[Federal Register Volume 62, Number 131 (Wednesday, July 9, 1997)]
[Rules and Regulations]
[Pages 36684-36691]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-17931]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300508; FRL-5728-3]
RIN 2070-AB78
Azoxystrobin; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final Rule.
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SUMMARY: This regulation establishes tolerances for residues of the
fungicide azoxystrobin (CAS Reg. No. 131860-33-8 and PC Code 128810)
and its Z-isomer in or on the raw agricultural commodities bananas,
grapes, peaches, peanuts, pecans, and tomatoes, and the processed foods
peanut oil and tomato paste. Zeneca Ag Products submitted three
petitions to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA)
as amended by the Food Quality Protection Act of 1996 (Pub. L. 104-170)
requesting the tolerances. Azoxystrobin has been processed as a reduced
risk pesticide for its uses in/on bananas, grapes, peaches, peanuts,
and tomatoes.
DATES: This regulation became effective on June 3, 1997. Written
objections and requests for hearings must be received on or before
September 8, 1997.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300508], may 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 should be identified by the
document control number and submitted to: Public Information and
Records Integrity Branch, Information Resources and Services (7506C),
Office of Pesticide Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. In person, bring copy of objections and
hearing requests to: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy.,
Arlington, VA 22202.
[[Page 36685]]
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@epamail.epa.gov. 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 in 5.1
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-300508]. 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, Product
Manager (22), Registration Division, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. Office location and telephone
number and e-mail address: Room 247, CM #2, 1921 Jefferson Davis
Highway, Arlington, VA (703-305-7740). e-mail: parker.cynthia@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of March 12, 1997
(62 FR 11442)(FRL-5589-6), EPA issued a notice pursuant to section
408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 346a(d),
announcing the filing of three pesticide tolerance petitions (PP
5F4541, 6F4642, and 6F4762) by Zeneca Ag Products, 1800 Concord Pike,
P.O. Box 15458, Wilmington, DE 19850-5458 to EPA requesting that the
Administrator amend 40 CFR part 180 by establishing tolerances for
residues of the fungicide, azoxystrobin, [methyl(e)-2-(2-(6-(2-
cyanophenoxy) pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate] and the Z-
isomer of azoxystrobin, [methyl(Z)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-
yloxy)phenyl)-3 methoxyacrylate] in or on the food commodities: grapes
at 1.0 ppm; pecans at 0.01 ppm; tomato at 0.2 ppm; tomato paste at 0.6
ppm; peanut at 0.01 ppm; peanut oil at 0.03 ppm; peanut hay at 1.5 ppm;
peach at 0.80 ppm; banana (whole fruit including peel) at 0.5 ppm;
banana pulp at 0.05 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; fat of cattle,
goats, poultry, sheep, hogs, and horses at 0.01 ppm; mbyp of cattle,
goats, poultry, sheep, hogs, and horses at 0.01 ppm; meat of cattle,
goats, poultry, sheep, hogs, and horses at 0.01 ppm; poultry liver at
0.01 ppm; and milk at 0.006 ppm.
As required by section 408(d) of the FFDCA, as recently amended by
the Food Quality Protection Act of 1996 (FQPA), Pub. L. 104-170, Zeneca
Ag Products included in the notice of filing a summary of the petition
and authorization for the summary to be published in the Federal
Register in a notice of receipt of the petition. The summary of the
petition prepared by the petitioner contained conclusions and
assessments to support its contention that the petition complied with
the FQPA elements set forth in section 408(d)(3) of the FFDCA. There
were no comments received in response to the notice of filing.
On May 7, 1997, Zeneca Ag Products withdrew the proposed tolerances
in/on peanut hay; banana pulp; wheat grain, bran, hay, and straw;
cattle, goat, hog, horse, and sheep fat, meat byproducts, and meat;
poultry fat, liver, meat byproducts, and meat; and milk. This leaves
the proposed bananas (whole fruit including peel), grapes, peaches,
peanuts, peanut oil, pecans, tomatoes, and tomato paste tolerances, at
their originally proposed values.
I. Statutory Background
Section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 301 et seq., as amended by the FQPA, Pub. L. 104-170, authorizes
the establishment of tolerances (maximum residue levels), exemptions
from the requirement of a tolerance, modifications in tolerances, and
revocation of tolerances for residues of pesticide chemicals in or on
food commodities and processed foods. Without a tolerance or exemption,
food containing pesticide residues is considered to be unsafe and
therefore ``adulterated'' under section 402(a) of the FFDCA, and hence
may not legally be moved in interstate commerce. For a pesticide to be
sold and distributed, the pesticide must not only have appropriate
tolerances under the FFDCA, but also must be registered under section 3
of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA, 7
U.S.C. 135 et seq.).
