[Federal Register Volume 73, Number 233 (Wednesday, December 3, 2008)]
[Rules and Regulations]
[Pages 73586-73592]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-28571]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2007-0147; FRL-8385-7]
Glyphosate; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes new tolerances for certain plant
commodities and all animal commodities, and revises other tolerances
for glyphosate and its metabolite N-acetyl-glyphosate (expressed as
glyphosate). These changes are detailed in Unit II of this document.
E.I. DuPont de Nemours and Company requested these tolerances under the
Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective December 3, 2008. Objections and
requests for hearings must be received on or before February 2, 2009,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2007-0147. All documents in the
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Vickie Walters, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: 703-305-5704; e-mail address: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to those
engaged in the following activities:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing electronically available documents at
http://www.regulations.gov, you may access this Federal Register
document electronically through the EPA Internet under the ``Federal
Register'' listings at http://www.epa.gov/fedrgstr. You may also access
a frequently updated electronic version of EPA's tolerance regulations
at 40 CFR part 180 through the Government Printing Office's pilot e-CFR
site at http://www.gpoaccess.gov/ecfr.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of FFDCA, 21 U.S.C. 346a, any person may file
an objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2007-0147 in the subject line on the first
page of your submission. All requests must be in writing, and must be
mailed or delivered to the Hearing Clerk as required by 40 CFR part 178
on or before February 2, 2009.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit this copy, identified by docket ID number
EPA-HQ-OPP-2007-0147, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov. Follow the
oN-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public Docket
(7502P), Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P), Environmental
Protection Agency, Rm. S-4400, One Potomac Yard (South Bldg.), 2777
Crystal Dr., Arlington, VA. Deliveries are only accepted during the
Docket Facility's normal hours of operation (8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays). Special arrangements
should be made for deliveries of boxed information. The Docket Facility
telephone number is (703) 305-5805.
[[Page 73587]]
II. Petition for Tolerance
In the Federal Register of May 9, 2007 (72 FR 26372) (FRL-8121-
5), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
6F7146) by E.I. DuPont de Nemours and Company, DuPont Crop Protection,
Laurel Run Plaza, P.O. Box 80, Newark, DE 19714-0030. The petition
requested that 40 CFR 180.364 be amended by establishing tolerances for
combined residues of the herbicide glyphosate, N-
(phosphonomethyl)glycine and its metabolite N-acetyl-glyphosate, N-
acetyl-N-(phosphonomethyl)glycine resulting from the application of
glyphosate, the isopropylamine salt of glyphosate, the ethanolamine
salt of glyphosate, the ammonium salt of glyphosate, and the potassium
salt of glyphosate to OptimumTMGATTM soybeans in
or on the food commodities: Cattle, kidney; cattle, liver; egg, goat,
kidney; goat, liver; hog, kidney; hog, liver; horse, kidney; horse,
liver; poultry, meat; poultry, meat byproducts; sheep, kidney; sheep,
liver; soybean, forage; soybean, hay; soybean, hulls; and soybean,
aspirated grain fractions at levels already established for glyphosate
alone. That notice referenced a summary of the petition prepared by
E.I. DuPont de Nemours and Company, the registrant, which is available
to the public in the docket, http://www.regulations.gov. Comments were
received on the notice of filing. EPA's response to these comments is
discussed in Unit IV.C.
DuPont has requested a Section 3 registration under the Federal
Insecticide, Fungicide, and Rodenticide Act (``FIFRA'') for the
preplant application of the herbicides glyphosate and pyrithiobac
sodium to glyphosate-tolerant soybean. The petitioner is also working
to commercialize a genetically modified soybean designated as
OptimumTMGATTM soybeans. N-acetyl-glyphosate is
produced when glyphosate is applied to
OptimumTMGATTM soybeans. As a result the
petitioner is requesting that the glyphosate tolerance expression be
modified from glyphosate per se to the combined residues of glyphosate
and N-acetyl-glyphosate. This petition was filed in conjunction with
Dupont's this requested change to its FIFRA registration.
Based upon review of the data submitted in support of the petition,
EPA has determined that the residues of concern in these commodities
are glyphosate and N-acetyl-glyphosate. The current tolerance
expression specifies residues of glyphosate
(N(phosphonomethyl)glycine). To address that N-acetyl-glyphosate was
the major residue in mature OptimumTMGATTM
soybean forage, hay, and seed, the Agency concluded that it is
necessary to include this compound in the tolerance expression. EPA is
splitting current Sec. 180.364(a) into paragraphs (a)(1) and (a)(2).
