Notice of Filing a Pesticide Petition to Establish a Certain Pesticide Chemical in or on Food

Note: EPA no longer updates this information, but it may be useful as a reference or resource.

[Federal Register: January 10, 2001 (Volume 66, Number 7)]
[Notices]
[Page 1981-1986]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10ja01-89]

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[PF-988; FRL-6760-8]

Notice of Filing a Pesticide Petition to Establish a Certain
Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-988, must be
received on or before February 9, 2001.

ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure
proper receipt by EPA, it is imperative that you identify docket
control number PF-988 in the subject line on the first page of your
response.

FOR FURTHER INFORMATION CONTACT: By mail: Cynthia L. Giles-Parker,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460; telephone number: (703) 305-7740; e-mail address:
giles-parker.cynthia@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

You may be affected by this action if you are an agricultural
producer, food manufacturer or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
Examples of
Categories NAICS codes potentially
affected entities
------------------------------------------------------------------------
Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide
manufacturing
------------------------------------------------------------------------

This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.

B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?

1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official record for
this action under docket control number PF-988. The official record
consists of the documents specifically referenced in this action, any
public comments received during an applicable comment period, and other
information related to this action, including any information claimed
as confidential business information (CBI). This official record
includes the documents that are physically located in the docket, as
well as the documents that are referenced in those documents. The
public version of the official record does not include any information
claimed as CBI. The public version of the official record, which
includes printed, paper versions of any electronic comments submitted
during an applicable comment period, is available for inspection in the
Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number PF-988 in the subject line on the
first page of your response.
1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
3. Electronically. You may submit your comments electronically by
e-mail to: opp-docket@epa.gov, or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-988. Electronic comments may
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with

[[Page 1982]]

procedures set forth in 40 CFR part 2. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person identified under FOR FURTHER INFORMATION
CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you used
that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Make sure to submit your comments by the deadline in this
notice.
7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.

II. What Action is the Agency Taking?

EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that this petition contains data or information
regarding the elements set forth in section 408(d)(2); however, EPA has
not fully evaluated the sufficiency of the submitted data at this time
or whether the data support granting of the petition. Additional data
may be needed before EPA rules on the petition.

List of Subjects

Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.

Dated: December 26, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the view of the
petitioner. EPA is publishing the petition summary verbatim without
editing it 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.

