Tembotrione; Pesticide Tolerance

[Federal Register: September 28, 2007 (Volume 72, Number 188)]
[Rules and Regulations]
[Page 55078-55085]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28se07-15]

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2006-0072; FRL-8148-2]

AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation establishes tolerances for combined residues
of tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione and its metabolite
(M5); 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-4,6-dihydroxy-1,3-cyclohexanedione in
or on corn (field, sweet and pop) and livestock commodities. Bayer
CropScience requested those tolerances under the Federal Food, Drug,
and Cosmetic Act (FFDCA).

DATES: This regulation is effective September 28, 2007. Objections and
requests for hearings must be received on or before November 27, 2007,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION ).

ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2006-0072. To access the
electronic docket, go to http://www.regulations.gov, select ``Advanced
Search,'' then ``Docket Search.'' Insert the docket ID number where
indicated and select the ``Submit'' button. Follow the instructions on
the regulations.gov website to view the docket index or access
available documents. All documents in the docket are listed in the
docket index available in regulations.gov. Although listed in the
index, some information is not publicly available, e.g., Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available in the electronic docket at http://www.regulations.gov, or,
if only available in hard copy, at the OPP Regulatory Public Docket in
Rm. S-4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr.,
Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The Docket Facility
telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: Eugene Wilson, Registration Division,
Office of Pesticide Programs, Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number:
(703) 305-6103; e-mail address: wilson.eugene@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to those
engaged in the following activities:
• Crop production (NAICS code 111), e.g., agricultural
workers; greenhouse, nursery, and floriculture workers; farmers.
• Animal production (NAICS code 112), e.g., cattle ranchers
and farmers, dairy cattle farmers, livestock farmers.
• Food manufacturing (NAICS code 311), e.g., agricultural
workers; farmers; greenhouse, nursery, and floriculture workers;
ranchers; pesticide applicators.
• Pesticide manufacturing (NAICS code 32532), e.g.,
agricultural workers; commercial applicators; farmers; greenhouse,
nursery, and floriculture workers; residential users.
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.

B. How Can I Access Electronic Copies of this Document?

In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at
http://www.regulations.gov, you may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of EPA's tolerance regulations at
40 CFR part 180 through the Government Printing Office's pilot e-CFR
site at http://www.gpoaccess.gov/ecfr.

C. Can I File an Objection or Hearing Request?

Under section 408(g) of FFDCA, 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-2006-0072 in the subject line on the first page of
your submission. All requests must be in writing, and must be mailed or
delivered to the Hearing Clerk as required by 40 CFR part 178 on or
before November 27, 2007.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit this copy, identified by docket ID number
EPA-HQ-OPP-2006-0072, by one of the following methods:
• Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
• Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
• Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket Facility telephone number is (703) 305-5805.

[[Page 55079]]

II. Petition for Tolerance

In the Federal Register of April 26, 2006 (71 FR 24690-24692)
(FRL-8063-6), EPA issued a notice pursuant to section 408(d)(3) of the
FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide
petition (PP 5F7009) by Bayer CropScience, 2 TW Alexander Drive, P.O.
Box 12014, RTP, NC 27709. The petition requested that 40 CFR part 180
be amended by establishing a tolerance for combined residues of the
herbicide AE 0172747 (tembotrione), 2-[2-chloro-4-(methylsulfonyl)-3-
[(2,2,2-trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione, and
metabolite (M5), AE 1417268 (2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-4,6-dihydroxy-1,3-cyclohexanedione
(expressed as tembotrione equivalents in or on corn, field, grain at
0.02 ppm; corn, field, forage at 0.5 ppm; corn, field, stover at 0.5
ppm; corn, sweet, kernel plus cob with husks removed at 0.03 ppm; corn,
sweet, forage at 1.0 ppm; corn sweet, stover at 1.0 ppm; popcorn, grain
at 0.01 ppm; Popcorn, stover, 0.25 ppm; cattle, liver at 0.5 ppm;
cattle, meat byproducts, except liver at 0.07 ppm; goat, liver at 0.5
ppm; goat, kidney at 0.07 ppm; Hog Liver at 0.5; Hog, Kidney at 0.07
ppm, sheep, kidney at 0.07 ppm; sheep, meat byproducts at 0.5 ppm ;
horse, kidney at 0.07 ppm; horse, meat byproducts at 0.5 ppm. There
were no comments received in response to the notice of filing.
Based on the aggregate exposure from food and feed commodities
resulting from the use-patterns proposed in the petition, the proposed
tolerances were revised to account for both tembotrione and its
metabolite M5, expressed as tembotrione equilivants. The aggregate risk
assessment is discussed in Unit III, below. The reasons for these
changes are also explained in Unit V.