Paragraph (a)(1) will include all of the commodities currently in
paragraph (a), except for the animal commodities and the commodities
grain, aspirated fractions; soybean, forage; soybean, hay; soybean,
hulls; and soybean, seed, which EPA is transferring to new paragraph
(a)(2). The tolerances in paragraph (a)(2) will cover application of
glyphosate to non-genetically modified soybeans, genetically-modified
soybeans currently in use, and OptimumTMGATTM
soybeans. Note that based on the submitted residue data on application
of glyphosate to OptimumTMGATTM soybeans, the
numerical value of the current soybean and livestock tolerances do not
need to be changed (only the tolerance expression is changing).
Combined residues of glyphosate and N-acetyl-glyphosate in soybean
commodities derived from glyphosate-treated
OptimumTMGATTM soybeans and livestock commodities
from animals which consume only glyphosate-treated
OptimumTMGATTM soybeans will not exceed the
existing tolerance level. Additionally, the change in tolerance
expression will not affect the application of the tolerance to soybean
commodities derived from glyphosate-treated non-genetically modified
soybean and livestock commodities from animals which consumed only
glyphosate-treated non-genetically modified soybean because these
commodities will have only glyphosate per se residues, and not N-
acetyl-glyphosate residues.
In the Federal Register of May 2, 2007 (72 FR 24188)(FRL-8122-8),
the Agency published a final rule revising the tolerance expression for
glyphosate to include the dimethylamine salt of glyphosate. Because
there is a potential for soybeans to be treated with product containing
the dimethylamine salt of glyphosate the Agency has determined that the
dimethylamine salt of glyphosate should be added to the tolerance
expression for paragraph (a)(2).
Based upon review of the soybean processing studies submitted
supporting the petition, EPA has determined that the currently
established tolerances for the commodities grain, aspirated fractions
and soybean, hulls need to be increased to 310 ppm and 120 ppm,
respectively. Currently established tolerance levels for all other
commodities in this rule are supported by available data.
III. Aggregate Risk Assessment and Determination of Safety
Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical
residue....''
Consistent with section 408(b)(2)(D) of FFDCA, and the factors
specified in section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure for the petitioned-for
tolerances for the combined residues of glyphosate, N-
(phosphonomethyl)glycine and its metabolite N-acetyl-glyphosate
(expressed as glyphosate) resulting from the application of glyphosate,
the isopropylamine salt of glyphosate, the ethanolamine salt of
glyphosate, the dimethylamine salt of glyphosate, the ammonium salt of
glyphosate, and the potassium salt of glyphosate on the food
commodities cattle, meat byproducts at 5.0 ppm; egg at 0.05 ppm; goat,
meat byproducts at 5.0 ppm; grain, aspirated fractions at 310 ppm; hog,
meat byproducts at 5.0 ppm; horse, meat byproducts at 5.0 ppm; poultry,
meat, at 4.0 ppm; poultry, meat byproducts at 1.0 ppm; sheep, meat
byproducts at 5.0 ppm; soybean, seed at 20.0 ppm; soybean, forage at
100.0 ppm; soybean, hay at 200.0 ppm, and soybean, hulls at 120 ppm and
soybean, seed at 20.0 ppm. EPA's assessment of exposures and risk
associated with establishing tolerances follows.
[[Page 73588]]
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. Specific information on the studies received and the nature
of the adverse effects caused by glyphosate and its metabolite N-
acetyl-glyphosate as well as the no-observed-adverse-effect-level
(NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the
toxicity studies can be found at http://www.regulations.gov in the
document entitled Petition: 6F7146. Glyphosate-Isopropylammonium and
Pyrithiobac Sodium. Human Health Risk Assessment for Application to
Glyphosate Tolerant Soybean; pages 7-10 in docket ID number EPA- HQ-
OPP-2007-0147 and identified as document EPA-HQ-OPP-2007- 0147-0007.
The toxicological profile of glyphosate is discussed in the risk
assessment referenced earlier in this section and in the risk
assessment referenced in the final rule published in the Federal
Register of December 20, 2006 (71 FR 76180) (FRL-8105-9) which
establishes tolerances for residues of glyphosate in or on noni at 0.20
ppm; pea, dry at 8.0 ppm; safflower at 85 ppm; sunflower at 85 ppm; and
vegetable, legume group 6 except soybean and pea, dry at 5.0 ppm.
Toxicological endpoints and current risk assessments for glyphosate
are discussed in the risk assessment referred to in the final rule
published in the Federal Register of December 20, 2006 (71 FR 76180)
(FRL-8105-9) which establishes tolerances for residues of glyphosate in
or on noni at 0.20 ppm; pea, dry at 8.0 ppm; safflower at 85 ppm;
sunflower at 85 ppm; and vegetable, legume group 6 except soybean and
pea, dry at 5.0 ppm.
