Federal Register / Vol. 66, No. 26 / Wednesday, February 7, 2001 / Notices 9323

ii. Drinking water. Unites States EPA’s

standard operating procedure (SOP) for

drinking water exposure and risk

assessments was used to perform the

drinking water assessment. This SOP

uses a variety of tools to conduct a

screening level drinking water

assessment. These tools include water

models such as screening concentration

ground water (SCI-GROW), generic

expected environmental concentration

(GENEEC), EPA’s pesticide root zone

model (PRZMS)/EXAMS, and

monitoring data. If monitoring data is

not available then the models are used

to predict potential residues in surface

and ground water and the highest value

is assumed to be the potential drinking

water residue. In the case of

foramsulfuron monitoring data do not

exist therefore model calculations were

used to estimate a water residue. The

calculated drinking water levels of

concern (DWLOC) for chronic exposures

for adults is 297,498 (ppb) parts per

billion (297 ppm). The chronic DWLOC

for children/toddlers is 84,999 ppb (84

ppm). The worst case chronic drinking

water estimated concentration (DWEC)

is 0.225 ppb based on a PRZM/EXAMS

simulation of runoff into surface water

in a standard EPA exposure assessment

scenario for corn (MLRA 111, Ohio).

The calculated DWLOCs for chronic

exposures for all adults and children

therefore greatly exceed the DWECs

from the models.

2. Non-dietary exposure. Exposure to

foramsulfuron for the mixer/loader/

ground boom/aerial applicator was

calculated using the pesticide handlers

exposure data base (PHED). It was

assumed that the product would be

applied to a maximum of 50 hectares

per day (125 A/day) by ground boom

applicatior and 140 hectares per day

(350 A/day) by aerial applicator at a

maximum use rate of 45 grams a.i./ha.

Normal work attire consisting of longsleeved shirt, long pants, and protective

gloves was assumed in the PHED

assessment. Margins of exposure

(MOEs) for a 70 kg operator were

calculated utilizing a dermal NOAEL of

1,000 mg/kg bwt/day from the rat

dermal toxicity study and an inhalation

NOAEL of 50 mg/kg bwt/day based on

an oral administration, developmental

toxicity study in the rabbit. There were

no signs of developmental toxicity in

the rabbit developmental toxicity study.

The combined MOE (inhalation plus

dermal) for foramsulfuron was 126,000

for a ground operator undertaking

mixing, loading, and spraying. For aerial

application where the mixer/loader was

assumed to be a different operator from

the pilot combined MOEs were 60,400

for the mixer/loader and 1,425,000 for

the pilot. The results indicate that large

margins of safety exist for the proposed

use of foramsulfuron.

The timing of foramsulfuron

application to corn is such that field

reentry shortly after spraying is atypical.

Therefore estimations of worker reentry

exposure were not considered

necessary.

D. Cumulative Effects

There is no available data at this time

to determine whether foramsulfuron has

a common mechanism of toxicity with

other substances or how to include this

pesticide in a cumulative risk

assessment. Therefore a cumulative

assessment was not done for this

chemical.

E. Safety Determination

1. U.S. population. Using the

conservative assumptions described

above, based on the completeness and

reliability of the toxicity data, it is

concluded that aggregate exposure, in

this case food only, to the proposed uses

of foramsulfuron will utilize <0.001% of

the reference dose for the U.S.

population. The actual exposure is

likely to be much less as more realistic

data and models are developed. EPA

generally has no concern for exposures

below 100% of the RfD because the RfD

represents the level at or below which

daily aggregate exposure over a lifetime

will not pose appreciable risk to human

health. DWLOC based on the dietary

exposure are much greater than highly

conservative estimated levels, and

would be expected to be well below the

100% level of the RfD, if they occur at

all. Therefore, there is a reasonable

certainty that no harm will occur to the

U.S. population from aggregate exposure

(food and drinking water) to

foramsulfuron.

2. Infants and children. No evidence

of increased sensitivity to fetuses was

noted in developmental toxicity studies

in rats or rabbits. There has been no

indication of reproductive effects or

indication of increased sensitivity to the

offspring in the 2–generation rat

reproduction study. No additional safety

factor to protect infants and children is

necessary as there is no evidence of

increased sensitivity in infants and

children.

