UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: 09/ 19/2013 

SUBJECT: Flumetsulam Chronic Aggregate Dietary (Food and Drinking Water) Exposure 

and Risk Assessment for Registration Review. 

PC Code: 129016 

Decision No.: 477891 

Petition No.: NA 

DP Barcode: D412998 

Registration No.: NA 

Regulatory Action: Registration Review 

Risk Assessment Type: Dietary CaseNo.: NA 

TXR No.: N/A CAS No.: 98967-40-9 

MRID No.: N/A 40 CFR: §180.468 

FROM: 

THROUGH: 

TO: 

P. 

Risk 

YvonneBarnes,Chemist 

Assessment Branch VI 

-zj?~ ~~ 

Health Effects Division (HED, 7509P) 

Thurston Morton, Chemist .;),---y ft 2/ ct" 

Seyed Tadayon, Chemis ,, Dietary Exposure Science )C'Cfvisory Council (DESAC) 

Mohsen Sahafeyan, Chemist 

Risk Assessment Branch VI 

Health Effects Division (HED, 7509P) 

Catherine St Clair, Chemical Review Manager 

Risk Management and Implementation Branch II 

Pesticide Re-evaluation Division (7508P) 

Page I of8 
Flumetsulam Dietary Exposure and Risk Assessment DP Number: 0 41 2998 

Executive Summary 

Chronic 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-FCIDTM) 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). In support of the 

registration review risk assessment, this analysis was conducted. This memorandum was 

reviewed by two peer reviewers in reference to DESAC SOP 2012.1. 

The chronic dietary exposure analysis included the following assumptions: 

(1) Tolerance-level residues offlumetsulam in or on all current RACs as recorded in the (eCFR 40 §180.468; and 

(2) l 00 percentage of crops treated(% CT) and default-processing factors; and 

(3) 14.8 ppb estimated drinking water concentration (EDWC) from ground water sources. 

Chronic Dietary Exposure Assessment 

This unrefined chronic dietary (food and water) assessment used DEEM-FCIDTM to obtain risk 

estimates. The input file for the assessment includes tolerance level residues, l 00 percentage 

crop treated (% CT), default processing factors and the highest estimated drinking water 

concentration point estimate from groundwater sources. This assessment concludes that for all 

registered commodities, the chronic dietary exposure and risk estimates do not exceed HED's 

level of concern for the U.S. population and all population subgroups. The dietary risk estimates 

is less than 1 percentage of the chronic population-adjusted dose (cPAD) for all population 

groups. 

I. Introduction 

Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute 

and chronic assessments, the risk is expressed as a percentage of a maximum acceptable dose 

(i.e., the dose that HED has concluded will result in no unreasonable adverse health effects). 

This dose is referred to as the population-adjusted dose (PAD). The PAD is equivalent to the 

point of departure (PoD, NOAEL, LOAEL, e.g.) divided by the required uncertainty or safety 

factor. 

For non-cancer chronic exposures, HED is concerned when estimated dietary risk exceeds 100% 

of the PAD. References that discuss the acute and chronic risk assessments in more detail are 

available on the EPA/pesticides web site: "Available Information on Assessing Exposure from 

Pesticides, A User's Guide," 21-JUN-2000, WEB Link: http://www.epa.gov/fedrgstr/EPAPEST/2000/July/Day-12/606l.pdf; or see SOP 99.6 (20-AUG-1999). The most recent dietary 

risk assessment for Flumetsulam was conducted by S. Ary (08/30/2004, D306279). 

Page 2 of8 
Flumetsulam Dietary Exposure and Risk Assessment DP Number: 0412998 

II. Residue Information 

• Tolerances have been established under 40 CFR § 180.468 for residues of flumetsulam (N2, 6-difluorophenyl)-5-methyl-(1, 2, 4)-triazolo-[1 ,Sa] - pyrimidine-2-sulfonamide) in/on 

field corn (forage, grain, and stover) and soybean each one at 0.05 ppm. Adequate residue 

data support these tolerances. 

