UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF PREVENTION. PESTICIDES AND TOXIC SUBSTANCES July 

### 30, 2001

MEMORANDUM SUBJECT: 

### HED Response to Data Waiver Request for Mepiquat Pentaborate. PC Code 109105. DP Barcode D276574. 

### FROM: Danette Drew, Chemist Reregistration Branch 3 Health Effects Division (7509C)
/- THRU: Catherine Eiden, Branch Senior Scientist

# c>*FA Reregistration Branch 

### 3 Health Effects Division (7509C) TO: CP Moran, CRM Cynthia Giles-Parker, 

### PM Registration Division 

### (7505W)

Action Requested BASF Corporation has submitted a Registration Application 

### for Mepiquat Pentaborate Plant Growth Regulator (Pix Ultra 11; EPA Reg No. 7969-XXX) for Use 

### on Cotton (July 20, 2000; PP# 1F6250). The application contains requests for translating existing toxicology and residue chemistry data 

### for mepiquat chloride @,N-dimethylpiperidinium chloride)to mepiquat pentaborate (N,N-dimethylpiperidinium pentaborate). Pix Ultra 

### (EPA reg. 

### No. 7969-149) is a mepiquat chloridepremix containing disodium octoborate tetrahydrate which isregistered for use on cotton. Theregistrant stated that mepiquate pentaborate will eventually replace mepiquat chloride for use on cotton. 

### Also submitted 

### was a dissociation study 

### (MRID45007102) indicating that theboron containing moiety in 

### Pix Ultra and 

### Pix Ultra 

### I1 exhibit identical dissociativebehavior 

### in aqueous solution, at application relevant levels.

# . The Health Effects Division (HED), asper Registration Division’s request, has evaluated these submissionswith regard to the toxicology and residue chemistry data waiver requests. Detailed considerations can be found in the attached memos: 

### 1) TOXSAC Memorandum of 6/14/01 meeting (J.Stewart),2) Memorandum dated 6/27/01 (A.Protze1to J.Stewart), 

### 3) Memorandum dated 2/23/89 (C.Kent to E.Tinsworth), 

### 4)Minutes of 5/16/01 ChemSAC meeting (HED Chemistry Science Advisov Council to HED Chemistry Interest Group). Executive Summary WED recommends for a conditional registration for Pix Ultra 

### I1 (mepiquat pentaborate). The conditionsofregistration are outlined as follows: 1.Fulfillment of any residue chemistry and toxicological data gaps identified for mepiquat chloride is required. It is recommended that any study not yet begun formepiquat chloride be performed using mepiquat pentaborate. 

### 2. A dissociation study in oil (forboth Pix Ultra and Pix Ultra 

### 11)is required ifoil is intended 

### as 

### an application vehicle as indicated in the proposed mepiquat pentaborate label. 3. In order to bridge residue data, three side-by-side field trials are required for Pix Ultra and Pix Ultra I1 with water as the diluent. An additional three side-by-side trials should also be performed using oil asthe diluent (Alternatively,the ultra low volume application directions, using oil as the diluent, can be removed from the label). Trials should take place in Regions 4, 

### 8, and 10. Tolerances are currently established under 

### 40 

### CFR 5180.384 for residues ofmepiquat chloride p,N-dimethylpiperidinium chloride] don cottonseed 

### (2.0 pprn), grapes 

### (1.O ppm), raisins (5.0 pprn), and for the fat,meat, and meat byproducts of cattle, goats,hogs, horses, and sheep (each at 0.1 ppm). HED recommends that the current tolerance expression for mepiquat chloride 

### [N,Ndimethylpiperidinium chloride] be modified to read “Tolerances are established for the residues ofthe plant growthregulator N,N-dimethylpiperidinium on the following raw agricultural cornmodities”. Additionally, HED recommends for the establishment of atolerance for mepiquat on cotton gin byproducts at 

### 6ppm (D239446, 

### 7/27/01, D.Drew). A new livestock maximum theoretical dietary burden (MTDB) was calculated using the recommended cotton gin byproduct tolerance of 

### 6ppm (seeTable 1).A feeding study showed residues in milk, muscle, and fat.were<0.05ppm 

### (<LOD) at the 

### 7X feeding level. It was determined previously that a 180.6 (a) (3) [noreasonable expectation offiniteresidues] situation exists for milk, poultry, and eggs and that these tolerances should be revoked (D218492, 1/96,

