[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: [email protected].

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:

------------------------------------------------------------------------
                                                              Parts per 
                         Commodity                             million  
------------------------------------------------------------------------
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