Clofentezine; Pesticide Tolerance

Note: EPA no longer updates this information, but it may be useful as a reference or resource.

[Federal Register: March 9, 2005 (Volume 70, Number 45)]
[Rules and Regulations]
[Page 11563-11572]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09mr05-12]

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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2005-0022; FRL-7699-8]

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

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

SUMMARY: This regulation establishes tolerances for residues of
clofentezine in or on grapes and persimmons. Makhteshim-Agan of North
America, Inc. and the Interregional Research Project Number 4 (IR-4)
requested these tolerances under the Federal Food, Drug, and Cosmetic
Act (FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA).

DATES: This regulation is effective March 9, 2005. Objections and
requests for hearings must be received on or before May 9, 2005.

ADDRESSES: To submit a written objection or hearing request, follow
the detailed instructions as provided in Unit VI of the SUPPLEMENTARY
INFORMATION. EPA has established a docket for this action under Docket
identification (ID) number OPP-2005-0022. All documents in the docket
are listed in the EDOCKET index at http://www.epa.gov/edocket. Although
listed in the index, some information is not publicly available, i.e.,
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 either electronically
in EDOCKET or in hard copy at the Public Information and Records
Integrity Branch (PIRIB), Room 119, Crystal Mall #2, 1801 S.
Bell Street, Arlington, VA 22202-4501. This docket facility is open
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The docket telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: Carmen Rodia, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Avenue, NW., Washington, DC 20460-0001; telephone
number: (703) 306-0327; fax number: (703) 305-6596; e-mail address:
rodia.carmen@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:
Crop production (NAICS 111), e.g., agricultural workers;
greenhouse, nursery, and floriculture workers; farmers.
Animal production (NAICS 112), e.g., cattle ranchers and
farmers, dairy cattle farmers, livestock farmers.
Food manufacturing (NAICS 311), e.g., agricultural
workers; farmers;

[[Page 11564]]

greenhouse, nursery, and floriculture workers; ranchers; pesticide
applicators.
Pesticide manufacturing (NAICS 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 provides
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 and Other
Related Information?

In addition to using EDOCKET (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/. A frequently updated electronic version of 40 CFR part 180
is available at E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/.
To access the OPPTS Harmonized Guidelines referenced in this
document, go directly to the guidelines at
http://www.epa.gov/opptsfrs/home/guidelin.htm/.

II. Background and Statutory Findings

In the Federal Register of July 12, 2000 (65 FR 43004) (FRL-6591-
8), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
0F6119) by Aventis CropScience, 2 T.W. Alexander Drive, Research
Triangle Park, NC 27709. The petition requested that 40 CFR 180.446 be
amended by establishing a tolerance for residues of the miticide
clofentezine [(3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine), in or on
grapes at 0.35 parts per million (ppm). Subsequently, Aventis
CropScience sold all proprietary rights for clofentezine to Makhteshim-
Agan of North America, Inc., 551 Fifth Avenue, Suite 1100, New York, NY
10176. Further, in the Federal Register of August 27, 2004 (69 FR
52688) (FRL-7676-3), EPA issued a similar notice announcing the filing
of a pesticide petition (PP 4E6824) by the Interregional Research
Project Number 4 (IR-4), 681 U.S. Highway 1 South, North Brunswick, NJ
08902, requesting that 40 CFR 180.446 be amended by establishing a
tolerance for residues of clofentezine, in or on persimmons at 0.05
ppm. These notices included a summary of the petitions prepared by the
registrants. In order to harmonize with existing Codex maximum residue
limits (MRLs) for grapes, the proposed tolerance level for grapes was
subsequently revised to 1.0 ppm. There were no substantive comments
received in response to these notices.
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.''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 of FFDCA and a complete
description of the risk assessment process, see the final rule on
Bifenthrin Pesticide Tolerances (62 FR 62961,
November 26, 1997) (FRL-5754-7).

III. Aggregate Risk Assessment and Determination of Safety

Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure, consistent with section
408(b)(2) of FFDCA, for a tolerance for residues of clofentezine per se
on grapes at 1.0 ppm and on persimmons at 0.05 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. The nature of the toxic effects caused by clofentezine are
discussed below in Table 1 as well as the no observed adverse effect
level (NOAEL) and the lowest observed adverse effect level (LOAEL) from
the toxicity studies reviewed.

