lodosulfuron-methyl-sodium Human Health Risk Assessment 04274 13 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: 1O-SEP-2015 

SUBJECT: lodosulfu ron-Methyl-Sodium. Draft Human Health Risk Assessment in 

Support of Registration Review. 

FROM: 

THRU: 

TO: 

PC Code: 12202 1 DP Ba rcode: 0 4274 13 

Decision No.: 505 183 Registration Nos.: NIA 

Petition No.: NIA Rc!!ulatorv Action : Re!!istration Review 

Rjsk Assessment Type: Single Chemical Aggregate Case No.: 7253 

TXR No.: NIA CAS No.: 144550-36-7 

MRID No.: none 40 CfR: 180.580 

Kelly M. Lowe, Environmental ~c j~;i~ p~ 

William D. Wassell, Chemist /Ntf./ '(/./JJ/?h''P'/ 

Jo

Moniqu

shua G. 

e M. 

Godshall, 

Perron, 

Bio

Sc.O., 

logist 

Toxico

y ~l/\ 

o~ist .j A ~ 

Risk Assessment Branch I (RAB I) 

Health Effects Division (HED; 7509P) 

Katherine St. Clair 

Pesticide Re-evaluation Division (PRO; 7508P) 

As part of Registration Review, PRO of the Office of Pesticide Programs (OPP) has requested 

that HED evaluate the hazard and exposure data and conduct occupational and residential 

exposure assessments, as needed, to estimate the risk to human health that will result from the 

currently registered uses of pesticides. This memorandum serves as HEO's draft human health 

risk assessment of the dietary, occupational, and residential exposure, and aggregate risk from 

the registered uses of iodosulfuron-methyl-sodium. 

Since the last human health risk assessment (S. Levy et. al; 12-NOV-2008; 0 350046) and 

scoping document (T. Bloem et. al; 07-MAR-2013; 0404948), the following updates have been 

incorporated for iodosulfuron-methyl-sodium: 

• The subchronic inhalation and subchronic neurotoxicity study requirements have been 

waived. 

• The acute dietary endpoint has been updated based on a submitted acute neurotoxicity 

(ACN) study. 

Page I of 40 
lodosulfuron-methyl-sodium Human Health Risk Assessment 0427413 

• The dermal absorption-factor has been updated to reflect current science policy. 

• The occupational and residential risk assessments have been updated to incorporate new 

science policies. 

• A high-end drinking water exposure value was used to assess screening-level dietary 

exposure/risk estimates. 

Page 2 of40 
Iodosulfuron-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 Chemical 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 Residential 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-application 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

Appendix 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.......................................... 40
Iodosulfuron-methyl-sodium Human Health Risk Assessment D427413

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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). Iodosulfuron-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, soybean, 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 are 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 has 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 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 current policy. 

For dietary exposure, HED has conducted screening-level acute and chronic 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. population 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 exposure (e.g., golf courses, 

residential, recreational, ornamental, and commercial turf), an updated quantitative residential 

exposure assessment (handler and post-application) has been completed. Assessments of 

residential post-application risk for iodosulfuron-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 estimated risks, including combined risks are above HED’s LOC for 

residential risk [margins of exposure (MOEs) >100] and are not of concern. 

Iodosulfuron-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

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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 from dietary (food and drinking water) and nondietary 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 intermediateterm 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, and commercial)) of 

iodosulfuron-methyl-sodium-based products. Therefore, there is a potential for dermal postapplication exposure to workers and a dermal risk assessment was performed. Post-application 

inhalation exposure is expected to be negligible. The 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 dermal 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 postapplication exposures to iodosulfuron-methyl-sodium. HED recommends 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 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.

HED has not identified any risk concerns associated with the registered uses of iodosulfuronmethyl-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 iodosulfuronmethyl-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, grain 
Iodosulfuron-methyl-sodium Human Health Risk Assessment D427413

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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 follows, 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 iodosulfuronmethyl-sodium, including its metabolites and degradates, in or on the commodities in the table 

below. Compliance with the tolerance levels specified below is to be determined by measuring 

only 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-methylsodium in/on wheat and corn 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#1F6299). 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). Solutions 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 quantification 

(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 FDA 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 metsulfuron-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

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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 Identity 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, corn (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 (field4.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.

REI1 = 12 hours.

Golf Courses, Sod Farms, Turf (Commercial/Industrial4 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

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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 Wheat4.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

RTI2 = 14 days

PHI3 = 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-entering 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 procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture’s (USDA’s) National Health and Nutrition Examination Survey/What We Eat in 

America, (NHANES/WWEIA), are used in pesticide risk assessments for all registered food uses 

of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the 

year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups and exposure assessments are performed when 
Iodosulfuron-methyl-sodium Human Health Risk Assessment D427413

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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 playing on treated areas post-application are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to the 

development of specialized software and models that consider exposure to bystanders and farm 

workers as well as lifestyle and traditional 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 

was 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 

tested 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 minimal 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, dermal, 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 supportive 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. 
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4.3 Toxicity Endpoint and Point of Departure Selections

The 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 current 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 points of departure (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-methylsodium. 

