HALOSULFURON-MET H YL Human H ealth Ri s k Assess m ent DP No
. 0428013 

### UNITED STATES ENVIRONMENTAL PR OT ECTION AGENCY WASHINGTON , D

. C. 20460



### MEMORAND U M DA T E: September 15 , 2015 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: Halosulfuron-Meth y l. Human H ea lth Draft Risk Assessment for Re gistra ti o n Review. 

### PC Co de: 1 28721 

### Deci s i o n No. : 506514 

### Petition No.: NA 

### Risk Assessment Type: Single Chemical / Aggregate 

### TXRNo
. : NA 

### MRID 

### No.: NA 

### DP Barcode: D4 28013 

### Registration Nos.: Numerous 

### Regul a tory Actio n: R egistration Review 

### Case No.: 7233

- 1 

### CAS No.: I 00784-20-1 

### 40 CFR: 1 80.479 F ROM: Nancy 

### J. Keller , _Ri sk Assessor, Chemist

## ~ Meheret Neguss 1 e, Chemist 

### /(e/-ie.Y'd J:kjC>rftfc:e. Whang Phang , Toxicologist 1**~** Risk Assessment Branch 3 ' l5 Health Effects Di vis ion (7509 P) THROUGH: Christine Olinger, Chief

## ( /
. _/

## ~ Risk Assessment Branch 3 ./-- / ' H ea lth Effects Division (7509 

### TO: Brittany Pruitt , C hemical R ev iew Manager Kelly Sherman , Branch Chief Risk Management and Implementation Branch 3 Pesticide Re-Evaluation Division (7508P) The Pesticide Re

- Evaluation Division (PRO) has requested a Draft Risk Assessment (DRA) from the H eal th Effects Di vis ion (HED) to provide information that supports th e registration review of halosulfuron-methyl. This assessment addresses the expos ures and r i sk estimates associated with all currentl y registered uses . Since the last risk assessment , there have been no changes to the ha losulfuron-methyl use profile , hazard profile , or residue profile (DP42 l 819, K. Rury , 06 1 10/2015). Nor have there been any policy changes that wou ld warrant an update to dietary, res ident ia l , aggregate, o r occupational risk estimates. However, a new assessment for ind i rect non - occupational spray drift has b een conducted for reg i stration review. Furthermore , there are no outstanding data deficienci es or conditi ons of reg istration for h a losu lfuron -m ethy l at t hi s time.
P age I of22HALOSULFURON-METHYL Human H eal t h Risk Assessment DP No. D428013


### Table of Contents 1.0 E xecutive Summary
... ...... .... .. .... . .. ... .... .. ... .. ... ... ... . .. ..... . ........ .. ...... . .. .. ... . .. .. ..... .. . .. ..... .. . . ... . . 2 2
. 0 Us e ProfLle
.. . ........... . . . ........ ... ........ . .... .. ......... .. ..................................................................... 2 3.0 Hazard Identificationffoxicology
...... . .......................... . .......... . .................. . ......... . ..... . .. . .. 3 3.1 S ummary of Toxicological E ffect s .................... . ........ . ....... .. ....... . ... . ... . .. . ... . .. . .. . ..... .. ..... 3 3.2 Safety Factor for Infants and Children (FQPA Safety Factor)
.. . . ... .. . .. ..... . ... . .. . . .. .. . .. 4 3.3 Toxicity E ndpoint and Point of Departure Selection s ..... .. ... . .. .. ...... . .. .. ..... . .. . ... . .. . ...... 4 4.0 Residue Chemistry
... . . ..... .. ........ .. ....... . ......... . ... . .... . ... . ..... . ....... . ... . .... . . .. ...... .. ........ .. ..... .. . .. .. 7 4.1 Tolerance C on s idera tion s ..... . .... . ... ... .... . ... ... ... .. ........ .. ....... . ....... . ....... . .. . ........................ 7 4.2 International Harmonization
. .. ... .. . ...... ... ........ . ...................................................... . .. . ... 8 5
. 0 Dietary Ri s k A ss ess m e nt
. .. .. ... ... ........ .. ......... . .... .. ........ .. ....... .. ...... . ... . ....... .. ..... . ...... . .. . ....... 9 6.0 Residential (Non-Occupational) Expo s ure/Ri s k Characteriz a tion
...... .. .. . ...... . ..... .. . .. . 10 

### 6.1 Spray Drift
.......................................................... . ................. .. ....... . ...... .. .. . .. . .. .. .. . .. . ... . .. 10 

### 6.2 Residential Bystander Post-Application Inhalation E xposure .. .. . .. ... . . ... . . .. ...... . . . .... 11 

### 7.0 Ag gre g ate E xpo s ure/Ri s k Characterization
...... . ......... . ........ . ....... . ................................ 1 1 8.0 Cumulative Expo s ure/ Ri s k Characterization
.................................. . ..... . ....... .. . . ...... . .. . . 1 2 

### 9
. 0 Occupation a l Exposure/Risk Characterization
.......... . ........................... . ..................... 13 

### 10.0 Reference s . ..... ... . .. ... .. . ... ... ... . .. ... ... ... .. .. .... .. .... .. ... .. ... ... .. .. ... .. .. .. .. ... . ... .. . .. .. ..... .. .. . ... ..... . .. . .... 13 

### Appendix A. Toxicolo gy Profil e for H a losulfuron-Meth y l
............................................ .. . . .. 15 

### Appendix B. International Residue Limit Status
..... . ......... . ................... . .......... . ...... . ..... .. . . .. 19
1.0 E xecutive Summary H alosu l furon-methyl is a su lfony l urea herbicide currentl y registered for pre- and post
- emergence co n tro l of ann u a l broad leaf wee d s a nd nu t se d ges o n vari o u s agri c ultura l cro p s, as we ll as residentia l turfgrass and ornamentals. It inh i bits aceto lactate syn th ase (A L S) , an enzyme found in p lants and mi c r o-o r gani s m s th at cata l yzes t h e fi r st ste p in the sy nt h es i s of t he b ranched

- chain amino acids such as valine , leucine , and iso leuc i ne. ALS i s also found in mammal s, but i ts fu nctio n a nd m o de o f act ion a r e unkn o wn . S in ce th e las t risk assessme nt , th ere h ave b ee n no c h a n ges to the h a los ul furo n -me thyl u se profile , hazard profile , o r residue profile (DP4218 l 9 , K. Rury. 06/ 10/ 2015). Furthe r more, there have b ee n no p o li cy c h anges th at wo uld warrant an upd ate t o di etary, resi de ntia l , aggrega te, o r occupational risk estimates. However , a new assess m ent for ind irect non - occupatio n a l spray d

rift h as b ee n condu cted fo r regis tra ti o n review
. T here are n o o u ts t and in g dat a d efic ie nc ies o r conditi ons of reg i stration for ha losulfuron-methyl at this time. T he re are no risk estimates of co nce rn i n d ietary, res id e n t i a l , occ u pat io n al , or agg regate assessmen t s . 

### 2.0 Use Profile C urrently , th e ac ti ve i n g red i e nt (ai), h al os ulfuro n - methy l i s o nly fo rmul a te d as a wate rdi s pe r sible granu le (WG). T hi s formulation is to be added to water , resulti n g 

### in a d i spersion of finely di v id e d he rb ic id e pa rticl es s u spe nd ed in wate r to be appli ed fo r wee d co ntro l. Cu rre n tl y regis tered labe l s inc l ude one technica l label , three agric u ltural labe l s , three state labe l s , and one
Page 2 of 22

### HALOSULFURON-METHYL Human H ealth Risk Assessme nt DP No. D428013 experimental use permit label. In addition to several agricultural food uses , halosulfuro n -methyl is also r eg i ste re d fo r use o n turf grass , orname ntals , and a variety of non-crop areas including , but not limi t ed to, airports, cemeteries , fallow non - crop areas , go l f courses, landscaped areas, p ub lic recrea ti on areas , residentia l property , roads ides, school grounds, sod or turf seed farms , sports fields, residential and commercial landscaped areas with established woody ornamentals, fa irgrounds , race tra cks, tennis courts , campgro u nds, and rights-of-way. In 

### genera l , halosu l furon-methyl may be applied up to twice a year. Application t iming varies depending on the target weed (pre

-/ post
- erne rge nt t o weeds or pre-/ pos t-e merge nt to crop plantings). The applicat io n rates range up to 0.10 l b ail A for a ll registered uses. D ependi n g on the use site , halosulfuron-methy l may be app l ied via ground , aeria l , che mi gat io n , o r h and held equipment. 

### 3 .0 H azard Id e ntification/Toxic o l o gy The toxicology database for halosu lfuro n -met hyl is complete and adequate for risk assess ment. At this time, the requ i rements for the s u bc hro n ic inh alat ion tox icity and immun otoxic i ty stud i es are wai ved (TXR 0054045, D

. 

### Smega l, 02 /22 /2012; TXR 0056723 , K. 

### Rury , 08 / 06/20 1 3). New toxicity and/or metabo li sm data have not bee n received si nce th e las t ris k assess me nt, and the selected toxicity endpoints and points of departure (PO 

### Os) remain the same. A summary of the acute , subchronic, and chro n ic tox icity profi l e is prese nted i n Appe ndi x A. 