Table 1.--Subchronic and Chronic Toxicity Profile of Clofentezine
Technical.
------------------------------------------------------------------------
Guideline No. Study Type Results
------------------------------------------------------------------------
870.3100 90-Day subchronic Incorporated into
feeding toxicity, the 2-year mouse
mouse oncogenicity
study.
------------------------------------------------------
870.3100 90-Day subchronic NOAEL (systemic):
feeding toxicity, 2.0 mg/kg/day
rat LOAEL (systemic):
20.0 mg/kg/day
based on
increased
cholesterol
levels, liver-to-
body weight
ratios, liver
weights, and
centrilobular
hepatocellular
enlargement.
------------------------------------------------------
870.3150 90-Day subchronic NOAEL was not
feeding, established.
nonrodent (dog) LOAEL (systemic):
< 80.0 mg/kg/day
based on
increased liver
weights in both
sexes and
electrocardiograp
hic changes in
females.
------------------------------------------------------

[[Page 11565]]

870.3700 Prenatal Maternal NOAEL:
Developmental 1,280 mg/kg/day
Toxicity, Rat (above the Limit
Dose of 1,000 mg/
kg/day)
Maternal LOAEL:
3,200 mg/kg/day
based on
differential
staining and
slight
enlargement of
the centrilobular
hepatocytes.
Developmental
NOAEL: >3,200 mg/
kg/day (above the
Limit Dose)
Developmental
LOAEL: >3,200 mg/
kg/day (above the
Limit Dose)
------------------------------------------------------
870.3700 Prenatal Maternal NOAEL:
Developmental 1,000 mg/kg/day
Toxicity, Rabbit (Limit Dose)
Maternal LOAEL:
3,000 mg/kg/day
based on
decreased body
weight and food
consumption.
Developmental
NOAEL: 1,000 mg/
kg/day (Limit
Dose)
Developmental
LOAEL: 3,000 mg/
kg/day based on
decreased mean
fetal weight.
------------------------------------------------------
870.3800 2-Generation Parental/Systemic
Reproductive and NOAEL: >=20.0 mg/
Fertility kg/day
Effects, Rat Parental/Systemic
LOAEL: >20.0 mg/
kg/day
Reproductive
NOAEL: >=20.0 mg/
kg/day
Reproductive
LOAEL: >20.0 mg/
kg/day
Offspring NOAEL:
³20.0 mg/kg/day
Offspring LOAEL:
>20.0 mg/kg/day
------------------------------------------------------
870.4100 Chronic Feeding NOAEL (systemic):
Toxicity, 1.25 mg/kg/day
Nonrodent (Dog) LOAEL (systemic):
25.0 mg/kg/day
based on
increased liver
weights,
hepatocellular
enlargement, and
increased serum
cholesterol,
triglycerides,
and alkaline
phosphatase
levels.
------------------------------------------------------
870.4200 Chronic NOAEL (systemic):
Carcinogenicity 50.70 mg/kg/day
(Feeding), Mouse LOAEL (systemic):
543.0 mg/kg/day
based on
decreased body
weights and body
weight gains,
increased
incidence of
eosinophilic
areas in
hepatocytes of
males. In
females,
increased
incidence of
basophilic and/or
eosinophilic foci
or areas of
hepatocyte
alterations,
mortality with
amyloidosis as a
contributing
factor for
increased
mortality. No
evidence of
carcinogenicity.
------------------------------------------------------
870.4300 Combined Chronic NOAEL (systemic):
Feeding Toxicity/ 1.72 mg/kg/day
Carcinogenicity LOAEL (systemic):
Study, Rat 17.3 mg/kg/day
based on
increased liver
weights and liver-
to-body weight
ratios and
increased
thyroxin levels;
and centrilobular
hepatocellular
hypertrophy and
vacuolation,
focal cystic
degeneration of
hepatocytes, and
diffuse
distribution of
fat deposits in
liver (M).
Evidence of
carcinogenicity
in male rats
[thyroid tumors].
------------------------------------------------------
870.5200 Mouse Lymphoma Non-mutagenic
(±)
activation.
------------------------------------------------------
870.5250 Gene Mutation, Non-mutagenic
Salmonella (±)
activation.
------------------------------------------------------
870.5395 In vitro Mammalian Non-mutagenic.
Cytogenetics Test
(Erythocyte
Micronucleus
Assay), Mice
------------------------------------------------------
870.5450 Rodent Dominant Non-mutagenic.
Lethal Assay, Rat
------------------------------------------------------
870.5575 Mitotic Gene Non-mutagenic and
Conversion in negative for
Saccharomyces mitotic
cerevisiae recombination.
------------------------------------------------------
870.7485 General Male and female
Metabolism, Rat rats given
clofentezine
technical at
1,000 mg/kg
manifested peak
plasma levels of
between 14 and 16
ppm at 6-8 hours
post-dosing which
then declined to
3 ppm at 24 hours
post-dosing.
Plasma half-life
was approximately
3.5 hours. Whole
body
autoradiography
of rats given a
10 mg/kg dose
indicated poor
gastrointestinal
absorption with
60-70% of the
given dose
excreted in the
feces during the
first 24 hours
and about 20%
excreted in the
urine. Major
metabolites were
3-(2'-methyl-thio-
3' hydroxy
phenyl)-6-(2'-
chloro-phenyl)-
1,2,4,5-tetrazine
and 3-,4-, and 5-
hydroxyclofentezi
ne. Both liver
and kidney had
the highest
tissue
concentration
after 72 hours.
------------------------------------------------------------------------

