### UNITED STATES ENV IRONM EN T AL PROT EC TION AGENCY W

ASHfNGTON , D.C. 20460

MEM O RAN D UM Date : 19 June 2015 OF F I CE OF CHEMICAL SAF ET Y AND POLUTION PREV E NSION

Subject: Fluensulfone

- Assessment of the Section 18 Use on Carrots in Michi gan PC Code : 050410 DP Barcode: 04272 29 Deci sio n No.: 503856 Re g istration No.: 66222-243 Petition No.: l 5 MI0 5 Regulatory Action: Sect ion 18 Risk Assessment T ype: Single C hemical Aggregate Case No.: None TXR No.: NA CAS No.: 318290-98-1 MRJO No.: None 40 CF R : 180 . 680 From: Michael A. D oherty , Ph.D. , Senio r Chemist 

# UJ**~** Zaida Figueroa , M.S., Indu stria l H yg ieni st 

### ;J**~~** H ea lth Effects Divi s ion (HED; 7509P) ' Ri sk Assessment Branch II (RA B II )**~** Thro ugh: Christina Swartz, Chief

# ~ HED , RAB II To: Stacey Groce/Tawanda Maignan (Team 09) Marion Johnson, Chief Re g i s tration Divi s ion (RD; 7505P) R i s k I ntegration , M inor Use , and Emergency Respons e B ranch In t rod u cti o n The Michigan Department of Agriculture ha s issued a cri s is exemption for the u se of fluensulfone to co ntrol a number of nematode species in carrot fields. This is the first Section 18 exemption for this use. Under the exemption , up to 2 , 000 acres of carrot fields will be treated with the N imitz ® 480 EC formulation offluensulfone (EPA Registration No. 66222-243). The Section 1 8 doc u me ntati on indicates that the use w ill be in counties of Lapeer, Montcalm, Newaygo , and Oceana. The u se seaso n is 14 April to 15 June 2015 , and the crisis exem ption was issued on 14 April 20 15. Flu e n s ulfone {5-Chloro

- 2-[(3 , 4 ,4

- tritluoro- 3 -buten-l-y l)sulfony l]th iazole} is a nematicide registered in 2014 for use on cuc urbit and fruiting vegetables, and the Agency ha s rece ived a Sectio n 3 request to register this ingredient for use on addit ional crops , including carrot. Page 1 o f20Fluensu lfone Aggreg ate Human Health Ri s k Assessment D427229 Agency Memoranda Used to S upport this Section 18 Exe mption Risk Assess m en t D403767. M. Doh erty , J. D ' Agostino , Z. Figueroa. 18 Jun e 2014 . Flu ens ul fone

- New Active Ingre dient Human Health Risk Assessment of Propo se d Uses o n C ucurbit Vegetables and Fruiting Vegetables. D40 38 1 3. M. D o herty. 4 Jun e 20 14. Fluensulfone. Petiti on fo r the Estab li s hm e n t of Perm a ne nt Tolerances and Re g istration for Use of the New Active Ingre di e nt o n Fruiting Vege tabl es (Crop Group 8- 1 0) and Cuc urbit Vegetables (Crop G roup 9). S ummary of Analytica l C he mi stry and Residue D ata from the OE CD Joint Review. D403814 , Z. Figueroa , 18 Jul y 201 4. Flu ens ul fo ne. Occupational and R eside nti a l Expo s ure an d Risk Assess ment to Support the Registratio n o f the New Active In gredient on Cuc urbits and Fruitin g Vegetab les. D418204 , M. D oherty, 10 June 2014. Fluensulfone Acute and Chro n ic Aggreg ate Di etary (Food a nd Drinkin g Water) Expos ure and Ri sk Assess me nts fo r th e Fir st Food Use Sec ti o n 3 R eg istration Action on Fruiting and Cucurbit Vegetab l es Assessment S umm ary Chemica l Id ent it y and Background Information. Fluensu l fo ne { 5

- Chloro-2

- ((3 ,4 ,4-trifluoro-3

- b uten-1- yl)s u lfonyl)thiazole} is the first nematicide in the fluoroalkenyl class and was registered as a new acti ve ingredient in the U .S. in September of20 14. It i s re g is tered for pre- plan t a pplicati on by bro adcast s pray or drip irri gation seve n da ys prior to trans plantin g cucurbit and fruiting vegetab les. Tolerances for res idu es in those cro p groups are established at 0.50 ppm , w ith enforcement based solely on re s idu es of th e triflu orobutene sulfonic ac id metabo lite (exp re ssed in term s of fluen s ul fone; 40 CF R 180 .68 0). Risk assess me nt s for flu e n s ulfon e are based on residues of t h e parent compound, 

### per se, due to the low toxicity of the butene sulfonic aci d and thi azo le su lfonic ac id metabolites. Th ere are no Ca n adian o r Codex MRLs fo r res idue s of fl ue n s ulfon e in carrot at thi s time , and international harmonization is not an iss ue for thi s Sect ion 1 8 . Sec tion I 8 Use Patte rn Information. Under the sp eci fic exemp tion , flu e n s ulfon e i s appl ie d as a singl e , pr e -plant application to c arrot fields by broadcast spray , band ed s pray, or drip irri gation . Appl ication will precede planting by no less th an 14 days , and the applied material will be watered into the so il two to fiv e days after app lication. Th e maximum application rate is 2.5 lb a.i./A, with the rate prorated to the actual treated a r ea in th e case of banded spray applicat io n . Toxicological Information. Th e toxico logy datab ase for flu ens ulfone i s co mpl e te for purposes of co nductin g an FQPA hum an health ris k assess ment. In mammals , expos ure to flu e n sulfon e results in effects o n the hematopo ietic sys tem ( d ec reased p latelets, increased white blood ce ll s , Page 2 o f 20Fluensulfone Aggregate Human Health Risk Assessment 0427229 hematocrit , and reticulocytes) , kidneys, and lun gs. Changes in c linical c hemi stry as well as in body weight were a lso observed across multiple studies and species. In rats , pup loss was noted , w ith the majority of deaths occurring on post-natal day 2. Overall , the most sensitive e ndpoint s for assessing human health risk are the increased pup-loss effects for acute dietary ex po s ure ; body weig ht , hematological and clinica l chemistry changes for chronic dietary and dermal exposures (short/intermediate term); and clotting time , decreased thymus weight, and portal-ofentry effects (histopathology of the epiglottis and nasal cav ity) for inhalation expos ures (s hort/intermediate term). Given the overall complete nes s of the toxicity database, the lack of uncertainty regarding susceptibil ity of infants and children , and the conservatisms in the human health exposure estimates , HED has reduced the Food Qua lity Protection Act Safety Factor (FQPA SF) from lOX to IX. For asses s ing occ upati onal oral and dermal exposures , the standard inter- and intra-species uncertainty factors of 1 OX are appropriate and result in a lev e l of co nc ern (LOC) of 100. For assess in g occupational inhalation exposure , the interspecies (to account for differences between rats and humans) factor has been reduced to 3X; however , an additional 1 OX factor is required because a no-observed-adverse-affect level (NOAEL) was not found for the porta l- of-entry effects, resulting in an LOC of 300. Table 1. Summary of Toxico l og i ca l Doses and End p oin t s for use in Fluens ulfon e Dietary a nd NonOcc up at io nal Hum an H ealth Risk Assessments. Exp os ure/ Point of U ncertainty/ RID , PAD , S tu dy and Toxicological Effects Scenario Departure FQPA Saf e ty Leve l of Factors Conc ern for Risk Asse s sment A c ute Dietary Off s pring UF A = !Ox Acute RfO = 2