### 3.1 Summary of Toxicologica l Effects With repeated dosing , the ava i lab le data did not de mo n strate a target or gan or ti ss ue in any of th e test animals. Reduction in body weig ht was seen in the 90

- day and I

- year oral toxicity studies in dogs. Red uced body weights were also see n in rat stud ies at highe r dose leve ls th an th ose seen in dogs. An 

### effect on the hematological parameters was de t ected in the dog studies , but the magnitude of changes was s li gh t an d the effect was co n si d e red to be ma rg in al. T hus , th e s li g ht hematological changes were not considered to be adverse. In the prenatal developme n tal toxicity study in rats , increases in resorptions, soft tissue (di lation of the latera l ventric les) and ske l eta l vari at io ns, and dec reases in bo d y weight s we re seen in the fetuses compared to cl inica l signs and decreases in body weig hts and food co n sumpt ion in the mate rn al anima ls at 

### a s imil ar dose leve l. 

### In th e rabbi t d eve lop mental toxic i ty study , inc reases i n resorptions and post-implantation losses and decreases in mean litter size we re observed i n the presence of dec reases in body we ig ht and food co n s ump ti on in m ate rn al an im a l s. T h e feta l effects seen in devel opmental tox ic i ty studies 

### in rats and rabbits represen ted a qual itative increase in s u sceptib ili ty
. However, a c l ear no observed adve rse effect l evel (N O AEL) for t h ese effects was estab l ished 

### in both rat and rabbit deve lopmental toxicity studies. Halosulfuron

methyl did not prod uce any effects o n rep rod ucti ve pa ramete rs 

### in the two-generati on rep roduction study in rats. Therefore, no quantitative susceptibility was found in studies following pre - and/or post- natal expos ures . No neuro tox ic effects we re obse rved in th e acute or subchronic neurotoxic ity studies up to 2000 mg/kg or 760 m g/ kg/day, respectively. In add i tion , Page 

### 3 of 22HALOSULFU R ON

- METHYL Hum an H ea lth Ri s k Assess m en t D P No. 04280 1 3

n o a d ve r se effect was fo u nd i n a 2 1 -day de rma l toxicity study at doses up to the limit dose (1000 mg/kg/ day). H a los ul fu r on -m et h y l is negative for mutage ni c ity in a battery of ge n otox ic i ty studies. I t is classifie d as " not li ke ly to be carcinogen ic to humans " based on lack of evidence fo r carc inogenicity in mice and rats fo ll owi n g l o n g - term dietary administration. H a losu lfuron

- methyl has low acute toxicity (Toxicity Category III- I V) by oral, de rmal , and inha lat ion routes of exposure. It is not a dennal sensitizer, but it pro d uced tran s i en t eye irritation w hich was c leared w it h in 24 h ou r s . 

### 3
. 2 S a fety Factor for Infant s and C hildren (F QPA S afety Factor) The F QPA Safety Factor has been reduced to 

### IX for the following rea sons: 

### (1) The toxicity databas e of halosu l furon-methy l is comple te and adequate to assess the q u a li tative o r q u ant it at ive s u sce p t i b il i t y i n the you n g; (2) There was no quantitative evidence of inc reased susceptibility following pre- and/or post-natal exposure. However, the qua li tative suscept i b ili ty observed in the deve lopme n tal toxic i ty studies in rats and rab b its was of low co n cern because (a) in both stud ies , the re were clear NOAELs / lowest observed adverse effect leve l s (LOAELs) for deve lop m ental and materna l toxicities; (b) th e deve lopm e nta l effec t s we r e seen in th e pr ese n ce of m aterna l tox icity; and (c) the effects were only see n at the h i gh dose levels
. I n rats, the developmental effects we re seen at a dose (750 m g/kg/day) which was approaching the l imit

- dose (1000 mg/kg/ day). Furthe rm ore , the P ODs for risk assessme nt are pro tect ive of the effects which occur at high doses ; (3) Halosulf ur on - methy l produced n o evidence of neurotoxicity; and (4) There are no res idua l uncerta i nties 

### in the exposure database , and expos u re estim ates are unli kely to u n d e rest imate r isk. 

### 3. 3 Toxicity Endpoint and Point of Dep a rture S el ec tion s The r e have been n o c h anges to the prior dose -response assessment and cancer classification (DP42 

### l 8 l 9, K. Rury , 06/ 10/2015). It should be noted that the stud ies in the h a losu lfuron

- methy l database , inc l uding those use d for endpo int se lection , h ave not been u pdated to reflect current po li cy and m ay be co n s ide red conservative since these updates would resu l t 

### in h ig her NOAEL/LOAEL values than those currently estab li shed. The curre n tly se lected P O D s are pro t ective of the effects observed in the h alos ul furo n - m ethy l database a n d any up da tes wou l d not imp ac t th e overall fi n di n gs of the ri sk assessment given the current risk picture for halosu l furonmethy l. Furthermore, the r i sk estimates calcu lated w i th these P ODs do not present
. any risk estimates of co n ce rn at this ti me.

Page 4 

### of 22

### HALOSULFURON-MET HYL Human Health Ri sk Assessme n t 

### DP No. D4280 I 3
Table 3.3. S u mmary of Toxicological Do ses and E ndpoint s for Halos u lfuron-Methy l for Use in Dietary, No n-Occup atio nal a nd Occ u pational Human Health Risk Assessments RID , Level Exposure/ Point of Uncertainty / of Concern Study and Toxicologica l Effects Scenario Departure Safety Factors for R isk Assessment Acute Acute RID = Developme n ta l Toxicity

- Rabbit UFA = JOX 0.5 Dietary NOAEL = UFH = !OX mg/k g/ day LOA EL = I 50 mg/kg/day based on increased ( Females I 3- 50 number of resorptions (total and per dam and 49 years of mg/k g/day FQPA SF = increa se d post- im plantation loss (developmental IX aPAD = 0.5 age) mg/ka /day toxicity). Acute Dietary No adverse effect attributable to a single dose was identified ; therefore , no dose/endpoint was (General selected for this exposu re scenario
. Population) UFA = IOX Chronic Rfl) Chronic NOAEL = UF11 = IOX = 0. 1 C h ronic Toxicit y - Dog Dietary (All 10 FQPA SF= mg/kg/day LOA EL = 40 mg/kg/day based on decreased Populations) mg/k g/day cPAD = 0.1 body weight in females. IX m !lfkg/ dav Incidental NOAEL = UFA = JOX Residential D eve lopm enta l To x i cit y - Rabbit Oral Short

- 50 UFH = !OX LOC for LOA EL = 150 mg/k g/day based on decrease d Tenn (J-30 mg/k g/day FQPA SF = MOE = JOO food consump tion and food efficiency (maternal davs) IX toxicitv). Dermal Short-Term A 21-day dem1al toxicity te s ted up to the limit dose (I 000 mg/k g/day) demonstrated no adverse ( 1-30 days) Interm edia te- effects and th ere was no evidence of quantitative s usce ptibility in the halos ulfuron -methyl Tenn (J-6 database. No dennal toxicity endpo int could be established. month sf UF A = IOX R esidential De ve lopm e ntal Toxicity

- Rabbit Inhalation NOAE L = a nd Sho rt-Term 50 UFH = !OX Occupational LOA E L = 150 m g/kg/day based on decreased (1 -30 days) mg/k g/day FQPA SF = LOC for food conswnption and food efficiency (maternal IX MOE = 100 toxic ity). Inh alat ion UFA = !OX R es id ential 13 Week S ub ch r on i c T ox icity

- Dog Intenn ediate- NOA EL= UF11 = IOX and LOAEL = 40 mg/kg/day based on decreased Tenn (1-6 IO FQPA SF = Occupational body weight ga in s and food e fficiency along month s) mg/kg/day IX LO C for with hematological and clinical chemistry MOE = 100 changes. Canc er (ora l, Classification: "not li ke ly to be carcinogenic to humans" by the oral route , based on no evidence dennal , inhalation) of carcinogenicity from studies in rat s and mice. Toxicity via th e inhalation rout e is pre sume d to be equivalent to oral tox icity. Point of Departure ( POD ) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning of ex trapolation to determine risk associa t ed with lower env ironmentall y relevant human exposures . NOA EL = no observed adverse effect level. LOAEL = lowe st observed adverse effect leve l. UF = uncertainty factor. UF , , = ex trapolation from animal to human (interspecies). UFH = potential variation in sensi ti vity among members of the human popu lation (intraspecies). FQPA SF = FQPA Safety Factor. P AD = population adj usted do se (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

