Diflubenzuron - Proposed Tolerance 4/96
[Federal Register: April 17, 1996 (Volume 61, Number 75)]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
DEPARTMENT OF TRANSPORTATION ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 0E3835/P648; FRL-5356-5]
Pesticide Tolerance for Diflubenzuron
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed Rule.
SUMMARY: EPA proposes to establish a tolerance for residues of the
insecticide diflubenzuron (N[[(4-chlorophenyl)amino]carbonyl]-2,6-
difluorobenzamide) in or on the raw agricultural commodity artichokes
at 6.0 parts per million (ppm). The proposed regulation to establish a
maximum permissible level for residues of the insecticide was requested
in a petition submitted by the Interregional Research Project No. 4
DATES: Comments, identified by the document control number [PP 0E3835/P648],
must be received on or before May 17, 1996.
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.
Comments and data may also be submitted to OPP by sending
electronic mail (e-mail) to: email@example.com. Electronic
comments must be submitted as an ASCII file avoiding the use of special
characters and any form of encryption. Comments and data will also be
accepted on disks in WordPerfect 5.1 file format or ASCII file format.
All comments and data in electronic form must be identified by the
docket number [PP 0E3835/P648]. Electronic comments on this proposed
rule may be filed online at many Federal Depository Libraries.
Additional information on electronic submissions can be found in the
SUPPLEMENTARY INFORMATION section of this document.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
"Confidential Business Information" (CBI). CBI should not be
submitted through e-mail. Information marked as CBI 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
Virginia address given above, from 8 a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Hoyt L. Jamerson,
Registration Division (7505W), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St. SW., Washington, DC 20460.
Office location and telephone number: Sixth Floor, Crystal Station #1,
2800 Jefferson Davis Highway, Arlington, VA 22202, 703-308-8783, e-mail
SUPPLEMENTARY INFORMATION: The Interregional Research Project No. 4
(IR-4), New Jersey Agricultural Experiment Station, P.O. Box 231,
Rutgers University, New Brunswick, NJ 08903, has submitted pesticide
petition (PP 0E3835) to EPA on behalf of the Agricultural Experiment
Station of California. This petition requests 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 180.377 by establishing a
tolerance for residues of the insecticide diflubenzuron (N[[4-
chlorophenyl)amino]carbonyl]-2,6-difluorobenzamide) in or on the raw
agricultural commodity artichoke at 6.0 ppm.
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 1-year chronic feeding study with dogs administered 0, 2, 10,
50 or 250 mg/kg/day with a no-observed-effect level (NOEL) established
at 2 mg/kg/day. Statistically significant increases in methemoglobin
and sulfhemoglobin in male and female dogs were observed at dose levels
of 10 mg/kg/day and higher. Signs of hemolytic anemia, destruction of
erythrocytes and of compensatory regeneration of erythrocytes were
observed at dose levels of 50 mg/kg/day and higher.
(2) A 2-year feeding/carcinogencity study with rats fed diets
containing 0, 156, 625, 2,500, or 10,000 ppm (equivalent to 0, 7.8, 31,
125, or 500 mg/kg/day) with statistically significant increases in
methemoglobin and sulfhemoglobin observed at all treatment levels
tested. Signs of hemolytic anemia and increased spleen and liver
weights were observed in males and females at treatment levels of 2,500
ppm and 10,000 ppm. Histological signs of erythrocyte destruction and
compensatory regeneration were observed in males and females at dose
levels of 156 ppm and higher. A no-observed-effect level was not
established for this study, since effects were observed at the lowest
dose tested. There were no carcinogenic effects observed under the
conditions of this study.
(3) A 91-week carcinogenicity study with mice fed diets containing
0, 16, 80, 400, 2,000, or 10,000 ppm (equivalent to 0, 2.4, 12, 60,
300, or 1,500 mg/kg/day). Increases in methemoglobin and sulfhemoglobin
were consistently observed in male and female mice at dose levels of 80
ppm and higher. Signs of hemolytic anemia, erythrocyte destruction and
compensatory regeneration, and histopathological effects in the liver
were observed at dose levels of 80 ppm and higher. No evidence of
carcinogenicity was observed under the conditions of this study.
(4) A 2-generation reproduction study with rats fed diets
containing 0, 500, 5,000, or 50,000 ppm (equivalent to 0, 25, 250, or
2,500 mg/kg/day). No effects on reproductive performance were observed
in the parental adults. The NOEL for reproductive effects in the
progeny is 250 mg/kg/day based on decreased body weight in the pups
from birth to 21 days postpartum.
(5) Developmental toxicity studies with rats and rabbits given
technical grade diflubenzuron by gavage at dose levels of 0 or 1,000
mg/kg/day with no maternal toxicity or toxicity to the developing fetus
observed under the conditions of the study.
