Federal Register / Vol. 63, No. 129 /Tuesday, July 7, 1998 / Notices 36681

Individuals requiring special

accommodation at SAB meetings,

including wheelchair access, should

contact the appropriate DFO at least five

business days prior to the meeting so

that appropriate arrangements can be

made.

Dated: June 30, 1998.

A. Robert Flaak,

Acting Staff Director, Science Advisory Board.

[FR Doc. 98–17965 Filed 7–6–98; 8:45 am]

BILLING CODE 6560–50–P

ENVIRONMENTAL PROTECTION

AGENCY

[PF–814; FRL–5795–6]

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–814, must be

received on or before August 6, 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 to: oppdocket@epamail.epa.gov. Follow the

instructions under ‘‘SUPPLEMENTARY

INFORMATION.’’ No confidential

business information should be

submitted through e-mail.

Information submitted as a comment

concerning this document may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI). CBI should not be submitted

through e-mail. Information marked as

CBI will not be disclosed except in

accordance with procedures set forth in

40 CFR part 2. A copy of the comment

that does not contain CBI must be

submitted for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments will be available for public

inspection in Rm. 1132 at the address

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

Monday through Friday, excluding legal

holidays.

FOR FURTHER INFORMATION CONTACT: The

product manager listed in the table

below:

Product Manager Office location/telephone number Address

Bipin Gandhi (PM 5) ...... Rm. 4W53, CS #2, 703–308–8380, e-mail:gandhi.bipin@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Cynthia Giles-Parker

(PM 22).

Rm. 229, CM #2, 703–305–7740, e-mail: giles-parker.cynthia@epamail.epa.gov. Do.

SUPPLEMENTARY INFORMATION: EPA has

received pesticide petitions as follows

proposing the establishment and/or

amendment of regulations for residues

of certain pesticide chemicals in or on

various food commodities under section

408 of the Federal Food, Drug, and

Comestic Act (FFDCA), 21 U.S.C. 346a.

EPA has determined that these petitions

contain data or information regarding

the elements set forth in section

408(d)(2); however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data supports granting of the

petition. Additional data may be needed

before EPA rules on the petition.

The official record for this notice of

filing, as well as the public version, has

been established for this notice of filing

under docket control number [PF–814]

(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: June 24,1998.

Peter Caulkins, Acting

Director, Registration Division, Office of

Pesticide Programs.

Summaries of Petitions

Petitioner summaries of the pesticide

petitions are printed below as required

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

summaries of the petitions were

prepared by the petitioners and

represent the views of the petitioners.

EPA is publishing the petition

summaries verbatim without editing

them in any way. The petition summary

announces the availability of a

description of the analytical methods

available to EPA for the detection and

measurement of the pesticide chemical

residues or an explanation of why no

such method is needed.

1. Rhodia Inc.

PP 6E4714

EPA has received a pesticide petition

(PP 6E4714) from Rhodia Inc., CN 7500

Cranbury NJ 08512-7500 proposing

pursuant to section 408(d) of the Federal

Food, Drug, and Cosmetic Act, 21 U.S.C.

346a(d), to amend 40 CFR 180.1001 to

establish an exemption from the

requirement of a tolerance for

Sucroglycerides derived from 21 CFRapproved fats and oils in or on the raw

agricultural commodity after harvest.

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
36682 Federal Register / Vol. 63, No. 129 /Tuesday, July 7, 1998 / Notices

the petition. Additional data may be

needed before EPA rules on the petition.

A. Toxicological Profile

As part of the EPA policy statement

on inert ingredients published in the

Federal Register of April 22, 1987 (52

FR 13305) (FRL 3190-1), the Agency set

forth a list of studies which would

generally be used to evaluate the risks

posed by the presence of an inert

ingredient in a pesticide formulation.

However, where it can be determined

without that data that the inert

ingredient will present minimal or no

risk, the Agency generally does not

require some or all of the listed studies

to rule on the proposed tolerance or

exemption from the requirement of a

tolerance for an inert ingredient.

The data we believe supports

establishing an exemption from

tolerances is summarized below. More

detailed information has been provided

to the Agency in previous submissions.

Sucroglycerides are a mixture of

substances, primarily of mono- and diglycerides and sucrose esters of fatty

acids. The product is produced through

a process of transesterification of an

edible fat or oil with sucrose in the

presence of a solvent. The resulting

crude mixture is purified by vacuum

distillation, counter-current extraction,

and further distillation to remove

solvent and other impurities.

Rhodia has conducted studies on the

physicochemical characteristics of a

sucroglyceride derived from palm oil.

The studies evaluated the product

chemistry, solubility, and the octanol/

water partition coefficient of

sucroglycerides.

1. Acute toxicity. The LD50 of palm

oil-derived sucroglyceride is estimated

to be greater than 30 grams/kg. In

addition, early studies of

sucroglycerides use in the diets of

bottle-feeding calves indicated a lack of

toxic response and an increased weight

gain and improved food utilization.

