Federal Register / Vol. 65, No. 81 / Wednesday, April 26, 2000 / Notices 24471

(NTIS) ATTN: Order Desk 5285 Port

Royal Road, Springfield, VA 22161.

Telephone: 1–800–553–6847. When

requesting a document from NTIS,

please provide its name and NTIS

Publication Number (PB). The NTIS

Publication for this version of the

Pesticide Data Submitters List is PB

2000–102113.

2. Electronically: The Pesticide Data

Submitters List is available of EPA’s

World Wide Web (WWW) site on the

Internet. The Internet address of EPA’s

web site is www.epa.gov. To Access the

Data Submitters List from the EPA

Home Page, select ‘‘Databases and

Software.’’ From the next page, select

‘‘Media Specific.’’

The Pesticide Data Submitters list

may be found by searching for the

keywords ‘‘datasubmitterslist’’ from the

EPA Home Page, or may be access

directly on the EPA web site, by going

directly to the address listed below.

Note that this address is case sensitive.

http://www.epa.gov./oppmsd1/

datasubmitterslist/index.html.

II. What Action is the Agency Taking?

The Pesticide Data Submitters List is

a compilation of names and addresses of

registrants who wish to be notified and

offered compensation for use of their

data. It was developed to assist pesticide

applicants in fulfilling their obligation

as required by sections 3(c)(1)(f) and

3(c)(2)(D) of the Federal Insecticide,

Fungicide, and Rodenticide Act (FIFRA)

and 40 CFR part 152 subpart E regarding

ownership of data used to support

registration. This notice announces the

availability of an updated version of the

Pesticide Data Submitters List which

supersedes and replaces all previous

versions.

List of Subjects

Environmental protection,

Administrative practice and procedure,

Pesticides and pests, Reporting and

recordkeeping requirements.

Dated: April 5, 2000.

Richard D. Schmitt,

Acting Director, Information Resources and

Services Division, Office of Pesticide

Programs.

[FR Doc. 00–10189 Filed 4–25–00; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–938; FRL–6554–2]

Notice of Filing a Pesticide Petition to

Establish a Tolerance for Certain

Pesticide Chemicals in or on Food

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

amended filing of a pesticide petition

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–938, must be

received on or before May 26, 2000.

ADDRESSES: Comments may be

submitted by mail, electronically, or in

person. Please follow the detailed

instructions for each method as

provided in Unit I.C. of the

‘‘SUPPLEMENTARY INFORMATION.’’

To ensure proper receipt by EPA, it is

imperative that you identify docket

control number PF–938 in the subject

line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By

mail: Susan Stanton, Registration

Division (7505C), Office of Pesticide

Programs, Environmental Protection

Agency, Ariel Rios Bldg., 1200

Pennsylvania Ave., NW., Washington,

DC 20460; telephone number: (703)

305–5218; e-mail address:

stanton.susan@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 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–

938. 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–938 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

24472 Federal Register / Vol. 65, No. 81 / Wednesday, April 26, 2000 / Notices

(7502C), Office of Pesticide Programs

(OPP), Environmental Protection

Agency, Ariel Rios Bldg., 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–938. Electronic comments

may also be filed online at many Federal

Depository Libraries.

D. How Should I Handle CBI That I

Want to Submit to the Agency?

Do not submit any information

electronically that you consider to be

CBI. You may claim information that

you submit to EPA in response to this

document as CBI by marking any part or

all of that information as CBI.

Information so marked will not be

disclosed except in accordance with

procedures set forth in 40 CFR part 2.

In addition to one complete version of

the comment that includes any

information claimed as CBI, a copy of

the comment that does not contain the

information claimed as CBI must be

submitted for inclusion in the public

version of the official record.

Information not marked confidential

will be included in the public version

of the official record without prior

notice. If you have any questions about

CBI or the procedures for claiming CBI,

please consult the person identified

under FOR FURTHER INFORMATION

CONTACT.

E. What Should I Consider as I Prepare

My Comments for EPA?

You may find the following

suggestions helpful for preparing your

comments:

1. Explain your views as clearly as

possible.

2. Describe any assumptions that you

used.

3. Provide copies of any technical

information and/or data you used that

support your views.

4. If you estimate potential burden or

costs, explain how you arrived at the

estimate that you provide.

5. Provide specific examples to

illustrate your concerns.

6. Make sure to submit your

comments by the deadline in this

notice.

7. To ensure proper receipt by EPA,

be sure to identify the docket control

number assigned to this action in the

subject line on the first page of your

response. You may also provide the

name, date, and Federal Register

citation.

II. What Action is the Agency Taking?

EPA has received a pesticide petition

as follows proposing the establishment

and/or amendment of regulations for

residues of certain pesticide chemical in

or on various food commodities under

section 408 of the Federal Food, Drug,

and 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 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: April 14, 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 petitioners.

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.

Novartis Crop Protection, Inc.

