[Federal Register Volume 65, Number 149 (Wednesday, August 2, 2000)]
[Notices]
[Pages 47498-47503]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-19378]


-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[PF-950; FRL-6592-1]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-950, must be 
received on or before September 1, 2000.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION.'' To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-950 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Cynthia Giles-Parker, 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-7740; e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under ``FOR FURTHER INFORMATION 
CONTACT.''

[[Page 47499]]

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' and then look up the entry for this document under the 
``Federal Register--Environmental Documents.'' You can also go directly 
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-950. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-950 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: ``[email protected],'' or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-950. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI 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. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under ``FOR FURTHER INFORMATION 
CONTACT.''

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: July 20, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioner. EPA is publishing the petition summary verbatim without 
editing it in any way. The petition summary announces the availability 
of a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.

Zeneca Ag Products

9F6058

    EPA has received pesticide petition 9F6058 from Zeneca Ag Products, 
1800 Concord Pike, P.O. Box 15458, Wilmington, DE 19850-5458 proposing, 
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act 
(FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a 
tolerance for residues of azoxystrobin (methyl (E-2-(2-

[[Page 47500]]

(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate)) and 
its Z isomer methyl (Z-2-(2-(6-(2-cyanophenoxy)pyrimidin-4-
yloxy)phenyl)-3- (methoxyacrylate)) in or on the raw agricultural 
commodities (RAC) apples at 1.5 parts per million (ppm); barley, bran 
at 0.2 ppm; barley, grain at 0.1 ppm; barley, hay at 15 ppm; barley, 
straw at 4 ppm; beet, sugar, dried pulp at 0.8 ppm; cattle, fat at 0.03 
ppm; cattle, meat by-products at 0.07 ppm; citrus, oil at 15 ppm; 
coriander, leaves at 30 ppm; coriander, seed at 30 ppm; corn, field, 
forage at 10 ppm; corn, field, grain at 0.05 ppm; corn, field, refined 
oil at 0.3 ppm; corn, field, stover at 25 ppm; corn, pop, grain at 0.05 
ppm; corn, pop, stover at 25 ppm; corn, sweet, kernal plus cob with 
husks removed at 0.02 ppm; corn, sweet, forage at 10 ppm; corn, sweet, 
stover at 25 ppm; cotton at 0.01 ppm; cotton, gin by-products at 0.01 
ppm; fruit, citrus, group at 3 ppm; fruit, citrus, dried pulp at 7 ppm; 
goat, fat at 0.03 ppm; goat, meat by-products at 0.07 ppm; horse, fat 
at 0.03 ppm; horse, meat by-products at 0.07 ppm; peanut at 0.2 ppm; 
peanut, hay at 15 ppm; peanut, refined oil at 0.6 ppm; sheep, fat at 
0.03 ppm; sheep, meat by-products at 0.07 ppm; soybean, seed at 0.5 
ppm; soybean, forage at 25 ppm; soybean, hay at 55 ppm; soybean, hulls 
at 1.25 ppm; soybean, seed at 0.5 ppm; rice, wild at 5 ppm; vegetable, 
bulb, group at 7.5 ppm; vegetable, leafy, except brassica vegetables, 
group at 30 ppm; vegetable, leaves of root and tuber, group at 50 ppm; 
and vegetable, root and tuber, group at 0.5 ppm. EPA has determined 
that the petition contains data or information regarding the elements 
set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully 
evaluated the sufficiency of the submitted data at this time or whether 
the data support granting of the petition. Additional data may be 
needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of azoxystrobin as well as the 
nature of the residues is adequately understood for purposes of the 
tolerances. Plant metabolism has been evaluated in four diverse crops: 
cotton, grapes, wheat, and peanuts, which should serve to define the 
similar metabolism of azoxystrobin in a wide range of crops. Parent 
azoxystrobin is the major component found in crops. Azoxystrobin does 
not accumulate in crop seeds or fruits. Metabolism of azoxystrobin in 
plants is complex with more than 15 metabolites identified. These 
metabolites are present at low levels, typically much less than 5% of 
the total recoverable residues (TRR).
    2. Analytical method. An adequate analytical method, gas 
chromatography with nitrogen-phosphorus detection (GC-NPD) or in mobile 
phase by high performance liquid chromatography with ultra-violet 
detection (HPLC-UV), is available for enforcement purposes with a limit 
of detection that allows monitoring of food with residues at or above 
the levels set in these tolerances. The analytical chemistry laboratory 
of the EPA concluded that the method(s) are adequate for enforcement. 
For azoxystrobin methods are also available for analyzing meat, milk, 
poultry, and eggs, and also underwent successful independent laboratory 
validations.
    3. Magnitude of residues. Eleven onion trials (green and dry bulb) 
were carried out in the United States of America (U.S.) in 1998. 
Maximum residues of 6.9 ppm resulted from multiple foliar applications. 
Twenty-three citrus fruit trials (grapefruit, lemon and orange) were 
carried out in the U.S. in 1997-1998, Fourteen citrus fruit trials were 
carried out in South Africa in 1995-1998. Maximum residues of 2.9 ppm 
resulted from multiple foliar applications. Twenty corn trials were 
carried out in the U.S. in 1998. Maximum residues of 0.05 ppm in grain, 
0.02 ppm in fresh kernals, 10 ppm in forage, and 25 ppm in stover 
resulted from multiple foliar applications. Twelve residue trials were 
carried out in the U.S. in 1997. Maximum residues of 0.01 ppm in 
cottonseed, and 0.01 ppm in cotton gin by-products resulted from in-
furrow application. Twenty-four leafy vegetable (excluding brassica) 
trials were carried out in 1998. Maximum residues of 30 ppm resulted 
from multiple foliar applications. Twenty trials on the leaves of root 
and tuber vegetable group were carried out in the U.S. in 1998, 
resulting in maximum residues of 45 ppm from multiple foliar 
applications. Twenty root and tuber vegetable trials were carried out 
in the U.S. in 1998. Maximum residues of 0.46 ppm in root and tuber 
vegetables resulted from multiple foliar applications. Sixteen potato 
trials were carried out in the U.S. in 1997, previously submitted under 
pesticide petition 8F4995. Maximum residues of 0.03 ppm in potatoes 
resulted from multiple foliar applications. Twelve peanut trials were 
carried out in the U.S. in 1997. Maximum residues of 0.14 ppm in 
peanut, nutmeat, and 13.7 ppm in peanut hay resulted from multiple 
foliar applications. Twenty soybean trials were carried out in the U.S. 
in 1998. Maximum residues were 0.36 ppm in soybean, seed, 9.1 ppm in 
soybean, forage and 54 ppm in soybean, hay. Concentration of residues 
was observed in barley, bran; citrus, dried pulp; citrus oil; corn, 
oil; sugarbeet, dried pulp; peanut, oil; and soybean, hulls.

