57338 Federal Register / Vol. 65, No. 185 / Friday, September 22, 2000 / Notices

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

This action is directed to the public

in general. This action may be of

particular interest to anyone who may

be affected if the AEGL values are

adopted by government agencies for

emergency planning, prevention, or

response programs, such as EPA’s Risk

Management Program under the Clean

Air Act and Amendments Section 112r.

It is possible that other Federal agencies

besides EPA, as well as State agencies

and private organizations, may adopt

the AEGL values for their programs. As

such, the Agency has not attempted to

describe all the specific entities that

may be affected by this action. If you

have any questions regarding the

applicability of this action to a

particular entity, consult the DFO listed

under FOR FURTHER INFORMATION

CONTACT.

B. How Can I Get Additional

Information, Including Copies of this

Document or Other Related Documents?

1. Electronically. You may obtain

electronic copies of this document, and

certain other related documents that

might be available electronically, from

the EPA Internet Home Page at http://

www.epa.gov/. To access this

document, on the Home Page select

‘‘Laws and Regulations,’’ ‘‘Regulations

and Proposed Rules,’’ and then look up

the entry for this document under the

‘‘Federal Register—Environmental

Documents.’’ You can also go directly to

the Federal Register listings at http://

www.epa.gov/fedrgstr/.

2. In person. The Agency has

established an official record for this

action under docket control number

OPPTS–00297. The official record

consists of the documents specifically

referenced in this action, any public

comments received during an applicable

comment period, and other information

related to this action, including any

information claimed as Confidential

Business Information (CBI). This official

record includes the documents that are

physically located in the docket, as well

as the documents that are referenced in

those documents. The public version of

the official record does not include any

information claimed as CBI. The public

version of the official record, which

includes printed, paper versions of any

electronic comments submitted during

an applicable comment period, is

available for inspection in the TSCA

Nonconfidential Information Center,

North East Mall Rm. B–607, Waterside

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

The Center is open from noon to 4 p.m.,

Monday through Friday, excluding legal

holidays. The telephone number of the

Center is (202) 260–7099.

II. Meeting Procedures

For additional information on the

scheduled meeting, the agenda of the

NAC/AEGL Committee, or the

submission of information on chemicals

to be discussed at the meeting, contact

the DFO listed under FOR FURTHER

INFORMATION CONTACT.

The meeting of the NAC/AEGL

Committee will be open to the public.

Oral presentations or statements by

interested parties will be limited to 10

minutes. Interested parties are

encouraged to contact the DFO to

schedule presentations before the NAC/

AEGL Committee. Since seating for

outside observers may be limited, those

wishing to attend the meeting as

observers are also encouraged to contact

the DFO at the earliest possible date to

ensure adequate seating arrangements.

Inquiries regarding oral presentations

and the submission of written

statements or chemical specific

information should be directed to the

DFO.

III. Future Meetings

Another meeting of the NAC/AEGL

Committee is tentatively scheduled for

December 2000. The exact date, location

of this meeting, and chemicals to be

discussed will be published in a future

Federal Register notice.

List of Subjects

Environmental protection, Chemicals,

Hazardous substances, Health.

Dated: September 15, 2000.

William H. Sanders III,

Director, Office of Pollution Prevention and

Toxics.

[FR Doc. 00–24439 Filed 9–21–00; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[PF–961; FRL–6737–8]

Notice of Filing Pesticide Petitions to

Establish Tolerances for Certain

Pesticide Chemicals in or on Food

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 docket

control number PF–961, must be

received on or before October 23, 2000.

ADDRESSES: Comments may be

submitted by mail, electronically, or in

person. Please follow the detailed

instructions for each method as

provided in Unit I.C. of the

SUPPLEMENTARY INFORMATION. To ensure

proper receipt by EPA, it is imperative

that you identify docket control number

PF–961 in the subject line on the first

page of your response.

FOR FURTHER INFORMATION CONTACT: By

mail: Mary L. Waller, Registration

Division (7505C), Office of Pesticide

Programs, Environmental Protection

Agency, 1200 Pennsylvania Ave., NW.,

Washington, DC 20460; telephone

number: (703) 308–9354; e-mail address:

waller.mary@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

You may be affected by this action if

you are an agricultural producer, food

manufacturer or pesticide manufacturer.

Potentially affected categories and

entities may include, but are not limited

to:

Categories NAICS

codes

Examples of potentially affected entities

Industry 111 Crop production

112 Animal production

311 Food manufacturing

32532 Pesticide manufacturing

This listing is not intended to be

exhaustive, but rather provides a guide

for readers regarding entities likely to be

affected by this action. Other types of

entities not listed in the table could also

be affected. The North American

Industrial Classification System

(NAICS) codes have been provided to

assist you and others in determining

whether or not this action might apply

to certain entities. If you have questions

regarding the applicability of this action

to a particular entity, consult the person

listed under FOR FURTHER INFORMATION

CONTACT.

B. How Can I Get Additional

Information, Including Copies of this

Document and Other Related

Documents?

1. Electronically. You may obtain

electronic copies of this document, and

Federal Register / Vol. 65, No. 185 / Friday, September 22, 2000 / Notices 57339

certain other related documents that

might be available electronically, from

the EPA Internet Home Page at http://

www.epa.gov/. To access this

document, on the Home Page select

‘‘Laws and Regulations’’ and then look

up the entry for this document under

the ‘‘Federal Register—Environmental

Documents.’’ You can also go directly to

the Federal Register listings at http://

www.epa.gov/fedrgstr/.

