PMEP Home Page --> Pesticide Active Ingredient Information --> Fungicides and Nematicides --> Fungicides, F to S --> Iprodione --> Iprodione - Pesticide Tolerance Petition Filing 1/97

Iprodione - Pesticide Tolerance Petition Filing for Cotton 1/97

CHEMICAL PROFILES/FUNGICIDE NEMATICIDE/iprodione
--------------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[PF-691; FRL-5583-6]

Rhone-Poulenc Ag Company; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of filing.
--------------------------------------------------------------------------

SUMMARY: This notice announces the filing of a pesticide petition proposing
the extension of the time-limited tolerance for the combined residues of the
fungicide iprodione [3-(3,5-dichlorophenyl)-N-(1- methylethyl)-2,4-dioxo-1-
imidazolidinecarboxamide], its isomer [3-(1- methylethyl)-N-(3,5-
dichlorophenyl)-2,4-dioxo-1- imidazolidinecarboxamide], and its metabolite [3-
(3,5-dichlorophenyl)- 2,4-dioxo-1-imidazolidinecarboxamide] (CAS Number 36734-
19-7, PC Code 109801) in or on the raw agricultural commodity (RAC) cottonseed
at 0.10 parts per million (ppm). The notice includes a summary of the petition
prepared by the petitioner, Rhone-Poulenc Ag Company.

DATES: Comments, identified by the docket number [PF-691], must be received on
or before February 24, 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-691]. Electronic comments on this
notice of filing 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 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Connie Welch, Product Manager (PM
21), Registration Division (7505W), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Crystal Mall #2, Room 227,
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 2F4111)
from Rhone-Poulenc Ag Company (Rhone-Poulenc), P.O. Box 12014, T.W. Alexander
Drive, Research Triangle Park, NC 27709 proposing pursuant to section 408(d)
of the Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C. 346(d), to amend
40 CFR part 180 by extending the time-limited tolerance for the fungicide
iprodione [3-(3,5- dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-
imidazolidinecarboxamide], its isomer [3-(1-methylethyl)-N-(3,5-
dichlorophenyl)-2,4-dioxo-1-imidazolidinecarboxamide], and its metabolite [3-
(3,5-dichlorophenyl)-2,4-dioxo-1- imidazolidinecarboxamide] in or on the RAC
cottonseed at 0.10 ppm. The current time-limited tolerance was established
under pesticide petition (PP) 2F4111 and expires on March 15, 1997. 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.

As required by section 408(d) of the FFDCA, as recently amended by the Food
Quality Protection Act, Rhone-Poulenc 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 Rhone-Poulenc. EPA is in the process of evaluating the petition. As
required by section 408(d)(3) of the FFDCA, EPA is including the summary as a
part of this notice of filing. EPA may have made minor edits to the summary
for the purpose of clarity.

I. Petition Summary

There is an extensive data base supporting the registration of iprodione. All
the studies required under the reregistration process mandated by the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) 88 have been submitted.
Most of these studies have been reviewed by the Agency and accepted.

The time-limited tolerance for iprodione on cottonseed at 0.10 ppm is
considered adequate to cover residues resulting from the use of iprodione on
cotton. No residues were detected in cottonseed field trial studies. A
processing study conducted at 12x the label rate showed no detectable
residues. The nature of the residue in plants is adequately defined. Plant
metabolism studies have been reviewed in connection with previous petitions
for tolerances. The residues of concern are iprodione, its isomer RP30228, and
its metabolite RP32490. The Phase IV Review concluded that additional plant
metabolism studies are not needed.

The nature of the residue in animals is adequately understood for the proposed
use of iprodione on cotton. Dietary contribution for animals from cottonseed
as a result of the proposed use will be very small and secondary residues in
animal commodities (ruminant and poultry) are expected to be nondetectable
(i.e. <0.01 ppm in milk and <0.05 ppm in other animal commodities). A
restriction is included in the use directions for cotton prohibiting grazing
and feeding of cotton forage to livestock. Furthermore, based on market share
information, only approximately 3% of the cotton crop is expected to be
treated with iprodione in 1997. The established tolerances for iprodione and
its metabolites in meat, milk, poultry, and eggs are therefore adequate to
cover secondary residues in animal commodities resulting from the use on
cotton.

An adequate analytical method, gas liquid chromatography using an electron-
capture detector, is available in the Pesticide Analytical Manual, Vol. II,
for enforcement purposes. In the Phase IV Review, EPA requested that a
substitute for benzene be used in the method of analysis used in new crop
field trials. In response to this request, Rhone-Poulenc developed a common
moiety GC method with a 0.05 ppm limit of quantitation (LOQ). An independent
laboratory validation for this method was submitted.

Iprodione is an important product for growers of several minor crops. These
include garlic, ginseng, chinese mustard, broccoli, caneberries (blackberries,
loganberries, and raspberries), and bushberries (blueberries, currant,
elderberries, gooseberries, and huckleberries).

Iprodione is also an important tool for cotton growers in controlling
Rhizoctonia solani, a seedling disease. The Cotton Disease Loss Estimate
Committee of the National Cotton Council ranks seedling diseases as the most
important cotton disease. Furthermore, based on the cotton use directions for
iprodione products, the maximum amount of product applied would be 0.2 lb
active ingredient/acre on a 40 inch row and 13,000 linear row ft. This is a
five- to six-fold decrease in active ingredient concentration compared to that
required for competitive soil applied cotton fungicides which control
Rhizoctonia solani. This allows for reduction of total pesticide usage in
cotton production and thus reduces pesticide exposure in the environment.
Another benefit is that iprodione is efficacious against all five anastomosis
groups of Rhizoctonia solani. Currently, there are no registered products
which possess this characteristic.

