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

. 20460



### MEMORANDUM D a te : Se ptemb er 16 , 2015 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SU BJE CT: Su lfosu lfuron. Re-evaluation of Enforcement Methods and Livestock T o lerances. Abbrev iated Residue Chemistry Rev iew 

### PC Code: 085601 

### Dec i s ion No .: 505178 

### DP Barcod e: D427730 

### Registration No. : NA 

### Petition No.: Not Applicable (NA) 

### Risk Assess m ent T y p e: NA 

### TXRNo. : NA 

### Reg ulatory Ac tion: Conditions of Review 

### Case No.: 7247 

### CASNo

. : 141776-32-1 

### MRI D No. : None 40 

### CFR: § 180.552 

### F ROM: Bonnie Cropp -K oh lli gian , Environmental ()

..... _ 

## \k.__ Risk Assessment Branch JV 

# vir Health Effects Division (7509P) 

### THROUGH: D ennis McNeil l y , Che mi st )( Risk Assessment Branch IV E ffects Di vis ion 

# -£o/\
P. Yvonne Barnes , Chemist ' Meheret Negussie , Chemist Chemistry Science Advisory Council (ChemSAC) Health Effects Division (7509P) 

### TO : Kelly B allard and Thomas Moriarty 

### (RM 51) Risk Management and Implementatio n Branch I Pesticide R e-Evaluation Division (7508 P)


### Exec uti ve S umm ary Sul fosulfuron 

### (N-[[ (4 , 6-d imethoxy-2-pyrimidin y l )amino]carbonyl]-2-( ethylsul fony l)imidazo [l ,2-a]pyridine

- 3-sulfonamide) is a selective broadleaf s ulfon yl urea (SU) herbic ide registered for foliar uses on wheat and grass. T he natu r e of the re s idue in regis tered crops and li ves tock is adequa tely understood. The Health Effects Division (HE D ) risk assessment team has determined that the re s idues of concern for tolerance e nforc e m e nt a nd ri sk assess m e n t are s ul fosulfuron and its metabolites w h ich are co nv e rtibl e to 2-(et h ylsu lfon y l ) -imid azo [1 ,2-a]p yridine ( i .e., the ethy l P age 1 of 

### 11Sulfosulfuron (08560 I) Abbreviated Residue Chemistry Review DP # : 427730

sulfone chemophore). Tolerances are established under 40CFR§180.552 in/on wheat and grass commodities at 0.02-25 ppm, in milk at 0.02 ppm and meat commodities at 0.005

- 0.3 ppm. This memorandum was rev i ewe d by two peer revi ewe rs of the Chem SAC and the following reeva luation of the enforcement methods was approved by the Analytica l Methods Focus Group of ChemSAC which included members of the Analytical Chemistry Branch of the Biological and Econom ic Analysis Division (ACB / B EAD). Previously, issues were identified regarding va lid at ion of the enforcement methods. Method RE S-082-94 (Vers ion 2) for tolerances in/on wheat commodities and Method RES-095-96 (Ve r sion 0) for tol erances in milk and meat commodities failed the tol erance m et hod validation r ev iew and laboratory trial (TMV-RL; former l y referTed to as a pet ition m e thod validation ( PMV)) conducted b y ACB/BEAD and a success ful TMV of M ethod ES-ME-1066-01 was a co ndition of re g i stration for the use of su lfo su lfuron on grass . A ll three of these methods are common moiety methods which convert s ulfo su lfuron and its metabolites co ntaining the intact imidazopyridine ring to the ethyl su lfon e chemophore by acid hydrolysis using essentially the s ame length y multi-step extraction/hydrolysis procedures whic h differ primarily by the addition of an amino solid-phase ex traction (S P E) cleanup ste p to the wheat extraction/hydrolysis procedure for Method RES-082-94 (Ve r sion 2). Residues are quantitated as the ethyl sulfone chemop hore and exp r e s sed as su lfo s ulfuron. Method RES-082-94 (Version 

### 2) and M e thod RES-095-96 (Version 

### 0) u se high performance liquid chromatography wi th fluorescence detection (HPLC w/tluorescence detection). While adequate radio va lid ation and independent laboratory va lidation ( I L V) data were provided for both methods , both failed the TMV-RL cond ucted by ACB/BEAD due to some inconsistent and/ or low residue recove ri es and concerns about the length y total analysis time for a sample set (> 24 hours). Afte r re-evaluation of the methods as written , supporti n g data , and the specific method revisions recommended in the TMV-RL which were expected to substantially improve residue recoveries , H E D find s that: (I) for th e li vestock enforcement m ethod , the original r equest to validate th e method at levels <0.01 ppm ma y have contributed to the TMV-RL failure of that method and (2) achieving 

