42980 Federal Register / Vol. 62, No. 154 / Monday, August 11, 1997 / Notices

sequences, an active ingredient not

included in any previously registered

product.

The application was approved on May

29, 1996, as CryIA(b) Form of the B.t.k.

Insect Control Protein for seed

propagation (EPA Registration Number

524–492). The chemical was amended

to read ‘‘Bacillus thuringiensis deltaendotoxin as produced by the CryIA(b)

gene and the genetic material necessary

for its production (PV-ZMCT01) in

corn.’’

A conditional registration may be

granted under section 3(c)(7)(C) of

FIFRA for a new active ingredient where

certain data are lacking, on condition

that such data are received by the end

of the conditional registration period

and do not meet or exceed the risk

criteria set forth in 40 CFR 154.7; that

use of the pesticide during the

conditional registration period will not

cause unreasonable adverse effects; and

that use of the pesticide is in the public

interest.

The Agency has considered the

available data on the risks associated

with the proposed use of Bacillus

thuringiensis delta-endotoxin as

produced by the CryIA(b) gene and the

genetic material necessary for its

production (PV-ZMCT01) in corn, and

information on social, economic, and

environmental benefits to be derived

from such use. Specifically, the Agency

has considered the nature and its

pattern of use, application methods and

rates, and level and extent of potential

exposure. Based on these reviews, the

Agency was able to make basic health

and safety determinations which show

that use of Bacillus thuringiensis deltaendotoxin as produced by the CryIA(b)

gene and the genetic material necessary

for its production (PV-ZMCT01) in corn

during the period of conditional

registration will not cause any

unreasonable adverse effect on the

environment, and that use of the

pesticide is in the public interest.

This product is conditionally

registered in accordance with FIFRA

section 3(c)(7)(C). If the conditions are

not complied with the registration will

be subject to cancellation in accordance

with FIFRA section 6(e).

Consistent with section 3(c)(7)(C), the

Agency has determined that this

conditional registration is in the public

interest. Use of the pesticides are of

significance to the user community, and

appropriate labeling, use directions, and

other measures have been taken to

ensure that use of the pesticides will not

result in unreasonable adverse effects to

man and the environment.

More detailed information on this

conditional registration is contained in

an EPA Pesticide Fact Sheet on Bacillus

thuringiensis CryIA(b) delta-endotoxin

and the genetic material necessary for

its production in corn.

A copy of the fact sheet, which

provides a summary description of the

chemical, use patterns and

formulations, science findings, and the

Agency’s regulatory position and

rationale, may be obtained from the

National Technical Information Service

(NTIS), 5285 Port Royal Road,

Springfield, VA 22161.

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

FIFRA, a copy of the approved label, the

list of data references, the data and other

scientific information used to support

registration, except for material

specifically protected by section 10 of

FIFRA, are available for public

inspection in the Public Information

and Records Integrity Branch,

Information Resources and Services

Division (7506C), Office of Pesticide

Programs, Environmental Protection

Agency, Rm. 1132, CM #2, Arlington,

VA 22202 (703–305–5805). Requests for

data must be made in accordance with

the provisions of the Freedom of

Information Act and must be addressed

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

20460. Such requests should: (1)

Identify the product name and

registration number and (2) specify the

data or information desired.

Authority: 7 U.S.C. 136.

List of Subjects

Environmental protection, Pesticides

and pests, Product registration.

Dated: July 30, 1997.

Janet L. Andersen,

Director, Biopesticides and Pollution

Prevention Division, Office of Pesticide

Programs.

[FR Doc. 97–21146 Filed 8-8-97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–755; FRL–5736–1]

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–755, must be

received on or before September 10,

1997.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch (7506C),

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 by following

the instructions under

‘‘SUPPLEMENTARY INFORMATION.’’

No confidential business information

should be submitted through e-mail.

Information submitted as a comment

concerning this document may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI). CBI should not be submitted

through e-mail. Information marked as

CBI will not be disclosed except in

accordance with procedures set forth in

40 CFR part 2. A copy of the comment

that does not contain CBI must be

submitted for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments will be available for public

inspection in Rm. 1132 at the address

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

Monday through Friday, excluding legal

holidays.

FOR FURTHER INFORMATION CONTACT: The

product manager listed in the table

below:

Product Manager Office location/telephone number Address

George LaRocca (PM

13).

Rm. 204, CM #2, 703–305–6100, e-mail: larocca.george@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Mary Waller, Acting (PM

21).

Rm. 265, CM #2, 703–308–9354, e-mail: waller.mary@epamail.epa.gov. Do.
Federal Register / Vol. 62, No. 154 / Monday, August 11, 1997 / Notices 42981

Product Manager Office location/telephone number Address

James Tompkins, Acting

(PM 25).

