[Federal Register Volume 61, Number 133 (Wednesday, July 10, 1996)]
[Rules and Regulations]
[Pages 36299-36302]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-17576]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4F4321/R2251; FRL-5381-7]
RIN 2070-AB78
Pesticide Tolerance for 1-[[2-(2,4-Dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]methyl]-1H-1,2,4-triazole
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes a tolerance for combined residues of the
fungicide 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-
yl]methyl]-1H-1,2,4-triazole and its metabolites determined as 2,4-
dichlorobenzoic acid and expressed as parent compound in or on the raw
agricultural commodity stonefruit group at 1.0 part per million (ppm).
The regulation to establish a maximum permissible level for residues of
the fungicide was requested in a petition submitted by the Ciba-Geigy
Corp.
EFFECTIVE DATE: This regulation becomes effective July 10, 1996.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 4F4321/R2251], may be submitted to:
Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M
St., SW., Washington, DC 20460. 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. 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.
An electronic copy of objections and hearing requests filed with
the Hearing Clerk may be submitted to OPP by sending electronic mail
(e-mail) to: [email protected]
Copies of electronic objections and hearing requests must be
submitted as an ASCII file avoiding the use of special characters and
any form of encryption. Copies of electronic objections and hearing
requests will also be accepted on disks in WordPerfect 5.1 file format
or ASCII file format. All copies of electronic objections and hearing
requests must be identified by the
[[Page 36300]]
docket number [PP 4F4321/R2251] . No ``Confidential Business
Information'' (CBI) should be submitted through e-mail. Copies of
electronic 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 (FRL-4971-5), published
in the Federal Register of November 15, 1995 (60 FR 57421), which
announced that Ciba-Geigy Corp., P.O. Box 18300, Greensboro, NC 27419
had submitted pesticide petition (PP) 4F4321 to EPA requesting that the
Administrator, pursuant to section 408(d) of the Federal Food, Drug,
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d ), establish a tolerance for
combined residues of the fungicide 1-[[2-(2,4-dichlorophenyl)-4-propyl-
1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole in or on the raw
agricultural commodity stonefruit group at 1.0 ppm part per million
(ppm). 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. Plant and animal metabolism studies.
2. Residue data for crop and livestock commodities.
3. Two enforcement methods and multiresidue method testing data.
4. A 90-day rat feeding study with a no-observable-effect level
(NOEL) of 12 mg/kg/day.
5. A 90-day dog feeding study with a NOEL of 1.25 mg/kg/day.
6. A rabbit developmental toxicity study with a maternal NOEL of
100 mg/kg/day and a developmental toxicity NOEL of greater than 400 mg/
kg/day (highest dose tested) (HDT)).
7. A rat teratology study with a maternal NOEL of 30 mg/kg/day and
a developmental toxicity NOEL of 30 mg/kg/day.
8. A two-generation rat reproduction study with a reproductive NOEL
of 125 mg/kg/day (HDT) and a developmental toxicity NOEL of 25 mg/kg/
day.
9. A 1-year dog feeding study with a NOEL of 1.25 mg/kg/day.
10. A 2-year rat chronic feeding/carcinogenicity study with a NOEL
of 5 mg/kg/day with no carcinogenic potential under the conditions of
the study up to and including approximately 125 mg/kg/day, the highest
dose tested.
11. A 2-year mouse chronic feeding/carcinogenicity study with a
NOEL of 15 mg/kg/day and with a statistically significant increase in
combined adenomas and carcinomas of the liver in male mice at
approximately 375 mg/kg/day, the highest dose tested.
12. Ames test with and without activation, negative.
13. A mouse dominant-lethal assay, negative.
14. Chinese hamster nucleus anomaly, negative.
15. Cell transformation assay, negative.
Ciba-Geigy submitted information which resolved the previously
outstanding concerns about the nature of the residue in ruminants, an
explanation of recovery calculations, and an explanation of the crop
field trial protocol. Data gaps exist concerning dosing in the mouse
carcinogenicity study. These data requirements were required under
reregistration, pursuant to the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA), 7 U.S.C. 136 et seq.
As part of EPA's evaluation of potential human health risks, 1-[[2-
(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-
triazole has been the subject of five Peer Reviews and one Scientific
Advisory Panel (SAP) meeting. 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]methyl]-1H-1,2,4-triazole was originally evaluated by the
Peer Review Committee on January 15, 1987, and classified as a Group C
(possible human) carcinogen with a recommendation made for the
quantification of estimated potential human risk using a linearized
low-dose extrapolation. The method resulted in the establishment of a
Q* of 7.9 x 10-2 (mg/kg/day)-1.
The Peer Review Committee's decision was presented to the FIFRA
Scientific Advisory Panel on March 2, 1988. The Panel did not concur
with the committee's overall assessment of the weight-of-evidence on
the carcinogenicity of 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]methyl]-1H-1,2,4-triazole. The Panel recommended placing
the chemical in Group D, indicating that the Group C classification was
based on minimal evidence. The Panel's determination that EPA's Group C
classification was based on minimal evidence was due to the fact that
the incidence of liver tumors in male mice only occurred when the mice
were given an excessive chemical dose.
As part of a fifth Peer Review, EPA considered additional
information provided by the registrant in support of the registrant's
argument that the high dose was excessively toxic in the mouse
carcinogenicity study. It further argued that the data from the high
dose (2,500 ppm) should not be included in the evaluation of
carcinogenic potential of 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]methyl]-1H-1,2,4-triazole. In support of these arguments,
the registrant provided two subchronic oral toxicity studies in mice.