- g e neration reproduction

- rat ( All NOA E L = UFH = IOx 0.16 mg/kg/day Offspring LOAEL = 122.0/ 169.1 Po pulati o ns , 16.2/23 .0 FQPA SF= Ix m g/kg/ day ( M/F) based on an increase in in c ludin g mg/k g/ day aPAD = 0.16 pup loss between PNO I and 4 in the FI Infants and (M/F) mg/k g/day and F2 off s pring with the majority of C hildren and deaths occurring on day 2. Females 13-49 ye ars of age)

Page 3 of20Fluensulfone Aggregate Human Health Risk Assessment 0427229 Tabl e 1. Summary o f Toxic o logica l Do ses a nd E ndp oin t s for u se in F l uens ul fone Dietar y and NonOccupationa l Human Health Ri s k Asses s m ents. Exposure/ Point of Uncertainty / RfD , PAD , Study and Toxicological Effects Scenario D eparture FQPA Safety Level of Factors Concern for Risk Assessment Chronic NOAEL = 3.1 UFA= IOx Chronic RID = Co-critical 90-day dog and chronic dog D ietary (All m g/ kg/ day UFH = IO x 0.03 Populations) FQ PA SF= Ix mg/kg/day Chronic: LOAEL = 16 mg/kg/day based on decreased body weight, increased cPAD = 0.03 mean he moglobin concentration mg/kg/day distribution width , and increased relative and absolute reticulocyte counts in both sexes, decreased prothrombin time in males and increa se d platelets in females. Subchronic: NOAEL = 1.6 mg/kg/ day LOAEL = 17 .1 mg/kg/ day based on decreased body weight in females and increased relativ e and absolute reticulocyte counts , decreased b il irubin , d ecrease d albumin, decreased A/G ratio , increased TSH , and pigmented Kupffer cells in both sexe s . Incidental Oral A dose and endpoint for incidental oral exposure were not selected because there are prese ntl y no All Durations residential uses for fluensulfone . Denna! All There are presently no re s id e nti a l uses for fluen s ulfon e. Durations Inh alation All There are presently no residential uses for tluensulfone. Durations Cance r (oral , Clas s ificati on: Suggestive evidence of carcinogenicity in humans based o n lung tumor s in dennal , inhal.) female rat s. The RfD is p rotective of potential cance r effects. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and u se d to mark th e beginning of extrapolation to detennine ri sk associated with lower e nvironmentally relevant human exposures. NOAEL = no observed adverse effect level. LOA EL = lowest observed adverse effec t level. UF = uncerta inty factor. UF A= extrapolation from animal to hum an (interspecies). UFH = potential variatio n in s ensitivity among members of the human population ( in traspecies). UF L = use ofa LOAEL to ex trapolate a NOAEL. FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute , c = chronic). RfD = reference dose.

Page 4 of20F l uensulfone Aggregate Human Health Risk Assessment 

### 04 27229 T ab le 2 . S umm ary o f Toxico log ica l D oses and Endpoints fo r u se i n Fluensulfo n e Occupationa l Human H ea lth Risk Asses s m e nt s. Ex posure/ Point of Departure U nce rtain ry Le vel of Study and Toxicological Effect s Scenario Factors Concern for MOE Dermal Short

- NOA EL = 3. 1 mg/kg/ day UF ,, = IOx Occupationa l Co-critical 90

- day dog and chronic an d U FH = I Ox LOC for MOE dog Int e rm ediate- O AF = 40.9% = 100 Term (1 -30 Chronic: LOAEL = 16 m g/kg/day days and 1

- 6 based o n decreased body month s) weight , increased mean he moglobin concentration di s tribution width , and increased relative and absolute re ticu locyte cou nts i n both sexes, d ec reased prothrombin time in mal es and increased platelets in females. Subchronic: NO AEL = 1.6 mg/k g/ day LOAEL = 17 . l m g/kg/day base d on decrease d body w eight in females and incre ase d re lat ive and absolute reticulocyt e coun ts, decreased b ilimbin, decreased a lbumin , decreased A/G ratio , increased TSH , and pigmented Kupffer cells in both sexes. Inh alatio n NOA E L= not es tabli s hed UF A=3x Occ upational 90-day inhalation toxiciry

- rat Short

- and (<0.04 mg/ L) U F 11 = lOx LOC for MO E LOAEL = 0.04 mg!L ( lowest dos e In termediate- UF L "" IO x = 300 te sted) based on w e i ght los s in Term ( 1-30 3 H EC = 0.00429 mg!L males, prolonged prothrombin time days and 1-6 b HE D = 0. 244 mg/kg/day in fema les, decreased thymu s m o nth s) ( low breathin g rate) , weight in ma les, hi s topathological = 0.491 m g/kg. day changes in th e epiglottis in both ( medium breathing rate) , sexes, and hi s topathological = 0.853 mg/k g/day changes in the nasal cavity of (high breathin g ra t e) mal es. Cance r (o ra l , Classification: Suggestive evidence of carcinogen ici ty in humans based on lung tumor s in dermal, inhal.) female mice . The RID is protective of po te nti a l c anc e r effects. Point of Departure (POD) = A data point or an estim ated point tha t i s derived from observed do se -re spo nse data and used to mark the beginning of ex trapo la ti o n to determine ri s k assoc iat ed with l owe r env ironmentally re leva nt human exposu res. NOA EL = no observed adve r se effec t leve l. LOA EL = low es t observed adverse effect level. U F = un certain t y factor. UFA = extrapolation from a nim a l to human ( int erspecies). UFH = potential variation in se n s itivity among memb e r s of t he human popul ation (in traspecie s). UFL = use of a LOA EL to extrap o l ate a NOAEL. MOE = margin of exposure. LOC = leve l of concern. OAF = dennal absorp t ion factor • HE C = rat OAEL x (daily duration adjustment) x weekly daily durati on adjustment x RDDR = 0.04 mg/L x (6 hr / 8 hr) x ( I ) x 0. 143 = 0.00429 mg/ L. b HED = HEC x human s pecific conversio n factor x activity factor for the exposure scenario x daily duration = 0.00429 mg/L x 11 . 8 L/hr-kg x (0.6 . 1.2. and 2.1 for low. medium , and high. re s pectiv e l y) x 8 hr. Pag e 5 of20Fluen su lfone Aggregate Human Health Ri sk Assessment D4 27229 Occupational Exposure and Risk Information . Occupational exposures and ri s ks from the u se of fluensu lfone on cucurbit and fruiting vegetable s were estimated in the last ri s k assessment , with margin s of ex pos ur e ( MO Es) ranging from 81 t o 270 for d ermal ex posure (level of concern i s dermal MOE < l 00) and fro m 290 to 1 , 300 for inhalation exposure ( leve l of co ncern i s inhalation MOE < 300). Ex po s ure input s are the s ame for carrot as thos e u sed in the pre v iou s assessm e nt fo r cucurbit and fruiti ng vegetabl es . The refore, H ED i s trans latin g the previou s occupationa l hand l er assessment to thi s Sect io n 18 assessment. 