Using the conservative assumptions

described in the exposure section above,

the percent of the reference dose that

will be used for exposure to residues of

foramsulfuron in food for non-nursing

infants (the most highly exposed sub

group) is <0.001%. The children (1–6)

exposure uses are also <0.001% of the

reference dose. As in the adult situation,

DWLOC are much higher than the worst

case DWEC and are expected to use well

below 100% of the RfD, if they occur at

all. Therefore, there is a reasonable

certainty that no harm will occur to

infants and children from aggregate

exposure to residues of foramsulfuron.

F. International Tolerances

There are no Codex Alimentarius

Commission (CODEX) maximum

residue levels (MRLs) established for

residues of foramsulfuron.

[FR Doc. 01–3093 Filed 2–6–01; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[PF–994; FRL–6764–8]

Notice of Filing Pesticide Petitions to

Establish Tolerances for a Certain

Pesticide Chemical in or on Food

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of pesticide petitions

proposing the establishment of

regulations for residues of a certain

pesticide chemical in or on various food

commodities.

DATES: Comments, identified by docket

control number PF–994, must be

received on or before March 9, 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–994 in the subject line on the first

page of your response.

FOR FURTHER INFORMATION CONTACT: By

mail: 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.

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:

9324 Federal Register / Vol. 66, No. 26 / Wednesday, February 7, 2001 / Notices

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–

994. 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–994 in the subject

line on the first page of your response.

1. By mail. Submit your comments to:

Public Information and Records

Integrity Branch (PIRIB), Information

Resources and Services Division

(7502C), Office of Pesticide Programs

(OPP), Environmental Protection

Agency, 1200 Pennsylvania Ave., NW.,

Washington, DC 20460.

2. In person or by courier. Deliver

your comments to: Public Information

and Records Integrity Branch (PIRIB),

Information Resources and Services

Division (7502C), Office of Pesticide

Programs (OPP), Environmental

Protection Agency, Rm. 119, Crystal

Mall #2, 1921 Jefferson Davis Highway,

Arlington, VA. The PIRIB is open from

8:30 a.m. to 4 p.m., Monday through

Friday, excluding legal holidays. The

PIRIB telephone number is (703) 305–

5805.

3. Electronically. You may submit

your comments electronically by e-mail

to: opp-docket@epa.gov, or you can

submit a computer disk as described

above. Do not submit any information

electronically that you consider to be

CBI. Avoid the use of special characters

and any form of encryption. Electronic

submissions will be accepted in

Wordperfect 6.1/8.0 or ASCII file

format. All comments in electronic form

must be identified by docket control

number PF–994. 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 pesticide petitions

as follows proposing the establishment

and/or amendment of regulations for

residues of a certain pesticide chemical

in or on various food commodities

under section 408 of the Federal Food,

Drug, and Cosmetic Act (FFDCA), 21

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

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 support granting of

these petitions. Additional data may be

needed before EPA rules on the

petitions.

List of Subjects

Environmental protection,

Agricultural commodities, Feed

additives, Food additives, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: January 25, 2001.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

Summaries of Petitions

The petitioner summaries of the

pesticide petitions are printed below as

Federal Register / Vol. 66, No. 26 / Wednesday, February 7, 2001 / Notices 9325

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

FFDCA. The summaries of the petitions

were prepared by the petitioner and

represent the view of the petitioner.

EPA is publishing the petitioner’s

summaries verbatim without editing it

in any way. The petitioner’s summaries

announces the availability of a

description of the analytical methods

available to EPA for the detection and

measurement of the pesticide chemical

residues or an explanation of why no

such method is needed.

Elf Atochem North America

PP 7F4867 and 7F4868

EPA has received pesticide petitions

PP 7F4867 and PP 7F4868 from Elf

Atochem North America, 2000 Market

Street, Philadelphia, PA 19103

proposing pursuant to section 408(d) of

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

40 CFR part 180 by establishing

tolerances for residues of endothall in or

on the raw agricultural commodities

cottonseed ((RAC) seed and processed

seed) at 2.0 parts per million (ppm) and

apples at 0.05 ppm. EPA has determined

that the petitions contain data or

information regarding the elements set

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

however, EPA has not fully evaluated

the sufficiency of the submitted data at

this time or whether the data support

granting of the petitions. Additional

data may be needed before EPA rules on

the petitions.

1. PP 7F4867

A. Residue Chemistry

1. Plant metabolism. Acala cotton was

treated by a single foliar application

with 14C-endothall formulated as the

dipotassium salt. The study identified

84– >100% of the radioactivity in/on

cotton calyx, forage, and lint. Endothall

accounted for ca. 94% and 83% of total

radioactive residue (TRR) in calyx and

lint, respectively, harvested 4 days

following application at 1x, and for ca.

