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.
66084 Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices

1. DowElanco

PP 6F4772

EPA has received a pesticide petition

(PP 6F4772) from DowElanco, 9330

Zionsville Road, Indianapolis, IN 46268,

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 fluroxypyr methylheptyl

ester (MHE) and its only significant

metabolite fluroxypyr, free and

conjugated, all expressed as fluroxypyr

in or on the raw agricultural

commodities wheat, barley, and oats as

follows: 0.5 parts per million (ppm)

(grain), 10 ppm (straw and forage), 20

ppm (hay), and 0.5 ppm (aspirated grain

fractions, wheat). Because residues of

fluroxypyr MHE or fluroxypyr, free or

conjugated, may occur in animal feeds

derived from wheat, barley, and oats,

the following meat and milk tolerances

are also being proposed: 0.1 ppm (meat,

fat, milk, and meat byproducts except

for kidney) and 0.5 ppm (kidney). The

proposed analytical method is based on

gas chomatography (GC) with mass

spectral (MS) 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 fluroxypyr MHE in plants (wheat)

and animals (goats and poultry) is

adequately understood for the purposes

of this tolerance. A rotational crop study

showed no carryover of significant

fluroxypyr MHE related residues in

representative test crops except for

cereal grains for which tolerances are

being proposed.

2. Analytical method. There is a

practical method (GC with MS

detection) for measuring levels of

fluroxypyr MHE in or on food with a

limit of detection that allows monitoring

of food with residues at or above the

levels set for the proposed tolerances.

Fluroxypyr has been tested through the

FDAs Multiresidue Methodology,

Protocols C, D. and E. The results have

been published in the FDA Pesticide

Analytical Manual, Volume I.

3. Magnitude of residues. Magnitude

of residue studies were conducted for

wheat, barley, and oats. Residues of

fluroxypyr MHE did not concentrate in

process fractions in samples treated at a

7.5 X application rate.

B. Toxicological Profile

1. Acute toxicity. Fluroxypyr MHE has

low acute toxicity. The rat oral LD50 is

>5000 mg/kg, the rabbit dermal LD50 is

>2000 mg/kg, and the rat inhalation

LC50 is >1.0 mg/l (1,000 mg/cubic

meter), the maximum attainable

concentration. In addition, fluroxypyr

MHE is not a skin sensitizer in guinea

pigs, has no dermal irritation in rabbits,

and shows mild ocular irritation in

rabbits. The end use formulation of

fluroxypyr MHE has a similar low acute

toxicity profile.

2. Genotoxicity. 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 vitrochromosomal aberration assay

using rat lymphocytes, and an in vivo

cytogenetic assay in the mouse bone

marrow (micronucleus test) have been

conducted with fluroxypyr MHE.

DowElanco believes that these studies

show a lack of genotoxicity. In addition,

short term assays for genotoxicity

consisting of an Ames metabolic

activation test, point mutations at the

HGPRT-Locus of Chinese hamster ovary

cells, in vivo and in vitro chromosomal

aberrations in the Chinese hamster

ovary cells, unscheduled DNA synthesis

in human embryonic cells, and an assay

in mouse lymphoma cells have been

conducted with fluroxypyr. DowElanco

believes that the weight of evidence also

indicates a lack of genotoxicity.

3. Reproductive and developmental

toxicity. Developmental studies in rats

and rabbits were conducted with both

fluroxypyr MHE and fluroxypyr. Studies

with fluroxypyr MHE showed maternal

and fetal no observed effect levels

(NOELs) of 300 milligram/kilogram (mg/

kg/day) (rat) and 500 mg/kg/day (rabbit).

Studies with fluroxypyr showed no

observed adverse effect levels (NOAELs)

in the rat of 250 mg/kg/day for maternal

effects and 500 mg/kg/day for fetal

effects and a NOEL in the rabbit of 250

mg/kg/day for both maternal and fetal

effects. DowElanco believes that these

studies show that fluroxypyr and

fluroxypyr MHE are not teratogenic nor

will they interfere with in utero

development. Two multi-generation

reproduction studies were conducted

with fluroxypyr in rats. The first in

Wistar rats showed no effect on fertility

or reproductive performance and had a

NOAEL of 500 mg/kg/day (highest dose

tested). The second study in SpragueDawley rats showed a parental NOEL for

systemic effects of 100 mg/kg/day in

male rats and 500 mg/kg/day in female

rats. The NOEL for reproductive effects

was 750 mg/kg/day for males and 1,000

mg/kg/day for females (highest dose

tested). The NOEL for neonatal effects

was 500 mg/kg/day.

4. Subchronic toxicity. Fluroxypyr

MHE showed a NOEL of 1,000 mg/kg/

day in a 90-day rat dietary study and a

21-day rabbit dermal study. Ninety day

feeding studies with fluroxypyr showed

NOELs of 80 mg/kg/day (Wistar rats),

700 mg/kg/day (Fischer 344 rats), 1342

mg/kg/day (male mice), and 1,748 mg/

kg/day (female mice). In a 4-week

dietary, range finding study with

fluroxypyr in dogs the NOEL was >50

mg/kg/day.

5. Chronic toxicity. Based on chronic

testing with fluroxypyr in the mouse,

dog, and rat (two studies), a reference

dose (RfD) of 0.8 mg/kg/day is proposed

for fluroxypyr and fluroxypyr MHE. The

RfD has incorporated a 100-fold safety

factor to the NOEL found in the rat

chronic test. NOELs found in the

chronic dietary studies are as follows:

150 mg/kg/day (dog), 300 mg/kg/day

(mouse), 80 mg/kg/day (Wistar rats), 100

mg/kg/day (male Fischer 344 rats), and

500 mg/kg/day (female Fischer 344 rats).

