15690 Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices

be in the drinking water. Plant viruses

are a natural component of the

environment and are present in soil and

water. Consequently, Cornell University

believes that coat proteins produced as

plant-pesticides would represent a

negligible addition to those existing in

drinking water.

2. Non-dietary exposure. Cornell

University believes that non-dietary

exposure to engineered coat proteins

will be minimal to non-existent because

the coat protein is expressed only

within the plant tissues.

E. Cumulative Exposure

Exposure through other pesticides

and substances with the common mode

of toxicity as this pesticide. Cornell

University believes that due to the lack

of toxicity/pathogenicity associated

with plant viruses or plant viral coat

proteins, cumulative effects with other

pesticides and substances will be nonexistent.

F. Safety Determination

1. U.S. population. There is no known

toxicity associated with coat proteins

from plant viruses. Consequently, a

safety assessment is not needed for

these proteins. Given the long history of

mammalian consumption of the entire

plant virus particle in foods, without

any adverse human health effects,

Cornell University reasonably believes

that consumption of a noninfectious

component of the PRV plant virus is

safe. There are no known data that

indicate aggregate exposure to plant

viral coat proteins under normal

conditions will result in harm to any

person.

2. Infants and children. Viral coat

proteins are ubiquitious in foods,

including those foods consumed by

infants and children. Moreover, there is

not reason to believe that plant viral

coat proteins are likely to occur in

different amounts in foods, consumed

by children and infants. Further, there

is no scientific evidence that viral coat

proteins used as plant-pesticides would

have a different effect on children that

on adults. Viral coat proteins are not

toxic and, therefore, Cornell University

believes with reasonable certainty that

no harm will result to infants and

children from aggregate exposure to coat

proteins from plant viruses.

G. Existing Tolerances

No tolerance or exemption from

tolerance has been previously granted

for PRV coat protein.

H. International Tolerance

International tolerance levels for

Papaya Ringspot Virus Coat Protein

have not been determined. However,

papaya fruit from trees infected with

papaya ringspot virus are consumed by

numerous people throughout the world.

Cornell University concludes that

plant viruses, including PRV coat

proteins, are not harmful to humans,

and that there is a reasonable certainty

that no harm will result from aggregate

exposure to Coat Protein of Papaya

Ringspot Virus and the genetic material

necessary for its production, including

all anticipated dietary exposures and all

other non-occupational exposures.

Accordingly, Cornell University

believes that the PRV coat protein

qualifies for an exemption from the

requirement of a tolerance in or on all

raw agricultural commodities.

[FR Doc. 97–8396 Filed 4–1–97; 8:45 am]

BILLING CODE 6560–50–F

[PF–723; FRL–5593–9]

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

agricultural commodities.

DATES: Comments, identified by the

docket control number PF–723, must be

received on or before May 2, 1997.

ADDRESSES: By mail submit written

comments to: Public Response and

Program Resources Branch, Field

Operations Divison (7505C), 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 by following

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 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: The

product manager listed in the table

below:

Product Manager Office location/telephone number Address

Connie Welch (PM 21) .. Rm. 227, CM #2, 703–305–6226, e-mail:welch.connie@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Cynthia Giles-Parker

(PM 22).

Rm. 229, CM #2, 703–305–5540, e-mail: giles-parker.cynthia@epamail.epa.gov. Do.

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 raw agricultural 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 grantinig 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–723

(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
Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices 15691

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 (insert docket

number) and appropriate petition

number. Electronic comments on this

proposed rule 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: March 24, 1997.

Stephen L. Johnson,

Director, Registration Division, Office of

Pesticide Programs.

Summaries of Petitions

Below summaries of the pesticide

petitions are printed. The summaries of

the petitions were prepared by the

petitioners. 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. Bayer’s Corporation

PP 6F4631

EPA has received a pesticide petition

(PP 6F4631) from Bayer Corporation,

8400 Hawthorne Road, Kansas City, MO

64120–0013, 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

tolerances for residues of the herbicide,

FOE 5043, N-(4-Fluorophenyl)-N-(1-

methylethyl)-2[[5-(trifluoromethyl)-

1,3,4-thiadiazol-2-yl]oxy]acetamide in

or on the raw agricultural commodities,

field corn grain at 0.05 parts per million

(ppm), field corn forage at 0.4 ppm, field

corn stover (fodder) at 0.4 ppm, soybean

seed at 0.1 ppm, milk at 0.01 ppm, meat

at 0.05 ppm, and meat byproducts at

0.05 ppm. The proposed analytical

method is gas chromatography/mass

spectrometry with selected ion

monitoring. (PM 22)

1. Chemical uses. FOE 5043 use on

field corn and soybeans provides

selective weed control for a wide

spectrum of annual grasses and smallseeded broadleaf weeds, with

exceptional strength on barnyard grass,

large crabgrass, fall panicum and foxtail

species. Application technique:

Products containing FOE 5043 can be

applied preplant surface, preplant

incorporated, or preemergence for

control of emerging weeds. Applications

can be made up to 45 days before

planting. Applications may be made

using standard low pressure ground

herbicide boom sprayers equipped with

suitable nozzles and screens. The

products containing FOE 5043 may be

applied either as a single or a split

application. Application rates range

from 0.442 to 0.884 pounds active

ingredient (a.i.) of FOE 5043 per acre

depending on the soil texture and soil

organic matter content. Tank mix

combinations with selected products

may provide additional weed control.

2. FOE 5043 Safety. Bayer has

submitted over 65 separate toxicology

studies in support of tolerances for FOE

5043. Among the submissions, a finding

of particular interest was the

observation that in the long-term data

compiled for FOE 5043, provided no

indications of a potential to induce

either carcinogenic or reproductive

signs of toxicity. In addition,

developmental no-observed-adverse

effects levels (NOAELs) of 25 milligrams

body weight per day (mg/kg bwt/day)

were established for both the rat and

rabbit.

The following mammalian toxicity

studies have been conducted to support

the tolerance of AXIOM DF (contains

FOE 5043 and metribuzin):

i. A rat acute oral study with an LD50

of 2,347 mg/kg (male) and 2,027 mg/kg

(female).

ii. A rabbit acute dermal with an LD50

of > 2,000 mg/kg.

iii. A rat acute inhalation with an

LD50 of > 977 mg/m3.

iv. A primary eye irritation study in

the rabbit which showed mild irritation.

v. A primary dermal irritation study

which showed no irritation.

vi. A primary dermal sensitization

study which showed no sensitization.

The following mammalian toxicity

studies, derived from exposure to the

technical form of the chemical, have

been conducted to support the tolerance

of FOE 5043:

i. A rat acute oral study with an LD50

of 1,617 mg/kg (male) and 589 mg/kg

(female).

ii. A rat acute dermal LD50 of 2,000

mg/kg bwt.

iii. A rat acute inhalation LC50 of

3,740 mg/m3 (male and female).

iv. A primary eye irritation study in

the rabbit which showed no irritation.

v. A primary dermal irritation study

which showed no irritation.

vi. A primary dermal sensitization

study which showed no sensitization.

vii. An acute neurotoxicity study with

a no-observed effect level (NOEL) for

FOB, motor and locomotor activity of 75

mg/kg bwt/day for males and females.

viii. A 90–day feeding study in the rat

with a NOEL of 1.7 mg/kg bwt/day.

ix. A 90–day subchronic neurotoxicity

study in the rat with a neurotoxicity and

overall NOEL of 120 ppm.

x. A 24–months chronic feeding/

oncogenicity study in the rat with an

overall NOEL of 1.2 mg/kg bwt/day in

males and females based on liver,

kidney, hematologic and thyroid effects.

