
                                       
                    UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                               WASHINGTON, D.C.  20460
                                       
                                       
                                                      OFFICE OF CHEMICAL SAFETY
                                                       AND POLLUTION PREVENTION
	

MEMORANDUM

Date		24-March-2011

Subject:	Glyphosate.  Section 3 Registration for Application of the Potassium Salt of Glyphosate to Roundup Ready[(R)] Field Corn.  Summary of Analytical Chemistry and Residue Data.  

PC Codes:  103613 and 417300
DP Barcode:  D383931
Decision No.:  437140
Registration Nos.:  524-537; 524-549
Petition No.:  0F7741
Regulatory Action:  Section 3
Risk Assessment Type:  not applicable
Case No.:  178
TXR No.:  not applicable
CAS No.:  70901-20-1
MRID No.:  47982201
40 CFR:  180.364 

From:			Tom Bloem, Chemist
			Risk Assessment Branch 1; Health Effects Division (RAB1/HED; 7509P)

Through:		George F. Kramer, Ph.D., Senior Chemist
			RAB1/HED (7509P)

To:			James Tompkins/Hope Johnson RM 25
			Registration Division (RD; 7505P)

Monsanto indicated that they have developed a new Roundup Ready[(R)] trait for field corn which enables properly timed glyphosate (N-(phosphonomethyl)glycine) applications to provide tassel control; Monsanto indicated that tassel control is desired as this will allow the generation of specific cross pollinations without the use of traditional methods to control self pollination.  This new Roundup Ready[(R)] trait will be used only in seed corn production and Monsanto termed the process Round Hybridization System[(TM)] (RHS[(TM)]).  The generation of RHS[(TM)] seed corn involves slightly later application timings than those currently registered.  

Executive Summary

Background:  Glyphosate is a nonselective Group 9 herbicide which disrupts the synthesis of the aromatic amino acids tyrosine, tryptophan, and phenylalanine through inhibition of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS).  Glyphosate is currently registered for pre- and post-emergence application to a variety of fruit, vegetable, and field crops.  Tolerances are currently established for residues of glyphosate in/on various plant commodities (including field corn) at 0.2-400 ppm (40 CFR §180.364(a)) and for the combined residues of glyphosate and N-acetyl-glyphosate (expressed as glyphosate) in/on field corn, soybean, aspirated grain fractions (AGF), and livestock commodities at 0.1-310 ppm.  The Glyphosate Reregistration Eligibility Decision (RED) document was issued September 1993.  A Registration Review Scoping document was completed in 2009 (D362745, J. Langsdale et al., 3-Jun-2009).  

The petitioner proposed a Section 3 registration for application of glyphosate to field corn used in RHS[(TM)] seed corn production.  The petitioner is also proposing a tolerance for residues of glyphosate only in/on field corn forage of 13 ppm (revisions to the currently-established field corn stover and grain tolerances are not requested).  Tolerances for the combined residues of glyphosate and N-acetyl-glyphosate (expressed as glyphosate; see Attachment 1 for structures) in/on field corn forage, stover, and grain are currently established at 6.0 ppm, 100 ppm, and 5.0 ppm, respectively (180.364(a)(2)).  HED notes that the tolerance expression includes residues of N-acetyl-glyphosate due to the introduction the Optimum GAT field corn variety (see Nature of the Residue Section in the Executive Summary for a description of this variety). 

Proposed Use:  The petitioner submitted proposed supplemental labels for Roundup WeatherMAX[(R)] (EPA Reg. No. 524-537) and Roundup Power MAX[(R)] (Reg. No. 524-549); both of these products are soluble-concentrate (SC) formulations consisting of glyphosate as the potassium salt at 4.51 lb ae/gallon.  The submitted supplemental labels indicate that the application scenarios are for use in research field trials and for seed production of corn hybrids using the RHS[(TM)] system.  Table 3 is a summary of the proposed application scenarios.  The proposed use directions are similar to that currently registered with the exception of the tassel control instructions (V8-V13); the maximum seasonal application rate is the same.  HED requests that the supplemental labels be altered to indicate the following (a revised Section B is requested):  (1) the minimum spray volume for ground and aerial application is >2 gallons per acre (GPA); (2) postemergent directions should indicate that they apply to field corn up to the V8 crop stage and that a maximum of 2.3 lb ae/acre/season may be applied; and (3) preharvest interval (PHI) of 30 days for forage and 7 days for grain and stover.