PP 7F4924

Amended Pesticide Petition

On June 5, 1998, EPA published a

notice that it had received a pesticide

petition (PP 7F4924) from Novartis Crop

Protection, Inc., P.O. Box 18300,

Greensboro, NC 27419 proposing

tolerances for the herbicide clodinafoppropargyl (propanoic acid, 2-[4-[(5-

chloro-3-fluoro-2-

pyridinyl)oxy]phenoxy]-2-propynyl

ester; CGA–184927) in or on the raw

agricultural commodities of wheat. EPA

has received an amendment to PP

7F4924 from Novartis Crop Protection,

Inc., P.O. Box 18300, Greensboro, NC

27419 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 to

increase, as requested by EPA, the

original proposed tolerances; thereby

establishing tolerances for the combined

residues of clodinafop-propargyl and its

acid metabolite, CGA–193469 ((R)-2-[4-

[(5-chloro-3-fluoro-2-

pyridinyl)oxy]phenoxy]-propanoic

acid), in or on the raw agricultural

commodities wheat, grain at 0.1 ppm;

wheat, forage at 0.1 ppm; wheat, hay at

0.1 ppm and wheat, straw at 0.5 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 metabolism

of clodinafop-propargyl in wheat is

understood for the purposes of the

proposed tolerances. Two studies, one

with the racemic mixture of the R (+)

and S (¥) forms and the other with the

pure R (+) form (CGA–184927

pyridyloxy labeled), gave similar

results. Metabolism involves hydrolysis

of the parent to the resulting acid

followed by conjugation,

arylhydroxylation at the 6 position of

the pyridyl ring followed by sugar

conjugation, and cleavage of the

pyridinyloxy-phenoxy ether bridge

which forms the breakdown products 2-

(4-hydroxyphenoxy) propanoic acid and

2-hydroxy-3-fluoro-5-chloropyridine.

2. Analytical method. Novartis has

submitted practical analytical methods

for the determination of clodinafoppropargyl and its major plant metabolite

CGA–193469 in wheat raw agricultural

commodities (RACs). ClodinafopVerDate 18<APR>2000 18:55 Apr 25, 2000 Jkt 190000 PO 00000 Frm 00028 Fmt 4703 Sfmt 4703 E:\FR\FM\26APN1.SGM pfrm01 PsN: 26APN1
Federal Register / Vol. 65, No. 81 / Wednesday, April 26, 2000 / Notices 24473

propargyl is extracted from crops with

acetonitrile, cleaned up by solvent

partition and solid phase extraction and

determined by column switching high

performance liquid chromotography

(HPLC) with ultra violet (UV) detection.

CGA–193469 is extracted from crops

with an acetone-buffer (pH=3) solution,

cleaned up by solvent partition and

solid phase extraction, and determined

by HPLC with UV detection. The limits

of quantitation (LOQ) for the methods

are 0.02 ppm for clodinafop-propargyl

in grain and forage, 0.05 ppm for

clodinafop-propargyl in straw, and 0.05

ppm for CGA–193469 in forage, straw

and grain.

3. Magnitude of residues. Both

Canadian and U.S. spring wheat residue

trials were conducted. Twelve residue

trials were conducted from 1989–1992

in the major spring wheat growing areas

of Manitoba, Alberta and Saskatchewan,

which share compatible crop zones with

the major spring wheat growing areas of

the United States (MT, ND, SD, MN).

Nine trials were conducted in 1989–91

with a tank mix of clodinafop-propargyl

and a safener as separate EC

formulations, and three trials in 1992

were conducted with clodinafoppropargyl and the safener as a pre-pack

EC formulation. All trials had a single

post-emergence application of

clodinafop-propargyl at a rate of 80

gram active ingredient/hectacre (g a.i./

ha).

In 1998, an additional six spring

wheat trials were conducted in the

major growing areas of the United

States. In these trials, clodinafoppropargyl was applied as a single

application of a 240EC formulation at a

rate of 70 g a.i./ha. Samples of 30–day

forage and hay, and mature straw and

grain treated 60 days prior to harvest

were taken for analysis. Grain treated at

an exaggerated rate in one trial was

processed under simulated commercial

processing conditions.

At pre-harvest intervals (PHIs) of 30

days for forage and hay in the U.S.

trials, and 60–97 days for mature straw

and grain in all trials, no detectable

residues of clodinafop-propargyl were

found. Residues of the metabolite CGA–

193469 were detected in mature straw

from four trials, with a maximum

Highest Average Field Trail (HAFT)

residue of 0.35 ppm. Separate decline

studies on green forage in both the

United States and Canada showed no

detectable residues of clodinafoppropargyl or the metabolite CGA–

193469 beyond the 7 days after

application interval. No residues of

clodinafop-propargyl or the metabolite

CGA–193469 were found in mature

grain or grain processed fractions in any

trial.

A freezer storage stability study

indicated reasonable stability of both

analytes for a period of 1 year, with

clodinafop-propargyl showing a decline

to 56% in grain and 47% in straw after

2 years. CGA–193469 remained stable

for at least 2 years.

B. Toxicological Profile

1. Acute toxicity. The acute oral and

dermal LD50 values for clodinafoppropargyl are 1,829 milligrams/

kilograms (mg/kg) and greater than

2,000 mg/kg for rats of both sexes,

respectively. Its acute inhalation LC50 in

the rat is greater than 2.33 milligram/

liter (mg/L), the highest attainable

concentration. Clodinafop-propargyl is

slightly irritating to the eyes, minimally

irritating to the skin of rabbits, but was

found to be sensitizing to the skin of the

guinea pig. This technical will carry the

EPA signal word ‘‘Caution.’’