### a limit of quantitation (LOQ) of 0.005 ppm may be beyond the limit s of these methods g iven the potential for back gro und level s in/on so m e matrices relati vely close to that level; and (3) the LOQ i n/on wheat , milk and meat commodities is 0.01 ppm based on avai lable method validation data taken together. Method RES-082-94 (Version 2) and Method RES-095-96 (Version 0) , as written , are acce ptabl e for residue determination for enforce ment purposes , excluding tolerances in hog commodities which a re no longer needed 

### (se e discussion below)

. Confirmation of re sid u es by oth e r means will be n ecessary and may be acco mplish ed using the co nfirmatory aspects of Method ES -M E-1066-0 I discussed below (i.e. , alternative column , mobile phase, gradient e lution program and/or detec ti o n method). In the case of sulfosu l furon , a n allowance will be m ad e for tota l ana l ys i s t ime taking longer than 24 hours and is discussed in greate r detail below. Method ES-ME-1066-0 I uses liquid chromatog raph y with tandem mass spectrometry detection (LC-MS/MS) and is 

### a modified vers ion of the HPLC w / fluorescence detection methods using a different column , mobile phas e and gradient elution program. H owever , the total analysis time is the same as the HPL C w/tl u oresce nce detection methods. Method ES-ME- I 066-01 monitors only one mass ion transit i on for quantitation (m/z 2111165) of residues. Radiovalidation and Pa ge 2of11Sulfosulfuron (08560 I) Abbreviated Residue Chemistry Review DP# : 427730


### IL V data were not provided for this method but are not required since the extrac ti on / hydrolysis procedures for Method ES-ME-1066-0 I 

### are esse nti a ll y the same as fo r the HPLC w/ fluorescence detection methods. Concurrent method validation data in grass forage and hay samp les fortified at 0 .0 05-50

.0 ppm were with in or very c lo se to ge nerally acceptable limits (70- 120 % ± 1 

### %), with one exc e ption in/on forage at the lowest fortification level (i.e. , one sample fortified at 0.005 ppm with 64% recovery). Residues were detected i nion contro ls; how eve r , du e to reporting limitations , it is not known ifresidues in controls were we ll below the lowest level of method validation (0.005 ppm). In accordance with the current Standard Operating Procedures (SOP Number ACB-0 19 dated 9/15 / 08) for a successful TMV review (TMV-R) but allowing for total analysis time taking longer than 24 hours (see discussion below), HED finds Method ES-ME

I 

### 066

- 0 l 

### acceptab le fo r residue determination for enforce ment purposes. Due to the lack of a s econd ion transition , confirmation of residue s by other means will be necessary and may be accomplished using the confirmatory aspects of the HPLC w / fluorescence detection method s discussed above (i.e ., alternative column , mobile phase , gradient elution program and/or detection method). C ollectively , these liquid chromatograp h y methods are adequate for enforceme nt and provide for confirmation of residues via alternate detection methods , columns , mobile phases and/or gradient elution programs. The LOQ for these methods is 0.01 ppm. Although analysis time for a samp le set using these methods w ill like l y exceed the genera ll y acceptable timeframe , this deviation will be allowed, in this case , since no acute dietary endpoint was identified for sulfosulfuron, c h ronic dietary risk est imates for s ulfo su lfuron are below the level of concern and most of the commodities with sulfosulfuron tolerances are not among the most perishable. These methods are availab le thro ugh ACB / BEAD. In conjunct ion w ith this re-evaluation of the enfo rc ement methods, li vestock tolerances we re reevaluated and it was determined that there is no reasonable expectation of finite residues of concern in swine (i.e ., Category 3 of 40 CFR J 

### 80.6(a)). Therefore, HED is recommending for the removal of estab li s hed tole rances for residues of su lfosulfuron in 

### fat (0 .0 05 ppm) , meat (0.005 ppm) and meat byproducts (0 .0 5 ppm) of hog. This recommendation is a lso a conseque nc e of the re-eva luation of the enfo rce m ent methods (D427730) and the finding that the limit of quantitation for these methods is 0

.01 ppm.

P age 3 of 11Sul fosul furon (08560 I) Abbreviated Re s idue Chem istry Review DP # : 42 77 30


### Detailed **Considerations 860.1340**  **Re si**  **due Ana**  **l ytica**  **l Methods**  **- Enforceme**  **nt Methods**  Methods RES -082-94/RE S- 0 95 -96

- HPL C w/ fluorescence detection Residue Chemistry Memos: DP#s 237683 / 239109 , S. Chun, 9/28 /98 (Wheat Petition (PP # 7F4840)). In cludes radiov a lidation , ILY and liv estoc k feeding st ud y data. DP#s 239393 / 239394 , P. Schermerhorn a nd L. Podh orniak (ACB / BE AD), 1112 1 99. In clude s TMV-RL Re s ult s Methods RES-08 2-94/ RES

-095-96. Previously , in support of the use of sulfosulfuron on wheat (D237683 / D 239l09) , Mo n santo Company su bmitted two com mon moi ety methods u si ng HPLC w/fluorescence detection for enforcement of tolerances in/on wheat and milk/meat commodities. The se meth ods, Method RES-082-94 (Version 2) for wheat commodities and Method RES-095