Sucrose esters of fatty acids are

approved for food use and mono- and

di-glycerides are GRAS-approved

additives; sucroglycerides are GRASapproved and approved for food use in

Europe; sucrose esters of fatty acids and

mono- and di-glycerides are unlikely to

be dermally absorbed.

Preliminary attempts to examine the

potential environmental toxicity of

Sucroglycerides have been made, but

were not possible due to the

physicochemical properties of the

material. Sucroglycerides have the

consistency of wax at low temperatures

and petroleum jelly when warmed. In

addition, as can be seen from the

determination of the octanol/water

partition coefficient, sucroglycerides are

not water soluble (estimated Ko/w >

3.38 x 106), thereby precluding aquatic

toxicity testing.

2. Genotoxicty. The components of

sucroglycerides already have regulatory

acceptance as agricultural inerts

exempted from tolerance;

sucroglycerides are a complex mixture

of sucrose esters of fatty acids and

mono- and di-glycerides derived from

FDA-approved edible fats and oils.

None of the components of

sucroglycerides are genotoxic.

3. Reproductive and developmental

toxicity. An early study of the potential

effects of Sucroglycerides on

reproduction in rats indicated that there

were no effects on reproduction, pup

survival and development, or pup

anomalies at dietary dose levels up to

2%.

4. Subchronic toxicity. In 1980 a 13-

week subchronic toxicity study of

Sucroglycerides with an 8-week

‘‘recovery period’’ was conducted in

beagle dogs. This study utilized doses as

high as 20% of the total dietary intake.

Decrease body weight gains (bwt) were

observed in the 10% and 20% dose

groups. These animals showed a

significant weight gain recovery during

the post-treatment period. No doserelated changes were noted in

hematology, urinalysis,

ophthalmoscopy, gross pathology or

organ weights. Increased alkaline

phosphatase and SGPT levels and fatty

changes in the liver were noted for some

animals in the high dose group, but

most returned to normal during the

recovery phase. Results should be

interpreted keeping in mind that 20% of

sucroglycerides in the diet represents a

significant change in the normal dietary

composition and could possibly cause

changes in the nutritional status of the

animals.

5. Chronic toxicity. A chronic

toxicity/carcinogenicity study of

Sucroglycerides was conducted in rats

in 1982. Sprague-Dawley rats received

0%, 5%, 10%, or 20% sucroglycerides

in the diet for 2-years. Clinical

observations associated with treatment

were pale feces and poor grooming.

Survival was greater among treated rats

than controls. Treated rats showed a

dose-related decrease in weight gain

during the early part of the study,

particularly in males. Weight gain then

became similar to that of controls until

the last few weeks of the study when

control rats lost more weight than did

treated rats. Alkaline phosphatase and

SGPT levels were elevated for high dose

animals until week 25, but were

comparable to controls during weeks 51-

102. No treatment-related changes in

hematology, ophthalmoscopy, gross

pathology, organ weights, or

tumorigenesis were reported.

6. Animal metabolism.

Sucroglycerides are derived from a

variety of 21 CFR-approved edible fats

and oils including, but not limited to,

lard, tallow, palm oil, rapeseed (canola)

oil, and coconut oil. Mono- and diglycerides are GRAS substances 21 CFR

184.1505 and already have regulatory

acceptance as agricultural inerts and

adjuvants exempted from tolerance

requirements (under 40 CFR 80.1001(c)),

as do sucrose, fatty acids conforming to

21 CFR 172.860, methyl esters of edible

fats and oils, and sucrose esters of fatty

acids such as sorbitan fatty acid esters.

7. Metabolite toxicology. The

components of sucroglycerides and

related substances already have

regulatory acceptance as agricultural

inerts exempted from tolerance

requirements

8. Endocrine disruption.

Sucroglycerides are not derived from,

nor contain any compounds which are

known to be, or are suspected to be,

endocrine disruptors. Sucroglycerides

are derived from a variety of 21 CFRapproved edible fats and oils including,

but not limited to, lard, tallow, palm oil,

rapeseed (canola) oil, and coconut oil.

Mono- and di-glycerides are GRAS

substances 21 CFR 184.1505 and already

have regulatory acceptance as

agricultural inerts and adjuvants

exempted from tolerance requirements

(under 40 CFR 180.1001(c)), as do

sucrose fatty acids conforming to 21

CFR 172.860, methyl esters of edible fats

and oils, and sucrose esters of fatty

acids such as sorbitan fatty acid esters.

B. Aggregate Exposure

Consistent with section 408(c)(2)(B) of

FFDCA, Rhodia, Inc. believes that,

based on our prior submissions (as

Rhone-Poulenc, Inc.), EPA now has

sufficient data to assess the hazards of

sucroglycerides and to make a

determination on aggregate exposure,

consistent with section 408(b)(2), for

tolerance exemptions for the residues of

sucroglycerides on growing crops, raw

agricultural commodities after harvest

and animals.

