### Ethaboxam (090205) Dietary Exposure and Risk Assessment DP Number 0411091 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460



### MEMORANDUM Date: April30, 2013 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: Ethaboxam. Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for the Non-food Use ofEthaboxam as a Seed Treatment for Legume Vegetables (Crop Group 6) except Cowpea and Field Pea, Cerea l Grains (Crop Group 15) except Rice and Wild Rice, and the Rapeseed Subgroup (20-A). PC Code : 090205 Decision No.: 456065 Petition No.: NA DP Barcode: 0411091 Registration No.: 59639-RIL Regulatory Action: Section 3 Case No.: 7053 Risk Assessment Type: Dietary TXRNo.: NA CAS No .: 162650-77-3 40 CFR: §180.622 MRIDNo.: NA FROM: Dennis McNeilly, Chemist 

# £?- Risk Assessment Branch II Health Effects Division (7509P) THROUGH: David Hrdy, Senior

# Biolggi~s, .'

# rr!!**J~** Jennifer Tyler, Chemist 

## /lMt f/ {,; 

### Dietary Exposure Sciendt Ad sory Co cil (DESAC) Health Effects Division (7509P) Michael Doherty, Ph.D, Senior Scientist

## ~**tf71~ .**  . · 

### and

## ~ Risk Assessment Branch II Health Effects Division (7509P) TO: Julie Chao/Venus Eagle, RM Team 1 Insect icide Branch/Regi stration Division (7505P)
Executive Summary A chronic aggregate dietary (food and drinking water) exposure and risk assessment was conducted using the Dietary Exposure Evaluation Model software with the Food CommodityIntake Database (DEEM

- FC IDTM) Version 3.16, which uses 2003

- 2008 food consumption data from the U.S
. Department of Agriculture's National Health and Nutriti on Examination Survey, What We Eat in America, (NHANES/WWEIA)
. The analysis was conducted in support of a human heal th risk assessment for the proposed seed treatment uses of ethaboxam on legume vegetables (crop gro up 6) except cowpea and field pea, cereal grains ( crop group 15) except rice and wild rice, and the rapeseed subgro u p (20-A) (D396490, D
. McNeilly). While the proposed seed treatment uses are assessed as non - food uses, these uses reflect th e first U.S. uses, and there is now a drinking water component to the dietary exposure. In addition, dietary exposure may occur from residues on imported grapes, which are accounted for in this assessment. An acute d ietary assessme nt was not performed because an acute endpoint attributable to a sing le dose exposure was no t identified. This memorandum was reviewed by two peer reviewers of the DESAC , per DESAC SOP 2012.1. Tolerances for residues of ethaboxam are listed in 40 CFR 

### § 180.622. Tolerances were established for the parent compound, on imported grapes. The chronic dietary analysis is based on tolerance-level re sidues and an assumption of 100% crop treated (CT). Very conservative assumptions were made regarding ethaboxam res idue s inion grape commodities, and also for res idues of ethaboxam in drinking water resulting from the non-food seed treatment uses. Usi n g assumptions considered to be hi ghly p rotective of human health , the chronic dietary risk estimates range from approximately 3% of the chronic population-adjusted dose (cPAD; youth 13- 19 years old) to approximately 3 5% of the cPAD (children 1-2 years old). Generally, HED is concerned when dietary risk estimates exceed 100% of the PAD; therefore, the chronic dietary risk estimates for ethaboxam are below HED' s level of concern (LOC) for all population subgroups, including those of infants and children
.. I . Introduction Dietary ri sk assessment incorporates both exposure and toxicity of a given pesticide. For 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 equiva lent to the point of departure (POD, NOAEL, LOAEL , e.g.) divided by the required uncerta inty or safety factors. For non-cancer chronic exposures, HED is concerned when estimated dietary ri sk exceeds 100% of th e PAD
. References that discuss the chronic risk assessments in more detail are available on the EPA/pesticides web site: "Available Information on Assessing Exposure f rom 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 -19~9** **.** The most recent dietary risk assessment for ethaboxam on imported grapes was conducted in 2006 (M. Doherty, D328148 , 27 April2006). II. Residue Information Tolerances have been estab li shed for ethaboxam (40CFR §180.622) to allow importation of Page 2 of9grapes/grape commodities treated with this fungicide outside of the U
. S. The proposed seed treatment uses on legume vegetables (crop group 6) except cowpea and field pea, cereal grains (crop group 15) except rice and wil d rice, and the rapeseed subgroup (20-A) reflect the first uses in the U.S. The chronic assessment is based on tolerance