2. Genotoxicity. The mutagenic

potential of clodinafop-propargyl was

investigated in six independent studies

covering different end points in

eukaryotes and prokaryotes in vivo and

in vitro. These tests included: Ames

reverse mutation with Salmonella

typhimurium and Chinese hamster V79

cells in vitro; chromosomal aberrations

using human lymphocytes in vitro and

the mouse micronucleus test in vivo;

and DNA repair using rat hepatocytes

and human fibroblasts in vitro.

Clodinafop-propargyl was found to be

negative in all these tests and, therefore,

is considered devoid of any genotoxic

potential at the levels of specific genes,

chromosomes, or DNA primary

structure.

3. Reproductive and developmental

toxicity. Dietary administration of

clodinafop-propargyl over 2–generations

at levels as high as 1,000 ppm did not

affect mating performance, fertility, or

litter sizes. Body weight was reduced in

parental animals at 500 and 1,000 ppm.

The physiological developmental and

the survival of the pups during the last

week of the lactation period were

slightly reduced at levels equal to or

greater than 500 ppm during the first

generation only. Target organs were

liver (adults) and kidney (adults and

pups). The treatment had no effect on

reproductive organs. The NOAEL for

toxicity to the parental rats and

offspring was 50 ppm, corresponding to

a mean daily intake of 3.2 mg/kg

clodinafop-propargyl. The NOAEL for

reproductive toxicity was 1,000 ppm

(64.2 milligram/kilogram body weight/

day (mg/kg bw/day)).

In a developmental toxicity study in

rats, the highest dose level of 160 mg/

kg resulted in reduced body weight gain

of the dams and signs of retarded fetal

body weight and incomplete ossification

of vertebrae and sternebrae. No

teratogenic activity of the test article

was detected. Novartis concluded that

the NOAEL for dams and fetuses was 40

mg/kg/day. The EPA’s Hazard

Identification Assessment Review

Committee (HIARC) concluded that

based on an increase in bilateral

distension and torsion of the ureters and

delayed ossification in the fetuses, the

developmental LOAEL was 40 mg/kg/

day and the NOAEL was 5 mg/kg/day.

In a developmental toxicity study in

rabbits, mortality was observed in dams

at dose levels of 125 and 175 mg/kg. No

teratogenic or fetotoxic effects were

noted. Novartis concluded that the

maternal NOAEL was 25 mg/kg/day and

the fetal NOAEL was 175 mg/kg/day.

The HIARC considered that the

developmental NOAEL was 125 mg/kg/

day due to significant mortality at 175

mg/kg/day.

4. Subchronic toxicity. A 90–day

feeding study in rats at 1,000 ppm

resulted in reduced body weight gain,

increased liver weights, hematological

changes, and increased serum activities

of the alkaline phosphatase. Target

organs were liver (increased weight),

thymus (atrophy) and spleen (reduced

weight). The changes were reversible

during 4 weeks of recovery. The NOAEL

was 15 ppm (0.92 mg/kg in males and

0.94 mg/kg in females). The EPA HIARC

suggested the NOAEL in female rats was

8.24 mg/kg bw/day.

In a 90-day feeding study in mice, 400

ppm resulted in reduced activity, one

death, markedly increased activities of

aminotransferases, alkaline

phosphatase, and albumin

concentration, increased liver weights,

hepatocellular hypertrophy, and single

cell necroses in all mice. Other findings

included intrahepatic bile duct

proliferation, Kupffer cell hyperplasia,

and higher incidence of inflammatory

cell infiltration. These findings were

considered to be secondary to the

hepatocyte necrosis. The NOAEL of 6

ppm was equivalent to a daily dose of

0.9 mg/kg in males and 1.05 mg/kg in

females.

In a 90–day study in beagle dogs,

levels of 500 and 1,000 ppm fed over 2

weeks clearly exceeded a maximum

tolerated dose and led to mortality and

severe toxicity. Effects at 50 and 200

ppm were limited to dermatitis and

clinical chemistry changes, which were

generally mild and transient. The

NOAEL of 10 ppm was equivalent to a

mean daily intake of 0.36 mg/kg in

males. The HIARC concluded that in

24474 Federal Register / Vol. 65, No. 81 / Wednesday, April 26, 2000 / Notices

females the NOAEL was 50 ppm (1.9

mg/kg bw/day).

5. Chronic toxicity. In a 12-month

feeding study in dogs, 500 ppm resulted

in transient dermatitis and reduced

body weight gain. Two females were

more severely affected and showed

inappetence, body weight loss, tremors,

and severe dermatitis, and necessitated

an interruption of the treatment in order

to avoid mortality. Histopathology

revealed slight hepatocellular

hypertrophy in one male and one

female. The NOAEL of 100 ppm was

equivalent to a mean daily intake of 3.38

mg/kg in males and 3.37 mg/kg in

female.

Lifetime dietary administration of

clodinafop-propargyl to mice resulted in

reduced body weights and reduced

survival in males treated at 250 ppm.

