41828 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

to a data call-in. In all cases, productspecific disposition dates will be given

in the cancellation orders.

Existing stocks are those stocks of

registered pesticide products which are

currently in the United States and

which have been packaged, labeled, and

released for shipment prior to the

effective date of the cancellation action.

Unless the provisions of an earlier order

apply, existing stocks already in the

hands of dealers or users can be

distributed, sold or used legally until

they are exhausted, provided that such

further sale and use comply with the

EPA-approved label and labeling of the

affected product(s). Exceptions to these

general rules will be made in specific

cases when more stringent restrictions

on sale, distribution, or use of the

products or their ingredients have

already been imposed, as in Special

Review actions, or where the Agency

has identified significant potential risk

concerns associated with a particular

chemical.

List of Subjects

Environmental protection, Pesticides

and pests, Product registrations.

Dated: July 21, 1998.

Linda A. Travers,

Director, Information Resources and Services

Division, Office of Pesticide Programs.

[FR Doc. 98–20767 Filed 8–4–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–817; FRL–5799–6]

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–817, must be

received on or before September 4,

1998.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch, Information

Resources and Services Division

(7502C), Office of Pesticides Programs,

Environmental Protection Agency, 401

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

person bring comments to: Rm. 119, CM

#2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically by following

the instructions under

‘‘SUPPLEMENTARY INFORMATION.’’

No confidential business information

should be submitted through e-mail.

Information submitted as a comment

concerning this document may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI). CBI should not be submitted

through e-mail. Information marked as

CBI will not be disclosed except in

accordance with procedures set forth in

40 CFR part 2. A copy of the comment

that does not contain CBI must be

submitted for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments will be available for public

inspection in Rm. 119 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

Hoyt Jamerson ............... Rm. 268, CM #2, 703–308–9368, e-mail:jamerson.hoyt@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Cynthia Giles-Parker ...... Rm. 247, CM #2, 703–305–7740, e-mail:giles-parker.cynthia@epamail.epa.gov.

Jim Tomopkins ............... 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 support 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–817]

(including comments and data

submitted electronically as described

below). A public version of this record,

including printed, paper versions of

electronic comments, which does not

include any information claimed as CBI,

is available for inspection from 8:30

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

excluding legal holidays. The official

record is located at the address in

‘‘ADDRESSES’’ at the beginning of this

document.

Electronic comments can be sent

directly to EPA at:

opp-docket@epamail.epa.gov

Electronic comments must be

submitted as an ASCII file avoiding the

use of special characters and any form

of encryption. Comment and data will

also be accepted on disks in

Wordperfect 5.1 file format or ASCII file

format. All comments and data in

electronic form must be identified by

the docket number (insert docket

number) and appropriate petition

number. Electronic comments on notice

may be filed online at many Federal

Depository Libraries.

List of Subjects

Environmental protection,

Agricultural commodities, Food

additives, Feed additives, Pesticides and

pests, Reporting and recordkeeping

requirements.

Dated: July 15, 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
Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41829

measurement of the pesticide chemical

residues or an explanation of why no

such method is needed.

1. BASF Corporation

PP 6F4695

EPA has received a pesticide petition

(PP 6F4695) from BASF Corporation,

Agricultural Products, PO Box 13528,

Research Triangle Park, NC 27709,

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 tolerances for

residues of sethoxydim (2-[1-

ethoxyimino]butyl)-5-[2-

(ethylthio)propyl]-3-hydroxy-2-

cyclohexen-1-one) and its metabolites

containing the 2-cyclohexen-1-one

moiety (calculated as the herbicide) in

or on the raw agricultural commodities

(RACs) grapes at 1.0 part per million

(ppm), succulent beans at 15.0 ppm,

bean forage at 15.0 ppm, soybeans at

16.0 ppm, and raisins at 2.0 ppm. BASF

Corporation also requested that the

established tolerances for raisin waste at

1.0 ppm and grape pomace (dry and

wet) at 6.0 ppm be revoked, since they

are considered insignificant animal feed

commodities and are no longer of

regulatory concern.

PP 4F4075

EPA has received a pesticide petition

(PP 4F4075) from BASF Corporation,

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 tolerances for

residues of sethoxydim (2-[1-

ethoxyimino]butyl)-5-[2-

(ethylthio)propyl]-3-hydroxy-2-

cyclohexen-1-one) and its metabolites

containing the 2-cyclohexen-1-one

moiety (calculated as the herbicide) in

or on the raw agricultural commodities

(RACs) rice grain at 0.1 ppm, rice straw

at 0.5 ppm, rice hulls at 0.2 ppm, and

rice bran at 0.2 ppm.

2. Interregional Research Project

Number 4 (IR-4)

PP 6E4753, 6E4725, 6E4698, 6E4697

EPA has received pesticide petitions

(PP 6E4753, 6E4725, 6E4698, and

6E4697) from IR-4, New Jersey

Agricultural Experiment Station,

Rutgers University, New Brunswick,

New Jersey 08903 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 tolerances for residues of

the herbicide sethoxydim (2-[1-

(ethoxyimino)butyl]-5-[2-

(ethylthio)propyl]-3-hydoxy-2-

cyclohexen-1-one) and its metabolites

containing the 2-cyclohexen-1-one

moiety (calculated as the herbicide)) in

or on the raw agricultural commodities

as follows:

PP 6E4753

Petition submitted on behalf of

Agricultural Experiment Stations of

Oregon and Washington proposing

tolerances for the leafy vegetable (except

Brassica) crop group at 4.0 ppm and

cilantro at 4.0 ppm. The petitioner also

requested that established tolerances for

combined residues of sethoxydim and

its metabolites on celery at 1.0 ppm,

head lettuce at 1.0 ppm, leaf lettuce at

2.0 ppm, spinach at 4.0 ppm, and

endive (escarole) at 2.0 ppm be

removed, since these commodities are

members of the leafy vegetable (except

Brassica) crop group.

