[Federal Register Volume 60, Number 31 (Wednesday, February 15, 1995)]
[Proposed Rules]
[Pages 8612-8615]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-3386]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 0E3882 and PP 4E4286/P598; FRL-4932-3]
RIN 2070-AC18
Pesticide Tolerances for Metolachlor
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA proposes to establish tolerances for the combined residues
of the herbicide metolachlor and its metabolites in or on the raw
agricultural commodities celery and dry bulb onion. [[Page 8613]] The
proposed regulation to establish maximum permissible levels for
residues of the herbicide was requested in petitions submitted by the
Interregional Research Project No. 4 (IR-4).
DATES: Comments, identified by the document control number, [PP 0E3882
and PP 4E4286/P598], must be received on or before March 17, 1995.
ADDRESSES: By mail, submit written comments 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 comments to: Rm. 1132, CM #2,
1921 Jefferson Davis Hwy., Arlington, VA 22202.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). Information so marked will
not be disclosed except in accordance with procedures set forth in 40
CFR part 2. A copy of the comment that does not contain CBI must be
submitted for inclusion in the public record. Information not marked
confidential may be disclosed publicly by EPA without prior notice. All
written comments will be available for public inspection in Rm. 1132 at
the address given above, from 8 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Hoyt L. Jamerson,
Registration Division (7505W), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location and telephone number: Sixth Floor, Crystal Station #1,
2800 Jefferson Davis Hwy., Arlington, VA 22202, (703)-308-8783.
SUPPLEMENTARY INFORMATION: The Interregional Research Project No. 4
(IR-4), New Jersey Agricultural Experiment Station, P.O. Box 231,
Rutgers University, New Brunswick, NJ 08903, has submitted pesticide
petition (PP) 0E3882 and PP 4E4286 to EPA on behalf of the named
Agricultural Experiment Stations. These petitions request that the
Administrator, pursuant to section 408(e) of the Federal Food, Drug,
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e), amend 40 CFR 180.368 by
establishing tolerances for combined residues (free and bound) of the
herbicide metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2methoxy-
1-methylethyl)acetamide], and its metabolites, determined as the
derivatives, 2-[(2-ethyl-6-methylphenyl)amino]-1-propanol, and 4-(2-
ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholinone, each expressed
as the parent compound in or on certain raw agricultural commodities as
follows:
1. PP 0E3882. Petition submitted on behalf of the Experimental
Stations of California, Florida, and Texas proposing a tolerance for
celery at 0.1 part per million (ppm).
2. PP 4E4286. Petition submitted on behalf of the Experimental
Stations of Arkansas, Michigan, New Jersey, New York, Oklahoma, and
Texas proposing a tolerance for dry bulb onion at 1.0 ppm. The
petitioner proposed that use of metolachlor on dry bulb onion be
limited to onion production areas east of the Rocky Mountains based on
the geographical representation of the residue data submitted.
Additional residue data will be required to expand the area of usage.
Persons seeking geographically broader registration should contact the
Agency's Registration Division at the address provided above.
The scientific data submitted in the petition and other relevant
material have been evaluated. The toxicological data considered in
support of the proposed tolerance include:
1. A 1-year feeding study with dogs fed diets containing 0, 100,
300, or 1,000 ppm with a systemic no-observed-effect-level (NOEL) of
300 ppm (9.7 mg/kg/day) based on decreased body weight in females.
2. A 2-year feeding/carcinogenicity study with rats fed diets
containing 0, 30, 300, 1,000 or 3,000 ppm (equivalent to 0, 1.5, 15,
50, or 150 mg/kg/day) with a compound-related increase in liver
adenomas and combined adenomas/carcinomas in female rats at the high-
dose level. This study was classified as supplemental data due to
inadequate clinical chemistry determinations and dietary preparation
records.