Rm. 239, CM #2, 703–305–5697, e-mail: tompkins.jim@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–755]

(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–755] 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: August 1, 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 7E4825

EPA has received a pesticide petition

(PP 7E4825) from Bayer Corporation,

8400 Hawthorn Road, Kansas City, MO

64120, 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

import tolerances for residues of the

fungicide Tolylfluanid in or on the raw

agricultural commodities apples and

grapes at 5.0 parts per million (ppm),

hops at 30 ppm and tomatoes at 1.0

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. Plant

metabolism studies were conducted

using radiolabeled tolylfluanid applied

to apples, grapes, and strawberries.

Unchanged parent tolylfluanid was the

major metabolite identified in these

studies.

2. Analytical method. Bayer has

developed an analytical method for the

determination of tolylfluanid residues

in raw agricultural and processed

commodities of apples, grapes,

tomatoes, and hops. Samples are

analyzed by gas chromatography using

thermionic nitrogen-phosphorus

detector or flame photometric detector

following extraction, filtration, and

cleanup procedures. The limit of

quantitation is 0.02 mg/kg for all

matrices, except it is 0.05 mg/kg for

raisins and wet apple pomace, 0.5 mg/

kg for green hop cones, and 1.0 mg/kg

for dried hop cones.

3. Magnitude of residues. Bayer has

conducted over 90 residue field trials in

seven countries on apples, grapes,

tomatoes, and hops. Residues of

tolylfluanid in or on grapes harvested

14, 21 or 35 days following treatment

according to recommended practices

ranged from 0.03 mg/kg to 3.45 mg/kg,

except residues of tolylfluanid were

5.08 mg/kg in one sample from a trial

conducted in Spain. Residues of

tolylfluanid ranged from 0.03 mg/kg to

0.66 mg/kg in tomatoes harvested 3 or

7 days following multiple applications

with tolylfluanid. Residues of

tolylfluanid ranged from 0.14 to 2.31

mg/kg in or on apples harvested 7 days

after multiple applications with

tolylfluanid. Residues of tolylfluanid in

or on hops harvested 14 days following

multiple applications ranged from 3.31

mg/kg to 27.0 mg/kg (dried cone) and

ranged from 3.8 mg/kg to 17.6 mg/kg

(green cone).

Studies have also been conducted to

evaluate the potential for concentration

of tolylfluanid residues during the

processing of apples, grapes, and

tomatoes. Tolylfluanid does not have

the potential to concentrate in the EPA

required processed commodities

consumed by humans for apples, grapes

and tomatoes. Residues of tolylfluanid

may have the potential to concentrate in

wet apple pomace, an animal feed item.

B. Toxicological Profile

1. Acute toxicity. Tolylfluanid

exhibits low acute oral, dermal, and

inhalation toxicity (LD50s >5,000 mg/kg

b.w.). An acute neurotoxicity study

showed no specific evidence of

neurotoxicity; non-specific signs of

toxicity were observed in this study (in

females only) at doses at and greater

than 150 mg/kg b.w. Tolylfluanid is a

severe dermal irritant, moderately

irritating to the eye, and a skin

sensitizer. Tolylfluanid showed no

systemic toxicity following subacute

dermal administration, but did cause

dermal irritation. Effects seen in the

acute as well as subacute inhalation
42982 Federal Register / Vol. 62, No. 154 / Monday, August 11, 1997 / Notices

study indicate tolylfluanid is a strong

respiratory irritant.

2. Genotoxicity. The genotoxic

potential of tolylfluanid was assessed in

several in vivo and in vitro studies. The

weight-of-the-evidence indicates that

tolylfluanid is not genotoxic.

3. Reproductive and developmental

toxicity. Tolylfluanid showed no

evidence of developmental toxicity

based on two rat developmental toxicity

studies. Tolylfluanid showed evidence

of developmental effects in rabbits but

only at a maternally toxic dose level.

Two complete 2-generation

reproductive toxicity studies in rats and

one supplementary 2-generation

reproductive toxicity rat study have

been conducted on tolylfluanid.

Reproductive toxicity (decreased body

weight development in pups and

decreased number of pups born, birth

weight, litter size, and lactation index)

was noted only in the presence of

parental toxicity (decreased body weight

gain, organ weight changes, and

hyperostosis of the crania).

4. Subchronic toxicity. Subchronic

toxicity studies have been done with

tolylfluanid in rats and dogs. Decreased

body weight gain, decreased liver

enzymes, slightly increased relative

liver weights, and thyroid toxicity were

noted in a subchronic rat dietary study

(no correlating histopathological

findings). Decreased body weight gain,

increased liver enzyme activity, slightly

increased relative liver weights, and

increased PAS staining in the liver

occurred in a subchronic dietary dog

study. A subchronic neurotoxicity study

in rats showed no evidence of

neurotoxicity.

5. Chronic toxicity. Chronic toxicity

studies on tolylfluanid were done in the

rat, mouse and dog. Tolylfluanid was

tested in two rat chronic dietary studies.