- 96 (Version 0) for milk and meat co mmoditi es , convert residues of s ulfo su lfuron and its metabolites co ntaining the int act imidazopyridine rin g to the eth yl su lfone ch e mophore by acid hydrolysis and differ by the add iti on of an amino solid-phase extrac ti on (SPE) cleanup s tep to the wheat extraction procedure. Residues are quantitated as the ethy l su lfon e chemophore and expressed as sulfosulfuron

. Adequate rad io va lidati on data were provided for both methods , as well as adequate independ ent laboratory validation (ILV ) data 

### in w h eat grai n at 0.01 and 0.05 ppm , wheat forage at 4.0 and 20 ppm , milk at 0.004 and 0.008 ppm and beef liver at 0.004 and 0.10 ppm (D237683/D239109). H E D requested a TMV-RL (fo rmerl y referred t o as a PMV ) of the wheat meth od by the ACB / BEAD in wheat g rain a t 0.01 a nd 0.02 ppm and in wheat forage at 0.01 , l .5 a nd 3.0 ppm. Given th e co ncurrent recommended tolerance le ve ls in milk (0.006 ppm) and meat commodities (0.005-0.05 ppm) , H ED requested a TMV-RL of the milk/meat co mmodit y method by the A CB/B E AD in milk at 0.003 and 0.004 ppm , beef liver at 0.005 , 0 .05 and 0.10 ppm and beef muscle at 0.005 and 0.0 I ppm. The A CB/B E AD conducted the TMV-RL using substitutions for the method prescribed co lumn , mobile phase and gradient e luti o n program to substantially reduc e HPL C ana lysis time (method run t ime was reduced from 53 to 15 minutes). The methods fa il ed the TMV-RL (D239393/D239394) due mainly to some inconsi ste nt a nd/o r low re s idu e recoverie s from the multi-step extraction/hydrolysis procedures and concern s about the l engthy extraction/hydrolysis / anal y sis time for a sample set (> 24 hours even wi th the ACB / BEAD time saving s ubstitutions / recommendations). However, for the milk/meat commodity enforcement method , H E D examined the TMV-RL and notes the following with regards to the attempt to validate the me thod at leve ls < 0.01 ppm in li ves tock commod iti es which m ay ha ve contributed to the TMV-RL failure related to residue recoveries : • Th e lowest calibration level in the method, as written , was 0.0112 ppm , as s ulfo sulfu ron , and above the lowe s t level of attempted method validation. • Example beef and liver chromatograms from the TMV-RL indicate residues in control s amp l es close to the lowest leve l of method va li dation (ca. 0.005 ppm). Detectable res idue s in contro l sam ples of mil k/c r ea m and tissues were also not ed in the cattle feeding study (0237683 /D 239 10 9). Enforcement methods cannot emp loy untreated control samples to correct residue s in treated sample s .
Page 

### 4 **of 11** Sulfosulfuron (08560 I ) Abbreviated Residue Chemistry Review DP# : 427730

HED also note s that s ince the liv es tock method TMV-RL was conducted, l ivestock tolerances have increased significant ly , excluding tolerances in h og commodities which are no lon ger needed 

### (see 860.1480 Meat, Milk, 

### Poult!y, and Eggs below), and va l idat ion of the method at < 0.0 I ppm is no longer nec essary. The extraction/hydrolys i s procedures of these m ethods are briefly described below along with the spe cifi c revi s ion s to these procedures that ACS/BEAD recomm e nded to improve res idue recoveries or analysis time 

### (0239393 / 0239394) and any HED re- eva luation of the issues. Excluded from this discussion are revisions/o bservation s that ACB/BEAD provided regarding laboratory technique (i.e., how to deal effect ive l y with the formation of em ul sio ns and the interpretation of typica l procedural in structions such as gentle shaking, etc.) given the level of expert ise expected for enforcement personnel. l. Homogenized samples are extracted with 100 mL acetonitrile (ACN):water ( I: I , v:v), filtered and concentrated. For dry crop samples s uch as straw and ha y, an additional 50 mL of extraction solve n t may be added

. The m e th od cautions that concentration of the initial ACN fraction is a crit ic al s t ep and mu st be done s lo w ly so that residues are not lost. 