Nature of the Residue  -  Primary Crops:  Metabolism studies conducted with nontransgenic corn, cotton, soybeans, and wheat were previously submitted and reviewed.  Based on these data, HED concluded that the residue of concern in nontransgenic plants is glyphosate (Memo, R. Perfetti, 19-Oct-1992; RED, R. Perfetti, 27-Oct-1992; Memo, R. Perfetti, 17-Mar-1994).  Metabolism studies have also been submitted on glyphosate-tolerant canola (D242628, T. Bloem, 30-Nov-1998) and glyphosate-tolerant field corn (Roundup Ready[(R)] field corn; D217539, G. Kramer, 14-Mar-1996).  The glyphosate-tolerant canola and field corn were genetically modified to express the EPSPS gene derived from Agrobacterium sp. (strain CP4) which codes for an EPSPS protein that has reduced affinity for glyphosate as compared to the endogenous EPSPS protein.  The glyphosate-tolerant canola and corn were also genetically engineered to express the oxireductase gene which converts glyphosate to the nonherbicidal AMPA (aminomethyl phosphonic acid).  Metabolism in these varieties of transgenic canola and corn was essentially the same as the nontransgenic plants.  Therefore, it was concluded that the terminal residue to be regulated, in nontransgenic plants and transgenic field corn and canola modified to express the Agrobacterium sp. EPSPS and oxireductase genes, is glyphosate.

Subsequent to this decision, HED approved DuPont requests permitting the commercialization of Optimum GAT soybean and Optimum GAT field corn (D346713, T. Bloem, 12-Mar-2008; D357880, T. Bloem, 29-Oct-2008; D361315, T. Bloem, 14-Jan-2010).  Optimum GAT soybean was engineered to express the gat4601 gene (derived from Bacillus licheniformis; soil bacterium) and Optimum GAT field corn was engineered to express the gat4621 gene (derived from Bacillus licheniformis; soil bacterium) and the zm-hra gene (modified version of maize acetolactate synthase (ALS) gene).  The gat4601 and the gat4621 genes confer tolerance to glyphosate via acetylation of the secondary amine group of glyphosate (results in formation of the nonherbicidal N-acetyl-glyphosate); the zm-hra gene in Optimum GAT field corn, encodes for an ALS protein which is not sensitive to the ALS-inhibiting herbicides.  As a result of the introduction of these seed lines, HED concluded that the residues of concern in plants for tolerance expression and risk assessment should change from glyphosate to the combined residues of glyphosate and N-acetyl-glyphosate (D346713, T. Bloem, 12-Mar-2008).  Subsequent to this decision, it was determined that only the tolerance expression for field corn and soybean would change from glyphosate to the combined residues of glyphosate and N-acetyl-glyphosate; the tolerance expression for all other crops would remain as glyphosate.  

The current action is requesting application of glyphosate to a new variety of genetically altered corn developed by Monsanto (MON 87427 and MON87441).  Monsanto indicated that MON 87427 and MON87441 are tolerant to glyphosate via insertion of the CP4 EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene which, as indicated above, encodes for an EPSPS protein which is not inhibited by glyphosate.  MON 87427 and MON 87441 were also genetically altered to utilize a promoter and intron combination to limit expression of CP4 EPSPS in pollen microspore and tapetum cells.  Therefore, little to no CP4 EPSPS protein is expressed in MON 87427 and MON87441 pollen, thus pollen from these events is susceptible to glyphosate.  Glyphosate application to MON 87427 and MON87441 at early tassel development allows specific cross pollinations to be made without using the traditional methods to control self pollination.  The petitioner indicated that the resulting hybrid corn seed has full vegetative and reproductive tolerance to glyphosate due to the dominance of the glyphosate-tolerant trait inherited from the male parent.  A metabolism study has been previously been conducted with  field corn genetically altered to express CP4 EPSPS with HED concluding that the residue of concern was glyphosate (see above).  HED concludes that these data and decisions are translatable to MON 87427 and MON87441.  