Increased growth of the incisors of the

upper jaw and skeletal changes

(hyperostosis in the skull and ribs)

resulted from the high fluorine content

of the compound. Hepatotoxicity and

renal toxicity were seen in rats, mice,

and dogs. Hepatotoxicity was evidenced

by hepatocellular cytoplasmic changes,

vacuolation, and focal fatty changes in

rats, hepatocellular hypertrophy and

single cell necrosis in mice, decreased

liver enzymes in rats, and increased

liver enzymes in mice and dogs. Renal

toxicity (microscopic kidney lesions,

increased relative kidney weights,

effects on urinalysis parameters) was

probably attributable to the effects of

fluoride on renal tubules. A second

chronic toxicity study in dogs is

currently ongoing (results not yet

available).

6. Oncogenicity. Tolylfluanid showed

no evidence of direct oncogenic activity

in rats or mice. In rats tolylfluanid

altered thyroid hormone levels and an

increased incidence of hyperplastic and

neoplastic lesions of the thyroid

(primarily adenomas) in rats was

observed. The thyroid neoplasia is

considered to be a secondary

(thresholdable) effect to altered

thyroidal iodine metabolism and does

not suggest a direct oncogenic effect. No

treatment-related neoplasms were seen

in the mouse oncogenicity study.

Based on the chronic toxicity data,

Bayer believes the RfD for tolylfluanid

is 0.08 mg/kg, based on the no observed

adverse effect level (NOAEL) of 8 mg/kg

b.w./day for parental and reproductive

toxicity identified in the second 2-

generation rat reproductive toxicity

study (Pinckel and Ricke, 1995) and an

uncertainty factor of 100. No unique

concern for toxicity to infants and

children was identified, therefore an

additional safety factor is not warranted.

(Note there is a seven-fold difference

between the NOAEL and lowest effect

level (LEL).

Using the Guidelines for Carcinogenic

Risk Assessment published in

September 1986, we believe the Agency

will classify tolylfluanid as a Group C

carcinogen (possible human carcinogen)

based on benign thyroid tumors seen in

the chronic rat studies). Mechanistic

studies with tolylfluanid have shown

that these tumors are induced through a

nonlinear threshold mechanism similar

to that discussed in EPA’s thyroid

policy document. Therefore,

tolylfluanid should be regulated using

the margin of exposure approach.

7. Animal metabolism. Metabolism

studies were conducted using hens and

goats. No residues of parent tolylfluanid

were detected in any tissues, organs,

milk, or eggs. Tolylfluanid is

metabolized and excreted rapidly and

efficiently in mammals.

C. Aggregate Exposure

1. Dietary exposure. Food and

drinking water/non-dietary exposure.

2. Food. A chronic dietary exposure

analysis was conducted for tolylfluanid.

The reference dose (RfD) was 0.08 mg/

kg/day based on a NOEL of 8 mg/kg/day

and an uncertainty factor of 100. The no

observed effect level (NOEL) was

obtained from the rat reproduction

study and the effect was decreased pup

viability and decreased body weights.

The RfD could change based on the

NOEL from a repeat chronic dog toxicity

study which is currently ongoing (doses

tested: 5, 20, and 80 mg/kg/day). The

final report for this study is expected to

be completed in the second part of 1997.

If necessary, revising the RfD will be

addressed at that time.

Tolylfluanid does not have the

potential to concentrate in processed

commodities consumed by humans. The

proposed MRLs for the respective crops

were used for the raw agricultural and

processed commodities for grapes (5

mg/kg), tomatoes, (1 mg/kg), and hops

(30 mg/kg). The anticipated residue

level for fresh apples and apple juice

was calculated by adjusting the

proposed MRL for apples (5 mg/kg) for

the percentage of fresh apples (4.8%)

and apple juice (59.7%) consumed in

the U.S. that are imported. No

adjustments were made for the

anticipated residue levels for grapes,

tomatoes and hops.

The results of the chronic dietary

exposure analysis for the overall U.S.

population and the three most highly

exposed population subgroups are

summarized as follows.. The exposure

estimate was compared against the RfD

of 0.08 mg/kg. The theoretical maximum

residue contribution (TMRC) as

percentage of the RfD, was 9.53% for the

U.S. population, 53.36% for nonnursing infants, 38.02% for nursing

infants (0-1 yr old), and 26.16% for

children (1-6 yrs old). The anticipated

residue contribution (ARC) as

percentage of the RfD was 5.97% for the

U.S. population, 23.29% for nonnursing infants, 15.41% for nursing

infants and 15.10% for children. As

seen above, chronic dietary exposure to

tolylfluanid is less than 24% of the RfD

for even the most highly exposed

subgroup. In addition, these exposure

estimates greatly over estimate the

anticipated risk for the following

reasons: (1) a relatively small percentage

of these crops will be treated with

tolylfluanid; (2) a small percentage of

the treated crops are imported to the

U.S.; (3) a small percentage of the total

U.S. consumption of these crops are

imported products; and (4) the actual

residues in the imported commodities

will likely be below the proposed MRLs.

3. Drinking water. Tolylfluanid

residue levels in tap water, non-tap

water, and water in commercially

prepared food were assumed to be zero

because tolylfluanid is not registered for

use in the United States and therefore,

the only exposure is from the

importation of tolylfluanid-treated

commodities.

