[Federal Register Volume 60, Number 244 (Wednesday, December 20, 1995)]
[Rules and Regulations]
[Pages 65578-65581]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-30976]
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[[Page 65579]]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 2F4105/R2191; FRL-4989-2]
RIN 2070-AB78
Metalaxyl; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes tolerances for combined residues of the
fungicide metalaxyl [N-(2,6-dimethylphenyl)-N-(methoxyacetyl) alanine
methyl ester] and its metabolites containing the 2,6-dimethylaniline
moiety and N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)-alanine
methyl ester, each expressed as metalaxyl, in or on clover, forage at
1.0 part per million (ppm) and clover, hay at 2.5 ppm. Ciba-Geigy 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 rule is effective on December 4, 1995.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 2F4105/R2191], 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 2F4105/R2191]. 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:
[email protected]
SUPPLEMENTARY INFORMATION: EPA issued a notice of filing, published in
the Federal Register of June 15, 1995 (60 FR 31465), which announced
that Ciba-Geigy Corp., P.O. Box 18300, Greensboro, NC 27419, had
submitted a pesticide petition, PP 2F4105, to EPA requesting that the
Administrator, pursuant to section 408(d) of the FFDCA, 21 U.S.C.
346a(d), establish tolerances for combined residues of the fungicide
metalaxyl [N-(2,6-dimethylphenyl)-N-(methoxyacetyl) alanine methyl
ester] and its metabolites containing the 2,6-dimethylaniline moiety
and N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl
ester, each expressed as metalaxyl, in or on the raw agricultural
commmodities cover, forage at 1.0 ppm and clover, hay at 2.5 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 3-month dietary study in rats with a no-observed-effect level
(NOEL) at 17.5 milligrams per kilogram (mg/kg) body weight (bwt)/day
(250 parts per million (ppm)).
2. A developmental toxicity study in rats with a NOEL of 50 mg/kg
bwt for developmental toxicity and maternal toxicity.
3. A developmental toxicity study in rabbits with a NOEL of 300 mg/
kg bwt highest dose tested (HDT). Metalaxyl did not cause developmental
toxicity, even in the presence of maternal toxicity.
4. Metalaxyl was negative in bacterial and mammalian gene mutation.
The fungicide also did not increase the frequency of reverse mutations
in yeast. Metalaxyl was negative in an in vivo cytogenetics assay
(hamsters) and a dominant-lethal assay (mice).
Metalaxyl did not increase unscheduled DNA synthesis in rat primary
hepatocytes or in human fibroblasts. These results suggest that
metalaxyl is not genotoxic.
5. A three-generation rat reproduction study with a NOEL of 63 mg/
kg bwt/day (1,250 ppm).
6. A 6-month dog feeding study with a NOEL of 6.3 mg/kg bwt/day
(250 ppm). Effects found at 25 mg/kg were increased serum alkaline
phosphatase activity and increased liver weight and liver-to-brain
weight ratios without histological changes.
7. A 2-year rat chronic feeding/carcinogenicity study with no
compound-related carcinogenic effects under the conditions of the study
at dietary levels up to 1,250 ppm. The NOEL is 13 mg/kg bwt/day (250
ppm). The lowest-observed-effect level (LOEL) is 63 mg/kg/day based
upon slight increases in liver weight to body weight ratios and
periacinar vacuolation of hepatocytes.
8. A 2-year mouse oncogenic study with no compound-related
carcinogenic effects under the conditions of the study at dietary
levels up to 190 mg/kg/day.
Because of concerns raised over some equivocal increases in tumor
incidences in the male mouse liver and the male rat adrenal medulla,
and the female rat thyroid, the two chronic feeding studies were
submitted to the Environmental Pathology Laboratories (EPL) for an
independent reading of the microscopic slides. The new pathological
evaluation by EPL and the original reports of the rat and mouse
oncogenicity studies were then both submitted for review to EPA's
Carcinogen Assessment Group (CAG). A final review of the
carcinogenicity studies and related material was performed by the Peer
Review Committee of the Toxicology Branch (TB) of the Office of
Pesticide Programs (OPP).