2. In person. The Agency has

established an official record for this

action under docket control number PF–

961. The official record consists of the

documents specifically referenced in

this action, any public comments

received during an applicable comment

period, and other information related to

this action, including any information

claimed as confidential business

information (CBI). This official record

includes the documents that are

physically located in the docket, as well

as the documents that are referenced in

those documents. The public version of

the official record does not include any

information claimed as CBI. The public

version of the official record, which

includes printed, paper versions of any

electronic comments submitted during

an applicable comment period, is

available for inspection in the Public

Information and Records Integrity

Branch (PIRIB), Rm. 119, Crystal Mall

#2, 1921 Jefferson Davis Highway,

Arlington, VA, from 8:30 a.m. to 4 p.m.,

Monday through Friday, excluding legal

holidays. The PIRIB telephone number

is (703) 305–5805.

C. How and to Whom Do I Submit

Comments?

You may submit comments through

the mail, in person, or electronically. To

ensure proper receipt by EPA, it is

imperative that you identify docket

control number PF–961 in the subject

line on the first page of your response.

1. By mail. Submit your comments to:

Public Information and Records

Integrity Branch (PIRIB), Information

Resources and Services Division

(7502C), Office of Pesticide Programs

(OPP), Environmental Protection

Agency, 1200 Pennsylvania Ave., NW.,

Washington, DC 20460.

2. In person or by courier. Deliver

your comments to: Public Information

and Records Integrity Branch (PIRIB),

Information Resources and Services

Division (7502C), Office of Pesticide

Programs (OPP), Environmental

Protection Agency, Rm. 119, Crystal

Mall #2, 1921 Jefferson Davis Highway,

Arlington, VA. The PIRIB is open from

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

Friday, excluding legal holidays. The

PIRIB telephone number is (703) 305–

5805.

3. Electronically. You may submit

your comments electronically by e-mail

to:‘‘opp-docket@epa.gov’’, or you can

submit a computer disk as described

above. Do not submit any information

electronically that you consider to be

CBI. Avoid the use of special characters

and any form of encryption. Electronic

submissions will be accepted in

Wordperfect 6.1/8.0 or ASCII file

format. All comments in electronic form

must be identified by docket control

number PF–961. Electronic comments

may also be filed online at many Federal

Depository Libraries.

D. How Should I Handle CBI That I

Want to Submit to the Agency?

Do not submit any information

electronically that you consider to be

CBI. You may claim information that

you submit to EPA in response to this

document as CBI by marking any part or

all of that information as CBI.

Information so marked will not be

disclosed except in accordance with

procedures set forth in 40 CFR part 2.

In addition to one complete version of

the comment that includes any

information claimed as CBI, a copy of

the comment that does not contain the

information claimed as CBI must be

submitted for inclusion in the public

version of the official record.

Information not marked confidential

will be included in the public version

of the official record without prior

notice. If you have any questions about

CBI or the procedures for claiming CBI,

please consult the person identified

under FOR FURTHER INFORMATION

CONTACT.

E. What Should I Consider as I Prepare

My Comments for EPA?

You may find the following

suggestions helpful for preparing your

comments:

1. Explain your views as clearly as

possible.

2. Describe any assumptions that you

used.

3. Provide copies of any technical

information and/or data you used that

support your views.

4. If you estimate potential burden or

costs, explain how you arrived at the

estimate that you provide.

5. Provide specific examples to

illustrate your concerns.

6. Make sure to submit your

comments by the deadline in this

notice.

7. To ensure proper receipt by EPA,

be sure to identify the docket control

number assigned to this action in the

subject line on the first page of your

response. You may also provide the

name, date, and Federal Register

citation.

II. What Action is the Agency Taking?

EPA has received a pesticide petition

as follows proposing the establishment

and/or amendment of regulations for

residues of certain pesticide chemical in

or on various food commodities under

section 408 of the Federal Food, Drug,

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

346a. EPA has determined that this

petition contains data or information

regarding the elements set forth in

section 408(d)(2); however, EPA has not

fully evaluated the sufficiency of the

submitted data at this time or whether

the data support granting of the petition.

Additional data may be needed before

EPA rules on the petition.

List of Subjects

Environmental protection,

Agricultural commodities, Feed

additives, Food additives, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: September 6, 2000.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

I. BASF Corporation Agricultural

Products

7E4885

EPA has received a pesticide petition

7E4885 from BASF Corporation,

Agricultural Products, P.O. Box 13528,

Research Triangle Park, NC 27709

proposing, pursuant to section 408(d) of

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

40 CFR part 180 by establishing

tolerances for residues of epoxiconazole,

(2RS,3SR)-3-(2-chlorophenyl)-2-(4-

fluorophenyl)-2-(1H-1,2,4-triazol-1-

yl)methyl oxirane in or on bananas at

0.5 parts per million (ppm) and in or on

banana pulp at 0.2 ppm. EPA has

determined that the petition contains

data or information regarding the

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

the FFDCA; however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data support granting of the petition.

Additional data may be needed before

EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism

in bananas was investigated using 14C

labeled epoxiconazole. On average 70%

of the total residue could be identified

as parent. This corresponds to

approximately 80% of the residue

extractable from the peel and

57340 Federal Register / Vol. 65, No. 185 / Friday, September 22, 2000 / Notices

approximately 90% of the residue

extractable from the edible portion,

pulp. Based on this result, a parent only

method was developed to analyze

residues from the magnitude of the

residue trials.

Under worst case practices (unbagged

bananas) residue in the whole fruit

ranged from <the limit of quantitation

(LOQ) (0.025 milligrams/kilograms (mg/

kg) to a maximum of 0.41 mg/kg.

Banana pulp residues from bagged

bananas ranged from < the LOQ (0.025

mg/kg) to 0.17 mg/kg and averaged

0.036 mg/kg. The average value was

calculated by assuming all values below

the LOQ were equal to one half the LOQ

or 0.0125 mg/kg.

