[Federal Register Volume 63, Number 200 (Friday, October 16, 1998)]
[Rules and Regulations]
[Pages 55533-55540]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-27835]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300744; FRL-6037-8]
RIN 2070-AB78
Azoxystrobin; Time-limited Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a time-limited tolerance for the
combined residues of azoxystrobin [methyl(E)-2-(2-(6-(2-
cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate] and
[[Page 55534]]
its Z isomer in or on potatoes. This action is in response to the
combined efforts of Wisconsin potato growers, University extension
specialists, Zeneca Ag Products, and EPA to generate the information
necessary for registration of the reduced risk fungicide, azoxystrobin,
for use against the pests late blight and early blight of potatoes.
This regulation establishes a maximum permissible level of 0.03 parts
per million (ppm) for residues of azoxystrobin and its Z isomer in this
food commodity pursuant to section 408(l)(6) of the Federal Food, Drug,
and Cosmetic Act, as amended by the Food Quality Protection Act of
1996. The tolerance will expire and is revoked on October 18, 1999.
DATES: This regulation is effective October 16, 1998. Objections and
requests for hearings must be received by EPA on or before December 15,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300744], 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-300744], 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 also 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-300744]. 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: John Bazuin, Jr.,
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: Crystal Mall #2,
1921 Jefferson Davis Hwy., Arlington, VA, (703) 305-7381, e-mail:
[email protected].
SUPPLEMENTARY INFORMATION: EPA, in cooperation with Wisconsin potato
growers, University extension specialists, and Zeneca Ag Products,
Inc., pursuant to sections 408(e) and (r) of the Federal Food, Drug,
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e) and (r), is establishing a
tolerance for combined residues of the fungicide azoxystrobin and its Z
isomer, in or on potatoes at 0.03 part per million (ppm). This
tolerance will expire and is revoked on October 18, 1999. EPA will
publish a document in the Federal Register to remove the revoked
tolerance from the Code of Federal Regulations. The only comments
received concerning the proposed rule were from the United States
Department of Agriculture, which requested some modifications to the
summary (these changes were made) and indicated their feeling that the
comment period of 15 days was very short (the reasons behind the use of
such a short comment period were explained in the proposed rule)(63 FR
48664, September 11, 1998)(FRL-6026-8)).
I. Background and Statutory Authority
The Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-170)
was signed into law August 3, 1996. FQPA amends both the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 301 et seq., and the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. 136 et
seq. The FQPA amendments went into effect immediately. Among other
things, FQPA amends FFDCA to bring all EPA pesticide tolerance-setting
activities under a new section 408 with a new safety standard and new
procedures. These activities are described below and discussed in
greater detail in the final rule establishing the time-limited
tolerance associated with the emergency exemption for use of
propiconazole on sorghum (61 FR 58135, November 13, 1996) (FRL-5572-9).
New section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) 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. . . .''
Section 5 of FIFRA authorizes EPA to issue an experimental use
permit for a pesticide. This provision was not amended by FQPA. EPA has
established regulations governing such experimental use permits in 40
CFR part 172. Section 408(r) of FFDCA authorizes EPA to issue time-
limited tolerances for pesticide residues resulting from FIFRA
experimental use permits.
II. Risk Assessment and Statutory Findings
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings. The Agency has determined that
azoxystrobin is a reduced risk pesticide for use on potatoes.
Consistent with section 408(b)(2)(D), 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 a time-limited tolerance for
combined residues of azoxystrobin and its Z isomer on potatoes at 0.03
ppm. EPA's assessment of the dietary and other exposures and risks
associated with establishing the tolerance follows.
[[Page 55535]]
A. Toxicity
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 are
discussed below.
