52544 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

the comment date. Protests will be

considered by the Commission in

determining the appropriate action to be

taken, but will not serve to make

protestants parties to the proceeding.

Any person wishing to become a party

must file a motion to intervene. Copies

of this filing are on file with the

Commission and are available for public

inspection.

Lois D. Cashell,

Secretary.

[FR Doc. 97–26665 Filed 10–7–97; 8:45 am]

BILLING CODE 6717–01–P

ENVIRONMENTAL PROTECTION

AGENCY

[PF–766; FRL 5746–9]

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–766, must be

received on or before November 7, 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 to: oppdocket@epamail.epa.gov. Follow the

instructions under ‘‘SUPPLEMENTARY

INFORMATION’’ of this document. No

Confidential Business Information (CBI)

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 CBI.

Information so marked 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

Cynthia Giles-Parker,

(PM 22).

Rm. 247, CM #2, 703–305–7740; e-mail: giles-parker cynthia@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Joanne Miller (PM 23) ... Rm. 237, CM #2, 703–305–6224; e-mail: miller joanne@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–766]

(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-766) 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: September 29, 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. AgrEvo USA Company (AgrEvo)

PP 7F4910 and 7E4911

EPA has received pesticide petitions

(PP 7F4910 and 7E4911) from AgrEvo

USA Company (AgrEvo), Wilmington,

DE 19808 proposing pursuant to section

408(d) of the Federal Food, Drug and

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

amend 40 CFR 180.473(c) and part 186

by establishing tolerances for residues of

glufosinate-ammonium in or on raw

agricultural commodities derived from

transgenic sugar beets and canola that

are tolerant to the herbicide, glufosinateammonium: sugar beet roots at 0.7 ppm,

sugar beet tops (leaves) at 1.3 ppm,

canola seed at 0.4 ppm and the

processed feeds: canola meal at 2.0 ppm

and sugar beet molasses at 5.0 ppm.

AgrEvo has also proposed to amend 40

CFR 180.473(a)(1) and part 185 by

establishing a tolerance for residues of

the herbicide, glufosinate-ammonium:

butanoic acid, 2-amino-4-

(hydroxymethylphosphinyl)-,

monoammonium salt and its metabolite,

3-methylphosphinico-propionic acid

expressed as glufosinate free acid
Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices 52545

equivalents in or on the following raw

agricultural commodity: potatoes at 0.4

ppm and the processed foods: potato

flakes at 1.3 ppm and processed

potatoes (including potato chips) at 1.0

ppm. The proposed analytical method

involves homogenization, filtration,

partition and cleanup with analysis by

gas chromatography. 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 support granting of the petition.

Additional data may be needed before

EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism

of glufosinate-ammonium in plants is

adequately understood for the purposes

of these tolerances. The crop residue

profile following selective use of

glufosinate-ammonium on transgenic

crops is different than that found in

conventional crops. The only crop

residue found after non-selective use is

the metabolite, 3-methylphosphinicopropionic acid, which is found in only

trace amounts. The principal residue

identified in the metabolism studies

after selective use of glufosinateammonium on transgenic crops is the

acetylated derivative of the parent

material, 2-acetamido-4-

methylphosphinico-butanoic acid, with

lesser amounts of glufosinate and 3-

methylphosphinico-propionic acid.

2. Analytical method. There is a

practical analytical method utilizing gas

chromatography for detecting and

measuring levels of glufosinateammonium and its metabolites in or on

food with a general limit of

quantification of 0.05 ppm. This method

allows monitoring of food with residues

at or above the levels proposed in these

tolerances. This method has been

validated by an independent laboratory

and the petitioner has been advised that

the EPA concluded its own successful

method try out.

3. Magnitude of residues. Field

residue trials with glufosinateammonium tolerant sugar beets and

canola have been conducted in 1995

and 1996 and 1993 and 1994

respectively at several different use rates

and timing intervals to represent the use

patterns which would most likely result

in the highest residue. In these trials,

the primary residue in all samples was

the combination of glufosinate and 2-

acetamido-4-methylphosphinicobutanoic acid which was typically

found at higher levels than 3-

methylphosphinico-propionic acid. In

sugar beets, the mean glufosinateammonium derived residues in treated

roots did not exceed 0.70 ppm in trials

conducted at 13 different sites

representing the 6 major sugar beet

producing regions in the U.S. The mean

glufosinate-ammonium derived residues

in treated tops (leaves) in these trials

did not exceed 1.29 ppm when sampled

at 60 days or more after treatment.

In canola, 11 out of 40 samples

produced detectable residue levels

above the limit of detection in harvested

seed following treatment with

glufosinate-ammonium at 14 trial

locations. The highest level of residue

found in these trials was 0.295 ppm and

the total mean glufosinate derived

residues in all samples containing

detectable residues was 0.136 ppm.

For both sugar beet and canola, the

tolerances levels have been proposed

assuming the following: (1) a seasonal

maximum rate of 1.1 pounds of active

ingredient per acre for sugar beets and

0.9 pound of active ingredient per acre

for canola and (2) a pre-harvest interval

of 60 days for sugar beets and 65 days

for canola.

Total residues of glufosinateammonium and its metabolite in

potatoes desiccated with glufosinateammonium were determined in more

than 40 trials conducted over

approximately 13 locations during the

period from 1987 to 1994. Within the

pre-harvest interval of 7 to 56 days, all

residue values (with one exception) did

not exceed 0.4 ppm. A pre-harvest

interval of 9 days is specified on the

product label for potato desiccation and

the seasonal maximum use rate is 0.4

pound of active ingredient per acre.

4. Residue in processed commodities.

Studies have been conducted to

determine the level of glufosinate

derived residues found in or on the

processed commodities from glufosinate

tolerant sugar beet roots, canola seed

and potatoes. The studies utilized

treatments at significantly exaggerated

rates to provide the necessary test

sensitivity. In the sugar beet processing

study, a concentration factor of 6.3x was

determined for sugar beet molasses

whereas there was no concentration of

residues in either refined sugar or dried

pulp.

In the canola processing study, a

concentration factor of approximately 4

times was observed for the meal when

the levels of terminal residues were

compared between the seed and the

toasted meal. There was no

concentration of residues in the canola

oil.

In the potato processing study,

glufosinate residues appear to

concentrate 2.3 fold in chips and 3.1

fold in flakes. Glufosinate residues do

not appear to concentrate in the peel.

B. Toxicological Profile

1. Acute toxicity. The acute oral LD50

values for glufosinate-ammonium

technical ranged from 1,510 to 2,000

mg/kg in rats and from 200 to 464 mg/

kg in mice and dogs. The acute dermal

LD50 was 2,000 mg/kg in rabbits and ≥

4,000 mg/kg in rats. The 4–hour rat

inhalation LC50 was 1.26 mg/L in males

and 2.6 mg/L in females. Glufosinateammonium was not irritating to rabbit

skin but was slightly irritating to the

eyes. Glufosinate-ammonium did not

cause skin sensitization in guinea pigs.