### Page 5 of 22

### HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013



### 3 .4 E n doc ri ne D is ru ption As required by FIFRA and FFDCA , E P A reviews numero u s s tudi es to assess po te nti al adverse outcomes from exp osure to chemicals. Collective ly, these studies include acute , subchronic and chronic toxicity , including assessme nt s of carc inoge nici ty , neurotoxicity , developmental , reproductive , and gene r a l or system ic toxicity. These studies include endpoints which may be s usceptible to e ndocrine influence , including effects on endocrine target organ histopathology , organ weig ht s, es tru s cyc li c ity, sex u al maturation , fert ili ty, pre g nanc y rates, rep roducti ve loss , and sex ratios in offspring. For ecological hazard assessments , E P A eva lu ates acute tests and c hroni c stud ie s that assess growt h , developmental and reproducti ve effec ts in differ e nt taxonomic gro up s. As part of its mo st rec ent registration decision for halos ul furon-methyl , E P A reviewed these data and selec ted the mo st sens iti ve endpo ints fo r relevant ri sk assessment sce nar ios from the exis tin g hazard database. However , as required by FFDCA sect ion 408(p), halosulfuron-methyl is subject to the endocrine screening part of t h e E nd ocrin e Di s rup to r Sc r eenin g Program (E DSP). E P A has developed t he EDS P to determine wh ether certa in substa n ces ( including pesticide active and othe r ingredie nt s) may have an effect in human s or wild li fe s imilar to an effec t produced by a " naturally occ urring es tro ge n , o r ot he r suc h en d ocrin e effec t s as t he Admin i st rator may designate. " The E D SP employs a two-tiered approach to making the statuto ril y required determinat ions. T i er 1 consists of a battery of 1 1 sc reen in g as says to identify the potential of a chemical s ubstance to interact with the estrogen , androgen , or thyroid (E , A , or T) hormonal syste m s . Chemicals that go through Tier 1 sc reeni ng and are found to have the potential to interact with E , A, or T h o rm onal systems will proc eed to the next s tage of the EDSP where EPA will determine which , if any, of the Tier 2 test s are neces sary based on th e avai l able data. Tier 2 testin g is designe d to identify any adverse endocr in e-re lated effects ca u se d by the substance, and establish a dose-response relati onsh ip between the d ose and the E, A. or T effect. Un der FFDCA section 408(p), the Agency mu st screen all pe sticide chemicals. B etween Oc t ober 2009 and February 20 1 0 , E P A i ssued test o rd e rs/ data cal l-i ns for the first g roup of 67 c hemicals, which co ntains 58 pesticide active ingred ients and 9 inert ingredients. A second li st of chemicals id e ntifi ed fo r E DSP screen in g was published on June 14 , 2013 1 

### and includes some pesticides sch edu led for Registration Re view and chemicals found in water. Neither of these lists sho uld be construed as a li st of known or li ke ly e ndocrine disruptor s . For further informati o n on the status of the EDSP, the policies and procedures , the lists of chem icals , futu r e li sts, th e test gu id e line s an d th e Tier 1 sc reen in g battery , please vis it our webs ite. 2

1 See http: //www.rcgulations.gov/ # !docu m cnt De t a il:D = EPA-HO-OPPT- 2009

- 0477

-0074 for the final second li s t of chemicals. 2 hnp: //www.epa.gov / endo/ 

### Page 6 of 22

### HALOSULFURON-METHYL Hum an Health Ri sk Assessment DP No. D428013


### 4.0 Re si due C hemi stry The nature of the residue in plant s h as been adeq uat ely delineated based on acce pt ab le metabolism s tudi es with com, s u garcane , and s oybean t reate d both pre- and postemergence. HED h as concl ud ed that th e re s idue of co nc e rn for enfo rc e ment and ri sk assessment in p lants (for the c urrent use patte rn ) i s parent h a lo s ulfuron-meth y l only. The need for addit i o n a l plant me tab o li s m studi es to s uppo rt future u ses wi ll be d ec ided o n a case-by -cas e basis. The nature of the res idu e in li ves to ck h as b ee n adequatel y d e lin eat ed ba se d o n metabo li s m studies wi th goats and hens
. The residue of concern for enforce ment i n ruminants is parent h alosu lfuron-meth y l onl y; ho weve r , becau se the approved e nforc eme nt meth o d for live s t oc k commod itie s quantifies the parent compound and metabolites co ntainin g the 3

- chlorosu l fonamide moi ety (3-CSA) by converting res idu es to 3-CS A , tolerances for residues in li ves to ck commod i ties are exp resse d in term s of h a los ul furon

- methy l and it s m etaboli t es determined as 3

- CSA, expressed as halosulfuron-m ethyl e qui va le nts. HE D previou s l y conc lud ed that there i s no reasonable expec tation of res idue s in poultry commod iti es ( l 80.6(a)(3))) and therefore tolerances for h alos ulfuron-m ethy l res id ues in p ou ltry co mm od iti es are not required. This decisio n is b ased o n the low use rates , low r esid ues of halo s ulfuron-methyl in po ult ry feedstuffs , and the low transfer rate of residues to poultry tissues fo r the current uses. Adequate analytical methods (GC/N PD ) ar e avai lable for the e n fo rc e me nt of tolerances for residues ofhalosulfuron-methy l in plant s (Me thod RES-109-97-4) , and for re s idu es of halosulfuron-methy l and it s 3-CSA metabo lite s in li vestock commodit ies (Metho d RES

- 046

- 93). The plant m ethod dete rn1in es h a losu l furon -m e th y l as it s re arran ge men t ester (RRE) , and the li vestoc k me thod converts residues of h alo s ulfuron-m e th y l and metabolites containing the 3

- CSA moiety to 3

- CSA for determination. B EA D/ AC B conducted successfu l p eti t ion method va lid at io n s ( PMV s) for b o th m e thod s ( 0250584 ; G.J. Herndon ; 28 October 1 998). Residues of halosulfuron-methyl and 3 -C SA are not adequa t e ly recove red by FD A Multires idu e Method protoco l s. The analytica l refe r e nce s tandard s for parent h alo s ulfuro n - me th y l with ex piration d ate of (5 / 31/20 1 7) and for met abo l ite 3

- CSA w ith ex piratio n date of (6/ 2 1/ 20 1 7) are c urre ntl y ava il able in EPA ' s Nat ional P es ti cide Standards Rep os itory (N P S R) , p er email co mmunication from Grego ry Verdin of the Bi o log i ca l and Econo mic Ana lysis Division's Ana lytical Chemist ry Branch ( B EA D/ ACB) on Ma y l l , 2 01 5. Adequate confined and limited field rotationa l crop data are ava il ab le. HED previously concluded that rotational crop tolerance s and res tric tions a r e not requir e d fo r h a losu lfuronm ethyl. 

### 4.1 Tolerance Cons id era tion s P e rman e nt tolerances are es tabli she d for re sidues of halosulfuron-methyl i n or on a variet y of plant co mm o ditie s , at levels ran g ing from 0.01 ppm in the grain, h ay and straw of proso mill et, to 2 0 ppm in the fo rage of g rass, forage , fodder and hay gro up 1 7(40CFR§180.479[a ][ 2]). Pe rm anent tolerances a r e a l so establ i she d for r es idu es of ha losulfuron- rn ethyl contain in g the 3

- Page 7 of 22

### HALOSULFURON-METHYL Human Health Risk Assessment DP No
. 0428013
chlorosulfonarnide acid (3-CSA) moiety in ruminant milk , fat , meat and meat byproducts , and in hog meat byproducts at 0.05

- 1.0 ppm (40CFR §1 80.479[a][l]). Tole rances are recommended for pome fruit gro u p 1 1 -10 and s mall vine climbing fruit except fuzzy k iwifruit s ubgroup l 3-07F ( Reg ional Re g istration). T he tolerance expression under 40 CFR 

### § 180.479 is correct and reflects measurement and compl iance of ha losu lfuron-methyl res idues. The incorrect entry for succule nt shelled pea and bean subgroup 6 should be removed from 40 CFR § I 80.479[a][2] ; no such subgroup exists. There is a crop grmm 

### 6 ( legume vegetab les), as opposed to a subgroup 6. The correct entry , succulent shelled pea and b ea n subgroup 6B, is li sted immediately beneath the incorrect entry. The existing US tolerance for apple (0 .05 ppm) need s to be removed from 40CFR§180.479(2) since this commodity is included in crop group pome fru its (0.05 ppm). T he existing US to lerance for pistachio (0.05 ppm) needs to be removed from 40 CFR § 180.4 79(2) since thi s commodity is included in crop group tree nut s (0.05 ppm). The ex i stin g US tole rance for okra (0.05 ppm) needs to be removed from 40CFR§180.479(2) s ince this commodity is includ ed in crop group fruiting vegetables (0 .05 ppm). The existing to le ranc es for fruiti ng vegetables and tr ee nuts nee d to be re v ised to establish as vegetab le , fruiti ng , group 8-10 and Nut, tree , group 14

- 12. The proposed tolerance changes are a result of revisions in the crop g roups. Th e revi s ions are presented in Table 2.1.

