[Federal Register Volume 60, Number 70 (Wednesday, April 12, 1995)]
[Proposed Rules]
[Pages 18555-18557]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-8728]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 2E4051/P608; FRL-4943-1]
RIN 2070-AC18
Difenoconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA proposes to establish import tolerances for residues of
the fungicide difenoconazole in or on the raw agricultural commodities
barley grain, rye grain, and wheat grain at 0.1 part per million; fat,
meat, and meat byproducts of cattle, goats, hogs, horses, poultry, and
sheep and eggs at 0.05 ppm; and milk at 0.01 ppm. Ciba-Geigy Corp.
requested the proposed regulation to establish a maximum permissible
level of the fungicide in or on the commodities.
DATES: Comments, identified by the document control number, [PP 2E4051/
P608], must be received on or before May 12, 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 Highway, Arlington, VA 22202. Information
submitted as a comment concerning this notice 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: Cynthia Giles-Parker, Product
Manager (PM) 22, Registration Division, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. Office location and
telephone number: Rm. 229, CM #2, 1921 Jefferson Davis Hwy., Arlington,
VA 22202, (703)-305-5540; e-mail: giles-parker.cynthia@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA is proposing to establish import
tolerances for residues of the fungicide difenoconazole, [(2S,4R)/
(2R,4S)]/[(2R,4R/2S,4S)] 1-(2-[4-(4-chlorophenoxy)-2-chlorophenyl]-4-
methyl-1,3-dioxolan-2-yl-methyl)-1H-1,2,4-triazole, in or on the raw
agricultural commodities (RACs) barley grain, rye grain, and wheat
grain at 0.1 ppm; fat, meat, and meat byproducts (mbyp) of cattle,
goats, hogs, horses, poultry, and sheep and eggs at 0.05 ppm; and milk
at 0.01 ppm. The proposed regulation to establish a maximum permissible
level of the fungicide in or on this commodity was requested in a
pesticide petition (PP 2E4051) submitted by Ciba-Geigy Corp., P.O. Box
18300, Greensboro, NC 27419-8300, that requested 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 180.475 by
establishing import tolerances for residues of the fungicide.
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 rat acute oral study with an LD50 of 1,453 milligrams
(mg)/kilogram (kg).
2. A 13-week rat feeding study with a no-observed-effect-level
(NOEL) of 20 ppm (1 mg/kg/day).
3. A 13-week mouse feeding study with a NOEL of 20 ppm (3.6 mg/kg/
day).
4. A 26-week dog feeding study with a NOEL of 1,000 ppm (3.3 mg/kg/
day).
5. A 21-day rabbit dermal study with a NOEL of 10 mg/kg and
reduction in body weight gain and food consumption from exposure to
doses equal to or greater than 100 mg/kg.
6. A carcinogenicity study in mice with a NOEL of 30 ppm (5 mg/kg/
day) and a lowest-effect-level (LEL) of 300 ppm (50 mg/kg/day) owing to
reductions in cumulative body weights. There was limited evidence of
carcinogenicity based on the occurrence of increased benign and/or
malignant liver tumors in males and females. The carcinogenic effects
observed are discussed below. [[Page 18556]]
7. A rat chronic feeding/carcinogenicity study with a NOEL of 20
ppm (1 mg/kg/day) for systemic effects and a LEL of 500 ppm (25 mg/kg/
day) owing to reductions in cumulative body weight gains and
hepatotoxicity in males. There was no evidence of carcinogenicity under
conditions of the study.
8. A 1-year dog chronic feeding study with a NOEL of 100 ppm (3.5
mg/kg/day); the LEL was 500 ppm (18 mg/kg/day) owing to reduction in
food consumption and increase in alkaline phosphatase in males at high
dose.
9. A two generation reproduction study in rats with a parental and
reproductive NOEL of 25 ppm (1.25 mg/kg/day) and an LEL of 250 ppm
(12.5 mg/kg/day) owing to reduction of female body weight gain and
significant reductions in male pup weight at day 21.
10. A developmental toxicity study in rabbits with a maternal NOEL
of 25 mg/kg and an LEL of 75 mg/kg/day owing to decreased body weight,
death of one doe and abortion, and a developmental NOEL of 25 mg/kg,
and an LEL of 75 mg/kg owing to increased postimplantation loss and
resorptions and significantly decreased fetal weight.
11. A developmental toxicity study in rats with a maternal NOEL of
16 mg/kg and an LEL of 85 mg/kg owing to excess salivation, and
decreased body weight gain and food consumption, and a developmental
NOEL of 85 mg/kg/day, and an LEL of 171 mg/kg owing to increase bifid
or unilateral ossification of thoracic vertebrate, increased average
number of ossified hyoid, and decrease in average number of sternal
centers of ossification.
12. A microbial gene mutation study and an unscheduled DNA
synthesis in rat hepatocyte study were both negative. An in vivo
micronucleus assay/ chromosomal analysis study showed no increase in
micronucleated polychromatic erythrocytes at any dose tested.