6. Animal metabolism. Both

fluroxypyr and fluroxypyr MHE have

been evaluated in rat metabolism

studies. In summary, these studies show

that fluroxypyr MHE is rapidly

hydrolyzed and the fate of the

hydrolysis products, fluroxypyr and 1-

methylheptanol, are independent of

whether they were given as the ester or

the acid. Fluroxypyr, per se, was

extensively absorbed and rapidly

excreted principally unchanged in the

urine. 1-Methylheptanol also was

rapidly absorbed and rapidly

eliminated. Repeated administration of

fluroxypyr MHE was not associated

with accumulation in tissues. Also, the

metabolism and pharmacokinetics of

methylheptanol are comparable to that

of the methylheptyl portion of

fluroxypyr MHE.

7. Metabolite toxicology.

Administration of fluroxypyr, as the

acid or methylheptyl ester, in a variety

of toxicological studies has produced

similar effects. The principal response

to sufficiently high dosages, whether

administered over the short-term or, in

some cases, over a lifetime, was

nephrosis. Fluroxypyr is an organic acid

that is actively excreted into the urine

by the kidney. Thus, the target organ

and dose response relationship for

fluroxypyr toxicity are entirely

consistent with the data on the

toxicokinetics of fluroxypyr.

Metabolism studies have shown that

fluroxypyr MHE is rapidly and

completely hydrolyzed to fluroxypyr

acid and methylheptanol.
Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices 66085

8. Carcinogenicity. Using the

Guidelines for Carcinogen Risk

Assessment published September 24,

1986 (51 FR 33992), it is proposed that

fluroxypyr and fluroxypyr MHE be

classified as Group E for carcinogenicity

(no evidence of carcinogenicity) based

on the results of carcinogenicity studies

in two species. DowElanco believes that

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 and rat

oncogenicity studies were 1,000 and 320

mg/kg/day, respectively. A maximum

tolerated dose was achieved at the top

dosage level tested in both of these

studies based on excessive renal

toxicity. Thus, the doses tested are

adequate for identifying a cancer risk.

Accordingly, DowElanco believes that a

cancer risk assessment is not needed.

9. Endocrine effects. There is no

evidence to suggest that fluroxypyr and

fluroxypyr HME have an effect on any

endocrine system.

C. Aggregate Exposure

1. Dietary exposure—i. Food. An over

estimation of dietary exposure from use

of fluroxypyr MHE on wheat, barley,

oats is determined by basing the TMRC

on the conservative assumptions that all

cereal grain commodities will have

tolerance level residues of fluroxypyr

and that 100% of the wheat, barley, and

oat crops grown in the U.S. are treated

with fluroxypyr MHE. 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. There are

no other established U.S. tolerances or

exemption from tolerances for

fluroxypyr MHE and no other registered

uses for fluroxypyr MHE on food or feed

crops in the United States. 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 fluroxypyr

MHE on wheat, barley, and oats that is

based on a conservative exposure

assessment.

ii. Drinking water. Another potential

source of dietary exposure are residues

in drinking water. Based on the

available environmental studies

conducted with fluroxypyr MHE and

fluroxypyr wherein the properties of

these materials show little persistence

in the soil environment, there is no

anticipated exposure to residues of

fluroxypyr MHE and fluroxypyr in

drinking water. In addition, there is no

established Maximum Concentration

Level for residues of fluroxypyr MHE

and fluroxypyr in drinking water.

2. Non-dietary exposure. There are no

other uses currently registered for

fluroxypyr MHE and fluroxypyr. The

proposed use on wheat, barley, and oats

involves application of fluroxypyr MHE

to crops grown in an agriculture

environment. Thus, the potential for

non-occupational exposure to the

general population is not expected to be

significant.

D. Cumulative Effects

The potential for cumulative effects of

fluroxypyr MHE and fluroxypyr and

other substances that have a common

mechanism of toxicity is also

considered. There is no reliable

information to indicate that toxic effects

produced by fluroxypyr MHE and

fluroxypyr would be cumulative with

those of any other pesticide chemical.

Thus, it is appropriate to consider only

the potential risks of fluroxypyr MHE

and fluroxypyr in an aggregate exposure

assessment.

E. Safety Determination

1. U.S. population. Using the

conservative exposure assumptions and

the proposed RfD, the dietary exposure

to fluroxypyr MHE use on wheat, barley,

and oats will utilize 0.2% 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. Since there are no

anticipated residues in drinking water

or from other non-occupational sources

and no reliable information exists on

cumulative effects due to common

mechanism of toxicity, the aggregate

exposure to fluroxypyr MHE is

adequately represented by the dietary

route. Thus, DowElanco believes that

there is reasonable certainty that no

harm will result from aggregate

exposure to fluroxypyr MHE residues on

wheat, barley, and oats.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

fluroxypyr MHE, 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.

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 toxicity and the completeness

of the database. Based on the current

toxicological data requirements, the

database for fluroxypyr MHE relative to

pre- and post-natal effects for children

is complete. Further, for fluroxypyr

MHE, the NOEL in the chronic feeding

studies which was used to calculate the

RfD (0.8 mg/kg/day) is already lower

than the NOELs from the developmental

studies in rats and rabbits by a factor of

more than three.

Concerning the reproduction studies

in rats, the pup effects shown at the

highest dose tested (1,000 mg/kg/day)

were attributed to maternal toxicity.

Therefore, DowElanco concludes that an

additional uncertainty factor is not

needed and that the RfD at 0.8 mg/kg/

day is appropriate for assessing risk to

infants and children.

As noted above for the general U.S.

population, aggregate exposure for

infants and children will result from the

dietary (i.e. not drinking water or nonoccupational) route of exposure. In

addition, there is no reliable

information that shows cumulative

effects based on a common mechanism

of toxicity for infants and children.

