[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: [email protected]. 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: 
[email protected].
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:
    [email protected]
    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