Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices 66077

1The finding is made pursuant to sections

110(a)(2)(H) and 110(k)(5) of the Clean Air Act, 42

U.S.C. 7410(a)(2)(H) and 7410(k)(5).

requested EPA delay in taking action for

one year in order to determine the

geographical extent and severity of the

CO problem. EPA agreed to this request.

According to the Montana DEQ, data

from the Idaho and Main CO monitoring

site in conjunction with the results from

the CO saturation study suggested the

CO problem was a traffic corridor

problem extending six- to eight-blocks

in either direction along Idaho and

Main. Montana DEQ determined that

the CO saturation study did not

sufficiently look at the effects of CO in

the surrounding neighborhoods.

Therefore, an additional CO monitoring

site was installed next to Laser School,

a residential site located one block north

of Highway 2 and approximately five

blocks north and east of the Idaho and

Main site. Data collection at Laser

School began on November 1, 1996.

II. Finding of Inadequacy

On January 10, 1980 (45 FR 2036),

EPA approved Montana’s plans for the

attainment and maintenance of the

national standards under section 110 of

the Clean Air Act. EPA now finds 1 the

SIP inadequate based on the reported

exceedances of the CO NAAQS in

Kalispell.

III. Call for SIP Revision

This finding of SIP inadequacy

requires Montana to submit a SIP

revision no later than 18 months from

the date of EPA’s letter to the Governor.

To ensure that the SIP deadline is met,

EPA requested the State to submit an

action plan for the development of the

SIP revision within 60 days from receipt

of EPA’s letter to the Governor. The

State submitted an action plan to EPA

on September 9, 1997. Any control

strategies adopted and implemented as

part of this SIP revision must provide

for attainment and maintenance of the

CO NAAQS within 5 years from the date

of EPA’s letter to the Governor. (See,

e.g., section 110(n)(2) of the Act.)

IV. Final Action

This finding of inadequacy does not

constitute a final agency action that is

ripe for judicial review. EPA’s action is

a first step in an administrative process

that will not be sufficiently concrete for

judicial resolution until additional

action is taken by EPA on a plan

submittal by the State of Montana.

The 60-day time period for filing a

petition for review under section 307(b)

of the CAA is tolled until EPA makes

the finding ripe by taking additional

action in reliance on it, such as

imposing sanctions on the State of

Montana for failure to submit a SIP

revision or promulgating approval of a

SIP revision. A time limitation on

petitions for judicial review can only

run against challenges ripe for review.

A technical support document (TSD)

is available from the contact person

listed above. The TSD discusses in more

detail the ambient standard and its

health effects, the SIP call and legal

authority, and the SIP revision

schedule.

Authority: Sections 101, 107, 110, 116 and

301(a) of the Clean Air Act, as amended [42

U.S.C. 7401, 7407, 7410, 7416 and 7610(a)].

Dated: November 17, 1997.

William P. Yellowtail,

Regional Administrator.

[FR Doc. 97–32931 Filed 12–16–97; 8:45 am]

BILLING CODE 6560–50–U

ENVIRONMENTAL PROTECTION

AGENCY

[PF–781; FRL–5758–3]

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–781, must be

received on or before January 16, 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. 1132,

CM #2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically to: oppdocket@epamail.epa.gov. Follow 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

James Tompkins (PM

25).

Rm. 265, CM #2, 703–305–7801, e-mail:tompkins.james@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Elizabeth Haeberer ........ Rm. 207, CM #2, 703–308–2891, e-mail: haeberer.elizabeth@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–781]
66078 Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices

(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 PF-781 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: December 4, 1997

Peter Caulkins,

Acting 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

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. Bayer Corporation

PP 5F4480

EPA has received a pesticide petition

(PP 5F4480) from Bayer Corporation,

8400 Hawthorn Rd., P.O. Box 4913,

Kansas City, MO 64120-0013. 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 tolerance for residues of

imidacloprid in or on the raw

agricultural commodity pecans at 0.05

parts per million (ppm). 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 imidacloprid in plants is adequately

understood for the purposes of these

tolerances. The residues of concern are

combined residues of imidacloprid and

its metabolites containing the 6-chloropyridinyl moiety, all calculated as

imidacloprid.

2. Analytical method. The analytical

method is a common moiety method for

imidacloprid and its metabolites

containing the 6-chloropyridinyl moiety

using a permanganate oxidation, silyl

derivatization, and capillary GC-MS

selective ion monitoring. This method

has successfully passed a petition

method validation in EPA labs. There is

a confirmatory method specifically for

imidacloprid and several metabolites

utilizing GC/MS and HPLC-UV which

has been validated by the EPA as well.

