52552 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

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, it is not appropriate to

assume that azoxystrobin has a common

mechanism of toxicity with other

substances.

E. Safety Determination

The chronic toxicity 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.

1.As part of the hazard assessment

process, the available toxicological

database was reviewed 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 1–day or

single event exposure by the oral route.

Therefore, an acute dietary risk

assessment is not required for

azoxystrobin at this time.

2. U.S. population. The chronic

dietary exposure analysis showed that

exposure from the proposed new

tolerances in or on tree nuts, pistachios,

cucurbits, rice, and wheat for the

general U.S. population would be 1.1%

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.

3. Infants and children. The chronic

dietary exposure analysis, using the

same tolerances and commodities that

were used for the same analysis for the

general U.S. population showed that the

exposure of Non-nursing Infants (the

subgroup with the highest exposure)

would be 4.1% of the RfD.

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 1/100th 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 intraspecies

variability. EPA believes that reliable

data support using the standard

hundredfold margin/factor not the

additional tenfold margin/factor when

EPA has a complete database 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 database 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.

F. 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 pf

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. There are currently no

data or information suggesting that

azoxystrobin has any endocrine effects.

G. International Tolerances

There are no Codex Maximum

Residue Levels established for

azoxystrobin. (Cynthia Giles-Parker)

[FR Doc. 97–26537 Filed 10–8–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–765; FRL–5745–9]

Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of pesticide petitions

proposing the establishment of

regulations for residues of certain

pesticide chemicals in or on various

food commodities.

DATES: Comments, identified by the

docket control number PF–765, must be

received on or before November 7, 1997.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch, Information

Resources and Services Division

(7506C), Office of Pesticides Programs,

Environmental Protection Agency, 401

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

person bring comments to: Rm. 1132,

CM #2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically to: oppdocket@epamail.epa.gov. Follow the

instructions under ‘‘SUPPLEMENTARY

INFORMATION.’’ No confidential

business information should be

submitted through e-mail.

Information submitted as a comment

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 email. 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: The

product manager listed in the table

below:
Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices 52553

Product Manager Office location/telephone number Address

Joe Tavano .................... Rm. 214, CM #2, 703–305–6411, e-mail: tavano.joe@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Bipin Gandhi, ................. Rm. 4W53, CS #1, 703–308–8380, e-mail: gandhi.bipin@epamail.epa.gov. 2800 Crystal Drive, Arlington,

VA

Eugene Wilson ............... Rm. 245, CM #2, 703–305–6103, e-mail: wilson.eugene@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

SUPPLEMENTARY INFORMATION: EPA has

received pesticide petitions as follows

proposing the establishment and/or

amendment of regulations for residues

of certain pesticide chemicals 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 these 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 petition.

The official record for this notice of

filing, as well as the public version, has

been established for this notice of filing

under docket control number [PF–765]

(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 official

record is located at the address in

‘‘ADDRESSES’’ at the beginning of this

document.

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. Comment and data will

also be accepted on disks in

Wordperfect 5.1 file format or ASCII file

format. All comments and data in

electronic form must be identified by

the docket number PF–765 and

appropriate petition number. Electronic

comments on notice may be filed online

at many Federal Depository Libraries.

List of Subjects

Environmental protection,

Agricultural commodities, Food

additives, Feed additives, Pesticides and

pests, Reporting and recordkeeping

requirements.

Dated: September 25, 1997.

James Jones,

Actinig Director, Registration Division, Office

of Pesticide Programs.

Summaries of Petitions

Petitioner summaries of the pesticide

petitions are printed below as required

by section 408(d)(3) of the FFDCA. The

summaries of the petitions were

prepared by the petitioners and

represent the views of the petitioners.

EPA is publishing the petition

summaries verbatim without editing

them 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.

1. B2E Corporation

PP 7E4907

EPA has received a pesticide petition

(PP 7E4907) from B2E Corporation, 16

School Street, Rye, NY 10580 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 to establish an exemption from the

requirement of a tolerance for 2-

Hydroxyacetophenone (2-HAP) in or on

the raw agricultural commodity. The

proposed analytical method involves

homogenization, filtration, partition and

cleanup with analysis by high

performance liquid chromatography

using UV detection. 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 supports granting of the

petition. Additional data may be needed

before EPA rules on the petition.

A. Toxicological Profile

1. Acute toxicity. A rat acute oral

study with an LD50 > 500 milligrams/

kilogram (mg)/(kg), a rabbit acute

dermal toxicity study with an LD50 >

2,000 mg/kg, a primary eye irritation

study in the rabbit showing no

irritation, a rabbit primary dermal

irritation study showing 2-HAP is not an

irritant, a skin sensitization study in

guinea pigs showing 2-HAP is a slight

skin sensitizer, and a 28 day rat

inhalation study with a no observedeffect-level (NOEL) of 160 milligrams/

cubic meter (mg)/(m3).

