[Federal Register Volume 62, Number 24 (Wednesday, February 5, 1997)]
[Notices]
[Pages 5406-5408]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-2468]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-696; FRL-5584-2]


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 filing of a pesticide petition 
proposing the establishment of a regulation for residues of cyprodinil 
in or on members of the stone fruit crop grouping under an experimental 
use permit (EUP). This notice contains a summary prepared by the 
petitioner, Ciba-Geigy Corporation.
DATES: Comments, identified by the docket number [PF-696], 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 Highway, Arlington, VA.
    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-696]. Electronic comments on this notice may be filed 
online at many Federal Depository Libraries. Additional information on 
electronic submissions can be found below in this document.
    Information submitted as comments concerning this notice may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). No CBI should 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 p.m., Monday through Friday, excluding legal 
holidays.

FOR FURTHER INFORMATION CONTACT: By mail, Connie Welch, Product Manager 
(PM) 21, Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
Office location, telephone number, and e-mail address: Rm. 227, CM #2, 
1921 Jefferson Davis Highway, Arlington, VA, (703) 305-6226; e-mail: 
[email protected].
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP) 
5G4553 from Ciba Crop Protection, Ciba-Geigy Corporation (``Ciba''), 
P.O. Box 18300, Greensboro, NC 27419, 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 temporary tolerance 
for residues of the fungicide cyprodinil (4-cyclopropyl-6-methyl-N-
phenyl-2-pyrimidinamine) in or on the agricultural commodities for the 
stone fruit crop grouping at 2.0 ppm. The proposed analytical method is 
by high performance liquid chromatography with UV detection. EPA has 
determined that the 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 supports granting of the petition. Additional data may be 
needed before EPA rules on the petition.
    As required by section 408(d) of the FFDCA, as recently amended by 
the Food Quality Protection Act (Pub. L. 104-170), Ciba included in the 
petition a summary of the petition and authorization for the summary to 
be published in the Federal Register in a notice of receipt of the 
petition. The summary represents the views of Ciba; EPA is in the 
process of evaluating the petition. As required by section 408(d)(3), 
EPA is including the summary as a part of this notice of filing. EPA 
has made minor edits to the summary for the purpose of clarity.

I. Petition Summary

A. Cyprodinil Uses

    Cyprodinil is the first fungicide in a new chemical class known as 
the anilinopyrimidine and is active against important Monilinia 
diseases of stone fruit when applied at rates of 0.25 to 0.5 lb active 
ingredient per acre. Cyprodinil has a unique mode of action which 
controls pathogens resistant to other chemical classes of fungicides.

B. Metabolism and Analytical Method

    1. Metabolism. Ciba believes the metabolism of cyprodinil has been 
well characterized in plants and animals. The metabolism profile 
supports the use of an analytical enforcement method that accounts for 
parent cyprodinil.
    2. Analytical methodology. Ciba has submitted a practical 
analytical method involving extraction, filtration, and solid phase 
cleanup of samples with analysis by HPLC and UV. The limits of 
quantitation (LOQ) for fruit is 0.02 ppm.

C. Magnitude of Residue

    This petition is supported by field residue trials conducted on 
representative members of the Stone Fruit Crop Grouping. All samples 
were analyzed for parent residues of cyprodinil. In stone fruit, 
maximum residues ranged from 0.82 ppm to 1.7 ppm. A temporary tolerance 
of 2.0 ppm has been proposed for the Stone Fruit Crop Grouping under 
this EUP. Since stone fruit commodities are not fed to animals, 
potential transfer of cyprodinil into milk and meat is not anticipated 
and tolerances in milk, meat, poultry, and eggs are not required.

[[Page 5407]]

D. International Tolerances

    There are no Codex Alimentarius Commission (CODEX) maximum residue 
levels (MRLs) established for residues of cyprodinil in or on raw 
agricultural commodities.

