### UNITED ST ATES ENVIRONMENT AL PROTECTION AGENCY

WASHINGTON, D

. C. 20460



### MEMORANDUM

Date: September 16

, 20 1 5 OFF I CE OFCHEM I CAL SAFETY

AND POLLUTION PREVENT I ON



### SUBJECT: S ul fos ulfur o n

. Draft Human Health Ri sk Assess ment in Support of R egis trati on
Review.



### PC Code: 08560 1



### Dec i s i o n No.: 505 1 78



### Pet i tio n N o .: Not A ppl i ca bl e (NA)


### Ri sk Assess m e n t Ty p e : Sing l e Chemical Aggregate



### TXRNo.: NA


### M RI D No. : NA 

### DP B arco d e: 427399



### R eg i s t ra tion Nos. : 52 4- 500, 524-525,

524

- 533, 524-534.



### R eg ula tory Actio n: Re g i st ration Revi ew 

### Case No.: 724 7


### CAS No

. : 141776- 32- 1

40 

### CFR: § 180.552



### F RO M : Bonni e Cropp-Kohlligian, Ri sk Assesso r

# -:rs**~ ~** **-'t\~\~** Abda llah Khasawinah, Ph.D.

, Toxico l og i st

### ~**~** Kelly O'Rourke, ORE Assessor**~** 

# n

. () 1**Y' ...a~**  Risk Assessment Branch (RAB) 

### T V

Health Effects Di v i s ion ( HED ) (7509 P)



### THROUGH: C harl es 

## w. S mith 

## m

, Act in g Branch C hief 

# C**~** RAB IV

, HED (7509P)



### TO: K e ll y Ballard and Thomas Moriarty 

### (RM 51)

Risk Manage m ent and Implementation Branch 

### I

Pe st i c id e R e- Eva l u at i on Divi s i o n (7508 P )

Sulfosu l furon is a se l ect i ve broad leaf h e rbi cide bel o n g in g to the s ulfon ylurea gro up of

h erbicides. This document eva luat es th e exis tin g u ses of s ulfo s ul furon as part of R eg i s tration

Review and r e pr ese nt s the draft ri sk assessme nt 

### ( ORA )

. Th e Age n cy i s reviewing a ll the sulfonylurea h erb i c id es jointly und e r Registration Revie w

.

S in ce the last human health r i sk assessme nt a nd scop in g document, the following

c han ges / updat es hav e been incorporated for s ulfo s ulfuron

.

1 ) The immunoto x ici ty and inhala t ion toxicity st udy r eq uir eme nt s ha ve been wa i ved.

P age 

### 1 of 28Sulfosulfuron (085601) Draft Human Health Risk Asse ss m en t DP # : 427399



### 2) Th e s hort-term incidenta l oral e n dpoint and point of departure hav e been changed and a r e

n ow based on a subchron ic toxicity study rather than a chro nic / carcinogenicity study

s inc e the subchronic study duration is cons id ered more approp riate for assessing this

exposure sce n ario.
3) The short -t erm incidental oral risk assessment has been updated to incorporate new

sc i e nc e policies. Co n seq uentl y, the short -term aggregate risk assessment ha s also been updated.
4) Previously identified deficiencies related to the enforcement method have been resolved.
5) A high-end drinking water exposure value was used to assess screening-leve l dietary

exposure / risk estimates and dietary a ssess ments were conducted with a n updated version

of DEEM which uses updated food consumption data.

Page 2 of 2 8Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 3 of 28 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ........... 4

2.0 HED Recommendations

................................ ................................ ................................ .... 5

2.1 To lerance Considerations

................................ ................................ ................................ . 5

3.0 Introduction

................................ ................................ ................................ ........................ 6

3.1 Chemical Identity and Physical/Chemical Characteristics

................................ ............... 6

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

................................ ............. 6

3.3 Consideration of Environmental J ustice

................................ ................................ .......... 8

4.0 Hazard Characterization and Dose

- Response Assessment

................................ ............ 8

4.1 Summary of Toxicological Effects

................................ ................................ .................. 9

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

................................ ....... 10

4.3 Toxicity Endpoint and Point of Departure Selections

................................ .................... 10

4.4 Endocrine Disruption

................................ ................................ ................................ ..... 11

5.0 Dietary Exposure and Risk Assessment

................................ ................................ ......... 12

5.1 Water Residue Profile

................................ ................................ ................................ .... 12

5.2 Food Residue Profile

................................ ................................ ................................ ...... 13

5.3 Dietary Exposure and Risk Estimates

................................ ................................ ............ 13

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

............................. 14

6.1 Spray Drift

................................ ................................ ................................ ...................... 15

7.0 Aggregat e Exposure/Risk Characterization

................................ ................................ .. 16

7.1 Short

- term Aggregate Risk

................................ ................................ ............................. 17

7.2 Chronic Aggregate Risk

................................ ................................ ................................ . 17

8. 0 Cumulative Exposure/Risk Characterization

................................ ............................... 17

9.0 Occupational Exposure/Risk Characterization

................................ ............................ 18

10.0 Public Health and Pesticide Epidemiology Data

................................ ........................... 18

11.0 Literature References

................................ ................................ ................................ ...... 18

12.0 References

................................ ................................ ................................ ......................... 19 Appendix A. Toxicology Profile and Executive Summaries

................................ ................ 20

A.1 Toxicology Data Requirements

................................ ................................ ...................... 20 A.2 Toxicity Profiles

................................ ................................ ................................ ................. 21 Appendix B. Dietary Exposure/Risk Modeling Input and Output

................................ ..... 24 Appendix C. Nomenclature and Physical/Chemical Properties

................................ .......... 26 Appendix D. Review of Human Research

................................ ................................ ............. 27 Appendix E. Submittal of Analytical Reference Standards (860.1650)

.............................. 27 Appendix F. TTR Data Waiver Criteria

................................ ................................ ............... 28Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 4 of 28 1 .0 Executive Summary

Sulfosulfur on ( N

- [[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]

- 2

- (ethylsulfonyl)imidazo [1,2

- a ]pyridine

- 3

- sulfonamide) is a selective broadleaf sulfonylurea ( SU ) herbicide registered f or the control of various annual grasses and /or broadleaf weeds in wheat, pastures, rangelands and highly managed residential and commercial non

- crop turf sites such as apartment complexes, athletic fields, cemeteries, golf courses, hotel properties, office complexes, parks, public turf areas, retail sites, school grounds, sod and turfgrass seed farms . It is also used in forestry and for

conifer release and on a numbe r of other non

- crop use sites such as roadsides, utility rights

- of

way, airports, fallow areas, ditch banks, dry ditches, dry canals, fencerows, industrial sites, lumberyards, manufacturing sites, petroleum tank farms, pumping installations, railroads, sto rage areas, utility substations, warehouse areas and wildlife areas

. T here is no explicit prohibition against purchase and/or use of sulfosulfuron products by homeowners

.

The most recent human health risk assessment for sulfosulfuron was completed in 2008 (D349702 ) . Since then, no new sulfosulfuron data have been received and the only condition of registration, completion of a petition method validation (PMV) of an enforcement method, has been satisfied ( D 427730 )

. A human health scoping document was co mpleted for sulfosulfuron in 2011 ( D 385545) and immunotoxicity and subchronic inhalation toxicity studies were identified as data gaps. However, the subchronic inhalation toxicity study was later waived by HED (D394271) and the HED Hazard and Science Po licy Council (HASPOC) has since

determined that both immunotoxicity and subchronic inhalation toxicity data are not required ( TXR 0056762, TXR 0056723 and TXR 0052986 )

.

The toxicology , residue chemistry and occupational/residential exposure ( ORE ) database s for

sulfosulfuron are considered complete for risk assessment

. HED is recommending for the

removal of established tolerances for residues of sulfosulfuron in hog commodities (D427730)

and t he current tolerance expression for sulfosulfuron must be updated in accordance with HED guidance (see Section 2.1) . A n analytical reference standard for the ethyl sulfone chemoph o re metabolite of sulfosulfuron must be submitted to the EPA National Pesticide Standards Repository ( see Appendix E ).

No toxicity endpoints have been identified for acute dietary, dermal or inhalation routes of exposure. The toxicity endpoint for chronic dietary exposure continues to be based on a

ch r onic/ca r cinogenicity study; however, the short

- term incidental oral endpoint is now based on a subchronic toxicity study rather than a chronic/carcinogenicity study since the subchronic study

duration is considered more appropriate for assessing this exposure scenario. S ulfosulfuron is not likely to be carcinogenic to humans at d oses that do not cause crystals with subsequent calculi formation resulting in cellular damage of the urinary tract.