- level residues of 6 ppm in all grapes and grape commodities (i
. e., 100% CT). For the proposed n ew seed treatment uses, t he registrant submi tted an adequate seed radiotracer study on canola, com, sorghum, soybeans, and wheat, and HED has determined that the proposed uses quali fy as no n -food (D398681, D. Dotson, Apri l 30, 20 13)
. A lis ting of the input file used in the chronic analyses is included as Attachment 1. Processing factors Empirica l data indicate that res idues of ethaboxam in processed grape commodities (e.g, juice, r aisins, etc . ) are not expected to exceed the tolerance level for grapes; therefore, no concent ration factors were used in these analyses
. Livestoc k There are no significant livestock feed items associa t ed with grapes, and the seed treatment uses have acceptable l abel restrictions prohi biti n g the feed ing of fo rage an d hay to li vestock. Ethaboxam currently is not registered for use in the U
. S. The Pesticide Data Program (PDP) has not analyzed fish samples for ethaboxam residues. As the proposed uses are non - food seed treatment uses, it is extremely unlikely that residues would end up in fish as a resu lt of the proposed u ses . III. Percent Crop Treated Information Percent CT informat ion was not used in the chronic analys i s (1 00% CT assumed). IV. Drinking Water Data The drinking water residu es used in these dietary risk assessments were prov ided by EFED (email: A. Shelby , 1 3 Ma r 20 1 3), and incorpo rated di rectly into the DEEM

-FC IDTM dietary assessments via entry into the food categories "water, direct , a ll sources" and "water, indirec t , all sources." Estimated drinking water concentrations (EDWCs) fo r ethaboxam were modeled using conservative assumptions for the new seed treatment use. The highest use rate of 0.6 fl oz/1 00 lb seed is for legume vegetab les (crop group 6) of which garden pea has the hig hest seed rate of 411 lbs seed/ac. Given that the product is 3
. 2lbs ac tive ingredient per gallon, the max imum app lication rate is 0.062lb/ac
. The adsorption coefficent of464 mL!g o.c. for ethaboxam (Koc) was taken as the lowest non - sand Koc from the submi tted unreviewed study MRID 48535669 because there was greater than a 3x variation between presented values. So lub ility is 12.4 ppm. The Agency has not comp leted its review of the environmental fate data for ethaboxam. Therefore, the E DWCs reflect the very conservative assumption that et h aboxam is stable to all Page 3 of9routes of metabolism and degradation. Given these inputs, ethaboxam EDWCs were modeled with EFED's Tier 1 surface water model (FIRST) and Tier I groundwater model (SCIGROW) with the following results: Surface water peak EDWC = 3
. 3 ppb Groundwater peak EDWC 

## = 0.09 ppb Typically, HED uses the higher of the surface or groundwater estimates for each duration when assessing dietary risk. For ethaboxam, the results from the surface water model are the highest estimates and were used in the dietary assessments. The models and their descriptions are available at the EPA internet website via the web link, http ://www
.epa. gov/oppefed 1/model s/water /
. V. DEEM-FCID Program and Consumption Information The ethaboxam chronic dietary exposure assessment was conducted using the Dietary Exposure Evaluation Mode l software with the Food Commodity Intake Database DEEM-FCID, Version 3.16, which incorporates consumption data from USDA's NHANE S/ WWEIA. This dietary survey was conducted from 2003 to 2008. The data are based on t h e 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. , app les, 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. Based on analysis of the 2003-2008 WWEIA consumption data, whic h 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 (<1 year o ld ), children 1-2, children 3-5, children 6

- 12, youth 13- 19 , adults 20

-49, females 13-49 , and adu lts 50

- 99 years o ld. 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 multip li ed by the average daily consumpti on estimate for that food/food form to produce a residue intake estimate. The resulting residue intake es timate for each food/food form is summed with the residue intake estimates for all other food/food forms on the commodity residue li st to arrive at the to tal average estimated exposure . Exposure is expressed in mglkg body weight/day and as a percent of the cPAD. This procedure is performed for each population subgroup. VI. Toxicological Information The toxico logy database for ethaboxam is complete. The scientific quality is relatively high and the toxicity profile of ethaboxam can be characterized for most effects, includ ing potential carcinogenic, mu tagenic, deve lopmental, and neurotoxic effects. No evidence of increased quantitative or qualitativ e susceptibility was seen in developmental 