### HED notes th at in 

### the previous occupational assess m e nt , u se of per so n a l protective eq uipm e nt (PPE) in 

### the form of chemic a l-resista nt gloves a nd engineering controls was nece ssary to achieve dermal MOEs above th e LOC. The Sectio n 18 lab el for u se on carrot should s pecify the same PP E as i s li s ted on the Se ction 3 l a b el for cucurbit and fruitin g vegetab les. Due to the use pattern and appli cation timin g ( i.e. , applied as a pre-plant broadcast applicati on prior to tran splanting ) , n o pos t-application expos ure is expected for worker s re - e ntering treated areas. F lu e n s ulfone i s cla ss ifi ed as Toxicity Categ ory III v ia the d ermal rout e and Toxicity Catego ry IV for sk in and eye irritation pote ntial. It is a sk in se nsitizer. T he RE I of 12 hours li s ted on the labe l i s adequate to protect agricultural workers fro m post-appli cati o n ex posures to fluen s ulfon e. Die tar y Expos ur e Information . The regi strant has petition e d the Age ncy to re g i ster fluen su lfon e for use o n a number of additional crops , includin g carrots. In order to support that reg istration request, the registrant pro vided data from s up erv ise d re s idu e trial s in carrot. Those data show quantifiab le residues of flu e n s ulfon e as well as the su lfonic ac id metabolites in carrots harves t ed from flu e n s ulfone -treated fi e l ds. In estimating dietary ri sk , HED used the max imum average field tri a l flu e n sulfone res idue value from the carrot study , th e residue l eve ls u sed in the prev i ous dietary assessme nt for flu e n s ulfone (0.0 1 ppm for cucurbit and fruiting vegetab les), and an assumption of 100% crop treate d for all commodities. Mod e led es tim ates of re s idue s in drinkin g water are th e s ame as tho se u se d in the prev i o u s Se ction 3 ri s k assess ment and are considered to be conservati ve , and therefore protective of potential r esidues in drinkin g wate r resu lting from the Section 18 use on carrots. The resulting sc ree ning-le ve l dietary risk est imates across all repre se ntat ive population gro up s range from 2% to 8 % of th e PAD for acute ex po s ure and from 3% to 1 1 % of the P AD fo r chronic exposure , and a ll di etary ri s k estimates are not of concern. Res id en tial Exposure Information . At this time, there are no uses for flu ens ulfon e that would result in direct non -di etary expos ure in a r es id entia l or recreat ional settin g. Aggregate Risk Information. Aggregate ri s k estimates are eq uivalent to the di etar y risk estim ates and are no t of co ncern for a ll popu l ation groups/scenario s.

Page 6 of20Fluensulfone Aggregate Human Health Ri s k Assessment D4 27229 Cumulative Ri sk Informal ion. The Agency h as not made a determination that fluensulfone s hares a common m ec hanism of t ox i c ity with other compounds and ha s not conducted a cumulative ri s k assessment w hich include s tl uens ulfon e. Conclusions. HED has no objectio n to the is suance of this Section 18 exemption. The available data support a tolerance for re s idues of flu e n s ulfone in/on carrot (as meas ure d by residue s of th e BSA m etabo li te expressed in parent-equiva l e n ts) at 2.0 ppm . RD shou ld e ns ure that the Section 18 labe l for use on carrot h as the same PPE as is currently liste d on the Section 3 label for u se o n cucurbit and fruiting vegetab les. 

### T o x ico log ica l Co n si d e ratio ns Fo r comp lete detail s, see 040 3 767 , M . D oh erty el al ., 18 Jun e 2 014. The hematopoietic system was the ma jor target of fluen sulfone activity in rats , d ogs, and mice. Effects o n the hematopoietic syste m includ e d increased wh ite blood ce ll s (rats an d mice), incre ased h e m atocri t ( mic e), d ec reased pl a te lets ( mice) , and in c r ease d reticu locytes (dogs) in subchroni c d ietary stud ies at th e lowe st observab l e effect lev e ls (LOAEL) with additional effects on the he matopo i etic system observe d at hjgher doses. Effects o n the hemat opo ieti c sys tem were also observed i n c hro ni c di etary studies for a ll spe cies and , in the case of the c hro nic rat and dog s tudies , the se effects were observed at the LOAELs. Effects on the hematopoiet ic system are cons i ste nt with res ults from rat metaboli sm s tudi es which demonstrated that tluensulfone can react w i th th e free thio l m o iety of globin, fo rmin g a coval e nt linkage t o t he th iazo le g roup di sp lacin g butene su lfinic ac id. This le d to s lowe r elimination of th e thi azo l e p o rtion of fluensulfone from who l e b lood (time from d ose to 50% of peak co ncentration , DT so = 6-9 day s) compared to plasma (D T so= 16-17 hours ). Other effects co mmonl y observed in the toxicological datab ase in a ll three spec ies included changes in clinical chemj stry parameter s and decreased body weights, both of which were often seen at the LOAELs in s ub c hronic and chronic studi es . Altered clinical chemistry parameter s included decreased plasma a lani ne amino transferase (ALA T, rats and dogs ), increased cholesterol (rats), increased trig lycerides (rats ), increased phospho lipid s (rats) , increased bilirubin ( mi ce) or decre ase d bilirubin ( dogs), decreased protein (dogs), de c reased albumin and a lbumin/g lo bulin ratio (dogs) , d e crease d g luco se (dogs) , and increase d TSH (dogs) in s ubchroni c studies. Fo r the hematolo g ical , c linical chemistry, and bod y weight effects observed in all three species, the dog app eared t o be s lig htl y more se n s itiv e than mice and rats . Fluensu lfone also caused effects on the kjdney in male rats; h owever, the effects are consistent wi th acc umul atio n of a.-2-m icrog lobulin which ha s been deemed not rele van t t o human s (USE P A 1 99 1). Effects on the lun g were observe d followin g c hronic di etary expos ure in mice and rats. The se effects consisted of an in creased inc id e nce and severi ty of lung interstitial inflammation in the 2- Page 7 of20Fluensulfone Aggregate Hum an Health R isk Assessment D427229 year rat study and an increased incidence of bronchio li zation (c hange from flatte ned ep ithe li um to c uboidal epithelium) in the 18