[[Page 11566]]

B. Toxicological Endpoints

The dose at which the NOAEL from the toxicology study identified as
appropriate for use in risk assessment is used to estimate the
toxicological level of concern (LOC). However, the LOAEL is sometimes
used for risk assessment if no NOAEL was achieved in the toxicology
study selected. An uncertainty factor (UF) is applied to reflect
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. An UF of 100 is routinely
used, 10x to account for interspecies differences and 10x for
intraspecies differences.
Three other types of safety or uncertainty factors may be used: The
``traditional uncertainty factor;'' the ``special FQPA safety factor;''
and the ``default FQPA safety factor.'' By the term ``traditional
uncertainty factor,'' EPA is referring to those additional uncertainty
factors used prior to FQPA passage to account for database
deficiencies. These traditional uncertainty factors have been
incorporated by the FQPA into the additional safety factor for the
protection of infants and children. The term ``special FQPA safety
factor'' refers to those safety factors that are deemed necessary for
the protection of infants and children primarily as a result of the
FQPA. The ``default FQPA safety factor'' is the additional 10x safety
factor that is mandated by the statute unless it is decided that there
are reliable data to choose a different additional factor (potentially
a ``traditional uncertainty factor'' or a ``special FQPA safety factor'').
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by an UF of
100 to account for interspecies and intraspecies differences and any
traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF).
Where a special FQPA safety factor or the default FQPA safety factor is
used, this additional factor is applied to the RfD by dividing the RfD
by such additional factor. The acute or chronic Population Adjusted
Dose (aPAD or cPAD) is a modification of the RfD to accommodate this
type of safety factor.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10x
to account for interspecies differences and 10x for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk). An example of how such a probability risk is expressed
would be to describe the risk as one in one hundred thousand (1 x
10-\5\), one in a million (1 x 10-\6\), or one in
ten million (1 x 10-\7\). Under certain specific
circumstances, MOE calculations will be used for the carcinogenic risk
assessment. In this non-linear approach, a ``point of departure'' is
identified below which carcinogenic effects are not expected. The point
of departure is typically a NOAEL based on an endpoint related to
cancer effects though it may be a different value derived from the dose
response curve. To estimate risk, a ratio of the point of departure to
exposure (MOE_cancer = point of departure/exposures) is calculated.
In general, clofentezine has low acute toxicity by the oral, dermal
and inhalation routes of exposure (Categories III and IV) although mild
eye irritation has been observed in rabbits. No appropriate
toxicological endpoint (effect) attributable to a single exposure
(dose) was identified in any study including the available oral studies
in the rat and developmental studies in the rat and rabbit; therefore,
an acute RfD was not established and no risk is expected from acute
exposure. Long-term dermal exposure and risk is not expected, based on
the current use pattern. In addition, based on the overall low toxicity
of clofentezine, there is minimal concern for short-, intermediate-,
and long-term inhalation exposure and risk. A summary of the
toxicological endpoints used for the clofentezine human health risk
assessment is shown below in Table 2.

Table 2.--Summary of Toxicological Dose and Endpoints for Clofentezine 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 UF
----------------------------------------------------------------------------------------------------------------
Chronic Dietary NOAEL= 1.25 mg/kg/day Special FQPA SF = 1x Chronic Feeding
(General U.S. Population including UF = 100............... cPAD = chronic RfD..... Toxicity, Nonrodent
infants and children). Chronic RfD =.......... Special FQPA SF = 0.013 (Dog)
0.013 mg/kg/day........ mg/kg/day. LOAEL = 25.0 mg/kg/day
....................... based on
histopathology in the
liver and elevated
serum cholesterol,
triglycerides, and
alkaline phosphatase
observed at the LOAEL.
----------------------------------------------------------------
Short-Term Dermal Oral study NOAEL = 2 mg/ LOC for MOE = 90-Day subchronic
(1 to 30 days)....................... kg/day 100 (Residential)...... feeding toxicity, Rat
(Residential)........................ (dermal absorption rate LOAEL = 20 mg/kg/day
= 1%). based on increased
cholesterol, increased
liver weights, thyroid
colloid depletion and
thyroid follicular
cell hypertrophy.
----------------------------------------------------------------
Intermediate-Term Dermal Oral study NOAEL = 2 mg/ LOC for MOE = 90-Day Subchronic
(1 to 6 months)...................... kg/day 100 (Residential)...... Feeding Toxicity, Rat
(Residential)........................ (dermal absorption rate LOAEL = 20 mg/kg/day
= 1%). based on increased
cholesterol, increased
liver weights, thyroid
colloid depletion and
thyroid follicular
cell hypertrophy.
----------------------------------------------------------------------------------------------------------------