Imidacloprid and its metabolites are

stable for at least 24 months in the

commodities when frozen.

3. Magnitude of residues. Field

studies were conducted to determine

imidacloprid residues on pecans

following treatment with either a single

soil or two foliar applications. Seven

field studies were conducted using a

single soil application of 0.5 lb active

ingredient per acre. 5–field studies were

conducted using two foliar applications

at a rate of 0.17 lb active ingredient per

acre, with a 10–day interval. After the

final foliar application or the soil

application, samples were collected at

earliest harvest which ranged from 4 to

21–days for the foliar application or 99

to 150 days for the soil application.

Maximum residues, in pecans, detected

following either 2 foliar applications or

1 soil application were >0.05 ppm.

Therefore, a tolerance of 0.05 ppm of

pecans is being proposed with a

preharvest interval defined as earliest

harvest (shuck split). CBTS has

concluded that existing poultry meat

and egg tolerances are adequate to

support the proposed new uses of

imidacloprid.

B. Toxicological Profile

1. Acute toxicity. The acute oral LD50

values for imidacloprid technical ranged

from 424 - 475 milligrams/kilogram/

bodyweight (mg/kg/bwt) in the rat. The

acute dermal LD50 was greater than

5,000 mg/kg in rats. The 4–hour rat

inhalation LC50 was >69 mg/m3 air

(aerosol). Imidacloprid was not irritating

to rabbit skin or eyes. Imidacloprid did

not cause skin sensitization in guinea

pigs.

2. Genotoxicty. Extensive

mutagenicity studies conducted to

investigate point and gene mutations,

DNA damage and chromosomal

aberration, both using in vitro and in

vivo test systems show imidacloprid to

be non-genotoxic.

3. Reproductive and developmental

toxicity. A 2–generation rat

reproduction study gave a no-observedeffect level (NOEL) of 100 ppm (8 mg/

kg/bwt). Rat and rabbit developmental

toxicity studies were negative at doses

up to 30 mg/kg/bwt and 24 mg/kg/bwt,

respectively.

4. Subchronic toxicity. 90–day feeding

studies were conducted in rats and

dogs. The NOEL’s for these tests were 14

milligrams/kilogram/bodyweight/day

(mg/kg/bwt/day) (150 pm) 5 mg/kg/bwt/

day (200 ppm) for the rat and dog

studies respectively.

5. Chronic toxicity. A 2–year rat

feeding/carcinogenicity study was

negative for carcinogenic effects under

the conditions of the study and had a

NOEL of 100 ppm (5.7 mg/kg/bwt in

male and 7.6 mg/kg/bwt female) for

noncarcinogenic effects that included

decreased body weight gain in females

at 300 ppm and increased thyroid

lesions in males at 300 ppm and females

at 900 ppm. A 1–year dog feeding study

indicated a NOEL of 1,250 ppm (41 mg/

kg/bwt). A 2–year mouse

carcinogenicity study that was negative

for carcinogenic effects under

conditions of the study and that had a

NOEL of 1,000 ppm 208 milligrams/

kilogram/day (mg/kg/day).

Imidacloprid has been classified

under ‘‘Group E’’ (no evidence of

carcinogenicity) by EPA’s OPP/HED’s

Reference Dose (RfD) Committee. There

is no cancer risk associated with

exposure to this chemical. The reference

dose (RfD) based on the 2–year rat

feeding/carcinogenic study with a NOEL

of 5.7 mg/kg/bwt and 100-fold

uncertainty factor, is calculated to be

0.057 mg/kg/bwt. The theoretical

maximum residue contribution (TMRC)

from published uses is 0.008187 mg/kg/

bwt/day utilizing 14.4% of the RfD.

6. Animal metabolism. The

metabolism of imidacloprid in animals
Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices 66079

is adequately understood. The residues

of concern are combined residues of

imidacloprid and its metabolites

containing the 6-chloropyridinylmoiety, all calculated as

imidacloprid.

C. Aggregate Exposure

Imidacloprid is a broad-spectrum

insecticide with excellent systemic and

contact toxicity characteristics with

both food and non-food uses.

Imidacloprid is currently registered for

use on various food crops, tobacco, turf,

ornamentals, buildings for termite

control, and cats and dogs for flea

control.

1. Dietary exposure. The EPA has

determined that the reference dose (RfD)

based on the 2–year rat feeding/

carcinogenic study with a NOEL of 5.7

mg/kg/bwt and 100-fold uncertainty

factor, is calculated to be 0.057 mg/kg/

bwt.

