[Federal Register Volume 60, Number 45 (Wednesday, March 8, 1995)]
[Rules and Regulations]
[Pages 12707-12709]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-5651]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 6F3392/R2105; FRL-4933-1]
RIN 2070-AB78
Pesticide Tolerance for Clofentezine
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes a tolerance for residues of the
insecticide clofentezine in or on the raw agricultural commodity
apples. AgroEvo USA Corp. (formerly Nor-Am Chemical Co.) requested this
regulation to establish a maximum permissible level for residues of the
insecticide.
EFFECTIVE DATE: This regulation is effective February 22, 1995.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 6F3392/R2105], 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.
FOR FURTHER INFORMATION CONTACT: By mail: Dennis H. Edwards, Product
Manager (PM) 19, Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 207, CM #2, 1921
Jefferson Davis Hwy., Arlington, VA 22202. (703)-305-3686.
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of June 4, 1986 (51 FR 20343), which announce that
Nor-Am Chemical Co. of Little Falls Centre One, 2711 Centerville Rd.,
Wilmington, DE 19803, had sumitted a pesticide petition to EPA
requesting that the Administrator, pursuant to section 408(d) of the
Federal Food, Drug and Costmetic Act (FFDCA), 21 U.S.C. 346a(d),
propose to amend 40 CFR 180.446 by establishing tolerances for residues
of the insecticide clofentezine 3,b-bis(2-chlorophenyl)-1,2,4,5-
tetrazine in or on the commodities apples at 0.05 part per million
(ppm), meat at 0.05 ppm, meat byproducts at 0.05 ppm, milk at 0.01 ppm,
and poultry and poultry byproducts at 0.05. A feed additive tolerance
was proposed for dry apple pomace at 1.0 ppm.
Subsequent to the orginal notice of filing, EPA issued a notice,
published Federal Register of May 27, 1992 (57 FR 22232), which
announced that the Nor-Am Chemical Co. was amending pesticide petition
6F3392 by increasing the proposed tolerance in/on apples to 0.01 ppm,
withdrawing the proposed feed additive tolerance, and withdrawing the
petition for animal tolerances since they have already been
established.
There were no comments or requests for referral to an advisory
committee received in response to the notice of filings.
The scientific data submitted in the petition and other relevant
material have been evaluated. The toxicological data considered in
support of the tolerance include a 1-year dog feeding study with a no-
observed-effect level (NOEL) of 50 ppm (1.25 mg/kg/day); a mouse
carcinogenicity study which was negative at the doses tested, 50 ppm
(7.5 mg/kg/day), 500 ppm (75 mg/kg/day), and 5,000 ppm (750 mg/kg/day);
a multi-generation rat study with a NOEL of 400 ppm (20 mg/kg/day)
(highest dose tested (HDT); a rat teratology study which was negative
at 3,200 mg/kg/day (HDT) and had a developmental NOEL of 3,200 mg/kg/
day; a rabbit teratology study which was negative at 3,000 mg/kg/day
(HDT) also had a NOEL of 1,000 mg/kg/day for maternal toxicity (reduced
litter and fetal body weights); and a 2-year rat chronic feeding/
carcinogenicity study which showed an increase in the incidence of
centrilobular hepatocyte hypertrophy and showed a statistically
significant increase in thyroid follicular cell tumors in male rats at
400 ppm (20 mg/kg/day (HDT). Gene mutation, chromosomal aberrations,
and diet DNA damage tests were negative for genetic toxicity.
The registrant (Nor-AM) also submitted additional thyroid studies
intended to show that there was an indirect mechanism for the
follicular cell tumors associated with clofentezine's liver toxicity.
The Agency has reviewed the data in accordance with criteria outlined
in a draft document entitled, ``Thyroid Follicular Cell Carcinogenesis:
Mechanistic and Science Policy Considerations,'' (December 15, 1987).
While this document is still undergoing Agency review, and the
assessment procedures set forth therein have not been adopted by the
Agency, the draft does provide a useful framework in which to consider
the issue. Although the additional thyroid function studies suggest the
possibility of an indirect mechanism for follicular cell tumor
induction that may be associated with clofentezine's liver toxicity,
the Agency believes that [[Page 12708]] additional data are necessary
to more completely define the mechanism of clofentezine's thyroid tumor
induction in terms of the criteria listed in the above document. Based
on the rat feeding/ carcinogenicity study, the Agency has classified
clofentezine as a possible human carcinogen (Group C). The qualitative
designation ``C'' refer to EPA's weight-of-evidence classification. The
classification is based on the Agency's ``Guidelines for Carcinogenic
Risk Assessment,'' published in the Federal Register of September 25,
1996 (51 FR 33992). The Agency believes a quantitative risk assessment
based on the thyroid incidence is not approprate for the following
reasons:
1. The increase tumor incidence was marginally increased above the
control incidence only at the highest dose tested (20 mg/kg/day) in the
chronic feeding study.