99%, 102%, and 95% of TRR in calyx,

forage and lint, respectively, harvested

14 days post-treatment. No other

metabolites were identified in calyx and

forage. The monomethyl and dimethyl

ester of endothall were minor (< 10%

TRR) metabolites in lint. No metabolites

were identified in seed.

2. Analytical method. The analytical

method for endothall in water is EPA/

ORD method 548, ‘‘Determination of

Endothall in Drinking Water by

Aqueous Derivatization, Liquid-Solid

Extraction and Gas Chromatography

with Electron-Capture Detection.’’ The

limit of detection (LOD) for this method

is 0.015 ppm.

3. Magnitude of residues. Endothall

was applied to cotton at a rate of 0.85

lb./acre with a 3–day pre-harvest

interval (PHI). Residues in RAC seed

were 0.46 ppm (0.071 to 1.1 ppm) and

residues in RAC gin trash were 21 ppm

(6.6 to 59 ppm).

B. Toxicological Profile

1. Acute toxicity. Endothall acid and

the dipotassium salt of endothall are

moderately toxic by oral ingestion and

inhalation (toxicity category II), slightly

toxic by dermal exposure (toxicity

category III) and severely irritating to

the eye. The diamine salt of endothall

is moderately toxic by oral, dermal, and

inhalation routes of exposure (toxicity

category II) and is severely irritating to

the eyes and skin.

2. Genotoxicity. A full battery of

genetic toxicology studies were

conducted for endothall. Endothall was

not mutagenic.

3. Reproductive and developmental

toxicity. In a teratology and postnatal

behavioral study, pregnant Sprague

Dawley rats were dose via oral gavage

on gestation days 6 through 15 with

endothall doses of 0, 10, 20, or 30

milligram/kilogram (mg/kg)/day. The

maternal no observed adverse effect

level (NOAEL) was 20 mg/kg/day due to

mortality seen at 30 mg/kg/day. The

developmental NOAEL was 30 mg/kg/

day. In a subsequent developmental

toxicity study, pregnant Sprague Dawley

rats were orally dosed with 0, 6.25, 12.5,

or 25.0 mg/kg/day from gestation day 6

through 15. The NOAEL for maternal

toxicity was 12.5 mg/kg/day. The

developmental NOAEL was 25.0 mg/kg/

day.

A developmental toxicity study was

conducted in female CD–1 mice. Groups

of pregnant mice were orally dosed with

0, 5, 20, or 40 mg/kg/day on days 6 to

16 of gestation. The NOAEL for

maternal toxicity was 5 mg/kg/day

based on mortality seen at 20 mg/kg/

day. The developmental NOAEL was 20

mg/kg/day. Developmental changes seen

at 40 mg/kg/day were related to the

severe maternal toxicity at that dose. A

developmental toxicity study was

conducted in New Zealand white

rabbits by oral exposure. Preliminary

studies indicated that the rabbit was

extremely sensitive to endothall. Groups

of pregnant rabbits were dose with 0,

0.3, 1.0, or 3.0 mg/kg/day on gestation

days 6 through 19. The fetal and

maternal toxicity NOAELs were 1.0 mg/

kg/day. A 2–generation reproduction

study was conducted in rats. In this

study, groups of rats received dietary

doses of 0, 30, 150, and 900 ppm (0, 1.9,

9.5, or 58.8 mg/kg/day for male and 0,

1.9–3.4, 9.6–18.5, or 59.0–106.5 mg/kg/

day for female F0 animals; 0, 2.1, 10.9,

or 77.1 for male and 0, 1.8–3.1, 9.5–17.3,

or 63.5–107.7 for female F1 animals).

The NOAEL for parental effects was 30

ppm based on dose related body weight

effects. The NOAEL for reproductive

toxicity was 900 ppm.

4. Subchronic toxicity. Male and

female Sprague Dawley rats were

exposed dermally to 0, 30, 100, and 300

mg/kg/day for 21 days. The lowest

observed effect level (LOAEL) was 30

mg/kg/day based on decreased body

weight gain and dermal irritation. A

NOAEL was not established. Male and

female Sprague Dawley rats were

exposed to oral concentrations of 0, 150,

600, or 1,800 ppm (0, 10, 39, or 118 mg/

kg/day for males; 0, 12, 51, or 153 mg/

kg/day for females respectively) for 13

weeks. The LOAEL was 1,800 ppm

based on decreases in body weight gain

and food intake. The NOAEL was 600

ppm. Male and female Beagle dogs were

exposed to oral concentrations of 0, 100,

400, or 1,000 ppm (0, 3.2, 11.7, or 27.5

mg/kg/day for males and 0, 3.2, 13.0, or

28.9 mg/kg/day for females respectively)

for 13 weeks. The LOAEL was 1,000

ppm based on decreases in body weight

gain and food intake. The NOAEL was

400 ppm.