There was no evidence of an oncogenic

response.

xi. A 90–day feeding study in dogs

with a NOEL of 50 ppm, based on liver

hematology, and thyroid effects.

xii. A 12–month feeding study in dogs

with a NOEL of 40 ppm, based on

hematology and thyroid effects.

xiii. A mouse oncogenicity study

which provided no evidence of

oncogenicity.

xiv. An oral teratology study in the rat

with maternal and developmental

NOAELs of 25 mg/kg bwt/day.

xv. An oral teratology study in the

rabbit with maternal and fetal NOELs of

5 and 25 mg/kg bwt/day respectively.

xvi. An two-generation reproduction

study in the rat with a NOEL for

reproductive and parental toxicity of

500 and 20 ppm, respectively.

xvii. Ames assay: Negative

xviii. Unscheduled DNA synthesis:

Negative

xix. Mouse Micronucleus Assay:

Negative.

3. Threshold effects— chronic effects.

Based on the available chronic toxicity

data, Bayer believes the Reference Dose

(RfD) for FOE 5043 should be 0.0114

mg/kg/day. The RfD for FOE 5043 is

based on a 1 year chronic toxicity study

in the dog with a threshold No Observed

Effect Level (NOEL) of 1.14 mg/kg/day

and an uncertainty factor of 100.

Acute toxicity. EPA recently proposed

a tiered approach to estimate acute

dietary exposure. The methods

proposed by the EPA were reviewed and

supported by the FIFRA Scientific

Advisory Panel (SAP, 1995). EPA’s Tier

1 method is based on the assumption

that residue concentrations do not vary.

The analysis assumes that all residues

have the same magnitude, typically the

highest field trial residue or tolerance

value. This value is assumed for all
15692 Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices

points along the consumption

distribution, resulting in a distribution

of dietary exposure.

For the acute analysis for FOE 5043,

a Tier 1 analysis was conducted for the

overall U.S. population, infants,

children 1 to 6 years of age, females 13

years and older, and males 13 years and

older. Using the NOEL of 138 mg/kg

derived from the acute oral toxicity

study in rats, the following margins of

exposure were calculated (margins of

exposure of 100 or more are considered

satisfactory):

Population Group Margin of Exposure

U.S. Population-All Seasons.94,741

Infants ................................ 64,986

Children 1 to 6 ................... 76,494

Women 13 to 50 years old 191,418

Men 13 years and older .... 109,805

4. Non-threshold Effects—

carcinogenicity. Using the Guidelines

for Carcinogen Risk Assessment, Bayer

believes FOE 5043 to be in Group E for

carcinogenicity—no evidence of

carcinogenicity—based on the results of

carcinogenicity studies in three species.

There was no evidence of

carcinogenicity in an 18–month feeding

study in mice, a 2–year feeding study in

rats, or a 1–year feeding study in dogs

at the dose levels tested. The doses

tested are adequate for identifying a

cancer risk. Thus, a cancer risk

assessment should not be necessary for

FOE 5043.

5. Aggregate Exposure. For purposes

of assessing the potential dietary

exposure under the proposed tolerances

for FOE 5043, the estimated aggregate

exposure was based on the Theoretical

Maximum Residue Concentrations

(TMRC) and the proposed tolerances

(The TMRC is a worst case estimate of

dietary exposure since it is assumed that

100 % of all crops for which tolerances

are established are treated and that

pesticide residues are present at the

tolerance levels.). Registration for FOE

5043 and AXIOM are currently being

sought on field corn and soybeans. FOE

5043 and AXIOM are not registered for

any uses. Tolerances are proposed

(pesticide petition number 6F 4631) for

FOE 5043 on the following Raw

Agricultural Commodities (RAC); field

corn grain (0.05 ppm), forage (0.4 ppm)

and stover (fodder) (0.4 ppm), soybean

seed (0.1 ppm), milk (0.01 ppm), meat

(0.05 ppm), and meat byproducts (0.05

ppm). The TMRC is obtained by

multiplying the tolerance level for these

commodities by consumption data

which estimates the amounts of corn

and soybean products eaten by various

human population subgroups.

Tolerances are proposed for milk, meat

and meat byproducts because residues

for FOE 5043 can be transferred from

corn and soybean based feeds through

livestock to humans.

This dietary exposure estimate

assumes that 100% of these crops are

treated with FOE 5043 and that the

residues of FOE 5043 found in these

crops would occur at the proposed

tolerance levels. These assumptions

result in an overestimate of exposure. In

making a safety determination for these

tolerances this conservative exposure

estimate has been taken into account.

Other potential sources of exposure of

the general population to residues of

FOE 5043 are residues in drinking water

and exposure from non-occupational

sources. In ongoing ground water

monitoring studies, trace levels of FOE

5043 residues (less that 1 part per

billion (ppb) total residues) have been

detected in ground water. These studies

are being performed at sites with

vulnerable shallow aquifers and large

amounts of irrigation are being applied

monthly. The highest residue level

detected is well below the anticipated

life-time Health Advisory Level of 84

ppb. If residues of FOE 5043 do occur

in ground water used for drinking water

they will be far below the level which

causes concern. Based on the available

data, no significant residues of FOE

5043 are anticipated to occur in surface

water used for drinking water. Since

registration is not being sought for any

residential or homeowner uses no other

potential for exposure to FOE 5043

residues exists.

The toxicological profile for FOE 5043

is fundamentally characterized by

structural- and functional-related

alterations in thyroid, hematologic and

hepatic parameters. These sort of

changes are not uncommon among

herbicides. Since residues of FOE 5043

and its degradates will occur in raw

agricultural commodities and processed

foods in the high parts per billion or low

parts per million range there is no

compelling evidence that suggests a

cumulative effect (i.e., potentiated,

additive, or synergistic response) might

occur or be anticipated in the human

following exposure to multiple chemical

agents with similar toxicological

profiles and/or mechanisms of toxicity.

6. Determination of safety for U.S.

population—Reference dose (RfD).

Using the conservative exposure

assumptions described above, based on

the completeness and reliability of the

toxicity data, the aggregate exposure to

FOE 5043 will utilize 2.1% of the RfD

for the U.S. population. EPA generally

has no concern for exposures below 100

% of the RfD. Therefore, based on the

completeness and reliability of the

toxicity data and the conservative

exposure assessment, Bayer concludes

that there is a reasonable certainty that

no harm will result from aggregate

exposure to residues of FOE 5043,

including all anticipated dietary

exposure and all other non-occupational

exposures.

7. Determination of Safety for Infants

and Children. The possibility of FOE

5043 induced developmental toxicity

was suggested in preliminary and nondefinitive toxicity studies using rats (>

175 mg/kg bwt/day) and rabbits (> 125

mg/kg bwt/day). However NOAELs for

developmental effects were ultimately

established in the definitive studies.

