30750 Federal Register / Vol. 63, No. 108 / Friday, June 5, 1998 / Notices

an EPA Pesticide Fact Sheet on

cyprodinil N-(4-cyclopropyl-6-methylpyrimidin-2-yl)-aniline.

A paper copy of this fact sheet, which

provides a summary description of the

chemical, use patterns and

formulations, science findings, and the

Agency’s regulatory position and

rationale, may be obtained from the

National Technical Information Service

(NTIS), 5285 Port Royal Road,

Springfield, VA 22161.

In accordance with section 3(c)(2) of

FIFRA, a copy of the approved label, the

list of data references, the data and other

scientific information used to support

registration, except for material

specifically protected by section 10 of

FIFRA, are available for public

inspection in the Public Information

and Records Intregrity Branch,

Information Resources and Services

Division (7502C), Office of Pesticide

Programs, Environmental Protection

Agency, Rm. 119, CM #2, Arlington, VA

22202 (703–305–5805). Requests for

data must be made in accordance with

the provisions of the Freedom of

Information Act and must be addressed

to the Freedom of Information Office (A101), 401 M St., SW., Washington, D.C.

20460. Such requests should: (1)

Identify the product name and

registration number and (2) specify the

data or information desired.

Authority: 7 U.S.C. 136.

List of Subjects

Environmental protection, Pesticides

and pests, Product registration.

Dated: May 27, 1998.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

[FR Doc. 98–15013 Filed 6–4–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–807; FRL–5791–4]

Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of pesticide petitions

proposing the establishment of

regulations for residues of certain

pesticide chemicals in or on various

food commodities.

DATES: Comments, identified by the

docket control number PF–807, must be

received on or before July 6, 1998.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch, Information

Resources and Services Division

(7502C), Office of Pesticides Programs,

Environmental Protection Agency, 401

M St., SW., Washington, DC 20460. In

person bring comments to: Rm. 119, CM

#2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically by following

the instructions under

‘‘SUPPLEMENTARY INFORMATION.’’

No confidential business information

should be submitted through e-mail.

Information submitted as a comment

concerning this document may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI). CBI should not be submitted

through e-mail. Information marked as

CBI will not be disclosed except in

accordance with procedures set forth in

40 CFR part 2. A copy of the comment

that does not contain CBI must be

submitted for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments will be available for public

inspection in Rm. 1132 at the address

given above, from 8:30 a.m. to 4 p.m.,

Monday through Friday, excluding legal

holidays.

FOR FURTHER INFORMATION CONTACT: The

product manager listed in the table

below:

Product Manager Office location/telephone number Address

Joanne Miller (PM 23) ... Rm. 237, CM #2, 703–305–6224, e-mail:miller.joanne@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Beth Edwards (PM 3) .... Rm. 206, CM #2, 703–305–5400, e-mail: edwards.beth@epamail.epa.gov. Do.

SUPPLEMENTARY INFORMATION: EPA has

received pesticide petitions as follows

proposing the establishment and/or

amendment of regulations for residues

of certain pesticide chemicals in or on

various food commodities under section

408 of the Federal Food, Drug, and

Comestic Act (FFDCA), 21 U.S.C. 346a.

EPA has determined that these petitions

contain data or information regarding

the elements set forth in section

408(d)(2); however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data supports granting of the

petition. Additional data may be needed

before EPA rules on the petition.

The official record for this notice of

filing, as well as the public version, has

been established for this notice of filing

under docket control number [PF–807]

(including comments and data

submitted electronically as described

below). A public version of this record,

including printed, paper versions of

electronic comments, which does not

include any information claimed as CBI,

is available for inspection from 8:30

a.m. to 4 p.m., Monday through Friday,

excluding legal holidays. The official

record is located at the address in

‘‘ADDRESSES’’ at the beginning of this

document.

Electronic comments can be sent

directly to EPA at:

opp-docket@epamail.epa.gov

Electronic comments must be

submitted as an ASCII file avoiding the

use of special characters and any form

of encryption. Comment and data will

also be accepted on disks in

Wordperfect 5.1 file format or ASCII file

format. All comments and data in

electronic form must be identified by

the docket number (insert docket

number) and appropriate petition

number. Electronic comments on notice

may be filed online at many Federal

Depository Libraries.

List of Subjects

Environmental protection,

Agricultural commodities, Food

additives, Feed additives, Pesticides and

pests, Reporting and recordkeeping

requirements.

