
[Federal Register Volume 78, Number 152 (Wednesday, August 7, 2013)]
[Rules and Regulations]
[Pages 48068-48075]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-18975]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2012-0262; FRL-9388-9]


Topramezone; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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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.

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

[[Page 48069]]

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 
20460-0001.
     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 
([3-(4,5-dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl)phenyl](5-
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 
inhibition.
    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 
abnormalities

[[Page 48070]]

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 
potential.
    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
                                                          bw.
----------------------------------------------------------------------------------------------------------------
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.
                                                          day.
                                                         aPAD = 0.005 mg/kg/
                                                          day.
----------------------------------------------------------------------------------------------------------------

[[Page 48071]]

 
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
                                                                               offspring.
----------------------------------------------------------------------------------------------------------------
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 
follows:
    i. Acute exposure. Quantitative acute dietary exposure and risk 
assessments are performed for a food-use pesticide, if a toxicological 
study has indicated the possibility of an effect of concern occurring 
as a result of a 1-day or single exposure. Such effects were identified 
for topramezone.
    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 
residues.
    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 
factors.
    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 
food commodities.
    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

[[Page 48072]]

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 
toxicity.
    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 
findings:
    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 
likely to

[[Page 48073]]

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 
and children.
    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 
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. 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: residuemethods@epa.gov.

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

[[Page 48074]]

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--
494.12-Jan-2011).
    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 
tolerance expression.

 V. Conclusion

    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-
(4,5-dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl)phenyl](5-
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 
recordkeeping requirements.

    Dated: July 29, 2013.
Lois Rossi,
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:

    Authority: 21 U.S.C. 321(q), 346a and 371.

0
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-
dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl)phenyl](5-hydroxy-1-

[[Page 48075]]

methyl-1H-pyrazol-4-yl)methanone) in or on the following commodities:

------------------------------------------------------------------------
                                                               Parts per
                          Commodity                             million
------------------------------------------------------------------------
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


