Fluoxastrobin; Pesticide Tolerances, 54640-54651 [05-18421]
Download as PDF
<![CDATA[
54640
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
Dated: September 6, 2005.
Donald S. Welsh,
Regional Administrator, Region III.
Accordingly, the added entry for
Delaware’s Regulation 1, Section 2, and
revised entries for Regulation 3,
Sections 1, 6, and 11 in 40 CFR
52.420(c) published at 70 FR 41147 are
withdrawn as of September 16, 2005.
I
[FR Doc. 05–18565 Filed 9–15–05; 8:45 am]
BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[OPP–2003–0129; FRL–7719–9]
Fluoxastrobin; Pesticide Tolerances
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes
tolerances for combined residues of
fluoxastrobin, (1E)-[2-[[6-(2chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, and its Z isomer, (1Z)-[2[[6-(2-chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, 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)-5fluoro-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
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
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 https://
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:
kish.tony@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by
this action if you are an agricultural
producer, food manufacturer, or
pesticide manufacturer. Potentially
affected entities may include, but are
not limited to:
• Crop production (NAICS 111), e.g.,
agricultural workers; greenhouse,
nursery, and floriculture workers;
farmers.
• Animal production (NAICS 112),
e.g., cattle ranchers and farmers, dairy
cattle farmers, livestock farmers.
• Food manufacturing (NAICS 311),
e.g., agricultural workers; farmers;
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
PO 00000
Frm 00032
Fmt 4700
Sfmt 4700
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 (https://
www.epa.gov/edocket/), you may access
this Federal Register document
electronically through the EPA Internet
under the ‘‘Federal Register’’ listings at
https://www.epa.gov/fedrgstr/. A
frequently updated electronic version of
40 CFR part 180 is available at E-CFR
Beta Site Two at https://
www.gpoaccess.gov/ecfr/. To access the
OPPTS Harmonized Guidelines
referenced in this document, go directly
to the guidelines at https://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-4pyrimydinyl]-oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, 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
E:\FR\FM\16SER1.SGM
16SER1
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
the combined residues of fluoxastrobin,
(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4pyrimydinyl]-oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, and its phenoxyhydroxypyrimidine metabolite, 6-(2chlorophenoxy)-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 Zisomer in/on rotated crops. As revised,
the petition seeks the establishment of
tolerances for combined residues of
fluoxastrobin, (1E)-[2-[[6-(2chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, and its Z isomer, (1Z)-[2[[6-(2-chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, 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 phenoxyhydroxypyrimidine metabolite, 6-(2chlorophenoxy)-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
54641
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.
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
PO 00000
Frm 00033
Fmt 4700
Sfmt 4700
E:\FR\FM\16SER1.SGM
16SER1
54642
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
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 toxicityrats
NOAEL was 1,000 mg/kg/day (the limit dose, 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-rabbits
Maternal NOAEL was 100 mg/kg/day.
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
effects-rats
Parental systemic NOAEL was 70.0 mg/kg/day 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/
carcinogenicity--rats
NOAEL was 53.0 mg/kg/day for males and 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
screening battery--rats
Neurotoxicity NOAEL was greater than or equal to 2,000 mg/kg (limit dose).
No LOAEL was identified.
870.6200
Subchronic neurotoxicity
screening battery--rats
Systemic NOAEL (systemic and neurotoxic) was 473.9/582.4 mg/kg/day for males
and females, respectively.
No LOAEL was identified.
870.5100
Gene Mutation-in vitro
bacterial reverse gene
mutation
Negative (considered non-mutagenic in Salmonella typhimurium cultures treated up
to cytotoxic/ precipitating levels).
870.5100
Gene Mutation--in vitro
bacterial reverse gene
mutation (the test substance was HEC 5725N
(E:Z ratio of 90%:10%)
Negative (considered non-mutagenic in this Salmonella typhimurium/microsome
test).
