[Federal Register Volume 64, Number 51 (Wednesday, March 17, 1999)]
[Rules and Regulations]
[Pages 13106-13112]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-6387]
[[Page 13106]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300801; FRL-6064-6]
RIN 2070-AB78
Azoxystrobin; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for combined residues
of azoxystrobin (methyl(E)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-
yloxy)phenyl)-3-methoxyacrylate and its Z isomer (methyl(Z)-2-(2-(6-(2-
cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate) in or on
almond hulls, aspirated grain fractions, bananas (postharvest), canola,
cucurbits, peanut hay, pistachios, potatoes, rice, stone fruits, and
wheat; and residues of azoxystrobin (only) on fat of cattle, goats,
hogs, horses, and sheep; meat of cattle, goats, hogs, horses, and
sheep; meat byproducts of cattle, goats, hogs, horses, and sheep; and
milk. Zeneca Ag Products requested these tolerances under the Federal
Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection
Act of 1996.
DATES: This regulation is effective March 17, 1999. Objections and
requests for hearings must be received by EPA on or before May 17,
1999.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300801], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to:
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk identified by the docket
control number, [OPP-300801], must also be submitted to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. In person,
bring a copy of objections and hearing requests to Rm. 119, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may be submitted electronically by sending electronic mail (e-
mail) to: [email protected]. Copies of objections and hearing requests
must be submitted as an ASCII file avoiding the use of special
characters and any form of encryption. Copies of objections and hearing
requests will also be accepted on disks in WordPerfect 5.1/6.1 file
format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket control
number [OPP-300801]. No Confidential Business Information (CBI) should
be submitted through e-mail. Electronic copies of objections and
hearing requests on this rule may be filed online at many Federal
Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location, telephone number, and e-mail address: Rm. 249, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA, 703-305-7740, giles-
[email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register of October 8, 1997
(62 FR 52544)(FRL-5746-9) and December 11, 1998 (63 FR 68458)(FRL-6043-
3), EPA issued notices pursuant to section 408 of the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the Food
Quality Protection Act of 1996 (FQPA) (Pub. L. 104-170) announcing the
filing of two pesticide petitions (PP) 8F4995 and 7F4864, for
tolerances by Zeneca Ag Products, 1800 Concord Pike, P.O. Box 15458,
Wilmington, DE 19850-5458. This notice included a summary of the
petition prepared by Zeneca Ag Products, the registrant. There were no
comments received in response to the notices of filing.
The petitions requested that 40 CFR part 180 be amended by
establishing tolerances for combined residues of the fungicide
azoxystrobin (methyl(E)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-
yloxy)phenyl)-3-methoxyacrylate) and its Z isomer (methyl(Z)-2-(2-(6-
(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate) in or on
almond hulls at 4.0 parts per million (ppm), bananas (postharvest) at
2.0 ppm, canola at 1.0 ppm, cucurbits at 0.3 ppm, peanut hay at 1.5
ppm, pistachios at 0.01 ppm, potatoes at 0.03 ppm, rice grain at 4.0
ppm, rice straw at 11 ppm, rice hulls at 20 ppm, stone fruits at 1.5
ppm, tree nuts at 0.01 ppm; wheat grain at 0.04 ppm, wheat bran at 0.12
ppm, wheat hay at 13.0 ppm, wheat straw at 4.0 ppm; wheat aspirated
grain fractions at 15.0 ppm, and for the residues of azoxystrobin
(only) in eggs at 0.4 ppm; fat of cattle, goats, hogs, horses, poultry,
and sheep at 0.01 ppm; kidney of cattle at 0.06 ppm; liver of cattle,
goats, horses, and sheep at 0.3 ppm; liver of hogs at 0.2 ppm; liver of
poultry at 0.4 ppm; meat of cattle, goats, hogs, horses, poultry, and
sheep at 0.01 ppm; and milk at 0.006 ppm.
I. Background and Statutory Findings
Section 408(b)(2)(A)(i) of the 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) 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) 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 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).
II. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed
the available scientific data and other relevant information in support
of this action. EPA has sufficient data to assess the hazards of
azoxystrobin and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for establishment of permanent
tolerances for combined residues of azoxystrobin (methyl(E)-2-(2-(6-(2-
cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate) and its Z
isomer (methyl(E)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-
methoxyacrylate) in or on almond hulls at 4.0 ppm, aspirated grain
fractions at 10 ppm, bananas (pre-harvest and postharvest) at 2.0 ppm
(of which not more than 0.1 ppm is
[[Page 13107]]
contained in the pulp), canola at 1.0 ppm, cucurbits at 0.3 ppm, peanut
hay at 2.0 ppm, pistachios at 0.01 ppm, potatoes at 0.03 ppm, rice
grain at 5.0 ppm, rice straw at 12 ppm, rice hulls at 20 ppm, stone
fruits at 1.5 ppm, tree nuts at 0.010 ppm, wheat grain at 0.10 ppm,
wheat bran at 0.20 ppm, wheat hay at 15 ppm, wheat straw at 4.0 ppm,
and for the residues of azoxystrobin (only) in fat of cattle, goats,
hogs, horses, and sheep at 0.010 ppm; meat of cattle, goats, hogs,
horses, and sheep at 0.01 ppm; meat byproducts of cattle, goats, hogs,
horses, and sheep at 0.010 ppm; and milk at 0.006 ppm. A permanent
domestic tolerance of 0.5 ppm already exists for bananas and will be
amended by this rule. Temporary tolerances already exist for fat of
cattle, goats, hogs, horses, and sheep at 0.01 ppm; kidney of cattle,
goats, hogs, and sheep at 0.06 ppm; liver of cattle, goats, horses, and
sheep at 0.3 ppm; liver of hogs at 0.2 ppm; meat of cattle, goats,
hogs, horses, and sheep at 0.01 ppm; cucurbits at 1.0 ppm; milk at
0.006 ppm; potatoes at 0.03 ppm; rice grain at 4 ppm; rice hulls at 20
ppm; and rice straw at 10 ppm. A tolerance of 0.8 ppm already exists
for peaches; this will be superseded by the stone fruits tolerance of
1.5 ppm that is being established in this rule. Several of the
tolerances that are being established by this rule are different from
(often higher than) those proposed by Zeneca Ag Products. EPA review of
the data submitted by the company lead to an Agency decision to modify
the proposed tolerances. During these reviews it was also determined
that azoxystrobin uses that have been registered so far do not lead to
a need to establish tolerances for poultry commodities (including
eggs). EPA's assessment of the exposures and risks associated with
establishment of the above 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 azoxystrobin is
discussed in this unit.
1. Acute toxicity. The acute oral toxicity study in rats of
technical azoxystrobin resulted in an LD50 of > 5,000
milligrams/kilogram (mg/kg) (limit test) for both males and females.
The acute dermal toxicity study in rats of technical azoxystrobin
resulted in an LD50 of > 2,000 mg/kg (limit dose). The acute
inhalation study of technical azoxystrobin in rats resulted in an
LC50 of 0.962 mg/liter (mg/L) in males and 0.698 mg/L in
females. In an acute oral neurotoxicity study in rats dosed once by
gavage with 0, 200, 600, or 2,000 mg/kg azoxystrobin, the systemic
toxicity no observable adverse effect level (NOAEL) was < 200 mg/kg and
the systemic toxicity lowest observed adverse effect level (LOAEL) was
200 mg/kg, based on the occurrence of transient diarrhea in both sexes.
There was no indication of neurotoxicity at the doses tested.
2. Mutagenicity. Azoxystrobin was negative for mutagenicity in the
salmonella/mammalian activation gene mutation assay, the mouse
micronucleus test, and the unscheduled DNA synthesis in rat
hepatocytes/mammalian cells (in vivo/in vitro procedure study). In the
forward mutation study using L5178 mouse lymphoma cells in culture,
azoxystrobin tested positive for forward gene mutation at the TK locus.
In the in vitro human lymphocytes cytogenetics assay of azoxystrobin,
there was evidence of a concentration related induction of chromosomal
aberrations over background in the presence of moderate to severe
cytotoxicity.
3. Rat metabolism. In this study, azoxystrobin--unlabeled or with a
pyrimidinyl, phenylacrylate, or cyanophenyl label--was administered to
rats by gavage as a single dose or as 14-day repeated doses. Less than
0.5% of the administered dose was detected in the tissues and carcass
up to 7 days post-dosing and most of it was in excretion-related
organs. There was no evidence of potential for bioaccumulation. The
primary route of excretion was via the feces, though 9- to 18% was
detected in the urine of the various dose groups. Absorbed azoxystrobin
appeared to be extensively metabolized. A metabolic pathway was
proposed showing hydrolysis and subsequent glucuronide conjugation as
the major biotransformation process. This study was classified as
supplementary but upgradeable; the company has submitted data intended
to upgrade the study to acceptable and these data have been scheduled
for review.
4. Sub-chronic toxicity. i. In a 90-day rat feeding study the NOAEL
was 20.4 mg/kg/day for males and females. The LOAEL was 211.0 mg/kg/day
based on decreased weight gain in both sexes, clinical observations of
distended abdomens and reduced body size, and clinical pathology
findings attributable to reduced nutritional status.
ii. In a subchronic toxicity study in which azoxystrobin was
administered to dogs by capsule for 92 or 93 days, the NOAEL for both
males and females was 50 mg/kg/day. The LOAEL was 250 mg/kg/day, based
on treatment-related clinical observations and clinical chemistry
alterations at this dose.
iii. In a 21-day repeated-dose dermal rat study using azoxystrobin,
the NOAEL for both males and females was greater than or equal to 1,000
mg/kg/day (the highest dosing regimen); a LOAEL was therefore not
determined.
