Federal Register / Vol. 66, No. 241 / Friday, December 14, 2001 / Notices 64823

relative to prenatal and postnatal effects

for children is complete. Further, for

spinosad, the NOAELs in the dog

chronic feeding study which was used

to calculate the RfD (0.027 mg/kg/day)

are already lower than the NOAELs

from the developmental studies in rats

and rabbits by a factor of more than 10–

fold. Concerning the reproduction study

in rats, the pup effects shown at the

HDT were attributed to maternal

toxicity. Therefore, it is concluded that

an additional uncertainty factor (UF) is

not needed and that the RfD at 0.027

mg/kg/day is appropriate for assessing

risk to infants and children. In addition,

EPA has determined that the 10X factor

to account for enhanced sensitivity of

infants and children is not needed

because:

i. The data provided no indication of

increased susceptibility of rats or rabbits

to in utero and/or postnatal exposure to

spinosad. In the prenatal developmental

toxicity studies in rats and rabbits and

2–generation reproduction in rats,

effects in the offspring were observed

only at or below treatment levels that

resulted in evidence of parental toxicity.

ii. No neurotoxic signs have been

observed in any of the standard required

studies conducted.

iii. The toxicology data base is

complete and there are no data gaps.

iv. Exposure data are complete or is

estimated based on data that reasonably

account for potential exposure.

Using the conservative exposure

assumptions previously described

(tolerance level residues), the percent

RfD utilized by the aggregate exposure

to residues of spinosad on existing crop

uses is 81.9% for children 1 to 6 years

old, the most sensitive population

subgroup from an EPA assessment based

on the cPAD (as posted in the Federal

Register of May 3, 2000). Additional

refinements to the dietary exposure

based on market share information

would reduce the exposure of children

1 to 6 years old to less than 50% the

cPAD. Grain treated under a temporary

tolerance is expected to contribute only

a negligible impact to the RfD. Thus,

based on the completeness and

reliability of the toxicity data and the

conservative exposure assessment, it is

concluded that there is a reasonable

certainty that no harm will result to

infants and children from aggregate

exposure to spinosad residues on the

above proposed uses, including existing

crop uses.

F. International Tolerances

There is no Codex maximum residue

levels established for residues of

spinosad.

[FR Doc. 01–30913 Filed 12–13–01; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[PF–1060; FRL–6813–2]

Notice of Filing Pesticide Petitions 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 pesticide petitions

proposing the establishment of

regulations for residues of a certain

pesticide chemical in or on various food

commodities.

DATES: Comments, identified by docket

control number PF–1060, must be

received on or before January 14, 2002.

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–1060 in the subject line on the first

page of your response.

FOR FURTHER INFORMATION CONTACT: By

mail: Shaja R. Brothers, Registration

Division (7505C), Office of Pesticide

Programs, Environmental Protection

Agency, 1200 Pennsylvania Ave., NW.,

Washington, DC 20460; telephone

number: (703) 308–3194; e-mail address:

brothers.shaja@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–

1060. 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

64824 Federal Register / Vol. 66, No. 241 / Friday, December 14, 2001 / Notices

imperative that you identify docket

control number PF–1060 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–1060. 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 a 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: November 29, 2001.

Peter Caulkins,

Acting Director, Registration Division, Office

of Pesticide Programs.

Summaries of Petitions

The petitioner’s summaries of

pesticide petitions are printed below as

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

FFDCA. The summaries of petitions

were prepared by the petitioner and

represents the view of the petitioner.

EPA is publishing the petitions

summaries verbatim without editing

them in any way. The petitions

summaries 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 methods are needed.

