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Glyphosate - Tolerance Petition 12/96

[Federal Register: December 24, 1996 (Volume 61, Number 248)] [Notices]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-679; FRL-5576-6]
Monsanto; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of Filing.
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SUMMARY: This notice is a summary of the pesticide petitions which proposes to
establish time-limited tolerances for residues of the herbicide glyphosate [N-
phosphonomethyl)glycine] in or on the raw agricultural commodities (RACs)
field corn grain at 1.0 parts per million (ppm), field corn forage at 1.0 ppm,
field corn fodder at 100 ppm, aspirated grain fractions at 200 ppm, grain
sorghum at 15 ppm, grain sorghum fodder at 40 ppm, and oats at 20 ppm. The
residues from treatment of field corn include residues from field corn
varieties which have been genetically modified to be tolerant of glyphosate.
Because additional time is needed for the petitioner to submit additional
details on residue and processing data, the Agency is proposing to grant these
tolerances with a 3-year expiration date. Monsanto Company requested these
tolerances in petitions submitted to EPA pursuant to the Federal Food, Drug,
and Cosmetic Act (FFDCA). A summary of the petition prepared by Monsanto is
being included in this notice.

DATES: Comments, identified by the docket control numbers [PF-679] must be
received on or before January 23, 1997.

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
Highway, Arlington, VA 22202. Comments and data may also be submitted
electronically by sending electronic mail (e-mail) to: 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.

Comments and data will also be accepted on disks in Word Perfect 5.1 file
format or ASCII file format. All comments and data in electronic form must be
identified by the Docket number [PF-679]. Electronic comments on this notice
may be filed online at many Federal Depository Libraries. Additional
information on electronic submissions can be found below in this document.

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. 1132 at
the address given above, from 8 a.m. to 4:30 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Robert J. Taylor, Product Manager
(PM) 23, Registration Division, (7505C), 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 Highway,
Arlington, VA 22202, 703-305-6027, e-mail: taylor.robert@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: Pursuant to section 408(d) of the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. section 346 a(d), EPA has received
several pesticide petitions (PP 8F3672, PP 8F3673, PP 6E4645 and PP 5F4555)
from Monsanto Company, 700 14th St., NW., Suite 1100, Washington, DC 20005.
These petitions propose amending 40 CFR part 180.364 by establishing a
regulation to permit residues of the herbicide glyphosate [N-
(phosphonomethyl)glycine], resulting from the application of the
isopropylamine salt and/or the monoammonium salt of glyphosate in or on the
raw agricultural commodities (RACs) field corn grain at 1.0 parts per million
(ppm), field corn forage at 1.0 ppm, field corn fodder at 100 ppm, aspirated
grain fractions at 200 ppm, grain sorghum at 15 ppm, grain sorghum fodder at
40 ppm, and oats at 20 ppm. PP 5F4555 specifically relates to field corn which
has been genetically modified to be tolerant to glyphosate.

As required by section 408(d) of the FFDCA, as recently amended by the Food
Quality Protection Act, Monsanto included in the petition a summary of the
petition and authorization for the summary to be published in the Federal
Register in a notice of receipt of the petition. The summary represents the
views of Monsanto; EPA is in the process of evaluating the petition. As
required by section 408(d)(3), EPA is including the summary as a part of this
notice of filing. EPA has made minor edits to the summary for the purpose of
clarity.

I. Monsanto Petition Summary

1. Glyphosate uses. Glyphosate is a postemergent, systemic herbicide with no
residual soil activity. It is generally non-selective and provides broad
spectrum control of many annual weeds, perennial weeds, woody brush and trees.
Glyphosate is registered for a variety of agricultural uses, including
preplant, preharvest, in-crop, fallow, reduced tillage, forestry and aquatic
applications, as well as non-crop applications. When applied at lower rates,
glyphosate also acts as a plant growth regulator. Glyphosate's primary mode of
action is inhibition of the biosynthesis of aromatic amino acids in plants.

2. Safety. Monsanto Company has submitted numerous toxicology studies in
support of glyphosate. According to Monsanto Company, the acute toxicity and
irritation potential of glyphosate is low. There are large margins of safety
for subchronic and chronic effects. Glyphosate does not produce reproductive
effects and is not a teratogen, mutagen, carcinogen or a neurotoxin. Risk
assessment calculations indicate the margin of safety for agricultural workers
and the population in general far exceed the EPA required level of 100.

The following mammalian toxicity studies have been conducted to support
glyphosate:

A rat acute oral study with a combined LD50 of >5,000 mg/kg. A rabbit acute
dermal LD50 of > 5,000 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. A 90-day
feeding study in rats fed dosage levels of 0, 1,000, 5,000 and 20,000 ppm with
a no-observable-effect level (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 2000 mg/kg/day with a NOEL of 2000 mg/kg/day based on no effects
even at the highest dose tested.

