[Federal Register Volume 78, Number 152 (Wednesday, August 7, 2013)]
[Rules and Regulations]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-18975]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Topramezone; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of
topramezone in or on multiple commodities which are identified and
discussed later in this document. BASF Corporation requested these
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective August 7, 2013. Objections and
requests for hearings must be received on or before October 7, 2013,
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-2012-0262, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), EPA West Bldg., Rm. 3334, 1301 Constitution
Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal
holidays. The telephone number for the Public Reading Room is (202)
566-1744, and the telephone number for the OPP Docket is (703) 305-
5805. Please review the visitor instructions and additional information
about the docket available at http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: Lois Rossi, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone
number: (703) 305-7090; email address: RDFRNotices@epa.gov.
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 http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR Part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2012-0262 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
October 7, 2013. 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-2012-0262, by one of
the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be CBI or other
information whose disclosure is restricted by statute.
Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC
Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.htm.
Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at http://www.epa.gov/dockets.
II. Summary of Petitioned-For Tolerance
In the Federal Register of May 23, 2012 (77 FR 30481) (FRL-9347-8),
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 2F7997)
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 tolerances for residues of the herbicide topramezone
hydroxy-1-methyl-1H-pyrazol-4-yl)methanone), in or on fish and
shellfish at 0.05 parts per million (ppm). That document referenced a
summary of the petition prepared by BASF Corporation, the registrant,
which is available in the docket, http://www.regulations.gov. There
were no comments received in response to the notice of filing.
Based upon review of the data supporting the petition, EPA has
revised the proposed commodity definitions and established tolerances
for livestock meat by-products, which are needed as a result of the
increased livestock dietary burden associated with the proposed use for
topramezone. The reasons for these changes are explained in Unit IV.C.
III. Aggregate Risk Assessment and Determination of Safety
Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical residue. . .
Consistent with FFDCA section 408(b)(2)(D), and the factors
specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for topramezone including exposure
resulting from the tolerances 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 is a member of the class of herbicides known as
HPPD inhibitors. Inhibition of the enzyme 4-hydroxyphenylpyruvate
dioxygenase (HPPD) results in decreased carotenoid synthesis and
ultimately bleaching of target plants. In mammals, HPPD is involved in
the catabolism of the amino acid tyrosine, and its inhibition causes
blood levels of tyrosine to rise; a condition known as tyrosinemia.
Some of the toxicities resulting from tyrosinemia in laboratory animals
include ocular, developmental, liver, and kidney effects. Topramezone
exhibits a mammalian toxicity profile that is consistent with HPPD
The primary target organs affected following oral administration of
topramezone in animal toxicity studies were the eyes, thyroid,
pancreas, and liver. The most sensitive species was the rat, and in
rats and dogs, males were more sensitive than females. The effects on
the eyes in chronic toxicity studies consisted of pannus
(vascularization) and keratitis (cloudiness) of the cornea in both
sexes. Hypertrophy and hyperplasia of the thyroid, hypertrophy and
focal necrosis in the liver, and degeneration of the pancreas were
among the histopathology findings reported across different subchronic
and chronic studies in rats and dogs. Results of chronic toxicity
studies in dogs, mice, and rats also suggest decrements in body
weights, body-weight gains, and food utilization (dogs only).
There was evidence for increased susceptibility following in utero
exposure to topramezone in rats and rabbits. In rabbits, fetal
including supernumerary thoracic vertebrae and supernumerary 13th rib
were observed in the presence of maternal toxicity in six of eight
developmental toxicity studies conducted in two different strains. In
rats, developmental effects consisting of skeletal variations occurred
in the presence of maternal toxicity. Increased maternal serum levels
of tyrosine were reported in several developmental toxicity studies
(several in rabbits and one in mice), consistent with the proposed mode
of action for topramezone involving HPPD inhibition. In the rat 2-
generation reproductive toxicity study, there was no evidence of
increased pre- or post-natal susceptibility; offspring effects occurred
in the presence of maternal effects. The offspring effects consisted of
decreased pup body weight/body-weight gain in F2 (both
sexes) and increased time to preputial separation (F1
males). Maternal effects were consistent with HPPD inhibition
(decreased body weights, decreased body-weight gains, increased thyroid
and kidney weights, and microscopic findings in the eyes, kidneys, and
thyroid). No reproductive effects were reported.
Topramezone did not show any evidence of neurotoxicity in the acute
(ACN) or subchronic (SCN) neurotoxicity studies, but in a rat
developmental neurotoxicity (DNT) study, where dosing with topramezone
took place during the prenatal as well as postnatal time periods, there
was evidence for increased qualitative susceptibility. In the maternal
animals, toxicity was limited to corneal opacity, whereas effects in
the offspring included neurobehavioral and neuropathological changes.