### F.Fort). As 

### the residues inmeat and fat were 

### also <

### 0.05 ppm 

### (<LO.D) at the 

### 7X feeding level, a 180.6(a) 

### (3) situation exists formeat and fat; HED now recommends that thosetolerances should 

### also berevoked.Considerations and Conclusions 1. The Toxicology Science Advisory Council (TOXSAC) has no objection to data waivers being granted for Tier 1 data (subchronicrodent oral toxicity study, developmental toxicity study, mutagenicity data) for mepiquat pentaborate (TOXSAC Memo of 6/14/01 meeting,J.Stewart) based on the considerations outlined below. However, if oil is used as an application vehicle, as indicated in the proposed Pix Ultra 

### I1 label, then dissociation data in oil would be required. All data gaps identified for mepiquat chloride are applicable to mepiquat pentaborate. It is recommended that any toxicity study which has not yet been started for mepiquat chloride be performed using mepiquat pentaborate instead. The only toxicological data gap listed in the human health 

### risk assessment for mepiquat chloride on grapes and raisins 

### (PP#1F0395) was a developmental neurotoxicity study in rats (D258184, 11/22/99,M.Collantesand M.Nelson). a) Theregistrant has submitted a battery of acute toxicity studies on mepiquait pentaborate which demonstrate that the acute toxicity is not significantly different 

### from that of mepiquat chloride. b) Theregistrant has submitted a dissociation study to demonstratethat mepiquat pentaborate dissociates in water in 

### an identical physical manner to mepiquat chloride with solubor;they both dissociate to the monoborate. c) The Tox Sacreceived an opinion from Alberto Protzel, Ph.D., ofthe Toxicology Branch indicating that Pix Ultra and Pix Ultra 

### 11, when comparedper unit ofmepiquat cation, are not significantly different asto impurities and the manufacture ofmepiquat pentaborate does not introduce any toxicologically significant new moieties. d) The registrant references 

### an Agency policy memorandum: Kent to Tinsworth dated 2/23/89 regarding data requirements for chemicalsthat contain mineral salts, esters, and amines of an acid parent compound. The memorandum statesthat for toxicology information, data on the acid are generally acceptedto support the mineral salts,thus no additional data would be required for those entities. For esters and amines, additional toxicology data (acutetoxicity studies; subchronic feeding study; 2 1 day dermal toxicity study, developmental toxicity study, mutagenicity studies and rat metabolism study) are required. 2. The Chemistry ScienceAdvisory Council (ChemSAC)has concluded that, for foliar application ofmepiquatpentaborate to cotton, a conditional registration would not be precluded based on existingresidue data for mepiquat chloride and on the results ofthe dissociation study (Minutes of 5/16/01 ChemSAC meeting). However, 

### fullregistration will be contingent onthe submission ofacceptable side-by-side field trials. Three side-by-side cotton field trials are recommended for Pix Ultra and Pix Ultra 

### I1 at maximum labelrates using water 

### as the diluent. Also, 

### an additional three side-by-side field trials are recommended using the oil based ultra-low volume 

### (ULV) application (Alternatively, the 

### ULV application directions, using oil 

### as the diluent, can be removed fromthe label). Trials should reflect adequate geographicrepresentation for cotton production. It isrecommended that 

### trialsbe performed in Regions 4,8, and 10(seeOPPTS Test Guidelines 860.1500). 3. Tolerances are currently established under 40 

### CFR 5180.384 for residues ofmepiquat chloride 

### [N,N-dimethylpiperidinium chloride] in/on cottonseed (2.0ppm), grapes (1 

### .O pprn), raisins 

### (5.0 ppm), and for the fat, meat, and meat byproducts of cattle, goats, hogs, horses, and sheep (each at 

### 0.1ppm). HED recommends that the current tolerance expression for mepiquat chloride be modified to read “Tolerances are established for the residues ofthe plant growth regulator N,Ndimethylpiperidinium on the following raw agricultural commodities”. Additionally, HED recommends for the establishment of a tolerance for mepiquat on cotton gin byproducts at 6 ppm (D239446, 7/27/01, D.Drew). A 180.6(a) (3) situation exists for meat and fat and HED recornmends that those tolerances should be revoked.
4. Any outstanding data gaps for mepiquat chloride are applicable to mepiquat pentaborate. The petitioner has proposed the mepiquat chloride ion chromatography method 