Dated: May 20, 1998.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

Summaries of Petitions

Petitioner summaries of the pesticide

petitions are printed below as required

by section 408(d)(3) of the FFDCA. The

summaries of the petitions were

prepared by the petitioners and

represent the views of the petitioners.

EPA is publishing the petition

summaries verbatim without editing
Federal Register / Vol. 63, No. 108 / Friday, June 5, 1998 / Notices 30751

them in any way. The petition summary

announces the availability of a

description of the analytical methods

available to EPA for the detection and

measurement of the pesticide chemical

residues or an explanation of why no

such method is needed.

1. Novartis Crop Protection, Inc.

PP 7F4924

EPA has received a pesticide petition

(PP 7F4924) from Novartis Crop

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

Greensboro, NC 27419-8300 proposing

pursuant to section 408(d) of the Federal

Food, Drug and Cosmetic Act, 21 U.S.C.

346a(d), to amend 40 CFR part 180 to

establish tolerances for Clodinafoppropargyl, Propanoic acid, 2-[4-[(5-

chloro-3-fluoro-2-

pyridinyl)oxy]phenoxy]-,2-propynyl

ester, in or on the raw agricultural

commodities wheat grain at 0.02 and

wheat straw at 0.05 parts per million

(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 CGA-184927 in wheat is understood

for the purposes of the proposed

tolerance. 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 CGA-184927

and its major plant metabolite CGA193469 in wheat raw agricultural

commodities (RACs). CGA-184927 is

extracted from crops with acetonitrile,

cleaned up by solvent partition and

solid phase extraction and determined

by column switching HPLC with

ultraviolet detection. CGA-193469 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

quantitation (LOQ) for the methods are

0.02 ppm for CGA-184927 in grain and

forage, 0.05 ppm for CGA-184927 in

straw, and 0.05 ppm for CGA-193469 in

forage, straw and grain.

3. Magnitude of residues. 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 US (MT, ND, SD,

MN). Nine trials were conducted in

1989-91 with a tank mix of CGA-184927

and a safener as separate EC

formulations, and three trials in 1992

were conducted with CGA-184927 and

the safener as a pre-pack EC

formulation. All trials had a single postemergence application of CGA-184927

at a rate of 80 g a.i./Ha. At PHIs of 66-

97-days, no detectable residues of CGA184927 or its metabolite CGA-193469

were found in mature grain and straw

from these trials. Separate decline

studies (3) on green forage showed no

detectable residues of CGA-184927 or

CGA-193469 beyond the 3-days after

application (DAA) interval. A freezer

storage stability study indicated

reasonable stability of both analytes for

a period of 1-year, with CGA-184927

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 1829 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 mg/liter, 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 would carry

the EPA signal word ‘‘Caution’’.

2. Genotoxicty. The mutagenic

potential of clodinafop-propargyl was

investigated in 6 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; chromosomal aberrations using

human lymphocytes and the mouse

micronucleus test; and DNA repair

using rat hepatocytes and human

fibroblasts. 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. 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

developmental and reproductive NOEL

was 50 ppm, corresponding to a mean

daily intake of 3.3 milligrams/kilogram

(mg/kg) clodinafop-propargyl.

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. The NOEL for dams and

fetuses was 40 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. The maternal NOEL was 25 mg/

kg/day and the fetal NOEL was 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 NOEL

was 15 ppm (0.92 mg/kg in males and

0.94 mg/kg in females).

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 NOEL 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 1-

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
30752 Federal Register / Vol. 63, No. 108 / Friday, June 5, 1998 / Notices

clinical chemistry changes, which were

generally mild and transient. The NOEL

of 10 ppm was equivalent to a mean

daily intake of 0.36 mg/kg in males and

females.

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 NOEL 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 test

substance was severely hepatotoxic at

100 and 250 ppm, with males being

more sensitive than females. 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 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 NOEL 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 hepatocellular

necroses were observed at dietary doses

of 300 and 750 ppm in males and at 750

ppm in females, giving evidence that

these dose levels exceeded a maximum

tolerated dose (MTD). Top dose group

males showed higher incidences of

prostate adenoma, while prostate

hyperplasia was reduced. The total

incidence of proliferative changes in the

prostate remained unchanged. Females

treated at the same high dose had higher

incidences of ovary tubular adenoma.

Both tumors also occur spontaneously

in the rat strain used. Their slightly

enhanced incidences are likely a

consequence of the severe disturbance

of the general physiological balance due

to excessive liver toxicity. There was no

progression to a malignant phenotype

and the tumors had no influence on

survival. In rats, feeding a dose of 750

ppm to males showed higher incidences

of prostate adenoma, while prostate

hyperplasia was reduced. The total

number of tumor-bearing animals

showed no dose-related trends. The

NOEL of 10 ppm was equivalent to a

mean daily dose of 0.32 mg/kg in males

and 0.37 mg/kg in females.