3. A 2-year feeding/carcinogenicity study with rats fed diets
containing 0, 30, 300, or 3,000 ppm (equivalent to 0, 1.5, 15, or 150
mg/kg/day) with a systemic NOEL of 300 ppm based on decreased body
weight at the 3,000-ppm dose level. A statistically significant
increase in liver neoplasia was found in female rats at the 3,000-ppm
dose level, as well as evidence for a neoplastic response in the nasal
turbinates of both sexes.
4. A 2-year carcinogenicity study in mice fed diets containing 0,
300, 1,000 and 3,000 ppm (highest dose level equivalent to 428 mg/kg/
day) with no treatment-related carcinogenic effects observed under the
conditions of the study.
5. A second 2-year carcinogenicity study in mice fed diets
containing 0, 300, 1,000, or 3,000 ppm with no treatment-related
carcinogenic effects observed under the conditions of the study.
6. A two-generation reproduction study in rats fed diets containing
0, 30, 300, or 1,000 ppm with a reproductive NOEL of 300 ppm
(equivalent to 23.5-26 mg/kg/day) based on reduced pup weights in the
F1a and F2a litters at the 1,000-ppm dose level (equivalent to 75.8 to
85.7 mg/kg/day). The NOEL for parental toxicity is equal to or greater
than the 1,000-ppm dose level.
7. A developmental toxicity study in rabbits given gavage doses at
0, 36, 120, or 360 mg/kg/day on gestation days 6 to 18. The NOEL for
maternal toxicity was established at 120 mg/kg/day based on
lacrimation, miosis, reduced food consumption, and body weight gain.
There was no developmental toxicity observed under the conditions of
the study.
8. A developmental toxicity study in rats given gavage doses of 0,
60, 180, or 360 mg/kg/day on gestation days 6 to 15. There were no
signs of maternal or developmental toxicity observed under the
conditions of the study.
9. A second developmental toxicity study in rats given gavage doses
of 0, 30, 100, 300, or 1,000 mg/kg/day on gestation days 6 to 15. The
NOEL's for maternal and developmental toxicity were established at 300
mg/kg/day. The NOEL for maternal toxicity was based on deaths,
salivation, lacrimation, convulsions, reduced body weight, and food
consumption at the 1,000-mg/kg/day dose level. The NOEL for
developmental toxicity was based on reduced mean fetal body weight,
reduced number of implantations/dam with resulting decreased litter
size, and a slight increase in resorptions/dam with resulting increase
in post-implantation loss.
10. Metolachlor was not found to be mutagenic in any tests.
Mutagenicity data include gene mutation assays in Salmonella and mouse
lymphoma cells; structural chromosome aberration tests including an in
vivo micronucleus assay in Chinese hamsters and a dominant lethal assay
in mice; and other genotoxic activity tests including DNA damage/repair
assays in rat hepatocytes and in human fibroblasts, and an in vivo/in
vitro unscheduled DNA synthesis assay.
11. Several metabolism studies have been performed with
metolachlor, and the available data indicate the compound is readily
absorbed after oral dosing and excreted in approximately equal amounts
in urine and feces. [[Page 8614]]
Metolachlor was evaluated by the Office of Pesticide Programs' Peer
Review Committee in 1991 and classified as a Group C (possible
carcinogen) with a recommendation for the quantification of estimated
potential human risk using a linearized low-dose extrapolation
(Q*). This recommendation was based on the finding of liver tumors
in female rats at the 3,000-ppm dose level in both rat studies and the
apparent induction of a small number of nasal turbinate tumors in both
sexes of rats at the 3,000-ppm dose level. Nasal turbinate tumors have
also been associated with dietary administration of acetochlor and
alachlor, structurally related herbicides that are classified as Group
B2 carcinogens (probable human carcinogens).
The Peer Review Committee's decision was presented to the FIFRA
Scientific Advisory Panel on September 18, 1991. The Panel concluded
that liver tumors were benign and hyperplasia was evident in rats of
both sexes. The Panel also concluded that the occurrence of nasal
turbinate tumors in rats was low and not statistically significant, but
of concern since metolachlor is structurally related to acetochlor and
alachlor. The Panel considered the carcinogenicity evidence to be
minimal but sufficient for the classification of metolachlor as a Group
C carcinogen.