- month mouse study. Flu e ns ulfone a lso appeared to cause portal-of-entry effects in rats. T hi s included th e forestomach (d i ffuse basal cell hyperplas ia) and pharynx (mononuclear infiltrates) in dietary s ubchronic studies; the ep ig lottis (squamo u s metaplasia, epithe li al hyperplasia , and focal mononuclear cell in filtrates) and n asal cavity (squamous epithel ial hyperplasia) in th e 90-day inhalation study; and a n increased in c id ence/sever ity of acanthosis/hyperkeratosis in th e 28 -d ay de rmal st ud y. The dermal effects were considered adaptive due to the mod erate degree of acanthos is/ hyperkerato s i s observed. Di sco loration of teeth was noted in two s ub chronic toxicity studi es , and increased l eve ls of total fluoride were observed with a st rong dose -response across numerou s s tudie s. Ne i ther th e discoloration nor the increased flouride levels are considered adverse (i.e . , severe dental fluorosis ); howev er , they do ind icate that expos ure to tluensulfon e may co n tribute to overall fluoride exposure. Residue data (see previous risk assessme nt) d e m onstrat e that total fluoride leve l s are indi stinguishabl e between flu ens ulfone-treated and untreated crops ; the refo re , HED has concluded that for the assessed use s, fluensulfone is not a sour ce of fluorid e exposure. T h ere was no ev id e nce of immunotoxicity in t he avail able stu di es, which includ ed a guid e lin e immunotoxicity stu dy in the rat. There is limi ted evidence that fluen s ulfone results in effect s on the nervous system. Decrea sed locomotor activity, decreased spo ntaneous activ ity , decreased re arin g, and i mpaired righti ng response was observed only on D ay l following acu t e exposure in the ac ute neurotoxicity stu d y. In contrast , no evi de nce sugges ti ve of neurotoxicity was observed i n any o ther study , includin g a subchro ni c neurotoxicit y study. Fo ll owing d ermal exposure for 28-days, systemic effects including increased r eticu locytes and increased cholestero l we re observed, b ut o nl y at a do se tw ice that of the limit do se. T here was evi d ence of increased qualitative su scep tibili ty of pups to the effects of fluen su lfone . Decreased pup weight, decreased spleen weigh t , and an increase i n post -n atal pup loss [po s tnatal days (PND) 1-4] were observed in the rat two - generation reproduc tive toxicity study at a dose ca u s in g d ecrease d body we ig ht in the pare nts. Th e fi ndin gs in the pups were conside r ed mo re severe than tho se seen i n the mate rn al animals. No ev id e nce of in c reased quantitativ e or qualitative suscep ti bility was see n in developmental tox icity stu di es in rats and rabbits. In th e rat developmental toxicity study , decreased fe t al weight was observed in the pre se nc e of decrea sed body weight in maternal an im als. In the rabbit developmental toxicity stu dy , d ecreased fetal we ight and in comp lete ossification of digit 5 of th e med ia l phalanx in both fore limb s were observed in th e presence of decreased body weight in maternal anima ls. Chronic dietary exposure to flue ns ul fo ne in female mice res ulted in an increa se d incidence of lung adenomas an d carcinomas. The Cancer Assessme nt Review Commi ttee (CARC) c lassified fluensulfone as having "Suggestive Evide nce of Carcinogenicity" based on an in crease d inc idence of a lveo lar/bronchiolar aden omas and carcinomas in the lung of m id- and high-d ose Page 8 of20Fluensulfone Aggregate Human Health Risk Assessment D427229 fema le mice in th e oncogenicity s tudy. A ll genotoxicity s tudi es that we r e conducted on fluensulfone and three of its m e tabolite s (thiazo le s ul fo nic ac id ; TS A , bute ne sulfo n ic acid; BS A , and methyl s ulfon e; MeS ) we re negative, except for MeS with 

### Salmonella typh im urium s train TA 100 in the absence of metabol ic activation during a bacterial reverse mutation assay. Testin g in acute lethality s tudi es with flu e nsul fo ne technical-grade material res ulted in low toxic ity cl ass ifi cation s via the oral (T oxic ity Category III) , d e rmal (Tox icity Category III), and inhalation (Toxicity Category IV) route s of exposure. Fluensulfone technic a l- g rade materia l was not an irri tant to eyes (Toxici ty Categ ory IV ) o r ski n (Toxicity Category IV ) but was a ski n se n s iti ze r. S imilar results were obtain ed in ac ute leth a li ty stud ies with an em ul sifiable conce ntr ate formulation (480 EC). Ora l acute l e thali ty st udi es were a lso conducted with th e m etabolites MeS , BSA, or TSA, eac h at 2000 mg/ kg bw. By the o ral route of exposure , MeS was of moderate toxicity (Toxicity Catego ry II ) and both BSA and TSA were of low toxicity (Toxicity Cat egory III ). HED note s that a ll animals treate d with B SA or T SA s urvi ved the entire stu dy period and that the to x i c ity category for those met aboli tes is based on the dosing level rather than o n actual LD so es timates . Furthermore in the BSA and T SA acute toxicity s tudi es , body wei ghts of all anim als we r e within the no rm a l range , no macro s copic finding s were recorded at necrop sy, and no clinical signs we re obse rv e d exce pt in thre e animal s which exhibite d s li g htly ruffled fur two h o urs after admi ni st ration of TSA , w hi c h p er s isted up to the thre e- hour observatio n in two anim a l s. In 28

- day ora l toxicity s tudie s w ith BSA and TSA, no treatm e nt-re l ated effects were ob served at any do s e (limit-dose = 1000 mg/kg/day). 

### Saf e ty Factor/or In fa nts and Childr e n (FQPA Safety Factor) The toxico logy and the ex posure databases for fluen s ulfone s upport a reduction of the required 1



### OX F QP A S F to I X b ased on the fo ll owing considerations: the completeness of th e toxicity data base includin g adeq ua te studies to assess th e pote ntial s u sce ptibi li ty 

### in the youn g; there i s no indication o f quantitative susceptibility in the de ve lop ment a l and re produ c ti ve tox ici ty s tudies , and there are no res idual uncertainties co ncernin g pre- or po s t-natal toxicity; the endpoints an d do ses chosen for risk assessment are protec ti ve of the qual itative susceptibility observed in the 2-generation repro du c ti o n study; acute and s ubchroni c neurotoxicity studies (ACN and SCN) are availabl e. In addition, al l en dpoint s used in the ri s k assessment are protective of the ev iden ce of neuro toxi c ity observed in the ACN, and a de ve lopmental ne u rotoxic ity study is not required. Th e dietary assessment is based o n re li ab le data and con s e rvati ve l y modeled drinking wat e r resid ues , and wi ll not underestimate ex posure. Fin ally , there are no regi s te red or reque s ted u ses fo r flu e n s ul fone that would result in residential ex pos ure.

