UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: 

Subject: 

May 21,2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Ethaboxam: Occupational and Residential Exposure/Risk Assessment of 

Ethaboxam for Seed Treatment Uses on Legume Vegetables, Cereal Grains 

(except Rice and Wild Rice) and Rapeseed. 

PC Code: 090205 DP Barcode: D409850 

Decision No.: 456065 Registration No.: 59639-185 

Petition No.: NA Regulatory Action: Section 3 Registration 

Risk Assessment Type: ORE Case No.: 7053 

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

MRIDNo.: NA 40 CFR: 180.622 

FROM: 

THROUGH: 

~ 'h' 

Risk 

MargaritaCollantes

Assessment Branch 

, Biologist 

II 

'/!!Ctt~ (: ~ 

Health Effects Division (7509P) 

Alexandra LaMay ({ ~ [ 

Kelly O'Rourke ~~ ;, ~ · 'C ~~~'-

Matthew Crowley Ji~ HED Exposure Scie{l.ce Advisory Council (ExpoSAC) 

and 

Christina Swartz, Chief C 

Risk Assessment Branch II 

Health Effects Division (7509P) 

TO: Dominic Schuler/Tony Kish, RM 22 

Fungicide Branch 

Registration Division (7505P) 

Introduction 

The Registration Division (RD) requested that the Health Effects Division (HED) conduct a risk 

assessment for proposed uses of ethaboxam. Valent USA Corporation has proposed the US 

registration of the new uses of ethaboxam for seed treatment of legume vegetables, cereal grains 

(except rice and wild rice) and rapeseed. It is HED policy to use the best available data to assess 

exposure. Sources of generic data, used as surrogate data in the absence of chemical-specific 

data, include the Standard Operating Procedures (SOPs) for Seed Treatment (Policy 14), Amount 

Page 1 of16 
of Seed Treated or Planted per Day (Policy 15) and Interim Guidance "Amount of Commercial 

Seed Treated per Day" (Policy 15.1). 

Note: This memorandum was reviewed by the Exposure Science Advisory Committee 

(ExpoSAC) on April4, 2013. 

Page 2 of16 
Page 3 of 16

Table of Contents

1.0 Executive Summary............................................................................................................. 4

2.0 Summary of Conclusions and Data Requirements .............................................................. 6

2.1 Summary of Risk Estimates............................................................................................. 6

2.2 Label Recommendations from Occupational Assessment............................................... 6

2.3 Label Recommendations from Residential Assessment .................................................. 6

2.4 Data Deficiencies and Requirements ............................................................................... 6

3.0 Hazard Characterization....................................................................................................... 6

4.0 Use Profile ........................................................................................................................... 8

5.0 Residential Exposure and Risk Estimates............................................................................ 9

5.1 Spray Drift and Residential Bystander Post-Application Inhalation Exposure ............... 9

6.0 Occupational Exposure and Risk Estimates ........................................................................ 9

6.1 Occupational Handler Exposure/Risk Estimates.............................................................. 9

Occupational Handler Exposure Data, and Assumptions..................................................... 10

6.2 Occupational Post-application Exposure/Risk Estimates .............................................. 15

Appendix A. Summary of Occupational Non-cancer and cancer Algorithms............................. 16
Page 4 of 16

1.0 Executive Summary

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an 

exposure and risk assessment for the active ingredient (ai), ethaboxam. Valent Corporation is 

requesting a new proposed use for ethaboxam as a commercial and on-farm seed treatment for

legume vegetables, cereal grains (except rice and wild rice), and rapeseed. The proposed product 

label specifies that seed should be treated using mechanical, slurry, or mist-type seed treating 

equipment and not applied in hopper or planter boxes at planting. Ethaboxam is currently only 

registered for use on imported grapes. This proposed new use will be the first U.S. registration 

action for ethaboxam. 

The product, V-10208 3.2 FS, is a systemic fungicide seed-protection product for use on a wide 

range of crops. The active ingredient, ethaboxam, provides protection against the Oomycete 

class of fungi including Pythium spp, Phytophthora spp and Aphanomyces spp. causing seed 

decay, seedling dieback, and root rot. The end-use product is formulated as a flowable

concentrate (FS) containing 34.2% active ingredient (ai) or 3.2 lb ai per gallon. There are no 

registered or proposed residential uses and residential exposure is not expected from the 

commercial use of this product; therefore, only occupational exposure is assessed in this 

memorandum.

