Flumetsulam Human Health Risk Assessment DP No. D411276 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 19-S EP- 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Flumetsulam. Preliminary Human Health Risk Assessment for Registration 

Review 

PC Code: 129016 

Decision No.: 477891 

Petition No.: NA 

Risk Assessment Type: Single 

Chemical/ Aggregate 

DP Barcode: D411276 

Registration No.: NA 

Regulatory Action: Registration Review 

Case No.: 7229 

TXR No.: NA CAS No.: 98967-40-9 

MRID No.: NA 40 CFR: 180.468 // 

FROM: Mohsen Sahafeyan, Risk Assessor vf/~ ~_,_____ P. 

Brid

Yvonne 

gett Bobowiec

Barnes, 

, 

Chemi

Biologi

st 

st 

-/? ~ 

· ~ 

~~ 

' 

Yung Yang, Ph.D., Toxicologist c,_;r7 G-. ?</---;r 

Risk Assessment Branch VI t7 (/ v 

Health Effects Division (7509P) 

THROUGH: Felecia Fort, Branch Chief ~" /' V 

Risk Assessment Branch VI -jP.~"{'/CJ -:jdt 1) 

Health Effects Division (7509P) 

TO: Katherine StClair, Chemical Review Manager 

Risk Management and Implementation Branch II 

Pesticide Re-Evaluation Division (7508P) 

Page 1 of 40 
Flumetsulam Human Health Risk Assessment DP No. D411276

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The Health Effects Division (HED) of the Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human health from exposure to pesticides. As part of Registration Review, 

the Pesticide Re-evaluation Division (PRD) of OPP has requested that HED evaluate the hazard 

and exposure data and conduct dietary, occupational, residential, and aggregate exposure 

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

uses of flumetsulam. 

HED has evaluated the toxicity and exposure databases for the active ingredient, Flumetsulam, 

and has conducted a human health risk assessment in support of Registration Review. Based on 

this assessment, HED has determined that there are no potential risk estimates of concern for the 

currently registered uses of Flumetsulam.

A summary of the findings and an assessment of human health risk resulting from the currently 

registered uses of Flumetsulam are provided in this document. The HED team members 

contributing to this risk assessment include Mohsen Sahafeyan (risk assessment), Bridgett 

Bobowiec (occupational risk assessment), P. Yvonne Barnes (chemistry and dietary exposure 

assessment) and Yung Yang (hazard assessment). James Wolf of the Environmental Fate and 

Effects Division (EFED) performed the drinking water assessment for Flumetsulam.
Flumetsulam Human Health Risk Assessment DP No. D411276

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2.0 Introduction ............................................................................................................... 7

2.1 Tolerances.........................................................................................................................7

2.2 International Harmonization ..............................................................................................7

2.3 Structure and Nomenclature ..............................................................................................8

2.4 Physical/Chemical Characteristics.......................................................................................8

2.5 Summary of Existing Uses...................................................................................................8

2.6 Anticipated Exposure Pathways .......................................................................................11

2.7 Consideration of Environmental Justice ............................................................................11

3.0 Hazard Characterization and Dose-Response Assessment ......................................... 12

3.1 Summary of Toxicological Effects......................................................................................12

3.2 Safety Factor for Infants and Children (FQPA Safety Factor) ..............................................13

3.2.1 Completeness of the Toxicology Database..........................................................................................13

3.2.2 Evidence of Neurotoxicity....................................................................................................................13

3.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal..........................................13

3.2.4 Residual Uncertainty in the Exposure Database..................................................................................13

3.3 Toxicity Endpoint and Point of Departure Selections.........................................................13

3.4 Endocrine Disruption .......................................................................................................14

4.0 Dietary Exposure and Risk Assessment...................................................................... 15

4.1 Degradate Residue Profile................................................................................................15

4.1.1 Summary of Environmental Degradation ............................................................................................16

4.1.2 Residues of Concern Summary and Rationale .....................................................................................16

4.1.3 Enforcement Analytical Method..........................................................................................................17

4.2 Food Residue Profile ........................................................................................................17

4.3 Water Residue Profile ......................................................................................................18

4.4 Dietary Risk Assessment...................................................................................................19

4.4.1 Description of Residue Data Used in Dietary Assessment...................................................................19

4.4.2 Percent Crop Treated Used in Dietary Assessment .............................................................................19

4.4.3 Acute Dietary Risk Assessment............................................................................................................19

4.4.4 Chronic Dietary Risk Assessment.........................................................................................................19

4.4.5 Cancer Dietary Risk Assessment..........................................................................................................20

4.4.6 Dietary Risk Assessment Summary Table ............................................................................................20

5.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................... 20

5.1 Spray Drift .......................................................................................................................20

5.2 Inhalation Post-application Exposure................................................................................22

6.0 Aggregate Exposure/Risk Characterization............................................................... 23

7.0 Cumulative Exposure/Risk Characterization.............................................................. 23

8.0 Occupational Exposure/Risk Characterization........................................................... 23

8.1 Occupational Handler Exposure and Risk ..........................................................................23
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8.1.1 Short-/Intermediate-Term Non-Cancer Handler Exposure and Risk ...................................................25

8.1.2 Cancer Handler Exposure and Risk ......................................................................................................28

8.2 Occupational Post-Application Exposure and Risk.............................................................28

8.2.1 Post-application Inhalation Exposure ..................................................................................................28

8.2.2 Post-application Dermal Exposure and Risk ........................................................................................28

8.2.2.1 Short-/Intermediate-Term Non-Cancer Post-application Exposure and Risk ...............................29

8.2.2.2 Cancer Post-application Exposure and Risk ....................................................................................29

References........................................................................................................................... 30

Appendix A. Toxicology Assessment.................................................................................. 32

A.1 Toxicology Data Requirements.........................................................................................32

A.2 Toxicity Profile.................................................................................................................33

Appendix B. Physical/Chemical Properties........................................................................... 36

Appendix C. Review of Human Research.............................................................................. 37

Appendix D. Occupational Exposure/Risk Summary Tables.................................................. 38

Appendix E. Summary of US and International Tolerances and Maximum Residue Limits..... 40
Flumetsulam Human Health Risk Assessment DP No. D411276

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1.0 Executive Summary

As part of Registration Review, the Pesticide Re-evaluation Division (PRD) of the Office of 

Pesticide Programs (OPP) has requested that the Health Effects Division (HED) evaluate the 

hazard and exposure data and conduct dietary, occupational, residential, and aggregate exposure 

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

uses of Flumetsulam. This document provides a summary of the findings and an assessment of 

human health risk resulting from the currently registered uses of flumetsulam.

Use Profile: Flumetsulam (N-(2,6-difluorophenyl)-5-methyl-(1,2,4)triazolo(1,5-a)pyrimidine-2-

sulfonamide) is an herbicide in the triazolopyrimidine chemical class used to control broadleaf 

weeds in field corn, dry bean and soybean, applied as a pre emergent and early post-emergent 

herbicide. HED notes that although dry bean is a registered primary crop, all labels for dry bean 

are inactive at present; any reference to use rate and use patterns for dry bean in this document 

are based on older inactive labels, field trial data, and previously reviewed 

occupational/residential exposure (ORE) assessment (Dow, Mark I., 2004, D306178). 

Flumetsulam can be applied by ground and by aerial application with restrictions. It is 

formulated as a water dispersible granular (WDG), a water dispersible granular packaged in 

water soluble packet (WSP), and as an emulsifiable concentrate (EC). The highest maximum 

application rate is 0.07 lb ai/A for field corn, soybeans, and dry beans. 

Hazard Assessment: The toxicology database for flumetsulam is complete. A subchronic 

inhalation study was not available; however, the HED Hazard and Science Policy Council 

(HASPOC) determined that a subchronic inhalation toxicity study is not needed for flumetsulam 

at this time (TXR# 0056689). 

The kidney appears to be the primary target organ of rats and dogs following exposure to high 

doses of flumetsulam in subchronic and chronic toxicity studies. Flumetsulam has low acute 

toxicity by oral, dermal, or inhalation routes of exposure. It is not a skin or eye irritant and is not 

a skin sensitizer. The available toxicity database shows that flumetsulam is not a neurotoxic or 

immunotoxic chemical and it does not induce developmental or reproductive toxicity. 

Flumetsulam is classified as “Group E”, (evidence of non-carcinogenicity for humans); 

mutagenicity studies conducted with flumetsulam were negative.

An acute reference dose has not been established for either the general population or for females 

13-49 years of age since there were no appropriate studies that demonstrated evidence of toxicity 

attributable to a single dose for these populations. For chronic dietary and other exposure 

scenarios, the chronic feeding study in the dog was selected because the study encompasses the 

appropriate exposure duration and provides a screening level hazard with a NOAEL of 100 

mg/kg/day and LOAEL of 500 mg/kg/day based on renal inflammatory and atrophic changes 

secondary to renal calculi and hepatic effects consisting of inflammation, focal necrosis, and 

biliary stasis. For the dermal exposure scenario, no systemic toxicity was found in the 21-day 

rabbit dermal study at the limit dose (1000 mg/kg/day). Quantification of dermal risk assessment 

is not required for this exposure due to a lack of dermal, systemic, neuro, or developmental 

toxicity concerns.
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The flumetsulam risk assessment team has recommended that the FQPA Safety Factor be 

reduced to 1X based on and adequate and complete toxicity database and exposure data. There 

is no evidence of qualitative or quantitative susceptibility in utero or during post-natal exposure

in developmental and reproduction studies and there is no evidence of neurotoxicity in the 

submitted studies. A developmental neurotoxicity study is not required since there was no 

evidence of neurotoxicity or neuropathy from the available studies.

Dietary Exposure (Food and Drinking Water): The residue chemistry data and environmental 

fate data are adequate to assess human exposure. Estimated drinking water concentrations 

(EDWCs) from surface water and groundwater sources were generated by the Environmental 

Fate and Effects Division (EFED) using computer modeling methods. 