Interregional Research Project Number

4 (IR–4) and Uniroyal Chemical

Company

PP 0E6167, 1E6347, and 1F6235

EPA has received pesticide petitions

(0E6167, 1E6347 and 1F6235) from the

Interregional Research Project Number 4

(IR-4), 681 US Highway #1 South, North

Brunswick, NJ 08902 and Uniroyal

Chemical Company Inc., Middlebury,

CT 06749 proposing, pursuant to section

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

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

346a(d), to amend 40 CFR 180.377 by

establishing tolerances for residues of

diflubenzuron, (N-(4-

chlorophenyl)amino]carbonyl-2,6-

difluorobenzamide) in or on the

following raw agricultural commodities:

• PP 0E6167 proposes the

establishment of a tolerance for pear at

0.5 part per million (ppm).

• PP 1E6347 proposes the

establishment of a tolerance for the

grass, forage, fodder, and hay group at

6.0 ppm.

• PP 1F6235 proposes the

establishment of tolerances for

stonefruit (except cherries) at 0.05 ppm,

tree nuts and pistachios at 0.05 ppm,

almond hulls at 5.0 ppm, peppers at 1.0

ppm, and meat-by-products at 0.15

ppm.

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. This notice of filing contains

a summary of the petition provided by

Uniroyal Chemical Company, Inc., the

registrant.

A. Residue Chemistry

1. Plant metabolism. The nature of the

residue in plants is adequately

understood. The metabolism of

diflubenzuron was investigated in

soybeans, oranges, and rice. The main

component of residues in rice was pchlorophenylurea (CPU); levels of pchloroaniline (PCA) were negligible to

non-detectable. The main component of

the residues in soybeans and oranges

was the parent diflubenzuron (DFB). A

considerable portion of the residues

were bound. DFB showed very limited

absorption and translocation in plants

Federal Register / Vol. 66, No. 241 / Friday, December 14, 2001 / Notices 64825

with most of the residues remaining on

the surface.

2. Analytical method. Practical

analytical methods for detecting levels

of DFB, CPU and PCA, in or on food

with a limit of detection that allows

monitoring of the residue at or above the

level set in the tolerance was used to

determine residues in the proposed

commodities. Residues of the individual

analytes are detectable and quantifiable

using three separate analytical methods.

Residues of DFB are extracted from the

proposed commodities with

dichloromethane. Extracts are purified

with deactivated florisil. An aliquot of

the extract is hydrolyzed with

phosphoric acid and the DFB is

partitioned into hexane. The resulting

extract is derivatized in

heptafluorobutyric anhydride (HFBA).

Quantification of DFB is accompanied

by gas chromatography using an

electron capture detector.

The analytical method for

quantitation of the 4-chlorophenylurea

requires ethyl acetate extraction of the

residue from the matrix. Column

chromatography is utilized for clean-up

of the extract immediately prior to

derivitization with HFBA. Derivatized

extracts are analyzed by gas

chromatography equipped with an

electron capture detector.

The analysis for the determination of

PCA residues from the proposed

commodities utilize an internal

standard method. Samples of matrix to

be analyzed are fortified with the

internal standard. Residues of 12C-PCA

and the internal standard are subjected

to acid and base hydrolysis. The final

extract is passed through florisil column

for clean-up and derivatized with HFBA

in hexane. An aliquot of the derivatized

extract is analyzed by gas

chromatography using a mass

spectrometry detector in the selective

ion monitoring mode. Recovery of PCA

is determined by the combined peak

areas for the two mass spectral ions

obtained from the derivatized 12C-PCA

relative to the response factor derived

from the combined areas of the

corresponding two mass spectral ions

from the internal standard.

3. Magnitude of residues. Individual

residue trials have been conducted with

diflubenzuron on the proposed

commodities. Analyses of these trials

show that the maximum total residue

for diflubenzuron and its conversion

products PCA and CPU will be at or

below the proposed tolerance levels.

B. Toxicological Profile

1. Acute toxicity. Studies for

diflubenzuron technical indicate the

acute oral toxicity in rats and mice is

>4,640milligram per kilogram (mg/kg),

and the acute dermal toxicity in rats is

>10,000 mg/kg. The acute inhalation

lethal concentration (LC)50 in rats is >35

mg/L (6 hours). Diflubenzuron technical

is not an eye or skin irritant to rabbits,

and is not a dermal sensitizer in guinea

pigs.

