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Glyphosate - Proposed Pesticide Tolerance 5/93

40 CFR Parts 180 and 185
[PP 0F3865, PP 2F4081, FAP 2H5635/P559; FRL 4583-3]
RIN 2070-AC18
Pesticide Tolerances for Glyphosate
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
------------------------------------------------------------
SUMMARY: This document proposes tolerances and food additive
regulations for residues of the herbicide glyphosate [(N-
phosphonometyhyl)glycine].
The specific proposals are as follows: an amended tolerance
in or on the raw agricultural commodities (RACs) wheat at 5.0
parts per million (ppm), wheat straw at 85 ppm, the tree nut
crop group at 1.0 ppm, almond hulls at 25 ppm, and a food additive
regulation for wheat milling fractions (except flour) at 20
ppm. Monsanto Co. submitted petitions requesting EPA to establish
the maximum permissible residues of the herbicide in or on these
RACs and the processed human food.

DATES: Written comments, identified by the document control
number, [PP 0F3865, PP 2F4081, FAP 2H5635/P559], must be received
on or before June 4, 1993.

ADDRESSES: By mail, submit comments to: Public Docket and Freedom
of Information Section, Field Operations Division (H7506C),
Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. In person, bring comments
to: Rm. 1128, 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. 1128 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, Robert J. Taylor,
Product Manager, Registration Division (H7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 241, CM
#2, 1921 Jefferson Davis Hwy., Arlington, VA, (703)-305-6800.

SUPPLEMENTARY INFORMATION: EPA issued a notice in the Federal
Register of July 18, 1990 (55 FR 29267), announcing that the
Monsanto Co., 700 14th St., NW., Washington, DC 20005, had submitted
a petition (PP 0F3865) proposing to amend 40 CFR 180.364 by
establishing a regulation under section 408 of the Federal Food,
Drug, and Cosmetic Act (FFDCA) (21 U.S.C. 346a), to permit combined
residues of the herbicide glyphosate, [N-(phosphonomethyl)glycine]
and its metabolite aminomethylphosphonic acid resulting from
the application of the isopropylamine salt in or on the RACs
wheat grain at 4 parts per million (ppm) and wheat straw at
85 ppm. In the Federal Register of June 10, 1992 (57 FR 24645),
the Agency issued notices which announced that Monsanto Co.
had submitted PP No. 2F4081 proposing to amend 40 CFR 180.364
under sec. 408 of FFDCA by establishing a regulation to permit
the residues of glyphosate and its metabolite resulting from
the application of isopropylamine salt of glyphosate and/or
the monoammonium salt of glyphosate in or on almond hulls at
25 ppm and tree nut crops at 1.0 ppm and FAP No. 2H5635 proposing
to amend 40 CFR 185.3500 under sec. 409 of FFDCA (21 U.S.C.
348) by establishing a food additive regulation to permit the
combined residues of glyphosate and its metabolite on wheat
milling fractions (excluding flour) at 12 ppm.