5. Chronic feeding toxicity and carcinogenicity. i. In a 2-year
feeding study in rats fed diets containing 0, 60, 300, and 750/1,500
ppm (males/females), the systemic toxicity NOAEL was 18.2 mg/kg/day for
males and 22.3 mg/kg/day for females. The systemic toxicity LOAEL for
males was 34 mg/kg/day, based on reduced body weights, food
consumption, and food efficiency; and bile duct lesions. The systemic
toxicity LOAEL for females was 117.1 mg/kg/day, based on reduced body
weights. There was no evidence of carcinogenic activity in this study.
ii. In a 1-year feeding study in dogs to which azoxystrobin was fed
by capsule at doses of 0, 3, 25, or 200 mg/kg/day, the NOAEL for both
males and females was 25 mg/kg/day and the LOAEL was 200 mg/kg/day for
both sexes, based on clinical observations, clinical chemistry changes,
and liver weight increases that were observed in both sexes.
iii. In a 2-year carcinogenicity feeding study in mice using dosing
concentrations of 0, 50, 300, or 2,000 ppm, the systemic toxicity NOAEL
was 37.5 mg/kg/day for both males and females. The systemic toxicity
LOAEL was 272.4 mg/kg/day for both sexes, based on reduced body weights
in both sexes at this dose. There was no evidence of carcinogenicity at
the dose levels tested.
According to the new proposed guidelines for Carcinogen Risk
Assessment (April, 1996), the appropriate descriptor for human
carcinogenic potential of azoxystrobin is ``Not Likely.'' The
appropriate subdescriptor is ``has been evaluated in at least two well
conducted studies in two appropriate species without demonstrating
carcinogenic effects.''
6. Developmental and reproductive toxicity. i. In a prenatal
development study in rats gavaged with azoxystrobin at dose levels of
0, 25, 100, or 300 mg/kg/day during days 7 through 16 of gestation,
lethality at the highest dose caused the discontinuation of dosing at
that level. The developmental NOAEL was greater than or equal to 100
mg/kg/
[[Page 13108]]
day and the developmental LOAEL was > 100 mg/kg/day because no
significant adverse developmental effects were observed. In this same
study, the maternal NOAEL was not established; the maternal LOAEL was
25 mg/kg/day, based on increased salivation.
ii. In a prenatal developmental study in rabbits gavaged with 0,
50, 150, or 500 mg/kg/day during days 8 through 20 of gestation, the
developmental NOAEL was 500 mg/kg/day and the developmental LOAEL was >
500 mg/kg/day because no treatment-related adverse effects on
development were seen. The maternal NOAEL was 150 mg/kg/day and the
maternal LOAEL was 500 mg/kg/day, based on decreased body weight gain.
iii. In a two-generation reproduction study, rats were fed 0, 60,
300, or 1,500 ppm of azoxystrobin. The reproductive NOAEL was 32.2 mg/
kg/day. The reproductive LOAEL was 165.4 mg/kg/day; reproductive
toxicity was demonstrated as treatment-related reductions in adjusted
pup body weights as observed in the F1a and F2a pups dosed at 1,500 ppm
(165.4 mg/kg/day).
B. Toxicological Endpoints
1. Acute toxicity. The Agency evaluated the existing toxicology
database for azoxystrobin and did not identify any acute dietary
endpoint because there were no effects of concern attributable to a
single dose (exposure) in oral toxicology studies including
developmental toxicity studies in the rat and rabbit and acute
neurotoxicity study in the rat. Therefore, this risk assessment is not
required.
2. Short- and intermediate-term toxicity. The Agency evaluated the
existing toxicology database for short-term and intermediate-term
dermal and inhalation exposure and determined that this risk assessment
is not required because no dermal or systemic effects were seen in the
repeated dose dermal study at the limit dose. The only registered
residential use for azoxystrobin is residential turf.
3. Chronic toxicity. EPA has established the Reference Dose (RfD)
for azoxystrobin at 0.18 mg/kg/day. This RfD is based on a NOAEL of
18.2 mg/kg/day from the rat chronic toxicity/carcinogenicity feeding
study. Effects observed at the LOAEL's (34 mg/kg/day for males, 117.1
mg/kg/day for females) included reduced body weights, food consumption
and efficiency. Males also had bile duct lesions. An uncertainty factor
of 100 was used to allow for interspecies sensitivity and intraspecies
variability. There was no evidence of increased susceptibility of
infants or children to azoxystrobin. Therefore, no additional
uncertainty factor to protect infants and children is needed at this
time.