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

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.

An oral developmental toxicity study with rats given doses of 0, 300, 1,000
and 3,500 mg/kg/day with a maternal 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 three-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 two-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.

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. Threshold effects-- chronic effects. The reference dose (RfD) for
glyphosate based on maternal effects in 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.

Acute toxicity. Based on the available acute toxicity data, glyphosate does
not pose any acute dietary risks.

4. Non-threshold effects--carcinogenicity. The Health Effects Division
Carcinogenicity Peer Review Committee has classified glyphosate in Group E
(evidence of noncarcinogenicity for humans), based upon lack of convincing
carcinogenicity evidence in adequate studies in two animal species. There was
no evidence of carcinogenicity in an 18-month feeding study in mice and a 2-
year feeding study in rats at the dosage levels tested. The doses tested are
adequate for identifying a cancer risk. Thus, a cancer risk assessment is not
appropriate.

5. Aggregate exposure. For purposes of assessing the potential dietary
exposure, Monsanto has estimated aggregate exposure based on the tolerances
for glyphosate on field corn grain at 1.0 ppm, field corn forage at 1.0 ppm,
field corn fodder at 100 ppm, corn aspirated grain fractions at 200 pm, grain
sorghum at 15 ppm, grain sorghum fodder at 40 ppm and oats at 20 ppm. Corn
forage and fodder, sorghum fodder and aspirated grain fractions are fed to
animals; thus exposure of humans to residues in these commodities might result
if such residues are transferred to meat, milk, poultry, or eggs. However,
based on the results of animal metabolism studies and the amount of glyphosate
residues expected in animal feeds, Monsanto has concluded that there is no
reasonable expectation that residues of glyphosate will exceed existing
tolerances in meat, milk, poultry or eggs. In conducting this exposure
assessment, Monsanto has made very conservative assumptions -- 100 percent 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,
Monsanto is taking into account this conservative exposure assessment. Other
potential sources of exposure of the general population to residues of
pesticides are residues in drinking water and exposure from non- occupational
sources. A Maximum Concentration Level (MCL) has been established for residues
of glyphosate in drinking water at 0.7 mg/l since glyphosate is approved for
direct application to water. The MCL represents the level at which no known or
anticipated adverse health effects occur, allowing for an adequate margin of
safety, and is based on the reference dose (RfD). Non-occupational exposure to
glyphosate is expected based on the currently-registered uses; however, due to
the low acute toxicity and lack of other toxicological concerns, the risk
posed by non-occupational exposure to glyphosate is minimal. Monsanto believes
that EPA consideration of a common mechanism of toxicity is not appropriate at
this time since Monsanto believes that EPA does not have information to
indicate that toxic effects produced by glyphosate would be cumulative with
those of any other chemical compound.

6. Determination of safety for U.S. population. RfD: The theoretical maximum
residue contribution (TMRC) for existing, published tolerances for glyphosate
is 0.021460 mg/kg bwt/day or 1.0 percent of the RfD for the overall U.S.
population. Using the conservative exposure assumptions described above, the
proposed new tolerances on corn, sorghum and oat commodities will contribute
0.0023 mg/kg/day to the TMRC. This aggregate exposure will utilize an
additional 0.12 percent of the RfD for the overall U.S. population. EPA
generally has 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, Monsanto concludes that there is a
reasonable certainty that no harm will result from aggregate exposure to
residues of glyphosate, including all anticipated dietary exposure and all
other non-occupational exposures.

7. Determination of safety for infants and children. In assessing the
potential for additional sensitivity of infants and children to residues of
glyphosate, data were considered from developmental toxicity studies in the
rat and rabbit and multi-generation reproduction studies in rats.

No birth defects were observed in the offspring of rats given glyphosate by
gavage at dose levels of 0, 300, 1,000, and 3,500 mg/kg/ day on days 6 through
19 of gestation. The NOEL for this study was 1,000 mg/kg/day based on maternal
and developmental toxicity observed at the highest dose tested, 3,500
mg/kg/day. The high-dose in this study was 3.5 times higher than the limit
dose that is currently required by the guidelines.

No birth defects were observed in the offspring of rabbits given glyphosate by
gavage at dose levels of 0, 75, 175, and 350 mg/kg/day on days 6 through 27 of
gestation. The NOEL for this study is considered to be 175 mg/kg/day based on
maternal toxicity at the high-dose of 350 mg/kg/day. Because no developmental
toxicity was observed at any dose level, the developmental NOEL is considered
to be 350 mg/kg/day.

