[Federal Register Volume 59, Number 206 (Wednesday, October 26, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-26469]
[[Page Unknown]]
[Federal Register: October 26, 1994]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF THE TREASURY
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 0E3907/P588; FRL-4907-4]
RIN 2070-AC18
Pesticide Tolerance for 3,5-Dichloro-N-(1,1-Dimethyl-2-
Propynyl)Benzamide
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: EPA proposes to establish a tolerance for combined residues of
the herbicide 3,5-dichloro-N-(1,1-dimethyl-2-propynyl)benzamide and its
metabolites in or on the raw agricultural commodity radicchio greens
(tops). The Interregional Research Project No. 4 (IR-4) submitted to
EPA the petition requesting the maximum permissible level for residues
of the herbicide.
DATES: Comments, identified by the document control number [PP 0E3907/
P588], must be received on or before November 25, 1994.
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. 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). Information so marked 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 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.
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) 0E3907 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), establish a tolerance for combined residues
of the herbicide 3,5-dichloro-N-(1,1-dimethyl-2-propynyl)benzamide
(also referred to in this document as pronamide) and its metabolites
(calculated as 3,5-dichloro-N-(1,1-dimethyl-2-propynyl)benzamide) in or
on the raw agricultural commodity radicchio greens (tops) at 2 parts
per million (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 90-day feeding study with rats administered pronamide in the
diet at concentrations of 0, 40, 200, 1,000, or 4,000 ppm (equivalent
to 0, 2.5, 12.3, 60.0, or 254.0 milligrams (mg)/kilogram (kg)/day in
males; 0, 3.1, 15.0, 74.6, or 289.2 mg/kg/day in females). A systemic
no-observed-effect level (NOEL) was established at 200 ppm (12.3 mg/kg/
day/male; 15 mg/kg/day/female). A systemic lowest-effect level (LEL)
was established at 1,000 ppm (60.0 mg/kg/day/male; 74.6 mg/kg/day/
female), based on increased liver relative weight and incidence of
liver histopathology in both sexes, decreased body/weight gain and feed
consumption in females, and increased blood cholesterol level in males.
Effects observed at the high dose (4,000 ppm) include decreases in body
weight/weight gain and feed consumption in both sexes, and increases in
liver-related effects and in the histopathology of the thyroid (both
sexes) and anterior pituitary (males).
2. A 52-week chronic feeding study with dogs fed diets containing
0, 300, 875, or 1,750 ppm (equivalent to 0, 11.9, 33.1, or 67.7 mg/kg/
day in males; or 0, 11.9, 36.1, or 69.0 mg/kg/day in females) with a
NOEL established at 300 ppm, based on increases in serum alkaline
phosphatase in males and thyroid weight in females, and in liver
pathology in both sexes at the 875-ppm dose level. Additional effects
observed at the highest dose tested (1,750 ppm) include decreases in
body weight/feed consumption, increases in serum alkaline phosphatase
and gamma glutamyl transferase in both sexes, increases in serum
alanine aminotransferase in females, and increases in testes relative
weight in males.
3. An 18-month carcinogenicity study with B6C3F1 mice fed diets
containing 0, 1,000, or 2,000 ppm (approximately 0, 150, or 300 mg/kg/
day) with a dose-related increase in incidence of hepatocellular
carcinomas in male mice sacrificed at 18 months. The increases in tumor
rates observed at 1,000 and 2,000 ppm were statistically significant by
pair-wise comparison with the control. There were no carcinogenic
effects observed in female mice under the conditions of the study.
4. A 24-month chronic feeding/carcinogenicity study with rats fed
diets containing 0, 40, 200, or 1,000 ppm (equivalent to 0, 1.73, 8.46,
or 42.59 mg/kg/day/male and 0, 2.13, 10.69, or 55.09 mg/kg/day/female).
The NOEL for systemic (nonneoplastic) effects was established at 8.46
mg/kg/day/males and 10.69 mg/kg/day females, based on decreased body
weight/body weight gain and increased liver weight, as well as an
increased incidence of hepatic centrilobular hypertrophy, eosinophilic
cell alterations, and thyroid follicular cell hypertrophy in both sexes
at the high-dose level. Rats fed at the high-dose level also showed an
increased incidence of thyroid tumor (thyroid follicular cell adenomas)
and testicular tumor (benign testicular interstitial cell tumors)
rates, which exceeded historical control ranges. There was no
progression from thyroid and testicular tumors to carcinomas.