Glufosinate-ammonium should be

classified as Tox Category II for oral

toxicity, Tox Category III for inhalation

and dermal toxicity and Tox Category IV

for skin irritation and eye irritation.

2. Genotoxicty. No evidence of

genotoxicity was noted in an extensive

battery of in vitro and in vivo studies.

The petitioner has been advised by the

EPA that negative studies determined

acceptable included Salmonella, E. Coli

and mouse lymphoma gene mutation

assays, a mouse micronucleus assay,

and an in vitro UDS assay.

3. Reproductive and developmental

toxicity. Three developmental toxicity

studies were conducted with rats, at

dose levels ranging from 0.5 to 250 mg/

kg/day. The No Observed Effect Levels

(NOEL’s) for maternal and

developmental effects were determined

to be 10 mg/kg/day for maternal toxicity

and 50 mg/kg/day for developmental

toxicity, based on the findings of

hyperactivity and vaginal bleeding in

dams at 50 mg/kg/day and increased

incidence of arrested renal and ureter

development in fetuses at 250 mg/kg/

day.

A developmental toxicity study was

conducted in rabbits at dose levels of 0,

2, 6.3 and 20 mg/kg/day. The maternal

NOEL for this study was determined to

be 6.3 mg/kg/day, based on increases in

abortion and premature delivery, and

decreases in food consumption and

weight gain at 20 mg/kg/day. No

evidence of developmental toxicity was

noted at any dose level; thus the

developmental NOEL was determined to

be 20 mg/kg/day.

A 2-generation rat reproduction study

was conducted at dietary concentrations

of 0, 40, 120 and 360 ppm. The parental

NOEL was determined to be 40 ppm (4

mg/kg/day) based on increased kidney

weights at 120 ppm. The NOEL for

reproductive effects was determined to

be 120 ppm (12 mg/kg/day) based on

reduced numbers of pups at 360 ppm.

4. Subchronic toxicity. A 90–day

feeding study was conducted in Fisher
52546 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

344 rats at dietary concentrations of 0,

8, 64, 500 and 4,000 ppm. Although

slight evidence of toxicity was observed,

there were no treatment-related

histopathological findings at any dose

level. The NOEL for this study was

determined to be 8 ppm, based on

increased kidney weights at 64 ppm.

A 90–day feeding study was

conducted in NMRI mice at dietary

concentrations of 0, 80, 320 and 1,280

ppm. There were no treatment-related

pathological findings at any dose level

but increases in absolute and relative

liver weights, serum AST, and serum

potassium levels were noted at 320 and/

or 1,280 ppm. Based on these findings,

the NOEL for this study was determined

to be 80 ppm (16.6 mg/kg/day).

A 90–day feeding study was

conducted in beagle dogs at dietary

concentrations of 0, 4, 8, 16, 64 and 256

ppm. There were no treatment-related

histopathological findings at any dose

level. However, because of reduced

weight gain and decreased thyroid

weights at 64 and/or 256 ppm, the

NOEL was determined to be 16 ppm

(0.53 mg/kg/day).

5. Chronic toxicity. A 12–month

feeding study was conducted in beagle

dogs at dose levels of 0, 2, 5 and 8.5 mg/

kg/day. The NOEL was 5 mg/kg/day

based on clinical signs of toxicity,

reduced weight gain and mortality at 8.5

mg/kg/day.

A 2–year mouse oncogenicity study

was conducted in NMRI mice at dietary

concentrations of 0, 20, 80 and 160

(males) or 320 (females) ppm. The

NOEL was determined to be 80 ppm

(10.8 and 16.2 mg/kg/day for males and

females, respectively) based on

increased blood glucose, decreased

glutathione levels and increased

mortality in the high-dose males and/or

females. No evidence of oncogenicity

was noted at any dose level.

A combined chronic toxicity/

oncogenicity study was conducted in

Wistar rats for up to 130 weeks at

dietary concentrations of 0, 40, 140 and

500 ppm. A dose-related increase in

mortality was noted in females at 140

and 500 ppm, while increased absolute

and relative kidney weights were noted

in 140 and 500 ppm males. Thus, the

NOEL for this study was determined to

be 40 ppm (2.1 mg/kg/day). No

treatment-related oncogenic response

was noted. However, the high-dose level

in this study did not satisfy the EPA

criteria for a Maximum Tolerated Dose

and thus a data gap currently exists for

a rat carcinogenicity study. All

glufosinate-ammonium tolerances

previously established by the EPA are

time-limited because of this gap. A new

rat oncogenicity study is currently being

conducted and is due to the EPA by July

1, 1998.

6. Animal metabolism. Numerous

studies have been conducted to evaluate

the absorption, distribution, metabolism

and/or excretion of glufosinateammonium in rats. These studies

indicate that glufosinate-ammonium is

poorly absorbed (5–10%) after oral

administration and is rapidly

eliminated, primarily as parent

compound. Small amounts of the

metabolites 3-methylphosphinicopropionic acid and 2-acetamido-4-

methylphosphinico-butanoic acid were

found in the excreta, although the latter

is believed to be a result of a revisable

acetylation and decetylation process by

intestinal bacteria.

7. Metabolite toxicology . The primary

residue resulting from the use of

glufosinate-ammonium in genetically

transformed sugar beets and canola that

are tolerant to the herbicide, glufosinateammonium, consists of the metabolites,

2-acetamido-4-methylphosphinicobutanoic acid and 3-

methylphosphinico-propionic acid.

Only the latter metabolite is formed in

conventional crops. A considerable

number of toxicity studies have been

conducted with these metabolites,

including developmental toxicity

studies in rats and rabbits with both

metabolites and a 2-generation rat

reproduction study with 2-acetamido-4-

methylphosphinico-butanoic acid.

Neither metabolite presents an acute

toxicity hazard and both were

determined to be non-genotoxic in an

extensive battery of in vitro and in vivo

genotoxicity studies. Neither metabolite

demonstrated significant developmental

toxicity to either rats or rabbits.

Subchronic studies in rats, mice and

dogs were conducted with both

metabolites with no clear evidence for

any specific target organ toxicity and

with NOEL’s or No Observed Adverse

Effects Levels (NOAEL’s) substantially

higher than those seen with glufosinateammonium. Thus, these studies indicate

that both metabolites are less toxic than

the parent compound and do not pose

any reproductive or developmental

concerns.

C. Endocrine Effects

No special studies investigating

potential estrogenic or endocrine effects

of glufosinate-ammonium have been

conducted. However, the standard

battery of required studies has been

completed. These studies include an

evaluation of the potential effects on

reproduction and development, and an

evaluation of the pathology of the

endocrine organs following repeated or

long-term exposure. These studies are

generally considered to be sufficient to

detect any endocrine effects but no such

effects were noted in any of the studies

with either glufosinate-ammonium or its

metabolites.