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. Single doses were

excreted more rapidly by female rats

than by males. Most likely due to

enzyme induction, differences were

much less pronounced after repeated

treatment. Both sexes excreted

clodinafop-propargyl 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 clodinafoppropargyl 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 well-characterized

substances with this property, CGA193469 caused peroxisome proliferation

in vitro in hepatocytes of the mouse and

rat, but not of the Guinea pig, marmoset,

or human. There is ample scientific

evidence that exposure to peroxisome

proliferators represents no risk of tumor

development in man. Clodinafoppropargyl is, therefore, not considered

to be 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. Therefore, these findings

are considered irrelevant.

C. Aggregate Exposure

1. Dietary exposure. For purposes of

assessing the potential exposure under

the proposed tolerances for clodinafoppropargyl, Novartis has estimated

aggregate exposure based on the

theoretical maximum residue

contribution (TMRC) from the residues

of the active ingredient, clodinafoppropargyl, or metabolites thereof.

Residues are below the detection limit

in wheat grains and other wheat

products, including green wheat used

for forage. Tolerances in wheat and

wheat products are proposed at the

detection limit of 0.02 ppm (LOQ) for

the parent active ingredient in wheat

grain. Although wheat commodities

may be fed to poultry or cattle and it is

common practice in some areas to graze

cattle on green wheat, tolerances in

meat or milk are not necessary because

forage commodities do not contain

detectable amounts of the parent

clodinafop-propargyl or its metabolites.

i. Chronic. The RfD of 0.0032 mg/ kg/

day is derived from the male rat NOEL

of 0.32 mg/ kg/ day. Based on the

assumption that 100% of all wheat used

for human consumption would contain

residues of clodinafop-propargyl and

anticipated residues would be at the

level of 1⁄2 the LOQ, the potential

dietary exposure was calculated using

the TAS (TAS Exposure Analysis,

Technical Assessment Systems Inc.,

Washington, DC.) exposure program

based on the food survey from the year

of 1977/1978. Calculations were made

for anticipated residues using 1⁄2 the

LOQ or 0.01 ppm. The proposed

tolerance (0.02 ppm) was set at the

lowest limit of detection for the active

ingredient in wheat commodities (grain)

because, with the available

methodology, there are no detectable

residues of clodinafop-propargyl in

wheat or wheat products. Residues in

milk, meat and eggs due to the feeding

of wheat grain, green wheat or other
Federal Register / Vol. 63, No. 108 / Friday, June 5, 1998 / Notices 30753

feed commodities will not occur and

tolerances for milk, meat and eggs are

therefore not required. Calculated on the

basis of the assumptions above, the

chronic dietary exposure of the U.S.

population to clodinafop-propargyl

would correspond to 0.000014 mg/kg/

day or 0.47% of its RfD. The margin of

exposure (MOE) against the NOEL in the

most sensitive species is 22,857-fold.

Using the same conservative exposure

assumptions, the percentage of the RfD

that will be utilized is 0.14% for nursing

infants less than 1-year old, 0.34% for

non-nursing infants, 1.05% for children

1-6 years old and 0.77% for children 7-

12 years old. It is concluded that there

is a reasonable certainty that no harm

will result to infants and children from

exposure to residues of clodinafoppropargyl.

ii. Acute. Using the same computer

software package used for the

calculation of chronic dietary exposure,

the acute dietary exposure was

calculated for the general population

and several sub-populations including

children and women of child bearing

age. The USDA Food Consumption

Survey from 1989-1992 was used,

however, instead of the 1977/78 survey

used for the chronic assessment.

Margins of exposure were calculated

against the NOEL of 1 mg/kg found in

a 90-day dietary toxicity study in rats,

which is the lowest NOEL observed in

a short term or reproductive toxicity

study. NOEL from reproductive or

developmental toxicity studies were

significantly higher and there was no

evidence that clodinafop-propargyl has

any potency to affect these endpoints.

The exposure model predicted that

99.9% of the general population will be

exposed to less than 0.000105 mg/kg of

clodinafop-propargyl per day, which

corresponds to a MOE of almost 9,529

when compared to the NOEL of 1 mg/

kg. Children 1-6 years constitute the

sub-population with the highest

predicted exposure. Predicted acute

exposure for this subgroup is less than

0.000136 mg/kg/day, corresponding to a

MOE of at least 7,362 for 99.9% of the

individuals.

