[Federal Register Volume 60, Number 85 (Wednesday, May 3, 1995)]
[Rules and Regulations]
[Pages 21728-21731]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-10862]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4F4317/R2125; FRL-4949-4l
RIN No. 2070-AB78
Myclobutanil; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes a tolerance for the combined residues of
the fungicide myclobutanil and a metabolite in or on the raw
agricultural [[Page 21729]] commodity cottonseed at 0.02 part per
million (ppm). The Rohm & Haas Co. requested establishment of this
tolerance.
EFFECTIVE DATE: This regulation became effective on March 30, 1995.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 4F4317/R2125], may be submitted to:
Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M
St., SW., Washington, DC 20460. 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 a copy of the objections and
hearing requests to Rm. 1132, CM #2, 1921 Jefferson Davis Hwy.,
Arlington, VA 22202. 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 objections and requests for hearings 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 requests for hearings must be submitted as an ASCII file
avoiding the use of special characters and any form of encryption.
Copies of objections and requests for hearings will also be accepted on
disks in WordPerfect in 5.1 file format or ASCII file format. All
copies of objections and requests for hearings in electronic form must
be identified by the docket number [PP 4F4317/R2125]. No Confidential
Business Information (CBI) should be submitted through e-mail.
Electronic copies of objections and requests for hearings 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)-305-6900; e-mail:
welch.connie@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of February 8, 1995 (60 FR 7539), which announced that
the Rohm & Haas Co., Independence Mall West, Philadelphia, PA 19105,
was proposing the establishment of a tolerance of 0.02 part per million
(ppm) in pesticide petition (PP) 4F4317 for the residues of the
fungicide myclobutanil, [alpha-butyl-alpha-(3-hydroxybutyl)-1H-1,2,4-
triazole-1-propanenitrile], and both the free and bound forms of its
metabolite, alpha-(3-hydroxybutyl)-alpha-(4-chlorophenyl)-1H-1,2,4-
triazole-1-propanenitrile, in or on the raw agricultural commodity
cottonseed. There were no comments received in response to the Federal
Register notice. The data submitted in support of the petition and
other relevant material have been evaluated. The pesticide is
considered useful for the purpose for which the tolerance is sought.
The toxicological data considered in support of the tolerance include
the following:
1. A 1-year dog feeding study using doses of 0, 10, 100, 400, and
1,600 ppm (equivalent to doses of 0, 0.34, 3.09, 14.28 and 54.22
milligrams/kilogram (mg/kg) body weight (bwt)/day in males and 0, 0.40,
3.83, 15.68 and 58.20 mg/kg bwt/day in females). The no-observed-effect
level (NOEL) is 100 ppm (3.09 mg/kg/day for males and 3.83 mg/kg/day
for females) based upon hepatocellular hypertrophy, increases in liver
weights, ``ballooned'' hepatocytes, and increases in alkaline
phosphatase, SGPT and GGT, and possible slight hematological effects.
The lowest-observed-effect level (LOEL) is 400 ppm (14.28 mg/kg/day for
males and 15.68 mg/kg/day for females).
2. A 2-year chronic feeding/carcinogenicity study in rats using
dietary concentrations of 0, 50, 200 and 800 ppm (equivalent to doses
of 0, 2.49, 9.84 and 39.21 mg/kg bwt/day in males and 0, 3.23, 12.86
and 52.34 mg/kg bwt/day in females). The NOEL for chronic effects other
than carcinogenicity is 2.49 mg/kg/day, and the LOEL is 9.84 mg/kg/day
based on testicular atrophy in males. No other significant effects were
observed in either sex at the stated dose levels over a 2-year period.
In addition, no carcinogenic effects were observed in either sex at any
of the dose levels tested. Based on the toxicological findings, the
maximum tolerated dose (MTD) selected for testing (based on the 90-day
feeding study) was not high enough to fully characterize the compound's
carcinogenic potential.