B. Toxicological Profile

    1. Acute toxicity. The acute oral toxicity study in rats of 
technical azoxystrobin resulted in a lethal dose 50% (LD50) 
of >5,000 milligrams/kilogram (mg/kg) (limit test) for both males and 
females. The acute dermal toxicity study in rats of technical 
azoxystrobin resulted in an LD50 of >2,000 mg/kg (limit dose 
(LTD)).
    The acute inhalation study of technical azoxystrobin in rats 
resulted in a lethal concentration 50% (LC50) of 0.962 
milligrams/liter (mg/L) in males and 0.698 mg/L in females. In an acute 
oral neurotoxicity study in rats dosed once by gavage with 0, 200, 600, 
or 2,000 mg/kg azoxystrobin, the systemic toxicity no observed adverse 
effect level (NOAEL) was 200 mg/kg and the systemic toxicity lowest 
observed adverse effect level (LOAEL) was 200 mg/kg, based on the 
occurrence of transient diarrhea in both sexes. There was no indication 
of neurotoxicity at the doses tested.
    2. Genotoxicty. Azoxystrobin was negative for mutagenicity in the 
salmonella/mammalian activation gene mutation assay, the mouse 
micronucleus test, and the unscheduled deoxyribonucleic acid (DNA) 
synthesis in rat hepatocytes/mammalian cells in an 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. Reproductive and developmental toxicity. In a prenatal 
development study in rats gavaged with azoxystrobin at dose levels of 
0, 25, 100, or 300 mg/kg/day during days 7 through 16 of gestation, 
lethality at the highest dose caused the discontinuation of dosing at 
that level. The developmental NOAEL was greater than or equal to 100 
mg/kg/day and the developmental lowest observed adverse effect level 
(LOAEL) was >100 mg/kg/day because no significant adverse developmental 
effects were observed. In this same study, the maternal NOAEL was not 
established; the maternal LOAEL was 25 mg/kg/day, based on increased 
salivation.