2. Analytical method. The method of

analysis includes extraction, liquid/

liquid partition, column clean-up

quantitation by gas chromatography/

electron capture detection. Forty–three

whole banana samples were fortified

with epoxiconazole at levels ranging

from 0.025 mg/kg to 0.5 mg/kg.

Recovery averaged 89.3% +/- 12.4%.

Forty–one banana pulp samples were

fortified with epoxiconazole at levels

ranging from 0.025 mg/kg to 0.25 mg/kg.

Recovery averaged 88.8% +/- 9.2.%.

3. Magnitude of residues. Fifteen crop

residue trials were conducted in the

banana growing regions of Mexico,

South and Central America including

three sites in Colombia, four sites in

Costa Rica, four sites in Ecuador, one

site in Guataemala, two sites in

Hondouras, and one site in Mexico.

Four sequential applications were made

at the 90 g/ha, slightly higher than the

maximum use rate 75 g/ha to both

bagged and unbagged bananas at each

site. Fruit from both the bagged and

unbagged treatments were harvested at

0 days following the last application.

Whole fruit (peel and pulp) samples

and pulp only samples were analyzed

from all treatments at all sites. Under

typical practices (bagged bananas)

residue in the whole fruit ranged from

< the LOQ (0.025 mg/kg) to a maximum

of 0.082 mg/kg. Banana pulp residues

from bagged bananas ranged from < the

LOQ (0.025 mg/kg) to 0.05 mg/kg and

averaged 0.013 mg/kg. The average

value was calculated by assuming all

values below the LOQ were equal to one

half the LOQ or 0.0125 mg/kg.

B. Toxicological Profile

1. Acute toxicity. The acute toxicity

studies place technical epoxiconazole in

acute toxicity category III for acute oral,

dermal, and inhalation; and in acute

toxicity category IV for skin and eye

irritation; and the technical material is

not a skin sensitizer.

2. Genotoxicty. A modified Ames test

(3 studies; point mutation): Negative; E.

coli reverse mutation assay (1 study;

point mutation): Negative; in vitro

chinese hampster ovary/hypoxanthine

guanine phophoribosyl transferase

(CHO/HGPRT) mammalian cell

mutation assay (1 study; point

mutation): Negative; in vitro

Cytogentics—CHO cells (1 study;

chromosome aberrations): Negative;

mouse micronucleus assay (1 study;

chromosome aberrations): Negative; in

vitro unscheduled DNA synthesis (UDS)

test using rat hepatocytes (1 study; DNA

damage and repair): Negative; in vivo

DNA binding in rats and mice (1 study;

DNA binding): Negative.

3. Reproductive and developmental

toxicity. i. A developmental study via

oral gavage in rabbits resulted in

dosages of 0, 20, 50, and 80 mg/kg/day

highest dose tested (HDT) with a

developmental toxicity no observed

adverse effect level (NOAEL) of 80 mg/

kg/day and a maternal toxicity of 20 mg/

kg/day based on the following:

a. Decreased body weight (bwt), food

consumption, uterus weight, and

increased resorption rate and postimplantation losses in the 80 mg/kg/day

dose level.

b. Slight decreases of body weight and

food consumption was seen in the 50

mg/kg/day dose level.

c. No substance-related findings were

observed in any fetus at all dose levels.

ii. A developmental study was

conducted via oral gavage in rats

resulted in dosages of 0, 5, 15, and 45

mg/kg/day HDT with a developmental

toxicity NOAEL of 5 mg/kg/day and a

maternal toxicity of 5 mg/kg/day based

on the following:

a. Signs of maternal toxicity, in the

form of decreased body weights, food

consumption, and increased placental

weights observed at the highest dose

tested.

b. Maternal animals in the 45 mg/kg/

day showed an increase in the number

of late resorptions as compared to

controls.

c. Increased placental weights in the

15 mg/kg/day dose level.

d. A significant number of fetuses

with skeletal variations (especially

rudimentary cervical and/or accessory

14th rib(s)) in the high dose group tested

were observed. However, no

malformations were observed in any

pups in this study.

iii. In a second developmental study

in rats via dermal exposure for 6 hours/

day on intact skin with dosages of 0,

100, 400, and 1,000 mg/kg/day (HDT)

with a development toxicity NOAEL of

400 mg/kg/day and a maternal toxicity

of 400 mg/kg/day based on increased

placental weights and a slight increase

in the number of fetuses with skeletal

variations was observed at the highest

dose tested.

iv. A combination of two multigeneration rat reproduction studies

(study A dose levels were 0, 3.0, 30, and

145 mg/kg/day and study B dose levels

were 0, 0.9, 2.3, and 23 mg/kg/day).

Study A was discontinued after extreme

systemic toxicity was observed at 145

mg/kg/day. The following discussion

summarizes the results from both

studies. A reproductive NOAEL of 2.3

mg/kg/day and with a parental NOAEL

of 2.3 mg/kg/day were determined based

on:

a. Dose levels ≥23 mg/kg/day resulted

in maternal death, clinical signs,

clinical chemical effects, liver effects

(i.e., damage), histopathology, and

limited number of pregnancy and pups

with reduced body weights which

increased in severity to the upper dose

levels, this also indicated that doses

above 23 mg/kg/day were considered to

be beyond the maximum tolerated dose

(MTD) for pregnant rats.

b. Questionable effects were observed

in the 3.0 mg/kg/day dose level.

c. No treatment-related clinical signs,

body weight changes, parameters of

fertility and gestation, or macro- or

histopathological changes were

observed for the parental F0, F1, and F2

at dose levels equal to and below 2.3

mg/kg/day.

