lodo s ulfuron-methyl-sodium H uman Health Ri sk Asses s ment 04 274 1 3 

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D.C. 20460

O FFI C E OF CH E MICA L SA FE TY AN D P O LLUTI O N PRE VE N TIO N



### M E MO RAN D U M

D a t e: 1O-S E P- 2 015

SU BJE C T : 

### lodo s ul fu r o n

- Met h y l

- S odi um

. Draft Human Health Risk Assessme n t in Support of Re g is t ration Re v iew.



### F ROM :

THRU :



### T O: P C Co d e: 12202 1 DP B a r co d e: 0 4 274 1 3

D ec i si on N o .: 505 183 R eg i s t rat i on Nos.: N I A
P e t i t i o n No.: N I A R c!! ul a t o r v Ac tion : R e!!is tr atio n Review
R

j s k A ss es s m ent T y pe: Single C hemical Agg r ega t e Case No

. : 7253

T X R No.: N I A CAS No.: 1 44550-36

- 7

MR ID No.: none 40 Cf R : 180.580



### K e lly M. Lowe
, Environmenta l**~c j~;i~** **p~** 

### William D

. Wa sse ll

, Chem i s t 

# /Ntf

. / '(/

. /JJ/?h' 'P'/ Moniqu e M. P e rron , Sc.O.,

## Toxico**o~ist** 

# . j A

## ~ Jo s hua G. Godshall, Bio l ogist 

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### Ri s k Assessme n t Branch I (RA B I) H eal th Effects Di v is i o n (HED; 7509P)

Kath e r in e St. Clair Pe s ticide R e -evalua t ion Division ( P RO ; 7508P )

A s p a rt of Regi s trati o n Re v ie w, PRO of the Office of Pest i cide Programs (OP P ) h as reque s ted th at HED eva luat e the hazard and exposure data and conduct occupatio n al and r e s i d entia l
exposure assessments , a s needed, to es timate the risk to human h e alth tha t w ill re s u lt from the
current l y r eg i s ter e d use s of pe s ticid es

. Thi s m e morandum serves as HEO 's draft human hea lt h ri sk assessment of the d i et ary, oc c upational

, and residential ex po s ur e, and aggregate risk from the r eg i s ter e d u ses of i odo s ulfuron-meth y l -sodium.

Si nc e th e la s t human h ea lth r i s k a ssess ment (S. Levy et. al; 

### 12-NOV-2008 ; 0 3500 4 6) and

sco ping document 

### (T. Bloe m 

## e t. al; 07-MAR- 2 013 ; 0404948)

, the fo ll owing updates have be e n in corpora t e d for i o do s ulfuron-met h y l- sod i um:

• Th e s ubchronic inh a lation and subchronic neurotoxicity st u dy r e qui r eme n ts h ave b ee n waived.

• The acute di e tar y endpoint ha s b ee n updat e d ba se d on a s ubmitted acute n e u rotoxic i ty (AC N ) s t ud y. P age I of 40

### l odosu lfuron-m et h y l- sodiu m Hum a n Health Ri sk A ssessme nt 0427413



### • T h e derma l absorption-factor ha s been updat e d to reflect current sc i e nc e p o li cy.

• The occ up ational and r es id e ntial risk assessments have b ee n updated to in corpo r ate n ew scie n ce policies.

• A high-end drinkin g water ex po s ur e value was us ed to assess scree nin g-leve l dietary
expos ur e / ri s k es tim a t es.

Pa ge 2 of40Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 3 of 40 

### Table of Contents 1.0 Executive Summary

................................ ................................ ................................ .................. 4 2.0 HED Recommendations

................................ ................................ ................................ ............ 5 2.1 Tolerances Considerations

................................ ................................ ................................ ......... 5 2.1.1 Enforcement Analytical Method

................................ ................................ ................ 6 2.1.2 International Harmonization

................................ ................................ ...................... 6 2.1.3 Tolerance Recommendations

................................ ................................ ..................... 6 2.2 Label Recommendations

................................ ................................ ................................ ............ 7 

### 3.0 Ingredient Profile

................................ ................................ ................................ ...................... 7 3.1 Ch emical Identity and Physical/Chemical Properties

................................ ................................ 7 3.2 Use Pattern

................................ ................................ ................................ ................................ . 7 3.3 Anticipated Exposure Pathways

................................ ................................ ................................ . 8 3.4 Consideration of Environmental Justice

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

### 4.0 Hazard Identification/Toxicology

................................ ................................ ............................. 9 4.1 Summary of Toxicological Effects

................................ ................................ ............................ 9 4.2 Safety Factor for Infants and Children (FQPA SF)

................................ ................................ ... 9 4.3 Toxicity Endpoint and Point of Departure Selections

................................ .............................. 10 4.4 Endocrine Disruption

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

### 5.0 Dietary Exposure and Risk Assessment

................................ ................................ ................. 12 5.1 Residue Chemistry

................................ ................................ ................................ ................... 12 5.2 Drinking Water

................................ ................................ ................................ ........................ 13 5.3 Dietary (Food + Drinking Water) Risk Assessment

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

### 6.0 Residential (Non

- Occupational) Exposure and Risk Assessment

................................ .......... 14 6.1 Residential Risk Estimates for Use in Aggregate Assessment

................................ ................ 16 6.2 Spray Drift

................................ ................................ ................................ ............................... 17 6.2.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications

.......... 17 6.3 Re sidential Bystander Post

- Application Inhalation Exposure

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

### 7.0 Aggregate Exposure and Risk Assessment

................................ ................................ ............. 18 8.0 Cumulative Exposure/Risk Characterization

................................ ................................ .......... 19 9.0 Occupational Exposure

................................ ................................ ................................ ........... 19 9.1 Occupational Handlers

................................ ................................ ................................ ............. 19 9.2 Occupational Post

- Application Exposure/Risk Estimates

................................ ....................... 23 9.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

....................... 23 9.2.2 Occupational Post

- ap plication Dermal Exposure/Risk Estimates

........................... 23 

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

................................ .... 26 Appendix A: Chemical Identity Tables.

................................ ................................ ...................... 27 Appendix B: Iodosulfuron

- methyl

- sodium Acute, Subchronic, and Chronic Toxicity Profile.

.. 28 Appendix C: Dietary Exposure/Risk Modeling Input and Output

................................ ............... 32 Append ix D: Review of Human Research

................................ ................................ ................... 36 Appendix E: Spray Drift Detailed Description

................................ ................................ ............. 37 Appendix F: International Residue Limit (IRL) Status Form

................................ ...................... 39 Appendix G. Analytical Standards for Iodosulfuron

- methyl

- sodium

................................ .......... 40Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 4 of 40 

### 1.0 Executive Summary

Iodosulfuron

- methyl

- sodium is a sulfonylurea (SU) herbicide (Group 2) which interferes with branched

- chain amino acid biosynthesis through inhibition of acetolactate synthase (ALS) in susceptible plants (annual/perennial grass and broadleaf weeds). Iodosulfur on

- methyl

- sodium is currently registered for foliar application to wheat, triticale, field corn, and turf ( e.g., commercial/industrial, sod farms, ornamental, golf course, recreational, and residential) and for application after harvest to cereal grains, s oybean, and cotton.

The toxicity database for iodosulfuron

- methyl

- sodium is adequate to support current registration requirements; currently, no additional toxicological studies are required. Subchronic inhalation and subchronic neurotoxicity studies a re not available for iodosulfuron

- methyl

- sodium; however, the Hazard and Science Policy Council (HASPOC) determined that these studies are not required at this time (J. Van Alstine; 28

- FEB

- 2013; TXR# 0052381).

The latest risk assessment was conducted in 2008 (S. Levy et. al ; 12

- NOV

- 2008; D350046). Since the last risk assessment, acceptable ACN and immunotoxicity studies have been submitted and reviewed. There have been no changes to the prior dose

- response assessment except the acute dietary endpoint h as been changed. Previously, the developmental rat toxicity study was used to evaluate acute dietary exposures; however, the effects seen in the study are not considered to be attributable to a single dose. Since the last risk assessment, an ACN study ha s been submitted and reviewed that provides a new endpoint for acute dietary exposures. Additionally, a new dermal

- absorption factor has been calculated to reflect current policy.

For dietary exposure, HED has conducted screening

- level acute and chroni c dietary risk assessments for iodosulfuron

- methyl

- sodium using 100% crop treated (CT)

, tolerance

- level residues and DEEM (ver. 7.81) default processing factors, and a SU

- class

- wide screening

- level estimate of residues in drinking water. The acute and chronic dietary (food + drinking water) exposure estimates are below HED’s level of concern (LOC) [<100% of the population

- adjusted dose (PAD) for the general U.S. populatio n and all population subgroups (<13% of the acute PAD (aPAD) and <37 % of the chronic PAD (cPAD)].

As not all registered products of iodosulfuron

- methyl

- sodium include the Restricted Use Pesticide (RUP) labeling, and some uses result in residential expos ure (e.g., golf courses, residential, recreational, ornamental, and commercial turf), an updated quantitative residential exposure assessment (handler and post

- application) has been complete d. Assessments of residential post

- application risk for iodosulfu ron

- methyl

- sodium have been conducted in previous risk assessments; however, this document includes an updated residential assessment (both handler and post

- application) in line with the revised 2012 Residential Standard Operating Procedures (SOPs). All e stimated risks, including combined risks are above HED’s LOC for residential risk [margins of exposure (MOEs) >100] and are not of concern.

I odosulfuron

- methyl can be applied via groundboom and, therefore, there is the potential for indirect exposure to iodosulfuron

- methyl related to spray drift. As a result, dermal risk estimates for adults, and dermal and incidental oral risk estimates for children were calculated. Both children (1 to <2 years old) combined incidental oral and dermal risk estimates, and adult dermal risk estimates from exposure to iodosulfuron

- methyl

- sodium related to spray drift result in no risks of concern at the field edge for groundboom applications. Based on the total applicable LOC of 100, all MOEs are ≥100.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 5 of 40 

### Acute and chronic aggregate assessments were conducted; however, the assessments only consider food and drinking water since acute and long

- term residential exposures are not anticipated. Therefore, the acute and chronic dietary exposure risk estimates are representative of aggregate risk estimates and are not of concern. An aggregate cancer risk assessment was not performed because iodosulfuron

- methyl

- sodium was classified as “not likely to be carcinogenic to humans.”

