Page 2 of 18

The chlorsulfuron risk assessment incorporates several conservative assumptions and is considered to be a very conservative estimate of risk to chlorsulfuron. The human health

risks are low due to its low toxicity (Toxicity Category III and IV), the minim al dietary and occupational/residential risk, and its “no evidence of carcinogenicity” classification.

The tox icology database for chlorsulfuron is considered substantially complete for the purposes of registration review risk assessment. An immunotoxici ty study is the only remaining data requirement.

The existing residue chemistry database for chlorsulfuron is adequate for risk assessment

purposes. The qual itative nature of the residues of chlorsulfuron in plants and animals has been adequately iden tified/characterized and adequate enforcement analytical methods are available. The current tolerance expression as listed in the 40 CFR§180.4 05 has not been updated to reflect current HED policies and thus may need to be revised during the registration r eview process.

The dietary exposure database is also adequate to support the existing registrations.

A cute and cancer dietary risk assessment s are not required for chlorsulfuron. In the last dietary assessment, the chronic dietary exposure for food only was not greater than 8 % of the cPAD for all population sub groups

. R isks from potential exposure to chlor sulfuron in drinking water from all sources were evaluated by comparing modeled surface and ground water estimates against calculated drinking water l evels of comparison (DWLOCs). This assessment indicated that the estimated drinking water concentration (EDWC) estimates for chlorsul furon residues in surface and ground water did not exceed the Agency’s estimated chronic DWLOC value. New chronic dietar y exposure and risk

assessments may be need ed during registration review, which incorporate current consumption information, updated residue values and percent crop treated information while directly incorporating drinking water values into the assessment. Further, an acute dietary assessment may need to be completed if new toxicity data are identified that indicate the need for an acute dietary risk assessment

.

The residential exposure database is adequate to support the registration review process

for c hlorsulfuron

. In accordance with the updated Part 158 data requirements (2007), a Turf Transferrable Residue (TTR) study is required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses. Based on HE D policy,

a TTR study is not required for chlorsulfuron at this time

. T he requirement of a TTR study may need to be reconsidered if application rates, use patterns, or points of departure change. The chlorsulfuron residential exposure risk assessment should be considered conservative because of the low use rates, minimal re

- applications (60 day interval) and high end values from the Residential Standard Operating Procedures (SOPs). HED

determined that the margin of e xposure (MOEs) were not of concern to adult residential

handlers (MOEs ranged from 8,800 to 190,000) or residential post

- application to adults

and toddlers ( MOEs ranged from 770 to 400,000 )

.

Based on the updated 2012 Residential SOPs, the Agency may reevaluate the residential handler and post

- application exposures from the uses of chlorsulfuron. Therefore, updated aggregate exposure and risk assessments may also be required under registration review based on the need to combine exposu re estimates from residential uses with dietary exposure estimates.Page 3 of 18

As noted above in the dietary section, the 2002 risk assessment did not directly incorporate drinking water into the dietary assessment and thus a new chronic dietary

assessment may be required during registration review. As a result, during registration review, new short

- term, intermediate

- term, and chronic aggregate risk assessments may required.

The occupational exposure database is adequate to support the registratio n review proce ss for chlorsulfuron

. In accordance with the updated Part 158 data requirements (2007), one

or more Dislodgeable Foliar Residu e (DFR) studies are required when a pesticide has residential or occupational uses that could result in post

- application dermal exposure

. Based on HED policy, a DFR study is not required for chlorsulfuron at this time . T he requirement of a DFR study may need to be reconsidered if application rates, use patterns, or points of departure change. In the 2002 exposure assessments, a l l of the non

cancer occupational handler risk estimates were below the Agency’s level of concern. No new occupational handler or post

- application worker studies are needed at this time. Revised occupational handler assessments would be based upon revisio ns to the Agency’s scenario

- specific surrogate handler exposure data ( http://www.epa.gov/pesticides/science/handler

- exposure

- table.pdf ).