2. Food. The theoretical maximum

residue contribution (TMRC) from this

proposed use on Pecans as well as all

published uses and pending uses is

0.008149 mg/kg/bwt/day utilizing

14.3% of the RfD for the general

population. For the most highly exposed

subgroup in the population, children

(1–6 years), the TMRC for the all uses

is 0.018367 mg/kg/day. This is equal to

32.2% of the RfD. Therefore, dietary

exposure from the existing uses

including the currently proposed

tolerance will not exceed the reference

dose for any subpopulation (including

infants and children).

3. Drinking water. Although the

various imidacloprid labels contain a

statement that this chemical

demonstrates the properties associated

with chemicals detected in ground

water, the Registrant is not aware of

imidacloprid being detected in any

wells, ponds, lakes, streams, etc. from

its use in the U.S. In studies conducted

in 1995, imidacloprid was not detected

in 17 wells on potato farms in Quebec,

Canada. In addition, ground water

monitoring studies are currently

underway in California and Michigan.

Therefore, contributions to the dietary

burden from residues of imidacloprid in

water would be inconsequential.

4. Non-dietary exposure— i.

Residential turf. Bayer has conducted an

exposure study to address the potential

exposures of adults and children from

contact with imidacloprid treated turf.

The population considered to have the

greatest potential exposure from contact

with pesticide treated turf soon after

pesticides are applied is young children.

Margins of safety (MOS) of 7,587 -

41,546 for 10–year–old children and

6,859 - 45,249 for 5–year–old children

were estimated by comparing dermal

exposure doses to the imidacloprid noobservable effect level of 1,000 mg/kg/

day established in a 15–day dermal

toxicity study in rabbits. The estimated

safe residue levels of imidacloprid on

treated turf for 10–year–old children

ranged from 5.6 - 38.2 g/cm2 and for 5–

year–old children from 5.1 - 33.5 g/cm2.

This compares with the average

imidacloprid transferable residue level

of 0.080 g/cm2 present immediately after

the sprays have dried. These data

indicate that children can safely contact

imidacloprid-treated turf as soon after

application as the spray has dried.

ii. Termiticide. Imidacloprid is

registered as a termiticide. Due to the

nature of the treatment for termites,

exposure would be limited to that from

inhalation and was evaluated by EPA’s

Occupational and Residential Exposure

Branch (OREB) and Bayer. Data indicate

that the Margins of Safety for the worst

case exposures for adults and infants

occupying a treated building who are

exposed continuously (24 hours/day)

are 8.0 × 107 and 2.4 × 108, respectively

- and exposure can thus be considered

negligible.

iii. Tobacco smoke. Studies have been

conducted to determine residues in

tobacco and the resulting smoke

following treatment. Residues of

imidacloprid in cured tobacco following

treatment were a maximum of 31 ppm

(7 ppm in fresh leaves). When this

tobacco was burned in a pyrolysis study

only 2% of the initial residue was

recovered in the resulting smoke (main

stream plus side stream). This would

result in an inhalation exposure to

imidacloprid from smoking of

approximately 0.0005 mg per cigarette.

Using the measured subacute rat

inhalation NOEL of 5.5 mg/m3, it is

apparent that exposure to imidacloprid

from smoking (direct and/or indirect

exposure) would not be significant.

iv. Pet treatment. Human exposure

from the use of imidacloprid to treat

dogs and cats for fleas has been

addressed by EPA’s OREB who have

concluded that due to the fact that

imidacloprid is not an inhalation or

dermal toxicant and that while dermal

absorption data are not available,

imidacloprid is not considered to

present a hazard via the dermal route.

D. Safety Determination

1. U.S. population. Using the

conservative exposure assumptions

described above and based on the

completeness and reliability of the

toxicity data, it can be concluded that

total aggregate exposure to imidacloprid

from all current uses including those

currently proposed will utilize little

more than 15% of the RfD for the U.S.

population. EPA generally has no

concerns 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 risks to human health.

Thus, it can be concluded that there is

a reasonable certainty that no harm will

result from aggregate exposure to

imidacloprid residues.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

imidacloprid, the data from

developmental studies in both rat and

rabbit and a 2–generation reproduction

study in the rat have been considered.

The developmental toxicity studies

evaluate potential adverse effects on the

developing animal resulting from

pesticide exposure of the mother during

prenatal development . The

reproduction study evaluates effects

from exposure to the pesticide on the

reproductive capability of mating

animals through two generations, as

well as any observed systemic toxicity.

