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

OFFICE OF CHEMICAL SAFETY AND POLLUTI ON PREVENTION 

### MEMORANDUM

Date: 09/ 19 /2 013



### SUBJECT: Flumetsulam Chronic Aggregate D ietary (Food and Drinkin g Water) Expo sure and Risk Assessment for Reg i st rati on Review.


### PC Code: 129016 

### Decision No.: 477891 

### Petition No.: NA DP Barcode: D412998 

### Registration No.: NA Regulatory Action: Regi stration Review 

### CaseNo.: NA Risk Assessment Type: Dietary 

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

### CFR: §180.468 

### MRID No. : N/A

FROM:

THROUGH:

TO: P. YvonneBarnes,Chemist

# -zj?~**~~** Risk Assessment Branch VI Health Effec ts Division (HED , 7509P)

Thurs ton Mo rton , Chem i st 

# .;), ---y

# ft 

# 2/ 

# ct" Seyed Tadayo n,

# Chemis**,,** Di etary Exposure Science)C'Cf visory Council (DESAC) Mohsen Sahafeyan, Chemist Risk A ssess ment Branch VI Health Effects Division (HED , 7509P)

Catherine S t Clair, Chemical Rev iew Manager Risk Man agement and Implementation Branch II Pesticide Re- eval uation Division (750 8P)

Page I of8Flumetsulam 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 s upport of the registration review risk assessment, thi s analys i s was conducted. Thi s memorandum was reviewed by two p eer reviewers in reference to DESAC SOP 2012.1. The chronic dietary exposure analysis included the following assumption s: ( 1) Tolerance-level residues offlumetsulam in or on a ll current RACs as recorded in the (eCFR 40 §180.468; and (2) l 00 percentage of crops treated(% CT) and default-pro cessing factors ; and (3) 14.8 ppb estimated drinking water concentration (EDWC) from ground water sources. Chronic Dietary Exposure Assessment T his unrefined chronic dietary (food and water) assessment used DEEM-FC IDTM to obtain risk estimates. The input file for the assessment includes tolerance leve l residues , l 00 percentage crop treated (% CT) , default processing factor s and the high est estimated drinking water concentration point estimate from groundwater so urces . 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 a ll 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 H ED has concluded will re su lt in no unreasonable adverse health e ffects). This dose is referre d to as the population-adju sted dose (PAD ). The PAD is equivalent to th e point of departure (PoD , NOAEL, LOAEL, e.g.) divided by the required uncertainty o r safety factor. For non-cancer chronic exposures, HED is concerned when estimated dietary ri sk exceeds 1 00% of the PAD. Referenc es 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. e pa.go v/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 (0 8/ 30 / 2004, D306279).

Page 2 of8Flumetsulam Dietary Exposure and Ri sk Assessment DP Number: 0412998
II. Residue Information

• To lerances have been established under 40 CFR 

### § 180.468 for res idue s 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.

• Th e residue of concern for risk the risk assessment of both food and drinking water is Flumetsulam (N. Dodd , Memorandum , 04/ 1611993 and N. Do dd, Metabol ism 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 co ncern 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), I00 percentage crop treated (% CT) and default processing factors; and 14.8 ppb estimated drinking water concent ration (EDWC) from grou nd so urces 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 Env ironmental Fate and Effects Division (EFED) in the following memorandum: "D rinkin g Water Assessment for Registration Review of F lumetsu lam" (D411277, J. Wolf, 08/16//2013) incorporated directly into this dietary assessment. Water residue s were incorporated in the DEEM-FCIDTM into the food categories "water, direct, all sources" and "water, indirect, all so urces." EFED exposure model s we re used to est imate the drinking water exposure concentrations for u se in the dietary risk assessment of flum ets ulam . T he estimated drinkin g 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. T h e 30

- year annual mean i s 0.76 Jl g/ 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 ave rage concentration after breakthro ugh (Table 1 below).

Page3of8Flumets ulam Dietary Exposure and Risk Assessment DP Number : 04 1 2998
Table 1 Maximum Flum et s ul am EDWCs for Corn scenario in Su rf ace Water an d G roundwate r 1-in-10 year 30- year Drinking Water Source Average (Model) Acute Chronic Cancer {J.tg!L /ppb ) Surface Water (PRZM/E XAMS) 6.68 1 .45 0.76 Groun dwater (PRZM

- GW)



## - 

# - - • E DWC s are converted from ppb to ppm for u se in the DE E M-F C IOTM dietary exposu re model. • The dr inking water model s and their descriptions are available at the EPA internet si te:

http: //www . epa.gov/ oppcfcd I/ mode ls/water /.