Introduction

Chlorsulfuron is a syst emic herbicide for use on barley, oats, wheat, fallow fields, and ornamental turf to control grasses and broadleaf weeds

. HED has reviewed the most recent exposure and risk assessments for chlorsulfuron , as well as toxicity data, exposure and usage databa ses, and the latest Agency science policy and risk assessment methodologies to determine if sufficient data are available and if updates are needed to support registration review. Additionally, the team conducted a screening

- level literature

search for an y information that would aid in assessing human health risks to

chlorsulfuron

.

Chemical Identity

Chlorsulfuron 2

- chloro

- N

- [ ( 4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino carbonyl]benezenesulfonamide is a systemic herbicide that is currently registered for use on barley, oats, wheat, fallow fields, and ornamental turf to control grasses and broadleaf

weeds

. The chemical structure and nomenclature of chlorsulfuron and the physicochemical properties of the technical grade of chlorsulfuron are presented in

Tab les 1 and 2.

Hazard Identification/Toxicology

The tox icology database for chlorsulfuron is nearly complete at the present time with the exception of an immunotoxicity study (Table 3). In 2002, the HIARC had identified the

21

- day dermal toxicity and subc hronic inhalation studies as data gaps for chlorsulfuron (TXR# 0050920, 2002). In addition, b ased on the current 40 CFR Part 158 Toxicology Data Requirements, the immunotoxi city, acute and subchronic neurot oxicity studi es are required for chlorsulfuron. In 2012 , t he Hazard and Science Policy Council (HASPOC), based on a WOE approach and considering a ll of the available chlorsulfuron hazard andPage 4 of 18

exposure information, recommend ed that the 21

- day dermal toxicity, inhalation toxicity, and neurotoxicity battery studies not be required at this time (TXR# 0056439, 2012 ). However, an immunotoxicity study is required to support the registered uses of

chlorsulfuron

.

Chlorsulfuron has low acute t oxicity by the oral, dermal, or inhalation route of exposure

. It is no t an eye or skin irritant , and is not a skin sensitizer. There is no evidence that

chlorsul furon is neurotoxic, teratogenic, reproductive, carcinogenic, mutagenic or clastogenic. The most prevalent effect observed across studies was on decreased body weight. For endpoint selection, there is n o appropriate toxicity endpoint available to quantitate risk from a single

- dose ad m i nistration of chlorsulfuron. Consequently, there is

no acute reference dose (aRfD). The c hronic reference dose (cRfD) i s based on decreased body weights in a chronic/carcinogenicity study in rats. The short

- and inter m ediate

- term
incidental oral endpoints as well as the short

- and inter m ediate term der m al and inhalation endpoints are based upon decreases in m aternal body weight and body weight gain seen in

a rabbit develop m ental toxicity study. The chronic endpoints for oral, dermal, and

inhalation routes of exposure are based upon decreased body weight observed in m ale rats
in a chronic/carcinogenicity study. 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. Therefore, a cancer risk assess m ent is not required. Since no der m al absorption data are available, toxicity by the der m al route was considered to be equivalent to toxicity by the

oral route of exposure, a default value of 100% der m al

- absorption (relative to oral absorption) was used.

There is no evidence for increased quantitative or qualitative susceptibility of the young following in utero (rats and rabbits) and pre

- and post

- natal exposure (rats) to

chlorsulfuron. In 2002, t he FQPA Safety Factor Co mm ittee (SFC) evaluate d the hazard

and exposure data for chlorsulfuron and reco mm ended that the FQPA safety factor be

re m oved (1x) in assessing the potential risk posed by this che m ical. In addition, the FQPA SFC deter m ined that a 3x database uncertainty factor should be applied to address

data deficiencies of a reproduction study

. Subsequently, a two

- generation reproduct ion study in rats (2005) was submitted which did not show any adverse effects on reproduction or toxicity to the offspring. The Points of Departure and the FQPA factor

will be re

- evaluated during registration review in accordance with current policy and submission of the outstanding data

.

Chlorsulfuron is rapidly absorbed, metabolized, and eliminated in rats following oral

administration. There is no remarkable sex

- , dose

- , or treatment

- regiment

- related difference in the absorption, distribution, and excretion of chlorsulfuron in rats. 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 3 days after dosing, with the highest concentrations being observed in the liver and whole blood in both

sexes

.

