48842 Federal Register / Vol. 62, No. 180 / Wednesday, September 17, 1997 / Notices

cereal grains are 0.1 mg/kg and is

0.01mg/kg for processed foods after

treatment with PH3 generated from

metal phosphides. This corresponds to

the levels set both by Environmental

Protection Agency/the NH & MRC of

Australia and the Codex Alimentarius

Commission of the WHO/FAO.

2. Analytical methodology. The

maximum residue limit recommended

by the Codex Alimentarius Commission

of the WHO/FAO for phosphine in raw

cereals is 0.1mg/kg and in milled cereals

and a range of foodstuffs including nuts

it is 0.01mg/kg. An improved method

for the determination of phosphine

residues in a range of stored foodstuffs

with a limit of detection better than

0.0001mg/kg is described by K.A.

Scudamore and G.Goodship (Ref:

‘‘Determination of Phosphine Residues

in Fumigated Cereals and other

Foodstuffs.’’ Pestic. Sci. 1986, 37; 385-

395). The method has been used to

obtain data on the amount of phosphine,

which remains in these commodities

after treatment at typical dosage levels

and on its persistence during storage.

Results show that in cereal grains and

nuts residues fall quickly to below.

Internationally recommended levels

although ultra trace amounts (less than

0.001 mg/kg) of phosphine could be

detected several months after treatment

in all the commodities examined.

3. Crop residue data. While

phosphine is not applied to growing

plants or crops it is a well-established

fumigant of cereal grain and stored

products.

4. Fate of residues. The possible

reactions of absorbed phosphine within

the commodity matrics to form

inorganic phosphorous compounds

have been detailed. In warm-blooded

animals, phosphorous acid and

phosphoric acid are formed or else

phosphate. The volatile nature of

phosphine (boiling point minus 87°C)

and its limited solubility ensures that

any phosphine absorbed in a foodstuff

during treatment would be negligible

and rapidly lost. Residue of phosphine

held for any length of time is less than

0.001 mg/kg i.e., 0.001 ppm. Phosphoric

acid has many uses including an

acidulate and flavor in beverages of the

soft drink type.

5. Maximum residue limits— i.

Overseas. The maximum residue limit

recommended by the Codex

Alimentarius Commission of the WHO/

FAO for phosphine in raw cereals is 0.1

mg/kg and in milled cereals and a range

of foodstuffs including nuts is 0.01 mg/

kg. (Ref: ‘‘Codex Maximum Limits for

Pesticide Residues’’ Codex Alimentarius

Commission Volume XIII, Rome 1983).

ii. Australia. The 100th session of the

National Health and Medical Research

Council, November 1985 gave the

maximum residue limit in cereal grains

of 0.1 mg/kg; and in flour and other

milled cereal products, breakfast

cereals, dried fruit, dried vegetables, all

other dried foods, spices, nuts, peanuts,

cocoa, beans and honey a limit of 0.01

mg/kg. The maximum residue limit is

set at or about the limit of analytical

determination. If the substance were to

occur at or below this limit it is

considered that no hazard to human

health would occur. (Ref: ‘‘Standard for

Maximum Residue Limits of Pesticides,

Agricultural Chemical, Feed Activities,

Veterinary Medicines and Noxious

Substances in Food’’ Commonwealth

Dept. of Health, Commonwealth of

Australia 1986. ISBN 0644 04688 0).

iii. U.S.A. Tolerances have been

established for commodities fumigated

by the fumigant PH3 generated from

metal phosphides. Maximum residue

limits for cereal grains are 0.1 mg/kg

and is 0.01mg/kg for processed foods

after treatment with PH3 generated from

metal phosphides.

E. Residue Detection and Removal

See Section D Above

F. Endocrine Effects

Phosphine degrades to phosphates

and phosphoric acid or else phosphates,

in warm-blooded animals (Ref: ‘‘The

Agrochemicals Handbook’’, Royal

Society of Chemistry, 1986). It has been

shown that there is no overt toxicity

associates with the residue low levels

(order 0.001 ppm) of phosphine

products, in fact, a major buffering

system of the body utilizes polybasic

phosphates; and phosphoric acid is

used as an acidulate and flavor in

beverages of soft drink type (Ref: The

Merck Index, 9th Edition, 7153).

G. Exposure to Infants and Children

Summary. Commodities fumigated

with PH3 at the recommended dosage

levels leaves very little residue in the

order of 0,001ppm (see part D) Long

term feeding studies showed that

ingestion of PH3 fumigated dirt by the

rat for 2 years does not cause any

marked modification of growth, food

intake, nitrogen balance, body

composition, functional behavior or the

incidence of type of tumors. The

product should however, at all times be

kept out of reach of children or other

uncertified applicators due to acute

inhalation toxicity.

H. Reasonable Grounds

ECO2FUMETM is a mixture of two

well known fumigants PH3 and CO2.

Tolerances have already been

established for PH3 generated from

Aluminum and Magnesium phosphide.

Maximum residue limits for cereal

grains are 0.1 mg/kg and is 0.01mg/kg

for processed foods after treatment with

PH3 generated from metal phosphides.

CO2 is exempt from tolerance. Use of

ECO2FUMETM results in approximately

75% less PH3 being used for fumigation

as compared to PH3 from metal

phosphides ECO2FUMETM has

recorded residue levels of below

0,001ppm. (PM 14)

[FR Doc. 97–24694 Filed 9–16–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–753; FRL–5735–5]

Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of pesticide petitions

proposing the establishment of

regulations for residues of certain

pesticide chemicals in or on various

food commodities.