Those values, as mentioned previously,

were 25 mg/kg bwt/day in the rat and

25 mg/kg bwt/day in the rabbit.

Reference Dose (RfD). Using the

conservative exposure assumptions

described previously, Bayer has

concluded that the percent of the RfD

utilized by aggregate exposure to

residues of FOE 5043 ranges from 1.1 %

for non-nursing infants, up to 5.2 % for

children 1 to 6 years old. EPA generally

has no concern for exposure below 100

% of the Reference Dose. Therefore,

based on the completeness and

reliability of the toxicity data and the

conservative exposure assessment,

Bayer concludes that there is a

reasonable certainty that no harm will

result to infants and children from

aggregate exposure to the residues of

FOE 5043, including all anticipated

dietary exposure and all other nonoccupational exposures.

8. Estrogenic Effects. No specific tests

have been conducted with FOE 5043 to

determine whether the pesticide may

have an effect in humans that is similar

to an effect produced by a naturally

occurring estrogen or other endocrine

effects.

9. Chemical Residue. The qualitative

nature of the residues in plants and

animals is adequately understood for

the purposes of registration. Residues of

FOE 5043 do concentrate slightly (1.6x)

in the processed commodity of corn

grits. No tolerance has been proposed

for residue of FOE 5043 in corn grits

because anticipated residues are less

than two times the limit of quantitation

for the analytical method. There are no

Codex maximum residue levels

established for residues of FOE 5043 on

any crop. Bayer has submitted a

practical analytical method for detecting

and measuring levels of FOE 5043 in or

on food with a limit of detection that

allows monitoring of food with residues

at or above the proposed tolerance

levels. EPA will provide information on
Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices 15693

this method to FDA. The method is

available to anyone who is interested in

pesticide residue enforcement from the

EPA’s Field Operations Division, Office

of Pesticide Programs.

Fifty-five separate residue trials have

been conducted with FOE 5043 on corn

and soybeans. Analysis of these trials

shows that the maximum total

combined residue for FOE 5043 and its

major metabolites in any commodity

will be at/below 9.75 ppm. Residues

occurred at this level in soybean dry

hay. However, no tolerances have been

proposed for residues of FOE 5043 on

soybean hay because the proposed

labels for products containing FOE 5043

do not allow livestock to be fed with

FOE 5043 treated soybean hay.

Tolerances have been requested for

residues of FOE 5043 and its major

metabolites on field corn grain (0.05

ppm), forage (0.4 ppm) and stover

(fodder) (0.4 ppm) and soybean seed

(0.1 ppm), milk (0.01 ppm), meat (0.05

ppm), and meat byproducts (0.05 ppm).

The proposed tolerance levels are

adequate to cover residues likely to be

present from the proposed use of FOE

5043. Therefore, no special processing

to reduce the residues will be necessary.

There is no need for tolerances in

poultry or eggs since there is no

reasonable expectation of residues in

these materials based on the results of

poultry metabolism studies, as well as

the corn and soybean metabolism and

rotational crop studies. Calculated

transfer factors are extremely low and

maximum expected residues in poultry

and eggs would be in the low parts per

billion or high parts per trillion range.

The anticipated residues in poultry

tissues and eggs resulting from feeding

poultry FOE 5043 treated corn and or

soybeans would be far below the limit

of quantitation of the analytical residue

method.

No FOE 5043 food additive tolerances

are proposed for field corn starch (wet

milling), field corn refined oil (wet

milling), field corn flour (dry milling)

and field corn refined oil (dry milling)

because no residues were detected

above the limit of quantitation in this

processed commodity.

Additionally, no FOE 5043 food

additive tolerances are proposed in field

corn grits (dry milling) field corn meal

(dry milling), soybean meal, soybean

hulls, and soybean refined oil because

the measured concentration, when

adjusted for the exaggerated application

rate, was less that two times the limit of

quantitation.

No feed additive tolerances are

proposed for FOE 5043 in the aspirated

grain fractions of corn and soybeans.

With pre-plant and or pre-emergent

modes of application for AXIOM DF and

FOE 5043 DF, no residues were

expected on the seed surface in the corn

and soybean magnitude of residue

studies. Therefore, no aspirated grain

fractions were collected for analysis. A

tolerance has not been proposed for

soybean forage because feeding soybean

hay and forage (silage) to livestock

animals is not permitted by the

proposed label.

Also, no feed additive tolerances are

proposed for soybean meal or hulls

since the measured concentration in the

soybean processing study for these

feeds, when adjusted for the exaggerated

application rate, was less that two times

the limit of quantitation.

No tolerances are proposed for corn

milled by-products. Table II (September

1995) advises use residue data for corn

dry-milled processed commodities

having the highest residues, excluding

oils. No residues were detected in the

dry-milled processed commodities

above the limit of quantitation.

10. Environmental Fate. Laboratory

studies indicate that FOE 5043 residue

has the potential to be moderately

mobile in soil. However the results of

field dissipation studies performed in

Wisconsin and North Carolina, both

corn and/or soybean producing states,

indicate that downward movement of

FOE 5043 residue is limited, with no

quantifiable residues being found below

18 inches. These studies were

conducted under conditions conducive

to downward movement of FOE 5043

and degradates (very high sand content,

low organic matter, and large volumes

of applied irrigation).

FOE 5043 has been found to be stable

to chemical hydrolysis in the pH range

of environmental concern. The

compound is also stable in water and

soil when exposed to artificial sunlight.

Microbial degradation is the principal

means of dissipation in soil. Half-lives

for aerobic microbial degradation range

from 10 to 34 days in varying soil types

at the anticipated field application rate.

Degradation of FOE 5043 in soil under

aerobic conditions occurs by cleavage of

the thiadiazole ring to form 3-

trifluoromethyl-1,3,4-thiadiazol2(3H)one (FOE thiadone) and the

corresponding alcohol, N-(4-

flurophenyl)-2-hydroxy-N-(1-

methylethyl)acetamide. The FOE

thiadone is further metabolized to CO2,

and the alcohol is subsequently

oxidized to [4-flurophenyl)(1-

methylethyl)amino]oxoacetic acid.

Another major degradation product of

FOE 5043 is 4-fluoro-Nmethylethylaniline-sulfoacetamide

which is proposed to form through the

oxidation of a cysteine conjugate

intermediate. (PM 22)

PP 5F4577

EPA has received a pesticide petition

(PP) 5F4577 from Bayer Corporation,

8400 Hawthorn Rd., P.O. Box 4913,

Kansas City, MO 64120-0013 proposing,

pursuant to section 408(d) of the Federal

Food, Drug and Cosmetic Act (FFDCA),

21 U.S.C. 346a, to amend 40 CFR

180.474 by establishing tolerances for

residues of the fungicide tebuconazole

in or on the raw agricultural

commodities grass forage at 8.0 ppm

and grass hay at 25.0 ppm and

tolerances for residues of the fungicide

tebuconazole in or on the raw

agricultural commodities cattle liver at

0.2 ppm, cattle kidney at 0.2 ppm, cattle

meat byproducts at 0.2 ppm, and milk

at 0.1 ppm. The proposed analytical

method for determining residues uses

gas-liquid chromatography coupled

with a thermionic detector. EPA has

determined that the petition contains

data or information regarding the

elements set forth in section 408(d)(2);

however EPA has not fully evaluated

the sufficiency of the submitted data at

this time or whether the data supports

granting of the petition. Additional data

may be needed before EPA rules on the

petition. (PM 21)

Tebuconazole is a sterol

demethylation inhibitor (DMI)

fungicide. It is systemic and shows

activity against rusts (Puccinia spp.) and

powdery mildew infecting grasses

grown for seed. Tebuconazole provides

protective activity by preventing

completion of the infection process. It is

rapidly absorbed by plants and is

translocated systemically in the young

growing tissues.