Short/intermediate

- term aggregate risk resulting fro m dietary (food and drinking water) and non

dietary sources of exposure (for this assessment, turf) were assessed for adults and children. For adults, the exposure pathways include the dietary, dermal, and inhalation routes. For children (11 to <16 and 6 to <11 years old), the exposure pathways include the dietary and dermal routes. For children (1 to <2 years old), the exposure pathways include the dietary, dermal and incidental oral routes. All aggregate MOEs are greater than 100; therefore, aggregate exposure to iodosulfuron

- methyl

- sodium is not of risk concern.

The occupational handler exposure and risk estimates indicate that the short

- and intermediate

term dermal and inhalation combined MOEs are not of concern to HED (i.e., MOEs > 100). At the baseline level of personal protection (i.e., no gloves and no respirator), all scenarios result in combined MOEs (dermal + inhalation) ranging from 9,500 to 1,400,000, which is considered protective using current labeling instructions (i.e., long

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

- resistant gloves).

Some of the registered uses involve foliar post

- emergence applications (e.g., wheat, triticale, golf courses, sod farms, and turf (ornamental, residential, recreational, an d commercial)) of iodosulfuron

- methyl

- sodium

- based products . Therefore, there is a potential for dermal post

application exposure to workers and a dermal risk assessment was performed. Post

- application inhalation exposure is expected to be negligible. T he results of the dermal post

- application exposure and risk assessment indicate that dermal MOEs ≥ 100 on day 0 for all scenarios, and, therefore, are not of concern to HED. Iodosulfuron

- methyl

- sodium is classified in Toxicity Category III for acute derma l and Toxicity Category IV for acute oral. It is not an eye irritant, dermal irritant, or dermal sensitizer. Therefore, the [156 subpart K] Worker Protection Statement (WPS) interim REI of 12 hours is adequate to protect agricultural workers from post

ap plication exposures to iodosulfuron

- methyl

- sodium. HED recommend s a 12

- hour REI for the iodosulfuron

- methyl

- sodium labels . It is noted that some products require a REI of 24 hours. For some of the iodosulfuron

- methyl

- sodium labels, multiple active ingre dients are included in the end

- use product and these additional active ingredients may require a longer REI; PRD should ensure the correct REI is listed for these labels.

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

methyl

- sodium. 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

Tolerances are established [40 CFR §180.580(a)] for residues of the herbicide iodosulfuron

methyl

- sodium (methyl 4

- iodo

- 2

- [3

- (4

- methoxy

- 6

- methyl

- 1,3,5 triazin

- 2 yl)ureidosulfonyl]benzoate, sodium salt) in or on field corn forage at 0.05 ppm, field corn, gr ainIodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 6 of 40 

### at 0.03 ppm, field corn stover at 0.05 ppm, wheat forage at 0.10 ppm, wheat grain at 0.02 ppm, wheat hay 0.05 ppm, and wheat straw at 0.05 ppm.

The tolerance expression for iodosulfuron

- methyl

- sodium has been reviewed and should be updated as follow s, based on HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 27

- MAY

- 2009).

40 CFR §180.580(a)(1) Tolerances are established for residues of the herbicide iodosulfuron

methyl

- sodium, including its metabolites and degradates, in or on the commod ities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only iodosulfuron methyl

- sodium (methyl 4

- iodo

- 2

- [[[[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]amino]sulfonyl]benzoate, sodium salt ), calculated as the stoichiometric equivalent of iodosulfuron

- methyl

- sodium, in or on the commodity.

2.1.1 Enforcement Analytical Method

An analytical enforcement method is available for the determination of iodosulfuron

- methyl

sodium in/on wheat and co rn commodities. The method is a high

- performance liquid chromatography (HPLC) method with ultraviolet (UV) or tandem mass spectroscopy (MS/MS) detection, Method BY/02/99 (MRID 45108715). Method BY/02/99 has been reviewed previously (PP#0F6160 and PP#1F62 99). Briefly, samples are extracted with acetonitrile (ACN). The extract is concentrated and partitioned with hexane, then evaporated to dryness. The residues are redissolved in dichloromethane (DCM) and cleaned up by solid

- phase extraction (SPE). Solu tions containing residues are evaporated to dryness, and residues are reconstituted in water:ACN (70:30, v:v) for HPLC/MS/MS analysis or ACN:water (50:50, v:v) for HPLC/UV analysis. Residues are determined using reverse

- phase columns with gradient mobile phases of ACN and 0.01 M phosphoric acid for HPLC/UV analysis or water and ACN each containing formic acid for HPLC/MS/MS analysis. For the MS/MS analysis, residues are quantified using the daughter ion (167 m/z ). The reported method limits of quantifica tion (LOQs) are 0.025 ppm for each analyte in corn and wheat grain and 0.05 ppm for each analyte in forage, stover, hay, and straw. An adequate method is available for enforcing the current wheat, and corn residue tolerances.

The registrant submitted F DA multiresidue methods testing data for iodosulfuron

- methyl

- sodium and its dehalogenated metabolite metsulfuron

- methyl. Testing was conducted by ABC Laboratories, Columbia, MO. These data indicate that iodosulfuron

- methyl

- sodium and its metabolite metsu lfuron

- methyl are not recovered through the FDA multiresidue methods. Additionally, iodosulfuron

- methyl

- sodium is not recoverable by the multiresidue method QuEChERS.

2.1.2 International Harmonization

There are no Mexican or Codex maximum residue limits (MRLs) established for residues of iodosulfuron

- methyl

- sodium. Canadian MRLs are established for wheat grain and corn grain at the same levels of the U.S. tolerances. Therefore, harmonization is not an issue at this time.

2.1.3 Tolerance Recommendations

The residue chemistry database supports the currently established tolerances as listed in 40 CFR §180.580. No changes to currently established tolerances are required at this time.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 7 of 40 

### 2.2 Label Recommendations

The label for Atlantic Herbicide (EPA Reg. No. 264

- 1103) should be modified to indicate the following pre

- harvest intervals: 21 days for forage, 50 days for grain and straw, and 50 days for hay.

3.0 Ingredient Profile

3.1 Chemical Iden tity and Physical/Chemical Properties

The chemical structure and nomenclature of iodosulfuron

- methy

- sodium and a detailed description of the physicochemical properties of iodosulfuron

- methyl

- sodium are provided in Appendix A.

3.2 Use Pattern

Iodosulfuron

- methyl

- sodium is registered as a water

- dispersible granule (WDG) formulation for control of annual and perennial broadleaf weeds and grasses in a variety of crops. There are six registered end

- use products for use on cereal grains, cotton, co rn (field, sweet, popcorn, and corn grown for seed), grain and forage sorghum, soybeans, triticale, wheat, and turf (residential, recreational, commercial, and ornamental). The maximum application rate is 0.009 lbs ai/A for applications to turf and wheat. Applications can be made using ground and handheld equipment only. Applications to wheat and triticale may be made between the 3

- leaf stage up to jointing. Applications to field corn, popcorn, sweet corn, corn grown for seed, cereals, grain and forage sorghum and soybeans may be made after fall harvest and at least 30 days prior to planting field corn, cereals, and grain and forage sorghum and at least 60 days prior to planting soybean, sweet corn, popcorn, or corn for seed. A summary of the registered uses are included in Table 3.2.1.

Table 3.2.1. Summary of Registered Uses for Iodosulfuron

- Methyl

- Sodium.
Applic. Timing, Type, and

Equip. Formulation

[EPA Reg. No.] Max

Application Rate Max Seasonal

Application Rate Use Directions and Limitations

Cereal Grains, Cotton, Sorghum, Corn (field 4 .b , sweet, pop, for seed) Soybeans

Postharvest burndown
treatment Groundboom only WDG

[264

- 856]

[264

- 843

– soybeans only]

[264

- 1134

– field corn & soybean only] 0.0019 lb ai/A 0.0019 lb ai/A/year Do not apply via aerial or chemigation equipment. Do not make more than 1 application per year. Do not graze livestock within 45 days of application.

Apply after fall harvest and at least 30 days prior to planting field corn, cereals, and grain and forage sorghum and at least 60 days prior to planting soybean, sweet corn, popcorn, or corn for seed. REI 1 = 12 hours. Golf Courses, Sod Farms, Turf (Commercial/Industrial 4 a , Ornamental, Recreational, Residential)

Foliar broadcast treatment Spot Treatment Groundboom WDG

[432

- 1507] [432

- 1404] 0.0089 lb ai/A

0.00013 lb ai/gal 0.0089 lb ai/A/year Do not apply via aerial or chemigation equipment.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 8 of 40 Table 3.2.1. Summary of Registered Uses for Iodosulfuron

- Methyl

- Sodium.
Applic. Timing, Type, and

Equip. Formulation

[EPA Reg. No.] Max

Application Rate Max Seasonal

Application Rate Use Directions and Limitations

REI = 24 hours for sod farm use only.
Triticale and Wheat 4 .c

Foliar/post

- emergence broadcast treatment Groundboom WDG

[264

- 820] [264

- 1103] 0.0089 lb ai/A 0.0089 lb ai/A/year Do not apply via aerial or chemigation equipment. Maybe applied up to 2 times a year.

REI = 12 hours

RTI 2 = 14 days

PHI 3 = 21

- 30 days for forage and 50

- 60 days for hay, grain, and straw.

1 REI = restricted entry interval.
2 RTI = retreatment interval.
3 PHI = pre

- harvest interval.

4 These products containing multiple ai’s. The other ai’s are:

a. Thiencarbazone

- methyl and Dicamba (EPA reg# 432

- 1507). b. Thiencarbazone

- methyl (EPA reg# 264

- 1134).

c. Mesosulfuron

- methyl (EPA reg# 264

- 1103).


### 3.3 Anticipated Exposure Pathways

Based on the registered application scenarios, dietary exposure is an anticipated exposure pathway as residues of iodosulfuron

- methyl

- sodium may be found in/on crops and drinking
water. There are residential uses of iodosulfuron

- methyl

- sodium, so exposure in residential or

non

- occupational settings can occur during handler and post

- application activities . In addition, there is a potential for spray drift that may result in exposures in residential and non

- occupational settings. In an occupational setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is also potential for post

- application exposure for workers re

- enter ing treated sites. This risk assessment considers all of the aforementioned exposure pathways based on the existing uses of iodosulfuron

- methyl

- sodium.