• The residue of concern for risk the risk assessment of both food and drinking water is 

Flumetsulam (N. Dodd, Memorandum, 04/1611993 and N. Dodd, Metabolism Committee 

Memorandum, 04/26/ 1993). 

The nature of the residue for each plant commodities, corn, dry bean and soybeans, is adequate 

based on acceptable plant metabolism studies. The Health Effects Division (HED) Metabolism 

Committee previously concluded that the residue of concern resulting from the uses on field 

com, dry bean, and soybeans is flumetsulam. Tolerance-level residues of flumetsulam in or on 

all current raw agricultural commodities ( e-CFR 40 § 180.468), I 00 percentage crop treated (% 

CT) and default processing factors; and 14.8 ppb estimated drinking water concentration 

(EDWC) from ground sources comprise the inputs for this assessment. 

III. Percent Crop Treated Information 

• This dietary assessment assumes 100% of the registered crops were treated. 

IV. Drinking Water Data 

The drinking water residues used in the dietary risk assessment were provided by the 

Environmental Fate and Effects Division (EFED) in the following memorandum: "Drinking 

Water Assessment for Registration Review of Flumetsulam" (D411277, J. Wolf, 08/16//2013) 

incorporated directly into this dietary assessment. Water residues were incorporated in the 

DEEM-FCIDTM into the food categories "water, direct, all sources" and "water, indirect, all 

sources." 

EFED exposure models were used to estimate the drinking water exposure concentrations for use 

in the dietary risk assessment of flumetsulam. The estimated drinking water concentrations 

(EDWC) for flumetsulam in surface water were estimated using PRZM/EXAMS. EDWCs for 

flumetsulam in groundwater are estimated with the Tier I/11 PRZM-GW and Tier I SCI-GROW 

models. 

For this EFED assessment, the surface water EDWCs are 6.7 JlgiL and 1.45 Jlg/L, for the 1-in-1 0 

year daily peak and annual flumetsulam concentration, respectively. The 30-year annual mean is 

0.76 Jlg/L. Based on PRZM-GW modeling, the highest flumetsulam concentration is 19.8 Jlg/L 

for the daily peak and 14.8 Jlg/L for the average concentration after breakthrough (Table 1 

below). 

Page3of8 
Flumetsulam Dietary Exposure and Risk Assessment DP Number: 04 12998 

Table 1 

Maximum Flumetsulam EDWCs for Corn scenario in Surface Water and Groundwater 

1-in-10 year 

30- year 

Drinking Water Source Average 

(Model) Acute Chronic Cancer 

{J.tg!L/ppb) 

Surface Water (PRZM/EXAMS) 6.68 1.45 0.76 

Groundwater (PRZM-GW) - - - • EDWCs are converted from ppb to ppm for use in the DEEM-FCIOTM dietary exposure model. 

• The drinking water models and their descriptions are available at the EPA internet site: 

http://www.epa.gov/oppcfcd I /models/water/. 

V. DEEM-FCID Program and Consumption Information 

30- year 

Simulation 

Acute Chronic 

- -

19.8 14.8 

Flumetsulam chronic dietary exposure assessment used the DEEM-FCIDTM, Version 3. 16, which 

incorporates 2003-2008 consumption data from USDA's NHANES/WWEIA. The data are 

based on the reported consumption of more than 20,000 individuals over two non-consecutive 

survey days. Foods "as consumed" (e.g., apple pie) are linked to EPA-defined food commodities 

(e.g., apples, peeled fruit- cooked; fresh or N/S; baked; or wheat flour- cooked; fresh or N/S, 

baked) using publicly available recipe translation files developed jointly by USDA/ARS and 

EPA. For chronic exposure assessment, consumption data are averaged for the entire U.S. 

population and within population subgroups. Based on analysis of the 2003-2008 WWEIA 

consumption data, which took into account dietary patterns and survey respondents, HED 

concluded that it is most appropriate to report risk for the following population subgroups: the 

general U.S. population, all infants (<l year old), children 1-2, children 3-5, children 6-12, youth 

13-19, adults 20-49, females 13-49, and adults 50-99 years old. 

