### UNITED STATES ENVIRONMENTAL PROTECTION AGENC Y WASHINGTON

, D .C. 20460

OF FI CE OF C HEM I CAL SAFE T Y A N D POLL U T I ON PREVE N T I O N



### MEMORANDUM

Date : 

### 14- SEP-20 1 5



### SU B J ECT: C hl ors ul furo n

. Draft Human I l ealth Ri sk Assessme n t i n Suppo r t of R eg istrati on Review.

PC Code: 11860 1 DP Barcode: 04 25536
Decision No.: 499856 Registration No s.: Various
Petition No.: None Regulatory Action: Registration Review
Assessment Type: Single Chemical Aggregate Reregi s tration Case No.: 7265 -1
TXR No.: No n e C AS No.: 64902-72

- 3
MRID No.: None 40 CFR: § 

### 180.405



### FROM: Julie Van Als

. tine, M.P.H., E n v ir onmen t al H ea lth Sc i ent i st 

# Q}O-

# ~ . I/ .1.

Monica H awkins

, Ph.D.

, M.P.H.

,

# Envi}~mental Health Scientist 

# IY{_**~ ~**  Yung Yang, Ph.D.

, Toxicologist

## ~7 

# G.**~u ·**  Risk Assessme nt Branch VI (RAB V I )

Hea l th Effects Di vision (HE D ; 7509P)



### T H RO UG H: D onna Davis

, Ac ting Branch

# Chief~**t~_.._ ~~** **~--"-.C.,...--**

TO: RAB VJ!HED (7509P)

Kelley Sherman/Miguel Zavala

Risk Management a nd I mplementati o n Branch JII 

### ( RMIB 

### W )

Pesticide Re- evaluation Division ( PRD ; 7508P)

As part of Registration Review, PRD of the Office of Pe s ticide Programs (O PP ) h as r equested
that HED evaluate the hazard and exposure data and conduct occupationa l and resid e ntial

exposu r e assess ments

, as ne e ded

, to estimate th e ri sk to human health that wi ll r esu lt from the currencly registered uses of pesticides. Thi s do c um e nt eva lu ates the existi n g u ses of

ch lor s ulfuron as part of Registration Review and repre sents the draft risk assessment (ORA).
The Agency i s reviewing all the su lfonylurea herbicide s joint l y u nder Regi s tration Revi ew.

S inc e the l as t human he a l th r isk assessment (F. Fort 

### et al., I 8- J UL-2002; 0266070) and scoping

document (M. Hawkins 

### e t al., 6-0EC-2012; 0403355)

, the follow in g upd ates h ave bee n in co rp orated for chlorsulfuron:



### • The toxi co logical endpoints and points of d e

parture (PODs) w e re r ee valuated considering the new toxicolo gy data that hav e been submilled s ince the last risk

assessment.

• The occupational risk assessment has been updated to incorporate new science polici es

.

• A spray drift ass es sm e nt was completed as part of R eg istration Review

• A r efi n e d

- screen estimated drinking water concentration (EDWC) was u sed t o assess chlorsu/.furon di e tar y exposure and risk.

Pag e I of30

### Chlorsulfuron Human Health Risk Assessment 0425536



### Tab l e of Contents

I .0 

### Executive Summary

........ . .......... ......... ... . ......... .. ............... ... ... . ......... .. ......... .. ......... . ................. 3


## 2.0 HED Reco1nn1endations

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

2.1 

### Tolerances Conside rati o n s

......................................................................................................... 4
3.0 

### In gredien t Profile

...................................................................................................................... 4
3. 1 

### C h e mi ca l I dentity and Physical / Chemical Properties

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


### 3.2 

### Use P attern

..................................................................................... . ................ .. ................ .. ....... 5
3.3 

### Anticipated Exposure Pathways

................................................................. . .... ......... ... .. ............. 6
3.4 Cons id eratio n of Env i ro nmental Justice

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

4.0 

### Hazard I dentification/Toxicology

. ... . .......... ... .. .. ............... .. .............. . ....................................... 6
4.1 

### Summary of Toxicological Effect s

............................................................................................. 7
4.2 Safety Factor for Infants and Children (FQPA SF)

................................... .. ............... .. .............. 7 4.3 Toxic it y Endpoint and P o int of D epa rtur e Selections

.......................... . ..................................... 7 4.4 E nd ocr in e Disruption

.... . ........... . ................................................................................................ 8
5.0 

### Dietary Exposure a nd Risk Assessment

................................................................................... 9
5. I Residue Chem i s try

.. .. ................................................................................................................. 9 5.2 Drinking Water.

........................................................................................................................ I 0 5.3 Dietary (Food + Drinking Water) Risk Asses s m en t

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


### 6.0 

### Residential (Non-Occupational) Exposure and Risk Assessment

.......................................... I I
6.1 

### Spray Drift

........................................................................................................ ... ... .......... . I I

6.1.1 

### Combined Risk Estimates from Lawn Deposition Adjace nt to Applications

.......... 11


### 6.2 

### Re s idential Bystander Post-Application Inh a lati on Exposure

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


### 7.0 Aggregate Exposure and Risk Assess ment

.. .......... .. .. .. ........................................................... 1 2

8.0 

### C umul at i ve Exposure / Risk C h aracte ri zation

.......................................................................... I 3
9.0 

### Occupational Exposure / Ri sk Characterization

....................................................................... 13
9.1 

### Occupational Handler Exposure / Risk Estimates

...................................................................... 1 3 

### 9.2 Occupationa l Post-Application Exp0sure/ Ri sk Estimates

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

### 9.2. I Occupa ti onal Post-application Inh alation Expos ur e / Risk Estimates

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


### 1 0.0 

### Public Health

, Pesticide Epidemiology, and Human Incidence Data

.................................. I 7
I 1.0 

### References

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

### Appendix A. Toxicology Profile T ables

...................................................................................... I 9 Appendix 8. 

### Chemical Identity

................................................................................................... 23 Append i x C. 

### Analytical Standards for Chlorsulfuron

.................................. . .. ......... .. .... .............. 24 Appendix D. Dietary Exposure / Ri sk Modeling I nput and Output Files

...................................... 25 Appendix E. Occupational Non-cance r Algorithms

.................................................................... 27 Appe ndix F

. Spray Drift Detailed Description

............................................................................. 29 Appendix G. DFR Data Waiver Rationale

.. ................................................................................ 30 

### Appendix H. Review of H uman Research

................................................................................... 30

Page 2 of30Chlorsulfuron Human Health Risk Assessment D425536

Page 3 of 30 

### 1.0 Executive Summary

Chlorsulfuron is a sulfonylurea herbicide that is used to control broadleaf weeds on a variety of agricultural crops. It is currently registered for use on barley, grasses grown for seed, oats, pastures, and rangeland, rights

- of

- way, triticale, w heat, and industrial and commercial turf. This document addresses exposures and risk estimates from the r egistered uses of chlorsulfuron using

worst

- case exposure scenarios (e.g., highest application rates and highest exposure scenarios).

The toxicity da tabase for chlorsulfuron is adequate to support current registration requirements; currently, no additional toxicological studies are required. T he Hazard and Science Policy Council (HASPOC) waived the requirement for the 21

- day dermal toxicity, subchronic inhalation, immunotoxicity, and neurotoxicity (acute and subchronic) studies for chlorsulfuron (TXR# 00 56439 , TXR# 0056723 ). A rat two

- generation reproduction study was submitted since the last risk assessment (D266070, F. Fort). The toxicologi cal endpoints and P ODs were reevaluated considering the new toxicology data. All of the endpoints for risk assessment remain the same as those used in the previous assessment.

The existing residue chemistry database for chlorsulfuron is complete and ad equate for risk assessment purposes. No additional residue chemistry data are required at this time.

HED has conducted a chronic dietary exposure and risk assessment for chlorsulfuron using
tolerance

- level residues in foods and EDWCs provided by the Environmental Fate and Effects Division (EFED). C hronic dietary exposure and risk estimates (food and drinking water) are ≤14% of the chronic population adjusted dose (cPAD) and are not of concern for the general
U.S. population or any other population su bgroup

. HED did not co nduct an acute dietary exposure and risk assessment due to the lack of an appropriate endpoint for acute dietary

asse ssment. Chlorsulfuron is classified as “not likely to be carcinogenic to humans”; t herefore,
cancer risk is not a concern

.

There are no registered residential uses or uses resulting in direct residential expos ure associated
with chlorsulfuron . Therefore, residential handler and conventional residential post

- application exposure assessments were not conducte d . A qua ntitative spray drift assessment was conducted to assess indirect exposure in residential settings . Risk estimates from groundboom and aerial applications are not of concern from the field edge for all scenarios considered. D uring Registration Review, th e A gency will use the Volatilization Screening Analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analys is is required for chlorsulfuron.

