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Glyphosate (Roundup) - Pesticide Petition Filing 2/98

[Federal Register: February 20, 1998 (Volume 63, Number 34)]
[Notices]
[Page 8635-8644]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20fe98-60]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-791; FRL-5768-9]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various agricultural commodities.

DATES: Comments, identified by the docket control number PF-791, must
be received on or before March 23, 1998.

ADDRESSES: By mail submit written comments to: Information and Records
Integrity Branch, Public Information and Services Divison (7502C),
Office of Pesticides Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119,
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following
the instructions under "SUPPLEMENTARY INFORMATION." No confidential
business information should be submitted through e-mail.
    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). 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. 119 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: James A. Tompkins, Product
Manager (PM) 25, Registration Division, (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 239, 1921 Jefferson
Davis Hwy., Arlington, VA., (703) 305-5697; e-mail:
Tompkins.jim@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various raw
agricultural commodities under section 408 of the Federal Food, Drug,
and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these
petitions contain data or information regarding the elements set forth
in section 408(d)(2); however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
supports grantinig of the petition. Additional data may be needed
before EPA rules on the petition.
    The official record for this notice, as well as the public version,
has been established for this notice of filing under docket control
number PF-791 (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 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The
official record is located at the address in "ADDRESSES" at the
beginning of this document.
    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. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 file format or
ASCII file format. All comments and data in electronic form must be
identified by the docket control number (insert docket number) and
appropriate petition number. Electronic comments on this notice may be
filed online at many Federal Depository Libraries.
    Authority: 21 U.S.C. 346a.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and

[[Page 8636]]

pests, Reporting and recordkeeping requirements.

    Dated: February 12, 1998.

Donald R. Stubbs,
Acting Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Below summaries of the pesticide petitions are printed. The
summaries of the petitions were prepared by the petitioners. The
petition summary announces the availability of a description of the
analytical methods available to EPA for the detection and measurement
of the pesticide chemical residues or an explanation of why no such
method is needed.

3. Monsanto Company

PP 2E4118 and 7F4886

    EPA has received a pesticide petitions (PP 2E4118 and 7F4886) from
Monsanto Company, 700 14th St.,NW., Suite 1100, Washington, D.C. 20005,
proposing pursuant to section 408(d) of the Federal Food, Drug and
Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish
an exemption from the requirement of a tolerance for glyphosate [(N-
phosphonomethyl) glycine] in or on the imported raw agricultural
commodities barley grain at 20 parts per million (ppm); barley, bran
and pearled barley at 60 ppm; cereal grains group (except wheat, corn,
oats, grain sorghum, and barley at 0.1 ppm; canola, seed at 10 ppm;
canola, meal at 25 ppm; legume vegetables (succulent or dried) group
(except soybeans) at 5 ppm. (PP 2E4118) and in or on the raw
agricultural commodities beets, sugar, tops (leaves) at 10 ppm; beets,
sugar, root at 10 ppm; and beets, sugar, pulp, dried at 25 ppm (PP
7F4886). EPA has determined that the petition contains data or
information regarding the elements set forth in section 408(d)(2) of
the FFDCA; however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of
the petition. Additional data may be needed before EPA rules on the
petition.

A. Residue Chemistry

    1. Plant metabolism. The nature of the residue in plants is
adequately understood and consists of the parent, glyphosate and its
metabolite AMPA (aminomethyl-phosphonic acid). Only glyphosate parent
is to be regulated in plant and animal commodities since the metabolite
AMPA is not of toxicological concern in food.
    2. Analytical method. Adequate methodology High Pressure Liquid
Chromatograpy (HPLC) with fluorometric detection is available for
enforcement purposes, and the methodology has been published in the
Pesticide Analytical Manual (PAM), Vol. II. This method has a limit of
detection (0.05 ppm) that allows monitoring of food with residues at or
above the levels set in these tolerances.
    3. Magnitude of residues. The submitted residue data adequately
support the proposed tolerances on Barley, grain (20 ppm); Barley, bran
and pearled barley (60 ppm); Canola, seed (10 ppm); Canola, meal (25
ppm); and Legume vegetables (succulent or dried) group (except
soybeans) (5 ppm), Sugar beet roots at 10 ppm, Sugar beet tops at 10
ppm and Sugar beet dried pulp at 25 ppm. Any secondary residues
occurring in liver or kidney of cattle, goats, horses, and sheep and
liver and kidney of poultry will be covered by existing tolerances.