Section 408 was substantially amended by the FQPA. Among other
things, the FQPA amends the FFDCA to bring all EPA pesticide tolerance-
setting activities under a new section 408 with a new safety standard
and new procedures. New section 408(b)(2)(A)(i) 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 food, drinking water, and from pesticide use
in gardens, lawns, or buildings (residential and other indoor uses) 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....''
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.
A. Toxicity
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 effects (the ``no-observed-effect level'' or ``NOEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOEL from
the study with the lowest NOEL 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 addresses the potential risks
to infants and children
[[Page 36686]]
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 NOEL from the appropriate animal study. Commonly, EPA
finds MOEs lower than 100 to be unacceptable. This hundredfold margin
of exposure is based on the same rationale as the hundredfold
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
relationships. Once a pesticide has been classified as a potential
human carcinogen, different types of risk assessments (e.g., linear low
dose extrapolations or margin of exposure (MOE) calculations based on
the appropriate NOEL) 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''. These assessments are defined
by the Agency as follows.
i. Acute risk. 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.
ii. Short-term risk. Short-term risk results from exposure to the
pesticide for a period of 1 to 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
enactment 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 to 7 days exposure, and the
toxicological endpoint/NOEL is selected to be adequate for at least 7
days of exposure. (Toxicity results at lower levels when the dosing
duration is increased.)
iii. Intermediate-term risk. 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.
iv. Chronic 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 outdoor 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 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, was not regionally based.
III. 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 below.
1. Acute toxicity. The acute oral toxicity study in rats of
technical azoxystrobin resulted in an LD50 of >
[[Page 36687]]
5,000 milligrams/kilogram (limit test) for both males and females. The
acute dermal toxicity study in rats of technical azoxystrobin resulted
in an LD50 of > 2,000 milligrams/kilogram (limit dose). The
acute inhalation study of technical azoxystrobin in rats resulted in an
LC50 of 0.962 milligrams/liter in males and 0.698
milligrams/liter in females. In an acute oral neurotoxicity study in
rats dosed once by gavage with 0, 200, 600, or 2,000 milligrams/
kilogram azoxystrobin, the systemic toxicity NOEL was <200 milligrams/="" kilogram="" and="" the="" systemic="" toxicity="" loel="" was="" 200="" milligrams/kilogram,="" based="" on="" the="" occurrence="" of="" transient="" diarrhea="" in="" both="" sexes.="" there="" was="" no="" indication="" of="" neurotoxicity="" at="" the="" doses="" tested.="" this="" acute="" neurotoxicity="" study="" is="" considered="" supplementary="" (upgradeable)="" but="" the="" data="" required="" are="" considered="" only="" to="" be="" confirmatory.="" the="" company="" has="" submitted="" the="" required="" confirmatory="" data;="" these="" data="" have="" been="" scheduled="" for="" review="" by="" the="" agency.="" 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="" or="" 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="" noel="" was="" 20.4="" mg/kg/day="" for="" males="" and="" females.="" the="" loel="" 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="" noel="" for="" both="" males="" and="" females="" was="" 50="" mg/kg/day.="" the="" loel="" 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="" noel="" for="" both="" males="" and="" females="" was="" greater="" than="" or="" equal="" to="" 1000="" mg/kg/day="" (the="" highest="" dosing="" regimen);="" a="" loel="" 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="" noel="" was="" 18.2="" mg/kg/day="" for="" males="" and="" 22.3="" mg/kg/day="" for="" females.="" the="" systemic="" toxicity="" loel="" for="" males="" was="" 34="" mg/kg/day,="" based="" on="" reduced="" body="" weights,="" food="" consumption,="" and="" food="" efficiency;="" and="" bile="" duct="" lesions.="" the="" systemic="" toxicity="" loel="" 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="" noel="" for="" both="" males="" and="" females="" was="" 25="" mg/kg/day="" and="" the="" loel="" 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="" noel="" was="" 37.5="" mg/kg/day="" for="" both="" males="" and="" females.="" the="" systemic="" toxicity="" loel="" was="" 272.4="" mg/kg/day="" for="" both="" sexes,="" based="" on="" reduced="" body="" weights="" in="" both="" 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="" noel="" was="" greater="" than="" or="" equal="" to="" 100="" mg/="" kg/day="" and="" the="" developmental="" loel="" was=""> 100 mg/kg/day because no
significant adverse developmental effects were observed. In this same
study, the maternal NOEL was not established; the maternal LOEL 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 NOEL was 500 mg/kg/day and the developmental LOEL was >
500 mg/kg/day because no treatment-related adverse effects on
development were seen. The maternal NOEL was 150 mg/kg/day and the
maternal LOEL 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 NOEL was 32.2 mg/
kg/day. The reproductive LOEL 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).