2. Drinking water. Other potential

sources of exposure of the general

population to residues of pesticides are

residues in drinking water. Although

clodinafop-propargyl has a slight to

medium leaching potential, the risk of

the parent compound to leach to deeper

soil layers is negligible under practical

conditions in view of the rapid

degradation of the product and its low

application rate. According to laboratory

and field studies there is no risk of

ground water contamination with

clodinafop-propargyl or its metabolites.

Thus, aggregate risk of exposure to

clodinafop-propargyl does not include

drinking water. Clodinafop-propargyl is

not intended for uses other than the

agricultural use on wheat. Thus, there is

no potential for non-occupational

exposure.

The Maximum Contaminant Level

Goal (MCLG) calculated for clodinafoppropargyl according to EPA’s procedure

leads to an exposure value substantially

above levels that are likely to be found

in the environment under proposed

conditions of use.

MCLG = RfD x 20% x 70 kg/2 L

MCLG = 0.0032 mg/kg x 0.2 x 70 kg/

2 L

MCLG = 0.0448 ppm = 44.8 ppb.

3. Non-dietary exposure. Exposure to

clodinafop-propargyl for the mixer/

loader/ground boom/aerial applicator

was calculated using the Pesticide

Handlers Exposure Database (PHED). It

was assumed that the product would be

applied 10-days per year by ground

boom application to a maximum of 300

acres per day by the grower, 450 acres

per day by the commercial ground boom

applicator and 741 acres per day by the

aerial applicator at a maximum use rate

of 28 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. These

assumptions were selected from PHED.

Daily doses were calculated for a 70 kg

person assuming 100% dermal

penetration. The results indicate that

large margins of safety exist for the

proposed use of clodinafop-propargyl.

Based upon the use pattern for

clodinafop, the NOEL (50 mg/kg/day)

from the 28-day rat dermal study is

appropriate for comparison to mixer/

loader-applicator exposure. The chronic

NOEL of 0.32 mg/kg/day from the 2-year

feeding study in rats is used to examine

longer term exposures.

For short-term exposure, MOEs for

clodinafop ranged from 2.9E+03 for

commercial open mixer-loader to

3.1E+04 for commercial groundboom

enclosed-cab applicator. For chronic

exposure, MOEs ranged from 6.9E+02

for commercial open mixer-loader to

7.4E+03 for commercial groundboom

enclosed-cab applicator. Aerial

application of clodinafop results in

short-term MOEs of 1.8E+03 for the

mixer-loader and 2.0E+03 for pilots.

Chronic MOEs are 4.2E+02 for the

mixer-loader and 4.7E+02 for the pilot.

In reality, the proposed label will

require more restrictive personal

protective equipment for applicators

and other handlers, resulting in

additional margins of safety.

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. Using the same

conservative exposure assumptions

described above, based on the

completeness and reliability of the

toxicity data, Novartis calculated that

the aggregate risk for clodinafoppropargyl for chronic dietary exposure

of the U.S. population would

correspond to 0.000014 mg/kg/day or

0.47% of its RfD. The margin of

exposure (MOE) against the NOEL in the

most sensitive species is 22,857-fold.

EPA generally has no concern for

exposures below 100% of the RfD

because the RfD represents the level at

or below which daily aggregate dietary

exposure over a lifetime will not pose

appreciable risks to human health.

Therefore, it is concluded that there is

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 teratogenic activity

of the test article was detected. The

NOEL for dams and fetuses was 40 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 NOEL was 25 mg/kg/day and

the fetal NOEL 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
30754 Federal Register / Vol. 63, No. 108 / Friday, June 5, 1998 / Notices

performance, fertility, or litter sizes.

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 developmental and

reproductive NOEL was 50 ppm,

corresponding to a mean daily intake of

3.3 mg/kg clodinafop-propargyl.

Section 408 FFDCA provides that EPA

may apply an additional safety factor for

infants and children in the case of

threshold effects to account for pre- and

post-natal toxicity and the completeness

of the database. Base on the current

toxicological data requirements, the

database relative to pre- and post-natal

effects for children is complete. Further,

for clodinafop-propargyl, the NOEL of

0.32 mg/kg/day from the combined

chronic/oncogenicity rat study, which

was used to calculate the RfD, is already

lower than the NOEL’s of 40 and 25 mg/

kg/day for the rat and rabbit

developmental toxicity studies,

respectively. Further, the developmental

and reproductive NOEL of 3.3 mg/kg/

day from the clodinafop-propargyl

reproduction study is 10- times greater

than the NOEL for the combined

chronic/oncogenicity rat study. These

data would indicate there is no

additional sensitivity of infants and

children to clodinafop-propargyl.