2. Genotoxicity. Diflubenzuron did

not show any mutagenic activity in

point mutation assays employing S.

typhimurium, S. cerevisiae, or L5178Y

Mouse Lymphoma cells. Diflubenzuron

did not induce chromosomal aberrations

in chinese hamster ovary (CHO) cells

and it did not induce unscheduled DNA

synthesis (UDS) in human WI–38 cells.

Diflubenzuron was also negative in

mouse micronucleus and mouse

dominant lethal assays and it did not

induce cell transformation in Balb/3T3

cells.

3. Developmental and reproductive.

In a rat developmental toxicity study,

diflubenzuron was administered by oral

gavage to pregnant female rats at dosage

levels of 0, 1, 2, and 4 mg/kg/day. No

treatment-related effects were seen. A

subsequent study was conducted in

pregnant Sprague Dawley rats at a dose

of 0 and 1,000 mg/kg/day. No maternal

toxicity was observed. The incidence of

fetuses with skeletal abnormalities was

slightly increased in the treated group,

but was within historical background

range. The no observed adverse effect

level (NOAEL) for maternal and

developmental toxicity in rats was

greater than 1,000 mg/kg/day.

Diflubenzuron was also administered

by oral gavage to pregnant New Zealand

white rabbits at dosage levels of 0, 1, 2,

and 4 mg/kg/day. No treatment-related

effects were seen. A subsequent study

was conducted in pregnant rabbits at a

dose of 0 and 1,000 mg/kg/day. No

maternal or developmental toxicity was

seen. The NOAEL for maternal and

developmental toxicity in rabbits was

greater than 1,000 mg/kg/day.

In a rat reproduction study,

diflubenzuron was fed to 2–generations

of male and female rats at dietary

concentrations of 0, 10, 20, 40, and 160

ppm. No effects were seen on parental

body weight gain and there were no

reproductive effects. A subsequent

study was conducted on one generation

(1 litter) of rats at dietary concentrations

of 0, 1,000, and 100,000 ppm. Systemic

effects were seen in adults at these

doses but there was no effect on

reproductive parameters. The NOAEL

for reproductive toxicity was greater

than 100,000 ppm (5 g/kg/day).

4. Subchronic toxicity. To assess

subchronic toxicity, a 4–week

inhalation study and a 3–week dermal

study were conducted. In the inhalation

study rats were exposed nose only to 10,

30, or 100 milligram per cubic meters

(mg/m3) for 6 hours per day, 5 days per

week for 4 weeks. Treatment-related

findings were a slight reduction in

erythrocytes, hemoglobin and

hematocrit in male and female rats at a

concentration of 100 mg/m3 and an

increase in total bilirubin in high dose

female rats. There was no effect on

methemoglobin concentration at any

dose level. The NOAEL for subchronic

inhalation toxicity was 30 mg/m3.

To assess subacute dermal toxicity,

diflubenzuron was applied to the backs

of male and female CD rats for 3 weeks

at dose levels of 20, 500, and 1,000 mg/

kg/day. Hematology evaluation showed

reductions in red blood cell (RBC),

hemoglobin (Hgb) and hematocrit values

at 500 and 1,000 mg/kg/day. An

increased incidence of polychromasia,

hypochromasia, and anisocytosis was

seen at 500 and 1,000 mg/kg/day. An

increase in methemoglobin and

sulfhemoglobin values was seen at 1,000

mg/kg/day. The NOAEL for systemic

toxicity was 20 mg/kg/day. Also, a

dermal absorption factor of 0.5%, for

systemic absorption, was derived from a

study where rats were dosed with either

0.005 or 0.05 mg/cm2 of (14C)

diflubenzuron technical. This value can

be used for converting dermal exposure

to oral equivalents.

