Federal Register / Vol. 65, No. 235 / Wednesday, December 6, 2000 / Notices 76253

certainty that no harm will result to

infants, children or adults from dietary

food consumption exposure to

clomazone residues from tuberous and

corm vegetable (except potato) crop

subgroup and cucurbit vegetable crop

group plus all other clomazone treated

human dietary food sources.

F. International Tolerances

There are Codex residue limits for

residues of clomazone in or on oilseed

rape, potatoes, tobacco, soybeans, rice,

cottonseed, sugarcane and peas.

[FR Doc. 00–31058 Filed 12–5–00; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[PF–983; FRL–6573–7]

Notice of Filing Pesticide Petitions to

Establish and to Extend Tolerances for

Certain Pesticide Chemicals in or on

Food

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of pesticide petitions

proposing the establishment of

regulations for residues of certain

pesticide chemicals in or on various

food commodities.

DATES: Comments, identified by docket

control number PF–983, must be

received on or before January 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–983 in the subject line on the first

page of your response.

FOR FURTHER INFORMATION CONTACT: For

Pesticide Petition (PP 9F5079) contact:

Cynthia Giles-Parker, Registration

Division (7505C), Office of Pesticide

Programs, Environmental Protection

Agency, 1200 Pennsylvania Ave., NW.,

Washington DC 20460; Telephone

number: (703) 305–7740; e-mail address:

giles-parker.cynthia@epa.gov.

For Pesticide Petitions (PP 8F3654

8F3674) contact: Mary Waller,

Registration Division (7505C), Office of

Pesticide Programs, Environmental

Protection Agency, 1200 Pennsylvania

Ave., NW., Washington DC 20460;

Telephone number: (703) 308–9354; email address: waller.mary@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

You may be affected by this action if

you are an agricultural producer, food

manufacturer or pesticide manufacturer.

Potentially affected categories and

entities may include, but are not limited

to:

Categories NAICS

codes

Examples of potentially affected

entities

Industry 111 Crop production

112 Animal production

311 Food manufacturing

32532 Pesticide manufacturing

This listing is not intended to be

exhaustive, but rather provides a guide

for readers regarding entities likely to be

affected by this action. Other types of

entities not listed in the table could also

be affected. The North American

Industrial Classification System

(NAICS) codes have been provided to

assist you and others in determining

whether or not this action might apply

to certain entities. If you have questions

regarding the applicability of this action

to a particular entity, consult the person

listed under FOR FURTHER INFORMATION

CONTACT.

B. How Can I Get Additional

Information, Including Copies of this

Document and Other Related

Documents?

1. Electronically. You may obtain

electronic copies of this document, and

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–

983. 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 (CM #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–983 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, CM#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–983. 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.

76254 Federal Register / Vol. 65, No. 235 / Wednesday, December 6, 2000 / Notices

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 pesticide petitions

as follows proposing the establishment

and/or amendment of regulations for

residues of certain pesticide chemicals

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

these petitions contain data or

information regarding the elements set

forth in section 408(d)(2); however, EPA

has not fully evaluated the sufficiency

of the submitted data at this time or

whether the data supports 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 21, 2000.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

Summaries of Petitions

Petitioner summaries of the pesticide

petitions are printed below as required

bysection 408(d)(3) of the FFDCA. The

summaries of the petitions were

prepared by the petitioners and

represent the views of the petitioners.

EPA is publishing the petition

summaries verbatim without editing

them 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.

1. ISK Biosciences Corporation (PP

9F5079)

Summary of Petition

EPA has received a pesticide petition

(PP 9F5079) from ISK Biosciences

Corporation, 5970 Heisley Road, Suite

200, Mentor, Ohio, 44060, 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 part

180 by establishing a tolerance for

residues of fluazinam in or on the raw

agricultural commodities potato and

peanut at 0.02 parts per million (ppm)

and wine grapes at 3.0 ppm. EPA has

determined that the petition contains

data or information regarding the

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

the FFDCA; however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data supports granting of the

petition. Additional data may be needed

before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The residue of

concern is best defined as the parent,

fluazinam. The metabolism of fluazinam

in plants (potatoes, peanuts, and wine

grapes) is adequately understood for the

purposes of these tolerances. The

metabolism of fluazinam involves initial

reduction of the nitro groups, hydrolysis

of the trifluoromethyl group as well as

replacement of chlorine by glutathione

with subsequent reactions along the

glutathione pathway. Parent fluazinam

is rapidly degraded and is either not

found or barely detectable in peanuts

and potatoes. Fluazinam parent was the

major identifiable residue in a grape

metabolism study. Identifiable residues

in plant metabolism studies either

closely resemble fluazinam in structure

or are the result of re-incorporation of

the fluazinam carbon pool into natural

products.

