Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices 29401

(trifluoromethyl)-1,3,4-thiadiazol-2-

yl]oxy]acetamide.

A paper copy of this fact sheet, which

provides a summary description of the

chemical, use patterns and

formulations, science findings, and the

Agency’s regulatory position and

rationale, may be obtained from the

National Technical Information Service

(NTIS), 5285 Port Royal Road,

Springfield, VA 22161.

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

FIFRA, a copy of the approved label, the

list of data references, the data and other

scientific information used to support

registration, except for material

specifically protected by section 10 of

FIFRA, are available for public

inspection in the Public Information

and Records Intregrity Branch,

Information Resources and Services

Division (7502C), Office of Pesticide

Programs, Environmental Protection

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

22202 (703–305–5805). Requests for

data must be made in accordance with

the provisions of the Freedom of

Information Act and must be addressed

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

20460. Such requests should: (1)

Identify the product name and

registration number and (2) specify the

data or information desired.

Authority: 7 U.S.C. 136.

List of Subjects

Environmental protection, Pesticides

and pests, Product registration.

Dated: May 13, 1998.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

[FR Doc. 98–14161 Filed 5–28–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–806; FRL–5791–2]

Monsanto Company; Pesticide

Tolerance Petitions Filing

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of a pesticide petition

proposing the establishment of

regulations for residues of a certain

pesticide chemical in or on various food

commodities.

DATES: Comments, identified by the

docket control number PF–806, must be

received on or before June 29, 1998.

ADDRESSES: By mail submit written

comments to: Information and Records

Integrity Branch, Public Information and

Services Divison (7502C), Office of

Pesticides Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person bring

comments to: Rm. 119, CM #2, 1921

Jefferson Davis Highway, Arlington, VA.

Comments and data may also be

submitted electronically by following

the instructions under

‘‘SUPPLEMENTARY INFORMATION.’’

No confidential business information

should be submitted through e-mail.

Information submitted as a comment

concerning this document may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI). CBI should not be submitted

through e-mail. Information marked as

CBI will not be disclosed except in

accordance with procedures set forth in

40 CFR part 2. A copy of the comment

that does not contain CBI must be

submitted for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments will be available for public

inspection in Rm. 1132 at the address

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

Monday through Friday, excluding legal

holidays.

FOR FURTHER INFORMATION CONTACT:

James A. Tompkins, Registration

Support Branch, Registration Division

(7505C), Office of Pesticide Programs,

Environmental Protection Agency, 401

M St., SW, Washington, DC 20460.

Office location, telephone number, and

e-mail address: Rm. 239, Crystal Mall

#2, 1921 Jefferson Davis Highway,

Arlington, VA 22202, (703) 305–5697; email: tompkins.james@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA has

received a pesticide petition as follows

proposing the establishment and/or

amendment of regulations for residues

of certain pesticide chemical 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 this petition

contains 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–806]

(including comments and data

submitted electronically as described

below). A public version of this record,

including printed, paper versions of

electronic comments, which does not

include any information claimed as CBI,

is available for inspection from 8:30

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

excluding legal holidays. The official

record is located at the address in

‘‘ADDRESSES’’ at the beginning of this

document.

Electronic comments can be sent

directly to EPA at:

opp-docket@epamail.epa.gov

Electronic comments must be

submitted as an ASCII file avoiding the

use of special characters and any form

of encryption. Comment and data will

also be accepted on disks in

Wordperfect 5.1 file format or ASCII file

format. All comments and data in

electronic form must be identified by

the docket number (insert docket

number) and appropriate petition

number. Electronic comments on this

proposed rule may be filed online at

many Federal Depository Libraries.

List of Subjects

Environmental protection,

Agricultural commodities, Food

additives, Feed additives, Pesticides and

pests, Reporting and recordkeeping

requirements.

Dated: May 14, 1998.

James Jones,

Director, Registration Division, Office of

Pesticide Programs.

Summaries of Petitions

Petitioner summaries of the pesticide

petitions are printed below as required

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

summaries of the petitions were

prepared by the petitioners and

represent the views of the petitioners.

EPA is publishing the petition

summaries verbatim without editing

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. Monsanto Company

PP 8F4937

EPA has received a pesticide petition

(PP 8F4937) from Monsanto Company,

700 14th St., NW., Suite 1100,

Washington, DC 20005. 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
29402 Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices

halosulfuron-methyl: methyl 5-[(4,6-

dimethoxy-2-pyrimidinyl)amino]

carbonyl aminosulfonyl-3-chloro-1-

methyl-1H-pyrazole-4-carboxylate in or

on the raw agricultural commodity

undelinted cotton seed & cotton gin byproducts at 0.05 parts per million

(ppm), rice grain at 0.05 ppm, rice straw

at 0.20 ppm, tree nut group (Group 14)

nutmeat at 0.05 ppm and hulls at 0.20

ppm, pistachio, nutmeat at 0.05 ppm,

pistachio, hulls at 0.2 ppm.

In addition, Monsanto proposes the

establishment of tolerances for

halosulfuron methyl (as parent only) in

or on the following raw agricultural

commodities:

Corn, field: grain at 0.05 ppm, forage

at 0.2 ppm, and fodder at 0.8 ppm.

Grain, sorghum (milo): grain at 0.05

ppm, forage at 0.05 ppm, and fodder/

stover at 0.10 ppm.

Monsanto also proposes removing 40

CFR 180.479 (b) which reads as follows:

Indirect or inadvertent tolerances.

Tolerances are established for indirect

or inadvertent residues of the herbicide

halosulfuron-methyl and its metabolites

determined as 3-chloro-1-methyl-5-

sulfamoylpyrazole-4-carboxylic acid

and expressed as parent equivalents, in

or on the following raw agricultural

commodities when present therein as a

result of the application of halosulfuronmethyl to growing crops.

Soybean, forage at 0.5 ppm, soybean,

hay at 0.5 ppm, soybean, seed at 0.5

ppm, wheat, forage at 0.1 ppm, wheat,

grain at 0.1 ppm. and wheat, straw at 0.2

ppm.

EPA has determined that the petition

contains data or information regarding

the elements set forth in section

408(d)(2) of the FFDCA; however, EPA

has not fully evaluated the sufficiency

of the submitted data at this time or

whether the data supports granting of

the petition. Additional data may be

needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism

of halosulfuron-methyl as well as the

nature of the residues in plants is

adequately understood for purposes of

these tolerances. Metabolism studies

were conducted in three crops, viz.;

field corn, sugarcane and soybeans.

Metabolism depends on the mode of

application. Preemergent applications

result in rapid soil degradation of

halosulfuron-methyl followed by crop

uptake of the resulting pyrazole moiety.

The pyrimidine ring binds tightly to soil

and is eventually converted to carbon

dioxide by microbial degradation. In

postemergent applications, little

metabolism and translocation take place

resulting in unmetabolized parent

compound as the major residue on the

directly treated foliar surfaces. Very low

residue levels of the metabolite 3-

chloro-1-methyl-5-sulfamoylpyrazole-4-

carboxylic acid (3-CSA) are found in the

grain.