   There were no comments or requests for referral to an advisory
committee received in response to these notices of filing.
   Subsequently, the petitioner amended PP 0F3865, FAP 2H5635,
and PP 2F4081 by submitting revised section Fs deleting the
metabolite from the expressions, increasing the proposed tolerances
on wheat grain to 5 ppm and wheat milling fractions (excluding
flour) to 20 ppm, and adding the monoammonium salt of glyphosate
to the wheat grain (5 ppm) and wheat straw (85 ppm) expression.
Because the increased tolerances for wheat grain at 5 ppm and
wheat milling fractions (excluding flour) to 20 ppm have not
been previously proposed, this document is being published as
a proposed rule to allow a period of 30 days for public comment.
   The data submitted in the petitions and other relevant material
have been evaluated. The glyphosate toxicological data listed
below were considered in support of these tolerances.
   1. Several acute toxicology studies placing technical-grade
glyphosate in Toxicity Category III and Toxicity Category IV.
   2. A 1-year feeding study with dogs fed dosage levels of
0, 20, 100, and 500 milligrams/kilogram/day (mg/kg/day) with
a no-observable-effect level (NOEL) of 500 mg/kg/day.
   3. A 2-year carcinogenicity study in mice fed dosage levels
of 0, 150, 750, and 4,500 mg/kg/day with no carcinogenic effect
at the highest dose tested (HDT) of 4,500 mg/kg/day.
   4. A chronic feeding/carcinogenicity study in rats fed dosage
levels of 0, 3, 10, and 31 mg/kg/day with no carcinogenic effects
observed under the conditions of the study at dose levels up
to and including 31 mg/kg/day (HDT) and a systemic NOEL of 31
mg/kg/day (HDT). Because a maximum tolerated dose (MTD) was
not reached, this study was classified as supplemental for carcinogenicity.
   5. A chronic feeding/carcinogenicity study in rats fed dosage
levels of 0, 100, 400, and 1,000 mg/kg/day with no carcinogenic
effects noted under the conditions of the study at dose levels
up to and including 1,000 mg/kg/day (HDT) and a systemic NOEL
of 400 mg/kg/day based on decreased body weight and body weight
gain in females, cataracts in males, decreased urinary pH in
males, increased relative liver weight (to body) at 12 months,
increased absolute and relative liver weight (to brain) at 24
months at 1,000 mg/kg/day (HDT).
   6. A developmental toxicity study in rats given doses of
0, 300, 1,000, and 3,500 mg/kg/day with a developmental NOEL
of 1,000 mg/kg/day based on an increase in number of litters
and fetuses with unossified sternebrae, and decrease in fetal
body weight at 3,500 mg/kg/day, and a maternal NOEL of 1,000
mg/kg/day based on decrease in body weight gain, diarrhea, soft
stools, breathing rattles, inactivity, red matter in the region
of nose, mouth, forelimbs, or dorsal head, and deaths at 3,500
mg/kg/day (HDT).
   7. A developmental toxicity study in rabbits given doses
of 0, 75, 175, and 350 mg/kg/day (HDT); a maternal NOEL of 175
mg/kg/day based on increased incidences of soft stool, diarrhea,
nasal discharge, and deaths at 350 mg/kg/day (HDT).
   8. A multigeneration reproduction study with rats fed dosage
levels of 0, 3, 10, and 30 mg/kg/day with a developmental NOEL
of 10 mg/kg/day based on increased incidence of focal tubular
dilation of the kidney (both unilateral and bilateral combined)
of male F3b pups.
   9. A two generation reproduction study with rats fed dosage
levels of 0, 100, 500, and 1,500 mg/kg/day with a developmental
NOEL of 500 mg/kg/day based on decreased pup body weight and
body weight gain on lactation days 14 and 21 at 1,500 mg/kg/day
(HDT).
   10. Mutagenicity data included chromosomal aberration in
vitro (no aberrations in Chinese hamster ovary cells were caused
with and without S9 activation); DNA repair in rat hepatocytes;
in vivo bone marrow cytogenic test in rats; rec-assay with B.
subtilis; reverse mutation test with S. typhimurium; Ames test
with S. typhimurium; and dominant-lethal mutagenicity test in
mice (all negative).
   The reference dose (RfD) based on a developmental study with
rabbits (NOEL of 175 mg/kg/ bwt/day) and using a hundred-fold
safety factor is calculated to be 2.0 mg/kg body weight/day.
The theoretical maximum residue contribution (TMRC) for published
tolerances and food and feed additive regulations is 0.011362
mg/kg bwt/day or 0.6 percent of the RfD for the overall U.S.
population. The current actions on tree nut crop group and wheat
grain and wheat milling fractions will contribute 0.000012 mg/kg/
bwt/day and 0.009217 mg/kg bwt/day, respectively, to the TMRC.
These tolerances and the food additive regulation will utilize
a total of 0.462 percent of the RfD for the overall U.S. population.
   For U.S. subgroup populations, nonnursing infants and children
1 to 6 years of age, the current action and previously established
tolerances and the food additive regulation utilize, respectively,
a total of 2.38 and 2.17 percent of the RfD, assuming that residue
levels are at the established tolerance levels and that 100
percent of the crop is treated.
   There are no desirable data lacking for this pesticide. There
are currently no actions pending against the continued registration
of this pesticide. No detectable residues of N-nitrosoglyphosate,
a contaminant of glyphosate, are expected to be present in the
commodities for which tolerances are established. The carcinogenic
potential of glyphosate was first considered by a panel, then
called the Toxicology Branch AD Hoc Committee, in 1985. The
Committee, in a consensus review dated March 4, 1985, classified
glyphosate as a Group C carcinogen based on an increased incidence
of renal tumors in male mice. The Committee also conlcluded
that dose levels tested in the 26-month rat study were not adequate
for assessment of glyphosate's carcinogenic potential in this
species. These findings, along with additional information,
including a reexamination of the kidney slides from the long-
term mouse study, were referred to the FIFRA Scientific Advisory
Panel (SAP). In its report dated February 24, 1986, SAP classified
glyphosate as a Group D Carcinogen (inadequate animal evidence
of carcinogenic potential). SAP concluded that, after adjusting
for the greater survival in the high-dose mice compared to concurrent
controls, that no statistically significant pairwise differences
existed, although the trend was significant.
   SAP determined that the carcinogenic potential of glyphosate
could not be determined from existing data and proposed that
the rat and/or mouse studies be repeated in order to classify
these equivocal findings. On reexamination of all information,
the Agency classfified glyphosate as a Group D Carcinogen and
requested that the rat study be repeated and that a decision
on the need for a repeat mouse study would be made upon completion
of review of the rat study.
   Upon receipt and review of the second rat chronic feeding/carcinogenicity
study, all toxicological findings for glyphosate were referred
to the Health Effects Division Carcinogenicity Peer Review Committee
on June 26, 1991, for discussion and evaluation of the weight
of evidence on glyphosate with particular emphasis on its carcinogenic
potential. The Peer Review Committee classified glyphosate as
a Group E (evidence of noncarcinogenicity for humans), based
upon lack of convincing carcinogenicity evidence in adequate
studies in two animal species. This classification is based
on the following findings: (1) None of the types of tumors observed
in the studies (pancreatic islet cell adenomas in male rat,
thyroid c-cell adenomas and/or carcinomas in male and female
rats, hepatocellular adenomas and carcinomas in male rats, and
renal tubular neoplasms in male mice) were determined to be
compound related; (2) glyphosate was tested up to the limit
dose on the rat and up to levels higher than the limit dose
in mice; and (3) there is no evidence of genotoxicity for glyphosate.
Accordingly, EPA concludes that glyphosate has not been "found
to induce cancer when ingested by man or animal." 21 U.S.C.
348(c)(3).
   The nature of the residue in plants is adequately understood,
adequate methodology (HPLC) is available for enforcement purposes,
and the methodology has been published in the Pesticide Analytical
Manual (PAM), Vol. II. Any secondary residues occurring in liver
and kidney of cattle, goats, horses, poultry, and sheep will
be covered by existing tolerances. The pesticide is considered
useful for the purpose for which the regulation is sought and
is capable of achieving the intended physical or technical effect.
   Based on the information cited above, the Agency has determined
that the establishment of tolerances by amending 40 CFR part
180 will protect the public health, and the establishment of
a food additive regulation by amending 40 CFR part 185 will
be safe. It is proposed, therefore, that the tolerances and
food additive regulation 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 regulations. Comments must bear a notation indicating
the document control number, [PP 0F3865, PP 2F4081, FAP 2H5635/P559].
All written comments filed in response to this petition will
be available in the Public Information Branch, at the address
given above, from 8 a.m. to 4 p.m., Monday through Friday, except
legal holidays.
   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 statment
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.