1. Threshold and non-threshold effects. For many animal studies, a
dose response relationship can be determined, which provides a dose
that causes adverse effects (threshold effects) and doses causing no
observed adverse effects (the ``no-observed adverse effect level'' or
``NOAEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOAEL
from the study with the lowest NOAEL by an uncertainty factor (usually
100 or more) to determine the Reference Dose (RfD). The RfD is a level
at or below which daily aggregate exposure over a lifetime will not
pose appreciable risks to human health. An uncertainty factor
(sometimes called a ``safety factor'') of 100 is commonly used since it
is assumed that people may be up to 10 times more sensitive to
pesticides than the test animals, and that one person or subgroup of
the population (such as infants and children) could be up to 10 times
more sensitive to a pesticide than another. In addition, EPA assesses
the potential risks to infants and children based on the weight of the
evidence of the toxicology studies and determines whether an additional
uncertainty factor is warranted. Thus, an aggregate daily exposure to a
pesticide residue at or below the RfD (expressed as 100% or less of the
RfD) is generally considered acceptable by EPA. EPA generally uses the
RfD to evaluate the chronic risks posed by pesticide exposure. For
shorter term risks, EPA calculates a margin of exposure (MOE) by
dividing the estimated human exposure into the NOAEL from the
appropriate animal study. Commonly, EPA finds MOEs lower than 100 to be
unacceptable. This 100-fold MOE is based on the same rationale as the
100-fold uncertainty factor.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short-term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or MOE calculation based on the appropriate NOAEL) will
be carried out based on the nature of the carcinogenic response and the
Agency's knowledge of its mode of action.
2. Differences in toxic effect due to exposure duration. The
toxicological effects of a pesticide can vary with different exposure
durations. EPA considers the entire toxicity data base, and based on
the effects seen for different durations and routes of exposure,
determines which risk assessments should be done to assure that the
public is adequately protected from any pesticide exposure scenario.
Both short and long durations of exposure are always considered.
Typically, risk assessments include ``acute,'' ``short-term,''
``intermediate term,'' and ``chronic'' risks. These assessments are
defined by the Agency as follows.
Acute risk, by the Agency's definition, results from 1-day
consumption of food and water, and reflects toxicity which could be
expressed following a single oral exposure to the pesticide residues.
High end exposure to food and water residues are typically assumed.
Short-term risk results from exposure to the pesticide for a period
of 1-7 days, and therefore overlaps with the acute risk assessment.
Historically, this risk assessment was intended to address primarily
dermal and inhalation exposure which could result, for example, from
residential pesticide applications. However, since enaction of FQPA,
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from
food, water, and residential uses when reliable data are available. In
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all
three sources are not typically added because of the very low
probability of this occurring in most cases, and because the other
conservative assumptions built into the assessment assure adequate
protection of public health. However, for cases in which high-end
exposure can reasonably be expected from multiple sources (e.g.
frequent and widespread homeowner use in a specific geographical area),
multiple high-end risks will be aggregated and presented as part of the
comprehensive risk assessment/characterization. Since the toxicological
endpoint considered in this assessment reflects exposure over a period
of at least 7 days, an additional degree of conservatism is built into
the assessment; i.e., the risk assessment nominally covers 1-7 days
exposure, and the toxicological endpoint/NOAEL is selected to be
adequate for at least 7 days of exposure. (Toxicity results at lower
levels when the dosing duration is increased.)
Intermediate-term risk results from exposure for 7 days to several
months. This assessment is handled in a manner similar to the short-
term risk assessment.
Chronic risk assessment describes risk which could result from
several months to a lifetime of exposure. For this assessment, risks
are aggregated considering average exposure from all sources for
representative population subgroups including infants and children.
B. Aggregate Exposure
In examining aggregate exposure, FFDCA section 408 requires that
EPA take into account available and reliable information concerning
exposure from the pesticide residue in the food in question, residues
in other foods for which there are tolerances, residues in groundwater
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses). Dietary exposure to
residues of a pesticide in a food commodity are estimated by
multiplying the average daily consumption of the food forms of that
commodity by the tolerance level or the anticipated pesticide residue
level. The Theoretical Maximum Residue Contribution (TMRC) is an
estimate of the level of residues consumed daily if each food item
contained pesticide residues equal to the tolerance. In evaluating food
exposures, EPA takes into account varying consumption patterns of major
identifiable subgroups of consumers, including infants and children.