4. Chronic toxicity. i. A series of two

1–year dog studies (study A dose levels

were 0, 1.6, 15, and 49 mg/kg/day for

which a NOAEL was established in

females, and study B dose levels were

0, 0.3, 0.6, 0.9, and 1.1 mg/kg/day to

determine a NOAEL in males. The

NOAEL was established as 1.1 mg/kg/

day based on the following effects:

a. Mortality in the 49.0 mg/kg/day

dose group with severe clinical signs

and evidence of liver damage in those

dogs which were sacrificed for humane

reasons.

b. Hematological examinations

demonstrated effects in either male or

female dogs at dose levels ≥1.6 mg/kg/

day.

c. Clinical chemical effects of varying

types were seen in either male and

female dogs at dose levels ≥15.0 mg/kg/

day.

d. No effects were observed in male

animals at levels of ≤1.1 or female dogs

at dose levels of ≤1.6 mg/kg/day.

ii. Separate chronic feeding and

oncogenicity studies in rats were

performed to assess the chronic toxicity

and oncogenic potential of

epoxiconazole. The chronic toxicity

study was conducted at dose levels of 0

and approximately 2, 8, 38, and 78 mg/

Federal Register / Vol. 65, No. 185 / Friday, September 22, 2000 / Notices 57341

kg/day. The oncogenicity study was

conducted at dose levels of 0 and

approximately 2, 7, 40, and 80 mg/kg/

day.

The results from the 2 studies are

combined and summarized as follows:

The NOAEL was determined to be 2.0

mg/kg/day based on the following

effects:

a. Decreases in body weights and food

consumption were observed in both

male and female rats at dose levels ≥38

mg/kg/day dose groups with a very

slight progression of severity to the

upper level.

b. Varying clinical chemical and

hematological effects were observed in

either male and/or female rats at dose

levels ≥8mg/kg/day with a very slight

progression of severity to the upper

levels.

c. Increased absolute and relative liver

weights were seen for males and/or

females at dose levels ≥38 mg/kg/day.

d. Microscopic findings were

observed in the liver for male and/or

female rats at dose levels ≥38 mg/kg/

day, in female adrenals at the highest

dose test, and in the ovaries at dose

levels ≥38 mg/kg/day.

e. An increased incidence of

neoplasms occurred at dose levels

greater than the MTD of 8 mg/kg/day in

the females for the adrenals and ovaries.

No increased number of neoplasms were

seen in male rats due to the fact that the

MTD in male rats was the HDT as

opposed to the female rat which was

significantly lower. Taking into account

the results obtained in these studies, it

is concluded that the reduction in body

weight gain at 38 and 78 mg/kg/day

levels met the criteria for a maximum

tolerated dose. It has been determined

that effects observed at the 10 mg/kg/

day dose level achieved or

approximated the MTD.

The effects on the ovaries were as

follows:

• Decreasing aromatase enzyme

activity which, is a response from

converting both testosterone and

adrostendione (male sex-steroids) into

female sex steroids (e.g., estradiol). This

action would result in decreased

estradiol (i.e., estrogen and prolactin)

and increased androgen levels (i.e.,

testosterone). As a consequence of

reduced estradiol levels, measured LH

and FSH concentrations are slightly

altered.

• The increased incidences of

neoplasms in the ovaries are considered

to be the result of a continuous cell

proliferation by these stimulating

hormones of the pituitary-gonadal axis

(LH and FSH).

The effects on the adrenals were as

follows:

• Decreasing adrenal-cortical enzyme

activity. This action would result in

decreased adrenal hormones such as

corticosterone levels. As a consequence

of reduced corticosterone levels,

pronounced ACTH concentrations are

found.

• The increased incidences of

neoplasms in the adrenals are

considered to be the result of a

continuous cell proliferation by these

stimulating hormones of the pituitaryadrenal axis (ACTH).

For risk assessment purposes the

results obtained at 38 and 78 mg/kg/day

dose levels should not be used because

an extrapolation to lower dose levels is

not justified due to the unphysiological

conditions in animals treated at dose

levels near or at the MTD. Under these

circumstances neoplastic and nonneoplastic mechanisms may be induced

which will not occur at dose levels in

which the animals are able to maintain

their normal physiological homeostasis.

The increases in tumor incidence in

endocrine organs due to hormonal

imbalance are considered to have a

threshold value, because at dose levels

which do not induce cellular alterations

via hormone levels in these organs, a

subsequent proliferation and hence

tumor formation cannot occur.

iii. An oncogenicity study in mice fed

dosages of 0, 0.17, 0.81, 35.3, and 70.4

(males) or 205.4 (females) mg/kg/day

with a NOAEL of 0.81 mg/kg/day for

male and female mice based on the

following effects:

a. Highly significant decreased body

weights were observed in both male

and/or female mice at the mid-high and

highest dose tested.

b. Clinical sign of deteriorated state of

general health were observed in high

dose female mice.

c. Increased liver weights and

microscopic findings were observed for

male and female mice at dose the

highest dose tested.

d. An increased incidence of

neoplasms occurred at dose levels (70.4/

205.4 mg/kg/day) greater than the MTD

of 35.3 mg/kg/day in the male and

female mice for the liver.

Taking into account the results

obtained in this study, the following

conclusions are drawn: The severe

reduction in body weight and body

weight gain at dose levels ≥35.3 mg/kg/

day indicates that these dose levels

exceeded the criteria for a MTD. It has

been determined that liver tumor effects

observed at the 70.4 and 205.4 mg/kg/

day dose levels clearly exceeded the

MTD. The liver necrosis observed in the

male and female mice, further support

the finding that the MTD was exceeded

in the 70.4 and 205.4 mg/kg/day dose

levels.