Nature of the Residue  -  Livestock:  The qualitative nature of the residue in livestock following dosing with glyphosate and AMPA is adequately understood.  Studies with lactating goats and laying hens fed a mixture of glyphosate and AMPA indicate that the primary route of elimination was by excretion (urine and feces).  HED determined that the terminal residue to be regulated in livestock is glyphosate (Memo, R. Perfetti, 19-Oct-1992; RED, R. Perfetti, 27-Oct-1992; Memo, R. Perfetti, 17-Mar-1994).  

Since the Optimum GAT soybean and field corn metabolism studies resulted in significant residues of N-acetyl-glyphosate, DuPont submitted summaries of in vitro (rumen fluid, fertile hen egg, and rat liver S9 supernatant) and in vivo (rat metabolism study) studies conducted with the N-acetyl-glyphosate metabolite and submitted goat and hen metabolism studies conducted with the N-acetyl-glyphosate metabolite.  Based on these data and the glyphosate metabolism studies, HED concluded that the residues of concern in livestock following consumption of glyphosate and N-acetyl-glyphosate, for tolerance expression and risk assessment purposes, are glyphosate and N-acetyl-glyphosate (D346713, T. Bloem, 12-Mar-2008; D361315, T. Bloem, 14-Jan-2010).  Based on these data and since MON 87427 and MON87441 field corn do not result in any addition metabolites, HED concludes that the previous decisions concerning the residues of concern in livestock remain appropriate.  

Magnitude of the Residue  -  Field Corn:  The petitioner submitted 10 field corn field trials conducted in the North American Free Trade Agreement (NAFTA) growing zones 5 (n=8) and 5A (n=2).  Each field trial consisted of two treated plots planted with inbred NK603 (tolerant to glyphosate vie insertion of the CP4 EPSPS gene) as the male pollen donator and either inbred MON 87427 or MON 87441 as the female parent (see Nature of the Residue section in the Executive Summary for a description of these varieties).  Provided a revised Section B is submitted as described above, the employed application scenarios adequately mimic the proposed application scenario.  The harvested field corn forage, stover, and grain samples were analyzed for residues of glyphosate and AMPA using an adequately-validated method (storage interval has also been validated).  The maximum glyphosate residue in the treated field corn forage, grain and stover samples were 9.19 ppm, 0.80 ppm, and 30.85 ppm, respectively.  HED has previously determined that glyphosate residues do not concentrate in corn processed commodities (D216229, W. Cutchin, 21-Mar-1996).
 
Since the maximum glyphosate residue in field corn stover and grain is significantly less than the currently-established tolerances, revision of the stover and grain tolerances is unnecessary.  However, the maximum glyphosate residue in field corn forage is greater than the currently- established tolerance.  HED entered the glyphosate field corn forage residue data into the Agency's tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data; the resulting recommended tolerance is 13 ppm.  Since the petitioner proposed field corn forage tolerance is for residue of glyphosate only, HED requests that a revised Section F be submitted proposing 13-ppm field corn forage tolerance for the combined residues of glyphosate and N-acetyl-glyphosate (expressed as glyphosate).   

HED notes that only 10 field trials were conducted and only in NAFTA growing zone 5.  Therefore, the petitioner has not fulfilled the geographical requirements suggested in OPPTS 860.1500 for a field corn registration.  The petitioner noted that trials were only conducted in Zone 5 as this is the major hybrid seed corn production region in the U.S.  Based on this and since residues in stover and grain were significantly lower than the currently-established tolerance and since the currently established 400 ppm nongrass animal feed and 300 ppm grass forage tolerances are significantly greater than the HED-recommend field corn forage tolerance, meaning that residues in field corn forage will not effect the currently-established ruminant tolerances, additional field trial data are not required.  