5. A two-generation reproduction study with rats fed diets
containing 0, 40, 200, or 1,500 ppm (approximately 0, 3.0, 15.4, or
114.0 mg/kg/day/P1 males and 0, 3.2, 16.5, or 127.3 mg/kg/day/P2 males
during pre-mating period; group time-weighted average approximately 0,
4.1, 20.2, and 158.2 mg/kg/day/P1 females and 0, 4.0, 19.8, or 157.4
mg/kg/day/P2 females). The reproductive NOEL was established at 200
ppm, based on decreased combined male/female pup weight per litter at
the 1,500-ppm dose level. A NOEL for parental systemic effects was
established at 200 ppm, based on decreased body weight and food
consumption and histopathology of the liver and adrenal in both sexes,
the thyroid in females, and the anterior pituitary in males at the
1,500-ppm dose level. These effects were observed in both P1 and P2
generations.
6. A developmental toxicity study with rabbits given gavage doses
of 0, 5, 20, or 80 mg/kg/day during gestation days 7 through 19 with a
developmental NOEL established at 20 mg/kg/day, based on late
resorption (2 of 5 abortions at the 80 mg/kg/day dose level each showed
one incidence of late resorption). The maternal NOEL was established at
20 mg/kg/day, based on one mortality, abortions in 5 of 16 animals,
body weight loss, and liver histopathology at the 80 mg/kg/day dose
level.
7. A developmental toxicity study with rats given gavage doses of
0, 5, 20, 80, or 160 mg/kg/day on gestation days 6 through 15 with no
clinical signs of toxicity under the conditions of the study.
8. Mutagenicity tests, including gene mutation (Ames test), forward
gene mutation (CH V79 cells), structural chromosome aberration in vitro
(CHO cells), structural chromosome aberration in vivo (mouse bone
marrow cells), and UDNA synthesis (primary hepatocytes of rats), were
all negative. The results of the mutagenicity test indicate that
pronamide does not appear to be mutagenic.
The Office of Pesticide Programs' Carcinogenicity Peer Review
Committee has classified pronamide as a Group B2 carcinogen (a probable
human carcinogen), based on the findings of two types of tumors in the
rat (uncommon benign testicular interstitial cell tumors and thyroid
follicular cell adenomas) and one type (liver carcinomas) in the mouse.
The upper limit on the carcinogenic risk from dietary exposure
resulting from established uses of pronamide and the proposed use on
radicchio is estimated at 4.9 X 10-7 for the general population.
The carcinogenic risk assessment for pronamide was calculated based on
a potency estimator (Q*) of 1.54 X 10-2 (mg/kg/day)-1
and an Anticipated Residue Contribution (ARC) calculated at 0.000032
mg/kg/body weight/day.
The reference dose (RfD) is established at 0.080 mg/kg of body
weight/day. The RfD is based on an NOEL of 8.46 mg/kg/day from the rat
2-year feeding study and an uncertainty factor of 100. The ARC from
established uses and the proposed use of pronamide utilizes less than 1
percent of the RfD for the U.S. population and all subgroups of the
population currently evaluated by EPA's Dietary Risk Evaluation System.
The nature of the residue in plants is adequately understood. The
residues of concern are pronamide and its metabolites containing the
3,5-dichlorophenyl moiety. An adequate analytical method, gas
chromatography, 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 of livestock
and poultry: radicchio greens are not considered to be livestock feed
items.
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 document in the Federal Register that this rulemaking proposal
be referred to an Advisory Committee in accordance with section 408(e)
of the FFDCA.
Interested persons are invited to submit written comments on the
proposed regulation. Comments must bear a notation indicating the
document control number, [PP 0E3907/P588]. All written comments filed
in response to this petition will be available in the Public Response
and Program Resources Branch, at the address given above from 8 a.m. to
4 p.m., Monday through Friday, except legal holidays.
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: October 3, 1994.
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. 180.317, by amending paragraph (a) in the table therein
by adding and alphabetically inserting the commodity radicchio greens
(tops), to read as follows:
Sec. 180.317 3,5-Dichloro-N-(1,1-dimethyl-2-propynyl)benzamide;
tolerances for residues.
(a) * * *
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
*****
Radicchio greens (tops).................................... 2.0
*****
------------------------------------------------------------------------
* * * * *
[FR Doc. 94-26469 Filed 10-26-94; 8:45 am]
BILLING CODE 6560-50-F