E. I. DuPont de Nemours and Company (DuPont)

PP 0F6070

EPA has received a pesticide petition (PP 0F6070) from E. I. DuPont
de Nemours and Company (DuPont), DuPont Agricultural Products, Barley
Mill Plaza, Wilmington, DE 19880-0038 proposing, pursuant to section
408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by
establishing a tolerance for residues of the fungicide famoxadone in or
on the raw agricultural commodities(RACs) potatoes at 0.05 parts per
million (ppm), cucurbit vegetable crop group (cucumbers, melons, and
squash) at 0.7 ppm, fruiting vegetable crop group (tomatoes and
peppers) at 1.0 ppm, and head lettuce at 15 ppm. EPA has determined
that the petition contains data or information regarding the elements
set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully
evaluated the sufficiency of the submitted data at this time or whether
the data support granting of the petition. Additional data may be
needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The plant metabolism of famoxadone is
adequately understood in 3 distinct crops to support these tolerances:
tomatoes, potatoes, and grapes. These studies showed no significant
metabolites all (< 10% total radioactive residue (TRR)) in the RACs
(tubers, tomato fruit, and grape berries). The only significant residue
in any of the studies was the parent compound, famoxadone, occurring
primarily as surface residues (grape berries, and tomato fruit). No
residues were detected in potato tubers. Thus, the proposed tolerance
expression is for the parent compound, famoxadone (DPX-JE874) only.
2. Analytical method. An analytical enforcement method is available
for determining famoxadone plant residues in or on potatoes, cucurbit
vegetables (cucumbers, melons, and squash), fruiting vegetables
(tomatoes, peppers), and head lettuce using gas-liquid chromatography
(GC) with nitrogen phosphorus detection (NPD). The method is applicable
to high and medium moisture, oily and non-oily crops and related
matrices. The limit of quantitation (LOQ) is 0.02 ppm.
The analytical enforcement for use on tomato processed fractions
and also the RAC, tomato, utilizes column switching liquid
chromatography with ultraviolet (UV) detection. The LOQ is 0.02 ppm.
The LOQ in each method allows monitoring of crops with famoxadone
residues at or above the levels proposed in these tolerances.
3. Magnitude of residues--i. Cucurbit vegetables. The magnitude and
decline of residues of famoxadone were determined on cucumber,
cantaloupe, and summer squash, the representative commodities for the
cucurbit vegetable crop group. Seventeen field trials were conducted in
1997 and 1998.
DPX-KP481 50DF, containing 25% cymoxanil and 25% famoxadone, was
applied as 7 broadcast applications, each at the maximum rate of 3 oz
famoxadone/Acre, for a maximum seasonal use rate of 21 oz famoxadone/
Acre. Applications were made approximately 5 days apart.
The target pre-harvest interval (PHI) was 3 days.
Residues of famoxadone in cucumbers from 6 test sites
ranged from <0.02 to 0.19 ppm.
Residues of famoxadone in cantaloupe from 6 test sites
ranged from 0.11 to 0.46 ppm.
Residues of famoxadone in summer squash from 5 test sites
ranges from <0.02 to 0.37 ppm.
ii. Fruiting vegetables. The magnitude and decline of famoxadone
residues were determined on tomatoes, and peppers (bell and non-bell),
the representative commodities for the fruiting vegetable crop group.
Twenty-one residue trials were conducted in 1996 and 1997.
DPX-KP481 50DF, containing 25% cymoxanil and 25% famoxadone, was
applied as nine broadcast applications at a maximum seasonal use rate
of 18 oz famoxadone/Acre. Applications were made approximately 5 days
apart. The target PHI was 3 days. Residues of famoxadone on peppers
(bell and non-bell) from 9 test sites ranged from 0.10-

[[Page 1983]]

0.70 ppm. Residues of famoxadone on tomatoes from 12 test sites ranged
from 0.06-0.48 ppm.
DPX-KP481 50DF, containing 25% cymoxanil and 25% famoxadone, was
applied to 1 site in California to determine the magnitude of residue
in tomato and the extent of potential residue concentration in tomato
processed fractions. DPX-KP481 50DF was applied in 9 broadcast
applications at 2 oz famoxadone/Acre (1X) and 10 oz famoxadone/Acre
(5X). Applications were made approximately 5 days apart. The target PHI
was 3 days. When applied at 5X the maximum seasonal use rate,
famoxadone residues decreased with washing and did not concentrate in
puree, with respect to the unwashed raw agricultural commodity (RAC).
Famoxadone residues concentrated in tomato paste derived from tomato,
treated at the 5X rate by a factor of 1.3. The 1.3 concentration factor
does not warrant a special tolerance for paste. At the 1X rate, the
proposed tomato tolerance for the RAC, 0.7 ppm, is adequate to cover
this level of concentration in the paste. A separate tolerance for
paste does not need to be established.
iii. Head lettuce. Residue trials for head lettuce were conducted
at 8 sites in 1997 and 1998. DPX-KP481 50DF, containing 25% cymoxanil
and 25% famoxadone, was applied as 7 broadcast applications, each at
the maximum rate of 3 oz famoxadone /Acre, for a maximum seasonal use
rate of 21 oz famoxadone /Acre. Applications were made approximately 5
days apart. The target PHI was 3 days. Residues of famoxadone on head
lettuce ranged from 0.64 to 14 ppm (with wrapper leaves) and 0.024 to
3.1 ppm (wrapper leaves removed).
iv. Potato. Residue trials for famoxadone were conducted at 16
sites in 1997. DPX-KP481 50DF, containing 25% cymoxanil and 25%
famoxadone, was applied as 6 broadcast applications, each at 3 oz
famoxadone/Acre, for a maximum seasonal use rate of 18 oz famoxadone/
Acre. Applications were made approximately 5 days apart. The target PHI
was 14 days. No quantifiable residues of famoxadone were seen in any
potato sample above the LOQ (0.02 ppm).
DPX-KP481 50DF, containing 25% cymoxanil and 25% famoxadone, was
applied to 1 test site in Washington to determine the magnitude of
residue in potato and the extent of potential residue concentration in
potato processed fractions. DPX-KP481 50DF was applied 6 times as a
broadcast spray, each at 15 oz famoxadone/Acre, for a total seasonal
application rate of 90 oz ai/Acre (5X). When applied under these
conditions, no quantifiable famoxadone residues were detected in
unwashed or washed potatoes/culls, chips, or granule fractions. Thus no
concentration occurred in these fractions. At the 5X rate, quantifiable
residues were detected in wet potato peels at 0.033 0.035 ppm. The
concentration factor was 1.12 (based on LOQ of 0.02 ppm). When
adjusting the residues in wet peels from the seasonal 5X to the 1X rate
(18 oz famoxadone/Acre), residues in peels are less than the LOQ.
Therefore, the negligible residues in the peels (less than 2X the LOQ)
are covered by the proposed tolerance for the RAC, 0.05 ppm, and no
separate tolerance for potato peels need be established.