5. Chronic toxicity. In a combined

chronic toxicity and oncogenicity study,

male and female Sprague Dawley rats

were fed endothall dietary

concentrations of 0, 150, 300, 900, and

1,800 ppm for 104 weeks. No evidence

of carcinogenicity was seen in this

study. The NOAEL was 150 ppm. The

incidence of acanthosis and

hyperkeratosis of the stomach was

slightly higher than control for the 150

ppm males. This finding was not

considered an adverse effect since the

incidence of this finding in the 300 ppm

males was similar to control. Beagle

dogs were fed diets containing 0, 100,

300, or 800 ppm disodium endothall

(equivalent to 0, 2, 6, or 16 mg/kg/day

endothall) for 24 months. No clinical

signs of toxicity were seen at any dose

level. The 100 ppm dietary

concentration (2 mg/kg/day) was the

NOAEL.

In a 52–week oral toxicity study,

groups of 4 male and 4 female Beagle

dogs were fed diets containing 0, 150,

450, or 1,350/1,000 ppm (0, 5.7, 17.1,

and 35.8 mg/kg/day for males; 0, 6.4,

18.8, and 36 mg/kg/day for females).

The 1,350 ppm dietary level had to be

1,000 ppm after 6 weeks of treatment

due to marked reductions in body

weight, food consumption, and

subsequent sacrifice of 5 animals from

this group. Minimal to very mild gastric

epithelial effects were seen in some of

the dogs receiving 150 ppm. This effect

9326 Federal Register / Vol. 66, No. 26 / Wednesday, February 7, 2001 / Notices

was considered as a low grade reaction

to chronic epithelial irritation and 150

ppm is considered a NOAEL. In an 18–

month oncogenicity study, Swiss Albino

mice were fed in the diet at

concentrations of 0, 50, 100, and 300

ppm (0, 8.1, 16.7, and 50 mg/kg/day for

males; 0, 10.8, 22.4, and 68 mg/kg/day

for females) for 92 weeks. The systemic

NOAEL was 100 ppm based on

decreased mean body weight in 300

ppm males. No evidence of

carcinogenicity was seen in this study.

In a second 18–month dietary

oncogenicity study, groups of 50 male

and 50 female Swiss Albino mice were

fed the disodium salt of endothall at

dietary concentrations of 0, 750, and

1,500 ppm (0, 122, and 258 mg/kg/day

for males; 0, 152, and 319 mg/kg/day for

females). Toxicity results for the 1,500

ppm dietary level clearly shows that the

maximum tolerance dose (MTD) was

exceeded. At 750 ppm, compoundrelated effects consisted of decreased

body weight gain, rectal prolapse and an

increase in the incidence and severity of

mucosal hyperplasia of the glandular

stomach. Endothall was not considered

carcinogenic in this study.

6. Animal metabolism. Following a

single oral administration of 14Cendothall to males and female rats, the

majority of the radioactivity was

excreted within 24 hours. The majority

of the radioactivity was found in the

feces. Chromatographic analysis of

extracts of the urine, feces, cecum, and

large intestine of both male and female

rats gave a single radioactive component

corresponding to unchanged endothall.

7. Endocrine disruption. Evaluation of

the results from the 2–generation

reproduction studies do not

demonstrate any effects suggestive of

disruption of hormonal stasis in the rat.

Further, histopathologic evaluation of

hormone sensitive tissues from

chronically exposed rats, mice, and dogs

did not reveal any changes suggestive of

an endocrine-related effect.

C. Aggregate Exposure

1. Dietary exposure—i. Food.

Endothall exposure via the diet will

occur from treated apples, sugar beets,

potatoes, cotton, and hops (adults).

Secondary residues are expected in

meat, milk, and eggs as well as shellfish,

fish, catfish, and crayfish.

ii. Drinking water. Drinking water

exposure to endothall may be expected.

However this exposure is not

considered to be significant due to the

seasonal intermittent use of the product

for aquatic weed control, its low

mobility in surface waters and rapid

degradation.

2. Non-dietary exposure. There are no

registered and proposed uses for

endothall products which would result

in non-occupational exposure.

