Federal Register / Vol. 66, No. 4 / Friday, January 5, 2001 / Notices 1129

1995, imidacloprid was not detected in

seventeen wells on potato farms in

Quebec, Canada. In addition, ground

water monitoring studies are currently

underway in California and Michigan.

Therefore, contributions to the dietary

burden from residues of imidacloprid in

water would be inconsequential.

2. Non-dietary exposure— i.

Residential turf. Bayer Corporation has

conducted an exposure study to address

the potential exposures of adults and

children from contact with imidacloprid

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 safety (MOS)

of 7,587 - 41,546 for 10 year old

children and 6,859 - 45,249 for 5 year

old children were estimated by

comparing dermal exposure doses to the

imidacloprid NOAEL of 1,000 mg/kg/

day established in a 15 day dermal

toxicity study in rabbits. The estimated

safe residue levels of imidacloprid on

treated turf for 10 year old children

ranged from 5.6 - 38.2 g/cm2 and for 5

year old children from 5.1 - 33.3 g/cm2.

This compares with the average

imidacloprid transferable residue level

of 0.080 g/cm2 present immediately after

the sprays have dried. These data

indicate that children can safely contact

imidacloprid-treated turf as soon after

application as the spray has dried.

ii. Termiticide. Imidacloprid is

registered as a termiticide. Due to the

nature of the treatment for termites,

exposure would be limited to that from

inhalation and was evaluated by EPA’s

Occupational and Residential Exposure

Branch (OREB) and Bayer Corporation.

Data indicate that the Margins of Safety

for the worst case exposures for adults

and infants occupying a treated building

who are exposed continuously (24

hours/day) are 8.0 x 107 and 2.4 x 108,

respectively, and exposure can thus be

considered negligible.

iii. Tobacco smoke. Studies have been

conducted to determine residues in

tobacco and the resulting smoke

following treatment. Residues of

imidacloprid in cured tobacco following

treatment were a maximum of 31 ppm

(7 ppm in fresh leaves). When this

tobacco was burned in a pyrolysis study

only two percent of the initial residue

was recovered in the resulting smoke

(main stream plus side stream). This

would result in an inhalation exposure

to imidacloprid from smoking of

approximately 0.0005 mg per cigarette.

Using the measured subacute rat

inhalation NOAEL of 5.5 mg/m3, it is

apparent that exposure to imidacloprid

from smoking (direct and/or indirect

exposure) would not be significant.

iv. Pet treatment. Human exposure

from the use of imidacloprid to treat

dogs and cats for fleas has been

addressed by EPA’s Occupational and

Residential Exposure Branch (OREB)

who have concluded that due to the fact

that imidacloprid is not an inhalation or

dermal toxicant and that while dermal

absorption data are not available,

imidacloprid is not considered to

present a hazard via the dermal route.

D. Cumulative Effects

No other chemicals having the same

mechanism of toxicity are currently

registered, therefore, there is no risk

from cumulative effects from other

substances with a common mechanism

of toxicity.

E. Safety Determination

1. U.S. population. Using the

conservative exposure assumptions

described above and based on the

completeness and reliability of the

toxicity data, it can be concluded that

total aggregate exposure to imidacloprid

from all current uses including those

currently proposed will utilize little

more than 15% of the RfD for the U.S.

population. EPA generally has no

concerns 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. The

TMRC from exposure to field corn for

the general population, is 0.000055 mg/

kg/bwt/day, which represents 0.1% of

the RfD. Thus, it can be concluded that

there is a reasonable certainty that no

harm will result from aggregate

exposure to imidacloprid residues.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

imidacloprid, the data from

developmental studies in both rat and

rabbit and a 2-generation reproduction

study in the rat have been considered.

The developmental toxicity studies

evaluate potential adverse effects on the

developing animal resulting from

pesticide exposure of the mother during

prenatal development. The reproduction

study evaluates effects from exposure to

the pesticide on the reproductive

capability of mating animals through 2

generations, as well as any observed

systemic toxicity.

FFDCA Section 408 provides that the

EPA may apply an additional safety

factor for infants and children in the

case of threshold effects to account for

prenatal and postnatal effects and the

completeness of the toxicity database.

Based on current toxicological data

requirements, the toxicology database

for imidacloprid relative to prenatal and

postnatal effects is complete. Further for

imidacloprid, the NOAEL of 5.7 mg/kg/

bwt from the 2-year rat feeding/

carcinogenic study, which was used to

calculate the RfD (discussed above), is

already lower than the NOAELs from

the developmental studies in rats and

rabbits by a factor of 4.2 to 17.5 times.