B. Toxicological Profile

1. Acute toxicity. A battery of acute toxicity tests with technical
famoxadone places it in the following toxicity categories:

Toxicity Categories
----------------------------------------------------------------------------------------------------------------
Acute toxicities Test animals Tolerances Categories
----------------------------------------------------------------------------------------------------------------
Oral LD50 Rat >5,000 milligrams/ Category IV
kilograms (mg/kg)
Dermal LD50 Rabbit >2,000 mg/kg Category III
Inhalation LC50 Rat >5.3 mg/L Category IV
Eye irritation Rabbit Transient redness; Category III
clear by 72 hours
Dermal irritation Rabbit Minimal irritation at Category IV
72 hours
Dermal sensitization Guinea pig Not a sensitizer
----------------------------------------------------------------------------------------------------------------

In an acute neurotoxicity test, famoxadone was not neurotoxic to
rats. The no observed adverse effect level (NOAEL) was 1,000 mg/kg in
males, based on systemic toxicity at 2,000 mg/kg. The NOAEL in females
was 2,000 mg/kg, the highest dose tested (HDT).
2. Genotoxicity. Famoxadone was tested in a battery of assays to
evaluate genotoxicity and chromosome aberrations with the following
results. Based on the weight-of-evidence, famoxadone is not considered
to be genotoxic or clastogenic.

------------------------------------------------------------------------

------------------------------------------------------------------------
Bacterial gene mutation Salmonella and E. Negative
Coli
Mammalian gene mutation in CHO/HGPRT Negative
vitro
Mammalian chromosome chinese hampter Positive without
aberrations in vitro ovary (CHO) activation negative
with
activation
Mammalian chromosome Mouse micronucleus Negative
aberrations in vivo
Unscheduled DNA synthesis in Primary rat Negative
vitro hepatocytes
Unscheduled DNA synthesis in Primary rat Negative
vivo hepatocytes
------------------------------------------------------------------------

3. Reproductive and developmental toxicity. The results of a series
of studies indicated that there were no reproductive, developmental or
teratogenic hazards associated with famoxadone.
In a 2-generation rat reproduction study, the NOAEL for both adults
and offspring was 200 ppm (11.3-17.5 mg/kg/day depending on gender and
generation) based on clinical signs, decreased body weights (bwt),
effects on nutritional parameters, and liver toxicity in adults and
decreased weight of pups. Effects on pups occurred only at a maternal
effect level and may have been due to altered growth and nutrition in
the dams. There were no effects on