2. The increased incidence was observed only in male rats.
3. The thyroid tumor incidence in the chronic feeding study's
highest dose group (20 percent) was slightly greater than the
historical range provided by limited control group data (7.5 to 15
percent) from two other studies.
4. The additional thyroid function studies suggest the possibility
of an indirect mechanism for follicular cell tumor induction that may
be associated with clofentezine's liver toxicity.
5. The mouse was negative for carcinogency effects at all dose
levels, i.e., 50, 500, 5,000 ppm (equivalent to 7.5, 75, 750 mg/kg/day,
respectively).
6. There are no close structural analogs with carcinogenic concerns
identified.
7. Clofentezine is not mutagenic in several acceptable studies.
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
Science Advisory Panel (SAP) also reviewed the weight-of-evidence
consideration and classification of the carcinogenic potential of
clofentezine. The SAP review included the additional thyroid studies
submitted by Nor-Am that were available at that time. The SAP concluded
that thyroid tumors in male rats from the chronic feeding/
carcinogenicity study with clofentezine did not provide adequate
evidence of a potential carcinogenic hazard to humans and that the
carcinogenic potential of clofentezine belongs to Group D (not
classifiable as a human carcinogen).
The Panel's interpretation was based on observed increases in
thyroid stimulation hormone (TSH) levels and the incidence of thyroid
follicular cell hyperplasia which may be responses to decreases in
blood levels of the circulating thyroid hormones (triiodothyroxine
(T3) and tetra-iodothyroxine (T4) observed in clofentezine-
treated rats. This sequence of reduced circulating thyroid hormones and
increased TSH levels and follicular cell hyperplasia is known to lead
to thyroid tumors in rats, and the Panel noted, ``Exposure to agents
that cause this sequence in rats has not resulted in increased TSH,
hyperplasia, and thyroid tumors in humans.'' Therefore, the Panel
concluded that there was inadequate data for suggesting human
carcinogenicity or a quantitative risk assessment.
Nor-Am has since submitted additional thyroid studies intended to
show the mechanism of clofentezine's thyroid tumor induction. The
Agency has reviewed these data, but as previously stated, the Agency
continues to believe that additional data are needed to more completely
define the mechanism of clofentezine's thyroid tumor induction and that
the available data are not sufficient to change the classification of
clofentezine from Category ``C'' to Category ``D.'' However, the Agency
does agree with the SAP that a quantitative risk assessment is not
appropriate.
The reference dose (RfD), based on the 1-year dog feeding/
carcinogenic study with a NOEL of 1.25 mg/kg/bwt and 100-fold
uncertainity factor, is calculated to be 0.013 mg/kg/bwt. The
theoretical maximum residue contribution (TMRC) from published uses is
0.000591 mg/kg/bwt/day. This represents 4.54 percent of the RfD. The
proposed tolerance contributes .000231 mg/kg/bwt/day. This represents
1.78 precent of the RfD. Dietary exposure from the existing uses and
proposed uses will not exceed the reference dose for any subpopulation
(including infants and children) based on the information available
from EPA's Dietary Risk Evaluation System.
The nature of the residue is understood. An adequate analytical
method, high-performance liquid chromatography (HPLC), is available for
enforcement.
Also, in an editorial amendment to the clofentezine tolerances in
40 CFR 180.446, EPA is removing the sole entry in paragraph (a), for
pears, and moving it to the table in paragraph (b). Paragraph (a) is
redundant and is being removed and designated as ``reserved.''
There are currently no actions pending against the continued
registration of this chemical.
This pesticide is considered useful for the purposes for which the
tolerances are sought and capable of achieving the intended physical or
technical effect. Based on the information and data considered, the
Agency has determined that the tolerances 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).
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 [[Page 12709]] 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: February 22, 1995.
Stephen L. Johnson,
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. 180.446, by removing paragraph (a) and designating it as
``reserved'' and by amending paragraph (b) by revising the table
therein, to read as follows:
Sec. 180.446 Clofentezine; tolerances for residues.
(a) [Reserved]
(b) * * *
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Parts per
Commodity million
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Almonds, hulls............................................. 5.0
Almonds, nutmeat........................................... 0.5
Apples..................................................... 0.01
Apricots................................................... 1.0
Cherries................................................... 1.0
Nectarines................................................. 1.0
Peaches.................................................... 1.0
Pears...................................................... 0.5
Walnuts.................................................... 0.02
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[FR Doc. 95-5651 Filed 3-7-95; 8:45 am]
BILLING CODE 6560-50-F