Hazard Characterization

The 28-day dermal study in the rat was selected for short- and intermediate-term dermal 

exposure. The no observed adverse effect level (NOAEL) of 300 mg/kg/day and the lowest 

observed adverse effect level (LOAEL) of 1000 mg/kg/day were based on decreased body 

weight, and body weight gains. The 13-week feeding study in the rat was selected for the shortand intermediate-term inhalation risk assessment. The NOAEL of 16.3 mg/kg/day and the 

LOAEL of 49.7 mg/kg/day were based on male reproductive and lung effects. Since inhalation 

absorption data are not available, toxicity by the inhalation route is considered to be equivalent to 

the estimated toxicity by the oral route of exposure. 

Ethaboxam is classified as having “Suggestive Evidence of Carcinogenicity.” However, potential 

human risk for Leydig cell tumorigenesis would not be expected at exposure levels that do not 

cause tumors in rats. The Agency has determined that a non-linear approach would adequately 

account for all chronic toxicity (including carcinogenicity) resulting from ethaboxam exposures.

HED recommends that the 10X Food Quality Protection Act (FQPA) Safety Factor (for the 

protection of infants and children) be reduced to 1X. In addition, there are no other uncertainty 

factors needed to account for missing data. Therefore, the level of concern (LOC) for dermal 

and inhalation risk assessments is a margin of exposure (MOE) of 100, based on the combined 

interspecies (10X) and intraspecies (10X) uncertainty factors.

Occupational Handler Exposure and Risk Estimates

Occupational handler dermal and inhalation risk estimates are not of concern (LOC = MOE > 

100) for all proposed uses assessed. The label-required PPE on the proposed label states that all 

handlers must wear long-sleeved shirt and long pants, chemical-resistant gloves, and socks and 

shoes.
Page 5 of 16

HED has new information to suggest that in commercial seed treatment facilities with high 

throughput for various seed types (e.g., corn or soybean), the durations of exposure for 

occupational handlers might exceed those typically considered in short- and intermediate-term 

assessments. However, HED decided not to conduct a long-term exposure assessment due to the 

conservative nature of the unit exposures which are based on open-pour systems rather than the 

closed and/or automated systems that would be used in larger facilities operating over longer 

durations. HED also notes that it would be unlikely for a single chemical to be used 

continuously, even in high throughput facilities, over long term durations. Using conservative 

assumptions, the short- and intermediate-term scenarios are considered protective of longer-term 

exposure and risk.

Short-term primary handler (seed treater) MOEs ranged from 14,000 for dermal exposure 

resulting from multiple activities while treating legume vegetable seeds to 410,000 for inhalation 

exposure resulting from treating canola (rapeseed). Since the short- and intermediate-term 

endpoints are the same, short-term exposure estimates are protective of intermediate-term 

exposure estimates and risk. The planter exposure estimates ranged from a dermal MOE of

39,000 for cereal grain seeds to an inhalation MOE of 7,800,000 for canola seeds.

All exposure estimates were calculated with baseline clothing (long sleeved shirt, long pants, 

socks and shoes) and gloves. HED notes that for loader/planter scenarios, the dermal unit 

exposures reflect the use of gloves for occupational workers loading the seed into the hopper, but 

not while driving the tractor during planting; this is considered to reflect typical agricultural 

practices.

Occupational Post-Application Exposure and Risk Estimates

A quantitative post-application exposure assessment is not required for seed treatment as

exposure is expected to be negligible, since there will be no residue on foliage from contact once 

plants are grown.

Restricted Entry Interval

No quantitative post-application assessment is required for exposure to treated seeds that have 

already been planted. Therefore, the labeling properly states the exception to the Agricultural 

Use Requirements restricted entry interval (REI) of 12 hours.

Human Studies Review

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 data, which include studies from 

Standard Operating Procedures (SOPs) for Seed Treatment, Policy 14, 15, and 15.1 are (1) 

subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are 

compliant with applicable ethics requirements. For certain studies, the ethics review may have 

included review by the Human Studies Review Board. Descriptions of data sources, as well as 

guidance on their use, can be found at http://www.epa.gov/pesticides/science/handler-exposuredata.html and http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
Page 6 of 16

2.0 Summary of Conclusions and Data Requirements

There are no residential/occupational risk estimates of concern associated with the proposed new 

uses of ethaboxam. There are no data gaps in the exposure database. 