Since a 100-fold uncertainty factor is

already used to calculate the RfD, it is

surmised that an additional uncertainty

factor is not warranted and that the RfD

at 0.057 mg/kg/bwt/day is appropriate

for assessing aggregate risk to infants

and children. Using the conservative

exposure assumptions described above,

EPA has concluded that the TMRC from

use of imidacloprid from published uses

is 0.008358 mg/kg/bwt/day utilizing

14.7% of the RfD for the general

population. For the most highly exposed

subgroup in the population, nonnursing infants (less than 1 year old),

the TMRC for the published tolerances

is 0.01547 mg/kg/day. This is equal to

27.1% of the RfD. The TMRC from

exposure to field corn to non-nursing

infants is 0.000131 mg/kg/bwt/day,

which represents 0.2% of the RfD. The

TMRC for children ages 1 to 6 years is

0.000130 mg/kg/bwt/day, which

represents 0.2% of the RfD. For nursing

infants, the TMRC is 0.000032 mg/kg/

bwt/day, which is 0.1% of the RfD. For

children ages 7 to 12 years, the TMRC

is 0.000098 mg/kg/bwt/day, which is

0.2% of the RfD. Thus, it can be

concluded that there is a reasonable

certainty that no harm will result from

additional exposure of infants and

children.

F. International Tolerances

No CODEX Maximum Residue Levels

(MRLs) have been established for

residues of imidacloprid on any crops at

this time.

[FR Doc. 01–370 Filed 1–4–01; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[PF–989; FRL–6761–4]

Notice of Filing a Pesticide Petition to

Establish a Tolerance for a Certain

Pesticide Chemical in or on Food

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of a pesticide petition

proposing the establishment of

regulations for residues of a certain

pesticide chemical in or on various food

commodities.

1130 Federal Register / Vol. 66, No. 4 / Friday, January 5, 2001 / Notices

DATES: Comments, identified by docket

control number PF–989, must be

received on or before February 5, 2001.

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–989 in the subject line on the first

page of your response.

FOR FURTHER INFORMATION CONTACT: By

mail: Indira Gairola, Registration

Division (7505C), Office of Pesticide

Programs, Environmental Protection

Agency, 1200 Pennsylvania Ave., NW.,

Washington, DC 20460; telephone

number: (703) 308–8375; e-mail address:

gairola.indira@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

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 PF–

989. 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–989 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–989. 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

Federal Register / Vol. 66, No. 4 / Friday, January 5, 2001 / Notices 1131

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 a certain pesticide chemical

in or on various food commodities

under section 408 of the Federal Food,

Drug, and Comestic Act (FFDCA), 21

U.S.C. 346a. EPA has determined that

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: December 21, 2000.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

Summary of Petition

The petitioner summary of the

pesticide petition is printed below as

required by section 408(d)(3) of the

FFDCA. The summary of the petition

was prepared by the petitioner and

represents the view of the petitioner.

EPA is publishing the petition summary

verbatim without editing it in any way.

The petition summary announces the

availability of a description of the

analytical methods available to EPA for

the detection and measurement of the

pesticide chemical residues or an

explanation of why no such method is

needed.

Morflex Inc.

PP 8E4966, PP 8E4967

EPA has received two pesticide

petitions (PP 8E4966, PP 8E4967) from

Morflex, Inc., 2110 High Point Road,

Greensboro, North Carolina 27403.

proposing, pursuant to section 408(d) of

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

amend 40 CFR part 180 to establish an

exemption from the requirement of a

tolerance for acetyl tributyl citrate

(Citroflex A4) and triethyl citrate

(Citroflex) when used as inert

ingredients in or on growing crops,

when applied to raw agricultural

commodities (RAC) after harvest or

when applied to animals (40 CFR

180.1001(c), and (e)). EPA has

determined that the petitions contain

data or information regarding the

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

the FFDCA; however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data support granting of the

petitions. Additional data may be

needed before EPA rules on the

petitions.

A. Residue Chemistry

Residue chemistry data are generally

not required by EPA regarding decisions

relevant to exemptions from the

requirement of a tolerance for inert

ingredient. However, applicable dietary

modeling data and environmental fate

data have been completed and is used

for the assessments included in these

petitions. Since Morflex is requesting an

exemption from the requirement of a

tolerance, an analytical method is not

required.

B. Toxicological Profile

1. Acute toxicity—i. Oral LD50 in rats.

Acetyl tributyl citrate (ATBC). The acute

oral LD50 for ATBC is 31.5 grams/

kilograms body weight (g/kg bwt).

Rising doses of ATBC were

administered to groups consisting of 5

rats per group of from 10.5 to 31.5 g/kg

bwt. Some animals appeared sluggish,

however, they recovered during the 21–

day post dosing observation period.

There were no mortalities at any dose.

ii. Triethyl citrate (TEC). The acute

oral LD50 of TEC in rats was determined

to be 7 milligrams/Liters (mL)/kg bwt.

The technical material triethyl citrate

was administered to groups of 5 rats by

stomach tube at doses ranging from 5 to

15 mL/kg bwt. Signs of toxicity occurred

within 1–hour and included weakness,

depression, ataxia, hyperexcitability,

unrest, urinary incontinence, irregular,

and labored respiration, convulsions

preceeding death in some animals.

Mortalities occurred in 2 hours to 3

days, while survivors recovered within

15 hours to 4 days.

iii. Oral LD50 in cats—ATBC. The

acute oral LD50 of ATBC was

determined to be greater than 50 mL/kg

bwt. The animals showed signs of slight

nausea, and within a few hours they

developed a diarrhea with oozing of the

oily material from the rectum. The

diarrhea subsided in less than 24 hours.