For chlorsulfuron, aggregate exposure and risk estimates are equivalent to the dietary exposure
and risk estimates ; therefore, aggregate risks are not of concern.

The occupational handler exposure estimates based on the scenario with the highest application
rate and amount handled result in short

- and interme diate

- term dermal and inhalation margins of exposure ( MOEs ) that range from 360 to 40,000 and are not of concern to HED (i.e., MOEs ≥ the level of concern (LOC) of 100). Occupational post

- application exposure estimates result in
dermal MOEs that range fro m 2,300 to 190,000 and are not of concern to HED on the day of application (i.e., MOE s ≥ LOC )

. Based on the Agency’ s current practices, a quantitative non

cancer occupational post

- application inhalation exposure assessment was not performed for
chlorsulfuron

.Chlorsulfuron Human Health Risk Assessment D425536

Page 4 of 30 

### The restricted entry interval (REI) of 4 or 12 hours specified on the registered labels is based on
the a cute toxicity of chlorsulfuron. Upon review of the criteria for the active ingredient only , it appears that chlor sulfuron is consistent with the criteria in PRN 95

- 3 that allow for a 4

- hour REI.
Note : The PR Notice also includes similar criteria for the end

- use product. These criteria have not been evaluated by HED. Based solely on the active ingredient criteria, HED would
recommend f

or reduction of the REI for chlorsulfuron

.

HED has not identified any risk concerns associated with the registered uses of chlorsulfuron

. There are no data gaps that would require submission of additional toxicity, residue chemistry, or exposure data.

2.0 HED Recommendations

2.1 Tolerances Considerations

The existing tolerances for residues of chlorsulfuron (40 CFR § 180. 405 ) are supported by the

av ailable residue chemistry data. Codex has not established maximum residue limits (MRLs) for
residues of chlorsulfuron

. The established Canad i a n MRLs for residues of chlorsulfuron are harmonized with U.S. tolerances.

The 40 CFR entry for chlorsulfuron is broken out into two sections: 40 CFR § 180. 405(a)(1) and
40 CFR § 180. 405(a)(2), with 40 CFR § 180. 405(a)(1) indicating that the parent and 5

- hydroxy metabolite should be measured for tolerance enforcement purposes and 40 CFR § 180. 405(a)(2) indicating that only parent should be measured for enforcement purposes. T he HED Metabolism
Committee determined that the residue of concern for risk assessment and enforcement in plant
and livestock commodities is the parent only ( Memo s , J. Abbotts , 0 4/ 11 / 1995, D213534, and J.
Abbotts , 0 8/ 0 9/ 1995, D 217473 ). HED notes that as previously recommended, the tolerance expression in 40 CFR § 180. 405 should be revised to reflect the recommendations of the Metabolism Committee (Memo, F. Fort et al.

, 0 7/18/02 ; D26607 0 ). The established tolerances
in 40 CFR § 180. 405(a)(1) and 40 CFR § 180. 405(a)(2) should be merged into one section, 40
CFR § 180. 405(a). The established tolerance values are not impacted by this change. The tolerance expression for chlorsulfuron in 40 C FR § 180.405(a) should be revised to state the following:

(a) General. Tolerances are established for residues of chlorsulfuron, including its metabolites and degradates, in or on the commodities in the table below. Compliance
with the tolerance levels s pecified below is to be determined by measuring only chlorsulfuron (2

- chloro

- N

- [[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]benzenesulfonamide) in or on the commodity.

3.0 Ingredient Profile

3.1 Chemical Identity and Physical/Chemical Proper ties

The chemical structure and nomenclature of chlorsulfuron and a description of the physicochemical properties of chlorsulfuron are provided in Appendix B

.Chlorsulfuron Human Health Risk Assessment D425536

Page 5 of 30 

### 3.2 Use Pattern

Chlorsulfuron is currently registered for use on barley, grasses grow n for seed, oats, pastures, rangeland, rights

- of

- way, triticale, wheat, and industrial and commercial turf. The end

- use products registered with c hlorsulfuron are formulated as water

- dispersible granules (WDG)/dry flowable (DF) formulations . The register ed products are applied either with aerial, groundboom,
hand

- held, or backpack equipment. The single application rate s of the registe red uses for
chlorsulfuron range from 0.016 to 0.14 lb ai/A.

Table 3.2 provides a summary of the highest application rate of the registered uses for
chlorsulfuron

.

Table 3.2. Summary of Registered Uses of Chlorsulfuron

.

Application Equipment Formulation Maximum Application
Rate REI Use Directions and
Limitations

Barley

Groundboom,
Aerial WDG/DF 0.016 lb ai/A 4 hours Do not apply this product through any type of irrigation system.

Non

- Crop Site: Industrial and Commercial Turf

Groundboom,
Aerial DF 0.02 lb ai/A 4 hours Do not apply through any type of irrigation system. Do not use on lawns, walks, driveways, tennis courts, or similar areas.

Grasses Grown for Seed

Groundboom,
Aerial WDG/DF 0.01 lb ai/A 4 hours Do not apply this product through any type of irrigation system.

Oats

Groundboom,
Aerial WDG/DF 0.02 lb ai/A 4 hours Do not apply this product through any type of irrigation system.

Non

- Crop Site: Agricultural Righ ts of Way/Fence Rows/Hedge Rows

Handgun WDG/DF 0.14 lb ai/A (0.0014 lb ai/gallon) 4 hours Do not apply this product through any type of irrigation system. Pastures, Rangeland

Groundboom,
Aerial WDG/DF 0.06 lb ai/A 4 hours Do not apply this product through any type of irrigation system.

Triticale

Groundbo om, Aerial WDG/DF 0.02 lb ai/A 4 hours Do not apply this product through any type of irrigation system.

Wheat

Groundboom,
Aerial WDG/DF 0.02 lb ai/A 4 or 12 hours Do not apply this product through any type of irrigation system

. WDG = water

- disper sible granule; DF = dry flowableChlorsulfuron Human Health Risk Assessment D425536

Page 6 of 30 

### 3.3 Anticipated Exposure Pathways

Individuals may be exposed to chlorsulfuron via their diet (food and drinking water). There are

no reg istered uses for chlorsulfuron that will result in direct non

- occupational exposures. However, there is the potential for indirect exposure (incidental oral and dermal) to chlorsulfuron related to spray drift. Agricultural workers may be exposed (dermal and inhalation) to chlorsulfuron during mixing, loading, and/or appl ying the herbicide and entering previously
treated areas. Based on the use pattern f or chlorsulfuron , short

- and intermediate

- term dermal
and inhalatio n exposures for occupational handlers are expected; long

- term exposures (greater than 6 months) are not anticipated. The chlorsulfuron labels require handlers to wear baseline attire (i.e.

, a long

- sleeved shirt , long pants, shoes plus socks) and chemical

- resistant gloves. This risk assessment considers all of the aforementioned exposure pathways based on the existing
uses of chlorsulfuron

.

3.4 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 Lo w

- 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 procedures. 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 arou nd the ho me that involve pesticide use in a residential 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/WWE IA), are used in pesticide risk assessments for all registered 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 subg roups and exposure assessments are performed when conditions 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 ente ring 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 an d farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Identification/Toxicology

The toxicology database for chlorsulfuron is complete and adequate for risk assessment. T he
HASPOC waived the requirement for the 21

- day dermal toxicity, subchronic inhalation, immunotoxicity, and neurotoxicity (acute and subchronic) studies for chlorsulfuron (TXR# 00 56439 , TXR# 0056723 ). A rat two

- generation reproduction study was submitted since the last risk assessment ( F. Fort et al. , 18

- JUL

- 2002; D266070 ). The toxicological endpoints and
PODs were reevaluated considering the new toxicology data. The TOXLINE (National Library of Medicine) database literature search did not identify any new toxicological info rmation not
al ready considered. All of the endpoints for risk assessment remain the same as those used in the previ ous assessment. See Appendix A for the toxicology profile tables for chlorsulfuron.Chlorsulfuron Human Health Risk Assessment D425536

Page 7 of 30 

### 4.1 Summary of Toxicological Effects

The chronic toxicity data provide no evidence that chlorsulfuron is particularly toxic to any organ or tissue. The most prevalent effect observed across studies was decreased body weight and body weight gain

. In the developmental toxicity stud ies in rats and rabbits, decrea sed fetal body weight was observed at or above the limit dose in the presence of maternal toxicity. No reproductive toxicity was observed in the updated two

- generation reproduction study. There is

no evidence of neurotoxicity, developmental

, or reproduct ive toxicity

. C h lorsulfuron is
classified as “ not likely to be carcinogenic to hu m ans ” based upon lack of evidence of carcinogenicity in rats and m i ce and the lack of effect s i n mutagenicity studies

.