### (BASF Method D96 10)for the determination ofresidues ofmepiquat pentaborate

### per se idoncotton and animal commodities (D244052, 7/27/01. D. Drew and D274482, 7/27/01, D.Drew). The validated method 

### LOQ for the method is 0.1 ppm for cottonseed and 

### 0.05ppm for beef liver. Adequate method recoveries were obtained for residuesofmepiquat pentaborate fiom fortified samples ofcottonseed (112-12 1%) and beef liver 

### (100-1

### 12%);however, we note.that the recoveries ofmepiquat chlorideper se in the same commodities were significantly lower: 

### 65­ 92% in cottonseed and 73-97% in beef liver (see DP Barcode D244052) using BASF Method D9610. An interferencepeak which elutes closely aftermepiquat pentaborate may be inflating the mepiquat pentaborate quantitation. The factthat the interference peak was observed both in cotton seed and beef liver samples seemsto indicate that the interference is not due to a m&ix coextractablebut may .bearising from the method. This could not be confirmed as the petitioner did not run a method blank. The interference was not observed in the standards used for the calibration curve. The petitioner should m&e some attempts to identify and removethe source ofthis interferencepeak. Method validation has been submitted for residues ofmepiquat chloride in cottonseed and cow liver. However, that study was not performed by an independent laboratory (both studies performed by Centre Analytical Laboratories [State College, PA]). An acceptable independent laboratory validation (ILV) ofmethod D9610 is required using an independent laboratory. It is recommended that the ILV be performed for mepiquat pentaborate as the registrant has stated that mepiquat pentaborate will eventually replace mepiquat chlorideuse on cotton. Once an acceptable ILV is submitted, the method will be submitted to EPA’s analytical laboratory for method tryout. Once acceptable Agency validation oftheproposed ion chromatography enforcementmethod 

### (D9610)hasbeen conducted, the method can be forwarded to FDA for inclusion in

### PAM Vol. 

### I1 asa numbered method for enforcement ofresidues ofmepiquat idon cotton 

### and animal tissues, milk, and eggs. 5. At this time, a human health risk assessment isnot required for mepiquat pentaborate foliar 

### use on cotton. Human health risk assessmentswere perfprmed previously formepiquat chloride4 on cotton (The HED Chapter ofthe FEDfor Mepiquat Chloride, D222017, 7/8/96, M.Clock) and for mepiquat chloride on grapes 

### (PP#1F03955. Mepiquat Chloride idonGrapes and Raisins. Human Health 

### hskAssessment, D258 184.1 1/22/99,M.Collantes and M-Nelson).A dietary assessment was performed for mepiquat chloride assuming tolerance level residues and 100% crop treated for cotton, grape, meat, fat, and meat by-products (D260557, 11/1/99,W. Cutchin). 

### Risk estimates for exposureto mepiquat chloride were below HED’s level of concern. Field trials for cotton gin byproducts were identified as a data gap in the HED Chapter ofthe RED for Mepiquat Chloride (D222017, 7/8/96, M.Clock ). A cotton gin byproduct field trial study (BASF 1997 submission, MRID 44379701) was recently reviewed (D239446, 7/27/01, D.Drew) and found to be acceptable. The results support the establishment of a tolerance for mepiquat 

### (N,N-dimethylpiperidinium) on cotton gin byproducts at 6 ppm. A new livestock maximum theoretical dietary burden (MTDB) was calculated using the recommended cotton gin byproduct tolerance of 6pprn (see Table 1).A feeding study showed maximum secondary residues of 0.19 ppm and 0.20 ppm mepiquat chloride in the liver and kidney, respectively, oflactating cows fed 13ppm mepiquat chloride 

### (7X the MTDB). Residues in milk, muscle, and fat were <0.05ppm (<LOD) at the 

### 7X feeding level. The data indicate that existing tolerances for mepiquat chloride in meat, kidney, liver and fat are adequate. It was determined that 

### a 180.6 (a) 

### (3) [no reasonable expectation of finite residues] situation exists for milk, poultry, and eggs and that these tolerances should be revoked (D218492, 1/96,F.Fort). As the residues in meat and fat were <0.05 pprn (<LOD) at the 7X feeding level, a 180.6 (a) (3) situation also exists for meat and fat and those tolerances should also be revoked. Anticipated residues (ARs) for meat byproducts from cattle fed at 1X the MTDB would be well below the tolerance of 0.1 ppm that was used in the previous dietary assessment (D260557, 11/1/99,W. Cutchin). A dietary exposure assessment incorporating these ARs would result in risk estimatesbelow HED’s level of concern and is therefore not required.