FFDCA section 408 provides that EPA

may apply an additional safety factor for

infants and children in the case of

threshold effects to account for pre- and

post- natal effects and the completeness

of the toxicity database. Based on

current toxicological data requirements,

the toxicology database for imidacloprid

relative to pre- and post-natal effects is

complete. Further for imidacloprid, the

NOEL of 5.7 mg/kg/bwt from the 2–year

rat feeding/ carcinogenic study, which

was used to calculate the RfD (discussed

above), is already lower than the NOELs

from the developmental studies in rats

and rabbits by a factor of 4.2 to 17.5

times. Since a 100-fold uncertainty

factor is already used to calculate the

RfD, it is surmised that an additional

uncertainty factor is not warranted and

that the RfD at 0.057 mg/kg/bwt/day is

appropriate for assessing aggregate risk

to infants and children.

Using the conservative exposure

assumptions described above, it can be

concluded that the TMRC from use of

imidacloprid from published and

pending uses is 0.008149 mg/kg/bwt/

day utilizing 14.3% of the RfD for the

general population. For the most highly

exposed subgroup in the population,

children (1–6 years), the TMRC for the

published tolerances is 0.018367 mg/kg/

day. This is equal to 32.2% of the RfD.

Therefore, dietary exposure from the

existing uses including the currently

proposed tolerances will not exceed the

reference dose for any subpopulation

(including infants and children).
66080 Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices

E. International Tolerances

No CODEX Maximum Residue Levels

(MRL’s) have been established for

residues of Imidacloprid on any crops at

this time. (Elizabeth Haeberer)

2. E. I. Du Pont de Nemours & Company

PP 5F4545

EPA has received a pesticide petition

(PP 5F4545) from E. I. Du Pont de

Nemours & Company (DuPont), P.O.

Box 80038, Wilmington, DE 19880-0038.

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 an exemption from

the requirement of a tolerance for

quizalofop (2-[4-(6-chloroquinoxalin-2-

yl)oxy) phenoxy]) - propanoic acid], and

quizalofop ethyl [ethyl-2- [4-(6-

chloroquinoaxalin-2-yl)oxy) phenoxy)

propanoat in or on the raw agricultural

commodities canola seed and canola

meal . 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. Quizalofop-p

ethyl ester is metabolized by cleavage at

three sites as follows:

(i) Primary pathway is hydrolysis of

the ethyl ester to form the quizalofop-p

acid, then (ii) Cleavage of the enol ether

linkage in the acid, between the phenyl

and quinoxalinyl rings, to form phenols,

and (iii) Cleavage of the ether linkage

between the isopropanic group and the

phenyl ring to form a phenol.

The plant metabolism data show that

quizalofop-p ethyl ester does not

translocate, but is rapidly hydrolyzed to

the corresponding acid; then the

phenols conjugate with the plant sugars.

Metabolism studies in soybeans using

the racemic mixture quizalofop ethyl

ester and the resolved D+ isomer show

nearly identical pathways.

The nature of the quizalofop-p ethyl

ester residue in plants is adequately

understood. The residues of concern are

quizalofop-p ethyl ester and its acid

metabolite, quizalofop-p, and the S

enantiomers of both the ester and the

acid, all expressed as quizalofop-p ethyl

ester.

2. Analytical method. An adequate

analytical methodology (high-pressure

liquid chromatography using either

ultraviolet or fluorescence detection) is

available for enforcement purposes in

Vol. II of the Food and Drug

Administration Pesticide Analytical

Method (PAM II, Method I).

Adequately validated residue

analytical methods, LAN-1 and LAN-3,

were used to gather the magnitude of

the quizalofop-p, its acid metabolite,

phenols 1, 2, and 4, residue data on

canola and canola processed

commodities.

3. Magnitude of residues. Dupont

proposes establishing tolerances for the

combined residues of quizalofop (2-[4-

(6-chloroquinoaxalin-2-yl)oxy)

phenoxy])-propionic acid], and

quizalofop ethyl [ethyl-2- [4-(6-

chloroquinoxalin-2-yl)oxy) phenoxy)

propanoat for the raw agricultural

commodities canola seed at 1.0 parts per

million (ppm) and canola meal at 1.5

ppm.

B. Toxicological Profile

1. Acute toxicity. Several acute

toxicology studies were conducted and

the overall results placed technical

grade quizalofop ethyl in toxicity

Category III. These include the

following studies in Category III: acute

oral toxicity (LD50s 1,480 and 1,670 for

female and male rats, respectively) and

eye irritation (mild effects; reversible

within 4–days). Dermal toxicity (LD50 >

5,000 mg/kg; rabbit), inhalation toxicity

(LC50 > 5.8 mg/L; rat) and dermal

irritation were classified within

Category IV. Technical quizalofop ethyl

was not a dermal sensitizer.

2. Genotoxicty. Technical quizalofop

ethyl was negative in the following

genotoxicity tests: bacterial gene

mutation assays with E. coli and S.

typhimurium; gene mutation assays in

Chinese hamster ovary(CHO) cells ; in

vitro DNA damage assays with B.

subtillis and in rat hepatocytes; and an

in vitro chromosomal aberration test in

CHO cells.