Severe hepatotoxicity was noted at 100

and 250 ppm in both sexes. Based on

markedly increased liver weights,

enhanced serum activities of hepatic

enzymes and hepatocellular necroses,

dietary levels of 100 ppm and 250 ppm

clearly exceeded maximum tolerated

doses in males and females,

respectively. The increased incidence of

benign liver tumors that occurred in

males treated at 250 ppm was, therefore,

considered a toxicologically irrelevant

response as the livers of these animals

were damaged significantly and this

finding was not interpretable. The

toxicity to liver can be associated with

the peroxisomal proliferating activity of

clodinafop-propargyl in the mouse.

Despite this mode of action, the

incidence of hepatocellular carcinoma,

in these clearly compromised mice,

remained within the historical control

range, although the incidence was

slightly increased in comparison to the

concomitant controls. Tumor incidences

in females were generally low and well

within the range of the historical

controls. The NOAEL of 10 ppm was

equivalent to a mean daily dose of 1.10

mg/kg in males and 1.25 mg/kg in

females.

Dietary treatment of rats with

concentrations over 2 years resulted in

initial inappetence in males and

reduced body weight development in

both sexes treated at 750 ppm. The main

target organ of toxicity was the liver.

Changes in plasma protein and lipid

levels, strongly enhanced serum

activities of liver enzymes, increased

liver weights, and severe liver necroses

were observed at dietary doses of 300

and 750 ppm in males and at 750 ppm

in females. The degenerative lesions

provide strong evidence that these dose

levels exceeded a maximum tolerated

dose (MTD). Top dose group males

showed a higher incidence of prostate

adenoma, while prostate hyperplasia

was reduced. However, the total

incidence of proliferative changes in the

prostate remained unchanged indicating

a progression from prostate hyperplasia

to adenoma. Females treated at the same

high dose had higher incidences of

ovary tubular adenoma. The slightly

enhanced incidences of these lesions are

likely a consequence of the severe

disturbance of the general metabolic

balance due to excessive liver toxicity.

In fact, male rats fed 750 ppm exhibited

a marked increase in peroxisomalβ

oxidation, and an increase in

cytochrome P450 4A1/ A3 and 4A2 in

their livers. Further, a decrease in

cytochrome P450 isoenzymes including

CYP 2A, CYP 3A, and male-specific

CYP 2C11 was observed. The total

oxidation rate of testosterone, aromatase

(CYP 19A1) activity plasma estradiol

concentration and plasmaβ—

dihydrotestosterone are altered at this

level of treatment. Clodinafop-propargyl

is a potent peroxisome proliferator in

the rat liver and this peroxisomal

prolifering activity manifests itself by

altering Cytochrome P450-dependent

monooxygenses which are involved in

steroid hormone homeostasis. The

NOAEL of 10 ppm was equivalent to a

mean daily dose of 0.32 mg/kg in males

and 0.37 mg/kg in females. The EPA

HIARC concluded that based on

hepatocellular hypertrophy and kidney

findings, the NOAEL was 1 ppm (0.031

in males and 0.034 in females.

Carcinogenicity. The EPA HIARC

recommended, based on the increased

incidence of prostate and ovarian

tumors in rats and hepatocellular

tumors in mice, that the Cancer

Assessment Review Committee review

clodinafop-propargyl. A Q1* value

based on the combined incidence of

liver tumors in male mice has been

calculated by the EPA Science Analysis

Branch. The Q1* value estimate is 1.29

× E¥1 (mg/kg/day)¥1 in human

equivalents.

6. Animal metabolism. In rats,

clodinafop-propargyl was rapidly

absorbed through the gastrointestinal

tract. Absorption through the skin of

rats is considerably slower with 15% of

a dermally applied dose being absorbed

within 8 hours. The EPA HIARC

estimated the dermal absorption rate for

clodinafop-propargyl to be 2.5% derived

by taking the ratio of the LOAEL from

the 28-day oral toxicity study in rats (5

mg/kg/day) and 28-day dermal toxicity

study in rats (200 mg/kg/day). Female

rats excreted single doses more rapidly

than males. Most likely due to enzyme

induction, differences were much less

pronounced after repeated treatment.

Both sexes excreted clodinafoppropargyl with urine and feces mainly

in the form of its propionic acid

derivative, CGA–193469. Simultaneous

administration of the safener,

cloquintocet-mexyl, did not alter the

rate of excretion of clodinafop-propargyl

or its metabolite pattern.

7. Metabolite toxicology. Clodinafoppropargyl acts as a typical peroxisome

proliferator in the rodent liver, which is

most likely induced by its propionic

acid derivative metabolite, CGA–

193469. Like other known wellcharacterized substances with this

property, CGA–193469 caused

peroxisome proliferation in vitro in

hepatocytes of the mouse and rat, but

not of the Guinea pig, marmoset, or

human. In addition, clodinafoppropargyl was unable to activate the

PPAR α-dependent human ACYL CoA

oxidase promoter which further

supports the evidence that humans are

refractory to peroxisome proliferation

and related changes. The scientific

evidence available amply demonstrates

that exposure to substances that

produce tumors by a peroxisome

proliferator mode of action does not

represent a risk of tumor development

in man. Novartis, therefore, has

concluded that clodinafop-propargyl is

not a carcinogen of relevance to

humans.