PP 6E4725

Petition submitted on behalf of the

Agricultural Experiment Stations of

California, Florida, Georgia, Illinois,

Michigan, New York, Oklahoma,

Oregon, South Carolina, Virginia,

Washington, and Wisconsin proposing

tolerances for the tuberous and corm

vegetable subgroup at 4.0 ppm and

garden beet at 1.0 ppm. The petitioner

also requested that established

tolerances for combined residues of

sethoxydim and its metabolites in or on

potato and sweet potato at 4.0 ppm be

removed, since these commodities are

members to the tuberous and corm

vegetable subgroup.

PP 6E4698

Petition submitted on behalf of the

Agricultural Experiment Station of

California proposing that the existing

tolerance for combined residues of

sethoxydim and its metabolites in or on

artichoke be increased from 3.0 ppm to

5.0 ppm

PP 6E4697

Petition submitted on behalf of the

Agricultural Experiment Station of

Oregon proposing a tolerance for the

caneberry crop subgoup at 5.0 ppm. The

petitioner also requested that the

established tolerance for combined

residues of sethoxydim and its

metabolites in or on raspberry at 5.0

ppm be removed, since the caneberry

subgroup includes raspberry.

EPA has determined that the petitions

contain 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 support granting of the

petitions. Additional data may be

needed before EPA rules on the

petitions. This notice includes a

summary of the petitions prepared by

BASF Corporation, Agricultural

Products, P.O. Box 13528, Research

Triangle Park, NC 27709.

A. Residue Chemistry

1. Plant metabolism. The qualitative

nature of the residues in plants and

animals is adequately understood for

the purposes of registration. Analytical

method for detecting levels of

sethoxydim and its metabolites in or on

food with a limit of detection that

allows monitoring of food with residues

at or above the levels set in these

tolerances were submitted to EPA.

2. Analytical method. The proposed

analytical method involves extraction,

partition, and clean-up. Samples are

then analyzed by gas chromatography

with sulfur-specific flame photometric

detection. The limit of quantitation is

0.05 ppm.

B. Toxicological Profile

1. Acute toxicity. Based on the

available acute toxicity data, BASF

concludes that sethoxydim does not

pose any acute dietary risks. A summary

of the acute toxicity studies follows.

i. Acute oral toxicity—Rat. Toxicity

Category III; lethal dose (LD)50=3125

milligram/kilogram (mg/kg) (male), 2676

mg/kg (female)

ii. Acute dermal toxicity-Rat. Toxicity

Category III; LD50≤5,000 mg/kg (male

and female)

iii. Acute inhalation toxicity—Rat.

Toxicity Category III; lethal

concentration (LC)50 (4-hour)=6.03 mg/

liter (L) (male), 6.28 mg/L (female)

iv. Primary eye irritation-rabbit.

Toxicity Category IV; no irritation

v. Primary dermal irritation-rabbit.

Toxicity Category IV; no irritation

vi. Dermal sensitization- guinea pig.

Waived because no sensitization was

seen in guinea pigs dosed with the enduse product Poast (18% active

ingedient).

2. Genotoxicity. Ames assays were

negative for gene mutation in

Salmonella typhimurium strains TA98,

TA100, TA1535, and TA 1537, with and

without metabolic activity.

A Chinese hamster bone marrow

cytogenetic assay was negative for

structural chromosomal aberrations at

doses up to 5,000 mg/kg in Chinese

hamster bone marrow cells in vivo.

Recombinant assays and forward

mutations tests in Bacillus subtilis,

Escherichia coli, and S typhimurium

were all negative for genotoxic effects at

concentrations of greater than or equal

to 100%.

3. Reproductive and developmental

toxicity. A developmental toxicity study
41830 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

in rats fed dosages of 0, 50, 180, 650,

and 1,000 mg/kg/day with a maternal

no-observed adverse effect level

(NOAEL) of 180 mg/kg/day and a

maternal lowest effect level (LEL) of 650

mg/kg/day (irregular gait, decreased

activity, excessive salivation, and

anogenital staining); and a

developmental NOAEL of 180 mg/kg/

day, and a developmental LEL of 650

milligram/killograms/day (mg/kg/day)

(21 to 22 percent decrease in fetal

weights, filamentous tail, and lack of

tail due to the absence of sacral and/or

caudal vertebrae, and delayed

ossification in the hyoids, vertebral

centrum and/or transverse processes,

sternebrae and/or metatarsals, and

pubes).

A developmental toxicity study in

rabbits fed doses of 0, 80, 160, 320, and

400 mg/kg/day with a maternal noobserved effect level (NOEL) of 320 mg/

kg/day and a maternal LOEL of 400 mg/

kg/day (37% reduction in body weight

gain without significant differences in

group mean body weights and decreased

food consumption during dosing); and a

developmental NOEL greater than 400

mg/kg/day (highest dose tested).

A 2-generation reproduction study

with rats fed diets containing 0, 150,

600, and 3,000 ppm (approximately 0,

7.5, 30, and 150 mg/kg/day) with no

reproductive effects observed under the

conditions of the study.

4. Subchronic toxicity. A 21-day

dermal study in rabbits with a NOAEL

of ≤1,000 mg/kg/day limit dose (LD).

The only dose-related finding was slight

epidermal hyperplasia at the dosing site

in nearly all males and females dosed at

1,000 mg/kg/day. This was probably an

adaptive response.

5. Chronic toxicity. A summary of the

chronic toxicity studies follows.

A 1-year feeding study with dogs fed

diets containing 0, 8.86/9.41, 17.5/19.9,

and 110/129 mg/kg/day (males/females)

with a NOEL of 8.86/9.41 mg/kg/day

(males/females) based on equivocal

anemia in male dogs at the 17.5-mg/kg/

day dose level.

A 2-year chronic feeding/

carcinogenicity study with mice fed

diets containing 0, 40, 120, 360, and

1,080 ppm (equivalent to 0, 6, 18, 54,

and 162 mg/kg/day) with a systemic

NOEL of 120 ppm (18 mg/kg/day) based

on non-neoplastic liver lesions in male

mice at the 360-ppm (54 mg/kg/day)

dose level. There were no carcinogenic

effects observed under the conditions of

the study. The maximum tolerated dose

(MTD) was not achieved in female mice.

A 2-year chronic feeding/carcinogenic

study with rats fed diets containing 0,

2, 6, and 18 mg/kg/day with a systemic

NOEL greater than or equal to 18 mg/kg/

day HDT. There were no carcinogenic

effects observed under the conditions of

the study. This study was reviewed

under current guidelines and was found

to be unacceptable because the doses

used were insufficient to induce a toxic

response and a MTD was not achieved.