4. Carcinogenicity. The Agency determined that azoxystrobin should
be classified as ``Not Likely'' to be a human carcinogen according to
the proposed revised Cancer Guidelines. This classification is based on
the lack of evidence of carcinogenicity in long-term rat and mouse
feeding studies.
C. Exposures and Risks
1. From food and feed uses. Permanent tolerances have been
established (40 CFR 180. 507(a)) for the combined residues of
azoxystrobin (methyl(E)-2(2-(6-(2-cyanophenoxy)pyrimidin-4-
yloxy)phenyl)-3-methoxyacrylate) and its Z isomer (methyl (Z)-2-(2-(6-
(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate)), in or on
the following raw agricultural commodities: pecans at 0.01 ppm, peanuts
at 0.01 ppm, peanut oil at 0.03 ppm, grapes at 1.0 ppm, bananas at 0.5
ppm, peaches at 0.80 ppm, tomatoes at 0.2 ppm, and tomato paste at 0.6
ppm. In addition, time-limited tolerances have been established for
crops, processed foods and animal commodities (40 CFR 180.507(b)) at
levels ranging from 0.006 ppm in milk to 20 ppm in rice hulls and
including cucurbits at 1.0 ppm, rice grain at 4 ppm, rice hulls at 20
ppm, rice straw at 10 ppm, and potatoes at 0.03 ppm. Risk assessments
were conducted by EPA to assess dietary exposures from azoxystrobin as
follows:
i. Acute exposure and risk. The Agency did not conduct an acute
risk assessment because no toxicological endpoint of concern was
identified during review of available data.
ii. Chronic exposure and risk. The Dietary Exposure Evaluation
Model (DEEM), a chronic exposure analysis, was used in conducting this
chronic dietary risk assessment. EPA has made very conservative
assumptions -- 100% of all commodities having azoxystrobin residues at
the level of the tolerance with the exception of raisins and grape
juice which are expected to result in an over estimation of human
dietary exposure. Thus, in making a safety determination for this
tolerance, the Agency is taking into account these conservative
exposure assessments. The following percentages of the RfD from dietary
exposure were calculated: U.S. population (48 states, all seasons), 2%;
all infants (< 1 year old), 7%; nursing infants (< 1 year old), 2%;
non-nursing infants (< 1 year old), 9%; children (1-6 years old), 5%;
children (7-12 years old), 3% and non-Hispanic (other than black or
white), 4%. The subgroups listed are infants/children and other
subgroups for which the percentage of the RfD occupied is greater than
the group U.S. population (48 states).
2. From drinking water. In the absence of reliable, available
monitoring data, EPA uses models to estimate concentrations of
pesticides in ground and surface water. For azoxystrobin, modeling was
used to estimate surface water concentrations because of very limited
surface water monitoring data. However, EPA does not use these model
estimates to quantify risk. Currently, EPA uses drinking water levels
of comparison (DWLOC's) as a surrogate to capture risk associated with
exposure to pesticides in drinking water. A DWLOC is the concentration
of a pesticide in drinking water that would be acceptable as an upper
limit in light of total aggregate exposure to that pesticide from food,
water, and residential uses. A DWLOC will vary depending on the residue
level in foods, the toxicity endpoint and with drinking water
consumption patterns and body weight for specific subpopulations. EPA
believes model estimates to be overestimations of concentrations of
azoxystrobin expected in drinking water. Azoxystrobin is moderately
persistent in soil in the absence of light and one of its metabolites
is potentially moderately mobile in coarse textured soils. The
potential mobility and persistence of some degradates based on batch
equilibrium studies, aerobic soil metabolism and some field dissipation
studies are similar to pesticides with a potential to leach into ground
water under some conditions. There is no established Maximum
Contaminant Level for residues of azoxystrobin in drinking water. No
health advisory levels for azoxystrobin in drinking water have been
established.
i. Acute exposure and risk. An assessment was not conducted because
no toxicological end-point of concern was identified.
ii. Chronic exposure and risk. Based on the chronic dietary (food)
exposure estimates, chronic DWLOC's for azoxystrobin were calculated
and are summarized as follows: U. S. Population (48 states) 6,200
g/L; females (13+) (using the highest TMRC for the 5 subgroups
of females), 5,200 g/L; infants/children (using the highest
TMRC for the 5 subgroups of infants/children) 1,600 g/L and
non-Hispanic (other than black or white), 6,100 g/L. The
highest EEC for azoxystrobin in surface water is from the application
of azoxystrobin on grapes (39 g/L) and is substantially lower
than the DWLOCs
[[Page 13109]]
calculated. Therefore, chronic exposure to azoxystrobin residues in
drinking water does not exceed EPA's level of concern.