Ruminant and poultry metabolism

studies demonstrated that the

transmittal of residues from the feed of

goats and hens through to meat, milk,

and eggs was low. Total 14C residues

were below 1 ppm in all tissues, milk

and eggs. Identifiable residues were less

than 2% of the administered dose in all

matrices, except for chicken fat and

liver.

2. Analytical method. An analytical

method using gas chromatography with

electron capture detection (GC-ECD) for

the determination of fluazinam residues

on potatoes, peanuts, grapes and the

processing fractions thereof has been

developed and validated. The method

involves solvent extraction followed by

liquid-liquid partitioning and

concentration prior to a final

purification using column

chromatography. The method has been

successfully validated by an

independent laboratory using peanut

nutmeat as the matrix. The limit of

quantitation of the method is 0.02 ppm

in peanuts and 0.01 ppm in potatoes

and grapes.

3. Magnitude of residues—i. Potatoes.

Data from 11 field trials in potatoes

showed that mean fluazinam residues

from duplicate samples were <0.01 ppm

in the RAC commodity at all locations.

The result of a processing study using

a 3.5X application rate showed no

concentration into the processing

fractions dry peels, french fries and

chips. A calculated processing factor of

2.4 for the animal feed commodity wet

peels was determined based on residue

levels just slightly above the limit of

quantitation.

ii. Peanuts. A total of 15 field trials

were conducted over three growing

seasons at nine sites representative of

peanut production. Residues of

fluazinam in nutmeat from all location

were below 0.01 ppm. Residues in

peanut hay, a grazing restriction

commodity, ranged from 0.16 to 10.2

ppm in the six locations where it was

harvested. In a processing study,

residues concentrated 3x in crude oil

and 5x in soapstock, but did not

concentrate in refined oil or presscake.

iii. Wine grapes. A total of 20 field

trials were conducted over three

growing seasons in major wine grape

growing regions worldwide. Residues of

fluazinam in grapes ranged from 0.03 to

2.27 ppm. Vinification of grapes from

two locations showed a reduction of

fluazinam in wine to non-detectable

levels.

iv. Secondary residues. Since levels of

fluazinam in potatoes and peanut

nutmeat were below detectable levels

Federal Register / Vol. 65, No. 235 / Wednesday, December 6, 2000 / Notices 76255

(the fluazinam label includes a peanut

hay grazing restriction, and only wine

grapes which are imported are included

in this tolerance petition), no residues of

concern are expected on animal feed

items. Furthermore, since animal

metabolism studies do not show

potential for significant residue transfer,

detectable secondary residues in animal

tissues, milk or eggs are not expected.

Therefore, tolerances are not needed for

these commodities.

B. Toxicological Profile

1. Acute toxicity. A battery of acute

toxicity studies was conducted which

placed technical fluazinam in Toxicity

Category III for oral LD50, dermal LD50,

dermal irritation, Category II for

inhalation LC50 and Category I for eye

irritation. Technical fluazinam showed

potential for dermal sensitization.

In an acute neurotoxicity study, the

no observed affect effect level (NOAEL)

for neurotoxicity was 2,000 milligram/

kilogram (mg/kg) highest dose tested

(HDT) and the NOAEL for systemic

effects was 50 mg/kg.

2. Genotoxicty. A battery of tests has

been conducted to assess the genotoxic

potential of technical fluazinam. Assays

conducted included two gene mutation

tests in bacteria, a chromosomal

aberration test in mammalian cells, a

mouse micronucleus test and a DNA

repair test in bacteria. Technical

fluazinam did not elicit a genotoxic

response in any of the studies

conducted.

3. Reproductive and developmental

toxicity. In a 2–generation reproductive

toxicity study, the NOAEL for

reproductive effects was 100 ppm (10.1

mg/kg/day). The NOAEL for parental

toxicity was 20 ppm (2.1 mg/kg/day).

In a rat developmental study, there

were no developmental effects observed

at non-maternally toxic doses. The

developmental NOAEL was 50 mg/kg/

day and the lowest observed adverse

effect level (LOAEL) was 250 mg/kg/

day, based upon statistically significant

decreased mean fetal body weight and

other evidence suggestive of delayed

fetal development related to maternal

toxicity. The maternal NOAEL was

shown to be 50 mg/kg/day.