IV. Aggregate Exposures
1. From food and feed uses. The primary route of human exposure to
azoxystrobin is expected to be dietary ingestion of both raw and
processed agricultural commodities from Bananas, Grapes, Peaches,
Peanuts, Pecans, and Tomatoes. A Dietary Risk Evaluation System (DRES)
chronic exposure analysis was conducted using tolerance level residues
and 100% crop treated information to estimate the TMRC for the general
population and 22 subgroups.
2. From potable water. There is no established Maximum
Concentration Level for residues of azoxystrobin in drinking water.
Data indicate moderate potential for soil mobility or leaching and
azoxystrobin is moderately persistent. In examining aggregate exposure,
the FQPA directs EPA to consider available information concerning
exposures from the pesticide residue in food and all other non-
occupational exposures. The primary non-food sources of exposure the
Agency looks at include drinking water (whether from groundwater or
surface
[[Page 36688]]
water), and exposure through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses).
Because the Agency lacks sufficient water-related exposure data to
complete a comprehensive drinking water risk assessment for many
pesticides, EPA has commenced and nearly completed a process for
identifying a reasonable yet conservative bounding figure for the
potential contribution of water related exposure to the aggregate risk
posed by a pesticide. In developing the bounding figure, EPA estimated
residue levels in water for a number of specific pesticides using
various data sources. The Agency then applied the estimated residue
levels, in conjunction with appropriate toxicological endpoints (RfDs
or acute dietary NOELs) and assumptions about body weight and
consumption to calculate, for each pesticide, the increment of
aggregate risk contributed by consumption of contaminated water. The
Agency has not yet pinpointed the appropriate bounding figure for
consumption of water contaminated with azoxystrobin but the ranges the
Agency is continuing to examine are all below the level that would
cause azoxystrobin to exceed the RfD if the proposed food uses were
granted. The Agency has therefore concluded that the potential
exposures associated with azoxystrobin in water, even at the higher
levels the Agency is considering as a conservative upper bound, would
not prevent the Agency from determining that there is a reasonable
certainty of no harm if the proposed uses of bananas, grapes, peaches,
peanuts, pecans, and tomatoes were granted.
3. From non-dietary uses. The Agency evaluated the existing
toxicological database for azoxystrobin and assessed appropriate
toxicological endpoints and dose levels of concern that should be
assessed for risk assessment purposes. Dermal absorption data indicate
that absorption is less than or equal to 4%. No appropriate endpoints
were identified for acute dietary or short term, intermediate term, and
chronic term (noncancer) dermal and inhalation occupational or
residential exposure. Therefore, risk assessments are not required for
these exposure scenarios and there are no residential risk assessments
to aggregate with the chronic dietary risk assessment.
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.'' 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
examinations 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. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
azoxystrobin does not appear to be structurally similar to any other
pesticide chemical at this time. No metabolites of azoxystrobin that
are of toxicological concern are known to the Agency. Azoxystrobin
appears to be the only pesticide member of its class of chemistry and
there are no reliable data to indicate that this chemical is
structurally or toxicologically similar to existing chemical substances
at this time. Therefore, it appears unlikely that azoxystrobin bears a
common mechanism of activity with 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.
V. Determination of Safety
A. Chronic Risk
The Reference Dose (RfD) for azoxystrobin is 0.18 mg/kg/day, based
on the NOEL of 18.2 mg/kg/day from the rat chronic toxicity/
carcinogenicity feeding study in which decreased body weight and bile
duct lesions were observed in male rats at the LOEL of 34 mg/kg/day.
This NOEL was divided by an Uncertainty Factor of 100, to allow for
interspecies sensitivity and intraspecies variability.