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 Low

- Income Populations," ( http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf )



### . As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedur es. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the ho me that involve pesticide use in a residential

s etting. Extensive data on food consumption patterns are compiled by the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey/What We Eat in America, (NHANES/WWEIA), are used in pesticide risk assessments for all regis tered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exp osure assessments are performed whenIodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 9 of 40 

### 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 entering or playi ng on treated areas post

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

4.0 Hazard Identification/Toxicology

The toxicology database for iodosulfuron

- methyl

- sodium is considered complete and adequate for risk assessment. Subchronic inhalation and subchronic neurotoxicity studies are not available for iodosulfuron

- methyl

- sodium, as required in accordance with the current 40 CFR Part 158 Toxicology Data Requirements. However, the HED HASPOC determined that these studies are not required at this time for iodosulfuron

- methyl

- sodium (J. Van Alstine; 28

- FEB

- 2013; TXR# 0052381). The TOXLINE (National Library of Medicine) database literature search did not identify any new toxicological information not already considered. The latest risk assessment

w as conducted in 2008 (S. Levy; 12

- NOV

- 2008; D350046). Since the last risk assessment, acceptable ACN and immunotoxicity studies have been submitted and reviewed. For a summary of the acute, subchronic, and chronic toxicity profile of iodosulfuron

- methyl

- sodium , see Appendix B.

4.1 Summary of Toxicological Effects

The primary targets following subchronic and chronic exposure to iodosulfuron

- methyl

- sodium are the liver (mice and dogs) and the hematopoietic system (dogs). The most sensitive species
teste d was the dog. Body

- weight decrements were also seen in rats. There is evidence of increased susceptibility in the rat developmental and reproduction toxicity studies. In the rat developmental studies, delayed ossification occurred at the same dose as m inimal maternal toxicity (salivation). In the reproduction toxicity study, increased pup mortality was seen in the absence of parental toxicity. There is evidence of neurotoxicity in the ACN study. Decreased motor activity, reduced body temperature, and clinical signs were seen at relatively high doses (≥500 mg/kg/day). There is no evidence that iodosulfuron

- methyl

- sodium is a reproductive, carcinogenic, mutagenic, or immunotoxic chemical. Iodosulfuron

- methyl

- sodium has low acute toxicity via oral, der mal, and inhalation routes of exposure (Toxicity Category III or IV). It is not an eye irritant, dermal irritant, or dermal sensitizer.

4.2 Safety Factor for Infants and Children (FQPA SF)

The 10

- fold Food Quality Protection Act (FQPA) Safety Factor (SF) is reduced to 1X. The toxicity database of iodosulfuron

- methyl

- sodium is considered complete and adequate to assess the qualitative or quantitative susceptibility in the young and exposure estimates are unlikely to underestimate risk. Although there is evidence of increased susceptibility, concern is low since there are clear no

- observed adverse

- effect level (NOAEL) and lowest

- observed adverse

- effect level (LOAEL) values, effects were seen at relatively high doses (>300 mg/kg/day), and the selected endpoints are protective of the observed effects. Although effects were seen in the ACN, concern for neurotoxicity is low since there is a clear NOAEL/LOAEL for the effect, there was no supportiv e neuropathological findings, the effect was seen at a relatively high dose, there was no evidence of neurotoxicity in the rest of the toxicological database, and selected endpoints are protective of the effects.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 10 of 40 

### 4.3 Toxicity Endpoint and Point of Depar ture Selections

Th e only change to the prior dose

- response assessment is the acute dietary endpoint. Previously, the developmental rat toxicity study was used to evaluate acute dietary exposures; however, the effects seen in the study are not considered to be attributable to a single dose. Since the last risk assessment, an ACN study has been submitted and reviewed that provides a new endpoint for acute dietary exposures. Additionally, a new dermal

- absorption factor has been calculated to reflect curren t policy.

It is recognized that the studies in the iodosulfuron

- methyl

- sodium database, including those used for endpoint selection, have not been updated to reflect current policy and may be considered conservative. The currently selected p oints of depar ture (PODs) are protective of the effects observed in the iodosulfuron

- methyl

- sodium database and any updates would not impact the overall findings of the risk assessment given the current risk picture for iodosulfuron

- methyl

sodium.

Table 4.3.1.1. Summary of Toxicological Doses and Endpoints for Iodosulfuron

- methyl

- sodium for Use in Dietary and Non

- Occupational Human Health Risk Assessments. Exposure Scenario Point of

Departure Uncertainty/

FQPA SFs RfD, PAD, LOC for

Risk Assessment Study and Toxic ological Effects

Acute Dietary (All Populations) NOAEL = 100

mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X aRfD = 1 mg/kg/day

aPAD = 1 mg/kg/day Acute Neurotoxicity Study (rat) LOAEL = 500 mg/kg/day based on decreased motor and locomotor activity and clinical signs of toxicity

.
Chronic Dietary (All Populations) NOAEL = 7.3

mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X cRfD = 0.073

mg/kg/day cPAD = 0.073 mg/kg/day Chronic Oral Toxicity Study (dog) LOAEL = 43.7 mg/kg/day based on gross histopathological changes obs erved in the hematopoietic system

.

Incidental oral (short

- and intermediate

term) NOAEL = 8.1

mg/kg/day UF A = 10X

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

MOE < 100 Subchronic Oral Toxicity Study (dog) LOAEL = 49 mg/kg/day based on changes in hematology (both sexes), microscopic pathology of the bone marrow (both sexes) and spleen (females), and changes in clinical chemistry (males) at termination

.

Dermal exposure (short

and intermediate

term) NOAEL = 8.1

mg/kg/day

Dermal absorption factor = 11% UF A = 10X

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

MOE < 100 Subchronic Oral Toxicity Study (dog) LOAEL = 49 mg/kg/day based on changes in hematology (both sexes), microscopic pathology of the bone marrow (both sexes) and spleen (females), and changes in cli nical chemistry (males) at termination

.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 11 of 40 Table 4.3.1.1. Summary of Toxicological Doses and Endpoints for Iodosulfuron

- methyl

- sodium for Use in Dietary and Non

- Occupational Human Health Risk Assessments. Exposure Scenario Point of

Departure Uncertainty/

FQPA SFs RfD, PAD, LOC for

Risk Assessment Study and Toxic ological Effects

Inhalation exposure (short

and intermediate

term) NOAEL = 8.1

mg/kg/day

Inhalation assumed equivalent to oral route. UF A = 10X

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

MOE < 100 Subchronic Oral Toxicity Study (dog) LOAEL = 49 mg/kg/day based on changes in hematology (both sexes), microscopic pathology of the bone marrow (both sexes) and spleen (females), and changes in clinical chemistry (males) at termination

. Cancer (oral, dermal, inhalation) Classified as “ not likely to be carcinogenic to humans” based on lack of evidence of

carcinogenicity in mice and rats

. 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 (i nterspecies). 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). RfD = reference dose (a = acute, c = chronic).

Table 4 .3.2.1

. Summary of Toxicological Doses and Endpoints for Iodosulfuron

- methyl

- sodium for Use in Occupational Human Health Risk Assessments

. Exposure/ Scenario Point of

Departure Uncertainty

Factors LOC for Risk

Assessment Study and Toxicological Effects

Dermal exposure (short

and intermediate

term) NOAEL = 8.1

mg/kg/day

Dermal absorption factor = 11% UF A = 10X

UF H = 10X

FQPA SF = 1X Occupational LOC for

MOE < 100 Subchronic Oral Toxicity Study (dog) LOAEL = 49 mg/kg/day based on changes in hematology (both sexes), microscopic pathology of the bone marrow (both sexes) and spleen (females), and changes in clinical chemistry (males) at termination

.

Inhalation exposure (short

and intermediate

term) NOAEL = 8.1

mg/kg/day

Inhalation assumed equivalent to oral route. UF A = 10X

UF H = 10X

FQPA SF = 1X Occupational LOC for

MOE < 100 Subchronic Oral Toxicity Study (dog) LOAEL = 49 mg/kg/day based on changes in hematology (both sexes), microscopic pathology of the bone marrow (both sexes) and spleen (females), and changes in clinical chemistry (males) at termination

. Cancer (oral, dermal, inhalation) Classified as “not likely to be carcinogenic to humans” based on lack of evidence of

carcinogenicity in mice and rats.
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 = lowes t

- 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. MOE = margi n of exposure. LOC = level of concern.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 12 of 40 

### 4.4 Endocrine Disruption

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (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 inclu de 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 e cological 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 registration decision for iodosulfuron

methyl

- sodium

, EPA revi ewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), iodosulfuron

- methyl

- sodium 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 occ urring 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 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. C hemicals 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 advers e endocrine

- related effects caused by the substance, and establish a dose

- response r elationship 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 201 0, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which c ontains 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, future lists, the test guidelines and the Tier 1 screening batte ry, please visit our website. 2



### 5.0 Dietary Exposure and Risk Assessment

5.1 Residue Chemistry

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final s econd list of chemicals.

2 http://www.epa.gov/endo/Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 13 of 40 

### Permanent tolerances are established for residues of iodosulfuron

- methyl

- sodium in/on corn and wheat commodities with tolerance levels ranging from 0.02 ppm to 0.10 ppm (40 CFR §180.580 (a)). There are currently no Section 18 Emergency Exemptions, tolerances with regional registrations, or tolerances for indirect/inadvertent residues in r otational crops.

Adequate methods are available for enforcing the current plant commodity tolerances. In all available magnitude of the residue and processing studies, samples were analyzed using the current enforcement methods. The analytical method ha s been deemed acceptable and forwarded to the FDA for publication (Memo, 04/11/2002, T. Bloem, D282138 and Memo, 04/01/2009, S. Levy, D363431).

Adequate wheat (triazinyl or phenyl labeled), dairy cow (phenyl labeled), and hen (phenyl labeled) metabolism s tudies, as well as adequate confined rotational crop studies (triazinyl labeled), are available to support the registered agricultural uses. Based on these data and the low application rates and low livestock dietary burdens, HED concluded that the residu e of concern in cereal grains, rotational crops, and livestock, for purposes of tolerance enforcement and risk assessment, is iodosulfuron

- methyl

- sodium (HED Metabolism Assessment Review Committee (MARC) decision memorandum, 10/25/2001, T. Bloem, D278092). It was noted that, depending on the proposed crop(s), application rates, and/or livestock dietary burdens associated with future petitions, these conclusions may be revisited and/or additional metabolism (plant and/or livestock) and confined rotational c rop studies may be required. HED advised that any future plant metabolism or confined rotational crop studies be conducted with the intended safener and correct ai to safener ratio. Metsulfuron

- methyl, a registered active ingredient (PC code 122010), was identified in the wheat and ruminant metabolism studies and in the confined rotational crop study but was not included as a residue of concern as, based on the application scenarios, residues are expected to be negligible.

Adequate crop field trial and processing data are available for all registered crops. There are outstanding issues related to the use directions, but not to tolerances.

