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 chloride premix containing disodium 

octoborate tetrahydrate which is registered for use on cotton. The registrant stated that 

mepiquate pentaborate will eventually replace mepiquat chloride for use on cotton. Also 

submitted was a dissociation study (MRID 45007102) indicating that the boron containing 

moiety in Pix Ultra and Pix Ultra I1 exhibit identical dissociative behavior in aqueous solution, at 

application relevant levels. 
. 

The Health Effects Division (HED), as per Registration Division’s request, has evaluated these 

submissions with 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.Protze1 to 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 

conditions of registration 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 for mepiquat chloride be 

performed using mepiquat pentaborate. 

2. A dissociation study in oil (for both Pix Ultra and Pix Ultra 11) is required if oil 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 as the 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 of mepiquat 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 

of the plant growth regulator N,N-dimethylpiperidinium on the following raw agricultural 

cornmodities”. 

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 new livestock maximum theoretical dietary 

burden (MTDB) was calculated using the recommended cotton gin byproduct tolerance of 6 ppm 

(see Table 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) [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 also 

< 0.05 ppm (<LO.D) at the 7X feeding level, a 180.6 (a) (3) situation exists for meat and fat; 

HED now recommends that those tolerances should also be revoked. 
Considerations and Conclusions 

1. The Toxicology Science Advisory Council (TOXSAC) has no objection to data waivers being 

granted for Tier 1 data (subchronic rodent oral toxicity study, developmental toxicity study, 

mutagenicity data) for mepiquat pentaborate (TOXSAC Memo of 6/14/0 1 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 (D258 184, 1 1/22/99, M.Collantes and M.Nelson). 

a) The registrant 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) The registrant has submitted a dissociation study to demonstrate that mepiquat pentaborate 

dissociates in water in an identical physical manner to mepiquat chloride with solubor; they both 

dissociate to the monoborate. 

c) The Tox Sac received an opinion from Alberto Protzel, Ph.D., of the Toxicology Branch 

indicating that Pix Ultra and Pix Ultra 11, when compared per unit of mepiquat cation, are not 

significantly different as to impurities and the manufacture of mepiquat 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 chemicals that contain mineral salts, esters, and amines of an 

acid parent compound. The memorandum states that for toxicology information, data on the acid 

are generally accepted to support the mineral salts, thus no additional data would be required for 

those entities. For esters and amines, additional toxicology data (acute toxicity studies; 

subchronic feeding study; 2 1 day dermal toxicity study, developmental toxicity study, 

mutagenicity studies and rat metabolism study) are required. 

2. The Chemistry Science Advisory Council (ChemSAC) has concluded that, for foliar 

application of mepiquat pentaborate to cotton, a conditional registration would not be precluded 

based on existing residue data for mepiquat chloride and on the results of the dissociation study 

(Minutes of 5/16/01 ChemSAC meeting). However, full registration will be contingent on the 

submission of acceptable side-by-side field trials. Three side-by-side cotton field trials are 

recommended for Pix Ultra and Pix Ultra I1 at maximum label rates 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 from the label). Trials should reflect adequate geographic representation 

for cotton production. It is recommended that trials be performed in Regions 4,8, and 10 (see 
OPPTS Test Guidelines 860.1500). 

3. Tolerances are currently established under 40 CFR 5180.384 for residues of mepiquat chloride 

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

0.1 ppm). HED recommends that the current tolerance expression for mepiquat chloride be 

modified to read “Tolerances are established for the residues of the 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 of residues of mepiquat pentaborate per se idon cotton and animal 

commodities (D244052, 7/27/0 1. D. Drew and D274482, 7/27/01, D.Drew). The validated 

method LOQ for the method is 0.1 ppm for cottonseed and 0.05 ppm for beef liver. 

Adequate method recoveries were obtained for residues of mepiquat pentaborate fiom fortified 

samples of cottonseed (1 12-12 1%) and beef liver (1 00-1 12%); however, we note. that the 

recoveries of mepiquat chloride per 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 interference peak which elutes closely after mepiquat pentaborate may be inflating 

the mepiquat pentaborate quantitation. The fact that the interference peak was observed both in 

cotton seed and beef liver samples seems to indicate that the interference is not due to a m&ix 

coextractable but may .be arising 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 remove the source 

of this interference peak. 