Using the conservative exposure

assumptions previously described, the

percent RfD utilized by the aggregate

dietary exposure to residues of

fluroxypyr MHE on wheat, barley, and

oats is 0.6% for children 1 to 6 years

old, the most sensitive population

subgroup. Thus, based on the

completeness and reliability of the

toxicity data and the conservative

exposure assessment, DowElanco

believes that there is a reasonable

certainty that no harm will result to

infants and children from aggregate

exposure to fluroxypyr MHE residues on

wheat, barley, and oats.

F. International Tolerances

There are no Codex maximum residue

levels established for residues of

fluroxypyr MHE and fluroxypyr on any

food or feed crop. (J. Miller)

2. E.I. du Pont de Nemours and

Company

PP 1F4032

EPA has received a pesticide petition

(PP 1F4032) from E.I. du Pont de

Nemours and Company, Barley Mill

Plaza, Walker’s Mill Bldg. 37,

Wilmington, DE 19880-0038, proposing
66086 Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices

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

ethametsulfuron in or on the raw

agricultural commodity canola at 0.1

ppm. EPA has determined that the

petition contains data or information

regarding the elements set forth in

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

however, EPA has not fully evaluated

the sufficiency of the submitted data at

this time or whether the data supports

granting of the petition. Additional data

may be needed before EPA rules on the

petition.

A. Residue Chemistry

1. Plant metabolism. The qualitative

nature of the residues of

ethametsulfuron methyl is adequately

understood. The unmetabolized parent

compound was the major residue found

in a canola metabolism study up to 30

days after application. The principal

route of metabolic breakdown of

ethametsulfuron methyl in canola is

dealkylation from the triazine ring. The

initial step in the metabolic breakdown

is deethylation to form O-deethyl

ethametsulfuron methyl. Further

metabolism forms N-demethyl-Odeethyl ethametsulfuron methyl and

more minor polar metabolites. For

purposes of establishing the proposed

tolerance, the parent compound

ethametsulfuron methyl is the only

residue of concern.

The available metabolism studies

indicate that total radioactive residues

found in mature seeds, when rapeseed

was treated at a rate equivalent to the

proposed application rate, ranged from

0.008 to 0.012 ppm. These terminal

residues may consist of the parent

compound, O-deethyl ethametsulfuron

methyl, O-deethyl-N-demethyl

ethametsulfuron methyl and other

minor metabolites.

2. Analytical method. Analytical

methods are available to measure the

parent compound in oil seeds, and in oil

seed processing fractions. The

quantification of ethametsulfuron

methyl is by normal phase high

performance liquid chromatography

(HPLC) using a photoconductivity

detector. The Limit of Quantitation

(LOQ) for the analytical method is 0.02

ppm.

3. Magnitude of residues—i.

Magnitude of the residue in plants. The

results of the seed analyses from canola/

seed show that no detectable residues of

ethametsulfuron methyl were found in

canola/seed harvested 60 to 137 days

after treatment at exaggerated rates of 3X

of the normal application rate.

ii. Magnitude of the residue in

processed commodities. Analyses of

canola processed fractions (whole seed,

pressed cake, desolventized meal, crude

oil, pressed oil, solvent extracted oil,

degummed oil, refined washed oil,

refined bleached oil, and deodorized

oil) show that levels of ethametsulfuron

methyl were found to be less than 0.02

ppm, the limit of quantitation of the

method in all of the fractions evaluated.

All of the processed fractions were

obtained from seed harvested 92 days

after application at proposed use rates

and exaggerated rates.

B. Toxicological Profile

1. Acute toxicity. Based on EPA

criteria, ethametsulfuron methyl is

relatively non-toxic, and be categorized

as Toxicity Category IV (oral and

inhalation routes) and Category III

(dermal exposure). LD50s are >5,000 mg/

kg for acute oral toxicity in rats, >2,000

mg/kg for acute dermal toxicity in

rabbits, and >5.7 mg/L for acute

inhalation toxicity in rats. For technical

grade active ingredient, primary eye

irritation in rabbits is classified as Tox

Cat II. For formulated product, primary

eye irritation in rabbits is classified as

Tox Cat IV. Primary dermal irritation in

rabbits is classified as Tox Cat IV.

Dermal sensitization in guinea pigs is

classified as ‘‘Not a skin sensitizer.’’

2. Genotoxicity. This compound was

negative in the following tests that have

been conducted to determine the

genotoxic and mutagenic potential of

ethametsulfuron methyl: Mutagenicity

assays conducted in bacteria (Ames test)

and in cultured Chinese Hamster Ovary

cells; a test that measures the induction

of chromosomal aberrations in bone

marrow cells isolated from rats treated

with ethametsulfuron methyl;

micronuclei induction in bone marrow

cells from mice; and negative in a text

that measures DNA damage in cultured

rat liver cells. Based on the weight of

these data, E.I du Pont concludes that

ethametsulfuron methyl is neither

genotoxic or mutagenic.

3. Reproductive and developmental

toxicity. A 2-generation, four litter

reproduction study with CD rats treated

with dietary levels of 0, 250, 5,000,

20,000 ppm of ethametsulfuron methyl

failed to reveal any evidence suggestive

of an adverse effect on reproductive

potential. A NOEL was indicated at the

mid dose level of 5,000 ppm (equivalent

to approx. 433 mg/kg b.w./day, actual

intake) based on significantly (p<0.5)

decreased body weights in the high dose

treated F0 and F1 generation males.

A developmental toxicity study of

ethametsulfuron methyl in rabbits

indicated that dams administered 4,000

mg/kg (highest dose tested) had a higher

mortality rate, lower food consumption

and body weight gains, increased

incidences of gross clinical signs of

toxicity and of abortions, and increased

absolute and relative liver weights.

Absolute and relative liver weights were

also slightly greater for dams

administered 1,000 mg/kg. There were

no compound-related effects observed

for dams administered 250 mg/kg.

Dams administered 4,000 mg/kg also

had a decrease in the number of live

fetuses. This was related to an increase

in the number of early resorptions.