2. Genotoxicty. 2-HAP was tested in

the Ames Salmonella/microsome plate

incorporation assay both in the presence

and the absence of a metabolic

activation system. Under the conditions

of the assay, 2-HAP did not exhibit

genetic activity according to the assay

criteria. It can therefore be considered

non-mutagenic.

3. Ecotoxicity. A study of acute

toxicity to Bluegill Sunfish was

conducted at five nominal

concentrations, selected on the basis of

preliminary toxicity screening, as well

as a control and the solvent (acetone).

The fish (10 in each replicate) were

observed at 24, 48, 72 and 96 hour

intervals for signs of toxic effects and

mortality. 2-HAP was determined to

have an LC50 (96 hours) of 115

milligrams/liter (mg)/(L) and a no

observed effect-concentration (NOEC) of

31.3 mg/L.

A study of acute toxicity to Daphnids

was conducted at five nominal

concentrations as well as a control and

solvent (acetone) over 48 hours (hrs).

They were observed at 24 and 48 hours

for signs of toxic effects and mortality.

2-HAP was calculated to have an EC50

(48 hr) of 57 mg/L under these

conditions. The NOEC was found to be

25 mg/L.

B. Environmental Fate

Aerobic soil metabolism was

evaluated by a Ready Biodegradation by

CO2 Production study. The test liquid

was added to test medium at 10 and 20

mg/L. Unacclimated diluted inoculum

(20 ml, 1.3 million CFU. ml) was added

to 2 liters of diluted test material,

positive control material (glucose at 20

milligrams/milliter (mg)/(ml) or control

medium. Carbon dioxide free air was

bubbled through the stirred 22.6–23.2 °

C. incubation mixtures and carbon

dioxide collected for 28 days. Carbon

dioxide was measured by titration of

barium hydroxide traps at regular

intervals of the study. Percent

biodegradation was estimated by

percent of theoretical carbon dioxide
52554 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

(TCO2) production achieved based on

the empirical formula, assuming that all

organic carbon in the test material is

converted to carbon dioxide, and by

measurement of total organic carbon

(TOC) remaining after the 28 day

incubation.

After a lag of about 1 day, test

material carbon dioxide production

achieved 93.2% (at 10 mg/L) and 86.7%

(at 20 mg/l) TCO2 28 days after study

start. The soluble organic carbon

content at study termination was < 0.5

mg/L and 0.7 mg/l initial concentrations

of test material respectively. This

corresponds to 100% (at 10 mg/L) and

98.6% (at 20 mg/L) removal of test

material also indication effective

mineralization.

The 2-HAP produced greater than

60% of the TCO2 within 28 days of

incubation and can be considered

readily biodegradable.

Anaerobic degradation is not expected

to be a factor given the application of

the product.

C. Aggregate Exposure

1. Dietary exposure. Dietary exposure

for 2-HAP is expected to be negligible

for the application of 2-HAP in non-food

use pesticides. If 2-HAP were to be

incorporated in pesticides used for food

crops, the level of 2-HAP would be at

most, a small fraction of the acceptable

tolerances of the pesticides. The use

level within the pesticide is only a

maximum of 0.1% by weight. The rapid

biodegradability make significant

uptake into plant tissue unlikely.

Human exposure may be expected to be

within acceptable (note: FDA classifies

this as a GRAS material for use in meat

products, poultry, condiments, soups

and seasonings) limits.

2. Drinking water. Although 2-HAP is

not considered to be hydrolyzable, it is

readily biodegradable. Use levels at a

maximum of 0.1% within pesticides

also make it unlikely that there will be

a presence in groundwater. Based on

this data, exposure to residues in

drinking water in not anticipated. The

EPA has not established a Maximum

Concentration Level for residues of 2-

HAP in drinking water.

3. Non-dietary exposure. Evaluations

by B2E Corporation of the estimated

non-occupational exposure to 2-HAP

have concluded that the potential

exposure for the general population may

be from residues in food crops

discussed above. Another possible

exposure is from the use on turf of

pesticides containing 2-HAP as an inert.

The route of exposure would be dermal

(assuming that people would be walking

barefoot on treated areas) and the

material has been shown to have a low

order of acute dermal toxicity (rabbit -

LD50 10,300 mg/kg).

D. Cumulative Effects

B2E Corporation considered the

potential for cumulative effects of 2-

HAP and similar substances that may

have a common mechanism of toxicity.

there is no information to indicate that

toxic effects that might be found at high

levels of exposure to 2-HAP would be

cumulative with other chemical

compounds. The potential risks of 2-

HAP are judged solely in its aggregate

exposure.

E. Safety Determination

1. U.S. population. Based on the

exposure assumptions and the toxicity

data described above, there is no

appreciable risk to human health. It can

be concluded that there is a reasonable

certainty that no harm will result from

aggregate exposure to 2-HAP residues.

2. Infants and children. Based on the

use patterns of the material and the

levels of exposure, there is a reasonable

certainty that no harm will result to

infants and children from aggregate

exposure to 2-HAP residue.

F. International Tolerances

No international tolerances have been

established.

