July
28, 2017. Objections and requests for
hearings must be received on or before
September 26, 2017, and must be filed
in accordance with the instructions
provided in 40 CFR part 178 (see also
Unit I.C. of the SUPPLEMENTARY
INFORMATION).
The docket for this action,
identified by docket identification (ID)
number EPA–HQ–OPP–2015–0825, 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:
Michael Goodis, Registration Division
(7505P), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave. NW., Washington,
DC 20460–0001; main telephone
number: (703) 305–7090; email address:
RDFRNotices@epa.gov.
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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?
SUMMARY:
VerDate Sep<11>2014
I. General Information
A. Does this action apply to me?
*
[FR Doc. 2017–15743 Filed 7–27–17; 8:45 am]
ADDRESSES:
SUPPLEMENTARY 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://www.ecfr.gov/cgi-bin/textidx?&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–2015–0825 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 26, 2017. 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–
2015–0825, by one of the following
methods:
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35115
• 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 22,
2016 (81 FR 40594) (FRL–9947–32),
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 5F8421) by BASF
Corporation, 26 Davis Drive, P.O. Box
13528, Research Triangle Park, NC
27709. The petition requested that 40
CFR 180.612 be amended by
establishing a tolerance for residues of
the herbicide topramezone, [3-(4,5dihydro-isoxazol-3-yl)-4methylsulfonyl-2-methylphenyl](5hydroxyl-1-methyl-1H-pyrazol-4yl)methanone, in or on sugarcane, cane
at 0.01 parts per million (ppm). That
document referenced a summary of the
petition prepared by BASF Corporation,
the registrant, which is available in the
docket, https://www.regulations.gov.
Comments were received on the notice
of filing. EPA’s response to these
comments is discussed 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
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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 topramezone
including exposure resulting from the
tolerance established by this action.
EPA’s assessment of exposures and risks
associated with topramezone 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.
Topramezone inhibits the enzyme 4hydroxyphenylpyruvate dioxygenase
(HPPD), which is involved in the
catabolism of the amino acid tyrosine.
HPPD-inhibition causes blood levels of
tyrosine to rise (tyrosinemia), resulting
in ocular, liver, kidney, and
developmental effects in laboratory
animals.
Similar to other HPPD inhibiting
chemicals, the rat was the most
sensitive species and males were found
to be more sensitive than females (in
rats and dogs). In rat subchronic and
chronic oral studies, topramezone
produced ocular (corneal
vascularization, opacity, and keratitis)
and kidney (microscopic findings and
increased organ weights) effects, which
are consistent with the mammalian
toxicity profile for HPPD inhibitors
caused by high tyrosine levels in the
blood. Histopathological findings in the
thyroid were frequently observed in rats
and dogs following topramezone
exposure. Thyroid tumors via a nonlinear mode of action involving thyroid
hormone disruption were seen in the
rat; however, topramezone is classified
as ‘‘not likely to be carcinogenic to
humans at doses that do not alter rat
thyroid hormone homeostasis.’’
Additional histopathological findings
were seen in the pancreas of rats and the
urinary bladder in dogs. Body weight
decrements were also noted in all
species, including the mouse, which did
not exhibit any other adverse effects in
the database.
There was evidence of increased
prenatal susceptibility following in
utero exposure to topramezone in the
developmental toxicity studies in rats
and rabbits, with fetal skeletal variation
and abnormalities observed in both
species that were consistent with those
reported in the toxicological databases
for other HPPD inhibiting chemicals and
typically seen in the absence of
maternal toxicity or less severe maternal
adverse effects. In the mouse
developmental toxicity study, elevated
tyrosine blood levels were noted in
maternal animals; however, there were
no developmental effects observed.
There was evidence for increased
qualitative offspring susceptibility in
the rat developmental neurotoxicity
study, where neurobehavioral and
neuropathological changes were
observed in the presence of limited
maternal toxicity (corneal opacity).
There was no evidence of increased preor postnatal susceptibility in the rat
reproduction toxicity study.
While neurobehavioral and
neuropathological offspring effects were
observed in the developmental
neurotoxicity study, which are
indicators of potential neurotoxicity, no
neurotoxic effects were observed in the
acute neurotoxicity study up to the limit
dose or the subchronic neurotoxicity
study, where systemic effects were
consistent with the rest of the
toxicological database.
Topramezone is classified as having
low acute toxicity (Toxicity Category III
or IV) via the oral, dermal, and
inhalation routes). It was found to be a
slight eye and dermal irritant, but it was
not found to be a dermal sensitizer.