A series of mechanistic studies were

performed to elucidate and define the

liver promotion properties of

epoxiconazole. The following

conclusions can be drawn from the data:

• The material is a potent inducer of

the hepatic cytocrome P–450 enzyme

system, similar to the drugphenobarbital.

• The material induced proliferation

of the smooth endoplasmatic reticulum

in the liver centrolobular hypertrophy

and induction of phase 1 and phase 2

enzymes of the xenobiotic metabolism.

• The material was determined not to

be an initiator of the carcinogenic

process, but a promoter of initiated cells

in the tumorgenesis as has been

similarly shown with drug—

phenobarbital.

As stated above, for risk assessment

purposes the results obtained at 70.4

and 205.4 mg/kg/day dose levels should

not be used because an extrapolation to

lower dose levels is not justified due to

the unphysiological conditions in

animals treated at dose levels exceeding

the MTD. Under these circumstances,

neoplastic and non-neoplastic

mechanisms may be induced which will

not occur at dose levels in which the

animals are able to maintain their

normal physiological homeostasis.

5. Animal metabolism. Since there are

no animal feed items associated with

bananas, there is no likelihood of

secondary residues in meat, milk,

poultry or eggs. Therefore, data

concerning metabolism in livestock is

not required.

6. Metabolite toxicology. Residues of

the parent molecule, epoxiconazole are

the only residues of concern.

7. Endocrine disruption. A series of

mechanistic studies were performed to

elucidate and define the aromatase

enzyme inhibition properties of

epoxiconazole. The following

conclusions can be drawn from the in

vivo data: The effects on the ovaries are

assessed to be the result of the

following:

• Decreasing aromatase enzyme

activity which is responsible for

converting both testosterone and

adrostendione (male sex-steroids) into

female sex steroids (e.g., estradiol). This

action would result in decreased

estradiol (i.e., estrogen) and increased

androgen. As a consequence of reduced

estradiol levels, measured LH and FSH

concentrations are slightly altered.

• The increased incidences of

neoplasms in the ovaries are considered

to be the result of a continuous cell

proliferation by these stimulating

57342 Federal Register / Vol. 65, No. 185 / Friday, September 22, 2000 / Notices

hormones of the regulating hormones of

the pituitary-gonadal axis (LH and FSH).

The changes adrenals are assessed to

be the result of the following:

• Decreasing adrenal-cortical enzyme

activity. This action would result in

decreased adrenal hormones such as

corticosterone levels. As a consequence

of reduced corticosterone levels,

pronounce ACTH concentrations are

found.

• The increased incidences of

neoplasms in the adrenals are

considered to be the result of a

continuos cell proliferation by these

stimulating hormones of the pituitaryadrenal axis ACTH.

C. Aggregate Exposure

1. Dietary exposure. For the purpose

of assessing the potential chronic

dietary exposure, BASF has estimated

aggregate exposure based on theoretical

maximum residue contribution (TMRC)

from the tolerance of epoxiconazole in

or on bananas at 0.2 ppm the maximum

residue found in banana pulp. The

TMRC is a ‘‘worst case’’ estimate of

dietary exposure since it is assumed that

100% of all the crops for which the

tolerances are established are treated

and that pesticide residues are always

found at tolerance levels. Based on the

expected reference dose (RfD) of 0.011

mg/kg/day (from the NOAEL

determined in the chronic dog study

and a 100–fold safety factor) and the

tolerance level residue chronic dietary

exposure of the general population is

less than 1% of the RfD.

i. Food. This is a new chemical and

there are no other food uses except for

the proposed use on bananas.

ii. Drinking water. No exposure is

expected from drinking water as this is

an import tolerance and no U.S.

registrations are expected.

2. Non-dietary exposure. There are no

non-occupational sources of exposure to

epoxiconazole for the general

population due to fact the action being

requested is to establish a tolerance for

import purposes only.

D. Cumulative Effects

BASF has considered the potential for

cumulative effects of epoxiconazole and

other substances which may have a

common mechanism of toxicity. BASF

is aware of other triazole fungicides but

has no reliable toxicology information

concerning those other materials which

would allow a determination regarding

similarity of toxicity mechanisms.

Therefore, BASF has considered only

the potential risks of epoxiconazole in

its exposure assessment.

E. Safety Determination

1. U.S. population. Using the

exposure assumptions described above,

based on the completeness and the

reliability of the toxicity data, BASF has

estimated that aggregate exposure to

epoxiconazole will utilize less than 1%

of the RfD for the U.S. population. 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

exposure assessment discussed above,

BASF concludes that there is a

reasonable certainty that no harm will

result from aggregate exposure to

residues of epoxiconazole, including all

anticipated dietary exposure and all

other non-occupational exposures.

2. Infants and children. The findings

in the rat and rabbit are most likely as

a result of excessive maternal toxicity,

treatment of pregnant rats and rabbits

with epoxiconazole induced

embryotoxic effects which manifested

themselves in the form of early

resorptions and structural anomalies in

the offspring. In both the rat and rabbit,

the dose-effect relationship was rather

steep and showed clear threshold levels.

At dose levels below the threshold of

maternal toxicity, reproductive

parameters as well as the offsprings

remained entirely unaffected.

This data demonstrate that the rat and

rabbit are similarly sensitive to

epoxiconazole. Additionally, the

NOAEL of 1.1 mg/kg/day from the

chronic dog study used to set the RfD is

4.5x and 72.7x lower than the maternal

developmental NOAELs established in

the rat and rabbit teratology studies,

respectively. The developmental effects

observed in either the rat or rabbit

occurred only at maternally toxic doses.

Therefore, no additional safety factor is

needed for children.