DATES: Comments, identified by the

docket control number PF–753, must be

received on or before October 17, 1997.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch (7506C),

Information Resources and Services

Division, Office of Pesticides Programs,

Environmental Protection Agency, 401

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

person bring comments to: Rm. 1132,

CM #2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically by following

the instructions under

‘‘SUPPLEMENTARY INFORMATION.’’

No confidential business information

should be submitted through e-mail.

Information submitted as a comment

concerning this document may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI). CBI should not be submitted

through e-mail. Information marked as

CBI will not be disclosed except in

accordance with procedures set forth in

40 CFR part 2. A copy of the comment

that does not contain CBI must be

submitted for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments will be available for public
Federal Register / Vol. 62, No. 180 / Wednesday, September 17, 1997 / Notices 48843

inspection in Rm. 1132 at the address

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

Monday through Friday, excluding legal

holidays.

FOR FURTHER INFORMATION CONTACT: The

product manager listed in the table

below:

Product Manager Office location/telephone number Address

Joanne Miller (PM 23) ... Rm. 237, CM #2, 703–305–6224, e-mail:miller.joanne@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

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–753]

(including comments and data

submitted electronically as described

below). A public version of this record,

including printed, paper versions of

electronic comments, which does not

include any information claimed as CBI,

is available for inspection from 8:30

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

excluding legal holidays. The official

record is located at the address in

‘‘ADDRESSES’’ at the beginning of this

document.

Electronic comments can be sent

directly to EPA at:

opp-docket@epamail.epa.gov

Electronic comments must be

submitted as an ASCII file avoiding the

use of special characters and any form

of encryption. Comment and data will

also be accepted on disks in

Wordperfect 5.1 file format or ASCII file

format. All comments and data in

electronic form must be identified by

the docket number [PF–753] and

appropriate petition number. Electronic

comments on this notice may be filed

online at many Federal Depository

Libraries.

List of Subjects

Environmental protection,

Agricultural commodities, Food

additives, Feed additives, Pesticides and

pests, Reporting and recordkeeping

requirements.

Dated: September 5,1997

James Jones,

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. DowElanco

PP 7F4851

EPA has received a pesticide petition

(PP 7F4851) from DowElanco, 9330

Zionsville Road, Indianapolis, IN

46268–1054, proposing pursuant to

section 408(d) of the Federal Food, Drug

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

amend 40 CFR part 180 by establishing

a tolerance for residues of flumethsulam

in or on the raw agricultural commodity

dry beans at 0.05 ppm. The proposed

analytical method involves

homogenization, filtration, partition and

cleanup with analysis by high

performance liquid chromatography

using UV detection. EPA has

determined that the petition contains

data or information regarding the

elements set forth in section 408(d)(2) of

the FFDCA; however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data supports granting of the

petition. Additional data may be needed

before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism

in plants is adequately understood. No

metabolites of significance were

detected in plant metabolism studies.

2. Analytical method. There is a

practical analytical method for detecting

and measuring levels of flumetsulam in

or on food with a limit of quantitation

(LOQ) of 0.010 ppm, and a limit of

detection of 0.005 ppm that allows

monitoring of food with residues at or

above the levels set in these tolerances.

EPA has provided information on this

method to FDA. The method is availabe

to anyone who is interested in pesticide

residue enforcement.

3. Magnitude of residues. No

detectable residues of flumetsulam were

found in any of the drybean samples

obtained from multiple sites and

multiple varieties and analyzed using a

method with a limit of detection of

0.005 ppm.

B. Toxicological Profile

1. Acute toxicity. Flumetsulam has

low acute toxicity. The rat oral LD50 is

>5,000 mg/kg or greater for males and

females. The rabbit dermal LD50 is

>2,000 mg/kg and the rat inhalation

LC50 is >1.2mg/L air (the highest

attainable concentration). In addition,

flumetsulam is not a skin sensitizer in

guinea pigs, is not a dermal irritant and

is not an ocular irritant. Therefore based

on the available acute toxicity data,

flumetsulam does not pose any acute

dietary risks.

2. Genotoxicty. Flumetsulam is not

genotoxic. The following studies have

been conducted and all were negative

for genotoxic responses: a dominant

lethal assay, an In vivo rat cytogenic

study, an In vitro Salmonella and

Saccharomyces assay, an in vivo mouse

host–mediated assay, and an

unscheduled DNA synthesis assay in

rats.

3. Reproductive and developmental

toxicity. In a 2–generation reproduction

study in rats, there was no compound–

related reproductive toxicity. The NoObserved-Effect Level (NOEL) was

greater than 1,000 mg/kg/day.

Developmental toxicity was studied

using rats and rabbits. The

developmental study in rats resulted in

a developmental NOEL greater than

1.000 mg/kg/day (highest dose tested)

and a maternal NOEL of 500 mg/kg/day.

A study in rabbits resulted in a
48844 Federal Register / Vol. 62, No. 180 / Wednesday, September 17, 1997 / Notices

developmental NOEL equal to or greater

than 700 mg/kg/day (highest dose

tested) with a maternal NOEL of 100

mg/kg/day and a maternal LOEL (lowest

observed effect level) of 500 mg/kg/day

evidenced by decreased body weight

gain. Based on all of the data for

flumetsulam, there is no evidence of

developmental toxicity at dose levels

that do not result in maternal toxicity.

4. Subchronic toxicity . In a 13–week

oral feeding study in mice at 5,000 mg/

kg/day, slight effects on the liver,

kidney, and cecum appeared to

represent adaptive responses to

treatment and have questionable

toxicological significance. The NOEL

was 1,000 mg/kg/day (limit dose). In a

13–week oral feeding study in dogs, the

lowest–observed–effect level (LOEL) for

both male and female dogs was 500 mg/

kg/day. A NOEL was not established for

males or females. In a 13–week dietary

study in rats, the NOEL was 250 mg/kg/

day and the LOEL was 1,000 mg/kg/day.