### toxicity studies in rats and rabbits. H owever, there was evidence of increased qualitat ive susceptibility in a reproduction study in rats. Decreased pup weights and viability in both Page 4 of9population subgroups. The results of the assessments are shown in Table 2, below. Ta ble 2. S um ma ry of Estimated Dietary (F ood+ Drinking W ater ) Exp o s ures a nd Risk for Thiamethoxam. cP AD , Chroni c Estimates P opulati on S ubgro u p mglkg/day Exposure , m g/ k g/ d ay Risk, %cP AD U .S. Population 0.003503 6.4 All infants ( < 1 year) 0.006954 13 Children 1-2 yrs 1 0.019334 35 Children 3-5 yrs 0.011694 2 1 Children 6-12 yrs 0.055 0.004728 8
. 6 You th 13

- 19 yrs 0.001569 2.9 Adults 20-49 yrs 0.002309 4.2 Adults 50-99 yrs 0.002660 4.8 Females 13

- 49 y r s 0.002422 4.4 I The populatiOn subgro up with th e h1ghest estimated ex posur e/nsk IS bolded
. The results reported in T ab le 2 are for the general U .S. population , all infants (<1 year o ld), chil dren 1-2 years old , children 3-5 years old, children 6

- 12 years old, youth 13-19 years old , females 13-49 years old , adults 20-49 years old, and adults 50

- 99 years old
. A complete li sting of chronic exposure and risk estimates can be found in Attachment 2. As previously stated HED is concerned when dietary risk exceeds 100% of the PAD. The analyses indicate that the requested action , coupled with previously established tolerances , will result in chronic dietary (food + drinking water) exposures that are below H ED ' s LOC for all popul ati on subgroups, including those of infants and chi l dren. The most highly exposed popul ati on subgroup is children 1

-2 years which utilizes 35% of the cPAD , while the general U.S. population utili zes 6.4% of the cPAD
. VIII. Characterization of Inputs/Outputs T his assessment is based on tolerance level residues derived from field trial residue data and assumes 1 00% CT. The exposure values represent high

- end estimates and should be considered to be h i ghly conservative, health

- protective estimates of dietary exposure and risk
. Various refinements could be made to the assessments. However, as there are no risk estimates of concern (including aggregate risk concerns), no refinements were incorporated. IX
. Conclusions Based on highly conservative assumptions , there are no dietary (food+ dri nking wa t er) risk est imates of concern for ethaboxam. HED is confident that the assessment does no t underestimate risk to the general U.S. populat ion or any population subgroup. There are no dietary risk considerations that would preclude Page 6 of9generations, and delayed sexual maturation were seen, with maternal toxicity limited to decreased body we ight and body weight gains. In paternal animals, adverse effects were observed in the male reproductive organs of both generations and there was decreased fertility in F l adult males. Although there is evidence of increased qualitative suscept ibility in the rep roduction study, there are no residual uncertainties with regard to pre- and/or postnatal toxicity following in utero exposure to rats or rabbits and pre and/or post-natal exposures to rats. Considering the overall toxicity profile and the doses and endpoints selected for ri sk assessment, the degree of concern for the effects observed in the study is low based on the following: the offspring effects observed in the study are well characterized and clear NOAELs/LOAELs have been identified in the study for the effects of concern. Additionally, the PODs selected for risk assessment are pro tective of potential offspring effects. Thus, the Agency beli eves the FQP A safety facto r can be reduced to I X and still be conservatively protective of human health risk. The doses and endpo ints are summarized in Table 1 and indicate than an acute dietary assessment was not performed because an acute endpoint attributable to a single dose exposure was not identified (see TOXSAC Report 16 Jan 20 13). All representative population groups have been assessed for chronic exposure .

Table 1. Toxicological Doses and Endpoints for Ethaboxam for Use in Dietary Risk Assessments Uncertainty/ RID, PAD, Level of Study and Toxicological Effects Exposure/ Point of FQPA Concern for Risk Scenario Departure Safety Assessment Factors Acute No appropriate endpoint attributable to a single dose identified
. D ietary (All populations)
Chronic NOAEL = UF: IOOx Chronic RID = 0.055 Combined Chronic/CarcinogenicityDietary (All 5.5 UFA = lOX mg/kg/day Rat Populations) mg/ kg/day UFH=lOX LOAEL (mg/kg/day) : 16.4 , based FQPA SF=lX cPAD on effects observed in the male = 0
.055 mg/kg/day reproductive organs (testes, ep id idymides, prostate, seminal vesicles). Cancer Classification: "Suggestive Evidence of Carcinogenicity , based on increased incidence of Leydig (oral, Cell tumors in males. dermal, inhalation) Pomt of Departure (POD) = A data pomt or an esttmated pomt that tS denved from observed dose-response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A= extrapolation from animal to human (interspecies). UFH= potential variation in sensitivity among members of the human population (intraspecies). PAD = population adjusted dose (a= acute, c = chronic). RID = reference dose. 

