[Federal Register Volume 60, Number 80 (Wednesday, April 26, 1995)]
[Proposed Rules]
[Pages 20471-20473]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-10252]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 3E4249/P613; FRL-4949-2]
RIN 2070-AC18
Fenarimol; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA proposes to establish a tolerance for the combined
residues of the fungicide fenarimol in or on the imported raw
agricultural commodity bananas at 0.5 part per million (ppm). Not more
than 0.25 ppm shall be present in the pulp after the peel is removed.
DowElanco petitioned for this regulation to establish a maximum
permissible level for combined residues of the fungicide.
DATES: Comments, identified by the document control number [PP 3E4249/
P613], must be received on or before May 26, 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 a copy of the 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: 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 is proposing to establish an import
tolerance for the combined residues of the fungicide fenarimol, [alpha-
(2-chlorophenyl)-alpha-(4-chlorophenyl)-5-pyrimidinemethanol] and its
metabolites [alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-1,4-dihydro-
5-pyrimidinemethanol and 5-(2-chlorophenyl)-(4-chlorophenyl)methyl]-
3,4-dihydro-4-pyrimidinol measured as the total of fenarimol and 5-[(2-
chlorophenyl)-(4-chlorophenyl)methyl]pyrimidine (calculated as
fenarimol)], in or on the raw agricultural commodity bananas at 0.5
part per million (ppm). Not more than 0.25 ppm shall be present in the
pulp after the peel is removed. The proposed regulation to establish a
maximum permissible level of the fungicide pursuant to section 408(e)
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, by
amending 40 CFR 180.421 to include this commodity was requested in a
pesticide petition, PP 3E4249, submitted by DowElanco, 9002 Purdue Rd.,
Indianapolis, IN 46268-1189. 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 the following:
1. A 1-year dog-feeding study using doses of 0, 1.25, 12.5, and 125
milligrams/kilogram (mg/kg) body weight (bwt)/day. The no-observed-
effects level (NOEL) is 12.5 mg/kg bwt/day. The 125 mg/kg bwt/day dose
level caused increased serum alkaline phosphatase, increased liver
weights, increased p-nitroanisole o-demethylase activity, and mild
hepatic bile stasis.
2. An initial 2-year chronic feeding/oncogenicity study in rats
using dietary concentrations of 0, 50, 130, and 350 ppm (equivalent to
doses of 0, 2.5, 6.5, and 17.5 mg/kg bwt/day). In a Federal Register
document published in the issue of March 5, 1986 (51 FR 7567), the
Agency indicated fenarimol to be oncogenic. In that document, the
Agency's initial conclusion that fenarimol was oncogenic was based on a
finding in the 2-year rat study of a statistically significant increase
in hepatic lesions (adenomas and [[Page 20472]] hyperplastic nodules)
at the highest dose tested (17.5 mg/kg bwt/day), when data for male and
female rats were combined.
Since that time, the compound has been reevaluated. The Agency now
considers it more appropriate to separate data for males and females
and also to separate hyperplastic nodules from tumors (adenomas and
carcinomas). When a reevaluation of the hepatic lesions for males and
females was performed separately with the elimination of hyperplastic
nodules, the data did not demonstrate a statistically significant
increased incidence in adenomas and/or carcinomas in either sex.
Moreover, the mouse oncogenicity study did not demonstrate oncogenic
potential at dose levels up to and including a dose level of 85.7 mg/kg
bwt/day (the highest dose level tested).
Because of the appearance of a low incidence of fatty change of the
liver (nonneoplastic pathological lesions) in the low-dose groups in
this study, it was unclear if a NOEL for fatty change of the liver was
established in this study.
3. Additional 2-year chronic feeding/oncogenicity studies in rats
using dietary concentrations of 0, 12.5, 25, and 50 ppm (equivalent to
doses of 0, 0.63, 1.25, and 2.5 mg/kg bwt/day). The purpose of these
additional studies was to assist in determining a NOEL for fatty liver
changes. The first of these two studies was compromised, however, by an
outbreak of chronic respiratory disease which reduced survival in all
experimental groups, including controls. The study was then repeated
with the same dose levels. In the second study, no fatty liver changes
or oncogenic effects were observed at the doses tested under the
conditions of the study. Using data from all three 2-year studies, a
NOEL for fatty liver change of 6.5 mg/kg bwt/day was established.