E. Toxicological Profile of Cyprodinil

    The following mammilian toxicity studies have been conducted to 
support the tolerances of cyprodinil:
    A rat acute oral study for cyprodinil with a LD50 of 2,796 mg/
kg. A rat acute dermal study for cyprodinil with a LD50 >2,000 mg/
kg.
    A rat inhalation study for cyprodinil with a LC50 >1.2 mg/
liter air.
    A primary eye irritation study in rabbits showing cyprodinil as 
minimally irritating.
    A primary dermal irritation study in rabbits showing cyprodinil as 
slightly irritating.
    A skin sensitization study in guinea pigs showing cyprodinil as a 
weak sensitizer.
    A 28-day dermal study in the rat with a No-Observed Effect Level 
(NOEL) of 5 mg/kg based on clinical signs.
    A 90-day feeding study in the dog with a NOEL of 1,500 ppm (37.5 
mg/kg) based on reduced food intake and body weight.
    A 90-day feeding study in the mouse with a NOEL of 500 ppm (75 mg/
kg) based on liver histologic changes.
    A 90-day feeding study in the rat with a NOEL of 50 ppm (5 mg/kg) 
based on hematologic and histologic findings.
    A 12-month feeding study in the dog with a NOEL of 2,500 ppm (62.5 
mg/kg) based on liver histologic changes.
    An 18-month oncogenicity feeding study in the mouse with a NOEL of 
2,000 ppm (300 mg/kg). The MTD was 5,000 ppm based on reduction in body 
weight gain and no evidence of oncogenicity was seen.
    A 24-month chronic feeding/oncogenicity study in the rat with a 
NOEL of 75 ppm (3.75 mg/kg) based on hematologic and histologic 
findings. The MTD was 2,000 ppm based on liver histopathology and no 
evidence of oncogenicity was seen. An oral teratology study in the rat 
with a maternal NOEL of 200 mg/kg based on reductions in body weight 
gain and food consumption and a fetal NOEL of 200 mg/kg based on 
decreased pup weight and delayed skeletal growth at 1,000 mg/kg. An 
oral teratology study in the rabbit with a maternal NOEL of 150 mg/kg 
based on reduction in body weight gain and a fetal NOEL of 400 mg/kg 
based on the absence of any fetal effects.
    A 2-generation reproduction study in the rat with a systemic NOEL 
of 100 ppm and a fetal NOEL of 1,000 ppm (100 mg/kg).
    A slight decrease in pup weight at birth and subsequent body weight 
gain during the lactation phase was observed only at the maternally 
toxic dose of 4,000 ppm without any effects on reproduction and 
fertility.
    In vitro gene mutation test: Ames assay - negative; Chinese hamster 
V79 cell test - negative; rat hepatocyte DNA repair test - negative.
    In vitro chromosome test: Chinese hamster ovary cell cytogenetic 
test - negative. In vivo mutagenicity test: mouse bone marrow test - 
negative.

F. Threshold Effects

    1. Chronic effects. Based on the available chronic toxicity data, 
Ciba believes the Reference Dose (RfD) for cyprodinil is 0.0375 mg/kg/
day. This RfD is based on a 2-year feeding study in rats with a NOEL of 
3.75 mg/kg/day (75 ppm) and an uncertainty factor of 100. No additional 
modifying factor for the nature of effects was judged to be necessary 
as liver sinusoidal dilatation was the most sensitive indicator of 
toxicity in that study.
    2. Acute toxicity. The risk from acute dietary exposure to 
cyprodinil is considered to be very low. The lowest NOEL in a short-
term exposure scenario, identified as 150 mg/kg in the rabbit 
teratology study, is 40-fold higher than the chronic NOEL. Since 
chronic exposure assessment did not result in any margin of exposure 
(MOE) less than 400 for even the most impacted population subgroup, 
Ciba believes the MOE is greater than 100 for any population subgroups; 
EPA considers margins of exposure of 100 or more as satisfactory.

G. Non-threshold Effects

     Using the Guidelines for Carcinogenic Risk Assessment published 
September 24, 1986 (51 FR 33992), Ciba believes cyprodinil to be in 
Group ``E''( no evidence of carcinogenicity). There was no evidence of 
carcinogenicity in an 18-month feed study in mice and a 24-month 
feeding in rats. Dosage levels in both the mouse and the rat studies 
were adequate for identifying a cancer risk.