In a rabbit developmental study, there

were no developmental effects observed

at non-maternally toxic doses. The

developmental NOAEL was 7 mg/kg/

day and the LOAEL was 12 mg/kg/day,

based on increased incidence of total

litter loss and possible slightly

increased incidences of fetal findings at

this dose. It was concluded that the

maternal NOAEL was 4 mg/kg/day.

4. Subchronic toxicity. The NOAEL

for the 13 week feeding study in rats

was 50 ppm (4.1 mg/kg/day). The

LOAEL was 500 ppm (41 mg/kg/day),

based on periacinar hepatocellular

hypertrophy and sinusoidal chronic

inflammation in males, increased liver

weights in males and increased lung

weights in females.

In a 13 week dog study, the NOAEL

was 10 mg/kg/day. The LOAEL was 100

mg/kg/day, based on ocular change

observed ophthalmoscopically and liver

effects consisting of increased relative

liver to body weight, bile duct

hyperplasia with or without

cholangiofibrosis and increased plasma

phosphatase levels.

In a 21 day dermal study, the NOAEL

for systemic effects was 10 mg/kg/day.

The LOAEL was 100 mg/kg/day, based

on hepatocelluar hypertrophy and

increases in AST and cholesterol levels.

In a subchronic neurotoxicity study,

no effects considered to be indicative of

neurotoxicity were observed at the

highest dose tested, 3,000 ppm (233 mg/

kg/day). The NOAEL for systemic

toxicity (body weight differences) was

1,000 ppm (74 mg/kg/day).

5. Chronic toxicity. Fluazinam was

not carcinogenic in rats. A NOAEL of 10

ppm (0.43 mg/kg/day) of fluazinam was

established based on the following

effects at 1,000 and/or 100 ppm: lower

food consumption and efficiency of food

utilization, slight anemia, elevated

cholesterol, increased liver weights, an

increased number of macroscopic liver

and testes lesions and an increased

incidence of microscopically observed

lung, liver, pancreas, lymph node and

testes lesions.

An additional study was conducted to

further define the NOAEL for long-term

effects in the rat. In the second study,

a NOAEL of 50 ppm (2.2 mg/kg/day)

was established based on liver and

testes effects.

Two long-term feeding studies were

conducted in mice. In the first, the

NOAEL for all effects was 10 ppm (1.14

mg/kg/day) and the LOAEL was 100

ppm (11.2 mg/kg/day) based on the

treatment-related effects observed in the

liver.

A second oncogenicity study in mice

was conducted at 1,000, 3,000 and 7,000

ppm to ensure that an maximum

tolerance dose (MTD) was studied.

Findings included increased female

mortality, reduced body weight gains,

increased brain weights and/or liver

weights. An impurity in the test

material used in this study resulted in

vacuolation of the white matter of the

brain and cervical spinal cord in treated

animals. A statistically significant

higher incidence of hepatocellular

adenomas was observed in the 3,000

ppm dose males. Hepatocellular

adenomas are common tumors in male

mice. There was no dose relationship in

the induction of the adenoma and no

increase in hepatocellular carcinomas. It

was concluded that fluazinam is not

carcinogenic in the mouse.

In a chronic dog study, the NOAEL

was determined to be 1 mg/kg/day. The

LOAEL was 10 mg/kg/day based on

generalized, nonspecific toxicity. No

ocular effects were observed

ophthalmoscopally at any dose in this

study.

6. Animal metabolism. After an oral

dose of fluazinam the median peak time

for blood concentration of radiolabel

activity for both sexes was 6 hours. The

major route of excretion was the feces

with urine contributing as a minor

route. Less than 1% of the administered

dose was found in the terminated

animals. The highest concentration was

found in the liver. There were no major

differences related to sex or dose level

in the findings. It was concluded that

fluazinam is metabolized by both

reduction and glutathione and

glucuronide conjugation and further

metabolism.

7. Metabolite toxicology. The same

metabolic processes occur in plants and

animals but metabolism in plants is

more extensive than in animals. All of

the major identified metabolites in both

plants and animals retain the

phenylpyridinylamine structure. Many

of the metabolites resulting from

fluazinam are similar in plants and

animals and, therefore, have already

been evaluated toxicologically.

Because of the rapid and complete

elimination (in animals) and reincorporation (in plants) of fluazinam,

the toxicity of metabolites is expected to

be similar to but lower than the toxicity

of the parent compound. The residue of

concern is parent fluazinam only.