The study was repeated at dose levels of 0 and 2,500 ppm (125 mg/
kg/day) in the diet, which approaches the MTD, in order to characterize
the carcinogenic potential. At 2,500 ppm the observed effects included:
decreases in absolute and relative testes weights, increases in the
incidences of centrilobular to midzonal hepatocellular enlargement and
vacuolation in the liver of both sexes, increases in bilateral
aspermatogenesis in the testes, increases in the incidence of
hypospermia and cellular debris in the epididymides, and increased
incidence of arteritis/periarteritis in the testes. In this study, a
NOEL could not be established because there were effects at the only
dose level tested. Myclobutanil was not oncogenic when tested under the
conditions of the study.
3. A 2-year carcinogenicity study in mice using dietary
concentrations of 0, 20, 100, and 500 ppm (equivalent to 0, 2.7, 13.7,
and 70.2 mg/kg/day in males and 0, 3.2, 16.5, and 85.2 mg/kg/day in
females). The NOEL for chronic effects other than carcinogenicity was
20 ppm (2.7 mg/kg/day in males and 3.2 mg/kg/day in females). The LOEL
was 100 ppm (13.7 mg/kg/day in males and 16.5 mg/kg/day in females)
based on a slight increase in liver mixed-function oxidase (MFO).
Microscopic changes in the liver were evident in both sexes at 500 ppm
(70.2 mg/kg/day in males and 85.2 mg/kg/day in females). There were no
carcinogenic effects in either sex at any dose level tested. The
highest selected dose was satisfactory for evaluating carcinogenic
potential in male mice but was lower than the MTD in females.
The above study was reevaluated since the increase in the MFO at 3
months in females was not considered to be significant enough to
establish an LOEL. The LOEL was raised to 500 ppm (70.2 mg/kg/day for
males and 85.2 mg/kg/day for females) based on increases in MFO in both
sexes, increases in SGPT values in females and in absolute and relative
liver weights in both sexes at 3 months, increased incidences and
severity of centrilobular hepatocytic hypertrophy, Kupffer cell
pigmentation, periportal punctate vacuolation and individual
hepatocellular necrosis in males, and increased incidences of focal
hepatocellular alteration and multifocal hepatocellular vacuolation in
both sexes. The NOEL has been raised to 100 ppm (13.7 mg/kg/day for
males and 16.5 mg/kg/day for females).
An 18-month study was conducted with female mice using a dose level
of 2,000 ppm, which approaches the MTD, to evaluate the carcinogenic
potential in female mice. In this study, a NOEL could not be
established because there were effects at the only dose level tested.
These effects included: decreases in body weight and body weight gain,
increases in liver weights, [[Page 21730]] hepatocellular hypertrophy,
hepatocellular vacuolation, necrosis of single hypertrophied
hepatocytes, yellow-brown pigment in the Kupffer cells and cytoplasmic
eosinophilia and hypertrophy of the cells of the zona fasciculata area
of the adrenal cortex. Myclobutanil was not oncogenic when tested under
the conditions of the study.
4. A rabbit developmental toxicity study at dosages of 0, 20, 60,
and 200 mg/kg/day administered by oral gavage. The LOEL for maternal
toxicity was 200 mg/kg/day, and the maternal toxicity NOEL was 60 mg/
kg/day based on reduced body weight and body weight gain during the
dosing period, clinical signs of toxicity, and possibly abortions. The
LOEL for developmental toxicity is 200 mg/kg/day, and the NOEL for
developmental toxicity is 60 mg/kg/day based on increases in
resorptions, decreases in litter size, and a decrease in the viability
index.
5. A developmental toxicity study on rats treated with dosages of
0, 31.26, 93.77, 312.58, and 468.87 mg/kg/day. The maternal toxicity
LOEL was 312.6 mg/kg/day, and maternal toxicity NOEL was 93.8 mg/kg/day
based on clinical signs of toxicity. The developmental toxicity LOEL
was 312.6 mg/kg/day, and the developmental toxicity NOEL was 93.8 mg/
kg/day based on increased incidences of 14th rudimentary and 7th
cervical ribs.