Acute: An acute dietary exposure assessment was not performed as no appropriate endpoints 

were identified from the available flumetsulam toxicity studies for the acute dietary scenario. 

Chronic: Both food and water were incorporated in the dietary exposure analysis. Tolerancelevel residues and 100% crop treated assumptions for all the crops were used in the chronic 

dietary exposure assessment. Flumetsulam residue in water was assumed to be 14.8 ppb 

according to EFED’s highest estimated chronic drinking water concentration. The estimated 

exposure for the general U.S. population and all population subgroups resulted in exposures less 

than 1 percentage of the chronic population adjusted dose (cPAD).

Cancer: A cancer dietary exposure assessment was not performed as flumetsulam is classified as 

Group E (Evidence of non-carcinogenicity for humans).

Residential Exposure: There are currently no registered residential uses associated with 

flumetsulam; therefore, a residential/non-occupational exposure assessment is not required. 

Aggregate Risk: Aggregate risk assessments evaluate the combined risk from dietary exposure 

(food and water) and any non-occupational (residential) uses. There are currently no registered 

residential uses associated with flumetsulam; therefore, a residential/non-occupational exposure 

assessment is not required. As a result, the flumetsulam aggregate risk assessment includes only 

dietary exposure (food and water). An acute dietary exposure assessment was not performed as 

no appropriate endpoints were identified from the available flumetsulam toxicity studies for the 

acute dietary scenario. The chronic dietary exposure estimates from food and drinking water do 

not exceed HED’s level of concern (<1% of cPAD). A cancer dietary exposure assessment was 

not performed as Flumetsulam is classified as Group E (Evidence of non-carcinogenicity for 

humans).

Occupational Exposure/Risk: The occupational database is complete. Occupational handler 

exposures to the existing uses of flumetsulam may occur via dermal and inhalation route. 

However, quantification of dermal risk is not required due to a lack of dermal, systemic, neuro, 

or developmental toxicity concerns. Therefore, only inhalation exposure was assessed for 

handlers.
Flumetsulam Human Health Risk Assessment DP No. D411276

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The short- and intermediate-term inhalation risk estimates for all occupational handler scenarios 

do not exceed HED’s level of concern, i.e., margin of exposures are greater than 100 (MOEs > 

100) at baseline personal protective equipment (PPE). The flumetsulam product labels direct 

mixers, loaders, applicators and other handlers to wear long-sleeved shirts, long pants, 

waterproof gloves, and shoes plus socks. Some of the labels require the PPE to include goggles 

or face shields because some end use products contain a mixture of chemicals with different 

acute toxicity categories than flumetsulam. HED recommends that the Registration Division 

(RD) ensure the appropriate safety directions and a 12 hour restricted entry interval (REI) are 

included in the label based on the acute toxicity of flumetsulam and that products that include a 

formulated mixture of active ingredients should retain the 48 hour REI.

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for flumetsulam at this time primarily because of the low acute 

inhalation toxicity, vapor pressure and the use rates. However, since handler inhalation exposure 

is likely to be higher than post-application exposure and the estimates for handler inhalation 

exposure are below the level of concern (MOE >100), it is expected that these handler inhalation 

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

exposure scenarios. If new policies or procedures are put into place, the Agency may revisit the 

need for a quantitative occupational post-application inhalation exposure assessment for 

flumetsulam.

Spray drift analysis was conducted for a hand to mouth (HtM) scenario for children ages 1<2 

years of age using Tier 1 screening parameters. The aerial and ground applications of 

flumetsulam at the current maximum application rates resulted in MOEs not of concern for field 

corn, soybeans, and dry beans.

There are no label recommendations from the occupational assessment. There are no data 

deficiencies or additional requirements for flumetsulam at this time. 

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 studies 

(listed in Appendix C) have been determined to require a review of their ethical conduct and all 

of the studies utilized in this assessment have received the appropriate review.

Data Deficiency: The databases for toxicology, residue chemistry, occupational and residential 

requirements are complete. There are no outstanding data deficiencies.

2.0 Introduction

2.1 Tolerances

Tolerances are established for the herbicide flumetsulam under 40 CFR: §180.468 for bean, dry, 

seed; corn, field, forage; corn, field, grain; corn, field, stover; soybean, seed, each at 0.05 ppm.

2.2 International Harmonization
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The Codex Alimentarius Commission has not established Maximum Residue Limits (MRLs) for 

residues of flumetsulam. Canadian MRLs are established for field corn and dry soybean each at 

0.05 ppm; Canada does not establish MRLs on feed stuffs. No harmonization is needed. For a 

summary of US and International Tolerances and Maximum Residue Limits, see Appendix E.

2.3 Structure and Nomenclature

Table 2.3 - Flumetsulam Nomenclature

Chemical structure

Common Name Flumetsulam

Company Experimental Name DE-498 and TSN-100986

Empirical Formula C12H9F2N5O2S

IUPAC Name 2-(2,6-difluorophenylsulphamoyl)-5-methyl(1,2,4)-Triazolo(1,5-a)pyrimidine

CAS Name N-(2,6-difluorophenyl)-5-methyl-(1,2,4)triazolo(1,5-a)pyrimidine-2-

sulfonamide

CAS Registry Number 98967-40-9

2.4 Physical/Chemical Characteristics

Listed in Appendix B are the physical and chemical properties as well as the relevant 

environmental fate parameters. Flumetsulam low vapor pressure (1.0 x 10-15 mm Hg at 25.0 °C)

indicates that flumetsulam is non-volatile. Flumetsulam is soluble in water and is stable under 

photolysis. Degradation studies indicate the aerobic soil half-life ranges from approximately two 

weeks to four months with the majority degrading in less than two months (mean of 69.5 days).

2.5 Summary of Existing Uses

Flumetsulam is a pre emergent and early post-emergent herbicide used to control broadleaf 

weeds in field corn, soybeans, and dry beans; HED notes that although dry bean is a registered 

primary crop, all labels for dry bean are inactive at present; any reference to use rate and use 

pattern for dry bean in this document are based on older inactive labels, field trial data, and 

previously reviewed ORE document (Dow, Mark I., 2004, D306178). Flumetsulam is in the 

triazolopyrimidine chemical class and has a mode of action similar to the sulfonylurea herbicides 

that are acetolactate synthase inhibitors, which regulate plant growth. Flumetsulam is formulated 

as water dispersible granular WDG, water dispersible granular packaged in water soluble packets

WSP, and as an emulsifiable concentrate EC. Flumetsulam can also be incorporated with liquid 

and dry bulk fertilizer. The water soluble packets must be combined with water to create slurry 

first before attempting to mix with a carrier fertilizer. Some of the registered products contain a 

mixture of flumetsulam and additional active ingredients which are not evaluated in this 

registration review document. 

N S

F

F

N

N

N

N CH3 O

H O
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Flumetsulam can be applied by ground and by air with restrictions. Chemigation is prohibited. 

Field corn and soybeans have application rates ranging from 0.035 lb ai/A to 0.07 lb ai/A. 

Flumetsulam application rates on dry beans range from 0.04 to 0.07 lb ai/A based on older 

inactive labels, field trial data, and previously reviewed ORE document (Dow, M., 2004, 

D306178). Rotational crop restrictions are directed on labels. Currently, there are two registered 

manufacturing-use products ; (EPA Reg. No. 62719-223) Flumetsulam Technical 98 % a.i., and 

(EPA Reg. No. 62719-300) Hornet MUP 23.1 % a.i. flumetsulam. Application rates and 

restrictions for all other labels are summarized in the following Table 2.5. 

Table 2.5 - Summary Use Profile for Flumetsulam

 

Registration 

Number and 

Product 

Name

Application 

Equipment.

Formulati

on

Applic. 

Rate (lb 

a.i./A)

Max. 

No. 

Applic. 

Per 

Season

Max. 

Seasonal 

Applic. 

Rate (lb 

a.i./A)

PHI 

(days)

Use Directions and 

Limitations

RE

I

Field Corn

352-612

DuPont 

Accent Gold

15.9 % a.i.

Ground with 

aerial 

application 

only in 

following 

states, 

Colorado, 

Iowa, 

Kansas, 

Minnesota, 

Nebraska, 

Oklahoma, 

South 

Dakota, and 

Texas Water 

dispersibl

e granular 

packaged 

in a 

soluble 

packet

0.035

1

0.035 85

Do not apply to popcorn 

or sweet corn. Can apply 

to corn up to 12 inches 

tall and when grass and 

broadleaf weeds are 

young or pre-emergent. 

Adequate soil moisture is 

required for residual 

activity. Use at least 15 

gallon water per acre for 

broadcast application and 

5 gallons per acre for 

aerial application. Do not 

apply a cumulative rate 

of more than 0.07 lbs of 

flumetsulam per year. 48 

ho

urs

352-593

Accent Gold

19.1 % a.i

Ground 

Broadcast or 

Branded

62719-278 

NAF-280

13.9 % a.i.

Ground

Do not apply 

aerially

0.07 0.07

85

Preplant, surface, 

incorporated, 

preemergence, or post 

emergence treatment. 

Adequate soil moisture is 

required for residual 

activity. Must make 

slurry to mix with 

fertilizer. Apply a 

minimum of 200 pound 

of dry impregnated 

fertilizer

Spray volume of 10 to 60 

gallons per acre

Post-emergent treatment 

should be applied with 

water

Do not apply aerially 

62719-253

Hornet

23.1 % a.i.

Ground

and aerially 

with 

supplemental 

labels New 

York 

Restrictions

62719-315

Hornet 

WDG

18.5 % a.i

Ground

New York 

Restrictions

0.07 0.07

62719-279

NAF-281

12.1 % a.i.