3. Reproductive and developmental

toxicity. Studies supporting the

registration include: A developmental

toxicity study in rats administered

dosage levels of 0, 30, 100, and 300

milligrams/kilogram/day (mg/kg/day)

highest dose tested (HDT). The maternal

toxicity no-observed effect level (NOEL)

was 30 mg/kg/day and a developmental

toxicity NOEL was greater than 300 mg/

kg/day (HDT). The maternal NOEL was

based on reduced food consumption

and increased liver weights. A

developmental toxicity study in rabbits

administered dosage levels of 0, 7, 20,

and 60 mg/kg/day with no

developmental effects noted at 60 mg/

kg/day (HDT). The maternal toxicity

NOEL was 20 mg/kg/day based on

decreases in food consumption and

body weight gain at 60/mg/kg/day

(HDT). A 2-generation reproduction

study in rats fed diets containing 0, 25,

100 or 400 ppm (or approximately 1,

1.25, 5, and 20 mg/kg/day, respectively)

with a developmental (systemic effects)

NOEL of 1.25 mg/kg/day for F2B

weanlings based on increased liver

weights and increased incidence of

eosinophilic changes in the livers at 5.0

mg/kg/day. These liver changes were

considered to be physiological or

adaptive changes to compound

exposure among weanlings. When

access to the mother’s feed is available,

it is a common observation that young

rats will begin consuming chow prior to

complete weaning at 21–days of age.

Consumption could not be quantified;

therefore, the maternal consumption

was assumed as the NOEL (if

normalized on a body weight basis,

exposures to the weanling rats were

likely higher). The parental NOEL of 5.0

mg/kg/day was based on decreased body

weight and premating weight gain in

males at 20 mg/kg/day (HDT).

4. Subchronic toxicity. A 90-day study

was conducted in rats fed diets

containing 0, 40, 128, 1,280 ppm (or

approximately 0, 2, 6.4 and 64 mg/kg/

day, respectively). The NOEL was 2 mg/

kg/day. This was based on increased

liver weights at 6.4 mg/kg. A 90–day

feeding study in mice was conducted

with diets that contained 0, 100, 316 or

1,000 ppm (or approximately 0, 15, 47.4,

and 150 mg/kg/day, respectively). The

NOEL was > 15 mg/kg/day lowest dose

tested (LDT) based on increased liver

weights and reversible histopathological

effects in the liver at the LDT. A 6-

month feeding study in dogs was

conducted with diets that contained 0,

25, 100 or 400 ppm (or approximately

0, 0.625, 2.5, and 10 mg/kg/day,

respectively). The NOEL was 2.5 mg/kg/

day based on increased blood urea

nitrogen at 10 mg/kg/day. A 21–day

dermal study was conducted in rabbits

at doses of 0, 125, 500 or 2,000 mg/kg/

day. The NOEL was 2,000 mg/kg/day

(HDT).

5. Chronic toxicity. An 18–month

carcinogenicity study was conducted in

CD-1 mice fed diets containing 0, 2, 10,

80 or 320 ppm (or approximately 0, 0.3,

1.5, 12, and 48 mg/kg/day, respectively).

There were no carcinogenic effects

observed under the conditions of the

study at levels up to and including 12

mg/kg/day. A marginal increase in the

incidence of hepatocellular tumors was

observed at 48 mg/kg/day, the (HDT)

which exceeded the maximum tolerated
Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices 66081

dose (MTD). (Please see the discussion

by the EPA HED Carcinogenicity Peer

Review Committee.)

A 2–year chronic toxicity/

carcinogenicity study was conducted in

rats fed diets containing 0, 25, 100 or

400 ppm (or 0, 0.9, 3.7, and 15.5 mg/kg/

day for males and 0, 1.1, 4.6, and 18.6

mg/kg/day for females, respectively).

There were no carcinogenic effects

observed under the conditions of the

study at levels up to and including 18.6

g/kg/day (HDT). The systemic NOEL

was 0.9 mg/kg/day based on altered red

cell parameters and slight/minimal

centrilobuler enlargement of the liver at

3.7 mg/kg/day.

A 1–year feeding study was

conducted in dogs fed diets containing

0, 25, 100 or 400 ppm (or approximately

0, 0.625, 2.5, and 10 mg/kg/day,

respectively). The NOEL was 10 mg/kg/

day (HDT).

The Carcinogenicity Peer Review

Committee (CPRC) of HED has evaluated

the rat and mouse cancer studies on

quizalofop along with other relevant

short-term toxicity studies, mutagenicity

studies, and structure activity

relationships. The CPRC concluded,

after three meetings and an evaluation

by the OPP Science Advisory panel, that

the classification should be a Category

D (not classifiable as to human cancer

potential). No new cancer studies were

required.