8. Endocrine disruption. The

toxicological profile of fluazinam shows

no evidence of physiological effects

characteristic of the disruption of the

hormone estrogen in mammalian

chronic studies or in mammalian or

avian reproduction studies. It is

therefore considered that there is an

adequate level of safety over the

reference dose for possible endocrine

effects and that an additional safety

factor for possible endocrine effects is

not warranted.

C. Aggregate Exposure

1. Dietary exposure. An RfD of 0.01

mg/kg/day is proposed for humans,

based on the NOAEL from the one year

dog study (1 mg/kg/day) and dividing

by an uncertainty factor of 100.

i. Food—a. Acute risk. Tier 1 acute

dietary exposure analyses were

76256 Federal Register / Vol. 65, No. 235 / Wednesday, December 6, 2000 / Notices

conducted for fluazinam in/on peanuts,

potatoes and imported wine grapes to

determine the exposure contribution of

these commodities to the diet and to

ascertain the acute risk potential. The

estimates were based on proposed

tolerance level residues for all three

crops, peanut and potato processing

studies, market share assumptions of

100% crop treated, and consumption

data from the 1994 through 1996 USDA

continuing survey of food intake.

Even using all of the worst case

exposure scenarios listed above, the Tier

1 acute assessment for the U.S.

population resulted in a margin of safety

(MOS) of 270,507 at the 95th percentile.

This corresponded to an estimated

exposure of 0.000185 mg/kg/day. The

highest acute exposure estimate (95th

percentile) was observed in the seniors

(55 years and over) subpopulation:

0.001285 mg/kg/day. This correlates to

an MOE of 38,908.

b. Chronic risk. Tier 1 dietary

exposure analyses were conducted for

fluazinam in/on peanuts, potatoes and

imported wine grapes to determine the

exposure contribution of these

commodities to the diet and to ascertain

the chronic risk potential. The estimates

were based on proposed tolerance level

residues for all three crops, peanut and

potato processing studies, market share

assumptions of 100% crop treated, and

consumption data from the 1994

through 1996 USDA continuing survey

of food intake.

Even using all of the worst case

exposure scenarios listed above, the Tier

1 chronic dietary exposure estimates

resulted in an estimated exposure for

the U.S. population of 0.000104 mg/kg/

day. This exposure corresponds to 1.0%

of the reference dose (RfD) of 0.01mg/

kg/day. The highest exposure estimate

was calculated for the Females 20+

years (non-pregnant/non-nursing)

population subgroup. This exposure

was determined to be 0.000156 mg/kg/

day (1.6% of the RfD).

It can be concluded that acute or longterm dietary exposure to fluazinam

through residues on treated peanuts,

potatoes and imported wine grapes

should not be of cause for concern.

ii. Drinking water. Since fluazinam is

intended for application outdoors to

field grown peanut and potato crops, the

potential exists for parent and or

metabolites to reach ground or surface

water that may be used for drinking

water. The calculated drinking water

levels of concern (DWLOC) for chronic

exposure for adult males, adult females

and toddlers were estimated to be 355

parts per billion (ppb), 296 ppb, and 149

ppb, respectively. The calculated

DWLOCs for acute exposure for all

adults, adult females and toddlers were

estimated to be 17,943 ppb, 14,993 ppb,

and 7,497 ppb, respectively. The

chronic and acute DWLOC values are

well above the modeled chronic and

acute DWECs of 0.17 ppb (GENEEC 56–

day/3) and 15.1 ppb (GENEEC

instantaneous value), respectively.

Therefore, there is comfortable certainty

that no harm will result from combined

dietary (food and water) exposure due to

the use of fluazinam on peanuts,

potatoes and imported wine grapes.

2. Non-dietary exposure. No petition

for registration of fluazinam is being

made for either indoor or outdoor

residential use. Non-occupational

exposure of fluazinam to the general

population is therefore not expected and

is not considered in aggregate exposure

estimates.

D. Cumulative Effects

Fluazinam is a phenylpyridinylamine

fungicide. Since there are no other

members of this class of fungicides, it is

considered unlikely that fluazinam

would have a common mechanism of

toxicity with any other pesticide in use

at this time.

E. Safety Determination

1. U.S. population. Based on a

NOAEL of 1 mg/kg bwt/day from a one

year feeding study in dogs, and using an

uncertainty factor of 100, a reference

dose of 0.01 mg/kg bwt/day is proposed

for assessment of long-term risk. The

estimate of dietary intake was based on

proposed tolerance level residues for all

three crops, peanut and potato

processing studies, market share

assumptions of 100% crop treated and

consumption data. Even using those

conservative intake estimates, the

proposed tolerances will utilize only

1% of the RfD for the U.S. population.

