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Quinoxyfen (IR-4). September 29,
2003. Pesticide Tolerance. Final Rule. Federal
Register.
http://www.epa.gov/fedrgstr/EPA-PEST/2003/September/Day-29/p24561.htm
[Federal Register: September 29, 2003 (Volume 68, Number 188)]
[Rules and Regulations]
[Page 55849-55858]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29se03-21]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2003-0218; FRL-7318-2]
Quinoxyfen; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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[[Page 55850]]
SUMMARY: This regulation establishes tolerances for residues of
quinoxyfen in or on sweet and tart cherry, grape, and hop, dried cones.
Interregional Research Project Number (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 September 29, 2003. Objections and
requests for hearings, identified by docket ID number OPP-2003-0218,
must be received on or before November 28, 2003.
ADDRESSES: Written objections and hearing requests may be submitted
electronically, by mail, or through hand delivery/courier. Follow the
detailed instructions as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION.
FOR FURTHER INFORMATION CONTACT: Hoyt Jamerson, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number:
(703) 308-9368; e-mail address: Jamerson.Hoyt@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)
¥ Animal production (NAICS 112)
¥ Food manufacturing (NAICS 311)
¥ Pesticide manufacturing (NAICS 32532)
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 Get Copies of this Document and Other Related Information?
1. Docket. EPA has established an official public docket for this
action under docket identification (ID) number OPP-2003-0218. The
official public docket consists of the documents specifically
referenced in this action, any public comments received, and other
information related to this action. Although a part of the official
docket, the public docket does not include Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. The official public docket is the collection of materials
that is available for public viewing at the Public Information and
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2,
1921 Jefferson Davis Hwy., Arlington, VA. 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.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/. http://www.access.gpo.gov/
nara/cfr/cfrhtml_00/Title_40/40cfr180_00.html, 
a beta site
currently under development. To access the OPPTS Harmonized Guidelines
referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
II. Background and Statutory Findings
In the Federal Register of May 30, 2003 (68 FR 32497) (FRL-7295-7),
EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a,
as amended by FQPA (Public Law 104-170), announcing the filing of
pesticide petitions (PP 1E6302 and 2E6474) by the Interregional
Research Project Number (IR-4), 681 U.S. Highway #1 South,
North Brunswick, NJ 08902. That notice included a summary of the
petitions prepared by Dow AgroSciences LCC, the registrant. The comment
period ended June 30, 2003.
The petitions requested that 40 CFR 180 be amended by establishing
tolerances for residues of the fungicide quinoxyfen, 5,7-dichloro-4-(4-
fluorophenoxy)quinoline, in or on grape at 0.70 parts per million (ppm)
(1E6302); hop, dried cones at 5 ppm (1E6302); and cherry at 0.4 ppm
(2E6474).
Section 408(b)(2)(A)(i) of the 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 the 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 the 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 the 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 the 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 the FFDCA, for tolerances for residues of quinoxyfen, 5,7-
dichloro-4-(4-fluorophenoxy)quinoline in or on cherry, sweet at 0.30
ppm; cherry, tart at 0.30 ppm; grape at 0.60 ppm; and hop, dried cones
at 3.0 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
[[Page 55851]]
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
quinoxyfen are discussed below and summarized in Table 1 of this unit
as well as the no-observed-adverse-effect-level (NOAEL) and the lowest-
observed-adverse-effect-level (LOAEL) from the toxicity studies
reviewed.
The primary target organs affected by quinoxyfen are the liver and
kidney. Liver effects were seen in rat and mouse subchronic and dog
chronic studies. Subchronic effects in rats and mice included increased
liver weights, hepatocellular hypertrophy and individual cell
hepatocellular necrosis. These effects were noted at high doses and not
observed in the chronic rat and mouse studies since they were performed
at lower doses. Chronic effects in the dog included increased liver
weights, increased alkaline phosphatase levels and increased incidences
of slight microscopic hepatic lesions (increased bile in canaliculi and
increased hepatocyte size). Kidney effects were noted only in the rat
combined chronic/carcinogenicity study which resulted in an increased
severity of chronic progressive glomerulonephropathy in the males.