A second chronic feeding/

carcinogenic study with rats fed diets

containing 0, 360, and 1,080 ppm

(equivalent to 18.2/23.0, and 55.9/71.8

mg/kg/day (males/females). The dose

levels were too low to elicit a toxic

response in the test animals and failed

to achieve a MTD or define a LEL. Slight

decreases in body weight in rats at the

1,080-ppm dose level, although not

biologically significant, support a freestanding NOAEL of 1,080 ppm (55.9/

71.8 mg/kg/day (males/females)). There

were no carcinogenic effects observed

under the conditions of the study.

In a rat metabolism study, excretion

was extremely rapid and tissue

accumulation was negligible.

6. Metabolite toxicology. As a

condition to registration, BASF had

been asked to submit additional

toxicology studies for the

hydroxymetabolites of sethoxydim.

BASF’s recommendation is to use the

most abundant metabolite, 5-OH-MSO2,

as surrogate for all metabolites. Based

on these data, it was concluded that the

toxicological potency of the plant

hydroxymetabolites is likely to be equal

to or less than that of the parent

compound. The tolerance expression for

sethoxydim measures sethoxydim and

its metabolites containing the 2-

cyclohexen-1-one moiety, measured as

parent. Hence, the hydroxymetabolites

are figured into all tolerance

calculations.

7. Endocrine disruption. No specific

tests have been performed with

sethoxydim to determine whether the

chemical may have an effect in humans

that is similar to an effect produced by

naturally-occurring estrogen or other

endocrine effects.

C. Aggregate Exposure

1. Dietary exposure. For purposes of

assessing the potential dietary exposure,

BASF has estimated aggregate exposure

based on the Theoretical Maximum

Residue Contribution (TMRC) from

existing and pending tolerances for

sethoxydim. (The TMRC is a ‘‘worst

case’’ estimate of dietary exposure since

it is assumed that 100% of all crops for

which tolerances are established are

treated and that pesticide residues are at

the tolerance levels.) The TMRC from

existing tolerances for the overall US

population is estimated at

approximately 35% of the RfD. Dietary

exposure to residues of sethoxydim in

or on food from these proposed

tolerances increases the TMRC by

approximately 8% of the RfD for the

overall US population. BASF estimates

indicate that dietary exposure will not

exceed the RfD for any population

subgroup for which EPA has data. This

exposure assessment relies on very

conservative assumptions that 100% of

crops will contain sethoxydim residues

and those residues would be at the level

of the tolerance which results in an

overestimate of human exposure.

2. Food-other- exposure. Other

potential sources of exposure of the

general population to residues of

pesticides are residues in drinking water

and exposure from non-occupational

sources. Based on the available studies

submitted to EPA for assessment of

environmental risk, BASF does not

anticipate exposure to residues of

sethoxydim in drinking water. There is

no established Maximum Concentration

Level (MCL) for residues of sethoxydim

in drinking water under the Safe

Drinking Water Act (SDWA).

BASF has not estimated nonoccupational exposure for sethoxydim.

Sethoxydim is labeled for use by

homeowners on and around the

following use sites: flowers, evergreens,

shrubs, trees, fruits, vegetables,

ornamental groundcovers, and bedding

plants. Hence, the potential for nonoccupational exposure to the general

population exists. However, these use

sites do not appreciably increase

exposure. Protective clothing

requirements, including the use of

gloves, adequately protect homeowners

when applying the product. The

product may only be applied through

hose-end sprayers or tank sprayers as a

0.14% solution. Sethoxydim is not a

volatile compound so inhalation

exposure during and after application

would be negligible. Dermal exposure

would be minimal in light of the

protective clothing and the low

application rate. Post-treatment (reentry) exposure would be negligible for

these use sites as contact with treated

surfaces would be low. Dietary risks

from treated food crops are already

adequately regulated by the established

tolerances. BASF concludes that the

potential for non-occupational exposure

to the general population is

insignificant.

D. Cumulative Effects

BASF also considered the potential

for cumulative effects of sethoxydim

and other substances that have a

common mechanism of toxicity. BASF

is aware of one other active ingredient

which is structurally similar, clethodim.

However, BASF believes that
Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41831

consideration of a common mechanism

of toxicity is not appropriate at this

time. BASF does not have any reliable

information to indicate that toxic effects

produced by sethoxydim would be

cumulative with clethodim or any other

chemical; thus BASF is considering

only the potential risks of sethoxydim in

its exposure assessment.

E. Safety Determination

1. U.S. population. Reference Dose

(RfD) using the conservative exposure

assumptions described above, BASF has

estimated that aggregate exposure to

sethoxydim will utilize 43% of the RfD

for the U.S. population. EPA generally

has no concern for exposures below

100% of the RfD. Therefore, based on

the completeness and reliability of the

toxicity data, and the conservative

exposure assessment, BASF concludes

that there is a reasonable certainty that

no harm will result from aggregate

exposure to residues of sethoxydim,

including all anticipated dietary

exposure and all other non-occupational

exposures.

2. Infants and children—i.

developmental toxicity. Developmental

toxicity was observed in a

developmental toxicity study using rats

but was not seen in a developmental

toxicity study using rabbits. In the

developmental toxicity study in rats a

maternal NOAEL of 180 mg/kg/day and

a maternal LEL of 650 mg/kg/day

(irregular gait, decreased activity,

excessive salivation, and anogenital

staining) was determined. A

developmental NOAEL of 180 mg/kg/

day and a developmental LEL of 650

mg/kg/day (21 to 22% decrease in fetal

weights, filamentous tail and lack of tail

due to the absence of sacral and/or

caudal vertebrae, and delayed

ossification in the hyoids, vertebral

centrum and/or transverse processes,

sternebrae and/or metatarsals, and

pubes). Since developmental effects

were observed only at doses where

maternal toxicity was noted, BASF

concludes that the developmental

effects observed are believed to be

secondary effects resulting from

maternal stress.

ii. Reproductive toxicity. A 2-

generation reproduction study with rats

fed diets containing 0, 150, 600, and

3,000 ppm (approximately 0, 7.5, 30,

and 150 mg/kg/day) produced no

reproductive effects during the course of

the study. Although the dose levels

were insufficient to elicit a toxic

response, the Agency has considered

this study usable for regulatory

purposes and has established a freestanding NOEL of 3,000 ppm

(approximately 150 mg/kg/day) (ref.