Offspring neurobehavioral effects consisted of a decreased auditory
startle reflex at postnatal day 24 in both sexes (20-30%) and at
postnatal day 60 for males (55%). There were also mild decreases in
offspring absolute brain weights and neuropathological effects
involving decreased brain morphometric measurements (e.g., hippocampus,
and parietal cortex).
Topramezone is 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 chronic reference dose (cRfD) is expected to be
protective of alterations in hormone homeostasis that may result in
thyroid tumor formation. Mutagenicity studies conducted on technical
topramezone and its major metabolites did not demonstrate any mutagenic
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 http://www.regulations.gov in document ``Topramezone: Human-Health Risk
Assessment for (1) New Uses in Non-Crop Aquatic Sites and (2) Increased
Maximum Application Rate for Currently Registered Terrestrial Uses in
the Maintenance of Bare Grounds (Roadsides, Utility and Railroad
Rights-of-Ways, Industrial Sites, and Tank Farms),'' pages 36-39 in
docket ID number EPA-HQ-OPP-2012-0262.
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 http://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for topramezone used for
human risk assessment is shown in the Table of this unit.
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 (General population LOAEL = 8 mg/kg bw.. UF = 100X (for Developmental Neurotoxicity Study
including infants and children). inter- and intra- in Rats.
species Offspring LOAEL = 8 mg/kg bw based
extrapolation). on decreased maximum auditory
FQPA SF = 10X...... startle reflex response,
aRfD = 0.008 mg/kg decreased brain weights, and
bw. changes in brain morphology.
aPAD = 0.008 mg/kg
Acute Dietary (Females 13-49 NOAEL = 0.5 mg/kg/ UF = 100X (for Developmental Toxicity Study in
years old). day. inter- and intra- Rabbits.
species Developmental LOAEL = 5 mg/kg/day
extrapolation). based on alterations in skeletal
FQPA SF = 1X....... ossification sites and increased
aRfD = 0.005 mg/kg/ number of pairs of ribs.
aPAD = 0.005 mg/kg/
Chronic Dietary (All populations) NOAEL= 0.4 mg/kg/day UF = 100X (for Chronic toxicity/Carcinogenicity
inter- and intra- Study in Rats.
species LOAEL = 3.6 mg/kg/day based on
extrapolation). increased incidences of corneal
FQPA SF = 1X....... opacity, decreased body weight
cRfD = 0.004 mg/kg/ and body-weight gains in males
day. and histopathological evaluations
cPAD = 0.004 mg/kg/ in the eyes, thyroid and pancreas
day. of both sexes.
Incidental Oral (Short- and NOAEL = 0.4 mg/kg/ Residential LOC for Two-Generation Reproduction Study
Intermediate-Term). day. MOE = 100. in Rats.
Offspring LOAEL = 4.2 mg/kg/day
based decreases in body weights
and body-weight gains in the F2
generation offspring and
increased time to preputial
separation in the F1 male
Short- and Intermediate-Term, Oral NOAEL = 0.4 mg/ Residential LOC for Two-Generation Reproduction Study
Dermal. kg/day. MOE = 100. in Rats.
(DAF = 2.6%)........ Parental LOAEL = 4.2 mg/kg/day
based on decreased body weight,
body-weight gain in males,
increased thyroid and kidney
weights of both sexes, and
microscopic findings in eyes,
kidney and thyroid of both sexes.
Short- and Intermediate-Term Oral NOAEL= 0.4 mg/ Residential LOC for Two Generation Reproduction Study
Inhalation. kg/day (inhalation MOE = 100. in Rats.
absorption = 100%). Parental LOAEL = 4.2 mg/kg/day
based on decreased body weight,
body-weight gain in males,
increased thyroid and kidney
weights of both sexes, and
microscopic findings in eyes,
kidney and thyroid of both sexes.
