linuron (Lorox) Proposed Pesticide Tolerance 9/95
[Federal Register: September 29, 1995 (Volume 60, Number 189)]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 5E4464/P629; FRL-4973-7]
Linuron; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
SUMMARY: EPA proposes to increase the established tolerance for
residues of the herbicide linuron in or on the raw agricultural
commodity asparagus. The proposed regulation to increase the maximum
permissible level for residues of linuron was requested in a petition
submitted by the Interregional Research Project No. 4 (IR-4) pursuant
to the Federal Food, Drug and Cosmetic Act (FFDCA).
DATES: Comments, identified by the document control number, [PP 5E4464/
P629], must be received on or before October 30, 1995.
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 Hwy., Arlington, VA 22202. Comments and data may
also be submitted to OPP by sending electronic mail (e-mail) to:
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 5E4464/P629]. 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 "SUPPLEMENTAL 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 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
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 Hwy., 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, submitted a pesticide
petition (PP 5E4464) to EPA on behalf of the IR-4 Agricultural
Experiment Stations of California, Indiana, Michigan, and New Jersey.
The petition requests that the Administrator, pursuant to section
408(e) of the FFDCA, 21 U.S.C. 346a(e), amend 40 CFR 180.184 by
increasing the established tolerance for residues of the herbicide
linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] in or on the
raw agricultural commodity asparagus from 3.0 parts per million (ppm)
to 7.0 ppm. IR-4 proposed the increased tolerance for asparagus in
response to the reregistration eligibility review and decisions on the
pesticide case linuron, which was completed by EPA on April 28, 1995.
The Reregistration Eligibility Decision (RED) requires that the
established tolerance for linuron on asparagus be increased to 7.0 ppm.
The scientific data submitted with 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 in dogs, which were fed diets containing
10, 25, 125, or 625 ppm (equivalent to 0.29, 0.79, 4.17, or 18.6
milligrams (mg)/kilogram (kg)/day for males; 0.3, 0.77, 3.49, or 16.1
mg/kg/day for females), with a no-observed-effect level (NOEL) for
systemic toxicity of 25 ppm. The lowest-observed-effect level (LOEL)
was established at 125 ppm based on hematology changes.
2. A 2-year feeding/carcinogenicity study in Sprague-Dawley rats,
which were fed diets containing 50, 125, or 625 ppm (equivalent to 2.5,
6.25, or 31.25 mg/kg/day), with systemic NOEL's of 50 ppm for females
and 625 ppm for males. The LOEL for systemic toxicity for females was
established at 125 ppm based on hematotoxicity (a decrease in the
percent hemoglobin). There was no decrease in percent hemoglobin in
male rats at any dosage level tested. Testicular interstitial cell
adenomas were observed at a significantly increased incidence in male
rats fed diets containing 125 and 625 ppm.
3. A 2-year feeding study in albino rats, which were fed diets
containing 25, 125, or 625 ppm (equivalent to 1.25, 6.25, or 31.25 mg/
kg/day), with a systemic NOEL of 125 ppm. Growth retardation and
findings indicative of red blood cell disintegration were observed at
the LOEL of 625 ppm.
4. An 18-month feeding study was conducted in rats to study the
effects of linuron on methemoglobin and sulfhemoglobin blood
concentrations. The dietary levels tested were 25, 125, or 625 ppm
(1.25, 6.25, or 31.25 mg/kg/day). Significant changes in blood pigment
were observed in the mid- and high-dose female rats and the high-dose
male rats. NOELs were established at 125 ppm for male rats and 25 ppm
for female rats.
5. A 2-year feeding/carcinogenicity in CD-1 mice, which were fed
diets containing 50, 150, or 1,500 ppm (12, 35, or 455 mg/kg/day),
showed a statistically significant increase in the incidence of hepatocellular
adenomas at 1,500 ppm for female mice, and borderline statistical significance
was attained for hepatocellular adenomas at 50 ppm for male mice.
6. A developmental toxicity study in rats at dietary levels of 50,
125, or 625 ppm (5.0, 12.1, or 49.8 mg/kg/day), administered on days 6
to 15 of gestation with NOELs for maternal systemic toxicity and
developmental toxicity established at 125 ppm. The LOEL of 625 ppm for
maternal systemic toxic effects was based upon decreased body weight
and food consumption values. The developmental toxicity LOEL of 625 ppm
was based on increases in post-implantation loss and increases in the
litter and fetal incidence of resorptions.