2. Analytical method. A practical

analytical method, gas chromatography

with an electron- capture detector

which detects and measures total

residues (halosulfuron-methyl and

metabolites) is available for enforcement

purposes with a limit of detection that

allows monitoring of food with residues

at or above the levels set in these

tolerances. This enforcement method

has been submitted to the Food and

Drug Administration for publication in

the Pesticide Analytical Manual, Vol. II

(PAM II). It has undergone independent

laboratory validation and validation at

the Beltsville laboratory. The Analytical

Chemistry section of the EPA concluded

that the method is adequate for

enforcement. Analytical method is also

available for analyzing meat by-products

which also underwent successful

independent laboratory and Beltsville

laboratory validations.

3. Magnitude of residues. In the tree

nut residue study, there were no

quantifiable residues found in nut meats

using an analytical method with limit of

quantitation (LOQ) of 0.05 ppm.

Residues ranging from <0.05 to 0.154

ppm were found in almond hulls when

treated at 1.4 times the recommended

rate. There were no detectable residues

found in cotton undelinted seed as well

as from the resulting processed

commodities even at treatment rates of

more than 5 times the maximum

recommended rate per season. No

quantifiable residues were found in

cotton gin byproducts. The residues in

the rice grain and rice processed

fractions were below the limit of

detection of 0.02 ppm at all locations. 5

of the 18 sites showed residues in rice

straw ranging from 0.06 to 0.17 ppm

while 13 sites had non-quantifiable

residues (<0.05 ppm). Results of the

aquatic sediment dissipation study

showed that the parent and major

metabolite residues dissipated rapidly

in both soil and water phases with DT50

values of 1.3 and 1.87 days and DT90 of

6.48 and 12 days from 2 sites,

respectively. The half-life of

halosulfuron-methyl in the paddy water

phase is calculated to be 0.87 days

following direct application to water.

The vertical mobility is not a major

route of dissipation. The residues

(parent and metabolites that are

hydrolyzable to 3-CSA) dissipated

rapidly in the upper soil layer but

showed no indication of significant

downward movement into the lower

soil layers.

B. Toxicological Profile

1. Acute toxicity. Acute toxicological

studies placing the technical-grade

halosulfuron-methyl in Toxicity

Category III. A 90-day feeding study in

rats resulted in a lowest-observed-effectlevel (LOEL) of 497 milligrams/

kilograms/day (mg/kg/day) in males and

640 mg/kg/day in females, and a noobserved-effect-level (NOEL) of 116 mg/

kg/day in males and 147 mg/kg/day in

females.

2. Genotoxicty. Bacterial/mammalian

microsomal mutagenicity assays were

performed and found not to be

mutagenic. Two mutagenicity studies

were performed to test gene mutation

and found to produce no chromosomal

aberrations or gene mutations in

cultured Chinese hamster ovary cells.

An in vivo mouse micronucleus assay

did not cause a significant increase in

the frequency of micronucleated

polychromatic erythrocytes in bone

marrow cells. A mutagenicity study was

performed on rats and found not to

induce unscheduled DNA synthesis in

primary rat hepatocytes.

3. Reproductive and developmental

toxicity. A developmental toxicity study

in rats resulted in a developmental

LOEL of 750 mg/kg/day, based on

decreases in mean litter size and fetal

body weight, and increases in

resorptions, resorptions/dam, postimplantation loss and in fetal and litter

incidences of soft tissue and skeletal

variations, and a developmental NOEL

of 250 mg/kg/day. Maternal LOEL was

750 mg/kg/day based on increased

incidence of clinical observations,

reduced body weight gains, and reduced

food consumption and food efficiency.

The maternal NOEL was 250 mg/kg/day.

A developmental toxicity study in

rabbits resulted in a developmental

LOEL of 150 mg/kg/day, based on

decreased mean litter size and increases

in resorptions, resorptions/dam and

post-implantation loss, and a

developmental NOEL of 50 mg/kg/day.

The maternal LOEL was 150 mg/kg/day

based on reduced body weight gain and

reduced food consumption and food

efficiency. The maternal NOEL was 50

mg/kg/day.

A dietary 2-generation reproduction

study in rats resulted in parental

toxicity at 223.2 mg/kg/day in males

and 261.4 mg/kg/day in females in the

form of decreased body weights,

decreased body weight gains, and

reduced food consumption during the

premating period. Very slight effects

were noted in body weight of the

offspring at this dose. This effect was
Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices 29403

considered to be developmental toxicity

(developmental delay) rather than a

reproductive effect. No effects were

noted on reproductive or other

developmental toxicity parameters. The

systemic/ developmental toxicity LOEL

was 223.2 mg/kg/day in males and 261.4

mg/kg/day in females; the systemic/

developmental toxicity NOEL was 50.4

mg/kg/day in males and 58.7 mg/kg/day

in females. The reproductive LOEL was

greater than 223.2 mg/kg/day in males

and 261.4 mg/kg/day in females; the

reproductive NOEL was equal to or

greater than 223.2 mg/kg/day in males

and 261.4 mg/kg/day in females.

4. Subchronic toxicity. A 21-day

dermal toxicity study in rats resulted in

a NOEL of 100 mg/kg/day in males and

greater than 1,000 mg/kg/day in females.

The only treatment-related effect was a

decrease in body weight gain of the

1,000 mg/kg/day group in males.

5. Chronic toxicity. A 1-year chronic

oral study in dogs resulted in a LOEL of

40 mg/kg/day based on decreased

weight gain and a NOEL of 10 mg/kg/

day for systemic toxicity. A 78-week

carcinogenicity study was performed on

mice. Males in the 971.6 mg/kg/day

group had decreased body weight gains

and an increased incidence of

microconcretion/mineralization in the

testis and epididymis. No treatmentrelated effects were noted in females.

Based on these results, a LOEL of 971.9

mg/kg/day was established in males and

NOELs of 410 mg/kg/day in males and

1,214.6 mg/kg/day in females were

established. The study showed no

evidence of carcinogenicity. A

combined chronic toxicity/

carcinogenicity study in rats resulted in

a LOEL of 225.2 mg/kg/day in males and

138.6 mg/kg/day in females based on

decreased body weight gains, and a

NOEL of 108.3 mg/kg/day in males and

56.3 mg/kg/day in females. The study

showed no evidence of carcinogenicity.

6. Animal metabolism. EPA stated

that the nature of the residue in

ruminants was determined to be

adequately understood. In the tissues

and milk of goats, the major extractable

residue was the unmetabolized parent

compound. Based on the low residues of

the parent compound in corn grain and

the low transfer of residues in the

metabolism study, tolerances on poultry

products were not required. In the rat

metabolism study, parent compound

was absorbed rapidly but incompletely.

Excretion was relatively rapid at all

doses tested with majority of

radioactivity eliminated in the urine

and feces by 72 hours. Fecal elimination

of parent was apparently the result of

unabsorbed parent.

7. Metabolite toxicology. The

toxicology studies listed below were

conducted with the 3-CSA metabolite.

Based on the toxicological data of the 3-

CSA metabolite, EPA concluded that it

has lower toxicity compared to the

parent compound and that it should not

be included in the tolerance expression.

The residue of concern is the parent

compound only.

i. A 90-day rat feeding study resulted

in a LOEL in males of >20,000 ppm and

a NOEL of 20,000 ppm (1,400 mg/kg/

day). In females, the LEL is 10,000 ppm

(772.8 mg/kg/day) based on decreased

body weight gains and a NOEL of 1,000

ppm (75.8 mg/kg/day).

ii. A developmental toxicity resulted

in a LOEL for maternal toxicity of

>1,000 mg/kg/day based on the absence

of systemic toxicity, a NOEL of 1,000

mg/kg/day. The developmental LOEL is

>1,000 mg/kg/day and the NOEL is

1,000 mg/kg/day.

iii. The microbial reverse gene

mutation did not produce any

mutagenic effect while the mammalian

cell gene mutation/chinese hamster

ovary cells did not show a clear

evidence of mutagenic effect in the

Chinese hamster ovary cells.

iv. The mouse micronucleus assay did

not show any clastogenic or aneugenic

effect.