### 2. The extract is refluxed with HCl overnigh t to hydrolyze sulfosulfuron to the e th yl su lfone chemophore. Alternatively, the s an1ple can be hydrol yze d by heating in a microwave oven for 

### 1 hour at 40 psi to save analysis time. AC B/B EAD selecte d the overnight h ydro ly s i s option but noted that , regardles s of the option se lected , the s ubsequent le ngth y extraction procedures would still take another working day and th e overnight hydrolysis provided a good stopping point in the proc ed ure. HED finds that this time sav in g measure plus others suggeste d by ACB/BEAD would not reduce the t o tal analysis time to <24 hour s. 3. The hydrolyzed extract is adjusted to at le ast pH 9 with NaOH. The m ethod caution s that if the sample is neutral or s li ght ly acid ic, in s ufficient cleanup will be observed. 4. The basic so lution is partitioned with methylene c hloride (MeCh) usin g a separatory funnel. The method prescribes gentle shaking of the se paratory funnel and cautions that an emu l sion may form if sa mple s are s hak en too v igorousl y. 5. The Me Cb is evapo rated to dryness b y rotary evaporation. The residue is re-dissolved in MeC'2 and diluted with isooctane. 6. The solution i s cleaned up through a Florisil SPE column, and re sid u es are e luted with 2% methanol (MeO H ):MeCh. The solvent is removed by evaporation to dry nes s by rot ary evaporati on. ACB /BEAD recommended spec ia l care during the evap oration procedure; however , thi s recommendation was only id e ntified as a relati ve ly s mall improv e m e nt ( I 0-20%) in the residue recoveries in milk samples which were fortified at very low levels (:S0

.004 ppm). Moreover , the method already includes a reasonable precaution that concentration/evaporation s teps can be crit ic a l in the procedure and must be done slowly so that re si due s are not lost. HED finds that the precautions in th e methods , as-written , adequately address the ACB/BEAD recommendation. 7. For wheat only , residues are re-dissolved in MeCh:isooctane and cleaned up throu g h an Amino SPE column , and res idu es are e l uted with 40% e th y l aceta te in iso

- octane. The solvent is removed by evaporation to dryness

. AC B / B EA D recommended that thi s step be e liminated to shorten analysis time. H oweve r , HED finds that this time saving measure plus others suggested by ACB/BEAD would not re duce the total analysis tim e to 

### <24 hour s. Page 5 of 11Sulfosulfuron (08560 I) Abbreviated Residue Chemistry Review DP# : 427730
8. Residues a r e re-d i sso lved in ACN:water (10:90, v:v) fo r a na lys i s. ACS / B EAD recommended that ACN sho ul d be added first to disso lve the residues before the water and n o t ed that li ve r samp les became cloudy with the add i tio n of the water, requiring filtration. ACB /B EA D found th at this proc e dure s ig nifi cant l y i ncreased r es idue recoveries in liver samp les. H owever, H E D notes tha t the method a lr eady includes a reaso n able precaution that it may be difficult to re-dissolve sa mple s after evaporation and t hat a sma ll amount of ACN is recommended. HED finds that the precautions in the meth ods, as - written , a de quate ly addr ess th e AC B recomm e ndation. As a co n sequence of the failed TMV-RL , Mo n santo Company was advised to rev i se both methods in accordance with th e ACB / B EAD recommendations provided in the TMV- RL and res u bmit the revi se d methods. In the meantime , th e ACB / BEAD developed a rev ised extrac ti on procedu re and agree d to prov ide instructi o n s to an y s tat e lab req ues ti ng th e me th o d. Howeve r , H E D has re - eva lu ate d the methods, ava il ab le data and th e TMY-RL and finds that: (1) the me thods , as writte n , adequately address most of the AC B recommendations regarding the extract ion procedures; (2) to tal analysis time wi ll likely exceed 24 ho ur s, even wi th th e time sav in g mea su res sugges te d by ACB ! B EA D ; and (3) ac hi ev in g a L OQ of 0.005 ppm ma y be beyond the limit s of th e me th ods for so me matrices. M ethod ES -M E-1066

- 01

- LC-MS!MS Re si due Chemistry Memos: DP # 328450 , S. Levy , 07/2 5/ 07 (Grass P etition (PP#6F7031 )). DP# 332807, S. L evy , 10/ 17 / 06 (TMV R equ es t Method ES- M E-1066

-0 1). MRID: 4675380 I (Method ES-ME-I 066 -0 I description and fortifica tion recovery da t a) Prev ious ly, in s upport of the u se of sulfosulfuron on grass (0 328450) , Monsan to Company subm itted Method ES-ME- I 066-01 (MR ID 4675380 I , pages 166-186), a modified ve r s i on of M e thod RE S -08 2-94 ( di sc u sse d above). Me thod ES- ME

- 1066-01 , is a conunon moiety method u s in g LC

- MS / MS. Radiova l idation and lL V data we r e not provided for this method but are not required since the extrac ti on/hydro l ysis procedures for Method ES-ME -1 066-0 1 are esse nti a ll y the sam e as fo r th e HPLC w/fl uore sce n ce detection methods. 