[[Page 1984]]

reproduction (mating, fertility, reproductive organs) up to and
including the highest concentration tested, 800 ppm (44.7-71.8 mg/kg/
day). In studies conducted to evaluate developmental toxicity
potential, famoxadone was neither teratogenic nor uniquely toxic to the
conceptus. In a rat developmental toxicity study, the maternal NOAEL
was 250 mg/kg/day based on decreased weight gain and food consumption
at 500 mg/kg/day. The fetal NOAEL was 1,000 mg/kg/day, the HDT. In
rabbits, NOAEL for compound-related systemic toxicity was 1,000 mg/kg/
day. There were no developmental effects at any dose level. Several
rabbits had weight loss, decreased food consumption, clinical signs,
fecal impactions, and subsequent abortion at 1,000 mg/kg/day. These
effects were considered due to the physical properties of the dosing
solution rather than systemic toxicity. Often fecal impaction preceded
abortions.
4. Subchronic toxicity. Subchronic (90-day) feeding studies were
conducted with rats, mice, and dogs. In addition, the following
subchronic feeding studies were conducted: A 90-day in rats to evaluate
neurotoxicity and 28-day feeding studies in rats and mice to evaluate
immunotoxicity. A 28-day dermal study was conducted in rats.
In a 90-day feeding study in rats, the NOAEL was considered to be
200 ppm (13 and 17 mg/kg/day) based on mild hepatotoxicity and mild
regenerative hemolytic anemia in both sexes and decreased bwt in
females at 800 ppm (52 and 66 mg/kg/day, in males and females
respectively) and higher. An effect on weight gain in female rats at 17
mg/kg/day was considered spurious since it was not duplicated in any
other rat studies including those of the same or longer duration.
In a subchronic neurotoxicity study in rats, there was no evidence
of neurotoxicity up to and including the highest concentration tested,
800 ppm (46.9 and 59.3 mg/kg/day for males and females, respectively).
The NOAEL for systemic toxicity was 200 ppm (11.7 and 14.4 mg/kg/day in
males and females, respectively) based on bwt and nutritional effects
at 800 ppm.
In mice, the subchronic NOAEL was 350 ppm (62.4 and 79.4 mg/kg/day
in males and females, respectively), based on hepatotoxicity and mild
anemic effects at higher concentrations.
In a 90-day feeding study in dogs, the NOAEL was 40 ppm (1.3 mg/kg/
day) in males. In females, 40 ppm (1.4 mg/kg/day) was a marginal effect
level for lens lesions. At 300 ppm, lens lesions were observed in males
and females upon ophthalmologic exam and confirmed by histopathology.
These lesions were not considered relevant to human health and to acute
risk assessment, since they did not occur in a 1-year primate study.
Excluding lens lesions, the NOAEL was 300 ppm (10.0 and 10.1 mg/kg/day
in males and females, respectively), based upon effects on body weight
and foodconsumption, hemolytic anemia, and hyperkalemia with associated
clinical signs at 1,000/600 ppm (23.8/21.2 and 23.3/20.1 mg/kg/day in
males and females, respectively). The test concentration was lowered to
600 ppm after 5.3 weeks because of the signs related to hyperkalemia.
Famoxadone was tested in 28-day feeding studies in rats and mice,
designed to evaluate immunotoxicity. The NOAEL in rats was 200 ppm (14
and 16 mg/kg/day in males and females, respectively) based on decreased
bwt, bwt gain, food consumption, food efficiency, and increased spleen
weights at 800 ppm (55 and 57 mg/kg/day for males and females,
respectively). There was no effect in response to anti-sheep red blood
cell (SRBC) challenge at any concentration tested. In mice, the NOAEL
was 2,000 ppm (327 and 417 mg/kg/day in males and females,
respectively) based on increased spleen weights and a minimal decrease
in humoral response to SRBC. Famoxadone is not considered immunotoxic
in rats and produced equivocal evidence of immunotoxicity in mice.
In a 28-day repeated dose dermal study, the NOAEL for male rates
was 250 mg/kg/day based on changes in liver enzymes at 500 mg/kg/day.
The NOAEL for female rats was 1,000 mg/kg/day, the HDT.
5. Chronic toxicity. Chronic studies with famoxadone were conducted
on rats, mice, dogs, and monkeys to determine oncogenic potential and/
or chronic toxicity of the compound. Effects generally similar to those
observed in the 90-day studies were seen in the chronic studies.
Famoxadone was not oncogenic.
Famoxadone was not oncogenic in rats. The chronic NOAEL was 200 ppm
(8.4 and 10.7 mg/kg/day in males and females, respectively) based on
hepatotoxicity and anemia in both sexes and decreased bwt, bwt gain,
and food efficiency in females at 400 ppm (16.8 and 23.0 mg/kg/day in
males and females, respectively).
In mice, the chronic NOAEL was 700 ppm (95.6 and 130 mg/kg/day for
males and females, respectively) based on hepatotoxicity in males and
females and amyloidosis in females at 2,000 ppm (274 and 392 mg/kg/day
in males and females, respectively). Famoxadone was not oncogenic in
mice.
In a 1-year feeding study in dogs, the only effect observed was
lens lesions at 300 ppm (8.8 and 9.3 mg/kg/day for males and females).
The NOAEL for these lesions was 40 ppm (1.2 mg/kg/day in both sexes).
Use of this NOAEL is considered very conservative since these lesions
are not considered appropriate to human risk assessment based on the
absence of this effect in a primate study.
In a 1-year gavage study, the NOAEL in cynomolgus monkeys was 100
mg/kg/day in both males and female based on slight hemolytic anemia in
both sexes at the 1,000 mg/kg/day dose level. There were no other
effects observed at any level.
6. Animal metabolism. Famoxadone was rapidly eliminated in the rat,
primarily by fecal excretion and to a lesser extent in the urine.
Absorption and metabolism of famoxadone was limited. There was no
accumulation in organs or tissues. Parent famoxadone was the major
component recovered. Hydroxylated parent compound and sulfated cleavage
products were also recovered to a much lesser extent.
7. Metabolite toxicology. There are no metabolites of toxicological
significance to mammals.
8. Endocrine disruption. Chronic, lifespan, and multi-generational
bioassays in mammals and acute and subchronic studies on aquatic
organisms and wildlife did not reveal endocrine effects. Any endocrine
related effects would have been detected in this definitive array of
required tests. The probability of any such effect due to agricultural
uses of famoxadone is negligible.