For a chronic dietary exposure assessment, an estimate of the residue level in each food or foodform (e.g., orange or orange juice) on the food commodity residue list is multiplied by the 

average daily consumption estimate for that food/food form to produce a residue intake estimate. 

The resulting residue intake estimate for each food/food form is summed with the residue intake 

estimates for all other food/food forms on the commodity residue list to arrive at the total 

average estimated exposure. Exposure is expressed in mglkg body weight/day and as a percent 

of the cP AD. This procedure is performed for each population subgroup. 

VI. Toxicological Information 

On March 24, 1993, the HED RID/Peer Review Committee evaluated the toxicology database 

for Flumetsulam and selected reference doses (RIDs) and toxicological endpoints for acute and 

chronic dietary exposure risk assessments (G. Ghali, RID/Peer Review Committee 

Memorandum, 03/24/ 1993). There are no studies that identify an acute hazard based on toxic 

effects observed following a single oral exposure (dose) of flumetsulam. Therefore, a dose and 

endpoint are not proposed for the general population including infants and children or females 

Page 4 of8 
Flumetsulam Dietary Exposure and Risk Assessment DP Number: D41 2998 

13-49 years of age. Flumetsulam has been classified as a "Group E" pesticide (evidence of noncarcinogenicity to humans) and is not mutagenic. The toxicity endpoints pertinent for human 

risk assessment are summarized below in Table 2 (D306277, E. Reaves, 08/31/2004). 

Table 2. Toxicological Doses and Endpoint for Use in Flumetsulam Dietary and NonOccupational Human Health Risk Assessments 

Exposure Point of Uncertainty RfD, PAD, Level of Study and /FQPA Safety Concern for Risk /Scenario Departure Factors Assessment Toxicological Effects 

Acute 

Dietary No appropriate endpoint identified including developmental toxicity studies in rats and rabbits. (All 

populations) 

UFA=lOX Chronic Chronic feeding, dog 

UFH =lOX LOAEL = 500 mg/kg/day Chronic FQPA SF = IX RID = 1 mg/kg/day based on renal inflammatory Dietary NOAEL = 100 

(All mg/kg/day cP AD = Chronic RID and atrophic changes 

populations) Total UF = IOOX FQPA SF secondary to renal calculi and 

hepatic effects (inflammation, = 1 mg/kg/day focal necrosis, biliary stasis) 

Cancer Flumetsulam is classified as GroupE (Evidence of non-carcinogenicity for humans) (oral, 

dermal, (06/23/ 1993) 

inhalation) Not mutagenic 

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), RID = reference dose, UF = uncertainty factor, UFA= extrapolation 

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

VII. Results/Discussion 

As stated above, for chronic assessments, HED is concerned when dietary risk exceeds 1 00% of 

the PAD. The DEEM-FCID analyses estimate the dietary exposure and risk of the U.S. 

population and various population subgroups. The results reported in Table 3 are for the general 

U.S. Population, all infants ( <1 year old), children 1-2, children 3-5, children 6-12, youth 13-19, 

females 13-49, adults 20-49, and adults 50-99 years. 

Table 3. Summary of Dietary (Food and Drinking) Exposure and Risk for Flumetsulam. 

Acute Dietary Chronic Dietary Cancer 

Population Subgroup Dietary % Dietary Dietary 

Exposure aPAD Exposure o/ocPAD Exposure Risk 

(mg/kg/day) (mg/kg/day) (mg/kg/day) 

General U.S. Population 0 . 000435 

All Infants (<1 year old) 0.001007 

N/A N/A <1 NIA N/A 

Children 1-2 years old 0 .000735 

Children 3-5 years old 0 . 000665 

Page 5 of8 
Flumetsulam Dietary Exposure and Risk Assessment DP Number: 04 12998 

Table 3. Summary of Dietary (Food and Drinking) Exposure and Risk for Flumctsulam. 