4. A 2-year oncogenicity study in mice using dietary concentrations
of 0, 50, 170, and 600 ppm (equivalent to 0, 7, 24.3, and 85.7 mg/kg
bwt/day) that was negative for oncogenic effects at all doses tested
under the conditions of the study. At 600 ppm, an increase in fatty
change of the liver was demonstrated. The NOEL for this effect was 170
ppm (24.3 mg/kg bwt/day).
5. A rabbit teratology study that was negative for teratogenic
effects at all doses tested (0, 5, 10, and 35 mg/kg).
6. A rat teratology study that demonstrated hydronephrosis at 35
mg/kg (doses tested were 0, 5, 13, and 35 mg/kg). A second study in
rats (with a postpartum evaluation) again demonstrated hydronephrosis
at 35 mg/kg, but also indicated that the dose level of 35 mg/kg was
associated with a maternal toxic effect (decreased body weight gain
during treatment). The Agency considers the NOEL for hydronephrosis and
for maternal toxicity to be 13 mg/kg.
7. A multigeneration reproduction study in rats that demonstrated
decreased fertility in males and delayed parturition and dystocia in
females at 5 mg/kg bwt/day. The NOEL for reproductive effects in this
study was 2.5 mg/kg bwt/day.
8. Multigeneration reproduction studies in guinea pigs and mice
that were negative for reproductive effects at doses up to 35 mg/kg
bwt/day (highest dose tested) and 20 mg/kg bwt/day, respectively.
9. An aromatase inhibition study in rats that showed fenarimol to
be a moderately weak inhibitor of aromatase activity.
The adverse reproductive effects observed in the rat
multigeneration reproduction study are considered to be a species-
specific effect caused by aromatase inhibition. This enzyme promotes
normal sexual behavior in rats and mice, but not in guinea pigs,
primates, or man. A NOEL of 35 mg/kg bwt/day for reproductive effects
relevant to humans was established in the multigeneration reproduction
study in guinea pigs.
10. A mouse lymphoma forward mutation assay, a DNA repair synthesis
study in rat liver culture systems, gene mutation assays in Salmonella
typhimurium (Ames test) and Escherichia coli, a dominant-lethal assay
in Wistar rats, an assay for transformation activity in the C3H/10T 1/2
embryonic mouse fibroblast, and an in vivo assay for chromosome
aberration in the Chinese hamster. Fenarimol did not demonstrate
mutagenic activity in any of these studies. Furthermore, fenarimol did
not induce altered foci or neoplastic nodules in an initiation and
promotion study in rat liver tissue.
Based on the above findings, the Agency concluded that fenarimol
was not oncogenic in long-term studies in rats and mice under the test
conditions in which the highest dose tested for both species approached
a maximum-tolerated dose as evidenced by increased fatty change in the
liver.
The acceptable daily intake (ADI) based on the 2-year rat chronic
feeding study (NOEL of 6.5 mg/kg bwt/day) with an uncertainty factor of
100 is calculated to be 0.065 mg/kg bwt/day. The theoretical maximum
residue contribution (TMRC) from previously established tolerances and
the tolerance established here is 0.000431 mg/kg/day for the general
population and utilizes 0.66% of the ADI. The percentage of the ADI for
the most highly exposed subgroup, non-nursing infants (less than 1 year
old), is 2.68%. The TMRC was calculated based on the assumption that
fenarimol occurs at the maximum legal limit in all of the dietary
commodities for which tolerances are proposed. Even with this probable
large overestimate of exposure/risk, the TMRC is well below the ADI for
the population as a whole and for each of the 22 subgroups considered.
Thus, the dietary risk from exposure to fenarimol appears to be
minimal.
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 1128C, 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 notice
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 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 document 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 3E4249/P613]. All written comments filed
in response to this petition will be available in the Public Response
and Program Resources Branch, at the address given above from
[[Page 20473]] 8 a.m. to 4 p.m., Monday through Friday, except legal
holidays.
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 requirements.
Dated: April 17, 1995.
Donald R. Stubbs,
Acting 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.
2. In Sec. 180.421(b) by revising the table therein, to read as
follows:
Sec. 180.421 Fenarimol; tolerances for residues.
* * * * *
(b) * * *
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Commodity Parts per million
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Bananas\1\......................... 0.5 (Not more than 0.25 ppm shall
be present in the pulp after peel
is removed)
Cherries........................... 1.0.
Grapes............................. 0.2.
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\1\There are no United States registrations for bananas as of April 26,
1995.
[FR Doc. 95-10252 Filed 4-21-95; 2:56 pm]
BILLING CODE 6560-50-F