A screening

- level chronic dietary exposure and risk assessment was conducted for sulfosulfuron using tolerance

- level residues and default processing factors for foods , 100% crop treated and a sulfonylurea

- class

- wide screening

- level estimate of residues for drinking water. Chronic d ietary risk estimates range from 3.2 to 1 1 % of the chronic population adjusted dose ( cPAD ) and are not
of conce rn to HED, being less than t he level of concern (LOC = 100% cPAD )

.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 5 of 28 Since there is no explicit prohibition against purchase and/or use of sulfosulfuron containing products by homeowners, base d on the use sites/ patterns, potential residential exposure scenarios

may include short

- term exposures to adult handlers (mixers, loaders, applicators, etc.) and post

application exposures to adults and children. However, no hazard via the dermal or inhalation

route has been identified (for any duration). O nly s hort

- term incidental oral exposure s (i.e.,

hand

- to

- mouth, object

- to

- mouth, and soil ingestion ) f rom residential turf use of sulfosulfuron are expected for children. The short

- term incidental oral exposures for children were assessed and

resulted i n m argins of exposure (MOEs) of ≥ 740,000 and are not of concern to HED, being greater than the LOC (100).

S hort

- term aggregate exposure for sulfosulfuron resulting from short

- term incidental oral exposure (from residential turf) and dietary exposure (fo od and water) is expected for children

. The short

- term a ggregate exposure for children from incidental oral and dietary exposures was assessed and resulted in a MOE of 6,300 and is not of concern to HED , being greater than the LOC (100)

. Chronic aggregate exposure for sulfosulfuron resulting from dietary exposure (food and water) is discussed above.

Occupational handlers/w orkers may be exposed to sulfosulfuron during mixing, loading, and/or applying the herbicide as well as dur ing post

- application activities. However, no hazard via the

dermal or inhalation route has been identified (for any exposure duration) ; hence, a qua ntitative occupational risk assessment was not conducted. Labels require personal protective equipment (PPE) consist ing of baseline attire only (i.e., long

- sleeved shirt, long pants

, and shoes plus socks )

and a restrict ed entry interval (REI) of 12 hours which are considered adequately protective

.

2.0 HED Recommendations

2.1 Tolerance Considerations

The exis ting tolerances (40 CFR § 180. 5 5 2 ) are supported by the available residue chemistry

data. There are no established Codex Canadian or Mexican maximum residue limits (MRLs) for residues of sulfosulfuron with the exception of a Canadian MRL in/on wheat grain which is

harmonized with the U.S. tolerance in/on wheat grain (0.02 ppm) with regards to both definition

and limits.

The current tolerance expression for sulfosulfuron should be revised , in accordance with the

HED Interim Guidance on Tolerance Expressions (S. Knizner, 5/27/ 20 09) , to the following:

Tolerances are established for residues of sulfosulfuron ( N

- [[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]

- 2

- (ethylsulfonyl)imidazo[1,2

- a ]pyridine

- 3

- sulfonamide)

, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only those sulfosulfuron residues con vertible to 2

- (ethylsulfonyl)

- im idazo[1,2

- a ]pyridine, expressed as the stoichiometric equivalent of sulfosulfuron

.

T olerances for residues of sulfosulfuron in livestock commodities were re

- evaluated (D427730) and it was determined that there is no reasonable expectation of finite residues of conce rn inSulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 6 of 28 swine ( i.e., Category 3 of 40 CFR 180.6(a) ) . Therefore, HED is recommending for the removal of established tolerances for residues of sulfosulfuron in fat (0.005 ppm), meat (0.005 ppm) and meat byproducts (0.05 ppm) of hog. This recommendation is a lso a consequence of the re

evaluation of the enforcement methods (D427730) and the finding that the limits of quantitation

for these methods is 0.01 ppm.

3.0 Introduction

3.1 Chemical Identity and Physical/Chemical Characteristics

Sulfosulfur on ( N

- [[ (4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]

- 2

- (ethylsulfonyl)imidazo [1,2

- a ]pyridine

- 3

- sulfonamide) is a selective broadleaf h erbicide belong to the s ulfonylurea class

of chemicals

. The chemical properties of sulfosulfuron do not suggest that there are any particular exposure issues that warrant special consideration . The compound has multiple dissociation constants, making its water solubility dependent on pH, with lower solubility under

more acidic conditions. The potential for sulfosulfuron to parti tion into fatty matrices is also pH dependent; however, based on the octanol/water partitioning coefficients, such partitioning is unlikely to occur. Sulfosulfuron has a relatively low vapor pressure , indicating that inhalation of

vapors is unlikely to be a significant source of exposure under ambient conditions. The structure

and physical/chemical properties of sulfosulfuron a re provided in Appendix C

.

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

Sulfosulfuron exhibits systemic post

- emer gence herbicidal activity on a broad spectrum of annual and perennial sedges, grasses, and broadleaf weeds, but does not injure many warm

season and some cool

- season grasses. Sulfonylurea herbicides disrupt amino acid biosynthesis in susceptible plants by binding to the acetolactate synthase (ALS) enzyme.

Sulfosulfuron is currently registered to Monsanto Company as a selective pre

- and post

- emergent herbicide for the control of various annual grasses and/or broadleaf weeds in wheat, pastures, rangelands and highly managed residential and commercial turf non

- crop sites such as apartment complexes, athletic fields, cemeteries, golf courses, hotel properties, office complexes, parks, public turf areas, retail sites, school grounds, sod and turfgrass seed farms . It is also used in forestry and for conifer release and on a number of other non

- crop sites such as roadsides, utility rights

- of

- way, airports, fallow areas, ditch banks, dry ditches, dry canals, fencerows, industrial sites, lumberyards, manufactur ing sites, petroleum tank farms, pumping installations, railroads, storage areas, utility substations, warehouse areas and wildlife areas

. Sulfosulfuron formulations include water dispersible granule (WDG ; 3 end

- use products ) and suspension concentrate (S C ; 1

end

- use product ) . Applications are made by ground or aerial equipment.

There is no explicit prohibition against purchase and/or use of sulfosulfuron products by homeowners; hence, potential residential exposure scenarios may occur. Also, sulfosulfuron may be applied by professional commercial operators to lawn areas (such as apartment complexes, parks, schools, recreational areas and public areas) where residents may be expected

to come into contact with sulfosulfuron residues.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 7 of 28 Individual s may be exposed to sulfosulfuron via their diet (food and water) and there is the potential for exposure in residential settings, including short

- term exposures to adult handlers (mixers, loaders, applicators, etc.) and post

- application exposures to adult s and children. Occupational handlers/ workers may be exposed (dermal and inhalation) to sulfosulfuron during mixing, loading, and/or applying the herbicide as well as dur ing post

- application activities. Based on the use pattern, the duration of exposure for occupational handlers is expected to be

short

- term and intermediate

- term but not long

- term. The personal protective equipment (PPE) requirement on the labels consists of baseline attire only (i.e., long

- sleeved shirt, long pants and shoes plus socks ). The restricted entry interval (REI) on all labels is 12 hours.

Table 3.2. Summary of Directions for Registered Use of Sulfosulfuron.

Applic. Type, and Equip ment Formulation

[EPA Reg No.] 1 Max. Applic.

Rate (lb ai/A /applic. ) Max. No.

Applic.

per Season Max. Yearly

Applic. Rate
(lb ai/A) PHI

(days) Use Directions and Limitations

Grass

– Pastures and Rangeland

B roadcast;

Ground or Aerial 75% WDG

[524

- 500] 0.09 2 0.125 0 forage 14 hay For use o n well

- established

pastures. Applications may be made from early spring through the fall; follow

- up applications may be made after suitable regrowth of weeds but no

sooner than 30 days after initial application. Addition of a nonionic surfactant (NIS) at 0.25% by volume is required.

Wheat Broadcast;

Ground or Aerial 75% WDG

[524

- 500] 0.03 1 0.03 0 forage 30 hay

55 straw 55 grain Applied either pre

- or post

emergence on winter wheat; apply only post

- emergence for spring wheat

. 75% WDG [524

- 525]

Ornamental s ( i.e., for use on woody ornamentals, perennial groundcovers and ornamental grasses growing in landscaped areas or field produc tion nurseries) Broadcast;

Ground or Aerial 75% WDG

[524

- 534 ] 0.09 2 0.125 N/A

Residential/ Commercial Turf
( i.e., for use on highly managed turf, sod farms and native grass sites such as apartment complexes, athletic fields, cemeteries, golf courses, hotel properties, office complexes, parks, public turf areas, retail sites, school grounds, sod and turfgrass seed farm s ) Broadcast;

Ground or Aerial 75% WDG

[524

- 5 34 ] 0.09 2 0.125 N/A Do not apply directly to or within 4 feet of golf course putting greens.

24.1% SC [524

- 533] Use limited to golf courses (excluding greens) and sod farms. Do not apply to golf

course greens or within 4 feet of

these sites.
Forestry and Conifer Release Broadcast;

Ground or Aerial 75% WDG

[524

- 500] 0.06

- 0.09 2 0.125 N/ASulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 8 of 28 Table 3.2. Summary of Directions for Registered Use of Sulfosulfuron.

Applic. Type, and Equip ment Formulation

[EPA Reg No.] 1 Max. Applic.

Rate (lb ai/A /applic. ) Max. No.