1. Dietary exposure—i. From food and

feed uses, drinking water, and nondietary exposures. For the purposes of

assessing the potential dietary exposure

under these exemptions, Rhodia, Inc.

considered that under these exemptions

sucroglycerides could be present in all

raw and processed agricultural

commodities although, due to a lack of

water solubility (octanol/water partition

coefficient was estimated as Ko/w >

3.38 x 106) no drinking water exposure
Federal Register / Vol. 63, No. 129 /Tuesday, July 7, 1998 / Notices 36683

was possible. Non-occupational, nondietary exposure is highly unlikely

given that the inhalation potential or

dermal absorption of these substances

are not feasible. No concerns for risks

associated with any potential exposure

scenarios are reasonably foreseeable.

ii. Sucroglycerides are derived from a

variety of 21 CFR-approved edible fats

and oils including, but not limited to,

lard, tallow, palm oil, rapeseed (canola)

oil, and coconut oil. Mono- and diglycerides are GRAS substances 21

CFR.184.1505 and already have

regulatory acceptance as agricultural

inerts and adjuvants exempted from

tolerance requirements (under 40 CFR

180.1001(c)), as do sucrose fatty acids

conforming to 21 CFR 172.860, methyl

esters of edible fats and oils, and

sucrose esters of fatty acids such as

sorbitan fatty acid esters.

iii. Sucroglycerides derived from

edible fats and oils have been granted

Self-Affirmed GRAS status in the U.S

and are approved for food use in Europe

and by the WHO Joint Expert Committee

on Foods (JECFA), with an Acceptable

Daily Intake (ADI) of 0-20 mg/kg/day.

Sucroglycerides are currently marketed

by Rhodia, Inc. for food use.

Sucroglycerides, including those

derived from palm oil, hydrogenated

palm oil, tallow, rapeseed oil, castor oil,

and coconut oil have been used safely

in foods in Europe since the early 1960s.

2. Drinking water. Sucroglycerides are

insoluble in water, hence exposure from

drinking water is not considered to be

a route of exposure.

3. Non-dietary exposure. Nonoccupational, non-dietary exposure is

highly unlikely given that the inhalation

potential or dermal absorption of these

substances are not feasible. No concerns

for risks associated with any potential

exposure scenarios are reasonably

foreseeable.

C. Cumulative Effects

Section 408(b)(2)(D)(v) of FFDCA

requires that, when considering whether

to establish, modify, or revoke a

tolerance or tolerance exemption, the

Agency consider ‘‘available

information’’ concerning the cumulative

effects of a particular chemical’s

residues and ‘‘other substances that

have a common mechanism of toxicity.’’

In the case of sucroglycerides, the lack

of observed toxicity of these substances

after acute and chronic exposure would

suggest that a cumulative risk

assessment is therefore not necessary.

D. Safety Determination

1. U.S. population. Sucroglycerides

derived from edible fats and oils have

been granted Self-Affirmed GRAS status

in the U.S and are approved for food use

in Europe and by the WHO Joint Expert

Committee on Foods (JECFA), with an

Acceptable Dietary Intake (ADI) of 0-20

mg/kg/day. Sucroglycerides are derived

from a variety of 21 CFR-approved

edible fats and oils including, but not

limited to, lard, tallow, palm oil,

rapeseed (canola) oil, and coconut oil.

Mono- and di-glycerides are GRAS

substances 21 CFR 184.1505 and already

have regulatory acceptance as

agricultural inerts and adjuvants

exempted from tolerance requirements

(under 40 CFR 180.1001(c)), as do

sucrose, fatty acids conforming to 21

CFR 172.860, methyl esters of edible fats

and oils, and sucrose esters of fatty

acids such as sorbitan fatty acid esters.

Based on these materials’ low-risk

profiles, there is a reasonable certainty

that no harm to the U.S. population will

result from aggregate exposure to

sucroglycerides.

2. Infants and children. FFDCA

section 408 provides that EPA shall

apply an additional tenfold margin of

safety for infants and children in the

case of threshold effects to account for

pre- and postnatal toxicity and the

completeness of the data base unless

EPA concludes that a different margin of

safety will be safe for infants and

children. Margins of safety are

incorporated into EPA risk assessments

either directly through the use of margin

of exposure analysis or through using

uncertainty (safety) factors in

calculating a dose level that poses no

appreciable risk to humans.

Due to the extensive available

toxicology database including a

reproductive toxicity study and studies

of sucroglycerides in the diets of bottlefed calves, and the low expected

toxicity of these compounds, Rhodia,

Inc. does not believe a safety factor

analysis is necessary in assessing the

risk of these compounds. For the same

reasons we believe the additional safety

factor is unnecessary.