D. Cumulative Effects

Elf Atochem has reviewed chemical

structure data to determine if any other

pesticide products are chemically

similar to endothall and produce

gastrointestinal changes specific to

endothall. Endothall appears to be

chemically and toxicologically

dissimilar to existing chemical

substances. Therefore, cumulative risk

should not be an issue for this chemical.

E. Safety Determination

1. U.S. population. For chronic

dietary risk, two scenarios were used.

Scenario 1 used tolerance values on all

registered and proposed crops, as well

as secondary residues in meat, milk, and

eggs, shellfish, fish, catfish, and

crayfish. Under this scenario, less than

5% of the reference dose (RfD) for the

total U.S. population was utilized.

Because of the high milk consumption

by children ages 1–6, this group

represents the highest exposed

subgroup. For children ages 1–6,

approximately 12.4% of the RfD is

utilized. In the second scenario which

included the above food exposure from

above plus tap water and non-food

based water, 28.3% of the RfD was

utilized for the total U.S. population.

Because of high water consumption

likely from reconstituted formula, all

infants utilized 103.7% of the RfD and

non-nursing infants utilized 130.7% of

the RfD. This scenario, however, is not

considered a realistic estimate of risk. It

is unlikely that endothall residues

would be significant in water

considering its intermittent and

seasonal use pattern, lack of movement

in surface water, rapid degradation and

label restriction for application within

600 feet of a potable water intake. The

acute dietary risk analysis has been

performed using TAS-Exposure software

which gives a distributional analysis of

exposure. For the total U.S. population,

children aged 7–12, and women aged 13

to 50 all margins of exposure (MOE)

exceeded 1,000 at the 95th percentile of

exposure for the first scenario

(excluding water). Under this scenario,

all Infants, non-nursing infants < 1–year

and children ages 1–6 had MOEs of 935,

852, and 988, respectively. When tap

water and non-food based water are

included in the analysis at tolerance

level (0.2 ppm), the highest exposed

subpopulation is again non-nursing

infants with a MOE of 98 at the 95th

percentile of exposure. For the total U.S.

population the 95th percentile of

exposure results in an MOE of 373. This

analysis included all commodities,

including water, at theoretical ‘‘worst

case’’ levels resulting in an extreme over

estimation of acute risk from dietary

exposure to potential endothall

residues. This analysis has not included

estimates of anticipated residues,

percent of crop treated, or the likelihood

of residues in water accounting for

endothall’s use pattern, movement and

degradation. Additionally, processing

effects on residue levels have not been

considered. Despite all of the worst case

assumptions, the dietary exposure

analysis for the U.S. population, and all

population subgroups except all infants

and non-nursing infants <1 year results

in acceptable MOE, i.e., >100. The MOE

for all infants and non-nursing infants

<1 year were 99 and 98, respectively.

Clearly these MOEs in this worst case

assessment would exceed 100 if

adjustments described above were

applied.

2. Infants and children. The exposure

to infants and children has been

calculated in both the acute and chronic

dietary assessments. In all cases, and all

age groups of infants and children, the

MOE is sufficient to protect the health

of infants and children.

F. International Tolerances

No international tolerances have been

established for endothall.

2. PP 7F4868

A. Residue Chemistry

1. Plant metabolism. The metabolism

of endothall was examined in three

crops types: alfalfa, cotton, and

sugarbeet. All three studies were

conducted using C–2 and C–3–(14C)

endothall and showed the same pattern

of metabolic breakdown. The parent

compound endothall accounted for the

majority of the total radioactive residue

(85–110%), with the monomethyl and

dimethyl esters of endothall present as

minor metabolites (<10%).

2. Analytical method. The analytical

method for endothall in water is EPA/

ORD method 548, ‘‘Determination of

Endothall in Drinking Water by

Aqueous Derivatization, Liquid-Solid

Extraction and Gas Chromatography

with Electron-Capture Detection.’’ The

limit of detection LOD for this method

is 0.015 ppm.

3. Magnitude of residues. Residue

trials in apples showed residue levels in

the RAC of 0.0086 ppm (residue range

of 0.005–0.023 ppm), 0.015 ppm (0.012–

0.020 ppm) for the processed RAC,

0.019 ppm (0.012–0.026 ppm) for apple

pomace, and 0.019 ppm (0.071–1.1

ppm) for apple juice.