B. Toxicological Profile

    1. Acute toxicity. A rat acute oral study with a combined
LD50 of > 5000 mg/kg.
    A rabbit acute dermal LD50 of > 5000 mg/kg.
    A primary eye irritation study in the rabbit which showed severe
irritation for glyphosate acid. However, glyphosate is normally
formulated as one of several salts and eye irritation studies on the
salts showed essentially no irritation.
    A primary dermal irritation study which showed essentially no
irritation.
    A primary dermal sensitization study which showed no sensitization.
    2. Genotoxicty. A number of mutagenicity studies were conducted and
were all negative. These studies included: chromosomal aberration in
vitro (no aberrations in Chinese hamster ovary cells were caused with
or without S9 activation); DNA repair in rat hepatocyte; 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.
    3. Reproductive and developmental toxicity. An oral developmental
toxicity study with rats given doses of 0, 300, 1,000 and 3,500 mg/kg/
day with a maternal no observable effect level (NOEL) of 1,000 mg/kg/
day based on clinical signs of toxicity, body weight effects and
mortality, and a fetal NOEL of 1,000 mg/kg/day based on reduced body
weights and delayed sternebrae maturation at the highest dose tested of
3,500 mg/kg/day.
    An oral developmental toxicity study with rabbits given doses of 0,
75, 175 and 350 mg/kg/day with a maternal of NOEL of 175 mg/kg/day
based on clinical signs of toxicity and mortality, and a fetal NOEL of
350 mg/kg/day based on no developmental toxicity at any dose tested.
    A 3-generation reproduction study with rats fed dosage levels of 0,
3, 10 and 30 mg/kg/day with a NOEL for systemic and reproductive/
developmental parameters of 30 mg/kg/day based on no adverse effects
noted at any dose level.
    A 2-generation reproduction study with rats fed dosage levels of 0,
100, 500 and 1,500 mg/kg/day with a NOEL for systemic and developmental
parameters of 500 mg/kg/day based on body weight effects, clinical
signs of toxicity in adult animals and decreased pup bodyweights, and a
reproductive NOEL of 1,500 mg/kg/day.
    4. Subchronic toxicity. A 90-day feeding study in rats fed dosage
levels of 0, 1,000, 5,000 and 20,000 ppm with a NOEL of 20,000 ppm
based on no effects even at the highest dose tested.
    A 90-day feeding study in mice fed dosage levels of 0, 5,000,
10,000 and 50,000 with a NOEL of 10,000 ppm based on body weight
effects at the high dose.
    A 90-day feeding study in dogs given glyphosate, via capsule, at
doses of 0, 200, 600 and 2,000 mg/kg/day with a NOEL of 2,000 mg/kg/day
based on no effects even at the highest dose tested.
    5. Chronic toxicity. A 12-month oral study in dogs given
glyphosate, via capsule, at doses of 0, 20, 100 and 500 mg/kg/day with
a NOEL of 500 mg/kg/day based on no adverse effects at any dose level.
    A 26-month chronic/feeding oncogenicity study with rats fed dosage
levels of 0, 3, 10 and 31 mg/kg/day (males) and 0, 3, 11 and 34 mg/kg/
day (females) with a systemic NOEL of 31 mg/kg/day (males) and 34 mg/
kg/day (females) based on no carcinogenic or other adverse effects at
any dose level.
    A 24-month chronic/feeding oncogenicity study with rats fed dosage
levels of 0, 89, 362 and 940 mg/kg/day (males) and 0, 113, 457 and
1,183 mg/kg/day (females) with a systemic NOEL of 362 mg/kg/day based
on body weight

[[Page 8643]]

effects in the female and eye effects in males. There was no
carcinogenic response at any dose level.