The estimated exposure of fluazinam

from drinking water, 0.17 ppb is at least

three orders of magnitude below the

calculated drinking water level of

concern, 355 ppb.

2. Infants and children. Data from

developmental toxicity studies in the rat

and rabbit and a 2–generation

reproduction study were considered.

These studies which were described

earlier, demonstrated no increased

sensitivity of rats or rabbits to in utero

exposure to fluazinam. In addition, the

multigeneration reproductive toxicity

study did not identify any increased

sensitivity of rats to in utero or postnatal

exposure. For all three studies, parental

NOAELs were lower than or equivalent

to the developmental or offspring

NOAELs. It is concluded that the

standard margin of safety will protect

the safety of infants and children and

that an additional safety factor is not

warranted.

The dietary exposure of fluazinam to

infants and children is estimated to be

much lower than adults because 80% to

90% of the exposure is expected from

sherry and wine. The proposed

tolerances will utilize <0.5% of the RfD

for infants and children. The estimated

exposure of fluazinam from drinking

water, 0.17 ppb is three orders of

magnitude below the calculated

drinking water level of concern, 149

ppb.

F. International Tolerances

There are presently no Codex

maximum residue levels established for

residues of fluazinam on any crop.

2. Novartis Crop Protection, Inc.,

Summary of Petitions:

EPA has received two pesticide

petitions (PP 8F3654, PP 8F3674) from

Novartis Crop Protection, Inc., P.O. Box

18300, Greensboro, NC 27419

proposing,pursuant to section 408(d) of

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

40 CFR part 180 by extending the

expiration date for tolerances for

residues of propiconazole in or on the

raw agricultural commodities corn,

field, stover (12.0 parts per million

(ppm)); corn, field, forage (12.0 ppm);

corn, field, grain (0.1 ppm); corn, sweet

(0.1 ppm); pineapple (0.1 ppm);

pineapple, fodder (0.1 ppm) (PP

8F3674); peanut (0.2 ppm); peanut, hay

(20 ppm); and peanut, hulls (1.0 ppm)

(PP 8F3654). EPA has determined that

the petition contains data or information

regarding the elements set forth in

section 408(d)(2) of the FFDCA;

however,EPA has not fully evaluated

the sufficiency of the submitted data at

this time or whether the data supports

granting of the petition. Additional data

may be needed before EPA rules on the

petition.

A. Residue Chemistry

1. Plant metabolism. Novartis believes

the studies supporting propiconazole

adequately characterize metabolism in

plants and animals. The metabolism

profile supports the use of an analytical

enforcement method that accounts for

combined residues of propiconazole and

its metabolites which contain the 2,4-

dichlorobenzoic acid (DCBA) moiety.

2. Analytical method. Novartis has

submitted a practical analytical method

involving extraction, filtration,

conversion, partition, derivitization, and

solid phase cleanup with analysis by

confirmatory gas chromatography using

electron capture detection (ECD). The

total residue method is used for

Federal Register / Vol. 65, No. 235 / Wednesday, December 6, 2000 / Notices 76257

determination of propiconazole and its

metabolites. The limit of quantitation

(LOQ) for the method is 0.05 ppm.

3. Magnitude of residues. Field

residue trials have been conducted at

various rates, timing intervals, and

applications methods to represent the

use patterns which would most likely

result in the highest residues. For all

samples, the total residue method was

used for determination of the combined

residues of parent and its metabolites

which contain the DCBA moiety.

B. Toxicological Profile

1. Acute toxicity. Propiconazole

exhibits low toxicity. Data indicated the

following: a rat acute oral LD50 of 1,517

milligrams/kilograms (mg/kg); a rabbit

acute dermal LD50 > 6,000 mg/kg; a rat

inhalation LC50 >5.8 g/liter air; minimal

skin and slight eye irritation; and

nonsensitization.

2. Genotoxicty. Propiconazole exhibits

no mutagenic potential based on the

following data: In vitro gene mutation

test (Ames assay, rat hepatocyte DNA

repair test, (human fibroblast DNA

repair test), In vitro chromosome test,

(human lymphocyte cytogenetic test), In

vivo mutagenicity test, (Chinese hamster

bone marrow cell nucleus anomaly test,

Chinese hamster bone marrow cell

micronucleus test, mouse dominant

lethal test), and other mutagenicity test

(BALB/3T3 cell transformation assay).