Acute Dietary Chronic Dietary Cancer 

Population Subgroup Dietary % Dietary Dietary 

Exposure aPAD Exposure %cPAD Exposure Risk 

(mg/kg/day) (mg/ke:/day) ( ml!fke:/day) 

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 

Population group wllh the h1ghest exposure IS bolded. 

VIII. Characterization of Inputs/Outputs 

Degree of Refinement 

• The cPAD for all populations is less than 1%, no refinements required. 

Residue Data 

• There are no risk estimates of concern for this analysis. This unrefined chronic dietary 

exposure and risk analysis incorporate tolerance-level residues, 100% crop treated and 

default-processing factors as assumptions. 

IX. Conclusions 

All population subgroups have risk estimates that are below HED's level of concern. HED is 

confident that the assessment does not underestimate risk to the general U.S. population or any 

population subgroup. 

X. List of Attachments 

• Chronic Residue Input file 

• Chronic Results File 

Page6of8 
Flumetsulam Dietary Exposure and Risk Assessment DP Number: 0 412998 

Chronic Residue Input file 

US EPA Ver. 3.16, 03 - 08 - d 

DEEM-FCID Chronic analysis for FLUMETSULAM 

Residue f i le: C: \Documents a nd Settings\pbarnes\My Documents\DEEM Versi on 

3 16old\Chronic 129016Flumetsul am.R08 

Adjust. #2 NOT used 

Analysis Date 09-10-2013 Residue file dated: 09-10- 2013/10:09 : 57 

Reference dose {RfD) = 1 mg/kg bw/day 

Comment:FLUMETSULAM - FOOD AND WATER 

Food Crop 

EPA Code Grp Food Name 

0603030000 6C 

0603032000 6C 

0603034000 6C 

060303 5000 6C 

0603036000 6C 

0603038000 6C 

0603039000 6C 

0603040000 6C 

0603041000 6C 

0603042000 6C 

0603098000 6C 

06 03098001 6C 

0603099000 6C 

1500120000 15 

15001 20001 15 

1500121000 15 

1500121001 15 

1500122000 1 5 

1500123000 15 

1500123001 15 

1500124000 15 

1500124001 15 

1500125000 1 5 

1500125001 15 

0603182 000 6C 

06 03 182001 6C 

060034 700 0 6 

0603348000 6C 

0603348001 6C 

0600349000 6 

0600349001 6 

0600350000 6 

0600350001 6 

8601000000 86A 

8602000000 86B 

Bean, b l ack, seed 

Bean, broad , seed 

Bean, cowpea , seed 

Bean, great northern, seed 

Bean, kidney, seed 

Bean, lima, seed 

Bean, mung, seed 

Bean, navy, seed 

Bean, pink, seed 

Bean, pinto, seed 

Chickpea, seed 

Chickpea, seed-babyfood 

Chickpea , flour 

Corn, field, flour 

Corn, fiel d , f lour-babyfood 

Corn, fie l d, meal 

Corn, field, meal - babyfood 

Corn, field, bran 

Corn, field, starch 

corn, field, starch- babyfood 

Corn, field, syrup 

corn, field, syrup-babyfood 

Corn, field, oil 

Corn, field , o il-babyfood 

Guar, seed 

Guar, seed -babyfood 

Soybean, seed 

Soybean, flour 

Soybean, flour-babyfood 

Soybean, soy mi l k 

Soybean, soy milk- babyfood or in 

Soybean, oil 

Soybean, oil- babyfood 

Water, direct, all sources 

water, indirect, a l l sources 

Page 7 of8 

Residue 

{ppm) 

