[Federal Register Volume 70, Number 179 (Friday, September 16, 2005)]
[Rules and Regulations]
[Pages 54640-54651]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-18421]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2003-0129; FRL-7719-9]


Fluoxastrobin; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for combined residues 
of fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-
pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, and its Z isomer, (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-
4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, in or on leaf petioles subgroup 4B; peanut; peanut, hay; 
peanut, refined oil; tomato, paste; vegetable, fruiting, group 8; and 
vegetable, tuberous and corm, subgroup 1C. This regulation also 
establishes tolerances for the indirect or inadvertent combined 
residues of fluoxastrobin and its Z isomer, in or on alfalfa, forage; 
alfalfa, hay; cotton, gin byproducts; grain, cereal, forage, fodder and 
straw, group 16; grass, forage; grass, hay; and vegetable, foliage of 
legume, group 7. This regulation additionally establishes tolerances 
for the combined residues of fluoxastrobin, its Z isomer, and its 
phenoxy-hydroxypyrimidine metabolite, 6-(2-chlorophenoxy)-5-fluoro-4-
pyrimidinol, expressed as fluoxastrobin, in or on cattle, fat; cattle, 
meat; cattle, meat byproducts; goat, fat; goat, meat; goat, meat 
byproducts; horse, fat; horse, meat; horse, meat byproducts; milk; 
milk, fat; sheep, fat; sheep, meat; and sheep, meat byproducts. Bayer 
CropScience 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 16, 2005. Objections and 
requests for hearings must be received on or before November 15, 2005.

ADDRESSES: To submit a written objection or hearing request follow the 
detailed instructions as provided in Unit VII. of the SUPPLEMENTARY 
INFORMATION. EPA has established a docket for this action under Docket 
identification (ID) number OPP-2003-0129. All documents in the docket 
are listed in the EDOCKET index at http://www.epa.gov/edocket. Although 
listed in the index, some information is not publicly available, i.e., 
CBI or other information whose disclosure is restricted by statute. 
Certain other material, such as copyrighted material, is not placed on 
the Internet and will be publicly available only in hard copy form. 
Publicly available docket materials are available either electronically 
in EDOCKET or in hard copy at the Public Information and Records 
Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 1801 S. 
Bell St., 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.

FOR FURTHER INFORMATION CONTACT: Tony Kish, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-9443; 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:
     Crop production (NAICS 111), e.g., agricultural workers; 
greenhouse, nursery, and floriculture workers; farmers.
     Animal production (NAICS 112), e.g., cattle ranchers and 
farmers, dairy cattle farmers, livestock farmers.
     Food manufacturing (NAICS 311), e.g., agricultural 
workers; farmers; greenhouse, nursery, and floriculture workers; 
ranchers; pesticide applicators.
     Pesticide manufacturing (NAICS 32532), e.g., agricultural 
workers; commercial applicators; farmers; greenhouse, nursery, and 
floriculture workers; residential users.
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Access Electronic Copies of this Document and Other 
Related Information?

    In addition to using EDOCKET (http://www.epa.gov/edocket/), you may 
access this Federal Register document electronically through the EPA 
Internet under the ``Federal Register'' listings at http://www.epa.gov/fedrgstr/. A frequently updated electronic version of 40 CFR part 180 
is available at E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/. 
To access the OPPTS Harmonized Guidelines referenced in this document, 
go directly to the guidelines at http://www.epa.gpo/opptsfrs/home/guidelin.htm/.

II. Background and Statutory Findings

    In the Federal Register of April 23, 2003 (68 FR 19991) (FRL-7303-
1), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
3F6556) by Bayer CropScience, 2 T.W. Alexander Drive, Research Triangle 
Park, North Carolina 27709. The petition requests that 40 CFR 180.609 
be amended by establishing tolerances for the combined residues of the 
fungicide fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-
pyrimydinyl]-oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, in or on the raw agricultural commodities (RACs) alfalfa, 
forage at 0.05 parts per million (ppm); alfalfa, hay at 1.0 ppm; 
cotton, gin byproducts at 0.02 ppm; grain, cereal, forage at 0.10 ppm; 
grain, cereal, hay at 0.10 ppm; grain, cereal, stover at 0.10 ppm; 
grain, cereal, straw at 0.10 ppm; grass, forage at 0.10 ppm; grass, hay 
at 0.50 ppm; legume, forage at 0.05 ppm; legume, hay at 0.05 ppm; 
legume, seed at 0.01 ppm; peanut at 0.01 ppm; peanut, hay at 20 ppm; 
peanut, refined oil at 0.10 ppm; tomato, paste at 2.0 ppm; vegetable, 
foliage of legume, group 7 at 0.05 ppm; vegetable, fruiting, group at 
1.0 ppm; vegetable, leafy, petioles, except brassica, subgroup at 5.0 
ppm; and vegetable, tuberous and corm, subgroup at 0.01 ppm. The 
petition also requests that 40 CFR 180.609 be amended by establishing 
tolerances for

[[Page 54641]]