D. Aggregate Exposure

Glufosinate-ammonium is a nonselective, post-emergent herbicide with

both food and non-food uses. As such,

aggregate non-occupational exposure

would include exposures resulting from

consumption of potential residues in

food and water, as well as from residue

exposure resulting from non-crop use

around trees, shrubs, lawns, walks,

driveways, etc. Thus, the possible

human exposure from food, drinking

water and residential uses has been

assessed below.

1. Food. For purposes of assessing the

potential dietary exposure from food

under the proposed tolerances, the

petitioner has been advised that the EPA

has estimated exposure based on the

Theoretical Maximum Residue

Contribution (TMRC) derived from the

initially established tolerances for

glufosinate-ammonium on apples,

grapes, tree nuts, bananas, milk and the

fat, meat and meat-by-products of cattle,

goats, hogs, horses and sheep as well as

the subsequently established tolerances

for glufosinate-ammonium on field corn,

soybeans, aspirated grain fractions, and

the eggs, fat, meat and meat-by-products

of poultry. The TMRC is obtained by

using a model which multiplies the

tolerance level residue for each

commodity by consumption data which

estimate the amount of each commodity

and products derived from the

commodity that are eaten by the U.S.

population and various population

subgroups. In conducting this exposure

assessment, the EPA has made very

conservative assumptions—100% of all

commodities will contain glufosinateammonium residues and those residues

would be at the level of the tolerance—

which result in a large overestimate of

human exposure. Thus, in making a

safety determination for these

tolerances, the Agency took into account

this very conservative exposure

assessment. In 62 FR 5333 (February 5,

1997), the Agency concluded that the

original tolerances for apples, nuts,

grapes and the secondary tolerances in

animal commodities utilize 2.07% of

the Reference Dose (RfD) and that the

subsequent tolerances for the corn and

soybean commodities will utilize 3.7%

of the RfD.

2. Drinking water. There is presently

no EPA Lifetime Health Advisory level

or Maximum Contaminant Level

established for residues of glufosinateammonium in water. The petitioner has
Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices 52547

been advised by the EPA that all

environmental fate data requirements

for glufosinate-ammonium have been

satisfied. The potential for glufosinateammonium to leach into groundwater

has been assessed in a total of nine

terrestrial field dissipation studies

conducted in several states and in

varying soil types. The degradation of

glufosinate-ammonium in these studies

was rapid, with half-lives ranging from

a low of 6 to a high of 23 days. Despite

the relatively high water solubility of

glufosinate-ammonium, this compound

did not appear to leach under typical

test conditions. This is a result of the

combination of its rapid degradation

and its tendency to bind to certain soil

elements such as clay or organic matter.

Based on these studies and the expected

conditions of use, the potential for

finding significant glufosinateammonium residues in water is minimal

and the contribution of any such

residues to the total dietary intake of

glufosinate-ammonium will be

negligible.

3. Non-dietary exposure. As a nonselective, post-emergent herbicide,

homeowner use of glufosinateammonium will consist primarily of

spot spraying of weeds around trees,

shrubs, walks, driveways, flower beds,

etc. There will be minimal opportunity

for post-application exposure since

contact with the treated weeds will

rarely occur. Thus, any exposures to

glufosinate-ammonium resulting from

homeowner use will result from dermal

exposure during the application and

will be limited to adults, not to infants

or children. These exposures are not

expected to pose any acute toxicity

concerns. Furthermore, based on the US

EPA National Home and Garden

Pesticide Use Survey (RTI/5100/17-01F,

March 1992), the average homeowner is

expected to use non-selective herbicides

only about 4 times a year. Thus, these

exposures would not normally be

factored into a chronic exposure

assessment.

E. Cumulative Effects

The potential for cumulative effects of

glufosinate-ammonium and other

substances that have a common

mechanism of toxicity must also be

considered. The precise mechanism of

action for the toxic effects of

glufosinate-ammonium in animals is not

known but is believed to result, at least

in part, from interference with the

neurotransmitter function of glutamate,

to which it is a close structural analog.

No other registered active ingredients

are known to have a similar mechanism

of action. Thus, no cumulative effects

with other substances are anticipated.

Furthermore, the residues in or on

transgenic crops will consist primarily

of the metabolites of glufosinateammonium, not glufosinate-ammonium

itself. These metabolites are less toxic

than glufosinate-ammonium and,

because they are not structural analogs

of glutamate, they should not cause the

same effects. Thus, consideration of a

common mechanism of toxicity is not

appropriate at this time and only the

potential risks of glufosinate-ammonium

need to be considered in its aggregate

exposure assessment.

F. Safety Determinations

1. U.S. population. Based on a

complete and reliable toxicity database,

the EPA has adopted an RfD value of

0.02 mg/kg/day using the NOEL of 2.1

mg/kg/day from the chronic rat toxicity

study and a 100-fold safety factor. Using

the Dietary Risk Evaluation System

(DRES) with raw agricultural

commodity residue values set at the

established and proposed tolerance

levels and with reasonable maximum

market share estimates applied

(‘‘realistic’’ case assessment), AgrEvo

has calculated that aggregate dietary

exposure to glufosinate-ammonium

from the previously established

tolerances and the proposed tolerances

on sugar beets, canola and potatoes will

utilize 2.1% of the RfD for the U.S.

population (48 states). There is

generally no concern for exposures

below 100% of the RfD because the RfD

represents the level at or below which

daily aggregate dietary exposure over a

lifetime will not pose appreciable risks

to human health. Therefore, there is a

reasonable certainty that no harm will

result from aggregate exposure to

glufosinate-ammonium residues to the

U.S. population in general.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

glufosinate-ammonium, one should

consider data from developmental

toxicity studies in the rat and rabbit and

a 2-generation reproduction study in the

rat. The developmental toxicity studies

are designed to evaluate adverse effects

on the developing organism resulting

from pesticide exposure during prenatal development. Reproduction

studies provide information relating to

reproductive and other effects on adults

and offspring from pre-natal and postnatal exposure to the pesticide.

Three developmental toxicity studies

in rats (including pre- and post-natal

phases), a developmental toxicity study

in rabbits, and a 2-generation rat

reproduction study have been

conducted with glufosinate-ammonium.