Ta b l e 4
. 1. T o l e r a nc e M o di fi ca ti o n R eco mm e nd atio n s for H a lo s ulfuro n-M etb y l Established Recommended Commodity To lerance Tole r ance Comme n ts (ppm ) (ppm) Apple 0.05 None Remove covered by Fruit, pome, group 11

- 10 Pea and bean, succulent 0.05 None Remove incorrec t entry s hell ed, subgroup 6 Vegetable, fruiting group 8 0.05 0.05 R ev i se to vegetable , fruiting , g roup 8-10 Okra 0.05 None Remove ; covered by vegetable , fruiting , group 8-10 Nut, !Tee , group 14 0.05 0.05 Establish as Nut , tree, grou p 14-1 2 Pistachio 0.05 None Remove; covered by Nut, tr ee, group 14-12 

### 4.2 Intern ati ona l H a rmonizati o n At this time , there are no Codex maximum residue limi ts (MRLs) estab li shed for residues of halosulfuron-m e thy l. The US tolerances for plants are harmonized with Canadi an MRLs, except asparagus. The tolerance and Canadian MRL for asparagus may be ab l e to be harmonized; the registrant s hould address opportun ities for harmoni zat ion in their re s pon se to this ri s k Page 8 of 22HALOSULFURON-METHYL Hum an H ealth Ri sk Assessme nt DP No. D428013

assessme nt. T he US h as es tabli s he d to lerances on crop group pome fru it s w he rea s Canada has estab li s hed a n MRL o n apple only. The US liv estock tolerances are not harmonized and could not be harmon ize d s inc e the Canad ian MRLs are lower. Li v estock feedstuffs are not harm o ni zed wit h Cana d a becau se Ca n a da does not es tabli s h MRLs on feedstuffs. R e f er to Appe ndi x 

### B. 5.0 Dietary Ri s k Assessment The re s id u e chem i s try d ata and e nvironmental fate data are adequate to assess human expos ure. T h e most recent di e tary expos ure assessme nt s previous l y co ndu c t ed for the re g i s te r e d u ses of halosu l furon-methyl are co n sidered up-to date , conservati ve, and based on re liabl e data that wi ll not und erestimate expo s ure/ ri sk ( DP4 26724 , K. Rur y , 0 5/ 25 / 20 15). There fo re, n ew di e tary expos ure assess m ents are not ne eded for R eg i s trati o n Re view
. The prev iou s assessment s are unrefined and were co ndu cted u s in g DEEM- FCID Ve r s i o n 3
. 16 ; w hich us es 2 003- 20 08 foo d cons umption data from th e U.S. D epartment of Agriculture ' s (US D A 's) National Health and N utrition Examination S u rvey , What We Ea t in America (NHANES / WWEIA). The acute and chron i c assessme nt s assumed tolerance-level residues and 100 % crop treated (C T ) for a ll co mm od ities . Additionally , defa ult process in g fac tors were assumed except fo r w he re tolerances were established fo r pro cesse d co mm od iti es o r wh e n pro cess in g s tudi es s ho we d n o co nce n trat ion. B ased on processing s tudie s, the d efault proces s ing facto r s were reduced to 1 for to ma to paste , tomato puree, p o ta to flour , and potat o g ranul es/ fl akes. The hi ghes t est im ate d d rinkin g wate r concentration ( EDWC ) of 59.2 μ g/L was in corporated into both acut e and chronic ass essm e nt s. This reco mm e nd ed E DW C resulted from the Ti e r I s urface water model for a reg iste red u se o n rice. Acu te There was n o indi cation of an adverse effe ct attributab l e to a s in g le dos e for th e ge ne ral U
. S. po pul at ion. How ever, a n aRfD was establi s he d for fe ma les 13-49 years old , a nd an ac ut e dietar y ex posure assessment was co nducted for that population subgroup. Th e unrefined acute di e tary ex posure estimate at th e 95th percentil e i s < 1% of the acute population adjust e d do se (aPAD) for fe mal es 13-4 9 years old , and i s below HED 's le ve l of concern ( < 100 % o f th e aPAD ). The res ults a re s ununari ze d below in Tabl e 5.0 ( DP42 6724 , K

. Rury , 05 / 25 / 20 1 5). C hronic The unrefined chro ni c di etary (foo d and drinking water) exposure to halosulfuron-meth y l i s below HED 's level of concern (< 100 % of the chronic p o pul at io n adj u s t e d do se (cPAD )) for th e ge nera l U .S
. population a nd all p op ulati on s ub g r o up s. Th e chro nic di e t ary expos ure estimates are 2.1% of th e c P AD for the gene ral U .S. population and 5.7% of the cPAD fo r children 1- 2 years o ld , the mo s t hi ghly ex po sed p opu lati o n s ub g roup . The re s ult s a r e summarized bel ow in Ta ble 5.0 (DP426724 , K. R ury , 05/ 25 / 20 1 5).

P age 

### 9 of 22HALO SULFU RON-METHYL Human H ealth Ri sk Assessme nt DP No
. 0428013

Tab l e 5.0. S u m m ary o f Di etary (Food and D ri n ki n g Wate r ) Ex p os ure and R i s k for Halos u lfu r on-Me t b y l Acute D ietary Ch r onic D ieta r y (95 t h Pe r cen til e) Pop ul ati on S u bg r ou p Di etary Expos u re Dietary Exposu r e ( m g/kg/day) % a P AD (mg/kg/ day) %cPAD General U.S. Population 0.002091 2 .1 All Infants (< I year old) 0 .0 04987 5.0 C hil dre n 1

- 2 years o ld 0.005740 5.7 Children 3-5 years old NI A 0.004025 4.0 NI A C hildr e n 6-12 years o ld 0.002488 2.5 Youth 1 3 -1 9 years old 0 .0 01597 1.6 Adults 20-49 year s o ld 0.001817 1.8 Ad ults 50-99 years old 0.001767 1.8 Fe m ales 1 3-49 yea r s o ld 0
. 004 1 39 < J 0.00181 2 1.8 The subpopu latio n (s) wi th the hi g he st risk estimates. Th e high es t ri sk es tim ate is bolded. 

### 6.0 Res id e n t ia l (No n -Occ up ati o n a l) Ex p os u re/Ri sk C h a r acte r iza ti o n T he re are existin g re s identi al u ses th at have b ee n previously assessed according to HED 's 20 1 2 Res id e ntial SOPs 3 a long with policy changes fo r body weig ht assumptions (DP42 l 8 l 9, K. Rury , 06110 120 1 5)
. Th e mo s t protective wo rs t- case res id e ntial handl er scenario ( mi xer / loader/applicator exposure of a liquid formulat ion via backpack sprayer or manuallypressurized h andwand to turf) res ulte d in a m argi n of exposure (MOE) of230 , 000 w hi c h exceed s the l eve l of concern ( i .e. the L OC i s an MOE < l 00) , a nd i s therefor e not of concern to H E D. The mos t protective worst-case resid e nt ial short-t erm po s t-application in cidenta l o ral scenario ( hand-to

- mouth expos ure from turf treated with a liquid form ul ation) for childr e n resulted in an MOE of24,000 which exceeds the L OC. and i s therefore not of concern to HED. 

### 6
. 1 Sp ray Drift Off

- target movement of pe s ticides can occur v ia many types of pathways and it i s governed by a varie ty of factors. Sprays that are released and do not deposit in the app li cat io n area e nd up off

t arget and can lead to exposures to those it may directly co nt act. They can a lso deposit on s urfac es w he re contact with re si due s can eventually lead to indirect exposures (e.g. children playing on lawn s where residues ha ve d eposi ted next to treated fields). T he potential ri s k est im ates from th ese residues can be calcu lated using drift mode lin g coupled with methods emp l oye d for res id e nt ial ri sk assessments for turf product s . The approac h to be u sed for quantitatively incorporating s pray drift int o ri s k assess ment is based o n a premi se of co mpliant applicat ions which, by definition , s hould not r es ult in direct exposures to indi vidua ls b ecau se of ex i sting l abel language and othe r re gu latory requirement s inte nded to preven t them. 4 Direct exposures would includ e i nh a l ati on of the spray plume or being sprayed

3 Ava i I ab le: http :/ /www.epa.gov/ pest ic ide s / sc icn ce / rc siden t ia I- ex po s ure-sop. htm I**~T hi** **s** approach i s consistent with the requ irements o f th e EPA's Wo r ker Protection Standard w hi c h , w hen in c lud ed o n all labe l s, precludes direct expos ure p at h ways. Page 10 of 22

### HALOSULFURON-METHYL Human Hea lth Ri sk Assessment DP No. D428013
di rectly. Rather, the exposures addressed here are thought to occur indirectly through contact with impacted areas, s uch as re sidential lawn s, when comp li ant applications are con du cted. G iven this premise , exposures for children (I to 2 years old) and adults who have contact with turf where residues are assumed to have deposited via spray dri ft thu s resulting in an indirect exposure are the focus of this ana lysis analogous to how exposures to turf p rod uct s are considered in risk assessment. EPA Reg
. No. 81880-24 i s an existing label for use on turf, thus it was evaluated to detennine whether the risk assessment for that us e ma y be considered protective of any type of exposure that would be associated with spray drift. 