Applic.

per Season Max. Yearly

Applic. Rate
(lb ai/A) PHI

(days) Use Directions and Limitations

Noncrop Areas
( i.e., roadsides, utility rights

- of

- way, airports, fallow areas, ditch banks, dry ditches, dry canals, fencerows, industrial sites, lumberyards, manufacturing sites, petroleum tank farms, pumping installations, railroads, storage areas, utility substations, warehouse areas , wildlife areas ) Broadcast;

Ground or Aerial 75% WDG

[524

- 500] 0.09 2 0.125 N/A Do not apply on or around athletic fields, commercial turf sites, golf courses, residential

turf sites or sod and turf

g rass seed farms.

1 There are four currently registered end

- use products containing sulfosulfuron as the active ingredient: (1) E PA Registration No. 524

- 500; Maverick Herbicide ; 75% Water (EPA Accept a nce Date 9/22/2010 ; ( 2) EPA Registration

No. 524

- 533; MON 44940 SC Herbicide (EPA Acceptance Date 2/27/2002) ; (3) EPA Registration No. 524

- 525;

Maverick C/A Herbicide ( EPA Acceptance Date 8/2/2001 ) ; and (4) EPA Registration No. 524

- 534 ; MON 44951

Herbicide (EPA Acceptance Date 12/4/2006) and Supplemental (EPA Acceptance Date 1//25/2010).



### 3.3 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf ). As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to

well

- established proce dures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residentia l setting. Extensive data on food consumption patterns are compiled by the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey/What We Eat in America, (NHANES/WWEIA), are used in pesticide risk assessments for all re gistered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when cond itions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas
post

- application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional di etary patterns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

The toxicology database for sulfosulfuron is complete and adequate for risk assessment. Immunotoxicity and inhalation studies are part of the current 40 CFR Part 158 Toxicology Data Requirements. However, the HASPOC determined that these studies are not required at this time for sulfosulfuron (TXR 0056762, TXR 0056723 and TXR 0052986 ). The TOXLINE (National Library of Medicine) database literature search did not identify any new toxicological information not already considered. No new toxicity and/or me tabolism data have been receivedSulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 9 of 28 since the most recent human health risk assessment for sulfosulfuron was completed in 2008 (D349702 ) . T he endpoints selected for the previous risk assessment remain the same except for

the short

- term incidental oral endpoi nt that is now based on a subchronic toxicity study rather than a chronic/carcinogenicity study since the subchronic study duration is considered more appropriate for assessing this exposure scenario. For a summary of the acute, subchronic and

chronic tox icity profile, see Appendix A.

4.1 Summary of Toxicolog ical Effects

Sulfosulfuron has low acute oral, dermal, and inhalation toxicity (Acute Toxicity Category IV for oral, dermal and inhalation). It is nonirritating to skin and slightly irritating to eyes (Category

III ). It is not a skin sensitizer. The subchronic toxicity studies in rats, mice, and dogs demonstrate that the primary effects of sulfosulfuron were observed at high doses, and included urinary crystals, bladder stones and associated pathology of the urinary bladder, kidney and

ureter.

In the chronic rat and mouse toxicity studies, urinary crystals, bladder stones and associated pathology of the urin ary bladder, kidney and ureter were also observed at high doses. In the rat, single incidences of rarely observed urinary bladder transitional cell papilloma and carcinoma were reported in 2 different females at 5,000 ppm (314.1 mg/kg/day) and in the mous e there was an increased incidence of benign mesenchymal bladder tumors in the male and a single renal adenoma in both high dose males and females.

In accordance with the Agency's Proposed Guidelines for Carcinogenic Risk Assessment (10

- APR

- 1996), the CAR C classified sulfosulfuron as “n ot likely to be carcinogenic to humans ” at doses that do not cause crystals with subsequent calculi formation resulting in cellular damage of the urinary tract. The current endpoint selected for chronic RfD is based on the NOAEL of 500 ppm (24.4 mg/kg/day) from the carcinogenicity study in rats and is considered protective of

cancer and noncancer effects.

The results of the 2

- generation reproduction and developmental toxicity studies indicate that

sulfosulfuron is not a developmental or reproductive toxicant. The acute and subchronic neurotoxicity studies show that sulfosulfuron is not neurotoxic.

The mutagenic test battery demonstrated that sulfosulfuron is not mutagenic at non

- cytotoxic

concentrations. An in vitro Chi nese hamster lung point mutation assay was positive, only under

conditions of non

- activation and at levels that caused precipitation.

The toxicity of sulfosulfuron appears to be dependent on saturation in the urine, followed by precipitation and formation of urinary crystals and bladder stones. The metabolism study in the rat shows that sulfosulfuron is excreted largely un

- metabolized (80%

- 90% of administered dose). Excretion at a low dose (10 mg/kg) occurs primarily in the urine (77%

- 87% of dose); wherea s, at a high dose (1,000 mg/kg), a large percentage of the administered dose is excreted in the feces (55%

- 63%). Sulfosulfuron is rapidly excreted and is not retained in tissues to any significant

extent.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 10 of 28 4.2 Safety Factor for Infants and Children (FQPA S afety Factor)

The toxicity database of sulfosulfuron is complete and adequate to assess the qualitative or quantitative susceptibility in the young. There is no evidence of increased qualitative or quantitative susceptibility in the young, there is no evi dence of neurotoxicity with sulfosulfuron

, and exposure estimates are unlikely to underestimate risk; therefore, the FQPA Safety Factor is

reduced to 1X.

4.3 Toxicity Endpoint an d Point of Departure Selections

There have been no changes to the prior dos e

- response assessment and cancer classification except for the short

- term incidental oral endpoint. In the previous risk assessment ( D349702 ) , the endpoint of toxicity for assessing this exposure scenario was based on the rat chronic/carcinogenicity study with a NOAEL of 24 mg/kg/day. The current assessment is based on a NOAEL of 100 mg/kg/day from a subchronic dog toxicity study where the study duration is more appropriate for assessing this exposure scenario.

Table 4.3. Sulfosulfuron Summary of Toxicol ogical Doses and Endpoints for Use in Dietary and

Occupational Human Health Risk Assessments.

Exposure Scenario Point of

Departure Uncertainty/

FQPA SFs Population

Adjusted Dose

for Risk

Assessment Study and Toxicological Effects

Acute Dietary (General Population including Infants and Children) A single dose effect relevant to the general US population including infants and children

was not identified in the toxicity studies conducted with sulfosulfuron [including developmental toxicity studies in the ra t and the rabbit (at up to 1,000 mg/kg/day) and an acute neurotoxicity study in the rat (at up to 2,000 mg/kg)]

. Acute dietary (Females 13

- 49 years of age) No appropriate endpoint was identified including developmental toxicity studies in rats and

rabbit s.

Chronic Dietary (All Populations) NOAEL = 24

mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x RfD= 0.24

mg/kg/day

cPAD = 0.24 mg/kg/day Chronic toxicity/carcinogenicity

-

rat; MRID 44295759 LOAEL = 244.2 mg/kg/day based on urinary tract pathology,

abnormal crystals and urinary calculi (both sexes); mineralization in heart, lung, pancreas, and skeletal muscles (male).

Short

- term
Incidental Oral NOAEL = 100

mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x LOC for MOE

= 100 Subchronic oral toxicity study

- dog,

MRID 44295751

LOAEL = 300 mg/kg/day based on lesions in the urinary bladder in females occurring subsequent to urinary formation/urolithiasis and on abnormal urinary crystals in

males and females.

Dermal (Any time period) This risk assessment is not required. No dermal or systemic toxicity was seen following

repeated dermal application at the limit dose in a 21

- day dermal toxicity study in rats.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 11 of 28 Table 4.3. Sulfosulfuron Summary of Toxicol ogical Doses and Endpoints for Use in Dietary and

Occupational Human Health Risk Assessments.

Exposure Scenario Point of

Departure Uncertainty/

FQPA SFs Population

Adjusted Dose

for Risk

Assessment Study and Toxicological Effects

Inhalation (Any time period) Based on the low acute inhalation toxicity (Ca tegory IV), and the low application rates for

the proposed use patterns ranging from 25

- 101 g ai/hectare (10

- 41 g ai/acre), there is negligible concern for potential inhalation exposure and risk. Therefore, a separate

inhalation risk assessment is not r equired. A subchronic inhalation study has been waived by HASPOC (TXR 0052986 )

Cancer Not likely to be carcinogenic to humans at doses that do not cause crystals with

subsequent calculi formation resulting in cellular damage of the urinary tract. The current endpoint selected for chronic RfD based on the NOAEL of 500 ppm (24.4 mg/kg/day) from the carcinogenicity study in rats i s considered protective of cancer and non

- cancer effects. 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 extrapolation to determine risk associated with low er environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in

sensiti vity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). LOC = level of concern. MOE = margin of exposure



### 4.4 Endocrine Disruption

As required by FIFRA a nd FFDCA, EPA reviews nu m erous studies to assess potential adverse

outco m es f

r om exposure to che m icals. Collecti v ely, these studies inclu d e acute, subchronic

and chronic toxicity, including ass e ss m ents of carcinogenicity, n e urotoxicity, develop m ental, reproductive , and general or syste m ic toxicity. These studies include e ndpoints which m ay be susceptible to endocrine influ e nce, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual m aturati o n, fertility, pregnancy rates, reproductive loss,

and sex rati o s in offspring. For ecol o gical h azard assess m ents, EPA evaluates ac u te tests and

chronic s t u d ies t h at a s sess growth, develop m ental and repro d uctive effects in different

taxono m ic groups. As part of its most recent registra tion decision for sulfosulfuron , EPA

reviewed these data and selected the m o st sen s iti v e endpoints for relevant risk assess m ent
scenarios f

rom the existing hazard database. However, as required by FFDCA section 408(p),

sulfosulfuron is subject to the endocrine screening part of the Endocrine D i sruptor Screening Program (EDSP).