the combined residues of fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-
5-fluoro-4-pyrimydinyl]-oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-
yl)methanone O-methyloxime, and its phenoxy-hydroxypyrimidine 
metabolite, 6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinol, in or on the 
RACs cattle, fat at 0.10 ppm; cattle, meat at 0.05 ppm; cattle, meat 
byproducts at 0.20 ppm; milk at 0.01 ppm; and milk, fat at 0.10 ppm. 
That notice included a summary of the petition prepared by Bayer 
CropScience, the registrant. Several comments concerning the notice 
were received. They are described and discussed in Unit V.
    Based on EPA's review, the aforementioned petition was revised by 
the petitioner by adjusting some tolerance levels, revising the 
tolerance expression, and revising the commodity nomenclature to 
reflect the correct commodity definitions. The tolerance expression was 
revised to reflect the fact that fluoxastrobin E-isomer, and not the 
mixture of E- and Z-isomers, is the proposed active ingredient. The 
petition was also revised, based on extensive field rotational crop 
data, to add indirect tolerances for the combined residues of 
fluoxastrobin and its Z-isomer in/on rotated crops. As revised, the 
petition seeks the establishment of tolerances for combined residues of 
fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4- 
pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, and its Z isomer, (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-
4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, in or on the RACs leaf petioles subgroup 4B at 4.0 ppm; 
peanut at 0.010 ppm; peanut, hay at 20.0 ppm; peanut, refined oil at 
0.030 ppm; tomato, paste at 1.5 ppm; vegetable, fruiting, group 8 at 
1.0 ppm; and vegetable, tuberous and corm, subgroup 1C at 0.010 ppm, 
the establishment of tolerances for indirect or inadvertent residues 
for the combined residues of fluoxastrobin and its Z isomer, in or on 
the RACs alfalfa, forage at 0.050 ppm; alfalfa, hay at 0.10 ppm; 
cotton, gin byproducts at 0.020 ppm; grain, cereal, forage, fodder, and 
straw, group 16 at 0.10 ppm; grass, forage at 0.10 ppm; grass, hay at 
0.50 ppm; and vegetable, foliage of legume, group 7 at 0.050 ppm; and 
the establishment of tolerances for the combined residues of 
fluoxastrobin, its Z isomer, and its phenoxy-hydroxypyrimidine 
metabolite, 6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinol, expressed as 
fluoxastrobin, in or on the RACs cattle, fat at 0.10 ppm; cattle, meat 
at 0.05 ppm; cattle, meat byproducts at 0.10 ppm; goat, fat at 0.10 
ppm; goat, meat at 0.05 ppm; goat, meat byproducts at 0.10 ppm; horse, 
fat at 0.10 ppm; horse, meat at 0.05 ppm; horse, meat byproducts 0.10 
ppm; milk at 0.02 ppm; milk, fat at 0.50 ppm; sheep, fat at 0.10 ppm; 
sheep, meat at 0.05 ppm; and sheep, meat byproducts at 0.10 ppm.
    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal upper limit for a pesticide chemical residue in or 
on a food) only if EPA determines that the tolerance is ``safe.'' 
Section 408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there 
is a reasonable certainty that no harm will result from aggregate 
exposure to the pesticide chemical residue, including all anticipated 
dietary exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical 
residue....''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 of FFDCA and a complete 
description of the risk assessment process, see the final rule on 
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-
5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2) of FFDCA, for the fluoxastrobin tolerances described in Unit 
II. EPA's assessment of exposures and risks associated with 
establishing these tolerances follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by fluoxastrobin are 
discussed 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.

                                Table 1.--Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
             Guideline No.                       Study Type                            Results
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity-rats   NOAEL was 70.4 milligrams/kilogram/day (mg/
                                                                      kg/day) for males; 162.9 mg/kg/day for
                                                                      females.
                                                                     LOAEL was 580.0 mg/kg/day for males based
                                                                      on reduced body weight gain and food
                                                                      intake, vacuolation in the zona
                                                                      fasciculate of the adrenal cortex, calculi
                                                                      in the urethra and kidney, and
                                                                      histological lesions in kidney, urinary
                                                                      bladder, and urethra; 1416.1 mg/kg/day for
                                                                      females based on increased liver weight
                                                                      (by 20%).
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity-mice   Neither a NOAEL nor a LOAEL were assigned.
                                                                      There was a dose related increase in liver
                                                                      weight in both sexes and in kidney weight
                                                                      in females, in addition to other effects
                                                                      whose toxicological relevance was
                                                                      considered uncertain. Among these effects
                                                                      were increased hepatocellular hypertrophy
                                                                      with cytoplasmic changes in the high-dose
                                                                      males and minimal to moderate kidney
                                                                      tubular hypertrophy in mid- and high-dose
                                                                      females.
----------------------------------------------------------------------------------------------------------------

[[Page 54642]]

 
870.3150                                 90-Day oral toxicity-dogs   NOAEL was 3.0 mg/kg/day (100 ppm) for both
                                                                      males and females.
                                                                     LOAEL was 24.8/24.2 mg/kg/day (800 ppm) for
                                                                      both males and females based on dose-
                                                                      related reductions in net body weight gain
                                                                      and food efficiency in addition to
                                                                      toxicity findings in the liver in both
                                                                      sexes (cholestasis) and in kidneys
                                                                      (increased relative weights in females and
                                                                      degeneration of the proximal tubular
                                                                      epithelium in males).
----------------------------------------------------------------------------------------------------------------
870.3200                                 28-Day dermal toxicity-     NOAEL was 1,000 mg/kg/day (the limit dose,
                                          rats                        for both systemic and dermal effects).
                                                                     No LOAEL was identified.
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal development-rats   Maternal NOAEL was greater than or equal to
                                                                      1,000 milligrams per kilogram bodyweight
                                                                      per day (mg/kg bw/day; limit dose).
                                                                     No maternal LOAEL was identified.
                                                                     Developmental NOAEL was greater than or
                                                                      equal to 1,000 mg/kg bw/day.
                                                                     No developmental LOAEL was identified.
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal development-       Maternal NOAEL was 100 mg/kg/day.
                                          rabbits                    Maternal LOAEL was 400 mg/kg/day based on
                                                                      cold ears, transient body weight loss, and
                                                                      decreased food consumption.
                                                                     Developmental NOAEL was greater than or
                                                                      equal to 400 mg/kg/day.
                                                                     No developmental LOAEL was identified.
----------------------------------------------------------------------------------------------------------------
870.3800                                 Reproduction and fertility  Parental systemic NOAEL was 70.0 mg/kg/day
                                          effects-rats                for males and 84.7 mg/kg/day for females.
                                                                     Parental systemic LOAEL was 665.0 mg/kg/day
                                                                      for males and 825.4 mg/kg/day for females
                                                                      based on decreased premating body weight
                                                                      gain of the P-generation males and females
                                                                      and decreased premating absolute body
                                                                      weight of the F1 males and females.
                                                                     Reproductive NOAEL was greater than 665.0
                                                                      mg/kg/day for males and greater than 825.4
                                                                      mg/kg/day for females.
                                                                     No reproductive LOAEL was identified.
                                                                     Offspring systemic NOAEL was 70.0 mg/kg/day
                                                                      for males and 84.7 mg/kg/day for females.
                                                                     Offspring systemic LOAEL was 665.0 mg/kg/
                                                                      day for males and 825.4 mg/kg/day for
                                                                      females based on decreased body weights,
                                                                      delayed preputial separation, and
                                                                      incomplete ossification in the F1 and/or
                                                                      F2 males and females.
----------------------------------------------------------------------------------------------------------------
870.4100                                 Chronic toxicity-dogs       NOAEL was 1.7 mg/kg/day for males and 1.5
                                                                      mg/kg/day for females.
                                                                     LOAEL was 8.1 mg/kg/day for males and 7.7
                                                                      mg/kg/day for females based on body weight
                                                                      reductions and hepatocytomegaly and
                                                                      cytoplasmic changes associated with
                                                                      increased serum liver alkaline phosphatase
                                                                      indicative of cholestasis.
----------------------------------------------------------------------------------------------------------------
870.4200                                 Carcinogenicity--mice       NOAEL was 775.6 mg/kg bw/day for males and
                                                                      1265.1 mg/kg bw/day for females.
                                                                     No LOAEL was identified.
                                                                     There was no evidence of carcinogenicity.
----------------------------------------------------------------------------------------------------------------
870.4300                                 Combined chronic toxicity/  NOAEL was 53.0 mg/kg/day for males and
                                          carcinogenicity--rats       181.3 mg/kg/day for females.
                                                                     LOAEL was 271.9 mg/kg/day for males and
                                                                      1083.2 mg/kg/day for females was based on
                                                                      decreased body weight, decreased body
                                                                      weight gain, and decreased food efficiency
                                                                      in both sexes; decreased spleen weight in
                                                                      males; and microscopic lesions in the
                                                                      uterus of females. The apparent increase
                                                                      in tumors in the uterus and thyroid were
                                                                      addressed and resolved by an Agency
                                                                      committee, which concluded that no
                                                                      carcinogenic concern exists for
                                                                      fluoxastrobin.
----------------------------------------------------------------------------------------------------------------
870.6200                                 Acute neurotoxicity         Neurotoxicity NOAEL was greater than or
                                          screening battery--rats     equal to 2,000 mg/kg (limit dose).
                                                                     No LOAEL was identified.
----------------------------------------------------------------------------------------------------------------
870.6200                                 Subchronic neurotoxicity    Systemic NOAEL (systemic and neurotoxic)
                                          screening battery--rats     was 473.9/582.4 mg/kg/day for males and
                                                                      females, respectively.
                                                                     No LOAEL was identified.
----------------------------------------------------------------------------------------------------------------
870.5100                                 Gene Mutation-in vitro      Negative (considered non-mutagenic in
                                          bacterial reverse gene      Salmonella typhimurium cultures treated up
                                          mutation                    to cytotoxic/ precipitating levels).
----------------------------------------------------------------------------------------------------------------
870.5100                                 Gene Mutation--in vitro     Negative (considered non-mutagenic in this
                                          bacterial reverse gene      Salmonella typhimurium/microsome test).
                                          mutation (the test
                                          substance was HEC 5725N
                                          (E:Z ratio of 90%:10%)
----------------------------------------------------------------------------------------------------------------