4. Non-dietary exposure. Tolylfluanid

is not registered in the United States,

therefore there is no non-occupational,

structural or residential exposure.

D. Cumulative Effects

Tolylfluanid is a fungicide that is

somewhat structurally similar to
Federal Register / Vol. 62, No. 154 / Monday, August 11, 1997 / Notices 42983

Captan, and appears to share a common

mechanism of fungicidal action with

this product. However, tolylfluanid does

not show a similar mammalian toxicity

profile to Captan, which has been

reported to produce mouse

gastrointestinal tumors and male rat

kidney tumors. No significant

cumulative toxicity to mammals based

on a common mechanism of action to

that of Captan is anticipated for

tolylfluanid.

Tolylfluanid alters the thyroid

hormone balance, but: (1) no data exist

showing specifically how tolylfluanid

causes thyroid changes; (2) tolylfluanid

is not known to be structurally similar

to other thyroid tumorigens; (3) no

common mechanism has been

established or proposed and (4) even if

it is eventually determined that the

mechanism for thyroid tumorigenesis

may be similar to other classes of

pesticides, this endpoint is seen with

tolylfluanid only at very high exposure

levels. If an RfD for tolylfluanid were

based on dose levels at which thyroid

hormone levels were altered, a very low

impact on a cumulative risk cup would

be anticipated because the potency of

tolylfluanid is very low.

Endocrine effects. Endocrine-related

effects of tolylfluanid exposure appear

to be limited to the thyroid. No evidence

of estrogenic or anti-estrogenic activity

was present in the available animal

studies. The developmental toxicity and

reproductive toxicity studies showed no

effects suggesting endocrine disruption,

(e.g., change in fetal sex ratios, change

in estrous cycles or mating performance,

change in fertility, or malformed or

altered reproductive organ

development).

E. Safety Determination

1. U.S. population. A chronic dietary

exposure analysis was conducted for

tolylfluanid. The chronic dietary

exposure to tolylfluanid is 5.97% of the

RfD for the U.S. population, using the

ARC.

2. Infants and children. A chronic

dietary exposure analysis was

conducted for tolylfluanid. The chronic

dietary exposure to tolylfluanid is

23.29% of the RfD for non-nursing

infants, the most highly exposed group,

using the ARC.

F. International Tolerances

The current Codex tolerances for

tolylfluanid are based on residues of

parent only. The Codex tolerances are:

5 mg/kg for currents (black, red, and

white), 2 mg/kg for Gherkins, 1 mg/kg

for head lettuce, 5 mg/kg for pome

fruits, 3 mg/kg for strawberries, and 2

mg/kg for tomatoes. (Mary Waller)

2. DowElanco

PP 5E4571

EPA has received a pesticide petition

(PP 5E4571) from DowElanco, 9330

Zionsville Road, Indianapolis, IN 46268-

1054, 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 the herbicide,

tebuthiuron and its related metabolites

in or on the food commodities refined

sugar and molasses at 0.05 parts per

million (ppm) from treatment of

sugarcane outside of the United States

with tebuthiuron. The proposed

analytical method involves

homogenization, filtration, partition and

cleanup with analysis by gas liquid

chromatography using flame

photometric 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 tebuthiuron has been investigated in

grasses. The residues of concern are the

parent compound and its metabolites

103 (OH) N-[5-(2-hydroxy-1,1-

dimethylethyl)-1,3,4-thiazol-2-yl]-

N,N’dimethylurea, 104 N-[5-(1,1-

dimethylethyl)-1,3,4-thiazol-2-yl]-Nmethylurea, and 109 N-[5-(1,1-

dimethylethyl)-1,3,4-thiazol-2-yl]-N’-

hydroxymethyl-N-methylurea.

Tebuthiuron and its metabolites 104 and

109 have been identified in sugarcane.

2. Analytical method. The method for

enforcement of plant commodities

tolerances is a GLC method with flame

photometric detection. The stated

detection limit for the parent compound

and metabolites 103 (OH), 104 and 109

is 0.01 ppm.

Enforcement methods for milk and

meat have been developed by

DowElanco and have been submitted to

the Agency as part of reregistration. An

adequate method (GC/flame

photometric detection) exists to

determine tebuthiuron and some

metabolites (104, 106, and 109) in milk

and ruminant tissue. The new

enforcement method is needed to

determine additional metabolites of

toxicological concern.

3. Magnitude of residues. Commercial

sugarcane samples were collected from

two major Brazilian sugarcane growing

regions. Tebuthiuron had been applied

at rates ranging from 750 to 1,500 g ai/

ha. Most of the samples were collected

approximately 12 months after

treatment. Analysis for tebuthiuron and

metabolites 104 and 109 occurred

within 60 days of sample collection. No

residues of tebuthiuron were found

above the LOQ (0.01 ppm). In many

samples there was no detection of

metabolites. In samples at one site

treated with 1,250 g ai/ha, however,

there were residues of the combined

metabolites at the LOQ.