Ground

Do not apply 

aerially

0.05 0.05
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Table 2.5 - Summary Use Profile for Flumetsulam

 

Registration 

Number and 

Product 

Name

Application 

Equipment.

Formulati

on

Applic. 

Rate (lb 

a.i./A)

Max. 

No. 

Applic. 

Per 

Season

Max. 

Seasonal 

Applic. 

Rate (lb 

a.i./A)

PHI 

(days)

Use Directions and 

Limitations

RE

I

unless by EPA approved 

supplemental labeling.

62719-570

Sure Start

1.3 % a.i

Emulsifia

ble 

concentrat

e

0.05 1 0.05

Contains 3 active 

ingredients. PPE includes 

gloves, eyewear, 

headgear, and apron.

Post emergent corn can 

be sprayed up to 11 

inches

Apply a minimum of 200 

pound of dry 

impregnated fertilizer

Spray volume of 10 to 60 

gallons per acre

12 

ho

urs

Soybeans

62719-299

Frontrow

Flumetsulam 

80 WDG

80% a.i.

Ground and

aerial 

application 

with 

supplemental 

labeling. 

Aerial 

application 

prohibited 

New York

Water 

dispersibl

e 

granulars 

in water 

soluble 

packets

0.006 2 0.012 70

Front Row is a co-pack 

product. Do not mix and 

apply separately water –

soluble packets. Use of 

product in Nassau and 

Suffolk counties in New 

York are prohibited. Do 

not graze of feed soybean 

forage.

12 

ho

urs

Field Corn and Soybeans

62719-224

Broad Strike 

formerly

XRM-6019

74 % a.i

Ground, 

Aerially (no 

aerial 

application 

in New

York)

Water 

dispersibl

e 

granulars 

0.07 1 0.07

85days 

for corn 

and 

soybean 

harvest

45 days 

for corn 

forage 

harvest

Preplant, surface, 

incorporated, 

preemergence, or post 

emergence treatment. 

Application may be made 

to field corn up to 12 

inches tall and soybeans 

in the first to fifth 

trifoliate leaf stage. Use 

at least 10 gallons of 

spray per acre for ground 

application. Apply a 

minimum of 200 pound 

of dry impregnated 

fertilizer. Must make 

slurry to mix with 

fertilizer. Do not make 

post emergence 

applications near 

freezing temperatures

12 

ho

62719-277 urs

Python 

WDG

80 % a.i.

Dry Beans1
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Table 2.5 - Summary Use Profile for Flumetsulam

 

Registration 

Number and 

Product 

Name

Application 

Equipment.

Formulati

on

Applic. 

Rate (lb 

a.i./A)

Max. 

No. 

Applic. 

Per 

Season

Max. 

Seasonal 

Applic. 

Rate (lb 

a.i./A)

PHI 

(days)

Use Directions and 

Limitations

RE

I

62719-239 

Broadstrike®

+ Dual 

20 % a.i.

Ground only

Emulsifia

ble 

concentrat

e

0.063 

1

0.07 lb 

ai/acre 85 days

Products may be applied 

10 - 14 days prior to 

planting as a soil 

incorporated application 

or as a surface 

application. It may be 

applied post-plant but 

prior to crop or weed 

emergence.

12 

ho

urs

62719-222

Broadstrike®

+ Treflan®

25 % a.i.

0.07

62719-277

Broadstrike 

WDG

80 % a.i.

Water 

dispersibl

e granule

0.067

1Dry bean labels are inactive. Use and rates are based on older inactive labels, field trial data, and previously reviewed ORE document (Dow, 

Mark I., D306178).

2.6 Anticipated Exposure Pathways

Humans may be exposed to flumetsulam in their diet resulting from residues present in foods 

treated with flumetsulam. Further, given the environmental fate parameters of flumetsulam and 

the registered agricultural uses, the potential exists for flumetsulam to reach water resources 

resulting in potential residues in drinking water. There are currently no residential uses of 

flumetsulam, so exposure in residential and non-occupational settings is not likely. There is a 

potential for occupational handler and post-application exposures.

2.7 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://www.eh.doe.gov/oepa/guidance/justice/eo12898.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 National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 
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Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults 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.

3.0 Hazard Characterization and Dose-Response Assessment

Previously, a comprehensive risk assessment for flumetsulam was conducted in 2004 (E. Reaves, 

D306238, 11/22/2004) and a scoping document was issued in 2008 (S. Recore, D349638, 

8/12/2008). Since then, new studies including acute and subchronic neurotoxicity and 

immunotoxicity studies were submitted. In addition, the Hazard and Science Policy Council 

(HASPOC) determined that a subchronic inhalation toxicity study is not needed for flumetsulam 

at this time (TXR# 0056689). Please refer to Appendix A for the hazard profile table. This 

assessment includes summaries of prior assessments.

3.1 Summary of Toxicological Effects

Flumetsulam has low acute toxicity by oral, dermal, or inhalation routes of exposure. It is not a 

skin or eye irritant and is not a skin sensitizer. The kidney appears to be the primary target organ 

of rats and dogs following exposure to high doses of flumetsulam in subchronic to chronic 

toxicity studies. Following subchronic oral exposure, rats developed bilateral tubular nephritis at 

concentrations equal to the limit dose; however, no renal effects were found in mice at doses five 

times the limit dose. In chronic dog and rat studies, renal calculi, inflammation, and atrophic 

changes were found in the kidney of male animals. These effects were not observed in female 

rats or dogs, or in treated male and female mice. There were no evidences of neurotoxicity, 

immunotoxicity, developmental, or reproductive toxicity in the submitted studies for 

flumetsulam.

Mutagenicity studies conducted with flumetsulam were negative. Flumetsulam did not alter the 

spontaneous tumor profile in these strains of rats and mice at the limit dose. Therefore, on the 

basis of the two studies, the Health Effects Division RfD/Peer Review Committee classified 

flumetsulam as a “Group E”, evidence of non-carcinogenicity for humans (TXR# 011039, 

03/24/1993).

Available metabolism and pharmacokinetics studies in mice and rats indicate that flumetsulam is 

primarily eliminated within 48 hours from all test animals following oral administration. The 

primary route was urinary excretion of unchanged flumetsulam. The rapid clearance of 

flumetsulam demonstrated little potential for bioaccumulation. Metabolic studies show that 

approximately 52-63% of the administered test material was absorbed by male and female rats. 

Plasma pharmacokinetic studies suggest that increased doses were associated with increased 

clearance, possibly due to saturation of plasma binding sites. In addition, there was a dose-
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dependent decrease in the rate of plasma absorption and elimination for both rats and mice. Two 

very minor metabolites were detected in the urine of mice (not identified). At the limit dose, 

mice showed a greater capacity for absorption and elimination than rats. 

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

The flumetsulam risk assessment team has recommended that the FQPA Safety Factor be 

reduced to 1X based on adequate toxicity database and exposure data. There is no evidence of 

qualitative or quantitative susceptibility in utero or during post-natal exposure in developmental 

and reproduction studies and there is no evidence of neurotoxicity in the submitted studies. A 

developmental neurotoxicity study is not required since there was no evidence of neurotoxicity 

or neuropathy from the available studies. 

3.2.1 Completeness of the Toxicology Database

The database for flumetsulam is complete and adequate to characterize potential pre- and/or 

post-natal risk for infants and children. 

3.2.2 Evidence of Neurotoxicity

There are acute and subchronic neurotoxicity studies available. No evidence of neurotoxicity 

was observed in any of the submitted studies for flumetsulam. A developmental neurotoxicity 

study is not required.

3.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

The available data do not provide evidence of any increased susceptibility or sensitivity in the 

offspring in either of the two developmental toxicity studies, nor in the two-generation 

reproduction study.

 

3.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties with regard to dietary exposure. Conservative, upper-bound 

assumptions were used to determine exposure through dietary sources (food and drinking water), 

such that these exposures have not been underestimated. There are currently no residential uses 

and no outstanding exposure data requirements for flumetsulam.

3.3 Toxicity Endpoint and Point of Departure Selections

Previously, HED has conducted a comprehensive risk assessment for flumetsulam ( E. Reeves 

and S. Ary, D306238, 11/22/2004). There have been no changes to the prior dose-response 

assessment and no changes to the prior recommendations for combining routes of exposure 

and/or cancer classification. 

An acute reference dose has not been established for either the general population or for females 

13-49 years of age since there were no appropriate studies that demonstrated evidence of toxicity 

attributable to a single dose for these populations. For chronic dietary and other exposure 
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scenarios, the chronic feeding study in the dog was selected because the study encompasses the 

appropriate exposure duration and provides a screening level hazard with a NOAEL of 100 

mg/kg/day and LOAEL of 500 mg/kg/day based on renal inflammatory and atrophic changes 

secondary to renal calculi and hepatic effects consisting of inflammation, focal necrosis, and 

biliary stasis. For dermal exposure scenario, no systemic toxicity was found in the 21-day rabbit 

dermal study at the limit dose (1000 mg/kg/day). Quantification of dermal risk assessment is not 

required for this exposure due to lack of dermal, systemic, neuro, or developmental toxicity 

concerns. The detailed endpoint selection is listed in the following Table 3.3.

Table 3.3 - Toxicological Doses and Endpoint for Use in Flumetsulam Dietary and NonOccupational and Occupational Human Health Risk Assessments

Exposure

/Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological 

Effects

Acute Dietary

(all populations)

An acute reference dose has not been established for either the general population or for females 

13-49 years of age since there were no appropriate studies that demonstrated evidence of 

toxicity attributable to a single dose for these populations.