The Office of Pesticide Programs' Health Effect Division
Carcinogenicity Peer Review Committee met on July 27, 1994, to
revaluate the weight-of-the-evidence on metolachlor, with particular
reference to its carcinogenicity, based on newly submitted metabolism
and mutagenicity studies. The registrant submitted data to show that
the metabolism of metolachlor is substantially different from the
metabolism of acetochlor and alachlor. Metolachlor does not metabolize
to form a reactive quinone imine, which is presumed to be the
carcinogenic metabolite of acetochlor and alachlor. There was also no
evidence for mutagenic potential of metolachlor. Based on these data
and in consideration of the full weight-of-the-evidence, the
Carcinogenicity Peer Review Committee concluded that the classification
of metolachlor should remain as a Group C carcinogen, but recommended
that the RfD approach should be used for quantification of human risk.
A NOEL of 15 mg/kg/day from the 2-year rat feeding study was
determined to be appropriate for use in the Margin of Exposure
carcinogenic risk assessment. The chronic reference dose (RfD) is
currently based on a systemic NOEL of 9.7 mg/kg/day from the 1-year
feeding study in dogs, and any cancer concerns from chronic exposure
are already addressed by the lower NOEL, which is the basis for the
current RfD.
The Reference Dose (RfD) is established at 0.1 mg/kg of body weight
(bwt)/day, based on a NOEL of 9.7 mg/kg/day and an uncertainty factor
of 100. Available information on anticipated residues and/or percent of
crop treated were used to estimate the Anticipated Residue Contribution
(ARC) from residues of metolachlor in the human diet. The ARC from
established tolerances and the proposed tolerances for celery and
onions is estimated at 0.0006 mg/kg bwt/day and utilizes 0.6 percent of
the RfD for the U.S. population. The ARC for non-nursing infants (the
subgroup most highly exposed) utilizes 2 percent of the RfD. EPA
believes these uses of metolachlor pose a negligible cancer risk to
humans.
An adequate analytical method, gas chromatography, is available for
enforcement purposes. The analytical method for enforcing this
tolerance has been published in the Pesticide Analytical Manual, Vol.
II (PAM II). The nature of the residue in plants is adequately
understood. 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
would protect the public health. Therefore, it is proposed that the
tolerances be established as set forth below.
Any person who has registered or submitted an application for
registration of a pesticide, under the Federal Insecticide, Fungicide,
and Rodenticide Act (FIFRA) as amended, which contains any of the
ingredients listed herein, may request within 30 days after publication
of this notice in the Federal Register that this rulemaking proposal be
referred to an Advisory Committee in accordance with section 408(e) of
the FFDCA.
Interested persons are invited to submit written comments on the
proposed regulation. Comments must bear a notation indicating the
document control number, [PP 0E3882 and PP 4E4286/P597]. All written
comments filed in response to these petitions will be available in the
Public Response and Program Resources Branch, at the address given
above from 8 a.m. to 4 p.m., Monday through Friday, except legal
holidays.
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: January 30, 1995.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR part 180 be 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.
[[Page 8615]] 2. In Sec. 180.368, paragraph (a) is amended by
adding and alphabetically inserting the entry for celery, and paragraph
(c) is amended by adding and alphabetically inserting the entry for
onion (dry bulb), to read as follows:
Sec. 180.368 Metolachlor; tolerances for residues.
(a) * * *
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Parts per
Commodity million
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* * * * *
Celery..................................................... 0.1
* * * * *
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* * * * *
(c) * * *
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Parts per
Commodity million
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Onion (dry bulb)........................................... 1.0
* * * * *
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[FR Doc. 95-3386 Filed 2-14-95; 8:45 am]
BILLING CODE 6560-50-F