The Points of Departures and toxicological endpoints of concern for the overall risk assessment (dietary and occupational) are presented in Table 4

.Page 5 of 18

Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and 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, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evalua tes acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its

re registration decision for chlorsulfuron , EPA reviewed these data and selected the most sensitive endpoints for r elevant risk assessment scenarios from 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 humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may des ignate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists 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

- related effects caused by the substance, and establish a

dose

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

Under FFDCA section 4 08(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients.

C hlorsulfuron is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will

issue future EDSP orders/data call

- ins, requiring the submission of EDSP screening assays f or chlorsulfuron. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.

Conclusions for Hazard Identification/Toxicology

The tox icology database for chlorsulfuron is nearly complete at the present time with the exception of an immunotoxicity study. Upon receipt o f the required toxicity study, HED

may re

- evaluate the points of departure and uncertainty factors for the dietary , residential and occupational exposure assessments.

Residue ChemistryPage 6 of 18

The existing residue chemistry database for chlorsulfuron is adequa te for risk assessment purposes. No additional data are required at this time. The qualitative nature of the residues of chlorsulfuron in plants and animals has been adequately identified,

characterized and is understood.

The HED Metabolism Assessment Re view Committee (MARC) reviewed the chlorsulfuron toxicology and metabolism data ( D213534, 4/4/95 and 7/18/95) and

recommend ed that the tolerance and risk expression for plant and livestock should include parent only. 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 met abolism and feeding studies.

Methods are available for the enforcement of chlorsulfuron tolerances in/on plant and animal commodities. An analytical method (AMR 3822

- 96) is adequate for data

collection and enforcement for chlorsulfuron residues in/on the plant commodities wheat, barley, oats (grain, forage and straw) and grasses (forage and hay). PAM Vol. II lists Methods I and II, HPLC methods with photoconductivity detection (PCD), for the determination of chlorsulfuron residues in plants and livestock commodities and milk.

The confined accumulation in rotational crop studies indicated that limited field studies are not required. N o tolerances are required for rotational crops , since product labels specify a plant

- back interval of 4 months which is cur rently on the label

.

Conclusions for Residue Chemistry

The database for chlorsulfuron is considered adequate for risk assessment and tolerance

assessment . No new residue chemistry data requirements have been identified for chlorsulfuron to support regis tration review.

Dietary Exposure and Risks

An unrefined (tolerance level residues and 100% crop treated) chronic dietary risk assessment was completed in 2002 using the Dietary Exposure Evaluation Model (DEEM

- FCIDTM) and USDA 1989

- 92 CSFII food consumptio n survey (F. Fort, D283507, 07/18/02).

Acute Acute doses and endpoints were not selected for the general U.S. population (including infants and children) or the females 13

- 50 yrs old population subgroup for chlorsulfuron; therefore, an acute dietary expos ure analysis was not performed.

Chronic Chronic dietary risk ( food only) estimates associated with the use of chlorsulfuron d id n ot exceed the Agency’s level of concern for any population subgroup, including the most highly exposed subgroup children 1

- 6 yrs (8% of the chronic population adjusted dose).

The 2002 dietary exposure assessment was the first dietary assessment that has b een conducted for chlorsulfuron.Page 7 of 18

Drinking Water

A Tier 1 (FIRST

- FQPA Index Reservoir Screening Tool) screening level drinking water

assessment was conducted to estimate pre

- treatment surface water concentrations of total chlorsulfuron residues (both parent and degradation products) resulting from two applications, at 60 day intervals, of the maximum use rate. The estimate of 41.3 ppb for chronic (average annual) exposure w as s elected. The most recent assessment did not directly incorporate drinking water residues into the dietary assessment . The assessment was conducted using the DWLOC (drinking water level of concern) approach.

Conclusions The dietary exposure database is adequate to support the existing registration. However, during registration review, a new drinking water assessment may be needed to incorporate the use of the most current drinking water models. The information available indicates that we may need to revisit the residues of concern de cis i on to discuss the degradates/metabolites in drinking water The revised assessment should include updated consumption information, any changes in the toxicology endpoints, and utilize the latest

version of DEEM

- FCID.