Magnitude of the Residue - Livestock:  The revised OPPTS 860.1000 Table 1 (J. Stokes; Jun-2008) indicates that field corn forage (roughage), stover (roughage), grain (carbohydrate concentrate), and milled byproducts (carbohydrate concentrate) may fed to dairy/beef cattle and grain and milled byproducts may be feed to poultry and hogs.  Since the current petition requires a revision to only the field corn forage tolerance (tolerance increased from 6.0 ppm to 13 ppm) and since the roughage portion of the beef/dairy cattle diet will be occupied by the currently established 400 ppm nongrass animal feed and 300 ppm grass forage tolerances, HED concludes that the currently-established livestock tolerances remain appropriate.  

Nature/Magnitude of the Residue - Rotational Crops:  Based on a previously-reviewed confined rotational crop studies (3.71 lb ae/acre; MRIDs 41543201 and 41543202, A. Abramovitch, 14-Oct-1992) which resulted in glyphosate residues of >0.01 ppm in barley grain only (0.018 ppm; 125-day plantback interval (PBI)) and the limit of quantitation (LOQ) for the tolerance enforcement method of 0.05 ppm, HED concluded that a 30-day PBI was appropriate for all nonlabeled crops (D200041, G. Kramer, 12-May-1994; field rotational crop study has not been submitted).  HED notes that the rate employed in the confined rotational crop study was 0.6x the proposed rate; however, based on the LOQ for the tolerance-enforcement method and since confined rotational crop study employed application to bare soil, HED concludes that the proposed 30-day PBI for all crops is acceptable.   

Analytical Enforcement Method:  The field corn forage, stover, and grain samples collected from the crop field trials submitted in support of the current petition were analyzed for residues of glyphosate using a method similar to the current enforcement method.  Based on this similarity and since the field trial study resulted in acceptable recoveries, HED concludes that the current enforcement method is adequate to enforce the tolerances associated with the current petition.  

Recommendations:  Provided the petitioner submits a revised Sections B and F (see below), HED concludes that the residue chemistry database supports an unconditional registration for the proposed application scenario.  A human-health risk assessment will be prepared as a separate document.  

Summary of Residue Chemistries Deficiencies:

●Section B:  HED requests that the supplemental labels be altered to indicate the following:  (1) the minimum spray volume for ground and aerial application is >2 GPA; (2) postemergent directions should indicate that they apply to field corn up to the V8 crop stage and that a maximum of 2.3 lb ae/acre/season may be applied; and (3) PHI of 30 days for forage and 7 days for grain and stover.
●Section F:  HED requests that a revised Section F be submitted proposing a 13-ppm field corn forage tolerance for the combined residues of glyphosate and N-acetyl-glyphosate (expressed as glyphosate).   
Background

Glyphosate is a nonselective Group 9 herbicide which disrupts the synthesis of the aromatic amino acids tyrosine, tryptophan, and phenylalanine through inhibition of EPSPS.  Glyphosate is currently registered for pre- and post-emergence application to a variety of fruit, vegetable, and field crops.  Tolerances are currently established for residues of glyphosate in/on various plant commodities (including field corn) at 0.2-400 ppm (40 CFR §180.364(a)) and for the combined residues of glyphosate and N-acetyl-glyphosate (expressed as glyphosate) in/on field corn, soybean, AGF, and livestock commodities at 0.1-310 ppm.  The Glyphosate RED document was issued September 1993.  A Registration Review Scoping document was completed in 2009 (D362745, J. Langsdale et al., 3-Jun-2009).  The chemical structure/nomenclature physicochemical properties of glyphosate are presented in Tables 1 and 2.  