[[Page 11567]]

C. Exposure Assessment

1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.446) for the residues of clofentezine per se,
in or on a variety of raw agricultural commodities (RACs).
Specifically, tolerances for clofentezine are established for almonds,
apples, apricots, cherries, nectarines, peaches, pears, and walnuts.
Risk assessments were conducted by EPA to assess dietary exposures from
clofentezine in food as follows:
i. Acute exposure. As discussed in Unit III.B, an acute dietary
exposure assessment was not performed because an endpoint of concern
attributable to a single oral dose was not selected for any population
subgroup (including infants and children).
ii. Chronic exposure. In conducting the chronic and cancer dietary
(food only) exposure assessments for clofentezine, EPA used the Dietary
Exposure Evaluation Model software with the Food Commodity Intake
Database (DEEM-FCID\TM\), Version 2.03, and the Lifeline\TM\Model,
Version 2.0, which incorporates food consumption data as reported by
respondents in the USDA 1994-1996 and 1998 Nationwide Continuing
Surveys of Food Intake by Individuals (CSFII), and accumulated exposure
to the chemical for each commodity. The following assumptions were made
for the chronic and cancer dietary exposure assessments: The Agency has
determined that clofentezine per se and the 3-(2-chloro-4-
hydroxyphenyl)-6-(2-chlorophenyl)-1,2,4,5-tetrazine metabolite are the
residues of concern for the chronic dietary analysis. The chronic
dietary analysis for clofentezine was based on anticipated residue
levels (ARs) in the form of average field trial residue values, and the
analysis included estimates for percent crop treated (PCT).
iii. Cancer. As explained in Unit III.C.1.ii above, the Agency
assessed cancer dietary exposure for clofentezine using the same
assumptions used for chronic dietary exposure. Cancer risk is
determined for the general U.S. population only. The estimated exposure
of the general U.S. population to clofentezine is 0.000023 mg/kg/day.
iv. Anticipated residue and PCT information. Section 408(b)(2)(E)
of the FFDCA authorizes EPA to use available data and information on
the anticipated residue levels of pesticide residues in food and the
actual levels of pesticide chemicals that have been measured in food.
If EPA relies on such information, EPA must, pursuant to section
408(f)(1), require that data be provided 5 years after the tolerance is
established, modified, or left in effect, demonstrating that the levels
in food are not above the levels anticipated. Following the initial
data submission, EPA is authorized to require similar data on a time
frame it deems appropriate. For the present action, EPA will issue such
data call-ins for information relating to anticipated residues as are
required by FFDCA section 408(b)(2)(E) and authorized under FFDCA
section 408(f)(1). Such data call-ins will be required to be submitted
no later than 5 years from the date of issuance of this tolerance.
Section 408(b)(2)(F) of FFDCA states that the Agency may use data
on the actual percent of food treated for assessing chronic dietary
(food only) risk only if the Agency can make the following findings:
Condition 1, that the data used are reliable and provide a valid basis
to show what percentage of the food derived from such crop is likely to
contain such pesticide residue; Condition 2, that the exposure estimate
does not underestimate exposure for any significant subpopulation
group; and Condition 3, if data are available on pesticide use and food
consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area. In addition, the
Agency must provide for periodic evaluation of any estimates used. To
provide for the periodic evaluation of the estimate of PCT as required
by section 408(b)(2)(F) of FFDCA, EPA may require registrants to submit
data on PCT. The Agency used PCT information as follows:
For existing uses, the Agency used estimates of PCT for the chronic
dietary (food only) risk assessment, which was determined using USDA's
National Agricultural Statistics Service (NASS) usage data and EPA 2003
proprietary usage data (DOANE 2003). Table 3 below displays the chronic
PCT estimates used for the existing uses of clofentezine. When the PCT
for a commodity is estimated as < 1%, the PCT used for risk assessment
purposes is 1%.