1. A summary of the data submitted in support of the metabolite N-
acetyl-glyphosate is listed below. Refer to the risk assessment
available in the public docket for this rule and identified above as
document EPA-HQ-OPP-2007-0147-0007 for more information.
i. An acute oral toxicity study in rats with an Acute Oral
LD50 greater than 5,000 milligrams/kilogram (mg/kg).
ii. A 90-day subchronic oral (feeding) study, in which no systemic
toxicity was observed in male and female rats at doses up to 18,000 ppm
(equal to 1157/1461 mg/kg/day in males/females, respectively).
iii. N-acetyl-glyphosate was negative for mutagenicity in a
bacterial reverse mutation assay (Ames test), an in vitro chromosomal
aberration assay in Chinese Hamster Ovary (CHO) cells, an in vitro
Mammalian Cell Gene Mutation Assay in CHO cells and an in vivo
cytogenetics (bone marrow) in mice, and a metabolism and
pharmacokinetics study.
2. N-acetyl aminomethylphosphonic acid (N-acetyl-AMPA) was detected
as one of the metabolites formed following oral administration of N-
acetyl-glyphosate. It is not expected to be absorbed quickly from the
gastrointestinal tract since it is a charged molecule at the
physiological pH. N-acetyl-AMPA is expected to be less toxic than N-
acetyl-glyphosate. Data submitted in support of this metabolite
included the following:
i. An acute oral toxicity study with an LD50 of greater
than 8,300 mg/kg.
ii. A bacterial reverse mutation assay (Ames test), in which N-
acetyl-AMPA was not mutagenic when tested up to 5,000 microgram
([micro]g)/plate in presence and absence of activation in S.
typhimurium strains of TA98, TA 100, TA1535, TA1537, and in Escheria
coli strain WP2uvrA.
iii. An in vitro Mammalian Chromosome Aberration Test in Human
Perpherral Blood Lymphocytes, in which N-acetyl-AMPA was negative for
the induction of structural and numerical chromosome aberrations in
both the non-activated and the S9-activated test systems when tested up
to 15.30 milligrams/milliliter (mg/ml).
iv. An in vitro Mammalian Cell Gene Mutation Test (CHO/HPRT) Test,
in which N-acetyl-AMPA was not mutagenic at the HGPRT locus in Chinese
hamster ovary cells tested up to 1,531 [micro]g/ml in the presence and
absence of metabolic activation.
v. An in vivo Mouse Bone Marrow Micronucleus Test, in which N-
acetyl-AMPA resulted in no detections of chromosomal aberrations were
detected in male and female mice at doses up to 2,000 mg/kg.
3. For the purpose of assessing the aggregate risk from glyphosate
tolerances, EPA has assumed that N-acetyl-glyphosate is equally toxic
to glyphosate. This conservative assumption is based on the structural
similarity of N-acetyl-glyphosate with glyphosate; a structure activity
relationships (SAR) analysis of N-acetyl-glyphosate with a lack or
structural alerts for carcinogenicity, mutagenicity and endocrine
effects; and toxicity data for N-acetyl-glyphosate showing low acute
toxicity, low subchronic toxicity and lack of mutagenicity, In all
probability, N-acetyl-glyphosate is of lower toxicity than glyphosate.
For example, subchronic toxicity testing with glyphosate showed no
systemic toxicity in male and female rats at doses up to 400 mg/kg/day
in males and females. Subchronic testing with N-acetyl-glyphosate
showed no systemic toxicity in male and female rats at doses up to
1157/1446 mg/kg/day in males/females, respectively.
The toxicity of N-acetyl-AMPA is considered low and of limited
concern based on the available data described above, and lack of any
structural alerts.
Amendment of the glyphosate soybean and meat and milk tolerances to
include N-acetyl-glyphosate in the tolerance expression does not result
in changes in the exposure or risk estimates reported in the previous
risk assessments for the reasons listed below and fully discussed in
the risk assessment referenced earlier in this section.
i. The Agency has determined that N-acetyl-glyphosate has no
greater toxicity than glyphosate and probably is of lower toxicity.
ii. The numerical value of all but two food tolerances will remain
the same.
iii. The most recent dietary analysis assumed tolerance level
residues and, 100% crop treated.
iv. The estimate of glyphosate levels in drinking water is based on
a glyphosate use involving direct application to water at 3.75 pounds
active ingredient per acre. Use of glyphosate on glyphosate-resistant
soybeans will not result in higher levels in drinking water.
v. Previously calculated dietary burdens to poultry were based on
alfalfa meal (400 ppm tolerance) and soybeans hulls (100 ppm tolerance)
as significant contributors to the diet. Based on the latest guidance,
although soybean seed, meal, and hulls are feed to poultry, soybean
hulls are is no longer considered a significant contributor to poultry
diets. The previously calculated dietary burdens to hog were based on
alfalfa meal and barley grain (20 ppm tolerance) being significant
contributors to the diet. Soybean seed and meal are fed to hogs;
however, the current action does not require an increase in tolerance
for soybean seed or meal. Based on these complications, the Agency
concludes that the application of glyphosate to
OptimumTMGATTM soybean will not result in
combined residues of glyphosate and N-acetyl-glyphosate (expressed as
glyphosate) in poultry or hog commodities greater than the residues of
glyphosate that result under the currently established glyphosate per
se tolerances.