Page 9 of20Fluensulfone Aggregate Human Health Risk Assessment 

### 0427229 Occupational Exposure Considerations There i s a potential for occupational exposure associated with hand ler activities (i.e., mixing , loading , and applying). Given that the Section 18 use pattern requires soil-incorporated app lic ation 14 days before planting , no post-appl ication exposure is expected for workers reentering treated areas. The duration of exposure for the use s on cucurbit and fruiting vegetab le s is expected to be short-term (1-30 day s) and intermediate -t erm (1-6 month s). For the Section 18 use , similar durations of exposure may occur. Long-term exposures (greate r than 

### 6 months) are not anticipated. Th e occupational handler (mixer, loader, applicator) exposure and risk estimates from the prev ious assessment are summarized in Table 3. Note that in order to mitigate occupational risk i ssues , the originally proposed application rate of 

### 3.5 lb a.i ./

### A was r educed to 

### 2.5 lb a.i ./ A on the reg istered Section 3 label, which matches th e application rate on th e Section 18 label. Table 3. Sho rt- and Int e rm e diate -Te rm Occupationa l Hand l er Non-Cancer Exposure a nd Risk Estimates for Fluen s ulfonc . Taken from 0403814, Z. Fi2ueroa , 18 Ju lv 2014. Exposure Mitigation Application Area Dermal Dermal Inhalation Inhal ation Scenario Level " Rate b Tre ated < Dosed MOE• Dose r MO ES (mg/kg/day) ( m g/k,g/day) Mixing/Loading Baseline 1.75 lb a i/ A 350 A 0.69 5 0.00168 290 Liquids for Eng in ee rin g 0.0269 120 0.000635 770 Chemigation Co ntrol s (AHETF/PHED) Baseline 2.50 lb a i/ A 0.9870 3.1 0.002400 200 Engineering 0.0385 81 0.000908 540 Co ntrol s Mixin g/ Loading Baseline 1.75 lb ai/A 80A 0 . 157 20 0.000384 1,300 Liquids for Single Layer, 0.0269 120 0.000384 1.300 Gro undb oom Gloves , No {AHETF / PHED) Respirator Baseline 2.50 lb a i/ A 0.2250 14 0.000548 900 Si ngl e Layer, 0.0384 81 0.000548 900 Gloves , No Respirator Applying Baseline 1.75 lb ai/ A 80 A 0.0562 60 0.000595 410 Liquids for S ingl e Layer, 0.0115 270 0 . 000595 410 Groundboom Gloves , Application No Respirator {AHETF/PHED) Baseline 2.50 lb a i/ A 0.0803 40 0.00085 290 Single Layer, 0.0165 190 0.00085 290 Gloves , No Respirator

.. a . M111ga11 on level or PP E. Baseline = long- s leeved shirt. lo ng pan ts . s hoes. soc k s . n o g lo ves. n o rc s p1rao r . b . App li ca ti on Rates based o n proposed use o n labe l (3 . 5 lb ai/A for all crop s ) . c . Ex po su r e Sc ience Advi so ry Co uncil Poli cy No. 9 . 1. d . De rmal Dose ( m g/kg/d a y)= Dail y Unit E xpo s ure ( μg/l b ai) x Dermal Ab so rpt io n Fa cto r (40. 9 %) x A ppli cati on Rate ( lb ai/g al ) x A rca T re a ted I Body Wei g ht (80 kg). c . Dermal M OE= NOA E L (3 . 1 mg/k g/day) I Dermal Daily Doic (mg/k g/ day) . LOC = 1 00 . f . Inhalati o n Dose ( mg/k g/day)= Dail y U nit Expo sure ( μg/l b ai ) x Applicati o n Rate ( lb ai/acre ) x Acres Treated I B ody W e ig ht ( 80 k g) . g. Inhalati o n MO E= HE D (0. 4 9 1 m g/kg/ dayMA. o r 0.244 m g/

k g/

dn y .. ) / Inhalati o n Dail y Dose (m g/kg/day). LOC = 3 00.

Page 10 of20Fluensu l fone Aggr egate Hum an H ealth Ri sk Assessme nt 0 427229 Re s idue Chemistry Co n s id erations Fo r d etai ls re gardin g the co re re s idue chemistry s tudi es, see 0403813 (M. D o herty , 4 June 2 014 ). Me tabolic Fate. Stu di es dep icting the nature of the res idu es 

### in target crop s (tomato , potato , and lettuce) , rotati on al crops (rad i sh, lettu ce , and wheat) and li vestoc k (laying h e n s and lactating goats) consistently show fluensulfone to be cleaved at the su lfon y l moiety , presumably via g lutathione conju gatio n , resulting in both hal ves of the molecule having a su l fony l functional group. Parent fluensulfone was identified o nl y in pou ltry fat and in rotational lettuce, radish fo lia ge, and w heat ha y , fo ra ge and straw at s ho rt plant-back intervals (30 da ys). With the exce ption of poultry fa t , flu e n s ulfone was not a major r es idue in any matrix. In both target and rotational crops, the c l eavage product s form thiazo l e s ulfonic acid (TSA) and butene sulfonic ac id ( B SA) . Th e butene su lfonic acid may the n be ox idize d to form s ma ll e r co mpounds that are incorporated into natural p l ant co mpone nt s or min era li zed to C02. In li vestock, the majori ty of the radiolabel was exc reted . Re tained fluensulfone is exte n s i vely m e tabo li zed, with the rad ioac ti v i ty b eing associated primarily with amino acids and triglycerides. Thi azo le meth y l sulfone and butene s ulfini c acid we re identifi ed in li vestock stu di es, but were observed only 

### in excreta. In the rat m e tabo li sm s tud y, significant res idu es were thiazole m ercapturate, thiazole g lu curonide, thiazole s ulfonic acid, buten e s ulfini c acid, and bute ne s ulfonfo acid . These are all co n s is tent with the g lu tathione-conjugation proc ess noted in the oth er m e taboli s m s tudies. F lue n su lfone was not d e tec ted as a significant residue ( i.e. , 

### < 0.1 

### % of the applied do se) in rats. Toxicology dat a for the TSA and BSA metabolites s how that t hey are n on-toxic at levels expected 

### in foods. As a result , inclu sion of the pare nt compo und in risk assessment , eve n at the limit of quantitation , is considered adequate to address risks that may be present from dietary expos ure to T SA and BSA. Enforcement of tolerances s hould be v ia mea s ure ment of residues of BSA o nl y . The parent compo und a lone is a poor indicator of mi s u se due to the lack of consistently quantifiable residues. The metabolites TSA and B SA both appear at quantifiable leve ls in the crop field trials and are good candidates for marker compounds. The TSA me tab o lite may persist fro m one year to the next; therefore , the potential for TS A to accu mul ate make s BSA a b etter indicator of misuse. Table 4. Summary o f Metabolite s and Degradates to be in cluded in t h e Ri s k As sess ment and To lerance Express ion of Flue n su l fone. Matrix Resid ues Included in Ri s k Assessment Residue s Includ ed i n To lerance Expressio n Plants Prim ary C rop Fluensulfo ne BSA· , as parent equivalen t Rotational Crop Fluensulfone BSA· , as parent equ ivalent Livestock Ruminant None None Poultry None None

Page 11 of20Fluensulfone Aggregate Human Health Risk Assessment 042 7229 T a bl e 4. S umm ary of M e t abo lit es a nd Degra d ates t o be in c lud ed in t h e Ri s k Assess m e nt a nd T o l e r ance Ex press io n of Fl u e n s u lfo n e. Matrix Residues included in Risk Assessment Residues lncluded in Tolerance Expression Drinking Water Fluensulfone + Mes· + de sc hloro- Not Applicable fluensulfone, expressed as parent equivalent • BSA refers to the butene su l fonic acid metabolite (3 , 4,4-trifluoro-but-3-ene-l-sulfonic acid ; Co mpany Code M3627); MeS refers to the methyl s u l fone metabolite (5-chloro-2-methyl sulfo nyl thiazole ; Company Code M3626). 

