20972 Federal Register / Vol. 65, No. 76 / Wednesday, April 19, 2000 / Notices

ENVIRONMENTAL PROTECTION

AGENCY

[PF–936; FRL–6554–3]

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

amendment of a pesticide petition

(PP7E4920), proposing the

establishment of regulations for residues

of a certain pesticide chemical in or on

various food commodities.

DATES: Comments, identified by docket

control number PF–936, must be

received on or before May 19, 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–936 in the subject line on the first

page of your response.

FOR FURTHER INFORMATION CONTACT: By

mail: Treva C. Alston, Registration

Support Branch, Registration Division

(7505C), Office of Pesticide Programs,

Environmental Protection Agency, Ariel

Rios Bldg., 1200 Pennsylvania Ave.,

NW., Washington, DC 20460; telephone

number: (703) 308–8373; e-mail address:

alston.treva@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:

CategoriesNAICS

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–

936. 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–936 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, 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–936. 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.

Federal Register / Vol. 65, No. 76 / Wednesday, April 19, 2000 / Notices 20973

2. Describe any assumptions that you

used.

3. Provide copies of any technical

information and/or data you used that

support your views.

4. If you estimate potential burden or

costs, explain how you arrived at the

estimate that you provide.

5. Provide specific examples to

illustrate your concerns.

6. Make sure to submit your

comments by the deadline in this

notice.

7. To ensure proper receipt by EPA,

be sure to identify the docket control

number assigned to this action in the

subject line on the first page of your

response. You may also provide the

name, date, and Federal Register

citation.

II. What Action is the Agency Taking?

EPA has received a pesticide petition

as follows proposing the establishment

and/or amendment of regulations for

residues of a certain pesticide chemical

in or on various food commodities

under section 408 of the Federal Food,

Drug, and Comestic Act (FFDCA), 21

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

this petition contains data or

information regarding the elements set

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

has not fully evaluated the sufficiency

of the submitted data at this time or

whether the data support granting of the

petition. Additional data may be needed

before EPA rules on the petition.

List of Subjects

Environmental protection,

Agricultural commodities, Feed

additives, Food additives, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: April 10, 2000.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

Summary of Petition

The petitioner summary of the

pesticide petition is printed below as

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

FFDCA. The summary of the petition

was prepared by the petitioner and

represents the view of the petitioner.

EPA is publishing the petition summary

verbatim without editing it in any way.

The petition summary announces the

availability of a description of the

analytical methods available to EPA for

the detection and measurement of the

pesticide chemical residues or an

explanation of why no such method is

needed.

Novartis Crop Protection, Inc.

7E4920

Amended Pesticide Petition

On April 15, 1998, EPA published a

notice that it had received a pesticide

petition (7E4920) from Novartis Crop

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

Greensboro, NC 27419, proposing

tolerances for the herbicide safener

cloquintocet-mexyl acetic acid, (5-

chloro-8-quinolinyl)oxy-,1-

methylhexylester; CGA-185072) in or on

raw agricultural commodities (RACs) of

wheat. EPA has received an amendment

to PP 7E4920 from Novartis Crop

Protection, Inc., 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 cloquintocetmexyl and its acid metabolite, CGA153433 (5-chloro-8-quinolinyl)oxyacetic acid), in or on the RACs wheat,

grain at 0.1 part per million (ppm);

wheat, forage at 0.1 ppm; wheat, hay at

0.1 ppm; and wheat, straw at 0.1 ppm.

EPA has determined that the petition

contains data or information regarding

the elements set forth in section

408(d)(2) of the FFDCA; however, EPA

has not fully evaluated the sufficiency

of the submitted data at this time or

whether the data support granting of the

petition. Additional data may be needed

before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism

of cloquintocet-mexyl in wheat has been

investigated. Total residues in all crop

samples are low. Metabolism involves

primarily rapid hydrolysis of the parent

to the resulting acid followed by

conjugation.

