Federal Register / Vol. 62, No. 48 / Wednesday, March 12, 1997 / Notices 11441

of the Surgeon General that adverse

health effects have not been found in

the U. S. population below 8 mg F/L

(0.23 mg/kg/day).

3. Non-dietary exposure. Cryolite is

used almost exclusively as an

agricultural crop protection insecticide.

Conceivably, cryolite also could be used

in outdoor homeowner/residential sites

for insect control in ornamentals and

shade trees. Cryolite is not registered for

either lawn or crack and crevice

treatments. EPA concluded in the RED

that a post-application exposure

assessment for cryolite (including both

occupational and residential exposure)

was not appropriate since no

toxicological endpoints relevant to nondietary exposure have been identified

for cryolite. The Task Force concludes

that non-dietary exposure represents a

negligible component of potential

aggregate exposure to cryolite and need

not be considered in the aggregate risk

assessment.

D. Cumulative Effects

The residue of toxicological concern

in cryolite is fluoride. Although fluoride

supplements in drinking water are not

considered to be pesticidal substances,

the dietary contribution of drinking

water to overall fluoride exposure has

been discussed elsewhere in this

summary. Current tolerances for

insecticidal fluorine-containing

compounds are limited to cryolite and

synthetic cryolite. For this reason,

consideration of potential cumulative

effects of residues from pesticidal

substances other than sodium

aluminofluoride with a common

mechanism of toxicity are not

applicable.

E. Safety Determination

1. U.S. population. As discussed

above, non-dietary exposure to cryolite

is negligible. For dietary exposure, EPA

has concluded that rather than

establishing a traditional Reference Dose

(RfD), a weight-of-the-evidence risk

assessment is a more appropriate

approach for cryolite. The toxicological

endpoint of concern for dietary

exposure to cryolite is skeletal fluorosis.

EPA has approximated that total dietary

fluoride levels in food plus drinking

water is 0.095 mg/kg/day. Of this total

exposure, the dietary (food) contribution

is about 0.020 mg/kg/day for the U.S.

population, and 0.038 mg/kg/day for the

highest exposed subgroup (females 20

years old and over). The proposed

potato tolerances have been estimated

by EPA to contribute approximately

0.00016 mg/kg/day to total dietary

exposure. These exposure estimates

likely overstate actual dietary exposure,

since marketbasket residue levels for

cryolite have not been considered. As

noted above, the Agency has concurred

with the findings of the Surgeon General

that adverse health effects (skeletal

fluorosis) have not been found in the

U.S. population below 8 mg F/L (0.23

mg/kg/day).

2. Infants and children. EPA has

concluded previously that in rats, the

developmental NOEL for cryolite is

3,000 mg/kg/day (1,584 mg/kg/day F),

that in mice, the developmental NOEL

is 100 mg/kg/day (52.8 mg/kg/day F),

and that in rabbits, the developmental

NOEL is 30 mg/kg/day (15.8 mg/kg/day

F). The NOEL for reproductive toxicity

of cryolite determined in a 2-generation

rat reproduction study was determined

by the Agency to be 46 mg/kg/day (24.3

mg/kg/day F).

These data show clearly that no

additional margin of safety is required

for exposure of infants and children to

cryolite. The developmental NOEL

ranges from more than 166x (rabbit) to

more than 16,000x (rat) for the

maximum combined exposure of infants

and children to residues of fluoride

from all agricultural uses of cryolite

plus drinking water. The reproductive

NOEL is about 256x greater than

maximum combined exposure of infants

and children to residues of fluoride.

F. International Tolerances

No Codex, EC or other international

tolerances are in effect for cryolite; thus,

potential dietary exposure to fluoride

from the agricultural use of cryolite on

crops would not include imported

foodstuffs.

II. Public Record

A record has been established for this

notice under docket control number

[PF–712] (including comments and data

submitted electronically as described

below). A public version of the 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 of the

Public Response and Resources Branch,

Field Operations 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 all comments received

electronically into printed, paper form

as they are received and will place the

paper copies in the official rulemaking

record which will also include all

comments submitted directly in writing.

The official rulemaking record is the

paper record maintained at the address

in ‘‘ADDRESSES’’ at the beginning of

this document.

List of Subjects

Environmental protection,

Administrative practice and procedure,

Agricultural commodities, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: February 24, 1997.

Peter Caulkins,

Acting Director, Registration Division, Office

of Pesticide Programs.

[FR Doc. 97–6015 Filed 3–11–97; 8:45 am]

BILLING CODE 6560–50–F

[PF–715; FRL–5589–6]

Zeneca Ag Products; Pesticide

Tolerance Petition Filing

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice of filing.

SUMMARY: This notice announces the

initial filing of three pesticide petitions

proposing the establishment of

tolerances for residues of azoxystrobin

(not accepted by ANSI) in or on raw

agricultural commodities of grape

(pesticide petition (PP) 5F4541), pecan

(PP 6F4642), and tomato, peach, banana,

peanut, and wheat (PP 6F4762). This

notice includes a summary of the

petitions that was prepared by the

petitioner, Zeneca Ag Products.

