Tebuconazole - Pesticide Tolerance 7/95
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 9F3818/R2153; FRL-4970-3]
Tebuconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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) for seed treatment in or on the raw
agricultural commodities barley grain, forage, hay, and straw at 0.05,
0.10, 0.10, 0.10 parts per million (ppm), respectively; oat grain, forage,
hay, and straw at 0.05, 0.10, 0.10, and 0.10 ppm, respectively; and wheat
grain, forage, hay, and straw at 0.05, 0.10, 0.10, 0.10 ppm, respectively.
Miles, Inc. (formerly Mobay Corp., Agricultural Chemicals Division, now
Bayer Corp.) submitted a petition pursuant to the Federal Food, Drug, and
Cosmetic Act (FFDCA) for the regulation to establish a maximum permissible
level for residues of the fungicide.
EFFECTIVE DATE: This regulation becomes effective August 9, 1995.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 9F3818/R2153], 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,
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: email@example.com. 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 9F3818/R2153]. 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
Hwy., Arlington, VA 22202, (703)-305-6226; e-mail:
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the Federal
Register of June 15, 1995 (60 FR 31465), 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) 9F3818 to EPA requesting that the
Administrator, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d),
establish a tolerance for residues of the fungicide tebuconazole (alpha-[2-
ethanol) for seed treatment in or on the raw agricultural commodities
barley grain, forage, hay, and straw at 0.05, 0.10, 0.10, 0.10 ppm,
respectively; oat grain, forage, hay, and straw at 0.05, 0.10, 0.10, and
0.10 ppm, respectively; and wheat grain, forage, hay, and straw at 0.05,
0.10, 0.10, and 0.10 ppm, respectively.
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
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 a 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 postimplantation
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 a 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 a 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
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
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
13. An unscheduled DNA synthesis (UDS) study that was negative for UDS in
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, 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
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 current action is estimated at 0.000078 mg/kg
bwt/day and utilizes 0.78% of the RfD for the general population of the 48
States. The TMRC for the most highly exposed subgroup, nonnursing infants
(less than 1 year old), is estimated at 0.000097 mg/kg/day and utilizes
less than 1% of the RfD.
The nature of the residue in barley, oats, and wheat is adequately
understood. An adequate analytical method using high-performance liquid
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, Vol. 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,
Tolerances for tebuconazole in or on animal commodities are not currently
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 tolerance established by amending 40 CFR part 180 will protect the
public health. Therefore, the tolerance is 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).
A record has been established for this rulemaking under docket number, [PP
9F3818/R2153] (including objections and hearing requests 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, excluding legal holidays. The
public record is located in Rm. 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 Hwy., Arlington, VA.
Written objections and hearing requests, identified by the document control
number, [PP 9F3818/R2153], may be submitted to: Hearing Clerk (1900),
Environmental Protection Agency, Rm. 3708, 401 M St., SW., Washington, DC
A copy of electronic objections and hearing requests can be sent directly
to EPA at:
A copy of electronic objections and hearing requests may be submitted as an
ASCII file avoiding the use of special characters and any form of
The official record for this rulemaking, the public version, as described
above will be kept in paper form. Accordingly, EPA will transfer any
objections and hearing requests 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 objections and hearing
requests 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 (58 FR 51735, October 4, 1993), the Agency must
determine whether the regulatory action is "significant" and therefore
subject to all the requirements of the Executive Order (i.e., Regulatory
Impact Analysis, review by the Office of Management and Budget (OMB)).
Under section 3(f), the order defines "significant" as those actions
likely to lead to a rule (1) having an annual effect on the economy of $100
million or more, or adversely and materially affecting a sector of the
economy, productivity, competition, jobs, the environment, public health or
safety, or State, local or tribal governments or communities (also known as
"economically significant"); (2) creating serious inconsistency or
otherwise interfering with an action taken or planned by another agency;
(3) materially altering the budgetary impacts of entitlement, grants, user
fees, or loan programs; or (4) raising novel legal or policy issues arising
out of legal mandates, the President's priorities, or the principles set
forth in this Executive Order.
Pursuant to the terms of this Executive Order, EPA has determined that this
rule is not "significant" and is therefore not subject to OMB review.
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).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and recordkeeping
Dated: July 28, 1995.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR part 180 is amended as follows:
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 revising the table therein, to read as follows:
Sec. 180.474 Tebuconazole (alpha-[2-(4-chlorophenyl)-ethyl]-alpha- (1,1-
dimethylethyl)-1H-1,2,4-triazole-1-ethanol); tolerances for residues.
* * * * *
Barley, forage............................................. 0.10
Barley, grain.............................................. 0.05
Barley, hay................................................ 0.10
Barley, straw.............................................. 0.10
Oat, forage................................................ 0.10
Oat, grain................................................. 0.05
Oat, hay................................................... 0.10
Oat, straw................................................. 0.10
Peanut, hulls.............................................. 4.0
Wheat, forage.............................................. 0.10
Wheat, grain............................................... 0.05
Wheat, hay................................................. 0.10
Wheat, straw............................................... 0.10
[FR Doc. 95-19528 Filed 8-8-95; 8:45 am]
BILLING CODE 6560-50-F