8. Endocrine disruption. No specific

tests have been conducted with

halosulfuron-methyl to determine

whether the chemical may have an

effect in humans that is similar to an

effect produced by a naturally occurring

estrogen or other endocrine effects.

However, there were no significant

findings in other relevant toxicity tests,

i.e., teratology and multi-generation

reproduction studies, which would

suggest that halosulfuron-methyl

produces effects characteristic of the

disruption of the estrogenic hormone.

C. Aggregate Exposure

1. Dietary exposure— i. Food. For

purposes of assessing the potential

dietary exposure from food under

existing tolerances, aggregate exposure

based on the Theoretical Maximum

Residue Contribution (TMRC) which is

an estimate of the level of residues

consumed daily if each food item

contained pesticide residues equal to

the tolerance. The calculated TMRC

value was 0.0005 mg/kg body weight/

day for the general US population

which will utilize only 0.51% of the

Reference Dose (RfD) for established

tolerances for halosulfuron-methyl and

its metabolites in/on raw agricultural

commodities of field corn, grain

sorghum (milo) and secondary

tolerances in meat and meat byproducts

(cattle, goats, hogs, horses, and sheep).

TMRC is obtained by multiplying the

tolerance levels for each commodity by

the average daily consumption of the

food forms of that commodity eaten by

the U.S. population and various

population subgroups. In conducting

this exposure assessment, conservative

assumptions were made, e.g., 100% of

all commodities will contain

halosulfuron-methyl residues and those

residues would be at the level of their

respective tolerances. This results in a

large overestimate of human exposure.

Monsanto conducted another dietary

exposure analysis to include food from

crops in subsequent petitions including

this petition. This analysis added

dietary exposure from the following raw

agricultural commodities using the

proposed tolerance levels of each

commodity, viz.; sweet corn (kernel +

cobs with husks removed at 0.05 ppm,

forage at 0.2 ppm, fodder/stover at 0.8

ppm), pop corn (grain at 0.05 ppm,

fodder/stover at 0.8 ppm), sugarcane

(cane at 0.05 ppm), tree nut crop

grouping (nut meat at 0.05 ppm, hulls

at 0.2 ppm), pistachio nuts (nutmeat at

0.05 ppm, hulls at 0.2 ppm), cotton

(undelinted seed at 0.05 ppm, gin

byproduct at 0.2 ppm) and rice (grain at

0.05 ppm and straw at 0.2 ppm). Food

consumption data from the USDA

Nationwide Food consumption survey

for 1989-1992 and the EXPOSURE-1

software by TAS, Inc. were used in the

calculation. Even with the same

conservative assumptions, the potential

dietary exposure to halosulfuron-methyl

from consumption of products for

which it is currently labeled and

proposed resulted in a TMRC of 0.00064

mg/kg body weight/day and represents

only 0.6% of the RfD for the general

U.S. population. Field corn and

sorghum forage and fodder are fed to

animals, thus exposure of humans to

residues from these commodities might

result if such residues are transferred to

meat, milk, poultry or eggs. However,

based on the results of animal

metabolism and the amount of

halosulfuron-methyl expected in animal

feeds, Monsanto concludes that there is

no reasonable expectation that residues

of halosulfuron-methyl will exceed

existing tolerances in meat. The

regulation of animal commodities and

poultry products are not required.

ii. Drinking water. There is no

Maximum Contaminant Level (MCL)

established for residues of halosulfuronmethyl. It is not listed for MCL

development or drinking water

monitoring under the Safe Drinking

Water Act nor is it a target of EPA’s

National Survey of Wells for Pesticides.
29404 Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices

Monsanto is not aware of any

halosulfuron-methyl detections in any

wells, ponds, lakes or streams resulting

from its use in the United States. A

Lifetime Health Advisory Level (HAL),

calculated using EPA procedures, may

be used as a preliminary acceptable

level in drinking water. The calculated

level is 700 ppb which assumes a 20%

relative contribution from water and

which is sufficient to provide ample

margins of safety. In addition, EPA has

concluded that potential levels of

halosulfuron-methyl or metabolites in

soil and water do not appear to have

significant toxicological effects on

humans or animals and presents a

negligible risk.

The EPA has expressed concern

regarding potential groundwater

contamination by the sulfonylurea (SU)

class of chemistry in general and has

required generic label warnings for

halosulfuron-methyl; however, results

of the field dissipation and lysimeter

studies and a recently completed

aquatic sediment study with

halosulfuron-methyl should mitigate the

concern for this chemical in particular.

Based on the very low level of

mammalian toxicity, lack of other

toxicological concerns and low use

rates, Monsanto believes that there is

reasonable certainty that no harm will

result from exposure to halosulfuronmethyl via drinking water sources.

iii. Non-dietary exposure.

Halosulfuron-methyl is labeled for use

on commercial and residential turf and

other non-crop sites which could have

minimal opportunity for exposure. The

agricultural uses including the proposed

uses in tree nut crop group, pistachio

nuts, cotton and rice will not increase

the non-occupational exposure

appreciably, if at all. Any exposure to

halosulfuron-methyl resulting from turf

use will result from dermal exposure

during application and will be limited

because of low use rates. In the 21-day

dermal study, no treatment related

adverse effects were observed and the

NOAEL was determined to be greater

than the highest dose tested, >1,000 mg/

kg. Halosulfuron-methyl is non-volatile

with a vapor pressure of <1 x 10-7 mm

Hg, hence, inhalation exposure during

and after application will not add

significantly to aggregate exposure.

Based on the physical and chemical

characteristics, low use rates, low acute

toxicity and lack of other toxicological

concerns, Monsanto believes that the

risk posed by non-occupational

exposure to halosulfuron-methyl is

minimal.

D. Cumulative Effects

Halosulfuron-methyl belongs to the

sulfonyl urea class of chemistry. The

mode of action of halosulfuron-methyl

is the inhibition of the plant enzyme

aceto lactase synthetase (ALS), which is

essential for the production of required

amino acid in plants. Although other

registered sulfonyl ureas may have

similar herbicidal mode of action, there

is no information available to suggest

that these compounds exhibit a similar

toxicity profile in the mammalian

system that would be cumulative with

halosulfuron-methyl. Thus,

consideration of a common mechanism

of toxicity is not appropriate at this

time. Monsanto is considering only the

potential risks of halosulfuron-methyl in

its aggregate exposure assessment.

E. Safety Determination

1. U.S. population—Chronic dietary

exposure. As stated above, the EPA’s

calculated aggregate chronic exposure to

halosulfuron-methyl from the

established tolerances for field corn and

grain sorghum raw agricultural

commodities utilizes only 0.51% of the

RfD using very conservative

assumptions. Monsanto’s subsequent

calculation to include the proposed

tolerances on sweet corn, pop corn,

sugarcane, tree nut crop grouping,

pistachio nuts, rice and cotton estimates

that it will utilize only 0.6% of the RfD

for the entire 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. Toxicology data

indicating low potential for mammalian

toxicity and lack of other toxicity

concerns plus the conservative

assumptions used in this calculation

support the conclusion that there is a

‘‘reasonable certainty of no harm’’ to the

U.S. population in general from

aggregate exposure to halosulfuronmethyl residues from all anticipated

dietary exposures and all other nonoccupational exposures.