Residential Exposure and Risks

Chlorsulfuron is registered for use on residential lawns, recreational areas (i.e., parks and sports fields), and on golf courses. Due to this use profile, adult residential homeowne rs may experience exposure to chlorsulfuron during application of the chemical (i.e., residential handler exposures). Adults and children may experience exposure to
chlorsulfuron when contacting previously treated areas (i.e., residential post

- application exposure).

Since the 2002 risk assessment, the He alth Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment were updated.

Residential Handlers

In 2002, HED conducted an occupational and residential expo sure assessment based on

the treatment to turf

. HED determined that the MOEs (ranged from 8,800 to 190,000)

were not of concern to adult residential handlers (i.e., MOEs ≥100) ( F. Fort, 7/18/02 )

. Residential handler exposures were estimated using the standard values and assumptions

from the Residential Exposure Assessment Standard Operating Procedures (September 1999)

.

For residential handler s , t he major exposure scenarios identified and assessed previously

include:

1) Mixer/loader/applicator: low pressure handwand

, 2) Mixer/loader/applicator: backpack sprayer

.

Residential Post

- ApplicationPage 8 of 18

In 2002, HED conducted an occupational and residential post

- application exposure

assessment based on the treatment to turf. H ED determined that the MOEs (ranged from 770 to 400,000) were not of concern for residential post

- application for adults and toddlers (i.e., MOEs ≥100) (F. Fort, 7/18/02).

For residential post

- application, t he major exposure scenarios identified and ass essed previously include:

1) Physical activities on turf: adults (dermal) and children (dermal and incidental oral)

.

Conclusions for Resident ial Exposure and Risks

The residential exposure database is adequate to support the registration review process

fo r chlorsulfuron

. In accordance with the updated Part 158 data requirements (2007), a TTR study is required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses. As part of the recent revision to the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment , HED analyzed all available data and selected new liquid and granular default values for the fraction of the application rate available for transfer after a turf application (F AR ). These defaults are 1% for formulations applied as liquids (i.e., emulsifiable concentrates, liquids, wettable powders, dry flowables, etc.) and 0.2% for granular formulations. Of the available TTR studies submitted to the Agency, the

maximum F AR value seen using a liquid product was 6.1% or 6.1 times higher than the

default residue transfer value. The maximum F AR value seen in a TTR study using a granular product was 0.69% or 3.5X the default residue transfer value. Ther efore, for both liquid and granular formulations, a calculated MOE of approximately 10 times higher than the level of concern (e.g., an MOE > 1,000 if the LOC = 100) using the default residue transfer values would provide an adequate margin of safety for a ny potentially higher residues seen in a chemical

- specific TTR study ( Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies . 6/7/2012, Exposure Science Advisory Council). For chlorsulfuron, a TTR stu dy is not required at this time since the dermal and/or hand

- to

- mouth MOE is greater than 1,000 based on default values for the fraction of application rate available for transfer after a turf application . The requirement of a TTR study may need to be

rec onsidered if application rates, use patterns, or points of departure change. An updated residential exposure assessment may be required under registration review based upon

revisions to HED’s 2012 Residential SOPs . An updated assessment may also be requi red if new data are identified which impact exposure estimates, new toxicological points o f departure, or revisions to exposure policies and procedures are made.

Aggregate Exposure and Risk Assessment

The most recent aggregate assessment was completed in 2002 ( F. Fort, 7/18/02)

. Aggregate exposure risk assessment s were assessed for the following scenar ios: short

term (food + drinking water + residential) and chronic aggregate exposure (food + drinking water). An acute aggregate risk assessment was not performed because no acute endpoint was identified to determine the aRfD for the general population or any population subgroup. Intermediate

- and long

- term aggregate

- risk assessments were notPage 9 of 18

performed because th ere are no registered or proposed uses of chlorsulfuron that result in

intermediate

- or long

- term residential exposures. An aggregate cancer risk assessment was not performed because chlorsulfuron is classified as “not likely to be carcinogenic to

humans”

.