EPA has developed the EDSP to deter m ine whether certain substances (including pesticide active and other ingredients) m ay have an effect in hu m ans or wildli f e si m ilar to an eff

ect produced by a “naturally occurring estrogen, or o t her such e n docrine effec t s as the

Ad m i nistrator m ay designate.” The EDSP e mploys a two

- tiered approach to m aking t h e statutorily required deter m inations. Tier 1 consists of a battery of 11 screening assays to

i d enti f y the pote n ti a l of a che m ical substance to i n teract with the estro g en, androgen, or thyroid (E, A, or T) hormonal syste m s. Che m icals that go t h rough Tier 1 screening and are found to have the potential to int e ract with E, A, or T hor m onal syste m s will proceed to the next sta g e of

the EDSP where EPA will deter m ine which, if any, of t h e Tier 2 tests are neces s ary bas e d on the available data. Tier 2 testing is de signed to id e nti f y any adverse endocrine

- related ef f ectsSulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 12 of 28 caused b y the su b stance, and establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency m ust screen all pesticide che m icals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67

che m icals, which contains 58 pes t icide active ingredien t s and 9 inert ingredients. A second

list of ch e m icals identified for EDSP screening was published on June 14, 2013 1 

### and includes

so m e pesticides scheduled for Registration Review and che m icals found in water

. Neither of

these lists should be construed as a list of kno w n or likely endocrine disruptors.

For further info r m ation on the status of the EDSP, the policies and procedures, the li s ts of

c h e m icals, f

uture lists, the test g u ideli n es and the Tier 1 screening battery, please visit our

website 2



### .

5.0 Dietary Exposure and Risk Assessment

5.1 Water Residue Profile

Screening groundwater

- sourced drinking water exposure estimates were generated with the

Pesticide Root Zone Model for GroundWater ( PRZM

- GW; v.1.07) for use in the sulfonylurea (SU) dietary risk assessments. Rather than produce chemical

- specific estimated drinking water concentrations (EDWCs) following the usual assessment procedures, EFED provided co arse

screen estimates that should exceed upper

- bound, chemical

- specific EDWCs for any SU. This was achieved by using model inputs that represent the use pattern of highest exposure from any SU, the highest soil mobility of any SU residue of concern, and t he highest persistence to any route of degradation over time. The resulting coarse

- screen EDWCs from PRZM

- GW were used as conservative estimates of exposure and are summarized in Table 5.1

. ( D427429 ).

The chronic dietary assessment for sulfosulfuron used the post

- breakthrough mean EDWC value

of 492 μg/L (0.492 ppm )

.

Table 5.1. PRZM

- GW Coarse

- Screen EDWCs for Sulfonylureas 1

.

Modeled Scenario K d or K OC 2 Initial Application Dates (days post

emergence) Max. Daily Conc.

(μg/L) Mean

Breakthrough

Time (yrs) Post

breakthrough Mean (μg/L)

WI corn K d 7 449 11.5 415

K OC 7 504 6.9 425

DMV corn K d 7 489 5.3 369

K OC 7 560 3.3 378

FL citrus K d 7 429 3.2 351

K OC 7 467 2.3 349

1 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.

2 http://w ww.epa.gov/endo/Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 13 of 28 Table 5.1. PRZM

- GW Coarse

- Screen EDWCs for Sulfonylureas 1

.

Modeled Scenario K d or K OC 2 Initial Application Dates (days post

emergence) Max. Daily Conc.

(μg/L) Mean

Breakthrough

Time (yrs) Post

breakthrough Mean (μg/L)

FL potato K d 7 375 2.6 272

K OC 7 407 2.2 275

GA peanut K d 7 197 5.2 156

K OC 7 206 3.9 158

NC cotton K d 7 640 8.7 492

K d 37 641 8.7 491

K d 67 637 8.7 490

K OC 7 742 5.7 484

K OC 37 751 5.7 483

K OC 67 744 5.7 482

1 Maximum values are bold ed.

2 K d = soil

- water partition coefficient. K
oc = organic carbon

- water partition coefficient.



### 5.2 Food Residue Profile

Sulfosulfuron is registered for use on wheat and a tolerance has been established for residues

in /on wheat grain at 0.02 ppm. Sulfosulfuron tolerances have also been established for residues in ruminant tissue ranging from 0.005

- 0.3 ppm and in milk at 0.02 ppm. In conducting this assessment, HED has assumed tolerance

- level residues, DEEM default processing factors, and 100 percent crop treated.

5.3 Dietary Exposure and Risk Est imates

Exposure and risk estimates were obtained from the Dietary Exposure Evaluation Model using the Food Commodity Intake Database (DEEM

- FCID; version 3.18). The model uses food consumption data from the 2003

- 2008 NHANES/WWEIA database, coupled with re cipe files and residues in foods, to derive estimates of dietary exposure and risk. Generally, HED is concerned when dietary exposure estimates exceed 100% of the population adjusted dose (PAD). In the case of sulfosulfuron, the chronic dietary risk esti mates (Table 5.3) range from 3.2 to 11%
of the cPAD and are below HED’s level of concern (LOC = 100% cPAD ) . Because of the very conservative assumptions used in the analysis (tolerance level residues, 100 % crop treated, DEEM default processing factors, u pper

- bound modeled drinking water estimates), actual exposure and risk are expected to be much lower than those shown in Table 5.3

. The listings of inputs and outputs to the assessment are included in A ppendix B . HED did not conduct an acute dietary expo sure/risk assessment due to the lack of an endpoint appropriate for acute dietary

assessment. Based on the cancer classification, a cancer dietary risk assessment is not required.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 14 of 28 Table 5

. 3

. Summary of dietary exposure and risk estimates for s ulfosulfuron

. Acute Estimates Chronic Estimates

Population Group Exposure, mg/kg bw Risk,

% aPAD Exposure,

mg/kg bw/day Risk,

% cPAD Total US Population Not Applicable 0.0 10480 4.4 All Infants (< 1 year old) 0.0 26819 11

Children 1

- 2 years old 0.0 15834 6.6

Children 3

- 5 years old 0.0 13104 5.5

Children 6

- 12 years old 0.00 9366 3.9

Youth 13

- 19 years old 0.00 7671 3.2

Adults 20

- 49 years old 0.010387 4.3

Adults 50

- 99 years old 0.010260 4.3

Female 13

- 49 years old 0.010351 4.3



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

Sulfo sulfuron is registered for weed control in landscaped areas including highly managed

residential and commercial non

- crop turf sites such as apartment complexes, athletic fields, golf courses, hotel properties, parks, public turf areas, school grounds, sod and turfgrass seed farms

. Previous risk assessments did not identify a residential turf scenario ; however, it is evaluated in this assessment as a screening measure. Although the re gistered products are intended for professional and commercial applicators, they are not labeled as restricted

- use products ; hence

, homeowners may purchase and use these products on residential lawns, resulting in the potential for residential handler expo sure. However, a quantitative handler expo sure assessment is not applicable due to the absence of toxicity endpoints and associated PODs for residential dermal and inhalation routes of exposure.

Post

- application exposures are also expected for adults and children following use of

sulfo sulfuron on residential sites. These exposures include dermal exposures for adults and children, and incidental oral ( i.e., hand

- to

- mouth, object

- to

- mouth, and soil ingestion) exposure

for children. Because there is no hazard associated with dermal exposure, only incidental oral exposure has been evaluated for children. A series of assumptions and exposure factors served as the basis for completing the residential post

- application risk a ssessment. Each assumption,

fact or and algorithm used to estimate residential post

- application exposure and dose is detailed in

the 2012 Residential SOPs 3 

### . Table 6.0 presents the risk estimates for hand

- to

- mouth, objects

- to

mouth, and soil ingestion ; all of which yield MOEs greater than the LOC of 100, and therefore

are not of concern. T here are no post

- application risks of concern associate d with residential

uses of sulfo sulfuron

.

3 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.htmlSulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 15 of 28 Table 6.0. Residential Post

- application Non

- cancer Exposure and Risk Estimates for Sulfosulfuron.

Lifestage Post

- application

Exposure Scenario Application

Rate 1 Dose

(mg/kg/day) 2 MOEs 3

Use Site Route of Exposure

Child Turf Incidental oral

Hand to mouth

0.09 lb ai/A 0.00014 740,000

Incidental oral Object to mouth 0.0000083 12,000,000

Incidental oral Soil ingestion 0.0000030 33,000,000

1 Based on registered label (EPA Reg. No

. 524

- 534 ).