3. Reproductive and developmental

toxicity. In an oral teratology study in

the rabbit, a maternal no observed

adverse effect level (NOAEL) of 30 mg/

kg was based on reduced food intake but

without any fetotoxicity even at the top

dose of 180 mg/kg. In an oral teratology

study in the rabbit, a maternal NOAEL

of 100 mg/kg was based on reductions

in body weight gain and food

consumption and a fetal NOAEL of 250

mg/kg was based on increased skeletal

variations at 400 mg/kg. In an oral

teratology study in the rat, a maternal

and fetal NOAEL of 100 mg/kg was

based on decreased survival, body

weight gain, and food consumption in

the dams and delayed ossification in the

fetuses at 300 mg/kg. In a second

teratology study in the rat, a maternal

and fetal NOAEL of 30 mg/kg was based

on reductions in body weight gain and

food consumption in the dams and

delayed development in the fetuses at

90 and 360/300 mg/kg. A supplemental

teratology study in the rat involving

eight times as many animals per group

as usually required showed no

teratogenic potential for the compound.

A 2-generation reproduction study in

the rat showed excessive toxicity at

5,000 ppm without any teratogenic

effects. A 2-generation reproduction

study in the rat showed no effects on

reproductive or fetal parameters at any

dose level. Postnatal growth and

survival were affected at the top dose of

2,500 ppm, and parental toxicity was

also evident. The NOAEL for

development toxicity is 500 ppm.

4. Subchronic toxicity. In a 21 day

dermal study in the rabbit, a NOAEL of

200 mg/kg was based on clinical signs

of systemic toxicity. In a 28 day oral

toxicity study in the rat, a NOAEL of 50

mg/kg was based on increased liver

weight. In a subchronic feeding study in

the mouse, a NOAEL of 20 ppm (3 mg/

kg) was based on liver pathologic

changes. In a 13 week feeding study in

the male mouse, a NOAEL of 20 ppm (3

mg/kg) was based on liver pathologic

changes. In a 90 day feeding study in

rats, the NOAEL was 240 ppm (24 mg/

kg) based on a reduction in body weight

gain. In a 90 day feeding study in

dogs,the NOAEL was 250 ppm (6.25 mg/

kg) based on reduced food intake and

stomach histologic changes.

5. Chronic toxicity. In a 12 month

feeding study in the dog, a NOAEL of

50 ppm (1.25 mg/kg) was based on

stomach histologic changes. In a 24

month oncogenicity feeding study in the

mouse, the NOAEL was 100 ppm (15

mg/kg). The MTD was exceeded at 2,500

ppm in males based on decreased

survival and body weight. Increased

incidence of liver tumor was seen in

these males but no evidence of

carcinogenicity was seen at the next

lower dose of 500 ppm in either sex. In

a 24 month chronic feeding/

oncogenicity study in the rat, a NOAEL

of 100 ppm (5 mg/kg) was based on

body weight and blood chemistry. The

MTD was 2,500 ppm based on reduction

in body weight gain and no evidence of

oncogenicity was seen. Based on the

available chronic toxicity data, Novartis

believes the Reference dose (RfD) for

propiconazole is 0.0125 mg/kg/day.

This RfD is based on a 1 year feeding

study in dogs with a NOAEL of 1.25 mg/

kg/day (50 ppm) and an uncertainly

factor of 100. No additional modifying

factor for the nature of effects was

judged to be necessary as stomach

mucous hyperemia was the most

sensitive indicator of toxicity in that

study.

Using the Guidelines for Carcinogenic

Risk Assessment published on

September 24, 1986 (51 FR 33992), the

USEPA has classified propiconazole in

group C for carcinogenicity (evidence of

possible carcinogenicity for humans).

The compound was tested in 24 month

studies with both rats and mice. The

only evidence of carcinogenicity was an

increase in liver tumor incidence in

male mice at a dose level that exceeded

the maximum tolerated dose (MTD).

Dosage levels in the rat study were

appropriate for identifying a cancer risk.

The Cancer Peer Review Committee

recommended the RfD approach for

quantitation of human risk. Therefore,

the RfD is deemed protective of all

chronic human health effects, including

cancer.