2. Analytical method. Novartis has

submitted practical analytical methods

for the determination of cloquintocetmexyl and its major plant metabolite

CGA-153433 in wheat RACs.

Cloquintocet-mexyl 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-153433 is

extracted from crops with an acetonebuffer (pH=3) solution, cleaned up by

solvent partition and solid phase

extraction, and determined by HPLC

with UV detection. The limits of

quantification (LOQ) for the methods

are 0.02 ppm for cloquintocet-mexyl in

forage and grain, 0.05 ppm for

cloquintocet-mexyl in straw, and 0.05

ppm for CGA-153433 in forage, straw

and grain.

3. Magnitude of residues. Both

Canadian and United States 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

active ingredient (a.i.) and the

cloquintocet-mexyl safener as separate

EC formulations and three trials in 1992

were conducted with clodinafoppropargyl and the cloquintocet-mexyl

safener as a pre-pack EC formulation.

All trials had a single post-emergence

application of CGA-185072 at a rate of

20 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, cloquintocetmexyl was applied as a safener in

conjunction with clodinafop-propargyl

as a 240EC formulation. The rate of

cloquintocet-mexyl applied was 17 g

a.i./ha as a single application. 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 55–97

days, no detectable residues of

cloquintocet-mexyl or its metabolite

CGA-153433 were found in mature grain

or straw from these trials. Separate

decline studies three on green forage

showed no detectable residues of

cloquintocet-mexyl or CGA-153433 at 3

days after application. Freezer storage

stability studies indicated reasonable

stability of both analytes for a period of

1 year, with cloquintocet-mexyl

declining to 83% in grain and 67% in

straw after 2 years, while CGA-153433

was stable for at least 2 years.

B. Toxicological Profile

1. Acute toxicity. The acute oral and

dermal LD50 values for cloquintocetmexyl are greater than 2,000 milligrams/

kilograms (mg/kg) for rats of both sexes,

respectively. Its acute inhalation LC50 in

the rat is greater than 0.935 milligram/

liter (mg/L), the highest attainable

concentration. Cloquintocet-mexyl 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.’’

20974 Federal Register / Vol. 65, No. 76 / Wednesday, April 19, 2000 / Notices

2. Genotoxicity. The mutagenic

potential of cloquintocet-mexyl 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.

Cloquintocet-mexyl 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

cloquintocet-mexyl over 2 generations at

levels as high as 10,000 part per million

(ppm) did not affect mating

performance, fertility, or litter sizes, but

a slightly reduced body weight

development of adults and pups was

noted at this level. The target organ was

the kidney in adults and pups. The

treatment had no effect on reproductive

organs. The no observed adverse effect

level (NOAEL) for toxicity to the

offspring and parental toxicity was

5,000 ppm, corresponding to a mean

daily intake of 370 to 422 mg/kg/day of

cloquintocet-mexyl. The reproductive

NOAEL was > 10,000 ppm (722 mg/kg/

day).

In a developmental toxicity study in

rats, the highest dose level of 400 mg/

kg bwt day resulted in reduced body

weight gain of the dams and signs of

retarded fetal development. No

teratogenic activity of the test article

was detected. The NOAEL for dams and

fetuses was 100 mg/kg bwt day.

In a developmental toxicity study in

rabbits, mortality was observed in dams

at dose levels of 300 mg/kg. No

teratogenic effects were noted. Fetuses

showed signs of slightly retarded

development. The NOAEL for both

dams and fetuses was 60 mg/kg bwt day.

EPA’s Hazard Identification Assessment

Review Committee (HIARC) suggested

the maternal NOAEL was 60 mg/kg, but

the developmental toxicity NOAEL is >

300 mg/kg/day.