The chronic dietary exposure analysis showed that exposure from the
proposed new tolerances in or on banana, grape, peach, peanut, peanut
oil, pecan, tomato, and tomato paste for Non-nursing Infants (the
subgroup with the highest exposure) would be 1% of the RfD. The
exposure for the general U.S. population would be less than 1% of the
RfD. This analysis used a value of 0.05 ppm for banana pulp rather than
the value of 0.5 that has been established for banana (whole fruit
including peel) because adequate data were submitted to support use of
the lower value in the dietary risk analyses. When the chronic dietary
exposure analysis was performed with the addition of the tolerances for
rice, milk, meat, eggs, and poultry that result from the granting of
section 18 registrations for use on rice to Louisiana and Mississippi,
about 1% of the RfD is used for the U.S. Population and about 5% of the
RfD is used for Non-nursing Infants.
As is discussed above, there is no established Maximum
Concentration Level for residues of azoxystrobin in drinking water. The
Agency has not yet pinpointed the appropriate bounding figure for
consumption of water contaminated with azoxystrobin but the ranges the
Agency is continuing to examine are all below the level that would
cause azoxystrobin to exceed the RfD if the proposed food uses were
granted. The Agency has therefore concluded that the potential
exposures associated with azoxystrobin in water, even at the higher
levels the Agency is
[[Page 36689]]
considering as a conservative upper bound, would not prevent the Agency
from determining that there is a reasonable certainty of no harm if the
proposed uses on bananas, grapes, peaches, peanuts, pecans, and
tomatoes were granted.
B. Acute Risk
As part of the hazard assessment process, the Agency reviews the
available toxicological database to determine if there are
toxicological endpoints of concern. For azoxystrobin, the Agency does
not have a concern for acute dietary exposure since the available data
do not indicate any evidence of significant toxicity from a one-day or
single event exposure by the oral route. Therefore, an acute dietary
risk assessment is not required for azoxystrobin at this time.
C. Conclusion
Based on these risk estimates EPA concludes that there is a
reasonable certainty of no harm from aggregate exposure to azoxystrobin
for consumers, including major identifiable subgroups and infants and
children.
VI. Additional Safety Factor for Infants and Children
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 analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. In either case, EPA generally defines the
level of appreciable risk as exposure that is greater than 1/100 of the
no observed effect level in the animal study appropriate to the
particular risk assessment. This hundredfold uncertainty (safety)
factor/margin of exposure (safety) is designed to account for combined
inter- and intra-species variability. EPA believes that reliable data
support using the standard hundredfold margin/factor but not the
additional tenfold margin/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
margin/factor. The data base for azoxystrobin is complete except that
the acute and subchronic neurotoxicity studies require upgrading. The
upgrade data are confirmatory only, have been submitted by the company,
and await review by the Agency.
There was no evidence of increased susceptibility of infants or
children to azoxystrobin. Therefore, no additional uncertainty factors
are considered necessary at this time.
VII. Other Considerations
1. Endocrine effects. EPA is required to develop a screening
program to determine whether certain substances (including all
pesticides and inerts) ``may have an effect in humans that is similar
to an effect produced by a naturally occurring estrogen, or such other
endocrine effect...''. The Agency is currently working with interested
shareholders, including other government agencies, public interest
groups, industry, and research scientists, to develop a screening and
testing program and a priority setting scheme to implement this
program. Congress has allowed three (3) years from the passage of FQPA
(August 3, 1999) to implement this program. When this program is
implemented, EPA may require further testing of azoxystrobin and end-
use product formulations for endocrine disrupter effects.
2. Metabolism in plants and animals. The metabolism of azoxystrobin
in plants is adequately understood for purposes of these tolerances.
Since the proposed label does not contain any commodities that are
considered to be significant items of livestock feed, the nature of the
residue in animals is not of concern at this time. There are no Codex
Alimentarius Commission (Codex) Maximum Residue Levels (MRLs) for
azoxystrobin. Adequate analytical methods, gas chromatography with
nitrogen-phosphorous detection and high performance liquid
chromatography with ultraviolet detection, are available for
enforcement purposes. Because of the long lead time from establishing
these tolerances to publication of the enforcement methodology in the
Pesticide Analytical Manual, Vol. II, the analytical method is being
made available in the interim to anyone interested in pesticide
enforcement when requested from: Calvin Furlow, Public Information and
Records Integrity Branch, Information Resources and Services Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. Office location and telephone
number: Room 1130A, CM #2, 1021 Jefferson Davis Highway, Arlington, VA
(703-305-5937).