There were no other compound-related

effects on the dams, nor were there any

effects on fetal weights, malformations

or variations incidences. The NOELs for

this study were 250 mg/kg for the dams

and 1,000 mg/kg for the fetus.

Ethametsulfuron methyl was neither

teratogenic in rabbits nor uniquely toxic

to the conceptus.

A developmental toxicity study was

also conducted in rats treated at doses

of 0, 60, 250, 1,000, or 4,000 mg/kg.

Among the dams of the groups given

ethametsulfuron methyl, no compoundrelated mortality or clinical

abnormalities were observed. For the

treatment period, the high dose group

had a lower weight gain and

significantly decreased food

consumption compared to the control

group. No other significant differences

in body weight changes or food

consumption were observed. A

significant trend was indicated for mean

fetal weight and the mean fetal weight

of the high dose group was lower than

that of the control group. No significant

differences were observed in the rates of

malformations or developmental

variations. Under the conditions of the

study, the apparent no effect level for

the dam and fetus was 1,000 mg/kg/day.

Thus ethametsulfuron methyl was not

uniquely toxic to the conceptus nor was

it teratogenic in rats.

4. Subchronic toxicity—i. Rat. A 90-

day feeding study followed by a 1-

generation reproduction phase in rats at

dietary levels of 0, 100, 1,000, and 5,000

ppm of ethametsulfuron methyl failed to

elicit any signs of overt toxicity or any

adverse effect on reproductive

performance at levels as high as 5,000

ppm (equivalent to 0.5% of the diet or

approximately 409 mg/kg b.w./day,

actual intake). The No Observed

Adverse Effect Level (NOAEL) for this

study was, therefore, the high dose level

of 5,000 ppm.

ii. Mouse. A 90-day dietary feeding

study in CD-1 mice at levels of 0, 50,

500, 2,500 and 5,000 ppm indicated a

No Observed Effect Level (NOEL) for

females and a NOAEL for males set at
Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices 66087

the high dose level of 5,000 ppm

(equivalent to approximate 687 mg/kg

b.w./day, actual intake for males).

iii. Dog. Dietary administration of

technical ethametsulfuron methyl to

dogs for 90 days at levels of 0, 100,

3,500 or 10,000 ppm failed to reveal any

evidence of treatment-related toxicity at

levels as high as 10,000 ppm (equivalent

to 1% of the diet or approximately 386

mg/kg b.w./day, based on actual intake).

5. Chronic toxicity—i. Rat.

Administration of ethametsulfuron

methyl to Sprague-Dawley rats for up to

24 months at dietary levels of 0, 50, 500

and 5,000 ppm revealed a NOAEL for

in-life parameters of 5,000 ppm

(equivalent to 238.5 mg/kg b.w./day,

actual intake), based on questionable

toxicological significance of decreased

(p<0.05) serum sodium levels in both

the 5,000 ppm treated males and

females during the first 12 months of

treatment. The effects on serum sodium

levels in the high dose groups were

described as mild (representing a

decrease in 2-6% of the control values)

and occurring in the absence of any

associated pathological changes in the

kidney. Treatment with the test material

at dietary levels as high as 5,000 ppm

(equivalent to 0.5% of the diet) failed to

elicit any evidence of treatment-related

neoplastic potential.

ii. Dogs. Chronic dietary

administration of the test material to

dogs at levels of 0, 250, 3,000 and

15,000 ppm for 1-year indicated a NOEL

of 3,000 ppm, equivalent to

approximately 87 mg/kg b.w./day actual

intake, based on compound-related

effects expressed in the 15,000 ppm

treated group as decreased body weight

gain and food efficiency values in the

males. Significantly decreased serum

sodium levels in both sexes at the high

dose treated level were not associated

with any evidence of renal pathology. In

the absence of any collaborative clinical

or pathological findings differences in

organ weights relative to body or brain

weight were considered to be of

doubtful biological significance.

iii. Mouse. Administration of the test

material to CD-1 mice at dietary levels

of 0, 25, 500, and 5,000 ppm for the

period of up to 78 weeks failed to reveal

any overt signs of treatment-related

toxicity of dietary levels of up to 5,000

ppm (equivalent to 818 mg/kg bwt/day,

actual intake). Although a direct effect

of treatment on body weights or weight

gains could not be established, overall

body weight gain in the 5,000 ppm

treated male mice was depressed (nonsignificant, p>0.05) by 10% when

compared to the controls. There was no

evidence of any treatment-related

oncogenic potential.

6. Animal metabolism. When

administered via oral gavage to rats,

ethametsulfuron methyl was rapidly

metabolized and excreted in the urine

and feces. Within 3 days, greater than

90% of the administered dose was

excreted by male rats and greater than

80% was excreted by females.

Approximately 50% of the administered

dose was excreted as unchanged

ethametsulfuron methyl. The remainder

was converted predominately to Ndemethyl ethametsulfuron methyl and

O-deethyl ethametsulfuron methyl,

which are considered by by-products of

cytochrome P450-mediated reactions.

Less than 0.02% of the administered

dose remained in the carcass or tissues.

There was no significant or preferential

accumulation of ethametsulfuron

methyl or its metabolites in any tissue.

Because of the short excretion half-life,

repeated daily exposures are not

expected to result in significant body

burdens of ethametsulfuron methyl.

7. Metabolite toxicology. There is no

evidence that the metabolites of

ethametsulfuron methyl as identified as

either the plant or animal metabolism

studies are of any toxicological

significance.

8. Endocrine effects. No special

studies investigating potential

estrogenic or endocrine effects of

ethametsulfuron methyl have been

conducted. However, the standard

battery of required toxicology studies

have been completed. These 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. Based on these

studies there is no evidence to suggest

that ethametsulfuron methyl has an

effect on the endocrine system.

C. Aggregate Exposure

1. Dietary exposure—i. Food. Based

on the residue data and the proposed

single-crop use, potential for dietary

exposure of ethametsulfuron methyl

from food sources is extremely low.