13. A rat metabolism study showed that difenoconazole was
adequately absorbed and mainly eliminated via the bile. No evidence of
bioaccumulation in any tissue was noted.
The Health Effects Division, Carcinogenicity Peer Review Committee,
has concluded that the available data provide limited evidence of the
carcinogenicity of difenoconazole in mice and has classified
difenoconazole as a Group C (possible human carcinogen with limited
evidence of carcinogenicity in animals) in accordance with Agency
guidelines, published in the Federal Register in 1986 (51 FR 33992;
Sept. 24, 1986) and recommended that quantitative risk assessment is
not appropriate for the following reasons:
1. The carcinogenic response observed with this chemical,
statistically significant increases in hepatocellular adenomas,
carcinomas, and combined adenomas/carcinomas in both sexes of CD-1
mice, occurred only at doses considered to be excessively high for
carcinogenicity testing.
2. There were no apparent tumor increases in either sex in Sprague-
Dawley rats at dietary levels up to 2,500 ppm.
3. Difenoconazole was not mutagenic in three well conducted
genotoxic assays.
Based on this evidence, EPA concludes that difenoconazole poses at
most a negligible cancer risk to humans and that for purposes of risk
characterization the Reference Dose (RfD) and Margin of Exposure (MOE)
approaches should be use for quantification of human risk. In a spring
wheat processing study, no residues were detected in grain or any
processed fraction. Therefore, food/feed additive tolerances are not
needed in conjunction with this use on barley, rye, and wheat.
Using a 100-fold safety factor and the NOEL of 1 mg/kg/day
determined from the rat chronic feeding study (the most sensitive
species), the Reference Dose RfD is 0.01 mg/kg/day. The theoretical
maximum residue contribution (TMRC) from the established and proposed
tolerances is 0.00042 mg/kg/day and utilizes 4 percent of the RfD for
the overall U.S. population. For exposure of the most highly exposed
subgroups in the population, children (ages 1 to 6 years old) and
nonnursing infants (less than 1 year old), the TMRC is 0.000947 mg/kg/
day and 0.000960 mg/kg/day and utilizes 9 and 10 percent of the RfD,
respectively.
The dietary acute exposure MOE for developmental toxicity effects
was calculated to be 62,500 for high exposure in the females 13+
subgroup. For substances whose acute NOEL is based on animal studies,
the Agency is not generally concerned unless the MOE is below 100.
The metabolism of difenoconazole in plants is adequately
understood. The tolerances established for milk, eggs, meat, fat, and
meat byproducts will cover any dietary exposure from secondary residues
in these RACs. There are currently no actions pending against the
continued registration of this chemical.
An adequate analytical method, gas chromatography with nitrogen
phosphorous detection, is available for enforcement purposes. Because
of the long lead time from establishing these tolerances to publication
of the enforcement methodology in the Pesticide Analytical Manual, Vol.
II, the analytical methodology is being made available in the interim
to anyone interested in pesticide enforcement when requested from:
Calvin Furlow, Public Information 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. 242, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202,
(703-305-4432).
Based on the information and data considered, the Agency has
determined that the tolerance established by amending 40 CFR part 180
would protect the public health. Therefore, it is proposed that the
tolerance 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 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 2E4051/P608]. 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 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 [[Page 18557]] 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 28, 1995.
James J. Jones,
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. 180.475, by adding new paragraph (c), to read as
follows:
Sec. 180.475 Difenoconazole; tolerances for residues.
* * * * *
(c) Tolerances are established for difenoconazole, [(2S,4R)/
(2R,4S)]/[(2R,4R/2S,4S)] 1-(2-[4-(4-chlorophenoxy)-2-chlorophenyl]-4-
methyl-1,3-dioxolan-2-yl-methyl)-1H-1,2,4-triazole, in or on the
following raw agricultural commodities:
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Parts per
Commodity million
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Barley, grain\1\........................................... 0.1
Cattle, fat................................................ 0.05
Cattle, meat............................................... 0.05
Cattle, mbyp............................................... 0.05
Eggs....................................................... 0.05
Goats, fat................................................. 0.05
Goats, meat................................................ 0.05
Goats, mbyp................................................ 0.05
Hogs, fat.................................................. 0.05
Hogs, mbyp................................................. 0.05
Horses, fat................................................ 0.05
Horses, meat............................................... 0.05
Horses, mbyp............................................... 0.05
Milk....................................................... 0.01
Poultry, fat............................................... 0.05
Poultry, meat.............................................. 0.05
Poultry, mbyp.............................................. 0.05
Rye, grain\1\.............................................. 0.1
Sheep, fat................................................. 0.05
Sheep, meat................................................ 0.05
Sheep, mbyp................................................ 0.05
Wheat, grain............................................... 0.1
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\1\ There are no U.S. registrations as of April 12, 1995 for use on
barley and rye.
[FR Doc. 95-8728 Filed 4-11-95; 8:45 am]
BILLING CODE 6560-50-F