5. Chronic toxicity. In a 1–year dietary

study in dogs, the NOEL was 100 mg/

kg/day and the LOEL was 500 mg/kg/

day. The animals were administered

feed containing 0, 20, 100, and 500 mg/

kg/day. Reduced body weights and

inflammatory and atrophic changes in

the kidneys occurred in the 500 mg/kg/

day dose groups. In a combined feeding

carcinogenicity/chronic study in mice

there were no treatment–related effects

and there was no evidence of a

carcinogenic response. Systemic NOEL

was greater than or equal to 1,000 mg/

kg/day (limit dose); a LOEL was not

established. In a combined feeding

carcinogenicity/chronic study in rats,

renal pathological alterations were seen

in males. No treatment-related effects

were seen in females at the highest dose

(1,000 mg/kg/day) which is the limit

dose. There was no carcinogenic

response. The NOELs were 500 mg/kg/

day in males and 1,000mg/kg/day in

females. The LOEL was 1,000 mg/kg/

day in males; a LOEL was not

established in females. Based on the

chronic toxicity data, EPA has

established the RfD for flumetsulam at

1.0 milligram (mg)/kilogram (kg)/day.

The RfD for flumetsulam is based on the

1–year chronic study in dogs with a

NOEL of 100 mg/kg/day and an

uncertainty (or safety) factor of 100.

Thus, it would not be necessary to

require the application of an additional

uncertainty factor above the 100–fold

factor already applied to the NOEL.

6. Animal metabolism. Disposition

and metabolism of flumetsulam were

tested in male and female rats and male

mice at an oral dose of 5 and 1,000 mg/

kg for rats and 1,000 mg/kg for mice

Flumetsulam was rapidly excreted. The

majority of a radioactive dose was

excreted in 48 hours of all dose groups.

The principle route for elimination was

the urine and to a lessor extent by fecal

elimination. Detectable levels of

residual radioactivity were observed in

the carcass and stomach at 72 hours

post–dose. HPLC and TLC analysis of

urine and fecal extracts showed no

apparent metabolism of flumetsulam.

7. Metabolite toxicology. There are no

flumetsulam metabolites of toxicological

significance.

8. Endocrine effects. There is no

evidence to suggest that flumetsulam

has an effectt on any endocrine system.

C. Aggregate Exposure

1. Food. For purposes of assessing the

potential dietary exposure under these

tolerances, exposure is estimated based

on the Theoretical Maximum Residue

Contribution (TMRC) from the existing

and pending tolerances for flumetsulam

on food crops. The TMRC is obtained by

multiplying the tolerance level residues

by the consumption data which

estimates the amount of those food

products eaten by various population

subgroups. Exposure of humans to

residues could also result if such

residues are transferred to meat, milk,

poultry or eggs. The following

assumptions were used in conducting

this exposure assessment: 100% of the

crops were treated, the RAC residues

would be at the level of the tolerance,

certain processed food residues would

be at anticipated (average) levels based

on processing studies and all current

and pending tolerances were included.

This results in an overestimate of

human exposure and a conservative

assessment of risk. Based on a NOEL of

100 mg/kg/day in a 1–year chronic

feeding study in the dog and a

hundredfold safety factor the reference

dose (RfK) would be 1.0 mg/kg/day. The

TMRC for the general population would

be 4.1 X 10–5 mg/kg/day or 0.0041% of

the RfD. For non–nursing infants, the

TMRC wold be 1.37 X 10–5 mg/kg/day

or 0.014% of the RfD.

2. Drinking water. Another potential

source of dietary exposure to residues of

pesticides are residues in drinking

water. There is no established

Maximum Concentration Level for

residues of flumetsulam in drinking

water. Although there has been limited

detections at ppb levels in some of the

specially designed studies under highly

vulnerable test conditions and at

elevated non–labeled application rates,

no ongoing monitoring studies, have

reported residues of flumetsulam in

ground or surface waters.

Based on the physical and chemical

characteristics of flumetsulam, such as

water solubility and its stability under

hydrolysis and photolysis, it has

potential for downward movement

through the soil profile. Degradation

based on over 20 laboratory studies

indicated a half–life range of 2 weeks to

4 months with 80% less than 2 months.

Degradation is driven primarily by

microbial processes. However based on

the low application rate and detection

in groundwater samples only under

extremely vulnerable soil conditions at

elevated non–labeled application rates

with detections in single digit ppb

levels, flumetsulam is not anticipated to

be a groundwater contaminant.

In summary, these data on potential

water exposure indicate insignificant

additional dietary intake of flumetsulam

and any exposure is more than

compensated for in the conservative

dietary risk evaluation. Therefore, it is

concluded that there is a reasonable

certainty of no harm even at potential

upper limit exposures to flumetsulam

from drinking water.

3. Non–dietary exposure. There are no

non–dietary uses for flumetsulam

registered under the Federal Insecticide,

Fungicide and Rodenticide Act.

Potential exposures for children is

therefore limited to dietary exposure.

D. Cumulative Effects

The potential for cumulative effects of

flumetsulam and other substances that

have a common mechanism of toxicity

was considered. The mammalian

toxicity of flumetsulam is well defined.

However, no reliable information exists

to indicate that toxic effects produced

by flumetsulam would be cumulative

with those of any other chemical

compound. Additionally, flumetsulam

does not appear to produce a toxic

metabolite produced by other

substances. Therefore, consideration of

a common mechanism of toxicity with

other compounds is not appropriate at

this time. Thus only the potential

exposures to flumetsulam were

considered in the aggregate exposure

assessment.