The TMRC is a ``worst case'' estimate since it is based on the
assumptions that food contains pesticide residues at the tolerance
level and that 100% of the crop is treated by pesticides that have
established tolerances. If the TMRC exceeds the RfD or poses a lifetime
cancer risk that is greater than approximately one in a million, EPA
attempts to derive a more accurate exposure estimate for the pesticide
by evaluating additional types of information (anticipated residue data
and/or percent of crop treated data) which show, generally, that
pesticide residues in most foods when they are
[[Page 55536]]
eaten are well below established tolerances.
Percent of crop treated estimates are derived from federal and
private market survey data. Typically, a range of estimates are
supplied and the upper end of this range is assumed for the exposure
assessment. By using this upper end estimate of percent of crop
treated, the Agency is reasonably certain that exposure is not
understated for any significant subpopulation group. Further, regional
consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations
including several regional groups, to pesticide residues. For this
pesticide, the most highly exposed population subgroup (non-nursing
infants (<1 year old)) was not regionally based.
III. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), 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 a time-limited tolerance for 12
months for combined residues of azoxystrobin and its Z isomer on
potatoes at 0.03 ppm. EPA's assessment of the dietary exposures and
risks associated with establishing the tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also 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 and The Agency's selection of
toxicological endpoints upon which to assess risk caused by
azoxystrobin are discussed below.
Both permanent and time-limited tolerances have been established
(40 CFR 180.507) for the combined residues of azoxystrobin and its Z
isomer, in or on a variety of raw agricultural commodities. Permanent
tolerances have been established for bananas, grapes, peaches, peanuts,
pecans, and tomatoes. Time-limited tolerances have been established for
the fat, liver, and meat of cattle, goats, hogs, horses, poultry, and
sheep; kidney of cattle; eggs; milk; cucurbits; parsley; rice; and
watercress. The time-limited tolerances stem from the issuance of
several FIFRA section 18 emergency exemptions for the use of
azoxystrobin. The risk assessments were conducted by EPA to assess
dietary exposures and risks from azoxystrobin as follows:
1. Acute toxicity. The Agency evaluated the existing toxicology
database for azoxystrobin. No acute dietary endpoint was identified, no
developmental toxicity was observed in the rabbit and rat studies
reviewed, and no primary neurotoxicity was seen in the acute
neurotoxicity study. Therefore, no risk has been identified for this
scenario and a risk assessment is not needed.
2. Short- and intermediate-term toxicity. The Agency evaluated the
existing toxicology database for short- and intermediate-term dermal
and inhalation exposure and determined that this risk assessment is
also not required. In a 21-day dermal toxicity study the NOAEL was
1,000 mg/kg/day at the highest dose tested (Acute inhalation toxicity
category III).
3. Chronic toxicity. EPA has established the RfD for azoxystrobin
at 0.18 milligrams/kilogram/day (mg/kg/day). This RfD is based on on a
chronic toxicity study in rats with a NOAEL of 18.2 mg/kg/day. The
endpoint effects were reduced body weights and bile duct lesions at the
lowest effect level (LEL) of 34 mg/kg/day. An Uncertainty Factor (UF)
of 100 was used to account for both the interspecies extrapolation and
the intraspecies variability.
4. Carcinogenicity. Carcinogenicity testing of azoxystrobin in two
appropriate species of mammals revealed no evidence that this fungicide
is carcinogenic. Therefore, EPA classifies azoxystrobin as ``not
likely'' to be a human carcinogen in line with the proposed revised
Cancer Guidelines.
B. 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 and its Z isomer, in or on a variety of raw agricultural
commodities at levels ranging from 0.01 ppm in pecans to 1.0 ppm in
grapes. In addition, time-limited tolerances have been established (40
CFR 180.507(b), at levels ranging from 0.006 ppm in milk to 20 ppm in
rice hulls, in conjunction with section 18 requests. Risk assessments
were conducted by EPA to assess dietary exposures and risks from
azoxystrobin as follows:
i. Acute exposure and risk. 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 1 day or single exposure. The Agency did not conduct an acute risk
assessment because no toxicological endpoint of concern was identified
during review of available data.