A. Residue Chemistry

1. Plant and livestock metabolism.

Bayer believes the nature of the residue

in plants and animals is adequately

understood. The residue of concern is

the parent compound only, as specified

in 40 CFR 180.474.

2. Analytical method. Bayer has

submitted an enforcement method for

plant commodities has been validated

on various commodities. It has

undergone successful EPA validation

and has been submitted for inclusion in

PAM II. The method should be adequate

for grasses grown for seed. The animal

method has also been approved as an

adequate enforcement method and will

be submitted to FDA for inclusion in

PAM II.

3. Magnitude of residue. Nine separate

residue trials have been conducted and

submitted to the EPA with tebuconazole

on grasses grown for seed. The EPA has
15694 Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices

determined that these data show that

residues of tebuconazole,α-[2-(4-

Chlorophenyl)ethyl]-α-(1,1-

dimethylethyl)-H-1,2,4-triazole-1-eth

anol, are not expected to exceed 8 ppm

in grass forage and 25 ppm in grass hay

as a result of the proposed use. In

addition, the EPA has determined that

tolerances are needed for the following

animal commodities: cattle liver, kidney

and meat byproducts at 0.2 ppm and

milk at 0.1 ppm. The tolerance

expression for the animal commodities

will include the HWG 2061

metabolite,α-[2-(4-Chlorophenyl)-ethyl]-

α-[(2-hydroxy-1,1-dimethyl)ethyl]-1H1,2,4triazole-1-ethanol, in addition to

the parent.

No processed commodities are

associated with the proposed use on

grasses grown for seed. In addition, due

to the nature of the crop, rotational

crops will not be an issue.

B. Toxicological Profile of Tebuconazole

1. Acute toxicity. i. Rat acute oral

study with an LD50 of > 5,000 mg/kg

(male) and 3,933 mg/kg (female)

ii. Rabbit acute dermal of LD50 of >

5,000 mg/kg

iii. Rat acute inhalation of LC50 of >

0.371 mg/l

iv. Primary eye irritation study in the

rabbit which showed mild irritation

reversible by day 7

v. Primary dermal irritation study

which showed no skin irritation

vi. Primary dermal sensitization study

which showed no sensitization

2. Genotoxicity. i. An Ames

mutagenesis study in Salmonella

showed no mutagenicity with or

without metabolic activation.

ii. A micronucleus mutagenesis assay

study in mice showed no genotoxicity.

iii. A sister chromatid exchange

mutagenesis study using CHO cells was

negative at dose levels 4 to 30 μg/mL

without activation or 15 to 120 μg/mL

with activation.

iv. An unscheduled DNA synthesis

(UDS) study was negative for UDS in rat

hepatocytes.

3. Reproductive and developmental

toxicity. i. A rat oral developmental

toxicity study with a maternal NOEL of

30 milligrams per kilogram of body

weight per day (mg/kg bwtt/day) and an

LEL of 60 mg/kg bwtt/day based on

elevation of absolute and relative liver

weights. For developmental toxicity, a

NOEL of 30 mg/kg bwtt/day and an LEL

of 60 mg/kg bwtt/day was determined,

based on delayed ossification of

thoracic, cervical and sacral vertebrae,

sternum, fore and hind limbs and

increase in supernumerary ribs.

ii. A rabbit oral developmental

toxicity study with a maternal NOEL of

30 mg/kg bwt/day and an LEL of 100

mg/kg bwt/day based on depression of

body weight gains and food

consumption. A developmental NOEL

of 30 mg/kg bwt/day and an LEL of 100

mg/kg bwt/day were based on increased

post-implantation losses, from both

early and late resorptions and frank

malformations in eight fetuses of five

litters.

iii. A mouse oral developmental

toxicity study with a maternal NOEL of

10 mg/kg bwt/day and an LEL of 20 mg/

kg bwt/day based on a supplementary

study indicating reduction in hematocrit

and histological changes in liver. A

developmental NOEL of 10 mg/kg bwt/

day and an LEL of 30 mg/kg bwt/day

based on dose-dependent increases in

runts/dam at 30 and 100 mg/kg bwt/day.

iv. A mouse dermal developmental

toxicity study with a maternal NOEL of

30 mg/kg bwt/day and an LEL of 60 mg/

kg bwt/day based on a supplementary

study indicating increased liver

microsomal enzymes and histological

changes in liver. The NOEL for

developmental toxicity in the dermal

study in the mouse is 1,000 mg/kg bwt/

day, the highest dose tested (HDT).

v. A two-generation rat reproduction

study with a dietary maternal NOEL of

15 mg/kg bwt/day (300 ppm) and an

LEL of 50 mg/kg bwt/day (1,000 ppm)

based on depressed body weights,

increased spleen hemosiderosis, and

decreased liver and kidney weights. A

reproductive NOEL of 15 mg/kg bwt/day

(300 ppm) and an LEL of 50 mg/kg bwt/

day (1,000 ppm) were based on neonatal

birth weight depression.

4. Subchronic toxicity. i. 28-day

feeding study in the rat with a NOEL of

30 mg/kg/day and a LEL of 100 mg/kg/

day based on changes in hematology

and clinical chemistry parameters.

ii. A 90–day rat feeding study with a

no-observed-effect level (NOEL) of 34.8

(mg/kg bwt/day) (400 ppm) and a

lowest-effect-level (LEL) of 171.7 mg/kg

bwt/day (1,600 ppm) in males, based on

decreased body weight gains and

histological changes in the adrenals. For

females, the NOEL was 10.8 mg/kg bwt/

day (100 ppm) and the LEL was 46.5

mg/kg bwt/day (400 ppm) based on

decreased body weights, decreased body

weight gains, and histological changes

in the adrenals.

iii. A 90–day dog-feeding study with

a NOEL of 200 ppm (73.7 mg/kg bwt/

day in males and 73.4 mg/kg bwt/day in

females) and an LEL of 1,000 ppm

(368.3 mg/kg bwt/day in males and

351.8 mg/kg bwt/day in females). The

LEL was based on decreases in mean

body weights, body weight gains, and

food consumption, and an increase in

liver N-demethylase activity.

5. Chronic toxicity i. A 2–year rat

chronic feeding study defined a NOEL

of 7.4 mg/kg bwt/day (100 ppm) and an

LEL of 22.8 mg/kg bwt/day (300 ppm)

based on body weight depression,

decreased hemoglobin, hematocrit, MCV

and MCHC, and increased liver

microsomal enzymes in females.