Rabbits were much more susceptible to the effects of quinoxyfen than
any other species. Systemic effects observed in the rabbit
developmental study included inanition, loss of body weight, perineal
soiling, blood in the cage pan associated with urine, and abortions.
Body weight decrements were noted in the rat and/or mouse subchronic,
chronic and carcinogenicity studies and the rabbit developmental and
rat reproduction studies. No effects were noted via the dermal route.
No evidence of neurotoxicity or neuropathology was seen in any of the
submitted studies, including the acute and subchronic neurotoxicity
studies. There was no evidence of carcinogenic potential in either the
rat chronic toxicity/carcinogenicity or mouse carcinogenicity studies
and no concern for mutagenicity. There was no evidence of increased
susceptibility in the oral rat or rabbit developmental studies. There
was an increased quantitative susceptibility of young animals following
pre/postnatal exposure to rats in the reproduction study. In this
study, no maternal effects were observed up to the highest dose tested
(100 milligrams/kilograms/day (mg/kg/day)); however, minimally reduced
F1a pup weights were noted at 100 mg/kg/day.
Table 1.--Subchronic, Chronic, and Other Toxicity
------------------------------------------------------------------------
Guideline No. Study Type Results
------------------------------------------------------------------------
870.3100 90-Day oral NOAEL = 10 mg/kg/
toxicity rodents day
(rat) LOAEL = 100 mg/kg/
day based on
decreased body
weight gain in
females,
increased liver
weights in males
and slight
hepatocellular
hypertrophy
(centrilobular
and midzonal;
both sexes)
------------------------------------------------------------------------
870.3100 90-Day oral NOAEL = 100 mg/kg/
toxicity rodents day
(mouse) LOAEL = 500 mg/kg/
day based on
increased liver
weights,
individual cell
hepatocellular
necrosis and
hepatocellular
hypertrophy in
both sexes
------------------------------------------------------------------------
870.3150 90-Day oral NOAEL = 100 mg/kg/
toxicity in day
nonrodents (dog) LOAEL = Not
identified
------------------------------------------------------------------------
870.3200 28-Day dermal NOAEL = 1,000 mg/
toxicity (rat) kg/day
LOAEL = Not
identified
------------------------------------------------------------------------
870.3700 Prenatal Maternal NOAEL =
developmental in 1,000 mg/kg/day
rodents (rat) LOAEL = Not
identified
Developmental
NOAEL = 1,000 mg/
kg/day
LOAEL = Not
identified
------------------------------------------------------------------------
870.3700 Prenatal Maternal NOAEL =
developmental in 80 mg/kg/day
nonrodents LOAEL = 200 mg/kg/
(rabbit) day based on
inanition,
clinical signs,
decreased body
weights, body
weight gains, and
food consumption
and on increased
incidences of
abortion
Developmental
NOAEL = 80 mg/kg/
day
LOAEL = 200 mg/kg/
day based on
increased
incidences of
abortion
------------------------------------------------------------------------
870.3800 Reproduction and Parental/Systemic
fertility effects NOAEL = 100 mg/kg/
(rat) day
LOAEL = Not
identified
Reproductive NOAEL
= 100 mg/kg/day
LOAEL = Not
identified
Offspring NOAEL =
20 mg/kg/day
LOAEL = 100 mg/kg/
day based on a
minimal decrease
in F1a pup
weights
------------------------------------------------------------------------
870.4100 Chronic toxicity See 870.4300
rodents
------------------------------------------------------------------------
[[Page 55852]]
870.4100 Chronic toxicity NOAEL = 20 mg/kg/
dogs day
LOAEL = 200 mg/kg/
day based on
increased
alkaline
phosphatase,
increased
absolute and
relative (to
body) liver
weights, and an
increased
incidence of very
slight to slight
microscopic
hepatic lesions
------------------------------------------------------------------------
870.4200 Carcinogenicity See 870.4300