2. Novartis Crop Protection, Inc.

PP 6F4616, 6F4617, 6F4618, & 6F4633

EPA has received a pesticide petition

(PP 6F4616, 6F4617, 6F4618, & 6F4633)

from Novartis Crop Protection, Inc., P.O.

Box 18300, Greensboro, NC 27419–8300

proposing pursuant to section 408(d) of

the Federal Food, Drug and Cosmetic

Act, 21 U.S.C. 346a(d), to amend 40 CFR

part 180 by establishing a tolerance for

residues of Fenoxycarb, ethyl[2-(4-

phenoxyphenoxy)ethyl]carbamate in or

on the raw agricultural commodities:

pome fruit at 0.02 parts per million

(ppm); nutmeat at 0.05 ppm; almond

hulls at 4.0 ppm; citrus fruit at 0.05

ppm; grass Forage (except Bluegrass) at

0.6 ppm; grass hay (except Bluegrass) at

0.5 ppm; milk, meat and meat

byproducts of cattle, goats, hogs, horses

and sheep at 0.01 ppm; and fat of cattle,

goats, hogs, horses and sheep at 0.05

ppm. The proposed analytical method

involves Column switching high

performance liquid chromatography and

UV detection. EPA has determined that

the petitions contain 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 supports

granting of the petition. Additional data

may be needed before EPA rules on the

petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism

of fenoxycarb in plants (apples, citrus

and grass) is well understood. Identified

metabolic pathways are similar in plants

and animals. It has been determined

that fenoxycarb, per se, is the residue of

concern for tolerance setting

purposes.The metabolism of fenoxycarb

in plants (apples, citrus and grass) is

well understood. Identified metabolic

pathways are similar in plants and

animals. It has been determined that

fenoxycarb, per se, is the residue of

concern for tolerance setting purposes.

2. Analytical method. Novartis Crop

Protection Inc. has submitted practical

analytical methodology for detecting

and measuring levels of fenoxycarb in or

on food. The limits of detection (2.5 ng)

and quantitation (0.01 ppm) allow

monitoring of food with residues at or

above the levels in the proposed

tolerances. All methods are based on

crop specific cleanup procedures and

determination nce liquid

chromatography with column-switching

and UV detection.

3. Magnitude of residues. Residue

trials: 15 residue trials in 8 states on

apples and pears; 16 field trials in 13

states on grasses; 13 residue trials in 4

states on citrus; 8 residue trials in 6

states on tree nuts. No residues of

fenoxycarb (0.01 ppm) were found in

apples or pears treated at the maximum

labeled rate. The maximum residues

found in grasses were 0.056 ppm in

forage and 0.041 in hay. Only one

detectable residue at 0.02 ppm was

found on citrus. This grapefruit sample

was aerially treated with the maximum

labeled rate. The maximum residue

found in nutmeats treated at the

maximum labeled rate was 0.02 ppm.

B. Toxicological Profile

1. Acute toxicity. The following acute

toxicity studies have been conducted to

support the proposed tolerance for

fenoxycarb. The studies indicate that

fenoxycarb has a low order of acute

toxicity with effects in catgegory III and

IV.

• Rat acute oral study with an LD50

>10,000 mg/kg.

• Rabbit acute dermal study with an

LD50 > 2,000 mg/kg.

• Rat inhalation study with an LC50

> 4.4 mg/L.

• Primary eye irritation study in the

rabbit showing slight eye irritation.

• Primary dermal irritation study in

the rabbit showing fenoxycarb is not a

skin irritant.
Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices 52555

• Skin sensitization study showing

fenoxycarb is not a skin sensitizer in the

Guinea pig.

• Dermal absorption study showing

a maximum of 30.2% of fenoxycarb is

absorbed by the rat following a 24 hour

dermal exposure.

2. Genotoxicty. Results from the

following assays indicate that

fenoxycarb is not genotoxic: Ames

Assay - Negative; Mouse Micronucleus

Test - Negative; Saccharomyces

cerevisiae D7 test - Negative.

3. Reproductive and developmental

toxicity. Novartis conducted a

teratogenicity study in the rat at doses

of 0, 50, 150, or 500 mg/kg/day by

gavage with maternal and

developmental NOELs of ≥ 500 mg/kg/

day.

Novartis also conducted a

teratogenicity study in the rabbit at

doses of 0, 30, 100, 200 or 300 mg/kg/

day. The maternal NOEL based on

reduced body weight gains was 100 mg/

kg/day. The developmental NOEL was ≥

300 mg/kg/day.

In a 2-generation reproduction study,

rats were dosed of 0, 200, 600 or 1,800

ppm. The systemic NOEL was 200 ppm

based on decreased body weight gains

and food consumption, increased gonad

weights (without effects on reproductive

performance or a morphological

correlate), liver hypertrophy and focal

necrosis and increased liver weights.

There were no effects on fertility or

reproductive performance. Based on

decreased pup weights and slight delays

in pinna unfolding and eye opening,

there was no clear developmental

NOEL. A derived NOEL (DNOEL),

determined using analysis of variance

and regression, was 40 ppm.

