FLUORIDE ACTION NETWORK PESTICIDE PROJECT

Return to FAN's Pesticide Homepage

Return to Fluazinam Index Page


Fluazinam (ISK). December 6, 2000, Petition to Extend Pesticide Tolerances on potato and peanut at 0.02 ppm and wine grapes at 3.0 ppm. Federal Register.


Note: there were 2 pesticide petitions in this Notice. We only include the one for Fluazinam.

http://www.epa.gov/fedrgstr/EPA-PEST/2000/December/Day-06/p31056.htm


[Federal Register: December 6, 2000 (Volume 65, Number 235)]
[Notices]
[Page 76253-76258]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06de00-68]

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

ENVIRONMENTAL PROTECTION AGENCY

[PF-983; FRL-6573-7]


Notice of Filing Pesticide Petitions to Establish and to Extend
Tolerances for Certain Pesticide Chemicals in or on Food

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 docket control number PF-983, must be
received on or before January 5, 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-983 in the subject line on the first page of your
response.

FOR FURTHER INFORMATION CONTACT:  For Pesticide Petition (PP 9F5079)
contact: Cynthia 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.
    For Pesticide Petitions (PP 8F3654 8F3674) contact: Mary Waller,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington DC 20460; Telephone number: (703) 308-9354; e-mail address:
waller.mary@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'' 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-983. 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 (CM #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-983 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, CM#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-983. 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 procedures set forth in 40 CFR part 2.

[[Page 76254]]

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 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.

List of Subjects

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

    Dated: November 21, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below
as required bysection 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. ISK Biosciences Corporation (PP 9F5079)

Summary of Petition

    EPA has received a pesticide petition (PP 9F5079) from ISK
Biosciences Corporation, 5970 Heisley Road, Suite 200, Mentor, Ohio,
44060, proposing, pursuant to section 408(d) of the Federal Food, Drug,
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180
by establishing a tolerance for residues of fluazinam in or on the raw
agricultural commodities potato and peanut at 0.02 parts per million
(ppm) and wine grapes at 3.0 ppm. EPA has determined that the petition
contains data or information regarding the elements set forth in
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated
the sufficiency of the submitted data at this time or whether the data
supports granting of the petition. Additional data may be needed before
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The residue of concern is best defined as the
parent, fluazinam. The metabolism of fluazinam in plants (potatoes,
peanuts, and wine grapes) is adequately understood for the purposes of
these tolerances. The metabolism of fluazinam involves initial
reduction of the nitro groups, hydrolysis of the trifluoromethyl group
as well as replacement of chlorine by glutathione with subsequent
reactions along the glutathione pathway. Parent fluazinam is rapidly
degraded and is either not found or barely detectable in peanuts and
potatoes. Fluazinam parent was the major identifiable residue in a
grape metabolism study. Identifiable residues in plant metabolism
studies either closely resemble fluazinam in structure or are the
result of re-incorporation of the fluazinam carbon pool into natural
products.
    Ruminant and poultry metabolism studies demonstrated that the
transmittal of residues from the feed of goats and hens through to
meat, milk, and eggs was low. Total 14C residues were below 1 ppm in
all tissues, milk and eggs. Identifiable residues were less than 2% of
the administered dose in all matrices, except for chicken fat and
liver.
    2. Analytical method. An analytical method using gas chromatography
with electron capture detection (GC-ECD) for the determination of
fluazinam residues on potatoes, peanuts, grapes and the processing
fractions thereof has been developed and validated. The method involves
solvent extraction followed by liquid-liquid partitioning and
concentration prior to a final purification using column
chromatography. The method has been successfully validated by an
independent laboratory using peanut nutmeat as the matrix. The limit of
quantitation of the method is 0.02 ppm in peanuts and 0.01 ppm in
potatoes and grapes.
    3. Magnitude of residues--i. Potatoes. Data from 11 field trials in
potatoes showed that mean fluazinam residues from duplicate samples
were 0.01 ppm in the RAC commodity at all locations. The result of a
processing study using a 3.5X application rate showed no concentration
into the processing fractions dry peels, french fries and chips. A
calculated processing factor of 2.4 for the animal feed commodity wet
peels was determined based on residue levels just slightly above the
limit of quantitation.
    ii. Peanuts. A total of 15 field trials were conducted over three
growing seasons at nine sites representative of peanut production.
Residues of fluazinam in nutmeat from all location were below 0.01 ppm.
Residues in peanut hay, a grazing restriction commodity, ranged from
0.16 to 10.2 ppm in the six locations where it was harvested. In a
processing study, residues concentrated 3x in crude oil and 5x in
soapstock, but did not concentrate in refined oil or presscake.
    iii. Wine grapes. A total of 20 field trials were conducted over
three growing seasons in major wine grape growing regions worldwide.
Residues of fluazinam in grapes ranged from 0.03 to 2.27 ppm.
Vinification of grapes from two locations showed a reduction of
fluazinam in wine to non-detectable levels.
    iv. Secondary residues. Since levels of fluazinam in potatoes and
peanut nutmeat were below detectable levels

