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Fludioxonil (Ciba-Geigy). February 5, 1997. Pesticide Tolerance Petition. Federal Register.


http://www.epa.gov/docs/fedrgstr/EPA-PEST/1997/February/Day-05/p2711.htm

[Federal Register: February 5, 1997 (Volume 62, Number 24)]
[Notices]
[Page 5403-5406]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]

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ENVIRONMENTAL PROTECTION AGENCY
[PF-695; FRL-5584-1]


Ciba-Geigy Corporation; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of Filing.

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SUMMARY: This notice announces the refiling of a pesticide petition
proposing the establishment of a regulation for residues of [4-(2,2-
difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole 3 carbonitrile] (fludioxonil)
in or on the raw agricultural commodity (RAC) potatoes. The notice
contains a summary of the petition prepared by the petitioner, Ciba-
Geigy Corporation.
DATES: Comments, identified by the docket number [PF-695], must be
received on or before March 7, 1997.

ADDRESSES: By mail, submit written comments to Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. In person, bring comments to Rm. 1132, CM #2,
1921 Jefferson Davis Hwy., Arlington, VA 22202.
    Comments and data may also be submitted electronically by sending
electronic mail (e-mail) to: 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. Comments 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-695]. Electronic comments on this proposed rule may
be filed online at many Federal Depository Libraries. Additional
information on electronic submissions can be found in unit II of this
document.
    Information submitted as comments concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 1132 at the
address given above from 8:30 a.m. to 4:00 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Connie Welch, PM 21,
Registration Division (7505C), Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. Office location, telephone number and
e-mail address: Rm 227, Crystal Mall #2, 1921 Jefferson Davis Highway,
Arlington, VA 22202. (703) 305-6226, e-mail:
welch.connie@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP
6F4694) from Ciba-Geigy Corporation (``Ciba''), 410 Swing Road,
Greensboro, NC 27401, proposing pursuant to section 408(d) of the
Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C. 346a, to amend
40 CFR part 180 by establishing a tolerance for residues of the
fungicide, fludioxonil, in or on the raw agricultural commodity
potatoes at 0.02 parts per million (ppm).
    The proposed analytical method is Method AG-597B. The Limit of
Detection is 0.5 ng and the Limit of Quantitation for potatoes is 0.01
ppm. In AG-597, a subsample of potato substrate or processed fraction
is homogenized twice with 90 percent acetonitrile (ACN)/10 percent
water. Both extracts are filtered through Whatman 2V and Reeve Angel
802 paper. A 40-mL aliquot (2-g equivalent) is taken and the

[[Page 5404]]

ACN is evaporated using rotary evaporation. The sample is diluted with
a saturated salt solution and partitioned twice with methyl tert-butyl
ether (MTBE). Toluene is added to the organic phase, the MTBE is
evaporated and hexane is added to the sample. Samples are cleaned up on
a 0.5-g silica Bond Elut column that has been preconditioned with 10
percent isopropyl alcohol/90 percent hexane and rinsed with hexane. The
sample is loaded onto the column and CGA-173506 is eluted with 50
percent DCM/50 percent toluene. The silica column eluate is evaporated
to dryness. The residue remaining is dissolved in methanol and water
and then loaded onto a preconditioned 0.5-g phenyl Bond Elut column.
Fludioxonil is eluted with acetone. The acetone solution is evaporated
to dryness, and the residue is dissolved in an appropriate amount of
mobile phase. Residues of fludioxonil are determined by using an Amino
column with normal phase HPLC and ultraviolet absorbance detection at
268 nm.
    EPA has determined that the petition contains data or information
regarding the elements set forth in FFDCA 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.