[[Page 54643]]

 
870.5100                                 Gene Mutation--in vitro     Negative (considered non-mutagenic in this
                                          bacterial reverse gene      Salmonella typhimurium/mammalian
                                          mutation (the test          activation gene mutation assay).
                                          substance was HEC 5725-
                                          phenoxy-hydroxy-
                                          pyrimidine)
----------------------------------------------------------------------------------------------------------------
870.5100                                 Gene Mutation--in vitro     Negative (considered non-mutagenic in this
                                          bacterial reverse gene      Salmonella typhimurium/mammalian
                                          mutation (the test          activation gene mutation assay).
                                          substance was HEC 5725-
                                          dihydroxy- pyrimidine)
----------------------------------------------------------------------------------------------------------------
870.5300                                 Gene mutation-in vitro      Negative (considered non-mutagenic in this
                                          mammalian forward gene      in vitro forward mutation V79-HPRT test).
                                          mutation
----------------------------------------------------------------------------------------------------------------
870.5375                                 Gene Mutation--in vitro     Negative (considered to be negative for
                                          mammalian chromosome        clastogenicity in this in vitro mammalian
                                          aberrations in Chinese      cell test).
                                          hamster lung (V79) cells
----------------------------------------------------------------------------------------------------------------
870.5395                                 Cytogenics-in vivo          Negative (considered non-clastogenic, as
                                          mammalian cytogenetics -    indicated by no increases in micronuclei
                                          micronucleus assay          in bone marrow).
                                          (mouse)
----------------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism and              Absorption, distribution, and metabolism
                                          pharmacokinetics-rat        were fully characterized in several rat
                                                                      metabolism studies using each of the three
                                                                      \14\C-radiolabeled rings in fluoxastrobin.
                                                                      Absorption was almost complete following a
                                                                      single oral low dose. Peak plasma
                                                                      concentrations were attained within 0.5 to
                                                                      8 hours depending on the dose and label
                                                                      position. Fecal excretion was the major
                                                                      route of elimination while renal excretion
                                                                      was a secondary route and elimination via
                                                                      expired air was negligible. Fluoxastrobin
                                                                      was extensively metabolized as evidenced
                                                                      by the extensive metabolite profiles from
                                                                      urine, feces, and bile and the relative
                                                                      absence of parent compound (except in the
                                                                      feces of rats given the high dose).
----------------------------------------------------------------------------------------------------------------
870.7600                                 Dermal penetration--monkey  Following an 8-hour dermal application in a
                                                                      male monkey, absorption was negligible
                                                                      (1.16% preliminary, 2.16% main). The
                                                                      normalized absorption value for the main
                                                                      study was 2.31%.
----------------------------------------------------------------------------------------------------------------
870.7800                                 Immunotoxicity-mouse        No clinical signs of toxicity or mortality
                                          (subacute feeding study)    were found and no treatment-related
                                                                      effects were found on body weight, food
                                                                      intake, or B-cell activated, T-cell
                                                                      mediated IgM response to SRBC. Based on
                                                                      these findings, and findings in the 90-day
                                                                      oral rat study (no difference between the
                                                                      control and treated animals in spleen cell
                                                                      count, macrophage activities after PMA
                                                                      stimulation and plaque-forming cell assay
                                                                      after challenge with sheep erythrocytes),
                                                                      it was concluded that fluoxastrobin is not
                                                                      immunotoxic. However, the study is
                                                                      considered unacceptable because of
                                                                      uncertainty in dietary test material
                                                                      intake, failure to report spleen weight of
                                                                      each mouse at necropsy, and failure of the
                                                                      laboratory to demonstrate its capability
                                                                      in performing this type of assay.
----------------------------------------------------------------------------------------------------------------

B. Toxicological Endpoints

    The highest 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 intraspecies differences.
    Three other types of safety or uncertainty factors may be used: 
``Traditional uncertainty factors;'' the ``special FQPA safety 
factor;'' and the ``default FQPA safety factor.'' By the term 
``traditional uncertainty factor,'' EPA is referring to those 
additional uncertainty factors used prior to FQPA passage to account 
for database deficiencies. These traditional uncertainty factors have 
been incorporated by the FQPA into the additional safety factor for the 
protection of infants and children. The term ``special FQPA safety 
factor'' refers to those safety factors that are deemed necessary for 
the protection of infants and children primarily as a result of the 
FQPA. The ``default FQPA safety factor'' is the additional 10X safety 
factor that is mandated by the statute unless it is decided that there 
are reliable data to choose a different additional factor