The residue chemistry database is adequate to support current Registration Review data requirements. Adequate m etabolism (crops, livestock, and rotational crops), storage stability, magnitude of the residue, and processing data are available to support the registered uses. Adequate methods are available for enforcement of the currently established tolerances.

5 .2 Drinking Water

The residues of concern in drinking water are adequately understood based on available environmental fate studies. The HED Metabolism Assessment Review Committee (MARC) concluded that the residue of concern for the drinking water risk a ssessment should include iodosulfuron

- methyl

- sodium and metsulfuron

- methyl. 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 SU dietary risk assessments. Rather than produce chemical

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

- screen estimates that should exceed upper

- bound chemical

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

- screen EDWCs from PRZM

- GW can be used as conservative estimates of exposure. The acute and chronic dietary assessments for iodosulfuron

- methyl

- sodium used the coarse

- screen maximumIodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 14 of 40 

### daily concentration of 751 μg/L (0.751 ppm) and the post

- breakthro ugh mean value of 492 μg/ L (0.492 ppm), respectively.

5.3 Dietary (Food + Drinking Water) Risk Assessment

In support of Registration Review, an updated acute and chronic dietary (food + drinking water) exposure and risk assessment was conducted using Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCID)

, ver. 3.16

, which incorporates consumption data from the USDA NHANES/WWEIA; 2003

- 2008. The analyses assumed tolerance

- level residues, 100% crop treated, DEEM (ver. 7.81) default processing factors, and modeled drinking water estimates. The EDWC s of 0.751 ppm (acute) and 0.492 ppm (chronic) were incorporated directly into the acute and chronic dietary analyses as “water, direct, all sources” and “water, indirect, all sources.” The acute and chronic dietary (food + drinking water) exposure estimates are below HED’s LOC (<100% PAD) for the general U.S. population and all population subgroups ( <13% of aPAD and < 37% of the cPAD) (see Table 5.3.1). The residue file for the chronic assessment as well as the results of the chronic assessment are provided in Appendix C. Iodosulfuron

- methyl

- sodium was classified as “not likely to be carcinogenic to humans”; therefore , a cancer dietary assessment was not performed.

Table 5.3.1. Summary of Chronic Dietary (Food + Drinking Water) Exposure and Risk for Iodosulfuron

- methyl

- sodium. 1
Population Subgroup aPAD (mg/kg/day) Exposure

(mg/kg/day) %aPAD cPAD (mg/kg/day) Exposure

(mg/kg/day) %cPAD
General U.S. Population

1.0 0.041046 4.1

0.073 0.010374 14 All Infants (<1 year old) 0.128384 13 0.026663 37 Children 1

- 2 years old 0.063348 6.3 0.015028 21 Children 3

- 5 years old 0.051696 5.2 0.012693 17 Children 6

- 12 years old 0.039253 3.9 0.009160 13
Youth 13

- 19 years old 0.034242 3.4 0.007598 10
Adults 20

- 49 years old 0.040456 4.1 0.010340 14
Adults 50

- 99 years old 0.036005 3.6 0.010202 14 Females 13

- 49 years old 0.040783 4.1 0.010299 14
1 The population subgroup with the highest exposure is in bold.



### 6.0 Residential (Non

- Occupational) Exposure and Risk Assessment

As not all registered products of iodosulfuron

- methyl

- sodium include the RUP labeling, and some uses could result in residential exposure from golf courses and turf (residential, recreational, ornamental, and commercial), an updated quantitative assessment of residential handlers and post

- application risks for iodosulfuron

- methyl

- sodium has been conducted in line with th e revised 2012 Residential SOPs. The exposure and risk estimates for handler and post

application exposure are provided in Tables 6.0.1 and 6.0.2 , respectively

. All estimated risks are above HED’s LOC for residential risk (MOE >100) and are not of concer n.

Since dermal and incidental oral exposure routes share a common toxicological endpoint, risk estimates have been combined for those routes. The incidental oral scenarios (i.e., hand

- to

mouth, object

- to

- mouth, and soil ingestion) should be considered inter

- related and it is likely that
t hey occur interspersed amongst each other across time. Combining these scenarios with the dermal exposure scenario would be overly

- conservative because of the conservative nature of each individual assessment. Therefore, the post

- application exposure sce narios that were combined for children 1 < 2 years old are the dermal and hand

- to

- mouth scenarios (Table 6.0.2)

. This combination should be considered a protective estimate of children’s exposure.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 15 of 40 Table 6.0.1. Residential Handler Non

- cancer Exposure and Risk Estimates for Iodosulfuron

- methyl

- sodium.

Exposure Scenario LOC Dermal Unit Exposure (mg/lb ai) 2 Inhalation

Unit Exposure (mg/lb ai) 2 Maximum

Application Rate 1 Amount Handled

Daily (gallons) Dermal Inhalation Total

Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6 MOE 7

Mixer/Loader/Applicator

- Turf (ornamental, residential, recreational, and commercial)

Manually

- pressurized handwand & backpack 100 69 1.1 0.0089 lb ai/gallon 5 0.0042 1,900 0.00061 13,000 1,700

Sprinkler can 8 100 58 0.0014 0.0089 lb ai/gallon 5 0.0035 2,300 0.00000078 10,000,000 2,300

1 Based on registered labels, See Section 3.2. 2 Based on HED’s 2012 Residential SOPs ( http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html ). 3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/gal) × Amount Handled (gallons/day) × Dermal

- Absorption Factor ( 11%) ÷ Body Weight (80 kg). 4 Dermal MOE = Dermal NOAEL (8.1 mg/kg/day) ÷ Dermal Dose (mg/kg/day). 5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/gal) × Amount Handled (gallons/day) ÷ Body We ight (80 kg). 6 Inhalation MOE = Inhalation NOAEL (8.1 mg/kg/day) ÷ Inhal ation Dose (mg/kg/day). 7 Total MOE = NOAEL (8.1 mg/kg/day) ÷ (Dermal Dose + Inhalation Dose)

. 8 Unit exposures for this scenario are based on the Garden/Trees category from the Residential SOPs Handler spreadsheet.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 16 of 40 Table 6.0.2. Summary of Residential Post

- application Exposure/Risk Estimates from Registered Turf Use 1

. Lifestage Activity Formulation Route of Exposure Dose (mg/kg/day) 2 MOEs 3 Combined MOEs 4

Adults high

- contact lawn

activities

DF/WDG Dermal 0.00038 22,000 N/A mowing 0.0000075 1,100,000 golfing 0.000029 280,000

Children (11 to <16 years) mowing 0.0000086 940,000 N/A golfing 0.000036 240,000

Children (6 to <11 years) golfing 0.000039 210,000 N/A

Children (1 to <2 years) high contact lawn activities Dermal 0.00073 11,000
9,300 Incidental Oral

– Hand

- to

- Mouth (HtM) 0.00014 60,000

Incidental Oral

– Object

- to

- Mouth (OtM) 0.0000041 2,000,000

N/A Incidental Oral

– Soil Ingestion 0.00000030 27,000,000

1 Based on registered labels (see Table 3.2.1). 2 Dose (mg/kg/day) calculated per algorithms in HED’s 2012 Residential SOPs ( http://www.epa.gov/pesticides/science/residential

- exposure

sop.html ). 3 MOE = POD (8.1 mg/kg/day) ÷ Dose (mg/kg/day). 4 Combined MOE = POD (8.1 mg/kg/day) ÷ (Dermal Dose (mg/kg/day) + Incidental Oral HtM Dose (mg/kg/day)). 

### 6.1 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.1 .1 reflects the residential risk e stimates that are recommended for use in the aggregate assessment for iodosulfuron

- methyl

- sodium.

 The recommended residential exposure for use in the adult aggregate assessment reflects dermal and inhalation exposure from applications to turf via backpack sprayer or manually

- pressurized handwand.

 The recommended residential exposure for use in the children 11 to <16 years old aggregate assessment reflects dermal post

- application exposure from golfing on turf that has been treated with a liquid formulation.

 The recommended residential exposure for use in the children 6 to <11 years old aggregate assessment reflects dermal post

- application exposure from golfing on turf that has been treated with a liquid formulation.

 The recommended residential exposure for us e in the children 1 to <2 years old aggregate assessment reflects combined dermal plus incidental oral (hand

- to

- mouth) post

application exposure from high contact activities on home lawns treated with a liquid formulation.

Table 6. 1 .1. Recommendations fo r the Residential Exposures for the Iodosulfuron

- methyl

- sodium Aggregate Assessment.

Lifestage Exposure

Scenario Dose (mg/kg/day) 1 MOE 2

Dermal Inhalation HtM Oral Total Dermal Inhalation Oral Total

Adult Manually

pressurized handwand & backpack 0.0042 0.00061

N/A 0.0048 1,900 13,000

N/A 1,700

Children (11 to <16 years) golfing 0.000036 N/A 0.000036 240,000 N/A 240,000Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 17 of 40 Table 6. 1 .1. Recommendations fo r the Residential Exposures for the Iodosulfuron

- methyl

- sodium Aggregate Assessment.

Lifestage Exposure

Scenario Dose (mg/kg/day) 1 MOE 2

Dermal Inhalation HtM Oral Total Dermal Inhalation Oral Total

Children (6 to <11 years) golfing 0.000039 0.000039 240,000 210,000

Children (1 to <2 years) high contact

lawn activities 0.00073 0.00014 0.00087 11,000 60,000 9,300

1 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. Total = dermal + inhalation + i ncidental oral

(where applicable). Doses extracted from Tables 6.0.1 and 6.0.2. 2 MOE = the MOEs associated with the highest residential doses. Total = POD (mg/kg/day) / Combined dose (dermal + inhalation +

incidental oral), where applicable.


### 6.2 Spray Dri ft

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. 2 .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 application scenarios. Iodosulfuron

- methyl

- sodium is an herbicide registered for use on: cereal grains, cotton, corn ( field, sweet, and pop), grain and forage sorghum, soybeans, triticale, wheat, sod farms, and turf (residential, recreational, commercial, and ornamental). Registered use products can be applied via groundboom and handheld equipment. The recommended drift scenario screening level options are listed below:

 Groundboom applications are based on the AgDrift ® 

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

### percentile results.

Both children (1 to <2 years old) combined incid ental oral and dermal risk estimates, and adult dermal risk estimates from exposure to iodosulfuron

- methyl

- sodium related to spray drift result in no risks of concern at the field edge for groundboom applications (Table 6.1.1.1). Based on the total applic able LOC of 100, all MOEs are ≥100.