III. Aggregate Risk Assessment and Determination of Safety

For tembotrione, aggregate exposure risk assessments were performed
for the following scenarios: acute aggregate exposure (food and
drinking water), and chronic aggregate exposure (food and drinking
water). Short- and intermediate-term assessments were not performed
because there are no registered or proposed residential non-food uses.
The chronic Reference Dose (cRfD) will be protective of cancer and non-
cancer effects, because tembotrione is classified as ``Suggestive
Evidence of Carcinogenicity'' and EPA's Cancer Assessment Review
Committee (CARC ) recommended that a separate quantification of cancer
risks is not required, while noting that the progression of non-
neoplastic related lesions in rats was biologically plausible by non-
genotoxic modes of action for the corneal tumors.
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....'' These provisions were added to FFDCA by the Food Quality
Protection Act (FQPA) of 1996.
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 the petitioned-for tolerance
for combined residues of tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-
[(2,2,2-trifluoroethoxy]methyl]benzoyl]-1,3-cyclohexanedione and
metabolite (M5), 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-4,6-dihydroxy-1,3-cyclohexanedione, in
or on corn, field, grain at 0.02 ppm; corn, field, forage at 0.60 ppm;
corn, field, stover at 0.45 ppm; corn, sweet, kernel plus cob with
husks removed at 0.04 ppm; corn, sweet, forage at 1.0 ppm; corn, sweet,
stover at 1.2 ppm; corn, pop, grain at 0.02 ppm; corn, pop, stover at
0.35 ppm; cattle, liver at 0.40 ppm; cattle, meat byproducts, except
liver 0.07 ppm; goat, liver at 0.40 ppm; goat, meat byproducts, except
liver at 0.07 ppm; horse, liver at 0.40 ppm; horse, meat byproducts
except liver at 0.07 ppm; sheep, liver at 0.40 ppm; sheep, meat
byproducts, except liver at 0.07 ppm; poultry, liver at 0.07 ppm. EPA's
assessment of exposures and risks associated with establishing the
tolerance 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. Specific information on the studies received and the nature
of the adverse effects caused by tembotrione, 2-[2-chloro-4-
(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy)methyl]benzoyl]-1,3-
cyclohexanedione 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. The
referenced document is available in the docket established by this
action, which is described under ADDRESSES, and is identified as EPA-
HQ-OPP-2006-0072 in that docket.

B. Toxicological Endpoints

For hazards that have a threshold below which there is no
appreciable risk, the toxicological level of concern (LOC) is derived
from the highest dose at which no adverse effects are observed (the
NOAEL) in the toxicology study identified as appropriate for use in
risk assessment. However, if a NOAEL cannot be determined, the lowest
dose at which adverse effects of concern are identified (the LOAEL) is
sometimes used for risk assessment. Uncertainty/safety factors (UFs)
are used in conjunction with the LOC to take into account uncertainties
inherent in the extrapolation from laboratory animal data to humans and
in the variations in sensitivity among members of the human population
as well as other unknowns. Safety is assessed for acute and chronic
risks by comparing aggregate exposure to the pesticide to the acute
population adjusted dose (aPAD) and chronic population adjusted dose
(cPAD). The aPAD and cPAD are calculated by dividing the LOC by all
applicable UFs. Short-, intermediate-, and long-term risks are
evaluated by comparing aggregate exposure to the LOC to ensure that the
margin of exposure (MOE) called for by the product of all applicable
UFs is not exceeded.
For non-threshold risks, the Agency assumes that any amount of
exposure will lead to some degree of risk and estimates risk in terms
of the probability of occurrence of additional adverse cases.
Generally, cancer risks are

[[Page 55080]]

considered non-threshold. 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/fedrgstr/EPA-PEST/1997/November/Day-26/p30948.htm.

A summary of the toxicological endpoints for tembotrione, 2-[2-
chloro-4-(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy)methyl]benzoyl]-
1,3-cyclohexanedione used for human risk assessment is shown in Table 1
of this unit.