[[Page 76255]]

(the fluazinam label includes a peanut hay grazing restriction, and
only wine grapes which are imported are included in this tolerance
petition), no residues of concern are expected on animal feed items.
Furthermore, since animal metabolism studies do not show potential for
significant residue transfer, detectable secondary residues in animal
tissues, milk or eggs are not expected. Therefore, tolerances are not
needed for these commodities.

B. Toxicological Profile

    1. Acute toxicity. A battery of acute toxicity studies was
conducted which placed technical fluazinam in Toxicity Category III for
oral LD50, dermal LD50, dermal irritation,
Category II for inhalation LC50 and Category I for eye
irritation. Technical fluazinam showed potential for dermal
sensitization.
    In an acute neurotoxicity study, the no observed affect effect
level (NOAEL) for neurotoxicity was 2,000 milligram/kilogram (mg/kg)
highest dose tested (HDT) and the NOAEL for systemic effects was 50 mg/
kg.
    2. Genotoxicty. A battery of tests has been conducted to assess the
genotoxic potential of technical fluazinam. Assays conducted included
two gene mutation tests in bacteria, a chromosomal aberration test in
mammalian cells, a mouse micronucleus test and a DNA repair test in
bacteria. Technical fluazinam did not elicit a genotoxic response in
any of the studies conducted.
    3. Reproductive and developmental toxicity. In a 2-generation
reproductive toxicity study, the NOAEL for reproductive effects was 100
ppm (10.1 mg/kg/day). The NOAEL for parental toxicity was 20 ppm (2.1
mg/kg/day).
    In a rat developmental study, there were no developmental effects
observed at non-maternally toxic doses. The developmental NOAEL was 50
mg/kg/day and the lowest observed adverse effect level (LOAEL) was 250
mg/kg/day, based upon statistically significant decreased mean fetal
body weight and other evidence suggestive of delayed fetal development
related to maternal toxicity. The maternal NOAEL was shown to be 50 mg/
kg/day.
    In a rabbit developmental study, there were no developmental
effects observed at non-maternally toxic doses. The developmental NOAEL
was 7 mg/kg/day and the LOAEL was 12 mg/kg/day, based on increased
incidence of total litter loss and possible slightly increased
incidences of fetal findings at this dose. It was concluded that the
maternal NOAEL was 4 mg/kg/day.
    4. Subchronic toxicity. The NOAEL for the 13 week feeding study in
rats was 50 ppm (4.1 mg/kg/day). The LOAEL was 500 ppm (41 mg/kg/day),
based on periacinar hepatocellular hypertrophy and sinusoidal chronic
inflammation in males, increased liver weights in males and increased
lung weights in females.
    In a 13 week dog study, the NOAEL was 10 mg/kg/day. The LOAEL was
100 mg/kg/day, based on ocular change observed ophthalmoscopically and
liver effects consisting of increased relative liver to body weight,
bile duct hyperplasia with or without cholangiofibrosis and increased
plasma phosphatase levels.
    In a 21 day dermal study, the NOAEL for systemic effects was 10 mg/
kg/day. The LOAEL was 100 mg/kg/day, based on hepatocelluar hypertrophy
and increases in AST and cholesterol levels.
    In a subchronic neurotoxicity study, no effects considered to be
indicative of neurotoxicity were observed at the highest dose tested,
3,000 ppm (233 mg/kg/day). The NOAEL for systemic toxicity (body weight
differences) was 1,000 ppm (74 mg/kg/day).
    5. Chronic toxicity. Fluazinam was not carcinogenic in rats. A
NOAEL of 10 ppm (0.43 mg/kg/day) of fluazinam was established based on
the following effects at 1,000 and/or 100 ppm: lower food consumption