Using the assumption stated for the

general population, BASF concluded

that the most sensitive child population

group is that of children <1–year. Using

the same RfD and the same conservative

exposure assumptions employed in the

dietary risk analysis for the general

population, it was calculated that the

exposure to this group is to be

approximately 2% of the RfD for the use

proposed in this document. Therefore,

based on the completeness and

reliability of the toxicity data, and the

exposure assessment discussed above,

BASF concludes that there is a

reasonable certainty that no harm will

result to infants and children from

aggregate exposure to residues of

epoxiconazole, including all anticipated

dietary exposure and all other nonoccupational exposures.

F. International Tolerances

A maximum residue level has not

been established by the Codex

Alimentarius Commission for

epoxiconazole in bananas.

II. Tomen Agro, Inc.

9E06020

EPA has received a pesticide petition

9E06020 from the TM–210 (SZX 0722)

Fungicide Task Force, comprised of

Tomen Agro, Inc., 100 First Street, Suite

1700, San Francisco, CA 94105, and

Bayer Corporation, 8400 Hawthorn

Road, Kansas City, MO 64120

proposing, pursuant to section 408(d) of

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

40 CFR part 180 by establishing a

tolerance for residues of iprovalicarb:

(1S)-2-methyl-1-[[[1-(4-

methylphenyl)ethyl] amino] carbonyl]

propyl] carbamic acid 1-methylethyl

ester in or on the raw agricultural

commodity imported grapes at 2 ppm

and on the processed commodity

imported raisins at 3 ppm. EPA has

determined that the petition contains

data or information regarding the

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

the FFDCA; however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data support granting of the petition.

Additional data may be needed before

EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism

of iprovalicarb was investigated in

grapes, potatoes and tomatoes, and the

metabolic pathway is similar in the

three crops. The rate of degradation on

plants is quite low, and the parent

compound was always the major

component, with quantitatively relevant

metabolites formed only in potatoes.

The metabolites observed in the potato

were also observed in the rat. Therefore,

iprovalicarb is the only residue of

concern. Plant metabolism proceeds

along three pathways:

i. Hydroxylation/glycosylation of

parent at the 4–methyl group on the

phenyl ring, followed by further

conjugations.

ii. Cleavage of the amide group

between the L-valine and p-methylphenethylamine moieties.

iii. Hydroxylation/glycosylation of

parent at the phenyl-ring 3 position.

2. Analytical method. The proposed

enforcement residue analytical method

is an HPLC method with ultra violet

(UV) detection. The limit of

determination is 0.05 ppm in grapes,

wine, juice and raisins, and the mean

recovery is 94%. DFG multiresidue

method S19 has been evaluated as an

Federal Register / Vol. 65, No. 185 / Friday, September 22, 2000 / Notices 57343

analytical method for the determination

of iprovalicarb residues in grapes and

other commodities. The limit of

quantitation (LOQ) of iprovalicarb in/on

grapes is 0.01 ppm. Recoveries in spiked

samples ranged from 79% to 119%,

with the standard deviations ranging

from 0.06 ppm to 0.16 ppm. DFG

multiresidue method S 19 (with

modified extraction) was successfully

validated as an analytical method for

the determination of residues in/on

grapes and other commodities.

3. Magnitude of residues. The

maximum measured residue resulting

from treatment according to the

proposed labels and representative

viticulture practices was 1.40 ppm in

grapes and 2.55 ppm in raisins.

Measured residues in juice and wine

were lower than the measured residues

in grapes.

B. Toxicological Profile

1. Acute toxicity. The acute oral LD50

in Wistar rats is greater than 5,000 mg/

kg body weight.

2. Genotoxicty. Iprovalicarb was nonmutagenic or non-clastogenic in six of

six assays:

i. Salmonella/microsome test, with

and without S9 mix.

ii. V79–HPRT forward mutation assay,

with and without metabolic activation.

iii. CHO cell assay, with and without

metabolic activation in vitro.

iv. In vitro rat primary hepatocyte

unscheduled DNA synthesis UDS assay.

v. Mouse micronucleus test.

vi. 32P-postlabelling assay of the

uterus and urinary bladder of rats.

Based upon these studies, iprovalicarb

is non-mutagenic and non-genotoxic

both in vitro and in vivo.

3. Reproductive and developmental

toxicity— i. In a 2–generation

reproduction study in Wistar rats

receiving 0, 100, 2,000 or 20,000 ppm

iprovalicarb in the diet, the parental

NOAEL was 2,000 ppm based upon

reduced body weight development and

increased liver weight at 20,000 ppm.

The reproductive toxicity NOAEL was

2,000 ppm (100 mg/kg bwt/day) based

upon delayed body weight development

in F1 and F2 pups during lactation,

slightly reduced mean litter weight at

birth and at day 28, increased relative

liver weights and a reduced lactation

index in F1 pups at 20,000 ppm.

ii. In a developmental toxicity study

in Wistar rats, the maternal and

developmental NOAEL was 1,000 mg/kg

bwt/day (limit dose for study and

highest dose tested (LD/HDT)).

iii. In a developmental toxicity study

in Russian rabbits, the maternal and

developmental NOAEL was 1,000 mg/kg

bwt/day LD/HDT.