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
PO 00000
Frm 00034
Fmt 4700
Sfmt 4700
E:\FR\FM\16SER1.SGM
16SER1
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
54643
TABLE 1.—SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.5100
Gene Mutation--in vitro
bacterial reverse gene
mutation (the test substance was HEC 5725phenoxy-hydroxy-pyrimidine)
Negative (considered non-mutagenic in this Salmonella typhimurium/mammalian activation gene mutation assay).
870.5100
Gene Mutation--in vitro
bacterial reverse gene
mutation (the test substance was HEC 5725dihydroxy- pyrimidine)
Negative (considered non-mutagenic in this Salmonella typhimurium/mammalian activation gene mutation assay).
870.5300
Gene mutation-in vitro
mammalian forward
gene mutation
Negative (considered non-mutagenic in this in vitro forward mutation V79-HPRT
test).
870.5375
Gene Mutation--in vitro
mammalian chromosome aberrations in
Chinese hamster lung
(V79) cells
Negative (considered to be negative for clastogenicity in this in vitro mammalian cell
test).
870.5395
Cytogenics-in vivo mammalian cytogenetics micronucleus assay
(mouse)
Negative (considered non-clastogenic, as indicated by no increases in micronuclei in
bone marrow).
870.7485
Metabolism and pharmacokinetics-rat
Absorption, distribution, and metabolism were fully characterized in several rat metabolism studies using each of the three 14C-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
(subacute feeding
study)
No clinical signs of toxicity or mortality 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
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
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
PO 00000
Frm 00035
Fmt 4700
Sfmt 4700
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
E:\FR\FM\16SER1.SGM
16SER1
54644
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
(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
Exposure Scenario
Dose Used in Risk Assessment; Interspecies,
Intraspecies, and any Traditional UF
Special FQPA SF and
Level of Concern for Risk
Assessment
Study and Toxicological Effects
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
UF = 100X
Special FQPA SF = 1X
cPAD = 0.015 mg/kg/day
Chronic Toxicology-Dog
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 days)
NOAEL = 3.0 mg/kg/day
UF = 100X
Residential LOC for MOE
= 100
90-Day Subchronic Oral 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 (1–6 months)
NOAEL = 3.0 mg/kg/day
UF = 100X
Residential LOC for MOE
= 100
90-Day Subchronic Oral 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.
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
PO 00000
Frm 00036
Fmt 4700
Sfmt 4700
E:\FR\FM\16SER1.SGM
16SER1
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
54645
TABLE 2.—SUMMARY OF TOXICOLOGICAL DOSE AND ENDPOINTS FOR FLUOXASTROBIN FOR USE IN HUMAN RISK
ASSESSMENT—Continued
Exposure Scenario
Dose Used in Risk Assessment; Interspecies,
Intraspecies, and any Traditional UF
Special FQPA SF and
Level of Concern for Risk
Assessment
Study and Toxicological Effects
Intermediate-Term Dermal (1–6
months)
NOAEL = 3.0 mg/kg/day
UF = 100X
Dermal absorption rate =
2.3%
Residential LOC for MOE
= 100
90-Day Subchronic Oral 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 Dermal (greater
than 6 months)
NOAEL = 1.5 mg/kg/day
UF = 100X
Dermal absorption rate =
2.3%
Residential LOC for MOE
= 100
Chronic Toxicology-Dog
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.
Short-Term Inhalation (1–30
days)
NOAEL = 3.0 mg/kg/day
UF = 100X
Residential LOC for MOE
= 100
90-Day Subchronic Oral 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 months)
NOAEL = 3.0 mg/kg/day
UF = 100X
Residential LOC for MOE
= 100
90-Day Subchronic Oral 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 months)
NOAEL = 1.5 mg/kg/day
UF = 100X
Residential LOC for MOE
= 100
Chronic Toxicology-Dog
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 fooduse pesticide, if a toxicological study
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
has indicated the possibility of an effect
of concern occurring as a result of a oneday 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-
PO 00000
Frm 00037
Fmt 4700
Sfmt 4700
FCIDTM version 2.0) and the LifelineTM
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.