2. Acute dietary exposure. The

detailed DRES acute exposure analysis

evaluates individual food consumption

and estimates the distribution of single

day exposures through the diet for the

US population and certain subgroups.

Since the toxicological effect to which

high end exposure is compared is

developmental toxicity, EPA

determined that the DRES subgroup of

concern is females (13+ years) which

approximates women of child-bearing

age. The appropriate NOEL to use to

assess safety in acute exposure is 50 mg/

kg body weight/day from a

developmental toxicity study in rabbits.

For shorter term risk, the Margin of

Exposure (MOE), a measure of how

closely the high end exposure comes to

the NOEL and is calculated as a ratio of

the NOEL to the exposure (NOEL/

exposure = MOE). For toxicological

endpoints established based upon

animal studies ,the agency is generally

not concerned unless the MOE is below

100. In this analysis, tolerance levels

were used to calculate the exposure of

the highest exposed individual (females,

13+ year subgroup). High end exposure

for this subgroup resulted in an MOE in

excess of 30,000. Therefore, the acute

dietary exposure to halosulfuron-methyl

does not represent a risk concern.

Monsanto has calculated the MOE for

all tolerances (established and

proposed) which resulted in an MOE of

31,623 for the entire U.S. population.

Monsanto’s calculation used the

individual food consumption data from

the 1989-1992 USDA Food

Consumption Surveys and the

EXPOSURE-4 software by TAS, Inc.

Therefore, Monsanto concludes that

there is a reasonable certainty that no

harm will result from acute aggregate

exposure to halosulfuron-methyl

residues.

3. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

halosulfuron-methyl, Monsanto

considered data from developmental

toxicity studies in the rat and rabbit and

a 2-generation reproduction study in the

rat. The developmental toxicity studies

are designed to evaluate the potential

for adverse effects on the developing

organism resulting from exposure

during prenatal development to the

female parent. Reproduction studies

provide information relating to effects

from exposure to the chemical on the

reproductive capability of both (mating)

parents and on off spring from pre-natal

and post-natal exposure to the pesticide

as well as systemic toxicity.

In a developmental toxicity study in

the rat, the NOEL for both maternal and

developmental toxicity was considered

to be 250 mg/kg/day. In a

developmental toxicity study in rabbits,

a NOEL for both developmental and

maternal toxicity was considered to be

50 mg/kg/day. A dietary 2-generation

reproduction study in rats resulted in

parental toxicity at 223.2 mg/kg/day in

males and 261.4 mg/kg/day in females

in the form of decreased body weights,

decreased body weight gains, and

reduced food consumption during the

premating period. Very slight effects

were noted in body weight of the

offspring at this dose. This effect was
Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices 29405

considered to be developmental toxicity

(developmental delay) rather than a

reproductive effect. No effects were

noted on reproductive or other

developmental toxicity parameters. The

systemic/developmental toxicity NOEL

was 50.4 mg/kg/day in males and 58.7

mg/kg/day in females. The reproductive

NOEL was equal to or greater than 223.2

mg/kg/day in males and 261.4 mg/kg/

day in females. In all cases, the

reproductive and developmental NOELs

were greater than the NOEL on which

the RfD was based, thus allowing for an

additional margin of safety and

indicating that halosulfuron-methyl

does not pose any increased risk to

infants or children.

4. Chronic analysis. Using the

conservative dietary exposure

assumptions described above, the TMRC

for the most exposed subgroups is

0.00117 mg/kg body weight/day for

nonnursing infants (less than 1-year old)

and 0.001008 mg/kg body weight/day

for children (1 to 6 years old), and that

this aggregate exposure to residues of

halosulfuron-methyl utilizes only 1.170

and 1.008% of the RfD, respectively

when existing tolerances are considered.

Monsanto’s subsequent analysis

included contribution from the

proposed tolerances in sugarcane, sweet

corn/popcorn, tree nut crop grouping,

pistachio nuts, rice and cotton. The

TMRC utilized only 1.7 and 1.3% of the

RfD, respectively.

FFDCA section 408 provides that EPA

may apply an additional safety factor

(up to 10) in the case of threshold effects

for infants and children to account for

pre- and post-natal toxicity and the

completeness of the data base. Based on

current toxicological data requirements,

the data base relative to pre- and postnatal effects in children is complete.

Further, the NOEL of 10 mg/kg/day from

the 1-year feeding study in dogs, which

was used to calculate the RfD (discussed

above), is already lower than the NOELs

from the reproductive and

developmental studies with

halosulfuron-methyl by a factor of at

least 25- and 5-fold, respectively. An

additional safety factor is not warranted

and the RfD of 0.1 mg/kg/day is

appropriate for assessing aggregate risk

to infants and children.

Therefore, based on complete and

reliable toxicity data and the

conservative exposure assessment,

Monsanto concludes that there is

reasonable certainty that no harm will

result to infants and children from

aggregate exposure to halosulfuronmethyl residues.

F. International Tolerances

Maximum residue levels have not

been established for residues of

halosulfuron-methyl on corn, sorghum,

sugarcane, sweet corn, pop corn, tree

nuts, pistachio nuts, rice or cotton or

any other food or feed crop by the

Codex Alimentarius Commission.

2. Norvartis Crop Protection Inc.

PP 3F4225

EPA has received a pesticide petition

(PP 3F4225) from Norvartis Crop

Protection INC., P.O. Box 18300,

Greensboro, NC 27419, 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

extending time limited tolerances for

residues of Triasulfuron in or on the raw

agricultural commodity grass, forage at

7.0 ppm, grass, hay at 2.0 ppm and

kidney of cattle, goats, hogs, horses, and

sheep at 0.5 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 nature of the

residue in plants is understood. The

metabolism of triasulfuron in wheat

proceeds by hydroxylation of the phenyl

ring and hydrolytic cleavage of the urea

bridge. The residue of regulatory

concern is parent triasulfuron. Because

the metabolism work in wheat can be

translated to grasses, parent compound

is the residue of regulatory concern for

grasses.

2. Analytical method. Triasulfuron in

grass was analyzed by Analytical

Method AG-500B which the validated

tolerance enforcement method.

According to Method AG-500B,

triasulfuron is extracted with a mixture

of methanol and phosphoric acid. The

extract is diluted with water.

Triasulfuron residues are partitioned

into dichloromethane and cleaned up

on a BondElut CN solid phase extraction

column. Residues are determined by

column-switching HPLC utilizing a

Lichrosorb CN column followed by a

Zorbax ODS column, with UV detection

at 232 nm.

3. Magnitude of residues. A total of 16

field trials have been conducted in 16

States. Seven sites tested bromegrass or

fescue, 5 used bluegrass, and 4 used

bermudagrass. A total of 69.6% of U.S.

pastureland was represented by these

trials. Two post broadcast spray

applications were made 60-days apart at

a rate of 12 grams active ingredient/A/

application. Time-limited tolerances

were previously established at 7 ppm in

grass, forage and 2 ppm in grass, hay

pending the submission of additional

residue trials. These additional field

trials which are included in the

numbers above did not show residues

exceeding the current tolerances in

either grass, forage (0-day PHI) or grass,

hay (30-days PHI). The feeding of either

substrate to beef or dairy cattle will not

result in existing tolerances in animal

commodities being exceeded.