Table 3.--Clofentezine Estimates of Percent Crop Treated for Existing
Uses.
------------------------------------------------------------------------
Commodity Percent Crop Treated
------------------------------------------------------------------------
Almonds < 1
------------------------------------------------------------------------
Apples 5
------------------------------------------------------------------------
Apricots 5
------------------------------------------------------------------------
Cherries < 1
------------------------------------------------------------------------
Nectarines 10
------------------------------------------------------------------------
Peaches 5
------------------------------------------------------------------------
Pears 5
------------------------------------------------------------------------
Prunes & Plums < 1
------------------------------------------------------------------------
Walnuts < 1
------------------------------------------------------------------------

For the new uses, the Agency used PCT estimates for the chronic
dietary (food only) risk assessment based on ``screening level'' usage
data for agricultural crops. This information was retrieved from 1998-
2003 USDA National Agricultural Statistics Service (NASS) usage data
and EPA 2003 proprietary usage data (DOANE 2003) for the historically,
most widely used miticide for control of pests for each crop. The 2003
NASS data were compared to the DOANE 2003 data, both yielded similar
results and did not make a difference. As a result of this comparison,
the highest, most conservative PCT estimate for each crop was used for
the chronic dietary (food only) risk assessment. These highly
conservative estimates should not underestimate actual usage of
clofentezine on the new crops/sites. Some of these numbers may be based
on information that does not cover all 50 states; therefore, it is
possible that if the remaining (usually minor states for the crop) had
been included, the quantity (pounds) of active ingredient would be
slightly higher.
To further support the reliability of these PCT estimates, as a
condition of registration, the registrant will be required to agree to
report annually on the market share attained for the new uses for which
clofentezine is registered. As a condition of registration, they will
also be required to agree to mitigate dietary risk as deemed
appropriate by the Agency should the market share data raise a concern
for increased dietary risk. The Agency will then compare that market
share information with the PCT estimates used to evaluate potential
dietary risk. In those instances where percent market share is
approaching or exceeding the predicted PCT estimate used in the
Agency's risk assessment, EPA will conduct a new dietary risk
assessment to evaluate the new dietary risk. If the market share data
raise a concern for increased pesticide risk, the Agency will act to
mitigate that dietary risk and

[[Page 11568]]

could employ several approaches, including but not limited to
production caps, geographical limitations, removal of uses, or other
means deemed appropriate by the Agency. Table 4 below displays the
chronic PCT estimates used for the new uses of clofentezine. When the
PCT for a commodity is estimated as < 1%, the PCT used for risk
assessment purposes is 1%.

Table 4.--Clofentezine Estimates of Percent Crop Treated for New Uses.
------------------------------------------------------------------------
Commodity Percent Crop Treated
------------------------------------------------------------------------
Grapes 13
------------------------------------------------------------------------
Persimmons < 1
------------------------------------------------------------------------

The Agency believes that the three conditions listed in this Unit
have been met. With respect to Condition 1, PCT estimates are derived
from Federal and private market survey data, which are reliable and
have a valid basis. EPA uses a weighted average PCT for chronic dietary
exposure estimates. This weighted average PCT figure is derived by
averaging State-level data for a period of up to 10 years, and
weighting for the more robust and recent data. A weighted average of
the PCT reasonably represents a person's dietary exposure over a
lifetime, and is unlikely to underestimate exposure to an individual
because of the fact that pesticide use patterns (both regionally and
nationally) tend to change continuously over time, such that an
individual is unlikely to be exposed to more than the average PCT over
a lifetime. As to Conditions 2 and 3, regional consumption information
and consumption information for significant subpopulations is taken
into account through EPA's computer-based model for evaluating the
exposure of significant subpopulations including several regional
groups. Use of this consumption information in EPA's risk assessment
process ensures that EPA's exposure estimate does not understate
exposure for any significant subpopulation group, and allows the Agency
to be reasonably certain that no regional population is exposed to
residue levels higher than those estimated by the Agency. Other than
the data available through national food consumption surveys, EPA does
not have available information on the regional consumption of food to
which clofentezine may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for clofentezine 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 physical
characteristics of clofentezine.
The Agency uses the FQPA Index Reservoir Screening Tool (FIRST) to
produce estimates of pesticide concentrations in an index reservoir.
The SCI-GROW model is used to predict pesticide concentrations in
shallow ground water. For a screening-level assessment for surface
water EPA will use FIRST (a tier 1 model) before using PRZM/EXAMS (a
tier 2 model). The FIRST model is a subset of the PRZM/EXAMS model that
uses a specific high-end runoff scenario for pesticides. Both FIRST and
PRZM/EXAMS incorporate an index reservoir environment, and both models
include a percent crop area factor as an adjustment to account for the
maximum percent crop coverage within a watershed or drainage basin.
None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water. The primary use of these models by the Agency at this
stage is to provide a screen for sorting out pesticides for which it is
unlikely that drinking water concentrations would exceed human health
levels of concern.
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs), which are the model estimates of a
pesticide's concentration in water. EECs derived from these models are
used to quantify drinking water exposure and risk as a %RfD or %PAD.
Instead, drinking water levels of comparison (DWLOCs) are calculated
and used as a point of comparison against the model estimates of a
pesticide's concentration in water. DWLOCs are theoretical upper limits
on a pesticide's concentration in drinking water in light of total
aggregate exposure to a pesticide in food, and from residential uses.
Since DWLOCs address total aggregate exposure to clofentezine, they are
further discussed in the aggregate risk sections in Unit III.E.
Based on the FIRST and SCI-GROW models, the EECs of clofentezine
for acute exposures are estimated to be 4.2 parts per billion (ppb) for
surface water and 0.1 ppb for ground water. The EECs for chronic
exposures are estimated to be 0.2 ppb for surface water and 0.1 ppb for
ground water.
3. From nondietary exposure. The term ``residential exposure'' is
used in this document to refer to nonoccupational, nondietary exposure
(e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets). Clofentezine is not
registered for use on any sites that would result in residential
exposure. Therefore, a residential exposure assessment was not conducted.
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.''
Unlike other pesticides for which EPA has followed a cumulative
risk approach based on a common mechanism of toxicity, EPA has not made
a common mechanism of toxicity finding as to clofentezine and any other
substances and clofentezine does not appear to produce a toxic
metabolite produced by other substances. For the purposes of this
tolerance action; therefore, EPA has not assumed that clofentezine has
a common mechanism of toxicity with other substances. For information
regarding EPA's efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA's OPP concerning
common mechanism determinations and procedures for cumulating effects
from substances found to have a common mechanism on EPA's web site 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 tenfold 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. Margins of safety are
incorporated into EPA risk assessments either directly through use of
an MOE analysis or through using uncertainty (safety) factors in
calculating a dose