C. Aggregate Exposure

1. Dietary exposure. The RfD for

propiconazole is 0.0125 mg/kg/day and

is based on a 1 year feeding study in

dogs with a NOAEL of 1.25 mg/kg/day

(50 ppm) and an uncertainly factor of

100.

i. Food—Acute risk. The risk from

acute dietary exposure to propiconazole

is considered to be very low. The lowest

NOAEL in a short term exposure

scenario, identified as 30 mg/kg in the

rat teratology study, is 24-fold higher

than the chronic NOAEL. Based on

worst-case assumptions, the chronic

exposure assessment did not result in

any margin of exposure (MOE) less than

150 for even the most impacted

population subgroup. Novartis believes

that the MOE for acute exposure would

be more than 100 for any population

groups; MOE of 100 or more are

considered satisfactory.

ii. Chronic risk. For the purposes of

assessing the potential dietary exposure

under the existing, pending, and

proposed tolerances for the residue of

propiconazole and its metabolites

determined as 2,4-dichlorobenzoic acid,

Novartis has estimated aggregate

exposure based upon the Theoretical

Maximum Residue Concentration

(TMRC). The TMRC is a ‘‘worst case’’

estimate of dietary exposure since it

assumes 100% of all crops for which

tolerances are established are treated

and that pesticide residues are at the

tolerance levels, resulting in an

overestimation of human exposure.

Currently established tolerances range

from 0.05 ppm in milk to 60 ppm in

grass seed screenings and include:

apricots (1.0 ppm); bananas (0.2 ppm);

barley grain (0.1 ppm); barley straw (1.5

ppm); cattle kidney and liver (2.0 ppm);

cattle meat, fat, and meat by products

except kidney and liver (0.1 ppm);

celery (5.0 ppm); corn forage and fodder

(12.0 ppm); corn grain and sweet (0.1);

eggs (0.1 ppm); goat kidney and liver

(2.0 ppm); goat meat, fat, and meat by

products except kidney and liver (0.1

ppm); grass forage (0.5 ppm); grass hay/

straw (40.0 ppm); grass seed screenings

(60.0 ppm); hogs kidney and liver (2.0

ppm); hog meat, fat, and meat by

products except kidney and liver (0.1

ppm); horses kidney and liver (2.0

ppm); horse meat, fat, and meat by

76258 Federal Register / Vol. 65, No. 235 / Wednesday, December 6, 2000 / Notices

products except kidney and liver (0.1

ppm); milk (0.05 ppm); mint tops (0.3

ppm - regional tolerance west of

Cascade Mountains); mushrooms (0.1

ppm); nectarines (1.0 ppm); oat forage

(10.0 ppm); oat grain (0.1 ppm); oat hay

(30.0 ppm); oat straw (1.0 ppm); peaches

(1.0 ppm); peanut hay (20.0 ppm);

peanut hulls (1.0 ppm); peanuts (0.2

ppm);, pecans (0.1 ppm); pineapple (0.1

ppm); pineapple fodder (0.1 ppm);

plums (1.0 ppm); poultry liver and

kidney (0.2 ppm); poultry meat, fat, and

meat by products except kidney and

liver (0.1 ppm); prunes, fresh (1.0 ppm);

rice grain (0.1 ppm); rice straw (3.0

ppm); wild rice (0.5 ppm regional

tolerance Minnesota); rye grain (0.1

ppm); rye straw (1.5 ppm); sheep kidney

and liver (2.0 ppm); sheep meat, fat, and

meat by products except kidney and

liver (0.1 ppm); stone fruit crop group

12 (1.0 ppm); wheat grain (0.1 ppm);

and wheat straw (1.5 ppm). In addition,

time-limited regional tolerances for

sorghum grain and stover at 0.1 ppm

and 1.5 ppm, respectively were

established to support a section 18

Crisis exemption in Texas (expiration

date December 31, 2000) and Nebraska,

Kansas, and Oklahoma (expiration date

September 30, 2000).

Additional uses of propiconazole

have been requested in several pending

petitions. Proposed tolerances include:

PP 5F4424 for use of propiconazole on

dry bean and soybean - dry bean forage

(8.0 ppm); dry bean hay (8.0 ppm); dry

bean vines (0.5 ppm); dry bean (0.5

ppm), soybeans (0.5 ppm); soybean

fodder (8.0 ppm); soybean forage (8.0

ppm); soybean hay (25.0 ppm); and

soybean straw (0.1 ppm); PP 5F4591 for

use of propiconazole on berries, carrots

and onions - berry crop grouping (1.0

ppm); dry bulb onion (0.3 ppm); green

onion (8.0); PP 5F3740 - tree nut crop

grouping (0.1 ppm); PP 5F4498 -

inadvertent/rotational crop tolerances

for alfalfa forage (0.1 ppm), alfalfa hay

(0.1 ppm), grain sorghum fodder (0.3

ppm), grain sorghum forage (0.3 ppm)

and grain sorghum grain (0.2 ppm).

ii. Drinking water. Other potential

sources of exposure of the general

population to residues of propiconazole

are residues in drinking water and

exposure from non-occupational

sources. Review of environmental fate

data by the Environmental Fate and

Effects Division of USEPA indicates that

propiconazole is persistent and

moderately mobile to relatively

immobile in most soil and aqueous

environments. No Maximum

Concentration Level (MCL) currently

exists for residues of propiconazole in

drinking water and no drinking water

health advisory levels have been

established for propiconazole.