[[Page 73589]]
vi. Previously calculated dietary burdens to dairy or beef cattle
were based on alfalfa hay (400 ppm tolerance) being the significant
contributor to the diet. The Agency concludes that the consumption of
glyphosate OptimumTMGATTM soybean will not result
in combined residues of glyphosate and N-acetyl-glyphosate (expressed
as glyphosate) in or on beef/dairy cattle commodities greater than the
currently established glyphosate per se tolerances for the reasons
below.
a. The high tolerance value for alfalfa hay (400 ppm) and alfalfa
hay occupies 40% of the total beef/dairy cattle diet.
b. The soybean hull tolerance is only increasing from 100 to 120
ppm and soybean hulls will occupy at most 20% of the beef/dairy cattle
dietary burdens.
c. Aspirated grain fractions occupy at most 5% of the beef cattle
dietary burden and are not feed to dairy cattle.
Accordingly, based on the risk assessments discussed in the notice
referenced above, EPA concludes that no harm will result to the general
population and to infants and children from aggregate exposure to the
combined residues of glyphosate and its metabolite N-acetyl-glyphosate
(expressed as glyphosate).
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (high performance liquid
chromatography (HPLC) with tandem mass spectrometry (MS/MS)) is
available to enforce the tolerance expression. The method may be
requested from: Chief, Analytical Chemistry Branch, Environmental
Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone
number: (410) 305-2905; e-mail address: [email protected].
B. International Residue Limits
There are Codex Maximum Residue Levels (MRL) established for
glyphosate (sum of glyphosate and AMPA, expressed as glyphosate) on
soybean, dry at 20 ppm; edible offal (mammalian) at 5 ppm; eggs at 0.05
ppm; poultry meat at 0.05 ppm and poultry, edible offal of at 0.5 ppm.
Canadian MRLs are established for glyphosate including the metabolite
aminomethylphosphonic acid (AMPA) on soybean seed at 20 ppm, kidney of
cattle, goats, hogs, poultry and sheep at 2.0 ppm; and liver of cattle,
goats, hogs, poultry, and sheep at 0.2 ppm. A Mexican MRL of 6 ppm is
established for glyphosate. The glyphosate tolerances EPA is
establishing in this action differ from the tolerance expression for
the CODEX, Canadian or Mexican MRLs, due to the inclusion of N-acetyl-
glyphosate in the expression. Additionally, the EPA tolerances differ
from the CODEX and Canadian MRLs in that the EPA tolerances do not
include AMPA in tolerance expression. At this time, harmonization
between the U.S. tolerances and the CODEX, Canadian or Mexican MRLs can
not be achieved because of the inclusion of N-acetyl-glyphosate in the
EPA tolerances is necessary to support use patterns in the United
States and EPA has concluded that AMPA should not be included in the
tolerance expression because it is not toxicologically significant. The
petitioner is seeking registration and amendment of the tolerance
expressionin other countries. This may lead to harmonization between
the U.S. tolerances and the CODEX, Canadian or Mexican MRLs.
C. Response to Comments
Three commenters submitted comments in response to the notice of
filing. A summary of the comments and EPA's response follows.
1. Comment. One commenter does not believe that DuPont has
submitted sufficient toxicological data to demonstrate that N-acetyl-
glyphosate is not of toxicological concern and that submitted data did
not support the claim of equivalent toxicity between glyphosate and N-
acetyl-glyphosate. The commenter argued that the single acute toxicity
EPA relied on actually suggests that N-acetyl-glyphosate is more toxic
than glyphosate. This commenter also believes that reproductive,
developmental, and chronic and carcinogenicity data on N-acetyl-
glyphosate should be generated and analyzed.
Another commenter expressed concern that sufficient data may not
have been submitted on the metabolite N-acetyl-glyphosate to satisfy
the requirements for EPA to establish tolerances or to support the
establishment of MRLs by other countries. The first commenter expressed
a similar concern that submitted data failed to meet requirements of
international authorities such as Joint FAO/WHO Meeting in Pesticide
Residues (JMPR), particularly when compared to the extensive data bases
required for other metabolites such as AMPA and N-acetyl-glufosinate.
