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Diflubenzuron. April 17, 1996. Proposed Pesticide Tolerance. Federal Register.
http://www.epa.gov/docs/fedrgstr/EPA-PEST/1996/April/Day-17/pr-652.html
[Federal Register: April 17, 1996 (Volume 61, Number 75)] [Proposed Rules]
[Page 16745-16747]
>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]
RIN 2070-AB18
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 (IR-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: opp-docket@epamail.epa.gov. 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 address: jamerson.hoyt@epamail.epa.gov.
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
[[Page 16746]]
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, and rats.
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<SUP>-6. The additional cancer risk from the proposed
tolerance for artichokes is estimated at 2 x 10<SUP>-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 negligible.
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 the FFDCA.
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:
opp-Docket@epamail.epa.gov
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
[[Page 16747]]
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: April 3, 1996.
Susan Lewis,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR part 180 be amended as follows:
PART 180--[AMENDED]
(a) * * *
Parts per
Commodities million