Chronic Dietary 

(all populations) 

NOAEL = 

100 

mg/kg/day

UFA = 10X 

UFH = 10X 

FQPA SF = 1X

Total UF = 100X

Chronic RfD 

= 1.0 mg/kg/day

cPAD = Chronic RfD

 FQPA SF

= 1.0 mg/kg/day

Chronic feeding study in 

dogs

LOAEL = 500 mg/kg/day 

based on renal inflammatory 

and atrophic changes 

secondary to renal calculi 

and hepatic effects 

(inflammation, focal 

necrosis, biliary stasis)

Incidental Oral

(short and 

intermediatedterm)

NOAEL = 

100 

mg/kg/day

UFA = 10X 

UFH = 10X 

FQPA SF = 1X

Residential LOC for 

MOE=100

Same as chronic dietary 

endpoint.

Dermal Exposure

(all durations)

No hazard identified. No systemic toxicity was found in the 21-day rabbit dermal study at the 

limit dose (1000 mg/kg/day). Quantification of dermal risk assessment is not required for this 

exposure due to lack of dermal, systemic, neuro, or developmental toxicity concerns.

Inhalation 

Exposure

(all durations)

Oral NOAEL= 100 

mg/kg/day

(inhalation absorption 

rate = 100%)

UFA = 10X 

UFH = 10X 

Total UF = 

100X

Occupational LOC 

for MOE = 100

Same as chronic dietary 

endpoint.

Cancer (oral, 

dermal, 

inhalation)

Flumetsulam is classified as Group E (Evidence of non-carcinogenicity for humans).

Not mutagenic.

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect 

level, PAD = population adjusted dose (a = acute, c = chronic), RfD = reference dose, LOC = level of concern, NA = Not Applicable. UFA= 

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

(intraspecies).

3.4 Endocrine Disruption

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

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 
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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 flumetsulam, 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), 

flumetsulam 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 

flumetsulam. 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

In the interim, EPA is making no human health or environmental safety findings associated with 

the EDSP screening of flumetsulam. Before completing this Registration Review, the Agency 

will make an EDSP FFDCA section 408(p) determination.

4.0 Dietary Exposure and Risk Assessment

4.1 Degradate Residue Profile

 

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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4.1.1 Summary of Environmental Degradation

Flumetsulam is classified as moderately persistent to persistent, and mobile to highly mobile in 

the environment. The environmental fate database for flumetsulam is largely complete. 

Environmental fate studies show that flumetsulam is moderately persistent in soil (aerobic halflives on the order of weeks to months), more persistent under anaerobic aquatic conditions (halflife of about 6 months) and aerobic aquatic conditions (half-life > 1 year), and stable to both 

hydrolysis and photolysis. However, the persistence and mobility of flumetsulam appear to be 

influenced by pH and organic carbon content. Flumetsulam has a low vapor pressure and 

Henry’s Law constant, and its physical properties indicate a low potential for volatilization. 

While flumetsulam is more soluble in neutral waters than in acidic water, it is very resistant to 

abiotic reactions (stable to hydrolysis, as well as photolysis in water and on soil). The major 

route of dissipation for flumetsulam is believed to be metabolism in aerobic soils, where 

metabolism half lives ranged from 13 days in sandy loam to 130 days in loam soil. Metabolites 

were less than 10% of applied radioactivity and were not identified. Metabolism in the aquatic 

environment is expected to be much slower, with a reported anaerobic aquatic half-life of 183 

days and an estimated aerobic aquatic half-life greater than a year. Under anaerobic aquatic 

conditions flumetsulam is reduced to flumetsulam hydrate. Oxidation will cause a transformation 

back to flumetsulam. 

Flumetsulam degrades to CO2 with no significant accumulation of intermediate degradates, 

except for reduced flumetsulam hydrate [N-(2,6 difluorophenyl)-4,5,6,7-tetrahydro-5-hydroxy-5-

methyl-(1,2,4)-triazolo(1,5-a)pyrimidine-2-sulfonamide], formed in the anaerobic aquatic study.

Flumetsulam hydrate accounted for 52% of the total applied radiation at day 360, and degraded 

with a half life of about 180 days. However, this degradate was found to accumulate less (max of 

<8% of total applied radiation) and degrade more quickly (t1⁄2 about 2 days) in a weakly anaerobic 

test system that became progressively more anaerobic with time. Flumetsulam degraded much 

slower in aerobic aquatic systems compared to anaerobic aquatic conditions. No degradation 

products were identified. Calculated pseudo-first order half-lives were 1762 and 1319 days for 

the 14C-pyrimidine and 14C-analine labels, respectively.

Since flumetsulam does not rapidly metabolize when in contact with soils and does not bind 

strongly to soil surfaces, there is a potential for runoff from application sites to adjacent surface 

waters. Persistence in water indicates that flumetsulam may persist long enough to present some 

concern to surface water and ground water resources. Volatilization is not expected to be a major 

route of dissipation from either water or soil for flumetsulam.

EFED provided an updated drinking water assessment which estimated flumetsulam in surface 

and ground water based on the latest product label information, newly available environmental 

data, exposure models, and model scenarios. 

4.1.2 Residues of Concern Summary and Rationale

On April 21, 1993, the HED Metabolism Committee concluded that the residue of concern 

resulting from the uses of flumetsulam on plant commodities is flumetsulam only. The basis for 
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this decision was on the low levels of total radioactive residues present in plant metabolism 

studies and the lack of toxicological concern for metabolites having the sulfonamide linkage 

intact (N. Dodd, HED Metabolism Committee Memorandum, 04/26/1993).

The HED Metabolism Committee has not determined the residue of concern in livestock; 

however, based on the previously submitted data, the nature of the residue in livestock (goats and 

hens) is adequately defined; no detectable residues of flumetsulam were found in feed items.

Table 4.1.2 Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Risk Assessment Residues included in Tolerance Expression

Plants Primary Crop Flumetsulam Flumetsulam

Livestock Ruminant NA1 NA1

Drinking Water Flumetsulam Not Applicable

1

HED previously concluded that there is no reasonable expectation of finite residues in ruminant and poultry commodities; i.e., 40 CFR 

§180.6(a)(3) situation.

4.1.3 Enforcement Analytical Method

The available analytical methodology (Gas Chromatography/Mass Spectrometry [GC/MS]) is 

considered adequate for tolerance enforcement of flumetsulam in/on plant commodities; 

DowElanco’s Method ACR 91.6 (Method I) on soybean grain and DowElanco’s Method ACR 

91.61S (Method II) on corn grain and corn fodder (D189444, N. Dodd, 03/29/1993) The method 

has been submitted for inclusion in the Pesticide Analytical Manual (PAM), Volume II. The 

stated limit of quantitation (LOQ) of the method is 0.010 ppm; however, Analytical BioChemistry Laboratories, Inc (ACB) validated the method LOQ at 0.05 ppm.

4.2 Food Residue Profile

Crop Field Trials

Adequate crop field trial data are available for flumetsulam in/on field corn, soybean and dry 

beans. All flumetsulam residues were below the LOQ at the maximum label rate for all the 

registered crops. The established tolerances are at 0.05 ppm (40 CFR §180.468).

Meat, Milk, Poultry, and Eggs

There are no registered direct livestock treatment uses for flumetsulam and no detectable 

residues of flumetsulam in/on the feed items except in soybean. However, for soybean, the 

registrant had proposed a tolerance for the soybean (bean) only and put grazing/feeding 

restrictions on the label; therefore, livestock analytical methods or feeding studies are not 

required (see memorandum by Dodd, N., “Issues to be Presented at the 4/21/93 Meeting of the 

HED Metabolism Committee.”). Restriction on soybean feed items for livestock consumption 

should be on all labels. Nature of residue studies for ruminant (goat) and poultry (hens) have 

been submitted and reviewed. The nature of the residue in animals is adequate for the current 

uses. HED previously concluded that the registered uses on corn, soybeans, and dry beans

results in a 40 CFR §180.6(a)(3) situation for ruminant and poultry commodities; i.e., there is no 
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reasonable expectation of finite residues in ruminant and poultry commodities. Therefore, 

additional data on the transfer of residues to meat, milk, and poultry are not required. However, 

for any future uses which may result in detectable residues in feed items, additional animal 

metabolism data on ruminants and poultry may be required. Such data may, in turn, trigger the 

need for magnitude of the residue (feeding) studies in livestock.

Processed Food and Feed

Processing studies for the currently registered flumetsulam uses are adequate. Flumetsulam 

processing studies are available for corn. Flumetsulam residues in the treated corn at 

exaggerated maximum application rate and in the processed fractions were non-detects. A 

processing study is not required for soybeans as no detectable residues were found in soybeans 

from exaggerated application rate (D188957, N. Dodd, 06/28/1993) and (PP# 1G4006, N. Dodd, 

03/27/1993).

Storage Stability

Storage stability studies using fortified samples of field corn and soybean for the currently 

registered flumetsulam uses are adequate. The results indicate that residues of flumetsulam are 

stable in corn grain, forage, and fodder stored for at least 555 days and in soybean for at up to 

thirty months (908 days) at -15 °C (N. Dodd, PP# 3F4185, 06/28/1993, and PP# 2F4036, 

04/14/1993 ). For dry beans, in the absence of specific storage stability data, it was assumed that 

residues on samples which were stored for 97 days will behave similarly in beans as in corn and 

soybeans S. Ary (D306242, 08/31/2004).

Rotational Crops

The current use labels for flumetsulam restricts crop rotation after treatment to four months or 

greater for all crops except soybean.