Proposed Rule 60 FR 13941).

iii. Reference dose. Based on the

demonstrated lack of significant

developmental or reproductive toxicity

BASF believes that the RfD used to

assess safety to children should be the

same as that for the general population,

0.09 mg/kg/day. Using the conservative

exposure assumptions described above,

BASF has concluded that the most

sensitive child population is that of

children ages 1 to 6. BASF calculates

the exposure to this group to be

approximately 85% of the RfD for all

uses (including those proposed in this

document). Based on the completeness

and reliability of the toxicity data and

the conservative exposure assessment,

BASF concludes that there is a

reasonable certainty that no harm will

result to infants and children from

aggregate exposure to the residues of

sethoxydim, including all anticipated

dietary exposure and all other nonoccupational exposures.

F. International Tolerances

A maximum residue level has not

been established for sethoxydim on

artichoke, caneberry, leafy vegetables

(except Brassica), root and tuber

vegetables, cilantro, grapes, succulent

beans, bean forage, soybeans or raisins

by the Codex Alimentarius Commission.

Individual countries have established

tolerances on beans ranging from 0.1 to

5.0 ppm and soybeans ranging from 0.05

ppm to 5.0 ppm. No tolerances have

been established for grapes in other

countries. The proposed tolerances for

leafy vegetables (except Brassica),

cilantro, and root and tuber vegetables

at 4.0 ppm are consistent with the

international tolerances as they fall

within the range of established

tolerances and reflect the differences in

application parameters and conditions

(e.g., application rate, pre-harvest

intervals, and environmental

conditions). (Hoyt Jamerson).

3. K-I Chemical U.S.A., Inc.

PP 8F4941

EPA has received a pesticide petition

(PP8F4941) from K-I Chemical U.S.A.,

Inc., Westchester Financial Center, 11

Martine Avenue, 9th Floor, White

Plains, NY 10606 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

cyclohexanecarboxylic acid, 3, 5-dioxo4-(1-oxopropyl)-, ion(1-), calcium,

calcium salt in or on the raw

agricultural commodity peanut nutmeat

and hay at 0.8 and 0.4 ppm respectively.

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

in plants (peanuts) is adequately

understood.

2. Analytical method. The proposed

analytical method involves

homogenization, extraction, filtration,

partition and cleanup, methylation and

analysis by a gas chromatography

system with a mass selective detector.

The limit of quantitation is 0.05 ppm.

3. Magnitude of residues. Peanut trials

were conducted with prohexadione

calcium in the principle peanut growing

regions of the country (NC, SC, GA, AL,

FL, OK, TX). Prohexadione calcium was

applied to peanuts 3- times at the rate

of 0.125 lbs ai/A. Peanut hay and

nutmeat were analyzed for residues of

prohexadione (free acid). Prohexadione

residues in the nutmeat ranged from

<0.05 to 0.30 ppm. Residues in hay

ranged from <0.05 to 0.26 ppm. A study

was conducted to determine the level of

prohexadione calcium derived resides

in or on processed commodites.

The proposed tolerance for

prohexadione calcium in/on peanut

nutmeat is 0.8 ppm and it is calculated

by converting the highest peanut

nutmeat RAC ppm for prohexadione

(0.3 ppm) to prohexadione calcium

equivalents (0.36 ppm), correcting for

50% storage stability loss (0.72), and

rounding up to 0.8 ppm. The proposed

tolerance for prohexadione calcium in/

on peanut hay is 0.4 ppm and it is

calculated by converting the highest

peanut hay RAC ppm for prohexadione

(0.26 ppm) to prohexadione calcium

equivalents (0.31 ppm) and rounding up

to 0.4 ppm.

Peanut samples treated at an

exaggerated rate were processed into

peanut meal and refined oil. Peanut

nutmeat and processed commodities

were analyzed for prohexadione.

Residues in the meal were less than in

the nuts, and no residues were detected

in the refined oil. Therefore, there was

no concentration of prohexadione

residues in processed commodities.

B. Toxicological Profile

1. Acute toxicity. Based on available

acute toxicity data prohexadione

calcium does not pose any acute toxicity

risks. The acute toxicity studies place

technical prohexadione calcium in
41832 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

acute toxicity category III for acute

dermal; and in acute toxicity category IV

for acute oral, acute inhalation, eye

irritation, and skin irritation and the

technical material is not a skin

sensitizer.

2. Genotoxicty. Ames Test (1 Study;

point mutation): Negative; In Vitro V79

Cells CH/HGPRT Locus Mammalian

Cell Mutation Assay (1 Study; point

mutation): Negative; In Vitro CHO

Cytogenetic Assay (1 Study;

Chromosome Damage): Negative; In

Vivo Mouse Micronucleus (1 Study;

Chromosome Damage): Negative; In vivo

Rat Bone Marrow Cytogenetic Assay (1

Study; Chromosomal Damage):

Negative; Rec Assay (1 Study; DNA

damage and repair): Negative; In Vitro

Rat Hepatocyte (1 Study; DNA damage

and repair): Negative.

Prohexadione calcium has been tested

in a total of 7 genetic toxicology assays

consisting of in vitro and in vivo studies.

Based on the results described above, it

can be stated in summary that

prohexadione calcium did not show any

mutagenic activity when tested under

the conditions of the studies mentioned

above. Therefore, prohexadione calcium

does not pose a mutagenic hazard to

humans.

3. Reproductive and developmental

toxicity-developmental toxicity— i. Rat.

A developmental study was conducted

via oral gavage in rats with dosages of

0, 100, 300, and 1,000 higest dose tested

(HDT) mg/kg/day with a No-AdverseEffect Level (NOAEL) of 1,000 mg/kg/

day the HDT for developmental and

maternal toxicity based on the fact that

no effects were observed for any test

parameter measured in this study.

