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norflurazon (Zorial, Solicam) Proposed Pesticide Tolerance 8/95

[Federal Register: August 30, 1995 (Volume 60, Number 168)]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4E4383/P627; FRL-4970-9] RIN 2070-AC18
Norflurazon; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA proposes to establish a tolerance for combined residues of 
the herbicide norflurazon and its desmethyl metabolite in or on the raw 
agricultural commodity caneberries. The Interregional Research Project 
No. 4 (IR-4) submitted a petition requesting the proposed regulation to 
establish a maximum permissible level for residues of norflurazon.
DATES: Comments, identified by the document control number [PP 4E4383/
P627], must be received on or before September 29, 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:
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 4E4383/P627]. 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 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.
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: 
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 4E4383) to EPA on behalf of the IR-4 Agricultural 
Experiment Stations of Virginia and Washington. 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 180.356 
by establishing a tolerance for residues of the herbicide norflurazon 
(4-chloro-5-(methylamino)-2-(alpha, alpha, alpha-trifluro-m-tolyl)-3-
(2H) pyridazinone) and its desmethyl metabolite ((4-chloro-5-(amino)-2-
alpha, alpha, alpha-trifluro-m-tolyl)-3(2H)-pyridazinone) in or on the 
raw agricultural commodity caneberries at 0.2 part per million (ppm). 
Caneberries are defined for tolerance purposes to include blackberries, 
loganberry, raspberries, and varieties and/or hybrids of these. 
Tolerances are already established for the combined residues of 
norflurazon and its desmethyl metabolite in or on blackberries at 0.1 
ppm and raspberries at 0.2 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. Acute oral and dermal toxicity studies were performed, placing 
technical norflurazon in toxicity Category IV and Category III for 
primary eye irritation.
2. A 6-month feeding study with dogs fed diets containing 0, 50, 
150, or 450 ppm (equivalent to 0, 1.53, 5.02, or 14.27 milligrams (mg)/
kilogram (kg)/day for males; 0, 1.58, 4.77, or 17.75 mg/kg/day for 
females) with a no-observed-effect level (NOEL) of 50 ppm, based on 
increased absolute and relative liver weight and increased cholesterol 
in both sexes at the 150-ppm dose level.
3. A developmental toxicity study in rats given oral gavage doses 
of 0, 100, 200, or 400 mg/kg/day with a NOEL for maternal toxicity of 
less than 100 mg/kg/day based on decreased body weight gain. The NOEL 
for developmental toxicity was established at 400 mg/kg/day. 
Developmental toxicity was suggested at the 400-mg/kg/day dose level in 
the form of an increase in bipartite thoracic vertebrae and an increase 
in rudimentary 14th ribs. These effects are believed to be secondary to 
the maternal effects observed at the 400-mg/kg/day dose level.
4. A developmental toxicity study in rabbits given oral gavage 
doses of 0, 10, 30, or 60 mg/kg/day with a NOEL for maternal toxicity 
of 30 mg/kg/day based on clinical toxicity and reduced body weight gain 
at the 60-mg/kg/day dose level. The NOEL for developmental toxicity was 
established at 30 mg/kg/day based on a statistical increase in skeletal 
variations at the 60-mg/kg/day dose level.
5. A three-generation reproduction study in rats fed diets 
containing 0, 125, 375, or 1,025 ppm (equivalent to 0, 6.25, 18.75. or 
51.25 mg/kg/day) with a NOEL for reproductive toxicity of 1,025 ppm. 
There were no apparent effects on reproductive performance in this 
study.
6. A carcinogenicity study in rats fed diets containing 0, 125, 
375, or 1,025 ppm (equivalent to 0, 6.25, 18.75, or 51.25 mg/kg/day) 
with a NOEL of 375 ppm and a lowest-effect-level (LEL) of 1,025 ppm 
based on increased kidney weight and accompanying microscopic 
pathologic changes, as well as an increase in liver weight in male and 
female rats, and an increase in thyroid weight in males. There were no 
carcinogenic effects attributable to norflurazon observed under the 
conditions of the study.