Therefore, it is concluded that an

additional uncertainty factor is not

warranted to protect the health of

infants and children from the use of

clodinafop-propargyl.

Using the conservative exposure

assumptions described above, it is

concluded that the percentage of the

RfD that will be utilized by aggregate

exposure to residues of clodinafoppropargyl for the proposed use on wheat

is 0.14% for nursing infants less than 1-

year old, 0.34% for non-nursing infants,

1.05% for children 1-6 years old and

0.77% for children 7-12 years old.

Therefore, based on the completeness

and reliability of the toxicity data and

the conservative nature of the exposure

assessment, it is concluded that there is

a 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.

(Joanne Miller)

2. Office of IR-4

PP 8G4964

EPA has received a pesticide petition

(PP 8G4964) from Office of IR-4, P.O.

Box 231, New Brunswick, N.J. 08903-

0321 proposing pursuant to section

408(d) of the Federal Food, Drug and

Cosmetic Act, 21 U.S.C. 346a(d), to

amend 40 CFR part 180 by establishing

a temporary tolerance exemption based

on no detectable residues in potatoes in

14 field trials and the limited nature of

the EUP program or a temporary

tolerance for residues of the insecticide

spinosad in or on the raw agricultural

commodity potatoes at 0.032 ppm

which is 2x the limit of quantitation of

the analytical method. The proposed

analytical method involves

homogenization, filtration, partition and

cleanup with analysis by high

performance liquid chromatography

using UV detection. 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 spinosad in plants (apples, cabbage,

cotton, tomato, and turnip) and animals

(goats and poultry) is adequately

understood for the purposes of these

tolerances. A rotational crop study

showed no carryover of measurable

spinosad related residues in

representative test crops.

2. Analytical method. There is a

practical method (HPLC with UV

detection) for detecting (0.004 ppm) and

measuring (0.01 ppm) levels of spinosad

in or on food with a limit of detection

that allows monitoring of food with

residues at or above the levels set for

these tolerances. The method has had a

successful method tryout in the EPA’s

laboratories. Additionally, an

Immunoassay has been developed.

3. Magnitude of residues. Magnitude

of residue studies were conducted for

potatoes at 14 sites in 7 States. No

residues in potatoes were found in these

studies with the lower limit of detection

of 0.005 ppm.

B. Toxicological Profile

1. Acute toxicity. Spinosad has low

acute toxicity. The rat oral LD50 is 3,738

mg/kg for males and >5,000 mg/kg for

females, whereas the mouse oral LD50 is

>5,000 mg/kg. The rabbit dermal LD50 is

>2,000 mg/kg and the rat inhalation

LC50 is >5.18 mg/l air. In addition,

spinosad is not a skin sensitizer in

guinea pigs and does not produce

significant dermal or ocular irritation in

rabbits. End use formulations of

spinosad that are water based

suspension concentrates have similar

low acute toxicity profiles.

2. Genotoxicty. Short term assays for

genotoxicity consisting of a bacterial

reverse mutation assay (Ames test), an

in vitro assay for cytogenetic damage

using the Chinese hamster ovary cells,

an in vitro mammalian gene mutation

assay using mouse lymphoma cells, an

in vitro assay for DNA damage and

repair in rat hepatocytes, and an in vivo

cytogenetic assay in the mouse bone

marrow (micronucleus test) have been

conducted with spinosad. These studies

show a lack of genotoxicity.

3. Reproductive and developmental

toxicity. Spinosad caused decreased

body weights in maternal rats given 200

mg/kg/day by gavage highest dose tested

(HDT). This was not accompanied by

either embryo toxicity, fetal toxicity, or

teratogenicity. The NOELs for maternal

and fetal effects in rats were 50 and 200

mg/kg/day, respectively. A teratology

study in rabbits showed that spinosad

caused decreased body weight gain and

a few abortions in maternal rabbits

given 50 mg/kg/day HDT. Maternal

toxicity was not accompanied by either

embryo toxicity, fetal toxicity, or

teratogenicity. The NOELs for maternal

and fetal effects in rabbits were 10 and

50 mg/kg/day, respectively. The NOEL

found for maternal and pup effects in a

rat reproduction study was 10 mg/kg/

day. Neonatal effects at 100 mg/kg/day

HDT in the rat reproduction study were

attributed to maternal toxicity.

