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linuron (Lorox) Proposed Pesticide Tolerance 9/95

[Federal Register: September 29, 1995 (Volume 60, Number 189)]
[Page 50582-50583]
40 CFR Part 180
[PP 5E4464/P629; FRL-4973-7]
RIN 2070-AC18
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 
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 
the FFDCA.
    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 
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: September 20, 1995.
Peter Caulkins,
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) *  *  *
                                                              Parts per 
                         Commodity                             million  
Asparagus..................................................      7.0
                  *        *        *        *        *                 
* * * * *