DATES: Comments, identified by the

docket control number [PF–715], must

be received on or before, April 11, 1997.

ADDRESSES: By mail, submit written

comments to Public Response and

Program Resources Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St. S.W.,

Washington, DC 20460. In person, bring

comments to Rm. 1132, CM #2, 1921

Jefferson Davis Highway, Arlington, VA

22202. Comments and data may also be

submitted electronically by sending

electronic mail (e-mail) to: oppdocket@epamail.epa.gov. Electronic

comments must be submitted as an

ASCII file avoiding the use of special

characters and any form of encryption.
11442 Federal Register / Vol. 62, No. 48 / Wednesday, March 12, 1997 / Notices

Comments and data will also be

accepted on disks in WordPerfect 5.1

file format or in ASCII file format. All

comments and data in electronic form

must be identified by docket control

number [PF–715]. Electronic comments

on this notice may be filed online at

many Federal Depository Libraries.

Additional information on electronic

submissions can be found below this

document.

Information submitted as comments

concerning this document may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI). CBI should not be submitted

through e-mail. Information marked as

CBI will not be disclosed except in

accordance with procedures set forth in

40 CFR Part 2. A copy of the comment

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. All written

comments will be available for public

inspection in Rm. 1132 at the address

given above, from 8:30 a.m. to 4 p.m.,

Monday through Friday, excluding legal

holidays.

FOR FURTHER INFORMATION CONTACT:

Cynthia Giles-Parker, Product Manager

(22), Registration Division (7505C),

Office of Pesticide Programs,

Environmental Protection Agency, 401

M St., SW., Washington, DC 20460.

Office location, telephone number, and

e-mail address: Rm. 229, CM #2, 1921

Jefferson Davis Highway, Arlington, VA.

22202, 703–305–5540, e-mail: gilesparker.cynthia@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA has

received three pesticide petitions (PP)

5F4541, 6F4642, and 6F4762 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, 21 U.S.C. section 346a(d),

to amend 40 CFR part 180 by

establishing a tolerance for residues of

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:

Commodity Part per million (ppm)

Grapes ...................................................................................................... 1.0 ppm

Pecans ...................................................................................................... 0.01 ppm

Tomato ...................................................................................................... 0.2 ppm

Tomato paste ............................................................................................ 0.6 ppm

Peanut ....................................................................................................... 0.01 ppm

Peanut oil .................................................................................................. 0.03 ppm

Peanut hay ................................................................................................ 1.5 ppm

Peach ........................................................................................................ 0.80 ppm

Banana (whole fruit including peel) .......................................................... 0.5 ppm

Banana pulp .............................................................................................. 0.05 ppm

Wheat grain .............................................................................................. 0.04 ppm

Wheat bran ............................................................................................... 0.12 ppm

Wheat hay ................................................................................................. 13.0 ppm

Wheat straw .............................................................................................. 4.0 ppm

Cattle, fat .................................................................................................. 0.01 ppm

Cattle, mbyp .............................................................................................. 0.01 ppm

Cattle, meat .............................................................................................. 0.01 ppm

Goats, fat .................................................................................................. 0.01 ppm

Goats, mbyp ............................................................................................. 0.01 ppm

Goats, meat .............................................................................................. 0.01 ppm

Hogs, fat ................................................................................................... 0.01 ppm

Hogs, mbyp ............................................................................................... 0.01 ppm

Hogs, meat ............................................................................................... 0.01 ppm

Horses, fat ................................................................................................ 0.01 ppm

Horses, mbyp ............................................................................................ 0.01 ppm

Horses, meat ............................................................................................ 0.01 ppm

Milk ............................................................................................................ 0.006 ppm

Poultry, fat ................................................................................................. 0.01 ppm

Poultry, liver .............................................................................................. 0.01 ppm

Poultry, mbyp ............................................................................................ 0.01 ppm

Poultry, meat ............................................................................................. 0.01 ppm

Sheep, fat ................................................................................................. 0.01 ppm

Sheep, mbyp ............................................................................................. 0.01 ppm

Sheep, meat ............................................................................................. 0.01 ppm

EPA has determined that the petitions

contain 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 supports granting of the

petition. Additional data may be needed

before EPA rules on the petitions.

The proposed analytical methods for

non-oily crops are gas chromatography

with nitrogen-phosphorus detection

(GC-NPD) or in mobile phase using high

performance liquid chromatography

with ultra-violet detection (HPLC-UV).

The proposed analytical method for

oily crops is GC-NPD.

The proposed analytical method for

animal tissue and eggs is (GC-NPD).

The analytical methods summarized

above have not been validated by the

Agency. Public versions of these

analytical methods can be obtained from

Pesticide Docket, U.S. Environmental

Protection Agency, Office of Pesticide

Programs, 401 M St., SW., Washington,

DC 20460, (703)305–5805.

As required by section 408(d) of the

FFDCA, as recently amended by the

Food Quality Protection Act, Zeneca Ag

Products included in the petition a

summary of the petition and

authorization for the summary to be
Federal Register / Vol. 62, No. 48 / Wednesday, March 12, 1997 / Notices 11443

published in the Federal Register in a

notice of receipt of the petition. The

summary represents the views of Zeneca

Ag Products; EPA, as mentioned above,

is in the process of evaluating the

petition. As required by section

408(d)(3) EPA is including the summary

as a part of this notice of filing. EPA

may have made minor edits to the

summary for the purpose of clarity.