4.3 Water Residue Profile

Flumetsulam is soluble in water and is stable under photolysis. Degradation studies indicate the 

soil half-life ranges from approximately two weeks to four months with majority degrading in 

less than two months (mean of 69.5 days). The Environmental Fate and Effects Division 

(EFED) provided estimated drinking water concentrations (EDWCs) by using either a Tier I 

Screening Concentration In Ground Water (SCI-GROW) and/or Pesticide Root Zone Model –

Ground Water (PRZM-GW) models for ground water; Tier II Pesticide Root Zone 

Model/Exposure Analysis Modeling System (PRZM/EXAMS) was used to obtain surface water 

concentrations. The estimated 1-in-10 year annual mean residue of flumetsulam for chronic

surface water using PRZM/EXAMS was 1.45 ppb, based on application on the Kansas corn

scenario. The estimated flumetsulam residue using PRZM-GW model for chronic ground water 

EDWC was 14.8 ppb (J. Wolf, D411277, 8/16/2013).
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Table 4.3 - Maximum Flumetsulam EDWCs for Corn scenario in Surface Water and 

Groundwater

Drinking Water Source

(Model)

1-in-10 year

30 - year 

Average

30 - year 

Simulation

Acute Chronic Cancer Acute Chronic

(μg/L/ppb)

Surface Water (PRZM/EXAMS) 6.68 1.45 0.76 - -

Groundwater (PRZM-GW) - - - 19.8 14.8

4.4 Dietary Risk Assessment

An aggregate dietary food and drinking water, exposure and risk assessment was conducted 

using the Dietary Exposure Evaluation Model software with the Food Commodity Intake 

Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption data 

from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition 

Examination Survey, What We Eat in America, (NHANES/WWEIA). The analysis also 

incorporated the highest estimated flumetsulam residue in water provided by EFED. In a chronic 

dietary risk assessment, risk is expressed as a percentage of a maximum acceptable dose (i.e., the 

dose which HED has concluded will result in no unreasonable adverse health effects). The 

population-adjusted chronic dose or cPAD is equivalent to the reference dose (RfD) divided by 

the Food Quality Protection Act (FQPA) Safety Factor. Dietary risk assessments incorporates 

both exposure and toxicity data for a given pesticide.

4.4.1 Description of Residue Data Used in Dietary Assessment

Tolerance-level residues were used for all registered commodities in the unrefined chronic 

aggregate dietary analysis for flumetsulam. For drinking water, the highest estimated chronic 

drinking water concentration of 14.8 ppb from ground water sources was used.

4.4.2 Percent Crop Treated Used in Dietary Assessment

It was assumed that 100% of the registered crops were treated (100%CT) in the unrefined 

chronic aggregate dietary analysis for flumetsulam.

4.4.3 Acute Dietary Risk Assessment

Since no appropriate endpoints were identified from the available flumetsulam toxicity studies,

an acute dietary exposure risk assessment is not required.

4.4.4 Chronic Dietary Risk Assessment

The chronic dietary exposure analysis results for the general U.S. population, all infants (less 

than 1 year old), children 1-2, children 3- 5, children 6-12, youth 13-19, females 13-49, adults 
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20-49, and adults 50-99 years. The resulting food exposure estimates are below HED’s level of 

concern for the U.S. population and all population subgroups at less than 1% of cPAD.

4.4.5 Cancer Dietary Risk Assessment

Since flumetsulam is classified as Group E (Evidence of non-carcinogenicity for humans), no 

cancer dietary risk exposure risk assessment is required.

4.4.6 Dietary Risk Assessment Summary Table

Table 4.4.6. Summary of Dietary (Food and Drinking) Exposure and Risk for Flumetsulam.

Population 

Subgroup

Acute Dietary Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% 

aPAD

Dietary Exposure

(mg/kg/day)

% 

cPAD

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. 

Population

N/A N/A

0.000435 

< 1 N/A N/A

All Infants (<1 

year old) 0.001007 

Children 1-2 

years old 0.000735 

Children 3-5 

years old 0.000665 

Children 6-12 

years old 0.000481 

Youth 13-19 

years old 0.000372 

Adults 20-49 

years old 0.000420 

Adults 50-99 

years old 0.000376 

Females 13-49 

years old 0.000412 

5.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are currently no registered residential uses associated with flumetsulam. Any future 

proposed residential uses could impact the human health aggregate risk assessment for 

flumetsulam.

5.1 Spray Drift

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up off-
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target and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to exposures (e.g., children playing on 

lawns where residues have deposited next to treated fields). The potential risk estimates from 

these residues can be calculated using drift modeling coupled with methods employed for 

residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment include 

assessing 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 exposure scenario. 

Aside from the predicted residues available for transfer, the routes of exposure and assessment 

methodology is analogous to how exposures to turf products are considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a 

residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of flumetsulam. 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. Exposures 

were considered for 50 feet wide lawns where the nearest side of the property was directly 

adjoining the treated field (at field edge) and at varied distances up to 300 feet downwind of a 

treated field. Once the deposited residue values were determined, the remainder of the spray drift 

assessment was based on the algorithms and input values specified in the recently revised (2012) 

Standard Operating Procedures For Residential Risk Assessment (SOPs). 

A screening approach was developed for situations where specific label guidance for 

application parameters is not available.3 AgDrift is appropriate for use only when applications 

are made by aircraft, airblast sprayers, and groundboom sprayers. When AgDrift was developed, 

a series of screening values (i.e., the Tier 1 option) were incorporated into the model and 

represent each equipment type and use under varied conditions. The screening options 

specifically recommended in this methodology were selected because they are plausible and 

represent a reasonable upper bound level of drift for common application methods in agriculture. 

In all cases, each scenario is to be evaluated unless it is not plausible based on the anticipated use 

pattern (e.g., herbicides are not typically applied to tree canopies) or specific label prohibitions 

(e.g., aerial applications are not allowed). 

The spray drift risk estimates are based on an estimated deposited residue concentration as a 

result of the screening level agricultural application scenarios. Flumetsulam is used on soybeans 

field corn, and dry beans. The chemical can be applied via groundboom and for field corn and 

soybeans by aerial 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. 

 

3

Note that for many cases the scenarios outlined in the screening approach represent actual use practice.
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Aerial applications are based on the use of AgDrift Tier 1 aerial option for a fine to 

medium spray type and a series of other parameters which will be described in more 

detail below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire 

application/drift event).

There are no dermal endpoints selected for flumetsulam, therefore adult and children (1<2 years 

old) dermal spray drift exposure was not assessed. However the HtM exposure for children 1<2 

years old was assessed using the incidental oral endpoint from a chronic oral dog study with an 

oral NOAEL of 100 mg/kg/day. The total applicable Level of Concern is 100 so MOEs < 100 

would be of concern. 

Results are presented in Table 1: Appendix D, “Residential Exposure to Flumetsulam from 

Agricultural Drift for Children Ages 1<2 years Hand to Mouth, HtM only.” The spray drift risk 

estimates indicate that there are no major risk concerns from aerial and ground boom 

applications to field corn, and soybeans from field edge. In addition there are also no major 

spray drift risk concerns for the ground application to flumetsulam to dry beans from field edge. 

All MOE estimates were ≥ 100 and ranged from 370,000 to 4,000,000 at edge. Risk estimates 

for the varying flumetsulam product formulations, (i.e. water dispersible granular and 

emulsifiable concentrate) were below the level of concern, MOEs <100. The risk can be even 

further reduced by changing nozzle types with coarser sprays resulting in less drift.

5.2 Inhalation Post-application Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for flumetsulam at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III and IV), low vapor pressure 1.0 x 10-15 mm HG @ 25 ̊ 

C, and the low proposed use rate (0.05 lb ai/A and 0.07 lb ai/A). However, 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, 20104. The Agency is in the process of evaluating the SAP report and may, as 

appropriate, develop policies and procedures to identify the need for and, subsequently, the way 

to incorporate post-application inhalation exposure into the Agency's risk assessments. If new 

policies or procedures are developed, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for flumetsulam.

An inhalation exposure assessment was performed for flaggers exposed from aerial application 

of flumetsulam. This exposure scenario is representative of a worse case inhalation (drift) 

exposure and may be considered protective of most outdoor agricultural and commercial postapplication inhalation exposure scenarios. The estimated MOE for flaggers is 930,000 which is 

well above the margin of concern of 100; i.e., not a risk concern.

 

4

Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
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6.0 Aggregate Exposure/Risk Characterization

Aggregate risk assessments evaluate the combined risk from dietary exposure (food and water) 

and any non-occupational (residential) uses. There are currently no registered residential uses 

associated with flumetsulam; therefore, a residential/non-occupational exposure assessment is 

not required. As a result, the flumetsulam aggregate risk assessment includes only dietary 

exposure (food and water). An acute dietary exposure assessment was not performed as no 

appropriate endpoints were identified from the available flumetsulam toxicity studies for the 

acute dietary scenario. The chronic dietary exposure estimates from food and drinking water do 

not exceed HED’s level of concern. A cancer dietary exposure assessment was not performed as 

flumetsulam is classified as Group E (Evidence of non-carcinogenicity for humans). Sections 

4.4.4 and 4.4.5 discuss the chronic and dietary (food and water) exposure assessments.

7.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to flumetsulam and any other substances. For the purposes of this assessment, therefore, EPA 

has not assumed that flumetsulam has a common mechanism of toxicity with other substances. 

For information regarding EPA’s efforts to determine which chemicals have a common 

mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy 

statements released by EPA’s Office of Pesticide Programs concerning common mechanism 

determinations and procedures for cumulating effects from substances found to have a common 

mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

8.0 Occupational Exposure/Risk Characterization

Flumetsulam is currently registered on field corn, soybean and dry bean by ground and aerial 

applications (see Table 2.3). Based on the existing use pattern for flumetsulam, there is potential 

for both occupational handler and occupational post-application exposure to occur. There is a 

potential for agricultural handlers and post-application workers to have dermal exposure to 

flumetsulam during the course of typical agricultural activities. However, quantification of 

dermal risk assessment is not required for this exposure due to lack of dermal, systemic, neuro, 

or developmental toxicity concerns. Therefore, only inhalation exposure was assessed for 

handlers.