B. Toxicological Profile

1. Acute toxicity. Tebuthiuron is

classified as a Moderate (Category II)

acute toxicant based upon the acute oral

LD50 value in the rat (387-477 mg/kg)

and rabbit (286 mg/kg. The LD50 for the

dermal toxicity in the rabbit was greater

than the limit dose of 5,000 mg/kg. The

acute inhalation LC50 in the rabbit was

greater than 3.696 mg/L. Tebuthiuron

produced slight irritation (slight

conjunctival hyperemia at 1 hour posttreatment; Category IV) and was not a

dermal irritant (Category IV) or dermal

sensitizer. The following table

summarizes the acute toxicity profile of

tebuthiuron.

Test Species Category

Oral Mouse III

Rat, Rabbit II

Dermal Rabbit IV

Inhalation Rat III

Eye Irritation Rabbit IV

Dermal Irritation Rabbit IV

Dermal Sensitization Guinea Pig none
42984 Federal Register / Vol. 62, No. 154 / Monday, August 11, 1997 / Notices

2. Genotoxicity. Results from a battery

of assays in vitro indicate that

tebuthiuron is not genotoxic. It was

inactive in the Ames S. typhimurium

reverse gene mutation assay with or

without metabolic activation. In the

mouse lymphoma assay, tebuthiuron

was negative without metabolic

activation and slightly positive

(mutation index of 2) with metabolic

activation at doses 700 mg/mL. In this

assay, cytotoxicity was observed at

doses 200 mg/mL. In Chinese Hamster

Ovary cells, there were chromosomal

aberrations and cytotoxicity at the

highest doses tested with (1,550 mg/mL)

and without (1,950 mg/mL) metabolic

activation. There was no Unscheduled

DNA Synthesis in primary rat

hepatocytes at 800 mg/mL, while

cytotoxicity was observed at 900 mg/

mL.

3. Reproductive and developmental

toxicity. In a 3-generation reproduction

study in which rats were fed 28 or 56

mg tebuthiuron/kg/day, F1b weanling

pups had reduced mean body weight

gains. No reproductive no observed

effect level (NOEL) could be determined

from this study.

In a 2-generation reproduction study,

rats were fed tebuthiuron at dietary

levels of 100, 200 or 400 ppm (7, 14, 28

mg/kg/day). There was a reduced rate of

body weight gain in the F1 females

during the premating period at the 14

and 28 mg/kg/day dose levels. The

systemic NOEL of this study was 7 mg/

kg/day and the reproductive NOEL was

the highest dose tested (28 mg/kg/day).

The RfD for tebuthiuron was determined

to be 0.07 mg/kg/day based upon the

systemic NOEL of this 2-generation

reproduction study with a Safety Factor

of 100.

In a developmental toxicity study in

which rats were fed 0, 15, 30, or 45 mg

tebuthiuron/kg/day, the maternal NOEL

was 30 mg/kg/day based upon reduced

body weight gain and food

consumption. There were no adverse

developmental effects observed in this

study. The developmental NOEL was

the highest dose tested (45 mg/kg/day).

Rabbits were administered 0, 10, or 25

mg tebuthiuron/kg/day by oral gavage

on gestation days 6-18. The maternal

toxicity NOEL was the highest dose

tested (25 mg/kg/day). Although there

was an apparent decrease in fetal

weights at the highest dose, this was

probably the result of an increased

number of fetuses per litter in the

highest dose group (5.7 fetuses/litter

versus 4.4 fetuses/litter in controls).

Therefore, no treatment-related adverse

affects were attributed to tebuthiuron.

These studies indicate that

tebuthiuron is not a developmental or

reproductive toxicant.

4. Subchronic toxicity. Rats were

exposed to tebuthiuron in the diet at the

exposure levels of 0, 20, 50, or 125 mg/

kg/day for 90 days. The NOEL was

determined to be 50 mg/kg/day based

upon reduced body weight, increased

relative liver, kidney, and gonad

weights, and slight vacuolization of

pancreatic acinar cells at 125 mg/kg/

day. In addition, males also had

increased relative spleen and prostate

gland weights at the highest dose.

Dogs were exposed to tebuthiuron in

the diet for 90 days at 0, 500, 1,000, or

2,500 ppm. The NOEL was determined

to be 500 ppm (12.5 mg/kg/day) based

upon anorexia, weight loss, increases in

blood urea nitrogen and alkaline

phosphatase activity, and increases in

spleen and thyroid gland weights at the

LOEL value of 1,000 ppm (25 mg/kg/

day).

Rabbits were exposed dermally to

1,000 mg tebuthiuron/kg/day for 6 hours

a day for 21 days. Slight erythema

occurred in these rabbits and resolved

by day 7. The NOEL was less than 1,000

mg/kg/day.

5. Chronic toxicity. Dogs were fed

tebuthiuron in capsules at doses of 0,

12.5, 25, or 50 mg/kg/day for 1-year. The

NOEL was determined to be 25 mg/kg/

day based upon the clinical signs of

anorexia, diarrhea, and emesis as well

as increased thrombocyte count, alanine

transferase, and alkaline phosphatase

activity, and increased liver, kidney,

and thyroid weights at the LOEL value

of 50 mg/kg/day.