Method validation has been submitted for residues of mepiquat 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) of method 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 chloride use 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 of the proposed ion chromatography 

enforcement method (D9610) has been conducted, the method can be forwarded to FDA for 

inclusion in PAM Vol. I1 as a numbered method for enforcement of residues of mepiquat idon 

cotton and animal tissues, milk, and eggs. 

5. At this time, a human health risk assessment is not required for mepiquat pentaborate foliar 

use on cotton. Human health risk assessments were perfprmed previously for mepiquat chloride 
4 

on cotton (The HED Chapter of the FED for Mepiquat Chloride, D222017, 7/8/96, M.Clock) and 

for mepiquat chloride on grapes (PP# 1 F03955. Mepiquat Chloride idon Grapes and Raisins. 

Human Health hsk Assessment, 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 exposure to 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 of the 

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 6 pprn (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, of lactating cows fed 13 ppm 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 estimates below 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 ,CP Moran (RD); C. Giles-Parker (RD) 

RDI: C. Eiden (7/30/01) 

D.Drew:CM-2, nn 821E, 305-6028 
UNITED STATES ENVIRONMENTALPROTECTION AGENCY 

WASHINGTON. D.C. 20460 

OFFICE OF 

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 , 

1I.>; I .x-.~

Toxicology Science Advisory Council , I 

Health Effects Division (H7509C) 

The Toxicology Science Advisory Council met on 6/14/2001 to consider a request from BASF 

Corporation (BASF) to waive the requirements for Tier I data (subchronic rodent oral toxicity 

study, developmental toxicity study, mutagenicity data etc, for mepiquat pentaborate. BASF 

intends to replace mepiquat chloride with mepiquat pentaborate. The basis 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 agricultural products 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 of Registration Division; and 

Dannette Drew 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 significantly different from that of mepiquat chloride. 

2. The registrant has submitted a dissociation stub; t.0 demonstrate that mepiquat pentaborate 

Internet Address (URL) http://www.epe.-oov 

Eecy:lraTlccyclablr .Printed wflh Vep!aS:e GI! Ead Ink on Recycled Paper (Minimumb25% Fcscunsumeri 
completely dissociates in water in an identical physical manner to mepiquat chloride with solubor; 

they both dissociate to the monoborate. 

3. The Tox Sac received an opinion from Albert0 Protzel, Ph.D., of the Toxicology Branch 

indicating that PIX ULTRA and mepiquat pentaborate when compared per unit of mepiquat 

cation, are not significantly different as to impurities and the manufacture of mepiquat pentaborate 

does not introduce any toxicologically significant new 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 requirements for chemicals that contain mineral salts, esters, and amines of an acid 

parent compound. The memorandum states that for toxicology information, data on the acid are 

generally accepted to support the mineral salts, thus no additional data would be required for 

those entities.. For esters and amines, additional toxicology data (acute toxicity studies; 

subchronic feeding study; 2 1 day dermal toxicity study, developmental toxicity study., 

mutagenicity studies and rat metabolism study) are required. The Toxicology Science Advisory 

Council has obtained a copy of the memorandum. The memorandum will be posted on the LAN in 

an appropriate file 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. Therefore the 

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 applicable to 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 of Pix 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 of the Parent 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: Determine ifthe composition of Mepiquat pentaborate and PIX ULTRA are significantly 

differently as to impurities and other toxicologically significant chemicals. 

CONCLUSION: The data examined indicate that PIX ULTRA and Mepiquat Pentaborate, when 

compared per unit of mepiquat cation, are not significantly different as to impurities and other 

toxicologically significant moieties. 
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. The basis for the 

request is: 

chloride ( as PIX ULTRA, a mixture of h4epiquat chloride wi 

is already registered for use in cotton. The production process 

and minvoduces no new by-products (MRID 450071 04). 

