[Federal Register Volume 68, Number 188 (Monday, September 29, 2003)]
[Rules and Regulations]
[Pages 55849-55858]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-24561]


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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: [email protected].

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:
    [sbull] Crop production (NAICS 111)
    [sbull] Animal production (NAICS 112)
    [sbull] Food manufacturing (NAICS 311)
    [sbull] 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/. A frequently updated 
electronic version of 40 CFR part 180 is available at 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: 
[email protected].

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 [email protected], 
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: [email protected]. 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 (65 FR 67249, 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.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

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

0
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]
BILLING CODE 6560-50-S