2 Dose (mg/kg/day) equations:
Hand

- to

- Mouth Dose = hand residue loading ( 0.000015 mg/cm 2 ) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm 2 ) × exposure time (1.5 hrs/day) × # of replenishment intervals/hr (4 int/hr) × (1

- ((1

- saliva extraction factor (0.5))^(Number of hand

- to

- mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (11 kg). Object

- to

- M

outh Dose = object residue loading ( 0.002 μg/cm 2 ) × unit conversion factor (0.001 mg/μg) × object surface area mouthed / event (10 cm 2 /event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1

- ((1

- saliva extraction factor (0.50)) ^(# Object

- to

- Mouth Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr)) ÷ body weight (11 kg). Soil Ingestion = soil residue ( 0.67 μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg).

TTR for solid application rate of 0.09 lb ai/A x 0.2% x (1

- 10%) 0 x conversion factor (ug/lb) x conversion factor (acre/cm 2 )= 0.002 μg/cm 2

. 3 Incidental Oral MOE = Oral NOAEL ( 100 mg/kg/day) ÷ Incidental oral Dose (mg/kg/day). Note: LOC is 100.



### In conjunction with the 2007 Part 158 Data Requirements, HED typically requires submission of a turf transferable residue (TTR) study in order to determine exposure and risk associated with children playing on treated turf. Since the estimated residential turf post

- application exposure

for residential turf using default TTR values for sulfosulfuron is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 10 times higher than the level of

concern, lowest MOE = 740,000 compared to the LOC of 100 ); EPA is waiving the 40CFR TTR data requirement. HED has reasonable certainty that no harm will result from this exposure since there is no toxicity associated with the dermal route of exposure to sulfo sulfuron , and

incidental oral risk estimates are minimal

. In this instance, it is unlikely that chemical

- specific TTR data would be needed to further refine exposure assessments or would add appreciably to

our general understanding of the availability of turf transferable pestici de residues (see Appendix F for further details)

.

6.1 Spray Drift

Off

- target movement of pesticides can occur via many types of pathways and it is governed by a variety of factors. Sprays that are released and do not deposit in the application area en d up off

target and can lead to exposures to those it may directly contact. They can also deposit on surfaces where contact with residues can eventually lead to indirect exposures ( e.g. children playing on lawns where residues have deposited next to treat ed fields). The potential risk estimates from these residues can be calculated using drift modeling coupled with methods employed for residential risk assessments for turf products.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 16 of 28 The approach to be used for quantitatively incorporating spray drift int o risk assessment is based on a premise of compliant applications which, by definition, should not result in direct exposures to individuals because of existing label language and other regulatory requirements intended to prevent them. 4 

### Direct exposures w ould include inhalation of the spray plume or being sprayed directly. Rather, the exposures addressed here are thought to occur indirectly through contact with impacted areas, such as residential lawns, when compliant applications are conducted.

Given th is premise, exposures for children (1 to 2 years old) and adults who have contact with turf where residues are assumed to have deposited via spray drift thus resulting in an indirect exposure are the focus of this analysis analogous to how exposures to tur f products are

considered in risk assessment.

EPA Reg. No. 524

- 534 is an existing label for use on turf, thus it was evaluated to determine whether the risk assessment for that use may be considered protective of any type of exposure

that would be assoc iated with spray drift. If the maximum application rate on crops, adjusted by the amount of drift expected, is less than or equal to existing turf application rates, the existing turf assessment is considered protective of spray drift exposure. For sulfo sulf uron, the registered residential uses on turf result in estimated exposure levels that are greater than the potential exposure from spray drift; therefore, no new residential assessment needs to be completed. The currently registered maximum single ap plication rate of sulfo sulfuron for all registered crops is

0. 09 lb ai/A

. The highest degree of spray drift noted for any application method immediately adjacent to a treated field (Tier 1 output from the aerial application using fine to medium spray qual ity) results in a deposition fraction of 0.26 of the application rate. A quantitative spray drift

assessment for sulfo sulfuron is not required because the maximum application rate to a crop/target site (i.e., 0.09 lb ai/A) multiplied by the adjustment fac tor for drift of 0.26 equals 0.023 lb ai/A, which is less than the maximum direct spray residential turf application rate of

0. 09 lb ai/A for any sulfo sulfuron product.

7.0 Aggregate Exposure/Risk Characterization

The Food Quality Protection Act of 1996 directs EPA to assess aggregate exposure to pesticide chemical residues, including all anticipated dietary exposures and all other exposures for which

there is reliable information. Toxicity e ndpoints for risk assessment through exposure via acute

and can cer dietary were not identified; therefore, quantitative aggregate risk assessments for these scenarios were not required. Additionally, no hazard via the dermal or inhalation route w as identified (for any duration). Chronic dietary exposure (food and wa ter) is expected for the U.S. population and all population subgroups and sho rt

- term aggregate exposure is expected for children resulting from short

- term incidental oral exposure (from residential turf) and d ietary exposure (food and water) . Intermediate

- and chronic

- term aggregate exposure is not expected for children resulting from incidental oral exposure based on the use pattern (30

- day application interval).

4 This approach is consistent with the requirements of the EPA’s Worker P rotection Standard which, when included on all labels, precludes direct exposure pathways.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 17 of 28 7

. 1 Short

- term Aggregate Risk

Due to the potential for post

- application exposure from lawn uses of sulfosulfuron, short

- term aggregate risks were assessed. The short

- term aggregate risk takes into account the exposure from potential residential sources in addition to average dietary residues from food and drinking

water. The short

- term ag gregate risk assessment was performed for children only, since non

dietary incidental oral exposure is not expected for other population subgroups (youth, adults).

As can be seen in Table 7.1 below, short

- term aggregate risk for children results in a MOE of
6, 300 and is, therefore, not of concern to HED , being greater than the LOC (100)

.

Table 7.1. Short

- Term Aggregate Risk Calculations.

Population Oral Exposure for Children Only

NOAEL (mg/kg/day) LOC 1 Max

Allowable Exposure 2 (mg/kg/day) Average

Food &

Water Exposure (mg/kg/day) Residential

Exposure 3 (mg/kg/day) Aggregate MOE

(food and residential) 4

Children, 1

- 2 years old 100 100 1.0 0.0 15834 0.00014 6 300

1 The LOC is 100, based on the standard 10X inter

- species and 10 X intra

- species UFs totaling 100.

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

. 3 Residential Exposure = [Oral Exposure]. Taken from the 2004 HED risk assessment ((DP # D304483, M. Clock

Rust , et al., 10/07/2004 ), Table 5, oral exposure.

4 Aggregate MOE = [NOAEL/ ( Avg

. Food & Water Exposure + Residential Exposure)]

.



### 7

. 2 Chronic Aggregate Risk

The chronic aggregate risk assessment considered exposure from food and water (chronic residential exposure is not anticipated); therefore, the screening

- level chronic dietar y exposure and risk analysis presented in Section 5.3 represents chronic aggregate risk for sulfosulfuron. As

can be seen in Table 5.3 , the DEEM

- FCID chronic exposure estimates were below the LOC (100% cPAD) f

or all populations subgroups, and n ot of concern to HED.

8.0 Cumulative Exposure/Risk Characterization

In 2015, EPA’s Office of Pesticide Programs released a guidance document entitled, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis [ http://www.epa.gov/oppfead1/cb/csb_pa ge/updates/2015/framework

- for

- screening

analysis.html ]. This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two

- step approach beginning with the evaluation of available toxicological information and if n ecessary, followed by a risk

- based screening approach. This framework supplements the existing guidance documents for establishing common mechanismSulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 18 of 28 groups (CMGs) 5 

### and conducting cumulative risk assessments (CRA) 6



### . The Agency has utilized

this framework t o evaluate the SUs of which sulfosulfuron is a member ( D428798). Although the SUs share some chemical and toxicological characteristics, the toxicological database does not support a testable hypothesis for a common mechanism of action. No further mechan istic data are required and no further cumulative evaluation is necessary.

The Agency is required to consider the cumulative risks of chemicals sharing a common mechanism of toxicity. The Agency has not determined that sulfosulfuron shares a common mechanism of toxicity with other chemical substances; therefore, a cumulative risk assessment to
support Registration Review is not required.

9.0 Occupational Exposure/Risk Characterization

Use of sulfo sulfuron for weed control in agri cultural, residential, commercial/industrial, and public areas will result in occupational handler and post

- application exposures

. However, there are no occupational handler or post

- application risks of concern associated with agricultural an d

non

- agricu ltural uses of sulfosulfuron based on the low toxicity. T he label

- specified PPE (i.e., long

- sleeved shirt, long pants and shoes with socks) is expected to provide adequate protection

for handlers. Post

- application exposures also are not of concern; worke rs may re

- enter treated areas after the Restricted Entry Interval (REI) of 12 hours base d on the acute toxicity of

sulfo sulfuron.

10.0 Public Health and Pesticide Epidemiology Data

An updated HED incident report was conducted in 2011 ( D387221 ) . Based on the low frequency and severity of incident cases, there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident

information.