[[Page 11569]]

level that poses no appreciable risk to humans. 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 safety factor value
based on the use of traditional uncertainty factors and/or special FQPA
safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. There is no indication of an
increased susceptibility of rat or rabbit fetuses/pups to in utero and/
or postnatal exposure in the developmental and reproductive toxicity
studies.
3. Conclusion. EPA has determined that there are reliable data
supporting removal of the additional 10x factor for the protection of
infants and children. This decision was based on the following conclusions:
i. The toxicology database is complete;
ii. There is no indication of increased susceptibility of rats or
rabbit fetuses/pups [quantitatively or qualitatively]
to in utero and/
or postnatal exposure to clofentezine in the developmental and
reproductive toxicity studies;
iii. A developmental neurotoxicity study (DNT) is not required;
iv. Exposure data are complete or are estimated based on data that
reasonably accounts for potential exposures; and
v. There are currently no registered residential uses of clofentezine.

E. Aggregate Risks and Determination of Safety

To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates DWLOCs
which are used as a point of comparison against EECs. DWLOC values are
not regulatory standards for drinking water. A DWLOC is a theoretical
upper limit on a pesticide's concentration in drinking water in light
of total aggregate exposure to a pesticide in food, drinking water, and
through residential uses. In calculating a DWLOC, the Agency determines
how much of the acceptable exposure (i.e., the PAD) is available for
exposure through drinking water (e.g., allowable chronic water exposure
(mg/kg/day) = cPAD - (average food + residential exposure)). This
allowable exposure through drinking water is used to calculate a DWLOC.
A DWLOC will vary depending on the toxicological endpoint, drinking
water consumption, and body weights. Default body weights and
consumption values as used by the EPA's Office of Water are used to
calculate DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult
female), and 1L/10 kg (child). Default body weights and drinking water
consumption values vary on an individual basis. This variation will be
taken into account in more refined screening-level and quantitative
drinking water exposure assessments. Different populations will have
different DWLOCs. Generally, a DWLOC is calculated for each type of
risk assessment used: Acute, short-term, intermediate-term, chronic,
and cancer.
When EECs for surface water and ground water are less than the
calculated DWLOCs, EPA concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which EPA has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because EPA considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, EPA will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
Human health aggregate risk assessments have been conducted for the
chronic and cancer (food + drinking water) exposure scenarios. An acute
aggregate risk assessment was not performed because an endpoint of
concern attributable to a single oral dose was not identified for any
population subgroup (including infants and children). Short-,
intermediate- and long-term aggregate risk assessments were not
performed because there are no registered or proposed residential uses
for clofentezine. All potential exposure pathways were assessed in the
aggregate risk assessment. All aggregate exposure and risk estimates do
not exceed EPA's LOC for the chronic and cancer (food + drinking water)
exposure scenarios.
1. Acute risk. As discussed in Unit III.E., clofentezine is not
expected to pose an acute risk because an endpoint of concern
attributable to a single oral dose was not identified for any
population subgroup (including infants and children).
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
clofentezine from food will utilize 0.1% of the cPAD for the general
U.S. population, 0.3% of the cPAD for all infants (< 1 year old), and
0.4% of the cPAD for children (1-2 years old). There are no residential
uses for clofentezine that result in chronic residential exposure to
clofentezine. In addition, there is potential for chronic dietary
exposure to clofentezine in drinking water. After calculating DWLOCs
and comparing them to the EECs for surface and ground water, EPA does
not expect the aggregate exposure to exceed 100% of the cPAD, as shown
below in Table 5.