Table 1.--Summary of Toxicological Dose and Endpoints for tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
Dose Used in Risk
Assessment, Special FQPA SF and
Exposure/Scenario Interspecies and Level of Concern for Study and Toxicological
Intraspecies and any Risk Assessment Effects
Traditional FQPA, SF
----------------------------------------------------------------------------------------------------------------
Acute dietary (General population LOAEL = 0.8 (mg/kg/day) Special FQPA SF = 1 Developmental
including infants and children) and SF = 1000.............. aPAD = acute RfD / Neurotoxicity Study:
Females 13 to 49 UFA = 10X.............. Special FQPA SF = Offspring NOAEL was
UFH = 10X.............. 0.0008 mg/kg. not
FQPA SF = 10X(includes established.Offspring
UFL = 10X). LOAEL = 0.8 mg/kg/day
Acute reference dose based on decreased
(RfD) = 0.0008 mg/kg. acoustic startle
response on PND 60
(males), and brain
morphometric changes
on PND 75 (males and
females).
----------------------------------------------------------------------------------------------------------------
Chronic dietary(All populations) NOAEL= .04 mg/kg/day Special FQPA SF = 1 Chronic/Carcinogenicity
SF = 100............... cPAD = chronic RfD Study LOAEL = 0.79 mg/
UFA = 10X.............. Special FQPA SF = kg/day based on
UFH = 10X.............. 0.0004 mg/kg/day. neovascularization and
FQPA SF = 1X........... edema of the cornea
Chronic RfD = 0.0004 mg/ and snow flake-like
kg/day. corneal opacity,
unilateral or
bilateral keratitis of
the eye, decreased
mean body weight and
mean body-weight gain,
increased total
cholesterol, higher
ketone levels and
lower pH values,
higher protein levels,
increased kidney
weight, kidney to body
weight and kidney to
brain weight ratios,
chronic nephropathy
and atrophy of the
sciatic nerve.
----------------------------------------------------------------------------------------------------------------
Short-term dermal (1 to 30 days) Oral study LOAEL= 0.8 LOC for MOE =1000 Developmental
(Residential) mg/kg/day neurotoxicity Study
UFA = 10X.............. Offspring NOAEL was
UFH = 10X.............. not
FQPA SF = 10X (includes established.Offspring
UFL = 10X) (dermal LOAEL = 0.8 mg/kg/day
absorption rate = 15 based on decreased
%). acoustic startle
response on PND 60
(males), and brain
morphometric changes
on PND 75 (males and
females).
----------------------------------------------------------------------------------------------------------------
Intermediate-term dermal (1 to 6 Oral study LOAEL= 0.8 LOC for MOE = 1000 Developmental
months) (Residential) mg/kg/day (Residential) neurotoxicity Study
UFA = 10X.............. Offspring NOAEL was
UFH = 10X.............. not
FQPA SF = 10X (includes established.Offspring
UFL = 10X) (dermal LOAEL = 0.8 mg/kg/day
absorption rate = 15 based on decreased
%). acoustic startle
response on PND 60
(males), and brain
morphometric changes
on PND 75 (males and
females).
----------------------------------------------------------------------------------------------------------------

[[Page 55081]]