4. Subchronic toxicity. Novartis

conducted a 21–day dermal study in

which fenoxycarb was applied to the

shaved skin of 5 male and 5 female New

Zealand White rabbits at dose levels of

0, 20, 200, or 2,000 mg/kg for 21

consecutive days. The only effect

observed was a slight increase in liver

weights at the high dose. However, there

was no histopathological correlate to

this finding and the change was

interpreted as representing an adaptive

response. The NOEL was 200 mg/kg.

In a 6–month oral (capsule) study of

dogs dosed at 0, 50, 150 or 500 mg/kg/

day, the NOEL was 150 mg/kg/day

based on reduced weight gain in

females.

In a 90–day feeding study, Sprague

Dawley rats were fed fenoxycarb at

dietary concentrations to result in doses

of 0, 80, 250 or 800 mg/kg/day. Based

on slight liver weight increases at 80

mg/kg/day, the NOEL was < 80 mg/kg/

day.

Novartis conducted a 90–day feeding

study in mice in which mice were fed

dietary concentrations of fenoxycarb to

result in doses of 0, 100, 300 or 900 mg/

kg/day. Based on increased liver weight

accompanied by fatty changes, glycogen

depletion and increased multinucleated

hepatocytes, the NOEL was 100 mg/kg/

day.

Rats in a 21–day inhalation study

were exposed to 0, 0.01, 0.10 or 1.13

mg/L for 6 hrs/day/5 days/week. Based

on decreased body weight gain in males

and increased liver weight in females

the NOEL was 0.10 mg/L.

5. Chronic toxicity. In a 52 week oral

(capsule) study, dogs were dosed at

levels of 0, 25, 80 or 260 mg/kg/day.

Based on decreased body weight gain

and food consumption and decreases in

adrenal weights and inorganic

phosphorous the NOEL was 25 mg/kg/

day.

In a 24–month chronic feeding and

oncogenicity study, rats were dosed at

levels of 0, 200, 600 or 1,800 ppm.

Based on liver toxicity (non-neoplastic

histopathology and increased liver

enzymes) the NOEL was 200 ppm.

There was no evidence of carcinogenic

potential.

In an 80–week chronic feeding and

oncogenicity study, mice were dosed at

0, 30, 110 or 420 ppm for males and 0,

20, 80 or 320 ppm for females. Systemic

toxicity was not observed at any level.

The NOEL for chronic toxicity was ≥

420 ppm and 320 ppm for males and

females, respectively. There was

evidence of carcinogenic potential. Lung

adenomas and combined adenoma/

carcinoma in addition to Harderian

gland tumor incidences were increased

in males at 420 ppm.

In an 18–month oncogenicity study,

mice were dosed at 0, 10, 50, 500 or

2,000 ppm with a NOEL of 50 ppm (5

– 6 mg/kg/day). A carcinogenic response

was noted in the lung in males and

females at 500 and 2,000 ppm and in the

liver of male mice at 500 and 2,000

ppm.

In a study investigating biochemical

parameters in livers, mice were treated

at doses of 0, 50, 500 or 2,000 ppm

showing that fenoxycarb is a strong

inducer of hepatic xenobiotic

metabolizing enzymes in the mouse and

can be classified as a peroxisome

proliferator..

6. Animal metabolism. The

metabolism of fenoxycarb in animals

(goat and rat) is well understood. It has

been determined that fenoxycarb, per se,

is the residue of concern in animal

commodities for tolerance setting

purposes.

C. Aggregate Exposure

1. Food. For purposes of assessing the

potential dietary exposure under the

proposed tolerances, Novartis has

estimated aggregate exposure based on

exposure from anticipated residues on

pome fruit, tree nuts, citrus, cattle meat

and milk. Since there were no

detections of fenoxycarb in pome fruit,

tree nuts or citrus treated according to

label directions, the anticipated residue

of 0.005 ppm, one-half the limit of

quantitation, was used. Exposure via

meat and milk comes from the possible

consumption by cattle of almond hulls,

grass, citrus pulp and apple pomace.

Theoretical residues in milk make up

greater than 50% of the possible

exposure to fenoxycarb. Almost all of

the theoretical residue in milk comes

from almond hulls in the theoretical

diet for cattle. The anticipated residue

in milk is greatly exaggerated since

almond hulls, in general, are not a

significant portion of cattle diet. Percent

crop treated figures for food crops and

cattle feed were also used in the

analysis.

2. Drinking water. The product

chemistry data for fenoxycarb indicate

that movement of fenoxycarb into

drinking water would be unlikely and

that fenoxycarb would be expected to

have a strong affinity for binding to the

soil. Soil metabolism data further

demonstrate that fenoxycarb and its

residues have an affinity for binding to

soil, and thus a low propensity to move

from the soil surface. Field studies in

Washington, Georgia and in California

showed that fenoxycarb did not move

below the top 6 inches of the soil. Based

on the available data, Novartis does not

anticipate exposure to residues of

fenoxycarb in drinking water. There is

no established Maximum Contaminant

Level for residues of fenoxycarb in

drinking water The product chemistry

data for fenoxycarb indicate that

movement of fenoxycarb into drinking

water would be unlikely and that

fenoxycarb would be expected to have

a strong affinity for binding to the soil.

