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, Cereal 

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 

Risk Assessment Type: Dietary Case No.: 7053 

TXRNo.: NA CAS No.: 162650-77-3 

MRIDNo.: NA 40 CFR: §180.622 

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 

Insecticide Branch/Registration 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 Commodity 
Intake Database (DEEM-FCIDTM) Version 3.16, which uses 2003-2008 food consumption data 

from the U.S. Department of Agriculture's National Health and Nutrition Examination Survey, 

What We Eat in America, (NHANES/WWEIA). The analysis was conducted in support of a 

human health risk assessment for the proposed seed treatment uses of ethaboxam on legume 

vegetables (crop group 6) except cowpea and field pea, cereal grains (crop group 15) except rice 

and wild rice, and the rapeseed subgroup (20-A) (D396490, D. McNeilly). While the proposed 

seed treatment uses are assessed as non-food uses, these uses reflect the 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 

dietary assessment was not performed because an acute endpoint attributable to a single dose 

exposure was not 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 residues and an assumption of 100% 

crop treated (CT). Very conservative assumptions were made regarding ethaboxam residues 

inion grape commodities, and also for residues of ethaboxam in drinking water resulting from the 

non-food seed treatment uses. Using assumptions considered to be highly protective of human 

health, the chronic dietary risk estimates range from approximately 3% of the chronic 

population-adjusted dose ( cP AD; youth 13-19 years old) to approximately 3 5% of the cP AD 

(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 risk 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 equivalent to the point of 

departure (POD, NOAEL, LOAEL, e.g.) divided by the required uncertainty or safety factors. 

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

of the PAD. References that discuss the 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-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 established for ethaboxam (40CFR §180.622) to allow importation of 

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grapes/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 wild 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 new seed treatment uses, the 

registrant submitted an adequate seed radiotracer study on canola, com, sorghum, soybeans, and 

wheat, and HED has determined that the proposed uses qualify as non-food (D398681, D. 

Dotson, April 30, 20 13). A listing of the input file used in the chronic analyses is included as 

Attachment 1. 

Processing factors 

Empirical data indicate that residues of ethaboxam in processed grape commodities (e.g, juice, 

raisins, etc.) are not expected to exceed the tolerance level for grapes; therefore, no concentration 

factors were used in these analyses. 

Livestock 

There are no significant livestock feed items associated with grapes, and the seed treatment uses 

have acceptable label restrictions prohibiting the feeding of forage and hay to livestock. 

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 result of the 

proposed uses. 

III. Percent Crop Treated Information 

Percent CT information was not used in the chronic analysis (1 00% CT assumed). 

IV. Drinking Water Data 

The drinking water residues used in these dietary risk assessments were provided by EFED 

(email: A. Shelby, 13 Mar 2013), and incorporated directly into the DEEM-FCIDTM dietary 

assessments via entry into the food categories "water, direct, all sources" and "water, indirect, all 

sources." 

Estimated drinking water concentrations (EDWCs) for 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 vegetables (crop group 6) of which garden pea has the highest seed rate of 411 

lbs seed/ac. Given that the product is 3.2lbs active ingredient per gallon, the maximum 

application rate is 0.062lb/ac. The adsorption coefficent of 464 mL!g o.c. for ethaboxam (Koc) 

was taken as the lowest non-sand Koc from the submitted unreviewed study MRID 48535669 

because there was greater than a 3x variation between presented values. Solubility is 12.4 ppm. 

The Agency has not completed its review of the environmental fate data for ethaboxam. 

Therefore, the EDWCs reflect the very conservative assumption that ethaboxam is stable to all 

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routes 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/models/water/. 

V. DEEM-FCID Program and Consumption Information 

The ethaboxam chronic dietary exposure assessment was conducted using the Dietary Exposure 

Evaluation Model software with the Food Commodity Intake Database DEEM-FCID, Version 

3.16, which incorporates consumption data from USDA's NHANES/WWEIA. This dietary 

survey was conducted from 2003 to 2008. 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. 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 (<1 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 cPAD. This procedure is performed for each population subgroup. 

VI. Toxicological Information 

The toxicology database for ethaboxam is complete. The scientific quality is relatively high and 

the toxicity profile of ethaboxam can be characterized for most effects, including potential 

carcinogenic, mutagenic, developmental, and neurotoxic effects. 