Long-term dermal (>6 months to Oral study NOAEL= 0.04 LOC for MOE = 100 Chronic/Carcinogenicity
lifetime) (Residential) mg/kg/day (Residential) Study LOAEL = 0.79 mg/
UFA = 10X.............. kg/day based on
UFH = 10X.............. neovascularization and
FQPA SF = 1X (dermal edema of the cornea
absorption rate = 15 % and snow flake-like
when appropriate). corneal opacity,
unilateral or
bilateral keratitis of
the eye, decreased
mean body weight and
mean body-weight gain,
increased total
cholesterol, higher
ketone levels and
lower pH values,
higher protein levels,
increased kidney
weight, kidney to body
weight and kidney to
brain weight ratios,
chronic nephropathy
and atrophy of the
sciatic nerve.
----------------------------------------------------------------------------------------------------------------
Short-term inhalation (1 to 30 days) Oral study LOAEL= 0.8 LOC for MOE = 1000 Developmental
(Residential) UFL = 10X) (inhalation (Residential) neurotoxicity Study
absorption rate = Offspring NOAEL was
100%). not established.
Offspring LOAEL = 0.8
mg/kg/day based on
decreased acoustic
startle response on
PND 60 (males), and
brain morphometric
changes on PND 75
(males and females).
----------------------------------------------------------------------------------------------------------------
Intermediate-term inhalation (1 to 6 Oral study LOAEL= 0.8 LOC for MOE = 1000 Developmental
months) (Residential) mg/kg/day (Residential) neurotoxicity Study]
UFA = 10X.............. Offspring NOAEL was
UFH = 10X.............. not
FQPA SF = 10X (includes established.Offspring
UFL = 10X) (inhalation LOAEL = 0.8 mg/kg/day
absorption rate = based on decreased
100%). acoustic startle
response on PND 60
(males), and brain
morphometric changes
on PND 75 (males and
females).
----------------------------------------------------------------------------------------------------------------
Long-term inhalation (>6 months) Oral study NOAEL= 0.04 LOC for MOE = 100 Chronic/Carcinogenicity
(Residential) mg/kg/day Residential Study LOAEL = 0.79 mg/
UFH = 10X............. kg/day based on
FQPA SF = 1X neovascularization and
(inhalation absorption edema of the cornea
rate = 100%). and snow flake-like
corneal opacity,
unilateral or
bilateral keratitis of
the eye, decreased
mean body weight and
mean body-weight gain,
increased total
cholesterol, higher
ketone levels and
lower pH values,
higher protein levels,
increased kidney
weight, kidney to body
weight and kidney to
brain weight ratios,
chronic nephropathy
and atrophy of the
sciatic nerve.
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation) Classification: ``Suggestive Evidence of Carcinogenic Potential'' based
on the observance of squamous cell carcinomas in a rat carcinogenicity
study. Quantification of cancer risk is not required.
----------------------------------------------------------------------------------------------------------------
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.
MOE = margin of exposure. LOC = level of concern.

C. Exposure Assessment

1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione, EPA considered
exposure under the petitioned-for tolerances. EPA assessed dietary
exposures from tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-tri

[[Page 55082]]

fluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione 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.
Effects were identified in the toxicological studies for
tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione; therefore, a
quantitative acute dietary exposure assessment was necessary. The acute
analysis assumed 100% crop treated (CT), Dietary Exposure Evaluation
Model (DEEM(TM)) 7.81 default processing factors, and
tolerance-level residues for all foods. For drinking water, the entire
distribution of estimated daily exposure values from the Pesticide Root
Zone Modeling-Exposure Evaluation Analysis Modeling System (PRZM-EXAMS)
run was incorporated in the acute probabilistic exposure analyses. The
resulting acute dietary (food + water) risk estimates were < 32% of the
aPAD for the general U.S. population and < 77% of the aPAD for all
infants (< 1 year old, the most highly-exposed population subgroup) at
the 95th percentile; less than HED's LOC (100% aPAD). Even though the
entire distribution of estimated daily drinking water exposure values
was incorporated, this analysis is still conservative since tolerance-
level residues, DEEM(TM) 7.81 default processing factors,
and 100% CT were assumed. Also, the distribution of estimated daily
drinking water exposure still assumes 100% CT and the maximum
application rate.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA, 1994-1996,
and 1998 Continuing Survey of Food Intake by Individuals. As to residue
levels in food, EPA assumed all foods for which there are proposed
tolerances were treated and contain tolerance-level residues. A
conservative chronic dietary assessment assuming tolerance-level
residues, DEEM(TM) 7.81 default processing factors, and 100%
CT was also conducted. The highest estimate of chronic surface water
exposure (1.05 parts per billion (ppb)) was used for drinking water in
this analysis.
iii. Cancer. There was only suggestive evidence of carcinogenic
potential based on the observance of squamous cell carcinomas in a rat
carcinogenicity study. Quantification of cancer risk is not required.
Dietary cancer risk concerns due to long-term consumption of
tembotrione residues are adequately addressed by the chronic exposure
analysis using the cPAD.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring data to complete a comprehensive dietary exposure
analysis and risk assessment for tembotrione, 2-[2-chloro-4-
(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy)methyl]benzoyl]-1,3-
cyclohexanedione in drinking water. Because the Agency does not have
comprehensive monitoring data, drinking water concentration estimates
are made by reliance on simulation or modeling taking into account data
on the environmental fate characteristics of tembotrione, 2-[2-chloro-
4-(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy)methyl]benzoyl]-1,3-
cyclohexanedione. Further, information regarding EPA drinking water
models used in pesticide exposure assessment can be found at http://www.epa.gov/oppefed1/models/water/index.htm.

