[Federal Register Volume 60, Number 220 (Wednesday, November 15, 1995)]
[Rules and Regulations]
[Pages 57361-57364]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-28068]



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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180

[PP 2F4072/R2188; FRL-4986-7]
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 equivalents, in or on the raw 
agricultural commodities brassica (cole) leafy vegetables group [except 
broccoli, cabbage, cauliflower, brussels sprouts, and mustard greens] 
at 0.1 part per million (ppm); brussels sprouts at 2.0 ppm; cabbage at 
1.0 ppm; cauliflower at 1.0 ppm; and mustard greens at 5.0 ppm. Ciba-
Geigy Corp. submitted a petition under 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 becomes effective on October 27, 1995.

ADDRESSES:  Written objections and hearing requests, identified by the 
document control number, [PP 2F4072/R2188], 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: [email protected]. 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 2F4072/R2188]. 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 2F4063, 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 equivalents, in or on the raw 
agricultural commodities brassica (cole) leafy vegetables group [except 
broccoli, cabbage, cauliflower, brussels sprouts, and mustard greens] 
at 0.1 part per million (ppm); brussels sprouts at 2.0 ppm; cabbage at 
1.0 ppm; cauliflower at 1.0 ppm; and mustard greens at 5.0 ppm. 

[[Page 57362]]

    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 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.

[[Page 57363]]

    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 2F4072/R2188] (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:
    [email protected]
    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.

[[Page 57364]]

    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: October 27, 1995.

Peter Caulkins,
Acting 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, in paragraph (a) by amending the table therein 
by revising the entries for Brassica (cole) leafy vegetables group, 
cabbage, and cauliflower and by adding new entries for brussels sprouts 
and mustard greens, to read as follows:


Sec. 180.408   Metalaxyl; tolerances for residues.

    (a) *  *  *

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                                                              Parts per 
                         Commodity                             million  
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                  *        *        *        *        *                 
Brassica (cole) leafy vegetables group [except broccoli,                
 cabbage, cauliflower, brussels sprouts, and mustard                    
 greens]...................................................          0.1
Brussels sprouts...........................................          2.0
                                                                        
                  *        *        *        *        *                 
Cabbage....................................................          1.0
                                                                        
                  *        *        *        *        *                 
Cauliflower................................................          1.0
                                                                        
                  *        *        *        *        *                 
Mustard greens.............................................          2.0
                                                                        
                  *        *        *        *        *                 
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[FR Doc. 95-28068 Filed 11-14-95; 8:45 am]
BILLING CODE 6560-50-F