4. Subchronic toxicity. In a 90-day

study, rats fed 6,000 ppm exhibited

reduced body weight gain and one male

died with acute nephritis and inflamed

urinary bladder. Reduced liver and

kidney weights were observed in males

fed 1,000 and 6,000 and in females fed

6,000 ppm. Target organs were

identified to be kidney and urinary

bladder. The NOAEL was 150 ppm (9.66

mg/kg in males and 10.2 mg/kg in

females). EPA’s HIARC concluded that

the NOAEL in females was 6,000 ppm

(407 mg/kg/day).

In a 90-day study in beagle dogs, a

level of 40,000 ppm resulted in

deterioration of general condition so

that the feeding level was reduced in a

stepwise fashion to 15,000 ppm.

Anemia was noted at 15,000 and 1,000

ppm. The NOAEL of 100 ppm was

equivalent to a mean daily intake of 2.9

mg/kg in males and females.

5. Chronic toxicity. In a 12-month

feeding study in dogs, 15,000 ppm

resulted in inappetence and body

weight loss. As a result, this feeding

level was adjusted to 10,000 ppm after

2 weeks. Animals fed this level

exhibited anemia and an elevation in

blood urea levels. The kidney was

considered the target organ. The NOAEL

of 1,500 ppm was equivalent to a mean

daily intake of 43.2 mg/kg in males and

44.8 mg/kg in females.

Lifetime dietary administration of

cloquintocet-mexyl to mice resulted in

reduced body weights in both sexes at

5,000 ppm. Overall body weight gain

was reduced by 17% to 22% in males

and females, respectively, indicating the

MTD was achieved or exceeded.

Histopathological examination revealed

chronic inflammation of the urinary

bladder. There was no indication of any

tumorigenic response due to treatment.

The NOAEL of 1,000 ppm was

equivalent to a mean daily dose of 111

mg/kg in males and 102 mg/kg in

females.

Rats were fed a top feeding level of

2,000 ppm, based on the 90-day

subchonic study, for a lifetime. This

feeding level was well-tolerated, but

produced hyperplasia of the thymus in

males at the top dose and hyperplasia of

the thyroid in females at 1,000 and

2,000 ppm. There was no increase in

tumors of any type and the total number

of tumor-bearing animals showed no

dose-related trends. The NOAEL of 100

ppm was equivalent to a mean daily

dose of 4.33 mg/kg in females. EPA’s

HIARC suggested that the NOAEL in

male rats was 1,000 ppm (36.4 mg/kg/

day).

6. Carcinogenicity. There is no

evidence supporting any oncogenic

potential associated with cloquincetmexyl. EPA’s HIARC classified

cloquintocet-mexyl as a ‘‘not likely’’

human carcinogen according to the

proposed guidelines for carcinogen risk

assessment.

7. Animal metabolism. In rats,

approximately 50% of an oral dose of

cloquintocet-mexyl was rapidly

absorbed through the gastrointestinal

tract and excreted via urine and bile.

The administered dose was excreted

independent of sex and was essentially

complete within 48 hours. Ninety-five

percent of the excreted dose was

associated with one metabolite, an acid

residue of cloquintocet-mexyl, CGA153433. Simultaneous administration of

the cloquintocet-mexyl and clodinafoppropargyl did not alter the rate of

excretion of cloquintocet-mexyl or its

metabolite pattern.

8. Metabolite toxicology. At the

present time there is no evidence which

affords an association of the toxicity

noted with the highest feeding levels of

cloquintocet-mexyl with its primary

metabolite, CGA-153433.

9. Endocrine disruption. A special

study was conducted to investigate a

histological finding of hyperplasia of

thyroid gland epithelium noted in the

female rat in the standard lifetime

combined chronic toxicity and

carcinogenicity study. This study was a

28-day oral gavage study with a 28-day

recovery period at dose levels as high as

400 mg/kg/day or approximately 4,000

ppm. No effect was noted on the level

of thyroid hormones at any of the

treatment levels. Although a slight

stimulation of the thyroid and an

accompanying increase in pituitary

basophilic cells were noted at the end

of 28-days, these effects were reversible

in the recovery period.