rats
------------------------------------------------------------------------
870.4200 Carcinogenicity NOAEL = 80 mg/kg/
mouse day
LOAEL = 250 mg/kg/
day based on
decreased body
weight gain in
both sexes
No evidence of
carcinogenicity
------------------------------------------------------------------------
870.4300 Combined chronic/ NOAEL = 20 mg/kg/
carcinogenicity day
(rat) LOAEL = 80 mg/kg/
day based on
increases in
severity of
chronic
progressive
glomerulonephropa
thy in the males
and minimal
decreases in body
weight and body
weight gain in
the males and
females
No evidence of
carcinogenicity
------------------------------------------------------------------------
870.5100 Gene mutation Negative for
(bacterial inducing reverse
reverse mutation) mutation in
bacteria exposed
to doses up to
5,000 [mu]g/plate
(-S9) and 1,000
[mu]g/plate (+S9)
------------------------------------------------------------------------
870.5300 Gene mutation (In Negative for
vitro mammalian inducing forward
cell gene mutation in CHO
mutation) (mammalian) cells
treated up to 20
[mu]g/ml (-S9)
and 80 [mu]g/ml
(+S9)
------------------------------------------------------------------------
870.5375 Cytogenetics (In Negative up to 100
vitro mammalian [mu]g/ml (- S9
chromosome and +S9)
aberration (RL))
------------------------------------------------------------------------
870.5395 Cytogenetics Negative up to
(mammalian 5,000 mg/kg
micronucleus
(mouse))
------------------------------------------------------------------------
870.6200 Acute NOAEL = 2,000 mg/
neurotoxicity kg
screening battery LOAEL = Not
(rat) identified
------------------------------------------------------------------------
870.6200 Subchronic NOAEL = 80 mg/kg/
neurotoxicity day
screening battery LOAEL = Not
identified
------------------------------------------------------------------------
[[Page 55853]]
870.7485 Metabolism and Quinoline-labeled
pharmacokinetics and phenyl-
(rat) labeled
quinoxyfen were
rapidly absorbed
with
approximately 68-
85% of the
administered dose
being eliminated
within 24 hours.
Overall recovery
of the dosed
radioactivity
ranged from 83.5-
96.2%. Sex, dose,
and multiple
dosing had little
or no effect on
the excretion
profile at 48
hours post-
dosing. Changing
the position of
the 14C-label
altered the
pattern of
excretion. The
major route of
elimination was
through the urine
in the phenyl-
labeled test
substance (44.9-
48.7% of dose in
urine and 38.2-
39.8% of dose in
feces) and
through the feces
in the quinoline-
labeled test
substance (65.8-
78.3% of dose in
feces and 13.4-
19.7% of dose in
urine). Biliary
excretion
increased its
contribution to
fecal
radioactivity as
the dose
increased.
Concentrations of
radioactivity in
the tissues were
generally
slightly lower in
the males than
females and in
the low-dose
compared to the
high-dose group.
The highest
concentrations of
radioactivity
were found in the
kidney, liver,
ovaries,
perirenal fat, GI
tract and
carcass. Maximum
plasma
concentration
occurred between
0.5 and 1.5
hours, and
elimination half-
lives were <= 1
hour and 15-19
hours (10 mg/kg
group) and 2-3
hours and 18-22
hours (500 mg/kg
group).
The presence of
several
radioactive
components was
determined in the
unhydrolyzed
urine (up to 12),
fecal extracts (
up to 8), and
bile (up to 6).
No differences in
the metabolite
profile were
observed that
were related to
sex or multiple
dosing.
Increasing
amounts of the
parent compound
were found in the
feces with
increasing dose.
No other dose-
related
differences were
observed.
Identified
metabolites
accounted for
41.0-42.8% dose
in the [Phenyl-U-
14C]
XDE-795
treated group,
and only 17.0-
31.7% dose in the
other treated
groups. The
[Phenyl-U-14C]
XDE-795 treated
group had no
urinary
metabolites in
common with the
[2-Quinoline-14C]
XDE-795 treated
groups suggesting
cleavage of the
parent molecule.