Feed Tolerance % in Diet % Dry Dietary Burden (pprn) (PPm) Matter
cotton gin byproducts 6 20 90 1.3 cotton, undelinted seed 2 25 88 0.6 MTDB = 1.9 ppm

cc:RF; List B File; D.Drew ,CPMoran (RD); C. Giles-Parker (RD) RDI: C. Eiden (7/30/01) D.Drew:CM-2, nn 821E, 305-6028UNITED STATES ENVIRONMENTALPROTECTIONAGENCY WASHINGTON. D.C. 20460

OFFICEOF PREVENTION,PESTICIDES AND TOXIC SUBSTANCES


### MEMORANDUM Subject: TOX-SAC Discussion on Data Waiver Request for Mepiquat Pentaborate, a new pesticide active ingredient; replacement salt for mepiquat chloride. 

### To: Deborah Smegal, Toxicologist Reregistration Action Branch Health Effects Division (H7509C) f From: Joycelyn

### E. Stewart, Ph.D., 

### Chair 

# 4s

, 1

# I.>;

I . x-.

~ Toxicology ScienceAdvisory Council 

# , I Health Effects Division (H7509C) The Toxicology ScienceAdvisory Council met on 6/14/2001 to consider a request from BASF Corporation 

### (BASF) to waive the requirements 

### for Tier 

### I data (subchronicrodent oral toxicity study, developmentaltoxicity study, mutagenicitydata etc, for mepiquat pentaborate. BASF intends 

### to replace mepiquat chloridewith mepiquat pentaborate. Thebasis for the request was stated as follows: There is a Registration for use of PlX Ultra (meDiauat chloride with ingredient 

### in the Pix Ultra formulation, and is listed as 

### an adjuvant. 

### A~,eae.rnptian~&~~~~ the requirements of a tolerance has been established

### for residues 

### ofi

- --I 

### in or 

### on raw agriculturalproducts when used pre-or post- harvest 

### in accordance with good agricultural practices. The request was presented by Debbie Smegal of

### RRAB 3. Attendees: TOX-SAC Members; Joycelyn Stewart (Chairman).Mike Ioannou, 

### Clark Swentzel, Ed Budd, Linda Taylor,Marion Copley, 

### John Doherty. Observers;C.P. Moran ofRegistration Division; and DannetteDrew and 

### John Liccione of

### RRAB3. Information Considered 1. The registrant has submitted a battery 

### of acute toxicity studies 

### on mepiquat pentaborate which demonstrates that the acute toxicity 

### is not significantlydifferent from that of mepiquat chloride. 2. The registrant has submitted a dissociation stub; t.0demonstratethat mepiquat pentaborate

InternetAddress (URL) http://www.epe.-oov Eecy:lraTlccyclablr .Printed wflh Vep!aS:e GI! Ead Inkon RecycledPaper (Minimumb25% Fcscunsumericompletely dissociates 

### in water 

### in an identical physical manner to mepiquat chloridewith solubor; they both dissociateto the monoborate. 3. The Tox Sac received 

### an opinion from Albert0 Protzel, Ph.D., ofthe Toxicology Branch indicatingthat PIX 

### ULTRA and mepiquat pentaborate when compared per unit 

### of mepiquat cation, are not significantlydifferent 

### as to impuritiesand the manufacture of mepiquat pentaborate does not introduce any toxicologically significantnew moieties (memorandum:Protzel to Stewart 6/16/2001 attached). It had been suggested that there is a formulation in 

### an oil vehide However,this could not be verified from the documentation provided by the registrant.
4. The registrant references 

### an Agency policy memorandum:Kent to Tinsworth dated 2)23/89 regarding data requirementsfor chemicals that contain mineral salts, esters, 

### and amines of 

### an acid parent compound.The memorandum statesthat for 

### toxicology information, data 

### on the acid are generallyaccepted to support the mineral salts, thus no additionaldata would be required for those entities..For esters and amines, additional toxicology data (acute toxicity studies; subchronic feeding study; 21 day dermal toxicity study, developmentaltoxicity study., mutagenicity studies

### and rat metabolism study) are required. The Toxicology Science Advisory Council has obtained a copy 

### ofthe memorandum.The memorandum will be posted on the 

### LAN in an appropriatefile 

### as soon as possible. Conclusion: The TOX-SAC considered that the dissociation study data presented by the registrant supported the data waiver request 