C. Aggregate Exposure

1. Dietary exposure. Cloquintocetmexyl is intended as a safener for the

postemergence herbicide, clodinafoppropargyl, used on wheat. The use rate

for cloquintocet-mexyl is very low

(formulated at a 1:4 ratio of safener to

active ingredient and results from plant

metabolism and residue studies show

that residues are below the detection

limit in wheat grain and other wheat

fractions. The tolerance expression will

include parent cloquintocet-methyl and

the corresponding hydrolysis product,

CGA-153433, and tolerances are being

proposed at 0.1 ppm in wheat grain,

forage, hay, and straw. No tolerances are

proposed for secondary residues in

animal commodities since residues

would be far below the LOQ of existing

analytical methodology.

i. Food. Chronic and acute dietary

exposure analyses were conducted

using the dietary exposure evaluation

model (DEEM) from Novigen Sciences

and the 1994–96 Continuing Survey of

Food Intake by Individuals (CSFII).

Chronic and acute tier one dietary

assessments were made assuming

tolerance-level residues and treatment

of 100% of all planted wheat.

a. Chronic. Chronic exposure was

compared to a reference dose (RfD) of

0.04 mg/kg/day which was derived from

Federal Register / Vol. 65, No. 76 / Wednesday, April 19, 2000 / Notices 20975

a NOAEL of 4.3 mg/kg/day in a chronic

toxicity/carcinogenicity study in female

rats and a 100x uncertainty factor (UF).

Exposure was calculated assuming that

100% of crop was treated and residues

were at the proposed tolerance levels of

0.1 ppm for wheat grain and associated

fractions. Exposure for the U.S.

population was minimal with 0.4% of

the RfD utilized and this result was the

same for the U.S. population through all

seasons and all ethnic groups. The most

sensitive subpopulation was children

(1–6 years old) with an exposure of

0.9% of the chronic RfD. These results

are extremely conservative since

tolerance values were used and are

reflective of the maximum application

rate and minimum PHI. In addition, it

was assumed that all planted acres are

treated. Therefore, there is more than a

reasonable certainty of no harm

resulting from exposure to residues of

cloquintocet-mexyl.

b. Acute. Acute exposure was

assessed for the female population (13+

years) only and was compared to an

acute RfD of 1.0 mg/kg/day based on a

NOAEL of 100 mg/kg/day from a

developmental toxicity study in rats and

a 100x UF. The resulting assessment

revealed that exposures to all female

subpopulations reported in the DEEM

were between 0.03%–0.04% of the RfD

at the 95th percentile of exposure. The

95th percentile is the appropriate

percentile to consider since this

assessment is based on tolerance-level

residues and 100% of crop treated was

assumed. Even at the 99.9th percentile of

exposure, the results show that females

(13–50 years old) utilize only 0.07% of

the acute RfD. EPA’s HIARC concluded

that no acute dietary assessment was

necessary for the general population

because a suitable toxicological

endpoint (resulting from a single dose

exposure) was not identified in either

the rat or rabbit developmental studies.

ii. Drinking water. Another potential

route of exposure to residues of

pesticides includes drinking water.

Field and laboratory study results have

demonstrated that cloquintocet-mexyl

and its degradation products have

minimal potential to reach surface or

ground water. Thus, drinking water

exposure to cloquintocet-mexyl and its

degradation products was not included

in the aggregate risk assessment. Also,

since cloquintocet-mexyl is not

intended for uses other than the

agricultural use on wheat, there is no

potential for non-occupational

exposure.