I. Petition Summary

    1. Chemical uses. Fludioxonil is a non-systemic, contact fungicide
that is being developed as a seed treatment for potatoes. Fludioxonil
provides high-level, broad-spectrum activity against a wide range of
seed-borne and soil-borne diseases caused by Ascomycetes,
Deuteromycetes and Basidiomycetes. On potatoes, fludioxonil provides
control of Fusarium dry rot seed decay, Rhizoctonia stem canker, and
silver scurf. Fludioxonil represents a new class of chemistry with a
unique mode of action. Fludioxonil is classified as a phenylpyrrole and
is structurally related to pyrrolnitrin. Pyrrolnitrin is a secondary
metabolite of a soil-inhabiting bacterium of the genus Pseudomonas. It
has significant activity against economically important soil-borne
fungi. In European field trials against foliar pathogens, fludioxonil
was highly effective against pathogens resistant or insensitive to
other chemical classes such as the benzimidazoles and dicarboximides.
    2. Fludioxonil safety. a. Ciba has submitted over 25 separate
toxicology studies in support of tolerances for fludioxonil. According
to Ciba, fludioxonil has a low order of acute toxicity by the oral,
dermal, and inhalation exposure routes. The compound is slightly
irritating to the eye, non-irritating to skin, and is not a dermal
sensitizer. It is not a teratogen and does not affect reproduction or
fertility. The kidney and liver have been identified as target organs
in subchronic and chronic toxicity studies. No mutagenic activity has
been seen in vivo. On September 19, 1996, the Health Effects Division
Carcinogenicity Peer Review Committee issued its finding on
fludioxonil. The consensus of the committee was that fludioxonil should
be placed in Group D - not classifiable as to human carcinogenicity.
    b. The following mammalian toxicity studies have been conducted to
support the tolerance of fludioxonil:
    i. The rat acute oral LD50 is >5,000 mg/kg.
    ii. The rat acute dermal LD50 is >2,000 mg/kg.
    iii. The rat acute inhalation LC50 is >2.6 mg/liter air.
    iv. The primary eye irritation study in the rabbit showed slight
irritation.
    v. The primary dermal irritation study showed no irritation.
    vi. The primary dermal sensitization study showed no sensitization.
    vii. In a 28-day oral study in rats, the no-observed-effect level
(NOEL) was 10 mg/kg/day.
    viii. In a 28-day dermal study in rats, the NOEL was 40 mg/kg/day.
    ix. In a 90-day subchronic dietary toxicity study in rats, the NOEL
was 10 ppm based on liver toxicity.
    x. In a 90-day subchronic dietary toxicity study in mice, the NOEL
was 100 ppm based on blue urine (a metabolite). The maximum tolerated
dose was 7,000 ppm.
    xi. In a 90-day oral toxicity study in dogs, the NOEL was 200 ppm
based on clinical observation. The maximum tolerated dose was clearly
exceeded at 15,000 ppm.
    xii. In a 1-year chronic toxicity study in dogs, the NOEL was 100
ppm based on body weight effects. The maximum tolerated dose was 8,000
ppm.
    xiii. Two 18-month dietary oncogenicity studies were performed in
mice. While a NOEL of 1,000 ppm was clearly established in the first
study, its highest feeding level (3,000 ppm) did not meet the criteria
for a maximum tolerated dose.
    xiv. In the second 18-month study, the maximum tolerated dose was
determined to be 5,000 ppm. There were no treatment-related increases
in neoplasia at any dose level tested. In a combined chronic toxicity/
oncogenicity study in rats, the incidence of liver tumors in top-dose
females (3,000 ppm) was marginally higher than the controls. The NOEL
for chronic toxicity was 1,000 ppm in both sexes.
    xv. In vitro point mutation test: Ames assay - negative; Chinese
hamster V79 cells - negative; hepatocyte DNA repair - negative.
    xvi. In vitro chromosome test: Chinese hamster ovary cells -
clastogenic effects and polyploidy at or near precipitating
concentration.
    xvii. In vivo mutagenicity test: rat hepatocyte micronucleus -
negative; mouse bone marrow - negative; cytogenetic test on Chinese
hamster bone marrow - negative; mouse dominant lethal - negative.
    xviii. In a teratology study in rats, fludioxonil was not
teratogenic at doses up to 1,000 mg/kg. The maternal NOEL was 100 mg/
kg, while the NOEL in the fetus was 1,000 mg/kg.
    xix. In a teratology study in rabbits, fludioxonil was not
teratogenic at doses up to 300 mg/kg. The maternal and fetal NOELs were
10 mg/kg and 300 mg/kg, respectively.
    xx. In a multigeneration reproduction study, fludioxonil had no
adverse effects on the reproductive performance of the rat at doses up
to 3,000 ppm. Fetal effects (reductions in pup body weights) were
observed only at 3,000 ppm, a dose level at which there were maternal
toxic effects. The NOEL was 300 ppm.
    3. Threshold effects-- a. chronic effects. Based on the available
chronic toxicity data, Ciba believes that the Reference Dose (RfD) for
fludioxonil is 0.025 mg/kg/day. This RfD is based on a 1-year feeding
study in dogs with a NOEL of 2.5 mg/kg/day (100 ppm) and an uncertainty
factor of 100. No additional modifying factor for the nature of effects
was judged to be necessary as body weight was the most sensitive
indicator of toxicity in that study.
    b. Acute toxicity. Based on the available acute toxicity data, EPA
has determined that fludioxonil does not pose any acute dietary risks.
The lowest NOEL in a short term exposure scenario, identified as 10 mg/
kg in the rabbit teratology study, is actually higher than the chronic
NOEL (see above). Ciba anticipates that the margin of exposure would be
in the thousands for any population group (margins of exposure of 100
or more are considered satisfactory).
    4. Non-threshold effects. Using the Guidelines for Carcinogenic
Risk Assessment published on September 24, 1986 (51 FR 33992), the
USEPA has classified fludioxonil in group D for carcinogenicity. The
compound was