Tebuthiuron was fed to 40 Harlan

(Wistar) rats/sex/group at

concentrations 400, 800, or 1,600 ppm

(20, 40, or 80 mg/kg/day) for 2 years.

There were 60 control rats/sex. The

systemic NOEL value was 40 mg/kg/day

and the lowest observed effect level

(LOEL) value was 80 mg/kg/day based

upon a reduction in weight gain and

elevated kidney weights. There were no

treatment-related carcinogenic effects.

In another study, tebuthiuron was fed

to 40 Harlan (ICR) mice/sex/group at

400, 800, or 1,600 ppm (57, 144, or 228

mg/kg/day) for 2 years. There were 60

control mice/sex. The systemic NOEL

value was the highest dose tested (228

mg/kg/day). Although there were no

compound-related carcinogenic effects,

the dose levels were judged to be

inadequate for carcinogenic testing. This

study was considered to be

supplemental to the rat study by the

Health Effects Division (HED) and the

Reference Dose (RfD) Committee, and

that no additional study would be

required. The HED RfD Committee has

classified tebuthiuron as a Group D

carcinogen (not classifiable as to human

carcinogenicity).

6. Animal metabolism. The

metabolism of tebuthiuron has been

investigated in ruminants. The residues

of concern in milk and meat are the

parent compound and its metabolites

104, 106 N-[5-(1,1-dimethylethyl)-1,3,4-

thiazol-2-yl]-urea, 108 [2-

dimethylethyl)-5-amino-1,3,4-

thiadiazole], and 109.

The metabolism of radiolabelled

tebuthiuron was conducted in four

laboratory species (rats, rabbits, dogs,

and mice) using a single administration

by gavage of 10 or 160 mg/kg. In all four

species, tebuthiuron was readily

absorbed, metabolized, and excreted. In

rats, rabbits and dogs, elimination in the

urine accounted for 84% to 95% of the

administered dose (the parent

compound accounting for 0.4% to 0.7%

of the dose). Biliary excretion was

demonstrated in the rat. Mice excreted

less radioactivity in the urine (66%;

with 23% as unchanged parent

compound) and more in the feces (31%)

as compared with the other species

examined. At least seven major

metabolites were excreted in the urine,

and there was no unusual tissue

distribution of metabolites.

C. Aggregate Exposure

Tebuthiuron currently is registered for

treatment of forage grasses and hay,

therefore, potential dietary exposure to

humans is from secondary residues in

milk and meat from livestock which

have consumed treated grasses. A

chronic dietary exposure analysis was

conducted for tebuthiuron using the

existing tolerances of 0.3 ppm in milk

and 2.0 ppm in meat and the proposed

tolerance of 0.05 ppm in cane sugar and

molasses. The exposure assessment

included the worst-case assumptions

that all ruminants and horses were fed

treated grasses, and sugar and molasses

available to consumers came from

treated sugarcane. As tebuthiuron was

detected in ground water at 23 ppb in

a small scale monitoring study under a

high exposure scenario, this value was

used in all water in the consumption

survey. In this estimation, exposure to

the U.S. population from water sources

represented 1.1% of the RfD (about 24%

of total exposure to tebuthiuron). The

following table summarizes the results

from the chronic aggregate exposure

analysis.
Federal Register / Vol. 62, No. 154 / Monday, August 11, 1997 / Notices 42985

Dietary Exposure (mg/kg BW/day) % of Rfd

All Infants 0.004971 7.1%

Nurs. Infants < 1 yr 0.001859 2.7%

Non-nurs. Inf. < 1 yr 0.006429 9.2%

Children 1-6 yrs 0.005732 8.2%

Children 7-12 yrs 0.004376 6.3%

Females 13-50 yrs 0.002394 3.4%

As the RfD was based upon decreased

body weight gains in the reproduction

toxicity study, the subpopulations

shown above represent the groups with

the highest potential impact from this

endpoint. This is a worst-case estimate

based upon tolerance values and the

assumption that all water sources will

have the residue concentration that was

found in the monitoring study. Even

with these worst-case estimations,

aggregate exposure levels were less than

10% of the RfD for any subpopulation.

D. Cumulative Effects

The potential for cumulative effects of

tebuthiuron and other substances that

have a common mechanism of toxicity

was considered. The mammalian

toxicity of tebuthiuron is well defined.

However, the biochemical mechanism

of toxicity of this compound is not well

known. No reliable information exists to

indicate that toxic effects produced by

tebuthiuron would be cumulative with

those of any other chemical compounds.

Therefore, consideration of a common

mechanism of toxicity with other

compounds is not appropriate. Thus

only the potential risks of tebuthiuron

are considered in the aggregate exposure

assessment.

E. Safety Determination

1. U.S. population. Based upon

maximum expected residues in meat,

milk, and refined sugar and molasses

from sugarcane, DowElanco concludes

that there is a reasonable certainty of no

harm resulting from aggregate exposure

of tebuthiuron to the general

population.