Specific information on the studies
received and the nature of the adverse
effects caused by topramezone as well
as the no-observed-adverse-effect-level
(NOAEL) and the lowest-observedadverse-effect-level (LOAEL) from the
toxicity studies can be found at https://
www.regulations.gov in document
Topramezone: Human Health Risk
Assessment for New Use on Sugarcane
in docket ID number EPA–HQ–OPP–
2015–0825.
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-science-andassessing-pesticide-risks/assessinghuman-health-risk-pesticides.
A summary of the toxicological
endpoints for topramezone used for
human risk assessment is shown in the
Table of this unit.
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TABLE—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR TOPRAMEZONE FOR USE IN HUMAN HEALTH RISK
ASSESSMENT
Point of departure and
uncertainty/safety
factors
Exposure/Scenario
Acute dietary (Females 13–49 years
old).
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NOAEL = 0.5 mg/kg/
day.
UFA = 10x .....................
UFH = 10x .....................
FQPA SF = 1x ..............
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RfD, PAD, LOC for
risk Assessment
aRfD = 0.005 mg/kg/
day.
aPAD = 0.005 mg/kg/
day.
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Study and toxicological effects
Rabbit Developmental Toxicity Study
Developmental LOAEL = 5 mg/kg/day based on alterations in skeletal
ossification sites and increased number of pairs of ribs.
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35117
TABLE—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR TOPRAMEZONE FOR USE IN HUMAN HEALTH RISK
ASSESSMENT—Continued
Point of departure and
uncertainty/safety
factors
Exposure/Scenario
Acute dietary (General population including infants and children, excluding females 13–49 years old).
Chronic dietary (All populations) ........
Incidental oral short-term (1 to 30
days) and intermediate (1–6
months) term.
Dermal short-term (1 to 30 days) and
intermediate (1–6 months) term.
Inhalation short-term (1 to 30 days)
and intermediate (1–6 month) term.
Cancer (Oral, dermal, inhalation) ......
RfD, PAD, LOC for
risk Assessment
Study and toxicological effects
LOAEL = 8 mg/kg/day ..
UFA = 10x .....................
UFH = 10x ....................
FQPA SF/UFL = 10x ....
NOAEL = 0.4 mg/kg/
day.
UFA = 10x .....................
UFH = 10x .....................
FQPA SF = 1x ..............
NOAEL = 0.4 mg/kg/
day.
UFA = 10x .....................
UFH = 10x .....................
FQPA SF = 1x ..............
aRfD = 0.08 mg/kg/day
aPAD = 0.008 mg/kg/
day.
Rat Developmental Neurotoxicity Study
LOAEL = 8 mg/kg/day based on decreased maximum auditory startle reflex response, decreased brain weights, and changes in brain morphology.
Rat Chronic Toxicity/Carcinogenicity Study
LOAEL = 3.6 mg/kg/day based on increased incidences of corneal opacity, decreased body weight and body-weight gains in males and
histopathological evaluations in the eyes, thyroid, and pancreas of
both sexes.
Rat Two-Generation Reproduction Study
Parental/Offspring LOAEL = 4.2 mg/kg/day based on decreased body
weight, increased thyroid and kidney weights, and microscopic findings in eyes, kidney, and thyroid of both sexes (parental); and decreases in body weights in the F2 generation and increased time to
preputial separation in the F1 male (offspring).
Rat Two-Generation Reproduction Study in Rats]
Parental/Offspring LOAEL = 4.2 mg/kg/day based on decreased body
weight, increased thyroid and kidney weights, and microscopic findings in eyes, kidney, and thyroid of both sexes (parental); and decreases in body weights in the F2 generation and increased time to
preputial separation in the F1 male (offspring).
Rat Two-Generation Reproduction Study in Rats]
Parental/Offspring LOAEL = 4.2 mg/kg/day based on decreased body
weight, increased thyroid and kidney weights, and microscopic findings in eyes, kidney, and thyroid of both sexes (parental); and decreases in body weights in the F2 generation and increased time to
preputial separation in the F1 male (offspring).
NOAEL = 0.4 mg/kg/
day (dermal absorption rate = 2.6%).
UFA = 10x .....................
UFH = 10x .....................
FQPA SF = 1x ..............
NOAEL = 0.4 mg/kg/
day (inhalation assumed equivalent to
oral).
UFA = 10x .....................
UFH = 10x .....................
FQPA SF = 1x ..............
cRfD = 0.004 mg/kg/day
cPAD = 0.004 mg/kg/
day.
LOC for MOE = <100 ...
LOC for MOE = <100 ...
LOC for MOE = <100 ...
In accordance with the 2005 EPA Guidelines for Carcinogen Risk assessment, topramezone was classified as ‘‘not likely to
be carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis.’’ EPA has determined that the thyroid
tumors arise through a non-linear mode of action and the cRfD of 0.004 mg/kg/day, which is derived from the NOAEL of 0.4
mg/kg/day from the rat chronic/carcinogenicity study, is not expected to alter thyroid hormone homeostasis nor result in thyroid tumor formation.