Table 6. 2 .1.1. Adult Dermal; Children (1 to <2 years old) Dermal & Incidental Oral Risk Estimates (MOEs) Related to Spray

- Drift Exposure for Iodosulfuron

- methyl

- sodium. Lifestage Crop Application Method Spray Type /

Nozzle Configuration Application

Rate (lb ai /A) Estimated

TTR t (ug/cm2) At Edge

Dermal MOE Adult Cereal grains, cotton, sorghum, soybeans,

& corn (field, sweet, pop, & unspecified)

Groundboom High Boom / Very fine to Fine 0.0019 0.00021 550,000

Wheat, Triticale, golf courses, sod farms, & turf (commercial, ornamental, recreational, & residential) 0.0089 0.00099 120,000

Combined MOE 1 Children 1 to <2 years old Cereal grains, cotton, sorghum, soybeans,

& corn (field, sweet, pop, & unspecified) 0.0019 0.00021 240,000

Wheat, Triticale, golf courses, sod farms, & turf (commercial, ornamental, recreational, & residential) 0.0089 0.00099 50,000Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 18 of 40 1 Combined MOE = 1/((1/Dermal MOE) + (1/HtM MOE))

.


### 6.3 Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The agency sought expert advice and input on issues related to volatilization of pesti cides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (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 agency has eva luated 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 agency will utilize this analysi s to determine if data (i.e., flux studies, route

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

- methyl

- sodium.

7.0 Aggregate Exposure and Risk Assessment

Acute, short/intermediate

- term, and chronic aggregate assessments were conducted for iodosulfuron

- methyl

- sodium. A cancer aggregate risk assessment was not performed because iodosulfuron

- methyl

- sodium is not classified by HED as “not likely to be carcinogenic to humans.”

Aggregate acute risk is equivalen t to acute dietary risk via food and drinking water exposure pathways and comprises 13% of the aPAD for the most highly exposed population, infants <1 year old. Likewise, chronic dietary risk comprises 37% of the cPAD for the most highly exposed populatio n, infants <1 year old.

There is potential short

- and intermediate

- term exposure to iodosulfuron

- methyl

- sodium via the dietary pathway (which is considered background exposure) and the residential pathway (which is considered the primary pathway). For ad ults, the exposure pathways includes the dietary, dermal, and inhalation routes. For children (11 to <16 and 6 to <11 years old), the exposure pathways include the dietary and dermal routes. For children (1 to <2 years old), the exposure pathways include the dietary, dermal and incidental oral routes. All aggregate MOEs are greater than 100; therefore, aggregate exposure to iodosulfuron

- methyl

- sodium is not of risk concern.

Table 7.0. Short

- and Intermediate

- Term Aggregate Risk Calculations.

Population Short

- or Intermediate

- Term Scenario

LOC for Aggregate Risk a Dietary exposure

(food + drinking water) b Residential Exposure c Aggregate MOE (food and residential) d Dermal Inhalation Incidental Oral
Adults

100 0.010374 0.0042 0.00061 NA 530
Children (11 to <16 years) 0.007598 0.000036 NA NA 1,100 Children (6 to <11 years) 0.00916 0.000039 NA NA 880 Children (1 to 2 years old) 0.015028 0.00073 NA 0.00014 510

a Adults and Children Level of Concern = 100 (based on inter

- and intra

- species uncertainty factors, each at 10X). b Dietary exposure (mg/kg/day) = chronic dietary exposure from Table 5.3.1.

c Residential exposure based on recommendations from Table 6.3.1. d Aggregate MOE = POD (8.1 mg/kg/day) ÷ Combined dose (dietary + residential, mg/kg/day)

.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 19 of 40 

### 8.0 Cumulative Exposure/Risk Characterization

In 2015, EPA’s Office of Pesticide Programs released a guidance document entitled, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis [ h ttp://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 cumulative evaluation using a two

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

- based screening approach. This framework supplements the existing guidance documents for establishing common mechanism groups (CMGs) [1] 

### and conducting cumulative risk assessments (CRA) [2]



### . The Agency has utilized this framework to evaluate the SUs of which iodosulfuron

- methyl

- sodium is a member (J. D’Agostino; D428798; 9/9/15). Although the SUs share some chemical and toxicological characteristics, the toxicological database does not suppor t 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

Based on the registered use pattern (summarized in Table 3.2.1), there is a potential for exposure to iodosulfuron

- methyl

- sodium in occupational settings from handling iodosulfuron

- methyl

sodium products during the application process (i.e., mixer/loaders, applicators, and mixer/loader/applicators) and from entering treated areas after application.

9.1 Occupational Handlers

Based on current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the registered use on cereal grains, cotton, corn (field, sweet, pop, and for seed), soybeans, sorghum, wheat, triticale, golf courses, sod farms, and turf (commercial, residential, recreational, and ornamental). Occupational handlers are anticipated to have short

- term (1

- 30 days) and intermediate

- term (1

- 6 months) dermal a nd inhalation exposures. Since the same endpoint and point of departure were selected for short

- and intermediate

- term durations, short

- term exposure and risk estimates are considered to be protective of intermediate

- term exposure and risk. Long

- term expos ures (more than 6 months) are not anticipated.

In support of Registration Review, an updated occupational exposure assessment for iodosulfuron

- methyl

- sodium was conducted for mixers/loaders and applicators for groundboom applications of a DF formulation, as well as mixer/loader/applicators performing spot treatments with handheld equipment. The assessment was based on the maximum registered application rate of 0.0089 lb ai /A (0.00013 lb ai /gallon), and maximum area treated per day or gallons handled. Han dler exposure and risk were calculated at baseline (long pants, a long

- sleeved shirt, no chemical

- resistant gloves, and no respirator) and with personal

- protective equipment (PPE) when necessary

. 

### Dermal and inhalation risk estimates were combined in this assessment, since the toxicological effects for these exposure routes were similar. Combined dermal + i nhalation risk estimates were not of concern (i.e., MOEs ≥ 100) with baseline protection (see Table 9.1.1). The lowest MOE of 9,500 is associated with mixing/loading a water dispersible granule formulation applied

[1] Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity (USEPA, 1999) [2] Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity (USEPA, 2002)Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 20 of 40 

### using groundboom equipment up to 200 acres per day. All other MOEs ranged from 9,800 to 1,400,000. PPE on registered labels recommen ds mixers/loaders and other handlers to wear long

- sleeved shirts, long pants, chemical

- resistant gloves, shoes plus socks, and protective
eyewear. No additional p ersonal protective e quipment ( PPE ) recommendations are needed on the registered labels.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 21 of 40 Table 9.1.1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Iodosulfuron

- methyl

- sodium.

Exposure Scenario Crop or Target Dermal Unit Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application Rate (lb ai/A) 2 Area

Treated (acres) 3 Dermal

(LOC = 100) Inhalation (LOC = 100) Total

(LOC = 100)

Mitigation Level Mitigation

Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Mixer/Loader Mixing/loading water

dispersible granules Groundboom application Golf course (trees and greens only) 227

(baseline) 8.96

(baseline) 0.0089 5 0.000016 500,000 0.0000058 1,400,000 370,000

Mixing/loading water

dispersible granules Groundboom application Golf course (fairways, trees, and greens) 227

(baseline) 8.96

(baseline) 0.0089 40 0.00013 63,000 0.000046 180,000 47,000

Mixing/loading water

dispersible granules Groundboom application Sod farm 227 (baseline) 8.96

(baseline) 0.0089 80 0.00026 31,000 0.000093 88,000 23,000

Mixing/loading water

dispersible granules Groundboom application Cereal grains, cotton, sorghum, soybeans, and corn (field, sweet, pop and unspecified) 227

(baseline) 8.96

(baseline) 0.0019 200 0.00014 59,000 0.000049 160,000 43,000

Mixing/loading water

dispersible granules Groundboom application Wheat and triticale 227 (baseline) 8.96

(baseline) 0.0089 200 0.00064 13,000 0.00023 35,000 9,500

Applicator Groundboom spray application Golf course (trees

and greens only) 78.6

(baseline) 0.34

(baseline) 0.0089 5 0.0000056 1,500,000 0.00000022 37,000,000 1,400,000

Groundboom spray application Golf course

(fairways, trees, and greens) 78.6

(baseline) 0.34

(baseline) 0.0089 40 0.000045 180,000 0.0000018 4,600,000 170,000

Groundboom spray application Sod farm 78.6 (baseline) 0.34

(baseline) 0.0089 80 0.000089 91,000 0.0000035 2,300,000 88,000

Groundboom spray application Cereal grains, cotton,

sorghum, soybeans, and corn (field, sweet, pop and unspecified) 78.6

(baseline) 0.34

(baseline) 0.0019 200 0.000048 170,000 0.0000019 4,300,000 160,000

Groundboom spray Wheat and triticale 78.6 0.34 0.0089 200 0.000046 36,000 0.00000877 920,000 35,000Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 22 of 40 Table 9.1.1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Iodosulfuron

- methyl

- sodium.

Exposure Scenario Crop or Target Dermal Unit Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application Rate (lb ai/A) 2 Area

Treated (acres) 3 Dermal

(LOC = 100) Inhalation (LOC = 100) Total

(LOC = 100)

Mitigation Level Mitigation

Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8
application (baseline) (baseline) Mixer/Loader/Applicator
Mixing/loading/applying
water

- dispersible granules via backpack applications Turf (ornamental, residential, recreational, and commercial) 8260

(baseline) 2.58

(baseline) 0.00013 lb

ai/gallon 40 gallons 0.0000686 120,000 0.000000194 42,000,000 120,000

Mixing/loading/applying
water

- dispersible granules via manually

- pressurized handwand applications Turf (ornamental, residential, recreational, and commercial) 100,000

(baseline) 30

(baseline) 0.00013 lb

ai/gallon 40 gallons 0.000829 9,800 0.00000226 3,600,000 9,800

Mixing/loading/applying
water

- dispersible granules via mechanically

pressurized handwand applications Golf courses and turf

(ornamental, residential, recreational, and commercial) 1,960

(baseline) 42

(baseline) 0.0089 5 0.000139 58,000 0.000027 300,000 49,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: Base line. 2 Based on registered labels. See Section 3.2. 3 Exposure Science Advisory Council Policy #9.1. 4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) × DA F (11 %) ÷ BW (80 kg). 5 Dermal MOE = Dermal NOAEL (8.1 mg/kg/day) ÷ Dermal Dose (mg/kg/day). 6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (80 kg). 7 Inhalation MOE = Inhalation NOAEL (8.1 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). 8 Total MOE = NOAEL (8.1 mg/kg/ day) ÷ (Dermal Dose + Inhalation Dose)

.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 23 of 40 

### 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 pe sticide (also referred to as re

entry exposure). Such exposures 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 ex posure 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 applicati ons, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

9.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post

- application inhalation exposure to in dividuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input o n 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 ). In terms of volatilization, the Agency 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 Agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for specific chemicals.