E. International Tolerances

Sucroglycerides derived from edible

fats and oils are approved for food use

in Europe and by the WHO JECFA, with

an ADI of 0-20 mg/kg/day.

Sucroglycerides are currently marketed

by Rhodia, Inc. for food use.

Sucroglycerides, including those

derived from palm oil, hydrogenated

palm oil, tallow, rapeseed oil, castor oil,

and coconut oil have been used safely

in foods in Europe since the early 1960s.

There are no Codex Alimentarius

Commission (Codex), Canadian or

Mexican residue limits for

sucroglycerides, which have been

granted self-affirmed GRAS status in the

U.S.

F. Conclusion

Based on the information and data

considered, Rhodia, Inc. proposes that

exemption from the requirements of a

tolerance be established for

Sucroglycerides derived from 21 CFRapproved fats and oils when used in

accordance with good agricultural

practice as inert ingredients in pesticide

formulations applied to growing crops

or to raw agricultural commodities after

harvest (under 40 CFR.180.1001(c)).

2. Rhone-Poulenc Ag Company

PP 8F4969

EPA has received a pesticide petition

(PP 8F4969) from Rhone-Poulenc Ag

Company, P.O. Box 12014, 2 T.W.

Alexander Drive, 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 a tolerance for residues of

fosetyl-Al (aluminum tris(Oethylphosphonate) in or on the raw

agricultural commodity bananas at 3.0

parts per million (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 fosetyl-Al in plants is adequately

understood. Adequate data on the

nature of the residues in plants,

including identification of major

metabolites and degradates of fosetyl-Al,

are available. Radiolabeled studies on

the uptake, translocation and

metabolism in plants show that the

chemical proceeds through hydrolytic

cleavage of the ethyl ester. The major

residues are fosetyl-Al, phosphorus acid

and ethanol. The tolerances are

established for the parent only, that is

fosetyl-Al. There is no reasonable

expectation of residues occurring in

eggs, milk, and meat of livestock and

poultry since there are no livestock feed

items associated with commodities

treated with fosetyl-Al. Relating

specifically to the proposed tolerance on

bananas, no processed food or livestock

feed items are associated with this

commodity. Accordingly, tolerances in

meat, animal byproducts and milk are

not necessary.
36684 Federal Register / Vol. 63, No. 129 /Tuesday, July 7, 1998 / Notices

2. Analytical method. Adequate

methods are available for enforcement

purposes. There are two analytical

methods acceptable for determining

residues of fosetyl-Al in plants: a gas

chromatography method is available for

enforcement of tolerance in pineapple

and is listed as Method I in PAM, Vol.

II; a GC/phosphorus specific flame

photometric detector (FPD-P) method

(Rhone-Poulenc Method No. 163) for

citrus has undergone a successful

method tryout on oranges and has been

sent to the FDA for inclusion in PAM as

Method II.

3. Magnitude of residues. Seven field

sites in six Latin American countries

were treated in two applications at the

rate of 4.8 Kg/ha/application. Two of the

seven trials also included a 2x rate

application. Applications were made by

two methods: foliar spray by ground

equipment and tree injection into the

pseudostem. The applications were

made approximately 70-days apart with

a PHI of 0- days for the foliar treatments

and 1-day for the injection treatments.

Each plot included both bagged and

unbagged bunches. Fosetyl-Al residues

greater than the LOT were found in 22

of the 96 treated banana samples.

Residues were highest in the 1x and 2x

foliar unbagged treatments, averaging

0.45 ppm from the 1x treatment and

0.69 ppm from the 2x treatment.

Residues were very low from all foliar

bagged and all injection treatments,

averaging at or below the LOT. Residues

from all treated samples ranged from no

detects to 1.99 ppm.

B. Toxicological Profile

1. Acute toxicity. Fosetyl-Al presents

a minimal acute hazard. The acute

toxicity data support that acute

exposure is unlikely to constitute any

significant risk. A complete battery of

acute toxicity studies for fosetyl-Al

technical have been conducted. The

LD50 from the acute oral rat is 5.4 g/kg

and the LD50 from an acute dermal

rabbit study is >2 g/kg. The LC50 for a

rat inhalation study is >1.73 mg/L. The

acute oral rat and primary dermal

irritation studies indicate category IV

toxicity. A guinea pig dermal

sensitization study shows fosetyl-Al is

not a skin sensitizer. The primary eye

irritation study in rabbits shows fosetylAl to be an eye irritant with Category I

toxicity.

2. Genotoxicity. Fosetyl-Al is neither

mutagenic nor genotoxic. The genetic

toxicity potential of fosetyl-Al was

assessed in several assays. Eight

mutagenicity tests performed with

fosetyl-Al were negative. The tests

included two Ames assays with S.

typhimurium, two phase induction

assays using E. coli, two micronucleus

studies in mice, one DNA repair assay

using E. coli and one mutation assay in

Saccharomyces cereviseae.