E. Safety Determination

1. U.S. population. Based on a NOEL

of 100 mg/kg/bwt/day from a one-year

dog feeding study with a reduced

weight and inflammatory and atrophic

kidney effect, and using an uncertainty

factor of 100 to account for the

interspecies extrapolation and

intraspecies variability, a Reference

Dose (RfD) of 1.0 mg/kg bwt/day was

used for this assessment of chronic risk.

As indicated, there is no endpoint of

concern identified with acute and

short–or intermediate–term exposures.

The existing and proposed tolerances
Federal Register / Vol. 62, No. 180 / Wednesday, September 17, 1997 / Notices 48845

would utilize 0.000041 mg/kg bwt/day

or less than 0.01% of the RfD for the

U.S. population. And, as indicated

previously, whatever upper limit might

be used for drinking water exposure, the

exposure estimate for flumetsulam

would not exceed the RfD. Generally,

exposures below 100 percent of the RfD

are of no concern because the RfD

represents the level at or below which

daily aggregate dietary exposure over a

lifetime will not pose appreciable risk to

human health. Thus, there is a

reasonable certainty that no harm will

result from aggregate exposure to

flumetsulam residues.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

flumetsulam, data from developmental

toxicity studies in the rat and rabbit and

a 2–generation reproduction study in

the rat were considered. The

developmental toxicity studies are

designed to evaluate adverse effects on

the developing organism during

prenatal development resulting from

pesticide exposure to one or both

parents. Reproduction studies provide

(1) information relating to effects from

exposure to the pesticide on the

reproductive capability of mating

animals and (2) data on systemic

toxicity.

As indicated previously, reproductive

and developmental toxicity was studied

using rats and rabbits. The data base is

complete and based on all of the data for

flumetsulam, there is no evidence of

reproductive or developmental toxicity

at dose levels that do not result in

maternal toxicity.

FFDCA section 408 provides that EPA

may apply an additional safety factor for

infants and children in the case of

threshold effects to account for pre- and

post–natal toxicity and the

completeness of the database. Based on

the current toxicological data

requirements, the database relative to

pre- and post–natal effects for children

is complete. These data suggest minimal

concern for developmental or

reproductive toxicity and do not

indicate any increased pre- or post–

natal sensitivity. Therefore, an

additional uncertainty factor is not

necessary to protect the safety of infants

and children and that the RfD at 1.0 mg/

kg/day is appropriate for assessing

aggregate risk to infants and children.

The percent of the RfD that will be

utilized by the aggregate exposure from

all tolerances to flumetsulamill be less

than 0.1% for non–nursing infants and

for children (1–6 years of age).

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 flumetsulam residues.

F. International Tolerances

There are no Codex maximum residue

levels established for flumetsulam.

(Joanne Miller)

2. Rohm and Haas Company

PP 2F4127

EPA has received a pesticide petition

(PP 2F4127) from Rohm and Haas

Company, 100 Independence Mall West,

Philadelphia, PA 19106–2399 proposing

pursuant to section 408(d) of the Federal

Food, Drug and Cosmetic Act (FFDCA),

21 U.S.C. 346a(d), to amend 40 CFR part

180 by establishing a permanent

tolerance for residues of [alpha-(2-(4-

chlorophenyl)-ethyl)-alpha-phenyl-3-

(1H-1,2,4-triazole)-1-propanenitrile

(fenbuconazole)] in or on the raw

agricultural commodities wheat grain;

wheat straw; milk; eggs; and meat, fat,

and meat by-products of cattle, goats,

horses, hogs, poultry, and sheep. The

analytical method involves soxhlet

extraction, partitioning, redissolving,

cleanup, and analysis by gas-liquid

chromatography using nitrogen specific

thermionic detection. EPA has

determined that the petition contains

data or information regarding the

elements set forth in section 408(d)(2) of

the FFDCA; however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data supports granting of the

petition. Additional data may be needed

before EPA rules on the petition.

A. Residue Chemistry

The tolerance expression for

fenbuconazole residues in or on wheat

grain or straw is: α-(2-(4-chlorophenyl)-

ethyl)-α-phenyl-(1H-1,2,4-triazole-1-

propanenitrile, plus cis-5-(4-

chlorophenyl)dihydro-3-phenyl-3-(1H1,2,4- triazole-1-ylmethyl-)-2(3H)-

furanone, plus trans-5-(4-

chlorophenyl)dihydro-3-phenyl-3-(1H1,2,4-triazole-1-ylmethyl-)-2(3H)-

furanone

Residues of these are combined and

expressed as parent compound to

determine the total RAC residue in or on

wheat grain and wheat straw.

The tolerance expression for

fenbuconazole residues in or on animal

fat is: α-(2-(4-chlorophenyl)-ethyl)-αphenyl-(1H-1,2,4-triazole-1-

propanenitrile, plus 4-chloro-α-

(hydroxymethyl)-α- phenylbenzenebutanenitrile

Residues are combined and expressed

as parent compound to determine the

total residue.

The tolerance expression for

fenbuconazole residues in or on animal

liver is: α-(2-(4-chlorophenyl)-ethyl)-αphenyl-(1H-1,2,4-triazole-1-

propanenitrile, plus cis-5-(4-

chlorophenyl)dihydro-3-phenyl-3-(1H1,2,4-triazole-1-ylmethyl-)-2(3H)-

furanone, plus trans-5-(4-

chlorophenyl)dihydro-3-phenyl-3-(1H1,2,4-triazole-1-ylmethyl-)-2(3H)-

furanone, plus 4-chloro-α-

(hydroxymethyl)-α-phenylbenzenebutanenitrile

Residues are combined and expressed

as parent compound to determine the

total residue.