No evidence of developmental toxicity

was noted in rabbits, even at the

maternally toxic dose level of 20 mg/kg/

day. No developmental or reproductive

effects were noted in rats except at

parentally toxic dose levels. The NOEL’s

for maternal and developmental toxicity

in the rat developmental toxicity studies

were determined to be 10 mg/kg/day

and 50 mg/kg/day, respectively, based

on findings of hyperactivity and vaginal

bleeding in dams at 50 mg/kg/day and

increased incidence of arrested renal

and ureter development in fetuses at

250 mg/kg/day. The parental and

reproductive NOEL’s in the 2-generation

rat reproduction study were determined

to be 40 ppm (4 mg/kg/day) and 120

ppm (12 mg/kg/day), respectively, based

on increased parental kidney weights at

120 ppm and decreased numbers of

pups at 360 ppm. In all cases, the

reproductive and developmental

NOEL’s were greater than or equal to the

parental NOEL’s, thus indicating that

glufosinate-ammonium does not pose

any increased risk to infants or children.

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. Further,

the NOEL at 2.1 mg/kg/day from the

chronic rat study with glufosinateammonium, which was used to

calculate the RfD (discussed above), is

already lower than the NOEL’s from the

reproductive and developmental studies

with glufosinate-ammonium by a factor

of at least 6-fold. Therefore, an

additional safety factor is not warranted

and an RfD of 0.02 mg/kg/day is

appropriate for assessing aggregate risk

to infants and children.

Using the DRES analysis with raw

agricultural commodity residue values

set at the established and proposed

tolerance levels and with reasonable

maximum market share estimates

applied (‘‘realistic’’ case assessment),

AgrEvo has calculated that aggregate

dietary exposure to glufosinateammonium from the previously

established tolerances and the proposed

tolerances on sugar beets, canola and

potatoes will utilize 5.5% of the RfD for

non-nursing infants (1– year old), the

most sensitive population sub-group

and 5.3% of the RfD for children (1–6

year old), the second most sensitive

population sub-group. Therefore, based

on the completeness and reliability of

the toxicity data and a comprehensive

exposure assessment, it may be

concluded that there is a reasonable

certainty that no harm will result to
52548 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

infants and children from aggregate

exposure to glufosinate-ammonium

residues.

G. International Tolerances

An analysis of the Codex

Alimentarius Commission (Codex)

tolerances has been conducted. While

no international Codex tolerances for

selective uses of tolerances for

glufosinate-ammonium in the

desiccation use pattern have been

established for conventional canola

(rapeseed) at 5 ppm, crude rapeseed oil

at 0.05 ppm and potatoes at 0.5 ppm.

These tolerances are established for the

sum of glufosinate-ammonium and 3-

methylphosphinico-propionic acid,

calculated as glufosinate (free acid). The

U.S. proposal for a 0.4 ppm tolerance for

residues of glufosinate-ammonium in

potatoes will be harmonized with the

Canadian tolerance which has already

been established at this level.

The Codex tolerances for glufosinateammonium in or on sugar beets have

been established at 0.05 ppm in the beet

and 0.1 ppm in the tops (leaves). AgrEvo

intends to propose higher tolerances to

the Codex commission for glufosinateammonium use on transgenic sugar

beets in order to harmonize these

tolerances with those proposed in the

U.S. and elsewhere. (Joanne Miller)

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

PP 7F4821

EPA has received an amendment to

pesticide petition (PP 7F4821) from KI Chemical U.S.A., Inc. , White Plains,

New York 10606, proposing pursuant to

section 408(d) of the Federal Food, Drug

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

amend 40 CFR part 180 by establishing

a tolerance for residues of herbicide,

fluthiacet-methyl in or on the raw

agricultural commodity popcorn grain at

0.02 ppm.

On April 14, l997, EPA announces

receipt of a pesticide petition (PP

7F4821) from K-I Chemical U.S.A., Inc.,

11 Martine Avenue, 9th Floor, White

Plains, NY 10606, proposing pursuant to

section 408(d) of the Federal Food, Drug

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

amend 40 CFR part 180 by establishing

a tolerance for residues of the herbicide

fluthiacet-methyl: Acetic acid, [[2-

chloro-4-fluoro-5-[(tetrahydro-3-oxo1H,3H-[1,3,4]thiadiazolo[3,4-a]

pyridazin-1-

ylidene)amino]phenyl]thio]-methylester

in or on the raw agricultural

commodities field corn grain and sweet

corn grain (K + CWHR) at 0.02 ppm and

corn forage and fodder at 0.05 ppm.

On September 4, 1997 K-I Chemical,

U.S.A., Inc., amended PP 7F4821 to

include a proposed tolerance for

popcorn grain at 0.02 ppm. EPA has

determined that the amended petition

contains data or information regarding

the elements set forth in section

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

has not fully evaluated the sufficiency

of the submitted data at this time or

whether the data supports granting of

the petition. Additional data may be

needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The nature of the

residues in corn is adequately

understood following application of

fluthiacet-methyl. Residue levels and

the metabolic pathway are consistent

with those in soybeans. Parent

fluthiacet-methyl was the primary

component of the residue seen in corn

grain, forage, fodder and silage. Results

of these studies have been submitted to

the EPA.

2. Analytical method. K-I Chemical

has submitted practical analytical

methods (AG–603B and AG–624) for

detecting and measuring the level of

fluthiacet-methyl in or on corn and corn

commodities and in animal tissues with

a limit of detection that allows

monitoring residues at or above the

levels set for the proposed tolerance.

The limit of quantitation of the crop

method is 0.01 ppm in corn and corn

commodities, 0.05 ppm in animal

tissues and 0.01 ppm in milk. The crop

method involves extraction, filtration,

and solid phase clean up. Residue levels

of fluthiacet-methyl are determined by

gas chromatographic analysis utilizing a

nitrogen phosphorus detector and a

fused-silica column. The animal tissue

method involves extraction, filtration,

and partition. Determination of residue

levels in animal tissues is by HPLC with

UV detection via column switching

using C1 and C18 columns. The analyte

of interest in animal tissues and milk is

the major animal metabolite CGA–

300403. Residues of fluthiacet-methyl in

corn are determined by gas

chromatography.

3. Magnitude of residues. The residue

of concern in corn is fluthiacet-methyl

per se. Twenty-one field residue studies

were conducted with corn grown in

nineteen states. Fifteen of the studies

were on field corn and six on sweet

corn. No studies were conducted with

popcorn, however K-I believes that the

data on field and sweet corn support a

tolerance in popcorn as well. Because

the proposed use rate and pattern is the

same for popcorn, it is reasonable to

conclude that residues in popcorn grain

will not exceed the proposed tolerance

of 0.02 ppm. Residues in field and sweet

corn forage after the day of application

were less than the proposed tolerance of

0.05 ppm. Popcorn forage is not a fed

commodity. Nonetheless, residues in

popcorn forage or fodder are not

expected to exceed the proposed

tolerance of 0.05 ppm. The proposed

tolerances of 0.02 ppm in field corn,

sweet corn, and popcorn grain and 0.05

ppm in field corn and sweet corn forage

and fodder are adequate to cover

residues likely to occur when Action

herbicide is applied to corn as directed.