### and that no precedent would be set by granting the waiver. Thereforethe Toxicology Science Advisory has no objection to data waivers be granted for the studies which the registrant has requested, provided that no oil vehicle is used. Dissociation data would be required if 

### an oil vehicle is used. It should be noted that the 

### HIARC had requested that a developmental neurotoxicity study be performed for mepiquat chloride.It should be understood that all data gaps applicableto mepiquat chloride are also applicable

### to mepiquat pentaborate. It is recommended that 

### any toxicity study which the registrant has not yet started on mepiquat chloride should be performed using mepiquat pentaborate. Information

### in this memorandum is filed on 

### LAN.HED/SAC/TOXSAC/TOXMIN 18 Attachments 1.Memorandum:Protzel 

### to Stewart; Comparison ofPix Ultra Plant Regulator and Mepiquat Pentaborate dated 6/27/2001. 2.Memorandum:Kent to Tinsworth;Data Requirements

### for Chemical Cases which contain salts, Esters or Amines oftheParent Compound dated 2/23/1989.UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON. D.C. 20460

OFFICE OF PREVENTION, PESTICIDESAND TOXIC SUBSTANCES

DATE: June 13,2001



### MEMORANDUM

SUBJECT: Comparison of PIX Ultra Plant Regulator and Mepiquat Pentaborate. A. 

### FROM: Albert0 Protzel Ph.D. 

### BSS Tox. Branch 

### I Health Effects Division (7509C)



### TO: Joycelyn Stewart, Ph.D. Chair Tox. SAC Health Effects Division (7509C)

ACTION:Determineifthecomposition 

### ofMepiquatpentaborateandPIXULTRAaresignificantly differently asto impurities and other toxicologically significant chemicals. CONCLUSION: 

### The dataexamined indicatethat PIX ULTRA andMepiquatPentaborate, when compared per unit of mepiquat cation, are not significantly different 

### as to impurities 

### and other toxicologically significantmoieties.1. Introduction. 

### BASF has submitted a residue chemism data and toxicity data waiver request for rnepiquat pentaborate (PIX

### ULTRA 11 Plant 

### Growth Regulator, Table 1)for use on cotton. 

### Thebasis for the request 

### is : chloride ( 

### as 

### PIX ULTRA, a mixture ofh4epiquat chloride 

### wi is alreadyregistered forusein cotton. Theproductionprocess andminvoduces 

### no newby-products 

### (MRID 45007104). 

### 2.Theboroncontainingmoiety 

### in Mepiquatchloride 

### (asPIX 

### ULTRA)

### and mepiquatpentaborate exhibit identical dissociationbehavior in solution, at application-relevantlevels, 

### asdetermined

### by 

### NMR spectroscopy 

### of 

### "B (MFUD 45007102)

11. Detailed Considerations.. .A.The Production Process for Mepiquat Pentaborate:

### B. Examination 

### ofthe 

### CSF forms: Table 2 displays 

### CSF datafor 

### various Mepiquat formulations. 

### Columns2,3and 

### 4 contain data for Mepiquat Pentaborate (thenew formulation, subjectof

### this memo). 

### Columns 

### 5 and 

### 6 contain data 

### . for PIX 

### ULTRA (the EPA-registered borate-containing formulation for Mepiquat chloride), and columns 7, 8 and 9 contain data for PIX plant Regulator (an EPA-registered formulation of Mepiquat chloride).

### Page - 

### is not included in this copy. Pages through
- 

### are not included in this copy.

The material not included contains the following type of information: Identity of product inert ingredients. Identity of product impurities. Description of the product manufacturing process. Description of quality control procedures. Identity of the source of product ingredients. Sales or other commercial/financial information. product label. The product confidential statement 

### of formula. Information about a pending registration action.

FIFRA 

### registration data. The document is a duplicate 

### of page(s) The document is not responsive to the request.

The information not included is generally considered confidential by product registrants. If you have any questions, please contact the individual who prepared the response to your request., Comparisonofcolumns

### 2,3,84(forMepiquatPentaborate)with columns

### 6

### and 7 

### for

### PIX ULTRA
o newimpurities aregenerated

### inthe

# TMepiquat pentaborate 

### (TGAI). The impurity Methylpipendine, 

### a syntheticprecursor ofmepiquat 

### ,is seen in hllepiquat ntaborate 

### (TGAI. col. 

### 2)and in the EPA-registered Pix 

### Plant Regulator (col. 

### 9) in the ratio of-The significance of thsratio is unclear, and may be exaggerated, as indicated by data below. Even though 1- Methylpipendineisnot reported inthe 