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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 (a = acute, c
= chronic). UF = uncertainty factor. 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.
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. In evaluating dietary
exposure to topramezone, EPA
considered exposure under the
petitioned-for tolerance as well as all
existing topramezone tolerances in 40
CFR 180.612. EPA assessed dietary
exposure from topramezone 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 one-day or
single exposure. Such effects were
identified for topramezone. In
estimating acute dietary exposure, EPA
used food consumption information
from the United States Department of
Agriculture (USDA) 2003–2008 National
Health and Nutrition Examination
Survey, What We Eat in America
(NHANES/WWEIA). As to residue levels
in food, EPA used tolerance levels and
100 percent crop treated (PCT) for the
acute dietary exposure assessment.
ii. Chronic exposure. In conducting
the chronic dietary exposure assessment
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EPA used the food consumption data
from the USDA 2003–2008 NHANES/
WWEIA. As to residue levels in food,
EPA used tolerance levels and 100 PCT
for the chronic dietary exposure
assessment.
iii. Cancer. Based on the data
summarized in Unit III.A., EPA has
concluded that topramezone does not
pose a cancer risk to humans. Therefore,
a dietary exposure assessment for the
purpose of assessing cancer risk is
unnecessary.
iv. Anticipated residue and Percent
crop treated (PCT) information. EPA did
not use anticipated residue and/or PCT
information in the dietary assessment
for topramezone. Tolerance level
residues and/or 100 PCT were assumed
for all food commodities.
2. Dietary exposure from drinking
water. The Agency used the highest
drinking water concentration expected
to result from the currently-registered
use of topramezone for direct, aquatic
applications. Further information
regarding EPA drinking water models
used in pesticide exposure assessment
can be found at https://www.epa.gov/
pesticide-science-and-assessing-
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pesticide-risks/about-water-exposuremodels-used-pesticide. For acute and
chronic dietary risk assessments, the
water concentration value of 45 ppb was
used to assess the contribution to
drinking water, based on the maximum
allowable topramezone concentration in
water bodies with potable water intakes
from direct aquatic use.
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).
Topramezone is currently registered
for turf and golf course uses that could
result in residential exposures.
Topramezone is also currently
registered for use in direct aquatic
applications that could result in
exposure during recreational swimming
activities. The following residential
exposure scenarios were used for
assessing aggregate exposures: Short-
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term dermal post-application exposure
resulting from the physical activities on
turf for adults, short-term dermal and
incidental oral (hand-to-mouth) postapplication exposures resulting from the
physical activities on turf for children 1
< 2 years, and intermediate-term
incidental oral exposure resulting from
soil ingestion from turf use for children
1 < 2 years. These post-application
exposure estimates from the turf use are
protective of post-application exposure
for older children more likely to engage
in recreational swimming activities.
Further information regarding EPA
standard assumptions and generic
inputs for residential exposures may be
found at https://www.epa.gov/pesticidescience-and-assessing-pesticide-risks/
standard-operating-proceduresresidential-pesticide.
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 topramezone to
share a common mechanism of toxicity
with any other substances, and
topramezone does not appear to
produce a toxic metabolite produced by
other substances. For the purposes of
this tolerance action, therefore, EPA has
assumed that topramezone 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/pesticide-science-andassessing-pesticide-risks/cumulativeassessment-risk-pesticides.
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
Food Quality Protection Act Safety
Factor (FQPA SF). In applying this
provision, EPA either retains the default
value of 10X, or uses a different
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additional safety factor when reliable
data available to EPA support the choice
of a different factor.
2. Prenatal and postnatal sensitivity.
There was evidence of increased
quantitative prenatal susceptibility
following in utero exposures to rats and
rabbits. Fetal skeletal variations and
abnormalities were observed in all of
the rat and rabbit developmental
studies, typically in the absence of
maternal toxicity or in the presence of
less severe maternal effects. Increased
qualitative susceptibility was also
observed in the developmental
neurotoxicity study where offspring
neurobehavioral and neuropathological
changes were observed in the presence
of limited maternal toxicity (corneal
opacity). Concern is low since the
effects are well-characterized and
endpoints selected for risk assessment
are protective of all observed offspring
effects. There was no evidence of
increased offspring sensitivity in the
two-generation rat reproduction toxicity
study.