C. Aggregate Exposure

Famoxadone is a new fungicide with proposed uses on the commercial
crops: Fruiting vegetables (tomatoes and peppers), cucurbit vegetables
(cucumbers, melons, and squash), head lettuce, and potatoes. There are
no residential uses for the famoxadone-containing fungicide.
1. Dietary exposure. The chronic reference dose (RfD) of 0.012 mg/
kg/day is based on a NOAEL of 1.2 mg/kg/day for lens lesions from a 1-
year dog feeding study and an uncertainty factor of 100. This is
considered highly conservative because these lesions were not produced
in a chronic monkey study. The acute NOAEL of 10.0 mg/kg bwt/day is
based upon bwt effects occurring early in a 90-day dog study. Since bwt
is not actually an acute effect, the acute NOAEL selected is highly
conservative and it is likely that the

[[Page 1985]]

actual acute NOAEL is much higher than 10.0 mg/kg/day.
i. Food--a. Chronic dietary exposure assessment. Chronic dietary
exposure, resulting from the proposed use of famoxadone on cucurbit
vegetables, fruiting vegetables, head lettuce, potatoes, and imported
grapes, is well within acceptable limits for all sectors of the
population. The chronic module of the dietary exposure evaluation model
(DEEM), Novigen Sciences, Inc., 1998 Version 6.4 (chronic) and 6.54
(acute)) was used to conduct the assessment with the anticipated RfD of
0.012 mg/kg/day. The analysis employed overall-mean field-trial values
and conservatively assumed that 30% of the crops on the proposed label
plus imported grapes would be treated with famoxadone.
For the general U.S. population, the estimated chronic dietary
exposure to famoxadone is 0.000335 mg/kg/day, and utilizes 2.8%of the
chronic RfD. The exposure for the potentially most highly exposed
subgroup in the population, children 1-6 years, is 0.000487 mg/kg/day
or 4.1% of the chronic RfD. The table below lists the results of this
analysis, which indicate large margins of exposure for each population
subgroup and very low probability of effects resulting from chronic
exposure to famoxadone. Since the RfDs are well below 100%, the chronic
dietary safety of famoxadone clearly meets the food quality protection
act (FQPA) standard of reasonable certainty of no harm.

