30200 Federal Register / Vol. 61, No. 116 / Friday, June 14, 1996 / Proposed Rules

as independent diagnostic information

to the ordering clinician. Examples are

IHC’s for immunologic detection and

semi-quantitative measurement of

specific ligand markers of proliferation,

such as Ki-67, or semi-quantitative

determination of other analytes, such as

hormone receptors, if they are reported

for their prognostic implications.

However, this classification does not

apply to estrogen and progesterone

receptors that are classified as class III

devices.

(3) Class III for IHC’s that generate

information that is reported directly to

the clinician to be used as the basis for

significant medical decisions, and that

either provide information substantially

independent of other pathological (or

cytopathological) aspects of the

specimen or that have novel claims not

supported by current widely accepted

scientific pathophysiologic principles.

Examples are markers used to identify

clinically significant genetic mutations

in tissues that are normal by

conventional histopathologic

examination.

(c) Date PMA or notice of completion

of a PDP is required. No effective date

has been established for the requirement

for premarket approval for the devices

described in paragraph(b)(3) of this

section. See § 864.3 for effective dates of

requirement for premarket approval.

Dated: May 31, 1996.

D.B. Burlington,

Director, Center for Devices and Radiological

Health.

[FR Doc. 96–15140 Filed 6–13–96; 8:45 am]

BILLING CODE 4160–01–F

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Part 180

[PP 5E4573/P662; FRL–5375–1]

RIN 2070–AC18

Fenarimol; Pesticide Tolerance For

Residues in or on Filberts

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Proposed rule.

SUMMARY: EPA proposes to establish a

tolerance for residues of the fungicide

fenarimol in or on the raw agricultural

commodity filberts. The proposed

regulation to establish a maximum

permissible level for residues of the

fungicide was requested in a petition

submitted by the Interregional Research

Project No. 4 (IR-4).

DATES: Comments, identified by the

docket number [PP 5E4573/P662], must

be received on or before July 15, 1996.

ADDRESSES: By mail, submit written

comments to: Public Response and

Program Resources Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person, bring

comments to: Rm. 1132, CM #2, 1921

Jefferson Davis Highway, Arlington, VA

22202.

Comments and data may also be

submitted to OPP by sending electronic

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

comments must be submitted as an

ASCII file avoiding the use of special

characters and any form of encryption.

Comments and data will also be

accepted on disks in WordPerfect 5.1

file format or ASCII file format. All

comments and data in electronic form

must be identified by the docket number

[PP 5E4573/P662]. Electronic comments

on this proposed rule may be filed

online at many Federal Depository

Libraries. Additional information on

electronic submissions can be found in

the ‘‘SUPPLEMENTARY

INFORMATION’’ section of this

document.

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 Virginia

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

p.m., Monday through Friday, excluding

legal holidays.

FOR FURTHER INFORMATION CONTACT: By

mail: Hoyt L. Jamerson, Registration

Division (7505W), Office of Pesticide

Programs, Environmental Protection

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

20460. Office location and telephone

number: Sixth Floor, Crystal Station #1,

2800 Jefferson Davis Highway,

Arlington, VA 22202, (703) 308–8783; email: jamerson.hoyt@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: The

Interregional Research Project No. 4 (IR4), New Jersey Agricultural Experiment

Station, P.O. Box 231, Rutgers

University, New Brunswick, NJ 08903,

has submitted pesticide petition (PP)

5E4573 to EPA on behalf of the Oregon

Filbert Commission.

This petition requests that the

Administrator, pursuant to section

408(e) of the Federal Food, Drug, and

Cosmetic Act (FFDCA), 21 U.S.C.

346a(e), amend 40 CFR 180.421 by

establishing a tolerance for residues of

the fungicide fenarimol [alpha-(2-

chlorophenyl)-alpha-(4-chlorophenyl)-5-

pyrimidine methanol] in or on the raw

agricultural commodity filberts at 0.02

parts per million (ppm).

The scientific data submitted in the

petition and other relevant material

have been evaluated. The toxicological

data considered in support of the

proposed tolerance include:

1. A 1–year feeding study with dogs

fed diets containing 0, 1.25, 12.5, or 125

milligrams/kilogram (mg/kg)/day. The

no-observed-effects level (NOEL) for this

study is established at 12.5 mg/kg/day.

The high dose level (125 mg/kg/day)

caused increased serum alkaline

phosphatase, increased liver weights, an

increase in p-nitroanisole o-demethylase

activity, and mild hepatic bile stasis.

