[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: 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-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:
welch.connie@epamail.epa.gov.
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:
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.
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