The total short

- term food and residential aggregated MOEs are ≥ 722. As this MOE is greater than 100, the short

- term aggregate risks do not exceed HED’s Level of Concern (LOC). Since there are no registered/proposed uses that result in chronic residen tial exposure, the chronic aggregate exposure assessment consists of exposure from food and drinking water only. T he chronic dietary exposure for food alone was not greater than

8% of the c PAD for all population group s and, therefore, do not exceed HED’s LOC.

Conclusions for Aggregate Exposure and Risk Assessment

Updated aggregate exposure and risk assessments may be required under registration

review based on the need for directly incorporating drinking water estimates into the dietary assessment . These revised aggregate exposure and risk assessments may also reflect any toxicological endpoint changes or other new data are received by the Agency that may impact exposure estimates.

Occupational Exposure and Risks

Chlorsulfuron 2

- chloro

- N

- [ ( 4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino carbonyl]benezenesulfonamide

, a systemic herbicide is currently registered for use on barley, oats, wheat, fallow fields, and ornamental turf to control grasses and broadleaf

weeds . It is applied by groundboom sprayer, handheld sprayers, and aerial application.

Occupational Handlers

In 2002 , HED conducted an occupational expo sure assessment for pasture and rangeland

grasses

. The proposed rate of 1 oz ai/A/season on rangeland and pasture grasses was

within rates currently registered on cereal grains (wheat, barley, and fallow fields). HED

determined that the MOEs (ranged from 1,000 to 56,000) were not of concern to

mixers /loaders and applica tors (i.e., MOEs ≥100) ( F. Fort, 7/18/02 ).

The major exposure scen arios identified and assessed previously include:

Mixer/Loaders

1) Mixing/loading dry flowable for aerial application (wheat, high acreage), 2) Mixing/loading dry flowable for aerial application (cereal grains only, low acreage), 3) Mixing/loading dry flowable f or groundboom application (cereal grains), 4) Mixing/loading dry flowable for groundboom application (grass areas), 5) Mixing/loading dry flowable for high pressure handwand application (grass areas).

ApplicatorsPage 10 of 18 1) Applying sprays by aerial application (wheat), 2) Applying sprays by aerial application (cereal grains only), 3) Applying sprays by groundboom application (cereal grains only), 4) Applying sprays by groundboom application (grass areas), 5) Applying sprays by high pressure handwand (cereal grains only ).

Flaggers

1) Flaggers for aerial application (cereal grains only)

.

These scenarios were assessed using the maximum application rate from the proposed label, exposure data from Pesticide Handlers Exposure Database (PHED) Version 1.1, (1998) and assumptions for area tre ated from Science Advisory Council for Exposure (ExpoSAC) Policy #9.1 (September 25, 2001).

Occupational Post

- application

An occupational post

- application exposure or risk estimate was not performed for

chlorsulfuron . Occupational post

- application expos ure is not expected due to the early

season (applied at germination or actively growing) and the use pattern on crops with minimal worker activity after application of chlorsulfuron ( F. Fort, 7/18/02)

.

Since chlorsulfuron is classified as Toxicity Category III for acute dermal and Toxicity Category IV for acute oral, and eye irritation , the Worker Protection Standard (WPS)

R estricted

- E ntry I nterval (REI) is 12 hours

. However, there are several labels where the

REI is 4 hours so this inform ation should be considered and resolved during the registration review process.

Conclusions for Occupational Exposure and Risks

The occupational exposure database is adequate to support the registration review process

for chlorsulfuron. In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are required when a pesticide has residential or occupational uses that could result in post

- application dermal exposure. As part of the recent revision to the

Healt h Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment , HED analyzed a number of DFR studies and selected a new default value for the fraction of the application rate available to be dislodged after a foliar application (F AR ). This default value is 25% and is based on an analysis of 19 DFR

studies where the F AR value ranged from 2% to 89%. This value is recommended for use in both residential and occupational postapplication assessments. Of the analyzed DFR studies, the maximum F AR value seen was 89% or 3.6 times higher than the default residue transfer value. Therefore, the HED has decided that a calculated MOE of approximately 4 times higher than the level of concern (e.g., an MOE > 400 if the LOC = 100) using the default dislodged residue values would provide an adequate margin of safety for any potentially higher residues seen in a chemical