7. A developmental toxicity study in rabbits given gavage dosages
of 5, 25, or 100 mg/kg/day on days 7 through 19 of gestation with a
NOEL for developmental toxicity of 25 mg/kg/day and a NOEL for maternal
toxicity of 5 mg/kg/day. The LOEL for maternal systemic toxicity
(reduced body weight) was established at 25 mg/kg/day. The LOEL for
developmental toxicity was established at 100 mg/kg/day based on an
increased number of abortions, decreased mean number of fetuses per
litter, decreased fetal body weight, and increased incidence of fetuses
with skeletal variations of the skull at that dosage level.
8. A two-generation reproductive toxicity study in rats, which were
fed diets containing 12.5, 100, or 625 ppm (equivalent to 0.84, 6.8, or
44.75 mg/kg/day for males; 1.0, 8.3, or 54.1 mg/kg/day for females),
with no evidence of adverse effects on fertility or reproductive
performance under the conditions of the study. The NOEL for parental
systemic toxicity was established at 12.5 ppm based upon decrements in
parental body weight gain. In addition, the results of this study
support the hypothesis that rats exposed to linuron could develop
interstitial cell hyperplasia and subsequent adenomas (Leydig cell
tumors) of the testicular tissue via a mechanism of sustained
hypersecretion of luteinizing hormone induced by the antiandrogenic
potential of linuron.
9. Linuron did not produce gene mutation in an Ames assay or in an
in vitro assay using Chinese hamster ovary cells. Linuron did not
induce bone marrow chromosome aberrations in vivo and in other tests
for genotoxicity. Linuron did not induce unscheduled DNA synthesis in
isolated rat hepatocytes.
10. Metabolism studies in rats show that linuron was extensively
metabolized by male and female rats when administered by gavage, and
there is no indication of accumulation of linuron or its metabolites in
tissues and organs.
Linuron was placed in Special Review for carcinogenicity in 1982.
It was later classified as a group C carcinogen (possible human
carcinogen) with quantified cancer risk on the basis of a dose-related
increase in interstitial cell hyperplasia and adenomas in the 2-year
rat feeding study and hepatocellular tumors that appeared in low-dose
male and high-dose female mice in a 2-year feeding study. Subsequent
review by the Office of Pesticide Programs, Health Effects Division,
Peer Review Committee and the Science Advisory Panel resulted in the
decision to regulate linuron as a possible human carcinogen without
quantified cancer risk. This decision was based on the weight-of-
evidence, which suggested that the carcinogenic potential of linuron in
humans is weak.
Dietary risk assessments for linuron were conducted using the
Reference Dose (RfD) to assess chronic exposure and risk and the Margin
of Exposure (MOE) for acute toxicity. The RfD for linuron is
established at 0.008 mg/kg of body weight/day, based on a NOEL of 0.77
mg/kg/day from the 1-year feeding study in dogs and an uncertainty
factor of 100. The anticipated residue contribution (ARC) from
published tolerances and the proposed 7-ppm tolerance for asparagus
utilizes 2 percent of the RfD for the general population. The ARC for
the subgroup most highly exposed, nonnursing infants (less than 1-year
old), utilizes 6 percent of the RfD. EPA concludes that established
tolerances and the proposed increased tolerance for asparagus pose a
negligible dietary risk to humans. The MOE is a measure of how closely
acute dietary exposure comes to the NOEL from the toxicity endpoint of
concern. For linuron, the MOE was calculated as a ratio of the NOEL (25
mg/kg/day) from the rabbit developmental toxicity study to dietary
exposure (0.03125 mg/kg/day), as estimated by the high-end exposure for
the population subgroup at greatest risk (females of childbearing age).
The MOE for this subgroup is estimated at 800 for high-end exposure.
Acute dietary margins of exposure of less than 100 are generally of
concern to EPA. A MOE of 800 poses minimal risk.
The nature of the residue in plants is adequately understood. An
adequate analytical method has been published in Pesticide Analytical
Manual, Vol. II (PAM Vol. II).
There is no reasonable expectation that secondary residues will
occur in milk, and eggs, or meat, fat and meat byproducts of livestock
and poultry; there are no livestock feed items associated with
There are currently no actions pending against the continued
registration of this chemical.
Based on the information and data considered, the Agency has
determined that amending 40 CFR 180.184 to increase the tolerance for
linuron from 3 ppm to 7 ppm 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 5E4464/P629] (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 Rm. 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 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: September 20, 1995.
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR part 180 be amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 346a and 371.
2. In Sec. 180.184, paragraph (a) is amended in the table therein
by revising the entry for asparagus, to read as follows:
Sec. 180.184 Linuron; tolerances for residues.
(a) * * *
* * * * *
* * * * *