Analytical methods to measure the

components of the residue in or on

wheat grain and wheat straw, and in or

on animal commodities have been

validated and accurately quantify

residues of fenbuconazole. The residues

of fenbuconazole will not exceed the

proposed Permanent Tolerances on

wheat or related commodities following

foliar or seed treatment of wheat.

1. Analytical method. Fenbuconazole

residues (parent plus lactones) are

measured at an analytical sensitivity of

0.01 mg/kg in wheat grain and straw by

soxhlet extraction of samples in

methanol, partitioning into methylene

chloride, redissolving in toluene, clean

up on silica gel, and gas-liquid

chromatography (GLC) using nitrogen

specific thermionic detection.

Fenbuconazole residues are measured at

an analytical sensitivity of 0.01 mg/kg in

fat and liver in essentially the same

manner except that one of the analytes

in these matrices, 4-chloro-α-

(hydroxymethyl)-α-phenyl–

benzenebutanenitrile, is measured at a

sensitivity of 0.05 ppm.

2. Magnitude of residues. Residue

studies have been conducted in

accordance with the geographic

distribution mandated by the EPA for

wheat. In the wheat grain, the raw

agricultural commodity, the

fenbuconazole residues ranged from no

detectable residue (NDR < LOQ=0.01

mg/kg) to approximately 0.01 ppm. In

wheat straw the fenbuconazole residues

ranged from approximately 0.05 ppm to

approximately 4.5 ppm. Residues were

measured in processed fractions of

wheat including cleaned grain, bread,

patent flour, flour, red dog, bran, shorts/

germ, and middlings. The EPA

concluded that no concentration above

the residue levels in the RAC occurred

so no tolerances for any of these

commodities were required. Tolerances

of 0.05 ppm in wheat grain and 10 ppm

in wheat straw are proposed based on

these data.
48846 Federal Register / Vol. 62, No. 180 / Wednesday, September 17, 1997 / Notices

B. Toxicological Profile

The toxicology of fenbuconazole is

summarized in the following sections.

There is no evidence to suggest that

human infants and children will be

more sensitive than adults, that

fenbuconazole will modulate human

endocrine systems at anticipated dietary

exposures, or cause cancer in humans at

the dietary exposures anticipated for

this fungicide. While the biochemical

target for the fungicidal activity of

members of the DMI class is shared, it

cannot be concluded that the mode of

action of fenbuconazole which produces

phytotoxic effects in plants or toxic

effects in animals is also common to a

single class of chemicals.

1. Acute toxicity. Fenbuconazole is

practically nontoxic after administration

by the oral, dermal and respiratory

routes. The acute oral LD50 in mice and

rats is >2,000 mg/kg. The acute dermal

LD50 in rats is >5,000 mg/kg.

Fenbuconazole was not significantly

toxic to rats after a 4–hour inhalation

exposure, with an LD50 value of >2.1

mg/L. Fenbuconazole is classified as not

irritating to skin (Draize score = 0),

inconsequentially irritating to the eyes

(mean irritation score = 0), and it is not

a sensitizer. No evidence exists

regarding differential sensitivity of

children and adults to acute exposure.

2. Genotoxicity. Fenbuconazole has

been adequately tested in a variety of in

vitro and in vivo mutagenicity tests. It is

negative in the Ames test and negative

in an in vitro and in vivo somatic and

germ cell tests; it did not induce

unscheduled DNA synthesis (UDS).

Fenbuconazole is not genotoxic.

3. Reproductive and developmental

toxicity. These data cited at 60–FR–

27419, May 24,1995. Fenbuconazole is

not teratogenic. The maternal no

observable effect level (NOEL) in rabbits

was 10 mg/kg/day and 30 mg/kg/day in

rats. The fetal NOEL was 30 mg/kg/day

in both species. The parental no

observable effect level (NOEL) was 4.0

mg/kg/day (80 ppm) in a 2–generation

reproduction study in rats. The

reproductive NOEL in this study was

greater than 40.0 mg/kg/day (800 ppm;

highest dose tested). Fenbuconazole had

no effect on male reproductive organs or

reproductive performance at any dose.

The adult lowest observed effect level

(LOEL) was 40.0 mg/kg/day (800 ppm;

highest dose tested). Systemic effects of

decreased body weight gain, maternal

deaths, hepatocellular, adrenal, and

thyroid follicular cell hypertrophy were

observed. No effects on neonatal

survival or growth occurred below the

adult toxic levels. Fenbuconazole does

not produce birth defects and is not

toxic to the developing fetus at doses

below those which are toxic to the

mother.

4. Subchronic toxicity. In a 21–day

dermal toxicity study in the rat, the

NOEL was greater than 1,000 mg/kg/

day, with no effects seen at this limit

dose.

5. Chronic Toxicity. In 2–year

combined chronic toxicity/oncogenicity

studies in rats, the NOEL was 80 ppm

(3.03 mg/kg/day for males and 4.02 mg/

kg/day for females) based on decreased

body weight, and liver and thyroid

hypertrophy. In a 1–year chronic

toxicity study in dogs, the NOEL was

150 ppm (3.75 mg/kg/day) based on

decreased body weight, and increased

liver weight. The LOEL was 1,200 ppm

(30 mg/kg/day). In a 78-week

oncogenicity study in mice, the NOEL

was 10 ppm (1.43 mg/kg/day). The

LOEL was 200 ppm (26.3 mg/kg/day,

males) and 650 ppm (104.6 mg/kg/day,

females) based on increased liver

weights and histopathological effects on

the liver. These effects were consistent

with chronic enzyme induction from

high dose dietary exposure.