Chlorsulfuron has low acute toxicity by the oral, dermal, o r inhalation route of exposure (Toxicity Category III or IV)

. It is not an eye or skin irritant, and is not a skin sensitizer

.

Chlorsulfuron is rapidly absorbed, metabolized, and eliminated in rats following the oral
administration. There were no remarkable differences in absorption, distribution, or excretion of
chlorsulfuron related to sex, dose, or route of administration

. The major routes of elimination are
via the urine (58

- 72% of the dose) and feces (20

- 35%). Negligible amounts (<0. 08%) of radioactivity are found in the expired air as carbon dioxide. Small amounts of radioactivity were
found in the tissues three days after dosing, with the highest concentrations observed in the liver
and whole blood in both sexes

.

4.2 Safety Factor for Infants and Children (FQPA SF)

HED has recommended that the required 10x Food Quality Protection Act (FQPA) Safety Factor (SF) b e reduced to 1x for chlorsulfuron . The toxicology database is complete, there is no evidence of increased susceptibility, no concerns/residual uncertainties with regard to pre

- and/or postnatal toxicity, and no concern for neurotoxicity. In addition, exposure estimates are unlikely

to u nderestimate risk

.

4.3 Toxicity Endpoint and Point of Departure Selections

The toxicological endpoint/PO Ds selected for risk assessment remain the same as in previous

assessment s

. The no

- observed adverse

- effect level s ( NOAELs ) and lowest

- observed adverse

effect level s (LOAEL s ) have not been revised to reflect current policy and are considered
conservative

. Therefore, the endpoints/PODs selected for risk assessment may be conservative. The PODs selected for risk assessment are protective of the ef fe cts observed in the chlorsulfuron
database. In the previous risk assessment document, the FQPA factor was reduced to 3x and applied to risk assessments to address data deficiencies regarding the reproduction study. Subsequently, an acceptable two

- gener ation reproduction study in rats was submitted which did not show any adverse effects on reproduction or toxicity to the offspring. Therefore, the 3x database uncertainty factor was removed

. The total UF for all exposure scenarios is 100x (10x
for inters pecies extrapolation, 10x for intraspecies variation, and 1x for FQPA Safety Factor when applicable ).Chlorsulfuron Human Health Risk Assessment D425536

Page 8 of 30 Table 4.3.1

. Toxicological Doses and Endpoint for Chlorsulfuron for Use in Dietary and Non

- Occupational
Human Health Risk Assessment s

. Exposure/Scenario Point of Departure Uncertainty/FQPA

Safety Factors RfD, PAD, Level of Concern

for Risk Assessment Study and Toxicological
Effects Acute Dietary (All populations) No appropriate endpoint attributable to a single dose was identified including developmental toxicity
studies in rats and rabbits. Chronic Dietary (all populations) NOAEL = 5 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X Chronic RfD

= 0.05 mg/kg/day

cPAD = 0.0 5 mg/kg/day Chronic toxicity/ carcinogenicity study in rats (MRID 00086003) LOAEL = 25 mg/kg based on decreased body weights and body weight gains in males.
Incidental Oral ( Short

- Term ) NOAEL=75 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X Residential LOC for

MOE= 1 00 Developmental toxicity study in
rabbits (MRID 41983101) LOAEL= 200 mg/kg/day based on decreased body weights and body weight gains. Cancer (oral, dermal, inhalation) Classification: Not likely to be carcinogenic to hu m ans. A quantitative carcinogenic risk assessment for chlorsulfuron is not required. 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 lower 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 sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic).

Table 4.3.2. Summary of Toxico l ogical Doses and Endpoints for C hlorsulfuron for Use in Occupationa l
Human Health Risk Assessments

.
Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of Concern

for Risk
Assessment Study and Toxicological

Effects

Dermal exposure (short

- and
intermediated

- term) Oral
NOAEL = 75 mg/kg/day UF A = 10x

UF H =10x
Dermal Absorption
= 100% Occupational LOC for

MOE = 100 Developmental toxicity study in rabbits (MRID 41983101) LOAEL= 200 mg/kg/day based on decreased body weights and body weight gains.

Inhalation exposure (Short

- & intermediate term) Oral
NOAEL = 75 mg/kg/day UF A = 10x

UF H =10x
Inhalation Absorption
= 100% Occupational LOC for

MOE = 100 Developmental toxicity study in rabbits (MRID 41983101) LOAEL= 200 mg/kg/day based on decreased body weights and body weight gains.

Cancer (oral, dermal, inhalation) Classification: Not likely to be carcinogenic to hu m ans. A quantitative carcinogenic risk assessment for chlorsulfuron is not required.

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 lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapo lation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human

po pulation (intraspecies) . MOE = margin of exposure. LOC = level o f concern.



### 4.4 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse

outco mes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, an d general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, re productive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent re

- registration decision for chlorsulfuron

, EPAChlorsulfuron Human Health Risk Assessment D425536

Page 9 of 30 

### reviewed these data and selected the most sensitive endpoints for relevant risk assessment
scenarios fro m the existing hazard database. However, as required by FFDCA section 408(p ),
chlorsulfuron is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in h umans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required
determinations. Tier 1 consi sts of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- relate d effects caused by the substance and
establish a dose

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test o rders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 1 

### and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, f

uture lists, the test guidelines and the Tier 1 screening battery, please visit our
website. 2



### 5.0 Dietary Exposure and Risk Assessment

5.1 Residue Chemistry

The existing residue chemistry database for chlorsulfuron is complete and adequate for risk assessment purposes. No additional residue chemistry data are required at this time. The qualitative nature of the residues of chlorsulfuron in plants and livestock are adequately understood, and adequate enforcement analytical methods are available. T he HED Metabolism
Committee determined that the residue of concern for risk assessment and tolerance enforcement
in plant and livestock commodities is the parent only ( Memo s , J. Abbotts , 0 4/ 11 / 1995, D213534,
and J. Abbotts , 0 8/ 0 9/ 1995, D 217473 ). The Agency has determined that tolerances for chlorsulfuron residues in eggs and poultry tissue are not required based on the results of the respective poultry metabolism and feeding studies. Analytical reference standards for
chlorsulfuron are currently available for chlorsulfuron and expire in December 2016 (Appendix
C ).

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

2 http://www.epa.gov/endo/Chlorsulfuron Human Health Risk Assessment D425536

Page 10 of 30 

### 5.2 Drinking Water

Screening ground water

- 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. EFED initially provided coarse

- screen estimates that should
exceed the upper

- bound chemical

- specific EDWCs for any SU; however, for several of the SUs,
the coarse

- screen EDWCs resulted in dietary risks of concern and EFED subsequently generated
refined

- screen EDWCs for these SUs. The application input s for the refined

- screen EDWCs represent the maximum application rate pattern for the chemical, considering the maximum single application rate first, then the maximum seasonal application rate, using usage data provided by Biological and Economics Analysi s Division (BEAD) if the labels do not provide a maximum seasonal rate. The modeled sorption coefficient is also chemical

- specific. All other inputs, including the screening assumptions of stability to degradation and application every year, remained the same as for the coarse screen. The resulting refined

- screen EDWCs from
PRZM

- GW can be used as a conservative estimate of exposure and are summarized in Table 5.2 (G. Orrick, 12

- AUG

- 2015; D427429 ).

The chronic dietary assessment for chlorsulfuron used the refined

- screen post

- breakthrough
mean value of 52 μg/L (0. 052 ppm).

Table 5.2 . PRZM

- GW Refined

- Screen EDWCs for Sulfonylureas 1

.

Sulfonylurea (Use) PRZM

- GW
Scenario Max. Daily Conc.

(μg/L) Post

breakthrough Mean (μg/L) Mean

Breakthrough Time (years)

Chlorsulfuron (non

- ag areas) NC cotton 78 52 5.9

Halosulfuron

- methyl (fallow) NC cotton 74 53 8.1
Nicosulfuron (rights

- of

- way) NC cotton 39 26 6.2
Prosulfuron (corn) NC cotton 15 13 12
Rimsulfuron (commercial areas) NC cotton 105 71 6.5

Triasulfuron (rangeland) NC cotton 21 19 16

Tribenuron

- methyl (corn) NC cotton 35 23 6.1

Triflusulfuron

- methyl (sugar beet) FL citrus 23 20 9.5

1 The EDWCs for chlorsulfuron are in bold.



### 5.3 Dietary (Food + Drinking Water ) Risk Assessment

HED has conducted a chronic dietary exposure and risk assessment for chlorsulfuron using
tolerance

- level residues in foods , 100% crop treated, and EDWCs provided by EFED . Exposure and risk estimates were obtained from the Dietary Exposure Evaluation Model using the Food
Comm odity Intak e Database (DEEM

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

- 2008 NHANES/WWEIA database, coupled with recipe files and residues in foods, to derive estimates of dietary exposure and risk.