- specific DFR study ( Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable

Foliar Residue (DFR) Studies . 6/7/2012, Exposure Science Advisory Council). For chlorsulfuron, a DFR study is not required at this time since the dermal MOE is greater than 400 based on default values for the fraction of application rate available for transferPage 11 of 18

after a f oliar application. The requirement of a DFR study may need to be reconsidered if application rates, use patterns, or points of departure change. Updated occupational handler exposure assessments may be required under registration review based upon

revisi ons to the Agency’s scenario

- specific surrogate handler exposure data ( http://www.epa.gov/pesticides/science/handler

- exposure

- table.pdf ). An occupational

post

- application asses sment may also be required under registration review if toxicological endpoints change or other new data are received by the Agency that impact exposure estimates

.

Human Studies

Past c hlorsulfuron risk assessments rely in part on data from studies in whi ch adult human subjects were intentionally exposed to a pesticide or other chemical. Studies such

as the Pesticide Handlers Exposure Database

, Outdoor Residential Exposure Task Force

, and Agricultural Handler Exposure Task Force have been reviewed by the Agency and found on the basis of available evidence to have been neither fundamentally unethical nor significantly deficient relative to standards of ethical research conduct prevailing when they were conducted. There is no barrier in EPA's "Protection of Human Subjects" regulation to reliance on these studies.

Public Health and Pesticide Epidemiology Data

An updated review of chlorsulfuron incident reports was recently prepared by HED (S.
Recore, D 40383 1 , 7 /3 1 /2012 )

. For this evaluation, the OPP Incid ent Data System (IDS) was consulted for pesticide incident data on the active ingredient chlorsulfuron

.

The IDS includes reports of alleged human health incidents from various sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Ac t (FIFRA) Section 6 (a) (2) reports from registrants, other federal and state health and environmental agencies and individual consumers. IDS contains reports from across the U.S. and most incidents have all relevant product information recorded. Reports submitted to the IDS represent anecdotal cases or allegations only, unless otherwise stated. IDS records incidents resulting in higher severity outcomes in more detail, in a module called the Main IDS module. This system stores incident data for death, major and moderate incidents, and it includes more details about the location, date and nature of the incident.

For the Main IDS, from January 1, 2007 to June 13, 2012 there are no cases reported that

involves the active ingredient chlorsulfuron

. In the Aggr egate IDS, from January 1, 2007

t o June 13, 2012 , there are 7 i ncident s reported for chlorsulfuron . Because it falls within the categories reported as counts (which includes minor, unknown or no effects), there is no unique report that provides detail s about the incident and single chemical incidents are not distinguished from multiple chemical incidents; however, a high frequency of incidents indicates there is a high potential for exposure and vice versa. For

chlorsulfuron , there appears to be a low potential for exposure. Chlor sulfuron is not included in the Agricultural Health Study (AHS), and therefore, does not provide information for this report.

Based on the low frequency and severity of incident cases, there does not appear to be a

concern a t this time that would warrant further investigation. The Agency may continuePage 12 of 18

to monitor the incident information and if a concern is triggered, additional analysis may be included during registration review.

Tolerance Assessment and International Harmonization

Tolerances are established under 40 CFR §180.4 05 for residues of the herbicide

chlorsulfuron parent and its metabolite , in or on a variety of food and feed crops

. There are currently no established or proposed Codex or Mexican MRLs for chlo rsulfuron

. Canada MRLs are harmonized with the established US tolerances for oat, wheat, and barley grain (see Table 5 )

.

The current tolerance expression as listed in the 40 CFR §180.4 05 has not been updated to reflect current HED policies. The toleranc e expression may need to be revised during the registration review process. The revised tolerance expression should be as follows:

Tolerances are established under 40 CFR §180.4 05 for residues of the herbicide

chlorsulfuron , including its metabolites an d degradates, in or on the following commodities. Compliance with the tolerance levels specified is to be determined by measuring only parent chlorsulfuron, 2

- chloro

- N

- [(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)aminocarbonyl]benzenesulfonamide in or on the commodity

.