Response. EPA does not agree with the contention that N-acetyl-
glyphosate is more toxic than glyphosate. The Agency concluded that N-
acetyl-glyphosate is not likely to be more toxic than glyphosate based
on the available toxicity studies and Structure Activity Relationship
(SAR). The available acute toxicity study with N-acetyl-glyphosate and
glyphosate indicate low toxicity (Acute Oral LD50 was
greater than 5,000 mg/kg bw). Both N-acetyl-glyphosate and glyphosate
are placed in acute Tox Category IV. There was evidence of some
mortality in an acute oral study with N-acetyl-glyphosate but not with
glyphosate. However, the evidence from very high doses in this acute
oral LD50 test suggesting that N-acetyl-glyphosate might be
more toxic than glyphosate is outweighed by the results of subchronic
tests with the two compounds. There was no evidence of systemic
toxicity in 90-day dietary toxicity studying rats with N-acetyl-
glyphosate conducted at well above the limit dose (18,000 PPM equal to
1,157/1,461 mg/kg/day in males and females, respectively). In a 90-day
dietary toxicity study in rats with glyphosate at 0, 1,000, 5,000 or
20,000 ppm (equivalent to 0, 63, 317, or 1,267 mg/kg/day in males and
0, 84, 404, or 1,623 mg/kg/day in females), glyphosate caused increased
serum phosphorus and potassium at all doses treated in both sexes and
occurrence of high dose pancreatic lesions in males (effect was not
evaluated at lower doses). Based on these findings systemic toxicity
NOAEL for glyphosate can be considered as less than 1,000 ppm
(equivalent to <63 mg/kg/day). Thus the subchronic study with N-acetyl
glyphosate clearly indicates that it is less toxic than glyphosate. The
available adequate battery of mutagenicity studies with N-acetyl
glyphosate and glyphosate indicate that they are not mutagenic. The
metabolism of N-acetyl glyphosate and glyphosate is well studied in
rats. These studies indicate that both compounds are rapidly absorbed
and excreted from the body and are not biosequestered. In fact, nearly
all of the orally administered N-acetyl-glyphosate was excreted
unchanged in the urine and feces. There is extensive database available
on glyphosate, which indicate that glyphosate is not mutagenic, not a
carcinogen, and not a developmental or reproductive toxicant. Based on
its structural similarities with glyphosate and available data, it is
reasonable to conclude that the N-acetyl-glyphosate is not likely to be
more toxic than the parent. The Agency evaluated available information
and data and concluded that additional data on N-acetyl-glyphosate was
not needed based on the weight of evidence described above. In
addition, Agency has accepted bridging data where evidence is clear in
order to reduce the animal usage.
EPA also disagrees with the claim that EPA has insufficient data on
N-acetyl-
[[Page 73590]]
glyphosate. EPA did review larger data sets on the metabolites AMPA and
N-acetyl-glufosinate but these larger data sets were submitted
voluntarily by pesticide registrants; EPA did not require these data to
be submitted. EPA's decision to review all data that was submitted
whether required or not (which is something the Agency does routinely)
can not be converted into an EPA determination that such data would be
required to make a safety finding for a similar pesticide metabolite.
For the reasons expressed above, EPA concludes it has sufficient data
on N-acetyl-glyphosate. For similar reasons, EPA also disagrees with
the commenter's suggestion that because the Joint FAO/WHO Meeting in
Pesticide Residues (JMPR) reviewed larger data sets on AMPA and N-
acetyl-glufosinate, EPA's data set on N-acetyl-glyphosate must be
deficient. The JMPR does not have any regulatory authority to require
data and the commenters do not claim that JMPR defined the
toxicological data needed to make the toxicity determinations with
regard to AMPA and N-acetyl-glufosinate. The JMPR reviewed the data
voluntarily submitted; it did not make a recommendation on the data
necessary to make the needed toxicity evaluation.
2. Comment. One commenter argues that the higher residues of N-
acetyl-glyphosate may be absorbed at a higher rate than glyphosate.
Taking into consideration the increased absorption for N-acetyl-
glyphosate compared to glyphosate are likely in meat, milk, poultry,
and eggs due to the high values of N-acetyl-glyphosate that are likely
in plants and the higher absorption in animals of N-acetyl-glyphosate
(when compared to glyphosate). The commenter notes that
OptimumTMGATTM soybeans were specifically
engineered to convert N-acetyl-glyphosate and thus is likely to result
in significant amounts of N-acetyl-glyphosate in soybeans. As to the
higher absorption in animals, the commenter references a rat metabolism
study and argues that indicates that higher absorption would occur in
poultry and livestock that ingest residues of N-acetyl-glyphosate in
feed and that the higher absorption would likely result in higher
residues in meat, milk, and eggs when compared with glyphosate.