Petition Summary:

A. Residue Chemistry

1. Plant metabolism. Plant

metabolism has been evaluated in three

diverse crops--grapes, wheat and

peanuts--which should serve to define

the 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, in fact very low

residues are found in wheat grain,

banana pulp, pecan nutmeat, and

peanut (nuts). 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

percent of the Total Recoverable

Residue (TRR).

Grapes: In grapes parent azoxystrobin

was the major component representing

between 34.6 percent and 64.6 percent

TRR. The metabolism of azoxystrobin

was complex, involving at least six

distinct metabolic pathways, yielding a

large number of minor metabolites. In

total 15 metabolites have been

identified. Metabolite Compound 28 (4-

hydroxy-6–(2-

cyanophenoxy)pyrimidine) was present

at levels of up to 5.2 percent TRR,

Compound 13 (2-cyanophenol) was

present at levels of up to 5.7 percent,

with no other metabolites present at

levels greater than 4.0 percent TRR.

Wheat: In wheat the total radioactive

residues in the grain were very low,

ranging from 0.075 to 0.077 ppm

azoxystrobin equivalents. As expected,

residues in forage and straw were higher

(1.02 to 2.79 ppm and 3.06 to 9.41 ppm,

respectively).

The only significant residue in the

grain was parent azoxystrobin (17.1

–22.0 percent TRR, 0.013 – 0.017 ppm).

No metabolite was present at > 3.3

percent TRR.

In wheat straw, the major component

of the residue was parent azoxystrobin

(22.1 – 43.3 percent TRR, 0.676 – 4.07

ppm). In total, 14 metabolites were

identified, the most significant of which

was Compound 28 (8.2 – 10.4 percent

TRR, 0.319 – 0.731 ppm – sum of free

conjugated and bound forms). The Zisomer was present at 2.1 – 3.5 percent

TRR (0.064 – 0.329 ppm). No other

metabolite was present at > 3.5 percent

TRR.

In wheat forage azoxystrobin was the

major component of the residue (54.9 –

64.7 percent TRR, 0.56 – 1.81 ppm). The

two most significant metabolites were

Compound 28 (3.2 – 3.7 percent TRR,

0.038 – 0.090 ppm - total) and Z-isomer

(1.9 – 2.9 percent TRR, 0.019 – 0.081

ppm). No other metabolite was present

at > 1.1 percent TRR.

Peanuts: In peanuts the total

radioactive residues in the nuts and

hulls were low compared to those in the

foliage.

The majority of the residue in the nuts

was identified as radiolabeled natural

products, resulting from the

mineralization of azoxystrobin in soil

and subsequent incorporation of the

evolved 14CO2 via photosynthesis. The

major radiolabeled natural products

identified were fatty acids and these

accounted for 42.1 – 49.1 percent TRR

(0.101 – 0.319 ppm). Incorporation of

radioactivity into simple sugars was also

confirmed, accounting for 5.8 – 8.5

percent TRR (0.014 – 0.042 ppm). The

presence of radiolabeled glutamic acid,

an amino acid, was also confirmed.

Azoxystrobin was not detected in the

nut (0.001 ppm) and no individual

metabolite was present at a level greater

than 0.002 ppm.

In the hay the major component of the

residue was parent azoxystrobin (33.0 –

43.8 percent TRR, 13.3 – 20.4 ppm). In

total 10 metabolites were identified, the

most significant of which was

Compound 28, in both the free and

conjugated forms (7.0 – 9.0 percent TRR,

2.74 – 3.62 ppm). The next most

significant metabolites were Compound

13 in both the free and conjugated forms

(6.3 percent TRR, 2.53 ppm) and Zisomer (2.4 – 2.8 percent TRR, 0.965 –

1.30 ppm).

2. Analytical Method. Non-oily Crops:

Azoxystrobin and Z-isomer residues in

grape and grain samples are extracted in

90:10/acetonitrile:water. An aliquot of

the extract is cleaned up by adsorption

chromatography on a silica sorbent. The

eluate is evaporated to dryness and

taken up in a known volume of acetone

for analysis by GC-NPD or in mobile

phase for analysis by high performance

liquid chromatography with ultraviolet

detection (HPLC-UV). The limit of

quantitation of the method is typically

0.02 to 0.05 ppm.

Oily Crops: Azoxystrobin and Zisomer residues in oily crop samples are

extracted in 90:10/ acetonitrile:water.

An aliquot of the extract is cleaned up

by passing through a C18 sep-pak. All

extracts were cleaned up by gel

permeation chromatography eluting

through alumina and Florisil solid

phase extraction cartridges. The eluate

was evaporated to dryness and

redissolved in a known volume of

acetone for analysis by GC-NPD. The

limit of quantitation of the method is

typically 0.01 ppm.