4. Subchronic toxicity. Spinosad was

evaluated in 13-week dietary studies

and showed NOELs of 4.9 mg/kg/day in

dogs, 6 mg/kg/day in mice, and 8.6 mg/

kg/day in rats. No dermal irritation or

systemic toxicity occurred in a 21-day

repeated dose dermal toxicity study in

rabbits given 1,000 mg/kg/day.

5. Chronic toxicity. Based on chronic

testing with spinosad in the dog and the

rat, the EPA has set a reference dose

(RfD) of 0.0268 mg/kg/day for spinosad.

The RfD has incorporated a 100-fold

safety factor to the NOELs found in the

chronic dog study. The NOELs shown in

the dog chronic study were 2.68 and

2.72 mg/kg/day, respectively for male

and female dogs. The NOELs shown in

the rat chronic study were 2.4 and 3.0

mg/kg/day, respectively for male and

female rats. Using the Guidelines for

Carcinogen Risk Assessment published

September 24, 1986 (51 FR 33992)

(FRL–2984–1), it is proposed that

spinosad be classified as Group E for
Federal Register / Vol. 63, No. 108 / Friday, June 5, 1998 / Notices 30755

carcinogenicity (no evidence of

carcinogenicity) based on the results of

carcinogenicity studies in two species.

There was no evidence of

carcinogenicity in an 18-month mouse

feeding study and a 24-month rat

feeding study at all dosages tested. The

NOELs shown in the mouse

oncogenicity study were 11.4 and 13.8

mg/kg/day, respectively for male and

female mice. The NOELs shown in the

rat chronic/oncogenicity study were 2.4

and 3.0 mg/kg/day, respectively for

male and female rats. A maximum

tolerated dose was achieved at the top

dosage level tested in both of these

studies based on excessive mortality.

Thus, the doses tested are adequate for

identifying a cancer risk. Accordingly, a

cancer risk assessment is not needed.

6. Animal metabolism. There were no

major differences in the bioavailability,

routes or rates of excretion, or

metabolism of spinosyn A and spinosyn

D following oral administration in rats.

Urine and fecal excretions were almost

completed in 48-hours post-dosing. In

addition, the routes and rates of

excretion were not affected by repeated

administration.

7. Metabolite toxicology. The residue

of concern for tolerance setting purposes

is the parent material (spinosyn A and

spinosyn D). Thus, there is no need to

address metabolite toxicity.

8. Neurotoxicity. Spinosad did not

cause neurotoxicity in rats in acute,

subchronic, or chronic toxicity studies.

9. Endocrine effects. There is no

evidence to suggest that spinosad has an

effect on any endocrine system.

C. Aggregate Exposure

1. Dietary exposure. For purposes of

assessing the potential dietary exposure

from use of spinosad on cotton gin

byproducts as well as from other

existing or pending uses, a conservative

estimate of aggregate exposure is

determined by basing the TMRC on the

proposed tolerance levels for spinosad

and assuming that 100% of the cotton

gin byproducts and other existing and

pending crop uses grown in the U.S.

were treated with spinosad. The TMRC

is obtained by multiplying the tolerance

residue levels by the consumption data

which estimates the amount of crops

and related foodstuffs consumed by

various population subgroups. The use

of a tolerance level and 100% of crop

treated clearly results in an overestimate

of human exposure and a safety

determination for the use of spinosad on

crops cited in this summary that is

based on a conservative exposure

assessment.

2. Drinking water. Another potential

source of dietary exposure are residues

in drinking water. Based on the

available environmental studies

conducted with spinosad wherein it’s

properties show little or no mobility in

soil, there is no anticipated exposure to

residues of spinosad in drinking water.

In addition, there is no established

Maximum Concentration Level (MCL)

for residues of spinosad in drinking

water.

3. Non-dietary exposure. Spinosad is

currently registered for use on cotton

with several crop registrations pending

all of which involve applications of

spinosad in the agriculture

environment. Spinosad is also currently

registered for use on turf and

ornamentals at low rates of application

(0.04 to 0.54 lb a.i. per acre). Thus, the

potential for non-dietary exposure to the

general population is not expected to be

significant.