Table 5. --Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Clofentezine.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Surface Water EEC/ Ground/Water EEC/
Population/Subgroup cPAD/mg/kg/day %/cPAD/(Food) (ppb) (ppb) Chronic/DWLOC (ppb)
--------------------------------------------------------------------------------------------------------------------------------------------------------
General U.S. population 0.013................. 0.1................... 0.2.................. 0.1.................. 450
-------------------------------------------------------------
All infants (< 1 year old) 0.013................. 0.3................... 0.2.................. 0.1.................. 130
-------------------------------------------------------------
Children (1-2 years old) 0.013................. 0.4................... 0.2.................. 0.1.................. 130
-------------------------------------------------------------
Females (13-49 years old) 0.013................. 0.1................... 0.2.................. 0.1.................. 390
--------------------------------------------------------------------------------------------------------------------------------------------------------

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). Clofentezine 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 do not exceed the Agency's LOC.
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). Clofentezine
is not

[[Page 11570]]

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 do not exceed the Agency's LOC.
5. Aggregate cancer risk for U.S. population. In conducting the
aggregate cancer risk assessment, only food and drinking water pathways
of exposure were considered. At this time, there are no uses for
clofentezine that would result in any non-occupational, non-dietary
exposure (i.e., there are no dermal or inhalation routes of exposure
that should be included in an aggregate assessment). The cancer risk
from exposure to clofentezine residues in food was calculated as 4.31 x
10-\7\. This is below EPA's level of concern for cancer risk
(risks in the range of one in a million). A DWLOC was derived for the
general U.S. population based on EPA's LOC for cancer or a risk in the
range of one in one million (using the value of 1 x 10-\6\
as a first Tier value in calculating a conservative estimate of DWLOC
that is consistent with the range of one in one million). The DWLOC is
compared to the EECs of clofentezine in surface and ground water and is
used to determine whether or not aggregate cancer exposures are likely
to result in risk estimates that exceed EPA's LOC. Table 6 below
summarizes the cancer aggregate exposure estimates to clofentezine residues.

Table 6.--Aggregate Risk Assessment for Cancer Exposure to Clofentezine.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Surface
Maximum Exposure (mg/ Food Exposure (mg/kg/ Maximum Water Ground/Water EEC/ Water
Population/Subgroup kg/day) day) Exposure (mg/kg/day) Cancer DWLOC (ppb) (ppb) EEC/
(ppb)
--------------------------------------------------------------------------------------------------------------------------------------------------------
General U.S. Population 2.66 x 10-\5\ 1.1 x 10-\5\ 1.56 x 10-\5\ 0.6 0.1 0.2
--------------------------------------------------------------------------------------------------------------------------------------------------------

The EECs calculated for ground and surface water are less than
EPA's calculated cancer DWLOC. Therefore, the cancer aggregate risk
associated with the proposed use of clofentezine does not exceed EPA's
level of concern for the general U.S. population and all population
subgroups.
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 U.S. population, and to infants and children, from
aggregate exposure to clofentezine residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

A high-performance liquid chromatography (HPLC) analytical method
exists for the determination of clofentezine residues. A petition
method validation (PMV) was successfully completed by the analytical
chemistry laboratory (ACL), and the method was found acceptable. The
limit of quantitation (LOQ) and limit of detection (LOD) reported were
0.01 ppm and 0.003 ppm, respectively. The Agency concluded that the
method was suitable for enforcement purposes. The method was forwarded
to FDA for inclusion in Pesticide Analytical Manual (PAM)-Volume II.
PAM-Volume I multiresidue methods are not acceptable for tolerance
enforcement.
Adequate enforcement methodology (example --gas chromatography) is
available to enforce the tolerance expression. The method may be
requested from: Chief, Analytical Chemistry Branch, Environmental
Science Center, 701 Mapes Road, Ft. Meade, MD 20755-5350; telephone
number: (410) 305-2905; e-mail address: residuemethods@epa.gov.

B. International Residue Limits

Codex MRLs exist for clofentezine on grapes. The Codex MRLs for
grapes and the U.S. tolerances established for clofentezine on grapes
by this rule are harmonized at 1.0 ppm. No Codex MRLs exist for
clofentezine on persimmons.

V. Conclusion

Therefore, tolerances are established for residues of clofentezine
per se, (3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine), in or on grapes at
1.0 ppm and persimmons at 0.05 ppm.