Results of Chronic Dietary Exposure Estimate
----------------------------------------------------------------------------------------------------------------
Maximum Dietary Exposure (mg/
Population Group kg/day) %RfD
----------------------------------------------------------------------------------------------------------------
U.S. population...................................... 0.000335 2.8
Non-nursing infants (<1-year)........................ 0.000111 0.9
Children (1-6 years)................................. 0.000487 4.1
Children (7-12 years)................................ 0.000391 3.3
Females (13+ years).................................. 0.000430 3.6
----------------------------------------------------------------------------------------------------------------

b. Acute dietary exposure. The acute dietary exposure to famoxadone
(99th percentile) is 0.001848 mg/kg/day, or 1.85% acute RfD
for the overall U.S. population. The exposure (99th
percentile) of the most highly exposed subgroup in the population,
children 1-6 years, is 0.002559 mg/kg/day or 2.56% RfD. The results of
this analysis are given in the table below. All of the results are
extremely reassuring, because they are based on several very
conservative assumptions. Foods that were considered in exposure
estimates were cucurbit vegetables, fruiting vegetables, head lettuce,
imported grapes, and potatoes. Since the percent RfDs are well below
100%, the acute dietary safety of famoxadone clearly meets the FQPA
standard of reasonable certainty of no harm.

Results of Acute Dietary Exposure Estimate

----------------------------------------------------------------------------------------------------------------
99th Percentile of Exposure 99.9th Percentile of Exposure
-------------------------------------------------------------------------------
Population Group Exposure (mg/kg/ Exposure (mg/kg/
day) % RfD day) % RfD
----------------------------------------------------------------------------------------------------------------
U.S. population................. 0.001848 1.85 0.006128 6.13
Non-nursing (<1-year)........... 0.000949 0.95 0.003667 3.67
Children (1-6 years)............ 0.002559 2.56 0.008944 8.94
Children (7-12 years)........... 0.002002 2.00 0.007364 7.36
Females (13-50 years)........... 0.001843 1.84 0.006072 6.07
----------------------------------------------------------------------------------------------------------------

ii. Drinking water. Famoxadone is highly unlikely to contaminate
ground water resources due to its immobility in soil, low water
solubility, high soil sorption, moderate soil half-life, and resulting
low ground and surface water exposure. Both acute and chronic drinking
water exposure analyses were calculated using EPA screening
concentration in ground water ((SCI-GROW) for ground water and generic
expected environmental concentration (GENEEC) for surface water).
Results indicate that a reasonable certainty exists that famoxadone
residues will not contribute significantly to the aggregate acute and
chronic human risk.
The predicted concentration for famoxadone in ground water under
worst case conditions was 0.0097 parts per billion (ppb). The predicted
peak concentration for famoxadone in surface water in a small non-
flowing pond, directly adjacent to treated fields (aerial application
at the maximum rate), was 2.49 ppb. The 56-day average concentration
predicted for the same pond scenario was 0.05 ppb.
The EPA uses drinking water levels of concern (DWLOC) as a
surrogate measure to capture risk associated with exposure to
pesticides in drinking water. The DWLOC is the concentration of a
pesticide in drinking water that would be acceptable as an upper limit
in light of total aggregate exposure to that pesticide from food,
water, and residential uses. A DWLOC will vary depending on the residue
level in foods, the toxicity endpoint, drinking water consumption
patterns, and body weights for specific subpopulations.
The chronic DWLOCs are 0.41 ppm for the U.S. population and 0.12
ppm for the most exposed population subgroup, children (1-6 years). The
DWLOCs are substantially higher than the GENEEC 56-day estimated
environmental concentration of 0.05 ppb for famoxadone in surface water
or the Sci-Grow estimate of 0.0097 ppb famoxadone in ground water.
Therefore, since the estimated famoxadone concentrations are well below
the chronic DWLOCs, the chronic dietary safety of famoxadone residues
from drinking water clearly meets the FQPA