Tebuconazole was not oncogenic at the

dose levels tested (0, 100, 300, and

1,000 ppm).

ii. A 1–year dog feeding study with a

NOEL of 1 mg/kg bwt/day (40 ppm) and

an LEL of 5 mg/kg bwt/day (200 ppm),

based on lenticular and corneal opacity

and hepatic toxicity in either sex (the

current Reference Dose was determined

based on this study). A subsequent 1–

year dog feeding study, using lower

doses to further define the NOEL for

tebuconazole, defines a systemic LOEL

of 150 ppm (based on adrenal effects in

both sexes) and a systemic NOEL of 100

ppm.

iii. A mouse oncogenicity study at

dietary levels of 0, 20, 60, and 80 ppm

for 21 months did not reveal any

oncogenic effect for tebuconazole at any

dose tested. Because the maximumtolerated-dose (MTD) was not reached

in this study, the study was classified as

supplementary. A follow-up mouse

study at higher doses (0, 500, and 1,500

ppm in the diet), with an MTD at 500

ppm, revealed statistically significant

incidences of hepatocellular adenomas

and carcinomas in males and

carcinomas in females. The initial and

follow-up studies, together with

supplementary data were classified as

core minimum.

6. Animal metabolism. A general rat

metabolism study at dietary levels of 2

and 20 mg/kg showed rapid elimination

from the rat in 3 days (some 99%

excreted by the feces and urine and

0.0304% in expired air). Increased

concentrations of radioactivity from the

active ingredient and metabolites were

found only in the liver. The bones and

the brain were among the tissues

showing the least amount of

radioactivity.

7. Metabolite toxicity. The residue of

concern in plants is the parent

compound, tebuconazole, only. For

animal commodities, the EPA has

determined that the tolerance

expression should include the HWG

2061 metabolite, α-[2-(4 -Chlorophenyl)-

ethyl]-α-[(2-hydroxy-1,1-

dimethyl)ethyl]-1H-1,2,4triazole-1-

ethanol. An acute oral toxicity study has

been submitted to the EPA on this

metabolite. This study shows an oral

LD50 of > 5,000 for female rats. This

value indicates that the HWG 2061

metabolite is relatively innocuous and

less acutely toxic than tebuconazole.
Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices 15695

8. Endocrine effects. No special

studies investigating potential

estrogenic or endocrine effects of

tebuconazole have been conducted.

However, the standard battery of

required studies has been completed.

These studies include an evaluation of

the potential effects on reproduction

and development, and an evaluation of

the pathology of the endocrine organs

following repeated or long-term

exposure. These studies are generally

considered to be sufficient to detect any

endocrine effects but no such effects

were noted in any of the studies with

either tebuconazole or its metabolites.

9. Carcinogenicity. EPA’s

Carcinogenicity Peer Review Committee

(CPRC) has classified tebuconazole as a

Group C carcinogen (possible human

carcinogen). This classification is based

on the Agency’s ‘‘Guidelines for

Carcinogen Risk Assessment’’ published

in the Federal Register of September 24,

1986 (51 FR 33992). The Agency has

chosen to use the reference dose

calculations to estimate human dietary

risk from tebuconazole residues. The

decision supporting classification of

tebuconazole as a possible human

carcinogen (Group C) was primarily

based on the statistically significant

increase in the incidence of

hepatocellular adenomas, carcinomas,

and combined adenomas/carcinomas in

both sexes of NMRI mice both by

positive trend and pairwise comparison

at the highest dose tested.

C. Aggregate Exposure

1. Dietary (food) exposure. For

purposes of assessing the potential

dietary exposure from food under the

proposed tolerances, Bayer has been

advised that the EPA has estimated

exposure based on the Theoretical

Maximum Residue Contribution

(TMRC) derived from the previously

established tolerances for tebuconazole

on cherries, peaches, bananas, barley,

oats, wheat, and peanuts as well as the

proposed tolerances for tebuconazole on

milk at 0.1 ppm and cattle liver, kidney

and meat byproducts at 0.2 ppm. The

TMRC is obtained by using a model

which multiplies the tolerance level

residue for each commodity by

consumption data which estimate the

amount of each commodity and

products derived from the commodities

that are eaten by the U.S. population

and various population subgroups. In

conducting this exposure assessment,

the EPA has made very conservative

assumptions—100% of all commodities

will contain tebuconazole residues, and

those residues would be at the level of

the tolerance—which result in a large

overestimate of human exposure. Thus,

in making a safety determination for

these tolerances, the Agency took into

account this very conservative exposure

assessment.

2. Dietary (drinking water) exposure.

There is no Maximum Contaminant

Level established for residues of

tebuconazole. Bayer was advised by the

Environmental Fate and Ground Water

Branch’s (EFGWB) May 26, 1993

memorandum for our application for

use on bananas and peanuts that all

environmental fate data requirements

for tebuconazole were satisfied. The

EFGWB had determined that

tebuconazole is resistant to most

degradative processes in the

environment, including hydrolysis,

photolysis in water and aerobic and

anaerobic metabolism. Only minor

degradation occurred in soil photolysis

studies. The photolytic half-life of

tebuconazole is 19 days. Laboratory and

field studies have shown that the

mobility of tebuconazole in soil is

minimal. Therefore, Bayer concludes

that tebuconazole bears no apparent risk

to ground water under most

circumstances.

3. Non-dietary exposure. Although

current registrations and the proposed

use for grasses grown for seed are

limited to commercial crop production,

Bayer has submitted an application to

register tebuconazole on turf. Bayer has

conducted an exposure study designed

to measure the upper bound acute

exposure potential of adults and

children from contact with tebuconazole

treated turf. The population considered

to have the greatest potential exposure

from contact with pesticide treated turf

soon after pesticides are applied are

young children. Margins of exposure

(MOE) of 1,518 8,561 for 10-year-old

children and 1,364 - 7,527 for 5-year-old

children were estimated by comparing

dermal exposure doses to the

tebuconazole no-observable effect level

of 1,000 mg/kg/day established in a

subacute dermal toxicity study in

rabbits. The estimated safe residue

levels for tebuconazole on treated turf

for 10-year-old children ranged from 4.8

- 27.3 μg/cm2 and for 5-year-old

children from 4.4 - 24.0 μg/cm2. This

compares with the average tebuconazole

transferable residue level of 0.319 μg/

cm2 present immediately after the

sprays have dried. Bayer concludes that

these data indicate that children can

safely contact tebuconazole-treated turf

as soon after application as the spray

has dried.

D. Cumulative Effects

At this time, the EPA has not made a

determination that tebuconazole and

other substances that may have a

common mechanism of toxicity would

have cumulative effects. Therefore, for

this tolerance, Bayer has considered

only the potential risks of tebuconazole

in its aggregate exposure.