5. Chronic toxicity. Diflubenzuron

was given by capsule to male and

female Beagle dogs for 1 year at dose

levels of 0, 2, 10, 50, and 250 mg/kg/

day. Body weight (bwt) gain was slightly

reduced in females at 250 mg/kg/day.

Absolute liver and spleen weights were

increased in males given 50 and 250

mg/kg/day. A reduction in hemoglobin

and mean corpuscular hemoglobin

concentration, with an elevation in

reticulocyte count, was seen at 50 and

250 mg/kg/day. Methemoglobin and

sulfhemoglobin values were increased at

doses of 10 mg/kg/day and greater.

Histopathological findings were limited

to pigmented macrophages and Kupffer

cells in the liver at doses of 50 and 250

mg/kg/day. The NOAEL for chronic

toxicity in dogs was 2 mg/kg/day.

Diflubenzuron was fed to male and

female Sprague Dawley rats for 2 years

at dose levels of 0, 156, 625, 2,500, and

10,000 ppm. Methemoglobin values

were elevated in female rats at all dose

levels and in male rats at the two

highest dose levels. Sulfhemoglobin was

elevated in females, only, at dose levels

of 2,500 and 10,000 ppm. Mean

corpuscular volume (MCV) and

reticulocyte counts were increased in

high dose females. Spleen and liver

weights were elevated at the two highest

doses. Histopathological examination

64826 Federal Register / Vol. 66, No. 241 / Friday, December 14, 2001 / Notices

demonstrated an increase in

hemosiderosis of the liver and spleen,

bone marrow and erythroid hyperplasia

and areas of cellular alteration in the

liver. In another study diflubenzuron

was administered to male and female

CD rats for 2 years at dose levels of 0,

10, 20, 40, and 160 ppm. Elevated

methemoglobin levels were seen in high

dose males and females. No additional

effects, including carcinogenic findings,

were observed. The NOAEL for chronic

toxicity in rats was 40 ppm (2 mg/kg/

day).

A 91–week carcinogenicity study in

CFLP mice was conducted at doses of 0,

16, 80, 400, 2,000, and 10,000 ppm.

There was no increase in tumor

incidence as a result of diflubenzuron

administration. Target organ effects

included: Increased methemoglobin and

sulfhemoglobin values, Heinz bodies,

increased liver and spleen weight,

hepatocyte enlargement, and

vacuolation, extramedullary

hemopoiesis in the liver and spleen,

siderocytosis in the spleen and

pigmented Kupffer cells. A NOAEL for

these effects was 16 ppm (2 mg/kg/day).

Diflubenzuron was fed to male and

female Sprague Dawley rats for 2 years

at dose levels of 0, 156, 625, 2,500, and

10,000 ppm. Methemoglobin values

were elevated in female rats at all dose

levels and in male rats at the two

highest dose levels. Blood

sulfhemoglobin was elevated in females,

only, at dose levels of 2,500, and 10,000

ppm. MCV and reticulocyte counts were

increased in high dose females. Spleen

and liver weights were elevated at the

two highest doses. Histopathological

examination demonstrated an increase

in hemosiderosis of the liver and spleen,

bone marrow and erythroid hyperplasia,

and areas of cellular alteration in the

liver. There was no increase in tumor

formation. In another study,

diflubenzuron was administered to male

and female CD rats for 2 years at dose

levels of 0, 10, 20, 40, and 160 ppm.

Elevated methemoglobin levels were

seen in high dose males and females. No

additional effects, including

carcinogenic findings, were observed.