E:\FR\FM\16SER1.SGM
16SER1
54646
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
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 (SCIGROW) 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 SCIGROW models, the EDWCs of
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
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 nonoccupational, 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 nonoccupational 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 intermediateterm endpoint was used for dermal risk
estimates, even though the nonoccupational 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
PO 00000
Frm 00038
Fmt 4700
Sfmt 4700
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 https://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 preand/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 screeninglevel assessments, chronic exposures
and risks will not be underestimated.
E:\FR\FM\16SER1.SGM
16SER1
54647
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
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 activityspecific 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/
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:
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
TABLE 3.—AGGREGATE RISK ASSESSMENT FOR CHRONIC (NON-CANCER) EXPOSURE TO FLUOXASTROBIN
cPAD mg/
kg/day
Population Subgroup
Surface
Water
EDWC
(ppb)
% cPAD
(Food)
Ground
Water
EDWC
(ppb)
Chronic
DWLOC
(ppb)
U.S. population
0.015
10
14
<1
470
All infants (less than 1 year old)
0.015
6.0
14
<1
140
Children 1 to 2 years old
0.015
25
14
<1
110
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-
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
term incidental oral and intermediateterm dermal exposure estimates (i.e., the
highest exposure estimates).
Using the exposure assumptions
described in this unit for intermediateterm 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
PO 00000
Frm 00039
Fmt 4700
Sfmt 4700
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:
E:\FR\FM\16SER1.SGM
16SER1
54648
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
TABLE 4.—AGGREGATE RISK ASSESSMENT FOR SHORT- AND INTERMEDIATE-TERM EXPOSURE TO FLUOXASTROBIN
Aggregate
MOE (Food
+ Residential)
Population Subgroup
Aggregate
Level of
Concern
(LOC)
Surface
Water
EDWC
(ppb)
Ground
Water
EDWC
(ppb)
Short- and
IntermediateTerm
DWLOC
(ppb)
U.S. population
1,000
100
28
<1
940
Females 13–49 years old
1,100
100
28
<1
820
180
100
28
<1
140
Children 1–2 years old
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 [highpressure 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 HPLCMS/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:
residuemethods@epa.gov.
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.
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
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
PO 00000
Frm 00040
Fmt 4700
Sfmt 4700
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 higherorder animal physiological responses
when exposed to a pesticide. EPA is
committed, however, to reducing the
use of animals whenever possible. EPArequired 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 14week 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
E:\FR\FM\16SER1.SGM
16SER1
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
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-(2chlorophenoxy)-5-fluoro-4pyrimidinyl]oxy phenyl)-5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime. 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 Eisomer 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
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
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
PO 00000
Frm 00041
Fmt 4700
Sfmt 4700
54649
grounds for the objections (40 CFR
178.25). If a hearing is requested, the
objections must include a statement of
the factual issues(s) on which a hearing
is requested, the requestor’s contentions
on such issues, and a summary of any
evidence relied upon by the objector (40
CFR 178.27). Information submitted in
connection with an objection or hearing
request may be claimed confidential by
marking any part or all of that
information as CBI. Information so
marked will not be disclosed except in
accordance with procedures set forth in
40 CFR part 2. A copy of the
information that does not contain CBI
must be submitted for inclusion in the
public record. Information not marked
confidential may be disclosed publicly
by EPA without prior notice.
Mail your written request to: Office of
the Hearing Clerk (1900L),
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001. You may also deliver
your request to the Office of the Hearing
Clerk in Suite 350, 1099 14th 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 email to: opp-docket@epa.gov. Please use
an ASCII file format and avoid the use
of special characters and any form of
encryption. Copies of electronic
objections and hearing requests will also
be accepted on disks in WordPerfect
6.1/8.0 or ASCII file format. Do not
include any CBI in your electronic copy.
You may also submit an electronic copy
of your request at many Federal
Depository Libraries.
B. When Will the Agency Grant a
Request for a Hearing?
A request for a hearing will be granted
if the Administrator determines that the
material submitted shows the following:
E:\FR\FM\16SER1.SGM
16SER1
54650
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
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
VerDate Aug<31>2005
15:20 Sep 15, 2005
Jkt 205001
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
PO 00000
Frm 00042
Fmt 4700
Sfmt 4700
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.