### It was s ubmitted to the ACB/ BEAD for a TMV (D332807) ju st before the standard operating procedure (S OP ) for reviewing tolerance m et ho d s was issued (SO P Number ACB-0 19 dated 9/15 / 08). A s uc cessfu l TMV for Method ES-ME-I 066-01 was identified as a co ndition of registration for sulfosulf uron on g rass (0328450)

. S in ce , there i s no reco rd that ACB!BEA D conducted thi s TMV, HED has co ndu c t e d a TMV rev i ew (T MV-R ) in acco rdanc e w ith the current SO P
. Method ES-M E

- I 066-0 l employs essentially the same extracti on/hy drol ysis procedures as the HPLC w/fl uo rescence detection method s discussed in detail above w ith the following significant improvements: (1) there is no amino so lid -p hase ex traction (S P E) cleanup s tep which should save analy s is time and (2) the vo lum e of the initial extraction so lv e nt ( i

.e., ACN:water ( 1: I , v:v)) is increased from 100 to 1 50 mL wh ic h m ay contribute to adequate resi due recoveries. It a lso uses a diffe rent co lumn , mobile phase an d grad ie nt e lution program than the HP LC w/ tluorescence detection m e thods; howeve r , the to tal anal ys is time is likely to be the same. Res idu es were quantitated as the ethyl su l fone chemophore and exp ressed as s ul fosulfuron. The me th o d mon i to rs only o n e m ass ion tran s ition for quantitation , m /z 2 1 I/ 165

. Conc urrent method val idat ion data in grass forage and hay samp les fortified at 0.005

- 50.0 ppm Pa ge 6 of 11Sulfosul furon (08560 I) Abbreviated Residue C he m istry Review DP # : 427730

were w ithin o r ve r y cl ose to g en e ra ll y acc e pt a bl e l imit s ( 70

- 12 0 % ± 1 % ) , with one ex ce p t ion inion fo ra ge at th e lowes t fo rtifi cati o n leve l ( i .e., o ne sam pl e fo rtifie d at 0.005 ppm wi th 64% recove r y). See Ta bl e l

. R es idu es w e r e d e tec ted i n c ont r ol s ( ba se d o n are a c o un t s re p orte d for co n trols , fortified sam pl es and calibra ti o n stand a rds); howeve r , it is n o t k no wn i f res id ues in co n trols we re we ll be low the low es t leve l of me th od va lidati o n (0

.005 ppm ) s ince they w e re n o t q u antifi e d ( i .e . , re p ort ed at 0. 0 0 pp m ).

T ab le 1. S umm ary o f C on c urr e nt R ecove r ies o f S u l fo s u l furo n R es idu e s fr o m G r as s Fo ra g e a nd H a y. Ma tr ix Fo rt ifica ti o n Leve l Sa mp le s i ze U n

co rrec t ed R ecove ries (ppm) (%) 0.005 5 6 4 ,93.93.97, JOO 0.0 10 4 106. 90. 81. 81 0.020 4 90 , 90,93.93 0.050 3 69

. 77. 99 0. 100 3 11 2. 90, 97 Grass. forage 0.200 4 105. 107. 1 11. 103 0.500 4 1 13 , 82 , 100. 99 1 .000 5 109. 92.98

. 99.96 2.000 6 113. 1 07.93.96. 1 01.90 5.000 5 JOO. 98. 1 15

. 108. 107 10.000 7 103. 1 12

. 105.94.89 20.000 2 99 , 104 0.005 2 85.8 1 0.0 10 2 88, 83 0.020 3 83.88

. 85 0.050 3 93.96. 1 10 0. 1 00 3 86. 9 1 , 82 0.200 I 94 Grass. hay 0.500 I 109 1.000 I 11 0 2.000 2 109. 107 5.000 1 113 1 0.000 I 96 20.000 I 99 50.000 2 106. 1 10 

### Co nclu s i ons . M e th o d RE S-0 8 2-94 ( V e rs io n 2) and Me thod RE S- 095

- 96 (Ver s io n 0 ) fai le d th e TMV

- RL co nd uc ted by AC B/ B EA D. Afte r re - eva luati o n o f Method RE S -08 2-94 (Ve rs io n 2) an d M eth od RE S

- 0 9 5

- 9 6 ( V e r s io n 0) as writte n , s upp o rti ng d a ta , and th e s pe cific me tho d revisions recomme n ded in th e TMV -R L w hi c h we r e e x p ec t ed t o s ub stantiall y imp rove res idu e re c ove r ie s , H E D fi nd s th at: ( 1) fo r the l ives t oc k e nfor ce m ent m e tho d , th e ori g i na l req ues t to val id ate t he me tho d at l eve ls <0

.01 p p m m ay have co ntr ibute d to th e T MV -R L fa ilur e of th at me th o d an d (2) ac hi ev in g a l imit of quant ita ti o n (L OQ) o f 0. 0 0 5 ppm m ay be beyo nd th e l imit s of t h ese me th o d s g ive n t he p o tenti a l fo r b ackgrou nd leve l s i n/o n so m e m atri ces re lat i ve l y cl o se to that leve l ; and (3 ) th e LOQ in/ o n w heat , milk a nd meat co mmodi t ies i s 0.01 ppm based o n avai lab le meth od va l ida ti o n d ata take n toget her. Me th o d RE S-0 8 2-9 4 ( V e rs i o n 2) and Me th o d RE S- 095 -96 (V e rs ion 0) , as writte n , a r e acce ptab le for res i du e d e te rm i n at ion fo r e n fo r ce me nt purposes , excl udin g to le r an ces in hog co mm o diti es w h ic h a r e no lo n g er n ee d e d 