6. Animal metabolism. DFB in rats at

a single dose of 100 mg/kg and 5 mg/

kg single and multiple oral doses

depicted limited absorption from the

gastrointestinal tract. No major

difference was observed between the

single and multiple doses. In single dose

treatments, after 7 days, 20% and 3% of

the applied dose 5 and 100 mg/kg,

respectively, were excreted in urine,

while 79% and 98% of the applied dose

5 and 100 mg/kg, respectively, were

eliminated in the feces. Very little

bioaccumulation in the tissues was

observed. In the feces, only unchanged

parent compound was detected. Several

metabolites were observed in the urine

which are, among others, 2,6-

diflurobenzoic acid (DFBA), 2,6-

difluorophippuric acid, 2,6-

difluorobenzamide (DFBAM), and 2-

hydroxydiflubenzuron (2-HDFB). An

unresolved peak that was characterized

as p-chloroaniline (PCA) and/or pchlorophenylurea (CPU) was found.

This latter peak accounted for about 2%

of the administered dose (5 mg/kg). To

resolve if PCA and CPU are indeed

metabolites of DFB, rats were

administered a single oral dose, 100 mg/

kg of 14C DFB. The major metabolites

identified in rat urine were 4-

chloroaniline-2-sulfate, accounting for

almost 50% of the total radioactive

residue (TRR) in the urine and N-(4-

chlorophenyl)oxamic acid which

accounted for about 15% of the (TRR).

Neither CPU, PCA nor their N-hydroxyl

derivatives were found in rat urine at a

limit of detection of 23 parts per billion

(ppb). As in the previous study, DFB

was the only residue found in the feces.

7. Metabolite toxicology. NCI/NTP

conducted chronic feeding and gavage

studies with p-chloroaniline (PCA), a

minor potential metabolite of

diflubenzuron, in Fischer 344 rats and

B6C3F1 mice.

PCA was administered in the diet to

Fischer 344 rats at dietary

concentrations of 250 and 500 ppm for

78 weeks, followed by a 24–week

observation period. A slight body

weight depression was seen in high

dose females rats, compared to controls.

Survival was reduced in high dose

males compared to controls. In male rats

there was a slight increase in

uncommon fibromas or fibrosarcomas of

the spleen, which was not statistically

significant. Non-neoplastic proliferative

and chronic inflammatory lesions were

found in spleens of treated rats. It was

concluded that, under the conditions of

the assay, sufficient evidence was not

found to establish the carcinogenicity of

PCA for Fischer 344 rats.

PCA was administered 5 days/week

by oral gavage, as a hydrochloride salt

in water, to male and female F344/N

rats at doses of 0, 2, 6, or 18 mg/kg/day.

Mean body weights of dosed rats were

generally within 5% of those of controls

throughout the study. High dose

animals generally showed mild

hemolytic anemia and dose-related

methemoglobinemia. Non-neoplastic

lesions seen were bone marrow

hyperplasia, hepatic hemosiderosis, and

splenic fibrosis, suggesting treatmentrelated effects on the hematopoietic

system. Adrenal medullary hyperplasia

was observed in high dose female rats.

The incidence of uncommon sarcomas

of the spleen was significantly increased

in high dose male rats. A marginal

increase in pheochromocytomas of the

adrenal gland was seen in high dose

male and female rats. It was concluded

that, under the conditions of this 2–year

gavage study, there was clear evidence

of carcinogenic activity of PCA

hydrochloride for male F344/N rats and

equivocal evidence of carcinogenic

activity of PCA hydrochloride for female

F344/N rats.

PCA was administered in the diet to

B6C3F6 mice at dietary concentrations

of 2,500 and 5,000 ppm for 78 weeks

followed by a 13–week observation

period. A body weight depression was

seen in treated mice of both sexes,

compared to controls. An increased

incidence of hemangiomas and

hemangiosarcomas in spleen, kidney,

liver, and other sites was seen in treated

mice of both sexes; however this

increase was not statistically significant

compared to controls. Non-neoplastic

proliferative and chronic inflammatory

lesions were found in spleens of treated

mice. The evidence was considered

insufficient to conclusively relate the

hemangiomatous tumors in mice to

compound administration. It was

concluded that, under the conditions of

the assay, sufficient evidence was not

found to establish the carcinogenicity of

PCA for B6C3F1 mice.