Response. As the commenter stated, the rat metabolism studies
indicate that N-acetyl-glyphosate may be absorbed at a higher rate than
glyphosate. Taking into consideration the increased absorption for N-
acetyl-glyphosate, the previously calculated livestock diets (driven by
400 ppm alfalfa hay/meal tolerances), and the previously revised
guidance concerning the construction of livestock diets (changes to the
percent each food feedstuff contributes to a livestock diet, livestock
diets are now constructed taking in to consideration nutritional
requirements), it was concluded that higher livestock tolerances are
not necessary. Note that the dietary analysis assumed tolerance level
residue for the livestock commodities (i.e. assumes all of the
commodities feed to livestock have tolerance level residues and all
livestock commodities consumed by humans have tolerance level
residues).
3. Comment. One commenter expressed concern that the petitioner had
stated its intent to increase glyphosate spray rates or change spray
timing and that residue data had not be submitted to reflect levels of
N-acetyl-glyphosate under actual use conditions.
Response. The petitioner submitted several
OptimumTMGATTM soybean magnitude-of-the-residue
studies which monitored for residues of glyphosate and N-acetyl-
glyphosate in forage and hay and soybean seed. (See document cited
earlier in this unit for detailed discussion of these data). The Agency
concluded that this data was acceptable and supported the proposed use
pattern. The Agency also concluded that additional field trial data
were not necessary and that the proposed tolerance levels discussed in
Unit II of this document were acceptable. The Agency has not received
an application requesting increased application rates or changes in
application timing at this time. The Agency will reevaluate the need
for additional magnitude-of-the-residue data if and when an application
of this type is received.
4. Comment. A concern expressed by two of the three commenters was
the possible amendment of FIFRA registration to allow higher
application rates on soybeans of ALS inhibitor herbicides such as
sulfonylureas already registered on soybeans or new uses of ALS
inhibitor herbicides on soybeans. Such amended uses or new uses, the
commenter urged, should be conditioned on the submission of additional
residue data or consideration of possible effects to non-target plants
and endangered species.
Response. The Agency has not received requests for increased use or
new uses of ALS inhibitor pesticides on
OptimumTMGATTM soybean seed to additional
herbicides at this time. The pre-plant use of pyrithiobac sodium in
soybeans remained unchanged for this action. However, as discussed on
page 3 of the risk assessment referenced in Section III of this
document, since ALS tolerance is conferred via modification of the
endogenous ALS gene such that the plant is no longer sensitive (i.e.
the tolerance is not conveyed via metabolism of the herbicide), the
Agency's current view is that the nature/magnitude of residues
submitted in support of registration of ALS-inhibiting herbicides to
nontransgenic soybean are applicable for application of these compounds
to OptimumTMGATTM soybean.
5. Comment. One commenter expressed a concern that the analytical
method submitted may not enable simultaneous quantification of the
combination of glyphosate, N-acetyl-glyphosate and
aminomethylphosphonic acid (AMPA), all of which could be present in
exported soybeans.
Response. Available information including Agency method trial
confirms that proposed analytical method (high performance liquid
chromatography (HPLC) with tandem mass spectrometry (MS/MS)) quantifies
residues of glyphosate, N-acetyl-glyphosate, and AMPA in crops and
animal commodities.
6. Comment. One commenter opposed the way the tolerance expression
was written in the notice of filing and the fact that a new paragraph
was being added to the tolerance expression allowing for duplicate
listings of the same commodities dependent on genetic makeup.
Response. Based on the submitted comments and the available
information the Agency has decided that 40 CFR 180.364(a) will be
redesignated as paragraph (a)(1) and that the current listings from
newly redesignated paragraph (a)(1) for soybean and animal commodities
will be transferred to new paragraph (a)(2). The revised tolerance
expression deletes any reference to genetic make up. See Unit II of
this document for discussion.
7. Comment. One commenter expressed a concern that current EPA
label policy allowing the use of general terminology such as
``glyphosate tolerant soybeans'' would permit use of any soybean seed
that satisfies the general ``glyphosate tolerant'' criteria if crop
seed such as OptimumTMGATTM soybean seed were
commercially available, even if appropriate data have not been reviewed
and tolerances granted.