### Analytical Methods. An analytical method suitable for enforcement purpose s ha s been approved by the Agency (0403813, M. Doherty , 4 Jun e 2014). That same method was u sed in the field trials fo r carrot and was shown to be appropriate for that crop. The method has an LOQ , defined as the lower lim it of method validation, of 0.01 ppm. For carrot, the method ha s a calculated LOQ of 0.005 ppm. 

### Residue Chem istry. T he regis trant submitted a study volume (MRI D 4955361 3) depicting crop field trials conducted in carrot. The study was submitted in s upport of several newly petitionedfor uses. In that study, 1 fi e ld trial was conducted eac h in Florida , Texas , New Mexico , Ohio , Washington , Nova Scotia, and Quebec ; two trials were conducted in Ontario , and three trials were conducted in Californ ia (12 trials total ). A granular formu lation of flu e n s ulfone was applied at 3.6 lb a.i ./ A ( nominal ), 6-8 days prior to planting. The applied material was incorporated into the soil by tilling. Carrots were harvested at maturity and sent to Golden Pacific Laboratorie s for analysis . Samples were sto red frozen for up to 526 days; and residues were shown to be stab le based o n concurrent storage stabi l ity data. Re s idues inion carrot ranged from < 0.0 1 to 0.495 ppm for fluen su lfon e and from < 0.01 to 1.24 ppm for BSA. The results from the field trial s may overestimate residues in/on carrot treated as part of the Section 1 8 exemption du e to the exaggerated rate (3 . 6 vs. 2.5 lb a. i ./ A), use of a granular rather than a liquid product , and the shorter pre-plant interval (7 vs. 14 days). Using the resu lts from the field trials as input to the OECD MRL/tolerance calculation procedures results in a to lerance for residues of fluensulfone (based on BSA as parent-equivalent) of 2.0 ppm. 

### Processed Food and Feed. There are no sig nificant proce sse d food/feed item s associated with carrot. 

### Meal , Milk, Poultry , and Eggs. Carrot cu ll s may be fed to dairy cattle. At this time, there are no other livestock feedstuffs associated with registered uses of fluensulfone. Studies delineating the metabolism of fluensulfone in livestock commodities indicates that the parent compound is cleaved forming BSA as an intermediate compound. Metabolism continues s uch th at fluensu lfone, and by extension BSA , is further broken down into its constituent components and incorporated into natural products. Based on OPP's under s tanding of the metabo lism of fluensulfone in livestock animals and on the low proportion of carrot cu ll s as a livestock feed item (maxi mum of 10 % in a reasonably balanced modeled diet), there is no expectation of finite Page 12 of20Fluensulfone Aggregate Human Health Ri s k Asse ss ment D427229

res idue s of BSA in livestock commodities , includin g milk; therefore, tol eran ces for res idue s of tluensulfone in live s tock commod ities are not nee ded at thi s time [40 CFR 1 80.6(a)(3)]. 

### Rotational Crop R e s trictions. Th e Section 18 lab e l s pecifie s that only crops on the registered l abe l may b e planted into a fi e ld within l year of applying th e product. 

### Int e rnational Res idu e Limits. At this time , there are no CODEX or Canadian MRLs that wi ll impact the sett ing of tolerances for th is Sec tion 18 exe mption. 

### Di e t ary E xp os ure A n a lys i s Acute and c hronic aggregate dietary (food and drinking water) exposure and risk assessments were co nducted usin g the D ietary Expo su re Evaluation Mod e l so ftware with the Food Co mmodity Intake Database (DEEM-FCfD ) Version 3 .16 , which use s 2003 -2008 food co ns umption data fro m the U.S. Departme nt of Agricu lture's National Health and N utri t ion Examinat ion Survey , What We Eat i n America, (NHANES/WWE IA). As previous ly noted , the re s idu e of concern for di et ary risk assessment is the pare nt compound fluensu lfone. The max imum fluensulfon e res idu e observed in the carrot fie ld tria l s was 0.495 ppm. HED ha s update d the prev ious dietar y exposure and ri s k a ssess m e nt (D 4 l 8204 , M. Do herty , 10 June 2014) to refl ec t a 0.5

- ppm residu e leve l on all carrot ( i. e., I 00 % c rop treated ). As an esti mated drinking water concentration of flu e n sulfone, HED u se d the values previo u s ly provided by EFED: 77.6 ppb fo r acute and 52.5 ppb for chronic (D417634 , J. Lin , January 20 14). The dietary exposure and risk es timates s hould be con s idered sc reening -l eve l estimates that like ly overestimate actua l exposures to fluensulfone that may r es ult from the Section 18 u se on carrot. Generally , H E D is conc e rned when dietary risk estimat es exceed I 00% of th e population

adju sted dose for any of the representat ive pop u lat ions wi thin the consumption database (general U.S . popu lation, infants, children 1

- 2 years old , ch i ld ren 3-5 years old , c hildren 6-12 ye ars old , youth 13 -1 9 years o ld , adults 20 -49 years old , adult s 50

- 99 years old , and females 13-49 years old). For fluens u lfon e, the dietary ri sk estimates are not of co ncern for a ll pop ul ation groups and fo r both acute and chronic exposure scenarios (Table 5). Compl e te input and output listin gs for the dietary ex posure analysis are pro v id ed in Attachments 2

- 5. Ta bl e 5. S umm a r y o f Ac u te a nd C h ro n ic Di eta r y Ex o os u re a nd Ri sk Estim a tes f o r F lu e n s ul fo n e. Acute (95th Perce ntile) Chroni c Population Subgroup Exposure, mg/k g/ day Risk , % aPAD Exposure, mg/k g/ day Risk,% cPAD Total US Population 0.0045 2 0.001 2 4 A ll I nfants 0.0138 8 0.0034 1 1 C hildren 1-2 0.0072 4 0.00 1 9 6 C hildren 3-5 0.0058 3 0.0015 5 C hildren 6-12 0.0042 2 0.0011 4 Youth 13-1 9 0 . 0036 2 0.0009 3 Adults 20-49 0.0043 2 0.0012 4 Page 13 of20Fluens ul fone Aggregate Human Health Risk Assessment 0427229 T a bl e 5 . S umm a r v of Ac u te a n d C hroni c D ietarv Ex p os ure a nd Ri s k Es tima tes for F lu e n s ul fo n e. Acute (95th P ercenti l e) Chronic Population Subgroup Exposure , mg/kg/day Risk ,% aPAD Exposure, mg/k g/day Risk ,% cPAD Adults 50 -99 0.0039 2 0.0012 4 Female 13-49 0.0043 2 0.0012 4 