PCA hydrochloride was administered

5 days/week by oral gavage to male and

female B6C3F1 mice at doses of 0, 3, 10,

or 30 mg/kg/day. Mean body weights of

high dose male and female mice were

generally within 5% of those of controls

throughout the study. The incidence of

hepatocellular adenomas or carcinomas

(combined) was increased in a nondose-dependent manner in treated male

mice. Metastasis of carcinoma to the

lung was seen in the high dose group.

An increased incidence of

hemangiosarcomas of the liver or spleen

was seen in high dose male mice. It was

concluded that, under the conditions of

this 2–year gavage study, there was

some evidence of carcinogenic activity

of PCA hydrochloride for male B6C3F1

mice and no evidence of carcinogenic

activity of PCA hydrochloride for female

B6C3F1 mice.

In addition to PCA, 4-

chlorophenylurea (CPU) is also a

potential minor metabolite of

diflubenzuron. By association with

PCA, EPA has concluded that CPU has

carcinogenic potential and the same

carcinogenic potency (q1*) as PCA. In

the NTP report of the PCA bioassay, it

is proposed that PCA undergoes Nhydroxylation to form the

corresponding N-hydroxylamine

Federal Register / Vol. 66, No. 241 / Friday, December 14, 2001 / Notices 64827

metabolites; N-hydroxylation of

aromatic amines is a well know

mechanism of aromatic amine

carcinogenicity. This metabolite, or

proximate carcinogen, is then

conjugated to form the ultimate

carcinogen capable of ionizing and

reacting with DNA to form adducts

which result in splenic tumor

formation. An alternate mechanism

involving toxicity resulting in

erythrocyte damage, splenic scavenging,

hemorrhage, hyperplasia and fibrosis

and ultimately splenic tumor formation

is also proposed, but both mechanisms

are based on the formation of N-hydroxy

PCA.

This metabolite also causes

methemoglobinemia in animals.

Therefore, methemoglobin formation

can be used as an indicator of the

presence of PCA and N-hydroxy

metabolite. However, in recent CPU rat

toxicity studies, both dietary (7–day)

and gavage, and a CPU rat metabolism

study, it has been demonstrated that

CPU does not induce methemoglobin

formation and it is neither metabolized

to PCA nor forms an N-hydroxylamine

derivative. Since N-hydroxylation is the

required first step in the mechanism of

action of PCA’s carcinogenicity, it can

be concluded that CPU’s mechanism of

action and toxicity is different from that

of PCA’s.

8. Endocrine disruption. The standard

battery of required studies has been

completed and evaluated to determine

potential estrogenic or endocrine effects

of diflubenzuron. These studies include

an evaluation of the potential effects on

reproduction and development, and an

evaluation of the pathology of the

endocrine organs following repeated or

long-term exposure. These studies are

generally considered to be sufficient to

detect any endocrine effects. No such

effects were noted in any of the studies

with diflubenzuron.

C. Aggregate Exposure

1. Dietary exposure. Since 1–day

single dose oral studies in rats and mice

indicated only marginal effects, an acute

exposure risk assessment is not needed,

as there were no significant acute effects

observed.

i. Food—a. Diflubenzuron. The

chronic dietary exposure from

diflubenzuron was estimated based on

the average residue values from the

various currently labeled raw

agricultural commodities (RACs) and

the proposed pear use. Percent of crop

treated was also factored into the

estimate. Residues in meat, milk, and

egg products were obtained from

extrapolation of metabolism study data

to anticipated livestock dietary burdens.

The dietary exposure analysis was

estimated based on 1989–1992 USDA

food consumption data.

For the U.S. population (total), the

dietary exposure of diflubenzuron was

estimated as 0.000027 mg/kg/day. For

nursing and non-nursing infants, the

exposure was estimated as and 0.000110

and 0.000304 mg/kg/day, respectively.