B. Toxicological Profile

1. Acute toxicity. Triasulfuron has a

low order of acute toxicity. The rat oral

LD50 is > 5,000 milligrams/kilogram

(mg/kg), the acute rabbit dermal LD50 is

> 2,000 mg/kg and the rat inhalation

LC50 is > 5.2 mg/L. Triasulfuron is

slightly irritating to the eye but not

irritating to skin. It is not a skin

sensitizer in guinea pigs. The

commercial formulation of triasulfuron

(75WP) has a similar acute toxicity

profile. Both the technical material and

the 75WP formulation require a

Category III CAUTION Signal Word on

the label.

2. Genotoxicty. Assays for

genotoxicity were comprised of tests

evaluating the potential of triasulfuron

to induce point mutations (Salmonella

typhimurium, Saccharomyces cerevisiae

and mouse lymphoma L5178Y/TK/+/-

cells), chromosome aberrations

(micronucleus test in Chinese hamsters)

and the ability to induce either

unscheduled DNA synthesis in rat

hepatocytes and human fibroblasts. The

results indicate that triasulfuron is not

mutagenic or clastogenic and does not

induce unscheduled DNA synthesis.

3. Reproductive and developmental

toxicity. The developmental and

teratogenic potential of triasulfuron was

investigated in rats and rabbits. The

results indicate that triasulfuron was

maternally toxic in the rat at doses of >

300 mg/kg/day. Developmental toxicity

in the form of delayed skeletal

maturation was observed only at the

highest dose tested (HDT) of 900 mg/kg/

day. The corresponding maternal and

developmental NOELs were established

at doses of 100 and 300 mg/kg/day,

respectively in the rat. In the rabbit,

maternal toxicity was observed at the

HDT of 240 mg/kg/day; no evidence of

developmental toxicity was present at

240 mg/kg/day. The maternal

developmental NOELs were 120 and

240 mg/kg/day, respectively. No

evidence of teratogenicity was observed

at the HDT in either the rat or rabbit.
29406 Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices

There was no effect of triasulfuron on

reproductive performance in a 2

generation rat reproduction study

conducted at doses of 1, 50 and 250 mg/

kg/day. Maternal and fetal toxicity as

indicated by decreased body weight

gain was noted at the HDT of 250 mg/

kg/day. The maternal and

developmental NOEL was 50 mg/kg/

day.

4. Subchronic toxicity. The

subchronic toxicity of triasulfuron was

evaluated in the rat and dog at high

doses. Triasulfuron was poorly tolerated

in the rat at doses of > 516 mg/kg/day

as indicated by increased mortality,

decreased body weight gain and kidney

damage due to the presence of

triasulfuron-containing calculi present

in the urogenital tract. The NOEL in the

rat was 10 mg/kg/day. Triasulfuron was

not well tolerated by the dog at doses of

10,000 ppm (250 mg/kg/day) as

indicated by body weight reduction,

anemia, and effects on the spleen, liver

and kidney. The NOEL was 1,000 ppm

(33 mg/kg/day).

5. Chronic toxicity. The chronic

toxicity of triasulfuron was investigated

in long term studies in the rat, mouse

and dog. Target organs included the

liver, kidney and blood. NOELs were

established at dose levels of 32.1, 1.2,

and 129 mg/kg/day, respectively. The

mouse is the most sensitive species with

a NOEL = 1.2 mg/kg/day. The

carcinogenicity studies on triasulfuron

showed no evidence of an oncogenic

response in either mouse or rat. The

chemical is classified in category E.

6. Animal metabolism. The

metabolism of triasulfuron has been

well characterized in standard FIFRA

rat, goat and poultry metabolism

studies. Parent triasulfuron accounts for

the majority of the excreted dose in

these species. Cleavage of the

sulfonylurea bridge occurs at a low rate

but it is more prevalent in goats and

hens than in rats. Hydroxylation of the

phenyl ring, which constitutes the major

metabolic pathway elucidated in wheat,

also was found in the rat. None of the

metabolites identified in these studies

are considered to be toxicologically

different than parent.

7. Metabolite toxicology. The

metabolism of triasulfuron has been

well characterized in rat, goat and

poultry metabolism studies. None of the

metabolites identified in these studies

are considered to be toxicologically

different than parent.

8. Endocrine disruption. Triasulfuron

does not belong to a class of chemicals

known or suspected of having adverse

effects on the endocrine system. There

was no effect of triasulfuron on

reproductive performance in a 2-

generation rat reproduction study

conducted at doses of 1, 50 and 250 mg/

kg/day. Although residues of

triasulfuron have been found in raw

agricultural commodities, there is no

evidence that triasulfuron

bioaccumulates in the environment.

C. Aggregate Exposure

1. Food. Novartis has estimated the

aggregate exposure to triasulfuron based

on the established and time-limited

tolerances for triasulfuron (40 CFR

180.459). The theoretical maximum

residue contribution to diet is obtained

by multiplying the tolerance level

residue for all these raw agricultural

commodities by the consumption data

which estimates the amount of these

products consumed by various

population subgroups. Because some of

these raw agricultural commodities (e.g.

wheat and barley forage and fodder,

grass forage and hay) are fed to animals,

the transfer of residues to animal

commodities has been calculated based

on a conservatively constructed cattle

diet. In addition, Novartis has

conservatively assumed that 100% of

the raw agricultural commodities

contain residues of triasulfuron at

tolerance levels.

2. Drinking water. Another potential

source of exposure of the general

population to residues of pesticides are

residues in drinking water. The

potential for triasulfuron to enter

surface or groundwater sources of

drinking water is limited because of the

low use rate. The Maximum

Contaminant Level Guideline (MCLG)

calculated for triasulfuron according to

EPA’s procedures is 84 ppb, a value that

is substantially greater than levels that

are likely to be found in the

environment under proposed conditions

of use.

3. Non-dietary exposure. Novartis has

evaluated the estimated nonoccupational exposure to triasulfuron

and concludes that the potential for

non-occupational exposure to the

general population is unlikely since

triasulfuron is not planned to be used in

or around the home, including home

lawns.

D. Cumulative Effects

Novartis also has considered the

potential for cumulative effects of

triasulfuron and other chemicals

belonging to this class that may have a

common mechanism of toxicity.

Novartis concluded that consideration

of a common mechanism of toxicity is

not appropriate at this time since there

is no data to establish whether a

common mechanism exists.

E. Safety Determination

1. U.S. population. Using the

conservative exposure assumptions

described above, based on the

completeness and reliability of the

toxicity data, Novartis has concluded

that aggregate exposure to triasulfuron

will utilize a maximum of 4.63% of the

RfD for the U.S. population based on

chronic toxicity endpoints. EPA

generally has no concern for exposures

below 100% of the RfD because the RfD

represents the level at or below which

daily aggregate dietary exposure over a

lifetime will not pose appreciable risks

to human health. Therefore, Novartis

concludes that there is a reasonable

certainty that no harm will result from

aggregate exposure to triasulfuron or

residues of triasulfuron that may appear

in raw agricultural commodities.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

triasulfuron, Novartis has considered

data from developmental toxicity

studies in the rat and rabbit and a 2-

generation reproduction study in the rat

on triasulfuron. The developmental

toxicity studies are designed to evaluate

adverse effects on the developing

organism resulting from chemical

exposure during prenatal development

to one or both parents. Reproduction

studies provide information relating to

effects from exposure to a chemical on

the reproductive capability of mating

animals and data on systemic toxicity.