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 for all exposure
scenarios except for acute dietary
exposure. The FQPA SF of 10X was
retained for acute dietary exposure to
account for the extrapolation of a
NOAEL from a LOAEL. This decision is
based on the following findings:
i. The toxicity database for
topramezone is adequate to assess the
risk of aggregate exposure to
topramezone. While a subchronic
inhalation study is not available for
topramezone, EPA concluded, using a
weight-of-evidence approach, that this
study is not required at this time.
ii. Although there was evidence of
potential neurotoxicity in the
developmental neurotoxicity study (e.g.,
changes in neurobehavioral and
neuropathological observations in
offspring), there was no additional
evidence of neurotoxicity in the rest of
the toxicological database and the
selected endpoints are protective of the
observed effect up to the limit dose.
iii. Although there was evidence of
increased prenatal susceptibility as
discussed in Unit III.D.2., there are clear
NOAELs associated with those effects,
and the Agency’s selected points of
departure are protective of those effects.
Therefore, there is no need to retain the
FQPA 10X SF to adequately protect
infants and children from these effects.
iv. There are no residual uncertainties
identified in the exposure databases.
The dietary food exposure assessments
were performed based on 100 PCT and
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tolerance-level residues. The maximum
allowable concentration in potable
water intakes was used to assess
exposure to topramezone 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 topramezone.
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.
1. Acute risk. Using the exposure
assumptions discussed in this unit for
acute exposure, the acute dietary
exposure from food and water to
topramezone will occupy 98% of the
aPAD for all infants less than 1 year old,
the population group receiving the
greatest exposure, and 50% of the aPAD
for females 13–49 years old.
2. Chronic risk. Using the exposure
assumptions described in this unit for
chronic exposure, EPA has concluded
that chronic exposure to topramezone
from food and water will utilize 62% of
the cPAD for all infants less than 1-yearold, the population group receiving the
greatest exposure.
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). Topramezone is
currently registered for residential turf
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 topramezone. 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 220 for
adults and 120 for children 1–2 years
old (a subgroup predicted to have the
highest residential and aggregate
exposure). Because EPA’s level of
concern for topramezone is a MOE of
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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).
Topramezone is currently registered for
turf uses that could result in
intermediate-term residential exposure,
and the Agency has determined that it
is appropriate to aggregate chronic
exposure through food and water with
intermediate-term residential exposures
to topramezone for children that are 1–
2 years old that may ingest soil on
treated turf. Using the exposure
assumptions described in this unit for
intermediate-term exposures, EPA has
concluded that the combined
intermediate-term food, water, and
residential exposures result in an
aggregate MOE of 270 for children 1–2
years old. Because EPA’s level of
concern for topramezone is a MOE of
100 or below, this MOE is not of
concern.
5. Aggregate cancer risk for U.S.
population. EPA has concluded that
topramezone does not pose a cancer risk
at exposure levels that do not alter
thyroid hormone homeostasis. The
chronic aggregate assessment, which
utilized a cRfD that is protective of
those effects did not indicate a chronic
risk above EPA’s level of concern;
therefore, topramezone 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 topramezone
residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology
(liquid chromatography with tandem
mass-spectrometry detection (LC/MS/
MS), BASF method D0007) is available
to enforce the tolerance expression for
sugarcane.
asabaliauskas on DSKBBXCHB2PROD with RULES
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
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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 a MRL
for topramezone in or on sugarcane.
V. Conclusion
Therefore, tolerances are established
for residues of topramezone, including
its metabolites and degradates, in or on
the following commodity. Compliance
with the following tolerance levels is to
be determined by measuring only
topramezone ([3-(4,5-dihydro-3isoxazolyl)-2-methyl-4(methylsulfonyl)phenyl](5-hydroxy-1methyl-1H-pyrazol-4-yl)methanone) in
or on the following commodity:
Sugarcane, cane at 0.01 ppm.
VI. Statutory and Executive Order
Reviews
This action establishes a tolerance
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
PO 00000
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Fmt 4700
Sfmt 4700
35119
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: May 15, 2017.
Michael L. Goodis,
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:
■
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35120
Federal Register / Vol. 82, No. 144 / Friday, July 28, 2017 / Rules and Regulations
Authority: 21 U.S.C. 321(q), 346a and 371.
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
§ 180.612 Topramezone; tolerances for
Public Reading Room is (202) 566–1744,
residues.
and the telephone number for the OPP
(a) * * *
Docket is (703) 305–5805. Please review
the visitor instructions and additional
Parts per
information about the docket available
Commodity
million
at https://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT:
Robert McNally, Biopesticides and
*
*
*
*
*
Sugarcane, cane ........................
0.01 Pollution Prevention Division (7511P),
Office of Pesticide Programs,
*
*
*
*
*
Environmental Protection Agency, 1200
Pennsylvania Ave. NW., Washington,
[FR Doc. 2017–15744 Filed 7–27–17; 8:45 am]
DC 20460–0001; main telephone
BILLING CODE 6560–50–P
number: (703) 305–7090; email address:
BPPDFRNotices@epa.gov.