    6. Carcinogenicity. A mouse oncogenicity study with mice fed dosage
levels of 0, 150, 750 and 4,500 mg/kg/day with a NOEL of 750 mg/kg/day
based on body weight effects and microscopic liver changes at the high
dose. There was no carcinogenic effect at the highest dose tested of
4,500 mg/kg/day.
    Glyphosate is classified as a Group E (evidence of non-
carcinogenicity 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) There were
no tumor findings in the chronic testing that 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.
    7. Animal metabolism. The nature of the residue in animals is
adequately understood and consists of the parent, glyphosate and its
metabolite AMPA (aminomethyl-phosphonic acid).
    8. Metabolite toxicology. Only glyphosate parent is to be regulated
in plant and animal commodities since the metabolite AMPA is not of
toxicological concern in food.
    9. Endocrine disruption. The toxicity studies required by EPA for
the registration of pesticides measure numerous endpoints with
sufficient sensitivity to detect potential endocrine-modulating
activity. No effects have been identified in subchronic, chronic or
developmental toxicity studies to indicate any endocrine-modulating
activity by glyphosate. In addition, negative results were obtained
when glyphosate was tested in a dominant-lethal mutation assay. While
this assay was designed as a genetic toxicity test, agents that can
affect male reproduction function will also cause effects in this
assay. More importantly, the multi-generation reproduction study in
rodents is a complex study design which measures a broad range of
endpoints in the reproductive system and in developing offspring that
are sensitive to alterations by chemical agents. Glyphosate has been
tested in two separate multi-generation studies and each time the
results demonstrated that glyphosate is not a reproductive toxin.

C. Aggregate Exposure

    1. Dietary exposure  -- Food. For purposes of assessing the
potential exposure under these tolerances, dietary exposure was
estimated based on the Theoretical Maximum Residue Contribution (TMRC)
from the all present tolerances for glyphosate and the additional
exposure that could result if the proposed tolerances are established
on barley grain at 20 ppm, barley bran and pearled barley at 60 ppm,
canola seed at 10 ppm, canola meal at 25 ppm, legume vegetables
(succulent or dried) group (except soybeans) at 5 ppm, sugar beet roots
at 10 ppm, sugar beet tops at 10 ppm and sugar beet dried pulp at 25
ppm. The TMRC is obtained by multiplying the tolerance level residue
for each food commodity by the consumption data which estimates the
amount of those products eaten by various population subgroups. In
conducting this exposure assessment, very conservative assumptions were
made -- 100% of these crops will contain glyphosate residues and those
residues would be at the level of the tolerance -- which result in an
overestimate of human exposure. Thus, in making a safety determination
for these tolerances, EPA is taking into account this conservative
exposure assessment.
    Secondary residues in animal commodities may occur from these uses
through the feeding of barley grain and canola meal to livestock. Since
these proposed tolerances do not arise from changes in U.S.
registrations involving the use of glyphosate herbicides on barley,
canola, or legume vegetables, it has been concluded that livestock feed
items derived from these crops are not likely to enter channels of