ii. Short- and intermediate-term exposure and risk. Short- and
intermediate-term risk assessments are performed for a food-use
pesticide if a toxicology study has indicated the possibility of an
effect of concern as a result of an exposure of 1 day to several
months. The Agency did conduct such an assessment because no
toxicological endpoint of concern was identified.
iii. Chronic exposure and risk. In conducting this chronic dietary
risk assessment, the Agency has made very conservative assumptions --
100% of potatoes and all other commodities having azoxystrobin
tolerances will contain azoxystrobin residues and those residues would
be at the level of the tolerance -- which result in an overestimation
of human dietary exposure. Thus, in making a safety determination for
this tolerance, HED is taking into account this conservative exposure
assessment.The existing azoxystrobin tolerances (published, pending,
and including the necessary section 18 tolerance(s)) result in a
Theoretical Maximum Residue Contribution (TMRC) that is equivalent to
the following percentages of the RfD:
------------------------------------------------------------------------
TMRC (mg/kg/
Population Sub-Group day) Percent RFD
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U.S. Population (48 States)................... 0.003 1.8
Nursing Infants (<1 year old)................. 0.004 2
Non-Nursing Infants (<1 year old)............. 0.011 8
Children (1-6 years old)...................... 0.007 4
Children (7-12 years old)..................... 0.004 2
Hispanics..................................... 0.004 2
Non-Hispanics Others.......................... 0.005 3
U.S. Population (summer season)............... 0.003 2
U.S. Population (Northeast region)............ 0.003 2
U.S. Population (Western region).............. 0.003 2
U.S. Population (Pacific region).............. 0.003 2
Females (13+, nursing)........................ 0.003 2
Females (13-19, not pregnant or nursing)...... 0.002 1
------------------------------------------------------------------------
[[Page 55537]]
Neither the U.S. population as a whole nor any of the subgroups
whose food consumption patterns were analyzed for dietary exposure and
risk to azoxystrobin reached even one-twelfth of the RfD under these
assumed theoretical maximum exposures to azoxystrobin for all
published, pending, and proposed tolerances. Moreover, real-world
exposure is likely to be substantially lower than this.
2. From drinking water. 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 acute risk assessment was not
appropriate since no toxicological endpoint of concern was identified
for this scenario during review of the available data.
ii. Short- and intermediate-term toxicity. A short- and
intermediate-term risk assessment was not appropriate since no
toxicological endpoint of concern was identified for this scenario
during review of the available data.
iii. Chronic exposure and risk. Based on the chronic dietary (food)
exposure estimates, chronic drinking water levels of concern (DWLOC)
for azoxystrobin were calculated and are summarized in Table 1.
Estimated environmental concentrations (EECs) using generic expected
environmental concentration modeling (GENEEC) for azoxystrobin on
bananas, grapes, peaches, peanuts, pecans, tomatoes, and wheat are
listed in the SWAT Team Second Interim Report (6/20/97). 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 drinking water levels of concern (DWLOCs) calculated.
Therefore, chronic exposure to azoxystrobin residues in drinking water
do not exceed the Agency's level of concern.
Table 1.-- Drinking Water Levels of Concern
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TMRC Food Max Water
Population Subgroup RfD(mg/kg/day) Exposure (mg/kg/ Exposure (mg/kg/ DWLOC 2,3,4
day) day)1 (g/L)
----------------------------------------------------------------------------------------------------------------
US Population (48 States)........... 0.18 0.0027 0.178 6200
Females (13 + years old, not
pregnant or nursing)............... 0.18 0.0019 0.178 5300
Non-nursing Infants (< 1 year old).. 0.18 0.0113 0.169 1680
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\1\ Maximum Water Exposure (mg/kg/day) = RfD (mg/kg/day) - TMRC from DRES (mg/kg/day)
\2\ DWLOC(g/L) = Max water exposure (mg/kg/day) * body wt (kg) /(10-3 mg/g)*water consumed
daily (L/day)
\3\ HED Default body wts for males, females, and children are 70 kg, 60 kg, and 10 kg respectively.