Therefore, these NOAEL values are

significantly higher than the NOAEL

from the 1-year feeding study in dogs

used to establish the RfD.

ii. Rabbit. A developmental study was

conducted via oral gavage in rabbits

with dosages of 0, 40, 200, and 750

(HDT) mg/kg/day with a development

toxicity NOAEL of 40 mg/kg/day and a

maternal toxicity NOAEL of 40 mg/kg/

day based on the following: (a)

Excessive maternal mortality of 4/20

and 16/20 was observed in the 200 and

750 mg/kg/day dose levels tested,

respectively; (b) significant weight loss

was similarly observed in the 200 and

750 mg/kg/day dose group with

accompanying clinical signs; (c)

microscopic findings in the 750 mg/kg/

day dose group revealed stomach

erosion and lung congestion in many of

the animals that died; (d) in the 40 mg/

kg/day dose group a single rabbit lost its

righting reflex and showed splayed

limbs on day 25 due to a back injury it

sustained; and (e) no teratogenic effects,

as well as incidence of malformations

and developmental effects were

observed at any dose level tested (DLT),

however due to the mortality seen in the

200 and 750 mg/kg/day dose groups and

limited number of fetuses produced at

these dose levels, an additional study

was performed. (It should be noted that

a oral gavage range-finding study of six

rabbits per dose level was performed at

dose levels of 0, 100, 250, 500, and

1,000 mg/kg/day, in which similar

excessive mortality was observed in the

500 and 1,000 mg/kg/day dose groups

test as shown above. Additionally, body

weight was affected for all dose groups

tested and the clinical signs and

macroscopic findings observed in the

study discussed above were also noted

in the range-finding study. However,

body weight gain (BWG) was not

affected in the lowest dose group

tested.)

The doses selected for the additional

teratology study in the same strain of

rabbits were 0, 30,75, and 150 mg/kg/

day with a development toxicity

NOAEL of 150 mg/kg/day and a

maternal toxicity NOAEL that could not

be determined in this study based on

the following: (a) one low-, two mid-,

and three high-dose animals died prior

to cesarean section on day 29, however,

at the high dose group one cause of

death was determined to be due to

gavage error during test substance

administration, another dam in this

dose level died as a result of

pneumonia, and all other deaths could

not be determined; (b) at cesarean

section one to three animals/test group

were found to be not pregnant, but this

was not considered to be dose related;

(c) as a result of the unusual sex ratio

in the control group, a statistically

significant change in sex distribution

was found at the low dose group level,

however, these finding in b and c were

not dose dependent and were

considered to be within the range of

historical control data of this laboratory,

they were not regarded as treatment

related; and (d) no teratogenic effects, as

well as incidence of malformations and

developmental effects were observed at

any dose level tested, however due to

the inconsistent mortality (0 (control)-1-

2-1) seen at all treated dose levels, an

additional study with a range-finder was

performed at a different independent

laboratory.

An oral range-finding gavage

teratology study in the same strain of

rabbits (5 animals/dose level) was

examined in another independent

laboratory. The dose levels selected

were 0, 20,100, 250, 500, and 1000 mg/

kg/day. The finding in this study consist

of the following: (a) one animal died in

the 500 and 1,000 mg/kg/day dose

groups, however, the animal which died

in the 500 mg/kg/day dose group was

due to administration error detected

after necropsy; (b) no clinical signs were

noted and body weights was unaffected

throughout gestation, however, bwg and

food consumption was effected

temporarily from 250 mg/kg/day

onwards during the early stages of test

substance administration (day 6 to 9 of

gestation); (c) the number of viable

fetuses and fetal weights were

unaffected; and (d) no teratogenic

effects, as well as incidence of

malformations and developmental

effects were observed at any dose level

tested.

Based on these results the dose levels

selected for the main study at this

independent laboratory were 0, 30, 100,

and 350 mg/kg/day with a development

toxicity NOAEL of 350 mg/kg/day and

a maternal toxicity NOAEL of 100 mg/

kg/day based on the following: (a)

clinical signs were restricted to

premature delivery in 2 dams at the 350

mg/kg/day dose level; (b) average body

weights and food intake was not

affected at any dose levels tested,

however, body weight gain was

temporarily affected at the beginning of

test substance administration period at

the high dose group level; and (c) no

teratogenic effects, as well as incidence

of malformations and developmental

effects were observed at any dose level

tested.

4. Conclusions from the teratology

studies. Conflicting results have been

reported from one laboratory (initial

laboratory) at comparable dose levels

using the same study protocol with

respect to maternal toxicity in New

Zealand White rabbits. The conclusion

from the second study that maternal

toxicity is obvious by effects on body

weight during test substance

administration and the death of one out

of 20 does at the low dose level (30 mg/

kg/day) does not appear to be plausible

because:

i. Mortalities in this study showed no

dose depended trend (O (control)-l-2-1).

The cause of death of the other four

animals including the one of the 30 mg/

kg body weight group remained

undetermined even after necropsy.

Typical treatment related signs (gastric

lesions) as described at high doses in

range-finding or main studies were not

reported. Furthermore no mortality was

observed up to 350 mg/kg/day

(approximately 12-fold the NOAEL of 30

mg/kg in question) in a collective of 54

dams (three test groups) of the same

strain of rabbits under comparable

experimental conditions in the

independent different laboratory.
Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41833

ii. The effect on body weight gain

showed no statistical significance at 30

mg/kg body weight and the standard

deviation was high. In addition, at the

dose of 40 mg/kg/day there was no

effect in the same strain of rabbits

examined by the same laboratory in a

previous study and no effect on body

weight, body weight gain or food

consumption were noted at doses of 30

or 100 mg/kg/day in a study performed

in the same animal strain by the

independent laboratory.

Thus the following overall NOAELs

can be derived for the teratology studies:

a. NOAEL maternal toxicity. 100 mg/

kg body weight (rabbit) and 1,000 mg/

kg body weight (rat).

b. NOAEL prenatal toxicity. 100 mg/

kg body weight (rabbit) and 1000 mg/kg

body weight (rat).

The overall NOAEL on maternal

toxicity in rabbits is based on the

independent laboratory rabbit study due

to reduction of bwg and food intake at

dose levels of 250 mg/kg body weight

onwards.