Federal Register / Vol. 66, No. 26 / Wednesday, February 7, 2001 / Notices 9327

B. Toxicological Profile

1. Acute toxicity. Endothall acid and

the dipotassium salt of endothall are

moderately toxic by oral ingestion and

inhalation (toxicity category II), slightly

toxic by dermal exposure (toxicity

category III) and severely irritating to

the eye. The diamine salt of endothall

is moderately toxic by oral, dermal, and

inhalation routes of exposure (toxicity

category II) and is severely irritating to

the eyes and skin.

2. Genotoxicity. A full battery of

genetic toxicology studies were

conducted for endothall. Endothall was

not mutagenic.

3. Reproductive and developmental

toxicity. In a teratology and postnatal

behavioral study, pregnant Sprague

Dawley rats were dose via oral gavage

on gestation days 6 through 15 with

endothall doses of 0, 10, 20, or 30 mg/

kg/day. The maternal NOAEL was 20

mg/kg/day due to mortality seen at 30

mg/kg/day. The developmental NOAEL

was 30 mg/kg/day. In a subsequent

developmental toxicity study, pregnant

Sprague Dawley rats were orally dosed

with 0, 6.25, 12.5, or 25.0 mg/kg/day

from gestation day 6 through 15. The

NOAEL for maternal toxicity was 12.5

mg/kg/day. The developmental NOAEL

was 25.0 mg/kg/day.

A developmental toxicity study was

conducted in female CD–1 mice. Groups

of pregnant mice were orally dosed with

0, 5, 20, or 40 mg/kg/day on days 6 to

16 of gestation. The NOAEL for

maternal toxicity was 5 mg/kg/day

based on mortality seen at 20 mg/kg/

day. The developmental NOAEL was 20

mg/kg/day. Developmental changes seen

at 40 mg/kg/day were related to the

severe maternal toxicity at that dose. A

developmental toxicity study was

conducted in New Zealand white

rabbits by oral exposure. Preliminary

studies indicated that the rabbit was

extremely sensitive to endothall. Groups

of pregnant rabbits were dosed with 0,

0.3, 1.0, or 3.0 mg/kg/day on gestation

days 6 through 19. The fetal and

maternal toxicity NOAELs were 1.0 mg/

kg/day. A 2–generation reproduction

study was conducted in rats. In this

study, groups of rats received dietary

doses of 0, 30, 150, and 900 ppm (0, 1.9,

9.5, or 58.8 mg/kg/day for male and 0,

1.9–3.4, 9.6–18.5, or 59.0–106.5 mg/kg/

day for female F0 animals; 0, 2.1, 10.9,

or 77.1 for male, and 0, 1.8–3.1, 9.5–

17.3, or 63.5–107.7 for female

F1animals). The NOAEL for parental

effects was 30 ppm based on dose

related body weight effects. The NOAEL

for reproductive toxicity was 900 ppm.

4. Subchronic toxicity. Male and

female Sprague Dawley rats were

exposed dermally to 0, 30, 100, and 300

mg/kg/day for 21 days. The LOAEL was

30 mg/kg/day based on decreased body

weight gain and dermal irritation. A

NOAEL was not established. Male and

female Sprague Dawley rats were

exposed to oral concentrations of 0, 150,

600, or 1,800 ppm (0, 10, 39, or 118 mg/

kg/day for males; 0, 12, 51, or 153 mg/

kg/day for female respectively) for 13

weeks. The LOAEL was 1,800 ppm

based on decreases in body weight gain,

and food intake. The NOAEL was 600

ppm. Male and female Beagle dogs were

exposed to oral concentrations of 0, 100,

400, or 1,000 ppm (0, 3.2, 11.7, or 27.5

mg/kg/day for males and 0, 3.2, 13.0, or

28.9 mg/kg/day for females respectively)

for 13 weeks. The LOAEL was 1,000

ppm based on decreases in body weight

gain and food intake. The NOAEL was

400 ppm.

5. Chronic toxicity. In a combined

chronic toxicity and oncogenicity study,

male and female Sprague Dawley rats

were fed endothall dietary

concentrations of 0, 150, 300, 900, and

1,800 ppm for 104 weeks. No evidence

of carcinogenicity was seen in this

study. The NOAEL was 150 ppm. The

incidence of acanthosis and

hyperkeratosis of the stomach was

slightly higher than control for the 150

ppm males. This finding was not

considered an adverse effect since the

incidence of this finding in the 300 ppm

males was similar to control. Beagle

dogs were fed diets containing 0, 100,

300, or 800 ppm disodium endothall

(equivalent to 0, 2, 6, or 16 mg/kg/day

endothall) for 24 months. No clinical

signs of toxicity were seen at any dose

level. The 100 ppm dietary

concentration (2 mg/kg/day) was the

NOAEL. In a 52–week oral toxicity

study, groups of 4 male and 4 female

Beagle dogs were fed diets containing 0,

150, 450, or 1,350/1,000 ppm (0, 5.7,

17.1, and 35.8 mg/kg/day for males; 0,

6.4, 18.8, and 36 mg/kg/day for females).

