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Propiconazole - Pesticide Tolerances 5/93

40 CFR Part 180
[PP 9F3758/R2000; FRL-4587-9]
RIN 2070-AB78
Pesticide Tolerances for 1-[[2-(2,4-Dichlorophenyl)-4-Propyl-
1,3-Dioxolan-2-yl]Methyl]-1H-1,2,4-Triazole and its Metabolites
Determined as 2,4-Dichlorobenzoic Acid and Expressed as Parent
Compound
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
------------------------------------------------------------
SUMMARY: This rule establishes a tolerance for a regional registration
for the State of Minnesota for residues of the fungicide 1-[[2-
(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-
triazole and its metabolites, determined as 2,4-dichlorobenzoic
acid and expressed as parent compound, in or on wild rice at
0.5 part per million (ppm). This document also establishes a
tolerance for this fungicide for apricots, peaches, plums, fresh
prunes, and nectarines at 1.0 ppm. This regulation was requested
by Ciba-Geigy Corp. in a petition and would establish the maximum
permissible levels for residues of propiconazole in or on the
above-listed commodities.

EFFECTIVE DATE: This regulation becomes effective May 17, 1993.

ADDRESSES: Written objections, identified by the document control
number, [PP 9F3758/R2000], may be submitted to: Hearing Clerk
(A-110), Environmental Protection Agency, Rm. 3708, 401 M St.,
SW., Washington, DC 20460.

FOR FURTHER INFORMATION CONTACT: By mail: Susan T. Lewis, Product
Manager (PM) 21, Registration Division (H7505C), Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location and telephone number: Rm. 227, CM .2, 1921 Jefferson
Davis Hwy., Arlington, VA 22202, (703)-305-6900.