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 Jus tice in Minority Populations and Low

Income Populations," http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf . The Office of Pesticide Programs (OP P) typically considers the highest potential exposures from the legal use of a pesticide when conducting human health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets within the U.S., and people who may be exposed when harvesting crops. Should these high exposures indicate potential risks of concern, OPP may further

refine the risk assessments to ensure that the risk estimates are based on the best available

inf ormation.

Cumulative Risk Assessment

At this time, EPA does not have available data to determine whether chlor sulfuron has a common mechanism of toxicity with other substances. EPA has not made a common

mech anism of toxicity finding as to chlorsulfuron and any other substances, and

chlorsulfuron does not appear to produce a toxic metabolite produced by other substances which have tolerances in the U.S. Therefore, EPA has not assumed that chlor sulfuron has a common mechanism of toxicity with other subst ances.

Data RequirementsPage 13 of 18

HED does not anticipate that additional residue chemistry, toxicology or occupational/residential exposure data may be required for the chlorsulfuron registration review process, with the exception of the following studies listed below:

Immunotoxicity Study (OPPTS 870.7800)Page 14 of 18

TABLE 1. Chlorsulfuron Nomenclature

Compound Chemical Structure

Common name Chlorsulfuron

IUPAC name 2

- chloro

- N

- [ (4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino carbonyl]benzenesulfo

namide

CAS name Chlorsulfuron

CAS # 64902

- 72

- 3

TABLE 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 availablePage 15 of 18

Table 3. Chlorsulfuron Toxicology Data Requirements

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

no yes

yes

yes 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 -

-
y es 1

yes 1

-

870.7485 General Metabolism

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

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

no

yes yes

-

no

1 HASPOC recommends that the 21

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

this time

.Page 16 of 18 Table 4

. Toxicological Dose s and Endpoint for Chlorsulfuron Human Health Risk Assessment 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 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

UF DB = 3X FQPA SF = 1X Chronic RfD

= 0.02 mg/kg/day

cPAD = Chronic RfD FQPA SF

= 0.0 2 mg/kg/day C hronic toxicity / carcinogenicity study in rats LOAEL = 25 mg/kg based on

de creased body weights in

males

. Incidental Oral Exposure

Oral

Short

- and

Intermediate

– Term NOAEL=75 mg/kg/day UF A = 10X

UF H = 10X

UF DB = 3X FQPA SF = 1X LOC for MOE= 300 Developmental toxicity study in

rabbits LOAEL=200 mg/kg/day based on decreased body weight gains. Dermal Exposure

Dermal

Short

- Term (1

- 30 days)

Intermediate

– Term (1

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

UF H = 10X

UF DB = 3X FQPA SF = 1X

Dermal Absorption

= 1 00 % Residential LOC for

MOE = 3 00 Occupational LOC for

MOE = 1 00 Developmental toxicity study in

rabbits LOAEL=200 mg/kg/day based on decreased body weight gains.

Dermal Long

– Term (>6 months) NOAEL = 5 mg/kg/day UF A = 10X

UF H = 10X

UF DB = 3X FQPA SF = 1X

Dermal Absorption

= 100% Residential LOC for

MOE= 300 Occupational LOC for

MOE= 100 Chronic toxicity/ carcinogenicity study in rats LOAEL = 25 mg/kg based on decreased body weights in

males.

Inhalation Exposure

Inhalation

Short

- Term (1

- 30 days)

Intermediate

– Term (1

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

UF H = 10X

UF DB = 3X FQPA SF = 1X

Inhalation Absorption

= 100% Residential LOC for

MOE= 300 Occupational LOC for

MOE= 100 Developmental toxicity study in

rabbits LOAEL=200 mg/kg/day based on decreased body weight gains.

Inhalation Long

– Term (>6 months) NOAEL = 5 mg/kg/day UF A = 10X

UF H = 10X

UF DB = 3X FQPA SF = 1X

Inhalation Absorption

= 100% Residential LOC for

MOE= 300 Occupational LOC for

MOE= 100 Chronic toxicity/ carcinogenicity study in rats LOAEL = 25 mg/kg based on decreased body weights in

males.

