Pendimethalin - Proposed Tolerance 4/93
Pesticide Tolerance for Pendimethalin
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
SUMMARY: This document proposes that a tolerance be established
for residues of the herbicide pendimethalin and its metabolite
in or on the raw agricultural commodity dry bulb onions. The
proposed regulation to establish a maximum permissible level
for residues of the herbicide in or on the commodity was requested
in a petition submitted by the Interregional Research Project
No. 4 (IR-4).
DATES: Comments, identified by the document control number [1E3965/P557],
must be received on or before May 14, 1993.
ADDRESSES: By mail, submit written comments to: Public Response
and Program Resources Branch, Field Operations Division (H7506C),
Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. In person, bring comments
to: Rm. 1132, CM 1B2, 1921 Jefferson Davis Hwy., Arlington,
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
FOR FURTHER INFORMATION CONTACT: By mail: Hoyt L. Jamerson,
Emergency Response and Minor Use Section (H7505W), Registration
Division, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: No. 1, Sixth
Floor, Crystal Station 1B1, 2800 Jefferson Davis Hwy., 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 1E3965 to EPA on behalf of the Agricultural
Experiment Stations of California, Michigan, New York, Tennessee,
and Puerto Rico. This petition requested that the Administrator,
pursuant to section 408(e) of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 346a(e)) propose the establishment of a tolerance
for residues of pendimethalin [N-(1-ethylpropyl)-3,4-dimethyl-
2,6-dinitrobenzenamine] and its metabolite 4-[(1-ethylpropyl)amino]2-
methyl-3,5-dinitrobenzyl alcohol in or on the raw agricultural
commodity dry bulb onions at 0.1 part per million (ppm).
The 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 2-year feeding study in dogs with a no-observed-effect-
level (NOEL) of 12.5 milligrams (mg)/kilogram (kg)/day based
on an increase in serum alkaline phosphatase and increased liver
weight and hepatic lesions.
2. A two-generation reproduction study in rats fed diets
containing 500, 2,500, or 5,000 ppm (equivalent to 25, 125,
or 250 mg/kg/day in males, and 35, 175, or 350 mg/kg/day in
females) with a reproductive NOEL of 500 ppm based on decreased
pup weight and a parental NOEL of 500 ppm based on a decrease
in body weight gain and food consumption.
3. A developmental toxicity study in rabbits given gavage
dosages of 1.5, 30, and 60 mg/kg/day was negative for developmental
4. A developmental toxicity study in rats given gavage dosages
of 125, 250, and 500 mg/kg/day was negative for developmental
5. Mutagenicity studies including gene mutation (positive
results in strains TA1538 and TA98 (frame-shift mutations) with
metabolic (S9) activation); structural chromosomal aberrations
(negative results with in vitro cytogenetic analysis using Chinese
hamster ovary cells, with and without activation); and other
genotoxic effects (negative results in DNA damage/repair test).
6. An 18-month carcinogenicity study in mice fed diets containing
0, 100, 500, or 5,000 ppm with no increases in neoplasms (tumors)
observed under the conditions of the study.
7. A 2-year chronic feeding/carcinogenicity study in rats
fed diets containing 0, 100, 500, or 5,000 ppm (approximately
0, 5, 25, or 250 mg/kg/day) with a NOEL for systemic effects
of 100 ppm (5 mg/kg/day) based on pigmentation of the thyroid
follicular cells in male and female rats. Pendimethalin was
associated with a statistically significant increased trend
in thyroid follicular cell adenomas (benign tumors) and a significant
increase using pair wise comparisons between the controls and
the groups fed diets containing 5,000 ppm. There was no statistically
significant increase in carcinomas at any feeding level tested.
8. A second 2-year chronic feeding/carcinogenicity study
in male rats fed diets containing 0, 1,250, 2,500, 3,750 or
5,000 ppm (approximately 0, 51, 103, 154 or 213 mg/kg/day) with
a NOEL of less than 1,250 ppm for systemic effects based on
nonneoplastic thyroid follicular cell changes and increased
liver weight. Pendimethalin was associated with a statistically
significant increased trend and pairwise comparison at 5,000
ppm for follicular cell adenomas of the thyroid.
Based on a weight-of-evidence determination, the Agency has
classified pendimethalin as a Group C carcinogen (possible human
carcinogen with limited evidence of carcinogenicity in animals).
This decision, which is in accordance with proposed Agency guidelines
published in the Federal Register of November 23, 1984 (49 FR
46294), was based on the following considerations:
1. There was positive evidence for benign thyroid tumors
in rats at the high dose feeding level (5,000 ppm).
2. The chemical was not associated with increases in tumors
when fed to mice at dose levels ranging from 100 to 5,000 ppm.
3. Pendimethalin induces gene mutation, but not chromosomal
aberrations or DNA damage/repair.
4. Structurally related compounds showed evidence of tumorigenic
activity; the thyroid follicular cell tumor response is also
seen in two other members of this class of compounds. Differences
in the chemical structures of pendimethalin and the related
compounds that show evidence of tumorigenic activity limit the
usefulness of structure-activity comparisons for pendimethalin.
Quantification of carcinogenic risk was considered inappropriate
for pendimethalin based on the uncertain significance of an
increased occurrence of benign thyroid tumors at the high dose
level (5,000 ppm) in rats and the lack of other conclusive evidence
of carcinogenicity. The Agency believes that the data do not
indicate a likelihood that this chemical poses a significant
human carcinogenic risk.
For purpose of risk characterization the Reference Dose (RfD)
is used for quantification of human risk resulting from dietary
exposure to residues of pendimethalin. The RfD is established
at 0.4 mg/kg of body weight (bwt)/day based on a NOEL of 12.5
mg/kg bwt/day from the 2-year feeding study in dogs and an uncertainty
factor of 300. The theoretical maximum residue contribution
(TMRC) from published and proposed uses of pendimethalin utilize
less than 1 percent of the RfD for the general population, or
2.0 percent of the RfD for the subgroup most highly exposed
(children aged one through six years).
The nature of the residue is adequately understood for the
purpose of the proposed tolerance, and an adequate analytical
method, gas chromatography, is available for enforcement purposes.
An analytical method for enforcing this tolerance has been published
in the Pesticide Analytical Manual (PAM), Vol. II. No secondary
residues in meat, milk, poultry, or eggs are expected since
dry bulb onions are not considered a livestock feed commodity.
There are presently no actions pending against the continued
registration of this chemical.
Based on the above information considered by the Agency the
tolerance established by amending 40 CFR 180.361 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 Federal Food, Drug,
and Cosmetic Act.
Interested persons are invited to submit written comments
on the proposed regulation. Comments must bear a notation indicating
the document control number, [PP 1E3965/P557]. 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
The Office of Management and Budget has exempted this rule
from the requirements of section 3 of Executive Order 12291.
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
Administrative practice and procedure, Agricultural commodities,
Pesticides and pests, Reporting and recordkeeping requirements.
Dated: March 25, 1993.
Lawrence E. Culleen,
Acting Director, Registration Division, Office of Pesticide
Therefore, it is proposed that 40 CFR part 180 be amended
1. The authority citation for part 180 continues to read
Authority: 21 U.S.C. 346a and 371.
2. In 1A180.361, paragraph (a) table is amended by adding
and alphabetically inserting the raw agricultural commodity
dry bulb onions, to read as follows:
1A180.361 Pendimethalin; tolerances for residues.
(a) * * *
Commodity Parts per
* * * * *
Onions, dry bulb............... 0.1
* * * * *
* * * * *
[FR Doc. 93-8570 Filed 4-13-93; 8:45 am]
BILLING CODE 6560-50-F