Generally, HED is concern ed when chronic dietary exposure estimates exceed 100% of the
cPAD

. C hronic dietary risk estimates (food and drinking water) are not of concern for the general U.S. population or any other population subgroup (Table 5.3 ). The chronic exposure
estimate is 4.5 % of the cPAD for the general U.S. population and 14 % of the cPAD for children
1

- 2 years old, the most highly

- exposed population subgroup. Because of the very conservative assumptions used in the analysis (tolerance

- level residues, 100% crop treated, upper

- boundChlorsulfuron Human Health Risk Assessment D425536

Page 11 of 30 

### 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 Appendix D

. HED did not co nduct an acute dietary exposure and risk assessment due to the lack of an appropriate endpoint for acute dietary asse ssment. Chlorsulfuron is classified as “not likely to be carcinogenic to humans”; t herefore, cancer risk is not a concern

.

Table 5.3

. Su mmary of Chronic Dietary Exposure (Food and Drinking Water) and Risk for
Chlorsulfuron 1

.

Population Subgroup Chronic Dietary

Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population 0.002263 4.5 All Infants (<1 year old) 0.004267 8.5
Children 1

- 2 years old 0.006917 14
Children 3

- 5 years old 0.004745 9.5
Children 6

- 12 years old 0.003012 6.0
Youth 13

- 19 years old 0.001856 3.7
Adults 20

- 49 years old 0.001906 3.8
Adults 50

- 99 years old 0.001790 3.6
Females 13

- 49 years old 0.001843 3.7

1 Population with the greatest exposure is in bold. Exposure and risk estimates calculated using DEEM version 3.18

.



### 6.0 Residential (Non

- Occupational) Exposure and Risk Assessment

There are no registered residential uses or occupational uses resulting in direct residential

exposure associated with chlorsulfuron . Therefore, a quantitative residential exposure assessment for direct residential uses was not performed.

6.1 Spray Drift

A detailed description about HED’s spray drift policy and how to evaluate the drift potential and associated risks is available in Appendix F.

6.1.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a result of the screening

- level agricultural appli cation scenarios. Chlorsulfuron is used on barley, grasses grown for seed, oats, pastures, rangeland, rights

- of

- way, triticale, wheat, and industri al
and commercial turf

, and can be applied via aerial, groundboom, and hand

- held equipment. The spray drift assessment was conducted using the registered application rate of 0.06 lb ai/acre for use on pastures and rangeland. The higher application rate o f 0.14 lb ai/acre for use on rights

- of

way and industrial turf was not assessed for spray drift because it is applied with hand

- held equipment in these areas. The recommended drift scenario screening

- level options are listed
below:

 Groundboom applicatio ns are based on the AgDrift ® 

### option for high boom height and using very fine to fine spray type using the 90 th 

### percentile results.

 Aerial applications are based on the use of AgDrift ® 

### Tier 1 aerial option for a fine

- to

medium spray type and a series of other parameters, which is described in more detail below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire application/drift event ).Chlorsulfuron Human Health Risk Assessment D425536

Page 12 of 30 

### Dermal risk estimates have been evaluated for adults. Dermal and incidental oral risk estimates were evaluated for children (1 to < 2 years old). The total applicable LOC is 100 so MOEs < 100 would be of concern. Children’s (1 < 2 years old) dermal and incidental oral risk estim ates and adult dermal risk estimat es from exposure to chlorsulfuron related to spray drift result in no risks of concern at the field edge for either groundboom or for aerial applications. Results are presented below in Tables 6.1.1 and 6.1.2

.

Table 6.1. 1. Adult Risk Estimates (MOEs) Related to Indirect Exposure to Sp ray Drift for Chlorsulfuron for the Dermal Route of Exposure

. Application Equipment Spray Type/

Nozzle Configuration Application

Rate (lb ai/A) Estimated or Adjusted

TTR (ug/cm2) At Edge

Dermal MOE

Pastures, Rangeland

Aerial Fine to Medium

0.06 0.006669 13,000

Groundboom High Boom Very

fine to Fine 18,000

Table 6.1.2. Children (1 < 2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Sp ray Drift for Chlorsulfuron for Combined Route of Exposure

. Application Equipment Spray Type/

Nozzle Configuration Application

Rate (lb ai/A) Estimated or

Adjusted TTR t (ug/cm2) At Edge

Combined MOE 1

Pastures, Rangeland

Aerial Fine to Medium
0.06 0.006669 6,400

Groundboom High Boom Very

fine to Fine 8,800

1. Dermal and incidental oral risks were combined for children 1 to < 2 years old.



### 6.2 Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to
individuals nearb y pesticide applications. The A gency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act
Scientif ic Advisory Panel ( FIFRA SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/ 2009/120109meeting.html). The
A gency has evaluated the SAP report and has developed a Volatilization Screening To ol and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219). D uring Registration Review, the A gency will use this analysis to determine if data (i.e., flux studies, route

- specific
inhalation tox icological studies) or further analysis is required for chlorsulfuron

.

7 .0 Aggregate Exposure and Risk Assessment

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. In the case of chlorsulfuron, agg regate exposure and risk estimates are equivalent to the dietary exposure and risk estimates in Section 5.3, and are not of concern.Chlorsulfuron Human Health Risk Assessment D425536

Page 13 of 30 

### 8.0 Cumulative Exposure/Risk Characterization

In 2015, EPA’s Office of Pesticide Programs released a guidance documen t entitled, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis ( http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/framework

- for

- screening

analysis.html )

. This document provides guidance on how to screen groups of pesticides for

cumu lative evaluation using a two

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

- based screening approach. This framework supplements the existing guidance documents for establishing com mon mechanism groups (CMGs) 3 

### and conducting cumulative risk assessments (CRA) 4



### . The Agency has utilized this framework to evaluate the SUs of which chlorsulfuron is a member (J. D’Agostino; D428798; 09

- SEP

- 2015 ). 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 mechanistic data are required and no further cumulative evaluation is necessary.

9.0 Occupational Exposure/Risk Characterization

Based on the registered use pa ttern (summarized in Table 3.2 ), there is a potential for exposure to
chlorsulfuron in occupational settings from handling chlorsulfuron products during the application process (i.e., mixer/loaders, applicators, and mixer/loader/applicators) and from entering treated areas after application.

9.1 Occupational Handler Exposure/Risk Estimates

Based on current labeling, types of equipment and techniques that can potentially be used, occupational exposur e associated with handler activities (i.e., mixing, loading, and applying) is expected from the registered use s on barley, grasses grown for seed, oats, pastures, rangeland, rights

- of

- way, triticale, wheat, and industrial and commercial turf

. The quantita tive exposure/risk assessment developed for occupational handlers is based on the scenarios listed in
Table 9.1.1. Based on the use patterns (i.e., 1 application per season) and resistance management practices, occupational exposure from the registered us es is expected to be short

- term (1

- 30 days) and in termediate

- term (1

- 6 months) in duration. Long

- term exposures (greater than 6 months) are not anticipated. The registered labels require handlers to wear baseline attire and
chemical

- resistant gloves.

The requirement for a dislodgeable foliar residue (DFR) study has been waived at this time for chlorsulfuron. For additional details, see Appendix G.

Occupational Handler Exposure Data and Assumptions

Application Rate : The highest application rate of t he registered uses is listed in Table 3.2.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical

- specific data,

3 Guidance For Identifying Pesticide Chemicals and Other Substances that h ave a Common Mechanism of Toxicity (USEPA, 1999)

4 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity (USEPA, 2002)Chlorsulfuron Human Health Risk Assessment D425536

Page 14 of 30 

### include Pesti cide Hand ler's Exposure Database (PHED) 1.1, the Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant

- submitted occupational exposure studies. Some of these data are

p roprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pe sticide Handler Unit Exposure Surrogate Reference Table 5 

### ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 6



### .

Area Treated or Amount Handled : The area treated or amount handled is based on HED ExpoSAC Policy No. 9. 1. Refer to Table 9.1.1. for these assumptions for each scenario.