There are no Codex tolerances for iprodione on cottonseed. The following
mammalian toxicity studies have been conducted to support the extension of the
tolerance for iprodione on cotton.

A. Toxicological Profile

Rhone-Poulenc's explanation of the toxicological profile of iprodione is being
published elsewhere in today's issue of the Federal Register in another notice
of filing [PF-689] for a tolerance for iprodione.

B. Aggregate Exposure

Rhone-Poulenc's explanation concerning aggregate exposure to residues of
iprodione is being published elsewhere in today's issue of the Federal
Register in another notice of filing [PF-689] for a tolerance.

C. Safety Determination

1. DRES--US population--infants--children (1-6 yrs old). According to EPA's
Dietary Risk Evaluation System (DRES) chronic analysis, the percent RfD falls
within a safe margin even when considering tolerance levels and 100% crop
treated. For the overall U.S. population, dietary exposure to iprodione uses
0.353% of the RfD when using Anticipated Residue Contribution (ARC) or 54.22 %
of the RfD when using tolerance levels. These figures remain the same when
cotton is included in the analysis. Exposure to iprodione resulting from the
use of the product on cotton is negligible considering that:

i. Residues above the LOQ (0.05 ppm) were not observed in cotton field trial
studies.

ii. A processing study conducted at 12x the label rate showed no detectable
residues.

iii. Only 3% of the cotton crop is expected to be treated with iprodione.
A DRES detailed acute exposure analysis was performed by EPA using
conservative values. The resulting high end margin of exposure value of 100
for the DRES subgroup of concern (females 13 + years) is above the acceptable
level and demonstrates no acute dietary concern.

For the reasons stated in Unit I.A.5. in a notice of filing for iprodione
published elsewhere in this issue of the Federal Register, Rhone-Poulenc
considers the use of a low dose quantitative risk assessment for iprodione to
be inappropriate. As previously indicated Rhone-Poulenc recommends the use of
a safety factor approach and a RfD of 0.0725--mg/kg/day. The use of the Q* (Q
star) value of 0.0439 (mg/kg/day)-1 previously calculated by EPA represents a
very conservative estimate of the lifetime cancer risk from potential residues
of iprodione.

Nevertheless, an assessment of the lifetime cancer risk from iprodione
residues in food using a Q* value of 0.0439 (mg/kg/day)- 1 has been conducted
to specifically demonstrate that the use of iprodione on cotton does not
measurably increase exposure above that estimated for current uses. The upper
bound cancer risk attributed to the use of iprodione on cotton is calculated
to be 1.8 x 10 to the -8. This assessment also indicates the total cancer risk
to be in the de minimus range of 10 to the -6, even with a very conservative
Q* value. Based on results of the analyses, Rhone-Poulenc concludes that the
added use on cotton will not measurably increase the cancer risk estimate for
any population subgroup, and iprodione residues in currently registered foods
would not be expected to result in significant levels of chronic toxicity to
any segment of the U.S. population.

2. Infants and children--adequate margin of safety. In assessing the potential
for additional sensitivity of infants and children to residues of iprodione,
the available teratology and reproductive toxicity studies and the potential
for endocrine modulation by iprodione were considered.

Developmental studies in two species indicate that iprodione has no
teratogenic potential, even at maternally toxic dose levels. Maternal and
developmental no observed effect levels and lowest observed effect levels were
generally comparable indicating no increased susceptibility of developing
organisms. Multigeneration rodent reproduction studies indicated that
iprodione has no adverse effects on reproductive performance, fertility,
fecundity or sex ratio. Effects on pup weight and viability were only noted in
the presence of severe parental toxicity.

The mechanism of endocrine modulation associated with iprodione (inhibition of
testosterone biosynthesis) appears to be distinct from that of anti-androgens
acting at the level of the androgen receptor and may help to explain the lack
of adverse effects on reproductive function observed with iprodione.

Therefore, based upon the completeness and reliability of the toxicity data
and the conservative exposure assessment, Rhone-Poulenc believes that there is
a reasonable certainty that no harm will result to infants and children from
exposure to residues of iprodione and no additional uncertainty factor is
warranted.

3. Endocrine discussion and conclusion. As indicated in Unit I.A.5. in a
notice of filing for iprodione published elsewhere in this issue of the
Federal Register, the primary lesion at the level of the target organs
(testes, ovaries adrenals) is likely to be related to an inhibition of
steroid/androgen biosynthesis. The resulting endocrine toxic effect due to
iprodione is fairly moderate compared to that produced by potent endocrine
disruptors such as flutamide (and other structural analogs) and is
insufficiently potent to produce effects on reproduction or development.

The increased incidence in tumors in both rats and mice was only observed when
animals were treated at or above the MTD. For all three tumor sites (testis,
liver, ovary) tumors only develop on pre-existing non-neoplastic lesions (cell
hypertrophy/vacuolation, hyperplasia) and a clear threshold level exist for
both non-neoplastic lesions and tumors. Those thresholds are far in excess of
those levels of iprodione that the general public would be exposed to.

Conclusion. Rhone-Poulenc believes that iprodione would not be expected to
induce any adverse effects related to endocrine disruption in members of the
general population via the consumption of food crops containing residues of
this compound.

II. Public Record

EPA invites interested persons to submit comments on this notice of filing.
Comments must bear a notation indicating the docket number, [PF-691].

A record has been established for this notice of filing under docket number
[PF-691] 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 15, 1997.

Stephen L. Johnson, Director
Registration Division
Office of Pesticide Programs

[FR Doc. 97-1765 Filed 1-23-97; 8:45 am]
[Federal Register: January 24, 1997 (Volume 62, Number 16)] [Notices]
[Page 3685-3688]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]