8. Endocrine disruption. No special

studies investigating potential

estrogenic or endocrine effects of

clodinafop-propargyl have been

conducted. However, the standard

battery of required studies has been

completed. 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. Although prostate

adenomas and ovarian adenomas were

observed to be statistically increased in

rats at the highest feeding level with

clodinafop-propargyl, this feeding level

clearly exceeded the MTD and the livers

in these rats were severely

compromised. These findings in the

endocrine organs were considered to be

secondary to the severe liver effects.

C. Aggregate Exposure

1. Dietary exposure. Chronic and

acute dietary exposure were calculated

for the use of clodinafop-propargyl and

the corresponding hydrolysis product,

CGA–193469 on wheat. Analyses were

conducted using the Dietary Exposure

Evaluation Model (DEEMTM) by Novigen

Sciences and the 1994–96 Continuing

Survey of Food Intake (CSFII). Chronic

and acute tier three assessments were

conducted to account for the

consumption of commodities containing

Federal Register / Vol. 65, No. 81 / Wednesday, April 26, 2000 / Notices 24475

wheat grain and residues were adjusted

with a projected percent of crop treated

value of 4%. Residues of parent

clodinafop-propargyl were below the

limit of quantitation (LOQ) of 0.02 ppm

in all grain samples. Residues of the

acid (CGA–193469) were also below the

LOQ (LOQ = 0.05 ppm) in grain. Since

no residues were observed in any of the

samples, a statistical limit of detection

(sLOD) was calculated for parent and

the corresponding acid metabolite and

one-half of the sLOD of each were

summed and entered into the chronic

and the acute assessments. Although

wheat fractions may be fed to livestock

and poultry, calculation of dietary

burden with subsequent transfer to

animal commodities shows secondary

residues are extremely negligible and do

not impact risk. Tolerances of 0.1 ppm

are being proposed for clodinafoppropargyl and the acid metabolite,

CGA–193469, for wheat grain, forage,

and hay and 0.5 ppm for straw.

Tolerances for meat, milk and eggs are

not required.

i. Food—a. Chronic. Chronic exposure

was compared to a chronic reference

dose (RfD) of 0.00003 mg/kg/day based

on a no-effect level of 0.03 mg/kg/day

from a 2-year chronic toxicity/

carcinogenicity study in rats and a

1,000X uncertainty factor. Exposure

results are compared against the

aforementioned reference dose as well

as the Agency’s Q1* value of 0.129.

Since all residues in grain were below

the LOQ, an sLOD was calculated for

parent and CGA–193469. One-half sLOD

values for parent clodinafop-propargyl

and the corresponding acid were 0.0049

ppm and 0.0147 ppm, respectively.

These values were summed and

adjusted with a market share value of

4% for the calculation of exposure. The

exposure results show that the U.S.

population utilizes 4.3% of the chronic

RfD. The most sensitive subpopulation

is children (1–6 years old) with an

exposure of 9.9% of the chronic RfD.

Using the Agency’s Q1* value of 0.129,

a lifetime risk of 1.35 x 10¥7 was

calculated. These results indicate there

is more than a reasonable certainty that

exposure to residues of clodinafoppropargyl and its corresponding acid

metabolite (CGA–193469) will result in

no harm.

b. Acute. Acute exposure to females

greater than 13 years old was compared

to an acute reference dose (aRfD) of

0.005 mg/kg/day based on a NOAEL of

5 mg/kg/day from a developmental

study in rats and a 1,000x uncertainty

factor. As in the chronic assessment,

one-half sLOD was used for parent

clodinafop-propargyl and the

corresponding acid (0.0049 ppm and

0.0147 ppm for parent and acid,

respectively). These values were

summed and zeroes were added to the

residue distribution file corresponding

to the percent of crop not treated (96%

not treated). For all female populations

in the DEEMTM, exposure ranged from

3.0% – 4.2% of the aRfD at the 99.9th

percentile of exposure. The most

sensitive female population was nursing

females (13+ years old) with an

exposure of 4.2% of the aRfD (99.9th

percentile). Acute exposure for the

general population excluding females (>

13 years old), was compared to an aRfD

of 0.025 mg/kg/day based on a NOAEL

of 25 mg/kg/day from a developmental

study in rabbits and a 1,000x

uncertainty factor (UF). Acute exposure

at the 99.9th percentile for the general

population, children and males (all

populations excluding females) ranged

from 0.18% (seniors, 55+) to 0.62% of

the aRfD for children (1–6 years old).

These results demonstrate that there is

a high degree of certainty of no harm

resulting from acute exposure to dietary

residues of clodinafop-propargyl.

ii. Drinking water. Another potential

route of exposure to residues of

pesticides includes drinking water.

Field and laboratory study results have

demonstrated that clodinafop-propargyl

and its degradation products have slight

to medium mobility in soil. However,

due to rapid degradation of the product

under field conditions and its low

application rate, the potential for it to

reach surface and ground water is

considered to be negligible. Thus,

drinking water exposure to clodinafoppropargyl and its degradation products

was not included in the aggregate risk

assessment. Also, since clodinafoppropargyl is not intended for uses other

than the agricultural use on wheat, there

is no potential for nonoccupational

exposure.

