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lactofen (Cobra) Proposed Pesticide Tolerance 3/96

[Federal Register: March 8, 1996 (Volume 61, Number 47)]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4E4418/P643; FRL-5353-2]
RIN 2070-AB18
Lactofen; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed Rule.
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SUMMARY: EPA proposes to establish a tolerance for the combined 
residues of the herbicide lactofen in or on the raw agricultural 
commodity snap beans at 0.05 part per million (ppm). The proposed 
regulation to establish a maximum permissible level for residues of the 
herbicide was requested in a petition submitted by the Interregional 
Research Project No. 4 (IR-4).
DATES: Comments, identified by the document control number [PP 4E4418/P643], 
must be received on or before April 8, 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. 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 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 address given above, 
from 8 a.m. to 4:30 p.m., Monday through Friday, excluding legal 
holidays.
    Comments and data may also be submitted electronically 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 4E4418/P643]. No CBI should be submitted through e-
mail. Electronic comments on this proposed rule may be filed online at 
many Federal Depository Libraries. Additional information on electronic 
submissions can be found in SUPPLEMENTARY INFORMATION of this document.
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:
                  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) 4E4418 to EPA on behalf of the Agricultural Experiment 
Stations of Arkansas, Florida, Georgia, Oregon, Tennessee, and 
Virginia. 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 180.432 by establishing a tolerance for 
the combined residues of lactofen, 1-(carboethoxy)ethyl-5-[2-chloro-4-
(trifluoromethyl)phenoxy]-2-nitrobenzoate, and its associated 
metabolites containing the diphenyl ether linkage expressed as lactofen 
in or on the raw agricultural commodity snap beans at 0.05 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 feeding study with dogs fed diets containing 0, 40, 
200, or 1,000/3,000 ppm with a no-observed-effect level (NOEL) of 200 
ppm (equivalent to 5 milligrams (mg)/kilogram (kg)/day). Systemic 
effects observed at the high dose level include decreased body weight, 
renal dysfunction, a significant decrease in erythrocytes, hemoglobin, 
and hematocrit, and a significant increase in blood platelets.
    (2) A 2-year feeding/carcinogenicity study in rats fed diets 
containing 0, 500, 1,000, or 2,000 ppm with a NOEL for systemic effects 
of 500 ppm (equivalent to 25 mg/kg/day). Increased pigmentation of the 
liver and kidney were observed in male and female rats at the 1,000 and 
2,000 dose levels. There was an increased incidence of cellular 
alterations and neoplastic nodules (benign) in the liver of rats 
administered 2,000 ppm (100 mg/kg/day).
    (3) An 18-month carcinogenicity study in mice fed diets containing 
10, 50, or 250 ppm with statistically significant increases in liver 
adenomas and carcinomas, and in the combined incidence of liver tumors 
(adenomas and carcinomas) in high dose males. Statistically significant 
increases in the incidences of liver adenomas and in combined liver 
tumors (adenomas and carcinomas) were observed in high dose females. 
Systemic effects include an increase in liver/body weight ratios and 
enlarged liver cells in all treated males and the mid- and high-dose 
females.
    (4) A developmental toxicity study in rats given 0, 15, 50, or 150 
mg/kg by oral gavage with no developmental toxicity observed under the 
conditions of the study. Evidence of fetotoxicity (bent ribs) was 
observed at the 150 mg/kg dose level.
    (5) A developmental toxicity study in rabbits given 0, 1, 4, or 20 
mg/kg/day by oral gavage with no evidence of developmental toxicity.
    (6) A 2-generation reproduction study in rats fed diets containing 
0, 50, 500, or 2,000 ppm with a NOEL at 50 ppm (equivalent to 2.5 mg/
kg/day) for reproductive and systemic effects. Reproductive effects 
observed at the lowest-observed-effect level (500 ppm) include reduced 
mean pup weight and increased pup heart and liver weights.
    (7) Lactofen did not cause an increase in chromosomal aberrations 
when tested with Chinese hamster ovary cells, was negative in a 
mammalian cell forward mutation assay, and did not induce unscheduled 
DNA synthesis in isolated rat hepatocytes. Lactofen did have a low 
covalent binding index to mouse liver DNA in vivo and was positive in 
the Ames Salmonella/microsome plate test using strain 1538.
    Lactofen has been classified by the Office of Pesticide Program's, 
Health Effects Division, Carcinogenicity Peer Review Committee (CPRC) 
as a Group B2 carcinogen (probable human carcinogen). Lactofen met the 
criteria of a B2 carcinogen in that it induced an increased incidence 
of malignant tumors or combined malignant and benign tumors in mice and 
rats. Although an increase in malignant tumors was not seen in rats, 
the Committee felt that a B2 classification was appropriate since a 
tumor response was seen in two species at the same site. In addition, 
lactofen is structurally similar to acifluorfen, nitrofen, oxyfluorfen 
and fomesafen, which have all been shown to produce liver tumors in 
rodents.
    Dietary risk assessments for lactofen indicate that there is 
minimal risk from established tolerances and the proposed tolerance for 
snap beans. Dietary risk assessments were conducted using the Reference 
Dose (RfD) and the cancer potency factor for lactofen to assess chronic 
risk from lactofen residues in the human diet.
    The RfD for lactofen is 0.002 mg/kg of body weight/day. The RfD is 
based on the lowest-observed effect level (1.5 mg/kg/day) from the 18-
month mouse feeding study and an uncertainty factor of 1,000. An 
uncertainty factor of 1,000 was used to calculate the RfD since a NOEL 
could not be established from the mouse study. Available information on 
anticipated residues and/or percent of crop treated was used in the 
analysis to estimate the Anticipated Residue Contribution (ARC) of 
existing uses of lactofen and the proposed use on snap beans. The ARC 
from existing uses and the proposed use utilizes less than 1 percent of 
the RfD for the U.S. population and all population subgroups.
    The upper-bound carcinogenic risk from dietary exposure to lactofen 
is calculated at 4.3  x  10<SUP>-7. The carcinogenic risk for lactofen 
was calculated using the ARC estimates for dietary exposure from 
existing uses and the proposed use on snap beans and a Q<SUP>* of 0.16 
(mg/kg/day)<SUP>-1.
    The nature of lactofen residues in snap beans is adequately defined 
for purposes of this tolerance. The residues of concern in snap beans 
are lactofen and its metabolites containing the diphenyl ether linkage. 
An adequate analytical method is available for enforcement purposes. 
The method is available in the Pesticide Analytical Manual, Volume II 
(PAM II).
    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 4E4418/P643] (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 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 
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 28, 1996.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
    Therefore, it is proposed that 40 CFR part 180 be 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. 180.432, Lactofen; tolerances for residues, by revising 
paragraph (a) to read as follows:
Sec. 180.432   Lactofen; tolerances for residues.
    (a) Tolerances are established for the combined residues of 
lactofen, 1- (carboethoxy)ethyl-5-[2-chloro-4-
(trifluoromethyl)phenoxy]-2-nitrobenzoate, and its associated 
metabolites containing the diphenyl ether linkage expressed as lactofen 
in or on the following raw agricultural commodities:
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                                                                  Parts 
                          Commodities                              per  
                                                                 million
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Beans, snap....................................................   0.05
Soybeans.......................................................   0.05
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