2. A 2–year chronic feeding/

carcinogenicity study in rats fed diets

containing concentrations of 0, 50, 130,

or 350 ppm (equivalent to 0, 2.5, 6.5, or

17.5 mg/kg/day) with a systemic NOEL

of 130 ppm (equivalent to 6.5 mg/kg/

day). An increase in fatty liver changes

was observed in rats fed diets

containing 350 ppm. There were no

carcinogenic effects observed under the

conditions of the study.

3. A second 2–year chronic feeding/

carcinogenicity study in rats fed diets

containing 0, 12.5, 25, or 50 ppm

(equivalent to 0, 0.63, 1.25, or 2.5 mg/

kg/day) with no systemic or

carcinogenic effects observed under the

conditions of the study.

4. A 2–year carcinogenicity study in

mice fed diets containing concentrations

of 0, 50, 170, or 600 ppm (equivalent to

0, 7, 24.3, or 85.7 mg/kg/day) with a

NOEL for systemic effects at 170 ppm.

An increase in fatty liver changes was

observed in mice at the 600 ppm dose

level. There were no carcinogenic efects

observed under the conditions of the

study.

5. A developmental toxicity study

with rabbits given oral doses of 0, 5, 10,

or 35 mg/kg/day with no developmental

toxicity observed under the conditions

of the study.

6. A developmental toxicity study

with rats given oral doses of 0, 5, 13, or

35 mg/kg/day demonstrated

hydronephrosis at 35 mg/kg/day. The

NOEL for developmental toxicity in this

study is established at 13 mg/kg/day.
Federal Register / Vol. 61, No. 116 / Friday, June 14, 1996 / Proposed Rules 30201

7. A second developmental toxicity

study in rats (with a postpartum

evaluation) again demonstrated

hydronephrosis at 35 mg/kg/day.

Maternal toxicity (decreased body

weight gain) was also observed at the 35

mg/kg/day. The NOEL’s for

developmental and maternal toxicity in

this study are established at 13 mg/kg/

day.

8. A 3–generation reproduction study

in rats fed diets containing 0, 12.5, 25,

or 50 ppm (equivalent to 0.625, 1.25, or

2.5 mg/kg/day) demonstrated decreased

mating in males at the 25 ppm and

delayed parturition and dystocia in

females at 25 ppm and 50 ppm. The

NOEL for reproductive effects in this

study is established at 12.5 ppm. The

infertility effect in male rats is

considered to be a species-specific effect

mediated by the inhibition of

testosterone aromatase which catalyzes

the conversion of testosterone to

estradiol in the hypothalamus. Estradiol

plays an essential role in the

development and maintenance of sexual

behavior of rats but not in man.

9. Multi-generation reproduction

studies that were negative for

reproductive effects at 35 mg/kg/day

(highest dose tested) in guinea pigs and

20 mg/kg/day (highest doses tested) in

mice.

10. An aromatase inhibition study in

rats that showed fenarimol to be a

moderately weak inhibitor of aromatase

activity.

The adverse reproductive effects

observed in the rat multi-generation

reproduction study are considered to be

a species-specific effect caused by

aromatase inhibition. The aromatose

enzyme promotes normal sexual

behavior in rats and mice, but not in

guinea pigs, or primates (including

humans). A NOEL of 35 mg/kg/day for

reproductive effects relevant to humans

was established based on the NOEL

from the multi-generation reproduction

study in guinea pigs.

11. Fenarimol tested negative in

several assay systems for gene mutation,

structural chromosome aberration and

other genotoxic effects. In a

micronucleus test in the mouse,

fenarimol did produce a significant

increase in the percent of polychromatic

erythrocytes with micronucleus at 24

hours, but not at 48 hours or 72 hours.

The significance of this finding is not

known, but the negative results of the

other assays demonstrate that the

mutagenic potential of fenarimol is very

low.

12. Metabolism studies in rats show

that fenarimol is rapidly metabolized

and excreted. Major metabolic pathways

were oxidation of the carbinol-carbon

atom, the phenyl rings and the

pyrimidine ring.

Based on the above findings, the

Agency concluded that fenarimol was

not carcinogenic in long-term studies in

rats and mice under the test conditions

in which the highest dose tested for

both species approached a maximumtolerated dose as evidenced by

increased fatty changes in the liver.

The Reference Dose (RfD) is

calculated at 0.065 mg/kg bwt/day. The

RfD is based on a NOEL of 6.5 mg/kg/

bwt/day from the 2–year rat chronic

feeding study and an uncertainty factor

of 100. The theoretical maximum

residue contribution (TMRC) from

previously established tolerances and

the proposed tolerance for filberts

utilizes less than 1 percent of the RfD

for the general population and less than

2 percent of the RfD for children 1 to 6

years of age (the population subgroup

most highly exposed to dietary residues

of fenarimol). EPA generally has no

concern for exposures below 100

percent of the RfD.