The NOAEL (100 mg/kg body weight)

for prenatal toxicity in rabbits is based

on abortions observed at doses equal or

above 200 mg/kg body weight. The

NOAEL for malformations and other

developmental effects is even higher

(350 mg/kg body weight). Due to

excessive lethality of dams at doses

above this value, no evaluation of

fetuses was possible. No teratogenic

effects have been observed up to the

HDT of 350 mg/kg BW which could be

evaluated for developmental effects.

The teratogenicity study in rabbits

resulted in a developmental toxicity

NOAEL of 100 mg/kg and a maternal

toxicity NOAEL of 100 mg/kg. These

NOAEL values are higher than the

NOAEL from the 1-year feeding study in

dogs used to establish the RfD.

B. Reproductive Toxicity

A 2-generation reproduction study

with rats fed dosages of 0, 500, 5,000,

and 50,000 ppm with a reproductive/

developmental NOAEL of 50,000 ppm

and a maternal/parental/offspring

toxicity NOAEL of 500 ppm based on

the following: (1) mortalities were noted

for two mid-dose males (week 7 or 11),

two males and one female of the highdose (week 1), and one female died on

gestation day 13 without visible

abnormalities prior to death; (2) in the

high-dose parental F0 and F1

statistically significant decreased body

weights and increased water

consumption was observed; (3) in the

mid-dose level similar reduced body

weights were observed in the F1

offspring and F1 parents and with

increased water consumption being seen

in the F0 and F1 animals; (4) for both

high-dose generations, offspring growth

was slightly reduced; (5) microscopic

lesions in the glandular and nonglandular stomach consisting of

papillary ancadthosis, diffuse

ancanthosis, and hyperkeratosis were

observed in male and female rats of the

mid-dose and high-dose levels tested

with slight progression of severity from

the mid- to upper dose level; and (6) no

effects on reproductive or fertility

parameter was observed for any dose

group tested.

Therefore, these NOAEL values are

similar for maternal toxicity and

significantly higher for reproductive

effects (above the limit dose of 1,000

mg/kg/day) than the NOAEL from the 1-

year feeding study in dogs used to

establish the RfD.

1. Subchronic toxicity— teratology—

Rat. A developmental study was

conducted via oral gavage in rats with

dosages of 0, 100, 300, and 1,000 HDT

mg/kg/day with a NOAEL of 1,000 mg/

kg/day the HDT for developmental and

maternal toxicity based on the fact that

no effects were observed for any test

parameter measured in this study.

2. Teratology— Rabbits. A

developmental study was conducted via

oral gavage in rabbits with dosages of 0,

40, 200, and 750 (HDT) mg/kg/day with

a development toxicity NOAEL of 40

mg/kg/day and a maternal toxicity

NOAEL of 40 mg/kg/day based on the

following: (a) excessive maternal

mortality of 4/20 and 16/20 was

observed in the 200 and 750 mg/kg/day

dose levels tested, respectively; (b)

significant weight loss was similarly

observed in the 200 and 750 mg/kg/day

dose group with accompanying clinical

signs; (c) microscopic findings in the

750 mg/kg/day dose group revealed

stomach erosion and lung congestion in

many of that animals that died; (d) in

the 40 mg/kg/day dose group a single

rabbit lost its righting reflex and showed

splayed limbs on day 25 due to a back

injury it sustained; and (e) no

teratogenic effects, as well as incidence

of malformations and developmental

effects were observed at any dose level

tested, however due to the mortality

seen in the 200 and 750 mg/kg/day day

dose groups and limited number of

fetuses produced at these dose levels, an

additional study was performed. (It

should be noted that an oral gavage

range-finding study of six rabbits per

dose level was performed at dose levels

of 0, 100, 250, 500, and 1,000 mg/kg/

day, in which similar excessive

mortality was observed in the 500 and

1,000 mg/kg/day dose groups test as

shown above. Additionally, body weight

was affected for all dose groups tested

and the clinical signs and macroscopic

findings observed in the study

discussed above were also noted in the

range-finding study. However, body

weight gain was not affected in the

lowest dose group tested.)

The doses selected for the additional

teratology study in the same strain of

rabbits were 0, 30, 75, and 150 mg/kg/

day with a development toxicity

NOAEL of 150 mg/kg/day and a

maternal toxicity NOAEL that could not

be determined in this study based on

the following: (a) one low-, two mid-,

and three high-dose animals died prior

to cesarean section on day 29, however,

at the high dose group one cause of

death was determined to be due to

gavage error during test substance

administration, another dam in this

dose level died as a result of

pneumonia, and all other deaths could

not be determined; (b) at cesarean

section one to three animals/test group

were found to be not pregnant, but this

was not considered to be dose related;

(c) as a result of the unusual sex ratio

in the control group, a statistically

significant change in sex distribution

was found at the low dose group level,

however, these finding in (b) and (c)

were not dose dependent and were

considered to be within the range of

historical control data of this laboratory,

they were not regarded as treatment

related; and (d) no teratogenic effects, as

well as incidence of malformations and

developmental effects were observed at

any dose level tested, however due to

the inconsistent mortality (0 (control)-1-

2-1) seen at all treated dose levels, an

additional study with a range-finder was

performed at a different independent

laboratory.

An oral range-finding gavage

teratology study in the same strain of

rabbits (5 animals/dose level) was

examined in another independent

laboratory. The dose levels selected

were 0, 20, 100, 250, 500, and 1000 mg/

kg/day. The finding in this study consist

of the following: (a) one animal died in

the 500 and 1,000 mg/kg/day dose

groups, however, the animal which died

in the 500 mg/kg/day dose group was

due to administration error detected

after necropsy; (b) no clinical signs were

noted and body weights was unaffected

throughout gestation, however, body

weight gain and food consumption was

effected temporarily from 250 mg/kg/

day onwards during the early stages of

test substance administration (day 6 to

9 of gestation); (c) the number of viable

fetuses and fetal weights were

unaffected; and (d) no teratogenic

effects, as well as incidence of

malformations and developmental
41834 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

effects were observed at any dose level

tested.

