[Federal Register Volume 62, Number 24 (Wednesday, February 5, 1997)]
[Notices]
[Pages 5403-5406]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-2711]


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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: [email protected]. 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: 
[email protected].
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:
    [email protected]


    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