The four major issues evaluated by CAG and the peer review group
included: (1) Perifollicular cell adenomas in the thyroid of female
rats; (2) adrenal medullary tumors (pheochromocytomas) in male rats;
(3) liver tumors in male mice; and (4) whether the HDT (1,250 ppm) in
the rat and mouse oncogenicity studies represented a maximum-tolerated
dose (MTD).
Regarding the thyroid tumors in female rats, the peer review group
concluded that the increased incidences of thyroid tumors in females of
treated groups were not compound related. This
[[Page 65580]]
conclusion was based on the following: (1) There was no progression of
benign tumors (adenomas) to malignancy (carcinomas); (2) there was no
increase in hyperplastic changes; (3) there was no dose-response
relationship; and (4) the two reevaluations of the microscopic slides
by the pathologists at EPL and TB in OPP further did not confirm any
apparent effects observed in the original report.
The issue of a possible treatment-related increase of adrenal
medullary gland tumors, namely, pheochromocytomas, in the male rat was
also reassessed by both CAG and the Peer Review Committee. Both
concluded that the data, especially in view of the reevaluation of the
microscopic slides performed by EPL, did not support a compound-related
increase of adrenal medullary tumors; the incidence of
pheochromocytomas more accurately represented spontaneous variations of
a commonly occurring tumor in the aged rat.
The analysis of the significance of the equivocal increase in the
incidence of liver tumors in male mice was very similar to that
performed for the rat thyroid and adrenal gland tumors. The original
pathological reading of the tissue slides reported an elevated increase
of tumors in some treatment groups; however, these increases were not
evident after a reevaluation of themicroscopic slides was performed by
an independent pathologist at EPL and by the reading of a CAG
pathologist. The Peer Review Committee concurred that the reevaluation
of the slides is reliable and does not show any compound-related
increase in the incidence of liver tumors in the mouse.
The Agency believes that the data from the rat and mouse long-term
studies are sufficient to support the conclusion that metalaxyl does
not show a carcinogenic potential in laboratory animals. This
conclusion is supported by the following: (1) The doses tested in both
the rat and mouse long-term studies approached an MTD based upon
compound-related changes in liver weight and/or liver histology; (2)
extensive available mutagenic evidence indicates no potential genotoxic
activity which correlates with the negative carcinogenic potential
demonstrated in long-term testing; (3) metalaxyl is not structurally
related to known carcinogens; and (4) under the conditions of the rat
and mouse tests, no indication of compound-related carcinogenic effects
was noted at any of the treatment doses, sexes, or species.
The reference dose (RfD), anticipated residue contribution (ARC),
and food additive regulations are covered by existing tolerances.
The nature of the residue is adequately understood. 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
Highway, Arlington, VA 22202, (703)-305-5232.
There are presently 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 2F4105/R2191] (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 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 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).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: December 4, 1995.
[[Page 65581]]
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. 180.408(a) by revising the introductory text and by
amending the table therein by adding and alphabetically inserting new
entries for clover, forage and clover, hay, to read as follows:
Sec. 180.408 Metalaxyl; tolerances for residues.
(a) Tolerances are established for the combined residues of the
fungicide metalaxyl [N-(2,6-dmethylphyenyl)-N-(methoxyacetyl) alanine
methylester] and its metabolites containing the 2,6-dimethylaniline
moiety, and N-(2-hydroxy methyl-6-methylphenyl)-N-(methoxyacetyl)-
alanine methyl ester, each expressed as metalaxyl equivalents, in or on
the following raw agricultural commodities:
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Parts per
Commodity million
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* * * * *
Clover, forage............................................. 1.0
Clover, hay................................................ 2.5
* * * * *
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[FR Doc. 95-30976 Filed 12-19-95; 8:45 am]
BILLING CODE 6560-50-F