Table 1:  Glyphosate Nomenclature.
Compound
                                       
Common name
Glyphosate (PC code 471300)
Company experimental name
DPX-B2856
IUPAC/CAS name
N-(phosphonomethyl)glycine
CAS registry number
1071-83-6

Table 2:  Physicochemical Properties of Technical Grade Glyphosate.
Melting point
189.5 +- 0.5 °C
The Pesticide Manual, 13[th] Edition
pH
1.9 at 20 °C

Density
1.705 g/cm[3] at 20 °C

Water solubility
10.5 g/L at 20 °C

Solvent solubility
acetone		0.078 g/L
methanol		0.231 g/L
hexane		0.026 g/L
ethyl acetate	0.012 g/L
dichloromethane	0.233 g/L
n-octanol		0.020 g/L
propan-2-ol	0.020 g/L
toluene		0.036 g/L
European Commission:  Glyphosate 6511/VI/99-final, 1/21/02
Vapor pressure
1.31 x 10[-2] mPa at 25 °C
The Pesticide Manual, 13[th] Edition
Dissociation constant, pKa
0.8 (1[st] phosphoric), 2.3 (carboxylate), 6.0 (2[nd] phosphoric), and 11.0 (amine)
Knuuttila.  1979 Acta Chem. Scand. B 33:623-626
Octanol/water partition coefficient, Log(KOW)
-3.2 (pH 2-5, 25 °C)
European Commission:  Glyphosate 6511/VI/99-final, 1/21/02
UV/visible absorption spectrum
ε = 0.086 (295nm)


860.1200  Directions for Use

The petitioner submitted proposed supplemental labels for Roundup WeatherMAX[(R)] (EPA Reg. No. 524-537) and Roundup Power MAX[(R)] (Reg. No. 524-549); both of these products are SC formulations consisting of glyphosate as the potassium salt at 4.51 lb ae/gallon.  The submitted supplemental labels indicate that the application scenarios are for use in research field trials and for seed production of corn hybrids using the RHS[(TM)] system.  Table 3 is a summary of the proposed application scenarios.  The proposed use directions are similar to that currently registered with the exception of the tassel control instructions (V8-V13); maximum seasonal application rate is the same.  HED requests that the supplemental labels be altered to indicate the following (a revised Section B is requested):  (1) the minimum spray volume for ground and aerial application is >2 GPA; (2) postemergent directions should indicate that they apply to field corn up to the V8 crop stage and that a maximum of 2.3 lb ae/acre/season may be applied; and (3) PHI of 30 days for forage and 7 days for grain and stover.

Table 3:  Summary of Proposed Roundup Ready(R) Field Corn Application Scenario.
                                  Formulation
                                (EPA Reg. No.)
                                 App. Timing 
                                   App. Rate
                                 (lb ae/acre)
                          Max. App. Rate (lb ae/acre)
                        Use Directions and Limitations
Roundup WeatherMAX[(R)] (EPA Reg. No. 524-537; SC; 4.51 lb ae/gal)

Roundup Power MAX[(R)] (EPA Reg. No. 524-549; SC; 4.51 lb ae/gal)
preplant, at planting, preemergence
                                 not specified
                                     3.72
-For use in research field trails and for seed production of corn hybrids using RHS[(TM)].  
-Allow a minimum of 10 days between postemergent applications.

postemergence
                                   0.56-0.78
                                 not specified


tassel control (V8-V13 or 100 growing degree units; before flowering)
                                   0.39-1.13
                                     2.26


preharvest
                                     0.78
                                 not specified


postharvest
                                 not specified
                                 not specified


maximum seasonal application rate
                                      --
                                     5.98


860.1300 Nature of the Residue - Plants and Livestock

See Executive Summary.