(6) Mutagenicity studies using diflubenzuron as the test material
were negative. These studies included a Salmonella/mammalian microsome
plate incorporation assay with and without metabolic activation, an in
vitro chromosome damage assay using cultures of Chinese hamsters ovary
cells with and without metabolic activation, and an unsheduled DNA
synthesis assay using cultures of primary rat hepatocytes.
The qualitative nature of the residue is adequately understood in
plants based on data from citrus, mushroom, and soybean metabolism
studies. Para-chloroaniline (PCA) and 4-chlorophenylurea (CPU) are
metabolites of diflubenzuron that have been observed in mushrooms but
not in citrus and soybeans. Diflubenzuron is also known to be
metabolized to PCA and CPU in lactating goats, lactating cows, poultry,
OPP's Health Effects Division Peer Review Committee has concluded
that there is no evidence of carcinogenicity for diflubenzuron per se
and has placed the chemical in Group E of EPA's classification system
for carcinogens. The Committee also classified PCA as a Group B2
carcinogen (a probable human carcinogen). The classification for PCA
was based on the results of National Toxicology Program studies in
which PCA was administered for 2 years by gavage to rats at doses of 0,
2, 6, or 18 mg/kg/day and to mice at doses of 0, 3, 10, or 30 mg/kg/
day. Treatment-related increased incidences of uncommon sarcomas
(fibrosarcomas, hemangiosarcomas and/or osteosarcomas) of the spleen
were observed in male rats, and increased incidences of liver adenomas
and carcinomas, and hemangiosarcomas in the spleen and/or liver were
observed in male mice.
The reference dose (RfD) for diflubenzuron is 0.02 mg/kg/day. The
RfD is based on the NOEL of 2.0 mg/kg/day from the 1-year chronic
feeding study in dogs and an uncertainty factor of 100. Available
information relating to anticipated residues and percent of crop
treated for established tolerances were used to calculate the
Anticipated Residue Contribution (ARC) from residues of diflubenzuron
in the human diet. The ARC from published tolerances is calculated at
0.00008 mg/kg/day, which utilizes less than 1 percent of the RfD for
the overall population. The ARC for children 1 to 6 years old, the
population subgroup most highly exposed, utilizes 1 percent of the RfD.
The Theoretical Maximum Residue Contribution from the proposed
tolerance for artichokes would utilize an additional 0.1 percent of the
RfD for the U.S. population and for children 1 to 6 years old. This
dietary risk assessment indicates that there is no appreciable risk
from the establishment of the proposed tolerance for artichokes.
A quantitative cancer risk assessment was performed for PCA and
CPU. Possible human exposure to PCA and CPU may occur as a result of
the ingestion of PCA and CPU formed in animals which have consumed
feeds containing diflubenzuron residues and from the metabolic
conversion of diflubenzuron to PCA and CPU in the human body. For the
purposes of this risk assessment, it was assumed that CPU has the same
carcinogenic potential and potency as PCA. Although there is strong
evidence supporting the carcinogenicty of PCA in rats and mice, the
assumption that CPU also may be carcinogenic is not based on direct
testing in animals, but rather on a comparison of the chemical
structures of CPU and PCA. An assumption of a 2 percent conversion of
diflubenzuron to PCA was used for the cancer risk assessment.
The upper-bound cancer risk from dietary exposure to residues of
PCA and CPU from existing uses of diflubenzuron is estimated at 1.3 x
10-6. The additional cancer risk from the proposed tolerance for
artichokes is estimated at 2 x 10-8. EPA concludes that the
potential cancer risk from residues of PCA and CPU resulting from
established tolerances and the proposed use on artichokes is
An adequate analytical method, gas chromatography using an electron
capture detector, is available for enforcement purposes. The analytical
method for enforcing this tolerance has been published in the Pesticide
Analytical Manual, Vol. II (PAM-II). There is no reasonable expectation
that secondary residues will occur in milk, eggs, or meat and meat
byproducts of livestock and poultry: there are no livestock feed items
associated with artichokes.
There are presently no actions pending against the continued
registration of this chemical.
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 notice in the Federal Register that this rulemaking proposal be
referred to an Advisory Committee in accordance with section 408(e) of
A record has been established for this rulemaking under docket
number [PP 0E3835/P648] (including comments and data submitted
electronically as described below). 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.
Electronic comments can be sent directly to EPA at:
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
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 all comments received electronically into printed,
paper form as they are received and will place the paper copies in the
official rulemaking record which will also include all comments
submitted directly in writing. The official rulemaking record is the
paper record maintained at the Virginia address in "ADDRESSES" at the
beginning of this document.
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 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
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
Dated: April 3, 1996.
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR part 180 be amended as
1. The authority citation for part 180 continues to read as
Authority: 21 U.S.C. 346a and 371.
2. In Sec. 180.377, the table in paragraph (a) is amended by adding
alphabetically the entry for artichoke to read as follows:
Sec. 180.377 Diflubenzuron; tolerances for residues.
(a) * * *
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