Soil metabolism data further

demonstrate that fenoxycarb and its

residues have an affinity for binding to

soil, and thus a low propensity to move

from the soil surface. Field studies in

Washington, Georgia and in California

showed that fenoxycarb did not move

below the top 6 inches of the soil. Based

on the available data, Novartis does not

anticipate exposure to residues of

fenoxycarb in drinking water. There is

no established Maximum Contaminant

Level for residues of fenoxycarb in

drinking water.
52556 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

3. Non-dietary exposure. Other

potential sources of exposure of the

general population to residues of

pesticides are exposure from nonoccupational sources. Novartis has

estimated non-occupational exposure to

fenoxycarb and concludes that the

potential for exposure is insignificant.

The potential for non-occupational

exposure to fenoxycarb resulting from

use of pet sprays or carpet sprays

containing fenoxycarb is not included in

safety determinations for the U.S.

population and infants (shown below)

since the registrations for these uses

have been canceled. Exposure through

turf uses of fenoxycarb as a fire ant bait

is also considered not significant. Used

as a fire ant bait, fenoxycarb is only

applied to turf with active fire ant

infestations and has no efficacy as a

preventive treatment. Turf infested with

fire ants is not commonly used for

recreational activities because of the

danger presented by fire ants. In

addition, studies demonstrate that >

95% of the bait applied to fire ant

infestations is removed by the ants

within 24 hours. Therefore opportunity

for exposure to fenoxycarb as a fire ant

bait through treated turf is extremely

small.

D. Cumulative Effects

Novartis also considered the potential

for cumulative effects of fenoxycarb and

other substances that have a common

mechanism of toxicity. Novartis

concluded that consideration of a

common mechanism of toxicity is not

appropriate at this time. Novartis does

not have reliable information to indicate

that toxic effects produced by

fenoxycarb would be cumulative with

those of any other chemical compounds;

thus Novartis is considering only the

potential risks from dietary exposure of

fenoxycarb in its aggregate exposure

assessment.

E. Safety Determination

1. U.S. population. Using the

exposure assumptions described above

and based on the completeness and

reliability of the toxicity data base for

fenoxycarb, Novartis has calculated that

aggregate exposure to fenoxycarb will

utilize 0.016% of the Reference Dose

(RfD) for the U.S. population - 48 states

- all seasons, based on chronic toxicity

endpoints. Lifetime carcinogenic risk for

dietary exposure based on quantitative

risk assessment and a Q1* of 5.6 × 10-2

(mg/kg/day)-1, is 7.31 × 10-7. EPA

generally has no concern for exposures

below 100% of the RfD or lifetime

carcinogenic risks less than 1 × 10-6.

Since anticipated residues of fenoxycarb

in food are extremely low and all short

term NOELs are at least an order of

magnitude higher than the chronic

NOEL, no acute risk from exposure to

residues of fenoxycarb is anticipated.

Therefore, Novartis concludes that there

is a reasonable certainty that no harm

will result from aggregate exposure to

fenoxycarb residues.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

fenoxycarb, Novartis considered data

from developmental toxicity studies in

the rat and rabbit and a 2-generation

reproduction study in the rat. No

evidence of developmental toxicity was

observed in rats or rabbits. Fenoxycarb

did not impair any reproductive or

postnatal development parameters and

was neither embryotoxic nor

teratogenic. The NOELs for maternal

and developmental toxicity in the rat

were determined to be ≥ 500 mg/kg/day.

The NOEL for maternal toxicity in the

rabbit, based on reduced body weight

gains, was 100 mg/kg/day and the NOEL

for developmental toxicity was ≥ 300

mg/kg/day. In a 2-generation

reproduction study in rats, the systemic

NOEL for parental animals was 200 ppm

based on decreased body weight gains

and food consumption, increased gonad

weights (without effects on reproductive

performance or a morphological

correlate), liver hypertrophy and focal

necrosis and increased liver weights.

There were no effects on fertility or

reproductive performance. Based on

decreased pup weights and slight delays

in pinna unfolding and eye opening,

there was no clear developmental

NOEL. A NOEL of 40 ppm was derived

using analysis of variance and

regression. The mild nature of the

effects of fenoxycarb on rat pups and the

lack of effects in the developmental

toxicity studies suggest that there is no

particular sensitivity to fenoxycarb for

infants and children.

Using the same exposure assumptions

used for the determination in the

general population, Novartis has

concluded that the percent of the RfD

that will be utilized by aggregate

exposure to residues of fenoxycarb is

0.038% for nursing infants less than 1

year old, 0.098% for non-nursing

infants, 0.048% for children 1–6 years

old and 0.028% for children 7–12 years

old. Therefore, based on the

completeness and reliability of the

toxicity data base, Novartis concludes

that there is a reasonable certainty that

no harm will result to infants and

children from aggregate exposure to

fenoxycarb residues.