D. Cumulative Effects

The potential for cumulative effects of

spinosad and other substances that have

a common mechanism of toxicity is also

considered. In terms of insect control,

spinosad causes excitation of the insect

nervous system, leading to involuntary

muscle contractions, prostration with

tremors, and finally paralysis. These

effects are consistent with the activation

of nicotinic acetylcholine receptors by a

mechanism that is clearly novel and

unique among known insecticidal

compounds. Spinosad also has effects

on the GABA receptor function that may

contribute further to its insecticidal

activity. Based on results found in tests

with various mammalian species,

spinosad appears to have a mechanism

of toxicity like that of many amphiphilic

cationic compounds. There is no

reliable information to indicate that

toxic effects produced by spinosad

would be cumulative with those of any

other pesticide chemical. Thus it is

appropriate to consider only the

potential risks of spinosad in an

aggregate exposure assessment.

E. Safety Determination

1. U.S. population. Using the

conservative exposure assumptions and

the proposed RfD described above, the

aggregate exposure to spinosad use on

potatoes (using 0.032 ppm residue level)

and other existing or pending crop uses

will utilize 20.8% of the RfD for the U.S.

population. No contribution to animal

feed from potato was utilized in this

analysis due to the limited scope of the

EUP. A more realistic estimate of dietary

exposure and risk relative to a chronic

toxicity endpoint is obtained if average

(anticipated) residue values from field

trials are used. Inserting the average

residue values in place of tolerance

residue levels produces a more realistic,

but still conservative risk assessment.

Based on average or anticipated residues

in a dietary risk analysis, the use of

spinosad on potatoes and other existing

or pending crop uses will utilize 4.6%

of the RfD for the U.S. population. EPA

generally has no concern for exposures

below 100% of the RfD because the RfD

represents the level at or below which

daily aggregate dietary exposure over a

lifetime will not pose appreciable risks

to human health. Thus, it is clear that

there is reasonable certainty that no

harm will result from aggregate

exposure to spinosad residues on

potatoes and other existing or pending

crop uses.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

spinosad, data from developmental

toxicity studies in rats and rabbits and

a 2-generation reproduction study in the

rat are considered. The developmental

toxicity studies are designed to evaluate

adverse effects on the developing

organism resulting from pesticide

exposure during prenatal development.

Reproduction studies provide

information relating to effects from

exposure to the pesticide on the

reproductive capability and potential

systemic toxicity of mating animals and

on various parameters associated with

the well-being of pups.

Section 408 FFDCA provides that EPA

may apply an additional safety factor for

infants and children in the case of

threshold effects to account for pre- and

post-natal toxicity and the completeness

of the database. Based on the current

toxicological data requirements, the

database for spinosad relative to preand post-natal effects for children is

complete. Further, for spinosad, the

NOELs in the dog chronic feeding study

which was used to calculate the RfD

(0.0268 mg/kg/day) are already lower

than the NOELs from the developmental

studies in rats and rabbits by a factor of

more than 10-fold.

Concerning the reproduction study in

rats, the pup effects shown at the HDT

were attributed to maternal toxicity.

Therefore, it is concluded that an

additional uncertainty factor is not

needed and that the RfD at 0.0268 mg/

kg/day is appropriate for assessing risk

to infants and children.

Using the conservative exposure

assumptions previously described

(tolerance level residues), the % RfD

utilized by the aggregate exposure to

residues of spinosad on potatoes and

other existing or pending crop uses is

38.4% for children 1 to 6-years old, the

most sensitive population subgroup. If

average or anticipated residues are used
30756 Federal Register / Vol. 63, No. 108 / Friday, June 5, 1998 / Notices

in the dietary risk analysis, the use of

spinosad on these crops will utilize

11.3% of the RfD for children 1 to 6-

years old. Thus, based on the

completeness and reliability of the

toxicity data and the conservative

exposure assessment, it is concluded

that there is a reasonable certainty that

no harm will result to infants and

children from aggregate exposure to

spinosad residues on cotton gin

byproducts and other existing or

pending crop uses.

F. International Tolerances

There are no Codex maximum residue

levels established for residues of

spinosad on cotton gin byproducts or

any other food or feed crop. (Beth

Edwards).

[FR Doc. 98–15014 Filed 6–4–98; 8:45 am]

BILLING CODE 6560–50–F

EXPORT-IMPORT BANK OF THE

UNITED STATES

Agency Information Collection

Activities: Submission for OMB

Review: Comment Request

AGENCY: Export-Import Bank of the

United States.

ACTION: In accordance with the

Paperwork Reduction Act of 1995, the

Export-Import Bank of the United States

(Ex-Im Bank) has submitted to the Office

of Management and Budget (OMB) a

request to review and approve a revision

of a currently approved collection

described below. A request for public

comment was published in 63 FR, No.