### If the maximum application rate on crops, adjusted by the amount of d rift expected, is less than or eq ual to exist in g turf app li cation rates, the ex i s tin g turf assessment is considered protective of spray drift exposure. For halosulfuron-methyl , the registered residentia l uses on turf result in esti mated exposure levels that are greater than the potential exposure from spray drift; therefore , no new residential assessmen t needs to be comp leted. The currently registered maximum single app li cation rate of ha losulfuron

- methyl for al I 

### registered c rop s is 0.094 l b ail A 

### The hi g hest degree of s pray drift noted for any app lication method immediately adjacent to a treated field (Tier 1 

### output from the aerial applicat ion using fine to medium spray qua li ty) results in a deposition fraction of 0.26 of the application rate. A quantitative spray drift assessment for halosulfuron-methyl is not required becau se the maximum application rate to a crop/ target si te multiplied by the adjustment factor for drift of 0.26 i s l ess than the maximum direct spray residential turf application rate 0.136 lb ai/A 5 

### for any halosulfuron-methy l products. The t urf post-application MOEs have been prev iou s ly assessed and are based on the 2012 Residential SOPs. 6. 2 Re s id en tial B ysta nder Post-Application Inh a l a tion E xpo s ur e 

### Volatilizati on of pesticides may be a source of post-app l ication inha lation exposure to individuals nearby pesticide applications. The agency sought expert advice and input on i ssues r elated to volatili zation of pe s ticide s from its Federa l Insecticide , Fun g icide , and Rode nti cide Act Scientific Advisory Panel (SAP) in December 2009 , and recei ved the SAP's final report on March 2, 20 I 0 (http: //www . epa.gov / scipoly/ SAP / meetings/ 2009/ 120109meeting.htm l). The agency has evaluated the SAP report and has developed a Volatil izat ion Screening Tool and a s ubsequent Volatilization Screening Analysis. 6 

### During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux stud ie s, route
- specific inhalation toxicological studies) or further analysis is required for mesosulfuron-methyl. 

### 7 .0 Agg regate E xpo s ure/Ri s k C h a r acte rization Acute The acute risk estimate for females 13-49 yea rs old, result in g from aggregate exposur e to halosulfuron-methyl in food and drinking wa ter, is below the Agency's LOC and is < l % 

### of the aPAD. There was no indication of an adverse effect attributable to a s ingle dose for the ge neral U.S. population.

5 0.094 lb a i/ A x 0.26 

### = 0.0244 lb ai/ A ::5 0 .1 36 lb ai/A 6 Available at: http: //www.regu lations.gov / # !docketDetail;D = EPA-HQ-OPP-20 14-0 219. 

### Page 11 of 22HALOSULFURON-METHYL Human Health Risk Assessment DP N o. 0428013
Short- and Intermediate T e rm The re is potentia l short- and intermed iate-term exposure to halosulfuron-meth y l via the dietary pathway (which is considered background exposure) and the residential pathway (which is co n s ide red the p rim ary pathway)
. For adults , s ince a dermal hazard was not ide n tified , the exposure pathways includ e only the dietary and inhalation ( re si dential handler) routes
. For child ren , the exposure pathway includes the dietary exposure and the incidental oral postapplication residential pathway. All aggregate MOEs are greater than 

### I 00; therefore , aggregate exposure to halosu lfuron-methy l is not of r i sk conce rn . The most conservative scenario was chosen for each population (e.g. M/L/A via handheld equipment to 

### turf for adults; and hand-to mouth exposure to treated turf for children 1 to < 2 years o ld). The MO Es for ad ult s and chi ldre n 

### 1 to <2 are 25,000 and 6,400, respectively (DP425728 , 

### K. Rury, 05 / 25 / 2015; DP396460 , N. Tsaur, 06/ 1 2/20 12 )
.

T a b le 7
. 0. S h ort-T e r m Aggre gate Ri s k Ca lc ul a tion s NOAEL LOC for Average Food and Residential Total Aggregate Popu lation Aggregate Water Exposureb Expos urec Exposured MOE (food and mg/kg /day Risk' mg/kg/day residential)c Adults f 0.001817 0.000215 0.002032 25,000 Ch ildren 50 100 (I to 2 years old) 0.00574 0.00207 0.007810 6 ,400
a Adults and C hildren Level of Concern= I 00 (based on inter- and intra- s pecie s uncertainty fac t ors, each at I OX). b Adults= 0.00 I 817 (Ad ults 20-49). Ch ildren = 0.00574 mg/k g/ day (Children 1-2 years old). c Resid e ntial MOE based on re s idential handler ex po s ure (for adults) and post-application exposure from

application to re s idential lawn s (for children). d Total Exposure = Average Food and Wat e r Exposure + Re s idential Exposu re e Aggregate MOE 

### = Short Tenn Oral NOAEL (50 mg/k g/day) + Total Exposure
. f Adult s (20-49) was se lec ted from the chronic d ietary expos ure as sess ment as the mo s t protect ive adult

subpopula tion. 

### 8
. 0 C u m ul ativ e E xpo s ure /Ri s k C h a racterizati o n In 2015, EPA 's Office of Pesticide Programs rele as e d a guidance document entitled , 

### P esticide Cumulative Risk Assessmen t: Framework for Screening Analysis [http: //www .epa.gov / oppfead l / cb/csb _page/ updates/ 2015 / framework

- for-screeninganalysis
. html). Th i s document provides guidance on how to screen groups of pesticides for cumulative eval u atio n u s ing a two
- step approach beginning with the evaluation of available toxicological information and if necessary , followed by a risk-based screening approach. Thi s framework supp lements the ex i sting guidance documents 

### for estab li shing common mechanism groups (CM Gs )ftJ and conducting cumulative ri sk assessments (CRA)l2 l
. The Agency ha s utilized this framework to eva luate t h e SUs of wh ich h a losu lfuron-methy l is a member (OP428798 , 

### J
. D ' Agostino , 09 / 09/ 2015)
. Although the SUs share so me chemical and

1 1 1 

### Guidance For Identifying Pes ticid e Chemicals and Oth e r Substances That Have a Common Mechanism a/Toxicity (USEPA , 1999) 1 2 1 

### Guidance on Cumulati ve Risk Assessment of Pe s ticide Chemicals That Hav e a Common Mechanism of Tox icily (USEPA , 2002) Page 12 of 22

### HALOSULFURON-METHYL Human Health Ri s k Asse ss ment DP No. D428013 toxicological characteristics, the toxicological database does not support a testable hypothesis for a commo n mec h anfam of action. No further mec h an i stic data are re q uired and no further c umulative evaluation is neces sa ry.


### 9. 0 O c cup a tion a l E xpo s ure /Ri s k C hara cterization Dermal exposure during hand l ing activities was not considered because systemic toxicity was not observed at the lim i t dose in the 2 1 -day derma l tox i c ity study in rats and there was no ev idence of quant itative s usceptibility in the halosulfuron-meth y l database. The occupational handler exposure and risk esti mates i ndicate that s hort- and intermediate-term n on-cancer inhalation MOEs are not of conc e rn to HED ( i.e. , MO**Es ~**  

### 100) at base l ine (no respirator) attire ( DP403362 , C. Walls , 01118 / 20 1 3). The lowest MOE of 1 ,200 rep rese nts t he most protec ti ve worst-case occupational sce nario: mixin g/ loading dry flowable s (water-dispersible granules) to s upport aerial applications to hi g h acreage crops (i.e. rice). These risk estimates are not of concern to HED. Derma l exposure during post
- application acti v it ies was not co n sidered becau se systemic toxicity was not observed at the limit dose in the dermal study and the re was no evidence of quantitative s usceptibi l ity in the halosulfuron-methyl database. Based on the Agency's c urre nt pract ices, a quantitative occ upational post-app l ication inhalation exposure assessment was not performed for halosulfuron-methy l at this time. 

### If n ew policies or proced ures are p ut i nto p lace, the Age ncy may r evis it the need for a quantitative occ upational post-application inhalation exposure assess ment for halo s ulfuron-methyl. 

### 10.0 Refe r e nc es Barrett, M. , 04115 / 2015 , DP4218 20, 

### Halosulfuron-methyl Drinking Water Assessment for Additional Foo d/Feed Uses on Pome Fruits Group 11-10 and Climbing Vines Subgroup 13- 0 7F. Rury , K., 08 / 06 /20 1 3, TXR0056723 , 

### Sulfonylureas: Summary of Hazard and Science Poli cy Counci l (HASPOC) Meeting on July 18 , 20 13 : Recommendat ions on Data Requirement for lmmunotoxicity Studies for Sulf onyfurea Pesticides
. Rury , K. , 05 / 25/20 1 5, DP426724, 

### Halosulfuron-lvf ethyl. Acute and Chronic Aggregate Dietar y (Food and Drinking Water) Exposure and Ri sk Assessments for the Section 3 Registration Action on Pom e Fruit Group 11-10 and Fru i t, Small Vine Climbing Subgroup J3-0 7F. Rury, K
. , 06/ 10 / 2015, DP421819, 

### Halosulfuron-lv!e thyl. Human Health Risk Assessment for a Proposed Use on Pom e Fruit Crop Group 11-10 and Small Fruit Vine Climbing Subgroup, Except Fuzzy Kiwifruit, Subgroup I3-0 7 F. Rury, K. , 05 / 25 /2015, DP425728 , 

### Halosulfuron-lv!ethyl. Occupational and Residential Exposure Assessment for a Proposed Use on Pom e Fruit Cro p Group 11-10 and Small Fruit Vine Climbing Subgrou p , Except Fuzzy Kiwifruit, Subgroup 13-0 7 F. Page 13 

### of 22

### HALOS U LFURON

- METHYL Human 

### Health R isk Assess m e nt DP N o. 04 2 801 3
Smegal, D. , 02 /22 / 20 1 2 , TXR0 05 4045 , Halosulfuron-methyl: Sum ma1 y of Ha zard and Sc i ence Polic y Council (HASPO C) Meeting of February 9, 2012: Reco mm e ndations on waive r re ques t s/ or 28-day inhalation s tudy. 