The degradation of propiconazole is

microbially mediated with an aerobic

soil metabolism half-life of 70 days.

While propiconazole is hydrolytically

and photochemically stable (T c >100

days), it binds very rapidly and tightly

to soil particles following application.

Adsorption/desorption and aged

leaching data indicate that

propiconazole and its degradates will

primarily remain in the top 0–6 inches

of the soil. It has been determined that

under field conditions propiconazole

will degrade with a half-life of

approximately 100 days.

2. Non-dietary exposure.

Propiconazole is registered for

residential use as a preservative

treatment for wood and for lawn and

ornamental uses. At this time, no

reliable data exist which would allow

quantitative incorporation of risk from

these uses into a human health risk

assessment. The exposure to

propiconazole from contacting treated

wood products is anticipated to be very

low since the surface of wood is usually

coated with paint or sealant when used

in or around the house. The nonoccupational exposure from lawn and

ornamental applications is also

considered to be minor. It is estimated

that less than 0.01% of all households

nationally use propiconazole in a

residential setting.

D. Cumulative Effects

Consideration of a common

mechanism of toxicity is not appropriate

at this time since there is no reliable

information to indicate that toxic effects

produced by propiconazole would be

cumulative with those of any other

types of chemicals. While other triazoles

are available on the commercial or

consumer market, sufficient structural

differences exist among these

compounds to preclude any categorical

grouping for cumulative toxicity.

Consequently, Novartis is considering

only the potential risks of propiconazole

in its aggregate exposure assessment.

E. Safety Determination

1. U.S. population—Reference dose.

Using the conservative exposure

assumptions described above (100%

stone fruit acres treated and tolerance

level residues) and based on the

completeness and reliability of the

toxicity data base for propiconazole,

Novartis has calculated aggregate

exposure levels for this chemical. The

calculation shows that only 16% of the

RfD will be utilized for the U.S.

population based on chronic toxicity

endpoints. EPA generally has no

concern for exposures below 100% of

the RfD because the RfD represents the

level at or below which daily aggregate

dietary exposure over a lifetime will not

pose appreciable risks to human health.

Novartis concludes that there is a

reasonable certainty that no harm will

result from aggregate exposure to

propiconazole residues.

2. Infants and children.

Developmental toxicity (e.g., reduced

pup weight and ossification) was

observed in the rat teratology studies

and 2–generation rat reproduction

studies at maternally toxic doses. Some

of these findings are judged to be

nonspecific, secondary effects of

maternal toxicity. The lowest NOAEL

for developmental toxicity was

established in the rat teratology study at

30 mg/kg, a level 24–fold higher than

the NOAEL of 1.25 mg/kg on which the

RfD is based.

3. Reference dose. Using the same

conservative exposure assumptions as

employed for the determination in the

general population, Novartis has

calculated that the percent of the RfD

that will be utilized by aggregate

exposure to residues of propiconazole is

26% for nursing infants less than 1 year

old, 65% for non-nursing infants less

than 1 year old, 35% for children 1–6

years old, and 23% for children 7–12

years old. Therefore, based on the

completeness and reliability of the

toxicity data base and the conservative

exposure assessment, Novartis

concludes that there is a reasonable

certainty that no harm will result to

infants and children from aggregate

exposure to propiconazole residues.

F. International Tolerances

International CODEX values are

established for almond, animal

products, bananas, barley, coffee, eggs,

grapes, mango, meat, milk, oat, peanutwhole, peanut grains, pecans, rape, rye,

stone fruit, sugar cane, sugar beets,

sugar beet tops, and wheat. The U.S.

residue definition includes both

propiconazole and metabolites

determined as 2,4-dichlorobenzoic acid

(DCBA), while the CODEX definition is

for propiconazole, per se, i.e. parent

only. This difference results in unique

tolerance expressions with the U.S.

definition resulting in the higher

tolerance levels.

[FR Doc. 00–31056 Filed 12–5–00; 8:45 am]

BILLING CODE 6560–50–S