[[Page 47501]]

    In a prenatal developmental study in rabbits gavaged with 0, 50, 
150, or 500 mg/kg/day during days 8 through 20 of gestation, the 
developmental NOAEL was 500 mg/kg/day and the developmental LOAEL was 
>500 mg/kg/day because no treatment-related adverse effects on 
development were seen. The maternal NOAEL was 150 mg/kg/day and the 
maternal LOAEL was 500 mg/kg/day, based on decreased body weight gain.
    In a 2-generation reproduction study, rats were fed 0, 60, 300, or 
1,500 ppm of azoxystrobin. The reproductive NOAEL was 32.2 mg/kg/day. 
The reproductive LOAEL was 165.4 mg/kg/day; reproductive toxicity was 
demonstrated as treatment-related reductions in adjusted pup body 
weights as observed in the F18 and F2 pups dosed at 1,500 ppm (165.4 
mg/kg/day).
    4. Subchronic toxicity. In a 90-day rat feeding study, the NOAEL 
was 20.4 mg/kg/day for males and females. The LOAEL was 211.0 mg/kg/day 
based on decreased weight gain in both sexes, clinical observations of 
distended abdomens and reduced body size, and clinical pathology 
findings attributable to reduced nutritional status.
    In a subchronic toxicity study in which azoxystrobin was 
administered to dogs by capsule for 92 or 93 days, the NOAEL for both 
males and females was 50 mg/kg/day. The LOAEL was 250 mg/kg/day, based 
on treatment-related clinical observations and clinical chemistry 
alterations at this dose.
    In a 21-day repeated-dose dermal rat study using azoxystrobin, the 
NOAEL for both males and females was greater than or equal to 1,000 mg/
kg/day (the highest dosing regimen); a LOAEL was therefore not 
determined.
    5. Chronic toxicity. In a 2-year feeding study in rats fed diets 
containing 0, 60, 300, and 750/1,500 ppm (males/females), the systemic 
toxicity NOAEL was 18.2 mg/kg/day for males and 22.3 mg/kg/day for 
females. The systemic toxicity LOAEL for males was 34 mg/kg/day, based 
on reduced body weights, food consumption, and food efficiency; and 
bile duct lesions. The systemic toxicity LOAEL for females was 117.1 
mg/kg/day, based on reduced body weights. There was no evidence of 
carcinogenic activity in this study.
    In a 1-year feeding study in dogs to which azoxystrobin was fed by 
capsule at doses of 0, 3, 25, or 200 mg/kg/day, the NOAEL for both 
males and females was 25 mg/kg/day and the LOAEL was 200 mg/kg/day for 
both sexes, based on clinical observations, clinical chemistry changes, 
and liver weight increases that were observed in both sexes.
    In a 2-year carcinogenicity feeding study in mice using dosing 
concentrations of 0, 50, 300, or 2,000 ppm, the systemic toxicity NOAEL 
was 37.5 mg/kg/day for both males and females. The systemic toxicity 
LOAEL was 272.4 mg/kg/day for both sexes, based on reduced body weights 
in both 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. Animal metabolism. In this study, azoxystrobin, either 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.
    7. Metabolite toxicology. There are no metabolites of concern based 
on a differential metabolism between plants and animals.
    8. Endocrine disruption. There is no evidence that azoxystrobin is 
an endocrine disrupter.