Residue studies have shown no residues

above the LOQ (residues <0.02 ppm) in

any canola seed samples evaluated,

including the canola oil processed

fractions. No dietary exposure is

anticipated from secondary residues in

meat or milk. Although canola meal is

considered a minor feedstuff for cattle

and poultry (representing a maximum of

15% of an animal’s diet), field residue

studies showed ethametsulfuron methyl

residues were all below the LOQ (<0.02

ppm) in all of the canola RACs and

processed fractions, including meal,

even when the crop was treated at 2-3X

the proposed maximum use rate.

Direct human consumption of canola

as a food commodity in the United

States is extremely low. Canola is a

minor crop in the U.S., and the only

canola fraction used as a food product

is the refined canola oil. A dietary risk

evaluation (DRES) was conducted to

determine the theoretical maximum

residue contribution of ethametsulfuron

methyl in the diet as a result of

agricultural use on canola.

Unfortunately, consumption data for

canola oil does not exist in the 1977-

1979 food consumption database used

in EPA’s DRES system, since at that

time, 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 when compared to other

edible oils such as soybean oil.

Conservative assumptions were used

to estimate canola consumption in the

United States. The USDA’s Oilseed

Analysis Division has indicated that an

average of 1.1 billion pounds of canola

oil was used in the United States

annually over the past 5 years. The

dietary exposures that might occur by

way of canola oil consumption can be

estimated by taking the average annual

use of canola oil in the United States

(includes both domestically produced

and imported canola oils) and dividing

it by the approximate US population of

266.3 million people. This provides a

per-capita consumption estimate for the

general population. Using this

approach, total canola oil consumption

on a grams per kg body weight per day

was calculated by dividing by the

average days in a year and average body

weight of a person (60 kg). The 60 kg

value is used by the US EPA as part of

their ‘‘Food Factor’’ system, and 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 of 70 kg and

assuming a 69 year life span (as

proposed in the review draft of the US

EPA’s Exposure Factors Handbook).

Using these assumptions, canola oil

consumption was calculated to be 0.088

g/kg bw/day.

While this method provides a useful

approximation of canola consumption,

this is clearly a conservative estimate for

risk assessment purposes, since this

estimate assumes that all of the canola

oil used in the US is indeed ingested. In

reality, not all the oil that is used in

cooking or deep-fat frying is consumed

but instead, is discarded or recycled.

Another indication that the

consumption value of 0.088 g/kg bw/

day is an over-estimate is from the

USDA’s 1989-1992 food survey (not yet

included in the EPA’s DRES system),
66088 Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices

which indicates canola oil consumption

is 0.00023 g/kg/day for the general U.S.

population.

Using the consumption estimate of

0.088 g canola oil/ kg bw/day for the

general US population, and assuming

that 100% of the canola crop is treated

with ethametsulfuron methyl and all

canola consumed contains residues at

the proposed tolerance level of 0.1 ppm,

the theoretical maximum residue

contribution of ethametsulfuron methyl

in the diet is calculated to be 0.00001

mg/kg/day or <0.01% of the RfD of 0.87

mg/kg/day.

ii. Drinking water. Another potential

source of dietary exposure to pesticides

are residues in drinking water. There is

no established Maximum Concentration

Level (MCL) for ethametsulfuron methyl

in water. Based on the low use rate of

ethametsulfuron methyl, and a use

pattern that is not widespread (since the

only proposed use is on a minor crop),

DuPont does not anticipate residues of

ethametsulfuron in drinking water and

exposure from this route is unlikely.

2. Non-dietary exposure.

Ethametsulfuron methyl is not

registered for any use which could

result in non-occupational, non-dietary

exposure to the general population.

Ethametsulfuron methyl is a herbicide

with proposed use only on canola.

There are no other food uses, nor are

there any residential or non-crop uses of

this active ingredient. Therefore, the

only potential for non-occupational

aggregate exposure would come from

dietary intake.

D. Cumulative Effects

Ethametsulfuron methyl belongs to

the sulfonylurea class of compounds.

Other compounds in this class are

registered herbicides. However, the

herbicidal activity of the sulfonylureas

is due to the inhibition of acetolactase

synthase (ALS), an enzyme only found

in plants. ALS is part of the biosynthetic

pathway leading to the formation of

branched chain amino acids. Animals

lack ALS and this biosynthetic pathway.

This lack of ALS contributes to the low

toxicity of the sulfonylurea compounds

in animals. There is no evidence to

indicate or suggest that ethametsulfuron

methyl 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 87

mg/kg and a Reference Dose (RfD) of

0.87 mg/kg/day, the proposed use of

ethametsulfuron methyl on canola is

expected to utilize 0.001% of the RfD

for the general U.S. population.

Generally, exposures below 100 percent

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, DuPont concludes

that there is a reasonable certainty that

no harm will result from aggregate

exposure to ethametsulfuron methyl

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

ethametsulfuron methyl, data were

considered from developmental toxicity

studies in the rat and rabbit, and a

multi-generation reproduction study in

rats. The developmental toxicity studies

demonstrated that even at the high oral

doses used in these studies (up to 4,000

mg/kg in rabbits and rats), no

teratogenic effects were found in either

species nor was the compound found to

be uniquely toxic to the conceptus.

The 2-generation reproduction study

in rats treated at dietary levels as high

as 20,000 ppm on a daily basis

throughout 2 generations (equivalent to

1,582 mg/kg/day for males and 1817

mg/kg/day for females), showed no

evidence of effects on reproductive

performance in the adults, or evidence

of gross or histopathological effects in

the adult or weanling rats in any test

group. This study indicates that

ethametsulfuron methyl is not a

reproductive toxicant.