E. Safety Determination

1. U.S. population. Chronic Dietary

Exposure: Based on a complete and

reliable toxicity database, the EPA has

adopted an RfD value of 0.03 mg/kg/

day. This RfD is based on a 1–year dog

study with a NOEL of 2.96 mg/kg/day

and an uncertainty factor of 100. Using

the conservative exposure assumptions

described above, Bayer has been advised

that the EPA has concluded that

aggregate dietary exposure to

tebuconazole from the previously

established and the proposed tolerances

will utilize 5.1 % of the RfD for the U.S.

population (48 states) and 30.7% of the

RfD for the most highly exposed

population subgroup (non-nursing

infants, <1 year old). There is generally

no concern for exposures below 100 %

of the RfD because the RfD represents

the level at or below which daily

aggregate exposure over a lifetime will

not pose appreciable risks to human

health. Therefore, Bayer concludes that

there is a reasonable certainty that no

harm will result from aggregate

exposure to tebuconazole.

2. Acute dietary exposure. EPA

recently proposed a tiered approach to

estimate acute dietary exposure. The

methods proposed by the EPA were

reviewed and supported by the FIFRA

Scientific Advisory Panel (SAP, 1995).

EPA’s Tier 1 method is based on the

assumption that residue concentrations

do not vary. The analysis assumes that

all residues have the same magnitude,

typically the highest field trial residue

or tolerance value. This value is

assumed for all points along the

consumption distribution, resulting in a

distribution of dietary exposure. Bayer

has been advised that the EPA

conducted an acute dietary analysis

using the NOEL of 10 mg/kg/day for

developmental toxicity in the mouse.

The EPA has calculated a high end

Margin of Exposure (MOE) value of

1,000 for the population subgroup of

concern (females 13+). In addition,

Bayer has calculated 95th percentile

MOE for the following population

groups: overall U.S. population (MOE =

2,528), infants (MOE = 711), children 1

to 6 years of age (MOE = 1,145) , females

13 years and older (MOE = 4,285), and

males 13 years and older (MOE = 3,685).

Therefore, since EPA considers values

of 100 or more satisfactory, there is no

concern from acute dietary exposure.

3. Infants and children. In assessing

the potential for additional sensitivity of
15696 Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices

infants and children to residues of

tebuconazole, the data from

developmental studies in both rat and

rabbit and a two-generation

reproduction study in the rat should be

considered. The developmental toxicity

studies evaluate any potential adverse

effects on the developing animal

resulting from pesticide exposure of the

mother during prenatal development.

The reproduction study evaluates any

effects from exposure to the pesticide on

the reproductive capability of mating

animals through two generations, as

well as any observed systemic toxicity.

A developmental toxicity study in the

rat, a developmental toxicity study in

the rabbit, two developmental studies in

the mouse and a 2-generation rat

reproduction study have been

conducted with tebuconazole. Maternal

and developmental toxicity NOELs of 30

mg/kg/day were determined in the rat

and rabbit studies. An oral mouse

developmental toxicity study had

maternal and developmental toxicity

NOELs of 10 mg/kg/day while the

mouse dermal developmental study had

a maternal NOEL of 30 mg/kg/day and

a developmental toxicity NOEL of 1,000

mg/kg/day. The parental and

reproductive NOELs in the 2-generation

rat reproduction study were determined

to be 15 mg/kg/day (300 ppm). In all

cases, the reproductive and

developmental NOELs were greater than

or equal to the parental NOELs. This

indicates that tebuconazole does not

pose any increased risk to infants or

children. 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 effects and the

completeness of the toxicity database.

Based on current toxicological data

requirements, the toxicology database

for tebuconazole relative to pre- and

post-natal effects is complete. Further

for tebuconazole, the NOEL of 2.96 mg/

kg/bwtt from the 1–year dog study,

which was used to calculate the RfD, is

already lower than the NOELs from the

developmental studies in rats (30 mg/kg

bwt/day) and rabbits (30 mg/kg bwt/

day) by a factor of 10 times. Since a

hundredfold uncertainty factor is

already used to calculate the RfD, Bayer

surmises that an additional uncertainty

factor is not warranted and that the RfD

at 0.03 mg/kg/bwtt/day is appropriate

for assessing aggregate risk to infants

and children. Using the conservative

exposure assumptions, Bayer has

concluded from the EPA’s recent

chronic dietary analysis that the percent

of the RfD utilized by aggregate

exposure to residues of tebuconazole

ranges from 14.2% for children 1 to 6

years old up to 30.7% for non-nursing

infants. EPA generally has no concern

for exposure below 100 % of the RfD.

Therefore, based on the completeness

and reliability of the toxicity data and

the conservative exposure assessment,

Bayer concludes that there is a

reasonable certainty that no harm will

result to infants and children from

aggregate exposure to the residues of

tebuconazole, including all anticipated

dietary exposure and all other nonoccupational exposures.

F. International Issues

No CODEX Maximum Residue Levels

(MRLs) have been established for

residues of tebuconazole on any crops at

this time. Data have not been submitted

to the Joint Meeting of the Food and

Agriculture Organization Panel of

Experts on Pesticide Residues in Food

and the Environment and the World

Health Organization Expert Group on

Pesticide Residues (JMPR) to establish

Codex MRLs for grasses grown for seed.

G. Mode of Action

Tebuconazole, the active ingredient of

Folicur 3.6 F is a sterol demethylation

inhibitor (DMI) fungicide. It is systemic

and shows activity against rusts

(Puccinia spp.) and powdery mildew

infecting grasses grown for seed.

Tebuconazole provides protective

activity by preventing completion of the

infection process by direct inhibition of

sterol synthesis. It is rapidly absorbed

by plants and translocated systemically

in the young growing tissues.

2. Ciba Crop Protection

6F4656/6H5746

EPA has received pesticide petitions

(PP) 6F4656/6H5746 from Ciba Crop

Protection, Ciba-Geigy Corporation, P.O.

Box 18300, Greensboro, NC 27419,

proposing pursuant to section 408(d) of

the Federal Food, Drug and Cosmetic

Act (FFDCA), 21 U.S.C 346a, to amend

40 CFR part 180 by establishing

tolerances for residues of the fungicide

cyprodinil (4-cyclopropyl-6-methyl-Nphenyl-2-pyrimidinamine) in or on the

agricultural commodities almond

nutmeats at 0.04 ppm, almond hulls at

0.1 ppm, grapes at 3.0 ppm, raisins at

3.0 ppm, the pomefruit crop grouping at

0.1 ppm, apple pomace - wet at 0.4

ppm, and the stone fruit crop grouping

at 2.0 ppm. The proposed analytical

method for determining residues uses

high performance liquid

chromatography with UV detection.

EPA has determined that the petition

contains data or information regarding

the elements set forth in section

408(d)(2); however EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data supports granting of the

petition. Additional data may be needed

before EPA rules on the petition. (PM

21)

A. Cyprodinil Uses

Cyprodinil is the first fungicide in a

new chemical class known as the

anilinopyrimidine and is active against

important Botrytis, Monilinia and

Venturia diseases of deciduous fruit and

nut crops. Cyprodinil with a unique

mode of action, controls pathogens

resistant to other chemical classes.

Application rates range from 0.125 to

0.5 lb active ingredient per acre per

application depending upon disease and

time of application.

B. Residue Chemistry

1. Metabolism. Ciba believes the

metabolism of cyprodinil has been well

characterized in plants and animals.