3. Data requirements. In accordance with section 408(b)(2)(E)(ii)
of the Federal Food, Drug, and Cosmetic Act (FFDCA), because
anticipated or actual residue levels are being relied on for banana
pulp, the Agency is requiring, pursuant to section 408(f)(1), that data
be provided 5 years after the date on which the tolerance is
established, modified, or left in effect, and thereafter as the
Administrator deems appropriate, demonstrating that such residue levels
are not above the levels so relied on. If such data are not so
provided, or if the data do not demonstrate that the residue levels are
not above the levels so relied on, the Administrator shall, not later
than 180 days after the date on which the data were required to be
provided, issue a regulation under section 408(e)(1), or an order under
section 408(f)(2), as appropriate, to modify or revoke the tolerance.
VIII. Summary of Findings
The analysis for azoxystrobin for all population subgroups examined
by EPA shows that the proposed uses on bananas, grapes, peaches,
peanuts, pecans, and tomatoes will not cause exposure at which the
Agency believes there is an appreciable risk.
Based on the information cited above, the Agency has determined
that the establishment of the tolerances by amending 40 CFR part 180
will be safe; therefore, the tolerances are established as set forth
below.
IX. 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 (1)(6) 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 these modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person may, by September 8, 1997, 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
[[Page 36690]]
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 proscribed by 40 CFR
180.33(i). If a hearing is requested, the objections must include a
statement of the factual issue(s) on which a hearing is requested, the
requestor's contention on such issues, and a summary of any evidence
relied upon by the objector (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 a genuine and substantial issue
of fact; there is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one or more
of such issues in favor of the requestor, taking into account
uncontested claims or facts to the contrary; and resolution of the
factual issue(s) in the manner sought by the requestor would be
adequate to justify the action requested (40 CFR 178.32). 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.
X. Public Docket
A record has been established for this rulemaking under the docket
number [OPP-300508] (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 1132, Public Information and Records
Integrity Branch, Information Resources and Services Division (7506C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall # 2, 1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments can be sent directly to EPA at:
opp-docket@epamail.epa.gov
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 rule-making record
which will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
address in ``ADDRESSES'' at the beginning of this document.
XI. Regulatory Assessment Requirements
This final rule establishes tolerances under section 408 of the
FFDCA and is in response to petitions received by the Agency requesting
the establishment of such tolerances. 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). In addition, 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, because tolerances that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA)(5 U.S.C. 601 et
seq.) do not apply. Prior to the recent amendments to the FFDCA,
however, EPA had treated such actions as subject to the RFA. The
amendments to the FFDCA clarify that no proposed rule is required for
such regulatory actions, which makes the RFA inapplicable to these
actions. Nevertheless, the Agency has 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 (46 FR 24950, May 4, 1981). In accordance with Small Business
Administration (SBA) policy, this determination will be provided to the
Chief Counsel for Advocacy of the SBA upon request.
XII. Submission to Congress and the General Accounting Office
Under 5 U.S.C. 801(a)(1)(A), as added by the Small Business
Regulatory Enforcement Fairness Act of 1996, the Agency 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 General Accounting Office prior to publication of this rule in
today's Federal Register. This is not a ``major rule'' as defined by 5
U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Administrative practice and procedure, Agricultural commodities,
Pesticides and pests, Recording and recordkeeping requirements
Dated: July 1, 1997.
Daniel M. Barolo,
Director, Office of Pesticide Programs.
Therefore, 40 CFR part 180 is amended as follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 236a and 371.
2. Section 180.507 is amended by adding the text of paragraph (a)
to read as follows:
Sec. 180.507 Azoxystrobin; tolerances for residues.
(a) General. Tolerances are established for residues of the
fungicide, azoxystrobin, [methyl(E)-2-(2-(6-(2-cyanophenoxy) pyrimidin-
4-yloxy)phenyl)-3-methoxyacrylate] and the Z-isomer of azoxystrobin,
[methyl(Z)-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3
methoxyacrylate] in or on the following raw agricultural commodities
and processed food:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Bananas.................................................... 0.5
Grapes..................................................... 1.0
Peaches.................................................... 0.80
Peanuts.................................................... 0.01
Peanut Oil................................................. 0.03
Pecans..................................................... 0.01
Tomatoes................................................... 0.2
[[Page 36691]]
Tomato Paste............................................... 0.6
------------------------------------------------------------------------
* * * * *
[FR Doc. 97-17931 Filed 7-8-97; 8:45 am]
BILLING CODE 6560-50-F