### VII. Results/Discussion The DEEM-FCID analyses estimate the dietary exposure of the US population and various Page 5 of9allowing the petitioned-for seed treatment use of ethaboxam on legume vegetables (crop group 6) except cowpea and field pea, cerea l grains (crop group 1 5) except rice and wild rice , and the rapeseed subgroup (20

- A). X . List of Attachments Attachment 1. Input file for the chronic dietary exposure analyses of thiamethoxam. Attachment 2
. Summary of the chronic dietary exposure analysis for thi amethoxam.

Page7of9Attachment 1. Input File for the Chron ic Dietary Exposure Estimates. US EPA DEEM-F C I D Chronic ana l ysis fo r ETHABOXAM Residue file: J:\Ethaboxam\Dietary\et h abo xa m .r08 Ana l ys i s Date 03

- 14

- 2013 Resid u e f i l e Refe r ence dose (R f D} = 0
. 0 55 mg/kg bw/day Ver
. 3 .1 6, 03

- 08

- d Adju s t . #2 NOT used da ted: 03 -1 4

- 2013/09:08:23



## ------------ ------ - - ----- -- - - - -- ---- ---- -- - ----- -------- -------------------- --- ---

Food Crop Residue Adj
. Factors EPA Code Grp Food Nam e (ppm ) Il l 112

---- ------ 

### ------------------------- ------ ----- ----- 13 04175000 130 Gra . pe 6
. 000000 1.000 1. 000 13041 7600 0 13D Grape, ju i c e 6
. 000000 1.0 00 1. 000 13041 760 0 1 1 30 Grape, j u ice

- babyfood 6.000000 1. 000 1. 000 9500177000 0 Grape, leaves 6
. 000000 1 .000 1. 000 9500178000 0 Grape, rai si n 6
. 000000 1.000 1 .00 0 1 30 41 79000 1 3D Grape, w i ne and sherry 6 .0 00000 1
. 000 1 .00 0 8601000000 86A Wate r , direct, all sources 0 .0 03300 1. 000 1 .00 0 8602000000 86B Water , indirect, all sources 0 .0 03300 1. 000 1
. 000



### Page 8 of9Attach ment 2. S ummary of tb e chronic dietary e xposure analy sis for thiamethoxam.

US EPA DEEM-FC I D Chr onic analysis for ETHABOXAM Residue file name: J:\Ethaboxam\Dietary\ethaboxam
. r08 Ver. 3 .1 6 , 03-0 8 -d NHANES 2003-2008 2- day Adjus tment faccor ij2 NOT used
. Analysis Date 03 -1 4-20 13/09 :09:05 Residue file dated: 03-14-2013/09:08 : 23 Reference dose (RfD, Chronic) 

### = . 055 mg/kg bw/day 

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

Population

Subgroup Total 

### us Popu l ation Hispanic Non

- Hisp-White Non-Hisp-Black Non-Hisp

- Other Nursing Infants Non

- Nurs i ng I nfants Female 13+ PREG Childr en 1- 6 Children 7 -1 2 Male 13-19 Female 13 -1 9/NP Male 20+ Female 20+/NP Seniors 55+ All Infants Female 1 3-50 Children 1

- 2 Children 3

- 5 Children 6

- 12 Youth 13-19 Adults 20-49 Adults 50

- 99 Female 13-49 Tot al Exposure mg/kg body wt/day 0.003503 0.002863 0.00362 1 0.00363 4 0 .003286 0. 002411 0.008982 0.002056 0.0 1 41 1 4 0.003818 0.001435 0.001703 0.002231 0.002675 0.002817 0 .006954 0.002408 0.019334 0.011694 0.004728 0.001569 0.002309 0.002660 0.002422



### Page 9 o f9 Percent of Rfd6.4% 5.2% 6.6% 6.6% 6.0% 4.4% 16
. 3%

3.7% 25.7%

6.9% 2.6% 3.1% 4.1% 4.9% 5.1% 12.6%

4.4% 35.2% 21.3%

8.6% 2.9% 4.2% 4.8% 4.4%