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 Toxicological Effects

Acute Dietary 

(All 

Populations)

NOAEL = 100 

mg/kg/day

UFA = 10X

UFH =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

UFA = 10X

UFH =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 

observed in the hematopoietic 

system.

Incidental oral 

(short- and 

intermediateterm)

NOAEL = 8.1 

mg/kg/day

UFA = 10X

UFH =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 (shortand 

intermediateterm)

NOAEL = 8.1 

mg/kg/day

Dermal 

absorption 

factor = 11%

UFA = 10X

UFH =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.
Iodosulfuron-methyl-sodium Human Health Risk Assessment D427413

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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 Toxicological Effects

Inhalation 

exposure (shortand 

intermediateterm)

NOAEL = 8.1 

mg/kg/day

Inhalation 

assumed 

equivalent to 

oral route.

UFA = 10X

UFH =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. UFA = 

extrapolation from animal to human (interspecies). UFH = 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 (shortand 

intermediateterm)

NOAEL = 8.1 

mg/kg/day

Dermal 

absorption 

factor = 11%

UFA = 10X

UFH =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 (shortand 

intermediateterm)

NOAEL = 8.1 

mg/kg/day

Inhalation 

assumed 

equivalent to

oral route.

UFA = 10X

UFH =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 = lowest-observed adverse-effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = level of concern.
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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 include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA 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 iodosulfuronmethyl-sodium, EPA reviewed 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 occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 20131and 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 battery, 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 second list of 

chemicals.

2 http://www.epa.gov/endo/
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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 rotational 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 has 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 studies, 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 residue 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 crop 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 metabolism (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 assessment 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 chemicalspecific estimated drinking water concentrations (EDWCs) following the usual assessment 

procedures, EFED provided coarse-screen estimates that should exceed upper-bound chemicalspecific EDWCs for any SU. This was achieved by using model inputs that represent the use 

pattern of highest exposure from any SU, the highest soil mobility of any SU residue of concern, 

and 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 maximum 
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daily concentration of 751 μg/L (0.751 ppm) and the post-breakthrough 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 EDWCs 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 the revised 2012 Residential SOPs. The exposure and risk estimates for handler and postapplication 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 concern.

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-tomouth, object-to-mouth, and soil ingestion) should be considered inter-related and it is likely that 

they 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 scenarios 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.
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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 

Rate1

Amount Handled 

Daily (gallons)

Dermal Inhalation Total

Dose 

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6 MOE7

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 can8 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 Weight (80 kg).

6 Inhalation MOE = Inhalation NOAEL (8.1 mg/kg/day) ÷ Inhalation 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

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Table 6.0.2. Summary of Residential Post-application Exposure/Risk Estimates from Registered Turf Use1.

Lifestage Activity Formulation Route of Exposure Dose (mg/kg/day)2 MOEs3 Combined 

MOEs4

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-exposuresop.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 estimates 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 use in the children 1 to <2 years old aggregate 

assessment reflects combined dermal plus incidental oral (hand-to-mouth) postapplication exposure from high contact activities on home lawns treated with a liquid 

formulation.

Table 6.1.1. Recommendations for the Residential Exposures for the Iodosulfuron-methyl-sodium 

Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE2

Dermal Inhalation HtM 

Oral Total Dermal Inhalation Oral Total

Adult

Manuallypressurized 

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 240,000
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Table 6.1.1. Recommendations for the Residential Exposures for the Iodosulfuron-methyl-sodium 

Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE2

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 + incidental 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 Drift

A detailed description about HED’s spray drift policy and how to evaluate the drift potential and 

associated risks is available in Appendix F.

6.2.1 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 90th percentile results. 

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 (Table 6.1.1.1). Based on

the total applicable 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 

TTRt

(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

MOE1

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 50,000
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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 pesticides 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 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 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 equivalent 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 

population, 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 adults, 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 

Riska

Dietary exposure 

(food + drinking 

water)b

Residential Exposurec Aggregate MOE 

(food and 

residential) Dermal Inhalation d

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).
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8.0 Cumulative Exposure/Risk Characterization

In 2015, EPA’s Office of Pesticide Programs released a guidance document entitled, Pesticide 

Cumulative Risk Assessment: Framework for Screening Analysis 

[http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/framework-for-screeninganalysis.html]. This document provides guidance on how to screen groups of pesticides for 

cumulative evaluation using a two-step approach beginning with the evaluation of available 

toxicological information and if 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 support a testable hypothesis for a common 

mechanism of action. No further mechanistic data are required and no further cumulative 

evaluation is necessary.

9.0 Occupational Exposure 

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-methylsodium 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 and 

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 exposures (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. Handler 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 + inhalation 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

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using groundboom equipment up to 200 acres per day. All other MOEs ranged from 9,800 to 

1,400,000. PPE on registered labels recommends mixers/loaders and other handlers to wear 

long-sleeved shirts, long pants, chemical-resistant gloves, shoes plus socks, and protective 

eyewear. No additional personal protective equipment (PPE) recommendations are needed on 

the registered labels. 
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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 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

Mixing/loading waterdispersible 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 waterdispersible 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 waterdispersible 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 waterdispersible 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 waterdispersible 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 35,000
Iodosulfuron-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 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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 mechanicallypressurized 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: Baseline.