A Reference Dose (RfD) for systemic

effects at 0.03 mg/kg/day was

established by EPA in 1995 based on the

NOEL of 3.0 mg/kg/day from the rat

chronic study. This RfD adequately

protects both adults and children.

6. Carcinogenicity. Twenty–four–

month rat chronic feeding/

carcinogenicity studies with

fenbuconazole showed effects at 800

and 1,600 ppm. Fenbuconazole

produced a minimal, but statistically

significant increase in the incidence of

combined thyroid follicular cell benign

and malignant tumors. These findings

occurred only in male rats following

life-time ingestion of very high levels

(800 and 1,600 ppm in the diet)

fenbuconazole. Ancillary mode–of–

action studies demonstrated that the

increased incidence of thyroid tumors

was secondary to increased liver

metabolism and biliary excretion of

thyroid hormone in the rat. This mode

of action is a nonlinear phenomenon in

that thyroid tumors occur only at high

doses where there is an increase in liver

mass and metabolic capacity of the

liver. At lower doses of fenbuconazole

in rats, the liver is unaffected and there

is no occurrence of the secondary

thyroid tumors. Worst–case estimates of

dietary intake of fenbuconazole in

human adults and children indicate

effects on the liver or thyroid, including

thyroid tumors, will not occur, and

there is a reasonable certainty of no

harm.

In support of the findings above,

EPA’s Science Advisory Board has

approved a final thyroid tumor policy,

confirming that it is reasonable to

regulate chemicals on the basis that

there exists a threshold level for thyroid

tumor formation, conditional upon

providing plausible evidence that a

secondary mode of action is operative.

This decision supports a widely-held

and internationally respected scientific

position.

In a 78–week oncogenicity study in

mice there was no statistically

significant increase of any tumor type in

males. There were no liver tumors in the

control females and liver tumor

incidences in treated females just

exceeded the historical control range.

However, there was a statistically

significant increase in combined liver

adenomas and carcinomas in females at

the high dose only (1,300 ppm; 208.8

mg/kg/day). In ancillary mode–of–

action studies in female mice, the

increased tumor incidence was

associated with changes in several

parameters in mouse liver following

high doses of fenbuconazole including:

an increase in P450 enzymes

(predominately of the CYP 2B type), an

increase in cell proliferation, an

increase in hepatocyte hypertrophy, and

an increase in liver mass (or weight).

Changes in these liver parameters as

well as the occurrence of the low

incidence of liver tumors were

nonlinear with respect to dose (i.e.,

were observed only at high dietary

doses of fenbuconazole). Similar

findings have been shown with several

pharmaceuticals, including

phenobarbital, which is not

carcinogenic in man. The nonlinear

relationship observed with respect to

liver changes (including the low

incidence of tumors) and dose in the

mouse indicates that these findings

should be carefully considered in

deciding the relevance of high-dose

animal tumors to human dietary

exposure.

The Carcinogenicity Peer Review

Committee (PRC) of the Health Effects

Division (HED) classified fenbuconazole

as a Group C tumorigen (possible

human carcinogen with limited

evidence of carcinogenicity in animals).

The PRC used a low-dose extrapolation

model. The Q1* risk factor applied (1.06

x 10–2 (mg/kg/day)–1) was based on the

rat oncogenicity study and surface area

was estimated by (body weight)3/4.

Since the PRC published the above

estimate they have agreed that low-dose

extrapolation for fenbuconazole, based

on rat thyroid tumors, is inappropriate

given the EPA’s policy regarding thyroid

tumors and the data which exist for

fenbuconazole. The PRC agrees that the

more appropriate data set for the low-
Federal Register / Vol. 62, No. 180 / Wednesday, September 17, 1997 / Notices 48847

dose extrapolation and risk factor

estimate is the mouse. From these data

a Q1* of (0.36 x 10-2(mg/kg/day)–1) is

calculated when surface area is

estimated by (body weight)3/4. All

estimates of dietary risk must be

adjusted to reflect this change.

Since fenbuconazole is unlikely to

leach into groundwater (see below),

there is no increased cancer risk from

this source. Neither is fenbuconazole

registered for residential use, so there is

no additional risk from this source

either. All estimates of excess risk to

cancer are from dietary sources.

7. Endocrine effects. The mammalian

endocrine system includes estrogen and

androgens as well as several other

hormone systems. Fenbuconazole does

not interfere with the reproductive

hormones. Thus, fenbuconazole is not

estrogenic or androgenic.

While fenbuconazole interferes with

thyroid hormones in rats by increasing

thyroid hormone excretion, it does so

only secondarily and only above those

dietary levels which induce metabolism

in the liver. These effects are reversible

in rats, and humans are far less sensitive

to these effects than rats. The RfD

protects against liver induction because

it is substantially below the animal

NOEL. As noted previously, maximal

human exposures are far below the RfD

level, and effects on human thyroid will

not occur at anticipated dietary levels.

We know of no instances of proven or

alleged adverse reproductive or

developmental effects to domestic

animals or wildlife as a result of

exposure to fenbuconazole or its

residues. In fact, no effects should be

seen because fenbuconazole has low

octanol/water partition coefficients and

is known not to bioaccumulate.

Fenbuconazole is excreted within 48

hours after dosing in mammalian

studies.