11.0 Literature References

A literature search was conducted for sulfosulfuron . The TOXLINE (National Library of Medicine) database search did not identify any new toxicological information not already

considered.

5 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity (USEPA, 1999)

6 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity (USEPA, 2002)Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 19 of 28 1 2 .0 References

Author Barcode /

TXR# Date Title

Craig, E. TXR

0052986 5/7/ 20 15 Sulfonylurea Pesticides: Summary of Hazard

. and Science Policy Council (HASPOC) Meeting on April 2, 2015: Recommendations on Data Requirement for Subchronic

Inhalation Studies. Cropp

- Kohlligian, B. D 427730 9/1 6 /2015 Sulfosulfuron. Re

- evaluation of Enforcement Methods

and Livestock Tolerances

. D’Agostino, J. D428798 9/9/2015 Sulfonylureas: Screening Analysis of Toxicological

Profiles to Consider Whether a Candidate Common Mechanism Group Can Be Established.
Daiss, B. D385545 6/7/2011 Sulfosulfuron: Human Health Risk Scoping Document in Support of Registration Review.
Daiss, B. D394271 10/18/2011 Sulfosulfuron: Response to Comments on the Human Health Risk Scoping Document in Support of Registration

Review.
Khasawinah, A. TXR

0056762 8/16/13 Sulfosulfuron: Response to GDCI

- 085601

- 1061 regarding Immunotoxicity study waiver request Knizner, S. None 5/27/2009 HED Interim Guidance on Tolerance Expressions Levy , S., et al. D34970 2 2/28/2008 AMENDMENT TO: Sulfosulfuron

. PP#6F7031. Human Health Risk Assessment for Proposed Uses of the Herbicide Sulfosulfuron on Grass Forage, Fodder and Hay (Crop Group 17), Forestry Conifer Release and Non

- crop Areas. DP#: 327363

. Oo, K. D 387221 3/1/2011 Sulfosulfuron : Review of Human Incidents.
Orrick, G. D 427429 8/12/2015 Drinking Water Exposure Assessment for the Registration Review of 22 Sulfonylurea Herbicides. Rury, K. TXR

0056723 8/6/13 Sulfonylureas: Summary of Hazard and Science Policy

Council (HASPOC) Meeting on July 18,2013 : Recommendations on Data Requirement for Immunotoxicity Studies for Sulfonylurea Pesticides

.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 20 of 28 A ppendix A

. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The toxicology requirements (40 CFR 158.340) for the sulfosulfuron food use are shown below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Test Technical Required Satisfied 870.1100 Acute Oral Toxicity 870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity 870.2400 Primary Eye Irritation 870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes 870.3100 Oral Subchronic (rodent) 870.3150 Oral Subchronic (non

- rodent)

870.3200 21

- Day Dermal

870.3250 90

- Day Dermal

870.3465 90

- Day Inhalation yes

yes

yes

no CR yes

yes

yes

- waived 1
870.3700a Developmental Toxicity (rodent) 870.3700b Developmental Toxicity (non

- rodent) 870.3800 Reproduction yes

yes

yes yes

yes

yes 870.4100a Chronic Toxicity (rodent) 870.4100b Chronic Toxicity (non

- rodent) 870.4200a Oncogenicity (rat) 870.4200b Oncogenicity (mouse) 870.4300 Chronic/Oncogenicity yes

yes

- yes

yes yes

yes

- yes

yes
870.5100 Mutagenicity

- Gene Mutation

- bacterial 870.5300 Mutagenicity

- Gene Mutation

- mammalian 870.5xxx Mutagenicity

- Structural Chromosomal A berrations 870.5xxx Mutagenicity

— Other Genotoxic Effects yes

yes

yes

yes yes

yes

yes

yes
870.6100a Acute Delayed Neurotox. (hen)

870.6100b 90

- Day Neurotoxicity (hen)

870.6200a Acute Neurotox. Screening Battery (rat)

870.6200b 90

- Day Neuro. Screening Battery (rat) 870.6300 Develop. Neuro no

no

yes

no

no -

- yes

yes

- 870.7485 General Metabolism

870.7600 Dermal Penetration 870.7800 Immunotoxicity yes

no

yes yes

- waived 2
Special Studies for Ocular Effects Acute Oral (rat) Subchronic Oral (rat)

Six

- month Oral (dog) no

no

no -

-

-

1 The requirement for this study has been waived (TXR 0052986 )

2 The requirement for this study has been waived (TXR 0056723 and TXR 0056762 )Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 21 of 28 A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile

– Sulfosulfuron.

Guideline

No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral rat 44295737 (1993) LD 50 >5,000 mg/kg IV

870.1200 Acute dermal rat 44295739 (1993) LD 50 >5,000 mg/kg III

870.1300 Acute inhalation rat 44295745 (1994) No mortality at 3.0 mg/L IV

870.2400 Acute eye irritation rabbit 44295741 (1993) Moderately irritating III

870.2500 Acute dermal irritation rabbit 44295743 (1993) Not an irritant IV

870.2600 Skin sensitization guinea pig 44295747 (1993) Not a sensitizer N/A

Table A.2.2. Subchronic, Chronic and Other Toxicity Profile

– Sulfosulfuron.

Guideline

No. Study Type MRID No. (year)/

Classification /Doses Results

870.3100 90

- Day oral

toxicity rat (with

1

- generation reproduction

range

- finding study) 44295750 (1995)

Acceptable/guideline 0, 20, 200, 2000, 6000 or 20000 ppm M: 0, 1.2, 12.1, 123.2,

370.3 or 1277.5 mg/kg/d F: 0, 1.5, 14.6, 144.3, 447.5 or 1489.1 mg/kg/d NOAEL = 370.3 mg/kg/day

LOAEL = 1277.5 mg/kg/day based on decreased body weight/weight gain in males, possible decreased weight gain in pregnant females during gestation days 14

- 21, and possible renal lesions related to formation of

calculi.

870.3150 90

- Day oral

toxicity dog 44295751 (1996)

Acceptable/guideline 0, 30, 100, 300 or 1000 mg/kg/d NOAEL = 100 mg/kg/day

LOAEL = 300 mg/kg/day based on lesions in the urinary bladder in females occurring subsequent to urinary formation/urolithiasis and on abnormal urinary crystals in males and

females.

870.3200 21/28

- Day

dermal toxicity

rat 44295752 (1994)

Acceptable/guideline 0, 100, 300 or 1000 mg/kg/d ; 5d/wk for 4 wks NOAEL > 1000 mg/kg/day

LOAEL was not determined.

870.3700a Prenatal

developmental in

rat 44295756 (199 7 )

Acceptable/guideline 0, 100, 300 or 1000 mg/kg/d; days 6

- 15. Maternal NOAEL > 1000 mg/kg/day

LOAEL was not determined. Developmental NOAEL > 1000 mg/kg/day

LOAEL was not determined.

870.3700b Prenatal

developmental in

rabbit 44295757 ( 1994)

Acceptable/guideline 0, 50, 250 or 1000 mg/kg/d; days 7

- 19. Maternal NOAEL > 1000 mg/kg/day

LOAEL was not determined. Developmental NOAEL > 1000 mg/kg/day

LOAEL was not determined.

870.3800 Reproduction

and fertility

effects

rat 44295758 (1996)

Acceptable/guideline 0, 50, 500, 5000 or 20,000

ppm M (P): 0, 31.6, 312.1 and 1318.2 mg/kg/d F (P): 0, 3.6, 36.2, 363.2 or 1454.1 mg/kg/d M (F1a): 0, 3.1, 31.1, 315.8 and 1378.8 mg/kg/d F (F1a): 0, 3.7, 37.7, 377.8 and 1598.o mg/kg/d Parental/Systemic NOAEL = 312.8 mg/kg/day

LOAEL = 1312.8 mg/kg/day based on decreased parental body weight gain during
premat ing, gestation and lactation. Reproductive NOAEL ≥1312.8 mg/kg/day

LOAEL ≥1312.8 mg/kg/day Offspring NOAEL = 312.1 mg/kg/day

LOAEL = 1312.8 mg/kg/day based on decreased body weight gain in post

- weaning

adolescent rats.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 22 of 28 Table A.2.2. Subchronic, Chronic and Other Toxicity Profile

– Sulfosulfuron.

Guideline

No. Study Type MRID No. (year)/

Classification /Doses Results

870.4100b Chronic toxicity

dog 44 295754 (1997)

Acceptable/guideline 0, 5, 20, 100 or 500 mg/kg / d NOAEL = 100 mg/kg/day

LOAEL = 500 mg/kg/day based on the presence of abnormal urinary crystals and bladder pathology secondary to formation of urinary tract calculi in males.

870.4200 Carcinogenicity

rat 44295759 (1997)

Acceptable/guideline 0, 50, 500, 5000 or 20000

ppm M: 0, 2.4, 24.4, 244.2 or 1178.3 mg/kg/d (20000 ppm male group terminated at day 259 due to excessive mortality) F: 0, 3.1, 30.4, 314.1 or 1296.5 mg/kg/d NOAEL = 24.4 mg/kg/day

LOAEL = 244.2 mg/kg/day based on increased incidence of urinary tract gross/microscopic lesions, mineralization in several tissues (males), abnormal urine crystals and possible albumin (males, termination). At the high dose, urinary bladd er transitional cell carcinoma and papilloma were observed in females (1/50 each vs. 0/controls) and were considered treatment

related.