### T sa ur , N
. , 06/ 12/ 20 1 3 , DP 396 460 , Halo s ulfuron-Methyl. Occupational Exposure Assessment for Propo se d Ne w Uses on Pro so Mille/ and Crop Group 17 (Grass , Forage , Fodder. and H a

y) with An Upda ted R es id ent ial Exposure Assessment of All Exis ting R es id en tial Uses.



### Pa ge 

### 14 of 22

### HALO SULFU RO N-MET HYL Human Health Ri sk Asse ss ment DP No. D428013


### A pp e ndi x A . T ox ico l ogy Pro fil e for Ha l os ulfuro n -Me th y l Ta b l e A. 1. T o x i co l ogy D ata R e quire me nt s T ec h n ica l Re quired S u b mi tted 870 .1100 Ac ute Oral Tox ic ity
........ ........... ..... ........ . ........ . ............. . . yes yes 870.1200 Acute D ermal T oxicity
.. .......... .. .. .. ........... .. ... ....... ...... ... .. yes yes 870 .1 300 Acute Inh a la tion Tox ici ty
. .... ... . ... ...... ....... .. .. .. ... ....... .. . ... . yes yes 870.2400 Primary Eye Irritation
. . ........... . ....................... .. ............... yes yes 870.2500 Primary Dermal Irr itation
..... .. ........................ .. ....... ....... . yes yes 870.2600 D e rma l Se n s itization
.. ......... ... . ............ . ...................... . .... yes yes 870.3100 90-Day Oral Toxicity in Rodents ... ....... .......... ... ... .......... yes yes 870.3150 90-Day Oral Toxicity in N o nrod en t s ..... . ..................... .. .. yes yes 870.3200 21 / 28-Day Dermal Toxicity
........................................ ... .. yes yes 870.3250 90-Day D e rm a l Toxicity
................. .. ........... .. ........ .. ........ no n o 870.3465 90-Day Inha lation Toxicity
... ................... ...... ....... ..... .... . CR" wa i vedb 870.3700a Prenatal Developmental Toxicity (rodent)
..... .. . ....... .... . . . yes yes 870.3700b P renatal Developmental Toxicity (nonrodent)
...... ... ...... yes yes 870.3800 Rep roduction an d Ferti lit y Effects ...... .. ........... ... .. ........... yes yes 870.4 1 OOa Chron ic Toxicity ( rodent)
. ...... ....... .. ........... .... ................ n/a 

### - 870.41 OOb C h ronic Toxicity ( non-rodent)
. ........... .. .......... ... ............. yes yes 870.4200a Oncogenicity ( rat)
. .. ...... ...... . .. .. ........ . ... . ....... .. ............. . ... n / a 

## - 870.4200b Oncogenicity (mouse)
.................................................... yes yes 870.4300 Ch r onic/ Oncogenicity (rat)
....................... .. ................. . ... yes yes 870.5100 Mutagenicity

- Bacterial Reverse Mutation T est
........ .. .. yes yes 870.5300 Mutagenicity

- Mammalian Ce ll Ge ne Mut atio n Test
... . yes yes 870.5375 Muta ge ni city

- Structural C hromo so mal Aberrations
..... yes yes 870.5395 Mutage nicity-Oth er Genotoxic Effec ts ..................... .. .. yes yes 870.6 1 OOa Acute Del aye d Neurotoxicity (hen)
................ .. .............. no no 870.61 OOb 90-Day Neurotoxicity (he n )
........................... . ................ n o no 870.6200a A c ute Ne urotoxi c ity Sc ree ning Battery ( r at)
. .... .......... .. . yes yes 870.6200b 90-Day Neurotox icity Screening Battery (ra t)
................ yes yes 870.6300 Dev elo pmental Neuro t oxicity
.......................................... no no 870.7485 General Metabolism
.. ........ ..... ....... ...... ... .......... ... ....... ..... yes yes 870.7600 Dermal Penetration
...... .. .................................. ... ............. n o no 870.7800 l mmunotox ici ty
.. .. ......... .. ................................................ yes waived c a C R = conditionally required. b The Hazard and Science Po li cy Co un cil ( HA S PO C) determined th at a subchronic inha lation s tud y i s not re quire d

at thi s time for halosulfuron-methyl (TXR#0054045, 02/ 22/ 20 12). c The Hazard and Science Policy Council ( HAS P OC) determined that an immunotoxieity s tudy is not r equired at thi s time fo r hal os ul furo n-m e th y l (TX R#0056723 , 08 /06/20 1 3)
.



### Pa ge 

### 15 of2 2

### HALOS U LFURON-METHYL Human Health Ri s k Ass essm e nt 

### DP No
. 0428013
Table A.2. 

### Acute Toxicity Profile - Test S ub sta nc e Guide lin e No. Study Type MRID Results To x ici ty Ca t egory LD so : Mal es= I 0 , 435 m g/kg 870. 11 00 Acut e oral

- rat 42139413 Fe mal es= 7758 m g/kg I V Co mbin e d = 8866 m g/ kg 870.1 2 00 Ac u te dermal

- rat 42 1 394 15 LD so > 2000 mg/k g ( limit t es t) Ill 870.1300 Ac ut e inhalation

- rat 42139417 LC so> 6 m g/L IV 870.2400 Acute eye irr itation

- rabbit 42139419 Mild tran s i e nt (<24 hr) irritation I V involving th e co njun ctiva a nd iri s . 870.2500 Acu t e dennal irritation

- rabbit 42139421 Non -i rritant IV 870
. 2600 S kin se n s iti zat ion

- g uin ea pig 42139423 Not a s kin se n s itizer NIA (maxim izati o n t es t )


### Table 

### A.3
. S ubchroni c, C hronic a nd Other Toxicity Profile of Halosulfuron-Meth y l

Guide lin e Stud y T ype MRID Numbe r (year) / R esu lt s Nu mb er Classificati on/Doses 870.3 100 S ubchronic ora l 4361630 I ( 1995)/ Acccptablc/ G uidcline OAEL = M ::'.: 1400. F = 7 5.8 (82 -1) toxicity s tudy in Doses: 0. I00. I 000. I 0000. o r 20000 mg/kg/day rats ppm (diet) (M/F: 6.717.6. 66.5 17 5.8
. LOAEL = M not determined. F = 772.8 682 .8 1772. 8. 1400/ 1 578 mg/kg/day) mg/kg/day based on decreased body we i ght ga in s. 870.3100 S ub c hronic oral 4 2 17 1 50 1 ( 198 8)/ NOAEL = M = 11 6, F = 147 mg/kg/day (82 -1 ) toxicit y st ud y in Acccptablc/Nonguideline LOAEL = M = 497, F = 640 mg/kg/day rat s (28 day range - Doses: 0
. I 00. 400. 1 600
. or 6400 ppm based on decreas ed organ weights and lindcr) ( diet ) c hanges in clini ca l chemi s t ry (M/F: 7.4 / 8.9. 28.8/ 37.3. 1161147. parameters. 497/ 640 mg/k g/dav) 870.3150 Subchronic oral 4217 1 502 ( 1991 )/ Acceptabl e/Guideline NOAEL = 1 0 mg/kg/day (82 -1 ) t ox i city s tud y in Doses: 0. 2.5. I 0. 40. and 1 60 LOAEL = 40 mg/kg/day based on !bwt. nonrodcnts - dogs mg/kg/day (capsu l e) c hol es t ero l. & a l bumin lev e l s. T he decrease was panicularly marked at th e next hi g her dose level. 1 60 m g/kg/day.
870.3200 2 1-d ay derma l 4266 1 4 1 7 ( 1990)/ Accep tab l e / G uid e lin e No adve rse effec ts was see n at the (82 -2) toxici ty in rat s Doses: 0. I 0. I 00. or I 000 mg/k g/day hi g hest dose level. NOAEL = 1000 mg/kg/day ( Hi ghest dose tested ) ( limit dose)
870.3465 90-day i nhalation The requirement of thi s s tud y was waived (TX R 0054045: 02 /22112) (82-4) s tudy in rats 870.4100 C hronic oral 42396211 ( 199 1 )/ Acceptabl e/G uideline NOAEL = J O mg/kg/day (83 -1 b) toxicity st ud y in Doses: 0. 0
.25. 1 .0
. I 0.0
. or 40 LOA EL = 40 mg/kg/day based on ! bwt dogs ( I -year) mg/k g/day (capsu l e)
. (9