\4\ HED Default Daily Drinking Rates are 2 L/Day for Adults and 1 L/Day for children
3. From non-dietary exposure. Azoxystrobin is not currently
registered for use on residential non-food sites.
4. Cumulative exposure to substances with common mechanism of
toxicity. Azoxystrobin is related to the naturally occurring
strobilurins. The Agency has recently registered another strobilurin
type pesticide for a nonfood use. 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.'' The Agency
believes that ``available information'' in this context might include
not only toxicity, chemistry, and exposure data but also scientific
policies and methodologies for understanding common mechanisms of
toxicity and conducting cumulative risk assessments. For most
pesticides, although the Agency has some information in its files that
may turn out to be helpful in eventually determining whether a
pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have the methodologies to resolve
the complex scientific issues concerning common mechanism of toxicity
in a meaningful way. EPA has begun a pilot process to study this issue
further through the examination of particular classes of pesticides.
The Agency hopes that the results of this pilot process will increase
the Agency's scientific understanding of this question such that EPA
will be able to develop and apply scientific principles for better
determining which chemicals have a common mechanism of toxicity and
evaluating the cumulative effects of such chemicals. The Agency
anticipates, however, that even as its understanding of the science of
common mechanisms increases, decisions on specific classes of chemicals
will be heavily dependent on chemical specific data, much of which may
not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically dissimilar to existing chemical substances (in which
case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances) and
pesticides that produce a common toxic metabolite (in which case common
mechanism of activity will be assumed).
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. For the purposes of this tolerance action, therefore, EPA
has not assumed that azoxystrobin has a common mechanism of toxicity
with other substances.
C. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. This risk assessment is not necessary since no acute
toxicological end-point of concern was identified for this exposure
scenario during review of the available data.
2. Chronic risk. Using the conservative TMRC exposure assumptions
described above, and taking into account the completeness and
reliability of the toxicity data, the Agency has estimated that
exposure to azoxystrobin from food will utilize 2% of the RfD for the
U.S. population as a whole. The Agency generally is not concerned about
exposures below 100 percent 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, the Agency
does not expect the aggregate exposure to exceed 100% of the RfD. Under
current Agency guidelines, the registered non-dietary uses of
azoxystrobin do not constitute a chronic exposure scenario and EPA
concludes that there is a reasonable
[[Page 55538]]
certainty that no harm will result from aggregate exposure to currently
registered azoxystrobin residues.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure. This risk assessment is not needed for
azoxystrobin because no dermal or systemic effects were seen in the
repeated dose dermal study at the limit dose. Additionally, no indoor
or outdoor residential exposure uses are currently registered for
azoxystrobin.
4. Aggregate cancer risk for U.S. population. This risk assessment
is also not needed. Azoxystrobin is classified as ``not likely'' to be
a carcinogen under the proposed revised Carcinogenicity Guidelines
because carcinogenicity testing was performed on two appropriate
species and no evidence of carcinogenicity was found.
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.
D. 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, the highest dose tested (HDT). Because there were no
treatment-related effects, the developmental LEL was >500 mg/kg/day.
The maternal NOAEL was 150 mg/kg/day. The maternal LEL 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 LEL 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 reproductive
toxicity study (MRID #43678144) in rats, the parental (systemic) NOAEL
was 32.3 mg/kg/day. The parental LEL 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 LEL of 165.4
mg/kg/day was based on increased weanling liver weights and decreased
body weights for pups of both generations.
iv. Conclusion. The pre- and post-natal toxicology database 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 to azoxystrobin than are
adults, based on the results of the rat and rabbit developmental
toxicity studies and the 2-generation reproductive toxicity study in
rats. Accordingly, EPA has determined that the standard margin of
safety will protect the safety of infants and children and the
additional tenfold safety factor can therefore be removed.
2. Chronic risk. Using the exposure assumptions described above,
EPA has concluded that aggregate exposure to azoxystrobin from food
will utilize 2 to 8% 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.