trade in the United States. Based on these considerations and the
results of animal feeding studies and the amount of glyphosate residues
expected in animal feeds, EPA has concluded that there is no reasonable
expectation that such secondary residues of glyphosate will exceed
existing tolerances in edible animal products.
    2. Drinking water. In examining aggregate exposure, FQPA directs
EPA to consider available information concerning exposures from the
pesticide residue via drinking water. The lifetime health advisory and
maximum contaminant level (MCL), for glyphosate are both 700 parts per
billion in the EPA Office of Drinking Water`s "Drinking Water Health
Advisory; Pesticides." The MCL represents the level at which no known
or anticipated adverse health effects will occur, allowing for an
adequate margin of safety, and is based on the reference dose (RfD).
Environmental Fate data for glyphosate indicate little potential for
the chemical to migrate to drinking. Glyphosate is not highly mobile
and not persistent in a soil or water environment. Because the Agency
lacks sufficient water-related exposure data to complete a
comprehensive drinking water risk assessment for many pesticides, EPA
has commenced and nearly completed a process to identify a reasonable
yet conservative bounding figure for the potential contribution of
water related exposures to the aggregate risk posed by a pesticide. In
developing the bounding figure, EPA estimated residue levels in water
for a number of specific pesticides using various data sources. The
Agency then applied the estimated residue levels, in conjunction with
appropriate toxicological endpoints (RfDs or acute dietary NOELs) and
assumptions about body weight and consumption, to calculate, for each
pesticide, the increment of aggregate risk contributed by consumption
of contaminated water. While EPA has not yet pinpointed the appropriate
bounding figure for consumption of contaminated water, the ranges the
Agency is continuing to examine are all below the level that would
cause glyphosate to exceed the RfD if the tolerances being considered
in this document were granted. The Agency has therefore concluded that
the potential exposures associated with glyphosate in water, even at
higher levels the Agency may consider a conservative upper bound, would
not prevent the Agency from determining that there is a reasonable
certainty of no harm if the tolerance is granted.
    3. Non-dietary exposure. Glyphosate is registered for use on non-
food sites such as around ornamental, shade trees, shrubs, walks,
driveways, flowerbeds, home lawns, farmsteads including building
foundations, along and in fences, in dry ditches and canals, along
ditchbanks, farm roads, shelterbelts, forestry, Christmas trees, and
industrial sites and other non-crop or industrial areas such as
airports, lumber yards, manufacturing sites, utility substations,
parking areas, petroleum tank farms, and pumping station.
    Margins of Exposure (MOEs) are determined for non-dietary exposure
based on toxicological endpoints and measured or estimated exposures.
Since glyphosate is a class E chemical (evidence of non-carcinogenicity
for humans), the 21 day dermal study lacked any observable effects at
the limit dose, and no adverse effects were observed in developmental
toxicity studies in rats up to 1,000 mg/kg/day and rabbits up to 175
mg/kg/day, no toxicological endpoints are applicable. Because available
data indicated no evidence of significant toxicity via the dermal or
inhalations routes, MOEs were not calculated and risk