Male and female rats were fed glyphosate at dose levels of 0, 3, 10, and 30
mg/kg/day every day throughout the production of three successive generations.
No adverse treatment-related effects on reproduction were observed. Because no
toxicity was noted even at the highest dose tested, a second reproduction
study at higher dose levels was performed and is described below.

Male and female rats were fed glyphosate at dose levels of 0, 100, 500, and
1,500 mg/kg/day every day throughout the production of two successive
generations. Reduced body weights and soft stools occurred at 1,500 mg/kg/day
(3 percent of the diet); therefore, the systemic NOEL is considered to be 500
mg/kg/day. Glyphosate did not affect the ability of rats to mate, conceive,
carry or deliver normal offspring at any dose level.

The results of these studies indicate that glyphosate does not produce birth
defects and is not a reproductive toxin.

Reference Dose (RfD). The TMRC for existing, published tolerances for
glyphosate ranges from 0.015561 for nursing infants to 0.049134 for non-
nursing infants (0.8 to 2.5 percent of the RfD). Using the conservative
exposure assumptions described above, the proposed new tolerances on corn,
sorghum and oat commodities will contribute 0.0158 mg/kg/day to the TMRC for
non-nursing infants. For non-nursing infants, the proposed new tolerances and
previously established tolerances will utilize a total of 3.2 percent of the
RfD. EPA generally has 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, Monsanto concludes that there is a
reasonable certainty that no harm will result from aggregate exposure to
residues of glyphosate, including all anticipated dietary exposure and all

other non-occupational exposures.

8. Estrogenic effects. 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.

9. Chemical residue. The nature of the residue in plants and animals is
adequately understood. The residue to be regulated is the parent glyphosate.
The submitted residue data adequately support the proposed tolerances on field
corn grain (1.0 ppm), field corn forage (1.0 ppm), field corn stover (100
ppm), aspirated grain fractions (200 ppm), grain sorghum (15 ppm), grain
sorghum fodder (40 ppm) and oats (20 ppm). Residues from genetically-modified
glyphosate tolerant field corn varieties did not exceed those from unmodified
varieties and there were no residues of metabolites which would be of
toxicological concern. Codex maximum residue levels (MRLs) have been
established for residues of glyphosate on oats at 20 ppm and on corn grain and
grain sorghum at 0.1 ppm. The Codex MRLS on corn and sorghum were established
based on preplant/preemergent uses of glyphosate, and are identical to the
exixting tolerances for these crops under the same use conditions in the
United States. The increased tolerances now being proposed on corn and sorghum
are based on the new preharvest uses of glyphosate to these crops in the
United States. Monsanto will be submitting a petition to request that the
Codex MRLs on these crops be increased; however the Codex Commission does not
generally begin the data review until the new use has been approved by a
member company. Any secondary residues occurring in milk, eggs, meat, fat,
liver and kidney of cattle, goats, horses, hogs, poultry and sheep are covered
by existing tolerances. There is a practical analytical method for detecting
and measuring levels of glyphosate in or on food with a limits of detection
(0.05 ppm) that allows monitoring of food with residues at or above the levels
set in these tolerances. EPA has provided information on this method to FDA.
This method is available to anyone who is interested in pesticide residue
enforcement from the Field Operations Division, Office of Pesticide Programs.

10. Environmental fate. Glyphosate adsorbs strongly to soil and is not
expected to move vertically below the 6-inch soil layer; residues are expected
to be immobile in soil. Glyphosate is readily degraded by soil microbes to
AMPA, which is degraded to carbon dioxide. Glyphosate and AMPA are not likely
to move to ground water due to their strong adsorptive characteristics.
However, due to its aquatic use patterns and through erosion, glyphosate does
have the potential to enter surface waters, where it will adsorb to sediment
and undergo microbial degradation.

Glyphosate is no more than slightly toxic to birds and is practically non-
toxic to fish, aquatic invertebrates and honeybees.

II. Administrative Matters

EPA invites interested persons to submit comments on this notice of filing.
Comments must bear a notification indicating the docket number [PF-679]. 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
8:30 a.m. to 4:00 p.m., Monday through Friday, except legal holidays.

A record has been established for this notice under docket numbers [PF-679]
(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 4:30 p.m., Monday through Friday, excluding
legal holidays. The public record is located in Room 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-docket@epamail.epa.gov

Electronic comments must be submitted as 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.

List of Subjects

Environmental protection, administrative practice and procedure, Agricultural
commodities, Pesticides and pests, Reporting and recordkeeping requirements.

Dated: December 16, 1996.

Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 96-32531 Filed 12-20-96; 10:00 am]