IV. Other Considerations
A. Metabolism In Plants and Animals
The metabolism of azoxystrobin as well as the nature of the
residues is adequately understood for purposes of the time-limited
tolerance. Plant metabolism has been evaluated in three diverse crops;
grapes, wheat and peanuts, which is required to define similar
metabolism of azoxystrobin in a wide range of crops. Parent
azoxystrobin is the major component found in crops. Azoxystrobin does
not accumulate in crop seeds or fruits. Metabolism of azoxystrobin in
plants is complex, with more than 15 metabolites identified. These
metabolites are present at low levels, typically much less than 5% of
the total radioactive residue level.
The qualitative nature of the residue in animals is adequately
understood for the purposes of this proposed 1-year time-limited
tolerance. Establishment of a time-limited tolerance of 0.03 ppm for
azoxystrobin in/on potatoes is not expected to lead to detectable
azoxystrobin residues in animal commodities.
B. Analytical Enforcement Methodology
An analytical method, gas chromatography with nitrogen-phosphorus
detection (GC-NPD) or, in mobile phase, by high performance liquid
chromatography with ultraviolet detection (HPLC-UV), is available for
enforcement purposes with a limit of detection that allows monitoring
of food with residues at or above the level proposed for this time-
limited tolerance. The Agency has concluded that the method is adequate
for enforcement of tolerances in/on other non-oily raw agricultural
commodities. The Agency also concludes that this method is adequate for
enforcement of the proposed time-limited tolerance in/on potatoes. The
method may be requested from: Calvin Furlow, PRRIB, IRSD (7502C),
Office of Pesticide Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. Office location and telephone number:
Rm 101FF, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA
22202, (703-305-5229).
[[Page 55539]]
C. Magnitude of Residues
Residues of azoxystrobin and its Z isomer are not expected to
exceed 0.03 ppm in/on potatoes as a result of this EUP use. A time-
limited tolerance should be established at this level.
D. International Residue Limits
There are no CODEX, Canadian, or Mexican Maximum Residue Limits for
azoxystrobin in/on potatoes.
E. 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 azoxystrobin tolerances.
V. Conclusion
Therefore, a time-limited tolerance is established for combined
residues of azoxystrobin and its Z isomer in potatoes at 0.03 ppm. This
tolerance will expire and is revoked on October 18, 1999. EPA will
publish a document in the Federal Register to remove the revoked
tolerance from the Code of Federal Regulations.
VI. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation issued by EPA under
new section 408(e) and (r) 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 December 15, 1998, 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 above (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 rulemaking. 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). 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.
VII. Public Record and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300744] (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 Highway, Arlington, VA.
Electronic comments may be sent directly to EPA at:
[email protected].
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this rulemaking, as well as the public
version, as described above 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 rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in ``ADDRESSES'' at the beginning of this document.
VIII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
This final rule establishes a time-limited tolerance under FFDCA
section 408(d). EPA is establishing this tolerance in cooperation with
Wisconsin potato growers, University extension specialists, and Zeneca
Ag Products, Inc. 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
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).
Pursuant to the requirements of the Regulatory Flexibility Act
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Agency
previously assessed whether establishing tolerances, exemption 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 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 Intergovernmental
Partnerships (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
[[Page 55540]]
the mandate is unfunded, EPA must provide to the Office of Management
and Budget (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 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.
IX. 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 to the Comptroller General of the
United States. EPA has submitted 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 today's publication of this 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, Feed additives, Food
additives, Reporting and recordkeeping requirements.
Dated: October 6, 1998.
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. 346a and 371.
2. Section 180.507(a) is amended by designating the text following
the paragraph heading as paragraph (a)(1) and adding paragraph (a)(2)
to read as follows:
Sec. 180.507 Azoxystrobin; tolerances for residues.
(a) * * *
(2) Time-limited tolerance. A tolerance to expire on October 18,
1999, is established for the combined residues of azoxystrobin
[methyl(E)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-
methoxyacrylate] and its Z isomer in or on the following commodity.
------------------------------------------------------------------------
Commodity Parts per million Expiration Date
------------------------------------------------------------------------
Potatoes........................ 0.03 October 18, 1999
------------------------------------------------------------------------
* * * * *
[FR Doc. 98-27835 Filed 10-15-98; 8:45 am]
BILLING CODE 6560-50-F