F. International Tolerances

No Codex MRLs have been

established for residues of fenoxycarb.

3. Novartis Crop Protection, Inc.

PP 7F4897

EPA has received a pesticide petition

(PP 7F4897) from Novartis Crop

Protection, Inc., Greensboro, NC 27419,

proposing pursuant to section 408(d) of

the Federal Food, Drug and Cosmetic

Act, 21 U.S.C. 346a(d), to amend 40 CFR

180.368 by establishing a tolerance for

residues of metolachlor in or on the raw

agricultural commodities sunflower

seed at 0.3 ppm and sunflower meal at

0.6 ppm. The proposed analytical

method involves extraction by acid

reflux, filtration, partition and cleanup

with analysis by gas chromatography

using Nitrogen/Phosphorous (N/P)

detection. 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 supports

granting of the petition. Additional data

may be needed before EPA rules on the

petition.

A. Residue Chemistry

1. Plant metabolism. The qualitative

nature of the metabolism of metolachlor

in plants is well understood.

Metabolism in plants involves

conjugation of the chloroacetyl side

chain with glutathione, with subsequent

conversion to the cysteine and thiolactic

acid conjugates. Oxidation to the

corresponding sulfoxide derivatives

occurs and cleavage of the side chain

ether group, followed by conjugation

with glucose.

2. Analytical method. Novartis Crop

Protection has submitted a practical

analytical method involving extraction

by acid reflux, filtration, partition and

cleanup with analysis by gas

chromatography using Nitrogen/

Phosphorous (N/P) detection. The

methodology converts residues of

metolachlor into a mixture of CGA–

37913 and CGA–49751. The limit of

quantitation (LOQ) for the method is

0.03 ppm for CGA–37913 and 0.05 ppm

for CGA–49751.

3. Magnitude of residues. Eight

residue trials were conducted in major

sunflower growing areas of the United

States [CA, KS, TX (2), MN(2), ND, IL).

Five tests were conducted with

metolachlor alone and three were

conducted as a tank mix of metolachlor

and another product. Metolachlor

residues were analyzed for in all trials.

Applications were made at the
Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices 52557

maximum labeled rate of 3.0 lbs. active

ingredient/Acre (ai/A) and at 2 times the

maximum labeled rate (6.0 lbs. ai/A). A

processing study was also conducted

with seeds processed into meal, hulls,

crude oil, refined oil and soapstock.

According to the Revised Table II of

Subdivision O, only meal and refined

oil are now required. Based on these

studies and an earlier EPA review of

these data, tolerances are proposed in

sunflower seeds at 0.3 ppm and in

sunflower meal at 0.6 ppm.

B. Toxicological Profile

1. Acute toxicity. Metolachlor has a

low order of acute toxicity. The

combined rat oral LD50 is 2,877 mg/kg.

The acute rabbit dermal LD50 is > 2,000

mg/kg and the rat inhalation LC50 is >

4.33 mg/L. Metolachlor is not irritating

to the skin and eye. It has been shown

to be positive in guinea pigs for skin

sensitization. End use formulations of

metolachlor also have a low order of

acute toxicity and cause slight skin and

eye irritation.

2. Genotoxicty. Assays for

genotoxicity were comprised of tests

evaluating metolachlor’s potential to

induce point mutations (Salmonella

assay and an L5178/TK+/- mouse

lymphoma assay), chromosome

aberrations (mouse micronucleus and a

dominant lethal assay) and the ability to

induce either unscheduled or scheduled

DNA synthesis in rat hepatocytes or

DNA damage or repair in human

fibroblasts. The results indicate that

metolachlor is not mutagenic or

clastogenic and does not provoke

unscheduled DNA synthesis.

3. Reproductive and developmental

toxicity. The developmental and

teratogenic potential of metolachlor was

investigated in rats and rabbits. The

results indicate that metolachlor is not

embyrotoxic or teratogenic in either

species at maternally toxic doses. The

NOEL for developmental toxicity for

metolachlor was 360 mg/kg/day for both

the rat and rabbit while the NOEL for

maternal toxicity was established at 120

mg/kg/day in the rabbit and 360 mg/kg/

day in the rat. A 2-generation

reproduction study was conducted with

metolachlor in rats at feeding levels of

0, 30, 300 and 1,000 ppm. The

reproductive NOEL of 300 ppm

(equivalent to 23.5 to 26 mg/kg/day) was

based upon reduced pup weights in the

F1a and F2a litters at the 1,000 ppm

dose level (equivalent to 75.8 to 85.7

mg/kg/day). The NOEL for parental

toxicity was equal to or greater than the

1,000 ppm dose level.

4. Subchronic toxicity. Metolachlor

was evaluated in a 21–day dermal

toxicity study in the rabbit and a 6–

month dietary study in dogs; NOELs of

100 mg/kg/day and 7.5 mg/kg/day were

established in the rabbit and dog,

respectively. The liver was identified as

the main target organ.