[[Page 54644]]

(potentially a traditional uncertainty factor or a special FQPA safety 
factor).
    For dietary risk assessment (other than cancer) the Agency uses the 
UF to calculate an acute or chronic reference dose (acute RfD or 
chronic RfD) where the RfD is equal to the NOAEL divided by an UF of 
100 to account for interspecies and intraspecies differences and any 
traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF). 
Where a special FQPA safety factor or the default FQPA safety factor is 
used, this additional factor is applied to the RfD by dividing the RfD 
by such additional factor. The acute or chronic Population Adjusted 
Dose (aPAD or cPAD) is a modification of the RfD to accommodate this 
type of safety factor.
    For non-dietary risk assessments (other than cancer) the UF is used 
to determine the LOC. For example, when 100 is the appropriate UF (10X 
to account for interspecies differences and 10X for intraspecies 
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to 
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and 
compared to the LOC.
    The linear default risk methodology (Q*) is the primary method 
currently used by the Agency to quantify carcinogenic risk. The Q* 
approach assumes that any amount of exposure will lead to some degree 
of cancer risk. A Q* is calculated and used to estimate risk which 
represents a probability of occurrence of additional cancer cases 
(e.g., risk). An example of how such a probability risk is expressed 
would be to describe the risk as one in one hundred thousand (1 X 
10-\5\), one in a million (1 X 10-\6\), or one in 
ten million (1 X 10-\7\). Under certain specific 
circumstances, MOE calculations will be used for the carcinogenic risk 
assessment. In this non-linear approach, a ``point of departure'' is 
identified below which carcinogenic effects are not expected. The point 
of departure is typically a NOAEL based on an endpoint related to 
cancer effects though it may be a different value derived from the dose 
response curve. To estimate risk, a ratio of the point of departure to 
exposure (MOEcancer = point of departure/exposures) is 
calculated.
    A summary of the toxicological endpoints for fluoxastrobin used for 
human risk assessment is shown in Table 2. of this unit:

    Table 2.--Summary of Toxicological Dose and Endpoints for Fluoxastrobin for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                          Dose Used in Risk
                                             Assessment;          Special FQPA SF and
          Exposure Scenario                 Interspecies,         Level of Concern for   Study and Toxicological
                                        Intraspecies, and any       Risk Assessment              Effects
                                            Traditional UF
----------------------------------------------------------------------------------------------------------------
Acute Dietary                          NOAEL = None             Not applicable           There was no indication
                                                                                          of an adverse effect
                                                                                          attributable to a
                                                                                          single dose. An aRfD
                                                                                          was not established.
----------------------------------------------------------------------------------------------------------------
Chronic Dietary (all populations)      NOAEL = 1.5 mg/kg/day    Special FQPA SF = 1X     Chronic Toxicology-Dog
                                       UF = 100X..............  cPAD = 0.015 mg/kg/day.  LOAEL = 8.1 mg/kg/day
                                                                                          for males and 7.7 mg/
                                                                                          kg/day for females
                                                                                          based on body weight
                                                                                          reductions,
                                                                                          hepatocytomegaly, and
                                                                                          cytoplasmic changes
                                                                                          associated with
                                                                                          increased serum liver
                                                                                          alkaline phosphatase
                                                                                          that is indicative of
                                                                                          cholestasis.
----------------------------------------------------------------------------------------------------------------
Incidental Short-Term Oral (1-30       NOAEL = 3.0 mg/kg/day    Residential LOC for MOE  90-Day Subchronic Oral
 days)                                 UF = 100X..............   = 100                    Toxicology-Dog
                                                                                         LOAEL = 24.8 mg/kg/day
                                                                                          (800 ppm) for males
                                                                                          and 24.2 mg/kg/day
                                                                                          (800 ppm) for females
                                                                                          based on dose-related
                                                                                          reductions in net body
                                                                                          weight gain and food
                                                                                          efficiency; toxicity
                                                                                          findings in the liver
                                                                                          (cholestasis) in both
                                                                                          sexes; and toxicity
                                                                                          findings in the
                                                                                          kidneys (increased
                                                                                          relative weights in
                                                                                          females and
                                                                                          degeneration of the
                                                                                          proximal tubular
                                                                                          epithelium in males).
----------------------------------------------------------------------------------------------------------------
Incidental Intermediate-Term Oral (1-  NOAEL = 3.0 mg/kg/day    Residential LOC for MOE  90-Day Subchronic Oral
 6 months)                             UF = 100X..............   = 100                    Toxicology-Dog
                                                                                         LOAEL = 24.8 mg/kg/day
                                                                                          (800 ppm) for males
                                                                                          and 24.2 mg/kg/day
                                                                                          (800 ppm) for females
                                                                                          based on dose-related
                                                                                          reductions in net body
                                                                                          weight gain and food
                                                                                          efficiency; toxicity
                                                                                          findings in the liver
                                                                                          (cholestasis) in both
                                                                                          sexes; and toxicity
                                                                                          findings in the
                                                                                          kidneys (increased
                                                                                          relative weights in
                                                                                          females and
                                                                                          degeneration of the
                                                                                          proximal tubular
                                                                                          epithelium in males).
----------------------------------------------------------------------------------------------------------------
Short-Term Dermal (1-30 days)          Not applicable           None                     None: A 28-day dermal
                                                                                          toxicity study in the
                                                                                          rat was negative up to
                                                                                          the limit dose and
                                                                                          there are no
                                                                                          developmental or
                                                                                          neurotoxicity
                                                                                          concerns.
----------------------------------------------------------------------------------------------------------------

[[Page 54645]]