There were no systemic toxicity signs as

judged by the general appearance and

behavior of the animals for periods up

to 2 months.

iv. TEC. The acute oral LD50 of TEC

was determined to be approximately 4

g/kg bwt in cats. TEC was administered

by stomach tube to cats fasted for 24

hours in doses ranging from 1.1 to 10.8

g/kg bwt. Signs of toxicity consisted of

nausea, vomiting, ataxia, weakness,

muscle twitching, tremors, lowered

body temperature, gasping, and shallow

respiration, prostration, convulsions,

respiratory failure and death. Mortalities

occurred in about 2 hours to 2 days.

Animals surviving recovered within 4

hours to 3 days depending upon the

dose administered. Postmortem

examinations showed no abnormalities

of the thoracic abdominal organs related

to the toxic signs.

v. Intraperitoneal LD50 in mice—

ATBC. The acute intraperitoneal LD50 of

ATBC was determined to be greater than

4g/kg bwt in Swiss Albino mice. The

animals were observed for gross effects

on appearance and behavior for 72

hours after dosing.

vi. TEC. The intraperitoneal LD50 of

TEC was determined to be 1.75 g/kg bwt

in Swiss Albino mice. Signs of toxicity

included rapid loss of righting reflex

without loss of consciousness, increased

respiration rate, and clonic convulsions.

Mortalities occurred during the first

hour post dosing.

vii. Intraperitoneal LD50 in rats. The

acute intraperitoneal LD50 of TEC in rats

is 4.2 mL/kg bwt for females and 4.0

mL/kg bwt for males. Most deaths

occurred within one hour post dosing

following a depression of respiration

and clonic convulsions. Pathological

examinations of the animals that died

indicated hemorrhage of the lung,

pancreas and thymus, and marked

congestion in the kidneys and liver.

viii. Acute subcutaneous LD50 in rats.

The subcutaneous administration of

TEC to rats resulted in LD50 of 6.7 mL/

kg bwt in females and 6.6 mL/kg bwt in

males. Mortalities typically occurred

within 24 hours of dosing. Pathological

examinations showed extensive

hemorrhage in the lungs, and thymus,

loss of hair, edema, and crust formation

at injection sites. In surviving animals,

at the end of the 14–day observation

period, necrotic ulcers were noted at

injection sites.

ix. Acute dermal LD50 in guinea pig

and rabbit. The dermal LD50 of TEC was

determined to be greater than 11.4 g/kg

bwt in guinea pigs and greater than 5.7

mg/kg bwt in rabbits.

x. Acute inhalation LC50 in rats. The

6–hour inhalation LC50 of TEC in rats

was determined to be approximately

1,300 ppm. In this study, groups of rats

were exposed to vaporized TEC for 6

hours at concentrations between 1,300

and 3,500 ppm.

xi. Skin irritation in rabbits—ATBC.

ATBC was found to be non-irritating to

rabbit skin when applied as the

undiluted technical material. The

abdomens of 3 male Albino rabbits were

clipped and 1 mL of ATBC was applied

1132 Federal Register / Vol. 66, No. 4 / Friday, January 5, 2001 / Notices

to the intact skin daily for 4 days. The

animals were observed for a period of 36

hours after the last application. There

was no evidence of irritation.

xii. TEC—TEC was determined to be

non-irritating to rabbit skin. Undiluted

TEC was applied to intact or abraded

rabbit skin for 24 hours under occlusion

before scoring for irritation.

xiii. Guinea pig sensitization—ATBC.

ATBC was found to be non sensitizing

to the skin of Guinea pigs following the

method Magnusson and Kligman’s

Guinea pig maximumization test.

Sensitization was induced in guinea

pigs by intradermal injections of the test

substance and complete Freunds

Adjuvant. The induction process was

supplemented 7 days later by

application of ATBC to the shoulder

injection sites under occlusion.

Fourteen days later the animals were

challenged by occluded patches.

Challenges were repeated after 1–week.

Evaluations for contact sensitization

were performed at 24 and 48 hours after

patch removal.

xiv. TEC. TEC was found to be a

strong sensitizer in 9 of 10 Guinea pigs

after the first challenge and in all 10

Guinea pigs after the second challenge.

TEC was tested for the potential to

induce contact dermatitis according to

the Magnusson-Kligman’s Guinea pig

maximization test method. Sensitization

was induced by intradermal injections

of both test substance and Freunds

Adjuvant and the induction process

supplemented 7 days later by the test

substance applied to the shoulder

injections sites under occlusion. The

animals were challenged by occluded

patch 14 days later.

xv. Human repeated insult patch

test—ATBC. ATBC was evaluated in 59

human subject panelists (males and

females) in the repeated insult patch test

of Draize. The test substance was found

not to induce dermal irritation or

contact sensitization. For this test, each

of the 59 panelists received a test patch

(20x20 cm) moistened with 0.4 mL of

ATBC to the upper arms 3 times a week

for 3 weeks. Patches were secured in

place for 24 hours before removal.