and efficiency of food utilization, slight anemia, elevated
cholesterol, increased liver weights, an increased number of
macroscopic liver and testes lesions and an increased incidence of
microscopically observed lung, liver, pancreas, lymph node and testes
lesions.
    An additional study was conducted to further define the NOAEL for
long-term effects in the rat. In the second study, a NOAEL of 50 ppm
(2.2 mg/kg/day) was established based on liver and testes effects.
    Two long-term feeding studies were conducted in mice. In the first,
the NOAEL for all effects was 10 ppm (1.14 mg/kg/day) and the LOAEL was
100 ppm (11.2 mg/kg/day) based on the treatment-related effects
observed in the liver.
    A second oncogenicity study in mice was conducted at 1,000, 3,000
and 7,000 ppm to ensure that an maximum tolerance dose (MTD) was
studied. Findings included increased female mortality, reduced body
weight gains, increased brain weights and/or liver weights. An impurity
in the test material used in this study resulted in vacuolation of the
white matter of the brain and cervical spinal cord in treated animals.
A statistically significant higher incidence of hepatocellular adenomas
was observed in the 3,000 ppm dose males. Hepatocellular adenomas are
common tumors in male mice. There was no dose relationship in the
induction of the adenoma and no increase in hepatocellular carcinomas.
It was concluded that fluazinam is not carcinogenic in the mouse.
    In a chronic dog study, the NOAEL was determined to be 1 mg/kg/day.
The LOAEL was 10 mg/kg/day based on generalized, nonspecific toxicity.
No ocular effects were observed ophthalmoscopally at any dose in this
study.
    6. Animal metabolism. After an oral dose of fluazinam the median
peak time for blood concentration of radiolabel activity for both sexes
was 6 hours. The major route of excretion was the feces with urine
contributing as a minor route. Less than 1% of the administered dose
was found in the terminated animals. The highest concentration was
found in the liver. There were no major differences related to sex or
dose level in the findings. It was concluded that fluazinam is
metabolized by both reduction and glutathione and glucuronide
conjugation and further metabolism.
    7. Metabolite toxicology. The same metabolic processes occur in
plants and animals but metabolism in plants is more extensive than in
animals. All of the major identified metabolites in both plants and
animals retain the phenylpyridinylamine structure. Many of the
metabolites resulting from fluazinam are similar in plants and animals
and, therefore, have already been evaluated toxicologically.
    Because of the rapid and complete elimination (in animals) and re-
incorporation (in plants) of fluazinam, the toxicity of metabolites is
expected to be similar to but lower than the toxicity of the parent
compound. The residue of concern is parent fluazinam only.
    8. Endocrine disruption. The toxicological profile of fluazinam
shows no evidence of physiological effects characteristic of the
disruption of the hormone estrogen in mammalian chronic studies or in
mammalian or avian reproduction studies. It is therefore considered
that there is an adequate level of safety over the reference dose for
possible endocrine effects and that an additional safety factor for
possible endocrine effects is not warranted.

C. Aggregate Exposure

    1. Dietary exposure. An RfD of 0.01 mg/kg/day is proposed for
humans, based on the NOAEL from the one year dog study (1 mg/kg/day)
and dividing by an uncertainty factor of 100.
    i. Food--a. Acute risk. Tier 1 acute dietary exposure analyses were

[[Page 76256]]