C. Aggregate Exposure

1. Food. The consumer dietary

exposure to fenbuconazole residues was

estimated for the most recently

approved tolerance in bananas

(memorandum of E.A. Doyle, 8 February

1995). The EPA used the Theoretical

Maximum Residue Contribution

(TMRC) for pecans and bananas, and

adjusted the TMRC for the stone fruit

crop group by excluding plums/prunes

and limiting sales volume to 12.8% of

the available stone fruit market. From

this EPA calculated an upper-bound risk

of 0.9 x 10-6 for additional cancer risk

(Q1* = 1.06 x 10-2 (mg/kg/day)-1). (60

FR 27419; 24 May 1995). This estimate

does not reflect the change in Q1*.

Using the EPA model and the new risk

factor based on the mouse data (Q1* =

0.36 x 10-2 (mg/kg/day)-1) the dietary

risk for currently registered uses is 0.3

x 10-6. The TMRC for existing tolerances

utilizes 17% of the RfD for the most

sensitive subpopulation, non-nursing

infants less than 1–year old. This is

unaffected by the change in Q1*.

For wheat, children 1 to 6 years old,

not infants, are the highest consumers

(g/kg bw/d basis). For children 1–6 the

dietary TMRC for existing tolerances

utilizes only 5% of the RfD. The dietary

TMRC for wheat in this group is

estimated to be 0.00016 mg/kg/day and

uses 0.52% of the RfD. Additional

dietary exposure (TMRC) to

fenbuconazole from residues which

might be transferred to animal fat and

liver from treated wheat is estimated to

be 0.00006 mg/kg/day and uses 0.22%

of the RfD. No residues occur in animal

meats, milk, or eggs. Thus, the TMRC,

the worst–case exposure, in the two

most sensitive subpopulations of

consumers, non–nursing infants less

than 1– year old and children 1 to 6

years old, still utilizes less than 18%

and less than 6%, respectively, of the

fenbuconazole RfD. The dietary TMRCs

for other children and for adults utilize

less than this.

The calculated additional cancer risk

for wheat (Q1* = 0.36 x 10-2 (mg/kg/

day)–1) has an upper–bound of 0.2 x

10-6. The calculated additional cancer

risk for animal fat and liver has an

upper–bound of 0.1 x 10-6. The upper

bound estimate on excess cancer risk for

all uses including wheat is 0.7 x 10-6.

The estimate shows that the TMRC, the

worst–case exposure, for consumers to

fenbuconazole presents a reasonable

certainty of no harm. The actual residue

contribution is anticipated to be

significantly less than this estimate.

2. Drinking water. Fenbuconazole has

minimal tendency to contaminate

groundwater or drinking water because

of its adsorptive properties on soil,

solubility in water, and degradation

rate. Data from laboratory studies and

field dissipation studies have been used

in the USDA PRZM/GLEAMS computer

model to predict the movement of

fenbuconazole. The model predicts that

fenbuconazole will not leach into

groundwater, even if heavy rainfall is

simulated. The modeling predictions are

consistent with the data from

environmental studies in the laboratory

and the results of actual field

dissipation studies. There are no data on

passage of fenbuconazole through water

treatment facilities and there are no

State water monitoring programs which

target fenbuconazole.

3. Non-Dietary Exposure.

Fenbuconazole has no veterinary

applications and is not approved for use

in swimming pools. It is not labeled for

application to residential lawns or for

use on ornamentals, nor is

fenbuconazole applied to golf courses or

other recreational areas. Therefore, there

are no data to suggest that these

exposures could occur. Any acute

exposures to children would come from

dietary exposure or inadvertent dermal

contact . As previously discussed,

fenbuconazole is neither orally or

dermally acutely toxic. Thus, there is a

reasonable certainty that no exposure

would occur to adults, infants or

children from these sources.

D. Cumulative Effects

The toxicological effects of

fenbuconazole are related to the effects

on rodent liver. These are manifest in

rats and mice differently.

Fenbuconazole causes liver toxicity in

rats and mice in the form of hepatocyte

enlargement and enzyme induction. In

rats the liver enzyme induction causes

increased biliary removal of thyroxin

and the hepatotoxicity leads to elevated

thyroid stimulating hormone levels with

subsequent development of thyroid

gland hyperplasia and tumors. This

process is reversible and demonstrates a

dose level below which no thyroid

gland stimulation can be demonstrated

in rats. Liver toxicity in the mouse is

manifest by hepatocyte enlargement,

enzyme induction, and hepatocellular

hyperplasia (cell proliferation). These

processes are associated with the

appearance of a small number of liver

tumors. In both cases, rats and mice, the

initiating event(s) do not occur below a

given dose, i.e., the effects are

nonlinear, and the processes are

reversible. Therefore, since the tumors

do not occur at doses below which

hepatocyte enlargement and enzyme

induction occur, the RfD protects

against tumors because it is

substantially below the NOEL for liver

effects and maximal human exposures

are below the RfD. Effects on human

thyroid will not occur at anticipated

dietary levels. The mode of action data

should be carefully considered in

deciding the relevance of these highdose animal tumors to human dietary

exposure.

Extensive data are available on the

biochemical mode of action by which

fenbuconazole produces animal tumors

in both rats and mice. However, there

are no data which suggest that the mode

of action by which fenbuconazole

produces these animal tumors or any

other toxicological effect is common to

all fungicides of this class. In fact, the

closest structural analog to

fenbuconazole among registered

fungicides of this class is not
48848 Federal Register / Vol. 62, No. 180 / Wednesday, September 17, 1997 / Notices

tumorigenic in animals even at

maximally tolerated doses and has a

different spectrum of toxicological

effects.