ENVIRONMENTAL PROTECTION
SUPPLEMENTARY INFORMATION:
AGENCY
I. General Information
40 CFR Part 180
A. Does this action apply to me?
2. In § 180.612, add alphabetically
‘‘Sugarcane, cane’’ in the table in
paragraph (a) to read as follows:
■
[EPA–HQ–OPP–2016–0284; FRL–9961–77]
Pseudomonas chlororaphis strain
AFS009; Exemption From the
Requirement of a Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
This regulation establishes an
exemption from the requirement of a
tolerance for residues of Pseudomonas
chlororaphis strain AFS009 in or on all
food commodities when used in
accordance with label directions and
good agricultural practices. AFS009
Plant Protection, Inc. submitted a
petition to EPA under the Federal Food,
Drug, and Cosmetic Act (FFDCA),
requesting an exemption from the
requirement of a tolerance. This
regulation eliminates the need to
establish a maximum permissible level
for residues of Pseudomonas
chlororaphis strain AFS009 under
FFDCA.
DATES: This regulation is effective July
28, 2017. Objections and requests for
hearings must be received on or before
September 26, 2017, 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–2016–0284, 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
asabaliauskas on DSKBBXCHB2PROD with RULES
SUMMARY:
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Jkt 241001
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 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.
C. How can I file an objection or hearing
request?
Under FFDCA section 408(g), 21
U.S.C. 346a(g), 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–2016–0284 in the subject line on
the first page of your submission. All
objections and requests for a hearing
PO 00000
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Fmt 4700
Sfmt 4700
must be in writing, and must be
received by the Hearing Clerk on or
before September 26, 2017. 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–
2016–0284, 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. Background
In the Federal Register of June 22,
2016 (81 FR 40594) (FRL–9947–32),
EPA issued a document pursuant to
FFDCA section 408(d)(3), 21 U.S.C.
346a(d)(3), announcing the filing of a
pesticide tolerance petition (PP 5F8410)
by AFS009 Plant Protection, Inc., 104
T.W. Alexander Dr., Building 18,
Research Triangle Park, NC 27709. The
petition requested that 40 CFR part 180
be amended by establishing an
exemption from the requirement of a
tolerance for residues of Pseudomonas
chlororaphis subsp. aurantiaca strain
AFS009 in or on all food commodities.
That document referenced a summary of
the petition prepared by the petitioner
AFS009 Plant Protection, Inc., which is
available in the docket via https://
www.regulations.gov. One comment was
received on the notice of filing. EPA’s
response to this comment is discussed
in Unit III.C.
Since the time the original notice of
filing was published, the petitioner
provided additional data on the identity
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Agencies
[Federal Register Volume 82, Number 144 (Friday, July 28, 2017)]
[Rules and Regulations]
[Pages 35115-35120]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-15744]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2015-0825; FRL-9960-37]
Topramezone; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a tolerance for residues of
topramezone in or on sugarcane, cane. BASF Corporation requested this
tolerance under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective July 28, 2017. Objections and
requests for hearings must be received on or before September 26, 2017,
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-2015-0825, 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: Michael Goodis, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone
number: (703) 305-7090; email address: 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 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-2015-0825 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 26, 2017. 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-2015-0825, 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 22, 2016 (81 FR 40594) (FRL-9947-
32), 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
5F8421) by BASF Corporation, 26 Davis Drive, P.O. Box 13528, Research
Triangle Park, NC 27709. The petition requested that 40 CFR 180.612 be
amended by establishing a tolerance for residues of the herbicide
topramezone, [3-(4,5-dihydro-isoxazol-3-yl)-4-methylsulfonyl-2-
methylphenyl](5-hydroxyl-1-methyl-1H-pyrazol-4-yl)methanone, in or on
sugarcane, cane at 0.01 parts per million (ppm). That document
referenced a summary of the petition prepared by BASF Corporation, the
registrant, which is available in the docket, https://www.regulations.gov. Comments were received on the notice of filing.
EPA's response to these comments is discussed 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
[[Page 35116]]
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 topramezone including exposure
resulting from the tolerance established by this action. EPA's
assessment of exposures and risks associated with topramezone 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.
Topramezone inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase
(HPPD), which is involved in the catabolism of the amino acid tyrosine.
HPPD-inhibition causes blood levels of tyrosine to rise (tyrosinemia),
resulting in ocular, liver, kidney, and developmental effects in
laboratory animals.