Risk Estimate Equations : The algorithms used to estimate non

- cancer exposure and dose for occupational han dlers can be found in Appendix E

.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates

The short

- and intermediate

- term dermal and inhalation risk estimates for the occupational handlers are greater than HED’s LOC (i.e ., MOEs ≥ 100) at baseline for all scenarios, with MOEs ranging from 360 to 40,000. Table 9.1.1 provides the worst

- case scenarios (e.g., highest application rates and exposure scenarios) for the registered uses for chlorsulfuron.

The Agency matches quant itative occupational exposure assessment with appropriate
characte rization of exposure potential. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural aviation has changed dramatically over the past
two decades

. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sources to best assess and characterize the exposure potenti al for human flaggers in agricultural aerial applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the engin eering control (enclosed cockpits) and baseline attire (long

- sleeve d shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilots are not required to wear protective gloves for the duration of the application. With this level of protection, there are no risk estimates of concern for applicators.

5 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

6 Available: http://www.epa.gov/pesticides/science/handler

- exposure

- data.htmlChlorsulfuron Human Health Risk Assessment D425536

Page 15 of 30 Table 9.1.1. Occupational Short

- term/Intermediate

- term Handler Exposure and Risk Estimates for
Chlorsulfuron

.

Exposure
Scenario Crop or

Target 1 Baseline

Dermal
Unit Exposure 2 Baseline

Inhalation
Unit Exposure 2 Maximum

Application
Rate 3 Area

Treated

or Amount
Handled Daily 4 Baseline Dermal Baseline Inhalation Total

Dose 5 MOE 6 Dose 5 MOE 6 MOE 7

μg/lb ai μg/lb ai lb ai/A

(unless
otherwise noted) Acres

(unless
otherwise noted) mg/kg/day LOC =

100 mg/kg/day LOC =

100 LOC =

100

Mixer/Loader
M/L WDG/DF
for Aerial Application Pastures,

Rangeland 227 8.96 0.06 1,200

acres 0.204 370 0.00806 9,300 360

M/L WDG/DF
for Groundboom Application Pastures,

Rangeland 227 8.96 0.06 200 acres 0.034 2,200 0.00135 56,000 2,100

M/L
WDG/DF for Mechanically

Pressurized Handgun Application Rights

- of

way (e.g., utilities, railroad, roadways) 227 8.96 0.0014 lb ai/gallon 1,000

gallons 0.00398 19,000 0.000156 480,000 18,000

Applicator Applying Sprays
for Aerial Application Pastures,

Rangeland 2.08

(EC) 0.0049 0.06 1,200

acres 0.00188 40,000 0.00000441 17

, 000

, 000 40,000

Applying Sprays
for Groundboom Application Pastures,

Rangeland 78.6 0.34 0.06 200 acres 0.0118 6,400 0.000051 1

, 500

, 000 6,400

Applying Sprays
for Mechanically

Pressurized Handgun Application Rights

- of

way (e.g., utilities, railroad, roadways) 1,300 3.9 0.0014 lb ai/gallon 1,000

gallons 0.0228 3,300 0.0000683 1

, 100

, 000 3,300

Flagger for
Aerial Application for Sprays Pastures,

Rangeland 11 0.35 0.06 350 acres 0.00289 26,000 0.0000919 820,000 25,000

Mixer/Loader/Applicator

M/L/A
WDG/DF for Backpack Application Rights

- of

way (e.g., utilities, railroad, roadways) 8,260 2.58 0.0014 lb ai/gallon 40

gallons 0.00579 13,000 0.0000018 42,000,000 13,000

M/L/A Liquids with Backpack Rights

- of

way (e.g., utilities, railroad, roadways) 8,260 2.58 0.0014 lb ai/gallon 40

gallons 0.00579 13,000 0.0000018 42,000,000 13,000

1 The worst

- case scenarios for the registered u ses for chlorsulfuron are listed in this table

. 2 “Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”; Level of mitigation = Baseline except for aerial applicator which includes engineering controls (EC).
3 Based on the currently registered labels (See Table 3.2 ).
4 Exposure Science Advisory Council Policy #9.1. 5 Dermal Dose = Dermal Unit Exposure (μg/lb ai) ) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated or Amount Handled Daily (A or gal/day) x DAF (%) ÷ BW (80 kg). Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Convers ion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated or Amount Handled Daily (A or gal/day) ÷ B W (80 kg). 6 Dermal MOE = Dermal NOAEL (75 mg/kg/day) ÷ Dermal Dose (mg/kg/day). Inhalation MOE = Inhalation NOAEL (75 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). 7 Total MOE = NOAEL (75 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.Chlorsulfuron Human Health Risk Assessment D425536

Page 16 of 30 

### 9.2 Occupational Post

- Application Exposure/Risk Estimates

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure). Such ex posures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce t he potential for post

- application exposure.

Occupational post

- application exposure is expected based on the registered agricultural products
for chlorsulfuron. Occupational post

- application exposure from rights

- of

- way and industrial turf

uses were not as sessed because an occupational worker would not re

- enter these areas to perform any job functions after chlorsulfuron is applied. The occupational post

- application exposure scenarios associated with the highest uses for chlorsulfuron are summarized in Tab le 9.2. All scenarios resulted in MOEs greater than the LOC of 100 (ranging from 2,300 to 190,000) on day 0 (12 hours after application); and therefore, are not of concern to HED. Table 9.2. provides the

worst

- case scenarios (highest exposure scenario ba sed on the application rates) for the registered
uses for chlorsulfuron.

Table 9.2. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Chlorsulfuron

.

Crop/Site Activities Transfer
Coefficient (cm 2 /hr) Application Rate

(lb ai/A) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3

Short

- and Intermediate

- term

Wheat Hand Weeding 70 0.02 0.06 0.0004 190,000

Wheat Scouting 1,100 0.02 0.06 0.006 12,000

Pastures, Rangeland Scouting 1,100 0.06 0.17 0.019 4,100

Pastures, Rangeland Irrigation 1,900 0.06 0.17 0.032 2,300

1 DFR = Application Rate × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2 ; where F = 0.25 and D = 0.10 per day

2 Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (100 %)]  BW (80 kg).

3 MOE = POD (mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR (μg/cm 2 ) × TC × 0.001 mg/μg × 8 hrs/day × dermal absorption factor (100 %)]  BW (80 kg).



### 9.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulat es that contain pesticides. The A gency sought expert advice and input on issues related to volatilization of pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009 /120109meeting.html ). The A gency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http: //www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219 ). During Registration Review, the A gency will use this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for chlo rsulfuron

.Chlorsulfuron Human Health Risk Assessment D425536

Page 17 of 30 

### In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the Agency will continue to identify the need for and, subsequ ently, the way to incorporate occupational post

- application inhalation exposure into the agency's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment w as performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

Restricted Entry Interval

Chlorsulfuron is classified as Toxicity Category III or IV based upon data for acute dermal toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irri tation. Upon
review of the criteria for the active ingredient only , it appears that chlorsulfuron is consistent
with the criteria in PRN 95

- 3 that allow for a 4

- hour REI. Note : The PR Notice also includes
simi lar criteria for the end

- use product. These criteria have not been evaluated by HED. Based solely on the active ingredient criteria, HED would recommend f or reduction of the REI for
chlorsulfuron

.

10. 0 Public Health, Pesticide Epidemiology, and Human Incidence Data

T he OPP Incident Data System (IDS) was consulted for pesticide incident data on the active ingredient chlorsulfuron. HED notes that chlorsulfuron is not included in the Agricultural Health Study ( AHS ). At the time of the scoping document for chlorsulfuron ( M. Hawkins et al. , 6

- DEC

- 2012; D403355 ), there was a low frequency and severity of incident cases reported; therefore, further investigation was not warranted at that time ( S. Recore, 31

- JUL

- 2012 ; D 403831 ). The Agency has continue d to monitor the incident information , but a concern has not
been triggered, and therefore, additional analyse s have not been included in this risk assessment.Chlorsulfuron Human Health Risk Assessment D425536

Page 18 of 30 

### 11.0 References

Table 11.0 HED Memoranda Relevant to Registration Review.

Authors Barcode Date Title

M. Hawkins et al. D403355 12/6/ 2012 Chlorsulfuron: Registration Review Scoping Document for
Human Health Assessments

.

J. Van Alstine TXR # :

0056439 2/8/ 2013 Chlorsulfuron: Summary of Hazard and Science Policy Council (HASPOC) Meeting of August 9, 2012: Recommendations on the need for the inhalation, dermal, acute and subchronic neurotoxicity studies.