870.4300 Carcinogenicity

mouse 44295755 (1997)

Acceptable/guideline 0, 30, 700, 3000 or 7000

ppm M: 0, 4.0, 93.4, 393.6 or 943.5 mg/kg/d F: 0, 6.5, 153.0, 634.9 or 1388.2 mg/kg/d NOAEL (M) = 93.4 mg/kg/day

LOAEL (M) = 393.6 mg/kg/day based on gross and microscopic effects related to urinary calculus formation in the urinary bladder of

males. The incidence of benign m esenchymal tumors of the urinary bladder was increased in males in the high dose (5/60) compared to controls (0/60).

Gene

Mutation

870.5100 Salmonella

typhimurium; E.

coli ) / mammalian activation gene mutation assay 44295760 (1995)

Acceptable/guideline 312, 624, 1250, 2500 or

5000 μ g/mL Negative for inducing reverse gene mutations with Salmonella typhimurium strains TA1535, TA1537, TA98, TA 100 or TA1O2 exposed in either the presence or absence of mammalian metabolic activation at doses up to 5,000

μg /p late. Cytotoxicity observed at ≥ 1,500

μg /plate. Cytogenetics

870.5300 In Vitro

mammalian cells in culture gene mutation assay in

Chinese hamster ovary cells 44295761 (1996 )

Acceptable/guideline

624

- 5000 μg /mL Negative for inducing forward gene mutations at the HGPRT locus in Chinese hamster ovary (CHO) cells exposed in either the presence or absence of S9 activation up to 5,000 μg /mL. Doses caused cytotoxicity at 5,000 μg /mL in

the absence of S9 but not in the presence of S9; however, MON 37500 was insoluble at or above 2,500 μg /mL.

Other Effects

870.5375 In vitro

mammalian

chromosome

aberration 44280201 (1996)

Acceptable/guideline 1000, 1250, 2000, 2500,

3000 or 5000 μg /mL Positive under non

- activated conditions; however, precipitation occurred Negative under activated conditions.

Other Effects

870.5375 In vitro

mammalian

chromosome

aberration 44295762 (1996)

Acceptable/guideline 100, 250, 500, 750 or

1000 μg /mL Negative for inducing structural chromosome damage in Cultured Human Lymphocytes exposed at levels up to 1,000 μg /mL in either the presence or absence of S9 and harvested either at 18 or 42 hrs post

- treatment. Cytotoxicity (decreased mitotic indices) were observed at 1,000 μg /mL with and without S9. MON 37500 was precipitated at 1,000 μg /mL.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 23 of 28 Table A.2.2. Subchronic, Chronic and Other Toxicity Profile

– Sulfosulfuron.

Guideline

No. Study Type MRID No. (year)/

Classification /Doses Results

Other Effects

870.5395 In vitro

mammalian

micronucleus

assay 44295763, 4429564

(1995) Acceptable/guideline 0, 1250, 2500 or 5000 mg/mL Negative for inducing micronu clei in polychromatic erythrocytes from male or

female CD

- 1 mice at dose levels up to 5,000 mg/kg. Although no indication of cytotoxicity was observed, a pharmacokinetic study

demonstrated that MON 37500 reached the

bone marrow in male CD

- 1 mice at 2 and 8 hrs following an oral gavage dose of 2.000 mg/kg.

870.6200a Acute

neurotoxicity screening battery 44295749 (1997)

Acceptable/guideline 0, 125, 500 or 2000 mg/kg/d NOAEL > 2000 mg/kg/day LOAEL > 2000 mg/kg/day.

870.6200b Subchronic

neurotoxicity screening battery 44295753 (1997)

Acceptable/guideline 0, 200, 2000 or 20000

ppm M: 0, 12, 122 or 1211 mg/kg/d F: 0, 14, 141 or 1467 mg/kg/d NOAEL = 1211 mg/kg/day LOAEL > 1211 mg/kg/day.

870.7485 Metabolism and

pharmacokinetics

rat 44295765 (1996 )

Acceptable/guideline Single oral dose of 10 or 1000 mg/kg Repeated oral dose of 10 mg/kg (14 doses, followed by 1 unlabeled dose) Single iv dose of 10 mg/kg 90% of radioactivity excreted over 72 hrs.

Between 77

- 87% excreted in the urine, 5

- 13% in the feces at low dose. At high dose, 55

- 63%

excreted in the feces and 32

- 33% excreted in the urine. Biliary excretion accounted for 5

- 9% of an iv dose. Urinary exc retion followed a biexponential pattern with half

- life of 2.2

- 5.8 hrs initial phase and 21.4

- 56.7 hrs terminal phase. Minimal radioactivity was retained in the tissues (>0.07%). Expiration of 14 CO 2 was insignificant. Parent was excreted mostly unchanged . Metabolism occurred via ring hydroxylation or demethylation. Major metabolites were desmethyl MON 37500 (3.5%), 5

- hydroxy MON 37500 (1.9%), and sulfonamide (2.9%). Other minor metabolites were also present.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 24 of 28 Appendix B

. Dietary Exposure/Risk Mode ling Input and Output

Filename: S ulfosulfuron \ 085601 \ Chronic.R08

Chemical: Sulfosulfuron RfD(Chronic): .24 mg/kg bw/day NOEL(Chronic): 0 mg/kg bw/day RfD(Acute): 0 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day
Date created/last modified: 02

- 05

- 2015/13:58:05 Program ver. 3.16, 03

- 08

- d

----------------------------------------------------------------------------------- EPA Crop Def Res Adj.Factors Comment Code Grp Commodity Name (pp m) #1 #2

---------- ---- ------------------------------- ---------- ------ ------ ------- 1500381000 15 Triticale, flour 0.020000 1.000 1.000
1500381001 15 Triticale, flour

- babyfood 0.020000 1.000 1.000 1500401000 15 Wheat, grain 0.020000 1.000 1.000 1500401001 15 Wheat, grain

- babyfood 0.020000 1.000 1.000
1500402000 15 Wheat, flour 0.020000 1.000 1.000
1500402001 15 Wheat, flour

- babyfood 0.020000 1.000 1.000 1500403000 15 Wheat, germ 0.020000 1.000 1.000
1500404000 15 Wheat, bran 0.020000 1.000 1.000
3100044000 31 Beef, meat 0.010000 1.000 1.000
3100044001 31 Beef, meat

- babyfood 0.010000 1.000 1.000 3100045000 31 Beef, meat, dried 0.010000 1.920 1.000 3100046000 31 Beef, meat byproducts 0.300000 1.000 1.0 00 3100046001 31 Beef, meat byproducts

- babyfood 0.300000 1.000 1.000
3100047000 31 Beef, fat 0.020000 1.000 1.000
3100047001 31 Beef, fat

- babyfood 0.020000 1.000 1.000

3100048000 31 Beef , kidney 0.300000 1.000 1.000
3100049000 31 Beef, liver 0.300000 1.000 1.000 3100049001 31 Beef, liver

- babyfood 0.300000 1.000 1.000
3200169000 32 Goat, meat 0.010000 1.000 1.000 3200170000 32 Goat, meat byproducts 0.300000 1.000 1.000
3200171000 32 Goat, fat 0.020000 1.000 1.000 3200172000 32 Goat, kidney 0.300000 1.000 1.000
3200173000 32 Goat, liver 0.300000 1.000 1.000
3300189000 33 Horse, meat 0.010000 1.000 1.000
3400290000 34 Pork, mea t 0.005000 1.000 1.000
3400290001 34 Pork, meat

- babyfood 0.005000 1.000 1.000
3400291000 34 Pork, skin 0.005000 1.000 1.000 3400292000 34 Pork, meat byproducts 0.050000 1.000 1.000 3400292001 34 Pork, meat byproducts

- babyfood 0.050000 1.000 1.000
3400293000 34 Pork, fat 0.005000 1.000 1.000
3400293001 34 Pork, fat

- babyfood 0.005000 1.000 1.000 3400294000 34 Pork, kidney 0.050000 1.000 1.000
3400295000 34 Pork, liver 0.050000 1.000 1.000 3500339000 35 Sheep, meat 0.010000 1.000 1.000 3500339001 35 Sheep, meat

- babyfood 0.010000 1.000 1.000 3500340000 35 Sheep, meat byproducts 0.300000 1.000 1.000 3500341000 35 Sheep, fat 0.020000 1.000 1.000 3500341001 35 Sheep, fat

- babyfood 0.020000 1.000 1.000 3500342000 35 Sheep, kidney 0.300000 1.000 1.000 3500343000 35 Sheep, liver 0.300000 1.000 1.000 3600222000 36 Milk, fat 0.020000 1.000 1.00 0
3600222001 36 Milk, fat