Developmental toxicity in the form of

delayed skeletal maturation was

observed in the rat only at the HDT of

900 mg/kg/day. The corresponding

maternal and developmental NOELs

were established at doses of 100 and 300

mg/kg/day, respectively in the rat. In the

rabbit, maternal toxicity was observed at

the HDT of 240 mg/kg/day; no evidence

of developmental toxicity was present at

240 mg/kg/day.

There was no effect of triasulfuron on

reproductive performance in a 2

generation rat reproduction study

conducted at doses of 1, 50 and 250 mg/

kg/day. Maternal and fetal toxicity as

indicated by decreased body weight

gain was noted at the HDT 250 mg/kg/

day. The maternal and developmental

NOELs were 50 mg/kg/day.

Section 408 of the FFDCA provides

that EPA may apply an additional safety

factor for infants and children in the

case of threshold effects to account for

pre- and post-natal toxicity and the

completeness of the database. Based on

the current toxicological data

requirements, the database relative to

pre- and post-natal effects for children

is complete. Further, for triasulfuron,
Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices 29407

the NOEL of 1.2 mg/kg/day from the

mouse oncogenicity study, which was

used to calculate the RfD of 0.01 mg/kg/

day, was approximately 50 times lower

than the developmental NOEL level

from the rat multigeneration

reproduction study. There is no

evidence to suggest that developing

organisms are more sensitive to the

effects of triasulfuron than are adults.

Using the conservative exposure

assumptions described above and the

chronic toxicity NOEL of 1.2 mg/kg/day

(RfD of 0.01 mg/kg/day), Novartis has

determined that the % of the RfD that

will be utilized by aggregate exposure to

residues of triasulfuron is 3.98% for

nursing infants less than 1-year old,

15.43% for non-nursing infants, 10.91%

for children 1 to 6-years old and 7.34%

for children 7 to 12-years old. Therefore,

based on the completeness and

reliability of the toxicity data and the

conservative exposure assessment,

Novartis concludes that there is a

reasonable certainty that no harm will

result to infants and children from

aggregate exposure to triasulfuron

residues.

F. International Tolerances

There are no Codex Alimentarius

Commission (CODEX) maximum

residue levels (MRL’s) established for

residues of triasulfuron in or on raw

agricultural commodities.

3. Zeneca Ag Products

PP 8F4954

EPA has received a pesticide petition

(PP 8F4954) from Zeneca Ag Products,

1800 Concord Pike, Wilmington, DE

19850-5458 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,

2-[4-(methylsulfonyl)-2-nitrobenzoyl]-

1,3-cyclohexanedione, in or on the raw

agricultural commodities field corn,

field corn fodder and field corn forage

at 0.01 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 nature of the

residue of 2-[4-(methylsulfonyl)-2-

nitrobenzoyl]-1,3-cyclohexanedione,

(hereafter referred to by the trade name

ZA1296) in plants is adequately

understood. ZA1296 is rapidly and

completely metabolized in corn. No

single extract or component accounted

for greater than 0.01 ppm in grain.

Numerous components were

characterised in forage and fodder,

including the metabolite 2-amino-4-

methylsulfonyl benzoic acid (AMBA)

and its conjugates and 4-

methylsulfonyl-2-nitrobenzoic acid

(MNBA). In addition to ZA1296, MNBA

was included in crop residue analysis.

2. Analytical method. The proposed

analytical method involves extraction,

partition, clean-up and separation of

ZA1296 and MNBA, oxidation of

ZA1296, reduction, clean-up and

detection of residues by reversed-phase

HPLC using fluorescence detection. The

limit of quantitation for ZA1296 and the

metabolite MNBA is 0.01 ppm.

3. Magnitude of residues. Twenty

residue trials were conducted in the US

(EPA regions I, II, V and VI). The

proposed use of ZA1296 does not result

in residues (LOQ of 0.01 ppm) of

ZA1296 or the metabolite MNBA in

field corn grain, forage or fodder.

B. Toxicological Profile

1. Acute toxicity. A battery of acute

toxicity tests were conducted which

place ZA1296 in acute oral toxicity

category IV, acute dermal toxicity

category III, acute inhalation toxicity

category IV, primary eye irritation

category III, and primary dermal

irritation category IV. ZA1296 is not a

skin sensitizer. ZA1296 is not a

neurotoxin in males and females at

2,000 mg/kg (limit test).

2. Genotoxicty. ZA296 was found to

be negative for mutagenicity in a battery

of mutagenicity tests (in vitro) Ames

Testing, Mouse Lymphoma, Human

Lymphocytes and in vivo Mouse

Micronucleus).

3. Reproductive and developmental

toxicity—i. Developmental toxicity

(rabbit). New Zealand white rabbits

were dosed orally by gavage with 0, 100,

250 or 500 mg/kg/day ZA1296 on days

8-20 of gestation. The top dose level in

this study was set on the basis of

significant maternal toxicity seen at

higher dose levels in a preliminary

study. At dose levels of 250 and 500 mg/

kg/day there was a low incidence of

whole litter losses. ZA1296 was not

associated with significant maternal

toxicity or evidence of teratogenicity.

Dose levels of 100 mg/kg/day or more

were associated with changes in the

ossification of the fetal skeleton but not

with structural malformation. The

changes in ossification are transient in

nature and considered not to be of

toxicological significance in terms of

post natal development. A

developmental NOAEL of 100 mg/kg/

day was established in this study.

ii. Developmental toxicity (rat). Rats

were dosed orally by gavage with 0, 100,

300 or 1,000 mg/kg/day ZA1296 on days

7-16 of gestation. Maternal toxicity, as

evidenced by reductions in body weight

and food consumption, was seen at dose

levels of 100, 300 or 1,000 mg/kg/day

ZA1296. Administration of ZA1296 at

dose levels of up to 1,000 mg/kg/day

produced no evidence of teratogenicity.

An increased incidence of minor

skeletal defects and skeletal variants

and increases in mean manus and pes

scores were seen at all dose levels and

were indicative of reduced ossification

or a disturbance in the normal pattern

of ossification. The changes in

ossification are transient in nature and

are considered not to be of toxicological

significance in terms of post-natal

development. Fetal weight was reduced

at 1,000 mg/kg/day. A developmental

NOAEL of 300 mg/kg/day was

established in this study.

iii. Reproductive toxicity (rat). In a 3-

generation study rats were fed diets

containing 0, 2.5, 10 or 2500 ppm

ZA1296. Dietary administration of

ZA1296 had no effect on mating

performance but was found to result in

reduced pup survival at a dose of 2,500

ppm in all 3-generations and at 100 ppm

in the second generation only. These

findings were not present in recovery

subgroups removed from treated diet in

the third generation. There was also a

reduction in the number of pups per

litter, and effects on body weights and

in the eye and kidney. In the third

generation, there were no effects in the

eyes or kidneys of offspring from

animals which were returned to control

diet 4 weeks prior to mating and effects

on litter size were less marked than in

the continuous treatment group. A

NOEL of 2.5 ppm ZA1296 (0.3 mg/kg/

day) was established in this study. In

light of the mechanism of toxicity,

investigations into the effects seen in

this study in pups are considered not to

be relevant to human risk assessment.

iv. Reproductive toxicity (mouse). In a

2-generation study mice were fed diets

containing 0, 10, 50, 350, 1,500 or 7.000

ppm ZA1296. There were no adverse

effect of ZA1296 on the reproductive

performance of the mouse, on fertility

and fecundity of the F0 and F1 adult

animals or on survival of their offspring.