3. Reproductive and developmental

toxicity. Fosetyl-Al is not a reproductive

toxicant and shows no evidence of

estrogenic or androgenic related effects.

In a 3-generation reproduction study,

fosetyl-Al was administered to rats at

dietary levels of 0, 6,000, 12,000 or

24,000 ppm. No adverse effects on

reproductive performance or pup

survival were observed in any dose

group. The LEL was established at

12,000 ppm based on effects on animal

weights and urinary tract changes. The

NOEL for all effects was 6,000 ppm.

Developmental toxicity studies were

conducted with technical grade fosetylAl in rats and rabbits. These studies are

summarized below.

i. Rat. A teratology study in rats dosed

via oral gavage at 500, 1,000 or 4,000

mg/kg/day showed a developmental

NOEL of 1,000 mg/kg. At 4,000 mg/kg,

there was maternal toxicity, as

evidenced by effects on animal weights,

maternal deaths, increased resorptions

and delayed fetal ossification.

ii. Rabbit. A rabbit teratology study

showed no toxic effects at oral doses up

to 500 mg/kg. Effects of fosetyl-Al on

fetal development were observed only

in the rat at a dose producing severe

maternal toxicity. In the absence of

maternal toxicity, no adverse effects on

fetal development were observed, i.e. at

1,000 milligram/kilograms/day (mg/kg/

day) in rats or at 500 mg/kg/day in

rabbits.

4. Subchronic toxicity. In subchronic

studies, no significant toxicity was

observed even at doses exceeding the

limit of 1,000 mg/kg/day.

i. A 21-day dermal study in rabbits

showed mild to moderate skin irritation

and a NOEL of 1.5 g/kg/day.

ii. A 90-day feeding study in rats

showed a NOEL of >5,000 ppm; the LEL

was 25,000 ppm with extramedullary

hematopoiesis in the spleen.

iii. A 90-day dog feeding study

showed a NOEL of 10,000 ppm and a

LEL at 50,000 ppm, at which the test

animals had a lower serum potassium

level than untreated animals.

5. Chronic toxicity. Chronic toxicity

studies have been conducted in dogs

and rats.

i. Dog. Fosetyl-Al was fed to dogs for

2-years at concentrations of 0, 10,000,

20,000, and 40,000 ppm. The NOEL was

10,000 ppm, equivalent to 250 mg/kg/

day. The LEL was 20,000 ppm based on

a slight degenerative effect on the testes.

These testicular changes, as well as a

few scattered clinical changes, were

seen in the high dose dogs. No effects

were observed in the urinary tract.

ii. Rat. Fosetyl-Al was administered

via admixture in the diet to CD rats at

target levels of 0, 2,000, 8,000, and

30,000/40,000 ppm for approximately 2-

years. Based on these levels, respective

doses were 100, 400 and 2,000/1,500

mg/kg/day. After 2-weeks at 40,000

ppm, this dietary level was reduced to

30,000 ppm due to the occurrence of red

coloration of the urine and a decrease in

body weight gain. Although these

findings were no longer apparent after

week 2, analytical verification of dietary

levels revealed that the highest dietary

level ranged from approximately 38,000

to 61,000 ppm during the first 32 weeks

of the study. No significant differences

in bwt or food consumption were noted

at 2,000 or 8,000 ppm. No biologically

significant differences were observed in

ophthalmoscopy, hematology, clinical

chemistry, or urinalysis for treated and

control animals. Calculi in the urinary

bladder were observed for several male

and female rats in the high dose group.

Non-neoplastic findings consisted of

epithelial hyperplasia and inflammation

in the urinary bladders of males at

30,000/40,000 ppm. Increased

incidences of hydronephrosis,

inflammation, and epithelial

hyperplasia in the kidney were also

observed in males from the high dose

group. Females from the same group

exhibited increased incidences of

epithelial hyperplasia in the urinary

bladder and hydronephrosis in the

kidney. The NOEL in the chronic rat

study was 8,000 ppm (400 mg/kg/day).

iii. Conclusion. The lowest NOEL for

chronic effects of fosetyl-Al is 10,000

ppm (250 mg/kg/day) based on the dog

study. This NOEL is based on minor

changes at 20,000 ppm. In the rat,

calculi in the urinary bladder and

related histopathological changes in the

bladder and kidneys of males and

females were observed at 30,000/40,000

ppm.

