[Federal Register Volume 59, Number 100 (Wednesday, May 25, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-12698]
[[Page Unknown]]
[Federal Register: May 25, 1994]
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DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT
40 CFR Part 180
[PP 8F3654/R2064; FRL-4865-9]
RIN 2070-AB78
Pesticide Tolerances 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 time-limited tolerances (with an
expiration date of December 31, 1998) for the fungicide propiconazole,
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
commodities peanuts at 0.2 part per million (ppm), peanut hay at 20.0
ppm, and peanut hulls at 1.0 ppm. This rule to establish the maximum
permissible levels for residues of propiconazole in or on the
commodities listed above was requested in a petition submitted by the
Ciba-Geigy Corp.
EFFECTIVE DATE: This regulation becomes effective May 13, 1994.
ADDRESSES: Written objections, identified by the document control
number, [PP 8F3654/R2064], may be submitted to: Hearing Clerk (1900),
Environmental Protection Agency, Rm. M3708, 401 M St., SW., Washington,
DC 20460.
FOR FURTHER INFORMATION CONTACT: By mail: Steve Robbins, Acting Product
Manager (PM) 21, Registration Division (7505C), 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.
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of October 12, 1988 (53 FR 39783), which announced
that the Ciba-Geigy Corp., P.O. Box 18300, Greensboro, NC 27419, had
submitted a pesticide petition (PP 8F3654) to EPA requesting that the
Administrator, pursuant to section 408(d) of the Federal Food, Drug,
and Cosmetic Act, 21 U.S.C. 346a(d), propose to amend 40 CFR 180.434 by
establishing tolerances for 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 commodities peanuts at 0.2 ppm, peanut hay at
20.0 ppm, and peanut hulls at 1.0 ppm. The were no adverse comments
received by the Agency in response to the notice of filing.
Because the above notice published more than 5 years ago, it was
republished in the Federal Register of March 30, 1994 (59 FR 14853).
There were no adverse comments received by the Agency in response to
the republication of the notice of filing.
The data submitted in the petition and other relevant materials
have been evaluated. The data considered include the following:
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 rat oral lethal dose (LD50) of 1,517 milligrams/kilogram
(mg/kg) of body weight.
5. A 90-day rat feeding study with a no-observable-effect level
(NOEL) of 12 mg/kg/day.
6. A 90-day dog feeding study with a NOEL of 1.25 mg/kg/day.
7. 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)).
8. A rat teratology study with a maternal toxicity NOEL of 30 mg/
kg/day and a developmental toxicity NOEL of 30 mg/kg/day.
9. 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.
10. A 1-year dog feeding study with a NOEL of 1.25 mg/kg/day.
11. 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, the highest dose
tested.
12. 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.
13. Ames test with and without activation, negative.
14. A mouse dominant-lethal assay, negative.
15. Chinese hamster nucleus anomaly, negative.
16. Cell transformation assay, negative.
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, 7
U.S.C. 136 et seq.
As part of EPA's evaluation of potential human health risks,
propiconazole has been the subject of five Peer Reviews and one
Scientific Advisory Panel (SAP) meeting.
Propiconazole 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 propiconazole. 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.
In the second, third, and fourth Peer Reviews that followed, the
Peer Review Committee considered recommendations of the SAP as well as
rebuttals by the registrant. Its conclusion, however, that
propiconazole should be classified as a Group C carcinogen with a
quantification of potential human risk remained unchanged.
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 propiconazole. 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 propiconazole 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 propiconazole in the 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 propiconazole,
no 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 propiconazole. Based on the
third pathology evaluation of the chronic study, the Peer Review
Committee agreed with Ciba-Geigy's argument that the study showed
excessive toxicity at the 2,500 ppm-dose and 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 propiconazole 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 carcinogenetic potential of
propiconazole, 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
propiconazole poses a negligible cancer risk to humans.
The reference dose (RfD) for propiconazole is 0.013 mg/kg/day,
based on a no-observable-effect level (NOEL) of 1.25 mg/kg/day and an
uncertainty factor of 100. The NOEL is taken from a 1-year feeding
study in dogs which demonstrated as an effect irritation of the stomach
in males.
The Agency has evaluated dietary exposure to the fungicide residues
based on the proposed tolerances and the commodities which have
established tolerances using data on anticipated residues and percent
crop treated data. The livestock burden was calculated using
anticipated residues in feed items multiplied by the expected percent
contribution to the diet. This dietary burden was then compared with
available data from feeding studies to determine anticipated residues
in meat and milk. Based on current registered uses of this chemical
only 7% of the RfD is being utilized for the general U.S. population.
The tolerances are expected to elicit only a minor increase in the
percent utilization of the RfD for the general U.S. population. The
most highly exposed subgroups, nursing and nonnursing infants less than
1 year, have Anticipated Residue Contributions (ARCs) from all
published tolerances of 1.97 X 10-3 and 3.97 X 10-3 mg/kg
bwt/day. These ARCs represent 15% and 31% of the Reference Dose for
these subgroups, respectively. The proposed tolerances will add 0.03%
and 0.05% of the RfD for nursing and nonnursing infants less than 1
year, respectively.
Available data on storage stability of propiconazole in peanuts are
unacceptable and must be redone for nutmeat, hulls, and hay. Once
review of all required residue data is submitted, the petitioner may
resubmit its petition for permanent tolerances.
The nature of the residue in plants and animals is adequately
understood, and adequate analytical methods (gas chromatography) are
available for enforcement purposes. Because of the long lead time for
establishing these tolerances and food additive regulations 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), 401 M St., S.W., 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
tolerances are being sought. For the reasons described above, the
Agency is establishing tolerances for residues of 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 following raw agricultural
commodities: peanuts, 0.2 ppm; peanut hay, 20 ppm; peanut hulls, 1 ppm.
Because of unacceptable storage stability data on peanuts, the Agency
is placing a time limitation on these tolerances. However, based on
available data the Agency concludes that the established interim
tolerances will protect public health. Therefore, the tolerances are
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 with the Hearing Clerk, at the address given above
(40 CFR 178.20). 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 178.127). A
request for a hearing will be granted if the Administrator determines
that the material submitted shows the following: There is a 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).
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 food
additive regulations or raising tolerance levels or food additive
regulations 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 (40 FR 24950).
Under Executive Order 12866 (58 FR 51735, October 4, 1993), the
Agency must determine whether the regulatory action is ``significant''
and therefore subject to review by the Office of Management and Budget
(OMB). Under section 3(f), the order defines ``significant regulatory
action'' as action that is likely to result in 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 referred to 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. The
Office of Management and Budget has exempted this rule from the
requirements of Executive Order 12866.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedures,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: May 13, 1994.
Douglas D. Campt,
Director, 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(c), by adding and alphabetically inserting three
new entries to the table therein, to read as 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.
* * * * *
(c) * * *
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Parts per Expiration
Commodity million date
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*****
Peanuts....................................... 0.2 12/31/98
Peanuts, hay.................................. 20.0 12/31/98
Peanuts, hulls................................ 1.0 12/31/98
*****
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[FR Doc. 94-12698 Filed 5-24-94; 8:45 am]
BILLING CODE 6560-50-F