Animal Tissues (Liver), Milk and Eggs:

Residues of azoxystrobin in tissue and

egg samples are extracted in acetonitrile

. An aliquot of the extract is cleaned up

by gel permeation chromatography

(GPC) eluting through alumina-n and

Florisil solid phase extraction

cartridges. The eluate is evaporated to

dryness and taken up in a known

volume of acetone for analysis by GCNPD. The limit of quantitation is

typically 0.01 ppm.

Residues of azoxystrobin in milk

samples are extracted in acetonitrile and

partitioned in dichloromethane. The

extract is again cleaned up by GPC

eluting through alumina-n and Florisil

solid phase cartridges. The eluate is

evaporated to dryness and taken up in

a known volume of acetone for analysis

by GC-NPD. The limit of quantitation is

typically 0.006 ppm.

3. Magnitude of residues. Grapes:

Trials were carried out in 1994 in 5

different states: California, New York,

Arkansas, Michigan, and Washington.

An additional 9 trials were conducted in

1995 in New York, California (6) and

Oregon and Washington.

Azoxystrobin 80WG was applied at a

rate of 0.25 lb ai/A. A total of 6

applications was made. The first

application was at 1 to 5 inch shoot

growth, the second at 8 to 12 inch shoot

growth. The third application was at

bloom plus or minus 2 days. The last

three applications were made at 46 (+/

– 3), 35 (+/– 3), and 12–14 days prior

to normal harvest.

Residues in grapes ranged between

0.20 and 0.84 ppm, supporting the

proposed tolerance of 1 ppm. No

concentration of residues was seen in

grape juice or raisins.

Pecans: Trials were carried out

between June and November 1994 in 4

different states: Alabama, Georgia,

Mississippi and Texas.

Azoxystrobin 80WG was applied at a

rate of 0.2 lb ai/A. A total of 6

applications was made. Applications

were made from bud break up to 42

days preharvest on a three week

application schedule.

Azoxystrobin and Z-isomer residues

on pecans after the final spray were <

0.01 ppm, supporting the proposed

tolerance of 0.01 ppm.

Banana: A total of 6 residue trials was

conducted in Hawaii, Florida, and

Puerto Rico during 1995–1996.

Azoxystrobin was applied eight times at
11444 Federal Register / Vol. 62, No. 48 / Wednesday, March 12, 1997 / Notices

a rate of 0.135 lb ai/A. Applications

were made every 12–14 days with the

last application just prior to harvest.

Immediately following the second

application, bags were placed over

several bunches of bananas in both the

treated and untreated plots. The bags

were left in place until harvest. Samples

of bagged and unbagged bananas were

collected immediately after the last

application, after the spray deposit had

dried. Samples of whole bananas and

banana pulp were analyzed for residues

of azoxystrobin and the Z-isomer.

Azoxystrobin residues on bagged

whole bananas sampled immediately

after the last application ranged from <

0.01 to 0.15 ppm. Azoxystrobin residues

on unbagged whole bananas sampled

immediately after the last application

ranged from 0.08 to 0.26 ppm. Residues

of azoxystrobin in banana pulp were

low in both bagged and unbagged

bananas ranging from < 0.01 to 0.03

ppm. Residues of Z-isomer were < 0.01

ppm in all samples of whole bananas

and banana pulp, both bagged and

unbagged. These data support the

proposed tolerances of 0.5 ppm in

whole bananas and 0.05 ppm in banana

pulp.

Peaches: Fourteen trials were carried

out in North Carolina (2), California (4),

Michigan (2), Texas, Arkansas,

Pennsylvania (2), Georgia, and South

Carolina on peaches during 1995.

Azoxystrobin was applied at 0.15 lb ai/

A starting at pink bud to 5 percent

blossom and repeating at 5–10 day

intervals. All the samples were analyzed

for azoxystrobin and the Z-isomer.

Azoxystrobin residues on peaches,

sampled 11–14 days after the final

spray, ranged from 0.07 – 0.70 ppm.

Residues of the Z-isomer were low and

ranged from < 0.01 – 0.05 ppm. These

data support the proposed tolerance of

0.8 ppm.

Peanuts: Twelve residue trials were

carried out in Georgia (2), North

Carolina (3), Oklahoma, Texas (2),

Florida, and Alabama on peanuts during

1994 and in 1995. Azoxystrobin was

applied as a foliar broadcast spray at 0.4

lb ai/A at two spray intervals: 8 to 9

weeks after planting and 12 to 13 weeks

after planting.

Azoxystrobin residues on peanut hay,

sampled about 50 days after the final

spray, ranged from 0.25–0.91 ppm.

Residues of the Z-isomer were low and

ranged from < 0.02 – 0.38 ppm. A trace

residue of azoxystrobin (0.01 ppm), was

found in one nutmeat sample only, all

the remainder were < 0.01 ppm. These

data support the proposed tolerances of

0.01 ppm in the peanut and 1.5 ppm in

peanut hay. Processing data indicate a

possible 3× concentration in peanut oil

supporting a proposed tolerance of 0.03

ppm.