SUPPLEMENTARY INFORMATION: EPA issued a notice, published in
the Federal Register of June 29, 1989 (54 FR 27422), which announced
that Ciba-Geigy Corp., P.O. Box 18300, Greensboro, NC 27419,
had submitted a tolerance petition (PP 9F3758) to EPA requesting
that the Administrator, pursuant to section 408(d) of the Federal
Food, Drug, and Cosmetic Act, 21 U.S.C. 346a(d), propose to
amend 40 CFR 180.434 by establishing tolerances for the fungicide
1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-
1H-1,2,4-triazole and its metabolites, determined as 2,4-dichlorobenzoic
acid and expressed as parent compound, in or on wild rice at
0.5 ppm (tolerance for a regional registration) and in or on
apricots, peaches, plums, fresh prunes, and nectarines at 1.0
ppm.
   There were no comments received in response to the notice
of filing.
   The toxicological data considered in support of the tolerances
include the following:
   1. Plant and animal metabolism studies.
   2. Residue data for crop and livestock commodities.
   3. Two enforcement methodologies and a multiresidue method
of analysis.
   4. A rat oral lethal dose (LD50) of 1,517 milligrams/kilogram
(mg/kg) of body weight.
   5. A 90-day rat feeding study with a no-observed-effect level
(NOEL) of 12 mg/kg/day.
   6. A 90-day dog feeding study with a NOEL of 1.25 mg/kg/day.
   7. A rabbit developmental toxicity study with a maternal
NOEL of 100 mg/kg/day and a developmental toxicity greater than
400 mg/kg/day (highest dose tested (HDT)).
   8. A rat teratology study with a maternal toxicity NOEL of
30 mg/kg/day and a developmental toxicity NOEL of 30 mg/kg/day.
   9. A two-generation rat reproduction study with a reproductive
NOEL of 125 mg/kg/day (HDT) and a developmental NOEL of 25 mg/kg/day.
   10. A 1-year dog feeding study with a NOEL of 1.25 mg/kg/day.
   11. A 2-year rat chronic feeding/carcinogenicity study with
a NOEL of 5 mg/kg/day with no carcinogenic potential under the
conditions of the study up to and including approximately 125
mg/kg, the highest dose tested.
   12. A 2-year mouse chronic feeding/carcinogenicity study
with a NOEL of 15 mg/kg/day and with a statistically significant
increase in combined adenomas and carcinomas of the liver in
male mice at approximately 375 mg/kg/day, the highest dose tested.
   13. Ames test with and without activation, negative.
   14. A mouse dominant-lethal assay, negative.
   15. Chinese hamster nucleus anomaly, negative.
   16. Cell transformation assay, negative.
   As part of EPA's evaluation of potential human health risks,
propiconazole has been the subject of five Peer Reviews and
one Scientific Advisory Panel (SAP) meeting.
   Propiconazole was originally evaluated by the Peer Review
Committee on January 15, 1987, and classified as a Group C (possible
human) carcinogen with a recommendation made for the quantification
of estimated potential human risk using a linearized low-dose
extrapolation. The method resulted in the establishment of a Q*
of 7.9 X 10*-2 (mg/kg/day)*-1.
   The Peer Review Committee's decision was presented to the
FIFRA Scientific Advisory Committee on March 2, 1988. The Panel
did not concur with the Committee's overall assessment of the
weight-of-evidence on the carcinogenicity of propiconazole.
The Panel recommended placing the chemical in Group D, indicating
that the Group C classification was based on minimal evidence.
The Panel's determination that EPA's Group C classification
was based on minimal evidence was due to the fact that the incidence
of liver tumors in male mice only occurred when the mice were
given an excessive chemical dose.
   In the second, third, and fourth Peer Reviews that followed,
the Peer Review group considered recommendations of the SAP
as well as rebuttals by the registrant. Its conclusion, however,
that propiconazole should be classified as a Group C carcinogen
with a quantification of potential human risk remained unchanged.
   As part of a fifth Peer Review, EPA considered additional
information provided by the registrant in support of the registrant's
argument that the high dose was excessively toxic in the mouse
carcinogenicity study. It further argued that the data from
the high dose (2,500 ppm) should not be included in the evaluation
of carcinogenic potential of propiconazole. In support of these
arguments, the registrant provided two subchronic oral toxicity
studies in mice. Ciba-Geigy also provided a reread of the pathology
slides from a mouse oncogenicity study which it felt indicated
sufficient concurrent liver toxicity at 2,500 ppm to document
that this dose was excessive. These findings were not present
in the original pathology report. Owing to the inconsistency
in Ciba-Geigy's report and the original report, the Agency requested
that an independent (third) evaluation of the pathology slides
be made to determine if the pathology reported could be confirmed.
The results of this (third) pathology evaluation were used in
the fifth Peer Review in place of data resulting from the earlier
evaluations provided by Ciba-Geigy.
   The Peer Review Committee considered the following facts
regarding the toxicology data on propiconazole in a weight-of-
evidence determination of carcinogenic potential:
   1. Increased numbers of adenomas (increased trend and pairwise
comparison) were found in the livers of male CD1 mice given
2,500 ppm of propiconazole in the diet.
   2. The treated animals had earlier fatalities than the controls.
   3. The numbers of carcinomas were increased (trend only)
in male mice only at the 2,500-ppm dose level. Tumors were not
significantly increased at the 500-ppm dose level. Adenomas
observed in the treated animals were larger and more numerous
than those in controls; however, the tumor type (adenoma) was
the same.
   4. No excessive number of tumors was found in female mice.
   5. In a rat study conducted with acceptable doses of propiconazole,
no excessive numbers of tumors were found.
   The Peer Review Committee determined, based on the additional
information submitted by Ciba-Geigy from two 90 day-subchronic
studies in mice that: The 2,500-ppm dose used in the 2-year
chronic study exceeded the maximum tolerated dose (MTD) based
on the endpoint of hepatic necrosis, and the 500-ppm dose used
in the chronic study was inadequate to assess the carcinogenicity
of propiconazole. Based on the third pathology evaluation of
the chronic study, the Peer Review Committee disagreed with
Ciba-Geigy's argument that the study showed excessive toxicity
at the 2,500-ppm dose. However, the Peer Review Committee concluded
that the 90-day subchronic studies are a better measure of what
would be an MTD.
   Based upon these findings, the Peer Review Committee agreed
that the classification for propiconazole should remain a Group
C (possible human) carcinogen. For the purpose of risk characterization
the Peer Review Committee recommended that the reference dose