Cancer Cancer (oral, dermal, inhalation) Classification: not likely to be carcinogenic to hu m ans

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic), RfD = reference dose, MOE = margin of exposure , LOC

= leve l of concern, NA = Not Applicable. UF A = extrapolation from animal to human (interspecies), UF H = potential variation in sensitivity among members of the human population (intraspecies). UF DB = to account for the absence of key data (i.e., lack of a critical study).

Note: The FQPA database uncertainty factor (UF DB ) may be re

- evaluated during registration review based on the results of all

available data.



### International Residue Limits

Table 5

. Summary of US and International Tolerances and Maximum Residue Limits for

Chlorsulfuron Residue Definition :
US Canada Mexico 1 Codex 2Page 17 of 18

Table 5

. Summary of US and International Tolerances and Maximum Residue Limits for

Chlorsulfuron Residue Definition :
US Canada Mexico 1 Codex 2

US [40 CFR §180.405(a)(1)]

Plants: Tolerances are established

for the combined residues of chlorsulfuron (2

- chloro

- N

- [(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)aminocarbonyl]benzenesulfonam ide) and its metabolite, 2

- chloro

- 5

- hydroxy

- N

- [(4

- methoxy

- 6

- methyl

1,3,5

- triazin

- 2

- yl)aminoca rbonyl]

benzenesulfonamide benzenesulfonamide, 2

- chloro

- N

- [[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]

- , including the metabolite benzenesulfonamide, 2

- chloro

- 5

- hydroxy

- N

- [[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]

- None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 Codex 2
Barley, grain 0.1 0.1
Barley, straw 0.5

Oat, forage 20.0
Oat, grain 0.1 0.1
Oat, straw 0.5
Wheat, forage 20.0
Wheat, grain 0.1 0.1
Wheat, straw 0.5

US Canada Mexico 2 Codex 2

US [40 CFR §180.405(a)(2)]

Livestock: Tolerances are

established for the residues of chlorsulfuron (2

- chloro

- N

- [(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)aminocarbonyl] benzenesulfonamide) None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 Codex 3

Cattle, fat 0.3

Cattle, meat 0.3
Cattle, meat byproducts 0.3

Goat, fat 0.3

Goat, meat 0.3
Goat, meat byproducts 0.3
Grass, forage 11.0
Grass, hay 19.0
Hog, fat 0.3
Hog, meat 0.3
Hog, meat byproducts 0.3

Horse, fat 0.3

Horse, meat 0.3
Horse, meat byproducts 0.3Page 18 of 18

Table 5

. Summary of US and International Tolerances and Maximum Residue Limits for

Chlorsulfuron Residue Definition :
US Canada Mexico 1 Codex 2

Milk 0.1
Sheep, fat 0.3
Sheep, meat 0.3
Sheep, meat byproducts 0.3

Completed: : M. Negussie; 07/16/2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the

CCPR and the CAC.

Table 6 : HED Memoranda Relevant to Registration Review

Author Barcode Date Title

J. Abbotts D213534 04/04/1995 Results of the HED Metabolism Committee Meeting Held on 4/4/95: Chlorsulfuron Residues to be Regulated

J. Abbotts None 07/18/1995 Results of the HED Metabolism Committee Meeting Held on 7/18/95: Chlorsulfuron

Residues to be Regulated in Animal

Commodities

F. Fort D283507 07/18/2002 Chlorsulfuron Chronic Dietary Exposure

Assessment for the TRED

F. Fort D235295 12/19/2002 Chlorsulfuron Analytical Method

F. Fort D266070 07/18/2002 Chlorsulfuron in/on Pasture Grasses. Health Effects Division (HED) Risk Assessment

S. Hanley D283856 07/01/2002 Chlorsulfuron Occupational and Residential Exposure and Risk

Assessment/Characterization for Reregistration Eligibility Decision Document and the Proposed Use on Pasture and Rangeland Grasses