[Federal Register Volume 61, Number 248 (Tuesday, December 24, 1996)]
[Notices]
[Pages 67804-67807]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-32531]
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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
[[Page 67805]]
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
[[Page 67806]]
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
[[Page 67807]]
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]
BILLING CODE 6560-50-F