2. The boron containing moiety in Mepiquat chloride (asPIX ULTRA) and mepiquat pentaborate 

exhibit identical dissociation behavior in solution, at application-relevant levels, as determined by 

NMR spectroscopy of "B (MFUD 45007102) 

11. Detailed Considerations.. 

.A. The Production Process for Mepiquat Pentaborate: 
B. Examination of the CSF forms: 

Table 2 displays CSF data for various Mepiquat formulations. Columns 2,3 and 4contain data for 

Mepiquat Pentaborate (the new 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 (for Mepiquat Pentaborate) with columns 6 and 7 for PIX ULTRA 

o 

Mepiquat 

new impurities pentaborate are generated (TGAI). in the 

The 

Timpurity 

Methylpipendine, a synthetic precursor of mepiquat ,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 ths ratio is unclear, and may be exaggerated, as indicated by data below. Even though 1-

Methylpipendine is not reported in the CSF data for PIX Ultra (cols. 5 and 6), other analyses shown 

below indicate that it is presenr in the PIX ULTRA formulation and at the same levels as in 

Mepiquat pentaborate. 

Relative levels of I -methylpipendine lvere determined in the hllepiquat formulations listed in Table 

3. The BAS 130 formulations are Mepiquat pentaborate formulations. BAS 083 45W is the EPAregistered boron-containing formulation PIX ULTRA. To perform the analyses (Table 3), ho~m 

dilutions of the ~wiousformulations were made and the areas of 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 found that the levels of 1 -methylpipendinewere comparable. 

i; As shown in Table 3, peak area of 1-methylpipendine per mg/ml Mepiquat cation is 5475 for PIX 

Ii!

!i? ULTRA and 543 1-6018 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 mepiquat pentaborate. Thimold increase seen using 

< the CSF data is not supported by the more accurate data in Table 3. 5 

5

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

K Table 2 of CA 450071-04 (BASF Reg. Doc. 99/5201). 
Examination of Table 4. indicates that per unit of mepiquat 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: 

Mepiquat pentaborate (asBAS 130 OOW and BAS 130 01 W) 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 of mono-. hi-:and pentaborate ions. At high 

concentrations all three species are present, at low concentration only the mono-form is present. 

Each of these forms gives a chemical shift at a defined position in the "B-NMR spectrum. Thus, 

comparison of "B-NMR spectra of borate solutions will indicate which species are present. 

Table 5. Chemical shifts' of Mepiquat formulations using "B-NMR spectra (MRID 45007102). 

I Dilution 1 BAS 130 OOW 1 BAS 130 01W ~ ___ I PIX ULTRA ~ ~____ 

Undiluted 19.7 I 14.8 12.4 21.0 I 15.4 13.3 20.2 I 14.8 12.4 

20% in millipore Not recorded 19.6 I 15.5 IND Not recorded 

water ~ ~~ 

1% in millipore water 17.2 / ND I ND 18.8 IND IND 18.2 I ND I ND 

AS shown in Table 5, the chemical shifts are consistent with the presence of the three species in 

the concentrated solutions, are seen to coalesce to 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 45007 102) 

I 
m: Charlea Lent, Chief

. Roregistration 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@ror 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~ificationoZ 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\@adeUto qtumtify . gxpoo~mrlmrrucpcirad 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 acid, mfneral salt, eater ar amine, 

. .. -. - . a * ... - - I* e ., . -.l­

.. mu on tha acid are generally accepted to uuppart th8 

mineral salts. A get of data is also required for sach ester anh

arniae. me specific requiromentu vi11 depand upon the use r 

. -- - pattern of the acid, ester or adnu. I-. r 

-.. -

.. . I .* . .. . . * . -.* I -,. . .. .. 

, 

I' 

1 

-rt 
6115101 

MEMORANDUM 

Subject: Minutes of 5/16/01 ChemSAC meeting 

From: HED Chemistry Science Advisory Council 

To: HED Chemistry Interest Group 

Meeting Attendees: 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 

and Analytical Methods. This is the first petition for this chemical and it has 

not been to the MARC yet. The SAC concluded that the document is consistent 

with current HED guidelines and SOPS with 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 need for 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 metabolism study 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 MTDB to beef and dairy 

cattle and hogs and the results of +b? goat metabolism study, the use of , 

bispyribac-sodium on rice falls urt - ::ategory 3 of 40 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 

identical to 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/diluents were 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 registration will 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 

underestimated by 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 California to determine the typical rotational crops and ,their plantback 

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 regard to iodomethane and free iodide concentrations in plant 

metabolism, crop field trial, and environmental fate studies. 

(2) The radioactivity in tomato and strawberry fruits 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.