An acid-labile
conjugate of 4-
fluorophenol was
found in the
urine of the
[Phenyl-U-14C]
XDE-795 treated
group (28.7-32.8%
dose). 5,7-
Dichloro-4-
hydroxyquinoline
was observed in
the urine of the
[2-Quinoline-14C]
XDE-795 treated
groups in small
quantities (0.7-
1.7% dose). Thus,
the identified
metabolites in
the urine
followed diaryl-
ether cleavage of
the parent
compound.
Fluorophenyl-ring-
OH-XDE-795 (two
isomers) were
found in the
feces of all
treated groups
(5.4-10.6% dose).
In the bile of
the treated
groups, two major
metabolites were
identified, a
glucuronide and/
or sulfate
conjugate(s) of
the two isomers
of fluorophenyl
ring-hydroxy-XDE-
795 (9-19% dose)
and an
unidentified
metabolite (13-
21% dose).
------------------------------------------------------------------------
B. Toxicological Endpoints
The dose at which no adverse effects are observed (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 lowest dose at which adverse effects of concern are
identified (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 intra species differences.
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 the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor (SF)
is retained due to concerns unique
[[Page 55854]]
to the FQPA, 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 FQPA SF.
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 is expressed as 1 x 10-6 or one in a million).
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 (MOEcancer = point of
departure/exposures) is calculated. A summary of the toxicological
endpoints for quinoxyfen used for human risk assessment is shown in
Table 2 of this unit:
Table 2.--Summary of Toxicological Dose and Endpoints for Quinoxyfen for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
FQPA SF* and Level of
Exposure Scenario Dose Used in Risk Concern for Risk Study and Toxicological
Assessment, UF Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (females 13-50 years of Not applicable Not applicable There were no toxic
age) and acute dietary (general effects attributable
population including infants and to a single dose.
children) Therefore, an endpoint
of concern was not
identified to
quantitate acute-
dietary risk to the
general population or
to the subpopulation
females 13-50 years
old
-----------------------------------------------------------------------------------------
Chronic dietary (all populations) NOAEL= 20 mg/kg/day FQPA SF = 1 Combined chronic
UF = 100............... cPAD = chronic RfD/FQPA toxicity/
Chronic RfD = 0.20 mg/ SF = 0.20 mg/kg/day. carcinogenicity study
kg/day. in rat
LOAEL = 80 mg/kg/day,
based upon increases
in severity of chronic
progressive
glomerulonephropathy
in the males and
minimal decreases in
body weight and body
weight gain in both
sexes
-----------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation) Classified as not Not applicable No evidence of
likely to be carcinogenicity in
carcinogenic to humans rats and mice
----------------------------------------------------------------------------------------------------------------
*The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique
to the FQPA.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Quinoxyfen is a new
chemical and therefore, these are the first tolerances to be
established for the residues of quinoxyfen. Risk assessments were
conducted by EPA to assess dietary exposures from quinoxyfen in food as
follows:
i. Acute exposure. Quantitative acute dietary risk assessments are
performed for a food-use pesticide if a toxicological study has
indicated the possibility of an effect of concern occurring as a result
of a one day or single exposure. There were no toxic effects
attributable to a single dose. Therefore, an endpoint of concern was
not identified to quantitate acute-dietary risk to the general
population or to the subpopulation females 13-50 years old. As a
result, no acute risk is expected from exposure to quinoxyfen and hence
no quantitative acute dietary risk assessment was performed.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment, EPA used the Dietary Exposure Evaluation Model software
with the Food Commodity Intake Database (DEEM-FCIDTM ) 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 acute exposure
assessments: An unrefined, Tier 1 chronic-dietary exposure assessment
using tolerance-level residues and assuming 100% CT for all proposed
commodities, and default DEEM Version 7.76 processing factors for all
commodities.
iii. Cancer. Quinoxyfen has been classified as not likely to be
carcinogenic to humans. Therefore, a quantitative risk assessment was
not conducted to assess cancer risk.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for quinoxyfen 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 quinoxyfen.