Based on these results the dose levels

selected for the main study at this

independent laboratory were 0, 30, 100,

and 350 mg/kg/day with a development

toxicity NOAEL of 350 mg/kg/day and

a maternal toxicity NOAEL of 100 mg/

kg/day based on the following: (1)

clinical signs were restricted to

premature delivery in 2 dams at the 350

mg/kg/day dose level; (2) average body

weights and food intake was not

affected at any dose levels tested,

however, body weight gain was

temporarily affected at the beginning of

test substance administration period at

the high dose group level; and (3) no

teratogenic effects, as well as incidence

of malformations and developmental

effects were observed at any dose level

tested.

3. Conclusions from the teratology

studies. i. Conflicting results have been

reported from one laboratory (initial

laboratory) at comparable dose levels

using the same study protocol with

respect to maternal toxicity in New

Zealand White rabbits. The conclusion

from the second study that maternal

toxicity is obvious by effects on body

weight during test substance

administration and the death of one out

of 20 does at the low dose level (30 mg/

kg/day) does not appear to be plausible

because: i. Mortalities in this study

showed no dose depended trend (O

(control)-l-2-1). The cause of death of

the other four animals including the one

of the 30 mg/kg body weight group

remained undetermined even after

necropsy. Typical treatment related

signs (gastric lesions) as described at

high doses in range-finding or main

studies were not reported. Furthermore

no mortality was observed up to 350

mg/kg/day (approximately 12-fold the

NOAEL of 30 mg/kg in question) in a

collective of 54 dams (three test groups)

of the same strain of rabbits under

comparable experimental conditions in

the independent different laboratory.

ii. The effect on BWG showed no

statistical significance at 30 mg/kg body

weight and the standard deviation was

high. In addition, at the dose of 40 mg/

kg/day there was no effect in the same

strain of rabbits examined by the same

laboratory in a previous study and no

effect on body weight, BWG or food

consumption were noted at doses of 30

or 100 mg/kg/day in a study performed

in the same animal strain by the

independent laboratory.

iii. Thus the following overall

NOAELs can be derived for the

teratology studies:

iv. NOAEL maternal toxicity. 100 mg/

kg body weight (rabbit) and 1,000 mg/

kg body weight (rat).

v. NOAEL prenatal toxicity. 100 mg/

kg body weight (rabbit) and 1,000 mg/

kg body weight (rat).

The overall NOAEL on maternal

toxicity in rabbits is based on the

independent laboratory rabbit study due

to reduction of BWG and food intake at

dose levels of 250 mg/kg body weight

onwards.

The NOAEL (100 mg/kg body weight)

for prenatal toxicity in rabbits is based

on abortions observed at doses equal or

above 200 mg/kg body weight. The

NOAEL for malformations and other

developmental effects is even higher

(350 mg/kg body weight). Due to

excessive lethality of dams at doses

above this value, no evaluation of

fetuses was possible. No teratogenic

effects have been observed up to the

highest dose level of 350 mg/kg body

weight which could be evaluated for

developmental effects.

4. Chronic toxicity. Based on review

of the available data, the Reference Dose

(RfD) for prohexadione calcium will be

based on a 1-year feeding study in dogs

with a threshold NOAEL of 20 mg/kg/

day. Using an uncertainty factor of 100,

the RfD is calculated to be 0.2 mg/kg/

day. The following are summaries of

studies submitted to EPA.

i. Chronic feeding - Nonrodent. A 1-

year feeding study in dogs fed dosages

of 0, 20, 200, or 1,000 mg/kg/day (HTD)

with a NOAEL of 20 mg/kg/day for

female and male dogs based on the

following effects: (a) clinical signs

consisting of pale colored feces were

observed with the highest incidence

being recorded at HDLT; (b) slightly

reduced clinical chemical values were

observed in high dose male and female

dogs for serum albumin and potassium

and increased phosphorus levels for

both male and female dogs of the HDT;

(c) red blood cell parameters (packed

cell volume, hemoglobin, and red blood

cell count) were slightly lower at the

HDT for males and females dogs, only

red blood cell counts were reduced in

the male and female dogs at the 200 mg/

kg/day dose level in week 52; and (d)

histopathological examination revealed

dilated/basophilic renal cortical tubules

with and without fibrosis in both male

and female dogs at the 200 and 1,000

mg/kg/day dose levels.

ii. Chronic feeding/oncogenicity —

Rats. A combined chronic/oncogenicity

in rats (Fischer 344) fed dosages of 0, 18,

94, 469, and 968 mg/kg/day for male

rats and 0, 22, 114, 572, and 1,180 mg/

kg/day for female rats with a NOAEL of

94 mg/kg/day for male rats and 114 mg/

kg/day for female rats based on the

following effects: (a) decreased in body

weights were observed in both male and

female rat at the 968 and 1,180 mg/kg/

day DLT; (b) clinical chemical effects

(i.e., lower potassium, bilirubin, and

glucose levels) were observed in male

and female rats at the 968 and 1,180 mg/

kg/day DLT, in the 469 mg/kg/day dose

level, reduced glucose levels were only

seen in the males, and increased

albumin/globulin ratios, sodium,

chloride and calcium levels were

observed only in the 1,180 mg/kg/day

dose level in females; (c) increased

urine volumes and lower specific

gravity were observed in the mid-high

and high-dose groups for both male and

female rats; (d) minor changes in organ

weights were noted for animals of the

high dose group only, which consisted

of increased relative liver, adrenal and

kidney weights, the latter also absolute

in females only, at week 26; at the end

of the study decreased liver weights and

increased relative brain and testis

weights were noted and these changes

were considered to be associated with

the decreased body weights; (e)

macroscopic finding revealed an

increase of pituitary nodules in the high

dose group tested for male and female

rats which was not confirmed

histopathologically and submucosal

ectopic tissue in the glandular stomach

was found in both male and female rats

in the highest dose levels that was

confirmed by histopathology which

showed an increase of squamous cell

hyperplasia in males and of basal cell

hyperplasia in the forestomach at this

dose level; (f) a higher incidence of

cellular hyperplasia was observed in the

thyroid in the mid-high and high dose

levels for male and female rats; and (g)

no increased incidence of neoplasms

occurred at any dose levels tested in this

study.