8.1 Occupational Handler Exposure and Risk

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 
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Based on the currently registered use patterns and types of equipment and techniques that can 

potentially be used, occupational handler exposure is expected for flumetsulam. The quantitative 

exposure/risk assessment developed for occupational handlers is based on the following 

scenarios: 

1) Mixing/loading water dispersible granular (WDG) for groundboom application,

2) Mixing/loading WDG for aerial application,

3) Mixing/loading water soluble packet (WSP) for groundboom application,

4) Mixing/loading WSP for aerial application,

5) Mixing/loading emulsifiable concentrate for ground application,

6) Impregnating dry bulk fertilizer with EC, WDG, and WSP formulations.

7) Applying liquid spray with a groundboom, 

8) Applying liquid spray with aerial application; and

9) Flagger scenario.

Field corn, soybeans, and dry beans are considered to be high acreage crops and it is unlikely 

that a farmer would apply the chemical with handheld equipment because of acreage size. 

Therefore, the handheld equipment scenario was not included in this assessment.

For impregnation of dry bulk fertilizer, the product labels provide the amount of product to be 

applied to a ton of fertilizer based on the pounds of fertilizer used per acre and amount of product 

recommended per acre. Flumetsulam labels require a minimum of 200 pounds of dry fertilizer 

per acre multiplied by the label rate per acre with a conversion fact of 2000 lbs per ton. HED 

does not have data regarding the mixing/loading or the application of flumetsulam impregnated 

dry bulk fertilizer. Additionally, HED does not have scenario specific exposure data for 

impregnated dry bulk fertilizer. However, a mixing and loading processing rate of dry bulk 

fertilizer has been calculated to be 960 tons of fertilizer processed per 8 hour day. This rate was 

supplied by a registrant concerning the chemical alachlor and is referenced in the RED document 

D330812. The processing rate and label specific information specifying a closed system for 

impregnating the fertilizer with flumetsulam was achieved using this exposure surrogate data. 

HED assumed closed mixing/loading for commercial applications as the exposure scenario. Onfarm application was then assessed using an open cab spreader as surrogate data with 320 

acres/day for commercial equipment.

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic occupational handler data, used as surrogate data in the absence of chemical-specific 

data, include the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the 

Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential 

Exposure Task Force (ORETF) database, or other registrant-submitted occupational exposure 

studies. Some of these data are proprietary (e.g., AHETF data) and subject to the data protection 

provisions of FIFRA. The standard values recommended for use in predicting occupational 

handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the 

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” 

(http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), which, along with 
Flumetsulam Human Health Risk Assessment DP No. D411276

Page 25 of 40

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at http://www.epa.gov/pesticides/science/handler-exposuredata.html.

8.1.1 Short-/Intermediate-Term Non-Cancer Handler Exposure and Risk

HED classifies exposures from 1 to 30 days as short-term and exposures 30 days to six months 

as intermediate-term. For flumetsulam based on the use pattern for application to field corn and 

soybeans, and dry beans short-term exposure is expected however it is possible that large 

agribusiness or commercial applicators could apply flumetsulam over a period of weeks. 

Therefore intermediate exposure could be expected as well. The same endpoints were selected 

for short-term and long term exposure. Long-term exposures are not expected; therefore, a longterm assessment was not conducted. 

Short- and intermediate-term occupational handler exposure and risks were estimated using 1) 

unit exposures taken from the “Occupational Pesticide Handler Unit Exposure Surrogate 

Reference Table”; 2) the maximum flumetsulam label application rates; and 3) amount 

handled/area treated values take from ExpoSAC SOP No. 9.1, “Standard Values for Daily Acres 

Treated in Agriculture”.

There is a potential for agricultural handlers and post-application workers to have dermal 

exposure to flumetsulam during the course of typical agricultural activities. However, there is no 

hazard identified for dermal exposure. Therefore, only inhalation exposure was assessed for 

handlers.

Table 8.1.1 presents the estimated inhalation occupational handler risk estimates for the currently 

registered uses of flumetsulam at baseline personal protective equipment (PPE). Baselines PPE 

is defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus 

socks, no protective gloves, and no respirator. The short- and intermediate-term risk estimates 

for all occupational handler scenarios do not exceed HED’s level of concern (MOEs > 100). The 

occupational handler inhalation risk estimates range from 11,000 to 19,000,000. HED notes that 

current flumetsulam labels require PPE consisting of a long-sleeved shirt, long pants, shoes plus 

socks, and pair of chemical-resistant gloves for all applicators and other handlers. 
Flumetsulam Human Health Risk Assessment DP No. D411276

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Table 8.1.1 - Occupational Handler Non-Cancer Exposure and Risk Estimates for Flumetsulam Use on Field Corn and 

Soybeans at Baseline 1

Exposure Scenario Crop

Inhalation Unit Exposure (μg/lb ai)2 Maximum

Application Rate3

Area Treated or 

Amount Handled Daily4

Inhalation

Mitigation Level Dose (mg/kg/day)5 MOE6

Mixer/Loader

Aerial

Water Dispersible Granular

Field Corn and 

Soybeans

8.96

No Respirator

0.07 lb a.i./acre

0.7 lb ai/ton of 

fertilizer

1200 acres

0.0094 11,000

Aerial

Water Soluble Packet7

Field Corn and 

Soybeans

0.24

EC 

0.0003 400,000

Ground 

Water Soluble Pack7

impregnating fertilizer 0.24

EC 

Closed System

960 tons of fertilizer

0.00201 50,000

Ground 

Water Dispersible Granular

impregnating fertilizer

Ground 

Emulsifiable Concentrate 

impregnating fertilizer Field Corn

0.083

EC

Closed System

0.05 lb a.i./acre

0.5 lb a.i/ton of 

fertilizer

0.0005 200,000

Ground

Emulsifiable Concentrate

0.219

No Respirator

200 acres

0.00003 3,600,000

Ground

Water Dispersible Granular Field Corn and 

Soybeans

8.96

No Respirator

0.07 lb a.i./acre

0.0016 64,000

Ground

Water Soluble Packet

0.24

EC

0.00004 2,400,000

Ground 

Emulsifiable Concentrate 

impregnating fertilizer

Dry beans10

0.083

EC

Closed System 0.07 lb a.i./acre

0.7 lb a.i./ton of 

fertilizer 

960 tons of fertilizer 0.0007 140,000

Ground

Emulsifiable Concentrate

0.219

No Respirator

200 acres

0.00004 2,600,000

Ground

Water Dispersible Granular

8.96

No Respirator 0.0016 64,000
Flumetsulam Human Health Risk Assessment DP No. D411276

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Table 8.1.1 - Occupational Handler Non-Cancer Exposure and Risk Estimates for Flumetsulam Use on Field Corn and 

Soybeans at Baseline 1

Exposure Scenario Crop

Inhalation Unit Exposure (μg/lb ai)2 Maximum

Application Rate3

Area Treated or 

Amount Handled Daily4

Inhalation

Mitigation Level Dose (mg/kg/day)5 MOE6

Applicator

Aerial8

Water Dispersible Granular 

within a Water Soluble 

Packet

Field Corn and 

Soybeans

0.0049

EC

Closed Cockpit

0.07 lb a.i./acre

1200 .0000052 19,000,000

Ground

Water Dispersible Granular 

and Water Dispersible 

Granular within a Water 

Soluble Packet

Field Corn, 

Soybeans, and 

Dry Beans 0.34

No Respirator

200

0.00006 1,700,000

Ground

Emulsifiable Concentrate

Field Corn s 0.05 lb a.i./acre 0.00004 2,400,000

Dry Beans 0.07 lb a.i./acre 0.00006 1,700,000

Impregnated Fertilizer9

Tractor drawn spreader

Field Corn, 

Soybeans, Dry 

Beans 1.2

No Respirator

0.07 lb a.i./acre 360 acres 0.00034 300,000

Impregnated Fertilizer9

Tractor drawn spreader

Field Corn and 

Soybeans 0.05 lb a.i./acre 360 acres 0.00024 420,000

Flagger

Sprays

Water Dispersible Granular 

within a Water Soluble 

Packet

Field Corn, and 

Soybeans

0.35

No Respirator 0.07 lb a.i./acre 350 0.00011 930,000

1 Baseline PPE includes long sleeved pants, long sleeved shirt, shoes and sock and no respirator.

2 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table; Level of mitigation: No respirator, EC = Engineering Controls 

3 Based on registered or proposed labels for flumetsulam. See Profile Table 4.1

4 Exposure Science Advisory Council Policy #9.1.

5 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated or Amount Handled Daily (A) ÷ BW (kg).

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

7 Water Soluble Packets, or WSPs are considered an engineering control. Unit exposures for chemicals packaged this way are lower than baseline which assumes no respirator

8 Aerial application is assumed to be done with closed cockpit which is considered an engineered control not baseline protection.

9 EPA reg number 62719-570 label notates for impregnating fertilizer use a minimum of 200 lb of dry bulk fertilizer per acre with maximum of 3 pints of product per acre.

10 Dry Bean use scenarios and application rates based on inactive registration numbers and 2004 memo D306178.
Flumetsulam Human Health Risk Assessment DP No. D411276

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8.1.2 Cancer Handler Exposure and Risk

A cancer handler exposure and risk assessment was not performed as flumetsulam is classified as

Group E (Evidence of non-carcinogenicity for humans). 

8.2 Occupational Post-Application Exposure and Risk

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.

8.2.1 Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for flumetsulam at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III and IV), low vapor pressure 1.0 x 10-15 mm HG @ 

25 ̊C, and the low proposed use rates (0.07 and 0.5 lb ai/A). However, there are multiple 

potential sources of post-application inhalation exposure to individuals performing postapplication 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 Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, 

and received the SAP’s final report on March 2, 20105. The Agency is in the process of 

evaluating the SAP report as well as available post-application inhalation exposure data 

generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and 

procedures, to identify the need for and, subsequently, the way to incorporate occupational postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for flumetsulam.

Although a quantitative 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.