The Agency uses the FQPA Index Reservoir Screening Tool (FIRST) or
the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/
EXAMS), to produce estimates of pesticide concentrations in an index
reservoir. The Screening Concentrations in Ground Water (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
[[Page 55855]]
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 coarse screen for sorting out pesticides for
which it is highly unlikely that drinking water concentrations would
ever 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) from these models 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 quinoxyfen, they are further
discussed in the aggregate risk sections see Unit E.
Based on the FIRST and SCI-GROW models, the EECs of quinoxyfen for
chronic exposures are estimated to be 0.8 parts per billion (ppb) for
surface water and 0.006 ppb for ground 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). Quinoxyfen 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 the FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA does not have, at this time, available data to determine
whether quinoxyfen has a common mechanism of toxicity with other
substances. 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 quinoxyfen
and any other substances and quinoxyfen 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 quinoxyfen 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 Office of
Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a
common mechanism on EPA's website at http://www.epa.gov/pesticides/
cumulative/.
D. Safety Factor for Infants and Children
1. In general. Section 408 of the 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 data base on toxicity and exposure
unless EPA determines 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 a MOE analysis or
through using uncertainty (safety) factors in calculating a dose level
that poses no appreciable risk to humans.
2. Prenatal and postnatal sensitivity. There is no quantitative or
qualitative evidence of increased susceptibility of rat and rabbit
fetuses to in utero exposure in developmental studies. There is
evidence of increased quantitative susceptibility (minimal decrease in
F1a pup weights) in the rat multi-generation reproduction
study, but the concern is low since: (1) The effects in pups are well-
characterized with a clear NOAEL; (2) the pup effects are minimal at
the LOAEL and only noted in the first-generation offspring; and (3) the
doses and endpoints selected for regulatory purposes would address the
concerns of the pup effects noted in the rat reproduction study.
Therefore, there are no residual uncertainties for prenatal/postnatal
toxicity in this study.
3. Conclusion. There is a complete toxicity data base for
quinoxyfen and exposure data are complete or are estimated based on
data that reasonably accounts for potential exposures. There are no
residual uncertainties for prenatal/postnatal toxicity. No additional
safety factor is needed for data base uncertainties. No clinical sign
of neurotoxicity or neuropathology was seen in the data base. A
developmental neurotoxicity study is not required. Therefore, EPA
determined that the 10X SF to protect infants and children should be
reduced to 1X.
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 the model estimates of
a pesticide's concentration in water EECs. DWLOC values are not
regulatory standards for drinking 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 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 toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the USEPA Office of Water are used to calculate
DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult female and
youth), 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
[[Page 55856]]
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.
1. Acute risk. An endpoint of concern was not identified to
quantitate acute-dietary risk to the general population or to the
subpopulation females 13-50 years old. As a result, no acute risk is
expected from exposure to quinoxyfen.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
quinoxyfen from food will utilize less than 1% of the cPAD for the U.S.
population, 1% of the cPAD for all infants (< 1 year old) and 1% of the
cPAD for children (1-2 years old), the children subpopulation at
greatest exposure. There are no residential uses for quinoxyfen that
result in chronic residential exposure to quinoxyfen. In addition,
there is potential for chronic dietary exposure to quinoxyfen in
drinking water. After calculating DWLOCs and comparing them to the EECs
for surface water and ground water, EPA does not expect the aggregate
exposure to exceed 100% of the cPAD, as shown in Table 3 of this unit:
Table 3.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Quinoxyfen
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup cPAD mg/kg/ %cPAD Water EEC Water EEC Chronic
day (Food) (ppb) (ppb) DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population 0.20 <1% 0.8 0.006 7,000
----------------------------------------------------------------------------------------
All infants (<1 year old) 0.20 1% 0.8 0.006 2,000
----------------------------------------------------------------------------------------
Children (1-2 years old) 0.20 1% 0.8 0.006 2,000
----------------------------------------------------------------------------------------------------------------
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). Quinoxyfen 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 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). Quinoxyfen 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 level of concern.