5. Chronic toxicity. A 1–year dog

study was conducted at dose levels of 0,

3.3, 9.7, or 32.7 mg/kg/day. The Agencydetermined RfD for metolachlor is based

on the 1–year dog study with a NOEL

of 9.7 mg/kg/day. The RfD for

metolachlor is established at 0.1 mg/kg/

day using a 100-fold uncertainty factor.

A combined chronic toxicity/

oncogenicity study was also conducted

in rats at dose levels of 0. 1.5, 15 or 150

mg/kg/day. The NOEL for systemic

toxicity was 15 mg/kg/day. An

evaluation of the carcinogenic potential

of metolachlor was made from two sets

of oncogenicity studies conducted with

metolachlor in rats and mice. Using the

Guidelines for Carcinogenic Risk

Assessment published September 24,

1986 (51 FR 33992) and the results of

the November, 1994 Carcinogenic Peer

Review, EPA has classified metolachlor

as a Group C carcinogen and

recommended using a Margin of

Exposure (MOE) approach to quantify

risk. This classification is based upon

the marginal tumor response observed

in livers of female rats treated with a

high (cytotoxic) dose of metolachlor

(3,000 ppm). The two studies conducted

in mice were negative for oncogenicity.

6. Animal metabolism. The qualitative

nature of the metabolism of metolachlor

in animals is well understood.

Metolachlor is rapidly metabolized and

almost totally eliminated in the excreta

of rats, goats, and poultry. Metabolism

in plants and animals proceeds through

common Phase 1 intermediates and

glutathione conjugation.

7. Metabolite toxicology. The

metabolism of metolachlor has been

well characterized in standard FIFRA

rat metabolism studies. The metabolites

found are considered to be

toxicologically similar to parent.

Metolachlor does not readily undergo

dealkylation to form an aniline or

quinone amine as has been reported for

other members of the chloroacetanilide

class of chemicals. Therefore, it is not

appropriate to include metolachlor with

the group of chloroacetanilides that

readily undergo dealkylation, producing

a common toxic metabolite (quinone

imine).

C. Aggregate Exposure

1. Dietary exposure. Dietary exposure

consists of exposures from food and

drinking water.

2. Food. For purposes of assessing the

potential dietary exposure to

metolachlor, aggregate exposure has

been estimated based on the TMRC from

the use of metolachlor in or on raw

agricultural commodities for which

tolerances have been previously

established (40 CFR 180.368). The

incremental effect on dietary risk

resulting from the addition of

sunflowers to the label was assessed by

conservatively assuming that exposure

would occur at the proposed tolerance

level of 0.3 ppm with 100% of the crop

treated.

The TMRC is obtained by multiplying

the tolerance level residue for all these

raw agricultural commodities by the

consumption data which estimates the

amount of these products consumed by

various population subgroups. Some of

these raw agricultural commodities (e.g.

corn forage and fodder, peanut hay,

sunflower meal) are fed to animals; thus

exposure of humans to residues in these

fed commodities might result if such

residues are transferred to meat, milk,

poultry, or eggs. Therefore, tolerances of

0.02 ppm for milk, meat and eggs and

0.2 ppm for kidney and 0.05 ppm for

liver have been established for

metolachlor. In an EPA review of

sunflower residue data previously

submitted by Novartis, the EPA has

indicated that any secondary residues in

meat, milk, poultry and eggs will be

covered by existing metolachlor

tolerances.

In conducting this exposure

assessment, it has been conservatively

assumed that 100% of all raw

agricultural commodities for which

tolerances have been established for

metolachlor will contain metolachlor

residues and those residues would be at

the level of the tolerance--which results

in an overestimation of human

exposure.

3. Drinking water. Another potential

source of exposure of the general

population to residues of pesticides are

residues in drinking water. Based on the

available studies used by EPA to assess

environmental exposure, it is not

anticipated that exposure to residues of

metolachlor in drinking water will

exceed 20% of the RfD (0.02 mg/kg/

day), a value upon which the Health

Advisory Level of 70 ppb for

metolachlor is based. In fact, based on

experience with metolachlor, it is

believed that metolachlor will be

infrequently found in groundwater (less

than 5% of the samples analyzed), and

when found, it will be in the low ppb

range.

4. Non-dietary exposure. Although

metolachlor may be used on turf and

ornamentals in a residential setting, that

use represents less than 0.1% of the

total herbicide market for residential

turf and landscape uses. Currently, there
52558 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

are no acceptable, reliable exposure data

available to assess any potential risks.

However, given the small amount of

material that is used, it is concluded

that the potential for non-occupational

exposure to the general population is

unlikely.

D. Cumulative Effects

The potential for cumulative effects of

metolachlor and other substances that

have a common mechanism of toxicity

has also been considered. It is

concluded that consideration of a

common mechanism of toxicity with

other registered pesticides in this

chemical class (chloroacetamides) is not

appropriate. Since EPA has concluded

that the carcinogenic potential of

metolachlor is not the same as other

registered chloroacetamide herbicides,

based on differences in rodent

metabolism (EPA Peer Review of

metolachlor, 1994), it is believed that

only metolachlor should be considered

in an aggregate exposure assessment.