Tomato: Sixteen residue trials were

carried out in California (10), Florida

(2), New Jersey, North Carolina, and

Indiana on tomatoes during 1994 and

1995. Azoxystrobin was applied at 0.1

lb ai/A starting at early fruiting and

repeating on a 6–8 day interval until

eight applications had been made.

Samples of mature fruits were taken 1

day after the final spray and analyzed

for azoxystrobin and the Z-isomer.

Azoxystrobin residues, one day after

the final spray, ranged from 0.01 – 0.16

ppm. Only traces of the Z-isomer

ranging from < 0.01 – 0.02 ppm were

found. These data support the proposed

tolerances of 0.2 ppm in tomato;

processing data showing a possible 3×

concentration in tomato paste support a

proposed tolerance of 0.6 ppm.

Wheat: Six magnitude of the residue

trials were carried out on wheat in

Georgia, Tennessee, Montana, Nebraska,

Virginia, and Oregon during 1994.

Azoxystrobin was applied twice at

growth stages Zadoks 43–45 and 55–59

at 0.2 lb ai/A Samples of hay, straw and

grain were analyzed for azoxystrobin

and the Z-isomer.

Azoxystrobin residues on hay,

sampled two weeks after the final spray,

were 0.19 to 6.5 ppm. At harvest, 33–

74 days after treatment, residues in

wheat grain were low and ranged from

< 0.01 – 0.03 ppm. Residues on straw

ranged from 0.03 – 3.4 ppm.

A total of 16 residue trials were

conducted in Mississippi, Illinois, Ohio,

Wisconsin, Texas (2), Nebraska,

Montana (2), North Dakota, Colorado,

Kansas (2), Oklahoma, New Mexico, and

California during 1995. Azoxystrobin

was applied 2 times at a rate of 0.2 lb

ai/A. Application timings were at

Zadoks 43–45 (boot) and 30–45 days

prior to grain harvest (no later than

Zadoks 58, head emergence).

Azoxystrobin residues on hay

sampled 13 to 33 days after the last

application ranged from 0.09 to 11.1

ppm. Residues of azoxystrobin on straw

sampled 36 to 52 days after the last

application ranged from 0.03 to 1.31

ppm. Residues of azoxystrobin on grain

sampled 36 to 52 days after the last

application were low, ranging from <

0.01 to 0.06 ppm.

Residues of Z-isomer on hay ranged

from < 0.01 to 0.8 ppm. Residues of Zisomer on straw were low, ranging from

< 0.01 to 0.13 ppm. Residues of the Zisomer on grain were < 0.01 ppm on all

samples. These data support proposed

tolerances of 0.04 ppm on grain, 4.0

ppm on straw and 13 ppm on hay.

Processing data indicate a possible 3×

concentration in wheat bran, supporting

a proposed tolerance of 0.12 ppm.

B. Toxicological Profile (Azoxystrobin

Technical)

1. Acute toxicity.

Study Type Study Results Tox. Category

Acute Oral Rat .................................................................... LD50 > 5,000 mg/kg ....................................................................... IV

Acute Dermal Rat ............................................................... LD50 > 2,000 mg/kg ....................................................................... III

Acute Inhalation Rat ........................................................... LC50 = 698 mg/l for females ..........................................................

..................................................................................... LC50 = 962 mg/l for males ............................................................. III

Eye Irritation Rabbit ............................................................ Slight irritant, no corneal effects .................................................... III

Skin Irritation Rabbit ........................................................... Slight irritant ................................................................................... IV

Skin Sensitization Guinea Pig ............................................ Not a skin sensitizer ......................................................................

2. Genotoxicity. Azoxystrobin gave a

weak clastogenic response in

mammalian cells in vitro at cytotoxic

doses. In the whole animal azoxystrobin

was negative in established assays for

chromosomal damage (clastogenicity)

and general DNA damage, at high dose

levels (≥ 2,000 mg/kg). The weak

clastogenic effects seen in vitro are not

expressed in the whole animal and

azoxystrobin is considered to have no

genotoxicity in vivo.

Assay Type Results

In vitro ................................................................................. Ames .............................................................................................. negative

..................................................................................... L5178Y .......................................................................................... weakly positive
Federal Register / Vol. 62, No. 48 / Wednesday, March 12, 1997 / Notices 11445

Assay Type Results

..................................................................................... IVC ................................................................................................. weakly positive

In vivo ................................................................................. Micronucleus .................................................................................. negative

..................................................................................... UDS ............................................................................................... negative

3. Reproductive and developmental

toxicity. Reproductive toxicity.

Azoxystrobin showed no evidence of

reproductive toxicity.

The No Observed Effect Level (NOEL)

for toxicity was judged to be 300 ppm

azoxystrobin, which for the premating

period, translates into a daily dose of 32

mg azoxystrobin/kg body weight/day

based on body weight reductions

relative to control and liver toxicity in

adult males.

The liver toxicity observed in the

reproductive toxicity study was

manifest as gross distension of the

common bile duct accompanied by

histological change. The histological

changes in the intraduodenal bile duct

were characterized by an increase (a

hyperplasia) in the number of lining

(epithelial) cells and bile duct

inflammation (cholangitis). In the liver,

there was an increased severity of

hepatic proliferative cholangitis. The

increased severity of the microscopic

liver effects were confined to those

animals showing gross bile duct

changes, suggesting that these effects

were secondary to biliary toxicity.