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

- application inhalation exposure data generated by the ARTF. Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post

- applicat ion inhalation exposure into the Agency's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Hand ler 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. Based on this, HED concludes that additional data pertaining to assessment of post

- application inhalation exposure are unnecessary

9.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

A quantitati ve dermal post

- application assessment was conducted for iodosulfuron

- methyl

sodium’s uses on wheat, triticale, golf courses

, and sod farms due to its use as a post

emergence/foliar application treatment. A quantitative post

- application dermal assessment w as not conducted for cotton, sorghum, soybean, or corn (field, sweet, pop, or unspecified) due to its
use as a pre

- planting burndown treatment with a 30

- to 60

- day pre

- planting interval; and turf (commercial, residential, recreational, or ornamental) due t o occupational workers not expected to be returning to the treatment site after applications. The results of the dermal post

- application exposure and risk assessment indicate that dermal MOEs ≥ LOC (MOEs ≥ 100) on day 0 for all scenarios, and, therefore, are not of concern to HED.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 24 of 40 

### Iodosulfuron

- methyl

- sodium is classified as Toxicity Category III for acute dermal, acute oral, and primary eye irritation; and Toxicity Category III for acute inhalation and primary skin irritation (see Appendix A.2.2). It i s not a skin sensitizer. Under 40 CFR 156.208 (c) (2) (iii), ai’s classified as Acute III or IV for acute dermal, eye irritation and primary skin irritation are assigned a 12

- hour REI. Therefore, the [156 subpart K] Worker Protection Statement (WPS) inte rim REI of 12 hours is adequate to protect agricultural workers from post

- application exposures to iodosulfuron

- methyl

- sodium. HED recommend s a 12

- hour REI for the iodosulfuron

- methyl

- sodium labels . It is noted that some products require a REI of 24 hour s. For some of the iodosulfuron

- methyl

- sodium labels, multiple active ingredients are included in the end

- use product and these additional active ingredients may require a longer REI; PRD should ensure the correct REI is listed for these labels.Iodosulfuron

- methyl

- sodium Human Health Risk Assessment D427413

Page 25 of 40 Table 9.2.1. Summary of Occupational Post

- application Dermal Exposure and Risk Estimates.

Crop ExpoSAC

Policy 3 TC Crop Group Crop

Height Foliage

Density Activity Transfer Coefficient (cm 2 /hr) Residue 1

(ug/cm 2 ) Dermal Dose 2

(mg/kg

- day) MOE 3

DAT (Day After Treatment) = 0 (12 hours)

Wheat (spring & winter) and Triticale Field / row crop / low/medium Low

Low Min

Full Scouting 1,100 0.02 0.00030 27,000

Weeding, Hand 70 0.000019 420,000

Golf Course Turf / sod Low Full Maintenance 3,700
0.001 0.000041 200,000

Low Full Maintenance (greens only) 2,500 0.000027 290,000

Sod Farm Turf / sod Low Full Maintenance Harvesting, Slab Transplanting/ Planting 6,700 0.001 0.000074 110,000

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 OR TTR = Application Rate × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2 ; where F = 0.1 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 ( 11%)]  BW ( 80 kg). 3 MOE = POD (8.1 mg/kg/day) / Daily Dermal Dose.Page 26 of 40



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

The following databases were consulted to identify potential patterns in the frequency and severity of the health effects attributed to iodosulfuron

- methyl

- sodium exposure (i.e. incident data): O PP Incident Data System (IDS) and the Centers for Disease Co ntrol and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk

- Pesticides (SENSOR)

. HED notes that iodosulfuron

methyl

- sodium is not included in the Agricultural Health Study ( AHS ). At the time of the scoping document for iodosulfuron

- methyl

- sodium ( T. Bloem et. al ; 07

- MAR

- 2013 ; D 404948), there was a low frequency and severity of incident cases reported; therefore, further investigation was not warranted at that time (D405837, S. Recore, 17

- Oct

- 2012). 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.Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 27 of 40 

### Ap pendix A : Chemical Identity Tables.

Table A.1. Iodosulfuron

- methyl

- sodium Nomenclature.

Chemical structure

Common name Iodosulfuron

- methyl

- sodium Company experimental name AE F115008
IUPAC name Sodium ({[5

- iodo

- 2

- (methoxycarbonyl)phenyl]sulfonyl}carbamoyl)(4

- methoxy

- 6

- methyl

1,3,5

- triazin

- 2

- yl)azanide
CAS name Sodium salt of methyl 4

- iodo

- 2

- [[[[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]amino]sulfonyl]benzoate CAS registry number 144550

- 36

- 7

Table A.2. Physicochemical Properties of Iodosulfuron

- Methyl

- Sodium.

Parameter Value Reference Melting point 152oC

RD Memorandum: D272474, H. Podall, 16

- May

- 2001 pH of 1% dispersion in water 6.7 Density 1.76 g/cm 3 Water solubility pH Solubility at 20oC (g/L) 7.6 (unbuffered) 60.0 4 0.02 5 0.17 7 25.0 9 65.0 10 45.0 Solvent solubility Solvent Solubility at 20oC (g/L)
acetone >380.0 DCM >500.0 ethyl acetate 23.0

n

- hexane ~1.2 × 10

- 3 methanol 12.0

n

- heptane ~1.1 × 10

- 3 2

- propanol 4.4 toluene 2.1 ACN 52.0 dimethyl sulfoxide >500.0 polyethylene glycol 87.0 Vapor pressure 2.6 × 10

- 9 Pa at 20oC; 6.7 × 10

- 9 Pa at 25oC Dissociation constant, pK a pK a = 3.22 ± 0.06 at 20 oC Octanol/water partition coefficient, Log (K OW ) pH 4: 1.96; pH 5: 1.07; pH 6: 0.07; pH 7:

- 0.70; pH 9:

- 1.22; pH 10:

- 1.15 (all at 25oC) UV/visible absorption spectrum Solvent λmax (nm) ε [L/(mol × cm)] MeOH 203 2.990 × 10 4 MeOH 238 3.184 × 10 4 MeOH + NaOH 239 3.170 × 10 4 (90/10, v/v); No observed absorption at λ 300

- 800 nm.Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 28 of 40 

### Appendix B: Iodosulfuron

- methyl

- sodium Acute, Subchronic, and Chronic Toxicity Profile.

Table B.1. Iodosulfuron

- methyl

- sodium 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 21/28

- Day Dermal

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

- Day Dermal

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

- Day Inhalation

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

no

no 1 yes

yes yes

--

-- 870.3700 Developmental Toxicity (rodent)

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

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

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

yes yes 870.4100a Chronic Toxicity (rodent)

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

................................ ....... 870.4200a Carcinogenicity (rat)

................................ ..................... 870.4200b Carcinogenicity (mouse)

................................ .............. 870.4300 Chronic Toxicity/Carcinogenicity (rodent)

.................. yes yes yes yes yes yes 2

yes yes 2
yes yes 870.5100 Mutagenicity

— Gene Mutation

- bacterial

.................... 870.5300 Mutagenicity

— Gene Mutation

- mammalian

............... 870.5375 Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5385 Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5395 Mutagenicity

— Other Genotoxic Effects

...................... 870. 5550 Mutagenicity

— Other Genotoxic Effects

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

yes yes yes yes yes 870.6100 Acute Delayed Neurotox. (hen)

................................ .... 870.6100 90

- Day Neurotoxicity (hen)

................................ ......... 870.6200a Acute Neurotox. Screening Battery (rat)

...................... 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

............. 870.6300 Developmental Neurotoxicity

................................ ...... no

no yes

no 1

no --

-- yes

--

-- 870.7485 General Metabolism

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

................................ ....................... 870.7800 Immunotoxicity

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

no yes yes

-- yes
1 HASPOC concluded the subchronic inhalation and subchronic neurotoxicity studies are not required at this time (J. Van Alstine; 28

- FEB

- 2013; TXR# 0052381 ).

2 The combined chronic/carcinogenicity study fulfills this requirement.Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 29 of 40 Table B.2. Acute Toxicity of Iodosulfuron

- methyl

- sodium Technical.
Guideline No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 45133404 LD 50 mg/kg (calculated) Males 2947 (2053

- 11146) Females 2448 (1632

- 5780) Combined 2678 (2175

- 4744) III

870.1200 Acute Dermal 45133405 LD 50 > 2,000 mg/kg (limit dose) III
870.1300 Acute Inhalation 45108805 LC 50 > 2.81 mg/L IV
870.2400 Primary Eye Irritation 45133407 Not an ocular irritant III
870.2500 Primary Skin Irritation 45133406 Non

- irritating IV
870.2600 Dermal Sensitization 45108806 Non sensitizer

--

Table B.3. Iodosulfuron

- methyl

- sodium Subchronic, Chronic , and Other Toxicity Profile.

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.3100 90

- Day oral toxicity rodents

- rat 45133408 (1997) Acceptable/guideline 0, 200, 1,000, 5,000

, or 10,000 ppm; 0/0, 13.8/15.4, 67/74, 347/388

, or 686/790 M/F mg/kg/day NOAEL = 67 mg/kg/day in males, 74 mg/kg/day in females. LOAEL = 347 mg/kg/day in males, 388 mg/kg/day in females based on reduced bo dy weight and overall body

- weight gains in both sexes.

870.3100 90

- Day oral toxicity rodents

- mouse 45108808 (1997) Acceptable/guideline 0, 700, 2,100, or 7,000 ppm 0/0, 119/139, 332/401, or 1311/1332 M/F mg/kg/day NOAEL = 119 mg/kg/day in males, n ot observed in females. LOAEL = 332 mg/kg/day in males, 139 mg/kg/day in females based on hepatotoxicity.

870.3150 90

- Day oral toxicity nonrodents

- dog 45108809, 45108807 (1998) Acceptable/guideline 0, 200, 1200, or 7200 ppm 0/0, 8.1/8.4, 49/51, or 301/317 M/F, mg/kg/day NOAEL = 8.1 mg/kg/day in males, 8.4 mg/kg/day in females. LOAEL = 49 mg/kg/day in males, 51 mg/kg/day in females based on changes in hematology, microscopic pathology of the bone marrow and spleen (females), clinical chemistry (males).