conducted for fluazinam in/on peanuts, potatoes and imported wine
grapes to determine the exposure contribution of these commodities to
the diet and to ascertain the acute risk potential. The estimates were
based on proposed tolerance level residues for all three crops, peanut
and potato processing studies, market share assumptions of 100% crop
treated, and consumption data from the 1994 through 1996 USDA
continuing survey of food intake.
    Even using all of the worst case exposure scenarios listed above,
the Tier 1 acute assessment for the U.S. population resulted in a
margin of safety (MOS) of 270,507 at the 95th percentile. This
corresponded to an estimated exposure of 0.000185 mg/kg/day. The
highest acute exposure estimate (95th percentile) was observed in the
seniors (55 years and over) subpopulation: 0.001285 mg/kg/day. This
correlates to an MOE of 38,908.
    b. Chronic risk. Tier 1 dietary exposure analyses were conducted
for fluazinam in/on peanuts, potatoes and imported wine grapes to
determine the exposure contribution of these commodities to the diet
and to ascertain the chronic risk potential. The estimates were based
on proposed tolerance level residues for all three crops, peanut and
potato processing studies, market share assumptions of 100% crop
treated, and consumption data from the 1994 through 1996 USDA
continuing survey of food intake.
    Even using all of the worst case exposure scenarios listed above,
the Tier 1 chronic dietary exposure estimates resulted in an estimated
exposure for the U.S. population of 0.000104 mg/kg/day. This exposure
corresponds to 1.0% of the reference dose (RfD) of 0.01mg/kg/day. The
highest exposure estimate was calculated for the Females 20+ years
(non-pregnant/non-nursing) population subgroup. This exposure was
determined to be 0.000156 mg/kg/day (1.6% of the RfD).
    It can be concluded that acute or long-term dietary exposure to
fluazinam through residues on treated peanuts, potatoes and imported
wine grapes should not be of cause for concern.
    ii. Drinking water. Since fluazinam is intended for application
outdoors to field grown peanut and potato crops, the potential exists
for parent and or metabolites to reach ground or surface water that may
be used for drinking water. The calculated drinking water levels of
concern (DWLOC) for chronic exposure for adult males, adult females and
toddlers were estimated to be 355 parts per billion (ppb), 296 ppb, and
149 ppb, respectively. The calculated DWLOCs for acute exposure for all
adults, adult females and toddlers were estimated to be 17,943 ppb,
14,993 ppb, and 7,497 ppb, respectively. The chronic and acute DWLOC
values are well above the modeled chronic and acute DWECs of 0.17 ppb
(GENEEC 56-day/3) and 15.1 ppb (GENEEC instantaneous value),
respectively. Therefore, there is comfortable certainty that no harm
will result from combined dietary (food and water) exposure due to the
use of fluazinam on peanuts, potatoes and imported wine grapes.
    2. Non-dietary exposure. No petition for registration of fluazinam
is being made for either indoor or outdoor residential use. Non-
occupational exposure of fluazinam to the general population is
therefore not expected and is not considered in aggregate exposure
estimates.

D. Cumulative Effects

    Fluazinam is a phenylpyridinylamine fungicide. Since there are no
other members of this class of fungicides, it is considered unlikely
that fluazinam would have a common mechanism of toxicity with any other
pesticide in use at this time.

E. Safety Determination

    1. U.S. population. Based on a NOAEL of 1 mg/kg bwt/day from a one
year feeding study in dogs, and using an uncertainty factor of 100, a
reference dose of 0.01 mg/kg bwt/day is proposed for assessment of
long-term risk. The estimate of dietary intake was based on proposed
tolerance level residues for all three crops, peanut and potato
processing studies, market share assumptions of 100% crop treated and
consumption data. Even using those conservative intake estimates, the
proposed tolerances will utilize only 1% of the RfD for the U.S.
population. The estimated exposure of fluazinam from drinking water,
0.17 ppb is at least three orders of magnitude below the calculated
drinking water level of concern, 355 ppb.
    2. Infants and children. Data from developmental toxicity studies
in the rat and rabbit and a 2-generation reproduction study were
considered. These studies which were described earlier, demonstrated no
increased sensitivity of rats or rabbits to in utero exposure to
fluazinam. In addition, the multigeneration reproductive toxicity study
did not identify any increased sensitivity of rats to in utero or
postnatal exposure. For all three studies, parental NOAELs were lower
than or equivalent to the developmental or offspring NOAELs. It is
concluded that the standard margin of safety will protect the safety of
infants and children and that an additional safety factor is not
warranted.
    The dietary exposure of fluazinam to infants and children is
estimated to be much lower than adults because 80% to 90% of the
exposure is expected from sherry and wine. The proposed tolerances will
utilize 0.5% of the RfD for infants and children. The estimated
exposure of fluazinam from drinking water, 0.17 ppb is three orders of
magnitude below the calculated drinking water level of concern, 149
ppb.

F. International Tolerances

    There are presently no Codex maximum residue levels established for
residues of fluazinam on any crop.