The metabolism of fenarimol in plants

is adequately understood for the

purposes of the proposed tolerance. The

residue of concern is fenarimol per se.

An adequate analytical method, is

available for enforcement purposes. The

analytical method is published in the

Pesticide Analytical Manual, Volume II

(PAM II).

There is no reasonable expectation

that secondary residues of fenarimol

will occur in milk, egg, or meat, fat, and

meat byproducts of livestock or poultry

as a result of this action; there are no

livestock feed commodities associated

with filberts.

There are presently no actions

pending against the continued

registration of this chemical.

Based on the information and data

considered, the Agency has determined

that the tolerance established by

amending 40 CFR part 180 would

protect the public health. Therefore, it is

proposed that the tolerance be

established as set forth below.

Any person who has registered or

submitted an application for registration

of a pesticide, under the Federal

Insecticide, Fungicide, and Rodenticide

Act (FIFRA) as amended, which

contains any of the ingredients listed

herein, may request within 30 days after

publication of this notice in the Federal

Register that this rulemaking proposal

be referred to an Advisory Committee in

accordance with section 408(e) of the

FFDCA.

Interested persons are invited to

submit written comments on the

proposed regulation. Comments must

bear a notation indicating the docket

number [PP 5E4573/P662].

A record has been established for this

rulemaking under docket number [PP

5E4573/P662] (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 a.m. to 4:30 p.m.,

Monday through Friday, excluding legal

holidays. The public record is located in

Room 1132 of the Public Response and

Program Resources Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, Crystal Mall #2,

1921 Jefferson Davis Highway,

Arlington, VA.

The official record for this

rulemaking, as well as the public

version, as described above will be kept

in paper form. Accordingly, EPA will

transfer all comments received

electronically into printed, paper form

as they are received and will place the

paper copies in the official rulemaking

record which will also include all

comments submitted directly in writing.

The official rulemaking record is the

paper record maintained at the address

in ‘‘ADDRESSES’’ at the beginning of

this document.

Under Executive Order 12866 (58 FR

51735, Oct. 4, 1993), the Agency must

determine whether the regulatory action

is ‘‘significant’’ and therefore subject to

all the requirements of the Executive

Order (i.e., Regulatory Impact Analysis,

review by the Office of Management and

Budget (OMB)). Under section 3(f), the

order defines ‘‘significant’’ as those

actions likely to lead to a rule (1) having

an annual effect on the economy of $100

million or more, or adversely and

materially affecting a sector of the

economy, productivity, competition,

jobs, the environment, public health or

safety, or State, local or tribal

governments or communities (also

known as ‘‘economically significant’’);

(2) creating serious inconsistency or

otherwise interfering with an action

taken or planned by another agency; (3)

materially altering the budgetary

impacts of entitlement, grants, user fees,

or loan programs; or (4) raising novel

legal or policy issues arising out of legal

mandates, the President’s priorities, or

the principles set forth in t his

Executive Order. Pursuant to the terms

of this Executive Order, EPA has

determined that this rule is not

‘‘significant’’ and is therefore not subject

to OMB review.

This action does not impose any

enforceable duty, or contain any
30202 Federal Register / Vol. 61, No. 116 / Friday, June 14, 1996 / Proposed Rules

‘‘unfunded mandates’’ as described in

Title II of the Unfunded Mandates

Reform Act of 1995 (Pub. L. 104–4), or

require prior consultation as specified

by Executive Order 12875 (58 FR 58093,

October 28, 1993), entitled Enhancing

the Intergovernmental Partnership, or

special consideration as required by

Executive Order 12898 (59 FR 7629,

February 16, 1994).

Pursuant to the requirements of the

Regulatory Flexibility Act (5 U.S.C.

601–612), the Administrator has

determined that regulations establishing

new tolerances or raising tolerance

levels or establishing exemptions from

tolerance requirements do not have a

significant economic impact on a

substantial number of small entities. A

certification statement explaining the

factual basis for this determination was

published in the Federal Register of

May 4, 1981 (46 FR 24950).

List of Subjects in 40 CFR Part 180

Environmental protection,

Administrative practice and procedure,

Agricultural commodities, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: June 3, 1996.

Stephen L. Johnson,

Director, Registration Division, Office of

Pesticide Programs.