2. Infants and children. The

toxicological data indicate that

tebuthiuron is not a developmental or

reproductive toxicant, and that infants

and children are not sensitive

subpopulations. There is a reasonable

certainty that no harm will result from

aggregate exposure of tebuthiuron to

infants and children.

F. International Tolerances

No Codex MRLs have been

established or proposed for residues of

tebuthiuron.

G. Endocrine Effects

An evaluation of the potential effects

on the endocrine systems of mammals

has not been determined; However, no

evidence of such effects were reported

in the chronic or reproductive

toxicology studies described above.

There was no observed pathology of the

endocrine organs in these studies. There

is no evidence at this time that

tebuthiuron causes endocrine effects.

(James Tompkins)

3. Merck Research Laboratories

PP 7F4844

EPA has received a pesticide petition

(PP 7F4844) from Merck Research

Laboratories, P.O. Box 450,

Hillsborough Road, Three Bridges, NJ.

The petition proposes, pursuant to

section 408 of the Federal Food, Drug,

and Cosmetic Act (FFDCA), 21 U.S.C.

346a(d). that EPA amend 40 CFR part

180 to establish tolerances for pesticide

chemical residues consisting of the

insecticide abamectin (avermectin B1)

and/or its delat 8,9- isomers in or on the

following food items: grapes, raisins,

and other grape-derived food items at

0.02 parts per million (ppm) and chili

peppers at 0.01 ppm. Abamectin has

been approved by EPA for use on many

other food crops, including various tree

fruits, nuts, and vegetables (including

bell peppers), as well as hops and

cotton. Tolerances corresponding to

these uses are in effect for abamectin

residues (including a tolerance for bell

peppers at 0.01 ppm); the most recent

rule, reissuing tolerances for abamectin

on citrus and cotton under the FFDCA

as amended by the Food Quality

Protection Act (FQPA), was published

in the Federal Register on March 24,

1997 (62 FR 13833). A notice of filing

with regard to that rulemaking had

earlier been published on December 10,

1996 (61 FR 65043). 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 abamectin in plants is adequately

understood and the residues of concern

include the parent insecticide,

abamectin or avermectin B1 (which is a

mixture of a minimum of 80%

avermectin B1a and a maximum of 20%

avermectin B1b) and the delta 8,9-

isomer of the B1a and of the B1b

components of the parent insecticide.

Animal metabolism also has been

studied but is not relevant to this

petition, since the crops involved are

not significant animal feed items.

2. Analytical method. Practicable

analytical methods (HPLC-fluorescence

methods) are available to detect residues

that would exceed the proposed

tolerances, and for enforcement. The

methods are sufficiently sensitive to

detect residues at or above the

tolerances proposed. All methods have

undergone independent laboratory

validation as required by PR Notice 88-

5.

3. Magnitude of residues. In residue

field trials on grapes, the highest residue

combined values in day 28 (or later)

samples was 6.7 ppb for abamectin B1a

plus its delta 8,9- photoisomer; there

were no detectable levels of abamectin

b1b residues in any of the day 28 (or

later) samples. In the two raisin samples

the levels for abamectin B1a ranged from

8.6 to 11.8 ppb. The residues did not

concentrate in grape juice. These data

support the proposed tolerance of 0.02

ppm for total toxic residues of

abamectin on the RACs grapes, grape

juice, and raisins and the proposed 28-

day PHI.

For chili peppers the primary B1a

component and its photoisomer, the

residues recovered on day 7 were all

either nonquantifiable (less than 5 ng/g,

but equal or greater to 2 ng/g) or

nondetectable (less than 2 ng/g). These

data support the proposed tolerance of

0.01 ppm for total toxic residues of
42986 Federal Register / Vol. 62, No. 154 / Monday, August 11, 1997 / Notices

abamectin on the RAC chili peppers and

the proposed 7-day PHI.

B. Toxicological Profile

All the toxicity data on which this

petition is based have previously been

submitted to EPA in support of other

petitions, and were summarized in the

recent notice of filing (61 FR 65043). In

the recent final rule (62 FR 13833) EPA

concluded that acute dietary exposure

risk evaluations should be based on a no

observed effect level (NOEL) of 0.06 mg/

kg bw/day (mouse pup NOEL in a

developmental toxicity study using the

delta 8,9-isomer of abamectin) and that

a margin of exposure of 300 should be

required. EPA determined that chronic

dietary exposure risk evaluations should

be based on a reference dose (RfD) of

0.0004 mg/kg bw/day, derived from a 2-

generation rat reproduction study with

a NOEL of 0.12 mg/kg/day and an

uncertainty factor of 300.

This petition contains a supplemental

a document setting forth new acute

exposure and chronic exposure and risk

analyses that corrects previously

submitted analyses to reflect newly

available residue data on chili peppers

(the previously submitted report used

data on bell peppers only) and to reflect

current Agency preferences regarding

the handling of blended foods. The

results of the old and new analyses are

substantially similar.