### (see discussion un der 860. 1 480). C o n firm a ti o n o f r es id ues by othe r m ea n s w ill b e n ecessary and m ay b e Page 7 of 11Sul fosu lfuron (08560 I) Abbrevia ted Residue Chemistry Re v iew DP # : 427730

acco mplish ed u s i ng the confirmatory aspec t s of Method ES -ME

- I 066-01 d isc u ssed below ( i .e. , a lternat ive co l umn , m ob il e phase , gradient e lution prog ram and/or detection met hod). In th e case of s ulfo su lfuron, an a ll owance w ill be m a de for total analysis tim e takin g lo nge r than 24 hours and is dis c u ss ed in g rea ter detail b e low. A s uccessful TMV o f Method ES -ME-1066-01 was a co ndition of registration for the u se of sulfos ulfuron o n grass . Method ES

- ME-1066

- 01 uses liquid c hromatograp hy wi th tandem ma ss s pe c trometry d etec tion (LC-MS/MS) and i s a modifi ed ve rsio n of the HPLC w/fluorescence d e tec tion meth o d s u s ing a diff erent co lumn , mobile pha se and gradie nt el uti on pro g ram. However , th e total analysis time is the same as th e HPL C w / flu o resce nce d e tection method s. Method ES

- ME-1066

- 01 monitors only one mas s ion transition fo r quantitation (rn/z 2 11 / 165) of res idues. Radi ovalidati o n a nd lLV dat a were not prov id ed for thi s me thod but are not required s in ce the extraction/hydro l ys is procedures for Method ES -ME-1066-01 are esse ntially th e sa me as fo r the HPLC w/ fluoresce nce detecti on methods. Co ncurrent m e thod va lid a ti o n data in g rass fo rage and ha y sample s fortified at 0.005-50.0 ppm we re w ithin or very close to ge nerall y acce pt a ble limit s (70 -120 % ± 1 %) , with one exce pti o n in/on forage at th e l owest fort ificati on le ve l (i.e., one sample fortified at 0.00 5 ppm with 64% rec overy)

. Res idu es were detected in/o n co ntrol s; howeve r , du e to r e p o rting limit at ion s, i t is no t known if res idue s in co ntrol were we ll be low the lowes t leve l of method va lid a ti on (0 .00 5 ppm ). In accordance with th e current S ta nd ard Operating P rocedu res (S OP Nu mb e r ACB-019 dated 9115 / 08) for a s uccessful TMV rev iew (TMV-R) but allowing for total a nal ys is time taking lon ge r than 24 hours (see di scuss i on be low) , H E D find s Method ES -ME-106 6- 01 acceptable for residu e determin ati o n for e n fo rcem e nt purposes. Du e to the la ck of a seco nd io n transiti o n , co nfirmation of residues by o th e r mean s wi ll be nec essary and ma y be acco mpli s hed u s in g th e confirmat ory aspects o f th e HPL C w/ fluorescence d e te ct io n meth o d s d isc us sed above ( i.e. , a lt e rnati ve co lumn , mobil e phase, g ra di e nt elution program a nd/ o r detection method). Co ll ecti ve l y , these liquid chro matography methods are adeq uat e fo r enforce ment and provid e fo r confi rmation of residues v i a a lternate detection methods , co lumn s , m ob ile ph ases and/or g radi en t e luti o n pro g ram s . The LOQ for the se meth o d s is 0.0 I ppm. A lth ough analysis time for a sample se t u s in g th ese method s wi ll like ly exceed the genera ll y accep tab le timefram e, thi s deviation will be a ll owed , in thi s case , s in ce no acute dietary e ndpoint was id e ntifi ed for s ul fos ul f uron , chronic dietary risk est im ates for s ul fosulfu ron are below the l eve l of co ncern and most of the commo diti es w ith sulfos ul furo n tol e rances are n o t a m o ng the m ost perishable. These methods are ava ilabl e throu g h the ACB!BEAD. 