No evidence of increased quantitative or qualitative susceptibility was seen in developmental 

toxicity studies in rats and rabbits. However, there was evidence of increased qualitative 

susceptibility in a reproduction study in rats. Decreased pup weights and viability in both 

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population subgroups. The results of the assessments are shown in Table 2, below. 

Table 2. Summary of Estimated Dietary (Food+ Drinking Water) Exposures and 

Risk for Thiamethoxam. 

cPAD, Chronic Estimates 

Population Subgroup mglkg/day Exposure, mg/kg/day Risk, 

%cPAD 

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 

Youth 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 yrs 0.002422 4.4 

I The populatiOn subgroup with the h1ghest estimated exposure/nsk IS bolded. 

The results reported in Table 2 are for the general U.S. population, all infants (<1 year old), 

children 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 listing 

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 HED's LOC for all 

population subgroups, including those of infants and children. The most highly exposed 

population subgroup is children 1-2 years which utilizes 35% of the cP AD, while the general 

U.S. population utilizes 6.4% of the cPAD. 

VIII. Characterization of Inputs/Outputs 

This 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 highly 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+ drinking water) risk 

estimates of concern for ethaboxam. 

HED is confident that the assessment does not underestimate risk to the general U.S. population 

or any population subgroup. There are no dietary risk considerations that would preclude 

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generations, and delayed sexual maturation were seen, with maternal toxicity limited to 

decreased body weight 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 

Fl adult males. 

Although there is evidence of increased qualitative susceptibility in the reproduction 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 risk 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 protective of 

potential offspring effects. Thus, the Agency believes the FQP A safety factor can be reduced to 

I X and still be conservatively protective of human health risk. 

The doses and endpoints 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. 

Dietary (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, 

epididymides, 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). UF H = 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 

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allowing the petitioned-for seed treatment use of ethaboxam on legume vegetables (crop group 

6) except cowpea and field pea, cereal grains (crop group 15) 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 thiamethoxam. 

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Attachment 1. Input File for the Chronic Dietary Exposure Estimates. 

US EPA 

DEEM-FCI D Chronic ana l ysis for ETHABOXAM 

Residue file: J:\Ethaboxam\Dietary\ethaboxam.r08 

Ana l ysi s Date 03 - 14 - 2013 Residue f i l e 

Refer ence dose (Rf D} = 0 . 055 mg/kg bw/day 

Ver . 3 .16, 03 - 08 - d 

Ad jus t . #2 NOT used 

dated: 03 -14 - 2013/09:08:23 

-------------------------------------------------------- -------------------------- Food Crop Residue Adj . Factors 

EPA Code Grp Food Name (ppm) Il l 112 

---------- ------------------------------- ---------- 1304175000 130 Gra.pe 6 . 000000 1.000 1. 000 

130417600 0 13D Grape, jui c e 6 . 000000 1.000 1. 000 

13041760 01 130 Grape, j u ice- babyfood 6.000000 1. 000 1. 000 

9500177000 0 Grape, leaves 6 . 000000 1 .000 1. 000 

9500178000 0 Grape, raisin 6 . 000000 1.000 1 .000 

13041 79000 1 3D Grape, wi ne and sherry 6 .000000 1 . 000 1 .000 

8601000000 86A Water , direct, all sources 0 .003300 1. 000 1 .000 

8602000000 86B Water , indirect, all sources 0 .003300 1. 000 1 . 000 

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Attachment 2. Summary of tbe chronic dietary exposure analysis for thiamethoxam. 

US EPA 

DEEM-FCI D Chr onic analysis for ETHABOXAM 

Residue file name: J:\Ethaboxam\Dietary\ethaboxam. r08 

Ver. 3 .16 , 03-08 -d 

NHANES 2003-2008 2-day 

Adjustment faccor ij2 NOT used . 

Analysis Date 03 -1 4-2013/09 :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 Popul ation 

Hispanic 

Non- Hisp-White 

Non-Hisp-Black 

Non-Hisp -Other 

Nursing Infants 

Non - Nursi ng I nfants 

Female 13+ PREG 

Childr en 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 

Children 3 - 5 

Children 6 - 12 

Youth 13-19 

Adults 20-49 

Adults 50- 99 

Female 13-49 

Total Exposure 

mg/kg 

body wt/day 

0.003503 

0.002863 

0.003621 

0.003634 

0 .003286 

0. 002411 

0.008982 

0.002056 

0.01 411 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 

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Percent of 

Rfd 

6.4% 

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%