These observations were confined to

male F0 and F1 adult rats and were not

detected in female animals or in pups.

Azoxystrobin in Diet (ppm) Dose (mg/kg/day)

60 .............................................................................................................. 6.5

300 ............................................................................................................ 32

1,500 ......................................................................................................... 162

Developmental Toxicity. There were

no adverse effects in the rat or rabbit on

the number, survival and growth of the

fetuses in utero. Azoxystrobin caused no

developmental toxicity in the rat or in

the rabbit up to and including dose

levels shown to be maternally toxic.

Study Type: Developmental Toxicity NOEL/LEL (mg/kg/day) Effect Description

Rabbit (by gavage) .................................... No developmental effects. NOEL for developmental toxicity > 500 mg/kg/day. NOAEL for

maternal toxicity = 50 mg/kg/day..

No developmental effects. NOAEL for maternal

toxicity = 50 mg/kg/day. LEL for maternal toxicity = 150 mg/kg/day; effects were reduced

body weight, clinical effects.

Rat (by gavage) ......................................... No developmental effects, NOEL = 25 mg/kg/day

for maternal and fetotoxicity.

LEL for fetotoxicity is 100 mg/kg/day; effect was

‘‘delayed ossification’’. LEL for maternal toxicity 100 mg/kg/day; effect was reduced body

weight.

4. Subchronic Toxicity. Azoxystrobin

is of low subchronic toxicity in 21–day

dermal testing.

5. Chronic Toxicity. Oncogenicity -

Rat: Azoxystrobin is non-oncogenic in

the rat.

Azoxystrobin in Diet (ppm) Male rat (mg/kg/day) Female rat (mg/kg/day)

60 ................................................................................ 3.6 ................................................................ 4.5

300 .............................................................................. 18.2 .............................................................. 22.3

1500/750 ..................................................................... 82.4 .............................................................. 117.6

The NOEL/NOAEL for azoxystrobin

in the rat is 18 mg/kg bwt/day.

Zeneca suggests that this chronic rat

study has the lowest No Observed

Adverse Effect Level (NOAEL) of the

chronic studies conducted with

azoxystrobin. The Reference Dose (RfD)

for azoxystrobin should be based upon

the NOAEL of 18 mg/kg bwt/day with

an uncertainty factor of 100, RfD = 0.18

mg/kg bwt/day.

A dietary inclusion level of 1,500

ppm was established as a Maximum

Tolerated Dose (MTD) in female rats,

where decrements in body weight gain

relative to control of approx. 19 percent

at week 53 and 11 percent at week 105

were observed. The maximum reduction

relative to control was seen at week 73

(approx. 20 percent). In male rats this

dose level was in excess of an MTD

(biliary toxicity), resulting in a

reduction in the top dose level from

1500 ppm to 750 ppm for the second

year of the study. Reductions in male

body weight gain relative to control

animals were seen throughout the

duration of the study with a maximum

reduction of approx. 11 percent in the

first year (at week 45), continuing into

the second year (maximum reduction of

approx. 13 percent at week 99).

In the rat, there was no statistical

increase in the number of tumor-bearing

animals, animals with malignant

tumors, benign tumors, multiple tumors,

single tumors or metastic tumors in

animals treated with azoxystrobin at

dose levels of up to 1,500 ppm (up to

117.1 mg azoxystrobin/kg bwt/day) for 2

years.

Oncogenicity - Mouse.

Azoxystrobin is non-oncogenic in the

mouse.
11446 Federal Register / Vol. 62, No. 48 / Wednesday, March 12, 1997 / Notices

Azoxystrobin in Diet (ppm) Male mouse (mg/kg/day) Female mouse (mg/kg/day)

50 ....................................................................... 6.2 ..................................................................... 8.5

300 ..................................................................... 37.5 ................................................................... 51.3

2000 ................................................................... 272.4 ................................................................. 363.3

There was no increased tumor

incidence or early onset of tumors in

mice receiving up to 2,000 ppm

azoxystrobin for up to 2 years. Dietary

administration of 2,000 ppm

Azoxystrobin was associated with

reduced growth and food utilization.

An MTD was established in the

mouse oncogenicity study based on

body weight gain depression and

decreased food utilization seen at the

highest dose test of 2000 ppm. At this

dose level body weight gain was

depressed 20 percent at week 13 and 28

percent at week 53 in males, and 11

percent at week 13 and 19 percent at

week 53 in females.

There was no statistically significant

change or alteration in tumor incidence

in the mouse attributable to treatment

with azoxystrobin at dose levels of up

to 2,000 ppm (up to 363.3 mg

azoxystrobin/kg bwt/day) for 2 years.

One-year Feeding Study - Dog.

Azoxystrobin was administered to

groups of 4 beagle dogs at dose levels of

0, 3, 25 and 200 mg/kg bwt/day, as a

daily oral dose.