The metabolism profile supports the use

of an analytical enforcement method

that accounts for only parent cyprodinil.

2. Analytical methodology. Ciba has

submitted a practical analytical method

involving extraction, filtration, and

solid phase cleanup of samples with

analysis by HPLC and UV. The limits of

quantitation (LOQ) for various

commodities are as follows: fruit, grain,

juice - 0.02 ppm; forage, fodder, straw

- 0.05 ppm; and grapes - 0.01 ppm.

C. Magnitude of Residue

This petition is supported by field

residue trials conducted on almonds,

grapes, and representative members of

the Pome Fruit and the Stone Fruit Crop

Groupings. All samples were analyzed

for parent residues of cyprodinil.

Residues found in the almond

nutmeats and hulls were all less than

respective LOQ’s of 0.02 ppm and 0.05

ppm. Tolerances at twice the LOQ for

these commodities have been proposed.

In grapes, the maximum residues found

for fresh fruit and raisins were 2.0 ppm

and 2.9 ppm, respectively. Residues did

not concentrate in grape juice.

Tolerances of 3.0 ppm for grapes and

raisins have been requested. In pome

fruit, maximum residues ranged from

0.030 ppm to 0.061 ppm. The results of

a processing study on apples using

exaggerated rates showed concentration

of residues in wet pomace with an

average concentration factor of 4X.

Residues in apple juice were not

detectable at the LOQ (< 0.01 ppm).

Tolerances of 0.1 ppm for the RAC of

the Pome Fruit Crop Grouping and 0.4

ppm for wet apple pomace have been

proposed. In stone fruit, maximum
Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices 15697

residues ranged from 0.82 ppm to 1.7

ppm. A tolerance of 2.0 ppm has been

proposed for the Stone Fruit Crop

Grouping. Based upon the results of a

three level dairy feeding study, Ciba

believes no transfer of residue to

animals is expected through their diet

and that tolerances in milk, meat,

poultry, and eggs are not required.

D. International Tolerances

There are no Codex Alimentarius

Commission (CODEX) maximum

residue levels (MRL’s) established for

residues of cyprodinil in or on raw

agricultural commodities.

E. Toxicological Profile of Cyprodinil

The following mammilian toxicity

studies have been conducted to support

the tolerances of cyprodinil:

1. A rat acute oral study for cyprodinil

with a LD50 of 2,796 mg/kg.

2. A rat acute dermal study for

cyprodinil with a LD50 > 2,000 mg/kg.

3. A rat inhalation study for

cyprodinil with a LC50 > 1.2 mg/liter air.

4. A primary eye irritation study in

rabbits showing cyprodinil as minimally

irritating.

5. A primary dermal irritation study

in rabbits showing cyprodinil as slightly

irritating.

6. A skin sensitization study in guinea

pigs showing cyprodinil as a weak

sensitizer.

7. A 28–day dermal study in the rat

with a NOEL of 5 mg/kg based on

clinical signs.

8. A 90–day feeding study in the dog

with a NOEL of 1500 ppm (37.5 mg/kg)

based on reduced food intake and body

weight.

9. A 90–day feeding study in the

mouse with a NOEL of 500 ppm (75 mg/

kg) based on liver histologic changes.

10. A 90–day feeding study in the rat

with a NOEL of 50 ppm (5 mg/kg) based

on hematologic and histologic findings.

11. A 12–month feeding study in the

dog with a NOEL of 2,500 ppm (62.5

mg/kg) based on liver histologic

changes.

12. An 18–month oncogenicity

feeding study in the mouse with a NOEL

of 2,000 ppm (300 mg/kg). The MTD

was 5,000 ppm based on reduction in

body weight gain and no evidence of

oncogenicity was seen.

13. A 24–month chronic feeding/

oncogenicity study in the rat with a

NOEL of 75 ppm (3.75 mg/kg) based on

hematologic and histologic findings.

The MTD was 2,000 ppm based on liver

histopathology and no evidence of

oncogenicity was seen.

14. An oral teratology study in the rat

with a maternal NOEL of 200 mg/kg

based on reductions in body weight gain

and food consumption and a fetal NOEL

of 200 mg/kg based on decreased pup

weight and delayed skeletal growth at

1,000 mg/kg.

15. An oral teratology study in the

rabbit with a maternal NOEL of 150 mg/

kg based on reduction in body weight

gain and a fetal NOEL of 400 mg/kg

based on the absence of any fetal effects.

16. A 2–generation reproduction

study in the rat with a systemic NOEL

of 100 ppm and a fetal NOEL of 1,000

ppm (100 mg/kg). A slight decrease in

pup weight at birth and subsequent

body weight gain during the lactation

phase was observed only at the

maternally toxic dose of 4,000 ppm

without any effects on reproduction and

fertility.

17. In vitro gene mutation test: Ames

assay - negative; Chinese hamster V79

cell test - negative; rat hepatocyte DNA

repair test - negative.

18. In vitro chromosome test: Chinese

hamster ovary cell cytogenetic test -

negative.

19. In vivo mutagenicity test: mouse

bone marrow test - negative.

F. Threshold Effects

1. Chronic effects. Based on the

available chronic toxicity data, Ciba

Crop Protection believes the Reference

dose (RfD) for cyprodinil is 0.0375 mg/

kg/day. This RfD is based on a 2–year

feeding study in rats with aNo-Observed

Effect Level (NOEL) of 3.75 mg/kg/day

(75 ppm) and an uncertainly factor of

100. No additional modifying factor for

the nature of effects was judged to be

necessary as liver sinusoidal dilatation

was the most sensitive indicator of

toxicity in that study.

2. Acute toxicity. The risk from acute

dietary exposure to cyprodinil is

considered to be very low. The lowest

NOEL in a short term exposure scenario,

identified as 150 mg/kg in the rabbit

teratology study, is fortyfold higher than

the chronic NOEL. Since chronic

exposure assessment did not result in

any margin of exposure less than 400 for

even the most impacted population

subgroup, Ciba believes the margin of

exposure is greater than 100 for any

population subgroups; EPA considers

margins of exposure of 100 or more as

satisfactory.

G. Non-threshold Effects

Using the Guidelines for Carcinogenic

Risk Assessment published September

24, 1986 (51 FR 33992), Ciba believes

cyprodinil to be in Group ‘‘E’’( no

evidence of carcinogenicity. There was

no evidence of carcinogenicity in an 18–

month feed study in mice and a 24–

month feeding in rats. Dosage levels in

both the mouse and the rat studies were

adequate for identifying a cancer risk.

H. Aggregate Exposure

1. Dietary exposure. For the purposes

of assessing the potential dietary

exposure under the proposed tolerances,

Ciba has estimated aggregate exposure

based upon the Theoretical Maximum

Residue Concentration (TMRC) from the

requested tolerances: Almonds — 0.04

ppm for the raw agricultural commodity

(RAC) and 0.1 ppm for hulls; Grapes —

3.0 ppm for the RAC and 3.0 ppm for

raisins; Pome Fruit Crop Grouping —

0.1 ppm for the RAC and 0.4 ppm for

apple wet pomace; and Stone Fruit Crop

Grouping — 2.0 ppm for the RAC. The

TMRC is a ‘‘worst case’’ estimate of

dietary exposure since it assumes 100 %

of all crops for which tolerances are

established are treated and that

pesticide residues are at the tolerance

levels. In conducting this exposure

assessment, Ciba has made very

conservative assumptions — 100% of all

almonds, grapes, pome fruit and stone

fruit commodities will contain

cyprodinil residues at tolerance levels

— which result in an overestimate of

human exposure.