The estimated exposures of

cloquintocet-mexyl and its main

environmental degradate were

combined and the hazards for both

compounds were based on the RfD

values determined for cloquintocetmexyl alone. The estimated water

concentrations for cloquintocet-mexyl

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 GENEEC and SCI–GROW models

respectively provided the estimated

surface water and ground water

concentrations. The estimated acute

exposures from drinking surface and

ground water were 0.04964 part per

billion (ppb) and 0.006166 ppb,

respectively. The females 13+ years subpopulation was the only subgroup

which was required for the acute

exposure assessment. The acute

exposures for females 13+ years were

based on 1.0 mg/kg/day. Based on the

95th percentile acute dietary assessment,

the females (13+/nursing) was the most

exposed female sub-population at 3.71E6 mg/kg/day. This resulted in an acute

DWLOC of 30,000 ppb. Therefore, the

estimated acute surface and ground

water exposures for cloquintocet-mexyl

and its degradate did not exceed the

exposure allowed by the risk cup. The

chronic dietary exposures for all subpopulations provided DWLOC values of

224 to 1,396 ppb. The estimated chronic

exposures from drinking surface and

ground water were 0.00316 ppb and

0.006166 ppb, respectively. Therefore,

the estimated acute and chronic

drinking water exposures of

cloquintocet-mexyl and its degradate

did not exceed the exposures allowed

by the risk cup.

2. Non-dietary exposure. Exposure to

cloquintocet-mexyl for the mixer/

loader/ground-boom/aerial applicator

and flagger was calculated using the

pesticide handlers exposure data base. 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 7.1

grams cloquintocet-mexyl 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 70 kg person 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 200 mg/kg/day from the

28-day rat dermal toxicity study was

used for short-term and intermediateterm dermal risk assessments. The

NOAEL of 100 mg/kg/day from the

developmental toxicity study in rats was

used for short-term inhalation risk

assessments. The NOAEL of 4.3 mg/kg/

day from the 2-year chronic toxicity

study in rats was used for intermediateterm risk assessments. Based on the use

pattern, no long-term dermal or

inhalation exposure is expected to occur

and long-term risk assessments are not

required.

Large margins of exposure (MOE)

exist for all occupational exposure

scenarios. Short-term dermal exposure

MOEs ranged from 6.4E+04 for the

commercial open mixer-loader to

2.8E+06 for the commercial or grower

groundboom enclosed-cab applicator.

Intermediate-term dermal exposure

MOEs ranged from 1.6E+06 for the

commercial open mixer-loader to

1.7E+08 for the grower ground-boom

enclosed-cab applicator. Short-term

inhalation exposure MOEs ranged from

2.8E+06 for the commercial open mixerloader to 1.3E+08 for the commercial or

grower ground-boom enclosed-cab

applicator. Intermediate-term inhalation

exposure MOEs ranged from 3.0E+06 for

the commercial open mixer-loader to

3.4E+08 for the grower ground-boom

enclosed-cab applicator.

Although there are no residential uses

of cloquintocet-mexyl, 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 100% and offsite drift of 15%

were assumed. 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 2.4E+07 for a 15 kg child

and 1.1E+08 for a 70 kg adult.

Inhalation MOEs were 1.8E+09 for a 15

kg child and 8.6E+09 for a 70 kg adult.

D. Cumulative Effects

Novartis has considered the potential

for a cumulative exposure assessment

for effects of cloquintocet-mexyl and

other substances with the same

mechanism of toxicity. It is concluded

that such a determination would be

20976 Federal Register / Vol. 65, No. 76 / Wednesday, April 19, 2000 / Notices

inappropriate at this time because of the

unique role of cloquintocet-mexyl as a

product-specific safener.

E. Safety Determination

1. U.S. population. Acute and chronic

dietary exposure is minimal for

cloquintocet-mexyl and corresponding

hydrolysis product, CGA-153433. Both

chronic and acute exposure estimates at

the 95th percentile showed that less

than 1.0% of the reference dose is

utilized in all populations. These

exposure estimates are extremely

conservative and are based on tolerancelevel residues and assume all planted

acres are treated.

Exposure through the consumption of

drinking water is minimal from both

surface water and ground water model

estimates and in all cases less than 1%

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

cloquintocet-mexyl 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 a more than a

reasonable certainty that no harm will

result from aggregate exposure to

residues of cloquintocet-mexyl.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

cloquintocet-mexyl, 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.