### R es id e ntial Ex po s ure At this time , there are no registered uses of fluensulfone that wi ll re sult in direct residential exposure . Spray Drift Spray drift is a potentia l source of expo sure to those nearby pes ticide applications. Th is i s particularly the case with aerial app licatio n , but , to a lesse r extent , spra y drift can also be a potential source of exposure from the ground app lication method s (e.g., g roundboom) employed for fluensulfone. The Agency has been working with the Spray Drift Task Force (a task force composed of vario u s registrants which was developed as a result of a Data Call- In issued by EPA) , EPA Regional Offices and State Lead A ge ncie s for pesticide regulation and other parti es to develop the best spray drift management practices (see the Agency's Spray Dri ft website for more information) 1 • The Agency has also developed a policy on how to appropriately consider spray dri ft as a potential source of exposure in risk asse ss ments for pest icides . The potential for spray drift will be quantitatively evaluated for each pesticide during the Reg istration Review process which ensures that all uses for that pesticide will be considered concurrently. The approach i s o utlined in the revised (20 12) Standard Operating Procedures for Re s id e ntial Risk Assess ment (S OPs)

- Residential Exposure Assess ment Standard Operating Procedures Addenda 1: Consideration of Spray Drift . This document outlines th e quantification of indirect non-occupational exposure to drift. Residential Bystander Post-Application Inhalation Exposure Volatilization of pe st ic ides may be a so urc e of post-application inhalation exposure to ind i v idual s nearby pe s t icide appl ications. The Agency so ug ht expert adv ice and input on i ss ues related to volatilization of pesticides from its Federal in sec ticid e , Fungicide , and Rodenticide Act Sc ientific Advisory Panel (SAP) in December 2009, and received the SAP ' s final report on March 2, 20 I 0 (h ttp: //www.e pa . gov/scipoly/SAP/meetings/2009/l 20 I 09meeting.html) . The Agency has evaluated the SAP report and ha s developed a Volatilization Sc ree nin g Tool and a subsequent Volatilization Screening Anal ysis (http: //www. regulations.gov/# !docketDetail ; D = EPA- H Q-0PP-2014-0219). Durin g Regi st ration Re v iew , the Agenc y will u se this anal ysis to de t erm ine if data ( i.e. , flux st udie s , route - specifi c inhala tion to xico lo gical studi es) or further analysis i s required for fluen s ulfone.

1 Available: http: / / www.epa.gov/ oppOOOO l /factsheets / s praydrift.htm.

Page 14of20Fluensulfone Aggregate Human Health Ri sk Assessment D427229 

### Aggregate Risk In accord a nce with the FQPA, HED mu st consider and aggregate (add) pestic ide ex posures and risks from three major sources: food , drinking water , and residential exposures. In an aggregate assessment, exposures fro m relevant so urces are added together and co mp a re d to quantitati ve estimates of h azard (e.g. , a NOAEL or PAD) , or the risks themselves can be aggregated. When aggregating exposures and risks from various sources , HED considers both th e route and duration of exposu re . As previously no ted, there are no resid e ntial u ses for fluen s ulfone at thi s time; therefore , dietary (food and water) exposure is the only pathway appropriate for assessment. Aggr egate risk estimates are equivalent to the di etary risk estimate s discussed a bo ve and are not of co ncern. 

### C um ul ative R isk Un li ke other pest icides for which EPA has followed a cumulative ri sk approac h based on a com mon mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to fluensu lfone and any other substances and fluensulfone does not appear to produce a toxic metabolite produced by othe r s ub stances. For the purp oses of this tole rance action, therefore, EPA has not assumed that flu ens ulfon e has a common mechanism of toxicity wi th other substances. For information regarding EPA ' s efforts to determine which c h emicals have a common m ec hani s m of toxicity a nd to evaluate the cumulative effects of s uc h chemicals, see the policy state ments released by EPA ' s Office of Pesticide Programs concerning commo n mechanism determinations and procedures for c umulating effects from substances found to have a commo n mechanism on EPA's webs ite at http: //www.epa.gov/pesticides / cumulative/ . 

### Attachments 1. Summary of OECD MRL([olerance Calculation Procedures 2. Input s to the Acute Di etary Assessme nt 3. Input s to the Chronic Dietary Assessment 4. Summary of th e Acute Dietary Assessment Resul ts 5. Summary of the C hronic Dietary Assessment Results

Page 15 of20F luensulfone Aggregate Human Health Risk Assessment Attachment 

### 1. Summary of OECD 

### MRLff olerance Calcu lation Procedures BSA as Fluensulfone Carrot

USA Preplant 2.5 lb ai/A Total number of data (n) Percentage of censored data Number of non-censored data Lowest residue Highest residue Median residue Mean Standard deviation (SD) Correction factor for censoring (CF) Proposed MRL estimate

- Highest residue

- Mean + 4 SD

- CF x 3 Mean Unrounded MRL Rounded MRL

Residues (mg/kg) n < 0 . 01 1 0 . 059 1 0 . 091 1 0 . 130 1 0 . 184 1 0 . 217 1 0 . 276 1 0 . 336 1 0 . 371 1 0 . 45 7 1 0 . 708 1

1. 20 1

Page 16 of20 12 8 % 11 0 . 010 1 . 204 0 . 247 0 . 337 0 . 335 0 . 944

1 . 204 1. 676 0 . 955 1. 676 2 0427229

### Fluensu lfone Aggregate Human Health Ri sk Assessment Attac hm ent 2. Input s to the Acute Dietary Assessment Filename : Acute Fluen**PRZM-G~I** Sl8 separate . rOB Chemical : Fluensulfone Systemic RfD(Chronic) : . 03 mg/kg bw/day NOEL(Chronic) : 0 mg/kg b w /day RfD(Acute) : . 18 mg/kg bw/day NOEL(Acute) : 0 mg/kg bw/day Date created/last modified : 05

- 29-2015/21 : 49 : 49 Program ver . 3 . 16 , 03-0B-d Crop EPA Code Grp Commodity Name Def Res (ppm) 010107B000 lAB 010107B001 lAB 0101079000 lAB OB01374000 BA OB01375000 SA OS01375001 SA OS01376000 SA OS01376001 SA OS01377000 SA OB01377001 SA OS0137SOOO SA 080137S001 SA OB01379000 SA OB013SOOOO BA OS02 1 4SOOO SBC 0B02234000 BBC OB02270000 SB OB02270001 BB 0802271000 8B OB02271001 SB 0802272000 BBC OS02272001 SBC OB02273000 BBC 0901075000 9A 0901187000 9A 0901399000 9A 0901400000 9A 0902021000 9B 09020SSOOO 9B 0902102000 9B 0902135000 9B 090230SOOO 9B 0902309000 9B 0902356000 9B 0902356001 9B 0902357000 9B 0902357001 96 S601000000 B6A S602000000 S6B Carrot Carrot-baby food Carrot , juice Tomatillo Tomato Tomato-baby food Tomato , paste Tomato , paste-babyfood Tomato , puree Tomato , puree - babyfood Tomato , dried Tomato , dried-babyfood Tomato , juice Tomato , Tree E

g gp l ant Okra Pepper , bell Pepper , bell

- babyfo o d Pepp er , be ll , dried Pepper , bell , dried-babyfood Pepper , nonbell Pepper , nonbell

- babyfood Pepper , nonbell , dried Cantaloupe Honeyde w melon Watermelon Watermelon , juice Balsam pear Chayote , fruit Chinese waxgourd cucumber Pumpkin Pumpkin , seed Squash , summer Squash , summe r- baby f ood Squash , winter Squash , winter-babyfood Water , direct , all sources Water , indirect , all sources 0 . 500000 0 . 500000 0 . 500000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 0 1 0000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 077600 0 . 077600