### 860.1360 **Multircsidue Methods**  Residue Chemi stry Memos: DP # s 237683 / 239 1 09. S

. C hun. 9/ 28 / 98 (Wheat Petition (PP # 7 F4840 )) DP # 239417 , S. Chun , 9/ 30/ 97 In s upport of th e petition for u se on wheat , acce ptabl e data were s ubmitte d re fl ec tin g te s tin g through the U.S. Food and Drug A dmini s tration ( FD A) Mu ltir es idu e Methods for su lfo sulfuron and it s su l fo namid e metabo lite. Sulfosulfuron and it s metabo lit e we re not recovered using Protoco l A: S ulfo s ulfuron appeared to deg rade und e r the condition s used in Protocol C. Based o n the res ult s of Protocol C te s ting , s ulfo s ulfuron and it s metab o lite were n ot t es t e d throu g h Protocols D , E , or F. The r es ults of the multi res idu e method s testing we re forwarded to FD A. Page 8 of 11Sul fosul furon (08560 I) Abbreviated Residue Chemistry Review DP # : 4277 30


### 860.1480 Meat, Mi lk , Pou ltry , and Eggs Residue Che mi stry M emos: DP # s 237683 / 239109, S. C hun , 9 / 28 / 98 (Whea t Pe tition (PP # 7F4840)) In cludes ruminant feeding s tudy data. DP # 328450, S. Levy, 7/ 25 / 07 (currently es tabli shed li ves tock t o lerances determined) The currently es tabli s hed livestock commodity tolerances reflect dietar y burd e ns fo r su lfosulfuron to beef cattle (33.6 1 ppm) , dairy cattle (22.41 ppm), poultry (0.016 ppm) and swine (0.016 ppm) calculated ( 0 32 8450) before th e most recent gu id a nce on constructing maximum reasonably balanced diets ( MRBD s; Gu id eline 860.1000 Table I Feedstuffs ( Jun e 2008)) was available. In accordance with Gu id eline 860.1000 Table I Feed stuffs (June 200 8) , the updated MRBDs for dairy cattle (21 ppm) , poultry (0.0 15 ppm ) and sw ine (0.0 1 0 ppm ) are little changed from the prior dietary burdens; however , the MRBD for beef cattle ( 1. 2 ppm) is much low e r because grass forage is no longer cons idered a feedstuff for beef cattl e. The calculated MRBDs are presented below in Table 2.

Tab l e 2. Calc ulation of Di eta r y Burd e n s of S ulfo s ulfuron to L ivestock. Feedstuff Type' %Dry % Diet 2 Re s idue Estimates 3 Mauer2 (ppm) Beef Cattl e ( 15 % R; 80%CC; 5%PC) Grass, hay R 88 15 7.14 Wheat , g rain 

## cc 89 20 0.02 Wheat , milled byproducts 

## cc 88 40 0.02 Untreated 

## cc

-- 20 

## -- Untreated PC


### -- 5 

## -- TOT AL BURDEN 

### -- 

## -- 100 

## -- Dair y Catt le ( 45 % R ; 45 %CC; 10 % PC) Grass, forage R 25 45 11.65 Wheat, grain 

## cc 89 20 0.02 Wheat, milled byproducts 

## cc 88 25 0.02 Untrea ted PC 

## -- 10 

## -- TOT AL BURDEN 

### -- -- 100 

## -- Poultry (75%CC; 25 % PC) Wheat, g rain 

## cc 89 75 0.02 Untreated PC 

## -- 25 

## -- TOT AL BURD EN 

### -- 

## -- 100 

## -- Swi ne (85%CC; 15 % PC) Wheat, milled byproducts 

## cc 88 50 0.02 Un treat ed 

## cc
-- 25 

## -- Untreated PC 

### -- 15 

## -- TOTAL BURDEN 

### -- 

## -- 100 

## -- I R: Roughage; CC: Carboh yd rate concentrate; PC: Protein concentrate. 2 Guideline 860.1000 Tab le I Feedstuffs (June 2008). 3 Wheat gra in and mill e d byproducts estimate based on tolerance lev e l inion grain. Grass hay and forage based on highe s t average field tri al (HAFT). 4 Contribution = ([tolerance / % OM] X % diet) for be e f and dairy cattle. Contribution = ((tolerance] X % diet) for poultry and swine. Pa ge 9of11 Dietary Contribution4 (ppm)

1.2 0.005 0.009

0.0 0.0 1.2
21.0 0.005 0.006

0.0 21
0.015

0.0 0.0 1 5
0.010

0.0 0.0 0.0 1 0Sulfosulfuron (08560 I) Abbreviated Residue Chemistry Review D P# : 427730

A n acce pt a bl e rumin a nt f ee din g stud y i s ava il ab le ( 0 23 7 683/ 0 23 9109)

. D a iry cattl e were d ose d fo r 28 co n s e c u ti v e d ays w ith s ul fos ulfuro n a t dose leve ls o f 8. 1 , 23.5 a nd 8 1

.7 ppm in th e di e t. T hese dose levels are approx im ate l y 0.39x , 1

. 1 x an d 3.9x th e reca lc ul ated M RB D for beef /dai ry cattle 

### (I. I pprn/2 1 p p m) and 8 1 Ox , 2,350x and 8 , l 70x t he recalculated MRBD for sw ine (0.010 p p m). Res idues appeared to plateau in m il k by D ay 4, and data for a ll ma trices were a pp rox i ma t e l y l in ear w ith th e d os in g leve l s. Th e m ax imum r es idu es of su l fos ul furo n fo un d in mil k a nd cow ti ss ues are l is te d in T abl e 3 b e low .