   Dated: April 22, 1993.

Douglas D. Campt,
Director, Office of Pesticide Programs.
   Therefore, it is proposed that chapter I of title 40 of the
Code of Federal
Regulations be amended as follows:

PART 180-[AMENDED]

   1. In part 180:
   a. The authority citation for part 180 continues to read
as follows:

   Authority: 21 U.S.C. 346a and 371.

   b. In . 180.364, by amending paragraph (a) in the table therein
by revising the entry "grain crops" and by adding new paragraph
(d), to read as follows:

. 180.364   Glyphosate; tolerances for residues.

   (a) * * *

--------------------------------------------------
Commodity                              Parts per
                                        million
--------------------------------------------------
*        *        *        *         *
Grain crops (except wheat).........      0.1 (N)
*        *        *        *         *
--------------------------------------------------

*     *     *     *     *
   (d) Tolerances are established for the residues of glyphosate
[N-(phosphonomethyl)glycine] resulting from the application
of the isopropylamine salt of glyphosate and/or the monoammonium
salt of glyphosate in or on the following raw agricultural commodities:

--------------------------------------------+-----------
Commodity                                   | Parts per
                                            |  million
--------------------------------------------+-----------
Almond hulls............................... |   25.0
Tree nut crop group........................ |    1.0
Wheat, grain............................... |    5.0
Wheat, straw............................... |   85.0
--------------------------------------------+-----------

PART 185-[AMENDED]

   2. In part 185:
   a. The authority citation for part 185 continues to read
as follows:

   Authority: 21 U.S.C. 348.

   b. In . 185.3500, by adding new paragraph (a)(3), to read
as follows:

. 185.3500   Glyphosate.
   (a) * * *
*     *     *     *     *
   (3) Glyphosate [N-(phosphonomethyl)glycine] resulting from
the application of the isopropylamine salt of glyphosate and
or the monoammonium salt of glyphosate for herbicidal purposes.

--------------------------------------------------+------------
                             Food                 |  Parts per
                                                  |   million
--------------------------------------------------+------------
Wheat milling fractions (excluding flour)........ |    20.0
--------------------------------------------------+------------
*     *     *     *     *
[FR Doc. 93-10577 Filed 5-4-93; 8:45 am]
BILLING CODE 6560-50-F