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 indicate 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 US

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 these

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 g canola oil/kg body

weight. If we use the additional

conservative assumptions that all the

canola oil consumed contains

ethametsulfuron methyl residues at

tolerance levels of 0.1 ppm, we calculate

that the maximum theoretical residue

concentration of ethametsulfuron

methyl in the infants’ and children’s

diets would be 0.00049 mg/kg/day or

<0.05% of the RfD.

As indicated above, DuPont

concludes that infants and children

have a low potential for

ethametsulfuron methyl exposure

because of both the low level of canola

oil in the diet, and the absence of

detectable residues in field-treated

canola. The toxicology profile of

ethametsulfuron methyl demonstrates

low mammalian toxicity, and results

from the developmental and

reproduction studies indicate that there

is no additional sensitivity for infants

and children. Therefore, DuPont

concludes that an additional safety

(uncertainty) factor is not warranted and

the RfD of 0.87 mg/kg body weight/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

ethametsulfuron methyl.

F. International Tolerances

Ethametsulfuron methyl and its enduse product Muster are registered only

in Canada on canola/rape and mustard

with a MRL value of 0.1 ppm. A CODEX

tolerance for ethametsulfuron methyl

has not been established. (Jim

Tompkins)

3. Monsanto

PP 7F4840

EPA has received a pesticide petition

(PP 7F4840) from Monsanto, Suite 1100,

700 14th St., NW., Washington, DC

2005, 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 sulfosulfuron

1-(4,6-dimethoxypyrimidin-2-yl)-3-[(2-

ethanesulfonyl-imdazo[1,2-a]pyridine-3-

yl)sulfony]urea in or on the raw

agricultural commodities. The proposed

analytical method involves hydrolyzing

sulfosulfuron and its imadazopyridinecontaining metabolites under acidic

conditions to the common chemophore,

ethyl sulfone. Ethyl sulfone is then

separated and quantitated by High

Performance Liquid Chromatography

(HPLC) with fluorescence detection.

EPA has determined that the petition
Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices 66089

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. Metabolism of

sulfosulfuron in plants is negligible. The

nature of the major sulfosulfuron

residues in wheat matrices depends

primarily on the mode of application

with reliance upon metabolism in the

soil.

Postemergence applications result in

residues that are mostly made up of

parent compound, with small amounts

of five to six metabolites that together

make up less than 15% of the total

radioactive residue.

Preemergence application result in

soil degradation of the parent

compound followed by uptake primarily

of the imidazopyridine ring-containing

metabolites and small amounts of the

parent compound. The pyrimidine ringcontaining metabolites under these

conditions are tightly bound to the soil,

resulting in negligible uptake of these

residues. Little further metabolism of

the imidazopyridine metabolites takes

place in the plant. The predominant

residues resulting from preemergence

applications were sulfonamide (22%

TRR) and guanidine (18.3% TRR).

In both cases, translocation of residue

to the grain is negligible. The highest

residues are observed following

postemergence applications and the

residues are primarily parent

compound.

In rotational crops, residues were low,

with the TRR’s not exceeding 0.01 ppm

in most crops. The most abundant

metabolite was sulfonamide, with low

levels of a sulfonamide-sugar conjugate

and parent compound also observed.

2. Analytical method. The primary

crop (wheat) residue and the secondary

(animal products) residues are analyzed

as total residue by hydrolyzing

sulfosulfuron and its imadazopyridinecontaining metabolites under acidic

conditions to the common chemophore,

ethyl sulfone. Ethyl sulfone is then

separated and quantitated by High

Performance Liquid Chromatography

(HPLC) with fluorescence detection.

3. Magnitude of residues. EPA has

received a pesticide petition from

Monsanto Company proposing to amend

40 CFR part 180 by establishing a

tolerance for residues of the herbicide

sulfosulfuron in or on the following:

Commodity Part per million

(ppm)

Wheat

grain 0.01 ppm (limit of

quantitation

0.008 ppm)

straw 0.1 ppm

hay 0.3 ppm

forage 3.0 ppm

Animal Products

milk 0.004 ppm

fat 0.004 ppm

meat 0.004 ppm

muscle 0.004 ppm

meat by-products 0.1 ppm

kidney 0.1 ppm

liver 0.1 ppm

B. Toxicological Profile

1. Acute toxicity. A rat acute oral

study with an LD50 of >5,000 mg/kg,

EPA Category IV. A rabbit acute dermal

study with an LD50 of >5,000 mg/kg,

EPA Category IV. A rat inhalation study

with and LC50 of >3.0 mg/l, the highest

concentration generated, EPA Category

IV. A primary eye irritation study in the

rabbit showing moderate eye irritation,

EPA Category III. A primary dermal

irritation study in the rabbit showing

essentially no irritation, EPA Category

IV. A dermal sensitization study in the

guinea pig showing no potential for

sensitization. Acute and subchronic

neurotoxicity studies in rats

demonstrating no neurotoxicity

potential. Sulfosulfuron has a low order

of acute toxicity.

2. Genotoxicity. An in vitro Ames/

Salmonella mutagenicity assay in five

commonly used strains was negative for

mutagenic potential.

An in vitro CHO/HGPRT Gene

Mutation assay was negative for

mutagenicity up to the limit of

solubility.

An in vitro chromosomal aberration

test in cultured mammalian cells

demonstrated the induction of

chromosomal aberrations only under

conditions of prolonged incubation at

high dose levels that exceeded the

solubility of the test material. The

mechanism responsible for this

induction and the biological relevance

of the effect is not clear. Other, more

relevant, chromosomal aberration tests

(see below) were negative.

An in vitro chromosome aberration

study in human lymphocytes was

negative for chromosomal aberrations.

An in vivo bone marrow micronucleus

assay in the mouse was negative for

chromosomal effects.

The weight of evidence demonstrates

that sulfosulfuron does not produce

significant genotoxic or mutagenic

effects.