3. From non-dietary exposure. The only registered indoor/outdoor
residential use for azoxystrobin is residential turf. The Agency
evaluated the existing toxicology database and determined that there
are no toxicological end points of concern.
4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider ``available information'' concerning the cumulative effects of
a particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.''
EPA does not have, at this time, available data to determine
whether azoxystrobin has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
azoxystrobin 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 azoxystrobin 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 final rule
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. There were no effects of concern attributable to a
single dose (exposure) in oral toxicological studies including
developmental toxicity studies in rat and rabbit and an acute
neurotoxicity study in rats. Accordingly, EPA concludes that
azoxystrobin does not pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this
unit, EPA has concluded that aggregate exposure to azoxystrobin from
food will utilize from 2% to 9% of the RfD for the U.S. population. The
major identifiable subgroup with the highest aggregate exposure is non-
nursing infants (<1 year old). EPA generally has no concern for
exposures below 100% of the RfD because the RfD represents the level at
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health. Based on the chronic (food
only) exposure, chronic DWLOC's were calculated. The lowest DWLOC of
1,600 g/L was for infants/children (using the highest TMRC for
the five subgroups of infants/children listed in the DEEM analysis).
The highest Estimated Environmental Concentration (EEC) in surface
water is from application to grapes (39 g/L) and is
substantially lower than the calculated DWLOC. The EEC's as a result of
application to the proposed uses are no higher than those calculated
for grapes. Therefore chronic exposure in drinking water does not
exceed the Agency's level of concern.
3. Short- and intermediate-term risk. Short- and intermediate-term
risk. No dermal or systemic effects were seen in the repeated dose
dermal study at the limit dose. The only indoor or outdoor residential
use currently registered for azoxystrobin is residential turf. EPA
concluded that azoxystrobin does not pose a short- or intermediate-term
risk.
4. Aggregate cancer risk for U.S. population. The Agency determined
that azoxystrobin should be classified as ``Not Likely'' to be a human
carcinogen according to the proposed revised Cancer Guidelines because
there was no evidence of carcinogenicity in valid chronic toxicity
studies using two species of mammals. The Agency has therefore
concluded that azoxystrobin does not pose a cancer risk.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to azoxystrobin residues as a result of current
use patterns.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children--i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of azoxystrobin, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure during gestation.
Reproduction studies provide information relating to effects from
exposure to the pesticide on the reproductive capability of mating
animals and data on systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre- and post-natal toxicity and the
completeness of the database unless EPA determines that a different
margin of safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a margin of exposure (MOE) analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. EPA believes that reliable data support
using the standard MOE and uncertainty factor (usually 100 for combined
inter- and intra species variability) and not the additional tenfold
MOE/uncertainty factor when EPA has a complete data base under existing
guidelines and when the severity of the effect in infants or children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard MOE/safety factor.
ii. Developmental toxicity studies-- a. Rabbit. In the
developmental toxicity study in rabbits, developmental NOAEL was 500
mg/kg/day, at the highest dose tested (HDT). Because there were no
treatment-related effects, the developmental LOAEL was greater than 500
mg/kg/day. The maternal NOAEL was 150 mg/kg/day. The maternal LOAEL of
500 mg/kg/day was based on decreased body weight gain during dosing.
b. Rat. In the developmental toxicity study in rats, the maternal
(systemic) NOAEL was not established. The maternal LOAEL of 25 mg/kg/
day at the lowest dose tested (LDT) was based on increased salivation.
The developmental (fetal) NOAEL was 100 mg/kg/day (HDT).
iii. Reproductive toxicity study. Rat. In the 2-generation
reproductive toxicity study in rats, the parental (systemic) NOAEL was
32.3 mg/kg/day. The parental LOAEL of 165.4 mg/kg/day was based on
decreased body weights in males and females, decreased food consumption
and increased adjusted liver weights in females, and cholangitis. The
reproductive NOAEL was 32.3 mg/kg/day. The reproductive LOAEL of 165.4
mg/kg/day was based on increased weanling liver weights and decreased
body weights for pups of both generations.
iv. Pre- and post-natal sensitivity. The pre- and post-natal
toxicology data base for azoxystrobin is complete with respect to
current toxicological data requirements. The results of these studies
indicate that infants and children are no more sensitive to exposure
than adults, based on the results of the rat and rabbit developmental
toxicity studies and the 2-generation reproductive toxicity study in
rats. There are no developmental effects in the rat and rabbit
developmental studies and the effects
[[Page 13110]]
observed in the offspring in the reproduction study occur at the same
dose levels in which toxicity was observed in the parents. The effects
in the young are not more severe than those observed with the parents
(decreased body weights in both parents and pups).
v. Conclusion. There is a complete toxicity database for
azoxystrobin and exposure data are complete or are estimated based on
data that reasonably account for potential exposures. Accordingly, EPA
has determined that the standard margin of safety of infants and
children and the additional tenfold safety factor can be removed.