- 1 3%): !R.B C. hematocrit. & hemoglobin: ! chol e sterol

426614 1 8 ( 1992) / NOAEL = M = 108.3. F= 56
. 3 mg/kg/day 

### Page 

### 16 of 22

### HALOS U LF U RO N-MET HYL Hum an Hea lth Ri sk Assessment D P No. D428013


### Tab l e 

### A.3. Subchronic , Chr on ic and Other Toxi city Pro fil e of Ha l o s u lf uron-Methy l Guide l ine Study Typ e MRID Number (year)/ R es ul ts Numbe r C lass ificatio n/ Dose s 870.4300 Co mbined Acceptable/ Guideline LOAEL = M =225. 6
. F = l38.6 (83-5) C hronic/ Doses: 0. I0. I00 , I000. or 2500. 5000 m g/ kg/day based on marginal decrease Ca rcin ogen icit y in (ma le s only) ppm (diet) in body weight gain in both males and rat s (M / F: 0.44 /0.56, 4.4 1 5.6. 43.8/ 56.3, f..:ma l es. I 08.3 / 1 38.6, 225.6 (M) mg/k g/day) No ev i de n ce of carci n oge n i c ity. 870.4200 Ca rcinogenicity 4266 1 419 ( 1 992) / Acceptable/Guideline NOAEL = M=4 IO.O. F > 1214 .6 (83

- 2) study in mice Doses: 0, 30
. 300. 3000 , or 7000 ppm m g/kg/ da y (d iet) LOAEL = M=97 I .9, F> 1 2 1 4.6 (WF: 4.0/ 5.2. 4 1 .11 51.0 , 410.0 / 509.1. o r mg/kg/day based on necrop sy linding s 971.9/12 14 .6 m g/kg/ da

y) (inc re ase incidence of microconcretion / mineralization in th e te s ti s and epididymis). No ev i dence or carc ino ge n i city. 870.3700 Deve lopmental 42139425 ( 1 990)/ Acceptablt: / G uid e line Materna l NOAEL = 250 mg/k g/ day. (83-3) toxicity in rats Doses: 0. 75
. 250. or 750 m g/kg/day Maternal LOAEL = 750 mg/k g/day
. (gavage) based on increas ed incidence of clinical ob se rvations. reduced food cons umption and food efficiency. Developmental NOAEL = 250 m g/ kg/ da y. De v elopmental LOAEL = 750 m g/ kg/day , based on de creased mean fetal body weight and mean l iner s ize. increased fetal and litter incidences of so ft tissu e and s ke l etal var iati ons. 870.3700 Developmental 42139426 ( 1990)/ Acceptabl e/G uideline Maternal NOl\EL = 50 mg/kg/ clay ( 83-3b) to xic it y s t11dy in Doses: 0. I 5 , 50. or 150 mg/k g/d ay Maternal LOA EL = 15 0 mg/kg/day rabb its (gavagc) based on reduc ed body weight ga in. food con s umption and food efficiency. De ve lopmental NOAEL = 50 m g/kg/ day Developmental LOAEL 

### = 150 mg/kg/day based on group decreased mean litt er size. increase d number of re so rption s and resorptions per dam , and increased po s timplantation loss . 870.3700 Developmental 436219 0 1(1995 )3

- chlorosulfonamide Maternal Tox icity N OA EL = > 1000 (83 -3b) toxicity s tud y in acid m g/kg/day rabbits Metabolite / M aternal Toxicity L OA E L > I 000 Acceptable/ Guideline m g/kg/day Doses: 0, 30, 300. or I 000 mg/k g/ day Developmental Toxicit y NOAEL = > I 000 mg/kg/day Developmental Toxici ty LOAEL > 1000 m g/ kg/ day 870.3800 Two

- Generati o n 42139427 ( 1991 ) / Accep table/ G uideline Parental / Syste mi c NOA E L = M = 50.5 , (83-4) re production s tudy Do ses: 0. I 00. 800, or 3600 ppm (diet) F = 58. 7 m g/ kg/ d ay in rats ( F o Males: 6.3. 50 .4. and 223.2 P a renta l/Systemic LOA E L = M :: 223.2 , mg/kg/ day: F o Female s: 7.4 , 58.7 , and f = 26 l .4 mg/k g/ day based On decreased 26 1.4 mg/k g/ day) body wei,e.hts and reduced food


### P age 17 of 22

### H ALOSULFURON -METHY L Human H ealth Risk Assessment 

### DP No. 0428013

Table 

### A.3
. Subchronic, Chronic a nd Other Toxicity Profi l e of Halosulfuron-Methyl

Gui de lin e S tud y T ype MRlD Number (year)/ Result s Number Classification/Doses consumption during the premating p e ri od in both sexes. Off s pring NOAEL = 5 1 / 59 mg/kg/ day Off s pring LOAEL = 223.2/261.4 mg/ kg/da y based on decreased body weight in the F 1 pups and margina l decreased body weight in F 2 pups. Reproductive NOAEL > = 223 .2/ 261.4 mg/kg/day.
870.5 1 00 Mut agc ni c - Ames 42139428 ( 1 99 1 ) / Acceptable Negat i ve. Co nc e ntration s=> 5000 (8 4-2 a) Salmone lla ( +/

- S9) 5 strains S. typh. Cone. : I

- microgm/platc found to be in so lub l e**~12 himurium**  and 10000 μglplatc: E. Co li WpuvrA Co ne.: and/or cytotoxic. E. Coli. 333

- I 0000**~lg/p ate**  870.5100 Mutagcn i c - Gene 436 1 6302 ( 1 995) / Acceptable Negative. Co nducted with 3

- (84 -2 a) Mutation ( +/

- S9) 5 s t rains S. typ h. Co ne.: 50

- ch l orosu l fo namid e acid-the principal 5000**~1 g/** **platc** soil metabolite ofhalosulfuron-meth y l. 870.5300 Mutagenic

- Gene 43616 303 ( 1 995)

- Metabolit e/ Negat i ve. Co ndu cte d with 3- (84-2) Mutation

- Acceptab le chlorosulfonamide acid-the principal H amster (C hine se) ( +/

- S9) Cone.: 350

- 3 1 00 it J?/mL so il metabolite of hal os ulfuron-m et hyl. 870 .530 0 Mut agc ni c - 42139431 ( 1 99 1 )- Metabolite / Conc lu s io n s ind efi nite due partl y t o ( 84-2) ( H G PRT)

- Unacceptable re la tivel y hig h negative and l ow H amster Co ne.: 100-1 000 μ g/ mL po s itive control va lue s . s olubilit y (C hin ese). problem s with test art i c l e. 870.5300 Mutagcn i c - 4266 1420 ( 1 993) / Acceptable Negat iv e. Did no t induce forward (8 4- 2) ( HGPRT)- ( +/

- S9) Co ne .: 50-900 μg/mL mutation s at the l I G PRT locu s in I l amstcr Chinese 1 l ams t er ovary cells. (Chine s e). Conce ntration s above 700 u g/ mL were in so luble
. 870.5375 Mutagcnic

- I n 42139429 ( 1 989)/ Acceptable Negat i ve. No chro mosomal aber ra ti ons. (84-2) vitro C l astoge nic

- { +/

- S9) Cone.: 4 4 9-18 1 0 μ g/ / mL H ams t er (C hine s e) 870 .539 5 Mutagc ni c - 436 1 6304 ( 1 995)

- Nega ti ve. Co nducted with 3

- ( 84

- 2 ) Micronucleu s Metabolite / Acceptable chlorosulfonamide acid-the principal A ssay - Mouse Dose s: 125 0. 2500 or 5000 mg/k g soil metabolite ofhalosulfuron -mcth y l. (C D-I ) No overt toxicity fo r th e treated animals or cytotoxicity for the target organ (bo ne marrow ce ll s) was ob se rved. 870.5395 Mutagenic

- 42 1 39430 ( 1989 ) / Acceptab l e cgat iv e. Did not indu ce s i gnificant ( 84-2) Micronuclcus Doses: 500. 1667 O r 5000 mg/kg. e l evati o n s in th e frequencie s of A ss ay - Mouse mieronucleated pol y chromatic c rvthro cv t es. 870.5500 Mutagcnic

- 42 1 39432 ( 1 990)/ Acceptable cga ti vc. Fail to induce unscheduled ( 84-2) U n sc heduled DNA (+/

- S9) Cone.: 25-1000 μ g/mL DNA sy nthe sis in primary rat sy nthe sis

- Rat hcpatoc y tc s . 870.6200a Ac ute 45754701 ( 1994 ) and 46199501 NOAEL = 600 mg/kg. (82

- 7) ncurotoxicity in ( 1 989)[positive control study] / LOAEL = 2000 mg/kg ( limit dose) rat s. Acceptab l e / Guide l ine bas ed on mortality in males. Doses : 0. 200. 600. or 2000 mg/kg (limit dose) 

### Page 18 

### of 22

### H ALOSU LF U RO N-MET HYL Human He alt h Ri sk Assessme nt DP No. D42801 3

Table A.3. S ubchronic , Chronic and Other Toxicity Profile of Halosulfuron-Methy l

Gu idelin e Study Type MRJD Number (yea r )/ Re su lts Number C lassific ation/ D oses 870.6200b Subchronic 45754702 ( 1992)/ Acceptab le /Guideli n e NOA EL= M 