Based on the PRZM/EXAMS and Screening Concentration in Ground Water
(SCI-GROW) models, the estimated environmental concentrations (EECs) of
tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione for acute
exposures are estimated to be 5.84 parts per billion (ppb) for surface
water and 0.0139 ppb for ground water. The EECs for chronic exposures
are estimated to be 1.05 ppb for surface water and 0.0139 ppb for
ground water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For acute dietary risk
assessment, the water concentration value of 5.84 ppb was used to
access the contribution to drinking water. For chronic dietary risk
assessment, the water concentration of value 1.05 ppb was used to
access 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).
Tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione is not registered
for use on any sites that would result in residential exposure.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
Tembotrione, belongs to a class of herbicides (including
mesotrione, pyrasulfotole, isoxaflutole and topramezone) that inhibit
the liver enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD). As
discussed above, EPA has concluded that the ocular effects caused by
these herbicides has limited relevance to humans. Nonetheless, as a
worst case scenario, EPA has assessed aggregate exposure to tembotrione
based on ocular effects in rats. For similar reasons, a semi-
quantitative screening cumulative assessment was conducted using the
rat ocular effects and 100% crop treated information. The results of
this screening analysis did not indicate a concern. In the future,
assessments of HPPD-inhibiting herbicides will consider more
appropriate models and cross species extrapolation methods.
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 website at
http://www.epa.gov/pesticides/cumulative.

D. Safety Factor for Infants and Children

1.In general. Section 408 of FFDCA provides that EPA shall apply an
additional (``10X'') tenfold margin of safety for infants and children
in the case of threshold effects to account for pre- and post-natal
toxicity and the completeness of the database on toxicity and exposure
unless EPA determines based on reliable data that a different margin of
safety will be safe for infants and children. This additional margin of
safety is commonly referred to as the FQPA safety factor. In applying
this provision, EPA either retains the default value of 10X when
reliable data do not support the choice of a different factor, or, if
reliable data are available, EPA uses a different additional FQPA
safety factor value based on the use of traditional UFs and/or special
FQPA safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. There is evidence of
increased susceptibility in rabbit and rat fetuses to in utero exposure
to tembotrione compared to the doses for the effects found in maternal
animals. In a developmental toxicity study in rabbits, the NOAEL of 1
milligram per kilogram of body weight per day (mg/kg bw/day) was based
on decreased growth and/or delayed development of the skeleton

[[Page 55083]]