2. Chronic risk. Using the exposure assumptions described in this
unit, EPA has concluded that aggregate exposure to azoxystrobin from
food will utilize from 2% to 9% of the RfD for infants and children.
EPA generally has no concern for exposures below 100% of the RfD
because the RfD represents the level at or below which daily aggregate
dietary exposure over a lifetime will not pose appreciable risks to
human health. Despite the potential for exposure to azoxystrobin in
drinking water and from non-dietary, non-occupational exposure, EPA
does not expect the aggregate exposure to exceed 100% of the RfD.
3. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to azoxystrobin
residues.
III. Other Considerations
A. Metabolism In Plants and Animals
The qualitative nature of the residue in plants is adequately
understood. A grape metabolism study was evaluated by the Agency in
December, 1995 and it was determined that the residues of concern in
grapes were the parent and its Z isomer. In peanut and wheat metabolism
studies the major residues were also azoxystrobin and its Z isomer.
Azoxystrobin does not accumulate in crop seeds or fruits. Metabolism of
azoxystrobin in plants is complex, with more than 15 metabolites
identified. However, these metabolites are present at low levels,
typically much less than 5% of the total radioactive residue level.
Based on parent being the predominant residue in the grape, wheat and
peanut metabolism studies, the Agency concludes that the residues of
concern in all directly treated crops are the parent and its Z isomer.
The nature of the residue in animals is adequately understood. The
Agency has determined that the residue of concern in livestock is
parent azoxystrobin only. This determination was based on the results
of metabolism studies performed on goats and poultry. The goat
metabolism study was reviewed in conjunction with PP 5F4541. The
poultry metabolism study was reviewed in conjunction with PP 6F4762.
Azoxystrobin and one metabolite (compound 28) were identified in egg
yolk and compound 28 alone was found in liver. Residues in extracts of
egg whites, muscle, and skin with underlying peritoneal fat were less
than 0.01 ppm. Residues of azoxystrobin were less than 0.01 ppm at a
feeding level of 1.4x in the radiolabeled study and also less than 0.01
ppm in a feeding study at 60 ppm (about 7x). As a result, there is no
reasonable expectation of finite residues of azoxystrobin in poultry
commodities.
The registrant submitted three analytical methods for the analysis
of the subject commodities.
1. The first method, RAM 243, is a gas chromatography with
nitrogen-phosphorus detection (GC/NPD) method which can be used for the
analysis of cereals, processed cereals, dried beans, peas, leafy crops,
bananas, soft fruits, processed soft fruits, citrus, fruiting
vegetables, root crops, stone fruits, wine, and citrus juice. This
method has been reviewed and validated by the Agency, and will be
submitted to the Food and Drug Administration (FDA) for inclusion in
PAM II.
2. The second method, RAM 260, is a GC/NPD method for the analysis
of azoxystrobin and its Z isomer in crops of high lipid content. The
registrant has used it for analysis of peanut kernel and hull,
processed peanut, pecan kernel, coffee bean, citrus skin, and canola
oil. This method has been validated by the Agency and will be submitted
to the FDA for inclusion in PAM II.
3. The third method, RAM 255, uses gas chromatography with
thermionic detection, nitrogen mode, for analysis of animal
commodities. It has been validated by the Agency for analysis of milk
and animal tissues. The laboratory will issue a written report shortly
and the method will be submitted to FDA for inclusion in PAM II.
Therefore, adequate analytical methodology is available to enforce
the tolerance expression. The method may be requested from: Calvin
Furlow, PIRIB, IRSD (7502C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office and telephone number: Rm. 101FF, Crystal Mall #2, 1921 Jefferson
Davis Hwy., Arlington, VA, (703) 305-5229.
B. Magnitude of Residues
Azoxystrobin has been subjected to FDA's multiresidue protocols. It
could not be recovered through application of any protocol. Residues of
azoxystrobin and its Z isomer are not expected to exceed the proposed
tolerance levels and the submitted data support tolerance levels for
combined residues of azoxystrobin (methyl(E)-2-(2-(6-(2-
cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate) and its Z
isomer (methyl(Z)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-
methoxyacrylate) in or on almond hulls at 4.0 ppm, aspirated grain
fractions at 10 ppm, bananas (pre-harvest and postharvest) at 2.0 ppm
(of which not more than 0.1 ppm is contained in the pulp), canola at
1.0 ppm, cucurbits at 0.3 ppm, peanut hay at 2.0 ppm, pistachios at
0.01 ppm, potatoes at 0.03 ppm, rice grain at 5.0 ppm, rice straw at 12
ppm, rice hulls at 20 ppm, stone fruits at 1.5 ppm, tree nuts at 0.010
ppm, wheat grain at 0.10 ppm, wheat bran at 0.20 ppm, wheat hay at 15
ppm, wheat straw at 4.0 ppm, and for the residues of azoxystrobin
(only) in fat of cattle, goats, hogs, horses, and sheep at 0.010 ppm;
meat of cattle, goats, hogs, horses, and sheep at 0.01 ppm; meat
byproducts of cattle, goats, hogs, horses, and sheep at 0.010 ppm; and
milk at 0.006 ppm. The submitted residue data support a tolerance level
of 2.0 ppm for residues of azoxystrobin in or on whole bananas and a
tolerance level of 0.1 ppm in or on banana pulp. The tolerance for
bananas must be listed as 2.0 ppm for the combined residues of
azoxystrobin and its Z isomer in/on bananas (whole fruit) and residues
in banana pulp must not exceed 0.1 ppm.