[[Page 1986]]

standard of reasonable certainty of no harm.
Using the appropriate inputs, the acute DWLOCs are 3.3 parts per
million (ppm) for the U.S. population, and 0.91 ppm for the most
exposed population subgroup, children (1-6 years). The estimated
maximum concentration of famoxadone in surface water (2.49 ppb, derived
from GENEEC) or in ground water (0.0097 ppb, derived from Sci-Grow) is
much lower than the acute DWLOC. Since the estimated famoxadone
concentrations in ground and surface water are well below acute DWLOCs,
the acute dietary safety of famoxadone residues from drinking water
clearly meets the FQPA standard of reasonable certainty of no harm.
2. Non-dietary exposure. Famoxadone products are not labeled for
residential non-food uses, thereby eliminating the potential for
residential exposure. Non-occupational, non-dietary exposure for
famoxadone has not been estimated because the proposed products are
limited to commercial crop production. Therefore, the potential for
non-occupational exposure is insignificant.

D. Cumulative Effects

EPA's consideration of a common mechanism of toxicity is not
necessary at this time because there is no indication that toxic
effects of famoxadone should be cumulative with those of any other
chemical. Famoxadone is a member of a new class of fungicides that acts
by inhibition of mitochondrial respiration. Famoxadone's biochemical
mode of action on fungi and toxicological profile in animals appear to
be unique.
Given the distinct chemical, biological and toxicological profile,
famoxadone's low acute toxicity, absence of genotoxic, oncogenic,
developmental or reproductive effects and low exposure potential, the
expression of cumulative human health effects with any other natural or
synthetic pesticide is not anticipated.

E. Safety Determination

1. U.S. population. Dietary and occupational exposure will be the
major routes of exposure to the U.S. population. Ample margins of
safety have been demonstrated for both situations. For the U.S.
population, the chronic dietary exposure to famoxadone is 0.000335 mg/
kg/day, which utilizes 2.8% of the RfD for the overall U.S. population,
assuming 30% of the crops are treated. The acute dietary exposure to
the U.S. population is 0.001848 mg/kg/day (99th percentile)
or 1.85% of the RFD (99th percentile). At the
99.9th percentile, the acute dietary exposure for the U.S.
population is 0.006128 mg/kg/day or 6.13% of the RfD.
Using only pesticide handlers exposure data base (PHED) data levels
A and B (those with a high level of confidence), the margin of exposure
(MOE) for occupational exposure are 2,665 to 5,329 for mixer/loaders,
34,418 for aerial applicators, and 1,096 for ground applicators. For
flaggers, the MOE is 13,500. Based on the completeness and reliability
of the toxicity data and the conservative exposure assessments, there
is a reasonable certainty that no harm will result from the aggregate
exposure of residues of famoxadone including all anticipated dietary
exposure and all other non-occupational exposures.
2. Infants and children. Chronic dietary exposure of the most
highly exposed subgroup in the population, children 1-6, is 0.000487
mg/kg/day or 4.1% of the RfD. The acute dietary exposure of the most
exposed subgroup, children 1-6, is 2.56% of the RfD (99th
percentile). For non-nursing infants (<1-year), the acute dietary
exposure is 0.95% RfD (99th percentile).
There are no residential uses of famoxadone and contamination of
drinking water is extremely unlikely. Based on the completeness and
reliability of the toxicity data, the lack of toxicological endpoints
of special concern, the lack of any indication of greater sensitivity
of children, and the conservative exposure assessment, there is a
reasonable certainty that no harm will result to infants and children
from the aggregate exposure to residues of famoxadone from all
anticipated sources of dietary and non-occupational exposure.
Accordingly, there is no need to apply an additional safety factor for
infants and children.

F. International Tolerances

To date, no Codex, Canadian or Mexican tolerances exist for
famoxadone.
[FR Doc. 01-576 Filed 1-9-01; 8:45 am]
BILLING CODE 6560-50-S

Notice of Filing a Pesticide Petition to Establish a Certain Pesticide Chemical in or on Food

Local Navigation