Page 17o f20 Ad j . Factors commen t 81 #2 1. 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1.000 1. 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1. 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1. 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1.000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 D4272 29Fluensulfo ne Aggregate Human Hea lth Ri sk Assessment Attachm e n t 3. Inp uts to the Ch ro ni c Di etary Assess m e nt Filename : Chronic Fluen PRZM-GW SlB separate . r oe Chemical : Fluensulfone Systemic RfD(ChronicJ: . 03 mg/kg bw/day NOEL(ChronicJ : 0 mg/kg bw/day R

fD( Acu te) : . lS mg/kg bw/ day NOEL(Acute) : 0 mg/kg bw/day Date created/last modified : 05-29

- 2015/21 : 50 : 21 Program ver. 3 . 16, 03-0S-d Cr op EPA Code Grp Commodity Name Def Res (ppm) 010107SOOO lAB 010107S001 lAB 0101079000 lAB 080137 4 000 SA OS01375000 SA OS01375001 SA OS01376000 SA OS01376001 BA OS01377000 SA OS01377001 SA OS0137SOOO SA OS0137S001 SA OS01379000 BA OS013SOOOO SA OS0214SOOO SBC OS0223 4 000 SBC OS02270000 SB OS02270001 SB 0802271000 SB OS02271001 SB 0802272000 SBC OS02272001 BBC OS02273000 BBC 0901075000 9A 09011S7000 9A 0901399000 9A 0901400000 9A 0902021000 9B 09020SSOOO 9B 0902102000 9B 0902135000 9B 090230S000 9B 0902309000 9B 0902356000 9B 0902356001 9B 0902357000 9B 0902357001 9B 8601000000 S6A S602000000 S6B Carrot Carrot

- baby food Carrot , juice Tomatillo Tomato Tomato-baby food Tomato , paste Tomato, paste - babyfood Tomato , puree Tomato , puree-babyfood Tomato , dried Tomato , dried-babyfood Tomato , juice Tomato , Tree Eggplant Okra Pepper , bell Pepper , bell

- babyfood Pepper , bell , dried Pepper, bell , dried-babyfood Pepper , nonbell Pep per , no nbe ll-babyfood Pepper , nonbell , dried Cantaloupe Honeydew melon Wa termelon Watermelon, juice Bal sam pear Chayote, fruit Chinese waxgourd Cucumber Pumpkin Pumpkin , seed Squash , summer Squash, summer-babyfood Squash, winter Squash , w inter-babyfood W

ater , direct , al l sources Water, indirect , all sources 0 . 500000 0 . 500000 0 . 500000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 010000 0 . 052500 0 . 052500

Page 18 of20 Adj . Factors Comment #1 #2 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1.000 1 . 000 1 . 000 1.000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1.000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1. 000 1 . 000 1 . 000 1. 000 1 . 000 1.000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1.000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1.000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1.000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 1 . 000 

### 0427229Fluen s ulfon e Aggregate Human Health Ri s k Assess ment D427229 Attachme nt 4. S ummary of the Ac ut e Dietary As sess ment R es ult s OPP Health Effects Division Ver . 3 . 16, 03-08-d DEEM -FCID AC UTE Ana lysis for FLUENSULFONE SYSTEMIC NHANES 2003

- 2008 2

- 0ay Residue file : Acute Fluen PRZ M- G W Sl8 separate . roe Adjustment factor #2 NOT used . Analysis Date : 05

- 29-2015/21 : 52 : 50 Residue file dated : 05

- 29-2015/21 : 49 : 49 RAC/FF inta ke summed over 24 hours Run Corrune n t : "" Surrunary calculations--per ca pita : 95th Percentile 99th Percentile 99 . 9th Per cent ile Exposure % aRf D Ex p osure % aRfD E xposure % a RfD



## ---------- ------- - 

## -- --- ---- - - --- --- - 

## - - -- ------ -------- Total us Population : 0 . 004466 2 . 48 0 . 007375 4 . 10 0 . 013782 7 . 66 All Infants : 0 . 013766 7 . 65 0 . 019161 10 . 65 0 . 026334 14 . 63 Children 1

- 2 : 0 . 007188 3 . 99 0 . 011105 6 . 17 0 . 024770 13 . 76 Chi ldren 3

- 5 : 0 . 005774 3 . 21 0 . 008336 4 . 63 0 . 013205 7 . 34 Chi ldr en 6

- 12 : 0 . 004210 2 . 34 0 . 007023 3 . 90 0 . 010497 5 . 83 Youth 13-19 : 0 . 003600 2 . 00 0 . 005865 3 . 26 0 . 008811 4 . 89 Adults 20

- 49 : 0 . 004267 2 . 37 0 . 006300 3 . 50 0 . 009049 5 . 03 Adults 50

- 99 : 0 . 003862 2 . 15 0 . 005791 3 . 22 0 . 0088 4 5 4 . 91 Female 13-49 : 0 . 004329 2 . 41 0 . 006373 3 . 54 0 . 008770 4 . 87

Pag e 19 of2 0Fluensulfone Aggregate Human Health Risk Assessment Attachment 5. S ummary of the C hronic Di etary Assessment Results OPP Health Effects Division DEEM -FC ID Chronic analysis for FLUENSULFONE SYSTEMIC Residue file name : Chronic Fluen PRZM-GW Sl8 separate . roe Ver . 3 . 16 , 03-08

- d NHANES 2003-2008 2-day Adjustment factor #2 NOT used . Analysis Date 05

- 29-2015/21 : 51 : 32 Residue file da ted : 05-29-2015/21 : 50 : 21 Reference dose (RfD , Chronic) = . 03 mg/kg bw/day Total exposure by population subgroup Total Exposure Population

Subgroup Total US Population Hispanic Non-Hisp-White Non-Hisp-B lack Non-Hisp-Other Nursing Infants Non-Nursing Infants Female 13+ PREG Children 1 -6 Children 7-12 Male 13-19 Female 13-19/NP M

ale 20+ Female 20+/NP Seniors 55+ All Infants Female 13-50 Children 1-2 Children 3-5 Children 6

- 12 Youth 13-19 Adults 20-49 Adults 50-99 Female 13-49 mg/ kg body wt/day 0 . 001195 0 . 001155 0 . 001227 0 . 000970 0 . 001411 0 . 001452 0 . 004293 0 . 001097 0 . 001658 0 . 001027 0 . 000812 0 . 000901 0 . 001090 0 . 001233 0 . 001143 0 . 003416 0 . 001164 0 . 001921 0 . 001549 0 . 001084 0 . 000857 0 . 001166 0 . 001161 0 . 001163

Page 20 of20 Percent of Rfd4 . 0% 3.8% 4 . 1% 3 . 2% 4.7% 4 . 8 % 14 . 3% 3 . 7% 5 . 5 % 3 . 4% 2 . 7% 3 . 0 % 3 . 6 % 4 . 1% 3 . 8 % 11. 4 % 3 . 9 % 6 . 4% 5 . 2 % 3 . 6 % 2 . 9 % 3 . 9 % 3 . 9% 3.9 % 0427229