8.2.2 Post-application Dermal Exposure and Risk

 

5

Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Flumetsulam Human Health Risk Assessment DP No. D411276

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8.2.2.1 Short-/Intermediate-Term Non-Cancer Post-application Exposure and Risk

A quantitative occupational post application dermal exposure assessment was not performed due 

to lack of dermal endpoint selection. 

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of flumetsulam. 

Flumetsulam is classified as Toxicity Category III or IV via the dermal route and skin irritation 

potential. It is not a skin sensitizer. Short- and intermediate-term post-application risk estimates 

were not a concern on day 0 (12 hours following application) for all post-application activities. 

Under 40 CFR 156.208 (c) (2) (iii), active ingredients classified as Acute III or IV for acute 

dermal, eye irritation and primary skin irrigation are assigned a 12-hour REI. Therefore, the 

[156 subpart K] Worker Protection Statement interim REI of 12 hours is adequate to protect 

agricultural workers from post-application exposures to flumetsulam. Products that include a 

formulated mixture of active ingredient should retain the 48 hour REI. 

8.2.2.2 Cancer Post-application Exposure and Risk

A cancer post-application exposure and risk assessment was not performed as flumetsulam is 

classified as Group E (Evidence of non-carcinogenicity for humans). 
Flumetsulam Human Health Risk Assessment DP No. D411276

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References

Ary, S. (2004). Flumetsulam. Summary of Analytical Chemistry and Residue Data for the 

Tolerance Reassessment Eligibility Decision (TRED) Document. PC Code: 129016, DP 

Number: D306242. August 31, 2004.

Barnes, P.Y. (2013). Flumetsulam Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessment for Registration Review. PC Code: 129016, DP Number: 

D412998, September 2013.

Bobowiec, B. (2013). Flumetsulam. Occupational and Residential Exposure Registration 

Review Assessment. PC Code: 129016, DP Number: D415189, September 2013.

Dodd, N (1993). Flumetsulam Metabolism in Soybeans and Field Corn, The 

HED Metabolism Committee Meeting Held on 04/21/1993. April 26, 1993

Dodd, N., “Issues to be Presented at the 4/21/93 Meeting of the HED Metabolism 

Committee.”

Dodd, N. (1993). PC Code: 129016, DP Numbers: D188957 and D190750. June 

28, 1993

Dodd, N. (1993). Flumetsulam (DE-498) on Soybeans and Corn. PC Code: 129016, DP 

Number: D189444). Evaluation of Method Trial Report dated 3/19/93.

Dodd, N (1993). Flumetsulam (DE-498) on Soybeans and Corn. Amendments 

dated 9/25/92, 10/8/92, 11/30/92, and 12/7/92. PC Code: 129016, DP Numbers: 

D183274, D184405/D184530, D185716, and D185720. 

Dow, Mark I. (2004). Flumetsulam - Exposure/Risk Assessment for Flumetsulam 

Applied to Dried Bean. PC Code: 129016, DP Number: D306178. August 10, 

2004.

Reaves, E. and Ary, S.(2004). [Flumetsulam:] Revised Phase 2 HED Chapter of the Tolerance 

Reassessment Eligibility Decision Document (TRED). PC Code: 129016, DP Barcode: 

D306238. November 22, 2004

Recore, S., S.C. Dapson, . Barnes, P.Y (2008). Flumetsulam. Amended Human Health 

Assessment Scoping Document in Support of Registration Review ; PC Code: 129016; DP 

Number: D349638. August 12, 2008. 

Recore, S. (2013). Flumetsulam: Review of Human Incidents for Preliminary Risk Assessment. 

PC Code: 129016, DP Number: D412985. July 10, 2013. 
Flumetsulam Human Health Risk Assessment DP No. D411276

Page 31 of 40

Van Alstine, J. (2013). Flumetsulam: Summary of Hazard and Science Policy Council 

(HASPOC) Meetings: Recommendations on the need for an inhalation study. Sept, 5, 2013, 

TXR No. 0056689.

Wolf, J.K. (2013). Registration Review Drinking Water Assessment for Flumetsulam. PC 

Code: 129016, DP Number: D411277. August 16, 2013.
Flumetsulam Human Health Risk Assessment DP No. D411276

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Appendix A. Toxicology Assessment

A.1 Toxicology Data Requirements

The requirements (40CFR §158.340) for food use of flumetsulam are in Table A.1. 

TABLE A.1 - Toxicology Data Requirements for Flumetsulam

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (non-rodent)

870.3200 21/28-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation

yes

yes

yes

no

yes

yes

yes

yes

no

yesa

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (non-rodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (non-rodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation (bacterial)

870.5300 Mutagenicity—Gene Mutation (mammalian)

870.5375 Mutagenicity—Structural Chromosomal Aberrations

870.5395 Mutagenicity—Other Genotoxic Effects 

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)

870.6100b 90-Day Neurotoxicity (hen)

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Developmental Neurotoxicity

no

no

yes

yes

no

no

no

yes

yes

no

870.7485 General Metabolism

870.7600 Dermal Penetration 

870.7800 Immunotoxicity

yes

no

yes

yes

no

yes

a

Inhalation study is waived by the HASPOC.
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A.2 Toxicity Profile

TABLE A.2.1 - Acute Toxicity Profile for Flumetsulam

Guideline 

Number

Study Type MRID(s) Results Toxicity 

Category

870.1100 Acute oral [Rat] 41263202 LD50>5000 mg/kg (M/F) IV

870.1200 Acute dermal [Rabbit] 41263203 LD50>2000 mg/kg (M/F) III

870.1300 Acute inhalation [Rat] 41556501 LC50>0.65 mg/L (M/F) IV

870.2400 Acute eye irritation [Rabbit] 41263204 Slight conjunctival reddening and 

chemosis and iridal redness at 1 hour

IV

870.2500 Acute dermal irritation [Rabbit] 41263205 Not an irritant IV

870.2600 Skin sensitization [Guinea pig] 41263206 Not a skin sensitizer NA

TABLE A.2.2 - Subchronic, Chronic, and other Toxicity Profile for Flumetsulam

Guideline Number/ 

Study Type

MRIDs/Year/Doses

Classification

Results

870.3100

90-Day oral toxicity, 

Rat

41263212 (1988)

0, 250, 1000, 

2000/2500 mg/kg/day

Acceptable/Guideline

NOAEL (M/F) 250 mg/kg/day

LOAEL (M/F) 1000 mg/kg/day based on severe bilateral 

tubular-interstitial nephritis.

870.3100

90-Day oral toxicity, 

Mice

41931704 (1987)

0, 100, 500, 1000, 

5000 mg/kg/day 

Acceptable/Guideline

NOAEL (M/F) 5000 mg/kg/day (98.6% a.i.)

LOAEL (M/F) Not identified. Statistically increased full 

cecum weights and decreased kidney weights were found 

at 5000 mg/kg/day but were considered adaptive and/or 

toxicologically irrelevant. 

870.3200

21-Day Dermal, 

Rabbit

41931706 (1990)

0, 100, 500, 1000 

mg/kg/day

Acceptable/Guideline

Systemic & dermal NOAEL (M/F) >1000 mg/kg/day. 

LOAEL (M/F) Not identified

Diffuse treatment-related epidermal hyperplasia observed 

at application site.

870.3700a

Developmental Toxicity, 

Rat

(GD 6-15)

41263213, 41615301 

(1990)

0, 100, 500, 1000, 

mg/kg/day

Acceptable/Guideline

Maternal NOAEL 500 mg/kg/day 

Maternal LOAEL 1000 mg/kg/day, based on statistically 

increased full cecum weights and decreased kidney 

weights, but considered adaptive and/or toxicologically 

irrelevant.

Developmental NOAEL >1000 mg/kg/day

Developmental LOAEL Not identified.

No developmental toxicity reported.

870.3700b

Developmental Toxicity, 

Rabbit

(GD 7-19)

41931709 (1989)

0, 100, 500, 700 

mg/kg/day

Acceptable/Guideline

Maternal NOAEL=100 mg/kg/day

Maternal LOAEL= 500 mg/kg/day based on anorexia, 

moribundity, and decreased body weight gain (GD 10-13 

at 500 and GD 7-10 at 700 mg/kg/day)

Developmental NOAEL> 700 mg/kg/day

Developmental LOAEL= Not identified 

870.3800

Reproduction (2-

41931710 (42474001) 

(1990)

0, 100, 500, 1000 

Reproductive NOAEL >1000 mg/kg/day

Reproductive LOAEL Not identified

Offspring NOAEL > 1000 mg/kg/day
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TABLE A.2.2 - Subchronic, Chronic, and other Toxicity Profile for Flumetsulam

Guideline Number/ 

Study Type

MRIDs/Year/Doses

Classification

Results

Generation), 

Rat

mg/kg/day

Acceptable/Guideline

Offspring LOAEL Not identified

Parental NOAEL >1000 mg/kg/day

Parental LOAEL Not identified

870.4100b

Chronic Feeding, 

Dog

41952103 (1991)

0, 20, 100, 500 

mg/kg/day

Acceptable/Guideline

Systemic NOAEL (M) = 100 mg/kg/day

Systemic NOAEL (F) >500 mg/kg/day

Systemic LOAEL (M) = 500 mg/kg/day based on renal 

inflammatory and atrophic changes secondary to renal 

calculi and hepatic effects consisting of inflammation, 

focal necrosis, and biliary stasis

LOAEL (F) Not identified

870.4200b

Carcinogenicity, 

Mouse

41931708 (1991)

0, 100, 500, 1000 

mg/kg/day

Acceptable/Guideline

Systemic NOAEL (M/F) > 1000 mg/kg/day

LOAEL (M/F) Not identified

Not evidence for carcinogenicity in M/F

870.4300

Chronic/Oncogenicity, 2-

YearRat

41931707 (1991)

0, 100, 500, 1000 

mg/kg/day

Acceptable/Guideline

NOAEL (M) = 500 mg/kg/day

NOAEL (F) > 1000 mg/kg/day

LOAEL (M) = 1000 mg/kg/day based on dilated renal 

pelvises containing renal calculi, atrophy of renal papillae, 

renal pelvic epithelial hyperplasia, and mineralization of 

pelvic epithelium

LOAEL (F) Not identified

Not evidence for carcinogenicity in M/F

870.5100

Ames bacterial 

mutagenicity test

41263214 (1988)

Acceptable/Guideline

Salmonella - Negative in strains TA98, TA100, TA1535, 

TA1537, and TA1538 with and without metabolic 

activation at concentrations of 0.01-1.0 mg/plate

870.5300

In vitro mammalian cell 

gene mutation test 

(Chinese hamster ovary 

cells)

41263217 (1988)

Acceptable/Guideline

The study was negative at concentrations from 500 to 

3000 μg/mL with and without metabolic activation with 

Arochlor 1254 induced rat liver S-9

870.5395

In Vivo Micronucleus 

Assay

41263216 (1988)

Acceptable/Guideline

Negative for micronucleus induction in bone marrow cells 

of male and female CD-1 mice at 24 hrs after oral gavage 

administration of 500 to 5000 mg/kg.