V. DEEM-FCID Program and Consumption Information 30- y ea r Simulati on Acute C hronic



## - - 19

. 8 1 4. 8

Flumetsulam chronic dietary ex p osure assess ment used the DEEM- FCIDTM , Ve rsion 3. 1 6 , whic h incorporates 2003

- 2008 consumpti on data from USDA's N HANES /WWE I A. The data are based on the reported consumption of more th an 20,000 individual s over two non-co n secut i ve s urv ey days. Food s "as consumed" (e.g., apple pie) are linked to EPA-defined food commodities (e.g., app les, p ee le d fruit- cooked; fre s h or N/S; b a ked; or wheat fl our- cooked; fresh or N/S, b ake d) using publicly avai labl e recipe transl ati o n files developed jointly by USDA/ARS and EPA. For chron ic exposure assessment, consumption data are averaged for t he entir e U.S. popu lati on and within population s ub group s. Based on analysis of the 2003-2008 WWEIA co n sumpt ion data, w h ic h took into account d ie tary patterns and survey respondents, HED co ncl uded that it i s most appropri ate to report ri sk for the following p opulation s ubgroup s: th e general U.S. population , a ll inf ants (<l year o ld) , children 1

-2, chi ldren 3-5 , chi ldren 6

- 12, you th 13

- 19, adults 20-49 , fema les 13-49, and adults 50-99 years old. For a chronic di etary expos ure assessment, an es timate of the residue le vel in each food or foodform (e.g., orange or o range juice) on the food co mmodity residue li st is multiplied by the average dai ly consumption estimate for th at food /food form to produce a residue intake es ti mate. The resulting res idu e intake es timat e for each food/food fo rm is summed with the residue i ntake es timates for a ll oth er food/food forms on the commodity residue li st to arri ve at the tota l ave rage estimated exposure. Exposure i s expressed in m glkg body weigh t/d ay and as a percent of the c PAD. T hi s procedure is performed for each population s ub gro up.

VI. Toxicological In formation O n March 24, 1993, the HED RID/Peer R ev i ew Co mmitte e evaluated the toxicology da t abase for Flumetsulam and selected reference doses (RIDs) and tox icolo gical endpoints for acu te and chroni c dietary exposure risk assessments (G. Ghali, RID/Peer Review Committee Memorandum, 03 / 24/ 1993). There are no studies that ide ntify an acute hazard based on t oxic effects observed followi n g a single oral exposure (dose) of flum etsulam. Therefore, a dose and endpoint are not proposed for the general popu lation including inf an ts and c h ildren or females

Page 4 of8Flumet sulam Dietary Exposure and Risk Assessment DP Number : D41 299 8
13-49 years of age. Flumetsu lam has been classified as a "Group E" p esti cide (evidence of n oncarc inogenicity to humans) and is not mutagenic. Th e toxicity endpoints pertinent for human risk assessment are s um marized 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 Di etary No appropriate endpo int identified including developm ental toxicity studies in ra ts and rabbits.

(All popul ations) UFA=lOX Chronic Ch ronic 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 population s) Total UF = IOOX FQPA SF secondary to renal calculi and hepatic effects (inflammation, = 1 mg/kg/day foc a l necrosis, bil iary stasis) Cancer Flumetsulam is c la ssified 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 , L OAEL = lowest observ e d adverse effect level, PAD = populati on adjusted dose (a = ac ute , c = chronic) , RID = reference dose, UF = uncertainty factor, UFA= ext r apo lation from animal to human (i nterspecies) , UFH =potential variation in se nsitivity among members of the human population (intraspecies).



### VII. Results/Discussion As stated above, for chronic assessme nts, HED is concerned when d ietary risk exceeds 1 00% of the PAD. The DEEM-FCID analyses estimate the dietary expos ure and ri s k of the 

### U.S. population and v arious popu l ation subgroups. The results reported in Table 3 are for th e general U.S. Population , all infants (< 1 year old), children 1-2, child ren 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 ye ars old 0 .00 0735 Children 3-5 years old 0

. 000665

Page 5 of8Flumetsulam Dietary Exposure and Risk Ass e ssment DP Number: 04 1 2998

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) Chi l dren 6-12 years o l d 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 w llh the h1ghest exposure IS bolded.