The highest dose level of 400 mg/kg/

day in a developmental toxicity study in

rats resulted in reduced body weight

gain of the dams and signs of retarded

fetal development. No teratogenic

activity due to the test article was

detected. The NOAEL for dams and

fetuses was 100 mg/kg/day. Although

mortality was observed in rabbit dams at

the dose level of 300 mg/kg/day, no

teratogenic effects were noted. The

maternal NOAEL was 60 mg/kg/day, but

the developmental NOAEL was > 300

mg/kg/day.

Dietary administration of

cloquintocet-mexyl over 2-generations

at levels as high as 10,000 ppm did not

affect mating performance, fertility, or

litter sizes in rats, but a slightly reduced

body weight development of adults and

pups was noted at this level. The target

organ was kidney in adults and pups.

The treatment had no effect on

reproductive organs. The parental and

developmental NOAEL was 5,000 ppm,

corresponding to a mean daily intake of

370 to 422 mg/kg/day of cloquintocetmexyl. The reproductive NOAEL was >

10,000 ppm (722 mg/kg/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 data base. Based on

the current toxicological data

requirements, the data base relative to

prenatal and postnatal effects for

children is complete. EPA’s HIARC

concluded that there was no concern for

an increased susceptibility for

cloquintocet-mexyl based on the

reproduction study in rats and the

developmental studies in rat and rabbit.

Further, for cloquintocet-mexyl, the

NOAEL of 4.3 mg/kg/day from the

combined chronic/oncogenicity study in

rats, which was used to calculate the

RfD, is already lower than the

developmental NOAEL of 100 mg/kg/

day for the rat developmental toxicity

study. Further, the developmental and

parental NOAEL of 370 mg/kg/day from

the cloquintocet-mexyl reproduction

study is nearly 100 times greater than

the NOAEL for the combined chronic/

oncogenicity rat study. These data

would indicate that there is no

additional sensitivity of infants and

children to cloquintocet-mexyl.

Therefore, it is concluded that an

additional UF is not warranted to

protect the health of infants and

children from the use of cloquintocetmexyl.

Using conservative exposure

assumptions, dietary exposure to the

most sensitive subpopulation, children

(1–6 years old), is 0.9% of the chronic

reference dose (RfD). Chronic dietary

exposure to infants (non-nursing, 1–6

years old) is 0.2% of the chronic RfD.

EPA’s HIARC concluded that no acute

dietary assessment was necessary for the

general population (infants and

children) because a suitable

toxicological endpoint (resulting from a

single dose exposure) was not identified

in either the rat or rabbit developmental

studies.

Although not required, acute dietary

exposure to infants and children was

assessed. Acute exposures for all infants

and children at the 95th percentile are

less than 1.0% of the acute RfD (0.08%

of the RfD for the most sensitive

subpopulation, children 1–6 years).

Exposures to drinking water for children

(1–6 years old) and infants utilize less

than 1% of the chronic and acute RfD

values (worst-case surface water

estimates). These results show that

aggregate exposure to residues of

cloquintocet-mexyl 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 cloquintocetmexyl.

F. International Tolerances

Cloquintocet-mexyl is used as a

safener for the herbicide, clodinafoppropargyl. There are no Codex

Alimentarius Commission (CODEX)

maximum residue levels (MRLs)

established for residues of cloquintocetmexyl in or on RACs.

[FR Doc. 00–9796 Filed 4–18–00; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[OPP–50868; FRL–6553–3]

Experimental Use Permit; Receipt of

Application

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces receipt

of an application 67986–EUP–E from

AgriPhi, Inc. requesting an experimental

use permit (EUP) for the microbial

bacteriophages. The Agency has

determined that the application may be

of regional and national significance.

Therefore, in accordance with 40 CFR

172.11(a), the Agency is soliciting

comments on this application.

DATES: Comments, identified by docket

control number OPP–50868, must be

received on or before May 19, 2000.

ADDRESSES: Comments and data 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