Therefore, 40 CFR part 180 is
amended as follows:
I
PART 180—[AMENDED]
1. The authority citation for part 180
continues to read as follows:
I
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.609 is added to read as
follows:
I
§ 180.609 Fluoxastrobin; tolerances for
residues.
(a) General. (1) Tolerances are
established for the combined residues of
fluoxastrobin, (1E)-[2-[[6-(2chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, and its Z isomer, (1Z)-[2[[6-(2-chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, in or on the following raw
agricultural commodities:
Commodity
Leaf petioles subgroup 4B .......
Peanut ......................................
Peanut, hay ..............................
Peanut, refined oil ....................
Tomato, paste ...........................
Vegetable, fruiting, group 8 ......
Vegetable, tuberous and corm,
subgroup 1C .........................
Parts per
million
4.0
0.010
20.0
0.030
1.5
1.0
0.010
(2) Tolerances are established for the
combined residues of fluoxastrobin,
(1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, its Z isomer, (1Z)-[2-[[6(2-chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, and its phenoxy-
E:\FR\FM\16SER1.SGM
16SER1
Federal Register / Vol. 70, No. 179 / Friday, September 16, 2005 / Rules and Regulations
hydroxypyrimidine metabolite, 6-(2chlorophenoxy)-5-fluoro-4-pyrimidinol,
in or on the following raw agricultural
commodities:
Parts per
million
Commodity
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 .............................
Sheep, meat byproducts ..........
0.10
0.05
0.10
0.10
0.05
0.10
0.10
0.05
0.10
0.02
0.50
0.10
0.05
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-(2chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, and its Z isomer, (1Z)-[2[[6-(2-chlorophenoxy)-5-fluoro-4pyrimydinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone Omethyloxime, 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
million
Commodity
Alfalfa, forage ...........................
Alfalfa, hay ................................
Cotton, gin byproducts .............
Grain, cereal, forage, fodder,
and straw, group 16 ..............
Grass, forage ............................
Grass, hay ................................
Vegetable, foliage of legume,
group 7 ..................................
0.050
0.10
0.020
0.10
0.10
0.50
0.050
[FR Doc. 05–18421 Filed 9–15–05; 8:45 am]
BILLING CODE 6560–50–S
DEPARTMENT OF DEFENSE
[DFARS Case 2004–D025]
Defense Federal Acquisition
Regulation Supplement; Provision of
Information to Cooperative Agreement
Holders
Department of Defense (DoD).
VerDate Aug<31>2005
15:20 Sep 15, 2005
C. Paperwork Reduction Act
Final rule.
DoD has adopted as final,
without change, an interim rule
amending the Defense Federal
Acquisition Regulation Supplement
(DFARS) to implement Section 816 of
the National Defense Authorization Act
for Fiscal Year 2005. Section 816
increased, from $500,000 to $1,000,000,
the threshold at which a DoD contract
must include a requirement for the
contractor to provide to cooperative
agreement holders, upon their request, a
list of the contractor’s employees who
are responsible for entering into
subcontracts.
SUMMARY:
DATES:
Effective September 16, 2005.
Ms.
Robin Schulze, Defense Acquisition
Regulations Council,
OUSD(AT&L)DPAP(DAR), IMD 3C132,
3062 Defense Pentagon, Washington, DC
20301–3062. Telephone (703) 602–0326;
facsimile (703) 602–0350. Please cite
DFARS Case 2004–D025.
FOR FURTHER INFORMATION CONTACT:
SUPPLEMENTARY INFORMATION:
Jkt 205001
DoD published an interim rule at 70
FR 8536 on February 22, 2005, to
implement Section 816 of the National
Defense Authorization Act for Fiscal
Year 2005 (Pub. L. 108–375). Section
816 amended 10 U.S.C. 2416(d) to
increase, from $500,000 to $1,000,000,
the threshold at which a DoD contract
must include a requirement for the
contractor to provide to cooperative
agreement holders, upon their request, a
list of the contractor’s employees who
are responsible for entering into
subcontracts. The interim rule amended
the prescription for use of the clause at
DFARS 252.205–7000, Provision of
Information to Cooperative Agreement
Holders, to reflect the new dollar
threshold.