and increased incidences of skeletal variations and anomalies in
fetuses seen at a LOAEL of 10 mg/kg/day. This LOAEL is ten-fold lower
than the dose resulting in maternal toxicity (100 mg/kg/day, few or no
feces, late abortion, decreased body weight and food consumption). In a
rat developmental toxicity study, increased skeletal variations (e.g.,
delayed ossifications) and other fetal effects (decreased fetal body
weights and an increased number of runts) occurred at a dose of 25 mg/
kg/day (the lowest dose tested), which is lower than the 125 mg/kg bw
dose that caused marginal maternal toxicity (decreased body-weight
gains and food consumption). In a rat developmental neurotoxicity study
(DNT), decreased post-weaning body weight (males), decreased acoustic
startle response and brain morphometric changes were seen in rat
fetuses at a dose of 0.8 mg/kg/day (the lowest dose tested) which was
lower than the dose of 16.3 mg/kg/day at which maternal toxicity
occurred (cornel opacity during lactation).
Although, these studies provide evidence of increased
susceptibility following pre- and post-natal exposures, the concern for
increased susceptibility is low for several reasons. First, a well
characterized NOAEL (with a sufficient margin from the LOAEL)
protecting fetuses has been established in the rabbit prenatal study.
Also, the prenatal developmental NOAELs or LOAELs for both the rabbit
and rat studies are approximately 12 to 30-fold higher than the LOAEL
used for the acute RfD. Although there were some marginal effects
reported in the offspring in the rat 2-generation reproduction study at
1.4 mg/kg/day (the lowest dose tested), these parameters (ocular,
decreased absolute brain weight, preputial separation) were also
evaluated at the lower dose in the rat DNT study but were not found at
the low dose tested (0.8 mg/kg/day). Therefore, a NOAEL has been
identified for these effects. Other effects indicative of neurotoxicity
(altered brain morphometrics, decrease in auditory startle response)
were seen in the rat developmental neurotoxicity study at the lowest
dose tested. The response for brain morphometrics seen at termination
is considered to be marginal or equivocal since the changes were small
and no clear dose response was observed. The decreased acoustic startle
response was not found in young pups (post-natal day 22) but only
observed in adult rats (post-natal day 60) and was statistically
significant at the mid and high dose but not at the lowest dose tested.
3. Conclusion. Given the above-described data on pre- and post-
natal effects, the only significant uncertainty concerns the acute RfD
due to the failure to identify a NOAEL for the brain morphometric
alterations found in the rat DNT. The LOAEL in the DNT is lower than
the NOAEL and the LOAEL from the rabbit and rat developmental studies,
and thus is the lowest dose reflective of potential acute effects.
Because of the uncertainty as to the NOAEL for the acute effects (brain
morphometric alterations) seen at 0.8 mg/kg/day in the DNT, EPA has
retained the additional 10X FQPA safety factor in calculating the acute
RfD. This is a conservative step given the equivocal nature of the
brain morphometric alterations seen at the LOAEL in the DNT.
EPA has determined that reliable data show that it would be safe
for infants and children to reduce the FQPA safety factor to 1X for
assessing chronic risk. That decision is based on the following findings:
i. For the reasons described in Unit III.D.2., the toxicity
database for tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione is adequate to
assess chronic risk.
ii. Despite evidence of sensitivity in pre- and post-natal studies,
as detailed in Unit III.D.2., the chronic RfD based on an adult animal
study (chronic rat study) is considered to be protective of the chronic
offspring toxicity found in the rat DNT and 2-generation reproduction
studies. The 2-generation reproduction study did not identify a NOAEL
for the chronic effects seen on brain weight and preputial separation
but a NOAEL can be characterized from the DNT, as discussed above, at
0.8 mg/kg/day. The NOAEL used to set the chronic RfD is 20-fold lower
than this 0.8 mg/kg/day dose and is not based on an effect as to which
the data have raised sensitivity concerns. Similarly, the chronic rat
study and the NOAEL from that study are protective of the chronic
effects seen in the DNT study and the other chronic effects found in
the 2-generation reproduction study. The endpoints of concern for the
chronic RfD are based on ocular toxicity, body weight decreases, kidney
toxicity, and changes in the clinical chemistry parameters. Target
organ toxicity such as ocular toxicity, kidney toxicity, body weight
changes and nervous system effects were assessed in the young through
pre- and post-natal exposure to tembotrione in the 2-generation
reproduction study and the DNT study. In those studies, these effects
were observed at higher doses in the young than in the adults in the
chronic rat study. Therefore, the chronic RfD is considered to be
protective of effects in the young. As noted, the NOAEL (0.04 mg/kg/
day) selected for the chronic RfD is 20-fold lower than the dose at
which developmental and neurological effects were observed in any
study; it is also 20-fold lower than the NOAEL for other chronic
effects seen in the young.
iii. There are no residual uncertainties identified in the exposure
data bases. The dietary food exposure assessments were performed based
on 100% CT and tolerance-level residues of tembotrione, 2-[2-chloro-4-
(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy)methyl]benzoyl]-1,3-
cyclohexanedione.

E. Aggregate Risks and Determination of Safety

Safety is assessed for acute and chronic risks by comparing
aggregate exposure to the pesticide to the aPAD and cPAD. The aPAD and
cPAD are calculated by dividing the LOC by all applicable UFs. For
linear cancer risks, EPA calculates the probability of additional
cancer cases given aggregate exposure. Short-, intermediate-, and long-
term risks are evaluated by comparing aggregate exposure to the LOC to
ensure that the MOE called for by the product of all applicable UFs is
not exceeded.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food and water
to tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione will occupy 77% of
the aPAD for the population group (infants (< 1 year old) receiving the
greatest exposure.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione from food and
water will utilize 48% of the cPAD for the population group (children 3
to 5 years old). There are no residential uses for tembotrione, 2-[2-
chloro-4-(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy)methyl]benzoyl]-
1,3-cyclohexanedione that result in chronic residential exposure to
tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione.
3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level).