Ciba-Geigy also provided a reread of the pathology slides from a mouse
oncogenicity study which it felt indicated sufficient concurrent liver
toxicity at 2,500 ppm to document that this dose was excessive. These
findings were not present in the original pathology report. Owing to
the inconsistency in Ciba-Geigy's report and the original report, the
Agency requested that an independent (third) evaluation of the
pathology slides be made to determine if the pathology reported could
be confirmed. The results of this (third) pathology evaluation were
used in the fifth Peer Review in place of data resulting from the
earlier evaluations provided by Ciba-Geigy.
The Peer Review Committee considered the following facts regarding
the toxicology data on 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]methyl]-1H-1,2,4-triazole in a weight-of-evidence
determination of carcinogenic potential:
1. Increased numbers of adenomas (increased trend and pairwise
comparison) were found in the livers of male CD1 mice given 2,500 ppm
of 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-
1,2,4-triazole in their diet.
2. The treated animals had earlier fatalities than the controls.
3. The numbers of carcinomas were increased (trend only) in male
mice only at the 2,500 ppm dose level. Tumors were not significantly
increased at the 500 ppm dose level. Adenomas observed in the treated
animals were larger and more numerous than those in controls; however,
the tumor type (adenoma) was the same.
4. No excessive number of tumors was found in female mice.
5. In a rat study conducted with acceptable doses of 1-[[2-(2,4-
dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole,
no
[[Page 36301]]
excessive numbers of tumors were found.
The Peer Review Committee determined, based on the additional
information submitted by Ciba-Geigy from two 90-day subchronic studies
in mice that the 2,500 ppm dose used in the 2-year chronic study
exceeded the maximum tolerated dose (MTD) based on the endpoint of
hepatic necrosis, and the 500 ppm dose used in the chronic study was
inadequate to assess the carcinogenicity of 1-[[2-(2,4-dichlorophenyl)-
4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole. Based on the
third pathology evaluation of the chronic study, the Peer Review
Committee disagreed with Ciba-Geigy's argument that the study showed
excessive toxicity at the 2,500 ppm dose. However, the Peer Review
Committee concluded that the 90-day subchronic studies are a better
measure of what would be an MTD.
Based upon these findings, the Peer Review Committee agreed that
the classification for 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]methyl]-1H-1,2,4-triazole should remain a Group C
(possible human) carcinogen and recommended against the previously used
Q* (viz. 0.079) for risk assessment purposes. For the purpose of
risk characterization the Peer Review Committee recommended that the
reference dose (RfD) approach should be used for quantification of
human risk. This decision was based on the disqualification of the high
dose (2,500 ppm), making the data inappropriate for the calculation of
Q*. Because the middle dose (500 ppm) was not considered
sufficiently high enough for assessing the carcinogenic potential of 1-
[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-
triazole, EPA has requested an additional mouse study at intermediate
dose levels in male mice only. EPA does not expect that these data will
significantly change the above cancer assessment that 1-[[2-(2,4-
dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole
poses a negligible risk to humans.
The reference dose for 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]methyl]-1H-1,2,4-triazole is 0.013 mg/kg/day, and based
on a NOEL of 1.25 mg/kg/day and an uncertainty factor of 100. The NOEL
is taken from a 1-year dog feeding study that demonstrated irritation
of the stomach in males as an endpoint effect. The Anticipated Residue
Contribution (ARC) from the current action is estimated at 0.000673 mg/
kg/day and utilizes 5 percent of the RfD of the general population of
the 48 states. The ARC for the most highly exposed subgroup, non-
nursing infants < 1 year is 0.002203 mg/kg/day (17 percent of the RfD).
The nature of the residue in plants and animals is adequately
understood and adequate analytical methods (gas chromatography) are
available for enforcement purposes. Adequate animal tissue, milk, and
egg tolerances exist to cover secondary residues incurred in those
commodities from the proposed uses.
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. 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 tolerance is 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).
A record has been established for this rulemaking under the docket
number [PP 4F4321/R2251] (including any comments and data submitted
electronically). 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, excluding legal holidays. The public
record is located in Room 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.
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 any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rule-making record
which will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Viginia address in ``ADDRESSES'' at the beginning of this document.
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)
[[Page 36302]]
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.
This action does not impose any enforceable duty, or contain any
``unfunded mandates'' as described in Title II of the Unfunded Mandates
Reform Act of 1995 (Pub. L. 104-4), or require prior consultation as
specified by Executive Order 12875 (58 FR 58093, October 28, 1993),
entitled Enhancing the Intergovernmental Partnership, or special
consideration as required by Executive Order 12898 (59 FR 7629,
February 16, 1994).
Under 5 U.S.C. 801(a)(1)(A) of the Administrative Procedure Act
(APA) as amended by the Small Business Regulatory Enforcement Fairness
Act of 1996 (Title II of Pub. L. 104-121, 110 Stat. 847), EPA submitted
a report containing this rule and other required information to the
U.S. Senate, the U.S. House of Representatives and the Comptroller
General of the General Accounting Office prior to publication of the
rule in today's Federal Register. This rule is not a ``major rule'' as
defined by 5 U.S.C. 804(2) of the APA as amended.
Pursuant to the requirements of the Regulatory Flexibility Act (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: July 2, 1996.
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. 180.434, the table in paragraph (a) is amended by adding
alphabetically an entry for stonefruit group to read a follows:
Sec. 180.434 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-
yl]methyl]-1H-1,2,4-triazole; tolerances for residues.
* * * * *
(a) * * *
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Parts per
Commodity million
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* * * * *
Stonefruit group........................................... 1.0
* * * * *
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* * * * *
[FR Doc. 96-17576 Filed 7-9-96; 8:45 am]
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