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 that the NOAEL (0.4 mg/kg/day) for deriving the cRfD will be protective
of thyroid hormone alterations and 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. UF = uncertainty factor.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to topramezone, EPA considered exposure under the petitioned-
for tolerances as well as all existing topramezone tolerances in 40 CFR
180.612. EPA assessed dietary exposures from topramezone in food as
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
In estimating acute dietary exposure for both the general U.S.
population (including infants and children) and for females 13-49 years
of age, EPA used food consumption information from the U.S. Department
of Agriculture's National Health and Nutrition Examination Survey, What
We Eat in America, (NHANES/WWEIA). As to residue levels in food, EPA
assumed 100 percent crop treated (PCT), Dietary Exposure Evaluation
Model (DEEM) 7.81 default processing factors, and tolerance-level
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the same food consumption data and assumptions of
tolerance-level residues, 100 PCT and DEEM 7.81 default processing
iii. Cancer. Based on the data summarized in Unit III.A., EPA has
concluded that topramezone does not pose a cancer risk to humans at
levels that do not alter rat thyroid hormone homeostasis, and doses at
or below the cRfD are not expected to alter thyroid homeostasis.
Therefore, a dietary exposure assessment beyond the chronic assessment
for the purpose of assessing cancer risk is unnecessary.
iv. Anticipated residue and PCT information. EPA did not use
anticipated residue or PCT information in the dietary assessment for
topramezone. Tolerance-level residues and 100 PCT were assumed for all
2. Dietary exposure from drinking water. The highest drinking water
concentrations are expected to result from the direct aquatic
applications. Estimates of drinking water exposure levels were based on
label instructions (i.e., proposed application rates, duration, and
water concentration of direct aquatic applications at potable surface
water intakes). For acute and chronic dietary risk assessment, the
water concentration value of 45 parts per billion (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). Topramezone is
currently registered for turf and golf course uses that could result in
residential exposures. Topramezone is also proposed for use in direct
aquatic applications that could result in exposure during recreational
swimming activities. EPA assessed
residential exposure using the following assumptions: For adults,
short-term aggregate assessment considered the post-application
exposure resulting from the physical activities on turf. For children,
short-term aggregate assessment considered combined dermal and
incidental oral (hand-to-mouth) post-application exposures to children
1 < 2 years old resulting from the registered turf use. 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 http://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
Topramezone belongs to a class of herbicides that inhibit the liver
enzyme HPPD, which is involved in the catabolism (metabolic breakdown)
of tyrosine (an amino acid derived from proteins in the diet).
Inhibition of HPPD can result in elevated tyrosine levels in the blood,
a condition known as tyrosinemia. HPPD-inhibiting herbicides have been
found to cause a number of toxicities in laboratory animal studies
including ocular, developmental, liver, and kidney effects. Of these
toxicities, the ocular effect (corneal opacity) is highly correlated
with the elevated blood tyrosine levels. In fact, rats dosed with
tyrosine alone show ocular opacities similar to those seen with HPPD
inhibitors. Although the other toxicities may be associated with
chemically induced tyrosinemia, other mechanisms may also be involved.
There are marked differences among species in the ocular toxicity
associated with HPPD inhibition. For example, treatments with HPPD
inhibitor herbicides result in ocular effects in the rat, but not the
mouse or monkey. The explanation of this species-specific response is
related to the species differences in the clearance of tyrosine. Some
species (such as the mouse and monkey) have a metabolic pathway that
exists to remove tyrosine from the blood. This pathway involves a liver
enzyme called tyrosine aminotransferase (TAT). Unlike rats, mice and
humans have a highly effective metabolic process for handling excess
tyrosine and are unlikely to achieve the levels necessary to produce
ocular opacities. In fact, HPPD inhibitors (e.g. nitisinone) are used
as an effective therapeutic agent to treat human patients suffering
from rare genetic diseases of tyrosine catabolism. The human experience
indicates that a therapeutic dose (1 mg/kg/day dose) has an excellent
safety record in infants, children, and adults and that serious adverse
health outcomes have not been observed in a population followed for
approximately a decade. Rarely, ocular effects are seen in patients
with high plasma tyrosine levels; however, these effects are transient
and can be readily reversed upon adherence to a restricted protein
diet. This indicates that HPPD inhibitor in it of itself cannot easily
overwhelm the tyrosine-clearance mechanism in humans.
Therefore, exposure to environmental residues of HPPD-inhibiting
herbicides are unlikely to result in the high blood levels of tyrosine
and ocular toxicity in humans due to an efficient metabolic process to
handle excess tyrosine. EPA has therefore not conducted cumulative risk
assessment with other HPPD inhibitors for purposes of this assessment
of topramezone for aquatic uses.
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA SF. In
applying this provision, EPA either retains the default value of 10X,
or uses a different additional safety factor when reliable data
available to EPA support the choice of a different factor.
2. Prenatal and postnatal sensitivity. In the prenatal
developmental toxicity study with rats, there was evidence for
increased qualitative, but not quantitative, susceptibility in the
offspring. Qualitative susceptibility was demonstrated by the
occurrence of decreased fetal body weight and increased incidences of
skeletal variations in the presence of decreased body weight gain in
the maternal animals.