E. Safety Determination

1. U.S. population. Using the

conservative exposure assumptions

described above, based on the

completeness and reliability of the

toxicity data, it is concluded that

aggregate exposure to metolachlor will

utilize 1.3% of the RfD for the U.S.

population. EPA generally has no

concern for exposures below 100% of

the RfD because the RfD represents the

level at or below which daily aggregate

dietary exposure over a lifetime will not

pose appreciable risks to human health.

Therefore, it is concluded that there is

a reasonable certainty that no harm will

result from aggregate exposure to

metolachlor or metolachlor residues.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

metolachlor, data from developmental

toxicity studies in the rat and rabbit and

a 2-generation reproduction study in the

rat have been considered. The

developmental toxicity studies are

designed to evaluate adverse effects on

the developing organism resulting from

chemical exposure during prenatal

development to one or both parents.

Reproduction studies provide

information relating to effects from

exposure to a chemical on the

reproductive capability of mating

animals and data on systemic toxicity.

Developmental toxicity (reduced

mean fetal body weight, reduced

number of implantations/dam with

resulting decreased litter size, and a

slight increase in resorptions/dam with

a resulting increase in post-implantation

loss) was observed in studies conducted

with metolachlor in rats and rabbits.

The NOEL’s for developmental effects in

both rats and rabbits were established at

360 mg/kg/day. The developmental

effect observed in the metolachlor rat

study is believed to be a secondary

effect resulting from maternal stress

(lacrimation, salivation, decreased body

weight gain and food consumption and

death) observed at the limit dose of

1,000 mg/kg/day.

A 2-generation reproduction study

was conducted with metolachlor at

feeding levels of 0, 30, 300 and 1,000

ppm. The reproductive NOEL of 300

ppm (equivalent to 23.5 to 26 mg/kg/

day) was based upon reduced pup

weights in the F1a and F2a litters at the

1,000 ppm dose level (equivalent to 75.8

to 85.7 mg/kg/day). The NOEL for

parental toxicity was equal to or greater

than the 1,000 ppm dose level.

FFDCA section 408 provides that EPA

may apply an additional safety factor for

infants and children in the case of

threshold effects to account for pre- and

post-natal toxicity and the completeness

of the database. Based on the current

toxicological data requirements, the

database relative to pre- and post-natal

effects for children is complete. Further,

for the chemical metolachlor, the NOEL

of 9.7 mg/kg/day from the metolachlor

chronic dog study, which was used to

calculate the RfD (discussed above), is

already lower than the developmental

NOEL’s of 360 mg/kg/day from the

metolachlor teratogenicity studies in

rats and rabbits. In the metolachlor

reproduction study, the lack of severity

of the pup effects observed (decreased

body weight) at the systemic lowest

observed-effect-level (equivalent to 75.8

to 85.7 mg/kg/day) and the fact that the

effects were observed at a dose that is

nearly 10 times greater than the NOEL

in the chronic dog study (9.7 mg/kg/

day) suggest there is no additional

sensitivity for infants and children.

Therefore, it is concluded that an

additional uncertainty factor is not

warranted to protect the health of

infants and children and that the RfD at

0.1 mg/kg/day based on the chronic dog

study is appropriate for assessing

aggregate risk to infants and children

from use of metolachlor.

Using the conservative exposure

assumptions described above, the

percent of the RfD that will be utilized

by aggregate exposure to residues of

metolachlor including the proposed use

on sunflowers is 1.1% for nursing

infants less than 1 year old, 3.3% for

non-nursing infants, 2.7% for children 1

to 6 years old and 2.0% for children 7

to 12 years old. Therefore, based on the

completeness and reliability of the

toxicity data and the conservative

exposure assessment, it is concluded

that there is a reasonable certainty that

no harm will result to infants and

children from aggregate exposure to

metolachlor residues.

F. International Tolerances

There are no Codex Alimentarius

Commission (CODEX) maximum

residue levels (MRL’s) established for

residues of metolachlor in or on raw

agricultural commodities.

[FR Doc. 97–26535 Filed 10–7–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–769; FRL 5748–6]

Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of pesticide petitions

proposing the establishment of

regulations for residues of certain

pesticide chemicals in or on various

food commodities.

DATES: Comments, identified by the

docket control number PF–769, must be

received on or before November 7, 1997.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch, Information

Resources and Services Division

(7506C), Office of Pesticides Programs,

Environmental Protection Agency, 401

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

person bring comments to: Rm. 1132,

CM #2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically to: oppdocket@epamail.epa.gov. Follow the

instructions under ‘‘SUPPLEMENTARY

INFORMATION’’ of this document. No

Confidential Business Information (CBI)

should be submitted through e-mail.

Information submitted as a comment

concerning this document 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 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.,