K. Rury TXR # :

0056723 8/ 6 / 2013 Sulfonylureas: Summary of Hazard and Science Policy Council (HASPOC) Meeting on July 18, 2013: Recommendations on Data Requirement for Immunotoxicity Studies for Sulfonylurea Pesticides.

J. Abbotts D213534 04/11/1995 Results of the HED Metabolism Committee Meeting Held on 4/4/95: Chlorsulfuron Residue to be Regulated. CBRS No. 15318, DP Barcode No. D213534, No MRID No.

J. Abbotts D217473 08/09/1995 Chlorsulfuron (118601), Reregistration Case No. 0631. Decision of the HED Metabolism Committee, Residues to be Regulated in Animal Commodities. CBRS No. 15880, DP Barcode No. 217473, No MRID No.

F. Fort et al. D266070 07/18/02 PP#: 0F06120. Chlorsulfuron in/on Pasture Grasses. Health Effects Division (HED) Risk Assessment. PC Code: 118601.
DP Barcode: D266070 Case #: 2929 04. Submission #:
S613409

S. Recore D403831 7/ 31 / 2012 Chlorsulfuron: Review of Human Incidents

G. Orrick D427429 08/12/2015 Drinking Water Exposure Assessment for the Registration Review of 22 Sulfonylurea Herbicides.

J. D’Agostino D428798 09/09/ 2015 Sulfonylureas: Screening Analysis of Toxicological Profiles to Consider Whether a Candidate Common Mechanism Group
Can Be Established.Chlorsulfuron Human Health Risk Assessment D425536

Page 19 of 30 

### Appendix A

. Toxicology Profile Tables

A

. 1. Toxicology Data Requirements

Table A.1 . Toxicology Data Requirements for Chlorsulfuron

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 (nonrodent)

................................ ......... 870.3200 21

- Day Dermal

................................ .............................. 870.3250 90

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

................................ .......................... yes
yes
yes

no CR yes

yes waived 1

- waived 1

870.3700a Developmental Toxicity (rodent)

................................ .. 870.3700b Developmental Toxicity (nonrodent)

............................ 870.3800 Reproduction

................................ ................................ . yes
yes
yes yes

yes
yes
870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Oncogenicity (rat)

................................ .......................... 870.4200b Oncogenicity (mouse)

................................ ................... 870.4300 Chronic/Oncogenicity

................................ ................... yes

no
yes
yes
yes yes

- yes
yes
yes
870.5100 Mutagenicity

— Gene Mutation

- bacterial

..................... 870.5xxx Mutagenicity

— Structural Chromosomal Aberrations

... 870.5xxx Mutagenicity

— Other Genotoxic Effects

....................... 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
yes

no -

- waived 1

waived 1

-

870.7485 General Metabolism

................................ ...................... 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity............................................... yes

no
yes yes

- Waived 1

1 HASPOC concluded that the 21

- day dermal, subchronic inhalation toxicity , immunotoxicity , and neurotoxicity battery studies are not required at
this time

.Chlorsulfuron Human Health Risk Assessment D425536

Page 20 of 30 

### A.2. Toxicity Profiles

Table A.2.1. Acute Toxicity of Chlorsulfuron Technical

Guideline No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 00031406 Rat LD 50 = 5.5 g/kg (M)
Rat LD 50 = 6.3 g/kg (F) IV

870.1200 Acute Dermal 00083956 Rabbit LD 50 = 3400 mg/kg III

870.1300 Acute Inhalation 00086825 Rat LC 50 = 5.9 mg/L IV

870.2400 Primary Eye

Irritation 46449005 Not an eye irritant IV

870.2500 Primary Skin

Irritation 46449006 Slightly irritating to skin IV

870.2600 Dermal

Sensitization 46449007 Not a skin sensitizer NA



### Table A.2.2. Subchronic, Chronic and Other Toxicity Profile for Chlorsulfuron

Guideline No./
Study Type MRID No. (year)/ Classification
/Doses Results

870.3100 [§82

- 1 (a)
Subchronic oral (90 days)

- Rats 00031418 [1980] Unacceptable/Guideline (0, 100, 500, 2500 ppm) M: 0, 6.5, 33.7, 161.1 mg/kg/day F: 0, 8.1, 40.4, 216.6 mg/kg/day NOAEL: 161.1 mg/kg/day [2500 ppm; HDT]. No effects were observed. Dosing inadequate; well below
the limit dose

870.3150 [§82

- 1 (b)]
Subchronic oral (6 months)

- Dogs 00031420 [1980] Acceptable/non

- guideline (0, 100, 500, 2500 ppm) 0, 3.7, 18.5, 82.3 mg/kg/day (M/F) NOAEL: 82.3 mg/kg/day LOAEL >82.3 mg/kg/day

870.3100 [§82

- 1 (a)]
Subchronic oral (90 days)

- Mice 00031421 [1980] Acceptable/non

- guideline (0, 500, 2500, 5000, 7500 ppm) M: 0, 150, 783, 1557, 2130 mg/kg/day F: 0, 220, 1214, 2134, 3176 mg/kg/day NOAEL: 1557 mg/kg/day LOAEL: 2130 mg/kg/day, based on an increased incidence of retinal dysplasia and adrenal capsular cell proliferation.

870.4100 [§83

- 1b]
Chronic feeding study

- Beagle dogs 41862601(1991) Acceptable/Guideline (0, 100, 2000, 7500 ppm) M: 0, 3.5, 65.6, 215 mg/kg/day F: 0, 3.5, 60.6, 254.5 mg/kg/day NOAEL: 60.6 mg/kg/day LOAEL: 215 mg/kg/day, based on decreased body weight gain, erythrocyte counts, and hemoglobin
levels

870.4300 [§83

- 5] Chronic feeding/ carcinogenicity study

- CD® rats 00086003 (1981) Acceptable/non

- guideline (0, 100, 500, 2500 ppm) M/F: 0, 5, 25, and 125 mg/kg/day (by a standard conversion factor) NOAEL: 50 ppm [5 mg/kg/day] LOAEL: 500 ppm [25 mg/kg/day], based on decreased body weight and body weight gain in males
There was no treatment

- related increase in tumor
incidence in either sex.

870.4200 [§83

- 2]
Carcinogenicity study

- CD

- 1 mice 00090030 [1981] Acceptable/Guideline (0, 100, 500, 5000 ppm) M/F: 0, 15, 108, 750 mg/kg/day (by a standard conversion factor) NOAEL = 500 ppm [108 mg/kg/day] LOAEL: 5000 ppm [750 mg/kg/day], based on decreased body weight and body

- weight gain.
There was no treatment

- related increase in tumor
incidence in either sex.

870.3700 [§83

- 3a] Developmental Toxicity

- Crl:CD®(SD)BR rats 41976406 (1991) Acceptable/Guideline 0, 55, 165, 500, 1500 mg/kg/day Maternal NOAEL: 165 mg/kg/day Maternal LOAEL: 500 mg/kg/day, based on clinical signs [vaginal discharge with associated alopecia. AtChlorsulfuron Human Health Risk Assessment D425536

Page 21 of 30 

### Table A.2.2. Subchronic, Chronic and Other Toxicity Profile for Chlorsulfuron

Guideline No./
Study Type MRID No. (year)/ Classification
/Doses Results

HDT, there were two deaths [GD 12 and 18], and
additi onal clinical signs [swollen limbs and faces].

Developmental NOAEL: 500 mg/kg/day Developmental LOAEL: 1500 mg/kg/day, based on decreased fetal body weight. 870.3700 [§83

- 3b] Developmental Study

- Hra:(NZW)SPF Rabbits 41983101 (1991) Acceptable/Guideline 0, 25, 75, 200, 400 mg/kg/day (original study); 400 and 1000 mg/kg/day (supplemental study) Maternal NOAEL: 75 mg/kg/day Maternal LOAEL: 200 mg/kg/day, based on decreased body weights and body

- weight gain s

. At 400 mg/kg/day , there were 8/20 deaths and 6
abortions.

Developmental NOAEL: 200 mg/kg/day Developmental LOAEL: 400 mg/kg/day, based on a slight increase in visceral malformations and decreased fetal body weight.

870.3800 [§83

- 4]

3

- Gen Reproduction Toxicity

- CD ® Rats 00086003 (1981) Unacceptable/non

- guideline (0, 100, 500, 2500 ppm) 0, 5, 25, 125 mg/kg/day Parental NOEL: 2500 ppm [125 mg/kg/day] Parental LOEL: >2500 ppm [125 mg/kg/day], no
effects observed.