For children, the exposure was 0.000046

and 0.000033 mg/kg/day for 1–6 year

olds and 7–12 year olds, respectively.

b. p-Chloroaniline. The chronic

dietary exposure from p-chloroaniline

(PCA) which has been detected in some

food products was also determined.

Average residues from field trials for

mushrooms, rice, pears, nut crops, and

pistachios, stonefruit (except cherries),

and peppers were used. Residues in

liver were obtained from extrapolation

of metabolism data to anticipated

livestock dietary burdens. EPA has

previously used a 2% in vivo conversion

factor of DFB to PCA for foods derived

from plant products. However, based on

results of a recent rat metabolism study

showing that no PCA is formed, this is

no longer appropriate. The percent

treated of each crop was also factored

into the exposure estimate.

For the U.S. population (total), the

dietary exposure of PCA was estimated

as <0.000001 mg/kg/day. For nursing

and non-nursing infants, the exposure

was estimated as 0.000002 and 0.000007

mg/kg/day, respectively. For children 1

to 6 years old and 7 to 12 years old, the

exposure was 0.000001 mg/kg/day.

ii. Drinking water. Diflubenzuron

degrades in soil relatively quickly with

an aerobic half-life ranging from 3 to 7

days. Major degradates include

difluorobenzoic acid (DFBA) and CPU.

DFBA is further metabolized through

decarboxylation and ring cleavage by

soil microbes whereas CPU is slowly

degraded to soil-bound entities. Under

anaerobic aquatic conditions,

diflubenzuron has a half-life of 34 days

with the main degradates being DFBA

and CPU. In surface water,

diflubenzuron is degraded by microbes

with a half-life of 5 to 10 days. The soil

mobility of diflubenzuron is considered

quite limited based on a number of

experimental studies as well as by

computer modeling. CPU has also been

shown to be relatively immobile in soil.

Although DFBA shows mobility in soil,

it is rapidly degraded. Therefore, based

on results of laboratory and field

studies, it is not likely that

diflubenzuron or its degradates will

impact ground water quality to any

significant extent.

Based on EPA’s PRZM/EXAMS

modeling, the average annual mean

concentration of diflubenzuron in

surface water sources is not expected to

exceed 0.05 ppb. These values were

determined using the maximum

concentrations for any diflubenzuron

crop uses including the proposed

commodities. The drinking water level

of concern (DWLOC) for chronic (noncancer) exposure to diflubenzuron in

drinking water was determined as 700

ppb for the U.S. population (total) and

approximately 200 ppb for infants and

children. The estimated maximum

concentration of diflubenzuron in

surface and ground water (0.05 ppb) is

much less than the DWLOCs as a

contribution to chronic (non-cancer)

aggregate exposure.

2. Non-dietary exposure.

Diflubenzuron is a restricted use

pesticide based on its toxicity to aquatic

invertebrates. This restricted use

classification makes it unavailable for

use by homeowners. Occupational uses

of diflubenzuron may expose people in

residential locations, parks, or forests

treated with diflubenzuron. However,

diflubenzuron has very low residues

detected in forestry dissipation studies,

low dermal absorption rate (0.05%), and

extremely low dermal and inhalation

toxicity.

D. Cumulative Effects

Uniroyal Chemical Co. has considered

the potential for cumulative effects of

diflubenzuron and other substances

with a common mechanism of toxicity.

The mammalian toxicity of

diflubenzuron is well defined. We are

not aware of any other pesticide product

registered in the United States that

could be metabolized to p-chloroaniline.

For this reason, consideration of

potential cumulative effects of residues

from pesticidal substances with a

common mechanism of action as

diflubenzuron is not appropriate. Thus

only the potential exposures to

diflubenzuron were considered in the

total exposure assessment.