The estimated exposures of

clodinafop-propargyl and its main

environmental degradate were

combined and the hazards for both

compounds were based on the RfD

values determined for clodinafoppropargyl alone. The estimated water

concentrations for clodinafop-propargyl

and the degradate were estimated,

weighted and combined based on

applications rates adjusted for the

maximum concentration of the

degradate present in the aerobic soil

metabolism studies.

The Screening Concentration in

Ground Water (SCI–GROW) model was

used to provide the estimated ground

water concentration of the combined

clodinafop-propargyl and degradate

residues, 0.006688 ppb. The Pesticide

Root Zone Model/Exposure Analysis

Modeling Systems (PRZM/EXAMS)

model using the Index Reservoir

scenario and the Percent Cropped Area

provided the estimated surface water

concentrations of the combined

clodinafop-propargyl and degradate

residues for a wheat application in

North Dakota. The estimated 90th

percentile acute peak concentration for

the combined residues was 0.792 part

per billion (ppb). The estimated 36-year

mean-yearly chronic concentration for

the combined residues was 0.0519 ppb.

Concerning the acute and chronic

exposures to clodinafop-propargyl and

the degradate, an additional 10×-safety

factor has been proposed by the EPA

HIARC for the protection of infants and

children. This additional safety factor

was applied to the acute and chronic

non-cancer RfD values for all subpopulations as a worse case estimate of

exposure. This resulted in an acute RfD

for females 13+ years of 0.005 mg/kg/

day and 0.025 mg/kg/day for all other

subgroups. This also resulted in a

chronic RfD for infants and children of

0.00003 mg/kg/day. A chronic lifetime

cancer risk exposure of 0.129 mg/kg/day

has also been proposed by the EPA. This

was applied to the adult population

exposures only.

For ground water, the acute dietary

assessment provided drinking water

levels of comparison (DWLOC) ranging

from 140 to 873 ppb. The estimated

ground water concentration, 0.006688

ppb, represented from 0.0008% to

0.0048% of the acute RfD for all subpopulations. The chronic dietary

exposures provided DWLOC values of

0.16 ppb (infants), 0.31 ppb (children),

and 0.2026 to 0.2363 ppb (lifetime

cancer risk for adults). The estimated

ground water concentration represented

3.98%, 1.93% and 2.5 to 2.9% of the

chronic risk, respectively.

For surface water, the acute dietary

assessment provided DWLOC values

ranging from 140 to 873 ppb. The

estimated acute surface water

concentration, 0.792 ppb, represented

from 0.09% to 0.57% of the acute RfD

for all sub-populations. The chronic

dietary exposures provided DWLOC

values of 0.16 ppb (infants), 0.31 ppb

(children), and 0.2026 to 0.2363 ppb

(lifetime cancer risk for adults). The

estimated surface water concentration,

0.0519 ppb, represented 31%, 15% and

19.1–to–22.3% of the chronic risk,

respectively. Therefore, the acute and

chronic drinking water exposures for

clodinafop-propargyl and its main

environmental degradate did not exceed

the exposures allowed by the risk cup.

2. Non-dietary exposure. Exposure to

clodinafop-propargyl for the mixer/

loader/ground-boom/aerial applicator

24476 Federal Register / Vol. 65, No. 81 / Wednesday, April 26, 2000 / Notices

and flagger was calculated using the

Pesticide Handlers Exposure Database

(PHED). It was assumed that the product

would be applied 6 days per year by

ground-boom application to a maximum

of 80 acres per day by the grower, 15

days per year by ground-boom

application to a maximum of 80 acres

per day by the commercial ground-boom

applicator and 15 days per year to a

maximum of 350 acres per day by the

aerial applicator, at a maximum use rate

of 28.3 grams active ingredient per acre.

For purposes of this assessment, it was

assumed that an applicator would be

wearing a long sleeved shirt and long

pants and the mixer/loader would, in

addition, wear gloves. Daily doses were

calculated for a person weighting 70 kg

assuming 100% dermal penetration.

Short-term and intermediate-term

dermal and inhalation risk assessments

were performed. Doses and endpoints

used for risk assessments were based on

Agency determined toxicological

endpoints recommended by the HIARC.

The NOAEL of 50 mg/kg/day from the

28–day rat dermal study was used for

short- and intermediate-term dermal

risk assessments. The NOAEL of 5 mg/

kg/day from the developmental toxicity

study in rats was used for short-term

inhalation risk assessments. The

NOAEL of 0.9 mg/kg/day based on a

subchronic oral toxicity study in rats

was used for intermediate-term

inhalation risk assessments. Based on

the use pattern of clodinafop-propargyl,

no long-term dermal or inhalation

exposure is expected to occur and longterm risk assessments are not required.

Large margins of exposure (MOEs)

exist for all occupational exposure

scenarios. Short-term dermal exposure

MOEs ranged from 4.0E+03 for the

commercial open mixer-loader to

1.8E+05 for the commercial or grower

ground-boom enclosed-cab applicator.