Adaptive liver responses were

observed at 25 and 200 mg/kg bwt/day

which were not considered to be

toxicologically significant. The adaptive

liver responses were increased liver

weights and increased serum liver

enzyme activities in the absence of any

liver histopathology. Liver weights were

increased in both sexes at 200 mg/kg

bwt/day, and in females at 25 mg/kg

bwt/day. Plasma alkaline phosphatase,

cholesterol and triglyceride levels were

elevated at the top dose in both sexes,

with plasma albumin elevated at 200

mg/kg/day in males only. Plasma

triglycerides were also elevated at 25

mg/kg bwt/day in males only. No such

effects were observed at 3 mg/kg bwt/

day.

These changes were not accompanied

by any histopathological change in the

liver. Such changes in the absence of

signs of a toxic lesion are generally

considered to reflect the liver

compensating for the increased work it

must perform in metabolizing the test

compound. While they can be

considered to be effects of azoxystrobin

treatment, these changes are of no

toxicological significance.

The NOEL in this study was 200 mg/

kg bwt/day.

6. Animal metabolism. Azoxystrobin

is well absorbed and completely

metabolized in the rat. Excretion is

rapid and there is no accumulation of

azoxystrobin or metabolites. There are

no significant plant metabolites that are

not animal metabolites.

7. Metabolite toxicology. Toxicity

testing results on the azoxystrobin

parent compound are indicative of the

toxicity of all significant metabolites

seen in either plants or mammals.

C. Aggregate Exposure

1. Dietary exposure. a. Food. For the

purpose of assessing the potential

dietary exposure from these proposed

tolerances, EPA generally estimates

aggregate exposure based on the

Theoretical Maximum Residue

Contribution (TMRC) from the

tolerances proposed for azoxystrobin as

listed above. The TMRC is obtained by

multiplying the tolerance level residue

for each food by the consumption data

which estimate the amount of food and

food products eaten by the U.S.

population and various population

subgroups. Animal feeds (such as wheat

forage) are fed to animals; thus,

exposure of humans to residue in the

animal feeds might result if such

residues are transferred to meat, milk or

poultry. Animal metabolism and feeding

studies indicate that low residues may

occur in meat and milk when

azoxystrobin is used as proposed. The

TMRC for each animal product is

obtained by multiplying the tolerance

(worst-case) level of residues possible in

meat and milk by the food consumption

data which estimate the amount of food

and food products eaten by various

population subgroups. These are very

conservative assumptions--100 percent

of foods, meat and milk products will

contain azoxystrobin residues and those

residues would be at the level of the

tolerance--that produce a very

conservative overestimate of human

dietary exposure. Zeneca performed

chronic dietary exposure analyses using

the food consumption data in the U.S.

Department of Agriculture’s (USDA)

Nationwide Food Consumption Survey

for 1989 through 1992 combined and

Technical Assessment System Inc.’s

‘‘EXPOSURE 1’’ analysis software. The

potential exposure for the U.S.

population is 0.0009 mg/kg bwt/day.

Potential exposure for children’s

population subgroups ranged from

0.0013 mg/kg bwt/day for children 7–12

Years Old to 0.0029 mg/kg bwt/day for

children 1–6 Years Old.

b. Drinking water. Azoxystrobin does

not leach. It is unlikely that

azoxystrobin could be present in

drinking water or groundwater.

Therefore it is not appropriate to assess

aggregate exposure from drinking water.

Azoxystrobin is an analogue of

naturally occurring strobilurins which

are sensitive to sunlight (photolysis).

Azoxystrobin, although more stable than

the strobilurins, has a favorable

environmental profile. Azoxystrobin is

degraded rapidly under agricultural

field conditions with a soil half-life of

less than 2 weeks. The compound is

non-volatile and does not leach, but it

is very susceptible to photolysis.

Photolysis accounts for the majority of

the initial loss of the compound, the

remainder being degraded microbially.

Based on laboratory data the

predicted mobility of azoxystrobin in

soil is relatively low. The soil

adsorption coefficient corrected for soil

organic matter (Koc) ranges from 300 to

1690. Consequently, the potential

mobility is low to medium. As a

measure of possible mobility the

standard GUS index value is 1.0; which

equates to a non-leacher.

Results from field trials support these

laboratory data. After using 14C-labeled

azoxystrobin as a ‘‘worst case’’ field

application - bare surface, irrigated and

poorly retentive soil (light texture and

low organic matter content), the

compound was retained in the upper 2

inches or so of the soil throughout its

lifetime.

As azoxystrobin does not leach it is

very unlikely to enter into water bodies

except by accidental, direct over-spray.

However, the compound in laboratory

tests degrades with a half-life of

approximately 7 weeks in flooded

anaerobic soils. There is also potential

for photolytic degradation in natural

aqueous environments; the aqueous

photolysis half-life is 11–17 days.

2. Non-dietary exposure. Other

potential sources of exposure of the

general population to residues of

pesticides is non-occupation exposure.

Since the proposed registrations for

azoxystrobin are limited to commercial

crop production, turf farms and golf

courses, the potential for nonoccupational exposure to the general

population is not expected to be

significant.
Federal Register / Vol. 62, No. 48 / Wednesday, March 12, 1997 / Notices 11447

D. Cumulative Effects

Azoxystrobin is a new class of

chemistry for pesticides, a betamethoxyacrylate fungicide.