6. Carcinogenicity. Long-term feeding

studies were conducted with technical

grade fosetyl-Al in mice and rats and

with monosodium phosphite, the

primary urinary metabolite of fosetyl-Al,

in rats. These studies, in addition to a

mechanistic study in rats, are described

below:

i. Rat. Fosetyl-Al was administered

via admixture in the diet to CD rats at

target levels of 0, 2,000, 8,000, and

30,000/40,000 ppm for approximately 2-

years. After 2-weeks at 40,000 ppm, this

dietary level was reduced to 30,000 ppm

due to the occurrence of red coloration

of the urine and a decrease in body

weight gain. Although these findings

were no longer apparent after week 2,
Federal Register / Vol. 63, No. 129 /Tuesday, July 7, 1998 / Notices 36685

analytical verification of dietary levels

revealed that the highest dietary level

ranged from approximately 38,000 to

61,000 ppm during the first 32 weeks of

the study. Calculi in the urinary bladder

were observed for several male and

female rats at 30,000/40,000 ppm.

Microscopic examination revealed

transitional cell carcinomas and

papillomas in the urinary bladders of

high dose males. In addition, a

statistically significant increase in

adrenal pheochromocytomas (benign

and malignant combined) was observed

in males at 8,000 and 30,000/40,000

ppm. The adrenal slides were

independently reread by two consulting

pathologists who found no significant

dose-related increases in the incidence

of pheochromocytomas or hyperplasia.

The NOEL for fosetyl-Al in the chronic

rat study was 8,000 ppm. A subsequent

mechanistic study in rats conducted

with dietary levels of 8,000, 30,000 and

50,000 ppm demonstrated that the

massive doses of 30,000 and 50,000

ppm fosetyl-Al alter calcium/

phosphorous homeostasis resulting in

severe acute renal injury, similar to that

observed in the chromic rat study, and

the formation of calculi in kidneys,

ureters, and bladder. Under conditions

of chronic exposure, these effects could

lead to the formation of bladder tumors

as seen in the chronic rat study. At

8,000 ppm, no evidence of renal injury

was observed, a result consistent with

the absence of bladder tumors. Thus, the

bladder tumors induced by fosetyl-Al

were the result of acute renal injury

followed by a chronic toxic reaction

rather than a true carcinogenic effect.

An oncogenicity study in rats was

conducted with monosodium phosphite

administered via dietary mixture at

levels of 2,000, 8,000, and 32,000 ppm.

No evidence of oncogenicity was

observed in this study.

ii. Mouse. A 2-year feeding/

carcinogenicity study was conducted in

mice fed diets containing fosetyl-Al at 0,

2,500, 10,000, or 20,000/30,000 ppm.

The 20,000 ppm dose was increased to

30,000 ppm during week 19 of the

study. The NOEL for all effects was

20,000/30,000 ppm (3,000/4,500 mg/kg/

day). There were no carcinogenic effects

observed under the conditions of this

study.

iii. Conclusion. The Office of

Pesticide Programs’, Health Effects

Division, Carcinogenicity Peer Review

Committee (CPRC) concluded in their

report of June 29, 1993 that the

pesticidal use of fosetyl-Al is unlikely to

pose a carcinogenic hazard for humans

given that:

a. Tumors develop in rats under

extreme conditions that are unlikely to

be achieved other than under laboratory

conditions (at a dose in excess of the

OPP dose limit for carcinogenicity

studies).

b. Tumors in rats are believed to

develop only at doses that produce

stones.

c. Human dietary exposure to fosetylAl is only about one-500,000th of the

NOEL for stone formation in the rat (the

most sensitive experimental model).

d. The dose of fosetyl-Al which can be

absorbed dermally by applicators is also

probably too low to result in stone

formation. EPA has therefore chosen to

use the Reference Dose (RfD) to quantify

dietary risk to humans.

7. Neurotoxicity. No evidence of

neurotoxic potential has ever been

observed with fosetyl-Al. Fosetyl-Al

does not have a chemical function

associated with neurotoxicity. No signs

of neurotoxicity have been recorded in

any study conducted with fosetyl-Al.

8. Animal metabolism. Rat

metabolism studies showed that most of

the radiolabel rapidly appeared in

exhaled carbon dioxide. There was also

some radiolabel excreted in the urine as

phosphite, along with a smaller amount

as the unchanged parent compound. It

appears that fosetyl-Al is essentially

completely absorbed after ingestion and

extensively hydrolyzed to carbon

dioxide which is exhaled. The

phosphite is excreted in the urine

without further oxidation to phosphate.

Aluminum does not appear to be

absorbed to a significant extent from the

gastrointestinal tract.

9. Metabolite toxicology. There are no

metabolites of toxicological concern.

The tolerances are established for the

parent only, that is fosetyl-Al.

10. Endocrine disruption. No

evidence of estrogenic or androgenic

effects were noted in any study with

fosetyl-Al. No adverse effects on mating

or fertility indices and gestation, live

birth, or weaning indices were noted in

a 3-generation rat reproduction study at

doses well above EPA’s limit of 1,000

mg/kg/day. Therefore, fosetyl-Al does

not have any effect on the endocrine

system.