Similar to other HPPD inhibiting chemicals, the rat was the most
sensitive species and males were found to be more sensitive than
females (in rats and dogs). In rat subchronic and chronic oral studies,
topramezone produced ocular (corneal vascularization, opacity, and
keratitis) and kidney (microscopic findings and increased organ
weights) effects, which are consistent with the mammalian toxicity
profile for HPPD inhibitors caused by high tyrosine levels in the
blood. Histopathological findings in the thyroid were frequently
observed in rats and dogs following topramezone exposure. Thyroid
tumors via a non-linear mode of action involving thyroid hormone
disruption were seen in the rat; however, topramezone is classified as
``not likely to be carcinogenic to humans at doses that do not alter
rat thyroid hormone homeostasis.'' Additional histopathological
findings were seen in the pancreas of rats and the urinary bladder in
dogs. Body weight decrements were also noted in all species, including
the mouse, which did not exhibit any other adverse effects in the
database.
There was evidence of increased prenatal susceptibility following
in utero exposure to topramezone in the developmental toxicity studies
in rats and rabbits, with fetal skeletal variation and abnormalities
observed in both species that were consistent with those reported in
the toxicological databases for other HPPD inhibiting chemicals and
typically seen in the absence of maternal toxicity or less severe
maternal adverse effects. In the mouse developmental toxicity study,
elevated tyrosine blood levels were noted in maternal animals; however,
there were no developmental effects observed. There was evidence for
increased qualitative offspring susceptibility in the rat developmental
neurotoxicity study, where neurobehavioral and neuropathological
changes were observed in the presence of limited maternal toxicity
(corneal opacity). There was no evidence of increased pre- or postnatal
susceptibility in the rat reproduction toxicity study.
While neurobehavioral and neuropathological offspring effects were
observed in the developmental neurotoxicity study, which are indicators
of potential neurotoxicity, no neurotoxic effects were observed in the
acute neurotoxicity study up to the limit dose or the subchronic
neurotoxicity study, where systemic effects were consistent with the
rest of the toxicological database.
Topramezone is classified as having low acute toxicity (Toxicity
Category III or IV) via the oral, dermal, and inhalation routes). It
was found to be a slight eye and dermal irritant, but it was not found
to be a dermal sensitizer.
Specific information on the studies received and the nature of the
adverse effects caused by topramezone 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 Topramezone: Human Health Risk
Assessment for New Use on Sugarcane in docket ID number EPA-HQ-OPP-
2015-0825.
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-science-and-assessing-pesticide-risks/assessing-human-health-risk-pesticides.
A summary of the toxicological endpoints for topramezone used for
human risk assessment is shown in the Table of this unit.
Table--Summary of Toxicological Doses and Endpoints for Topramezone 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 (Females 13-49 NOAEL = 0.5 mg/kg/ aRfD = 0.005 mg/kg/ Rabbit Developmental Toxicity
years old). day. day. Study
UFA = 10x........... aPAD = 0.005 mg/kg/ Developmental LOAEL = 5 mg/kg/day
UFH = 10x........... day. based on alterations in skeletal
FQPA SF = 1x........ ossification sites and increased
number of pairs of ribs.
[[Page 35117]]
Acute dietary (General population LOAEL = 8 mg/kg/day. aRfD = 0.08 mg/kg/ Rat Developmental Neurotoxicity
including infants and children, UFA = 10x........... day. Study
excluding females 13-49 years UFH = 10x........... aPAD = 0.008 mg/kg/ LOAEL = 8 mg/kg/day based on
old). FQPA SF/UFL = 10x... day. decreased maximum auditory
startle reflex response,
decreased brain weights, and
changes in brain morphology.
Chronic dietary (All populations) NOAEL = 0.4 mg/kg/ cRfD = 0.004 mg/kg/ Rat Chronic Toxicity/
day. day. Carcinogenicity Study
UFA = 10x........... cPAD = 0.004 mg/kg/ LOAEL = 3.6 mg/kg/day based on
UFH = 10x........... day. increased incidences of corneal
FQPA SF = 1x........ opacity, decreased body weight
and body-weight gains in males
and histopathological evaluations
in the eyes, thyroid, and
pancreas of both sexes.
Incidental oral short-term (1 to NOAEL = 0.4 mg/kg/ LOC for MOE = <100. Rat Two-Generation Reproduction
30 days) and intermediate (1-6 day. Study
months) term. UFA = 10x........... Parental/Offspring LOAEL = 4.2 mg/
UFH = 10x........... kg/day based on decreased body
FQPA SF = 1x........ weight, increased thyroid and
kidney weights, and microscopic
findings in eyes, kidney, and
thyroid of both sexes (parental);
and decreases in body weights in
the F2 generation and increased
time to preputial separation in
the F1 male (offspring).
