
[Federal Register: December 3, 2008 (Volume 73, Number 233)]
[Rules and Regulations]               
[Page 73586-73592]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03de08-9]                         

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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: walters.vickie@epa.gov.

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: residuemethods@epa.gov.

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