Intermediate-term dermal exposure

MOEs ranged from 9.7E+04 for the

commerical open mixer-loader to

1.1E+07 for the grower ground-boom

enclosed-cab applicator. Short-term

inhalation exposure MOEs ranged from

3.6E+04 for the commercial open mixerloader to 1.7E+06 for the commercial or

grower ground-boom enclosed-cab

applicator. Intermediate-term inhalation

exposure MOEs ranged from 1.6E+05 for

the commercial open mixer-loader to

1.8E+07 for the grower ground-boom

enclosed-cab applicator.

Although there are no residential uses

of clodinafop-propargyl, there is

potential for residential exposure to

spray drift resulting from aerial

application. No standard operating

procedure exists for performing this risk

assessment; however, a very

conservative risk assessment was

performed assuming dermal exposure

equal to total deposition to outside

clothing for a flagger as well as

inhalation exposure equivalent to a

pesticide flagger, as reflected in PHED.

A dermal absorption factor of 2.5%, as

estimated by HIARC, was assumed.

Offsite drift was assumed to be 15% and

the area assumed to be adjacent to the

sensitive area was one acre. Large MOEs

exist for this potential exposure

scenario. Dermal exposure MOEs were

6.0E+07 for a 15 kg child and 2.8E+08

for a 70 kg adult. Inhalation MOEs were

2.3E+07 for a 15 kg child and 1.1E+8 for

a 70 kg adult.

D. Cumulative Effects

A cumulative exposure assessment for

effects of clodinafop-propargyl and

other substances with the same

mechanism of action is not appropriate

because there is ample evidence to

indicate that humans are not sensitive to

the effects of clodinafop-propargyl and

other peroxisome proliferators. Thus,

the calculations outlined below were

done for clodinafop-propargyl alone.

E. Safety Determination

1. U.S. population. Acute and chronic

dietary exposure is minimal for

clodinafop-propargyl and the

corresponding acid metabolite. Both

chronic and acute exposure estimates

showed that less than 10% of the RfD

is utilized in all populations.

Exposure through the consumption of

drinking water is minimal from both

surface water and ground water model

estimates and in all cases less than 35%

of the risk cup is utilized. The estimated

water concentrations are very

conservative since conservative model

parameters were assumed.

There are no residential uses of

clodinafop-propargyl that would result

in non-dietary exposure. However, there

is a remote possibility that spray drift

resulting from aerial application could

lead to residential exposure. Since

exposure from spray drift would be an

unlikely event, it is not appropriate to

include non-dietary exposure into the

aggregate assessment. Therefore, it is

concluded that there is more than a

reasonable certainty that no harm will

result from aggregate exposure to

residues of clodinafop-propargyl.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

clodinafop-propargyl, data from

developmental toxicity studies in the rat

and rabbit and a 2-generation

reproduction study in the rat have been

considered. The developmental toxicity

studies are designed to evaluate adverse

effects on the developing organism

resulting from chemical exposure

during prenatal development to one or

both parents. Reproduction studies

provide information relating to effects

from exposure to a chemical on the

reproductive capability of mating

animals and data on systemic toxicity.

Retarded fetal body weight and

incomplete ossification of vertebrae and

sternebrae were observed at a

maternally toxic dose of 160 mg/kg/day

in rats; however, no developmental

toxicity of the test article was detected.

Novartis believes that the NOAEL for

dams and fetuses was 40 mg/kg/day.

The EPA’s HIARC concluded that based

on an increase in bilateral distension

and torsion of the ureters and delayed

ossification in the fetuses, the

developmental LOAEL was 40 mg/kg/

day and the NOAEL was 5 mg/kg/day.

Although mortality was observed in

rabbit dams at dose levels of 125 and

175 mg/kg, no teratogenic or fetotoxic

effects were noted. The maternal

NOAEL was 25 mg/kg/day and the fetal

NOAEL was 175 mg/kg/day.

Clodinafop-propargyl fed over 2-

generations to rats at levels as high as

1,000 ppm did not affect mating

performance, fertility, or litter sizes.

Body weight was reduced in parental

animals at 500 and 1,000 ppm.

Physiological developmental and the

survival of the pups during the last

week of the lactation period were

slightly reduced at levels equal to or

greater than 500 ppm during the first

generation only. Target organs were

liver (adults) and kidney (adults and

pups). The NOAEL for toxicity to the

parental animals and offspring was 50

ppm, corresponding to a mean daily

intake of 3.2 mg/kg bw/day of

clodinafop-propargyl. The NOAEL for

reproductive toxicity was 1,000 ppm

(64.2 mg/kg bw/day).

FFDCA section 408 provides that EPA

may apply an additional safety factor for

infants and children in the case of

threshold effects to account for prenatal

and postnatal toxicity and the

completeness of the database. Based on

the current toxicological data

requirements, the database relative to

prenatal and postnatal effects for

children is complete. The results from

the 2-generation reproduction study and

the rabbit developmental toxicity study

would indicate there is no additional

sensitivity of infants and children to

clodinafop-propargyl. The HIARC

selected the developmental NOAEL of 5

mg/kg/day from the rat developmental

toxicity as opposed to the maternal

NOAEL of 40 mg/kg bw/day. Therefore,

the HIARC recommended the 10x safety

Federal Register / Vol. 65, No. 81 / Wednesday, April 26, 2000 / Notices 24477

factor should be retained based on this

increased susceptibility.