860.1340 Residue Analytical Methods

The field corn forage, stover, and grain samples collected from the crop field trials submitted in support of the current petition were analyzed for residues of glyphosate and AMPA using an adequately-validated high-performance liquid chromatography (HPLC) equipped with a fluorescence detector method.  Briefly, samples were extracted with chloroform:aqueous 0.1 N HCl (1:3).  The aqueous layer was collected and applied to a Chelex(R) 100 column eluted with 6 N HCl followed by an anion exchange resin also eluted with 6 N HCl.  The sample was concentrated, dissolved in water, and analyzed.  Based on the lowest level of method validation (LLMV), the LOQ is 0.05 ppm for each analyte/matrix.  Apparent residues of glyphosate and AMPA were <LOQ in all control samples.  Based on the acceptable recoveries and since interfering residues were <LOQ in controls, the employed analytical method is adequate for data-collection purposes.  

The data-collection method is similar to the current enforcement method (Memo, R. Perfetti, 10/27/92).  Based on this similarity and since acceptable recoveries were attained in the field trials, HED concludes that the current enforcement method is adequate to enforce the tolerances associated with the current petition.  

860.1360 Food and Drug Administration (FDA) Multiresidue Methods (MRMs) Protocols

The Pestrak database (1990) indicates that recoveries are not likely for glyphosate under FDA Multiresidue Methods.  No further data regarding multiresidue methods are required for this proposed use. 

860.1380 Storage Stability

The maximum interval from collection to extraction for the forage, stover, and grain samples was 284 days (9.5 months).  Previously submitted data indicate that glyphosate is stable for 31 months in/on fortified and frozen corn, sorghum straw, clover, tomato, and soybean forage; residues of AMPA fluctuated from 50-99% in the same time period (D206278, C. Eiden, 17-Nov-1994).  Since AMPA is not a residue of concern in plants (Memo, R. Perfetti, 17-Mar-1994), HED concludes that the available storage stability data are sufficient to validate the residue data submitted in support of the current petition.    

860.1480 Meat, Milk, Poultry, and Eggs

The revised OPPTS 860.1000 Table 1 (J. Stokes; Jun-2008) indicates that field corn forage (roughage), stover (roughage), grain (carbohydrate concentrate), and milled byproducts (carbohydrate concentrate) may fed to dairy/beef cattle and grain and milled byproducts may be feed to poultry and hogs.  Since the current petition requires a revision to only the field corn forage tolerance (tolerance increased from 6.0 ppm to 13 ppm) and since the roughage portion of the beef/dairy cattle diet will be occupied by the currently established 400 ppm nongrass animal feed and 300 ppm grass forage tolerances, HED concludes that the currently-established livestock tolerances remain appropriate.  

860.1500 Crop Field Trials
47982201.der.doc

The petitioner submitted 10 field corn field trials conducted in the NAFTA growing zones 5 (n=8) and 5A (n=2).  Each field trial consisted of two treated plots planted with inbred NK603 (tolerant to glyphosate vie insertion of the CP4 EPSPS gene) as the male pollen donator and either inbred MON 87427 or MON 87441 as the female parent (see Nature of the Residue section in the Executive Summary for a description of these varieties).  Table 4 is a summary of the employed application scenarios; provided a revised Section B is submitted as described above, the employed application scenarios adequately mimic the proposed application scenario.  All applications were broadcast sprays made with Roundup WeatherMAX[(R)] (EPA Reg. No. 524-537; water-soluble concentrate formulation of glyphosate formulated as the potassium salt (4.5 lb ae/gal; 540 g ae/l)) and included (NH4)2SO4 and a nonionic surfactant (NIS).  The harvested field corn forage, stover, and grain samples were analyzed for residues of glyphosate and AMPA (aminomethyl phosphonic acid) using an adequately-validated method (storage interval has also been validated).  Table 5 is a summary of the residue data.  In general, residues were higher under the treatment 2 application scenario as compared to the treatment 3 application scenario (only slightly higher in grain).  
Conclusions:  Tolerances for the combined residues of glyphosate and N-acetyl-glyphosate (expressed as glyphosate) in/on field corn forage, stover, and grain are currently established at 6.0 ppm, 100 ppm, and 5.0 ppm, respectively (180.364(a)(2)).  HED notes that the tolerance expression includes residues of N-acetyl-glyphosate due to the introduction the Optimum GAT field corn variety (see Nature of the Residue Section in the Executive Summary for a description of this variety).  