Dermal short-term (1 to 30 days) NOAEL = 0.4 mg/kg/ LOC for MOE = <100. Rat Two-Generation Reproduction
and intermediate (1-6 months) day (dermal Study in Rats]
term. absorption rate = Parental/Offspring LOAEL = 4.2 mg/
2.6%). kg/day based on decreased body
UFA = 10x........... weight, increased thyroid and
UFH = 10x........... kidney weights, and microscopic
FQPA SF = 1x........ findings in eyes, kidney, and
thyroid of both sexes (parental);
and decreases in body weights in
the F2 generation and increased
time to preputial separation in
the F1 male (offspring).
Inhalation short-term (1 to 30 NOAEL = 0.4 mg/kg/ LOC for MOE = <100. Rat Two-Generation Reproduction
days) and intermediate (1-6 day (inhalation Study in Rats]
month) term. assumed equivalent Parental/Offspring LOAEL = 4.2 mg/
to oral). kg/day based on decreased body
UFA = 10x........... weight, increased thyroid and
UFH = 10x........... kidney weights, and microscopic
FQPA SF = 1x........ findings in eyes, kidney, and
thyroid of both sexes (parental);
and decreases in body weights in
the F2 generation and increased
time to preputial separation in
the F1 male (offspring).
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation) In accordance with the 2005 EPA Guidelines for Carcinogen Risk assessment,
topramezone was classified as ``not likely to be carcinogenic to humans at
doses that do not alter rat thyroid hormone homeostasis.'' EPA has
determined that the thyroid tumors arise through a non-linear mode of action
and the cRfD of 0.004 mg/kg/day, which is derived from the NOAEL of 0.4 mg/
kg/day from the rat chronic/carcinogenicity study, is not expected to alter
thyroid hormone homeostasis nor result in thyroid tumor formation.
----------------------------------------------------------------------------------------------------------------
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 (a = acute, c = chronic).
UF = uncertainty factor. 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.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to topramezone, EPA considered exposure under the petitioned-
for tolerance as well as all existing topramezone tolerances in 40 CFR
180.612. EPA assessed dietary exposure from topramezone 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 one-day or single exposure. Such effects were
identified for topramezone. In estimating acute dietary exposure, EPA
used food consumption information from the United States Department of
Agriculture (USDA) 2003-2008 National Health and Nutrition Examination
Survey, What We Eat in America (NHANES/WWEIA). As to residue levels in
food, EPA used tolerance levels and 100 percent crop treated (PCT) for
the acute dietary exposure assessment.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA 2003-2008
NHANES/WWEIA. As to residue levels in food, EPA used tolerance levels
and 100 PCT for the chronic dietary exposure assessment.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has
concluded that topramezone does not pose a cancer risk to humans.
Therefore, a dietary exposure assessment for the purpose of assessing
cancer risk is unnecessary.
iv. Anticipated residue and Percent crop treated (PCT) information.
EPA did not use anticipated residue and/or PCT information in the
dietary assessment for topramezone. Tolerance level residues and/or 100
PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. The Agency used the
highest drinking water concentration expected to result from the
currently-registered use of topramezone for direct, aquatic
applications. Further information regarding EPA drinking water models
used in pesticide exposure assessment can be found at https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/about-water-exposure-models-used-pesticide. For acute and chronic dietary
risk assessments, the water concentration value of 45 ppb was used to
assess the contribution to drinking water, based on the maximum
allowable topramezone concentration in water bodies with potable water
intakes from direct aquatic use.
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).
Topramezone is currently registered for turf and golf course uses
that could result in residential exposures. Topramezone is also
currently registered for use in direct aquatic applications that could
result in exposure during recreational swimming activities. The
following residential exposure scenarios were used for assessing
aggregate exposures: Short-
[[Page 35118]]
term dermal post-application exposure resulting from the physical
activities on turf for adults, short-term dermal and incidental oral
(hand-to-mouth) post-application exposures resulting from the physical
activities on turf for children 1 < 2 years, and intermediate-term
incidental oral exposure resulting from soil ingestion from turf use
for children 1 < 2 years. These post-application exposure estimates
from the turf use are protective of post-application exposure for older
children more likely to engage in recreational swimming activities.
Further information regarding EPA standard assumptions and generic
inputs for residential exposures may be found at https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide.
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 topramezone to share a common mechanism of
toxicity with any other substances, and topramezone does not appear to
produce a toxic metabolite produced by other substances. For the
purposes of this tolerance action, therefore, EPA has assumed that
topramezone 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/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.
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 Food Quality
Protection Act Safety Factor (FQPA SF). In applying this provision, EPA
either retains the default value of 10X, or uses a different additional
safety factor when reliable data available to EPA support the choice of
a different factor.