Response. The EPA label policy is intended to allow the use of
glyphosate on any approved glyphosate tolerant seed. The Agency does
not regulate or approve the glyphosate tolerant seed, only the use of
glyphosate on the crops grown from the glyphosate tolerant
[[Page 73591]]
seed. The approval of the seed itself is handled by the United States
Department of Agriculture (USDA) Animal and Plant Health Inspection
Service (APHIS). Information on approval of the
OptimumTMGATTM soybean seed is available in a
notice published in the Federal Register of July 24, 2008 (73 FR 43203)
which advised the public of their determination that a soybean line
developed by Pioneer HI-Bred International, Inc., designated as
transformation event 356043, which has been genetically engineered for
tolerance to glyphosate and acetolactate synthase-inhibiting
herbicides, is no longer considered a regulated article under their
regulations governing the introduction of certain genetically
engineered organisms, and the public docket established for that action
by USDA/APHIS, which is available at http://www.regulations.gov and is
identified as docket identification number APHIS-2007-019.
8. Comment. One commenter expressed a concern that
OptimumTMGATTM soybeans are plants that have high
levels of a new abnormal enzyme that creates new untested metabolites.
The commenter referenced an article (Science, 21 May 2004, vol. 34 pp
1151-1154) which shows that the new ``shuffled enzyme'' (N-acetylate)
can react with common amino acids L-aspartate, L-serine, phosphor-L-
serine, L-threonine, L-glutamate, L-aspargine, and L-cysteine to form
new N-acetylated versions of these common amino acids. The commenter
stated that toxicology data may be necessary to address the safety of
these N-acetylated metabolites.
Response. This issue concerns componets of the
OptimumTMGATTM soybean and not residues of the
pesticide glyphosate and is not relevant to EPA's determination of
safety under section 408 of the FFDCA. However, similar comments were
received and addressed by APHIS during the course of their review of
the OptimumTMGATTM soybean seed which is fully
discussed in the Federal Register notice of July 24, 2008 and the APHIS
public docket referenced earlier in this unit. In summary APHIS
reviewed available information toxicity data available for both the
356043 soybean seed and N-acetyl-L-aspartic acid (NAA) and determine
that additional toxicological assessment was unwarranted. APHIS
determined that quantification of other acetylated amino acids did not
need to be measured based on the fact that the GAT4601 enzyme has
different kinetic and specificity properties than the native enzymes
from Bacillus licheniformis which have the ability to use additional
amino acids as substrates under specific in vitro conditions. The study
conducted with GAT4601 demonstrated the kinetic parameters could only
be established for aspartate and glutamate. Additional information
concerning this conclusion can be found in the APHIS public docket
referenced earlier in this unit.
9. Comment. One commenter expressed concern that sufficient data
may not have been submitted on the metabolite N-acetyl-glyphosate to
satisfy the requirements for EPA to establish tolerances or to support
the establishment of MRLs by other countries and Agencies. A second
commenter expressed a similar concern that submitted data failed to
meet requirements of international authorities such as Joint FAO/WHO
Meeting in Pesticide Residues (JMPR), particularity when compared to
the extensive databases required for other metabolites such as AMPA and
N-acetyl-glufosinate.
Response. The Agency has determined that the submitted data
discussed above and in the referenced risk assessments provided
sufficient information for the Agency to make the required human safety
determination required in the FFDCA and satisfy data requirements for
establishment of tolerances and registration in the United States.
10. Comment. One commenter expressed concern that the proposed
unilateral change to the glyphosate residue definition to include the
new metabolite N-acetyl-glyphosate has significant potential to disrupt
the international trade of soybeans for U.S. growers until the
glyphosate residue definition is implemented globally. The commenter
further noted that the data submitted to EPA may not be sufficient for
other countries to modify their tolerance expressions.
Response. The petitioner submitted a summary of a metabolism study
conducted with OptimumTMGATTM soybean. This study
indicated that both glyphosate and N-acetyl-glyphosate were significant
residues in/on OptimumTMGATTM soybean forage and
straw. For mature OptimumTMGATTM soybean seed,
only N-acetyl-glyphosate was a significant residue (glyphosate
represented a minor component of the total residue). Since N-acetyl-
glyphosate was the major residue in mature
OptimumTMGATTM soybean forage, hay, and seed, EPA
concluded that it is necessary to include this compound in the
tolerance expression.
EPA believes that the new metabolite N-acetyl glyphosate is not
likely to disrupt international trade of soybean for U.S. growers.
DuPont is seeking registration in various countries. The Agency expects
that the various countries will come to similar conclusion as the
United States for OptimumTMGATTM soybean and
amend their tolerance expressions which will alleviate the potential
trade issue. The current analytical method would detect glyphosate,
AMPA and N-acetyl glyphosate allowing enforcement of the tolerances in
other countries. Growers in the United States have the option of
growing conventional soybeans or other varieties of glyphosate tolerant
seed until any trade issues in other countries with
OptimumTMGATTM soybeans are resolved.
11. Comment. Several comments were received from a private citizen
objecting to establishment of tolerances.