[[Page 5405]]

tested in two mouse oncogenicity studies and a 24-month rat chronic
study. Dosage levels in both the mouse and the rat studies were
adequate for identifying cancer risk.
    5. Aggregate exposure. For purposes of assessing the potential
dietary exposure under the proposed tolerance, Ciba has estimated
aggregate exposure based on the tolerance level of 0.02 ppm in or on
the RAC potatoes (potato tubers). This is a worse case estimate of
dietary exposure since it is assumed that 100 percent of all crops for
which tolerances are established are treated and that pesticide
residues are present at the tolerance levels.
    Fludioxonil's current registered use for seed treatment on corn and
sorghum seeds does not contribute to dietary exposure because there are
no detectable residues. EPA has ruled that these uses are food uses not
requiring tolerances. For potato seed treatment, the use described in
this petition, a residue tolerance level of 0.02 ppm is being proposed
although the highest actual level seen in field trials is around 0.01
ppm. In conducting this exposure assessment, very conservative
assumptions--100 percent of potatoes will contain fludioxonil residues
and those residues would be at the level of the tolerance--have been
used, resulting in an overestimate of human exposure.
    Exposures of the general population to residues of this pesticide
from other potential sources, drinking water and other non-occupational
sources, Ciba considers to be unlikely. The movement of fludioxonil
into groundwater is highly unlikely. The EPA has not established a
Maximum Contaminant Level for residues of fludioxonil in drinking
water. Non-occupational exposure for fludioxonil has not been
calculated since the current registration for fludioxonil is limited to
commercial crop production. Since the chemical is not used in or around
the home, Ciba considers the potential for non-occupational exposure to
the general population to be non-existent.
    Consideration of a common mechanism of toxicity is not appropriate
at this time since Ciba is unaware of any reliable information that
indicates that toxic effects produced by fludioxonil would be
cumulative with those of any other chemical compounds. Consequently,
Ciba is considering only the potential risks of fludioxonil in its
aggregate exposure assessment.
    6. Determination of safety for U.S. population. Using the
conservative exposure assumptions described above and based on the
completeness and reliability of the toxicity data base for fludioxonil,
Ciba has calculated aggregate exposure levels for this chemical. The
calculation shows that only 0.09 percent of the RfD will be utilized
for the U.S. population based on chronic toxicity endpoints. EPA
generally has no concern for exposures below 100 percent 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. Ciba concludes that there is a reasonable certainty that
no harm will result from aggregate exposure to fludioxonil residues.
    7. Determination of safety for infants and children. Developmental
toxicity (decreased pup weight) was observed in the 2-generation rat
reproduction study at a maternally toxic dose. The NOEL for this effect
was established at 30 mg/kg (300 ppm). This finding is judged to be a
nonspecific, secondary effect of maternal toxicity. No developmental
toxicity was observed at all in any of the teratology studies
conducted. Ciba concludes that infants and children are not uniquely
sensitive to fludioxonil.
    Using the same conservative exposure assumptions used for the
determination in the general population, Ciba has concluded that the
percentage of the RfD that will be utilized by aggregate exposure to
residues of fludioxonil is 0.03 percent for nursing infants less than 1
year old, 0.11 percent for non-nursing infants, 0.18 percent for
children 1 to 6 years old, and 0.13 percent for children 7 to 12 years
old. Therefore, based on the completeness and reliability of the
toxicity data base and the conservative exposure assessment, Ciba