Duplicate challenges were made 2

weeks after the final serial applications,

1 set of patches to original sites and 1

set to adjacent sites. Patch sites were

scored prior to patch applications and

scored at 48 and 96 hours after

applications.

xvi. TEC. Triethyl citrate was tested in

an adaptation of the repeat insult patch

test of Draize in 59 human subject

panelists (males and females). A

quantity of 0.4 mL of undiluted TEC

was applied to each test patch prior to

application. Patches were applied to

each panelist 3 times a week for 3

consecutive weeks. Instructions were

given to each panelist to keep the

patches dry and to remove them 24

hours after application. Duplicate

challenge applications were made 2

weeks after the final serial applications;

1 at the original site and 1 at an adjacent

site. The patch sites were evaluated at

48 and 96 hours after application. There

was no evidence of dermal irritation and

no reactions suggestive of contact

sensitization in any of the panelists.

2. Genotoxicty—i. ATBC. Ames

Salmonella/microsome reverse mutation

assay. ATBC did not exhibit mutagenic

activity in the Ames assay with or with

metabolic activation. ATBC was tested

in a preincubation modification of the

Ames assay with Salmonella

typhimurium tester strains TA98,

TA100, TA1535, and TA1537. Tests

were performed in all strains, both with

and without metabolic activation using

S–9 rat liver systems. Assays were

repeated twice in all strains. Another

test was performed with ATBC using

Salmonella typhimurium strains TA98,

TA100, TA1535, TA1537 and TA1538,

with and without metabolic activation

using rat liver S–9 mix or hamster liver

S–9 mix. Results were negative for

mutagenicity in all 5 strains in the

presence of both rat and hamster liver

S–9 mix and in the absence of metabolic

activation.

ii. Mouse lymphoma mutagenesis

assay. ATBC produced a negative

response in cultures with and without

metabolic activation using Arochlor

induced rat liver S–9 mix. The test

article was assayed for mutagenic

potential using thymidine kinase locus

of L51784 TK+/-mouse lymphoma cells.

iii. In vitro chromosomal aberration

assay in rat lymphocytes. ATBC did not

exhibit clastogenic activity (increases in

chromosomal aberrations) in cultured

rat lymphocytes as compared with

negative controls, either in the presence

or absence of metabolic activation.

ATBC was evaluated in a cytogenic

assay using rat lymphocyte cells with

and without rat liver S–9 mix metabolic

activation. Frequencies of chromosomal

aberrations, based upon mitotic indicies

were determined from ATBC treated

cultures and were found not to be

significantly different than negative

controls. Based upon the results of this

study, ATBC did not exhibit clastogenic

activity in cultured rat lymphocytes.

iv. Chinese hamster ovary cell/

hypoxanthine-guanine-phosphoribosyl

transferase (CHO/HGPRT) forward

mutation assay. In this forward

mutation assay, ATBC in 2 independent

tests, did not induce a mutagenic

response. ATBC was evaluated both in

the absence and presence of rat liver S–

9 mix metabolic activation. The forward

mutation frequencies of ATBC treated

cultures were not significantly different

from those of negative controls,

indicating no mutagenic response.

v. Unscheduled DNA synthesis in

rats. ATBC did not induce unscheduled

DNA systhesis (UDS) in livers from rats

treated with commercial material at a

dose of 10 mL/kg.

3. Genotoxicity—TEC. Microbial

assays, Salmonella typhimurium and

Saccaromyces cerevisiae. TEC was not

mutagenic in Salmonella typhimurium

strains TA1535, TA1537, and TA1538

and in Saccharomyces cerevisiae strain

D4, without metabolic activation, and

with metabolic activation using S–9 mix

from male mouse, rat and monkey

livers. Plate tests and suspension tests

were performed with the indicator

strains of both test organisms. Based

upon cell toxicity studies,

concentrations from 0.4 to 1.7% were

employed as the dose levels in the

mutagenicity assays. Results were

negative for mutagenicity with both

bacteria and yeast organisms, with both

the plate and suspension tests, with and

without metabolic activation.

4. Reproductive and developmental

toxicity—i. ATBC. A 2–generation

reproduction study in rats. A 2–

generation reproduction study

conducted with ATBC in Sprague

Dawley rats resulted in a no observed

effect level (NOEL) of 100 milligrams/

kilogram body weight mg/kg bwt/day

based upon the lowest observed effect

level (LOEL) of 300 mg/kg bwt/day for

decreased maternal bwts gains and

water consumption and reduced bwts

and slightly higher mortalities among

their offspring. This 2–generation

reproduction study was conducted in

Sprague Dawley rats with ATBC at

dietary levels of 100, 300, or 1,000 mg/

kg bwt/day to evaluate the potential

effects on reproductive performance and

on the survival and growth of offspring

through 2–generations. In this study, 4

groups of male and female rats received

control or 1 of the 3 dietary levels of

ATBC continuously. Prior to mating,

males were treated for 77 days and

females for 21 days. After mating, males

of the F0 generation were removed and

pregnant females were continued on

diet through gestation, delivery and

lactation. Subsequent F1 offspring were

maintained on the same diets as their

parents for at least 10 weeks prior to

mating within groups. The resulting F2

generation litters were also maintained

on the same diets as their parents for at

least 14 days.

ii. TEC. Developmental toxicity in the

developing chicken embryo. Treatment

Federal Register / Vol. 66, No. 4 / Friday, January 5, 2001 / Notices 1133

of chicken embryos with TEC resulted

in a negative teratogenic response. In

this study, TEC was dissolved in

ethanol to deliver a maximum of 10 mg

per egg. The test substance in solution

was administered by 2 routes, into the

yolk and through the air sac. For each

route, eggs were treated at 2 stages of

incubation: preincubation (0–hour), and

at the fourth day (96– hour).