C. International Residue Limits
There are no Codex, Canadian or Mexican Maximum Residue Limits
(MRL) established for azoxystrobin for bananas, curcurbits, potatoes,
or stone fruits.
D. Rotational Crop Restrictions
Rotational crop data were previously submitted. Based on this
information, a 45-day plantback interval is appropriate for all crops
other than those having tolerances for azoxystrobin and its Z isomer.
IV. Conclusion
Therefore, tolerances are established for combined residues of
azoxystrobin (methyl(E)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-
yloxy)phenyl)-3-methoxyacrylate) and its Z isomer (methyl(Z)-2-(2-(6-
(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate) in or
[[Page 13111]]
on almond hulls at 4.0 ppm, aspirated grain fractions at 10 ppm,
bananas (pre-harvest and postharvest) at 2.0 ppm (of which not more
than 0.1 ppm is contained in the pulp), canola at 1.0 ppm, cucurbits at
0.3 ppm, peanut hay at 2.0 ppm, pistachios at 0.01 ppm, potatoes at
0.03 ppm, rice grain at 5.0 ppm, rice straw at 12 ppm, rice hulls at 20
ppm, stone fruits at 1.5 ppm, tree nuts at 0.010 ppm, wheat grain at
0.10 ppm, wheat bran at 0.20 ppm, wheat hay at 15 ppm, wheat straw at
4.0 ppm, and for the residues of azoxystrobin (only) in fat of cattle,
goats, hogs, horses, and sheep at 0.010 ppm; meat of cattle, goats,
hogs, horses, and sheep at 0.01 ppm; meat byproducts of cattle, goats,
hogs, horses, and sheep at 0.010 ppm; and milk at 0.006 ppm.
V. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation as was provided in
the old section 408 and in section 409. However, the period for filing
objections is 60 days, rather than 30 days. EPA currently has
procedural regulations which govern the submission of objections and
hearing requests. These regulations will require some modification to
reflect the new law. However, until those modifications can be made,
EPA will continue to use those procedural regulations with appropriate
adjustments to reflect the new law.
Any person may, by May 17, 1999, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given under the ``ADDRESSES'' section (40
CFR 178.20). A copy of the objections and/or hearing requests filed
with the Hearing Clerk should be submitted to the OPP docket for this
regulation. The objections submitted must specify the provisions of the
regulation deemed objectionable and the grounds for the objections (40
CFR 178.25). Each objection must be accompanied by the fee prescribed
by 40 CFR 180.33(i). EPA is authorized to waive any fee requirement
``when in the judgement of the Administrator such a waiver or refund is
equitable and not contrary to the purpose of this subsection.'' For
additional information regarding tolerance objection fee waivers,
contact James Tompkins, Registration Division (7505C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location, telephone number, and e-mail
address: Rm. 239, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, (703) 305-5697, [email protected]. Requests for
waiver of tolerance objection fees should be sent to James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460.
If a hearing is requested, the objections must include a statement
of the factual issues on which a hearing is requested, the requestor's
contentions on such issues, and a summary of any evidence relied upon
by the requestor (40 CFR 178.27). A request for a hearing will be
granted if the Administrator determines that the material submitted
shows the following: There is genuine and substantial issue of fact;
there is a reasonable possibility that available evidence identified by
the requestor would, if established, resolve one or more of such issues
in favor of the requestor, taking into account uncontested claims or
facts to the contrary; and resolution of the factual issues in the
manner sought by the requestor would be adequate to justify the action
requested (40 CFR 178.32). 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.
VI. Public Record and Electronic Submissions
EPA has established a record for this regulation under docket
control number [OPP-300801] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
Objections and hearing requests may be sent by e-mail directly to
EPA at:
[email protected].
E-mailed objections and hearing requests must be submitted as an
ASCII file avoiding the use of special characters and any form of
encryption.
The official record for this regulation, as well as the public
version, as described in this unit will be kept in paper form.