0 . 050000 

0. 05000 0 

0.05000 0 

0.050000 

0.050000 

0.050000 

0 .050000 

0 . 050000 

0.050000 

0.050000 

0.050 000 

0 . 0 50000 

0 . 0 50000 

0.050000 

0.050 000 

0.050000 

0 .050000 

0 . 050000 

0 . 050000 

0 . 050000 

0.050000 

0.050000 

0.050000 

0.050 000 

0.050000 

0.050000 

0 . 050000 

0 .050000 

0 .050000 

0 .050000 

0.050000 

0.050000 

0 . 050000 

0 . 014800 

0 .014800 

Adj.Factors 

Ill #2 

1 . 000 

1.000 

1 .000 

1.000 

1.000 

1.000 

1.000 

1.000 

1.000 

1.000 

1 . 000 

1 . 000 

1.000 

1.000 

1 .000 

1. 000 

1. 000 

1.000 

1.000 

1.000 

1.500 

1.000 

1.000 

l. 000 

1 . 000 

1.000 

1.000 

1.000 

1.000 

1.000 

1.000 

1.000 

1.000 

1.000 

1.000 

1. 00 0 

l. 0 00 

l. 0 00 

1 .000 

1.000 

1 .000 

1 .000 

1.000 

1.000 

1 . 000 

1 . 000 

1.000 

1. 000 

1 . 000 

1.000 

1.000 

1. 000 

1.000 

1.000 

1.000 

1.000 

1.000 

l. 000 

1. 0 00 

1 . 000 

l. 000 

1 .000 

1.000 

1.000 

1. 000 

1.000 

1.000 

1 . 000 

1.000 

1.000 
Flumetsulam Dietary Exposure and Risk Assessment DP Number: D4 12998 

Chronic Results File 

US EPA Ver. 3.16, 03-08-d 

DEEM-FCID Chronic analysis for FLUMETSULAM NHANES 2003 - 2008 2-day 

Residue file name: C:\Documents and Settings\ pbarnes\ My Documents\DEEM Version 

3 16old\Chronic_1 29016Flumetsulam.R08 

Adjustment factor #2 NOT used . 

Analysis Date 09-10 - 2013/10: 10 :57 Residue file dated: 09-10-2013/10:09:57 

Reference dose (RfD, Chronic) = 1 mg/ kg bw/day 

COMMENT 1: FLUMETSULAM - FOOD AND WATER 

Total e xposu re b y population subgroup 

Total Exposure 

Population 

Subgroup 

Total us Population 

Hispanic 

Non-Hisp -White 

Non-Hisp -Black 

Non -Hisp-Other 

Nursing Infants 

Non-Nursing Infants 

Fema le 13+ PREG 

Children 1-6 

Children 7-12 

Male 13 - 19 

Female 13 - 19/NP 

Male 20+ 

Female 20+/NP 

Seniors 55+ 

All Infants 

Female 13 -50 

Children 1- 2 

Ch ildren 3-5 

Ch ildren 6 - 12 

You th 13-19 

Adults 20 -49 

Adults 50-99 

Female 13-49 

mg/kg 

body wt/day 

0 . 000435 

0 . 000451 

0.000437 

0.000388 

0.000478 

0.000360 

0.001296 

0.000404 

0 . 000682 

0.000457 

0 .000375 

0.000368 

0.000392 

0. 000409 

0 . 000366 

0 . 001007 

0.000412 

0 . 000735 

0 . 000665 

0.000481 

0.000372 

0 .000420 

0.000376 

0.00041 2 

Page 8 of8 

Percen t o f 

Rfd 

0 . 0% 

0 . 0% 

0 . 0% 

0.0% 

0.0% 

0.0% 

0.1% 

0.0% 

0.1% 

0.0% 

0.0% 

0.0% 

0.0% 

0 . 0% 

0 . 0% 

0. 1% 

0.0% 

0 . 1% 

0.1% 

0.0% 

0.0% 

0. 0 % 

0 . 0% 

0.0%