Since the maximum glyphosate residue in field corn stover (30.85 ppm) and grain (0.80 ppm) is significantly less than the currently-established tolerances, revision of the stover and grain tolerances is unnecessary.  However, the maximum glyphosate residue in field corn forage (9.19 ppm) is greater than the currently-established tolerance.  HED entered the glyphosate field corn forage residue data from the treatment 2 scenario (resulted in higher residues) into the Agency's tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data (see attachment 2); the resulting recommended tolerance is 13 ppm (see Attachment 3).  Since the petitioner proposed field corn forage tolerance is for residue of glyphosate only, HED requests that a revised Section F be submitted proposing a 13-ppm field corn forage tolerance for the combined residues of glyphosate and N-acetyl-glyphosate.   

HED notes that only 10 field trials were conducted and only in NAFTA growing zone 5.  Therefore, the petitioner has not fulfilled the geographical requirements suggested in OPPTS 860.1500 for a field corn registration (zones 1 (n=1), 2 (n=2), 5 (n=17), and 6 (n=1)).  The petitioner noted that trials were only conducted in Zone 5 as this is the major hybrid seed corn production region in the U.S.  Based on this and since residues in stover and grain were significantly lower than the currently-established tolerance and since the currently established 400 ppm nongrass animal feed and 300 ppm grass forage tolerances are significantly greater than the HED-recommend field corn forage tolerance, meaning that residues in field corn forage will not affect the currently-established ruminant tolerances, additional field trial data are not required.

Table 4:  Summary of Application Scenarios.

                             lb ae/acre (kg ae/ha)

                                 premeergence
                                     V3-V4
                                     V7-V8
                                    V9-V10
                                    V12-V13
                                   late dent
                                     total
treatment 2
                                   0.76-0.80
                                  (0.85-0.90)
                                   1.09-1.15
                                  (1.22-1.29)
                                   1.09-1.15
                                  (1.22-1.29)
                                   1.0-1.17
                                  (1.20-1.31)
                                   1.12-1.15
                                  (1.26-1.29)
                                   0.77-0.81
                                  (0.86-0.91)
                                   6.00-6.15
                                  (6.73-6.89)
treatment 3
                                   1.54-1.58
                                  (1.73-1.77)
                                   1.12-1.16
                                  (1.26-1.30)
                                   1.10-1.15
                                  (1.23-1.29)
                                   0.77-0.80
                                  (0.86-0.90)
                                   0.77-0.80
                                  (0.86-0.90)
                                   0.77-0.81
                                  (0.86-0.91)
                                   6.14-6.23
                                  (6.86-6.98)
retreatment interval (RTI; days)
                                      --
                                     16-35
                                     9-25
                                     6-11
                                     4-11
                                     55-88
                                      --

Table 5:  Summary of Glyphosate and AMPA Residues.
                                    Analyte
                                   Commodity
                                   Treatment
                                Residues (ppm)
                                       
                                       
                                       
                                     Range
                                     Mean
glyphosate
                                    forage
                                       2
                                   2.59-9.19
                                     5.73

                                       
                                       3
                                   1.95-6.88
                                     4.34

                                    stover
                                       2
                                  11.08-30.85
                                     18.05

                                       
                                       3
                                  4.26-21.47
                                     12.42

            grain (collected 1 day prior to the final application)
                                       2
                                   0.19-0.77
                                     0.40

                                       
                                       3
                                   0.15-0.45
                                     0.26

             grain (collected 7 days after the final application)
                                       2
                                   0.19-0.80
                                     0.46

                                       
                                       3
                                   0.16-0.74
                                     0.34
AMPA
                                    forage
                                       2
                                   0.07-0.25
                                     0.15

                                       
                                       3
                                   0.07-0.19
                                     0.12

                                    stover
                                       2
                                   0.14-0.41
                                     0.28

                                       
                                       3
                                   0.07-0.34
                                     0.21

            grain (collected 1 day prior to the final application)
                                       2
                                   0.05-0.11
                                     0.08

                                       
                                       3
                                 <0.05-0.08
                                     0.06

             grain (collected 7 days after the final application)
                                       2
                                   0.06-0.10
                                     0.08

                                       
                                       3
                                 <0.05-0.08
                                     0.06

860.1520 Processed Food and Feed

HED has previously determined that glyphosate residues do not concentrate in corn processed commodities (D216229, W. Cutchin, 21-Mar-1996).

