Glyphosate - Proposed Pesticide Tolerance 7/95
[Federal Register: July 7, 1995 (Volume 60, Number 130)] [Proposed Rules]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4E4404/P618; FRL-4962-1]
Glyphosate; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
SUMMARY: EPA proposes to establish pesticide tolerances for residues of
glyphosate in or on the raw agricultural commodities peppermint and
spearmint. The Interregional Research Project No. 4 (IR-4) requested in a
petition submitted to EPA pursuant to the Federal Food, Drug and Cosmetic
Act (FFDCA) this proposed regulation to establish maximum permissible
levels for residues of the pesticide in or on the commodities.
DATES: Comments, identified by the document control number [PP 4E4404/
P618], must be received on or before August 7, 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. 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.
Comments and data may also be submitted electronically by sending
electronic mail (e-mail) to: email@example.com. 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 4E4404/P618]. Electronic comments on this proposed rule may be
filed online at many Federal Depository Libraries. Additional information
on electronic submissions can be found below in this document.
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; e-mail: firstname.lastname@example.org.
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)
4E4404 to EPA on behalf of the Agricultural Experiment Station of
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 180.364(d) by establishing tolerances for
residues of glyphosate (N-(phosphonomethyl)glycine) resulting from the
application of the isopropylamine salt of glyphosate, in or on the raw
agricultural commodities peppermint and spearmint at 200 parts per million
The scientific data submitted in the petition and other relevant material
have been evaluated. The toxicological data considered in support of the
proposed tolerances include:
1. Several acute toxicology studies placing technical-grade glyphosate in
Toxicity Category III (acute oral and dermal).
2. A 1-year chronic feeding study in dogs fed glyphosate in gelatin
capsules containing 0, 20, 100, or 500 milligrams (mg)/kilogram (kg)/ day
with a no-observed-effect level (NOEL) established at 500 mg/kg/ day. There
were no toxic effects observed under the conditions of the study.
3. A 26-month chronic feeding carcinogenicity study in rats fed diets
containing 0, 30, 100, or 300 ppm glyphosate (equivalent to 0/0, 3/3,
10/11, 31/34 mg/kg/day for males/females) with a NOEL for systemic toxicity
established at 300 ppm. There were no treatment related systemic effects
observed under the conditions of the study. The following findings were
observed, however, in the high-dose groups when compared to the concurrent
controls: (1) increased incidence of thyroid C-cell carcinomas in females;
and (2) increased incidence of interstitial cell (Leydig cell) testicular
tumors in males. EPA concluded that these neoplasms were not treatment
related, and glyphosate was not considered to be carcinogenic in this study
because the incidence of thyroid carcinomas was not statistically
significant and the incidence of testicular tumors was within the
historical incidence. This study is not considered an acceptable
carcinogenic study since the feeding levels were not high enough to assess
the carcinogenicity of glyphosate.
4. A 2-year chronic feeding/carcinogenicity study in rats fed diets
containing 0, 2,000, 8,000, or 20,000 ppm (equivalent to 0/0, 89/113,
362/457, or 940/1,183 mg/kg/day for males/females) with a NOEL established
at 8,000 ppm. Treatment-related systemic effects, which were only observed
in the high-dose group, included decreased body weight gains in females,
increased incidence of cataracts and lens abnormalities, decreased urinary
pH, increased absolute liver weight, and increased liver/brain weight ratio
in males. The study also showed slightly increased incidence of (1)
pancreatic islet cell adenomas in the low-dose and high-dose males; (2)
hepatocellular (liver) adenomas in the low-dose and high-dose males; and
(3) thyroid C-cells adenomas in the mid-dose and high-dose male and
females. EPA concluded that these adenomas were not treatment related, and
glyphosate was not considered to be carcinogenic in this study.
5. A carcinogenicity study in mice fed diets containing 0, 150, 750, or
4,500 mg/kg/day for 18 months with a systemic NOEL established at 750
mg/kg/day. The following findings were observed in the high-dose group: (1)
decreased body weight gain in males and females; (2) increased incidence of
hepatocellular hypertrophy, hepatocellular necrosis and interstitial
nephritis in males; (3) increased incidence of proximal tubule epithelial
basophilia and hypertrophy in females; and (4) slightly increased incidence
of renal tubular adenomas in males. EPA concluded that the occurrence of
the renal tubular adenomas in male mice was spontaneous rather than
compound induced because the incidence of these in males was not
statistically significant when compared with the concurrent controls.