VI. Objections and Hearing Requests

Under section 408(g) of FFDCA, as amended by FQPA, any person may
file an objection to any aspect of this regulation and may also request
a hearing on those objections. The EPA procedural regulations which
govern the submission of objections and requests for hearings appear in
40 CFR part 178. Although the procedures in those regulations require
some modification to reflect the amendments made to FFDCA by FQPA, EPA
will continue to use those procedures, with appropriate adjustments,
until the necessary modifications can be made. The new section 408(g)
of FFDCA provides essentially the same process for persons to
``object'' to a regulation for an exemption from the requirement of a
tolerance issued by EPA under new section 408(d) of FFDCA, as was
provided in the old sections 408 and 409 of FFDCA. However, the period
for filing objections is now 60 days, rather than 30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket ID number OPP-2005-0022 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 on or before May 9, 2005.
1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issues(s) on which a
hearing is requested, the requestor's contentions on such issues, and a
summary of any evidence relied upon by the objector (40 CFR 178.27).
Information submitted in connection with an objection or hearing
request may be claimed confidential by marking any part or all of that
information as CBI. Information so marked will not be disclosed except
in accordance with procedures set forth in 40 CFR part 2. A copy of the
information that does not contain CBI must be submitted for inclusion
in the public record. Information not marked confidential may be
disclosed publicly by EPA without prior notice.
Mail your written request to: Office of the Hearing Clerk (1900L),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001. You may also deliver your request to the
Office of the Hearing Clerk in Suite 350, 1099 14th Street, NW.,
Washington, DC 20005-3419. The

[[Page 11571]]

Office of the Hearing Clerk is open from 8 a.m. to 4 p.m., Monday
through Friday, excluding legal holidays. The telephone number for the
Office of the Hearing Clerk is (202) 564-6255.
2. Copies for the Docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit VI.A, you
should also send a copy of your request to the PIRIB for its inclusion
in the official record that is described in ADDRESSES. Mail your
copies, identified by docket ID number OPP-2005-0022, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Avenue, NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the
PIRIB described in ADDRESSES. You may also send an electronic copy of
your request via e-mail to: opp-docket@epa.gov.
Please use an ASCII
file format and avoid the use of special characters and any form of
encryption. Copies of electronic objections and hearing requests will
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format.
Do not include any CBI in your electronic copy. You may also submit an
electronic copy of your request at many Federal Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
genuine and substantial issue of fact; there is a reasonable
possibility that available evidence identified by the requestor would,
if established resolve one or more of such issues in favor of the
requestor, taking into account uncontested claims or facts to the
contrary; and resolution of the factual issues(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).

VII. Statutory and Executive Order Reviews

This final rule establishes a tolerance under section 408(d) of
FFDCA in response to petitions 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 due to its lack of
significance, 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). 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., or 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). 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); or OMB review or any Agency action under Executive
Order 13045, entitled Protection of Children from Environmental Health
Risks and Safety Risks (62 FR 19885, April 23, 1997). 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). 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. In addition, the Agency has determined that this
action will not have a substantial direct effect on States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government, as specified in Executive Order 13132, entitled Federalism
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to
develop an accountable process to ensure ``meaningful and timely input
by State and local officials in the development of regulatory policies
that have federalism implications.'' ``Policies that have federalism
implications'' is defined in the Executive order to include regulations
that have ``substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government.'' This final rule directly regulates growers, food
processors, food handlers and food retailers, not States. This action
does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. For these same reasons, the Agency has
determined that this rule does not have any ``tribal implications'' as
described in Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (59 FR 22951, November 6,
2000). Executive Order 13175, requires EPA to develop an accountable
process to ensure ``meaningful and timely input by tribal officials in
the development of regulatory policies that have tribal implications.''
``Policies that have tribal implications'' is defined in the Executive
order to include regulations that have ``substantial direct effects on
one or more Indian tribes, on the relationship between the Federal
Government and the Indian tribes, or on the distribution of power and
responsibilities between the Federal Government and Indian tribes.''
This rule will not have substantial direct effects on tribal
governments, on the relationship between the Federal Government and
Indian tribes, or on the distribution of power and responsibilities
between the Federal Government and Indian tribes, as specified in
Executive Order 13175. Thus, Executive Order 13175 does not apply to
this rule.

VIII. Congressional Review Act

The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
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 record
keeping requirements.

Dated: February 25, 2005.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

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

[[Page 11572]]

PART 180--[AMENDED]

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

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

? 2. Section 180.446 is amended by alphabetically adding commodities to
the table in paragraph (a) to read as follows:

Sec. 180.446 Clofentezine; tolerances for residues.

(a) * * *

------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
* * * * *
Grapes 1.0
* * * * *
Persimmons 0.05
* * * * *
------------------------------------------------------------------------

* * * * *

[FR Doc. 05-4335 Filed 3-8-05; 8:45 am]
BILLING CODE 6560-50-S

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