The 1,350 ppm dietary level had to be

1,000 ppm after 6 weeks of treatment

due to marked reductions in body

weight and food consumption and

subsequent sacrifice of 5 animals from

this group. Minimal to very mild gastric

epithelial effects were seen in some of

the dogs receiving 150 ppm. This effect

was considered as a low grade reaction

to chronic epithelial irritation and 150

ppm is considered a NOAEL. In an 18–

month oncogenicity study, Swiss Albino

mice were fed in the diet at

concentrations of 0, 50, 100, and 300

ppm (0, 8.1, 16.7, and 50 mg/kg/day for

males; 0, 10.8, 22.4, and 68 mg/kg/day

for females) for 92 weeks. The systemic

NOAEL was 100 ppm based on

decreased mean body weight in 300

ppm males. No evidence of

carcinogenicity was seen in this study.

In a second 18–month dietary

oncogenicity study, groups of 50 male

and 50 female Swiss Albino mice were

fed the disodium salt of endothall at

dietary concentrations of 0, 750, and

1,500 ppm (0, 122, and 258 mg/kg/day

for males; 0, 152, and 319 mg/kg/day for

females). Toxicity results for the 1,500

ppm dietary level clearly shows that the

MTD was exceeded. At 750 ppm,

compound-related effects consisted of

decreased body weight gain, rectal

prolapse and an increase in the

incidence and severity of mucosal

hyperplasia of the glandular stomach.

Endothall was not considered

carcinogenic in this study.

6. Animal metabolism. Following a

single oral administration of 14Cendothall to males and female rats, the

majority of the radioactivity was

excreted within 24 hours. The majority

of the radioactivity was found in the

feces. Chromatographic analysis of

extracts of the urine, feces, cecum and

large intestine of both male and female

rats gave a single radioactive component

corresponding to unchanged endothall.

7. Endocrine disruption. Evaluation of

the results from the 2–generation

reproduction studies do not

demonstrate any effects suggestive of

disruption of hormonal stasis in the rat.

Further, histopathologic evaluation of

hormone sensitive tissues from

chronically exposed rats, mice, and dogs

did not reveal any changes suggestive of

an endocrine-related effect.

C. Aggregate Exposure

1. Dietary exposure— i. Food.

Endothall exposure via the diet will

occur from treated apples, sugar beets,

potatoes, cotton, and hops (adults).

Secondary residues are expected in

meat, milk, and eggs as well as shellfish,

fish, catfish,and crayfish.

ii. Drinking water. Drinking water

exposure to endothall may be expected.

However this exposure is not

considered to be significant due to the

seasonal intermittent use of the product

for aquatic weed control, its low

mobility in surface waters and rapid

degradation.

2. Non-dietary exposure. There are no

registered and proposed uses for

endothall products which would result

in non-occupational exposure.

D. Cumulative Effects

Elf Atochem has reviewed chemical

structure data to determine if any other

pesticide products are chemically

similar to endothall and produce

gastrointestinal changes specific to

9328 Federal Register / Vol. 66, No. 26 / Wednesday, February 7, 2001 / Notices

endothall. Endothall appears to be

chemically and toxicologically

dissimilar to existing chemical

substances. Therefore, cumulative risk

should not be an issue for this chemical.

E. Safety Determination

1. U.S. population. For chronic

dietary risk, two scenarios were used.

Scenario 1 used tolerance values on all

registered and proposed crops, as well

as secondary residues in meat, milk, and

eggs, shellfish, fish, catfish, and

crayfish. Under this scenario, less than

5% of the RfD for the total U.S.

population was utilized. Because of the

high milk consumption by children ages

1–6, this group represents the highest

exposed subgroup. For children ages 1–

6, approximately 12.4% of the RfD is

utilized. In the second scenario which

included the above food exposure from

above plus tap water and non-food

based water, 28.3% of the RfD was

utilized for the total U.S. population.