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) × DAF (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

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9.2 Occupational Post-Application Exposure/Risk Estimates

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry 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 exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce 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 individuals 

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 on issues related to volatilization of 

pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on March 

2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). 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-application 

inhalation exposure into the Agency's risk assessments.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios. 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 quantitative dermal post-application assessment was conducted for iodosulfuron-methylsodium’s uses on wheat, triticale, golf courses, and sod farms due to its use as a postemergence/foliar application treatment. A quantitative post-application dermal assessment was 

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 to 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

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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 is 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) 

interim REI of 12 hours is adequate to protect agricultural workers from post-application 

exposures to iodosulfuron-methyl-sodium. HED recommends 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 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

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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 

(cm2/hr)

Residue1 

(ug/cm2)

Dermal Dose2

(mg/kg-day)

MOE3

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/cm2; 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/cm2; where F = 0.1 and D = 0.10 per day.

2 Daily Dermal Dose = [DFR (μg/cm2) × 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): OPP Incident Data System (IDS) and the Centers for Disease Control and 

Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event 

Notification System for Occupational Risk-Pesticides (SENSOR). HED notes that iodosulfuronmethyl-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; D404948), 

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 continued

to monitor the incident information, but a concern has not been triggered, and therefore, 

additional analyses have not been included in this risk assessment.
Iodosulfuron-methyl sodium Human Health Risk Assessment D427413

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Appendix 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-methyl1,3,5-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/cm3

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, pKa pKa = 3.22 ± 0.06 at 20 oC

Octanol/water partition coefficient, 

Log (KOW)

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 × 104

MeOH 238 3.184 × 104

MeOH + NaOH 239 3.170 × 104

(90/10, v/v); No observed absorption at λ 300-800 nm.

I S

N N

H

O

O

O

O

CH3

N

N

CH3

O

CH3

O

N

Na

+
Iodosulfuron-methyl sodium Human Health Risk Assessment D427413

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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

no1

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

yes2

yes

yes2

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

no1

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 D427413

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Table B.2. Acute Toxicity of Iodosulfuron-methyl-sodium Technical.

Guideline

No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 45133404

LD50 mg/kg (calculated)

Males 2947 (2053-11146) 

Females 2448 (1632-5780) 

Combined 2678 (2175-4744)

III

870.1200 Acute Dermal 45133405 LD50 > 2,000 mg/kg (limit dose) III

870.1300 Acute Inhalation 45108805 LC50 > 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 body 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, not 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 = not observed.

Developmental: NOAEL = 400 mg/kg/day (HDT).

LOAEL = not 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/day

NOAEL = 41.8 mg/kg/day in males, 7.25 mg/kg/day in females.

LOAEL = not 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 D427413

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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 without 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, 1000, 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-methylsodium was tested up to cytotoxic concentrations (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

45108727-45108733 and 45108801-

45108803 (1996)

10 or 500 mg/kg single

100 mg/kg/day repeated dose for 7 

days

Total recovery 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 

complete 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 dose 

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 iodosulfuronmethyl-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-

triazin-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 minor 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 distinct 
Iodosulfuron-methyl sodium Human Health Risk Assessment D427413

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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/cm2

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 bodyweight gains.

Immunotoxicity NOAEL = 242 mg/kg/day.

Immunotoxicity LOAEL = not established.
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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, 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 1.000 

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 1.000 
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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 (Acute) = 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 1182 
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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, field, 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 1.000 

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 0.492000 1.000 1.000 

8602000000 86B Water, indirect, all sources 0.492000 1.000 1.000 
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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 bw/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+ 0.009656 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%

Female 13-49 0.010299 14.1%
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Appendix D: Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data are subject to ethics review 

pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics 

requirements. For certain studies that review may have included review by the Human Studies 

Review Board. Descriptions of data sources as well as guidance on their use can be found at: 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
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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 offtarget 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 them3. [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, such 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 indirect 

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 scenario, 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 available45. 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 conditions. 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 with 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 anticipated 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 outlined in the screening approach represent actual use practice so risk 

assessors should be aware and characterize these appropriately.
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In many cases, risks 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 considered. These drift 

estimates represent plausible options for pesticide labels. 
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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 Mexico1 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-iodo2-[[[[(4-methoxy-6-methyl1,3,5-triazin-2-

yl)amino]carbonyl]amino]sulf

onyl]benzoate

None

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

US Canada Mexico1 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.
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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 maintain reasonable amounts of the reference standards for iodosulfuron-methylsodium in 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 Code is required, or the mail will be 

returned to the registrant. 

 USEPA

 National Pesticide Standards Repository

 Analytical Chemistry Branch/BEAD/OPP

 701 Mapes Road

 Fort George G. Meade, MD 20755-5350

The letter of transmittal should include the assay of the standard, name of the analytical method 

used, a statement of principal impurities, purification procedures employed, storage 

requirements, and 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.