The body weights of the offspring were

reduced at 1,500 and 7,000 ppm

ZA1296. A NOEL of 350 ppm ZA1296

(71 mg/kg/day) was established in this

study.

4. Subchronic toxicity—i. 21-day

dermal (rabbits). Rabbits were

repeatedly dosed with ZA1296 at 0, 10,
29408 Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices

500 or 1,000 mg/kg/day for 21 days. The

NOEL for sub-acute dermal toxicity was

>1,000 mg/kg/day (limit dose).

ii. 90-day rodent (rat). In a first study

male and female rats were dosed with

0, 1, 125, 1,250 or 12,500 ppm ZA1296

in the diet for 90-days. The NOEL was

determined to be 1ppm for males and

females (0.09 and 0.1 mg/kg/day,

respectively) based on reduced

bodyweight and increased liver weight

in males and females at 125 ppm and

increased kidney weight and ocular

keratitis in males at 125 ppm. 125 ppm

(13 mg/kg/day) was a NOEL for the

ocular keratitis in females. In a second

study in male rats dosed with ZA1296

at 0, 10, 20 or 150 ppm ZA1296 in the

diet for 90-days, a NOEL of 20 ppm (1.7

mg/kg/day) was determined for reduced

bodyweight. At the 10 ppm dose level

ocular keratitis and increased liver and

kidney weights were observed. In a

third study in male and female rats

dosed with ZA1296 at 0, 2.5, 5.0, 7.5 or

150 ppm in the diet for 90-days, NOELs

of 5 ppm (0.41 mg/kg/day) for ocular

keratitis and increased kidney weight

and 7.5 ppm (0.63 mg/kg/day) for

reduced bodyweight were determined in

males. NOELs of 7.5 ppm (0.71 mg/kg/

day) for reduced bodyweight and

increased liver weight and 150 ppm (14

mg/kg/day) for increased kidney weight

were determined in females. At 2.5 ppm

in males increased liver weight was

observed. In light of investigations into

the mechanism of toxicity, these

changes are all considered not to be

relevant to human risk assessment.

iii. 90-day rodent (mouse). Mice were

dosed 0, 50, 350 or 7,000 ppm in the

diet for 90-days. In females no clear

toxic effects were observed at 7,000 ppm

(1,500 mg/kg/day). In males 7,000 ppm

(1,200 mg/kg/day) was associated with a

reduced growth rate and food

utilization. In males and females 350

ppm (62 and 80 mg/kg/day,

respectively) produced no effects which

were considered to be toxicologically

significant.

iv. 90-day non-rodent (dog). Beagle

dogs were dosed with ZA1296 at 0, 100,

600 or 1,000 mg/kg/day as a daily oral

dose by capsule, for a period of 90-days.

The NOEL in the dog over 90-days was

100 mg/kg/day. Minimal toxicity was

observed at 600 and 1,000 mg/kg/day,

evident as reduced bodyweights in

males and a microcytic polycythemia in

both sexes. Mesothelial proliferation of

the atrium of the heart was evident in

2 male dogs at 1,000 mg/kg/day.

v. 90-day neurotoxicity (rat). Rats

were dosed with ZA1296 at 0, 2.5, 100

or 5,000 ppm in the diet for 90-days.

The NOAEL for subchronic

neurotoxicity was determined to be

5,000 ppm (400 and 460 mg/kg/day for

males and females, respectively) based

on the absence of changes indicative of

neurotoxicity.

5. Chronic toxicity—i. 1-year nonrodent (dog). Beagle dogs were dosed

with ZA1296 at 0, 10, 100 or 600 mg/

kg/day as a daily oral dose by capsule,

for a period of 1-year. The NOEL in this

study was 100 mg/kg/day. At 600 mg/

kg/day males showed a significant

reduction in bodyweight and both sexes

showed a slight microcytic

polycythemia, indicating that a

maximum tolerated dose had been

achieved. Minimal ocular keratitis was

observed in 1 male and 1 female at 600

mg/kg/day.

ii. 1-year rodent (mouse). Mice were

dosed with ZA1296 at 0, 10, 50, 350 or

7,000 ppm in the diet for 1 year. The

NOEL in males and females was 350

ppm (56 and 72 mg/kg/day,

respectively). At 7,000 ppm (limit dose)

bodyweight was reduced in males, and

there was an increased incidence of

eosinophilic change in the gall bladder

of females.

iii. Combined rodent chronic toxicity/

oncogenicity (rat). Rats were dosed with

ZA1296 at 0, 7.5, 100 or 2,500 ppm in

the diet for up to 2 years. In addition

rats were fed diet containing 1 or 2.5

ppm ZA1296 for up to 2-years to

determine the chronic ocular toxicity.

Oral administration of 7.5, 100 or 2,500

ppm ZA1296 for at least 2-years caused

ocular keratitis, reduced bodyweights,

increased liver and kidney weights, and

an increased incidence of common

spontaneous lesions in the Alderley

Park rat. In light of investigations into

the mechanism of toxicity, these

changes are all considered not to be

related to human risk assessment.

Satellite groups of rats fed 1 and 2.5

ppm ZA1296 showed that dietary levels

of 2.5 ppm in males and 7.5 ppm in

females were without ocular effect.

ZA1296 was considered not to be

carcinogenic in the rat in this study. A

NOEL of 7.5 ppm ZA1296 was

established for females.

iv. Oncogenicity in the rodent

(mouse). Mice were fed diets containing

0, 10, 350 or 7,000 ppm ZA1296 for up

to 80-weeks. Oral administration of

7,000 ppm (900-1,100 mg/kg/day)

ZA1296 (limit dose) for at least 80-

weeks produced no evidence of

carcinogenicity in male or female mice.

6. Animal metabolism. The

absorption, distribution, metabolism

and excretion of ZA1296 has been

thoroughly investigated in rats and

studied in mice. In both species ZA1296

is well absorbed following an oral dose.

Elimination of ZA1296 is rapid in both

species, with most of the ZA1296

eliminated, in the urine, unchanged

with only minor amounts of the urinary

and fecal metabolites, including MNBA

and AMBA, detected. In poultry

ZA1296 is excreted generally

unchanged. In ruminants ZA1296 is

extensively metabolised and excreted.

AMBA dosed to ruminants is readily

absorbed and excreted, generally

unchanged. AMBA is not accumulated

in edible tissues or milk.

7. Metabolite toxicology. In acute oral

toxicity studies in male and female rats

both MNBA and AMBA had an oral

LD50 of >5,000 mg/kg. In the Ames

assay, both MNBA and AMBA were

found to be negative for mutagenicity in

the absence and presence of metabolic

activation.

8. Endocrine disruption. EPA is

required to develop a screening program

to determine whether certain substances

(including all pesticides and inerts)

‘‘may have an effect in humans that is

similar to an effect produced by a

naturally occurring estrogen, or such

other endocrine effect.’’ EPA is

currently working with interested

shareholders, including other

government agencies, public interest

groups, industry, and research

scientists, to develop a screening and

testing program and a priority setting

scheme to implement this program.