H. Aggregate Exposure

    1. Dietary exposure. For the purposes of assessing the potential 
dietary exposure under the proposed temporary tolerance, Ciba has 
estimated aggregate exposure based upon the Theoretical Maximum Residue 
Concentration (TMRC) from the requested tolerance for members of the 
Stone Fruit Crop Grouping at 2.0 ppm. The TMRC is a ``worst case'' 
estimate of dietary exposure since it assumes 100 percent of all crops 
for which tolerances are established are treated and that pesticide 
residues are at the tolerance levels. In conducting this exposure 
assessment, Ciba has made very conservative assumptions -- 100 percent 
of all stone fruit commodities will contain cyprodinil residues at 
tolerance levels -- which result in an overestimate of human exposure. 
Ciba has also calculated aggregate exposure based upon the scale of the 
requested 950-acre EUP. It is estimated that a maximum of 0.25 percent 
of the stone fruit market would receive applications of cyprodinil 
under this EUP and that dietary exposure would be proportionately less 
than under the ``worst case'' assumptions given above.
    2. Drinking water exposure.  Cyprodinil is rapidly degraded in the 
environment via photolysis and microbial degradation; aqueous and soil 
photolysis half lives for cyprodinil are 12 days and 67 days, 
respectively. The aerobic metabolism half life is 25 days and the 
leaching potential for cyprodinil is low (Koc = 1,550 to 2,030). 
Based on these data, Ciba does not anticipate exposure to residue of 
cyprodinil in drinking water.
    3. Non-dietary exposure. Ciba believes that the potential for non-
occupational exposure to the general public is unlikely except for 
potential residues in food crops discussed above. The proposed uses for 
cyprodinil are for agricultural crops and the product is not used 
residentially in or around the home.
    Ciba believes that consideration of a common mechanism of toxicity 
is not appropriate at this time since there is no information to 
indicate that toxic effects produced by cyprodinil would be cumulative 
with those of any other chemicals. Consequently, Ciba is considering 
only the potential exposure to cyprodinil in its aggregate risk 
assessment.

I. Safety To the U.S. Population

    Reference dose. Using the conservative exposure assumptions 
described above (100 percent stone fruit acres treated and tolerance 
level residues) and based on the completeness and reliability of the 
toxicity data base for cyprodinil, Ciba has calculated aggregate 
exposure levels for this chemical. Based on chronic toxicity endpoints, 
only 2 percent of the RfD will be utilized for the U.S. general 
population. Under the scale of this EUP (0.25 percent stone fruit acres 
treated) it is estimated that only 0.005 percent of the RfD will be 
utilized for the U.S. general population. EPA usually has no

[[Page 5408]]

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 cyprodinil residues.

J. Safety to Infants and Children

    Developmental delays (reduced pup weight and ossification) were 
observed in the rat teratology study and 2-generation rat reproduction 
study at maternally toxic doses. The lowest NOEL for this effect was 
established in the 2-generation study at 100 mg/kg (1,000 ppm). The 
finding is judged to be a nonspecific, secondary effect of maternal 
toxicity. No developmental toxicity was observed in the rabbit 
teratology study.
    Reference dose. Using the same conservative exposure assumptions as 
employed for the determination in the general population (100 percent 
stone fruit acres treated and tolerance level residues), Ciba has 
calculated the utilization of RfD by aggregate exposure to residues of 
cyprodinil to be 9 percent for nursing infants less than 1 year old, 17 
percent for non-nursing infants less than 1 year old, 4 percent for 
children 1 to 6 years old, and 3 percent for children 7 to 12 years 
old. Under the scale of this EUP (0.25 percent stone fruit acre 
treated) the utilization of RfD by aggregate exposure to residues of 
cyprodinil is estimated to be 0.023 percent for nursing infants less 
than 1 year old, 0.043 percent for non-nursing infants less than 1 year 
old, 0.011 percent for children 1 to 6 years old, and 0.007 percent for 
children 7 to 12 years old. Ciba believes that under the worst case 
assumptions which overestimate exposure to infants and children, there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to cyprodinil residues. Under the 
scale of this EUP resultant exposure will be proportionately less.

K. Estrogenic Effects

    Cyprodinil does not belong to a class of chemicals known or 
suspected of having adverse effects on the endocrine system. 
Developmental toxicity studies in rats and rabbits and a reproduction 
study in rats gave no indication that cyprodinil might have any effects 
on endocrine function related to development and reproduction. The 
chronic studies also showed no evidence of a long-term effect related 
to the endocrine system.

II. Public Record

    EPA invites interested persons to submit comments on this notice of 
filing. Comments must bear a notification indicating the docket control 
number [PF-696]. All written comments filed in response to this 
petition will be available, in the Public Response and Program 
Resources Branch, at the address given above from 8:30 a.m. to 4 p.m., 
Monday through Friday, except legal holidays.
    A record has been established for this notice under docket control 
number [PF-696] (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 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 an ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this notice of filing, 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. 97-2468 Filed 1-4-97; 8:45 am]
BILLING CODE 6560-50-F