860.1850 & 860.1900 Confined and Field Accumulation in Rotational Crops

Based on a previously-reviewed confined rotational crop studies (3.71 lb ae/acre; MRIDs 41543201 and 41543202, A. Abramovitch, 14-Oct-1992) which resulted in glyphosate residues of >0.01 ppm in barley grain only (0.018 ppm; 125-day PBI) and the LOQ for the tolerance enforcement method of 0.05 ppm, HED concluded that a 30-day PBI was appropriate for all nonlabeled crops (D200041, G. Kramer, 12-May-1994; field rotational crop study has not been submitted).  HED notes that the rate employed in the confined rotational crop study was 0.6x the proposed rate; however, based on the LOQ for the tolerance-enforcement method and since confined rotational crop study employed application to bare soil, HED concludes that the a  30-day PBI for all nonlabeled crops is acceptable.   

860.1550 Proposed Tolerances

Table 6 is a summary the proposed and HED-recommended tolerances for the combined residues of glyphosate and N-acetyl-glyphosate (expressed as glyphosate); a revised Section F is requested.  There are no Mexican, Canadian, or Codex field corn forage maximum residue limits (MRLs) but there is a Canadian MRL in/on "corn" of 3.0 ppm and a Codex MRLs in/on "maize" of 5 ppm which could be applied to any corn commodity (see Attachment 1).  Regardless, since the residues of concern differ, harmonization is not possible.  

Table 6.  Tolerance Summary.
                                   Commodity
                           Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                                   Comments
corn, field, forage
                                      13
                                      13
The petitioner proposed tolerance is for residues of glyphosate only while the HED-recommended tolerance is for the combined residues of glyphosate and N-acetyl glyphosate; a revised Section F is requested.

Attachment 1 - International Residue Limit Status sheet
Attachment 2 - Chemical Name and Structure Table
Attachment 3 - Tolerance Spreadsheet Summary

RDI: RAB1 Chemists (8-Dec-2010)
T. Bloem:S10945:Potomac Yard 1:703-605-0217:7509P:RAB1
Attachment 1  -  Glyphosate International Residue Limit Status Sheet

Summary of US and International Tolerances and Maximum Residue Limits 
Residue Definition:
                                      US
                                    Canada
                                   Mexico[2]
                                     Codex
40 CFR 180.364(a)(2): glyphosate and N-acetyl-glyphosate
N-(phosphonomethyl) glycine, including the metabolite aminomethyl phosphonic acid
                                      --
glyphosate
Tolerance (ppm) /Maximum Residue Limit (mg/kg)
Commodity[1]
                                      US
                                    Canada
                                   Mexico[2]
                                     Codex
Corn, field, forage
                                      13
                                  3.0 (corn)
                                      --
                                   5 (maize)
Completed  M. Negussie; 12/01/2010
[1]  Includes only commodities of interest for this action.  Tolerance values should be the HED recommendations and not those proposed by the applicant.
[2]  Mexico adopts US tolerances and/or Codex MRLs for its export purposes.



Attachment 2 - Chemical Structures

                                   Compound
                                   Structure
Glyphosate

N-(phosphonomethyl)glycine
                                       
N-acetyl-glyphosate

N-acetyl-N-(phosphonomethyl)glycine
                                       P
O
O
H
O
H
N
O
H
O
O
C
H
3
AMPA

(aminomethyl)phosphonic acid
                                       
N-acetyl-AMPA

[(acetylamino)methyl]phosphonic acid
                                       


Attachment 3:  Tolerance Spreadsheet Summary