Therefore, it is proposed that 40 CFR

part 180 be amended as follows:

PART 180—[AMENDED]

1. The authority citation for part 180

continues to read as follows:

Authority: 21 U.S.C. 346a and 371.

2. In § 180.421, the table in paragraph

(a) is amended by adding alphabetically

the entry for filberts, to read as follows:

§ 180.421 Fenarimol; tolerances for

residues.

(a) * * *

Commodity Parts per

million

* * * * *

Filberts ...................................... 0.02

* * * * *

* * * * *

[FR Doc. 96–15041 Filed 6–13–96; 8:45 am]

BILLING CODE 6560–50–F

40 CFR Part 180

[OPP–300426; FRL–5374–4]

RIN 2070–AC18

Vinyl Pyrrolidone-Acrylic Acid

Copolymer; Tolerance Exemption.

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Proposed rule.

SUMMARY: This document proposes to

establish an exemption from the

requirement of a tolerance for residues

of vinyl pyrrolidone-acrylic acid

copolymer when used as an inert

ingredient (adhesive, dispersion

stabilizer and coating for sustained

release granules) in pesticide

formulations applied to growing crops,

raw agricultural commodities after

harvest, and applied to animals. This

proposed regulation was requested by

International Specialty Products.

DATES: Written comments, identified by

the docket number [OPP–300426], must

be received on or before July 15, 1996.

ADDRESSES: By mail, submit written

comments to Public Response and

Program Resources Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person,

deliver comments to: Rm. 1132, CM #2,

1921 Jefferson Davis Hwy., Arlington,

VA 22202. 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). 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

will be included in the public docket by

EPA without prior notice. All written

comments will be available for public

inspection in Rm. 1132 at the address

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

Monday through Friday, excluding legal

holidays.

Comments and data may also be

submitted electronically by sending

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

comments must be submitted as an

ASCII file avoiding the use of special

characters and any form of encryption.

Comments and data will also be

accepted on disks in WordPerfect 5.1

file format or ASCII file format. All

comments and data in electronic form

must be identified by the docket number

[OPP–300426]. No Confidential

Business Information (CBI) should be

submitted through e-mail. Electronic

comments on this proposed rule may be

filed online at many Federal Depository

Libraries. Additional information on

electronic submissions can be found

below in this document.

FOR FURTHER INFORMATION CONTACT: By

mail: Bipin Gandhi, Registration

Support Branch, Registration Division

(7505W), Environmental Protection

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

DC 20460. Office location and telephone

number: 2800 Crystal Drive, North

Tower, 6th Floor, Arlington, VA 22202,

(703)–308–8380, e-mail:

gandhi.bipin@epamail.epa.gov.

SUPPLEMENTARY INFORMATION:

International Specialty Products, 1361

Alps Road, Wayne, NJ 07470, submitted

pesticide petition (PP) 6E04659 to EPA

requesting that the Administrator,

pursuant to section 408(e) of the Federal

Food Drug, and Cosmetic Act (FFDCA)

(21 U.S.C. 346 a(e)), propose to amend

40 CFR part 180.1001(c) and (e) by

establishing an exemption from the

requirement of tolerance for residues of

vinyl pyrrolidone-acrylic acid

copolymer (CAS Reg. No. 28062–44–4),

when used as an inert ingredient

(adhesive, dispersion stabilizer and

coating for sustained release granules)

in pesticide formulations applied to

growing crops or to raw agricultural

commodities after harvest, under 40

CFR 180.1001(c) and applied to animals

under 40 CFR 180.1001(e).

Inert ingredients are all ingredients

that are not active ingredients as defined

in 40 CFR 153.125, and include, but are

not limited to, the following types of

ingredients (except when they have a

pesticidal efficacy of their own):

solvents such as alcohols and

hydrocarbons; surfactants such as

polyoxyethylene polymers and fatty

acids; carriers such as clay and

diatomaceous earth; thickeners such as

carrageenan and modified cellulose;

wetting, spreading, and dispersing

agents; propellants in aerosol

dispensers; microencapsulating agents;

and emulsifiers. The term ‘‘inert’’ is not

to imply nontoxicity; the ingredient may

or may not be chemically active.

The data submitted in the petition

and other relevant material have been

evaluated. As part of the EPA policy

statement on inert ingredients published

in the Federal Register of April 22, 1987

(52 FR 13305), the Agency set forth a list

of studies which would generally be

used to evaluate the risks posed by the

presence of an inert ingredient in a

pesticide formulation. However, where

it can be determined without that data

that the inert ingredient will present