3. Reproductive and developmental

toxicity. A developmental study in the

rat demonstrated no signs of maternal or

developmental toxicity up to the

maximum dose level of 1,000 mg/kg/

day. The NOEL was considered to be

1,000 mg/kg/day.

A developmental study in the rabbit

demonstrated no signs of maternal or

developmental toxicity up to the

maximum dose level of 1,000 mg/kg/

day. The NOEL was considered to be

1,000 mg/kg/day.

A 2-generation reproduction study in

the rat demonstrated a subchronic

toxicity NOEL of 5,000 ppm based on

body weight and food consumption

decreases, urinary bladder calculi

formation and minor bladder and

kidney pathology. There were no effects

on reproduction or fertility up to 20,000

ppm, the highest dose tested.

Sulfosulfuron demonstrates no

reproductive effects in rats and no

teratogenic or developmental effects in

rats and rabbits.

4. Subchronic toxicity. A 28-day

dermal study in the rat with a NOEL of

at least 1,000 mg/kg/day, the highest

dose tested. A 90-day feeding study in

the rat resulted in only mild body

weight/weight gain effects at 20,000

ppm, the highest dose tested. The NOEL

for both males and females was

considered to be 6,000 ppm. A 90-day

feeding study in the dog demonstrated

subchronic toxicity, primarily in the

urinary bladder, secondary to urinary

crystal formation and urolithiasis at

dose levels of 300 and 1,000 mg/kg/day

in females and at 1,000 mg/kg/day in

males. The NOEL was considered to be

100 mg/kg/day in females and 300 mg/

kg/day in males. Sulfosulfuron has a

low order of subchronic toxicity, related

only to the precipitation of test material

in the urinary bladder of dogs at high

doses.

5. Chronic toxicity. A 1-year study in

the dog demonstrated toxicity in the

urinary bladder secondary to urinary

crystal and calculus formation at 500

mg/kg/day in a single male animal.

Urinary crystal formation was observed

in females at 500 mg/kg/day with no

subsequent pathology. The NOEL was

considered to be 100 mg/kg/day for

male and female dogs.

A combined chronic toxicity/

oncogenicity study in the rat

demonstrated chronic toxicity,

primarily in the urinary bladder, in

males and females at 5,000 and females

at 20,000 mg/kg/day. The NOEL for

chronic toxicity was considered to be

500 ppm or 24.4 mg/kg/day. This is the
66090 Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices

lowest NOEL and is used in the

calculation of the Reference Dose (RfD).

An 18-month oncogenicity study in

the mouse demonstrated chronic

toxicity, primarily in the urinary

bladder, of male mice at 3,000 and 7,000

ppm. No chronic toxicity was observed

in females. The NOEL for chronic

toxicity was considered to be 700 ppm

for male mice and 7,000 ppm for female

mice. Sulfosulfuron demonstrates

chronic toxicity related only to the

formation of crystals and calculi of the

compound in the urinary bladders of

mice, rats and dogs.

6. Carcinogenicity. An 18-month

oncogenicity study in the mouse

demonstrated a small increase in the

incidence of benign mesenchymal

tumors of the urinary bladder

submucosa in male mice with urinary

bladder calculi at 7,000 ppm. However,

these tumors are reportedly unique to

Swiss-derived mice and were

considered to be of biological relevance

only to the mouse by a Independent

Working Group on Mouse Mesenchymal

Tumors convened by the International

Life Sciences Institute (ILSI).

A combined chronic toxicity/

oncogenicity study in the rat (same as

above) demonstrated a urinary bladder

transitional cell carcinoma and a

urinary bladder transitional cell

papilloma in two females at 5,000 mg/

kg/day, probably secondary to urinary

system calculi formation and (chronic)

irritation.

The low incidences of oncogenicity

observed in the oncogenicity studies

conducted with sulfosulfuron are either

considered to be relevant to the mouse

only or a secondary threshold effect

related to chronic irritation resulting

from bladder stone formation at high

doses. Sulfosulfuron is not considered

to be a primary oncogen.

Using the Guidelines for Carcinogenic

Risk Assessment published September

24, 1986, Monsanto believes that the

EPA would classify sulfosulfuron as a

Group ‘‘C’’ carcinogen, without

quantitative risk assessment, i.e., using

the margin of exposure (MOE) approach

for risk assessment. Under the proposed

guidelines published April 10, 1996,

however, Monsanto believes that

sufosulfuron should be included in the

‘‘Not Likely Human Carcinogen’’

category based upon mechanistic

considerations. To quote the 1996 EPA

guideline document discussing a similar

effect in a rat study:

‘‘A major uncertainty is whether the

profound effects of (substance 5) may be

unique to the rat. Even if (substance 5)

produced stones in humans, there is

only limited evidence that humans with

bladder stones develop cancer. Most

often human bladder stones are either

passed in the urine or lead to symptoms

resulting in their removal.’’

In either case, a Margin of Exposure

assessment or reference dose (RfD)

approach would be utilized. Since the

chronic NOEL for male rats is lower

than the oncogenic NOEL for female rats

(24 mg/kg/day vs 30 mg/kg/day), the

male rat chronic NOEL was used with

a 100 fold safety factor for a reference

dose of 0.24 mg/kg/day, for the

quantitation of human risk.

7. Animal metabolism. An animal

metabolism study was conducted in the

rat using sulfosulfuron radiolabeled in

both the pyrimidine and

iminodazopyridine rings to detect

possible cleavage of the sulfonylurea

bond. Following oral dosing of

sulfosulfuron, absorption was found to

be greater at low doses (>90%) than at

the higher doses ( 40%). Sulfosulfuron

was readily excreted, mostly

unchanged, with urinary excretion the

major route of elimination at low doses

and fecal excretion the major route at

high doses. Greater than 90% of the

dose was excreted 3 days after

administration. Expiration as carbon

dioxide or volatiles was not a significant

route of elimination. Metabolism of

sulfosulfuron in the rat occurred to only

a limited extent with demethylation and

pyrimidine ring hydroxylation as the

major metabolic routes, yielding

desmethyl-sulfosulfuron and 5-hydroxysulfosulfuron as the major metabolites.