This position is based on section

180.34(d) of the CFR which states that

‘‘If the pesticide chemical is not

absorbed into the living plant or animal

when applied (is not systemic), it may

be possible to make a reliable estimate

of the residues to be expected on each

commodity in a group of related

commodities on the basis of less data

than would be required for each

commodity in the group, considered

separately.’’ And, section 180.34(e)

states that ‘‘Each of the following groups

of crops lists raw agricultural

commodities that are considered to be

related for the purpose of paragraph (d)

of this section; field corn, popcorn,

sweet corn (each in grain form).’’

Residues of fluthiacet-methyl in

treated field and sweet corn grain and

sweet corn ears were less than the

method LOQ (<0.01 ppm). Because the

proposed use rate and pattern is the

same for popcorn, it is reasonable to

conclude that residues in popcorn grain

will not exceed the proposed tolerance

of 0.02 ppm. Residues in field and sweet

corn forage after the day of application

were less than the proposed tolerance of

0.05 ppm. Popcorn forage is not a feed

commodity. Nonetheless, residues in

popcorn forage or fodder are not

expected to exceed the proposed

tolerance of 0.05 ppm. The proposed

tolerances of 0.02 ppm in field corn,

sweet corn, and popcorn grain and 0.05

ppm in field corn and sweet corn forage

and fodder are adequate to cover

residues likely to occur when Action

herbicide is applied to corn as directed.

B. Toxicological Profile

1. Acute toxicity.

•A rat acute oral study with an LD50

> 5,000 mg/kg.

•A rabbit acute dermal study with an

LD50 > 2,000 mg/kg.

•A rat inhalation study with an LC50

> 5.05 mg/liter.

•A primary eye irritation study in the

rabbit showing moderate eye irritation.

•A primary dermal irritation study in

the rabbit showing no skin irritation.

•A primary dermal sensitization study

in the Guinea pig showing no

sensitization.
Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices 52549

•Acute neurotoxicity study in rats.

Neurotoxic effects were not observed.

The NOEL was 2,000 mg/kg.

2. Genotoxicity. In vitro gene

mutation tests: Ames test - negative;

Chinese hamster V79 test - negative; rat

hepatocyte DNA repair test - negative; E.

Coli letal DNA damage test - negative.

In vitro chromosomal aberration tests:

Chinese hamster ovary - positive at

cytotoxic doses; Chinese hamster lung -

positive at cytotoxic doses; human

lymphocyes - positive at cytotoxic

doses. In vivo chromosome aberration

tests: Micronucleus assays in rat liver -

negative; mouse bone marrow test -

negative.

3. Reproductive and developmental

toxicity. Reproductive and

developmental toxicity. Teratology

study in rats with a maternal and

developmental NOEL equal to or greater

than 1,000 mg/kg/day.

Teratology study in rabbits with a

maternal NOEL greater than or equal to

1,000 mg/kg/day and a fetal NOEL of

300 mg/kg based on a slight delay in

fetal maturation. 2-generation

reproduction study in rats with a NOEL

of 36 mg/kg/day, based on liver lesions

in parental animals and slightly reduced

body weight development in parental

animals and pups. [The treatment had

no effect on reproduction or fertility.]

4. Subchronic toxicity. 90–day

subchronic neurotoxicity study in rats.

The NOEL was 0.5 mg/kg/day based on

reduced body weight gain. No clinical

or morphological signs of neurotoxicity

were detected at any dose level. 28–day

dermal toxicity study in rats with a

NOEL equal to or higher than the limit

dose of 1,000 mg/kg.

6–week dietary toxicity study in dogs

with a NOEL of 162 mg/kg/day in males

and 50 mg/kg/day in females based on

decreased body weight gain and modest

hematological changes.

90–day subchronic dietary toxicity

study in rats with a NOEL of 6.2 mg/kg/

day based on liver changes and

hematological effects.

5. Chronic toxicity. 24–month

combined chronic toxicity/

carcinogenicity study in rats with a

NOEL of 2.1 mg/kg/day. Based on

reduced body weight development and

changes in bone marrow, liver, pancreas

and uterus the MTD was exceeded at

130 mg/kg/day. A positive trend of

adenomas of the pancreas in male rats

treated at 130 mg/kg/day and above may

be attributable to the increased survival

of the rats treated at high doses. 18–

month oncogenicity study in mice with

a NOEL of 0.14 mg/kg/day. Based on

liver changes, the MTD was reached at

1.2 mg/kg/day. The incidence of

hepatocellular tumors was increased in

males treated at 12 and 37 mg/kg/day.

C. Endocrine effects

Based on the results of short-term,

chronic, and reproductive toxicity

studies there is no indication that

fluthiacet-methyl might interfere with

the endocrine system. Considering

further the low environmental

concentrations and the lack of

bioaccumulation, there is no risk of

endocrine disruption in humans or

wildlife.

Animal metabolism. The results from

hen and goat metabolism studies,

wherein fluthiacet-methyl was fed at

exaggerated rates, showed that the

transfer of fluthiacet-methyl residues

from feed to tissues, milk and eggs is

extremely low. No detectable residues of

fluthiacet-methyl (or metabolite CGA–

300403) would be expected in meat,

milk, poultry, or eggs after feeding the

maximum allowable amount of treated

corn and soybeans. This conclusion is

based on residue data from the corn and

soybean metabolism and field residue

chemistry studies coupled with the

residue transfer from feed to tissues,

milk and eggs obtained in the goat and

hen metabolism studies.

D. Aggregate Exposure

Aggregate exposure includes exposure

from dietary exposure from food and

drinking water; and non-dietary

exposure from non-dietary uses of

pesticides products containing the

active ingredient, fluthiacet-methyl.

1. Dietary exposure. Dietary exposure

consists of exposures from food and

drinking water.

2. Food. In this assessment, K-I

Chemical has conservatively assumed

that 100% of all soybeans and corn used

for human consumption would contain

residues of fluthiacet-methyl and all

residues would be at the level of the

proposed tolerances. The potential

dietary exposure to fluthiacet-methyl

was calculated on the basis of the

proposed tolerance which is based on

an LOQ of 0.01 ppm in soybeans and

0.02 ppm in corn (2 x LOQ). The

anticipated residues in milk, meat and

eggs resulting from feeding the

maximum allowable amount of soybean

and corn commodities to cattle and

poultry were calculated, and the

resulting quantities were well below the

analytical method LOQ. Therefore,

tolerances for milk, meat and eggs are

not required. Assuming 100% crop

treated values, the chronic dietary

exposure of the general U.S. population

to fluthiacet-methyl would correspond

to 2.3% of the RfD.