### CSFdataforPIX Ultra (cols. 

### 5 and 

### 6),otheranalyses

### shown below indicate that it is presenr in the PIX 

### ULTRA formulation and at the same levels as in Mepiquat pentaborate. Relativelevelsof

### I-methylpipendinelveredeterminedinthe hllepiquatformulationslisted in Table 

### 3. The 

### BAS 130formulationsareMepiquatpentaborate formulations. 

### BAS 083 

### 45W istheEPAregisteredboron-containing formulation PIX

### ULTRA. Toperform the analyses(Table 

### 3), ho~m dilutionsofthe

### ~wious formulationsweremadeand theareasof 1-methylpipendinepeaks in HPLC 

# 8 runs were determined



### . When the peak areas of 1-methylpipendine were normalized for unit 

### �3 

# 8 mepiquat cation concentration it \vas foundthat the levels of 1-methylpipendinewere comparable. 

### i; As shown in Table 

### 3, peak area of 1-methylpipendineper mg/ml Mepiquat cation 

### is 

### 5475 for 

### PIX Ii! 

# !i? ULTRA and 5431-601

### 8 the mepiquat pentaborate formulations. 

# E a Thus one may conclude that I-methylpipendine is not increwed, relative to its levels in the registered products, in the produclion of mepiquatpentaborate. 

### Thimold increase seen using < the 

### CSF data is not supported by the more accuratedata in Table 3. 

# 5 5 

# E Table 

### 3. Ratios of 1-methylpipendine to mepiquat cation in various formulations. Adapted from

K Table2 

### of CA 

### 450071-04 (BASF Reg. 

### Doc. 99/5201).Examination of Table 4. indicates that per unit 

### ofmepiquat cation 

### PIX ULTRA (alternate formulation)contains-f boron, 

### as 

### B. as hlepiquat pentaborate. It 

### is noted that PIX ULTRA(basic formulation) containsworon 

### as PIX ultra.

### Page - 

### is not included in this copy. Pages

# \tf; through are not included in this copy.

The material not included contains the following type of 

### information: Identity of product inert ingredients. Identity of product impurities. Description of the product manufacturing process. Description of quality control procedures. Identity of the source of product ingredients. Sales or other commercial/financial information. draft product label. 

# s”’“

The product confidential statement of formula. Information about a pending registration action.
FIFRA registration data. The document 

### is 

### a duplicate of page(s) The document is not responsive to the request.

The information not included is generally considered confidential by product registrants. If you have any questions, please contact the individual who prepared the response to your request.C.Comparison 

### of dissociation behavior of Boron 

### in 

### PIX 

### ULTRA and in Mepiquat pentaborate: Mepiquatpentaborate 

### (asBAS 130 OOW and BAS 

### 13001W) and 

### PIX 

### ULTRA were studied by NMR spectroscopy 

### of IlB (MRID 45007102). As noted by the authors, the pentaborate ion dissociates in aqueous solution to give a mixture 

### ofmono-. hi-: and pentaborate ions. At high concentrations all three species are present, at low concentration only the mono-form is present. Each ofthese forms gives a chemical shift at a defined position in the "B-NMR spectrum.Thus, comparison 

### of "B-NMR spectra 

### ofborate solutions will indicate which species arepresent. Table 

### 5. Chemical 

### shifts' ofMepiquat formulationsusing "B-NMR spectra (MRID 45007102). 

# I Dilution 

# 1 BAS 130 OOW 

# 1 BAS 13001W

~ ___ 

# I PIX ULTRA

~ ~____ Undiluted 

### 19.7I 14.8 12.4 21.0 I 15.4 13.3 

### 20.2 I 14.8 12.4 20% in millipore Not recorded 

### 19.6I 15.5 IND Not recorded water

~ ~~ 1% in millipore water 

### 17.2/ND IND 18.8INDIND 18.2 IND IND

AS shown in Table 

### 5, the chemical shifts are consistent with the presence 

### ofthe three species in the concentrated solutions, are seen to coalesceto the monoborate species at the highest dilutions. 