Accordingly, EPA will transfer any copies of objections and hearing
requests received electronically into printed, paper form as they are
received and will place the paper copies in the official record which
will also include all comments submitted directly in writing. The
official record is the paper record maintained at the Virginia address
in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
This final rule establishes a tolerance under section 408(d) of the
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). 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) (Pub. L. 104-4). Nor does
it require any prior consultation as specified by Executive Order
12875, entitled Enhancing the Intergovernmental Partnership (58 FR
58093, October 28, 1993), or special considerations as required by
Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), or require OMB review in
accordance with Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997).
In addition, since tolerances and exemptions that are established
on the basis of a petition under FFDCA section 408(d), such as the
tolerances 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. Nevertheless, the Agency
previously assessed whether establishing tolerances, exemptions from
tolerances, raising tolerance levels or expanding exemptions might
adversely impact small entities and concluded, as a generic matter,
that there is no adverse economic impact. The factual basis for
[[Page 13112]]
the Agency's generic certification for tolerance actions published on
May 4, 1981 (46 FR 24950), and was provided to the Chief Counsel for
Advocacy of the Small Business Administration.
B. Executive Order 12875
Under Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may
not issue a regulation that is not required by statute and that creates
a mandate upon a State, local or tribal government, unless the Federal
government provides the funds necessary to pay the direct compliance
costs incurred by those governments. If the mandate is unfunded, EPA
must provide to OMB a description of the extent of EPA's prior
consultation with representatives of affected State, local, and tribal
governments, the nature of their concerns, copies of any written
communications from the governments, and a statement supporting the
need to issue the regulation. In addition, Executive Order 12875
requires EPA to develop an effective process permitting elected
officials and other representatives of State, local, and tribal
governments ``to provide meaningful and timely input in the development
of regulatory proposals containing significant unfunded mandates.''
Today's rule does not create an unfunded Federal mandate on State,
local, or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.
C. Executive Order 13084
Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19, 1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide OMB, in a separately identified
section of the preamble to the rule, a description of the extent of
EPA's prior consultation with representatives of affected tribal
governments, a summary of the nature of their concerns, and a statement
supporting the need to issue the regulation. In addition, Executive
Order 13084 requires EPA to develop an effective process permitting
elected officials and other representatives of Indian tribal
governments ``to provide meaningful and timely input in the development
of regulatory policies on matters that significantly or uniquely affect
their communities.''
Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the Agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and 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 the rule in the Federal Register. This 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: March 5, 1999.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
Sec. 180.507 [Amended]
2. In Sec. 180.507, paragraph (a)(1), by removing from the table
the commodities ``Bananas'', and ``Peaches''.
3. Section 180.507 is further amended in paragraph (a)(1) by
changing the words ``raw agricultural commodities'' to read ``food
commodities'', by alphabetically adding the following commodities to
the table in paragraph (a)(1), by redesignating paragraph (a)(2) as
paragraph (a)(3), and by adding a new paragraph (a)(2) to read as
follows:
Sec. 180.507 Azoxystrobin; tolerances for residues General.
(a) General. (1) * * *
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
Almond hulls.............................. 4.0
Aspirated grain fractions................. 10
Bananas (pre-harvest and post harvest).... 2.0 (of which not more than
0.1 is contained in the
pulp)
Canola.................................... 1.0
Cucurbits................................. 0.3
* * * * *
Peanut hay................................ 2.0
Pistachios................................ 0.010
Potatoes.................................. 0.03
Rice grain................................ 5.0
Rice hulls................................ 20
Rice straw................................ 12
Stone fruits.............................. 1.5
* * * * *
Tree nuts................................. 0.010
Wheat bran................................ 0.20
Wheat grain............................... 0.10
Wheat hay................................. 15
Wheat straw............................... 4.0
------------------------------------------------------------------------
(2) Tolerances are established for residues of the fungicide,
azoxystrobin [methyl(E)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-
yloxy)phenyl)-3-methoxyacrylate] in or on the following food
commodities.
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Cattle, fat................................................ 0.010
Cattle, meat............................................... 0.01
Cattle, meat byproducts.................................... 0.010
Goats, fat................................................. 0.010
Goats, meat................................................ 0.01
Goats, meat byproducts..................................... 0.010
Hogs, fat.................................................. 0.010
Hogs, meat................................................. 0.01
Hogs, meat byproducts...................................... 0.010
Horses, fat................................................ 0.010
Horses, meat............................................... 0.01
Horses, meat byproducts.................................... 0.010
Milk....................................................... 0.006
Sheep, fat................................................. 0.010
Sheep, meat................................................ 0.01
Sheep, meat byproducts..................................... 0.010
------------------------------------------------------------------------
* * * * *
[FR Doc. 99-6387 Filed 3-16-99; 8:45 am]
BILLING CODE 6560-50-F