Congress has allowed 3-years from the

passage of FQPA (August 3, 1999) to

implement this program. When this

program is implemented, EPA may

require further testing of ZA1296 and

end-use product formulations for

endocrine disrupter effects.

9. Reference dose. As required by the

Food Quality and Protection Act of

1996, the mechanism of toxicity of

ZA1296 has been thoroughly

investigated in studies (FQPA) in the

rat, mouse and man. These data clearly

demonstrate that the response to

ZA1296 administration in man is very

similar to that seen in the mouse which

should therefore, be used in preference

to the rat when assessing the safety of

ZA1296 to humans. The proposed

reference dose (RfD) for use in the

assessment of risk from chronic

exposure is 0.56 mg/kg/day and is

derived from the 1 year chronic toxicity

study in the mouse with a NOEL of 56

mg/kg/day and a 100-fold uncertainty

factor.

C. Aggregate Exposure

1. Dietary exposure. The potential

dietary exposure to ZA1296 was

estimated from tolerance levels and

100% crop treated. No tolerances are

proposed for meat, milk and eggs. The

total dietary exposure for the U.S.

population and the most highly exposed
Federal Register / Vol. 63, No. 103 / Friday, May 29, 1998 / Notices 29409

subgroup in the population, nonnursing infants, is 0.000011 mg/kg/day

and 0.000027 mg/kg/day, respectively.

2. Drinking water. Drinking water

estimated concentrations (DWEC) were

calculated using EPA models for

groundwater and surface water - SCIGROW, GENEEC and PRZM/EXAMS.

Chronic Drinking Water Levels of

Concern (DWLOC) were calculated

according to the EPA SOP and

compared to the DWEC. Estimated

average contributions of ZA1296 in

surface and groundwater are less than

the levels of concern for ZA1296 in

drinking water as a contribution to

chronic aggregate exposure.

3. Non-dietary exposure. Zeneca has

not estimated non-occupational

exposure for ZA1296 since the only

pending registration for ZA1296 is

limited to commercial crop production

use. ZA1296 products are not labelled

for any residential uses therefore,

eliminating the potential for residential

exposure. The potential for nonoccupational exposure to the general

population is considered to be

insignificant.

D. Cumulative Effects

Zeneca also considered the potential

for cumulative effects of ZA1296 and

other substances that have a common

mechanism of toxicity. Zeneca has

concluded that consideration of a

common mechanism of toxicity is not

appropriate at this time since there is no

indication that toxic effects produced by

ZA1296 would be cumulative with

those of any other chemical compounds.

Triketone chemistry is new and ZA1296

has a novel mode of action compared to

currently registered active ingredients.

E. Safety Determination

1. U.S. population. Dietary and

occupational exposure will be the major

routes of exposure to the U.S.

population and ample margins of safety

have been demonstrated for both

situations. The total dietary exposure for

the U.S. population is 0.000011 mg/kg/

day. This utilizes only 0.002% of the

RfD. The MOE for occupational

exposure is >5,500. Based on the

completeness and reliability of the

toxicity data and the conservative

exposure assessments, there is

reasonable certainty that no harm will

result from the aggregate exposure of

residues of ZA1296 including all

anticipated dietary exposure.

2. Infants and children. The total

dietary exposure for the most highly

exposed subgroup in the population,

non-nursing infants, is 0.000027 mg/kg/

day. This utilizes only 0.0048% of the

RfD. There are no residential uses of

ZA1296 and the estimated average

contributions of ZA1296 in surface and

groundwater are less than the levels of

concern for ZA1296 in drinking water as

a contribution to chronic aggregate

exposure. Based on the completeness

and reliability of the toxicity data and

the conservative exposure assessments,

there is reasonable certainty that no

harm will result from the aggregate

exposure of residues of ZA1296

including all anticipated dietary

exposure.

F. International Tolerances

A maximum residue level has not

been established for ZA1296 by the

Codex Alimentarius Commission.

[FR Doc. 98–14160 Filed 5–28–98; 8:45 am]

BILLING CODE 6560–50–F

FEDERAL COMMUNICATIONS

COMMISSION

[CC Docket No. 91–141; DA 98–839]

Local Competition Survey

AGENCY: Federal Communications

Commission.

ACTION: Notice.

SUMMARY: On May 8, 1998, the Common

Carrier Bureau issued a Public Notice to

solicit comment on how the

Commission can collect sufficient

information about local competition to

achieve the regulatory flexibility, procompetition, and universal service

objectives of the Telecommunications

Act of 1996 (1996 Act) while

minimizing filing burdens on

respondents. The Public Notice seeks

comment on what information should

be collected as well as on such issues as

whether periodic data collection should

be mandatory and which

telecommunications carriers should

provide information.

DATES: Comments to the Public Notice

are due on or before June 7, 1998. Reply

comments are due on or before June 22,

1998.

ADDRESSES: Comments and reply

comments should be sent to the Office

of the Secretary, Federal

Communications Commission, 1919 M

Street, N.W., Suite 222, Washington,

D.C. 20554, with a copy to Ms. Terry

Conway of the Common Carrier Bureau,

Federal Communications Commission,

2033 M Street, N.W., Suite 500,

Washington, D.C. 20554. Parties should

also file one copy of any documents

filed in this docket with the

Commission’s copy contractor,

International Transcription Services,

Inc. (ITS), 1231 20th St., NW,

Washington, DC 20036, (202) 857–3800.

FOR FURTHER INFORMATION CONTACT:

Thomas J. Beers, Deputy Chief of the

Industry Analysis Division, Common

Carrier Bureau, at (202) 418–0952, or

Ellen Burton, Industry Analysis

Division, Common Carrier Bureau, at

(202) 418–0958. Users of TTY

equipment may call (202) 418–0484.

SUPPLEMENTARY INFORMATION: This is a

summary of the Bureau’s Public Notice

released May 8, 1998 (DA 98–839). The

full text of this Public Notice is

available for inspection and copying

during normal business hours in the

FCC Reference Center, Room 239, 1919

M Street, Washington, D.C. 20554. The

complete text also may be purchased

from the Commission’s copy contractor,

International Transcription Service,

Inc., (202) 857–3800, 1231 20th St., NW,

Washington, DC 20036.

Summary of the Public Notice

The Commission requires timely and

reliable information on the pace and

extent of development of competition

for local telecommunications services in

different geographic markets to evaluate

the effectiveness of decisions taken to

implement the pro-competition

provisions and to achieve the universal

service goals of the Telecommunication

Act of 1996 (47 U.S.C. Section 151 et

seq.). The Commission also requires

such information to identify services

and geographic markets where local

competition has developed sufficiently

to allow the Commission to exercise its

regulatory forbearance authority (47

U.S.C. Section 160(a)).

The Commission has previously

concluded (Expanded Interconnection

with Local Telephone Company

Facilities, Memorandum Opinion and

Order, 59 FR 38922 (August 1, 1994), CC

Docket No. 91–141, 9 FCC Rcd 5154,

5177 (1994)) that an information

collection program is necessary to

monitor the state of local competition in

diverse areas of the country so that the

Commission might make its regulatory

requirements more flexible as

competition develops in particular

areas. The Commission delegated

authority to the Chief, Common Carrier

Bureau, to formulate the detailed

elements of a reporting program, to

decide which service providers must

provide information, and to specify the

format and timing of reports.

I. Background

3. Only a limited amount of

information on the state of local

competition can be derived from

sources currently reported to the