Because of high water consumption

likely from reconstituted formula, all

infants utilized 103.7% of the RfD and

non-nursing infants utilized 130.7% of

the RfD. This scenario, however, is not

considered a realistic estimate of risk. It

is unlikely that endothall residues

would be significant in water

considering its intermittent and

seasonal use pattern, lack of movement

in surface water, rapid degradation and

label restriction for application within

600 feet of a potable water intake. The

acute dietary risk analysis has been

performed using TAS-Exposure software

which gives a distributional analysis of

exposure. For the total U.S. population,

children ages 7–12, and women ages 13

to 50 all MOEs exceeded 1,000 at the

95th percentile of exposure for the first

scenario (excluding water). Under this

scenario, all infants, non-nursing infants

<1–year and children ages 1–6 had

MOEs of 935, 852, and 988,

respectively. When tap water and nonfood based water are included in the

analysis at tolerance level (0.2 ppm), the

highest exposed subpopulation is again

non-nursing infants with an MOE of 98

at the 95th percentile of exposure. For

the total U.S. population the 95th

percentile of exposure results in an

MOE of 373. This analysis included all

commodities, including water, at

theoretical ‘‘worst case’’ levels resulting

in an extreme over estimation of acute

risk from dietary exposure to potential

endothall residues. This analysis has

not included estimates of anticipated

residues, percent of crop treated, or the

likelihood of residues in water

accounting for endothall’s use pattern,

movement and degradation.

Additionally, processing effects on

residue levels have not been considered.

Despite all of the worst case

assumptions, the dietary exposure

analysis for the U.S. population, and all

population subgroups except all infants

and non-nursing infants <1–year results

in acceptable MOE, i.e., >100. The MOE

for all infants and non-nursing infants

<1–year were 99 and 98, respectively.

Clearly these MOEs in this worst case

assessment would exceed 100 if

adjustments described above were

applied.

2. Infants and children. The exposure

to infants and children has been

calculated in both the acute and chronic

dietary assessments. In all cases and all

age groups of infants and children, the

margins of exposure are sufficient to

protect the health of infants and

children.

F. International Tolerances

No international tolerances have been

established for endothall.

[FR Doc. 01–3092 Filed 2–6–01; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION

AGENCY

[OPP–00697; FRL–6765–5]

Acute Toxicity Data Requirements For

Granular Pesticide Products, Including

those with Granular Fertilizers in the

Product; Notice of Availability

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice of availability.

SUMMARY: EPA is announcing the

availability of guidance whichintends to

streamline the acute toxicity review and

classification process for certain

granular pesticide products, including

those products that contain granular

fertilizers. The policies should achieve

the following objectives: Significantly

reduce the number of animals subject to

testing; reduce the use of Agency

resources while maintaining protection

of the public health and environment,

and decrease the time required to

register qualifyinggranular pesticide

products. Pesticide Registration (PR)

Notice 2001–2 is effective now, but

comments will be accepted for 30 days,

after which the Agency may revise the

notice.

DATES: Comments, identified by docket

control number OPP–00697, must be

received on or before March 9, 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. of the

SUPPLEMENTARY INFORMATION. To ensure

proper receipt by EPA, it is imperative

that you identify docket control number

OPP–00697 in the subject line on the

first page of your response.

FOR FURTHER INFORMATION CONTACT: By

mail: John Redden,Registration Division

(7505C), Office of Pesticide Programs,

Environmental Protection Agency, 1200

Pennsylvania Ave., NW., Washington,

DC 20460; telephone number: (703)

305–1969; fax number: (703) 308–9382;

e-mail address: redden.john@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

This action is directed to the public

in general. This action may, however, be

of interest to those persons who are

required to conduct testing of chemical

substances under the Federal

Insecticide, Fungicide, and Rodenticide

Act (FIFRA). Since other entities may

also be interested, 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 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

the PR Notice from the Office of

Pesticide Programs’ Home Page at http:/

/www.epa.gov/pesticides/. You can also

go directly to the listings from the EPA

Internet Home Page at http://

www.epa.gov/. To access this

document, on the Home Page select

‘‘Laws and Regulations,’’ ‘‘Regulations

and Proposed Rules,’’ and then look up

the entry for this document under the

‘‘Federal Register—Environmental

Documents.’’ You can also godirectly to

the Federal Register listings at http://

www.epa.gov/fedrgstr/.

2. Fax–on–demand. You may request

a faxed copy of the PR Notice titled,

‘‘Acute Toxicity Data Requirements For

Granular Pesticide Products, Including

those with Granular Fertilizers in the

Product,’’ by using a faxphone to call

(202) 401–0527 andselecting item 6136.

You may also follow the automated

menu.

3. In person. The Agency has

established an official record for this

action under docket control number

OPP–00697. The official record consists

of the documents specifically referenced