C. Aggregate Exposure

1. Dietary exposure—i. Chronic risk.

Based upon all available data, EPA has

established an RfD of 3.0 mg/kg/day

using a 100 fold safety factor to account

for inter- and intra-species differences

and a NOEL of 250 mg/kg/bwt/day from

a 2-year feeding study in dogs. A

chronic dietary risk assessment was

prepared using established and

proposed tolerance residue levels, 1987

food consumption data, and 100% crop

treated. The calculated potential

exposure for the U.S. population is

0.065760 mg/kg bwt/day. Potential

exposure for nursing and non-nursing

infants less than 1-year old, children

aged 1 to 6-years, and children aged 7

to 12-years is calculated to be 0.022485,

0.134076, 0.116682, and 0.069637 mg/

kg bwt/day, respectively. This results in

utilization of 2.2, 4.5, 3.9, and 2.3% of

the RfD for the whole U.S. population,

non-nursing infants less than 1-year old,

children aged 1 to 6- years, and children

aged 7 to 12-years, respectively. Thus,

the dietary exposure for fosetyl-Al is

well below the RfD of 3.0 mg/kg/day

and is negligible for all segments of the

population including infants and

children.

ii. Acute risk. Based on a lack of acute

toxicity and the large margins of

exposure in the chronic dietary

assessment, fosetyl-Al does not pose any

acute dietary risks.

2. Food. The dietary exposure

assessment accounts for all anticipated

dietary exposure for a tolerance of 3.0

ppm on bananas, which is the subject of

this request, and all other active and

pending tolerances for fosetyl-Al. The

active tolerances are for asparagus,

avocados, blueberries, brassica,

caneberries, citrus, cucurbits, ginseng,

hops (dried), leafy vegetables,

pineapple, onions (dry bulb), pome

fruit, strawberries, and tomatoes.

Pesticide petitions proposing the

establishment of tolerances for FosetylAl on grapes and macadamia nuts (IR4) have also been submitted to the

Agency.

3. Drinking water. There is no

established maximum contaminant level

(MCL) or health advisory level (HAL) for

fosetyl-Al. The potential for ground

water and/or surface water

contamination by fosetyl-Al and its

degradates is expected to be very low,

in most cases, due to the rapid

degradation of the compound in soil to

non-toxic degradates under both aerobic

and anaerobic conditions. Under aerobic

laboratory conditions, the half-life of

fosetyl-Al is between 1 and 1.5 hours in

loamy sand, silt loam, and clay loam

and 20 minutes in sandy loam soil. The

degradation proceeds through the

hydrolysis of the ethyl ester bond,

resulting in the formation of

phosphorous acid and ethanol. The

ethanol is further degraded into carbon

dioxide. Based on the short half-life of

fosetyl-Al and the known fate of

phosphates under anaerobic conditions,

EPA determined that an anaerobic soil

metabolism study was not necessary. An

anaerobic aquatic soil metabolism study

was conducted. When anaerobic

conditions were established by flooding

soil, the half-life was 40 hours with silty
36686 Federal Register / Vol. 63, No. 129 /Tuesday, July 7, 1998 / Notices

clay loam, and 14 hours with sandy

loam soil.

4. Non-dietary exposure. In addition

to agricultural uses, fosetyl-Al is

registered on ornamentals and turf

under the brand names CHIPCO Aliette

WDG, and Aliette HG. CHIPCO Aliette

WDG is sold to professional applicators

only, which includes lawn care

operators (LCO). All residential uses of

CHIPCO Aliette WDG are applied by an

LCO. Typically, LCOs use fungicides for

ornamentals and turf on an as needed

basis only in part because of high cost,

variable performance, and little residual

control. In 1994, LCOs made an

estimated 206,200 acre treatments in

total for all fungicides representing less

than 1% of the available acreage of

32,740,000 assuming each acre was

treated once (Kline & Company, Inc.).

CHIPCO Aliette WDG is estimated to

have been used on less than 3% of the

acres treated with commercial

landscapes (turf and ornamentals)

constituting the majority of the use by

LCOs. Therefore, fosetyl-Al is used by

LCOs on less than 0.03% of the total

available acres. Aliette HG is not

currently being sold but plans are to

introduce this product on the market in

1998 on a limited geographical scale.

The product will be available to the

home consumer in single dose packages

for residential use on turf and

ornamentals. Available market research

information indicates that a total of 1.7

million pounds fungicide (active

ingredient) are sold annually for use by

the home owner. Since Aliette HG will

just be entering the market, only very

small quantities of the product are

expected to be sold. The maximum

amount expected to be sold for the next

few years is approximately 1% of the

total 1.7 million pounds of fungicide

products available to the home owner

for residential use on turf and

ornamentals. This use of the product is

therefore expected to have a negligible

impact on the aggregate exposure for

fosetyl-Al.