E. Safety Determination

1. US population. The Rohm and Haas

Company estimates the risk to the U.S.

adult population from use of

fenbuconazole on wheat as utilizing

approximately 0.36% of the RfD. Using

the EPA low dose extrapolation model

and the risk factor based on the mouse

data (0.36 x 10-6 (mg/kg/day)-1) the

excess cancer risk from dietary sources

for fenbuconazole use on wheat and the

associated animal commodities is

estimated at 0.3 x 10-6. The upper bound

estimate on excess cancer risk for all

uses including wheat is 0.7 x 10-6.

This assumes that all of the wheat

consumed in the U.S. will contain

residues of fenbuconazole (in actuality a

small fraction of the total crop is likely

to be treated). The combined risk for

wheat plus registered uses will not

exceed either the dietary risk standard

established by the Food Quality

Protection Act (FQPA) for the US

population, (one x 10-6), or the RfD.

The sole acute risk would be for

women of childbearing age. The EPA/

OREB calculated that the worst-case

Margin of Exposure (MOE) for

fenbuconazole measured against the

developmental LOEL would be greater

than 30,000. This is clearly adequate.

The MOE would be even higher for

consumer dietary exposure from any

source. Thus, there is adequate safety

for this group and there is a reasonable

certainty that no harm will result from

fenbuconazole use on wheat.

2. Infants and children. The

reproductive and developmental

toxicity data base for fenbuconazole is

complete. There is no selective increase

in toxicity to developing animals. Thus,

there is no evidence that prenatal and

postnatal exposure would present

unusual or disproportionate hazard to

infants or children. Therefore, there is

no need to impose an additional

uncertainty factor to protect infants and

children.

The EPA calculated the dietary risk to

infants and children for existing

tolerances. The estimated dietary

exposure (TMRC) for this subpopulation

is 0.00522 mg/kg/day which represents

only 17% of the RfD; no other subgroup

used in excess of 17% of the RfD. The

EPA estimated lifetime oncogenic risk

in the range of one in a million at 0.9

x 10-6, using (Q1* = 1.06x10-2 (mg/kg/

day)-1). (60 FR 27420; May 24,1995).

For the wheat use the most sensitive

subgroup is children 1 to 6 years old

and the estimated risk to this subgroup

is less than 18% of the RfD. Utilizing

the risk factor (Q1* = 0.36x10-2 (mg/kg/

day)-1), the estimated excess cancer risk

for the U.S. population is less than 1 x

10-6. Therefore the wheat use is safe

within the meaning of the FQPA and

there is a reasonable certainty that no

harm will result to infants or children

from the approval of fenbuconazole use

on wheat.

F. International Tolerances

There are no Codex Maximum

Residue Levels (MRLs) for

fenbuconazole, but the fenbuconazole

database will be evaluated by the WHO

and the FAO Expert Panels at the Joint

Meeting on Pesticide Residues (JMPR)

in September 1997. An Allowable Daily

Intake (ADI (RfD)) of 0.03 mg/kg/day is

proposed and a total of 36 Codex MRLs

are proposed in the data submission.

G. Environmental Fate Summary

Fenbuconazole has little to no

mobility in soil (Koc = 4425). It is stable

to hydrolysis and aqueous photolysis in

buffered solutions, but does degrade

photolytically in natural waters and soil

(half–life 87 and 79 days, respectively).

Laboratory soil metabolism half–lives or

DT50 values for fenbuconazole range

from 29 to 532 days under terrestrial

conditions and from 442 to 906 in soil

exposed to aquatic conditions. Fieldtrial soil dissipation studies had half–

lives ranging from 157 to 407 days and

indicated no significant downward

movement of residues. These field trials

show fenbuconazole degrades more

rapidly outdoors than in laboratory

metabolism studies. When material was

applied in a single application,

fenbuconazole degraded to about 50%

of the applied material in less than 60

days. In wheat the DT50 in green heads

was measured as 18 days and in green

wheat stalks the DT50 was 84.4 days.

These results only reflect foliar

dissipation in wheat at the particular

growth stage(s) during the study and not

at all stages of wheat. The results of

residue decline analyses in a number of

environmental media support the EPA

conclusion that there is no

environmental hazard associated with

the proposed agricultural use of this

chemical.

[FR Doc. 97–24693 Filed 9–16–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–754; FRL–5735–8]

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 and/or

amendment of regulations for residues

of certain pesticide chemicals in or on

various food commodities.

DATES: Comments, identified by the

docket control number PF–754, must be

received on or before October 17, 1997.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch, Information

Resources and Services Division

(7506C), Office of Pesticides Programs,

Environmental Protection Agency, 401

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

person bring comments to: Rm. 1132,

CM #2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically by following

the instructions under

‘‘SUPPLEMENTARY INFORMATION.’’

No confidential business information

should be submitted through e-mail.

Information submitted as a comment

concerning this document may be

claimed confidential by marking any

part or all of that information as

‘‘Confidential Business Information’’

(CBI). CBI should not be submitted

through e-mail. Information marked as

CBI will not be disclosed except in

accordance with procedures set forth in

40 CFR part 2. A copy of the comment

that does not contain CBI must be

submitted for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments will be available for public

inspection in Rm. 1132 at the address

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

Monday through Friday, excluding legal

holidays.

FOR FURTHER INFORMATION CONTACT: By

mail: Sidney Jackson, Product Manager

(PM) 43, Minor Use, Inerts, Emergency

Response Branch, Registration Division

(7505C), Office of Pesticide Programs,

Environmental Protection Agency, 401

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

Office location and telephone number:

Rm. 274, CM#2, 1921 Jefferson Davis

Highway, Arlington, VA., (703) 305–

7610. e-mail:

jackson.sidney@epamail.epa.gov.