### = F = I000 ppm (M /F : (82

-7) neurotoxicity Doses: M : 0. I 00. I 000. or I 0.000 ppm: 62.8/ 82.6 m g/kg/day)
. stud y in rats. F: 0. 1 00. 1000. or 4000 ppm (diet ) LOAEL = M = 1 0.000 ppm : F = 4000 (M/F : 0 1 0. 6.3 /8. I
. 62.8/82 .6, or ppm ( M: 706.0 mg/k g/day) in males 706.0/3 15.9 m g/kg/day) b ased on de creased body weight a n

d body weight gai n and (F: 315.9 m

g/kg/day) in females based on decreased body**wei~ht** ga in. 870.7485 Metabolism 42139433 ( 1990) / Acceptable /Guideline Absorption was rapid. incomplete and (83

- 6) 5 or 250 m g/kg s in gle dose or 5 similar in both sexes. E limin atio n was mg/kg/day repeated doses mo st l y by urin e and feces within 72 hours. appearing to be independent of dose and sex. Desmethyl NC-319 and the 5-h yd r oxy der ivative we r e the major urin ary and fecal metabolites. 870. 78 00(83

- 6) lmmunotoxi c it y This requirement of this stu dy was waived (TX: 0056723: 08/ 06/20 13)
A pp e ndix B. Intern at i o nal Re s idue Limit S tatu s Table B.1. Sum m ary o f US To leranc es and I ntern ational Maximum R es idu e Limits R es idue Definition 

## us Cana d a Mexico' Codex 40 CF R 180.479 (a) ( 1 ): Co mpliance with M e th y l 3-chloro-5-[[[[( 4 , 6- None t h e toleran c e l eve l s spec ifi ed in th e dim e th oxy-2

- fo ll ow in g table i s to be dete rmin ed by pyrimid in y l)a min o]car b ony l ]a measuring o nl y those hal os ulfuron-m ethyl mino ]s ul fo ny l]-1- m ethy l

- I H res id u es co ntainin g the 3- py razo le- 4-c arb oxy late c hl orosu l fo namid e (3

- CSA) moiety , ex pre ssed as th e s toic hi o metric e quiva lent of h alos ul furo n -methyl Co mmodity Tol eran ce (p/Jm) / Max imum R es idu e Li mit ( mf!/kf!) 

## us Ca nada Mexico' Codex Cattle, fat 0.05 0.01 Ca nte , meat 0.05 Catt le , meat byproducts 1.0 0.2 Goat, fat 0.05 0.0 1 Goat, meat 0
. 05 Goat , meat byproducts 1.0 0.2 Ho!?. , meat byp roducts 0.1 Horse. fat 0 .05 0.01 Ho r se, meat 0.05 H o r se, meat byproducts 1.0 0.2 Milk 0.05 S h eeo, fat 0.05 0.01 Sheeo, meat 0.05 S h ee p , mea t byproducts 1.0 0.2 

### P age 19 

### of2 2

### HALOS ULFURO N-METHYL Human 

### H ealth Risk Assess m en t DP No
. 0428013

Ta bl e B . 1. S umm a ry o f US T o leran ces and Int e rn a tion a l Ma ximum R es idu e Limits US (40 C FR § 180 .479(a)(2) ] Canada M ex ico' Co dex (2) Com pli ance with th e tolerance levels Same as above None s pecified in the following table is t o be detennined by m easuring only halo s ulfuronmethyl Co mmodity To le ran ce (pom) / Maximum R es idue Limit (mKlkg) 

# us Canada M exi c o 1 Codex Alfalfa, forage 1.0 Alfa l fa, ha y 2.0 Almond , hull s 0.2 Apple 0.05 0 .05 Artich o ke 0.05 As paragu s 0.8 I Bean , dry, see d 0.05 0.05 Dry (a dzuki beans. bean s, blac keyed peas , broad beans, catjang seeds , chickpeas, cowpea seeds, g u ar seeds , kidney beans , l ablab bean s, lim a bean s, m o th beans , mung bean s, navy beans , pink b eans , pinto bean s, ri ce bean s, southe rn peas, t e p ary b ea n s, urd beans , grain lu pin Bush berry , s ub group 13-07 8 0.05 0 .05 aronia berri es, buffa lo currants , Chilean guavas, currants e l

d erbe rri es, Eu ropean b arb e rrie s , gooseberries , highbu sh (blueber r i

es, cranberries) , hone ys uckle , huckleb e rrie s, jo s t aberri es, J uneb e rri es (Sask at oon berries) , lingonberrie s, lowbu s h b l ueberries , native currants. s alal be rri es. sea bu ck thorn C aneberry s ubgroup 1 3-07 A 0.05 0.05 Bla ckberri es, loganberries, raspberries, wild raspberries Co m , field , forage 0.2 Co rn , field, grain 0.05 0.05 Com , field, s tover 0.8 Com , DOD , gra in 0.05 0.05 Com, pop , s tover 0.8 Co rn , swee t , fo r age 0
. 2 Corn , s weet , kern e l plu s co b w ith 0
. 05 0.05 husk s r emoved Corn , s weet , s tover 0
. 8 C ott on. g in bvoroducts 0.05 Cotton , und eli nted seed 0.05 Grass , forage , fodder, and hay , group 20 17 , forage Gras s, forage , fodder, and hay , group 0.05 17,hay 

### Pag e 20 of 22

### HALOSULFURON

- METHYL Human Health Risk Assessment D P No. D4280 13

T a b le B.1. S umm a r y of US To lera nce s a nd Inte rn ation a l Maximum R es idu e Li m its Me lon s ub g roup 9A 0.1 0.1 citron melon s, cantaloupe s, muskme lon s (other than tho se li s ted in thi s item) , watermelon s Mill et , pros o , fora ge 10 Millet, pro s o , grain 0.01 0.01 Millet , pro s o , hay 0
.01 Millet, pros o , straw 0.01 Nut , tree, g roup 14 0.05 0.05 African tree nu ts, almond nu ts, beechnuts, bla c k walnut s, Bra z il nuts, Brazili a n pin e nut s, bunya n ut s, bur oak nuts, butternut s, Cajou nuts, candl e nuts , ca s hew nuts, chestnuts , chinquapin nuts, coconuts, coquito nuts , dika nuts, En g li s h w a lnuts , g ink g o nut s, Guian a ch e stnuts , hazelnuts (filbert) , he artnut s, hickory nuts, Japanese hors e-ch estnuts , macadamia nuts , mongongo nuts , monkey-pot nuts , monkey pu zz le nuts, Okari nut s, P

ac hira nuts, peach palm nuts, pecan nuts, pequi nuts , Pili nuts , pine nuts , pi stachio nuts , Sapucaia nut s, tropi ca l almond nuts , ye llow horn nut s Okra 0.05 0.05 Pea and b ean , suc c ulent s he ll ed , 0.0 5 s ub g roup 6 Pea and bean , succulent s h e ll ed , 0
.05 0.05 ed i ble podded Uackbean s, s ub g roup 6 8 moth bean s, runner be ans , s nap b e

an s, sword bean s, wax bean s , va rdlong be ans) Pi s tachi o 0.05 0.05 Rhubarb 0.05 0.0 5 Rice , grain 0.05 Ri ce, s traw 0. 2 S org hum , g rain , forage 0.0 5 Sorg hum , gr ain , grain 0.05 0.0 5 So r g hum, g r a in , s tove r 0.1 Soy bean , seed 0.05 Squas h/Cucumb e r s ubgroup 98 0.5 0. 5 balsam apple s, balsam pears C hay ot e ( fruit ), Chin es e cucumber s, Chinese waxgourd , cucumbers, edible gourds ( other than tho se li s ted in thi s item ), pumpkin , s ummer s quash , wes t I ndian gherkins , winte r squas h S ug arcan e, c an e 0.0 5



### Page 

### 2 1 of 22

### HALOSULFURON-METHYL Human Health Risk Assessme nt DP No. D428013

Table B.1. Summary of US To lerances and International Maximum Residue Limits Vegetable, fruiting , group 8 0.05 0.05 African eggplan ts, bell peppers , bush tomato es, coconas , currant tomatoes, eggplants , garden huckleberries , g oji berries , groundcherries , martynias , naranjilla s, nonbell peppers , okras. pea eggplants , pepinos. roselles , scarlet eggplants, sun berries. tom ati llo s, tomatoes , tree t omatoes Vegetable, tuberous and corm, 0.05 s ubgroup I C R ecommended Tol e rances 40CFR § I 80.479(a)(2) Fruit, pome, g roup 11-10 0.05 0.05 apple 40CFR §I 80.479(c) Fruit. s mall , vin e climbing , except 0.05 fuzzy kiwifruit, s ub .group 13-0?F. MRls witlt NO US Eq uivale 11t Agave I Bamboo shoots I Ce ltu ce I Edible fems I Fresh Florence fenne l leaves and I s talks Kohlrabie s I Palm heart s I Prickl y pear pads I Sea ka les I Completed by: M. Negussie; 06/16 / 2015 1 Mex ico adopts US tolerances and/or Codex MRL s for i t s export purpose s.



### Pa ge 22 of 22