Azoxystrobin has the same biochemical

mode of action as the naturally

occurring strobilurins, inhibition of

electron transport. Since there are no

other registered pesticides in this

chemical class or with this mode of

action or mechanism of action,

cumulative exposure assessment is not

appropriate at this time.

No evidence or information exists to

suggest that toxic effects produced by

azoxystrobin would be cumulative with

those of any other chemical compounds.

E. Safety Determination

1. U.S. population in general. Using

the conservative assumptions described

above, based on the completeness and

reliability of the toxicity data, Zeneca

estimates that the aggregate exposure to

azoxystrobin will utilize 0.5 percent of

the RfD for the U.S. population. This

chronic dietary exposure analysis is

based on food consumption for the

combined years 1989–1992 in the

USDA’s Nationwide Food Consumption

Survey and analysis using Technical

Assessment Systems, Inc.’s ‘‘EXPOSURE

1’’ analysis software. Generally there are

no concerns for exposures below 100

percent of the RfD. The EPA defines the

RfD to represent the level at or below

which daily aggregate dietary exposure

over a lifetime will not pose appreciable

risk to human health.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

azoxystrobin Zeneca has considered the

2–generation reproduction study in the

rat and the developmental toxicity

studies in the rat and rabbit.

Azoxystrobin showed no evidence of

reproductive toxicity. Azoxystrobin

caused no developmental toxicity in the

rat or rabbit up to and including dose

levels shown to be maternally toxic.

There were no adverse effects, in the rat

or rabbit, on the number, survival and

growth of the fetuses in utero.

Based on the current toxicological

data requirements, the database relative

to pre- and post- natal effects for

children is complete. Further,

azoxystrobin shows no evidence of

reproductive or developmental toxicity,

therefore we suggest that use of an

additional uncertainty factor is not

warranted and that the RfD of 0.18 mg/

kg/day is appropriate for assessing

aggregate risk to infants and children.

Using the conservative exposure

assumption described above, Zeneca

concludes that the percent of the RfD

that will be utilized by aggregate

exposure to residues of azoxystrobin

ranges from 0.8 percent for the

population subgroups Nursing infants

and children 7–12 years old up to 1.6

percent for the population subgroup

Children 1–6 years old. Zeneca

concludes that there is 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.

II. Public Record

Interested persons are invited to

submit comments on this notice of

filing. Comments must bear a notation

indicating the docket control number,

[PF–715]. All written comments filed in

response to this petition will be

available in the Public Response and

Program Resources Branch, at the

address given above from 8:30 a.m. to 4

p.m., Monday through Friday, except

legal holidays.

A record has been established for this

notice under docket control number

[PF–715] (including comments and data

submitted electronically as described

below). 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 Rm. 1132 of the

Public Response and Program Resources

Branch, Field Operations 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 ASCII files avoiding the

use of special characters and any form

of encryption.

The official record for this notice, as

well as the public version, as described

above will be kept in paper form.

Accordingly, EPA will transfer all

comments received electronically into

printed, paper form as they are received

and will place the paper copies in the

official record which will also include

all comments submitted directly in

writing. The official record is the paper

record maintained at the address in

‘‘ADDRESSES’’ at the beginning of this

document.

Authority: 21 U.S.C. 346a.

List of Subjects

Environmental protection,

Administrative practice and procedure,

Agricultural commodities, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: February 24, 1997.

Peter Caulkins,

Acting Director, Registration Division, Office

of Pesticide Programs.

[FR Doc. 97–5683 Filed 3–11–97; 8:45 am]

BILLING CODE 6560–50–F

[OPP–181035; FRL 5591–3]

Mancozeb; Receipt of Application for

Emergency Exemption, Solicitation of

Public Comment

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: EPA has received a specific

exemption request from the Wisconsin

Department of Agriculture, Trade, and

Consumer Protection (hereafter referred

to as the ‘‘Applicant’’) to use the

pesticide, mancozeb (CAS 8018–01–7),

formulated as Dithane DF, to treat up to

5,000 acres of ginseng to control stem

and leaf blight. Since this request

proposes a use which has been

requested or granted in any 3 previous

years, and a complete application for

registration and petition for tolerance

has not yet been submitted to the

Agency; and since mancozeb has also

been the subject of a Special Review,

EPA is soliciting public comment before

making the decision whether or not to

grant the exemption, in accordance with

40 CFR 166.24(a)(5) and (6).

DATES: Comments must be received on

or before March 27, 1997.

ADDRESSES: Three copies of written

comments, bearing the identification

notation ‘‘OPP–181035,’’ should be

submitted by mail to: Public Response

and Program Resource Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person, bring

comments to: Rm. 1132, Crystal Mall #2,

1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically by sending

electronic mail (e-mail) to: oppdocket@epamail.epa.gov. Electronic

comments must be submitted as an

ASCII file avoiding the use of special

characters and any form of encryption.

Comments and data will also be

accepted on disks in WordPerfect in 5.1