[[Page 8644]]

assessments are not required for non-occupational (residential uses).

D. Cumulative Effects

    EPA does not have, at this time, available data to determine
whether glyphosate has a common mechanism of toxicity with other
substances or how to include it in a cumulative risk assessment. Unlike
other pesticides for which EPA has followed a cumulative risk approach
based on common mechanism of toxicity, glyphosate does not produce a
toxic metabolite which is common to other substances. For the purposes
of this tolerance action, therefore EPA has assumed that glyphosate
does not have a common mechanism of toxicity with other substances. A
condition of the registrations associated with these tolerances will be
that the registrant will provide common mechanism data in a timely
manner when and if the Agency asks for it. After EPA develops
methodologies for more fully applying common mechanism of toxicity
issues to risk assessments, the Agency will develop a process to
reexamine those tolerance decisions made earlier.

E. Safety Determination

    1. U.S. population --i. Acute dietary exposure. Based on the
available acute toxicity data, glyphosate does not pose any acute
dietary risks, and an acute dietary risk assessment is not required.
    ii. Chronic dietary exposure. Using the TAS Exposure 1 software and
1977-78 consumption data, a chronic dietary exposure estimate was based
on 100% of the crops treated and all residues at tolerance levels to
provide the TMRC. Based this assessment the combined new proposed
tolerances contribute dietary exposure equal to 0.36% of the RfD for
U.S. population and 0.69% of the RfD for non- nursing infants under 1
year old. Total estimated dietary exposure from glyphosate residues in
food, taking into account both existing and these proposed uses will be
1.4% of the RfD for the overall U.S. population and 3.1% of the RfD for
non- nursing infants, the most highly exposed population subgroup. An
additional risk assessment for residential uses was not required
because of no evidence of significant toxicology via dermal or
inhalation routes. Even though an appropriate bounding figure for
consumption of contaminated water has not been determined, the ranges
being examine are all below the level that would cause glyphosate to
exceed the RfD. Generally there is no concern for exposures below 100
percent of the RfD. Therefore, based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, there is reasonable certainty that no harm will occur from
aggregate exposure to glyphosate.
    2. Infants and children. FFCDA section 408 provides that an
additional tenfold margin of exposure (safety) for infants and children
in the case of threshold effects to account for pre- and post-natal
toxicity and the completeness of the database unless it is determined
that a different margin of exposure (safety) will be safe for infants
and children. Monsanto believes that reliable data support using the
standard margin of exposure (usually 100 x  for combined inter- and
intra-species variability) without the additional tenfold margin of
exposure when a complete data base under existing guidelines exists and
when the nature of the findings from these studies do not raise
concerns regarding the adequacy of the standard margin of exposure.
    The toxicological database for evaluating pre- and post-natal
toxicity for glyphosate is considered to be complete at this time. Risk
to infants and children for glyphosate was determined by the use of two
developmental toxicity studies in rats and rabbits and a two-generation
reproduction study in rats. The developmental toxicity studies
evaluates the potential for adverse effects on the developing organism
resulting from exposure during prenatal development. The reproduction
study provides information relating to effects from exposure to the
chemical on the reproductive capability of both (mating) parents and on
systemic toxicity, in addition to information on prenatal development.
The results of these studies indicate that glyphosate does not produce
birth defects and is not a reproductive toxin.
    In the rabbits, no developmental toxicity was observed at the
highest dose tested (HDT) where significant maternal toxicity occurred
(death and clinical signs at 350 mg/kg/day, highest dose tested HDT).
Because no developmental toxicity was observed at any dose level, the
developmental NOEL is considered to be 350 mg/kg/day. In the rat
developmental toxicity study, severe maternal (systemic) and
developmental toxicity was noted at 3,500 mg/kg/ day HDT. The HDT in
this study was 3.5 times higher than the limit dose that is currently
required by the guidelines. The maternal and developmental (pup) NOEL
was 1,000 mg/kg/day. No effects on reproductive parameters were
observed.
    In the rat 2-generation reproduction study, parental toxicity was
observed at 1,500 mg/kg/day as soft stools, decreased food consumption
and body weight gain; therefore, the systemic NOEL is considered to be
500 mg/kg/day. Developmental (pup) toxicity was also only exhibited at
1,500 mg/kg/day as decreased body weight gain of the F1a,
F2a, and F2b male and female pups during the
second and third weeks of lactation. Glyphosate did not affect the
ability of rats to mate, conceive, carry or deliver normal offspring at
any dose level.
    The RfD is based on the NOEL for maternal toxicity in the rabbit
developmental study. No developmental effects were noted in the study.
In the rat developmental study, effects were noted only at doses 20-
fold higher than the NOEL used for the RfD. No pre- or post-natal
effects were seen in any study in the absence of maternal toxicity. In
the rat reproduction study, developmental effects were noted at doses 5
times higher than the NOEL used for the RfD. The Agency does not
believe the effects seen in these studies are of such concern to
require an additional safety factor. Accordingly, the Agency believes
the RfD has an adequate margin of protection for infants and children.
The dietary exposure from current and proposed uses of glyphosate
ranges from 1% of the RfD for nursing infants (less than 1 year old) to
3% for non-nursing infants and children 1 to 6 years old. Monsanto has
concluded that there is reasonable certainty that no harm will occur to
infants and children from aggregate exposure to glyphosate.

F. International Tolerances

    Codex MRLs have been established for residues of glyphosate in or
on Barley Grain at 20 ppm, Dry Peas at 5 ppm, Dry Beans at 2 ppm, and
Rape (Canola) Seed at 10 ppm. The proposed tolerances will achieve
harmonization with these existing MRLs. The increase in U.S. tolerances
on legume vegetables up to 5 ppm was recommended in 1993 in the
glyphosate Reregistration Eligibility Decision.
    The proposed U. S. tolerances are also consistent with the MRLs
presently established for these commodities by other trade partner
countries such as Canada, the European Union, and Japan.

[FR Doc. 98-4187 Filed 2-19-98; 8:45 am]
BILLING CODE 6560-50-F