- baby food/infant formu 0.020000 1.000 1.000
3600223000 36 Milk, nonfat solids 0.020000 1.000 1.000
3600223001 36 Milk, nonfat solids

- baby food/in 0.020000 1.000 1.000
3600224000 36 Milk, water 0.020000 1.000 1.000
3600224001 36 Milk, water

- babyfood/infant form 0.020000 1.000 1.000 3600225001 36 Milk, sugar (lactose)

- baby food/ 0.020000 1.000 1.000
3800221000 38 Meat, game 0.010000 1.000 1.000 3900312000 39 Rabbit, meat 0.010000 1.000 1.000
8601000000 86A Water, direct, all sources 0.492000 1.000 1.000 8602000000 86B Water, indirect, all sources 0.492000 1.000 1.000Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 25 of 28 US EPA Ver. 3.16, 03

- 08

- d

DEEM

- FCID Chronic analysis for SULFOSULFURON NHANES 2003

- 2008 2

- day

Residue fil e name: Sulfosulfuron \ 085601 \ Chronic.R08 Adjustment factor #2 used. Analysis Date 04

- 13

- 2015/14:10:52 Residue file dated: 04

- 13

- 2015/13:21:15 Reference dose (RfD, Chronic) = .24 mg/kg bw/day

======== ======================================================================= Total exposure by population subgroup

-------------------------------------------------------------------------------

Total Exposure

----------------------------------- Population mg/kg Percent of Subgroup body wt/day Rfd

--- ----------------------------------- ------------- ---------------- Total US Population 0.010480 4.4% Hispanic 0.010052 4.2%

Non

- Hisp

- White 0.010772 4.5%

Non

- Hisp

- Black 0.008649 3.6%

Non

- Hisp

- Other 0.012056 5.0% Nursing Infants 0.009405 3.9%

Non

- Nursing Infants 0.034596 14.4%

Female 13+ PREG 0.009841 4.1%

Children 1

- 6 0.013898 5.8%

Children 7

- 12 0.008901 3.7%

Male 13

- 19 0.007261 3.0%

Female 13

- 19/NP 0.008074 3.4%

Male 20+ 0.009707 4.0% Female 20+/NP 0.010919 4.5%

Seniors 55+ 0.010061 4.2%

All Infants 0.026819 11.2%

Female 13

- 50 0.010362 4.3%

Children 1

- 2 0.015834 6.6%

Children 3

- 5 0.013104 5.5%

Children 6

- 12 0.009366 3.9%

Youth 13

- 19 0.007671 3.2%

Adults 20

- 49 0.010387 4.3%

Adults 50

- 99 0.010260 4.3%

Female 13

- 49 0.010351 4.3%

-------------------------------------------------------------------------------Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 26 of 28 Appendix C

. Nomenclature and Physical/Chemical Properties

Table C .1. Sulfosulfuron Nomenclature

Chemical structure

Common name Sulfosulfuron

Company experimental name MON 37500; TKM

- 19

IUPAC name 1

- (4,6

- dimethoxypyrimidin

- 2

- yl)

- 3

- (2

- ethylsulfonylimidazo[1,2

- a ]pyridin

- 3

- ylsulfonyl)urea

CAS name N

- [[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]

- 2

- (ethylsulfonyl)imidazo[1,2

-

a ]pyridine

- 3

- sulfonamide

CAS registry number 141776

- 32

- 1

Chemical structure of ethyl sulfone chemophore

2

- (ethylsulfonyl)

- imidazo [1,2

- a ]pyridine

Table C

. 2. Physicochemical Properties of Sulfosulfuron.

Parameter Value Reference

Melting range 180.9

- 184.1oC MRID 44295704; Memo, S. Chun, 28

- SEP

- 1998; D P#:

237683 pH 4.76

Density 1.55 g/mL at 20oC

Water solubility ppm at 20oC pH 5 17.60 ± 2.71 pH 7 1626.8 ± 39.8 pH 9 482.44 ± 8.35

Solvent solubility ppm at 20oC Heptane <1 Xylene 160

Methanol 330 Ethyl acetate 1010

Dichloroethane 4350

Vapor pressure 2.29 x 10

- 10 mm Hg at 20oC

6.61 x 10

- 10 mm Hg at 25oC

Dissociation constant, pK
a pK
a = 3.51 at 20oC

Octanol/water partition coefficient, Log (K OW ) pH 5: K OW = 6.38; pK OW = 0.81 pH 7: K OW = 0.14; pK OW =

- 1.01 pH 9: K OW = 0.036; pK OW =

- 1.37

UV/visible absorption spectrum UV MAX = 208 nm ε = 187,150 L/mol cm (pH >10.0, 1.06% by weight in water, 26oC)Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 27 of 28 Appendix D

. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. For certain studies that review may have included review by the Human Studies Review Board. Descriptions of data sources as well as guidance on their use can be found a t : http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pe sticides/science/post

- app

- exposure

- data.html

.

Appendix E

. Submittal of Analytical Reference Standards (860.1650)

An analytical reference standard for su lfosulfuron is currently available in EPA’s National Pesticide Standards Repository (NPSR) and ha s an expiration date of 4/30/2016 ; however, an analytical reference standard for the ethyl sulfone chemoph o re metabolite is not currently available (e mail communication between T. Cole and B. Cropp

- Kohlligian, 5/8/2015) and must

be submitted . The registra nt is required to maintain reasonable amounts of the reference

standards for sulfosulfuron and its ethyl sulfone chemophore metabolite i n the NPSR as long as tolerances remain published in 40 CFR §180. 552

. When necessary, new reference standards, or updat ed certificates of analysis (COAs), should be sent to the Analytical Chemistry Branch (ACB), which is located at Fort Meade, MD. It should be sent to the attention of either Theresa Cole or Thuy Nguyen at the address listed below, alon g with a letter of t ransmittal. Please note

that the full 9

- digit ZIP Code is required, or the mail will be returned to the registrant.

USEPA National Pesticide Standards Repository Analytical Chemistry Branch/BEAD/OPP 701 Mapes Road Fort George G. Meade, MD 20755

- 5350

The letter of transmittal should include the assay of the standard, name of the analytical metho d used, a statement of principal impurities, purification procedures employed, storage requirements, and special precautions for safe handling. Replacement of standards, or updated COAs, may be required periodically if supplies are exhausted, if the stand ards expire, or if decomp osition occurs during storage. Material Safety Data Sheets (MSDSs) must accompany all analytical standards as specified by the Occupational Safety and Health Administration (OSHA) in 29CFR §1910.1200.Sulfosulfuron (085601) Draft Human Health Risk Assessment DP#: 427399



### Page 28 of 28 Appendix F. TTR Data Wai ver Criteria

Turf Transferrable Residue (TTR) : In accordance with 40CFR158, TTR data are required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses that could result in post

- application exposure to turf. In the absence of chemical

- specific TTR data, EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of all TTR data, available at the time, which resulted in the selection of revised liquid and granular default values for the fraction of the application rate available for transfer after a turf application (FAR). These values are based on an analysis of 59 TTR studies performed with the Modified California Roller Method (36 studies using liquids, 11 studies using wetta ble powders/water dispersible granules, and 12 studies using granules). The liquid results (N=131) indicate a range of FAR values from 0.0005% to 6.1% and the granular results (N=37) indicate a range of 0.00064% to 0.69%. In both the liquid and granular data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in FAR values is not expected when considering TTR data for a single chemical. HED selected 1% and 0.2% as high

- end default values for liquid and granular products, respectively

. Because TTR data are not available for sulfosulfuron

, EPA is using the default value of 0.2% f or the granular product. Although there may be a small degree of uncertainty in the use of the default TTR value for sulfosulfuron (i.e., there is a small

cha nce that the FAR value may exceed the applicable default value), it is likely that the health

protective aspects of EPA’s residential post

- application turf assessment methodology will more than compensate for this potential uncertainty (i.e., the methodol ogy is likely to overestimate exposure by a factor greater than the factor than the highest measured FAR values exceed the defaults ). For example, when assessing residential post

- application turf exposure, EPA assumes the following: exposures occur to zero

- day (i.e., day of application ) residues every day of the assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, the grass is not mowed, etc); individuals perform the same post

- application

activities performed in the turf transfer coefficient study day after day (e.g., tumbling, playing on turf with toys, etc.); and individuals engage in these post

- application activities for a high

- end amount of time every day that is represented by data reflecting ti me children spend outdoors and not specifically engaged in activities on turf, when in actuality children do not spend all of their outdoor time on turf and high

- end levels of activity will not occur every day.

Given the conservatisms discussed above a nd the potential compounding nature of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated.

Since the estimated residential turf post

- application exposure for residential turf using default

TTR values for sulfosulfuron is minimal in comparison to the level of concern (i.e., the

calculated lowest MOE is greater than 10 times higher than the level of concern, MOE = 740,000 compared to the LOC of 100 ); EPA is waiving the 40CF R TTR data requirement. In this instance, it is unlikely that chemical

- specific TTR data would be needed to further refine exposure assessments or would add appreciably to our general understanding of the availability

of turf tran sferable pesticide residu es.