5. Subchronic toxicity—i. ATBC.

Fourteen–day range finding dietary

toxicity in rats. In a 14–day range

finding feeding study with ATBC, the

NOEL was determined to 1,000 mg/kg

bwt/day. In this study ATBC was

administered in the diet at

concentrations of 1%, 2.5% and 5%

equivalent to doses of 1,000, 2,700 and

5,000 mg/kg bwt/day. Observations

included clinical signs of toxicity, bwts,

food intake, test substance intake,

complete gross pathology including

organ weights, and histopathologic

examinations of livers. Food intake was

initially decreased in all test groups,

however, differences persisted in only

among males of the 5,000 mg/kg bwt/

day group. The initial differences are

likely related to the unpalatability of the

diet. Body weights were significantly

lower among animals of the 2,700 mg/

kg bwt/day and 5,000 mg/kg bwt/day

treatment groups throughout the study.

Organ weight determinations resulted in

significantly increased relative liver

weights among high dose females. Upon

microscopic examinations of the livers

there were increased cytoplasmic

eosinophilia and a concomitant

reduction of glycogen content of

hepatocytes in periportal areas from

animals of the 2,700 mg/kg bwt/day and

5,000 mg/kg bwt/day dose groups.

ii. Ninety–day dietary toxicity in rats.

The results of a 90–day feeding study

with ATBC resulted in a NOEL of 300

mg/kg bwt/day based upon the LOEL of

1,000 mg/kg bwt/day for minor changes

is relative liver weights, liver enzymes

and bilirubin levels. This study was

conducted Sprague Dawley rats

receiving dietary levels of ATBC of 0,

100, 300, or 1,000 mg/kg bwt/day for 90

days. All animals were observed daily

for clinical signs of toxicity.

Ophthalmoscopic observations were

conducted in all animals of the highest

dose group at pretest, and just prior to

the treatment period. Body weights were

recorded daily for all animals on day 1

of treatment and weekly thereafter. Food

consumption was measured over 1 week

periods, while water consumption was

measured in each animal during the first

and eleventh week of dosing. The

results of clinical chemistries,

hematology and urinalysis were

recorded and complete necropsies with

histological examinations were

performed. A few statistically

significant differences were noted

between animals of the high dose group

(1,000 mg/kg bwt/day) and controls

including increased relative liver

weights, liver enzymes, and bilirubin

levels. However, there were no

histopathological findings indicative of

treatment related effects.

iii. TEC. Subchronic oral toxicity in

mice. TEC was evaluated for subchronic

toxicity in a group of 20 mice receiving

350 mg/kg bwt/day of commercial grade

test substance (purity >99%) in 3%

acacia intraperitoneally, daily for 14

consecutive days. A control group

consisting of the same number of mice

received 3% acacia daily under the

same schedule. Body weight gains of

TEC treated mice were significantly

lower as compared with controls by day

7. There were no significant differences

in red and white blood cell counts,

clotting times, and hemoglobin levels

between treated and control mice.

Under the conditions of the study, the

LOEL was established at 350 mg/kg bwt/

day, when given intraperitoneally for 14

days.

iv. Subchronic dietary toxicity in rats.

In an 8 week dietary feeding study in

rats with TEC, the NOEL was

established at 4 g/kg bwt/day. Groups of

approximately 4 males and 4 females

were administered TEC in the diet at

concentrations of 0, 0.5, 1.0, or 2.0%.

These dietary concentrations were

estimated to be equivalent to 0, 1, 2, or

4 g/kg bwt/day TEC. TEC administered

daily in the diet at doses up to

approximately 1/2 of the rat oral LD50

had no significant effect on growth.

Blood counts including red and white

blood cell counts, differential cell

counts were not significantly among

treatment and control groups. There

were no, gross findings in thoracic or

abdominal organs at necropsy.

Histological sections of organs,

including the heart, lungs,

gastrointestinal tract, liver, pancreas,

spleen, and kidneys, revealed no

differences between treatment and

control animals.

v. Subchronic toxicity in dogs. In this

study, 4 dogs were given daily doses of

2.5 to 3.5 mL/kg bwt/day (2,840 to 3,975

mg/kg bwt/day) as rising doses for 7 to

12 weeks. The study report indicates

bwt gains were normal as were results

of urinalysis and serum chemistries.

Hematology results suggested a

tendency to anemia. Organ weights were

normal except for one abnormally heavy

liver. At these doses severe and

widespread liver pathology was evident.

Other organs were reportedly normal.

As the purpose of the study was to

determine the toxic dose for repeated

administrations of TEC, the NOEL was

not established.

6. Chronic toxicity—i. ATBC. 2–year

chronic toxicity in rats. A 2–year

chronic toxicity study conducted with

ATBC in Sherman rats at dietary

concentrations of 0, 200, 2,000, or

20,000 ppm (equivalent to 0, 10, 100, or

1,000 mg/kg bwt/day) resulted in a

NOEL of 1,000 mg/kg bwt/day. Animals

were observed for physical appearance

and behavior throughout the study as

were individual bwts. All animals that

died and those sacrificed at the end of

the study were examined for gross and

histological changes. No differences in

behavior or physical appearance was

noted among treated and control

animals. There were no statistically

significant differences between the

growth of animals treated with ATBC

and controls. There were no statistical

differences in mortalities among

treatment and control animals.