3. Drinking water. Although

fluthiacet-methyl has a slight to medium

leaching potential; the risk of the parent

compound to leach to deeper soil layers

is negligible under practical conditions

in view of the fast degradation of the

product. For example, the soil

metabolism half-life was extremely

short, ranging from 1.1 days under

aerobic conditions to 1.6 days under an

aerobic conditions. Even in the event of

very heavy rainfalls immediately after

application, which could lead to a

certain downward movement of the

parent compound, parent fluthiacetmethyl continues to be degraded during

the transport into deeper soil zones.

Considering the low application rate of

fluthiacet-methyl, the strong soil

binding characteristics of fluthiacetmethyl and its degradates, and the rapid

degradation of fluthiacet-methyl in the

soil, there is no risk of ground water

contamination with fluthiacet-methyl or

its metabolites. Thus, aggregate risk of

exposure to fluthiacet-methyl does not

include drinking water

4. Non-dietary exposure. Fluthiacetmethyl is not registered for any other

use and is only proposed for use on

agricultural crops. Thus, there is no

potential for non-occupational exposure

other than consumption of treated

commodities containing fluthiacetmethyl residue.

E. Cumulative Effects

A cumulative exposure assessment is

not appropriate at this time because

there is no information available to

indicate that effects of fluthiacet-methyl

in mammals would be cumulative with

those of another chemical compound.

F. Safety Determination

1. U.S. population. Using the very

conservative exposure assumptions

described above coupled with toxicity

data for fluthiacet-methyl, K-I Chemical

calculated that aggregate, chronic

exposure to fluthiacet-methyl will

utilize no more than 2.3% of the RfD for

the U.S. population. Because the actual

anticipated residues are well below

tolerance levels and the percent crop

treated with fluthiacet-methyl is

expected to be less than 25% of planted

corn or soybeans, a more realistic

estimate is that dietary exposure will

likely be at least 20 times less than the

conservative estimate previously noted

(the margins of exposure will be

accordingly higher). Exposures below

100% of the RfD are generally not of

concern because the RfD represents the

level at or below which daily aggregate

dietary exposure over a lifetime will not

pose appreciable risks to human health.
52550 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

Also the acute dietary risk to

consumers will be far below any

significant level; the lowest NOEL from

a short term exposure scenario comes

from the teratology study in rabbits with

a NOEL of 300 mg/kg. This NOEL is

2,000-fold higher than the chronic

NOEL which provides the basis for the

RfD (see above). Acute dietary exposure

estimates which are based on a

combined food survey from 1989 to

1992 predict margins of exposure of at

least one million for 99.9% of the

general population and for women of

child bearing age. Margins of exposure

of 100 or more are generally considered

satisfactory. Therefore, K-I Chemical

concludes that there is a reasonable

certainty that no harm will result from

aggregate exposure to fluthiacet-methyl

residues.

2. Infants and children. In assessing

the potential for additional sensitivity of

infants and children to residues of

fluthiacet-methyl, K-I Chemical

considered data from developmental

toxicity studies in the rat and rabbit and

a 2-generation reproduction study in the

rat. A slight delay in fetal maturation

was observed in a teratology study in

rabbits at a daily dose of 1,000 mg/kg.

In a 2-generation reproduction study

fluthiacet-methyl did not affect the

reproductive performance of the

parental animals or the physiological

development of the pups. The NOEL

was 500 ppm for maternal animals and

their offspring, which is 50,000 fold

higher than the RfD.

3. Reference dose. Using the same

conservative exposure assumptions as

was used for the general population, the

percent of the RfD that will be utilized

by aggregate exposure to residues of

fluthiacet-methyl is as follows: 1.5% for

nursing infants less than 1 year old,

5.9% for non-nursing infants, and 5.2%

for children 1–6 years old. K-I Chemical

concludes that there is a reasonable

certainty that no harm will result to

infants and children from aggregate

exposure to residues of fluthiacetmethyl.

G. International Tolerances

No international tolerances have been

established under CODEX for fluthiacetmethyl. (Joanne Miller)

3. Zeneca Ag Products

PP 7F4864

EPA has received a pesticide petition

(PP 7F4864) from Zeneca Ag Products,

1800 Concord Pike, P.O. Box 15458,

Wilmington, DE 19850-5458] proposing

pursuant to section 408(d) of the Federal

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

346a(d), to amend 40 CFR 180.507 by

establishing a tolerance for residues of

azoxystrobin (methyl(E)-2-(2-(6-(2-

cyanophenoxy)pyrimidin-4-

yloxy)phenyl)-3- methoxyacrylate) and

the Z-isomer of azoxystrobin (methyl(Z)-

2-(2-(6-(2-cyanophenoxy) pyrimidin-4-

yloxy)phenyl)-3-methoxyacrylate)] in or

on the raw agricultural commodities

almond hulls at 4.0 ppm, cucurbits

(chayotes, Chinese waxgourds, citron

melons, cucumbers, gherkins, edible

gourds, Mordica spp., cantaloupes,

casabas, crenshaw melons, golden

pershaw melons, honeydew melons,

honey balls, mango melons, Persian

melons, summer squashes, winter

squashes, and watermelons) at 0.3 ppm,

peanut hay at 1.5 ppm, pistachios at

0.01 ppm, rice grain at 4.0 ppm, rice

hulls at 20 ppm, rice straw at 11 ppm,

tree nuts (almonds, beech nuts, Brazil

nuts, butternuts, cashews, chestnuts,

chinquapins, filberts, hickory nuts,

macadamia nuts, pecans, and walnuts)

at 0.01 ppm, wheat bran at 0.12 ppm,

wheat grain at 0.04 ppm, wheat hay at

13.0 ppm, and wheat straw at 4.0 ppm.

It is also proposed that 40 CFR 180.507

be amended by establishment of a

tolerance for the residues of

azoxystrobin (methyl (E)-2-[2-[6-(2-

cyanophenoxy)pyrimidin-4-

yloxy]phenyl]-3-methoxyacrylate) in or

on the following animal products: eggs

at 0.4 ppm, cattle kidney at 0.06 ppm,

liver of cattle, goat, horse, and sheep at

0.3 ppm, hog liver at 0.2 ppm, poultry

liver at 0.4 ppm, meat and fat of cattle,

goat, horse, sheep, poultry and swine at

0.01 ppm, and milk at 0.006 ppm. The

proposed analytical methods use gas

chromatography with nitrogenphosphorous detection (GC-NPD) or, in

mobile phase, high performance liquid

chromatography with ultraviolet

detection (HPLC-UV). 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 azoxystrobin as well as the nature of

the residues is adequately understood

for purposes of the tolerances. Plant

metabolism has been evaluated in three

diverse crops, grapes, wheat, and

peanuts, which should serve to define

the similar metabolism of azoxystrobin

in a wide range of crops. Parent

azoxystrobin is the major component

found in crops. Azoxystrobin does not

accumulate in crop seeds or fruits.

Metabolism of azoxystrobin in plants is

complex, with more than 15 metabolites

identified. These metabolites are present

at low levels, typically much less than

5% of the TRR.

