[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: [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 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: giles-
[email protected].
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:
    [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 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
------------------------------------------------------------------------

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[FR Doc. 97-17931 Filed 7-8-97; 8:45 am]
BILLING CODE 6560-50-F