Inflammatory disease of the lungs was

the most common finding at autopsy,

however, there was no treatment related

differences. There were no differences

in tumor frequencies among treatment

and control animals. There was no

reported evidence of effects on the

endocrine system.

ii. TEC. 2–year chronic dietary

toxicity in rats. In this study, TEC

administered to rats for 2 years via

dietary administration resulted in no

significant effects at the highest dose

tested, equivalent to 1,500 mg/kg bwt/

day. Sprague Dawely rats (15 per sex per

dose group) were fed diets containing

TEC at concentrations of 0, 0.33, 1.0, or

3.0% for 2 years. These dietary

concentrations are estimated to be

equivalent to 0, 165, 500, or 1,500 mg/

kg bwt/day. Clinical observations were

made daily and individual bwts were

measured weekly. Blood and urine

evaluations were conducted at specified

intervals. Scheduled interim sacrifices

of animals included macroscopic

examinations of thoracic and abdominal

organs and microscopic examinations of

the kidney and liver tissues. All animals

that died spontaneously during the

study, as well as all animals remaining

at the termination of study (1 or 2

years), were examined by a pathologist.

At terminal sacrifice, microscopic

examinations were made of kidney,

liver, heart, lungs, spleen, stomach,

small intestine, adrenals, ovaries,

uterus, testes, and seminal vesicles.

There were transiently lower bwts

among males of the high dose group

animals, possibly related to the

unpaletibility of the diet. There were no

significant differences observed between

treated and control groups for the

1134 Federal Register / Vol. 66, No. 4 / Friday, January 5, 2001 / Notices

following blood examinations:

hemoglobin, erythrocyte count, nonprotein nitrogen, and sugar

determination. Urine tests for reaction,

albumin, reducing substances, and

microscopic evaluation were all

considered to be normal. Terminal and

interim autopsies disclosed no findings

that were significant or attributable to

TEC treatment. Size and weight of

organs of the principal tissues at the

time of autopsy were unremarkable.

There were no significant differences

between treated and control animals in

comparison to the pathological findings.

iii. Six months dietary toxicity in

dogs. In a 6 month dietary toxicity study

in dogs, TEC did not exhibit any toxic

effects and the NOEL is greater than 280

mg/kg bwt/day the highest dose tested

(HDT). Groups of 4 Beagle or Beagle

type dogs (males and females) were

administered 6 days per week for 6

months at dietary levels of TEC

equivalent to 55 or 280 mg/kg bwt/day.

The dogs were observed daily, weighed

weekly and urinalysis were conducted

at 3 and 6 months after initiation of the

study. Blood samples were taken at 2, 4,

and 6 months after initiation of dosing

for hematological examinations. Dogs

were sacrificed at the end of the in-life

dosing phase and necropsied. Body

weight gain and clinical observations

were normal throughout the study. No

significant changes or abnormalities

were reported in hematology, serum

chemistry or urinalysis during the

course of the study. Gross examinations

of major organs and organ weights at

necropsy were normal. Histopathologic

examinations of the major organs did

not show any abnormalities.

7. Animal metabolism—i. ATBC.

Metabolism and disposition of acetyl

tributyl citrate in male Sprague Dawley

rats. The metabolism of ATBC using

14C–ATBC in rats receiving single oral

doses of 70 mg/kg. ATBC was

determined to be rapidly absorbed and

excreted with an elimination half-life of

3.4 hours. Greater than 98% of

administered 14C was achieved via

urine, feces and in expired air 48 hours

after dosing. Urinary metabolites

identified in this study include acetyl

citrate, monobutyl citrate, acetyl

monobutyl citrate, dibutyl citrate, and

acetyl dibutyl citrate.

ii. Metabolism of acetyltributylcitrate

(ATBC) and tributylcitrate (TBC) in

human serum and rat liver

homogenates. The metabolism of ATBC

and the intermediate deacetylated

metabolite tributylcitrate (TEC), was

studied in vitro using human serum and

rat liver homogenates. At a

concentration of 100 μg/mL in human

serum, ATBC was found to undergo

extensive metabolism with a half-life of

approximately 32 hours. Also, at a

concentration of 100 μg/mL in rat liver

homogenate, ATBC was found to

undergo extensive and complete

metabolism with a half-life of

approximately 10 minutes. There is very

little or no emonstrable TBC in the 2 test

systems because of the rapid further

metabolism of this intermediate

metabolite. The metabolic half-life of

TBC in human serum and rat liver

homogenate was approximately 4 hours

and a few seconds, respectively. These

studies confirm the ready and complete

conversion of ATBC and TBC via ester

hydrolysis to acetic acid, citric acid and

butanol. Butanol would be expected to

undergo oxidation to butyric acid and

further metabolism by b-oxidation.

iii. TEC. Absorption, distribution,

metabolism and excretion of tiethyl

citrate in the rat. Following a single oral

2 mg/kg dose of 14C–TEC in rats, a peak

blood concentration of about 1.48 μg

eq./g blood was achieved at 15 minutes

post-administration, blood

concentration rapidly decreased to

about 0.05 μg eq./gm blood after 1 hour

and was barely detectable after 24

hours. Tissue distribution was

examined after single oral

administration of a 2 mg/kg dose of 14C–

TEC to rats. At 15 minutes postadministration, relatively high 14C

concentrations were found in the

didney (37.81+ 5.02 μg eq./g tissue),

stomach (10.00+ 3.53 μg eq./g tissue),

small intestines including contents

(10.65 + 3.15 μg eq./g tissue) and liver

(4.40 + 0.77 μg eq./g tissue). By 24 hours

after dosing, the 14C concentrations

detected in most tissues had decreased

to near the detection limit (0.01 μg eq./

g tissue), with the exception of the large

intestine including contents.

Cumulative urinary, fecal and

expiratory excretions of 14C–TEC were

93, 0.2 and 1%, respectively, 8 hours

after administration of a single 2 mg/kg

dose of 14C–TEC. At 120 hours after

dosing, the total 14C excretion of urine,

feces and expiration had reached 99%.

Metabolism of 14C–TEC was

investigated using the 24–hour urine of

rats after a single oral administration of

a 2 mg/kg dose. Three major metabolites

were separated by thin-layer

chromatography and identified using

gas chromatography (GC/MS). Two of

the metabolites were isomers of diethyl

citrate and 1 was found to be monoethyl

citrate.

8. Endocrine disruption. Chronic and

reproductive toxicity data conducted

with ATBC and chronic toxicity data

conducted with TEC are without

adverse effects to reproductive or the

endocrine system. Also, the compounds

do not share structural similarities with

currently known or chemicals suspected

to have endocrine disruptive properties.

C. Aggregate Exposure

1. Dietary exposure—i. Food. ATBC

and TEC are currently classified as

generally recognized as safe (GRAS) for

use in foods and food packaging,

cosmetics, pharmaceuticals, and as

plasticizers for consumer and packaging

products. The current petition, requests

the exemption from tolerances for these

compounds when used as inert

ingredients in agricultural formulations

for use on growing crops for post

harvest applications to food crops and

applications to animals. Although

residue data are generally not required

for inert ingredient exemptions from

tolerances, Morflex, Inc. has developed

worst case assumptions using Novigen

Sciences Dietary Exposure Evaluation

Model (DEEM) with data inputs based

upon the model of Kenaga and Hoergers:

Maximum Expected Residues on

Vegetation. The Kenega nomogram is

used to predict maximum residue levels

present on day 0 following different

application rates of a chemical to 1 of

6 different categories of plants or plant

parts. The 3 basic features of the Kenaga

nomogram-catagories of plants and

plant parts, maximum predicted residue

levels, and a linear dose-residue

relationship. Crops and crop groups

selected for this analysis include the

following: leafy vegetables (succulent or

dried), fruiting vegetables, cucurbit

vegetables, citrus fruits, pome fruits,

stone fruits, berries, cereal grains,

grapes, and bananas. The reference dose

chosen for this analysis, was derived

from the NOEL resulting from a chronic

rat (2–year) study conducted with

ATBC. This study was conducted at

dietary concentrations of 0, 200, 2,000,

and 20,000 ppm equivelant to 0, 10,

100, and 1,000 mg/kg bwt/day of ATBC.

No effects were reported up to the HDT.

Therefore, for the purposes of this

assessment, a chronic reference dose

(RfD) of 10 mg/kg bwt/day was used.

The chronic RfD includes an

uncertainty factor of 100 to account for

intra-species and inter-species

variations. Food consumption data from

the United States Department of

Agriculture (USDA) CSFII conducted in

1994 through 1996, were used to

estimate dietary exposure. The levels of

ATBC and TEC can vary depending

upon the percent of ATBC and TEC in

the formulation and/or the application

rate of the product. For purposes of this

screening level assessment, an

application rate of 3 pounds per acre of

ATBC or TEC was assumed. Also, no

adjustment was made for percent crop

Federal Register / Vol. 66, No. 4 / Friday, January 5, 2001 / Notices 1135

treated and all commodities contain

residues at predicted day zero levels.

For this screening level assessment with

an application rate of 3 pounds ATBC

or TEC per acre, the following 0–time

level residues are predicted from the

nomogram: leafy vegetables–375 ppm,

legume vegetables–36 ppm, fruiting

vegetables, cucurbit vegetables, citrus

fruits, pome fruits, stone fruits, berries,

cereal grains, grapes, and bananas–21

ppm.. Using the above modeling

parameters, chronic exposure was

estimated for the overall U.S.

population and 25 population

subgroups. Chronic exposure for the

overall U.S. population was estimated to

be 0.492873 mg/kg bwt/day,

representing 4.9% of the RfD. The

exposure estimate for the most highly

exposed population subgroup, children

1-6 years of age, was 0.984312 mg/kg

bwt/day, or 9.8%.

ii. Drinking water. Based upon the

chemical and physical properties, and

the environmental fate characteristics,

ATBC and TEC are not expected to

persist environmentally, nor result in

significant concentrations in drinking

water sources.