### Thus. the authors concluded that the boron containing moiety in Mepiquat chloride (as

### PIX 

### ULTRA) and mepiquat pentaborate exhibit identical dissociation behavior in solution, at application-relevant levels. 

### as determined by NMR spectroscopy of "B (MRID 45007102) 

# I

# m: Charlea 

### Lent, Chief 

### Roregistrat

### ion Branch

# '?

. To: 

### EUvin F. Tinsworth, Director spacial 

### Review and 

### Reragfstration Ofvirion 

### some choaricai 

### cues contain 

### mor. than 

### ora cheaticai tt.a:, the 

### acid 

### pasmt ccmpaund ind 

### the 

### mineraz =it, 

### aat@r 

### or amine '

### of 

### tha acid). It 

### has 

### been Agsacy 

### policy to 

### requirr data 

### on tbe -ti, 

### eatera and 

### rmines a8 

### well a0 

### on tho acid. 

### bgi~ttmtr 

## tar. guldaacs 

### in marmining which rtudies, 

### in a$ditian to 

### those to 

## pe canbuctecl 

### on the acid, 

### should 

### be canductad 

### to support LISO of 

### the 

## mineral salts, esters anb 

### amines. 

### In the 

### absence 

### of such gufdanca, 

### tne Agency 

### would have to 

### delay until 

### me Iv 

### s~ification oZ 

### studies needed 

## on mineral SUM, 

### e8tlrrd MQ

. 

# ....

# -- e 

## When data aro 

### needed to 

### quantify data 

## on the acid 

### are generally 

### aceeptrd for 

## all member4 of 

### the 

### chersical cam.

v-. 

### When 

## data 

## are t\@adeU

### to qtumtify

. 

### gxpoo~mrlmrr ucpcirad 

### to 

### part-applicrtian 

### rrriduos of aid, 

## mineral salts, 

## asters Or 

## amine, data 

### mast b8 

### rubntitted far 

### each chemical, Th8 

### Specific Etrrdies 

### requited dspnad 

### up011 the t~se 

### pattern 

### of the 

### chaafcal. 

### Data 

### on the acid 

### are generally 

### acceptd to 

## supporr fh8 

### ainrral 

## tales, 8



### Data requitad 

## on technicaa 

## formulations of 

### acids, 

### salts,. 

## esters and awles. 

# -

Data 

## an the acid 

### are 

### generally, acceptad to 

### rupport the 

### mfnatrL silts. 

### Data are neodsd 

### to 

### doternine 

### whrthrr tne 

### prosante of 

### an 

### argrnfc 

## eater 

## or 

## amine affects the 

### metabolism of 

### the acid

. ?:mOhty, fOl&Wb: a r. c 4,;. 

### .. 'A'< 

## Nature of the 

## residue 

## in plants 

## an8 aninrals USidlU 

### mthOd8­ 

# -

Data 

## on tha 

## aci@ (VI) 

### grnrtrlly rcceptlsd 

### to

## ruppo*-.ehe minora rafts. 

## mta ate 

### needad td 

### detrrmine vhrthet 

### the 

### presence af 

### the 

## rstar or aiqe 

### moiety 

### affects the 

### rate 

## of degradation of tlae 

## parant compound. Data 

## are also needed to deteraclne 

### the

- ' ibmity, 

## nature of 

### dogradation 

### products 

## or mobility of the degradation 

### products' in tbe 

## envirownt 

## for 

## ootn thr acid and 

### the 

### aster or 

### amine moietfas. The 

### specific 

### requirements will depend 

### upan the WQ 

### pattern 

### of the 

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### -rt6115101 MEMORANDUM Subject: Minutes of 5/16/01 ChemSAC meeting From: HED Chemistry Science Advisory Council To: HED Chemistry Interest Group
MeetingAttendees: W. Hazel, 

### R. Loranger, 

### G. Kramer,W. Smith, 

### W. Donovan, J. Punzi, W. Wassell, T. Morton, M. Doherty, 

### F. Fort, D. Drew, L. Cheng, 

### J. Tyler. Agenda Item 1. PP# 9F06044. Bispyribac-sodium in/on Rice. Evaluation of Residue 

### Data andAnalytical Methods. This is the first petition for this chemical and it has not beento the MARC yet. The SAC concludedthat the document is consistent with current HED guidelines and 