4. Subchronic toxicity— i. In the 13–

week feeding study in Wistar rats, the

doses were 0, 1,250, 5,000 and 20,000

ppm. The NOAEL was 5,000 ppm (372.7

mg/kg bwt/day in males; 561.4 mg/kg

bwt/day in females) based upon reduced

body weight gain, increased feed intake

(females only), changed clinical

chemistry parameters (including liver

enzyme induction) and elevated

absolute liver weights at 20,000 ppm.)

ii. In the 13–week feeding study in

B6C3F1 mice, the doses were 0, 280,

1,400, 7,000, and 14,000 ppm in the

diet. The NOAEL in males was 1,400

ppm (325.0 mg/kg bwt/day) based upon

elevated water intake and a changed

hematological parameter (MCV) at 7,000

ppm (1,724.6 mg/kg bwt/day). The

NOAEL in females was 7,000 ppm

(3,599.5 mg/kg bwt/day) based upon

elevated water intake, changed

parameter in the red blood count, and

increased liver weights at 14,000 ppm

(6,869.0 mg/kg bwt/day).

iii. In the 13–week feeding study in

Beagle dogs, the doses were 0, 250,

2,500 and 50,000 ppm iprovalicarb in

the diet (0, 9.1, 62.5 and 1,250 mg/kg

bwt/day). The NOAEL was 250 ppm (9.1

mg/kg bwt/day) for males and females

based upon liver effects (increased

activity of alkaline phosphatase and

hepatocellular hypertrophy in one

animal) at 2,500 ppm.

5. Chronic toxicity— i. Wistar rats

received 0, 500, 5,000 or 20,000 ppm

iprovalicarb in the diet for 24 months.

The NOAEL in females was 500 ppm

(31.7 mg/kg bwt/day) based upon

decreased body weights, changed

clinical chemistry parameters (increased

cholesterol concentration and decreased

total bilirubin concentration), increased

relative liver weights and

histopathological findings (increased

incidences of hepatocellular

hypertrophy) at 5,000 ppm. The NOAEL

in males was 5,000 ppm (262.5 mg/kg

bwt/day) based upon decreased body

weights, increased APh-activity, and

slight increase of tumor incidences at

20,000 ppm. The histopathological

NOAEL was 5,000 ppm (262.5 mg/kg

bwt/day in males and 326.3 mg/kg bwt/

day in females).

To further evaluate the results of the

chronic feeding study in rats:

a. A special 2–day/13–week

metabolism study was conducted in

Wistar rats at 500 ppm and 20,000 ppm

in the diet. Some quantitative

differences (shift in diastereomer ratio

in favor of S,R; relative higher amounts

of p-methyl-phenethylamine, higher

proportions of unchanged parent

compound in feces) after administration

of 20,000 ppm compared to the low

dose of 500 ppm were observed.

b. Plasma concentrations were

investigated in a special 12–week

feeding study in HsdCpb:WU rats. The

plasma concentrations of parent

compound increased to a measurable

level at a dose of 20,000 ppm in the diet.

The concentration of parent in plasma

was very low due to extensive

metabolism during the first pass in the

liver. At a dose of 20,000 ppm, the

iprovalicarb-carboxylic acid (S,R)

diastereomer increased in relation to the

corresponding (S,S) diastereomer when

compared to the low dose.

c. A bioavailability study was

conducted in Wistar rats.

Administration of thermodynamically

stable and thermodynamically labile

modifications of iprovalicarb to Wistar

rats at concentrations of 2,000 and

20,000 ppm for 2 weeks resulted in no

toxicologically relevant differences

based upon the concentration of the

main metabolite, iprovalicarb-carboxylic

acid, in plasma. Therefore, the

thermodynamically stable and

thermodynamically labile modifications

of iprovalicarb demonstrated no

significant differences in intestinal

absorption and bioavailability.

d. An in vivo 32P–postlabelling assay

of uterus and urinary bladder

epithelium was conducted in female

Wistar rats dosed at 10,000 or 20,000

ppm in the diet for 7 days. Iprovalicarb

was determined to be inactive in the

assay.

e. A liver foci test was conducted in

male Bor: WISW (SPF-Cpb) rats that

were dosed by oral gavage with 0 or

1,000 mg/kg iprovalicarb for 28 days,

followed by a promotion treatment with

phenobarbital over a period of 8 weeks.

Iprovalicarb was determined to not have

a tumor initiating potential.

Based upon the 24–month chronic

feeding study in rats, plus the special

studies, a dose of 20,000 ppm exerts a

continuous stress on the xenobiotic

metabolizing capacity of the liver that is

not observed at lower doses. Moreover,

iprovalicarb has no genotoxic potential

and no tumor initiation potential.

Therefore, iprovalicarb is not

carcinogenic in rats.

ii. B6C3F1 mice received 0, 280,

1,400, or 7,000 ppm iprovalicarb in the

diet for up to 105 weeks. The NOAEL

in males was 1,400 ppm (283.4 mg/kg

bwt/day) based upon slightly higher

food and water intake and slightly lower

body weights at 7,000 ppm (1,566.8 mg/

kg bwt/day). The NOAEL in females was

7,000 ppm (2,544 mg/kg bwt/day), the

HDT. No oncogenic potential was

observed in mice.

iii. Beagle dogs received 0, 80, 800 or

8,000 ppm iprovalicarb in the diet for 53

weeks. The NOAEL was 80 ppm (2.62

57344 Federal Register / Vol. 65, No. 185 / Friday, September 22, 2000 / Notices

mg/kg bwt/day in males and 2.68 mg/kg

bwt/day in females) based upon liver

effects (increased serum activities of

ALT and APh, cellular hypertrophy and

periportal fatty change) at 800 ppm

(24.69 mg/kg bwt/day in males and

28.10 mg/kg bwt/day in females). A

follow-up study was conducted in

Beagle dogs that received 0, 10, 20, 40,

or 80 ppm iprovalicarb in their diet for

28 days. The NOAEL for microsomal

liver enzyme induction was determined

to be 20 ppm (0.77 mg/kg bwt/day).

Microsomal liver enzyme induction was

observed at the higher doses, and

reversal of induction was observed

within a 4–week recovery period in the

80 ppm dose group (2.93 mg/kg bwt/

day).