870.3700a Prenatal developmental in rodents

- rat 45108820, 45108819 (1996) Acceptable/guideline 0, 100, 315

, or 1,000 mg/kg/day Maternal : NOAEL = 315 mg/kg/day. LOAEL = 1,000 mg/kg/day based on increased salivation. Developmental : NOAEL = 315 mg/kg/day

. LOAEL =1000 mg/kg/day based on delayed ossification.

870.3700b Prenatal developmental in nonrodents

- rabbit 45108901, 45108821 (1996) Unacceptable/guideline (not upgradable) 0, 25, 100

, or 400 mg/kg/day Maternal : NOAEL = 400 mg/kg/day (HDT). LOAEL = n ot observed. Developmental : NOAEL = 400 mg/kg/day (HDT). LOAEL = n ot observed.

870.3800 Reproduction and fertility effects

- rat 45108818, 45108817 (1998)

Acceptable/guideline 0, 50, 500

, or 5000 ppm 0/0, 3.43/3.90, 34.2/39.7

, or 346/390.4 M/F mg/kg/day Parental/Systemic NOAEL = 346 mg/kg/day in males, 390 mg/kg/day in females (HDT). LOAEL = not established. Reproductive NOAEL = 346 mg/kg/day in males, 390 mg/kg/day in females (HDT). LOAEL = not established. Offspring NOAEL = 34.2 mg/kg/day in males, 39.7 mg/kg/day in females. LOAEL = 346 mg/kg/day in males, 390 mg/kg/day in females (HDT) based on pup mortality.

870.4100b Chronic toxicity

- dog 45108810 (1998) Acceptable/guideline 0, 30, 200 or 1200 ppm 0/0, 1.03/1.08, 7.37/7.25

, or 41.8/43.7 M/F mg/kg/da y NOAEL = 41.8 mg/kg/day in males, 7.25 mg/kg/day in females. LOAEL = n ot established in males, 43.7 mg/kg/day in females based on gross and histopathological changes observed in the hematopoietic system.

870.4300 Chronic/ Carcinogenicity

- rat 45108815, 45133408 (1998)

Acceptable/guideline 0, 70, 700, or 7,000 ppm 0/0, 2.96/3.91, 29.7/39.1, or 331/452 M/F mg/kg/day NOAEL = 29.7 mg/kg/day in males, 39.1 mg/kg/day in females. LOAEL = 331 mg/kg/day in males and 452 mg/kg/day in females based on reduced body weight and body

- weight gains in males and on reduced body weight, body

- weight gains and food efficiency in females.Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 30 of 40 Table B.3. Iodosulfuron

- methyl

- sodium Subchronic, Chronic , and Other Toxicity Profile.

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

No evidence of carcinogenicity.

870.4300 Carcinogenicity

-
mouse 45108816 (1998) Acceptable/guideline 0, 35, 350 or 1,750 ppm 0/0, 5.15/5.72, 54.2/57.6

, or 279/277 M/F mg/kg/day NOAEL = 54.2 mg/kg/day in males, 57.6 mg/kg/day in females. LOAEL = 279 mg/kg/day in males, 277 mg/kg/day in females based on increased liver weights and histopathological changes in the liver. No evidence of carcinogenicity at doses tested.

870.5100 Gene Mutation 45133409 (1993) Acceptable/guideline 4, 20, 100, 500, 2500

, or 5000 μg/plate Non

- mutagenic when tested up to 5000 ug/plate, in presence and absence of metabolic activation, in S. typhimurium strains TA98, TA100, TA1535 and TA1537 and E.coli strain WP2uvra.

870.5300 Gene Mutation 45108811 (1996) Acceptable/guideline 5

- 7 doses ranging from 100 to 2649 μg/mL Negative for induction of forward mutation at the HPRT locus in Chinese hamster V79 lung fibroblasts, in the presence or absence of S9

- activation at doses up to limit of solubility (2649 μg/mL).

870.5375 Chromosome aberration 45108812 (1996)

Acceptable/guideline 0, 500, 1500, or 2649 μg/mL with S9 activation and 0, 100, 250, or 500 μg/mL wi thout S9 activation Did not induce structural chromosome aberration in Chinese hamster lung (V79) cell cultures in the presence and absence of activation up to cytotoxic concentrations.

870.5385 Chromosomal aberration 45108814 (1996)

Acceptable/guideline 200, 1000

, or 2000 mg/kg Non

- mutagenic in NMRI mouse bone marrow micronucleus chromosomal aberrations assay up to the limit dose (2000 mg/kg).

870.5550 Other Genotoxicity 45108813 (1996)

Acceptable/guideline 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300, 1 000, 3000, or 5000 μg/mL No evidence that unscheduled DNA synthesis was induced by iodosulfuron

- methyl

- sodium, as determined by radioactive tracer procedures [nuclear silver grain counts]. Iodosulfuron

- methyl

sodium was tested up to cytotoxic concentratio ns (  3000 μg/mL). UDS activity was assessed at 0.01 to 1000 μg/mL.

870.6200a Acute Neurotoxicity 47577101 Acceptable/guideline 0, 100, 500, or 2000 mg/kg NOAEL = 100 mg/kg

. LOAEL = 500 mg/kg based on decreased motor and locomotor activity and clinical signs of toxicity. Decreased body temperature was also seen in females at 2000 mg/kg.

870.7485 Metabolism and pharmacokinetics

- rat 45108727

- 4510 8 733 and 45108801

- 45108803 (1996) 10 or 500 mg/kg single 100 mg/kg/day repeated dose for 7 days Total recove ry of the administered dose was 95.9

- 102.4% for all treatment groups. No radioactivity was detected in exhaled air or organic volatiles. Elimination of radioactivity occurred primarily in the urine, mostly within 24 hours of dosing, and was essentially

c omplete within 3 days of dosing. Overall urinary excretion accounted for 78.5% and 85.8% of the dose for males and females, respectively, and fecal elimination accounted for 19.2% and 10.1% of the dose, respectively. By 3 days post

- dose,  0.5% of the dos e remained in the blood and tissues of both sexes of rats from the low

- and high

- dose groups. Rats excreted the majority of the dose as unchanged parent via the urine (48.7

- 86.3% dose) or feces (1.1

- 11.1% dose). Minor routes of metabolism for iodosulfuro n

methyl

- sodium included hydrolysis of the methylester to form 4

- iodo

- 2

- [3

- (4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)ureidosulfonyl] benzoic acid (AE F145740; 0.9

- 4.5% dose); O

- demethylation of the triazine ring to form methyl 2

- [3

- (4

- hydroxy

- 6

- methyl

- 1,3,5

- t riazin

- 2

- yl)ureidosulfonyl]

- 4

- iodobenzoate (AE F148741; 1.5

- 8.2% dose); or hydroxylation of the methyl group on the triazine ring to form methyl 2

- [3

- (4

- hydroxymethyl

- 6

- methoxy

- 1,3,5

- triazin

- 2

- yl)ureidosulfonyl]

- 4

- iodobenzoate (AE F168532; 0.3

- 6.6% dose). Each of these mi nor metabolites was present in both the urine and feces. The remaining metabolites each accounted for <3% of the dose.

870.7485 Metabolism and pharmacokinetics

- dog 45108804 (1998)

Acceptable/guideline 6 or 200 mg/kg single oral dose Within 72 hours of oral dosing, 90

- 94% of the dosed radioactivity was recovered in the excrement and cage wash of both dose groups. Renal excretion accounted for 64

- 74% of the dose and elimination in the feces accounted for 14

- 17% of the radioactive dose. Most of the dose was excreted within 24 hours. Quantitative RP

- HPLC analyses isolated up to 6 distinctIodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 31 of 40 Table B.3. Iodosulfuron

- methyl

- sodium Subchronic, Chronic , and Other Toxicity Profile.

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

radioactive components in urine and feces. The major isolated fraction was the parent: urine (54

- 61% dose) and feces (8

- 11%).

In the rat, the major isolated fraction was also the parent, while the major metabolite was AE F145741. The metabolites identified in the dog were consistent with those identified in the rats.

870.7600 Dermal Penetration

- rat 45108915 (1998) Supplementary 0.023 or 0.376 mg/c m 2 Absorbed dose was low at both dose levels (<1

- 6%). Levels in the carcass and excreted increased after cessation of exposure with a corresponding decrease at the application site, indicating continued absorption of the chemical from the application site

.

870.7800 Immunotoxicity

- rat 48592801 (2011)

Acceptable/guideline 0, 14, 73, or 242 mg/kg/day Systemic NOAEL = 73 mg/kg/day

. Systemic LOAEL = 242 mg/kg/day based on decreased body

weight gains

. Immunotoxicity NOAEL = 242 mg/kg/day

. Immunotoxicity LOAEL = not established

.Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 32 of 40 

### Appendix C: Dietary Exposure/Risk Modeling Input and Output

Acute Dietary Exposure File & Results

Filename: J: \ Work Files \ $ Iodosulfuron \ DEEM \ 05_22_2015_Acute_Iodosulfuron.R08 Chemical: Iodosulfuron RfD(Chronic): .073 mg/kg bw/day NOEL(Chronic): 7.3 mg/kg bw/day RfD(Acute): 1 mg/kg bw/day NOEL(Acute): 100 mg/kg bw/day Date created/last modified: 05

- 22

- 2015/10:23:56 Program ver. 3.16, 03

- 08

- d

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

---------- ---- ------------------------------- ---------- ------ ------ 1500120000 15 Corn, field, flour 0.030000 1.000 1.000 1500120001 15 Corn, field, flour

- babyfood 0.030000 1.000 1.000 1500121000 15 Corn, field, meal 0.030000 1.000 1.000 1500121001 15 Corn, fie ld, meal

- babyfood 0.030000 1.000 1.000 1500122000 15 Corn, field, bran 0.030000 1.000 1.000 1500123000 15 Corn, field, starch 0.030000 1.000 1.000 1500123001 15 Corn, field, starch

- babyfood 0.030000 1.000 1.000 1500124000 15 Corn, field, syrup 0.030000 1.000 1.000 1500124001 15 Corn, field, syrup

- babyfood 0.030000 1.000 1.000 1500125000 15 Corn, field, oil 0.030000 1.000 1.000 1500125001 15 Corn, field, oil

- babyfood 0.030000 1.000 1.000 1500401000 15 Wheat, grain 0.020000 1.000 1.000 1500401001 15 Wheat, grain