6. A two-generation rat reproduction study with dosage rates of 0,
50, 200, and 1,000 ppm (equivalent to 0, 2.5, 10, and 50 mg/kg/day).
The parental (systemic) toxicity LOEL was 200 ppm (10 mg/kg/day), and
the parental (systemic) toxicity NOEL was 50 ppm (2.5 mg/kg/day) based
on hepatocellular hypertrophy and increases in liver weights. The
reproductive toxicity LOEL was 1,000 ppm (50 mg/kg/day) and
reproductive toxicity NOEL was 200 ppm (10 mg/kg/day) based on an
increased incidence in the number of stillborns and atrophy of the
testes and prostate. The developmental toxicity LOEL was 1,000 ppm (50
mg/kg/day) and the developmental toxicity NOEL was 200 ppm (10 mg/kg/
day) based on a decrease in pup body weight gain during lactation.
7. A reverse mutation assay (Ames), point mutation in CHO/HGPRT
cells, in vitro and in vivo (mouse) cytogenetic assays, unscheduled DNA
synthesis, and a dominant-lethal study in rats, all of which were
negative for mutagenic effects.
The Reference Dose (RfD) based on the 2-year rat chronic feeding
study (NOEL of 2.49 mg/kg bwt/day) and using a hundredfold uncertainty
factor, is calculated to be 0.025 mg/kg bwt/day. The theoretical
maximum residue contribution (TMRC) from previously established
tolerances and the tolerance established here is 0.002075 mg/kg bwt/day
for the general population and utilizes 8% of the RfD. The percentage
of the RfD for the most highly exposed subgroup, nonnursing infants
(less than 1 year old) is 49%. The TMRC was calculated based on the
assumption that myclobutanil occurs at the maximum legal limit in the
dietary commodity for which a tolerance is proposed. Even with this
probable large overestimate of exposure/risk, the TMRC is well below
the RfD for the population as a whole and for each of the 22 subgroups
considered. Thus, the dietary risk from exposure to myclobutanil
appears to be minimal for the use on cottonseed.
The nature of the residues is adequately understood, and adequate
analytical methodology is available for enforcement. Prior to their
publication in the Pesticide Analytical Manual, Vol. II, the
enforcement methodology is being made available in the interim to
anyone who is interested in pesticide enforcement when requested from:
Calvin Furlow, Public Information Branch, Field Operations Division
(7505C), 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.
The pesticide is considered useful for the purpose for which the
tolerance is sought. 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 tolerances are
established as set forth below. By way of public reminder, this
document also reiterates the registrant's responsibility under section
6(a)(2) of FIFRA, to submit additional factual information regarding
adverse effects on the environment and to human health by these
pesticides.
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 issues(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 4F4317/R2125] (including any objections and requests for
hearings 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 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.
Written objections and requests for hearings, identified by the
document control number [4F4317/R2125], may be submitted to the Hearing
Clerk (1900), Environmental Protection Agency, Rm. 3708, 401 M St.,
SW., Washington, DC 20460.
A copy of electronic objections and requests for hearings can be
sent directly to EPA at:
opp-Docket@epamail.epa.gov
A copy of electronic objections and requests for hearings 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 any copies of objections and requests for hearings
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 [[Page 21731]] 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 (58 FR 51735, Oct. 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 requirements.
Dated: March 30, 1995.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
Therefore, chapter I of the title 40 of the Code of Federal
Regulations is amended as follows:
PART 180--[AMENDED]
1. In part 180:
The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 346a and 371.
2. In Sec. 180.443(a), by amending the table therein by adding and
alphabetically inserting an entry for cottonseed, to read as follows:
Sec. 180.443 Myclobutanil; tolerances for residues.
(a) * * *
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Parts per
Commodity million
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* * * * *
Cottonseed................................................. 0.02
* * * * *
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* * * * *
[FR Doc. 95-10862 Filed 5-2-95; 8:45 am]
BILLING CODE 6560-50-F