Tab le 3

. Max i mum Su l fo s u lfur o n Re s idue s b y Feedi n g Leve l from the R u minant F e edin g Stud y. Matrix Max im um Residues (ppm) Dose 8

. 1 ppm Dose 23.5 p pm Dose 8 1 .7 ppm 0.39x Cattle D iet 1 I. I x Cattle D iet' 3.9x Cattle Di et 1 8 1

Ox Sw in e D ie t 2 2 , 350x Sw in e Di et2 8 , I70x Sw in e D ie t 2 Milk 0.004 0.019 0.034 Skim milk 0.009 0.024 Cream 0.005 0.006 0.0 1 2 F at $ 0.005 0.007 0

. 070 Mu sc l e $ 0. 0 05 0.006 0.024 K idney 0. 1 15 0.223 1.006 Liver 0.095 0.276 0.556 1 Based on MRBD for dairy cattle (21 ppm). which is substantially higher than the MR BD for beef cattle (1.2 ppm). 2 Based on MRDB for swine (0.010 ppm). A p o ultr y fee din g s tud y h as not b e en s ubmitte d

. HE D pr e vi o u s ly co nclud e d that , due to th e low resi du e leve ls in th e he n m e t ab o li s m s tud y an d l ow res idu e leve ls fo und in w heat g ra in , a po u ltry feed i ng study was not n ecessary, and to lerances fo r res id ues i n po ul t r y com modi t ies we r e not requi red ( D 237683/D239 I 09). Co11c/ 11 sio11s. B ase d o n t he res ult s of th e ava il ab le fee din g st ud y, the es t a bli s hed to le ran ces fo r re s idu es o f s ul fos ulfu ro n in milk ( 0.0 2 ppm ) a nd in fa t ( 0

. 0 2 ppm ), mea t ( 0

. 01 ppm) and m ea t byprod u c t s (0.3 pp m ) of cattl e , goa t , ho rse a nd s h ee p are appro pri a te; h oweve r , g i ven th e ve r y l ow dietary b urde n fo r sw in e (0.0 1 0 p pm) , th e estab l ished tolerances fo r residues of sulfosu l furo n i n th e fat (0.005 pp m ), mea t (0.005 p pm ) and meat byproducts (0.05 pp m ) of hog are n ot needed a nd s h ou ld be re m oved since the re is no reaso n ab l e expec t ation of res i d ues in sw in e co mm od it ies ( i .e., Catego ry 3 of 40 CF R l 8 0

.6(a))

. Fur the rmore, the re is no reaso n ab le ex p ec ta ti o n o f fini te res idu es of s ul fos ulfu ro n in p o ultry g i ve n the ve ry low di e tary burd e n fo r p o ul try (0.0 1 5 pp m ) ( i .e., Category 3 of 40 CF R l 8 0.6(a)).

Page 10o f 11Sulfosulfuron (085601) Abbrevia ted Residue Chemistry Review DP# : 427730


### References DP # : Subjec t : Fro m: To: D ate: MR ID # : DP # : Subject:

From: T o: D ate : MRID #s : DP # s : Subject:

From: To: Date: MRID # : DP# : Subject: From: To: Date: MRlD # :

DP# : Subject: From: To: D ate: MRID # : 239417 PP# 7F04840

. M ultiresid ue Method T es tin g of MON 3 7500 and Sulfonamide Metabolite (C P 147937 ). S

. C hun F.D. G riffith 30-S EP

- 199 7 44295713 237683 a nd 239 109 PP # 7F04840. New Chemica l

- Su l fosu l furo n ( i.e. MON37500 , MaverickTM) in/o n Wheat. Evaluation of Residue D a ta and A nalytical Meth o d s. C hemi ca l No. 08560 I. Case No. 28887 8. 

### S. C hw1 

### J
. TompkinsN

. Wa l ters 28-SE P-19 98 44 295702

- 04 , 44 295 707-ll , 442957 1 3- 14 , 442957 1 6- 18 , 44295735 , 44309301 232393 a nd 232394 PP # 7F04840. Sulfosu lfu ron (M ON37500 ) on Wheat a nd Anim a l RACs. Request for Petition M e thod Valid at ion: 

### I ) Wheat RA Cs MR10 #44 2957- l 0 and 2) Animal Commodities MRID #442957 -l I

. AC B # 898-(2,3)

. P
. Sc h e rm e rh o rn an d 

### L. Pod homi ak E. Zager a nd D. Stubbs 12-JAN-1999 442957 10 -11 3328 0 7 Sulfosulfuro n . Registration Request for Crop Group 17 (Grass Forage, Fo dd er, and Ha y) . R eq ue s t fo r P etiti o n Method V a lid at io n (PMV). S. Levy F. Siegelman 17-0CT-2006 46753801

328450 Su l fosulfuron. New Uses on Grass Forage, Fodde r , and H ay (Cro p Gro up 1 7). S. Levy J

. To mp kins 25-JUL-2007 46753801

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