There was no evidence of bio-retention

of sulfosulfuron or its metabolites;

tissue and blood levels were negligible,

with no individual tissue showing

levels exceeding 0.2% of the dose.

8. Metabolite toxicology. Dietary

residues are comprised almost entirely

of parent sulfosulfuron and the

imidazopyridine-containing metabolites

sulfonamide and guanidine. Specific

toxicology data is not available on these

metabolites, but the structures do not

suggest any specific toxicologic concern

and the level of dietary exposure is low.

These metabolites are not considered to

present a significant toxicological risk.

C. Aggregate Exposure

1. Dietary exposure—i. Food.

Estimates of dietary exposure to

residues of sulfosulfuron utilized the

proposed tolerance-level residues for

wheat grain (0.01 ppm) and for the

following animal products: milk (0.004

ppm), fat (0.004 ppm), meat (0.004 ppm)

and meat by-products (0.1 ppm,

including kidney and liver). Onehundred percent market share was

assumed as well as the assumption that

no loss of residue would occur due to

processing and cooking. A Reference

Dose (RfD) of 0.24 mg/kg/day was

assumed based on the low NOEL from

the chronic/oncogenicity study in rats (≈

24 mg/kg/day) with a safety factor of

100. Since the present label lists only

wheat or fallow as approved rotations,

no residues were entered for rotational

crops. Using these conservative

assumptions, dietary residues of

sulfosulfuron contribute only 0.000149

mg/kg/day (0.006% of the RfD) for

children 1-6 years, the most sensitive

sub-population. For the U.S. Population

as a whole, the exposure was only

0.000048 mg/kg/day (0.02% of the RfD).

ii. Drinking water. Given the low use

rates, rapid soil degradation, strong soil

binding characteristics and low soil

mobility of sulfosulfuron, the risk of

significant ground and surface water

contamination and exposure via

drinking water is considered to be

negligible. Assuming that 10% of the

RfD is allocated to drinking water

exposure (0.024 mg/kg/day), and the

average, 70 kg human consumes 2 liters

of water per day, a Maximum Allowable

Concentration value for drinking water

of 0.84 mg/l is proposed for

sulfosulfuron.

2. Non-dietary exposure.

Sulfosulfuron is proposed for a variety

of non-crop uses including roadsides,

fencerows, industrial sites, parks,

apartment complexes, schools and other

public areas. Exposure assessments have

been made for mixer/loaders and

applicators in these situations

(occupational exposure) and the

cumulative (amortized) daily exposure

from both these activities has been

estimated to be less than 0.5 μg/kg/day,

or approximately 0.2% of the RfD. The

non-occupational exposure in these

locations to the casual passer-by would

be expected to be orders of magnitude

less. The exposure in either instance

does not present a significant exposure

risk.

D. Cumulative Effects

Sulfosulfuron falls into the common

category of sulfonylurea (SU)

herbicides; however there is no

information to suggest that any of the

SU’s have a common mechanism of

mammalian toxicity or even produce

similar effects. It is not appropriate to

combine exposures in this case, and

Monsanto is considering only the

potential risk of sulfosulfuron in its

aggregate exposure assessment.

E. Safety Determination

1. U.S. population. As presented

above, the exposure of the U.S. General

population to sulfosulfuron is low, and

the risks, based on comparisons to the

reference dose, are negligible. Margins
Federal Register / Vol. 62, No. 242 / Wednesday, December 17, 1997 / Notices 66091

of safety are expected to be

considerable. Monsanto concludes that

there is a reasonable certainty that no

harm will result to the U.S. Population

from aggregate exposure to

sulfosulfuron residues.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

sulfosulfuron, Monsanto considered

data from developmental toxicity

studies in the rat and rabbit and a twogeneration reproduction study in rats.

No developmental or reproductive

effects were observed up to the highest

dose tested in each of the three studies.

The Observed NOEL’s were 1,000 mg/

kg/day, 1,000 mg/kg/day and 20,000

ppm, respectively. Using the same

conservative assumptions that were

made previously for the dietary

exposure analysis for the U.S. General

population, the percent of the RfD

utilized by pre-adult sub-populations

are: all infants-0.03%; nursing infants0.005%; non-nursing infants-0.04%;

children, 1-6 years-0.06%; children, 7-

12 years-0.04%. Monsanto concludes

that there is a reasonable certainty that

no harm will result to infants and

children from aggregate exposure to

sulfosulfuron residues.

F. International Tolerances

There are currently no international

(Codex) tolerances established for

sulfosulfuron. Sulfosulfuron is currently

registered on wheat in Switzerland,

Poland, the Czech Republic, Slovakia

and South Africa. Petitions for

tolerances for sulfosulfuron in/on wheat

have been submitted in Canada,

Australia and the European Union. (Jim

Tompkins)

[FR Doc. 97–32936 Filed 12–16–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–785; FRL–5760–5]

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–785], 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:

Amelia M. Acierto, Registrtion Division

(7505W), Office of Pesticide Programs,

U.S. Environmental Protection Agency,

401 M Street, S.W., Washington, D.C.

20460. Office location, telephone

number and e-mail address: Rm. 4W60

4th floor, CS1, 2800 Crystal Drive,

Arlington VA, (703)308-8377, e-mail:

acierto.amelia@epamail.epa.gov.

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–785]

(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–785] 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. Ecolab Inc.

PP 7E4922

EPA has received a pesticide petition

(PP 7E4922) from Ecolab Inc., 370 N.

Wabasha Street, St. Paul, Minnesota

55102, proposing pursuant to section

408(d) of the Federal Food, Drug and

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

amend 40 CFR 180.1001(c) to establish

an exemption from the requirement of a

tolerance for the residues of