870.5550

Unscheduled DNA 

Synthesis

41263215 (1988)

Acceptable/Guideline

Negative at concentrations from 3.16 x 10-6to 3.16 x 10-4 

M

870.7485

General Metabolism,

Rat and Mouse

41931711 (1991)

41993801 (1988)

Acceptable/Guideline

Absorbed test material (52-63%) excreted unchanged in 

urine. Unabsorbed test material eliminated unchanged in 

feces. Test material essentially eliminated within 48 hours 

by male and female rats. Plasma 14C exhibited a dosedependent increase in absorption and elimination. 

Increasing dose associated with increasing clearance 

possibly due to saturation of plasma binding sites. Male 

mice exhibited faster absorption and elimination at 1000 
Flumetsulam Human Health Risk Assessment DP No. D411276

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TABLE A.2.2 - Subchronic, Chronic, and other Toxicity Profile for Flumetsulam

Guideline Number/ 

Study Type

MRIDs/Year/Doses

Classification

Results

mg/kg than male rats. Urine primary elimination route in 

both male and female rats and mice. Two minor 

metabolites identified in urine in mice.

870.6200

Acute Neurotoxicity

Rat

48297902 (2009)

0,250,1000, 2000 

mg/kg

Acceptable/Guideline

Systemic/neurotoxicity NOAEL=2000 mg/kg

No evidence of neurotoxicity

870.6200

Subchronic Neurotoxicity

Rat

48798101 (2012)

0, 100, 300, 1000 

mg/kg/day

Acceptable/Guideline

Systemic/neurotoxicity NOAEL=1000 mg/kg/day

No evidence of neurotoxicity.

870.7800

Immunotoxicity

Rat

48694401 (2011)

0, 1000 mg/kg/day

Acceptable/Guideline

Systemic/Immunotoxicity NOAEL=1000 mg/kg/day

No evidence of immunotoxicity
Flumetsulam Human Health Risk Assessment DP No. D411276

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Appendix B. Physical/Chemical Properties

Table B.1- Physicochemical Properties of the Technical Grade Test Compound 

Flumetsulam. 

Parameter Value Reference /Comment

Melting point 252.9 °C N. Dodd, PP# 1G4006, 

03/27/1992

pH 3.44 at 24.4 °C for a 10% suspension in water 

Density 1.77 g/cm3at 21°C

Water solubility 49.1 ± 0.5 mg/L at 25 °C, pH 2.5

5.65 ± 0.01 g/L at 25 °C, pH 7.0

Solvent solubility (g/L)

17.0 g/L in acetone N. Dodd, PP# 2F4036, 

5.2 g/L in acetonitrile 04/14/1993

0.0016 g/L in aromatic 100

9.0 g/L in cyclohexanone

261.0 g/L in dimethylformamide

Less than 0.001 g/L in hexane

3.3 g/L in methanol

Less than 0.001 g/L in o-xylene

0.06 g/L in octanol

11.0 g/L in tetrahydrofuran

Vapor pressure 1.0 x 10-15 mm Hg at 25 °C N. Dodd, PP# 1G4006, 

03/27/1992

Dissociation constant pKa = 4.6

Octanol/water partition coefficient 

Log(KOW)

log P = 0.21

Henry’s Law Constant 

(25 oC) 

6.14e-15 atm-m

3

/mol @25°C Calculated

Aerobic Soil Metabolism Half-life (ASM) 

(T1/2)

93, 48, 47, 30, 23, 44, 88, 36,19, 81,51,28, 44, 130, 

13, 17, 20, 46, 60, 59, 102 days

[range 13 to 130 days; mean = 51.0 days]

T1/2 indentified in the 

problem formulation 23, 60, 

93, 102 days; mean = 69,5 

days (MRID 41263230).

Anaerobic Aquatic Soil Metabolism 183 days

Aerobic Aquatic Metabolism Half-life 

(days)

1762 [14C-pyrimidine ring] days

1319 [14C-analine ring] days

Studied reviewed but DER 

has not been completed by 

EFED.

 
Flumetsulam Human Health Risk Assessment DP No. D411276

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Appendix C. 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 studies, which comprise the 

Pesticide Handlers Exposure Database (PHED), the Outdoor Residential Exposure Task Force 

(ORETF) Database, the Agricultural Handler Exposure Task Force (AHETF), and the 

Agricultural Reentry Task Force (ARTF) have been determined to require a review of their 

ethical conduct, have received that review, and have been determined to be ethically conducted.
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Appendix D. Occupational Exposure/Risk Summary Tables

Table D.1- Residential Exposure to Flumetsulam from Agricultural Drift for Children Ages 1<2 years Hand to Mouth, HtM 

only

Crop/Rate 

Group

Spray Type/ 

Nozzle 

Configuration 

Application 

Rate (lb 

ai/A)

Estimated 

or 

Adjusted 

TTRt

(ug/cm2)

At Edge 10 Feet 25 Feet 50 Feet 75 Feet 100 Feet 125 Feet 150 Feet 200 Feet 250 Feet 300 Feet 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

HtM 

MOE 

Soybeans, Field Corn, and Dry Beans1

Aerial

Fine to 

Medium

0.07 0.0077805

370000 450000 560000 730000 960000 1200000 1500000 1700000 2300000 2800000 3400000

Medium to 

Coarse 440000 600000 820000 1100000 1600000 2100000 2700000 3200000 4500000 5900000 7200000

Coarse to Very 

Coarse 510000 760000 1100000 1800000 2500000 3400000 4300000 5200000 7200000 9400000 12000000

Very Fine to 

Fine 250000 280000 310000 360000 420000 480000 540000 610000 740000 870000 990000

AT401, M, 10 

mph, 37% SD 400000 510000 660000 890000 1200000 1600000 1900000 2200000 2900000 3600000 4500000

WASP, M, 10 

mph, 37% SD 430000 550000 730000 1100000 1500000 1900000 2300000 2800000 3600000 4500000 5200000

AT401, C, 10 

mph, 25% SD 470000 670000 950000 1400000 2000000 2600000 3200000 3900000 5500000 7200000 8500000

WASP, C, 10 

mph, 25% SD 550000 780000 1100000 1800000 2500000 3400000 4100000 5200000 7200000 9400000 10000000

AT401, VC, 10 

mph, 20% SD 540000 820000 1300000 2100000 3000000 4100000 5200000 6700000 9400000 12000000 16000000

WASP, VC, 10 

mph, 20% SD 680000 1100000 1600000 2600000 3800000 4900000 6700000 7800000 12000000 13000000 16000000

Groundboom

High Boom 

Very fine to 

Fine

500000 1000000 1700000 2700000 3800000 4700000 5500000 6700000 8500000 12000000 13000000

Low Boom 

Very fine to 

Fine

1100000 2900000 4700000 7200000 9400000 12000000 13000000 16000000 19000000 23000000 31000000

High Boom 

Fine to 

Medium/Coarse

1900000 4900000 7200000 10000000 13000000 16000000 19000000 19000000 23000000 31000000 31000000

Low Boom 

Fine to 

Medium/Coarse

2800000 7800000 12000000 16000000 19000000 23000000 31000000 31000000 47000000 47000000 47000000

Field Corn

Groundboom

High Boom 

Very fine to 

Fine

0.05 0.0055575 700000 1400000 2300000 3800000 5300000 6600000 7700000 9400000 12000000 16000000 19000000
Flumetsulam Human Health Risk Assessment DP No. D411276

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Low Boom 

Very fine to 

Fine

1500000 4100000 6600000 10000000 13000000 16000000 19000000 22000000 26000000 33000000 44000000

High Boom 

Fine to 

Medium/Coarse

2700000 6900000 10000000 15000000 19000000 22000000 26000000 26000000 33000000 44000000 44000000

Low Boom 

Fine to 

Medium/Coarse

4000000 11000000 16000000 22000000 26000000 33000000 44000000 44000000 66000000 66000000 66000000

1 No aerial application to dry beans. Only field corn and soybeans
Flumetsulam Human Health Risk Assessment DP No. D411276

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Appendix E. Summary of US and International Tolerances and Maximum Residue Limits

Table E.1 - Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.468

Plant/Livestock: N-(2,6-difluorophenyl)-

5-methyl-(1,2,4)triazolo(1,5-

a)pyrimidine-2- sulfonamide) 

[1,2,4]triazolo[1,5-

a]pyrimidine-2-sulfonmide, 

N-(2,6-difluorophenyl)-5-

methylNone

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

US Canada Mexico2 Codex

Bean, dry, seed 0.05

Corn, field, forage 0.05

Corn, field, grain 0.05 0.05 field corn

Corn, field, stover 0.05

Soybean, seed 0.05 0.05 dry soybeans

Completed: M. Negussie; 05/09/13

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