5. Aggregate cancer risk for U.S. population. Quinoxyfen has been
classified as not likely to be carcinogenic to humans. Therefore,
quinoxyfen is not expected to pose a cancer risk.
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, and to infants and children from aggregate
exposure to quinoxyfen residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
IR-4 has proposed a gas chromatography (GC) method with mass-
selective detection (MSD) entitled Determination of DE-795 Residues in
Grape Wine, Must, and Pomace ERC95.26 (and its supplement S1) for the
enforcement of proposed tolerances for residues of quinoxyfen in/on
grapes, cherries, and hops. Method ERC 95.26 is classified as
acceptable and conforms with the criteria of OPPTS Harmonized Guideline
860.1340. The petitioner has submitted a study which investigated the
behavior of quinoxyfen through MRMs outlined in FDA's Pesticide
Analytical Manual (PAM), Volume I, Appendix II. The study summary
reported that depending on spike levels, certain MRM Protocols (D, E,
and F) yielded partial (incomplete) to complete recoveries of
quinoxyfen in grapes (non-fatty matrix) and ground beef (fatty matrix).
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 are no Mexican, Canadian or Codex maximum residue limits
established for quinoxyfen on sweet and tart cherries, grapes, or hops.
Therefore, no compatibility problems exist for these tolerances.
V. Conclusion
Therefore, tolerances are established for quinoxyfen, 5,7-dichloro-
4-(4-fluorophenoxy)quinoline in or on cherry, sweet at 0.30 ppm;
cherry, tart at 0.30 ppm; grape at 0.60 ppm; and hop, dried cone at 3.0
ppm.
VI. Objections and Hearing Requests
Under section 408(g) of the FFDCA, as amended by the 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
the FFDCA by the FQPA, EPA will continue to use those procedures, with
appropriate adjustments, until the necessary modifications can be made.
The new section 408(g) of the 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 the 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-2003-0218 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 November
28, 2003.
1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the
[[Page 55857]]
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 (1900C),
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 Rm. 104, Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA. The 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
(703) 603-0061.
2. Tolerance fee payment. If you file an objection or request a
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must
mail the fee to: EPA Headquarters Accounting Operations Branch, Office
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please
identify the fee submission by labeling it ``Tolerance Petition Fees.''
EPA is authorized to waive any fee requirement ``when in the
judgement of the Administrator such a waiver or refund is equitable and
not contrary to the purpose of this subsection.'' For additional
information regarding the waiver of these fees, you may contact James
Tompkins by phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov,
or by mailing a request for information to Mr. Tompkins at Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001.
If you would like to request a waiver of the tolerance objection
fees, you must mail your request for such a waiver to: James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
3. 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 Unit I.B.1. Mail your
copies, identified by docket ID number OPP-2003-0218, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the
PIRIB described in Unit I.B.1. 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 the
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 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 the 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 the FFDCA. For these same reasons,
the Agency has determined that this rule does not have any ``tribal
implications''
[[Page 55858]]
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
recordkeeping requirements.
Dated: September 23, 2003.
James Jones,
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), 346(a) and 371.
¥ 2. Section 180.588 is added to subpart C to read as follows:
Sec. 180.588 Quinoxyfen; tolerances for residues.
(a) General. Tolerances are established for residues of the
fungicide quinoxyfen, 5,7-dichloro-4-(4-fluorophenoxy)quinoline in or
on the following raw agricultural commodities:
----------------------------------------------------------------------------------------------------------------
Commodity Parts per million
----------------------------------------------------------------------------------------------------------------
Cherry, sweet.................................................... 0.30
Cherry, tart..................................................... 0.30
Hop, dried cones................................................. 3.0
Grape............................................................ 0.60
----------------------------------------------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 03-24561 Filed 9-26-03; 8:45 am]
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