Reproductive NOEL: 100 ppm [5 mg/kg/day] Reproductive LOEL: 5 00 ppm [25 mg/kg/day], based on decreased female fertility.

Offspring NOEL 2500 ppm [125 mg/kg/day] Offspring LOEL >2500 ppm, no effects observed.
870.3800

2

- Gen Reproduction

- Crl:CD ® (SD) Rats 46493201 (2005)
Acceptable/Guideline
(0, 100, 500, 2500, 7500 ppm)
M: 0, 6, 30, 151, 456 mg/kg/day
F: 0, 7, 39, 188, 591 mg/kg/day Parental NOAEL: 2500 ppm (151/188 mg/kg/day; M/F)
Parental LOAEL: 7500 ppm (456/591 mg/kg/day; M/F) based on decreased body weight, weight gain and food consumption.
Reproductive N OAEL: 7500 ppm (456/498 mg/kg/day) (HDT)
Offspring NOAEL; 7500 ppm ppm (456/498 mg/kg/day) (HDT)

870.5100

Gene mutation
S. typhimurium/E.coli 47179902 (2007)

10

- 5000 μg/plate, +/

- S9
Acceptable/Guideline Negative, (+/

- ) S9 m ix

870.5100 Ames, reverse mutation S. typhimurium 00031425
6

- 30 μg/plate, +/

- S9 Unacceptable /upgradeable Negative, (+/

- ) S9 m ix

870.5300

M a mm alia n cell s i n cultur e

- g e n e m

utation [HGPRT] 00083943
0.028

- 2.8 mM, +/

- S9 Unacceptable /upgradeable Negative

870.5395
Mouse bone marrow
micronucleus 47179903 (2003) 0, 500, 1000, 2000 mg/kg, gavage Acceptable/Guideline Negative

870.5385.
in vitro cytogenetics assay;
chromosome aberration [CHO

- WBI cells] 00088755
16.7

- 5000 μg/mL, +/

- S9 Acceptable Negative

870.5450. Dominant lethal assay 00083944 100, 500, 5000 ppm Unacceptable Negative

870.5450 00090008

0.0002

- 2.0 mg/mL NegativeChlorsulfuron Human Health Risk Assessment D425536

Page 22 of 30 

### Table A.2.2. Subchronic, Chronic and Other Toxicity Profile for Chlorsulfuron

Guideline No./
Study Type MRID No. (year)/ Classification
/Doses Results

Unscheduled DNA synthesis primary rat hepatocyte assay Confirmatory: 0.0004

- 4.0 mg/mL
Unacceptable /upgradeable

870.7485[§85

- 1]
Metabolism 42540701 [1989] Acceptable/guideline Chlorsulfuron is rapidly absorbed, metabolized, and eliminated following oral exposure [single low, single high, and repeated low dosing regimens] to rats. There
were no remarkable sex

- , dose

- , or treatment

- related differences in the absorption, distributi on, and excretion of chlorsulfuron in rats. The major routes of elimination are the urine [58%

- 72%] and feces [20%

- 35%]. Small amounts [0.1%

- 0.2% of administered dose] were found in the tissues 3 days after dosing. The highest concentrations were in the li ver and whole blood in both sexes. A major and a minor metabolic pathway were identified.Chlorsulfuron Human Health Risk Assessment D425536

Page 23 of 30 

### Appendix B

. Chemical Identity

TABLE B. 1. Chlorsulfuron Nomenclature. Compound Chemical Structure

Common name Chlorsulfuron
IUPAC name 1

- (2

- chlorophenylsulfonyl)

- 3

- (4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)urea
CAS name 2

- chloro

- N

- [[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]benzenesulfonamide
CAS # 64902

- 72

- 3

TABLE B. 2. Physicochemical Properties of the Technical Grade Chlorsulfuron

. Parameter Value Reference Melting point/range 170

- 173 D182353, A. Aikens,
12/4/1992 pH 3.8 Density 1.48 g/cm 3 Water solubility ( 25  C) 3.18 g/100 grams water Solvent solubility (mg/L at __  C) 3.7 g/100 ml acetone 2.1 g/100 ml acetonitrile 1.5 g/100 ml methanol Vapor pressure at 25  C 2.3 x 10

- 11 mmHg Dissociation constant (pK a ) 3.4 Octanol/water partition coefficient Log(K OW ) 2.13 at pH 5

UV/visible absorption spectrum Not availableChlorsulfuron Human Health Risk Assessment D425536

Page 24 of 30 

### Appendix C. Analytical Standards for Chlorsulfuron

A nalytical reference standard s for chlorsulfuron are current ly available in EPA’s National Pesticide Standards Repository ( NPSR ) and have an expiration date of 12/19/2016 ( email communication between G. Verdin and J. Van Alstine, 0 5/ 0 7/2015 )

. T he registrant is required to
maintain reasonable amount s of the reference standard s for chlorsulfuron in the NPSR as long as tolerances remain published in 40 CFR §180. 405

. When nece ssary, new reference standard s, or updated certificates of analysis ( COA s), 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 addres s listed below, along with a letter of transmittal. Please note
that the full 9

- digit Z IP 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 method used, a statement of principal impurities, purification procedures employed, storage requirements, and spec ial precautions for safe handling. Replacement of standards , or updated certificates of analysis

, may be required periodically if supplies are exhausted, if the standards expire, or if decomposition occurs during storage. Material Safety Data Sheets (MSD Ss) must accompany all analytical standards as specified by the Occupational Safety and Health Administration (OSHA) in 29CFR §1910.1200.Chlorsulfuron Human Health Risk Assessment D425536

Page 25 of 30 

### Appendix D. Dietary Exposure/Risk Modeling Input and Output Files

DEEM

- FCID Chronic Input s File

Filename: C: \ Us ers \ jlangsda \ Documents \ Chemicals \ SUs \ Chlorsulfuron \ Dietary

Assessment \ Chlorsulfuron_Chronic.r08
Chemical: Chlorsulfuron RfD(Chronic): .05 mg/kg bw/day NOEL(Chronic): 5 mg/kg bw/day RfD(Acute): 0 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day Date created/last modified: 05

- 20

- 2015/15:56:32 Program ver. 3.16, 03

- 08

- d Comment: UFa=10x; UFh=10x; FQPA SF=1x

----------------------------------------------------------------------------------- EPA Crop Def Res Adj.Fact ors Comment Code Grp Commodity Name (ppm) #1 #2

---------- ---- ------------------------------- ---------- ------ ------ ------- 1500025000 15 Barley, pearled barley 0.100000 1.000 1.000
150002 5001 15 Barley, pearled barley

- babyfood 0.100000 1.000 1.000 1500026000 15 Barley, flour 0.100000 1.000 1.000 1500026001 15 Barley, flour

- babyfood 0.100000 1.000 1.000 1500027000 15 Barley, bran 0.100000 1.000 1.000 1500231000 15 Oat, bran 0.100000 1.000 1.000 1500232000 15 Oat, flour 0.100000 1.000 1.000 1500232001 15 Oat, flour

- babyfood 0.100000 1.000 1.000 1500233000 15 Oat, groats/rolled oats 0.100000 1.000 1.000 1500233001 15 Oat, groats/rolled oats

- babyfood 0.100000 1.000 1.000
1500381000 15 Triticale , flour 0.100000 1.000 1.000 1500381001 15 Triticale, flour

- babyfood 0.100000 1.000 1.000 1500401000 15 Wheat, grain 0.100000 1.000 1.000 1500401001 15 Wheat, grain

- babyfood 0.100000 1.000 1.000 1500402000 15 Wheat, flour 0.100000 1.000 1.000 1500402001 15 Wheat, flour

- babyfood 0.100000 1.000 1.000 1500403000 15 Wheat, germ 0.100000 1.000 1.000 1500404000 15 Wheat, bran 0.100000 1.000 1.000 3100044000 31 Beef, meat 0.300000 1.000 1.000 3100044001 31 Beef, meat

- babyfood 0.300000 1.000 1.000 3100045000 31 Beef, m eat, dried 0.300000 1.920 1.000 3100046000 31 Beef, meat byproducts 0.300000 1.000 1.000 3100046001 31 Beef, meat byproducts

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

- babyfood 0.300000 1.000 1.000 3100048000 31 Beef, kidney 0.300000 1.000 1.000 3100049000 31 Beef, liver 0.300000 1.000 1.00 0 3100049001 31 Beef, liver

- babyfood 0.300000 1.000 1.000 3200169000 32 Goat, meat 0.300000 1.000 1.000 3200170000 32 Goat, meat byproducts 0.300000 1.000 1.000 3200171000 32 Goat, fat 0.300000 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 0.300000 1.000 1.000 3400290000 34 Pork, meat 0.300000 1.000 1.000 3400290001 34 Pork, meat