The first CPRC review tentatively

concluded that quizalofop should be

classified as a Category B2 (probable

human carcinogen). That classification

was based on liver tumors in female

rats, ovarian tumors in female mice, and

liver tumors in male mice. This

classification was downgraded to a

Category C (possible human carcinogen)

at a second CPRC review. The change in

classification was due to a

reexamination of the liver tumors in

female rats and ovarian tumors in

female mice. The first peer review had

found a statistically significant positive

trend for liver carcinomas in female rats.

Subsequent to this conclusion the tumor

data was reevaluated, and the

revaluation showed a reduced number

of carcinomas. Although there remained

a statistically significant positive trend

for carcinomas in the study, the CPRC

concluded that the carcinomas were not

biologically significant given the few

carcinomas identified (one at the middose and two at the high dose). Noting

that this level of carcinomas was within

historical levels, the CPRC concluded

that administration of quizalofop did

not appear to be associated with the

liver carcinomas.

As to the ovarian tumors in female

mice, the CPRC had first attached

importance to the fact that these tumors

were statistically significant at the high

dose as compared to historical control

values although statistically significant

when compared to concurrent controls.

However, review of further historical

control data showed that the level of

ovarian tumors in the quizalofop study

was similar to the background rate in

several other studies. Given this

information and that the quizalofop

study showed no hyperplasia of the

ovary, no signs of endocrine activity

related to ovarian function, and no dose

response relationship, the CPRC

concluded that the ovarian tumors were

probably not compound-related.

The findings of the second CPRC

review were presented to EPA’s

Scientific Advisory Panel (SAP). The

SAP concurred with the CPRC

conclusion that the liver tumors in

female rats and the ovary tumors in

female mice showed no evidence of

carcinogenicity. However, the SAP

disagreed with CPRC’s classification of

quizalofop as a Category C based on the

liver tumors in male mice. The SAP

concluded that the mouse liver tumors

did not support such a classification

because the tumors occurred at a dose

above the MTD and because they were

not statistically significant if a ‘‘p’’ value

of less than 0.05. The SAP believed that

such greater statistical rigor was

appropriate for variable tumor

endpoints such as male mouse liver

tumors.

Following the SAP review, the CPRC

changed the classification for quizalofop

to Category D. The Category D

classification is based on an

approximate doubling in the incidence

of male mice liver tumors between

controls an the high dose. This finding

was not considered strong enough to

warrant the finding of a Category C

(possible human carcinogen) since the

increase was of marginal statistical

significance, occurred at a high dose

which exceeded the predicted MTD,

and occurred in a study in which the

concurrent control for liver tumors was

somewhat low as compared to the

historical controls, while the high dose

control group was at the upper end of

previous historical control-groups.

EPA has found the evidence on the

carcinogenicity of quizalofop-p ethyl

ester in animals to be equivocal and

therefore concludes that quizalofop-p

ethyl ester does not induce cancer in

animals within the meaning of the

Delaney clause. Important to this

conclusion was the following evidence:

(1) The only statistically significant

tumor response that appears compoundrelated was seen at a single dose in a

single sex in a single species; (2) the

response was only marginally

statistically significant; (3) the response

was only significant when benign and

malignant tumors were combined; (4)

the tumors were in the male mouse

liver; (5) the tumors were within

historical controls; and (6) the

mutagenicity studies were negative.

Although in some circumstances a

finding of animal carcinogenicity would

be made despite any one, or even

several, of the six factors noted, the

combination of all of these factors here

cast sufficient doubt on the

reproducibility of the response in the

high dose male mouse that EPA

concludes the evidence on

carcinogenicity is equivocal.

6. Animal metabolism. The

metabolism of quizalofop ethyl in

animals (rat, goat and poultry) is well

understood. 14C-phenyl and 14Cquinoxaline quizalofop ethyl ester

metabolism studies have been

conducted in each species. There are

similarities among these species with

respect to metabolism. Quizalofop ethyl

is rapidly and extensively metabolized

and rapidly excreted by rats. The

principal metabolites were the

quizalofop-p acid and two

dechlorinated hydroxylated forms of the

acid. Tissue residues were minimal and

there was no evidence of accumulation

of quizalofop ethyl or its metabolites in

the rat.

The primary pathway in ruminants is

hydrolysis of the ethyl ester to form the

quizalofop-p methyl ester. In poultry,

the primary metabolic pathway is also

the hydrolysis of the ethyl ester to form

the quizalofop-p acid, then the methyl

esterification to form the quizalofop

methyl ester becomes a minor pathway.