Response. The Agency has received similar comments from this
commenter on numerous previous occasions. Refer to the Federal Register
of March 14, 2007 (72 FR 11784; FRL-8117-2) for the Agency's response
to these objections. In addition the commenter noted that bees and
turkey vultures are dying. These comments are not relevant to human
safety determination which is the sole focus of tolerance actions under
section 408 of the FFDCA. For informational purposes, EPA would note
that pesticide effects on wildlife are addressed in the FIFRA
registration process. In a honey bee contact test with glyphosate,
mortality was low in all treatment levels. The results indicate that
glyphosate is classified as practically nontoxic to honeybees. Although
the Agency does not require testing on turkey buzzards specifically,
the potential for avian mortality to glyphosate has been assessed using
bobwhite quail acute oral LD50 study and bobwhite quail and
mallard duck 8-day dietary LC50 studies. These data indicate
that glyphosate is practically nontoxic to avian species on an acute
oral basis and no more than slightly toxic on a subacute dietary basis.
The potential effects to avian growth and reproduction from glyphosate
have been assessed using avian reproduction studies with mallard duck
and bobwhite quail. These data indicate that glyphosate is not expected
to cause reproductive impairment. The commenter did not submit any
information to support a revision of Agency conclusions.
V. Conclusion
Therefore, tolerances are established for combined residues of
glyphosate, N-(phosphonomethyl)glycine and its metabolite N-acetyl-
glyphosate (expressed as glyphosate) resulting from the application of
glyphosate, the
[[Page 73592]]
isopropylamine salt of glyphosate, the ethanolamine salt of glyphosate,
the dimethylamine salt of glyphosate, the ammonium salt of glyphosate,
and the potassium salt of glyphosate on the food commodities cattle,
meat byproducts at 5.0 ppm; egg at 0.05 ppm; goat, meat byproducts at
5.0 ppm; grain, aspirated fractions at 310 ppm; hog, meat byproducts at
5.0 ppm; horse, meat byproducts at 5.0 ppm; poultry, meat, at 4.0 ppm;
poultry, meat byproducts at 1.0 ppm; sheep, meat byproducts at 5.0 ppm;
soybean, seed at 20.0 ppm; soybean, forage at 100.0 ppm; soybean, hay
at 200.0 ppm, and soybean, hulls at 120 ppm as discussed in Unit II of
this document.
VI. Statutory and Executive Order Reviews
This final rule establishes tolerances under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this final rule has been
exempted from review under Executive Order 12866, this final rule is
not subject to Executive Order 13211, entitled Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
Protection of Children from Environmental Health Risks and Safety Risks
(62 FR 19885, April 23, 1997). This final rule does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any
special considerations under Executive Order 12898, entitled Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Public Law 104-4).
This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
note).
VII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule as defined by 5 U.S.C.
804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: November 19, 2008.
Donald R. Stubbs,
Director, Registration Division, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. Section 180.364 is amended as follows:
0
a. By removing the entries cattle, meat byproducts; egg; goat, meat
byproducts; grain, aspirated fractions; hog, meat byproducts; horse,
meat byproducts; poultry, meat; poultry, meat byproducts; sheep, meat
byproducts; soybean, forage; soybean, hay; soybean, hulls; and soybean,
seed from the table in paragraph (a).
0
b. By redesignating paragraph (a) introductory text and the remainder
of the table as paragraph (a)(1) and by adding paragraph (a)(2) to read
as follows:
Sec. 180.364 Glyphosate, Tolerance for residue.
(a) * * * (1) * * *
(2) Tolerances are established for combined residues of glyphosate,
N-(phosphonomethyl)glycine and its metabolite N-acetyl-glyphosate
(expressed as glyphosate) resulting from the application of glyphosate,
the isopropylamine salt of glyphosate, the ethanolamine salt of
glyphosate, the dimethylamine salt of glyphosate, the ammonium salt of
glyphosate, and the potassium salt of glyphosate on the food
commodities:
------------------------------------------------------------------------
Parts per
Commodity Million
------------------------------------------------------------------------
Cattle, meat byproducts............................... 5.0
Egg................................................... 0.05
Goat, meat byproducts................................. 5.0
Grain aspirated fractions............................. 310.0
Hog, meat byproducts.................................. 5.0
Horse, meat byproducts................................ 5.0
Poultry, meat......................................... 4.0
Poultry, meat byproducts.............................. 1.0
Sheep, meat byproducts................................ 5.0
Soybean, forage....................................... 100.0
Soybean, hay.......................................... 200.0
Soybean, hulls........................................ 120.0
Soybean, seed......................................... 20.0
------------------------------------------------------------------------
* * * * *
[FR Doc. E8-28571 Filed 12-2-08; 8:45 am]
BILLING CODE 6560-50-S