[[Page 55084]]

Tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione is not registered
for use on any sites that would result in residential exposure.
Therefore, the aggregate risk is the sum of the risk from food and
water, which does not exceed the Agency's level of concern.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).
Tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione is not registered
for use on any sites that would result in residential exposure.
Therefore, the aggregate risk is the sum of the risk from food and
water, which does not exceed the Agency's level of concern.
5. Aggregate cancer risk for U.S. population. Dietary cancer risk
concerns due to long-term consumption of tembotrione residues are
adequately addressed by the chronic exposure analysis using the cPAD.
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 tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

An Adequate enforcement methodology, liquid chromatography/mass
spectroscopy (LC/MS/MS) method 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; e-mail address:
residuemethods@epa.gov.

B. International Residue Limits

There is neither a Codex proposal, nor Canadian or Mexican limits
for residues of tembotrione and its metabolites in or on crops or
livestock commodities.

C. Response to Comments

There were no comments received on the Notice of Filing of the
pesticide petition.

V. Conclusion

Therefore, the tolerance is established for combined residues or
residues of tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
(trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione, metabolite; 2-
[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-trifluorethoxy)methyl]benzoyl]-
4,6-dihydroxycyclohexanedione, in or on corn, field, grain at 0.02 ppm;
corn, field, forage at 0.60 ppm; corn, field, stover at 0.45 ppm; corn,
sweet, kernel plus cob with husks removed at 0.04 ppm; corn, sweet,
forage at 1.0 ppm; corn sweet, stover at 1.2 ppm; corn, pop, grain at
0.02 ppm; corn, pop, stover at 0.35 ppm; cattle, liver at 0.40 ppm;
cattle, meat byproducts, except liver 0.07 ppm; goat, liver at 0.40
ppm; goat, meat byproducts, except liver at 0.07 ppm; horse, liver at
0.40 ppm; horse, meat byproducts except liver at 0.07 ppm; sheep, liver
at 0.40 ppm; sheep, meat byproducts, except liver at 0.07 ppm; poultry,
liver at 0.07 ppm.

VI. Statutory and Executive Order Reviews

This final rule establishes a tolerance under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this rule has been
exempted from review under Executive Order 12866, this rule is not
subject to Executive Order 13211, Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355,
May 22, 2001) or Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997). This final rule does not contain any information collections
subject to OMB approval under the Paperwork Reduction Act (PRA), 44
U.S.C. 3501 et seq., nor does it require any special considerations
under Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian 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 6, 2000) do not apply to this rule. In addition, This
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) (Public Law 104-4).
This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement Act
of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note).

VII. Congressional Review Act

The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

Dated: September 23, 2007.
Debra Edwards,
Director, Office of Pesticide Programs.

• Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

• 1. The authority citation for part 180 continues to read as follows:

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

[[Page 55085]]

• 2. Section 180.634 is added to subpart C to read as follows:

Sec. 180.634 Tembotrione; tolerances for residues.

(a) General. Tolerances are established for residues of the
herbicide, tembotrione, 2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-1,3-cyclohexanedione and its metabolite
2-[2-chloro-4-(methylsulfonyl)-3-[(2,2,2-
trifluoroethoxy)methyl]benzoyl]-4,6-dihydroxycyclohexane-1,3-dione in
or on the following commodities:

------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Cattle, liver........................................... 0.40
Cattle, meat byproducts, except liver................... 0.07
Corn, field, forage..................................... 0.60
Corn, field, grain...................................... 0.02
Corn, field, stover..................................... 0.45
Corn, pop, grain........................................ 0.02
Corn, pop, stover....................................... 0.35
Corn, sweet, forage..................................... 1.0
Corn, sweet, kernel plus cob with husks removed......... 0.04
Corn, sweet, stover..................................... 1.2
Goat, liver............................................. 0.40
Goat, meat byproducts, except liver..................... 0.07
Horse, liver............................................ 0.40
Horse, meat byproducts, except liver.................... 0.07
Poultry, liver.......................................... 0.07
Sheep, liver............................................ 0.40
Sheep, meat byproducts, except liver.................... 0.07
------------------------------------------------------------------------

(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]

[FR Doc. E7-19230 Filed 9-27-07; 8:45 am]
BILLING CODE 6560-50-S

Notices For
2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994

Tembotrione; Pesticide Tolerance

Local Navigation