The nature of the quizalofop ethyl

ester residue in livestock is adequately

understood. The residues of concern are

quizalofop ethyl, quizalofop methyl,

and quizalofop, all expressed as

quizalofop ethyl.

7. Metabolite toxicology. There is no

evidence that the metabolites of

quizalofop ethyl as identified as either

the plant or animal metabolism studies

are of any toxicological significance.

C. Aggregate Exposure

1. Dietary exposure. Quizalofop ethyl

is a herbicide with proposed use on

canola. The only potential for nonoccupational aggregate exposure would

come from dietary intake.

An analysis of chronic dietary risk

was conducted to determine the impact

of the possible addition of canola to the

Assure label. A Reference Dose (RfD) of

0.009 mg/kg/day was used in the

analyses. Consumption data for canola
66082 Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices

had to be estimated using various

production and usage statistics.

2. Food. The first step in the analysis

was to run the TAS (Tolerance

Assessment System) program using

current tolerances with an RfD of 0.009

mg/kg/day. The Theoretical Maximum

Residue Concentration (TMRC), based

on the current tolerances, was 0.000288

mg/kg/day for the U.S. population (48

states) and 0.000759 mg/kg/day for the

population subgroup with the highest

estimated exposure (non-nursing infants

> 1–yr. old). For the U.S. population

subgroup this represents approximately

3.2% of the RfD while for the most

exposed population this represents

approximately 8.4% of the RfD. Based

on the risk estimates arrived at in this

analysis, chronic dietary risk from the

current uses of Assure is minimal.

Unfortunately the 1977–1979 food

consumption database does not contain

any consumption data for canola oil. At

the time the survey was conducted,

canola oil was not a significant part of

the U.S. diet. Since 1977 more canola

oil is used in U.S. homes, although total

production and usage are still minor as

compared to soybean oil. Conservative

assumptions were used to estimate

canola consumption in the U.S. The

USDA’s Oilseed Analysis Division

indicated that an average of 1.1 billion

pounds of canola oil was used in the

U.S. annually over the past 5–years. The

dietary exposures that might occur by

way of consumption of canola oil can be

estimated by taking the average annual

consumption of canola oil in the U.S.

(includes both domestically produced

and imported canola oils) and dividing

it by the approximate U.S. population of

266.3 million people. This gives a percapita consumption estimate for the

general population. To calculate

exposure, this number is divided by the

average number of days in a year and

the average body weight of a person (60

kg). (This weight is the same that was

used by EPA as part of their ‘‘Food

Factor’’ system that predated the current

Tolerance Assessment System). This

value is also supported by taking the

average weight of children between the

ages of 6–months to 19–years (36 kg)

and the average weight of adults (70 kg),

and assuming that an average person

lives to be 69–years old (Review Draft of

the Exposure Factors Handbook, U.S.

EPA). Using these assumptions, canola

oil consumption was calculated to be

0.088 g/kg bw/day.

While this method provides a useful

estimate of exposure, it is clearly a

conservative estimate for risk

assessment purposes, since this estimate

assumes that all the canola oil used in

the U.S. is indeed ingested. In reality

some percentage of any commodity is

lost between production and

consumption. In addition, oil may be

used in cooking activities such as deepfat frying where most of the oil is not

actually eaten but is discarded or

recycled. With the understanding that

the dietary analysis will be very

conservative, the consumption data for

canola used in the DRES analysis for all

population subgroups was set at 0.088

g/kg bw/day. This was done by entering

a consumption estimate of 0.088 for

‘‘rapeseed’’ for all population subgroups

(there is no agricultural commodity in

TAS for canola oil).

When a tolerance for canola (1.0 ppm)

was added to the current tolerances, the

TMRC was 0.000376 mg/kg/day for the

U.S. population (48 states) and 0.000847

mg/kg/day for the highest population

subgroup (non-nursing infants >1–yrs.

old). When expressed as a percentage of

the RfD, the U.S. population (48 states)

was approximately 4.2% and the

highest population subgroup was

approximately 9.4%. These results

indicate that predicted chronic exposure

after the addition of a canola tolerance

is well below the RfD even with the

conservative (high) nature of the

assumptions that were made in

calculating consumption.

3. Drinking water. Another potential

source of dietary exposure to pesticides

is residues in drinking water. There is

no established Maximum Concentration

Level (MCL) for quizalofop ethyl in

water. Based on the low use rate of

quizalofop ethyl, and a use pattern that

is not widespread (since the current and

proposed uses are on minor crops),

DuPont does not anticipate residues of

quizalofop in drinking water and

exposure from this route is unlikely.