Glyphosate was not considered to be carcinogenic in this study.
6. A developmental toxicity study in rats given gavage doses of 0, 300,
1,000, or 3,500 mg/kg/day of glyphosate during days 6 through 19 of
gestation with a NOEL for developmental toxicity established at 1,000
mg/kg/day. There was an increase in the number of litters and fetuses with
unossified sternebrae and a decrease in the fetal body weight at the 3,500-
7. A developmental toxicity study in rabbits given gavage doses of 0, 75,
175, or 350 mg/kg/day of glyphosate during days 6 through 27 of gestation.
Developmental toxicity was not observed at any dose tested. The NOEL for
developmental toxicity was established at 175 mg/kg/day. Due to high
maternal mortality (10 of 16 females rabbits died) at the 350-mg/kg/day
dose level, too few liters were available to adequately assess
developmental toxicity at the high dose.
8. A three-generation reproductive study in rats fed diets containing 0, 3,
10, or 30 mg/kg/day with a systemic and reproductive NOEL of 30 mg/kg/day
and a developmental NOEL of 10 mg/kg/day. The only effect observed was an
increased incidence of focal tubular dilation of the kidney (both
unilateral and bilateral combined) in the high-dose male F3b pups.
9. A two-generation reproductive study in rats fed diets containing 0, 100,
500, or 1,500 mg/kg/day of glyphosate with systemic and developmental
NOEL's of 500 mg/kg/day and a reproductive NOEL of 1,500 mg/kg/day.
Treatment-related effects, which were observed only in the high-dose group,
include soft stools in the F0 and F1 males and females, decreased food
consumption and body weight gain of the F0 and F1 males and females; and
decreased body weight gain of the F1a, F2a, and F2b male and female pups
during the second and third week of lactation.
10. A battery of mutagenicity studies including: gene mutation assay (Ames
Test and assay in mammalian cells), negative; structural chromosomal
aberration assay (cytogenic in vivo), negative; and other genotoxicity
assays (rec-assay using Bacillus subtilis and reverse mutation assay using
Escherichia coli), negative.
11. Metabolism studies in rats show that glyphosate is excreted in the
urine and feces as the parent compound. Aminomethylphosphonic acid was the
only metabolite excreted. Less than 1.0 percent of the absorbed dose
remained in the tissues and organs, primarily in the bone tissue.
The dietary risk assessment for glyphosate indicates that there is minimal
risk from established tolerances and the proposed tolerances for peppermint
and spearmint. A cancer risk assessment is not appropriate for glyphosate
since the pesticide is assigned to "Group E" (no evidence of
carcinogenicity) of EPA's cancer classification system. Dietary risk
assessments for the pesticide were conducted using the Reference Dose (RfD)
to assess chronic exposure.
The RfD is calculated at 2 mg/kg/ of body weight/day based on a NOEL of 175
mg/kg/day from the rabbit developmental toxicity study and an uncertainty
factor of 100. The theoretical maximum residue contribution (TMRC) from
existing tolerances and the proposed tolerances utilizes l percent of the
RfD for the general population, or 3 percent of the RfD for non-nursing
infants less than 1 year old (the subgroup population most highly exposed).
The nature of the residue is adequately understood in plants and animals.
An adequate analytical method utilizing highpressure liquid 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 peppermint and spearmint are not considered livestock feed
There are currently no actions pending against the continued registration
of this chemical. EPA concludes that all uses of currently registered
products containing the isopropylamine and sodium salts of glyphosate, when
used in accordance with the labeling specified in the Reregistration
Eligibility Document (RED), issued September 1993, will not pose
unreasonable risks of adverse effects to humans or the environment and are
eligible for reregistration.
Based on the information and data considered, the Agency has determined
that the tolerances established by amending 40 CFR 180.364 would protect
the public health. Therefore, it is proposed that the tolerances 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
4E4404/P618] (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
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
Dated: June 23, 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. 180.364, paragraph (d) is amended by adding and alphabetically
inserting the entries for peppermint and spearmint, to read as follows:
Sec. 180.364 Glyphosate; tolerances for residues.
* * * * *
(d) * * *
* * * * *
* * * * *
[FR Doc. 95-16753 Filed 7-6-95; 8:45 am] BILLING CODE 6560-50-F