C. Aggregate Exposure

    The Agency has concluded from review of available data that there 
is no acute toxicological endpoint of concern from the review of 
available data. Therefore, an acute risk assessment is not necessary. 
For azoxystrobin, only a chronic (noncancer) risk assessment is 
necessary.
    1. Dietary exposure. Permanent tolerances have been established (40 
CFR 180.507(a)) for the combined residues of azoxystrobin and its Z 
isomer in or on a variety of RAC at levels ranging from 0.01 ppm on 
tree nuts to 20.0 ppm on rice hulls. Included in these tolerances are 
the numerous ones for animal commodities which were established in 
conjuction with tolerances for rice and wheat commodities. Time-limited 
tolerances range from 0.1 ppm in soybeans to 100 ppm in fresh parsley.
    i. Food. In conducting a chronic dietary risk assessment, Zeneca 
has made the very conservative assumptions that 100% of all commodities 
having azoxystrobin tolerances or proposed tolerances will contain 
azoxystrobin residues at the level of the tolerance. Default 
concentration factors have been removed where data show no 
concentration of residues (grapes, juice, grapes, raisins, tomatoes, 
juice, tomatoes, puree, and potatoes, white (dry)). The chronic RfD of 
0.18 mg/kg/day that was used as the endpoint value was derived from the 
NOAEL of 18.2 mg/kg/day from the rat chronic toxicity/carcinogenicity 
feeding study. The endpoint effects were decreased body weight and bile 
duct lesions that were observed in male rats at the LOAEL of 34 mg/kg/
day. This NOAEL was divided by an uncertainty factor of 100 to allow 
for intraspecies and interspecies variability.
    The Novigen Dietary Exposure Evaluation Model (DEEM) system was 
used for this Chronic Dietary Exposure Analysis. The analysis evaluates 
individual food consumption as reported by respondents in the United 
States Department of Agriculture (USDA) Continuing Surveys of Food 
Intake by Individuals (CSFII) survey that was conducted from 1989 
through 1992. The model accumulates exposure to the chemical for each 
commodity and expresses risk as a function of dietary exposure.
    The existing azoxystrobin tolerances (both published and pending; 
section 18 tolerances have been excluded in this analysis because most 
are included as pending tolerances in this petition), result in a 
theoretical maximum residue contribution (TMRC) that is equivalent to 
the following percentages of the chronic reference dose (RfD). Since 
the 10x safety factor was removed by EPA, the chronic RfD is equal to 
the chronic population-adjusted dose (cPAD) and the exposure given as a 
percentage of the total allowable is reported as the percentage of the 
cPAD. The U.S. population group will have a food exposure that is 
estimated as 0.023894 mg/kg/day (13.3% of the cPAD), the subgroup all 
infants (less than 1-year old) will have an estimated exposure of 
0.029771 mg/kg/day (16.5% of the cPAD), the subgroup nursing infants 
(less than 1 year old) will have an estimated exposure of 0.014637 mg/
kg/day (8.1% of the cPAD), the subgroup non-nursing infants (less than 
1-year old) will have an estimated exposure of

[[Page 47502]]

0.036140 mg/kg/day (20.1% of the cPAD), the subgroup children (1-6 
years old) will have an estimated exposure of 0.047270 mg/kg/day (26.3% 
of the cPAD), the subgroup children (7-12 years old) will have an 
estimated exposure of 0.032101 mg/kg/day (17.8% of the cPAD), the 
subgroup hispanics will have an estimated exposure of 0.026050 mg/kg/
day (14.5% of the cPAD), the subgroup non-hispanic/non-white/non-black 
will have an estimated exposure of 0.030275 mg/kg/day (16.8% of the 
cPAD), and the subgroup females (13+ years old, nursing) will have an 
estimated 0.028866 mg/kg/day (16.0% of the cPAD).
    ii. Drinking water. There is no established maximum concentration 
level for residues of azoxystrobin in drinking water. No health 
advisory levels for azoxystrobin in drinking water have been 
established. The concentration of azoxystrobin in surface water is 
based on Generic Estimated Environmental Concentration (GENEEC) 
modeling and in ground water is based on Screening Concentration in 
Ground Water (SCI-GROW) modeling (both models belong to EPA).
    Based on the chronic dietary (food) exposure estimates, chronic 
drinking water levels of concern (DWLOC) for azoxystrobin were 
calculated and are summarised below. The group and subgroups that were 
analyzed are the group U.S. population and the two general subgroups 
females 13-50 and children. Within each of these two general subgroups, 
the specific subgroup with the highest food exposure was chosen for the 
analysis. EPA has determined that the highest estimated environmental 
concentration (EEC) of azoxystrobin in surface water is from the 
application of azoxystrobin to grapes (39 micrograms per liter 
(g/L)). The EEC for ground water is 0.064 g/L 
resulting from use on turf. For purposes of risk assessment, the 
maximum EEC for azoxystrobin in drinking water (39 g/L) should 
be used for comparison to the back-calculated human health DWLOC for 
the chronic (non-cancer) endpoint. The maximum (chronic) water exposure 
(in mg/kg/day) is calculated by starting with the value for the chronic 
RfD (in mg/kg/day) and subtracting the food exposure (in mg/kg/day). 
The DWLOC (in micrograms per liter) (g/L) is calculated by 
multiplying the maximum water exposure (in mg/kg/day) by the body 
weight (in kilograms), then dividing by 10-3 times the water 
consumed daily (in liters per day). The default body weights used were 
70 kilograms (kg) for the group U.S. population, 60 kg for subgroups of 
females (13+ years old), and 10 kg for the subgroups of infants and 
children. The default drinking water rates used were 2 liters per day 
(L/day) for adults and 1 L/day for children. The scenarios for various 
groups and subgroups, leading up to the DWLOC for each, are summarized 
as follows. For the group U.S. population, the RfD is 0.18 mg/kg/day, 
the theoretical maximum residue contribution (TMRC) food exposure is 
0.023894 mg/kg/day, the maximum water exposure is 0.156106 mg/kg/day, 
and the DWLOC is 5,463.71 g/L. For the subgroup females (13+, nursing), 
the RfD is 0.18 mg/kg/day, the TMRC food exposure is 0.028866 mg/kg/
day, the maximum water exposure is 0.151134 mg/kg/day, and the DWLOC is 
4,534.02 g/L. For the subgroup children (1-6 years old), the RfD is 
0.18 mg/kg/day, the TMRC food exposure is 0.047270 mg/kg/day, the 
maximum water exposure is 0.13273 mg/kg/day, and the DWLOC is 1,327.3 
g/L.
    2. Non-dietary exposure. Azoxystrobin is registered for residential 
use on ornamentals and turf. The Agency evaluated the existing 
toxicological data base 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 exposure. 
Therefore, risk assessments are not required for these exposure 
scenarios.