2. Non-dietary exposure. ATBC and

TEC are currently used in non-food use

pesticide formulations, as well as in

food, food packaging, cosmetics,

medical devices and pharmaceuticals,

and as plasticizers.

D. Cumulative Effects

Cumulative effects are not expected

since ATBC and TEC are rapidly

degraded to natural substances.

E. Safety Determination

1. U.S. population. Based upon the

dietary residue exposure analysis using

the Kenega nomogram, the most

sensitive population, children 1–6

years, was 0.984312 mg/kg bwt/day or

9.8% of the RfD for the crops and crop

groups used in this assessment. Results

of a 2–generation reproduction study

with ATBC did not reveal

developmental or reproduction effects at

doses up to 100 mg/kg bwt/day. Also,

based on the absence of pup toxicity up

to the dose level (1,000 mg/kg bwt/day)

producing maternal effects, there is no

evidence of special post-natal sensitivity

to infants and children. It is concluded

that there is reasonable certainty that no

harm will result to infants and children

from aggregate exposure to acetyl

tributyl citrate (ATBC) or triethyl citrate

(TEC) when used as inert ingredients in

agricultural formulations of pesticides.

2. Infants and children. No

embryotoxic, developmental, or

teratogenic effects have been associated

with acetyltributyl citrate (ATBC) or

triethyl citrate (TEC).

F. International Tolerances

Morflex Inc. is unaware of any

International tolerances or CODEX

maximum residue limits (MRL’s) for

acetyltributyl citrate (ATBC) or triethyl

citrate (TEC) on any crop or livestock

commodities.

[FR Doc. 01–369 Filed 1–4–01; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[FRL–6930–2]

Notice of Tentative Approval, Request

for Comments and Solicitation of

Requests for a Public Hearing for

Public Water System Supervision

Program Revision for the

Commonwealth of Virginia

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice of Tentative Approval

and Solicitation of Requests for a Public

Hearing.

SUMMARY: Notice is hereby given in

accordance with the provision of section

1413 of the Safe Drinking Water Act as

amended, and the rules governing

National Primary Drinking Water

Regulations that the Commonwealth of

Virginia has revised its approved Public

Water System Supervision Primacy

Program. Specifically, Virginia has

adopted Consumer Confidence Report

regulations requiring annual drinking

water quality reports from community

water suppliers. EPA has determined

that these regulations are no less

stringent than the Federal provisions

and satisfy the requirements of the

Federal regulations. Therefore, EPA has

decided to tentatively approve the

program revisions. All interested parties

are invited to submit written comments

on this determination and may request

a public hearing.

DATES: Comments or a request for a

public hearing must be submitted by

February 5, 2001. This determination

shall become effective on February 5,

2001 if no timely and appropriate

request for a hearing is received and the

Regional Administrator does not elect to

hold a hearing on his own motion, and

if no comments are received which

cause EPA to modify its tentative

approval.

ADDRESSES: Comments or a request for

a public hearing must be submitted to

Patti Kay Wisniewski, Drinking Water

Branch (3WP22), U.S. Environmental

Protection Agency Region III, 1650 Arch

Street, Philadelphia, PA 19103–2029.

All documents relating to this

determination are available for

inspection between the hours of 8:00

a.m. and 4:30 p.m., Monday through

Friday, at the following offices:

• Drinking Water Branch, Water

Protection Division, U.S. Environmental

Protection Agency, Region III, 1650

Arch Street, Philadelphia, Pennsylvania

19103–2029; and

• Virginia Department of Health,

Division of Water Supply Engineering,

1500 East Main Street, Richmond,

Virginia 23218.

FOR FURTHER INFORMATION CONTACT: Patti

Kay Wisniewski at the Philadelphia

address given above; telephone (215)

814–5668 or fax (215) 814–2318.

SUPPLEMENTARY INFORMATION: All

interested parties are invited to submit

written comments on this determination

and may request a public hearing. All

comments will be considered, and, if

necessary, EPA will issue a response.

Frivolous or insubstantial requests for a

hearing may be denied by the Regional

Administrator. However, if a substantial

request for a public hearing is made by

February 5, 2001, a public hearing will

be held. A request for public hearing

shall include the following: (1) The

name, address, and telephone number of

the individual, organization, or other

entity requesting a hearing; (2) a brief

statement of the requesting person’s

interest in the Regional Administrator’s

determination and of information that

the requesting person intends to submit

at such a hearing; and (3) the signature

of the individual making the request; or,

if the request is made on behalf of an

organization or other entity, the

signature of a responsible official of the

organization or other entity.

Dated: December 27, 2000.

Bradley M. Campbell,

Regional Administrator, EPA, Region III.

[FR Doc. 01–362 Filed 1–4–01; 8:45 am]

BILLING CODE 6560–50–M

FEDERAL COMMUNICATIONS

COMMISSION

Notice of Public Information

Collection(s) Being Reviewed by the

Federal Communications Commission

December 20, 2000.

SUMMARY: The Federal Communications

Commission, as part of its continuing

effort to reduce paperwork burden

invites the general public and other

Federal agencies to take this

opportunity to comment on the

following information collection(s), as