5. Conclusion. Considering that

fosetyl-Al is applied by LCOs on about

0.03% of available lawn acres (the

majority being commercial landscapes),

the likelihood of post application

exposure occurring, particularly in a

residential situation, is extremely low.

The use of fosetyl-Al by the homeowner

constitutes a minor use of the product

since only small quantities are expected

to be sold in 1998. Other applications by

professional operators, e.g. golf courses,

nurseries, sod farms, present only very

limited exposure to a limited population

of adults but do not pose any exposure

to small children. Thus, the ornamental

and turf uses are not expected to add

significantly to the aggregate exposure

for fosetyl-Al, and only dietary exposure

has been taken into consideration for

risk assessment purposes.

D. Cumulative Effects

Effects associated with fosetyl-Al are

unlikely to be cumulative with any

other compound. The formation of

calculi and bladder tumors in rats is the

only significant toxicological effect

observed with fosetyl-Al. These effects

were observed in rat only at a dose

which not only exceeds estimated

human exposure by several orders of

magnitude but is in excess of the OPP

dose limit for carcinogenicity studies.

Therefore, an aggregate assessment

based on common mechanisms of

toxicity is not appropriate as exposure

to humans will be well below the levels

producing calculi and bladder tumors in

rats. Further, considering the rapid

elimination of fosetyl-Al in the rat

metabolism study, any effects associated

with fosetyl-Al are unlikely to be

cumulative with any other compound.

Based on these reasons, only the

potential risks of fosetyl-Al are

considered in the exposure assessment.

E. Safety Determination

1. U.S. population. Based upon all

available data, EPA has established an

RfD of 3.0 mg/kg/day using a 100 fold

safety factor to account for inter- and

intra-species differences and a NOEL of

250 mg/kg bwt/day from a 2-year

feeding study in dogs. A chronic dietary

risk assessment using established and

proposed tolerance residue levels, 1987

food consumption data, and 100% crop

treated results in utilization of 2.2, 4.5,

3.9, and 2.3% of the RfD for the whole

U.S. population, non-nursing infants

less than 1-year old, children aged 1 to

6-years, and children aged 7 to 12-years,

respectively. Thus, the dietary exposure

for fosetyl-Al is well below the RfD of

3.0 mg/kg/day and is negligible for all

segments of the population including

infants and children.

2. Infants and children—Adequate

margin of safety. In assessing the

potential for additional sensitivity of

infants and children to residues of

fosetyl-Al, the available developmental

and reproductive toxicity studies and

the potential for endocrine modulation

were considered. Developmental

toxicity studies in two species indicate

that fosetyl-Al has no teratogenic

potential at any dose level. Further, no

adverse effects on fetal development

were observed in rabbits at doses up to

500 mg/kg/day or in rats at doses up to

1,000 mg/kg/day. In a 3-generation rat

reproduction study, no adverse effects

on reproductive performance or pup

survival were observed up to 24,000

ppm (equivalent to a dose well above

EPA’s limit dose of 1,000 mg/kg/day).

Maternal and developmental NOELs

and LELs were comparable in all studies

indicating no increase in susceptibility

of developing organisms. Further,

fosetyl-Al has no endocrine-modulation

characteristics as demonstrated by the

lack of endocrine effects in

developmental, reproductive,

subchronic, and chronic studies. Since

registration of fosetyl-Al in 1983, EPA

has assessed the safety of this molecule

several times and has concluded

repeatedly that the level of dietary

exposure is sufficiently low to provide

ample margins of safety to guard against

any potential adverse effects of fosetylAl. Considering the conservative

exposure assumptions in setting the

tolerances and the dietary risk

assessment assuming 100% crop

treated, less than 5% of the RfD is

utilized for non-nursing infants less

than 1-year old, children aged 1 to 6-

years, and children aged 7 to 12-years.

The probability of non-occupational

sources of exposure to fosetyl-Al is

negligible. Therefore, based upon the

completeness and reliability of the

toxicity data and the conservative

exposure assessment, there is a

reasonable certainty that no harm will

result to infants and children from

exposure to the residues of fosetyl-Al

and no additional uncertainty factor is

warranted.

F. International Tolerances

There are presently no Codex

maximum residue levels established for

residues of fosetyl-Al on any crop.

[FR Doc. 98–17808 Filed 7–6–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[FRL–6121–3]

Proposed CERCLA Administrative De

Minimis Contributor Settlement With

Mesa Oil, Inc.—Rocky Flats Industrial

Park Site in Jefferson County,

Colorado

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice and request for public

comment.

SUMMARY: In accordance with the

requirements of section 122(i) of the

Comprehensive Environmental

Response, Compensation, and Liability

Act, as amended (‘‘CERCLA’’), 42 U.S.C.

9622(i), notice is hereby given of a

proposed administrative de minimis