In six of eight rabbit studies, there was evidence for increased
qualitative susceptibility. In the does, maternal toxicity was
characterized as decreases in body weight, body weight gain, and food
consumption, all in the presence of increased serum levels of tyrosine.
In the fetuses, developmental toxicity was manifested as increased
incidences of visceral findings (i.e., absent kidney and ureter) and/or
multiple skeletal variations (i.e., delayed ossification, supernumerary
13th rib and/or 27th presacral vertebrae). In two studies, skeletal
variations were observed at high doses in the absence of any maternal
In the 2-generation reproduction study with rats, there was no
evidence of increased susceptibility. Offspring toxicity was
characterized as decreased pup weight and weight gain in F2
male and female pups and increased time to preputial separation in the
F1 males. These effects were observed in the presence of
parental/systemic toxicity that included: Decreased body weight,
decreased body-weight gain in males, increased thyroid and kidney
weights of both sexes, and microscopic findings in the eyes, kidney,
and thyroid of both sexes.
In the developmental neurotoxicity (DNT) study, there was evidence
for qualitative susceptibility. In the maternal animals, toxicity was
limited to corneal opacity whereas effects in the offspring manifested
as: Neurobehavioral changes (decreased auditory startle reflex),
decreases in absolute brain weight, and decreases in brain morphometric
measurements (e.g., hippocampus, and parietal cortex).
3. Conclusion. While EPA is retaining the 10X FQPA safety factor
for the acute dietary risk assessment for the U.S. general population
including infants and children, 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 the acute dietary risk assessment
for females of child-bearing age (i.e., 13-49 years old), the chronic
dietary risk assessment for the U.S. general population, and all non-
dietary exposure scenarios. That decision is based on the following
i. The toxicity database for topramezone is complete, except for an
immunotoxicity study. A database uncertainty factor (UFDB)
is not required for the lack of an immunotoxicity study since the PODs
used for overall risk assessments are based on effects seen in target
organs (e.g., eyes, thyroid, and liver) consistent with the actions of
this chemical as an HPPD inhibitor. An immunotoxicity study is not
yield a lower POD and the preliminary results of the retrospective
analyses provide strong support for not retaining the UFDB
as no immunotoxicity study available thus far has provided sensitive
endpoints for use in deriving points of departure.
ii. There is some indication that topramezone is a neurotoxic
chemical for developing animals. While there was no evidence of
neurotoxicity or neuropathology to the adult nervous system following a
single oral administration to rats at the limit dose in the ACN study
or following repeated dietary administration to rats in the SCN study
or in the maternal animals of the DNT study, there were neurobehavioral
as well as neuropathological effects observed in the offspring of the
DNT study as described above.
The LOAEL of 8 mg/kg/day of the DNT study is based on decreased
auditory startle reflex, decreases in brain weight, and brain
morphometric parameters at the lowest dose tested. A NOAEL was not
established. Nevertheless, the LOAEL (8 mg/kg/day) was employed as the
point of departure in assessing the risk for the general U.S.
population, including infants and children, since the offspring were
exposed to topramezone both in utero and during the lactation period.
The 10X FQPA safety factor is retained as a UFL (i.e., use
of a LOAEL to extrapolate a NOAEL.)
iii. As discussed in Unit III.D.2., there is evidence that
topramezone results in increased susceptibility in the prenatal
developmental studies in rats and rabbits. But the degree of concern
for the effects seen in those studies is low because there were clear
NOAELs for the offspring effects and EPA selected points of departure
that are protective of those effects. As explained in Unit III.D.3.ii.,
EPA is retaining the 10X FQPA safety factor for the lack of a NOAEL in
the DNT study and believes that doing so will be protective of infants
iv. There are no residual uncertainties in the exposure database.
The dietary and residential exposure analyses are conservative in
nature. The dietary exposure assessment uses tolerance-level residues
and assumes 100 PCT. EPA used similarly conservative assumptions to
assess post-application exposure to children/adults. The residential
exposure assessment uses chemical-specific turf transferable residue
data and the 2012 Residential Standard Operating Procedures (SOPs) and
is considered health-protective. 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. Acute aggregate risk is made up only of dietary
sources; therefore, the acute exposure estimates provided in the acute
dietary exposure analysis represent acute aggregate exposures. EPA has
concluded that acute exposure to topramezone from food and drinking
water will utilize 98% of the aPAD for the most highly exposed
population subgroup (all infants <1 year old) and 50% of the aPAD for
females 13-49 years of age. The acute dietary assessment did not result
in exposure estimates above EPA's level of concern.