- babyfood 0.300000 1.000 1.000 3400291000 34 Pork, ski n 0.300000 1.000 1.000 3400292000 34 Pork, meat byproducts 0.300000 1.000 1.000 3400292001 34 Pork, meat byproducts

- babyfood 0.300000 1.000 1.000 3400293000 34 Pork, fat 0.300000 1.000 1.000 3400293001 34 Pork, fat

- babyfood 0.300000 1.000 1.000 3400294000 34 Pork, kidney 0.300000 1.000 1.000 3400295000 34 Pork, liver 0.300000 1.000 1.000 3500339000 35 Sheep, meat 0.300000 1.000 1.000 3500339001 35 Sheep, meat

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

- babyfood 0.300000 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 0.100000 1.000 1.000 3600222001 36 Milk, fat

- baby food/infant formu 0.100000 1.000 1.000 3600223000 36 Milk, nonfat solids 0.100000 1.000 1.00 0 3600223001 36 Milk, nonfat solids

- baby food/in 0.100000 1.000 1.000 3600224000 36 Milk, water 0.100000 1.000 1.000Chlorsulfuron Human Health Risk Assessment D425536

Page 26 of 30 3600224001 36 Milk, water

- babyfood/infant form 0.100000 1.000 1.000 3600225001 36 Milk, sugar (lactose)

- baby food/ 0.100000 1.000 1.000 3800221000 38 Meat, game 0.100000 1.000 1.000 3900312000 39 Rabbit, meat 0.100000 1.000 1.000 8601000000 86A Water, direct, all sources 0.052000 1.000 1.000 8602000000 86B Water, indirect, all sources 0.052000 1.000 1.000



### DEEM

- FCID Chronic Results File

U.S. EPA Ver. 3.16, 03

- 08

- d

DEEM

- FCID Chronic analysis for CHLORSULFURON NHANES 2003

- 2008 2

- day
Residue file name: C: \ Users \ jlangsda \ Documents \ Chemicals \ SUs \ Chlorsulfuron \ Dietary

Assessment \ Chlorsulfuron_Chronic.r08 Adjustment factor #2 used.

Anal ysis Date 05

- 20

- 2015/15:57:47 Residue file dated: 05

- 20

- 2015/15:56:32 Reference dose (RfD, Chronic) = .05 mg/kg bw/day COMMENT 1: UFa=10x; UFh=10x; FQPA SF=1x

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

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

Total Exposure

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

-------------------------------------- ------------- ---------------- Total US P opulation 0.002263 4.5% Hispanic 0.002423 4.8%

Non

- Hisp

- White 0.002281 4.6%

Non

- Hisp

- Black 0.001903 3.8%

Non

- Hisp

- Other 0.002471 4.9% Nursing Infants 0.001499 3.0%

Non

- Nursing Infants 0.005503 11.0%
Female 13+ PREG 0.001955 3.9%
Children 1

- 6 0.005399 10.8%
Children 7

- 12 0.002830 5.7%
Male 13

- 19 0.001972 3.9%
Female 13

- 19/NP 0.001744 3.5%

Male 20+ 0.001878 3.8% Female 20+/NP 0.001835 3.7%
Seniors 55+ 0.001770 3.5%
All Infants 0.004267 8.5%

Female 13

- 50 0.001840 3.7%
Children 1

- 2 0.006917 13.8%
Children 3

- 5 0.004745 9.5%
Children 6

- 12 0.003012 6.0%
Youth 13

- 19 0.001856 3.7%
Adults 20

- 49 0.001906 3.8%
Adults 50

- 99 0.001790 3.6%
Female 13

- 49 0.001843 3.7%

--------------------- ----------------------------------------------------------Chlorsulfuron Human Health Risk Assessment D425536

Page 27 of 30 

### Appendix E . Occupational Non

- cancer Algorithms

Occupational Non

- C ancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = exposure (mg ai/day),
UE = unit exposure (μg ai/lb ai),
AR = maximum application rate according to proposed label (lb ai A or lb ai/gal), and
A = area treated or amount handled (e.g., A/day, gal/day).

The daily d oses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),
E = exposure (mg ai/day),
AF = absorption factor (dermal and/or inhalation), and
BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and inhalation dose receive d by occupational handlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= POD

ADD

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),
POD = point of departure (mg/kg/day), and
ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).Chlorsulfuron Human Health Risk Assessment D425536

Page 28 of 30 

### Occupational Non

- C ancer Post

- application Algorithms

Potential daily exposures for occupational post

- application workers are calculated using the following formulas:

DFR t 

### =AR * F* (1

- D) t 

### * ( 4.54E8 ug
lb ) * ( 2.47E

- 8 A

cm 2 

### )

where:

DFR t 

### = dislodgeable foliage residue on day "t" (μg/cm 2 

### ),
AR = application rate (lb ai/acre),
F = fraction of ai retained on foliage or 25% (unitless),
D = fraction of residue that dissipates daily or 10% (unitless), and

t = number of days after application day (days).

E=TC * DFR t 

### * ET * 0.001 mg

ug

where:
E = exposure (mg ai/day),
TC = transfer coefficient (cm 2 

### /h r),
DFR t 

### = dislodgeable foliar residue on day “t” (μg/cm 2 

### ), and
ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),
E = exposure (mg ai/day),
AF = absorption factor (dermal and/or inhalation), and
BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicologica l endpoint to the daily dose of concern. The daily dermal dose received by occupational post

- application workers is compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational post

- application workers. All
MOE values are calculated u sing the following formula:

MOE= POD

ADD

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),
POD = point of departure (mg/kg/day), and
ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).Chlorsulfuron Human Health Risk Assessment D425536

Page 29 of 30 

### Appendix F. Spray Drift Detailed Description

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 end up off

target and can lead to e xposures to those it may directly contact. They can also deposit on surfaces where contact with residues can eventually lead to exposures (e.g

. , children playing on lawns where residues have deposited next to treated 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.

The approach to be used for quantitatively incorporating spray drift into risk assessment include assessing expo sures 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 exposure scenario. Aside from the predicted residues available for transfer, the routes of exposu re and assessment methodology is analogous to how exposures to turf products are considered in risk assessment.

In order to evaluate the drift potential and associated risks, an approach based on drift modeling coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a residential turf assessment based on exposure to deposited residues has been completed to address drift from the agricultural applications of chlorsulfuron . In the spray drift scenario, the depo sited residue value was determined based on the amount of spray drift that may occur at varying distances from the edge of the treated field using the AgDrift ® 

### (v2.1.1) model. Exposures were considered for 50 feet wide lawns where the nearest side of the property was directly adjoining the treated field (at field edge) and at varied distances up to 300 feet downwind of a treated field. Once the deposited residue values were determined, the remainder of the spray drift assessment was based on the algorithm s and input values specified in the recently revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

.

A screening approach was developed for situations where specific label guidance for application parameters is not availa ble. 7

, 8 

### AgDrift ® 

### is appropriate for use only when applications are made by aircraft, airblast sprayers, and groundboom sprayers. When AgDrift ® 

### was developed, a series of screening values (i.e., the Tier 1 option) were incorporated into the model and represent each equipment type and use under varied conditions. The screening options specifically recommended in this methodology were selected bec ause they are plausible and represent a reasonable upper bound level of drift for common application methods in agriculture. In all cases, each scenario is to be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides a re not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are not allowed ). Section 6.1.1 provides the screening level drift related risk estimates. These drift estimates represent plausible options based on the available pesticide
labels.

7 http://www.agdrift.com/

8 Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk assessors sho uld be aware and characterize these appropriately.Chlorsulfuron Human Health Risk Assessment D425536

Page 30 of 30 

### Appendix G. DFR Data Waiver Rationale

Dislodgeable Foliar Residue (DFR): In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are required when a pesticide has residential or occupatio nal uses that could result in post

- application dermal exposure. HED developed a waiver policy for DFR studies. The MOEs from the assessment, using default values are evaluated. If those are 2 times higher than the LOC the DFR studies can be waived.

S ince the highest estimated occupational post

- application exposure using default DFR values for
chlorsulfuron is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 2 times higher than the level of concern, MOE = 2,300 co mpared to the LOC of
100 ); EPA is waiving the 40CFR DFR data requirement. In this instance, it is unlikely that
chemical

- specific DFR data would be needed to further refine exposure assessments or would add appreciably to our overall understanding of the availability of dislodgeabl e foliar pesticide
residues for chlorsulfuron

.

Appendix H. 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 at: http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

.