E. Safety Determination

1. U.S. population. Based on the

available toxicology and exposure data

base for diflubenzuron, Uniroyal has

determined that the total possible nonoccupational aggregate exposure from

diflubenzuron would occur from the

dietary route. Dietary exposure to the

U.S. population (total) from

diflubenzuron was estimated at

0.000027 mg/kg/day. Based on the 0.02

mg/kg/day RfD (reference dose) derived

from the dog chronic NOAEL of 2 mg/

kg/day and a 100–fold safety factor, this

dietary exposure is 0.1% of the RfD.

Despite the potential for exposure to

diflubenzuron in drinking water,

64828 Federal Register / Vol. 66, No. 241 / Friday, December 14, 2001 / Notices

aggregate exposure is not expected to

exceed 100% of the RfD.

For PCA, Uniroyal has also

determined that the total possible nonoccupational aggregate exposure would

occur from the dietary route. Dietary

exposure to the U.S. population (total)

from PCA was estimated as less than

0.000001 mg/kg/day. The risk from

diflubenzuron-derived PCA can be

estimated using a linear extrapolation of

the dose-response from the rat chronic

study conducted by the National

Toxicology Program in which rats were

dosed via gavage with p-chloroaniline

(hydrochloride) for 24 months. EPA has

determined the q1* as 0.0638 based on

the combined sarcoma incidence in the

spleen of male rats.

In view of the results of recent CPU

rat mechanistic and metabolism studies,

and the DFB rat metabolism study, the

dietary risk assessment included here

considers only actual residues of PCA

found in food and animal by-products.

This is consistent with a parent

compound, such as diflubenzuron,

which is negative (category E) for

carcinogenicity.

Using the q1* of 0.0638, the risk to the

U.S. population (total) from dietary

exposure to diflubenzuron-derived PCA

is 3.09 x 10-8.

2. Infants and children. The same

assumptions as for the U.S. population

were used for the dietary exposure risk

determination in infants and children.

The dietary exposure of diflubenzuron

was calculated as 0.000110 and

0.000304 mg/kg/day, respectively for

nursing and non-nursing infants. These

values are 0.6% and 1.5%, respectively

of the RfD for diflubenzuron. The

dietary exposure from diflubenzuron in

children 1 to 6 years and 7 to 12 years

old was determined as 0.000046 mg/kg/

day and 0.000033 mg/kg/day,

respectively. These values are 0.2% of

the RfD.

As previously discussed, the NOAELs

for maternal and developmental toxicity

in rats and rabbits were greater than

1,000 mg/kg/day, and the NOAEL for

reproductive toxicity was greater than

5,000 mg/kg/day. Therefore, based on

the completeness and reliability of the

toxicity data and the conservative

exposure assessment, Uniroyal

concludes that there is reasonable

certainty that no harm will result in

infants and children from aggregate

exposure to residues of diflubenzuron

and its conversion products containing

the p-chloroaniline moiety.

F. International Tolerances

There is a Codex maximum residue

limit (MRL) for pears at 1.0 mg/kg, a

Mexican MRL at 1.0 mg/kg, and no

limits set for Canada for pears. A Codex

MRL has also been established for

plums (including prunes) at 1.0 mg/kg.

There are no Codex maximum residue

limits established for other stonefruit,

tree nuts or peppers.

[FR Doc. 01–30914 Filed 12–13–01; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[PF–1057; FRL–6812–4]

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.

DATES: Comments, identified by docket

control number PF–1057, must be

received on or before January 14, 2002.

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–1057 in the subject line on the first

page of your response.

FOR FURTHER INFORMATION CONTACT: By

mail: Dani Daniel, Registration Division

(7505C), Office of Pesticide Programs,

Environmental Protection Agency, 1200

Pennsylvania Ave., NW., Washington,

DC 20460; telephone number: (703)

305–5409; e-mail address:

daniel.dani@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

Categories NAICS

codes

Examples of potentially affected entities

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’’ 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–

1057. 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.