Using conservative exposure

assumptions, dietary exposure to the

most sensitive subpopulation, children

(1–6 years old) utilizes 9.9% of the

chronic reference dose. Chronic dietary

exposure to infants (non-nursing, 1–6

years old) is 2.0% of the chronic RfD.

Acute exposure for all infants and

children is less than 1.0% of the acute

RfD (0.62% of the RfD for the most

sensitive subpopulation, children 1–6

years old). Exposure to drinking water

for children (1–6 years old) utilizes 31%

of the chronic RfD (surface water

estimate). Children (1–6 years old)

utilize 15% of the chronic RfD (surface

water estimate). For acute exposure to

drinking water, the worst case estimates

(surface water) for infants show that

only 0.57% of the aRfD is utilized and

children (1–6 years old) utilize 0.27% of

the aRfD. These results show that

aggregate exposure to residues of

clodinafop-propargyl in the diet and

drinking water is negligible. Based on

the completeness and reliability of the

toxicity data and the conservative

nature of the exposure assumptions, it is

concluded that there is a more than

reasonable certainty that no harm will

result to infants and children from

exposure to residues of clodinafoppropargyl.

F. International Tolerances

There are no Codex Alimentarius

Commission (CODEX) maximum

residue levels (MRLs) established for

residues of clodinafop-propargyl in or

on raw agricultural commodities.

[FR Doc. 00–10432 Filed 4–25–00; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[OPP–66276; FRL–6552–8]

Notice of Receipt of Requests To

Voluntary Cancel Certain Pesticide

Registrations

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: In accordance with section

6(f)(1) of the Federal Insecticide,

Fungicide and Rodenticide Act (FIFRA),

as amended, EPA is issuing a notice of

receipt of requests by registrants to

voluntarily cancel certain pesticide

registrations.

DATES: Unless a request is withdrawn,

the Agency will approve these use

deletions and the deletions will become

effective on October 23, 2000.

FOR FURTHER INFORMATION CONTACT: By

mail: James A. Hollins, Office of

Pesticide Programs (7502C),

Environmental Protection Agency, Ariel

Rios Building, 1200 Pennsylvania Ave.,

NW., Washington, DC 20460. Office

location for commercial courier

delivery, telephone number and e-mail

address: Rm. 224, Crystal Mall #2, 1921

Jefferson Davis Highway, Arlington, VA

22202, telephone number: (703) 305–

5761; e-mail: hollins.james@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

This action is directed to the public

in general. Although this action may be

of particular interest to persons who

produce or use pesticides, the Agency

has not attempted to describe all the

specific entities that may be affected by

this action. If you have any questions

regarding the information in this notice,

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. Contact James A. Hollins

at 1921 Jefferson Davis Highway, Crystal

Mall #2, Rm. 224, Arlington, VA.,

telephone number (703) 305–5761.

Available from 7:30 a.m. to 4:45 p.m.,

Monday thru Friday, excluding legal

holidays.

II. What Action Is the Agency Taking?

This notice announces receipt by the

Agency of applications from registrants

to cancel some 163 pesticide products

registered under section 3 or 24 of

FIFRA. These registrations are listed in

sequence by registration number (or

company number and 24 number) in the

following Table 1.

TABLE 1.—REGISTRATIONS WITH PENDING REQUESTS FOR CANCELLATION

Registration No. Product name Chemical name

000070–00179 Kill-Ko Seed Treater O,O-Diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl)

phosphorothioate cis-N-Trichloromethylthio-4-cyclohexene1,2-dicarboximide

000070–00190 Kill-Ko Fruit Tree Spray Methoxychlor (2,2-bis(p-methoxyphenyl)-1,1,1-trichloroethane)

O,O-Dimethyl phosphorodithioate of diethyl

mercaptosuccinate cis-N-Trichloromethylthio-4-cyclohexene1,2-dicarboximide

000100 OR–98–0021 Supracide 25WP Insecticide-Miticide O,O-Dimethyl phosphorodithioate, S-ester with 4-

(mercaptomethyl)-2-

000100 OR–99–0022 Maxim – MZ Potato Seed Protectant Gas cartidge (as a device for burrowing animal control) Zinc ion

and manganese ethylenebisdithiocarbamate, coordination

product 1H-Pyrrole-3-carbonitrile, 4-(2,2-difluoro-1,3-

benzodioxol-4-yl)- (9CI)

000264 OR–81–0055 Rovral Fungicide 3-(3,5-Dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-

imidazolidinecarboxamide

000264 WA–81–0052 Rovral Fungicide 3-(3,5-Dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-

imidazolidinecarboxamide

000270–00053 Farnam Ready-To-Use Stable & Horse Fly Spray Pine oil

2,2-Dichlorovinyl dimethyl phosphate

000270–00284 Security Brand Cygon* 2-E Systemic Insecticide O,O-Dimethyl S-((methylcarbamoyl)methyl) phosphorodithioate

000270–00285 Security Brand Fungi-Gard Tetrachloroisophthalonitrile

000270–00287 Security Brand Systemic Rose & Flower Booster O,O-Diethyl S-(2-(ethylthio)ethyl) phosphorodithioate