4. Non-dietary exposure. Quizalofop

ethyl is not registered for any use which

could result in non-occupational, nondietary exposure to the general

population.

D. Cumulative Effects

There is no evidence to indicate or

suggest that quizalofop p-ethyl has any

toxic effects on mammals that would be

cumulative with those of any other

chemicals.

E. Safety Determination

1. U.S. population. Using the

conservative exposure assumptions

described above and based on the most

sensitive species chronic NOEL of 0.9

mg/kg and a reference dose (RfD) of

0.009 mg/kg/day, the existing tolerances

and proposed use of quizalofop ethyl on

canola are expected to utilize 4.2% of

the RfD for the general U.S. population.

Generally, exposures below 100% of the

RfD are of no concern because the RfD

represents the level at or below which

daily aggregate dietary exposure over a

lifetime will not pose risk to human

health. Thus, there is a reasonable

certainty that no harm will result from

aggregate exposure to quizalofop ethyl

resulting from proposed agricultural use

on canola.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

quizalofop ethyl, data were considered

from developmental toxicity studies in

the rat and rabbit, and a multigeneration reproduction study in rats.

There were no developmental effects

observed in the absence of maternal

toxicity in the rat and rabbit

developmental studies. Minimal

adaptive or physiological effects were

observed in livers of weanlings in the 2–

generation rat reproduction study

described earlier. However, this effect

was only observed at a dose that far

exceeds any expected human exposure.

Further, the NOEL of 0.9 mg/kg/day

from the 2–year rat study with

quizalofop ethyl which was used to

calculate the RfD (discussed above), is

already lower than any of the NOEL’s

defined in the developmental and

reproductive toxicity studies with

quizalofop ethyl.

As mentioned previously, canola oil

is a very minor component of the diet,

and thus had not been included as part

of the 1977–79 food survey used in

EPA’s DRES system. DuPont is not

aware of specific food survey data

concerning consumption of canola oil

by infants and children. However, the

1977–79 food survey database does

provide consumption data for other

edible oils for each of the population

subgroups, including infants and

children. This data indicates that nonnursing infants consume more soybean

and coconut oil than any of the other 22

population subgroups, specifically

consuming 4.2 times more soybean oil

and 49.1 times more coconut oil than

the consumption by the general U.S.

population. The data also show that

children 1–6 consume more corn,

cottonseed, peanut, and sunflower oil

than any other subgroup listed, to a

maximum of 2 times more than the

general U.S. population. Using this data

and making the most conservative

assumption to extrapolate to canola oil,

we can estimate that infants and

children consume 49 times more canola

oil than does the U.S. population, and

calculate an approximate daily

consumption of 4.3 grams canola oil/kg

body weight. If we use the additional

conservative assumptions that all the

canola oil consumed contains
Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices 66083

quizalofop ethyl residues at tolerance

levels of 1.0 ppm, we calculate that the

TMRC in the infants’ and children’s

diets would be 0.000847 mg/kg/day or

9.4% of the RfD.

As indicated above, infants and

children have a low potential for

quizalofop ethyl exposure because of

both the low levels of canola oil in the

diet, and the absence of detectable

residues in field-treated canola. The

toxicology profile of quizalofop ethyl

demonstrates low mammalian toxicity.

Because there was no evidence that

offspring were uniquely susceptible to

the toxic effects of quizalofop ethyl, an

additional 10-fold uncertainty factor

should not be required to protect infants

and children. Therefore, the RfD of

0.009 mg/kg/day, which utilizes a 100-

fold safety factor, is appropriate to

assure a reasonable certainty of no harm

to infants and children from aggregate

exposure to quizalofop ethyl.

F. International Tolerances

Harmonization of Tolerances: Since

there are no Mexican or Codex MRLs/

tolerances, compatibility is not a

problem at this time. Compatibility

cannot be achieved with the Canadian

negligible residue type limit at 0.1 ppm

at the USA use pattern, which had

findings of real residues above 0.1 ppm.

(James Tompkins)

[FR Doc. 97–32935 Filed 12–16–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–782; FRL–5759–1]

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–782, must be

received on or before January 16, 1998.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch (7502C),

Information Resources and Services

Division, Office of Pesticides Programs,

Environmental Protection Agency, 401

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

person bring comments to: Rm. 1132,

CM #2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically to: oppdocket@epamail.epa.gov. Follow 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

James Tompkins (PM

25).

Rm. 239, CM #2, 703–305–5697, e-mail: tompkins.james@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–782]

(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 5.1/6.1 or ASCII file

format. All comments and data in

electronic form must be identified by

the docket control number [PF–782] and

appropriate petition number. Electronic

comments on this 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: December 3, 1997.

Peter Caulkins,

Acting 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

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.