59, 13437, March 27, 1998. No

comments have been received.

SUMMARY: The Export-Import Bank of

the United States (Ex-Im Bank) is

soliciting comments from members of

the public concerning the proposed

collection of information to: (1) Evaluate

whether the proposed collection is

necessary for the proper performance of

the functions of the agency, including

whether the information will have

practical utility; (2) evaluate the

accuracy of the agency’s estimate of the

burden of the proposed collection of

information; (3) enhance the quality,

utility, and clarity of the information to

be collected; and (4) minimize the

burden of collection of information for

those who are to respond; including

through the use of appropriate

automated collection techniques or

other forms of information technology,

e.g., permitting electronic submission of

responses.

DATES: Interested persons are invited to

submit comments on or before July 6,

1998.

ADDRESSES: Comments and

recommendations concerning the

submission should be sent to the OMB

Desk Officer for Ex-Im Bank at the

Office of Management and Budget,

Information and Regulatory Affairs New

Executive Office Building, Washington,

DC 20503, (202) 395–7340.

FOR FURTHER INFORMATION CONTACT:

Copies of these submissions and any

additional information may be obtained

from Dan Garcia, Export-Import Bank of

the United States, 811 Vermont Ave.,

NW., Washington, DC 20571, (202) 565–

3335.

SUPPLEMENTARY INFORMATION:

Abstract: OMB 3048–0005: Two

applications fall under this collection.

EIB–95–9 is the Ex-Im Bank Letter of

Interest Application Form and EIB–95–

10 is the Ex-Im Bank Preliminary

Commitment and Final Commitment

Application Form. There are no changes

to either EIB–95–9 or EIB–95–10 other

than a three-year extension of the

expiration date.

Burden Statement Summary

Type of request: Extension of

expiration date.

OMB Number: 3048–0005.

Form Number: EIB–95–9 and EIB–95–

10.

Title: EIB–96–9—Ex-Im Bank Letter of

Interest Application Form and EIB–95–

10—EX-Im Bank Preliminary

Commitment and Final Commitment

Application Form.

Frequency of Use: Submission of

Applications.

Respondents: Any U.S. or foreign

bank, other financial institution, other

responsible party including the exporter

or creditworthy borrowers in a country

eligible for Ex-Im Bank assistance.

Estimated total number of annual

responses: EIB–95–9: 900, EIB–95–10:

550.

Estimated total number of hours

needed to fill out the form: EIB–95–9: 20

minutes, EIB–95–10: 1 hour.

Dated: June 3, 1998.

Dan Garcia,

Agency Clearance Officer.

[FR Doc. 98–15167 Filed 6–4–98; 8:45 am]

BILLING CODE 6690–01–M

FEDERAL COMMUNICATIONS

COMMISSION

FCC To Hold Open Commission

Meeting Tuesday, June 9, 1998

June 2, 1998.

The Federal Communications

Commission will hold an Open Meeting

on the subjects listed below on Tuesday,

June 9, 1998, which is scheduled to

commence at 3:00 p.m. in Room 856, at

1919 M Street, NW., Washington, D.C.

Item No. Bureau Subject

1 Common Carrier ............... Title: Federal-State Joint Board on Universal Service (CC Docket No. 96–45); and Access Charge

Reform (CC Docket No. 96–262).

Summary: The Commission will consider action concerning proposals to ensure the accuracy and

completeness of billing disclosures made by telecommunications carriers.

2 Common Carrier ............... Title: Federal-State joint Board on Universal Service (CC Docket No. 96–45).

Summary: The Commission will consider action concerning the collection levels for the schools and

libraries and rural health care universal service support mechanisms for the third and fourth quarters of 1998.

3 Common Carrier ............... Title: Federal-State Joint Board on Universal Service (CC Docket No. 96–45); Access Charge Reform (CC Docket No. 96–262); and Petition of Southwestern Bell Telephone Company, Pacific Bell,

and Nevada Bell for Waiver of Sections 61.44–45 of the Commission’s Rules (CCB/CPD 98–19).

Summary: The Commission will consider action concerning issues related to local exchange carrier

recovery of universal service contribution obligations.

Additional information concerning

this meeting may be obtained from

Maureen Peratino or David Fiske, Office

of Public Affairs, telephone number

(202) 418–0500; TTY (202) 418–2555.

Copies of materials adopted at this

meeting can be purchased from the

FCC’s duplicating contractor,

International Transcription Services,

Inc. (ITS, Inc.) at (202) 857–3800; fax

(202) 857–3805 and 857–3184; or TTY