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

- babyfood 0.020000 1.000 1.000 1500403000 15 Wheat, germ 0.020000 1.000 1.000 1500404000 15 Wheat, bran 0.020000 1.000 1.000 8601000000 86A Water, direct, all sources 0.751000 1.000 1.000 8602000000 86B Water, indirect, all sources 0.751000 1.000 1.000Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 33 of 40 US EPA Ver. 3.18, 03

- 08

- d
DEEM

- FCID ACUTE Analysis for IODOSULFURON NHANES 2003

- 2008 2

- Day Residue file: 05_22_2015_Acute_Iodosulfuron.R08 Adjustment factor #2 NOT used. Analysis Date: 05

- 22

- 2015/10:29:14 Residue file dated: 05

- 22

- 2015/10:23:56 NOEL (Acut e) = 100.000000 mg/kg body

- wt/day RAC/FF intake summed over 24 hours Run Comment: ""

=============================================================================

Summary calculations

-- per capita:

- 95th Percentile

---- --- 99th Percentile

---- --- 99.9th Percentile

- Exposure %aRfD MOE Exposure % aRfD MOE Exposure % aRfD MOE

------------------------------------------------------------------------------------ Total US Population: 0.041046 4.10 2436 0.067547 6 .75 1480 0.128700 12.87 776 All Infants: 0.128384 12.84 778 0.174237 17.42 573 0.255599 25.56 391 Female 13

- 50: 0.040783 4.08 2451 0.060062 6.01 1664 0.085093 8.51 1175 Children 1

- 2: 0 .063348 6.33 1578 0.095676 9.57 1045 0.233291 23.33 428 Children 3

- 5: 0.051696 5.17 1934 0.079271 7.93 1261 0.126390 12.64 791 Children 6

- 12: 0.039253 3.93 2547 0.064402 6.44 1552 0. 099263 9.93 1007 Youth 13

- 19: 0.034242 3.42 2920 0.056298 5.63 1776 0.085153 8.52 1174 Adults 20

- 49: 0.040456 4.05 2471 0.060012 6.00 1666 0.087216 8.72 1146 Adults 50

- 99: 0.036005 3.60 2777 0.054390 5.44 1838 0.085735 8.57 1166 Female 13

- 49: 0.040945 4.09 2442 0.060036 6.00 1665 0.084535 8.45 1182Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 34 of 40 

### Chronic Dietary Exposure File & Results

Filename: J: \ Work Files \ $ Iodosulfuron \ DEEM \ 05_22_2015_Chronic_Iodosulfuron.R08 Chemical: Iodosulfuron RfD(Chronic): .073 mg/kg bw/day NOEL(Chronic): 7.3 mg/kg bw/day RfD(Acute): 1 mg/kg bw/day NOEL(Acute): 100 mg/kg bw/day Date created/last modified: 05

- 14

- 2015/16:01:06 Program ver. 3.16, 03

- 08

- d

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

-------------- ----------------------------------------------------------- 1500120000 15 Corn, field, flour 0.030000 1.000 1.000 1500120001 15 Corn, field, flour

- babyfood 0.030000 1.000 1.000 1500121000 15 Corn, f ield, meal 0.030000 1.000 1.000 1500121001 15 Corn, field, meal

- babyfood 0.030000 1.000 1.000 1500122000 15 Corn, field, bran 0.030000 1.000 1.000 1500123000 15 Corn, field, starch 0.030000 1.000 1.000 1500123001 15 Corn, field, starch

- babyfood 0.030000 1.000 1.000 1500124000 15 Corn, field, syrup 0.030000 1.000 1.000 1500124001 15 Corn, field, syrup

- babyfood 0.030000 1.000 1.00 0 1500125000 15 Corn, field, oil 0.030000 1.000 1.000 1500125001 15 Corn, field, oil

- babyfood 0.030000 1.000 1.000 1500401000 15 Wheat, grain 0.020000 1.000 1.000 1500401001 15 Wheat , grain

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

- babyfood 0.020000 1.000 1.000 1500403000 15 Wheat, germ 0.020000 1.000 1.000 1500404000 15 Wheat, bran 0.020000 1.000 1.000 8601000000 86A Water, direct, all sources 0.492000 1.000 1.000 8602000000 86B Water, in direct, all sources 0.492000 1.000 1.000Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 35 of 40 US EPA Ver. 3.16, 03

- 08

- d
DEEM

- FCID Chronic analysis for IODOSULFURON NHANES 2003

- 2008 2

- day Residue file name: J: \ Work Files \ $ Iodosulfuron \ DEEM \ 05_22_2015_Chronic_Iodosulfuron.R08 Adjustment factor #2 NOT used. Analysis Date 05

- 22

- 2015/10:27:02 Residue file dated: 05

- 22

- 2015/10:25:25 Reference dose (RfD, Chronic) = .073 mg/kg b w/day

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

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

Total Exposure

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

-------------------------------------- ------------- ---------------- Total US Population 0.010374 14.2% Hispanic 0.009921 13.6%
Non

- Hisp

- White 0.010666 14.6%
Non

- Hisp

- Black 0.008574 11.7%
Non

- Hisp

- Other 0.011940 16.4% Nursing Infants 0.009363 12.8%
Non

- Nursing Infants 0.034389 47.1% Female 13+ PREG 0.009764 13.4% Children 1

- 6 0.013364 18.3% Children 7

- 12 0.008712 11.9% Male 13

- 19 0.007177 9.8% Female 13

- 19/NP 0.008011 11.0% Male 20+ 0.0 09656 13.2% Female 20+/NP 0.010868 14.9% Seniors 55+ 0.010000 13.7% All Infants 0.026663 36.5% Female 13

- 50 0.010311 14.1% Children 1

- 2 0.015028 20.6% Children 3

- 5 0.012693 17.4% Children 6

- 12 0.009160 12.5% Youth 13

- 19 0.007598 10.4% Adults 20

- 49 0.010340 14.2% Adults 50

- 99 0.010202 14.0%
F emale 13

- 49 0.010299 14.1%Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 3 6 of 40 

### Appendix D : Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a p esticide or other ch emical. 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. Descript ions 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

.Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 37 of 40 

### Appendix E: 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 exposures to those the chemical may directly contact. Sprays can also deposit on surfaces where individuals come into contact with residues on these surfaces, leading to indirect exposures (e.g., children playing on lawns where residues have deposited next to treated fields ).

The approach to be used for quantitatively incorporating spray drift into risk assessment is based on a premise of compliant applications which, by definition, should not result in direct exposures to individuals because of existing label language and other regulatory requirements intended to prevent them 3 

### . [Direct exposures would include inhalation of the spray plume or being sprayed directly.] Rather, the exposures addressed here are thought to occur indirectly through contact with impacted areas, s uch as residential lawns, when compliant applications are conducted. Given this premise, exposures for children (1 to 2 years old) and adults who have contact with turf where residues are assumed to have deposited via spray drift

, thus resulting in an ind irect exposure are the focus of this analysis 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 sulfometuron. In the spray drift scenari o, the deposited 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 and the Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift Policy

. Once the deposited residue values were determined, the remainder of the spray drift assessment was based on the algorithms and input values specified in the 2012 Standard Operating Procedures for Residential Risk Assessment (SOPs)

. A screening approach was developed based on the use of the AgDrift ® 

### model in situations where specific label guidance that defines application parameters is not available 4 5 

### . AgDrift ® 

### is appropriate for use only when applications are made by aircraft, airblast orchard 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 conditio ns. The screening options specifically recommended in this methodology were selected because they are plausible and represent a reasonable upper bound level of drift for common application methods in agriculture. These screening options are consistent wi th how spray drift is considered in a number of ecological risk assessments and in the process used to develop drinking water concentrations used for risk assessment. In all cases, each scenario is to be evaluated unless it is not plausible based on the a nticipated use pattern (e.g., herbicides are not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are not allowed). Section 6. 2 .1 provides the screening level drift related risk estimates.

3 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.

4 http://www.agdrift.com/

5 Note that for many cases the scenarios outline d in the screening approach represent actual use practice so risk assessors should be aware and characterize these appropriately.Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 38 of 40 

### In many cases, risk s are of concern when the screening level estimates for spray drift are used as the basis for the analysis. In order to account for this issue and to provide additional risk management options additional spray drift deposition fractions were also consider ed. These drift estimates represent plausible options for pesticide labels.Iodosulfuron

- methyl sodium Human Health Risk Assessment D 427413

Page 39 of 40 

### Appendix F: International Residue Limit (IRL) Status Form

International Residue Limits

Iodosulfuron

- Methyl (122021 ; 05/11/2015) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 Codex 40 CFR 180.580:

Plant: Iodosulfuron

- Methyl

- Sodium (methyl 4

- iodo

- 2

- [3

- (4

- methoxy

- 6

- methyl

- 1,3,5 triazin

- 2 yl)ureidosulfonyl]benzoate, sodium salt)

Livestock: N/A sodium salt of methyl 4

- iodo

2

- [[[[(4

- methoxy

- 6

- methyl

1,3,5

- triazin

- 2

- yl)amino]carbonyl]amino]sulf onyl]b enzoate None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 1 Codex Corn, field, forage 0.05 Corn, field, grain 0.03 0.03 Corn, field, stover 0.05 Wheat, forage 0.10 Wheat, grain 0.02 0.02 Wheat, hay 0.05 Wheat, straw 0.05

Completed: M. Negussie; 05/19/2015

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

- methyl sodium Human Health Risk Assessment D 427413

Page 40 of 40 

### Appendix G. Analytical Standards for Iodosulfuron

- methyl

- sodium



### Analytical reference standards for iodosulfuron

- methyl

- sodium are currently available in EPA’s National Pesticide Standards Repository (NPSR) and have an expiration date of 09/20/2016 (email communication between G. Verdin and J. Van Alstine, 5/11/2015). The registrant is required to maint ain reasonable amounts of the reference standards for iodosulfuron

- methyl

sodium i n the NPSR as long as tolerances remain published in 40 CFR §180. 580 . When necessary, new reference standards, or updated certificates of analysis (COAs), should be sent to the Analytical Chemistry Branch (ACB), which is located at Fort Meade, MD. It should be sent to the attention of either Theresa Cole or Thuy Nguyen at the address listed below, along with a letter of transmittal. Please note that the full 9

- digit ZIP Cod e 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, purificat ion procedures employed, storage requirements, and special precautions for safe handling. Replacement of standards, or updated COAs, may be required periodically if supplies are exhausted, if the standards expire, or if decomposition occurs during storage . Material Safety Data Sheets (MSDSs) must accompany all analytical standards as specified by the Occupational Safety and Health Administration (OSHA) in 29 CFR §1910.1200.