2. Drinking water exposure.

Cyprodinil is rapidly degraded in the

environment via photolysis and

microbial degradation; aqueous and soil

photolysis half lives for cyprodinil are

12 days and 67 days, respectively. The

aerobic metabolism half life is 25 days

and the leaching potential for cyprodinil

is low (Koc = 1,550 to 2,030). Based on

these data, Ciba does not anticipate

exposure to residue of cyprodinil in

drinking water.

3. Non-dietary exposure. Ciba believes

that the potential for non-occupational

exposure to the general public is

unlikely except for potential residues in

food crops discussed above. The

proposed uses for cyprodinil are for

agricultural crops and the product is not

used residentially in or around the

home.

Ciba believes that consideration of a

common mechanism of toxicity is not

appropriate at this time since there is no

information to indicate that toxic effects

produced by cyprodinil would be

cumulative with those of any other

chemicals. Consequently, Ciba is

considering only the potential exposure

to cyprodinil in its aggregate risk

assessment.

I. Safety To the U.S. Population

Reference dose. Using the

conservative exposure assumptions

described above and based on the

completeness and reliability of the

toxicity data base for cyprodinil, Ciba
15698 Federal Register / Vol. 62, No. 63 / Wednesday, April 2, 1997 / Notices

has calculated aggregate exposure levels

for this chemical. Based on chronic

toxicity endpoints, only 4% of the RfD

will be utilized for the U.S. general

population. EPA usually 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. Ciba

concludes that there is a reasonable

certainty that no harm will result from

aggregate exposure to cyprodinil

residues.

J. Safety to Infants and Children

Developmental delays (reduced pup

weight and ossification) were observed

in the rat teratology study and 2-

generation rat reproduction study at

maternally toxic doses. The lowest

NOEL for this effect was established in

the 2-generation study at 100 mg/kg

(1,000 ppm). The finding is judged to be

a nonspecific, secondary effect of

maternal toxicity. No developmental

toxicity was observed in the rabbit

teratology study.

Reference dose. Using the same

conservative exposure assumptions as

employed for the determination in the

general population, Ciba has calculated

the utilization of RfD by aggregate

exposure to residues of cyprodinil to be

12% for nursing infants less than 1 year

old, 22% for non-nursing infants less

than 1 year old, 12% for children 1 to

6 years old, and 6% for children 7 to 12

years old. Ciba believes that under the

worst case assumptions which

overestimate exposure to infants and

children, there is a reasonable certainty

that no harm will result to infants and

children from aggregate exposure to

cyprodinil residues.

K. Estrogenic effects

Cyprodinil does not belong to a class

of chemicals known or suspected of

having adverse effects on the endocrine

system. Developmental toxicity studies

in rats and rabbits and a reproduction

study in rats gave no indication that

cyprodinil might have any effects on

endocrine function related to

development and reproduction. The

chronic studies also showed no

evidence of a long-term effect related to

the endocrine system.

[FR Doc. 97–8397 Filed 4–1–97; 8:45 am]

BILLING CODE 6560–50–F

[OPP–181041; FRL 5597–8]

Cymoxanil, Propamocarb

Hydrochloride and Dimethomorph;

Receipt of Applications for Emergency

Exemptions, Solicitation of Public

Comment

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: EPA has received specific

exemption requests from the Florida

Department of Agriculture and

Consumer Services (hereafter referred to

as the ‘‘Applicant’’) to use the pesticides

cymoxanil (CAS 57966–95–7),

propamocarb hydrochloride (CAS

25606–41–1) and dimethomorph (CAS

110488–70–5) to treat potentially up to

50,000 acres of tomatoes to control

immigrant strains of late blight which

are resistant to historically used control

materials. The Applicant proposes the

use of either new (unregistered)

chemicals or the first food use of an

active ingredient therefore, in

accordance with 40 CFR 166.24, EPA is

soliciting public comment before

making the decision whether or not to

grant the exemptions.

DATES: Comments must be received on

or before April 17, 1997.

ADDRESSES: Three copies of written

comments, bearing the identification

notation ‘‘OPP–181041,’’ 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 following

the instructions under

‘‘SUPPLEMENTARY INFORMATION’’

of this document. No Confidential

Business Information (CBI) should be

submitted through e-mail.

Information submitted in any

comment concerning this notice 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 provided by the

submitter for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments filed pursuant to this notice

will be available for public inspection in

Rm. 1132, Crystal Mall No. 2, 1921

Jefferson Davis Highway, Arlington, VA,

from 8:30 a.m. to 4 p.m., Monday

through Friday, except legal holidays.

FOR FURTHER INFORMATION CONTACT: By

mail: Libby Pemberton, Registration

Division (7505W), Office of Pesticide

Programs, Environmental Protection

Agency, 401 M St., SW., Washington,

DC 20460. Office location, telephone

number and e-mail: Floor 6, Crystal

Station #1, 2800 Jefferson Davis

Highway, Arlington, VA, (703) 308–

8326; e-mail:

pemberton.libby@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: Pursuant

to section 18 of the Federal Insecticide,

Fungicide, and Rodenticide Act (FIFRA)

(7 U.S.C. 136p), the Administrator may,

at her discretion, exempt a state agency

from any registration provision of

FIFRA if she determines that emergency

conditions exist which require such

exemption. The Applicant has requested

the Administrator to issue specific

exemptions for the use of cymoxanil,

propamocarb hydrochloride, and/or

dimethomorph on tomatoes to control

late blight. Information in accordance

with 40 CFR part 166 was submitted as

part of this request.

Recent failures to control late blight in

tomatoes as well as potatoes with the

registered fungicides, have been caused

almost exclusively by immigrant strains

of late blight Phytophthora infestans,

which are resistant to the control of

choice, metalaxyl. Before the immigrant

strains of late blight arrived, all of the

strains in the U.S. were previously

controlled by treatment with metalaxyl.

The Applicant states that presently,

there are no fungicides registered in the

U.S. that will provide adequate control

of the immigrant strains of late blight.

The Applicant states that each of these

requested chemicals has been shown to

be effective against these strains of late

blight. Each active ingredient holds

current registrations throughout many

European countries for control of this

disease. The Applicant indicates that at

least a 30 percent yield reduction is

expected based on the current

infestation. Net revenues are expected to

be reduced by over $12 million for the

affected acreage without the use of these

requested chemicals.

The Applicant proposes to apply

propamocarb hydrochloride,

manufactured by AgrEvo USA

Company, as Tattoo C, at a maximum

rate of 0.9 lbs. active ingredient [(a.i.)],

(2.3 pt of product) per acre by ground

or air, with a maximum of 5

applications per season. A 7–day PHI

will be observed. Use under this

exemption could potentially amount to