2. Prenatal and postnatal sensitivity. There was evidence of
increased quantitative prenatal susceptibility following in utero
exposures to rats and rabbits. Fetal skeletal variations and
abnormalities were observed in all of the rat and rabbit developmental
studies, typically in the absence of maternal toxicity or in the
presence of less severe maternal effects. Increased qualitative
susceptibility was also observed in the developmental neurotoxicity
study where offspring neurobehavioral and neuropathological changes
were observed in the presence of limited maternal toxicity (corneal
opacity). Concern is low since the effects are well-characterized and
endpoints selected for risk assessment are protective of all observed
offspring effects. There was no evidence of increased offspring
sensitivity in the two-generation rat reproduction toxicity study.
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 for all exposure scenarios except for acute
dietary exposure. The FQPA SF of 10X was retained for acute dietary
exposure to account for the extrapolation of a NOAEL from a LOAEL. This
decision is based on the following findings:
i. The toxicity database for topramezone is adequate to assess the
risk of aggregate exposure to topramezone. While a subchronic
inhalation study is not available for topramezone, EPA concluded, using
a weight-of-evidence approach, that this study is not required at this
time.
ii. Although there was evidence of potential neurotoxicity in the
developmental neurotoxicity study (e.g., changes in neurobehavioral and
neuropathological observations in offspring), there was no additional
evidence of neurotoxicity in the rest of the toxicological database and
the selected endpoints are protective of the observed effect up to the
limit dose.
iii. Although there was evidence of increased prenatal
susceptibility as discussed in Unit III.D.2., there are clear NOAELs
associated with those effects, and the Agency's selected points of
departure are protective of those effects. Therefore, there is no need
to retain the FQPA 10X SF to adequately protect infants and children
from these effects.
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. The maximum allowable
concentration in potable water intakes was used to assess exposure to
topramezone 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 topramezone.
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.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food and water
to topramezone will occupy 98% of the aPAD for all infants less than 1
year old, the population group receiving the greatest exposure, and 50%
of the aPAD for females 13-49 years old.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
topramezone from food and water will utilize 62% of the cPAD for all
infants less than 1-year-old, the population group receiving the
greatest exposure.
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). Topramezone
is currently registered for residential turf 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 topramezone. 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 220 for adults and 120 for
children 1-2 years old (a subgroup predicted to have the highest
residential and aggregate exposure). Because EPA's level of concern for
topramezone is a MOE of
[[Page 35119]]
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). Topramezone is currently registered for turf uses that could
result in intermediate-term residential exposure, and the Agency has
determined that it is appropriate to aggregate chronic exposure through
food and water with intermediate-term residential exposures to
topramezone for children that are 1-2 years old that may ingest soil on
treated turf. Using the exposure assumptions described in this unit for
intermediate-term exposures, EPA has concluded that the combined
intermediate-term food, water, and residential exposures result in an
aggregate MOE of 270 for children 1-2 years old. Because EPA's level of
concern for topramezone is a MOE of 100 or below, this MOE is not of
concern.
5. Aggregate cancer risk for U.S. population. EPA has concluded
that topramezone does not pose a cancer risk at exposure levels that do
not alter thyroid hormone homeostasis. The chronic aggregate
assessment, which utilized a cRfD that is protective of those effects
did not indicate a chronic risk above EPA's level of concern;
therefore, topramezone 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 topramezone residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (liquid chromatography with tandem
mass-spectrometry detection (LC/MS/MS), BASF method D0007) is available
to enforce the tolerance expression for sugarcane.
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 a MRL for topramezone in or on
sugarcane.
V. Conclusion
Therefore, tolerances are established for residues of topramezone,
including its metabolites and degradates, in or on the following
commodity. Compliance with the following tolerance levels is to be
determined by measuring only topramezone ([3-(4,5-dihydro-3-
isoxazolyl)-2-methyl-4-(methylsulfonyl)phenyl](5-hydroxy-1-methyl-1H-
pyrazol-4-yl)methanone) in or on the following commodity: Sugarcane,
cane at 0.01 ppm.
VI. Statutory and Executive Order Reviews
This action establishes a tolerance 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: May 15, 2017.
Michael L. Goodis,
Director, Registration Division, 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:
[[Page 35120]]
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. In Sec. 180.612, add alphabetically ``Sugarcane, cane'' in the
table in paragraph (a) to read as follows:
Sec. 180.612 Topramezone; tolerances for residues.
(a) * * *
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
* * * * *
Sugarcane, cane............................................. 0.01
------------------------------------------------------------------------
* * * * *
[FR Doc. 2017-15744 Filed 7-27-17; 8:45 am]
BILLING CODE 6560-50-P