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 (<1 year old), the population group receiving the greatest
exposure. Based on the explanation in Unit III.C.3., regarding
residential use patterns, chronic residential exposure to residues of
topramezone is not expected.
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). 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 the
general U.S. population and 120 for children 1-2 years old (a subgroup
predicted to have the highest dietary burden as well as the highest
residential exposure. Because EPA's level of concern for topramezone is
a MOE of 100 or below, these MOEs are not of concern.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level). 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
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. 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. As noted in Unit
III.C.1.iii., EPA has concluded that topramezone does not pose a cancer
risk of concern 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 the Agency'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 (BASF method D0104) is available
to enforce the tolerance expression. The method may be requested from:
Chief, Analytical Chemistry Branch, Environmental Science Center, 701
Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905;
email address: email@example.com.
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
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. There are no Codex
maximum residue limits (MRLs) in/on fish/shellfish.
C. Revisions to Petitioned-For Tolerances
The proposed tolerance definition, ``fish'' is being revised to
``fish-freshwater finfish'' and ``fish-saltwater finfish.'' The
proposed tolerance definition, ``shellfish'' is being revised to
``fish-shellfish, crustacean'' and ``fish-shellfish, mollusk.'' EPA is
also establishing meat byproduct tolerances for cattle, goat, horse,
sheep (0.80 ppm), hog (0.40 ppm), and poultry (0.02 ppm) as a result of
the additional dietary burden resulting from the consumption of treated
water by livestock since consumption of treated water by livestock is
not restricted on the proposed labeling for aquatic uses. With the
establishment of these tolerances, the currently established kidney
(cattle, goat, horse, and sheep) and liver (cattle, goat, horse, and
sheep) tolerances are being removed as it is now general policy to
establish meat byproduct tolerances rather than separate liver and
kidney tolerances (Chemistry Science Advisory Council (ChemSAC); min--
Finally, EPA has revised the tolerance expression to clarify that,
as provided in FFDCA section 408(a)(3), the tolerance covers
metabolites and degradates of topramezone not specifically mentioned;
and that compliance with the specified tolerance levels is to be
determined by measuring only the specific compounds mentioned in the
Therefore, tolerances are established for residues of topramezone,
including its metabolites and degradates, in or on fish-freshwater,
finfish; fish-saltwater, finfish; fish-shellfish, crustacean; and fish-
shellfish, mollusk at 0.05 ppm. To account for additional dietary
burden to livestock from residues in drinking water for the proposed
aquatic use, tolerances are being established for cattle, goat, horse,
and sheep meat byproducts at 0.80 ppm; hog meat byproducts at 0.40 ppm
and poultry meat byproducts at 0.02 ppm. Compliance with the following
tolerance levels is to be determined by measuring only topramezone ([3-
hydroxy-1-methyl-1H-pyrazol-4-yl)methanone) in or on the commodities.
VI. Statutory and Executive Order Reviews
This final rule establishes tolerances under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled ``Regulatory Planning and
Review'' (58 FR 51735, October 4, 1993). Because this 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 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 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 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 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) (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 of 1995 (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
Dated: July 29, 2013.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.612 is revised to read as follows:
Sec. 180.612 Topramezone; tolerances for residues.
(a) General. Tolerances are established for residues of the
herbicide topramezone, including its metabolites and degradates, in or
on the following commodities. Compliance with the following tolerance
levels is to be determined by measuring only topramezone ([3-(4,5-
methyl-1H-pyrazol-4-yl)methanone) in or on the following commodities:
Cattle, meat byproducts..................................... 0.80
Corn, field, forage......................................... 0.05
Corn, field, grain.......................................... 0.01
Corn, field, stover......................................... 0.05
Corn, pop, grain............................................ 0.01
Corn, pop, stover........................................... 0.05
Corn, sweet, forage......................................... 0.05
Corn, sweet, kernel plus cob with husks removed............. 0.01
Corn, sweet, stover......................................... 0.05
Fish-freshwater finfish..................................... 0.05
Fish-saltwater finfish...................................... 0.05
Fish-shellfish, crustacean.................................. 0.05
Fish-shellfish, mollusk..................................... 0.05
Goat, meat byproducts....................................... 0.80
Hog, meat byproducts........................................ 0.40
Horse, meat byproducts...................................... 0.80
Poultry, meat byproducts.................................... 0.02
Sheep, meat byproducts...................................... 0.80
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 2013-18975 Filed 8-6-13; 8:45 am]
BILLING CODE 6560-50-P