DoD received no comments on the
interim rule. Therefore, DoD has
adopted the interim rule as a final rule
without change.
This rule was not subject to Office of
Management and Budget review under
Executive Order 12866, dated
September 30, 1993.
DoD certifies that this final rule will
not have a significant economic impact
on a substantial number of small entities
within the meaning of the Regulatory
Flexibility Act, 5 U.S.C. 601, et seq.
While the rule reduces administrative
burdens for contractors, the economic
impact is not expected to be substantial.
PO 00000
Frm 00043
Fmt 4700
Sfmt 4700
The information collection
requirements of the clause at DFARS
252.205–7000, Provision of Information
to Cooperative Agreement Holders, have
been approved by the Office of
Management and Budget, under Control
Number 0704–0286, for use through
September 30, 2007.
List of Subjects in 48 CFR Part 205
Government procurement.
Michele P. Peterson,
Editor, Defense Acquisition Regulations
System.
Interim Rule Adopted as Final Without
Change
Accordingly, the interim rule
amending 48 CFR Part 205, which was
published at 70 FR 8536 on February 22,
2005, is adopted as a final rule without
change.
I
[FR Doc. 05–18476 Filed 9–15–05; 8:45 am]
BILLING CODE 5001–08–P
DEPARTMENT OF DEFENSE
A. Background
B. Regulatory Flexibility Act
48 CFR Part 205
AGENCY:
ACTION:
54651
48 CFR Part 217
[DFARS Case 2004–D024]
Defense Federal Acquisition
Regulation Supplement; Multiyear
Contracting
Department of Defense (DoD).
Final rule.
AGENCY:
ACTION:
SUMMARY: DoD has adopted as final,
without change, an interim rule
amending the Defense Federal
Acquisition Regulation Supplement
(DFARS) to implement Section 8008 of
the Defense Appropriations Act for
Fiscal Year 2005 and Section 814 of the
National Defense Authorization Act for
Fiscal Year 2005. Sections 8008 and 814
contain requirements related to the
funding of multiyear contracts.
DATES: Effective September 16, 2005.
FOR FURTHER INFORMATION CONTACT: Ms.
Robin Schulze, Defense Acquisition
Regulations Council,
OUSD(AT&L)DPAP(DAR), IMD 3C132,
3062 Defense Pentagon, Washington, DC
20301–3062. Telephone (703) 602–0326;
facsimile (703) 602–0350. Please cite
DFARS Case 2004–D024.
SUPPLEMENTARY INFORMATION:
A. Background
DoD published an interim rule at 70
FR 24323 on May 9, 2005, to implement
Section 8008 of the Defense
Appropriations Act for Fiscal Year 2005
(Pub. L. 108–287) and Section 814 of the
E:\FR\FM\16SER1.SGM
16SER1
]]>Agencies
[Federal Register Volume 70, Number 179 (Friday, September 16, 2005)]
[Rules and Regulations]
[Pages 54640-54651]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-18421]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2003-0129; FRL-7719-9]
Fluoxastrobin; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
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 https://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: kish.tony@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS 111), e.g., agricultural workers;
greenhouse, nursery, and floriculture workers; farmers.
Animal production (NAICS 112), e.g., cattle ranchers and
farmers, dairy cattle farmers, livestock farmers.
Food manufacturing (NAICS 311), e.g., agricultural
workers; farmers; 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 (https://www.epa.gov/edocket/), you may
access this Federal Register document electronically through the EPA
Internet under the ``Federal Register'' listings at https://www.epa.gov/
fedrgstr/. A frequently updated electronic version of 40 CFR part 180
is available at E-CFR Beta Site Two at https://www.gpoaccess.gov/ecfr/.
To access the OPPTS Harmonized Guidelines referenced in this document,
go directly to the guidelines at https://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
https://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% cro