7. A carcinogenicity study in mice fed diets containing 0, 85, 340, 
or 1,360 ppm (equivalent to 0, 12.8, 58.7, or 218.8 mg/kg/day) with a 
NOEL for systemic effects of 85 ppm for male mice and 340 ppm for 
female mice. The LEL is established at 340 ppm for male mice based on 
the increased incidence of enlarged spleen, increased absolute and 
relative liver weight, and increased incidence of nephritis. The LEL 
for female mice is established at 1,360 ppm based on the increased 
incidence of enlarged liver and cystic ovaries, the increased absolute 
and relative liver weight, and the increased incidence of 
pyelonephritis, a significant positive trend in hepatocellular adenomas 
and in combined hepatocellular adenomas and/or carcinomas. A 
significant pairwise increase in hepatocellular adenomas and 
hepatocellular adenomas/carcinomas combined was observed at the 204 mg/
kg/day dose level in males. There were no statistically significant 
increases in tumor incidence with incremental doses of norflurazon in 
females.
8. Mutagenicity assays including an in-vitro cytogenetic assay in 
Chinese hamster ovary cells for chromosome aberrations, negative; and 
an unscheduled DNA synthesis test in primary rat hepatocytes for DNA 
repair, negative for potential mutagenic activity.
9. In a rat metabolism study norflurazon was rapidly absorbed from 
the gastrointestinal tract and extensively metabolized.
Based on a weight-of-the evidence determination, EPA has classified 
norflurazon as a possible human carcinogen (Group C). This 
classification is based on the presence of benign tumors in only one 
sex of one species at one dose level, adequate but negative 
mutagenicity studies, and no finding of carcinogenicity in structurally 
related compounds. EPA has determined that for purposes of risk 
characterization the reference dose (RfD) should be used to quantify 
dietary risk.
Dietary risk assessments for norflurazon indicate that there is 
minimal risk from established tolerances and the proposed tolerance for 
caneberries. Dietary risk assessments for the herbicide were conducted 
using the Reference Dose (RfD) to assess chronic exposure and risk and 
the Margin of Exposure (MOE) for acute toxicity.
The RfD is calculated at 0.02 mg/kg/of body weight/day based on a 
NOEL of 1.53 mg/kg/day from the 6-month dog feeding study and an 
uncertainty factor of 100. The theoretical maximum residue contribution 
(TMRC) from existing tolerances and the proposed tolerance for 
caneberries utilize 10 percent of the RfD for the general population 
and 47 percent of the RfD for nonnursing infants less than 1-year in age.
The MOE is a measure of how closely the high-end acute dietary 
exposure comes to the no-observed-effect (NOEL) level from the toxicity 
endpoint of concern. For norflurazon the MOE was calculated as a ratio 
of the NOEL (30 mg/kg/day) from the rabbit developmental toxicity study 
to dietary exposure, as estimated for the population subgroup at 
greatest risk (females of child-bearing age). The MOE for this subgroup 
is estimated at 5,000 for high-end exposure. Acute dietary margins of 
exposure of less than 100 are generally of concern to EPA. A MOE of 
5,000 poses minimal risk.
The nature of the residues in caneberries is adequately understood 
for the purposes of the proposed tolerance. An adequate analytical 
method is available for enforcement purposes. Because of the long lead 
time from establishing these tolerances to publication of the 
enforcement method in the Pesticide Analytical Manual, Volume II, the 
analytical method is being made available to anyone with an interest in 
pesticide enforcement when requested from: Calvin Furlow, Public 
Response and Program Resources Branch, Field Operations Division 
(7506C), Office of Pesticide Programs, Environmental Protections 
Agency, 401 M St., SW., Washington, DC 20460. Office location and 
telephone number: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., 
Arlington, VA 22202, (703)-305-5937.
No secondary residues are expected in meat, milk, poultry, or eggs 
since caneberries are not considered a livestock feed commodity.
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 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 4E4383/P627] (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: 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: August 11, 1995.
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.
Sec. 180.356   [Amended]
2. In Sec. 180.356 Norflurazon; tolerances for residues by amending 
the table therein by adding and alphabetically inserting an entry for 
caneberries at 0.2 part per million (ppm) and by removing the entries 
for blackberries and raspberries.
[FR Doc. 95-21516 Filed 8-29-95; 8:45 am]