concludes that there is reasonable certainty that no harm will result
to infants and children from aggregate exposure to fludioxonil
residues.
    8. Estrogenic effects. No specific tests have been conducted with
fludioxonil to determine whether the pesticide may have an effect in
humans that is similar to an effect produced by a naturally occurring
estrogen or other endocrine effects.
    9. Chemical residues. The nature of the residue is adequately
understood in animals and plants. The metabolism of fludioxonil in
plants has been characterized in potatoes, rice, and spring wheat.
Residues of fludioxonil do not concentrate in processed commodities.
There are no Codex maximum residue levels established for residues of
fludioxonil on potatoes. Ciba has submitted a practical analytical
method for detecting and measuring levels of fludioxonil in or on food
with the limit of quantitation that allows monitoring of food with
residues at or above the levels set in the proposed tolerances. EPA
will provide information on this method to FDA. The method is available
to anyone who is interested in pesticide residue enforcement from the
Field Operations Division, Office of Pesticide Programs.
    This petition is supported by 23 field residue tests where
fludioxonil, in the form of Maxim T Potato Seed Protectant, was applied
to potato seed pieces. These trials indicate that the maximum residue
of fludioxonil will be at or below 0.011 ppm at the 0.7X rate of 1.75g
a.i./100 kg. A tolerance of 0.02 ppm is proposed for raw agricultural
commodities (tubers) of potatoes.
    No residues greater than or equal to 0.01 ppm were detected in the
tubers before processing, in peeled and rinsed potatoes, sliced and
peeled potatoes, potato chips, or potato granules from field trials
conducted in Michigan and North Dakota.
    The results from all four processed field trials indicate that
residues in potato processing waste (wet peel and trimmings) and potato
culls will not exceed the tolerance established for potato tubers.
    Based on the results of rotational crop studies, Ciba proposes a 1-
year restriction on rotation to crops other than leafy vegetables, root
and tuber vegetables, and registered crops (potatoes, corn, and
sorghum).
    Using the worst case theoretical diet for beef and dairy cattle, no
detectable residues would be expected in tissues or milk. Processed
potato products are not fed to poultry. Therefore, there is no need for
tolerances in meat, milk or eggs.
    10. Environmental fate. Since the Agency classifies seed treatment
uses as ``Indoor,'' the only environmental fate data requirement is
hydrolysis. Fludioxonil is hydrolytically stable in solution at
25 deg.C at pH 5, 7, or 9. At pH 1 and 13, fludioxonil is extensively
degraded.

II. Public Record

    EPA invites interested persons to submit comments on this notice of
filing. Comments must bear a notification indicating the docket number
[PF-695].
    A record has been established for this notice under docket numbers
[PF-695] (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 public
record is located in Room 1132 of the

[[Page 5406]]

Public Response and Program Resources Branch, Field Operations Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov


    Electronic comments must be submitted as ASCII file avoiding the
use of special characters and any form of encryption.
    The official record for this notice, as well as the public version,
as described above will be kept in paper form. Accordingly, EPA will
transfer all comments received electronically into printed, paper form
as they are received and will place the paper copies in the official
record which will also include all comments submitted directly in
writing. The official record is the paper record maintained at the
address in ADDRESSES at the beginning of this document.

List of Subjects

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

    Dated: January 22, 1997.

Stephen L. Johnson,

Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 97-2711 Filed 2-4-97; 8:45 am]
BILLING CODE 6560-50-F