D. Cumulative Effects

    Azoxystrobin is related to the naturally occurring strobilurins. 
There are two other members of this class of fungicides registered with 
EPA. Zeneca concluded that further consideration of a common mechanism 
of toxicity is not appropriate at this time since there are no data to 
establish whether a common mechanism exists with any other substance.

E. Safety Determination

    The acute safety analysis was not applicable since no suitable 
toxicological end-point of concern was identified during Agency review 
of the available data. The short-term and intermediate-term safety 
assessment also was not applicable, in this case because no indoor and 
outdoor residential exposure uses are currently registered for 
azoxystrobin. Therefore, only a chronic analysis was needed.
    The chronic RfD for azoxystrobin is 0.18 milligrams per kilogram 
per day (mg/kg/day), based on the NOAEL of 18.2 mg/kg/day from the rat 
chronic toxicity/carcinogenicity feeding study in which endpoint 
effects of decreased body weight and bile duct lesions were observed in 
male rats at the LOAEL of 34 mg/kg/day. This NOAEL was divided by an 
uncertainty factor of 100, to allow for interspecies sensitivity and 
intraspecies variability.
    1. U.S. population. The chronic dietary exposure analysis showed 
that exposure from the proposed new tolerances in or on apples; barley; 
coriander; corn, field; corn, pop; corn, sweet; cotton; fruit, citrus, 
group; rice, wild; vegetable, bulb, group; vegetable, leafy, except 
brassica vegetables, group; vegetable, leaves of root and tuber, group; 
vegetable, root and tuber, group; and soybeans for the group U.S. 
population would be 13.3% of the RfD.
    2. Infants and children. The chronic dietary exposure analysis 
showed that exposure from the proposed new tolerances in or on apples; 
barley; coriander; corn, field; corn, pop; corn, sweet; cotton; fruit, 
citrus, group; rice, wild; vegetable, bulb, group; vegetable, leafy, 
except brassica vegetables, group; vegetable, leaves of root and tuber, 
group; vegetable, root and tuber, group; and soybeans for the subgroup 
children (1-6 years old) (the subgroup with the highest exposure) would 
be 26.3% of the RfD.
    FFDCA section 408 provides that EPA shall apply an additional ten-
fold margin of safety for infants and children in the case of threshold 
effects to account for prenatal and postnatal toxicity and the 
completeness of the data base 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 a margin of exposure analysis or else through use of 
Uncertainty (Safety) Factors in calculation of 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 hundred-fold uncertainty (safety) 
factor/margin of exposure (safety) is designed to account for combined 
interspecies and intraspecies variability. EPA believes that reliable 
data support using the standard hundred-fold margin/factor without the 
additional ten-fold FQPA 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

[[Page 47503]]

regarding the adequacy of the standard margin/factor. The Agency ad hoc 
FQPA safety factor committee removed the additional 10x FQPA safety 
factor that would otherwise be used to account for increased 
sensitivity of infants and children.
    Zeneca has considered the potential aggregate exposure from food, 
water, and non-occupational exposure routes, concluding that aggregate 
exposure is not expected to exceed 100% of the RfD and that there is a 
reasonable certainty that no harm will result to infants and children 
from aggregate exposure to azoxystrobin residues.

F. International Tolerances

    There are no Codex maximum residue levels established for 
azoxystrobin.
[FR Doc. 00-19378 Filed 8-1-00; 8:45 am]
BILLING CODE 6560-50-F