iii. Oncogenicity - Mice. A

carcinogenicity study in B6C3F1 mice

fed dosages of 0, 55, 279, 2,847, and

5,911 mg/kg/day for male mice and 0,

68, 351, 3,489, and 7334 mg/kg/day for

female mice with a NOAEL of 279 mg/

kg/day for male mice and 351 mg/kg/

day for female mice based on the

following effects: (a) statistically

significant decreases in body weights

were observed in male mice at the 2,847

and 5,911 mg/kg/day dose levels and in

female mice at the 7,334 mg/kg/day

dose levels tested; (b) a variety of

changes in hematological parameter was

noted in the respective investigations at

weeks 52, 78, and 104, however, most

of the changes were not dose related or

consistent over time; (c) increased

absolute and/or relative heart, brain,

testes, liver, ovary, and kidney weights
Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41835

were observed in the mid-high and

highest dose group test with a slight

progression of severity to the highest

dose group tested; (d) a higher incidence

of splenomegaly was observed only in

the male mice of the highest dose group;

(e) histopathological examinations

revealed an ectopic proliferation of the

mucosal and glandular epithelium in

the submucosal layer of the glandular

stomach in male and female mice in the

highest dose group tested, these changes

were assessed to represent heteroplastic,

ectopic proliferative changes

accompanied by lumen dilatation and

cytological degeneration; (f) a higher

incidence of hyperkeratosis of the

forestomach was observed in both male

and female mice and hyperplasia of the

squamous epithelium of the

forestomach of female male mice was

observed in the highest dose group

tested; (g) vacuolic changes in the

exocrine pancreas of the high dose

female was observed; (h) no increased

incidence of neoplasms occurred at any

dose levels tested in this study.

iv. Carcinogenicity. Prohexadione

calcium was shown to be noncarcinogenic in mice, rats, and dogs.

Therefore, based on the results of the

carcinogenicity studies in mice, rats,

and dogs and the results of genotoxicity

testing, the threshold approach to

regulating prohexadione calcium is

appropriate

5. Animal metabolism. The

metabolism in animals (goats and

poultry) is adequately understood.

6. Endocrine disruption. No specific

tests have been conducted with

prohexadione calcium 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

studies, i.e., teratology and multigeneration reproductive studies, which

would suggest that prohexadione

calcium produces endocrine related

effects.

C. Aggregate Exposure

1. Dietary exposure. For purposes of

assessing the potential dietary exposure,

K-I has estimated aggregate exposure

based on the Theoretical Maximum

Residue Contribution (TMRC) from the

proposed tolerance for prohexadione

calcium in/on peanut nutmeat at 0.8

ppm. The TMRC is a ‘‘worse case’’

estimate of dietary exposure since it is

assumed that 100% of all crops for

which tolerances are established are

treated and that pesticide residues are

always found at the tolerance levels.

Dietary exposure to residues of

prohexadione calcium in or on food will

be limited to residues on peanut

nutmeat. Peanut hay and meal are fed to

animals; thus exposure of humans to

residues in peanut hay and meal might

result if such residues carry through to

meat, milk, poultry, or eggs. However,

K-I has concluded that there is no

reasonable expectation that measurable

residues of prohexadione calcium will

occur in meat, milk, poultry, or eggs

from this use. There are no other

established U.S. tolerances for

prohexadione calcium, and there are no

currently registered uses for

prohexadione calcium on food or feed

crops in the U.S.

Dietary exposure to residues of

prohexadione calcium from the

proposed tolerances on peanuts would

account for less than 0.14% of the RfD

(0.20 mg/kg/day) for the general

population of the US and all

subpopulation groups. The most highly

exposed group in the subpopulation

groups would be non-nursing infants (<

1 year old), which uses 0.39% of the

RfD.

2. Drinking water. Other potential

sources of exposure to prohexadione

calcium for the general population are

residues in drinking water and exposure

from non-occupational sources.

Exposure to residues of prohexadione

calcium in drinking water is not

anticipated. There is no established

Maximum Concentration Level (MCL) or

Health Advisory Level (HAL) for

prohexadione calcium under the Safe

Drinking Water Act (SDWA).

3. Non-dietary exposure.

Prohexadione calcium is not currently

registered for any nonagricultural use.

The potential for non-occupational

exposure to the general population is

therefore not present.

D. Cumulative Effects

The potential for cumulative effects of

prohexadione calcium and other

substances that have a common

mechanism of toxicity has been

considered. No evidence or information

exists to suggest that toxic effects

produced by prohexadione calcium

would be cumulative with those of any

other chemical compound.

E. Safety Determination

1. U.S. population— Reference dose

(RfD). Using the conservative exposure

assumptions described above and based

on the completeness and the reliability

of the toxicity data, it has estimated that

aggregate exposure to prohexadione

calcium will utilize 0.14% of the RfD for

the U.S. population. K-I concludes that

there is a reasonable certainty that no

harm will result from the aggregate

exposure to residues of prohexadione

calcium, including anticipated dietary

exposure and non-occupational

exposures.

2. Infants and children. Since

developmental and reproductive

toxicity occurs at levels at or above the

levels shown to exhibit parental toxicity

and since these levels are significantly

higher than those used to calculate the

RfD, K-I believes the RfD of 0.20 mg/kg/

day is an appropriate measure of safety

for infants and children.

Using the conservative exposure

assumptions described above, it is

concluded that the portion of the RfD

that will be utilized by aggregate

exposure to residues of prohexadione

calcium resulting from the proposed

tolerances will be less than 0.14% for all

populations of infants and children. The

most highly exposed group in the

subpopulation groups would be nonnursing infants (< 1 year old) which

uses 0.39% of the RfD. Therefore, based

on the completeness and reliability of

the toxicity data and the conservative

exposure assessment, it is concluded

that there is a reasonable certainty that

no harm will result to infants and

children from aggregate exposure to the

residues of prohexadione calcium,

including all anticipated dietary

exposure and all other non-occupational

exposures.

F. International Tolerances

A maximum residue level has not

been established for prohexadione

calcium by the Codex Alimentarius

Commission.

[FR Doc. 98–20768 Filed 8–4–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–818; FRL–6017–1]

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–818, must be

received on or before September 4,

1998.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch, Information

Resources and Services Division