C. Aggregate Exposure

1. Dietary exposure. The March 1997

rule was based on an exposure analysis

submitted by Merck that included

exposure attributable to grapes and

peppers. The exposure contribution for

chili peppers was calculated using data

on bell peppers. With the present

petition, Merck is submitting new

residue data on chili peppers and a

revised acute and chronic risk

assessment that incorporates that data;

the exposure levels have not changed

significantly. The chronic exposure for

the U.S. population at large is estimated

to be 0.000006 mg/kg bw/day, and for

children aged 1-6, the highest exposure

group, chronic exposure is estimated to

be 0.000014 mg/kg bw/day. The

estimated acute exposure (at the 99.9th

percentile level) is for the U.S.

population at large, 0.000025 mg/kg bw/

day.

2. Drinking water. In the final rule

EPA also concluded that drinking water

exposure assumptions were not of

concern.

3. Non-dietary exposure. In the final

rule published on March 24, 1997, EPA

concluded that there is no likelihood of

significant exposure from the registered

residential indoor and outdoor nonfat

use of abamectin. Approval of

tolerances for grapes and chili peppers

would not change that conclusion.

D. Cumulative Effects

Abamectin is a member of the

avermectin family of natural and semisynthetic compounds. Ivermectin,

another member of that family, is very

closely similar to abamectin in

structural standpoint; it is used as a

human and animal drug. Emamectin, a

proposed new pesticide, is made from

abamectin but is less similar to

abamectin than is avermectin. These

compounds are all Merck products.

Other companies product certain other

drugs have certain structural

similarities. Merck in not aware of any

information indicating what, if any,

cumulative effect would result from

exposure to two or more of these

compounds. The March 1997 rule

discussed cumulative effects and stated

that in view of the lack of information

on how to evaluate possible common

mechanisms, it would not assume that

abamectin has a common mechanism of

toxicity with any other substance.

E. Safety Determination

In the recently issued final rule (62 FR

13833, March 24, 1997) EPA discussed

analyses of risks from chronic and acute

exposure for all existing or pending

tolerances. Those analyses included

exposure to grapes and peppers, among

other previously-approved and thenpending uses. In the final rule, EPA

found the risks to be acceptable, with

regard to both the general U.S.

population and with regard to infants

and children. As noted earlier, Merck

now has submitted specific residue data

on chili peppers, but the exposure

analyses are not significantly affected

thereby.

F. International Tolerances

Codex has not issued abamectin

tolerances for grapes and chili peppers.

(George LaRocca)

[FR Doc. 97–21147 Filed 8–8–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[FRL–5873–4]

Four Documents Required Under the

Safe Drinking Water Act as Amended

AGENCY: Environmental Protection

Agency.

ACTION: Notice of Availability.

SUMMARY: In this notice, the

Environmental Protection Agency (EPA

or the Agency) is publishing two

documents, and announcing the public

availability of three other documents.

All the documents relate to provisions

in the Safe Drinking Water Act, as

amended in 1996 (SDWA), and were

issued by the Agency on August 6, 1997.

The documents that can be obtained

from the Agency are: (1) EPA 816–R–

97–009, ‘‘State Source Water and

Assessment Guidance’’ which is

guidance for states to follow in

developing state source water

assessment and petition programs

(SDWA sections 1453 and 1454); (2)

EPA 816–R–97–010, ‘‘Guidance for

Future State Ground Water Protection

Grants’ which establishes procedures for

application for state ground water

protection program assistance and

identifies key elements of state ground

water protection programs (SDWA

section 1429(b)); and (3) EPA–815–R–

97–002, ‘‘Small System Compliance

Technology List for the Surface Water

Treatment Rule’’ which contains

detailed information on the list of

technologies published in this notice.

Published in this notice are the list of

small system compliance technology

that meets the Surface Water Treatment

Rule (SWTR) for three population sizes

of small drinking water systems as

required by SDWA section

1412(b)(4)(E)(v) and alternative

monitoring guidelines for states to

follow in proposing alternative

monitoring requirements for chemical

contaminants as required by SDWA

1418(b)(2). The alternative monitoring

guidelines are also available as a

separate document, EPA 816–R–97–001.

DATES: The documents are available

beginning August 6, 1997.

ADDRESSES: Copies of these documents

are available from the Safe Drinking

Water Act Hotline, telephone (800) 426–

4791 or e-mail hotlinesdwa@epamail.epa.gov. Copies are also

available from the Office of Water

Resource Center (RC4100), U.S. EPA,

401 M Street, SW, Washington, DC

20460, (202) 260–7786. The Center is

open from 8:30 a.m. until 5:00 p.m.

Monday through Friday. The documents

are available, as of August 6, 1997, on

EPA’s Web Site at the following address:

‘‘http://www.epa.gov/OGWDW’’.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. State Source Water Assessment and

Protection Programs Guidance

II. Guidance for Future State Ground Water

Protection Grants

III. Small System Compliance Technology

List for the Surface Water Treatment

Rule

IV. Alternative Monitoring Guidelines