2. Analytical method. An adequate

analytical method, gas chromatography

with nitrogen-phosphorous detection

(GC-NDP) or, in mobile phase, by high

performance liquid chromatography

with ultraviolet detection (HPLC-UV), is

available for enforcement purposes with

a limit of detection that allows

monitoring of food with residues at or

above the levels set in these tolerances.

The Analytical Chemistry Section of the

EPA concluded that the method(s) are

adequate for enforcement. Analytical

methods are also available for analyzing

meat, milk, poultry, and eggs and also

underwent successful independent

laboratory validations.

B. Toxicological Profile

1. Acute toxicity. The acute oral

toxicity study in rats of technical

azoxystrobin resulted in an LD50 of

>5,000 milligrams/kilogram (limit test)

for both males and females. The acute

dermal toxicity study in rats of technical

azoxystrobin resulted in an LD50 of

>2,000 milligrams/kilogram (limit dose).

The acute inhalation study of technical

azoxystrobin in rats resulted in an LC50

of 0.962 milligrams/liter in males and

0.698 milligrams/liter in females. In an

acute oral neurotoxicity study in rats

dosed once by gavage with 0, 200, 600,

or 2,000 milligrams/ kilogram

azoxystrobin, the systemic toxicity no

observed effect level (NOEL) was 200

milligrams/kilogram and the systemic

toxicity lowest observed effect level

(LOEL) was 200 milligrams/kilogram,

based on the occurrence of transient

diarrhea in both sexes. There was no

indication of neurotoxicity at the doses

tested. This acute neurotoxicity study is

considered supplementary (upgradable)

but the data required are considered

only to be confirmatory. Zeneca has

submitted the required confirmatory

data; these data have been scheduled for

review by the Agency.

2. Genotoxicty (mutagenicity).

Azoxystrobin was negative for

mutagenicity in the salmonella/

mammalian activation gene mutation

assay, the mouse micronucleus test, and

the unscheduled DNA synthesis in rat

hepatocytes/mammalian cells (in vivo/

in vitro procedure study). In the forward

mutation study using L5178 mouse

lymphoma cells in culture, azoxystrobin

tested positive for forward gene

mutation at the TK locus. In the in vitro

human lymphocytes cytogenetics assay

of azoxystrobin, there was evidence of a

concentration related induction of
Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices 52551

chromosomal aberrations over

background in the presence of moderate

to severe cytotoxicity.

3. Reproductive and developmental

toxicity. In a prenatal development

study in rats gavaged with azoxystrobin

at dose levels of 0, 25, 100, or 300 mg/

kg/day during days 7 through 16 of

gestation, lethality at the highest dose

caused the discontinuation of dosing at

that level. The developmental NOEL

was greater than or equal to 100 mg/kg/

day and the developmental lowest

observed effect level (LOEL) was >100

mg/kg/day because no significant

adverse developmental effects were

observed. In this same study, the

maternal NOEL was not established; the

maternal LOEL was 25 mg/kg/day,

based on increased salivation.

In a prenatal developmental study in

rabbits gavaged with 0, 50, 150, or 500

mg/kg/day during days 8 through 20 of

gestation, the developmental NOEL was

500 mg/kg/day and the developmental

LOEL was >500 mg/kg/day because no

treatment-related adverse effects on

development were seen. The maternal

NOEL was 150 mg/kg/day and the

maternal LOEL was 500 mg/kg/day,

based on decreased body weight gain.

In a 2-generation study, rats were fed

0, 60, 300, or 1,500 ppm of

azoxystrobin. The reproductive NOEL

was 32.2 mg/kg/day. The reproductive

LOEL was 165.4 mg/kg/day.

Reproductive toxicity was demonstrated

as treatment-related reductions in

adjusted pup body weights as observed

in the F18 and F2. pups dosed at 1500

ppm (165.4 mg/kg/day).

4. Subchronic toxicity. In a 90-day rat

feeding study the NOEL was 20.4 mg/

kg/day for males and females. The LOEL

was 211.0 mg/kg/day based on

decreased weight gain in both sexes,

clinical observations of distended

abdomens and reduced body size, and

clinical pathology findings attributable

to reduced nutritional status.

In a subchronic toxicity study in

which azoxystrobin was administered to

dogs by capsule for 92 or 93 days, the

NOEL for both males and females was

50 mg/kg/day. The LOEL was 250 mg/

kg/day, based on treatment-related

clinical observations and clinical

chemistry alterations at this dose.

In a 21-day repeated-dose dermal rat

study using azoxystrobin, the NOEL for

both males and females was greater than

or equal to 1,000 mg/kg/day (the highest

dosing regimen); a LOEL was therefore

not determined.

5. Chronic toxicity and

carcinogenicity. In a 2–year feeding

study in rats fed diets containing 0, 60,

300, and 750/1,500 ppm (males/

females), the systemic toxicity NOEL

was 18.2 mg/kg/day for males and 22.3

mg/kg/day for females. The systemic

toxicity LOEL for males was 34 mg/kg/

day, based on reduced body weights,

food consumption, and food efficiency;

and bile duct lesions. The systemic

toxicity LOEL for females was 117.1 mg/

kg/day, based on reduced body weights.

There was no evidence of carcinogenic

activity in this study.

In a 1–year feeding study in dogs to

which azoxystrobin was fed by capsule

at doses of 0, 3, 25, or 200 mg/kg/day,

the NOEL for both males and females

was 25 mg/kg/day and the LOEL was

200 mg/kg/day for both sexes, based on

clinical observations, clinical chemistry

changes, and liver weight increases that

were observed in both sexes.

In a 2–year carcinogenicity feeding

study in mice using dosing

concentrations of 0, 50, 300, or 2,000

ppm, the systemic toxicity NOEL was

37.5 mg/kg/day for both males and

females. The systemic toxicity LOEL

was 272.4 mg/kg/day for both sexes,

based on reduced body weights in both

at this dose. There was no evidence of

carcinogenicity at the dose levels tested.

According to the new proposed

guidelines for Carcinogen Risk

Assessment (April, 1996), the

appropriate descriptor for human

carcinogenic potential of azoxystrobin is

‘‘Not Likely’’. The appropriate

subdescriptor is ‘‘has been evaluated in

at least two well conducted studies in

two appropriate species without

demonstrating carcinogenic effects’’.

6. Animal metabolism. In the study of

metabolism in the rat, azoxystrobin--

unlabeled or with a pyrimidinyl,

phenylacrylate, or cyanophenyl label--

was administered to rats by gavage as a

single or 14-day repeated doses. Less

than 0.5% of the administered dose was

detected in the tissues and carcass up to

7 days post-dosing and most of it was

in excretion- related organs. There was

no evidence of potential for

bioaccumulation. The primary route of

excretion was via the feces, though 9 to

18% was detected in the urine of the

various dose groups. Absorbed

azoxystrobin appeared to be extensively

metabolized. A metabolic pathway was

proposed showing hydrolysis and

subsequent glucuronide conjugation as

the major biotransformation process.