 
Intermediate-Term Dermal (1-6 months)  NOAEL = 3.0 mg/kg/day    Residential LOC for MOE  90-Day Subchronic Oral
                                       UF = 100X..............   = 100                    Toxicology-Dog
                                       Dermal absorption rate                            LOAEL = 24.8 mg/kg/day
                                        = 2.3%.                                           (800 ppm) for males
                                                                                          and 24.2 mg/kg/day
                                                                                          (800 ppm) for females
                                                                                          based on dose-related
                                                                                          reductions in net body
                                                                                          weight gain and food
                                                                                          efficiency; toxicity
                                                                                          findings in the liver
                                                                                          (cholestasis) in both
                                                                                          sexes; and toxicity
                                                                                          findings in the
                                                                                          kidneys (increased
                                                                                          relative weights in
                                                                                          females and
                                                                                          degeneration of the
                                                                                          proximal tubular
                                                                                          epithelium in males).
----------------------------------------------------------------------------------------------------------------
Long-Term Dermal (greater than 6       NOAEL = 1.5 mg/kg/day    Residential LOC for MOE  Chronic Toxicology-Dog
 months)                               UF = 100X..............   = 100                   LOAEL = 8.1 mg/kg/day
                                       Dermal absorption rate                             for males and 7.7 mg/
                                        = 2.3%.                                           kg/day for females
                                                                                          based on body weight
                                                                                          reductions,
                                                                                          hepatocytomegaly, and
                                                                                          cytoplasmic changes
                                                                                          associated with
                                                                                          increased serum liver
                                                                                          alkaline phosphatase
                                                                                          that is indicative of
                                                                                          cholestasis.
----------------------------------------------------------------------------------------------------------------
Short-Term Inhalation (1-30 days)      NOAEL = 3.0 mg/kg/day    Residential LOC for MOE  90-Day Subchronic Oral
                                       UF = 100X..............   = 100                    Toxicology-Dog
                                                                                         LOAEL = 24.8 mg/kg/day
                                                                                          (800 ppm) for males
                                                                                          and 24.2 mg/kg/day
                                                                                          (800 ppm) for females
                                                                                          based on dose-related
                                                                                          reductions in net body
                                                                                          weight gain and food
                                                                                          efficiency; toxicity
                                                                                          findings in the liver
                                                                                          (cholestasis) in both
                                                                                          sexes; and toxicity
                                                                                          findings in the
                                                                                          kidneys (increased
                                                                                          relative weights in
                                                                                          females and
                                                                                          degeneration of the
                                                                                          proximal tubular
                                                                                          epithelium in males).
----------------------------------------------------------------------------------------------------------------
Intermediate-Term Inhalation (1-6      NOAEL = 3.0 mg/kg/day    Residential LOC for MOE  90-Day Subchronic Oral
 months)                               UF = 100X..............   = 100                    Toxicology-Dog
                                                                                         LOAEL = 24.8 mg/kg/day
                                                                                          (800 ppm) for males
                                                                                          and 24.2 mg/kg/day
                                                                                          (800 ppm) for females
                                                                                          based on dose-related
                                                                                          reductions in net body
                                                                                          weight gain and food
                                                                                          efficiency; toxicity
                                                                                          findings in the liver
                                                                                          (cholestasis) in both
                                                                                          sexes; and toxicity
                                                                                          findings in the
                                                                                          kidneys (increased
                                                                                          relative weights in
                                                                                          females and
                                                                                          degeneration of the
                                                                                          proximal tubular
                                                                                          epithelium in males).
----------------------------------------------------------------------------------------------------------------
Long-Term Inhalation (greater than 6   NOAEL = 1.5 mg/kg/day    Residential LOC for MOE  Chronic Toxicology-Dog
 months)                               UF = 100X..............   = 100                   LOAEL = 8.1 mg/kg/day
                                                                                          for males and 7.7 mg/
                                                                                          kg/day for females
                                                                                          based on body weight
                                                                                          reductions,
                                                                                          hepatocytomegaly, and
                                                                                          cytoplasmic changes
                                                                                          associated with
                                                                                          increased serum liver
                                                                                          alkaline phosphatase
                                                                                          that is indicative of
                                                                                          cholestasis.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)               Classification: Not likely to be carcinogenic to humans.
----------------------------------------------------------------------------------------------------------------

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. As is described in 
Unit II., tolerances for fluoxastrobin are being established on a 
variety of raw agricultural commodities. Risk assessments were 
conducted by EPA to assess dietary exposures from fluoxastrobin in food 
as follows:
    i. Acute exposure. 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. The toxicological database for fluoxastrobin 
identified no adverse effect attributable to a single dose, therefore 
an acute dietary exposure assessment was not performed.
    ii. Chronic exposure. In conducting the chronic dietary risk 
assessment EPA used the Dietary Exposure Evaluation Model software with 
the Food Commodity Intake Database (DEEM-FCID\TM\ version 2.0) and the 
Lifeline\TM\ model, version 2.0, both of which incorporate food 
consumption data as reported by respondents in the USDA 1994-1996 and 
1998 Nationwide Continuing Surveys of Food Intake by Individuals 
(CSFII). The assumptions made for the chronic dietary exposure 
assessments were that residues, for all commodities, were present at 
100% of the tolerance levels and fluoxastrobin was applied to 100% of 
each crop to which it may be applied.

[[Page 54646]]

    2. Dietary exposure from drinking water. The Agency does not have 
drinking water monitoring exposure data to use in a comprehensive 
dietary exposure analysis and risk assessment for fluoxastrobin, a new 
pesticidal chemical. Because of this the Agency made drinking water 
concentration estimates by use of simulation or modeling, which takes 
into account data on the physical and chemical characteristics of 
fluoxastrobin.
    The Agency used the Pesticide Root Zone Model/Exposure Analysis 
Modeling System (PRZM/EXAMS (PRZM version 3.12 beta and EXAMS version 
2.98.04)), to produce estimates of pesticide concentrations in an index 
reservoir (the surface water concentration estimates). The Screening 
Concentrations in Ground Water (SCI-GROW) model was used to predict 
pesticide concentrations in shallow ground water (the ground water 
concentration estimates). The surface water concentration analysis was 
based on the turf use, which has the highest labeled annual application 
rate and assumes the highest default value of 87% percentage cropped 
area (PCA) land use around the index reservoir. The assumptions in this 
analysis are therefore also conservative. The ground water 
concentration analysis was based on the maximum pesticide use rate (the 
turf use again), the persistence of fluoxastrobin in soil, and the 
ability of fluoxastrobin to leach.
    None of these models include consideration of the impact processing 
(mixing, dilution, or treatment) of raw water for distribution as 
drinking water would likely have on the removal of pesticides from the 
source water. The primary use of these models by the Agency at this 
stage is to provide a screen for sorting out pesticides for which it is 
unlikely that drinking water concentrations would exceed human health 
levels of concern.
    Estimated drinking water concentrations (EDWCs) derived from these 
models are used to calculate drinking water levels of comparison 
(DWLOCs). The DWLOCs are used as points of comparison against the 
EDWCs. DWLOCs are theoretical upper limits on the concentration of a 
pesticide that could occur in drinking water without exceeding the size 
of the risk cup, considering the aggregate exposure to that pesticide 
in food and from residential uses. Since DWLOCs represent maximum 
allowable exposure to fluoxastrobin in drinking water, they are further 
discussed in the aggregate risk sections in Unit III.E.
    Based on the PRZM/EXAMS and SCI-GROW models, the EDWCs of 
fluoxastrobin for acute exposures are 28 parts per billion (ppb) for 
surface water and less than 1 ppb for ground water. The EDWCs for 
chronic exposures are 14 ppb for surface water and less than 1 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).
    There is potential for homeowner exposure to fluoxastrobin in 
residential settings by entry to turf areas where this fungicide has 
previously been applied, such as lawns where children might play or 
golf courses that adults might be active on. Therefore, risk 
assessments have been performed for residential postapplication 
scenarios. However, only professional pest control operators will be 
allowed to make the turf applications so residential handler exposure 
was not evaluated.
    Since chemical-specific data were unavailable, the Agency used 
general current approaches for non-occupational assessment and believes 
that the calculated risks represent screening level estimates. Maximum 
application rates have been used for all scenarios, and the risk 
estimates assume no dissipation of residues after day zero and do not 
consider removal of residues as a result of periodic cutting of the 
grass. Additionally, the intermediate-term endpoint was used for dermal 
risk estimates, even though the non-occupational exposure duration is 
believed to mostly be short-term (as a result of the use pattern), 
because no short-term dermal toxicity endpoint was identified.
    4. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    Unlike other pesticides for which EPA has followed a cumulative 
risk approach based on a common mechanism of toxicity, EPA has not made 
a common mechanism of toxicity finding as to fluoxastrobin and any 
other substances and fluoxastrobin 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 fluoxastrobin has 
a common mechanism of toxicity with other substances. For information 
regarding EPA's efforts to determine which chemicals have a common 
mechanism of toxicity and to evaluate the cumulative effects of such 
chemicals, see the policy statements released by EPA's OPP concerning 
common mechanism determinations and procedures for cumulating effects 
from substances found to have a common mechanism on EPA's web site at 
http://www.epa.gov/pesticides/cumulative/.

D. Safety Factor for Infants and Children

    1. In general. Section 408 of FFDCA provides that EPA shall apply 
an additional tenfold margin of safety for infants and children in the 
case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the data base on toxicity and exposure 
unless EPA determines based on reliable data that a different margin of 
safety will be safe for infants and children. Margins of safety are 
incorporated into EPA risk assessments either directly through use of a 
MOE analysis or through using uncertainty (safety) factors in 
calculating a dose level that poses no appreciable risk to humans. In 
applying this provision, EPA either retains the default value of 10X 
when reliable data do not support the choice of a different factor, or, 
if reliable data are available, EPA uses a different additional safety 
factor value based on the use of traditional uncertainty factors and/or 
special FQPA safety factors, as appropriate.
    2. Prenatal and postnatal sensitivity. The toxicity database for 
fluoxastrobin, including acceptable developmental toxicity studies in 
rats and rabbits, as well as a two-generation reproduction toxicity 
study, provides no indication of prenatal and/or post-natal 
sensitivity.
    3. Conclusion. There is a complete toxicity data base for 
fluoxastrobin and exposure data are complete or are estimated based on 
data that reasonably accounts for potential exposures. The Agency 
therefore has recommended reducing the special FQPA SF to 1X, based on 
the following additional considerations. First, there are no low risk 
concerns indicated by the various hazard studies. The study data are of 
high quality, and there are no residual uncertainties with regard to 
the pre- and/or postnatal toxicity of this chemical. Second, the 
dietary food exposure assessment utilizes proposed tolerance level or 
higher residues and 100% crop treated information for all commodities. 
By using these screening-level assessments, chronic exposures and risks 
will not be underestimated.

[[Page 54647]]

 Third, the dietary drinking water assessments utilize values generated 
by models and associated modeling parameters which are designed to 
provide conservative, health protective, high-end estimates of water 
concentrations. Fourth, the residential exposure assessment utilizes 
activity-specific transfer coefficients and turf transferable residues 
(TTR), as well as maximum application rates for the postapplication 
scenario. The residential assessment is based on reliable data and is 
unlikely to underestimate exposure/risk.

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 EDWCs. DWLOC values 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, not regulatory standards for drinking water . 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 the source of the 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 EPA's Office of Water are used to calculate 
DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult female), and 
1L/10 kg (child). Default body weights and drinking water consumption 
values vary on an individual basis. This variation will be taken into 
account in more refined screening-level and quantitative drinking water 
exposure assessments. Different populations will have different DWLOCs. 
Generally, a DWLOC is calculated for each type of risk assessment used: 
Acute, short-term, intermediate-term, chronic, and cancer.
    When EDWCs for surface water and ground water are less than the 
calculated DWLOCs, OPP concludes with reasonable certainty that 
exposures to the pesticide in drinking water (when considered along 
with other sources of exposure for which OPP has reliable data) would 
not result in unacceptable levels of aggregate human health risk at 
this time. Because OPP considers the aggregate risk resulting from 
multiple exposure pathways associated with a pesticide's uses, levels 
of comparison in drinking water may vary as those uses change. If new 
uses are added in the future, OPP 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. The toxicological database for fluoxastrobin 
identified no adverse effect attributable to a single dose, therefore 
fluoxastrobin is not expected to pose an acute dietary risk.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
fluoxastrobin from food will utilize 10% of the cPAD for the U.S. 
population, 6% of the cPAD for all infants less than 1 year old, and 
25% of the cPAD for children 1 to 2 years old, the children 
subpopulation with the greatest exposure. Based on the use pattern, 
chronic residential exposure to residues of fluoxastrobin is not 
expected. However, there is the potential for chronic dietary exposure 
to fluoxastrobin in drinking water. After calculating DWLOCs and 
comparing them to the EDWCs for surface 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 Fluoxastrobin
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                cPAD mg/kg/     % cPAD     Water EDWC   Water EDWC    Chronic
                                                     day         (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                        0.015           10           14          < 1          470
------------------------------------------------
------------------------------------------------
----------------------------------------------------------------------------------------------------------------

    3. Short- and intermediate-term risk. Short- and intermediate-term 
aggregate exposures both take into account residential exposure plus 
chronic exposure to food and water (considered to be a background 
exposure level). Because all short- and intermediate-term quantitative 
hazard estimates (via the dermal and incidental oral routes) for 
fluoxastrobin are based on the same endpoint, a screening level, 
conservative aggregate risk assessment was conducted that combined the 
short-term incidental oral and intermediate-term dermal exposure 
estimates (i.e., the highest exposure estimates).
    Using the exposure assumptions described in this unit for 
intermediate-term exposures, EPA has concluded that food and 
residential exposures aggregated result in aggregate MOEs of 1,000 for 
the U.S. population, 1,100 for females 13-49 years old, and 180 for 
children 1-2 years old. These aggregate MOEs do not exceed the Agency's 
level of concern for aggregate exposure to food and residential uses. 
In addition, short- and intermediate-term DWLOCs were calculated and 
compared to the EDWCs for chronic exposure to fluoxastrobin in ground 
and surface water. After calculating DWLOCs and comparing them to the 
EDWCs for surface and ground water, EPA does not expect short- and 
intermediate-term aggregate exposure to exceed the Agency's level of 
concern, as shown in Table 4. of this unit:

[[Page 54648]]



         Table 4.--Aggregate Risk Assessment for Short- and Intermediate-Term Exposure to Fluoxastrobin
----------------------------------------------------------------------------------------------------------------
                                                             Aggregate                               Short- and
                                                Aggregate     Level of     Surface       Ground    Intermediate-
             Population Subgroup               MOE (Food +    Concern     Water EDWC   Water EDWC    Term DWLOC
                                              Residential)     (LOC)        (ppb)        (ppb)         (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                      1,000          100           28          < 1           940
------------------------------------------------------------
---------------------------------------------
----------------------------------------------------------------------------------------------------------------

    4. 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 fluoxastrobin residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (liquid chromatography/mass 
spectrometry/mass spectrometry methods) is available to enforce the 
tolerance expression. The methods are LC/MS/MS Method No. 00604, 
entitled ``Analytical Determination of Residues of the Fungicide HEC 
5725 In/On Cereals, Cereal Processed Products and Vegetables by HPLC-
MS/MS [high-pressure liquid chromatography--mass spectrometry/mass 
spectrometry],'' and LC/MS/MS Method No. 00649, entitled ``Analytical 
Method 00649 for the Determination of Residues of HEC 5725 In/On 
Matrices of Plant Origin by HPLC-MS/MS.'' The methods 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 currently no Mexican, Canadian, nor CODEX maximum residue 
limits established for fluoxastrobin.

C. Conditions

    The following conditions are being imposed on Bayer CropScience 
(the petitioner) for the registration of fluoxastrobin.
    1. Submit additional information concerning weather conditions, 
confirmatory raw data, and soil characteristics data for the crop field 
trial and field rotational crop studies.
    2. Submit additional data concerning the chromatograms and 
chromatography in the goat metabolism study.
    3. The enforcement methods must be rewritten to include 
instructions for the analysis of all crops, and to specify the 
additional ions to be monitored for quantitation.
    4. A new peanut processing study must be submitted.
    5. Submit reference standard materials for fluoxastrobin and 
several molecules related to it, including isotopically labeled 
internal standard reference materials, to the EPA National Pesticide 
Standards Repository.
    6. Submit additional information concerning the grass forage and 
hay rotational crop field trials.
    7. Submit confirmatory data and additional information concerning 
the storage stability data.
    8. Submit additional information concerning the mouse 
immunotoxicity subacute feeding study.

V. Comments

    In response to the notice of filing one communication was received 
from Susie Wilcher in the role of private citizen and one 
communication, undersigned by Ellen Connett, was received from the 
Fluoride Action Network (FAN). The communications objected to 
establishment of the proposed tolerances for several reasons, some of 
them specific and others involving generalized and unsubstantiated 
disagreement with EPA's risk assessment methodologies or safety 
findings.
    Ms. Wilcher's comments contained general objections to the use of 
pesticides on food and to the use of animal testing to determine the 
safety of pesticides. The Agency understands the commentor's concerns 
and recognizes that some individuals believe that pesticides should be 
banned completely. However, under the existing legal framework provided 
by section 408 of the FFDCA EPA is authorized to establish pesticide 
tolerances or exemptions where persons seeking such tolerances or 
exemptions have demonstrated that the pesticide meets the safety 
standard imposed by that statute.
    The Agency disagrees with the commenter's objections to animal 
testing. Since humans and animals have complex organ systems and 
mechanisms for the distribution of chemicals in the body, as well as 
processes for eliminating toxic substances from their systems, EPA 
relies on laboratory animals such as rats and mice to mimic the 
complexity of human and higher-order animal physiological responses 
when exposed to a pesticide. EPA is committed, however, to reducing the 
use of animals whenever possible. EPA-required studies include animals 
only when the requirements of sound toxicological science make the use 
of an animal absolutely necessary. The Agency's goal is to be able to 
predict the potential of pesticides to cause harmful effects to humans 
and wildlife by using fewer laboratory animals as models and have been 
accepting data from alternative (to animals) test methods for several 
years. As progress is made on finding or developing non-animal test 
models that reliably predict the potential for harm to humans or the 
environment, EPA expects that it will need fewer animal studies to make 
safety determinations.
    FAN submitted a number of different comments. First, FAN asked 
whether fluoxastrobin was already registered in the United States and 
what are the names of the fluoxastrobin products used on residential 
turf and golf courses. Fluoxastrobin is not currently registered but 
with the completion of this tolerance regulation that registration 
should be granted shortly. To the best of EPA's knowledge, the product 
name under which fluoxastrobin is marketed for turf and golf course use 
is HEC 480 SC Fungicide.
    Second, FAN suggested that a 14-week feeding study using dogs 
showed an effect on the thyroid, which seems to conflict with the 
statement that ``...There is no evidence to suggest that fluoxastrobin 
has any primary

[[Page 54649]]

endocrine disruptive potential.'' FAN stated that a ``discussion or 
rationale'' addressing this should have been provided. EPA does believe 
that the thyroid effects seen in the dog study indicated that 
fluoxastrobin is an endocrine disruptor. An effect on the thyroid 
gland, even though this gland is part of the endocrine system, does not 
necessarily mean that endocrine disruption has or will occur. In this 
case, the effects observed in the thyroid gland were induced by effects 
fluoxastrobin had on liver enzymes and are therefore considered 
secondary.
    Third, FAN claimed that a ``fuller discussion and description of 
the metabolites of fluoxastrobin should have been presented.'' The 
notice states: ``The residue of concern is parent fluoxastrobin (sum of 
E and Z isomers).'' According to the Compendium of Pesticide Common 
Names, Fluoxastrobin ``was provisionally approved for the (EZ)-isomer 
[193740-76-0] in April 2002. The definition was changed to the (E)-
isomer in January 2003 at the request of the sponsor...Because of this 
change it is not clear from the information supplied in this notice 
what isomer/metabolite are of concern.''
    Fluoxastrobin is the accepted common name for the pesticidally 
active E-isomer of (2-[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy 
phenyl)-5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime. The Z-
isomer of fluoxastrobin is typically present at much lower levels (E:Z 
ratio of approximately 90:10). Additionally, the Z-isomer of 
fluoxastrobin is considered to be a metabolite (photo-degradate) of 
fluoxastrobin. The CAS Number Bayer CropScience initially obtained for 
fluoxastrobin pertained to both isomers combined. After consultation 
with the Agency, the petitioner requested that fluoxastrobin (the 
pesticidally active E-isomer only) be designated as the active 
ingredient. The tolerances that are being established today include 
both fluoxastrobin (i.e. the E-isomer) and the Z-isomer and the risk 
assessment for these tolerances was based on exposures resulting from 
both isomers.
    Fourth, FAN requested that the Agency begin to incorporate the 
Chemical Abstract Service (CAS) numbers for ``every chemical, and its 
metabolite(s)'' in ``all future reports, especially those published in 
the Federal Register.'' EPA is evaluating the feasibility of such a 
step. EPA would note, however, that not every molecule or substance has 
a CAS number. Many metabolites do not have a CAS number, for example, 
because no application for a CAS number was made or is required. CAS is 
also often not willing to assign CAS numbers to substances it believes 
are not able to be characterized well enough (some petroleum 
distillates, for example). In addition, CAS numbers may be 
inappropriate in some types of reports. However, the CAS number could 
be a useful identifier in certain documents for molecules which have 
one.
    FAN also commented that the data references cited in the notice of 
filing were not available in the docket, and that without this 
information, it was not possible to comment on the findings presented. 
In response, the Agency transmitted to FAN the human health risk 
assessment and the toxicological studies used in that risk assessment.

VI. Conclusion

    Therefore, tolerances requested for fluoxastrobin in the revised 
petition are established.

VII. Objections and Hearing Requests

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

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

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number OPP-2003-0129 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 
15, 2005.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900L), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Suite 350, 1099 14\th\ St., NW., 
Washington, DC 20005. 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 (202) 564-6255.
    2. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit VII.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in ADDRESSES. Mail your 
copies, identified by docket ID number OPP-2003-0129, 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 he PIRIB 
described in ADDRESSES. 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:

[[Page 54650]]

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 issue(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

VIII. Statutory and Executive Order Reviews

    This final rule establishes tolerances under section 408(d) of 
FFDCA in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this rule has been 
exempted from review under Executive Order 12866 due to its lack of 
significance, this rule is not subject to Executive Order 13211, 
Actions Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001). This final rule does 
not contain any information collections subject to OMB approval under 
the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose 
any enforceable duty or contain any unfunded mandate as described under 
Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 
104-4). Nor does it require any special considerations under Executive 
Order 12898, entitled Federal Actions to Address Environmental Justice 
in Minority Populations and Low-Income Populations (59 FR 7629, 
February 16, 1994); or OMB review or any Agency action under Executive 
Order 13045, entitled Protection of Children from Environmental Health 
Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does 
not involve any technical standards that would require Agency 
consideration of voluntary consensus standards pursuant to section 
12(d) of the National Technology Transfer and Advancement Act of 1995 
(NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since 
tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of FFDCA, such as the tolerance in this 
final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply. In addition, the Agency has determined that this 
action will not have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132, entitled 
Federalism(64 FR 43255, August 10, 1999). Executive Order 13132 
requires EPA to develop an accountable process to ensure ``meaningful 
and timely input by State and local officials in the development of 
regulatory policies that have federalism implications.'' ``Policies 
that have federalism implications'' is defined in the Executive order 
to include regulations that have ``substantial direct effects on the 
States, on the relationship between the national government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government.'' This final rule directly regulates 
growers, food processors, food handlers and food retailers, not States. 
This action does not alter the relationships or distribution of power 
and responsibilities established by Congress in the preemption 
provisions of section 408(n)(4) of FFDCA. For these same reasons, the 
Agency has determined that this rule does not have any ``tribal 
implications'' as described in Executive Order 13175, entitled 
Consultation and Coordination with Indian Tribal Governments (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.

IX. 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 2, 2005.
James Jones,
Director, Office of Pesticide Programs.

0
Therefore, 40 CFR part 180 is amended as follows:

PART 180--[AMENDED]

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

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

0
2. Section 180.609 is added to read as follows:


Sec.  180.609  Fluoxastrobin; tolerances for residues.

    (a) General. (1) Tolerances are established for the combined 
residues of fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-
pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, and its Z isomer, (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-
4-pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, in or on the following raw agricultural commodities:

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Leaf petioles subgroup 4B..................................          4.0
Peanut.....................................................        0.010
Peanut, hay................................................         20.0
Peanut, refined oil........................................        0.030
Tomato, paste..............................................          1.5
Vegetable, fruiting, group 8...............................          1.0
Vegetable, tuberous and corm, subgroup 1C..................        0.010
------------------------------------------------------------------------

    (2) Tolerances are established for the combined residues of 
fluoxastrobin, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-
pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, its Z isomer, (1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-
pyrimydinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-
methyloxime, and its phenoxy-

[[Page 54651]]

hydroxypyrimidine metabolite, 6-(2-chlorophenoxy)-5-fluoro-4-
pyrimidinol, in or on the following raw agricultural commodities:

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Cattle, fat................................................         0.10
Cattle, meat...............................................         0.05
Cattle, meat byproducts....................................         0.10
Goat, fat..................................................         0.10
Goat, meat.................................................         0.05
Goat, meat byproducts......................................         0.10
Horse, fat.................................................         0.10
Horse, meat................................................         0.05
Horse, meat byproducts.....................................         0.10
Milk.......................................................         0.02
Milk, fat..................................................         0.50
Sheep, fat.................................................         0.10
Sheep, meat................................................         0.05
Sheep, meat byproducts.....................................         0.10
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. Tolerances are established 
for the indirect or inadvertent combined residues of fluoxastrobin, 
(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-
dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, and its Z isomer, 
(1Z)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimydinyl]oxy]phenyl](5,6-
dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, in or on the 
following raw agricultural commodities when present therein as a result 
of the application of fluoxastrobin to the growing crops listed in 
paragraph (a)(1) of this section:

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Alfalfa, forage............................................        0.050
Alfalfa, hay...............................................         0.10
Cotton, gin byproducts.....................................        0.020
Grain, cereal, forage, fodder, and straw, group 16.........         0.10
Grass, forage..............................................         0.10
Grass, hay.................................................         0.50
Vegetable, foliage of legume, group 7......................        0.050
------------------------------------------------------------------------


[FR Doc. 05-18421 Filed 9-15-05; 8:45 am]
BILLING CODE 6560-50-S