(RfD) approach should be used for quantification of human risk.
This decision was based on the disqualification of the high
dose (2,500 ppm), making the data inappropriate for the calculation
of Q*. Because the middle dose (500 ppm) was not considered
sufficiently high enough for assessing the carcinogenetic potential
of propiconazole, EPA has requested an additional mouse study
at intermediate dose levels in male mice only. EPA does not
expect that these data will significantly change the above cancer
assessment.
   The reference dose (RfD) for propiconazole is 0.013 mg/kg/day,
based on a no-observed-effect level (NOEL) of 1.25 mg/kg/day
and an uncertainty factor of 100. The NOEL is taken from a 1-
year feeding study in dogs which demonstrated as an effect irritation
of the stomach in males. The Peer Review Committee changed the
classification of propiconazole from a Group Cq to a Group C
(possible human) carcinogen and recommended against the use
of the previously used Q* (viz. 0.079) for risk assessment
purposes. Propiconazole and its metabolite, 2,4-dichlorobenzoic
acid expressed as the parent compound, are to be considered
for risk analyses. Data gaps currently exist concerning dosing
in the mouse carcinogenicity study. These data have been requested
under reregistration.
   A dietary risk chronic exposure analysis was performed using
tolerance level residues and 100 percent crop treated information
to estimate the Theoretical Maximum Residue Contribution (TMRC)
for the general population and 22 population subgroups. The
use of anticipated residues and percent crop treated information
to further refine the exposure estimates was used for some commodities
to calculate the Anticpated Residue Contribution (ARC) for those
same population subgroups.
   The ARC for the general population from all published tolerances
is 3.2 X 10.-4 mg/kg body weight (bwt)/day, representing 3 percent
of the RfD. The tolerance proposed for wild rice contributes
2.0 X 10.-7 mg/kg bwt/day, or 0.002 percent of the RfD. The
fruits (apricots, nectarines, peaches, plums, and fresh prunes)
contribute an additional 3.3 X 10.-4 mg/kg bwt/day, or 2.5
percent of the RfD. The residue contribution for the proposed
tolerances, assuming residues at tolerance values and 100 percent
crop treated, is 3.302 X 10.-4 mg/kg bwt/day, representing
2.5 percent of the RfD. If proposed tolerances are granted for
this chemical the resulting ARC will be 6.5 X 10.-4 mg/kg/day,
occupying 6 percent of the RfD.
   The most highly exposed subpopulations are nursing and nonnursing
infants less than 1 year old. A commodity contribution revealed
that the consumption of the commodity peaches caused the greatest
exposure for these subgroups. Exposure due to wild rice consumption
was not calculated because age-specific consumption values are
not available. The proposed new tolerances for fruits result
in ARCs of 2.0 X 10.-3 mg/kg/day for nursing infants and 3.1
X 10.-3 mg/kg/day for nonnursing infants, representing 13 percent
and 24 percent of the RfDs. Total exposure from all published
and proposed new uses (excluding wild rice) is estimated to
be 14 percent and 25 percent for these groups.
   The Agency considers the dietary risk from propiconazole
use on wild rice and apricots, nectarines, peaches, plums, and
fresh prunes to be of minimal concern. Also, considering that
the potential exposure for the proposed uses was assessed assuming
residues at tolerance levels and 100 percent crop treated, there
is likely overestimation of exposure. Exposure to the proposed
commodities alone represents only 3 percent of the RfD for the
U.S. general population. The dietary risk from the proposed
uses for propiconazole is minimal.
   The nature of the residue is adequately understood, and an
adequate analytical method (gas chromatography) is available
for enforcement purposes. Because of the long lead time for
establishing these tolerances and food additive regulations
to publication of the enforcement methodology in the Pesticide
Analytical Manual, Vol. II, the analytical methodology is being
made available in the interim to anyone interested in pesticide
enforcement when requested from: Calvin Furlow, Public Information
Branch, Field Operations Division (H7506C), 401 M St., SW.,
Washington, DC 20460. Office location and telephone number:
Rm. 1128C, CM .2, 1921 Jefferson Davis Hwy., Arlington, VA 22202,
(703)-305-5232.
   The pesticide is considered useful for the purpose for which
the tolerances are being sought. Based on the information and
data considered, the Agency concludes that the amendment of
the tolerance for wild rice grown in Minnesota and for apricots,
peaches, plums, fresh prunes, and nectarines will protect the
public health.
   Based on the above information the Agency concludes that
the establishment of the tolerances will protect the public
health. Therefore, the tolerances are established as set forth
below.
   Any person adversely affected by this regulation may, within
30 days after publication of this document in the Federal Register,
file written objections with the Hearing Clerk, at the address
given above. 40 CFR 178.20. The objections submitted must specify
the provisions of the regulation deemed objectionable and the
grounds for the objections. 40 CFR 178.25. Each objection must
be accompanied by the fee prescribed by 40 CFR 180.33(i). If
a hearing is requested, the objections must include a statement
of the factual issue(s) on which a hearing is requested, the
requestor's contentions on each such issue, and a summary of
any evidence relied upon by the objector. 40 CFR 178.27. A request
for a hearing will be granted if the Administrator determines
that the material submitted shows the following: There is a
genuine and substantial issue of fact; there is a reasonable
possibility that available evidence identified by the requestor
would, if established, take into account uncontested claims
or facts to the contrary; and resolution of the factual issue(s)
in the manner sought by the requestor would be adequate to justify
the action requested. 40 CFR 178.32.
   Pursuant to the requirements of the Regulatory Flexibility
Act (Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator
has determined that regulations establishing new tolerances
or raising tolerance levels or establishing exemptions from
tolerance requirements do not have a significant economic impact
on a substantial number of small entities. A certification statement
to this effect was published in the Federal Register of May
4, 1981 (46 FR 24950).
   The Office of Management and Budget has exempted this rule
from the requirements of section 3 of Executive Order 12291.
List of Subjects in 40 CFR Part 180
   Administrative practice and procedures, Agricultural commodities,
Pesticides and pests, Reporting and recordkeeping requirements.
Dated: May 17, 1993.

Douglas D. Campt,
Director, Office of Pesticide Programs.

   Therefore, 40 CFR part 180 is amended as follows:

PART 180-[AMENDED]
   1. The authority citation for part 180 continues to read
as follows:
   Authority: 21 U.S.C. 346a and 371.
   2. By revising . 180.434, to read as follows:
. 180.434   1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-
2-yl]methyl]-1H-1,2,4-triazole; tolerances for residues.
   (a) Tolerances are established for residues of 1-[[2-(2,4-
dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-
triazole and its metabolites determined as 2,4-dichlorobenzoic
acid and expressed as parent compound, in or on the following
raw agricultural commodities:
------------------------------------------------+-------------+---------------
                   Commodity                    |  Parts per  |  Expiration
                                                |   million   |     date
------------------------------------------------+-------------+---------------
                                                |             |
Apricots....................................... |         1.0 |      ......
Bananas........................................ |         0.2 |      ......
Barley, grain.................................. |         0.1 |      ......
Barley, straw.................................. |         1.5 |      ......
Cattle, fat.................................... |         0.1 |      ......
Cattle, kidney................................. |         2.0 |    06/21/93
Cattle, liver.................................. |         2.0 |    06/21/93
Cattle, meat................................... |         0.1 |      ......
Cattle, mbyp (except kidney and liver)......... |         0.1 |      ......
Celery......................................... |         5.0 |      ......
Eggs........................................... |         0.1 |      ......
Goats, fat..................................... |         0.1 |      ......
Goats, kidney.................................. |         2.0 |    06/21/93
Goats, liver................................... |         2.0 |    06/21/93
Goats, meat.................................... |         0.1 |      ......
Goats, mbyp (except kidney and liver).......... |         0.1 |      ......
Grass, forage.................................. |         0.5 |    06/21/93
Grass, hay..................................... |         5.0 |    06/21/93
Grass, seed screenings......................... |        10.0 |    06/21/93
Hogs, fat...................................... |         0.1 |      ......
Hogs, kidney................................... |         2.0 |    06/21/93
Hogs, liver.................................... |         2.0 |    06/21/93
Hogs, meat..................................... |         0.1 |      ......
Hogs, mbyp (except kidney and liver)........... |         0.1 |      ......
Horses, fat.................................... |         0.1 |      ......
Horses, kidney................................. |         2.0 |    06/21/93
Horses, liver.................................. |         2.0 |    06/21/93
Horses, meat................................... |         0.1 |      ......
Horses, mbyp (except kidney and liver)......... |         0.1 |      ......
Milk........................................... |        0.05 |      ......
Nectarines..................................... |         1.0 |      ......
Peaches........................................ |         1.0 |      ......
Pecans......................................... |         0.1 |      ......
Plums.......................................... |         1.0 |      ......
Poultry, fat................................... |         0.1 |      ......
Poultry, kidney................................ |         0.2 |      ......
Poultry, liver................................. |         0.2 |      ......
Poultry, meat.................................. |         0.1 |      ......
Poultry, mbyp (except kidney and liver)........ |         0.1 |      ......
Prunes, fresh.................................. |         1.0 |      ......
Rice, grain.................................... |         0.1 |      ......
Rice, straw.................................... |         3.0 |      ......
Rye, grain..................................... |         0.1 |      ......
Rye, straw..................................... |         1.5 |      ......
Sheep, fat..................................... |         0.1 |      ......
Sheep, kidney.................................. |         2.0 |    06/21/93
Sheep, liver................................... |         2.0 |    06/21/93
Sheep, meat.................................... |         0.1 |      ......
Sheep, mbyp (except kidney and liver).......... |         0.1 |      ......
Wheat, grain................................... |         0.1 |      ......
Wheat, straw................................... |         1.5 |      ......
------------------------------------------------+-------------+---------------
   (b) A tolerance with regional registration, as defined in
180.1(n), is established for residues of 1-[[2-(2,4-dichlorophenyl)-
4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole and its
metabolites determined as 2,4-dichlorobenzoic acid and expressed
as parent compound, in or on the following raw agricultural
commodity:
------------------------------------------------------------------------------
                           Commodity                              Parts per
                                                                   million
------------------------------------------------------------------------------
Wild rice......................................................          0.5
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[FR Doc. 93-12130 Filed 5-20-93; 8:45 am]
BILLING CODE 6560-50-F