### VIII

. Characterization of Inputs/Outputs Degree of Refi neme nt

• The c PAD for all p opul ations i s less than 1%, no refinements requ ired. Resi due Data

• There are no ri s k es timates of conc ern for thi s analysis. This unrefined chro nic dietary exposure a nd risk analys is incorporate tolerance- lev el residu es, 100% crop treated and default-processing factors as as s umpti ons.


### IX. Conclusions All popu lation subgroups have risk estimates th at are b elow HED 's leve l of co ncern. HED is confident that the assessment does not underes timate ri sk to the gen eral U.S. po p ulation or any population subgroup.



### X. List of Attachments

• Chro nic Residue Input file • Chron ic Results F il e

Page6of8Flumetsulam Dietary Ex posure and Ri sk A ssess ment DP Number: 0 4129 98
Ch ron ic Res id u e In put fil e

US E PA Ver. 3.16, 03

- 08

- d DEEM-FCID Chronic ana ly sis for FLUMETSULAM Resi due f i le: C : \Documents a nd Setting s\pbarnes\My Documents\DEEM Vers i on 3 16o ld\Chronic 12 9016Flu metsu l am.R08 Adjust. #2 NOT used Analysis Date 09-10-2013 Residue file dat ed: 09-10

- 2013/10:09 : 57 Reference dose {RfD) 

### = 1 mg/kg bw/day Comment:FLUMETSULAM

- FOOD AND WATER Crop Food EPA Cod e Grp Food Name 0603030000 6C 0603032000 6C 0603034000 6C 060303 500 0 6C 0603036000 6C 0603038000 6C 0603039000 6C 0603040000 6C 0603041000 6C 0603042000 6C 0603098000 6C 06 03098001 6C 0603099 0 00 6C 1500120000 15 1500 1 2000 1 15 1500121000 15 1500121001 15 1500122000 1 5 1500123000 15 1500123001 15 1500 124 000 15 1500124001 15 1500125000 1 5 1500125001 15 0603182 000 6 C 06 03 1 82001 6C 06003 4 700 0 6 0603348000 6C 060334800 1 6C 0600349000 6 0600349001 6 0600350000 6 060035000 1 6 8601000000 86A 8602000000 86B Bean, b l ac k, 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, see d-babyfoo d Chickpea , flo ur Corn, field, flour Corn, fie l d , f lo ur -babyfood Corn, fie l d, mea l Corn, field, me al

- babyfood Corn, field, bran Corn, field, starch corn, field, starch

- babyfood Corn, field, syrup corn, field, syrup-babyfood Corn, field, oi l Corn, field , o il-bab yfood Guar, seed Guar, see d -bab yfood 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

. 0 50 0 00 0. 0500 0 0 0.0 500 0 0 0.0 50 000 0.0 50 000 0.050000 0 .05000 0 0

. 050000 0.050000 0.05 0000 0.0 50 000 0

. 0 50 000 0

. 0 50000 0.050000 0.05 0 00 0 0.050000 0 .05 0000 0

. 050000 0

. 050000 0

. 050000 0.050000 0.050000 0.050000 0.0 50 000 0.050000 0.050000 0

. 050000 0 .05 0 00 0 0 .0 50000 0 .050000 0.050000 0.050000 0

. 050000 0

. 014800 0 .0148 00 Adj.Factors Ill #2 1

. 000 1.000 1 .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 1.500 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. 00 0 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 .0 00 1.000 1.000 1. 000 1.000 1.000 1

. 000 1.000 1.000F lum e t s ul am Dietary Exposure and Ri s k A ssess men t DP N umber: 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 \DEE M Version 3 16old\Chronic_1 29016Flumetsulam.R08 Adjustment factor #2 NOT used

. Analysis Date 09-10

- 2013/10: 1 0 :5 7 Residue file dated: 09-10-2013/10:09:57 Reference dose (RfD, Chronic) = 1 mg / k g bw/day COMMENT 1: FLUMETSULAM

- FOOD AND W A

TE R Total e x pos u re b y population subgroup

Total Exposure Population

Subgroup Total 

### us Population Hispanic Non-Hisp

- White Non-Hisp

- Black Non -Hisp-Ot her 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 Ch il dre n 1- 2 Ch ildren 3-5 C

h ildren 6

- 12 Yo u 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. 000 409 0

. 000366 0

. 001007 0.000412 0

. 000735 0

. 000665 0.000481 0.00 0 372 0 .000420 0.000376 0.000 41 2

Page 8 of8 Perce n t o f Rf d 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%