6. Animal metabolism. Iprovalicarb is

readily absorbed, and greater than

97.8% of the total radioactivity was

eliminated in urine and feces within 48

hours of dosing. Iprovalicarb is

extensively metabolized in the rat. The

primary metabolites (>58% of the

administered dose) were diastereomers

of iprovalicarb-carboxylic acid. Eight

minor metabolites, each representing

less than 2% of the administered dose,

were quantified.

7. Metabolite toxicology. The toxicity

of p-methyl-phenethylamine, a rat, plant

and soil metabolite, was investigated in

2 studies:

i. The acute oral LD 50 in Wistar rats

was determined to be in the range of 300

to 500 mg/kg bw.

ii. No mutagenic activity was

observed in the Salmonella/microsome

test. p-Methyl-phenethylamine was

found at concentrations of <0.2% and

has been determined to not be

toxicologically significant.

8. Endocrine disruption. No endocrine

disruption potential was observed in the

2–generation reproduction study,

developmental toxicity studies,

subchronic feeding studies, and chronic

feeding studies.

C. Aggregate Exposure

1. Dietary exposure. There are no

registered uses of iprovalicarb in the

U.S., and no registrations or other

tolerances are pending. Dietary

exposure to iprovalicarb in the U.S. is

limited to residues in/on imported

grapes, grape juice, wine, and raisins.

i. Food. The anticipated residue in/on

fresh grapes based upon the field

studies is 0.50 ppm, and 35.71% of the

fresh grapes consumed in the U.S. are

imported. The anticipated residue in

grape juice based upon the field and

processing studies is 0.050 ppm, and

37.05% of the grape juice consumed in

the U.S. is imported. The anticipated

residue in wine based upon the field

and processing studies is 0.32 ppm, and

17.38% of the wine consumed in the

U.S. is imported. The anticipated

residue in raisins based upon the field

and processing studies is 0.91 ppm, and

8.165% of the raisins consumed in the

U.S. are imported. Assuming 100% of

the imported commodities are treated

and have the average residue resulting

from the maximum international use of

iprovalicarb, the total anticipated

residue is 0.000021 mg/kg bwt/day in

the U.S. diet and 0.000056 mg/kg bwt/

day for the most exposed subpopulation, children 1 to 6 years old.

ii. Drinking water. Iprovalicarb is not

registered for use in the United States.

Therefore, there is no exposure to

iprovalicarb through drinking water in

the United States.

2. Non-dietary exposure. Iprovalicarb

is not used in the United States.

Therefore, there is no non-dietary

exposure to iprovalicarb in the United

States.

D. Cumulative Effects

Iprovalicarb is a member of a new

class of chemistry and does not have a

mode of action that is common with

other registered pesticides. Therefore,

there are no cumulative effects.

E. Safety Determination

1. U.S. population. The reference dose

(RfD) is 0.03 mg/kg bwt/day. Based

upon anticipated residues in imported

commodities and assuming 100% of the

imported commodities contain residue

resulting from the proposed European

use of iprovalicarb, the estimated

chronic dietary margin of exposure of

the U.S. population is 0.07% of the RfD.

Therefore, there is a reasonable certainty

of no harm to the U.S. population

resulting from exposure to iprovalicarb

residues in/on imported commodities.

2. Infants and children. The

population subgroup with the maximum

estimated dietary exposure is children

age 1 to 6 years old. For this subgroup,

and using the same assumptions as

listed for the U.S. population, the

estimated chronic dietary margin of

exposure is 0.18% of the RfD. Therefore,

there is a reasonable certainty of no

harm to infants and children in the U.S.

resulting from exposure to iprovalicarb

residues in/on imported commodities.

F. International Tolerances

The following maximum residue

levels are pending in the European

Union: 2.0 mg/kg in/on grapes; 0.5 mg/

kg in animal fat; 0.05 mg/kg in potatoes,

animal meat, animal edible offal and

eggs; and 0.01 mg/kg in milk.

[FR Doc 00–24436 Filed 9–21–00; 8:45 a.m.]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[OPPTS–51952; FRL–6746–8]

Certain New Chemicals; Receipt and

Status Information

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: Section 5 of the Toxic

Substances Control Act (TSCA) requires

any person who intends to manufacture

(defined by statute to include import) a

new chemical (i.e., a chemical not on

the TSCA Inventory) to notify EPA and

comply with the statutory provisions

pertaining to the manufacture of new

chemicals. Under sections 5(d)(2) and

5(d)(3) of TSCA, EPA is required to

publish a notice of receipt of a

premanufacture notice (PMN) or an

application for a test marketing

exemption (TME), and to publish

periodic status reports on the chemicals

under review and the receipt of notices

of commencement to manufacture those

chemicals. This status report, which

covers the period from August 14, 2000

to August 25, 2000, consists of the

PMNs and TMEs, both pending or

expired, and the notices of

commencement to manufacture a new

chemical that the Agency has received

under TSCA section 5 during this time

period.

ADDRESSES: Comments may be

submitted by mail, electronically, or in

person. Please follow the detailed

instructions for each method as

provided in Unit I. of the

SUPPLEMENTARY INFORMATION. To ensure

proper receipt by EPA, it is imperative

that you identify docket control number

OPPTS–51952 and the specific PMN

number in the subject line on the first

page of your response.

FOR FURTHER INFORMATION CONTACT:

Barbara Cunningham, Director, Office of

Program Management and Evaluation,

Office of Pollution Prevention and

Toxics (7401), Environmental Protection

Agency, 1200 Pennsylvania Ave., NW.,

Washington, DC 20460; telephone

number: (202) 554–1404; e-mail address:

TSCA-Hotline@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

This action is directed to the public

in general. As such, the Agency has not

attempted to describe the specific

entities that this action may apply to.

Although others may be affected, this

action applies directly to the submitter

of the premanufacture notices addressed