This study was classified as

supplementary but upgradable; the

company has submitted data intended

to upgrade the study and these data

have been reviewed.

C. Dietary Exposure

1. Food. The primary route of human

exposure to azoxystrobin is expected to

be dietary ingestion of both raw and

processed agricultural commodities

from bananas, grapes, peaches, peanuts,

tomatoes, tree nuts, pistachios, rice,

cucurbits, and wheat. A chronic dietary

exposure analysis (combined years 1989

- 1992 U.S. Department of Agriculture’s

Nationwide Food Consumption Survey

using the Technical Assessment

Systems, Inc. ‘‘EXPOSURE 1’’ software)

was conducted using tolerance level

residues and 100% crop treated

information to estimate the TMRC for

the general population and 22

subgroups.

2. Drinking water. There is no

established Maximum Concentration

Level for residues of azoxystrobin in

drinking water. The potential exposures

associated with azoxystrobin in water,

even at the higher levels the Agency is

considering as a conservative upper

bound, would not prevent the Agency

from determining that there is a

reasonable certainty of no harm if the

proposed uses were granted.

3. Non-dietary exposure. The Agency

evaluated the existing toxicological

database for azoxystrobin and assessed

appropriate toxicological endpoints and

dose levels of concern that should be

assessed for risk assessment purposes.

Dermal absorption data indicate that

absorption is less than or equal to 4%.

No appropriate endpoints were

identified for acute dietary or short

term, intermediate term, and chronic

term (noncancer) dermal and inhalation

occupational or residential exposure.

Therefore, risk assessments are not

required for these exposure scenarios

and there are no residential risk

assessments to aggregate with the

chronic dietary risk assessment.

D. Cumulative Effects

Section 408(b)(2)(D)(v) requires that,

when considering whether to establish,

modify, or revoke a tolerance, the

Agency consider ‘‘available

information’’ concerning the cumulative

effects of a particular pesticide’s

residues and ‘‘other substances that

have a common mechanism of toxicity.’’

EPA does not have, at this time,

available data to determine whether

azoxystrobin has a common mechanism

of toxicity with other substances or how

to include this pesticide in a cumulative

risk assessment. Unlike other pesticides

for which EPA has followed a

cumulative risk approach based on a

common mechanism of toxicity,

azoxystrobin does not appear to be

structurally similar to any other

pesticide chemical at this time. No

metabolites of azoxystrobin that are of

toxicological concern are known to the

Agency. Azoxystrobin appears to the

only pesticide member of its class of
52552 Federal Register / Vol. 62, No. 195 / Wednesday, October 8, 1997 / Notices

chemistry and there are no reliable data

to indicate that this chemical is

structurally or toxicologically similar to

existing chemical substances at this

time. Therefore, it appears unlikely that

azoxystrobin bears a common

mechanism of activity with other

substances. For the purposes of this

tolerance action, it is not appropriate to

assume that azoxystrobin has a common

mechanism of toxicity with other

substances.

E. Safety Determination

The chronic toxicity Reference Dose

(RfD) for azoxystrobin is 0.18 mg/kg/

day, based on the NOEL of 18.2 mg/kg/

day from the rat chronic toxicity/

carcinogenicity feeding study in which

decreased body weight and bile duct

lesions were observed in male rats at the

LOEL of 34 mg/kg/day. This NOEL was

divided by an Uncertainty Factor of 100,

to allow for interspecies sensitivity and

intraspecies variability.

1.As part of the hazard assessment

process, the available toxicological

database was reviewed to determine if

there are toxicological endpoints of

concern. For azoxystrobin, the Agency

does not have a concern for acute

dietary exposure since the available data

do not indicate any evidence of

significant toxicity from a 1–day or

single event exposure by the oral route.

Therefore, an acute dietary risk

assessment is not required for

azoxystrobin at this time.

2. U.S. population. The chronic

dietary exposure analysis showed that

exposure from the proposed new

tolerances in or on tree nuts, pistachios,

cucurbits, rice, and wheat for the

general U.S. population would be 1.1%

of the RfD. This analysis used a value

of 0.05 ppm for banana pulp rather than

the value of 0.5 that has been

established for banana (whole fruit

including peel) because adequate data

were submitted to support use of the

lower value in the dietary risk analyses.

3. Infants and children. The chronic

dietary exposure analysis, using the

same tolerances and commodities that

were used for the same analysis for the

general U.S. population showed that the

exposure of Non-nursing Infants (the

subgroup with the highest exposure)

would be 4.1% of the RfD.

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 post-natal toxicity and the

completeness of the database unless

EPA determines 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 use of a margin

of exposure analysis or through using

uncertainty (safety) factors in

calculating a dose level that poses no

appreciable risk to humans. In either

case, EPA generally defines the level of

appreciable risk as exposure that is

greater than 1/100th of the no observed

effect level in the animal study

appropriate to the particular risk

assessment. This hundredfold

uncertainty (safety) factor/margin of

exposure (safety) is designed to account

for combined inter- and intraspecies

variability. EPA believes that reliable

data support using the standard

hundredfold margin/factor not the

additional tenfold margin/factor when

EPA has a complete database under

existing guidelines and when the

severity of the effect in infants or

children or the potency or unusual toxic

properties of a compound do not raise

concerns regarding the adequacy of the

standard margin/factor. The database for

azoxystrobin is complete except that the

acute and subchronic neurotoxicity

studies require upgrading. The upgrade

data are confirmatory only, have been

submitted by the company, and await

review by the Agency.

There was no evidence of increased

susceptibility of infants or children to

azoxystrobin. Therefore, no additional

uncertainty factors are considered

necessary at this time.

F. Endocrine Effects

EPA is required to develop a

screening program to determine whether

certain substances (including all

pesticides and inerts) ‘‘may have an

effect in humans that is similar to an

effect produced by a naturally occurring

estrogen, or such other endocrine

effect...’’. The Agency is currently

working with interested shareholders,

including other government agencies,

public interest groups, industry, and

research scientists, to develop a

screening and testing program and a

priority setting scheme to implement

this program. Congress has allowed

three (3) years from the passage pf

FQPA (August 3, 1999) to implement

this program. When this program is

implemented, EPA may require further

testing of azoxystrobin and end-use

product formulations for endocrine

disrupter effects. There are currently no

data or information suggesting that

azoxystrobin has any endocrine effects.

G. International Tolerances

There are no Codex Maximum

Residue Levels established for

azoxystrobin. (Cynthia Giles-Parker)

[FR Doc. 97–26537 Filed 10–8–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–765; FRL–5745–9]

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–765, must be

received on or before November 7, 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 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 email. 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: