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Tebuconazole - Pesticide Tolerance 11/95

[Federal Register: December 13, 1995 (Volume 60, Number 239)]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 3F4222/R2192; FRL-4989-4]
RIN 2070-AB78
Tebuconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.

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SUMMARY: This rule establishes tolerances for residues of the fungicide
tebuconazole (alpha-[2-(4-chlorophenyl)ethyl]-alpha-(1,1-dimethylethyl)-1H-
1,2,4-triazole-1-ethanol) in or on the raw agricultural commodities cherries
at 4.0 parts per million (ppm) and peaches (includes nectarines) at 1.0 ppm.
Miles, Inc. (now Bayer Corp.) submitted a petition pursuant to the Federal
Food, Drug and Cosmetic Act (FFDCA) for the regulation to establish these
maximum permissible levels for residues of the fungicide.

EFFECTIVE DATE: The effective date of this rule is November 22, 1995.

ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 3F4222/R2192], may be submitted to:
Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M
St., SW., Washington, DC 20460. Fees accompanying objections shall be
labeled Tolerance Petition Fees and forwarded to EPA Headquarters
Accounting Operations Branch, OPP (Tolerance Fees), P. O. Box 360277M,
Pittsburgh, PA 15251. A copy of any objections and hearing requests
filed with the Hearing Clerk should be identified by the document
control number and submitted 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 copy of objections and hearing requests to
Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202.
A copy of any objections and hearing requests filed with the
Hearing Clerk may also be submitted electronically by sending
electronic mail (e-mail) to: opp-docket@epamail.epa.gov. Copies of
objections and hearing requests must be submitted as an ASCII file
avoiding the use of special characters and any form of encryption.
Copies of objections and hearing requests will also be accepted on
disks in WordPerfect in 5.1 file format or ASCII file format. All
copies of objections and hearing requests in electronic form must be
identified by the document number [PP 3F4222/R2192]. No Confidential
Business Information (CBI) should be submitted through e-mail.
Electronic copies of objections and hearing requests on this rule may
be filed online at many Federal Depository Libraries. Additional
information on electronic submissions can be found below in this
document.

FOR FURTHER INFORMATION CONTACT: By mail: Connie B. Welch, Product
Manager (PM) 21, Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 227, CM #2, 1921
Jefferson Davis Highway, Arlington, VA 22202, (703)-305-6226; e-mail:
welch.connie@.epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of August 17, 1995 (60 FR 42885), which announced that
Miles, Inc., Agricultural Division (formerly Mobay Corp., Agricultural
Chemicals Division, now Bayer Corp.), P.O. Box 4913, Kansas City, MO
64120-0013, had submitted pesticide petition (PP) 3F4222 to EPA
requesting that the Administrator, pursuant to section 408(d) of the
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d),
establish a tolerance for residues of the fungicide tebuconazole
(alpha-(4-chlorophenyl)ethyl]-alpha-(1,1-dimethylethyl)-1H-1,2,4-
triazole-1-ethanol) in or on the raw agricultural commodities cherries
at 4.0 parts per million (ppm) and peaches (includes nectarines per 40
CFR 180.1(h)) at 1.0 ppm.

There were no comments received in response to the notice of
filing. The scientific data submitted in the petition and other
relevant material have been evaluated. The toxicological data
considered in support of the tolerance include:

1. A 90-day rat feeding study with a no-observed-effect level
(NOEL) of 34.8 milligrams per kilogram of body weight per day (mg/kg
bw/day) (400 ppm) and a lowest-effect-level (LEL) of 171.7 mg/kg bw/day
(1,600 ppm) in males, based on decreased body weight gains and
histological changes in the adrenals. For females, the NOEL was 10.8
mg/kg bw/day (100 ppm) and the LEL was 46.5 mg/kg bw/day (400 ppm)
based on decreased body weights, decreased body weight gains, and
histological changes in the adrenals.

2. A 90-day dog-feeding study with a NOEL of 200 ppm (73.7 mg/kg
bw/day in males and 73.4 mg/kg bw/day in females) and an LEL of 1,000
ppm (368.3 mg/kg bw/day in males and 351.8 mg/kg bw/day in females).
The LEL was based on decreases in mean body weights, body weight gains,
and food consumption, and an increase in liver N-demethylase activity.

3. A 1-year dog feeding study with a NOEL of 1 mg/kg bw/day (40
ppm) and an LEL of 5 mg/kg bw/day (200 ppm), based on lenticular and
corneal opacity and hepatic toxicity in either sex (the current
Reference Dose was determined based on this study). A subsequent 1-year
dog feeding study, using lower doses to further define the NOEL for
tebuconazole, defines a systemic LOEL of 150 ppm (based on adrenal
effects in both sexes) and a systemic NOEL of 100 ppm.

4. A 2-year rat chronic feeding study defined, a NOEL of 7.4 mg/kg
bw/day (100 ppm), and an LEL of 22.8 mg/kg bw/day (300 ppm) based on
body weight depression, decreased hemoglobin, hematocrit, MCV and MCHC,
and increased liver microsomal enzymes in females. Tebuconazole was not
oncogenic at the dose levels tested (0, 100, 300, and 1,000 ppm).

5. A rat oral developmental toxicity study with a maternal NOEL of
30 mg/kg bw/day and an LEL of 60 mg/kg bw/day based on elevation of
absolute and relative liver weights. For developmental toxicity, a NOEL
of 30 mg/kg bw/day and an LEL of 60 mg/kg bw/day was determined, based
on delayed ossification of thoracic, cervical and sacral vertebrae,
sternum, fore and hind limbs and increase in supernumerary ribs.

6. A rabbit oral developmental toxicity study with a maternal NOEL
of 30 mg/kg bw/day and an LEL of 100 mg/kg bw/day based on depression
of body weight gains and food consumption. A developmental NOEL of 30
mg/kg bw/day and an LEL of 100 mg/kg bw/day were based on increased
post-implantation losses, from both early and late resorptions and
frank malformations in eight fetuses of five litters.

7. A mouse oral developmental toxicity study with a maternal NOEL
of 10 mg/kg bw/day and an LEL of 20 mg/kg bw/day based on a
supplementary study indicating reduction in hematocrit and histological
changes in liver. A developmental NOEL of 10 mg/kg bw/day and an LEL of
30 mg/kg bw/day based on dose-dependent increases in runts/dam at 30
and 100 mg/kg bw/day.

8. A mouse dermal developmental toxicity study with a maternal NOEL
of 30 mg/kg bw/day and an LEL of 60 mg/kg bw/day based on a
supplementary study indicating increased liver microsomal enzymes and
histological changes in liver. The NOEL for developmental toxicity in
the dermal study in the mouse is 1,000 mg/kg bw/day, the highest dose
tested (HDT).

9. A two-generation rat reproduction study with a dietary maternal
NOEL of 15 mg/kg bw/day (300 ppm) and an LEL of 50 mg/kg bw/day (1,000
ppm) based on depressed body weights, increased spleen hemosiderosis,
and decreased liver and kidney weights. A reproductive NOEL of 15 mg/kg
bw/day (300 ppm) and an LEL of 50 mg/kg bw/day (1,000 ppm) were based
on neonatal birth weight depression.

10. An Ames mutagenesis study in Salmonella that showed no
mutagenicity with or without metabolic activation.

11. A micronucleus mutagenesis assay study in mice that showed no
genotoxicity.

12. A sister chromatid exchange mutagenesis study using CHO cells
that was negative at dose levels 4 to 30 ug/mL without activation or 15
to 120 ug/mL with activation.

13. An unscheduled DNA synthesis (UDS) study that was negative for
UDS in rat hepatocytes.

Additionally, a mouse oncogenicity study at dietary levels of 0,
20, 60, and 80 ppm for 21 months did not reveal any oncogenic effect
for tebuconazole at any dose tested. Because the maximum-tolerated-dose
(MTD) was not reached in this study, the study was classified as
supplementary. A followup mouse study at higher doses (0, 500, and
1,500 ppm in the diet), with an MTD at 500 ppm, revealed statistically
significant incidences of hepatocellular adenomas and carcinomas in
males and carcinomas in females. The initial and followup studies,
together with supplementary data submitted by Miles, Inc., were
classified as core minimum.

The Office of Pesticide Programs' Health Effects Division's
Carcinogenicity Peer Review Committee (CPRC) has classified
tebuconazole as a Group C carcinogen (possible human carcinogen). This
classification is based on the Agency's "Guidelines for Carcinogen
Risk Assessment" published in the Federal Register of September 24,
1986 (51 FR 33992). The Agency has chosen to use the reference dose
calculations to estimate human dietary risk from tebuconazole residues.
The decision supporting classification of tebuconazole as a possible
carcinogen (Group C) rather than a probable carcinogen (Group B) was
primarily based on the statistically significant increase in the
incidence of hepatocellular adenomas, carcinomas, and combined
adenomas/carcinomas in both sexes of NMRI mice both by positive trend
and pairwise comparison at the HDT, and the structural correlation with
at least six other related triazole pesticides that produce liver
tumors.

The Reference Dose (RfD) is established at 0.01 mg/kg of body
weight (bwt)/day, based on a no-observed-effect level (NOEL) of 1.00
mg/kg bwt/day and an uncertainty factor of 100. The NOEL is based on a
1-year dog-feeding study that demonstrated lenticular and corneal
opacity and hepatic toxicity as an endpoint effect. A 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 subgroups.
The Theoretical Maximum Residue Contribution (TMRC) from the
published uses is estimated at 0.000008 mg/kg bwt/day and utilizes
0.075% of the RfD for the general population of the lower 48 States.
The proposed use on peaches, cherries, and necatrines contributes
0.000377 mg/kg bwt/day (3.8% of the RfD) which raises the TMRC to
0.000385 mg/kg bwt/day or 3.9% of the RfD.

The TMRC for the most highly exposed subgroup, nonnursing infants
(less than 1-year old) is 0.000003 mg/kg bwt/day which represents 0.03%
of the RfD. The proposed use on peaches, cherries, and nectarines for
nonnursing infants (less than 1-year old) raises the TMRC to 0.002525
or 25.3% of the RfD.

The nature of the residue in cherries, peaches, and nectarines is
adequately understood. An adequate analytical method using gas
chromatography is available for enforcement purposes.
The enforcement methodology has been submitted to the Food and Drug
Administration for publication in the Pesticide Analytical Manual,
Volume II (PAM II). Because of the long lead time for publication of
the method in PAM II, the analytical methodology is being made
available in the interim to anyone interested in pesticide enforcement
when requested from: Calvin Furlow, Public Response and Program
Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location and telephone number: Rm. 1132,
CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703)-305-5232.

There is no reasonable expectation that secondary residues will
occur in milk, eggs, or meat of livestock and poultry since there are
no livestock feed items associated with this action.

There are currently no actions pending against the continued
registration of this chemical.

Based on the information and data considered, the Agency has
determined that the tolerances established by amending 40 CFR part 180
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 to the regulation and may also request a hearing on
those objections. Objections and hearing requests must be filed with
the Hearing Clerk, at the address given above (40 CFR 178.20). A copy
of the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. 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 such issues, 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 genuine and substantial issue
of fact; there is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one or more
of such issues in favor of the requestor, taking 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).
EPA has established a record for this rulemaking under docket
number [PP 3F4222/R2192] (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 a.m. to 4:30 p.m., Monday through Friday, except
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 rulemaking, 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 rulemaking record which will also include all comments
submitted directly in writing. The official rulemaking record is the
paper record maintained at the address in ADDRESSES at the beginning of
this document.

Under Executive Order 12866, EPA must judge whether a rule is
"major" and therefore requires a Regulatory Impact Analysis. This
rule was submitted to the Office of Management and Budget (OMB) for
review as required by Executive Order 12866.

Under the Regulatory Flexibility Act (5 U.S.C. 605(b)), EPA 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).

OMB has approved the information collection requirements contained
in this rule under the provisions of the Paperwork Reduction Act, 44
U.S.C. 3501 et seq.

List of Subjects in 40 CFR Part 180

Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

Dated: November 22, 1995.

Stephen L. Johnson,
Director, Registration Division, 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. In Sec. 180.474, by amending the table therein by adding and
alphabetically inserting new entries for cherries and peaches (includes
nectarines), to read as follows:

Sec. 180.474 Tebuconazle (alpha-[2-(4-chlorophenyl)-ethyl]-alpha-
(1,1-dimethylethyl)-1H-1,2,4-triazole); tolerances for residues.

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Parts per
Commodity million
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Cherries................................................... 4.0

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Peaches (includes necatrines).............................. 1.0

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