### SOPSwith the following recommendations, changes or comments: The document should not be finalized until after the MARC decision. A provision should be added to tolerance recommendationsconcerning the need for Agency validation of the plant analytical enforcement method. The SAC concurs that there is no needfor a numerical PHI on the label as application directions are related to a well defined growth phase, Le. panicle formation. However, field trials should adequately reflect geographic and varietal variations in the interval between panicle formation and harvest. The SAC concurs with the conclusion that a metabolismstudy using benzenelabeled active ingredient will not be needed if studies under review by EFED confirm the petitioner claims that the only unique benzene-labeled metabolite produced in the environment is y-resorcylic acid (2,6-DBA), which is a natural product and basic constituent of lignin and various plant phenols. The SAC concurs with the conclusion that, based on the MTDBto beef and dairy cattle and hogs and the results of +b? goat metabolism study, the use of

, bispyribac-sodiumon rice falls 

### urt 

### - ::ategory 

### 3 of40 

### CFR §180.6(a) for

# ..

ruminant and hog commodities; there is no expectation of finite residues of bispyribac-sodium in ruminant or hog Commodities. No ruminant feeding studies or tolerances for residues in ruminant or hog commodities are required. The SAC made several editorial suggestions to the reviewers for incorporation in the final document. Agenda Item 2. 

### BASF request for a mepiquat pentaborate waiver from cotton field trial requirement based on dissociative properties of the pentaborate salt being identicalto mepiquat chloride for which there is field trial data. The SAC discussed the options of either accepting the registrant’s waiver request or requiring bridging data to determine if residues from application of the pentaborate salt would be comparable to those from application of the chloride salt. Two types of application methods/diluentswere considered in the discussion:A ground-applied spray with water as the diluent and an aerial ULV application using oil as the diluent. The SAC recommendations are as follows: For foliar application of mepiquat pentaborate to cotton, the SAC recommend for a conditional registration based on available field trial data for the chloride salt. Full registrationwill be contingent on submission of the following field trial data: Three .side-by-sidefield trials of the pentaborate and chloride salt formulations applied as per the labels as a more dilute spray using water as the diluent are recommended. Three side-by-side trials are also recommended for the oil-based ULV application, assuming we already have data for the oil-based ULV chloride salt formulation; if we do not have data to support the chloride salt ULV then we recommend a full set of field trial data to support the pentaborate salt ULV product. Agenda Item 3. The SAC was asked if it is appropriate to estimate anticipated residues of triclopyr in livestock commodities based on a livestock feeding study in which a 3-day preslaughter interval was observed after the final feeding. Current labels for triclopyr impose a 3-day preslaughter interval on livestock grazing on triclopyr treated grass. The SAC concluded that estimation of transfer of triclopyr residues from grass to livestock commodities

### would not be underestimatedby using such a feeding study. ZJ, I<Agenda Item 4. Tomen Agro is requesting a waiver of the confined rotational crop study for iodomethane (methyl iodide; 

### TM-425),which is being developed as an alternative for the soil fumigation use of methyl bromide. At this time the waiver is being requested in conjunction with soil treatment prior to planting of strawberries and tomatoes only. At HED's request the registrant has researched the tomato and strawberry practices in Florida and Californiato determine the typical rotational crops and ,theirplantback intervals. In addition, Tomen has provided summaries of ongoing residue chemistry and environmental fate studies in support of their waiver request. In summary, Tomen Agro has tested maximum use rates of 235 Ib methyl iodide per acre and found no detectable residues of the fumigant or free iodide ion in edible portions of strawberries (planted 7-28 days after treatment) and tomatoes. Residues in soil are also short-lived. Although radioactivity in fruits has yet to be identified in the C14 studies, the polar nature of the residue and the absence 

### of free iodide indicates that intact fumigant is not taken up into the fruit and thaf the activity likely represents bioincorporation into natural products. Given the length 

### of time until rotational crops would be planted and harvested,the registrant states that "the probability of having iodomethane residues in rotational crops is nonexistent." Therefore, they request that the confined rotational crop study not be required. The SAC concurs with the HED reviewer's conclusion that the confined rotational crop study will not be required for the proposed uses of iodomethane on tomatoes and strawberries provided the following conditions are met: (I) Detailed review of the completed studies confirms 

### all the information summarized above with regardto iodomethane and free iodide concentrations in plant metabolism, crop field trial, and environmentalfate studies. 

### (2) The radioactivity in tomato and strawberryfruits is shown not to represent any residue of concern. 

### (3) The fumigant label imposes a plantback interval of at least four months for all crops except strawberries and tomatoes.