2.1 Summary of Risk Estimates

Occupational exposure scenarios assessed resulted in risk estimates that do not exceed HED's 

level of concern, with MOEs significantly greater than 100 (i.e., LOC = MOEs ≥ 100) for 

ethaboxam dermal and inhalation exposures, at the specified clothing (baseline) and PPE (e.g.,

gloves, and no respirator) mitigation level.

2.2 Label Recommendations from Occupational Assessment 

There are no label recommendations based on the occupational assessment.

2.3 Label Recommendations from Residential Assessment

There are no proposed or registered residential uses associated with ethaboxam at this time.

2.4 Data Deficiencies and Requirements

There are no data deficiencies or data requirements for the active ingredient, ethaboxam.

3.0 Hazard Characterization

Acute Toxicity

Acute exposure to ethaboxam resulted in low toxicity and was classified as Category IV for all 

routes of exposure. Ethaboxam is not an eye irritant or dermal sensitizer. A summary of the 

acute toxicity profile is provided in Table 3.1 below.

Table 3.1 Acute Toxicity Profile for Ethaboxam (99.0%) Technical

Guideline 

Number

Study Type

Classification

MRID

Number

Results Toxicity Category

870.1100 Acute-oral 46378518 LD50 Males and females > 5,000 mg/kg 

LD50 Combined >5,000 mg/kg IV

870.1200 Acute-dermal 48535632 LD50 Males and females > 5,000 mg/kg IV

870.1300 Acute-inhalation 48535633 LC50 Males and females> 4.89 mg/L IV

870.2400 Acute-eye 

irritation-rabbit

48535634 No corneal involvement or iritis 

observed. No positive conjunctival 

irritation in 1/3 rabbits at 24 hrs. (a 

score of 1 for redness)

All irritation cleared by 48 hours.

IV

870.2500 Acute-dermal 

irritation-rabbit

48535635 Not a dermal irritant IV

870.2600 Skin sensitization -

guinea pig

48535636 Not a skin sensitizer Negative
Page 7 of 16

Toxicological PODs Used for Risk Assessment

The 28-day dermal study in the rat was selected for short- and intermediate-term dermal 

exposure. The NOAEL of 300 mg/kg/day and the LOAEL of 1000 mg/kg/day were based on 

decreased body weight, and body weight gains. In the absence of a route-specific inhalation 

toxicity study, the 13-week feeding study in the rat was selected for the short- and intermediateterm inhalation risk assessment. The NOAEL of 16.3 mg/kg/day and the LOAEL of 49.7

mg/kg/day were based on male reproductive and lung effects. 

Cancer Risk

In accordance with EPA’s Final Guidelines for Carcinogen Risk Assessment (March, 2005), the 

Cancer Assessment Review Committee (CARC) classified ethaboxam as having “Suggestive 

Evidence of Carcinogenicity.” Although there is evidence of benign Leydig Cell tumors, the 

NOAEL used (5.5 mg/kg/day) for establishing the chronic reference dose is approximately 6-

fold lower than the lowest dose that induced tumors (35.8 mg/kg/day). The Agency has 

determined that quantification of cancer risk using a non-linear approach would adequately 

account for all chronic toxicity (including carcinogenicity) that could result from exposure to 

ethaboxam. 

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. Furthermore, there is no evidence that ethaboxam is neurotoxic and 

there are no residual uncertainties with respect to dietary and occupational exposure. 

Therefore, HED recommends that the 10X FQPA Safety Factor (for the protection of infants and 

children) be reduced to 1X. In addition, no other uncertainty factors are needed to account for 

missing data. The LOC for dermal and inhalation risk assessments is a MOE of 100, based on 

the combined interspecies (10X) and intraspecies (10X) uncertainty factors. A summary of the 

toxicological endpoints for ethaboxam is provided in Table 3.2 below.
Page 8 of 16

Table 3.2. Summary of Toxicological Doses and Endpoints for Ethaboxam for Use in Occupational Human 

Health 

 Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal 

Short-Term 

(1-30 days); 

Intermediate

-Term (1-6 

months) 

NOAEL =

300 

mg/kg/day

UFA = 10X

UFH = 10X

Occupational 

LOC for 

MOE = 100 

28-Day Dermal Toxicity – Rat

LOAEL (mg/kg/day): 1000 mg/kg/day, based 

on decreased body weight (up to 10%) and 

body weight gains (41%).

Inhalation 

Short-Term 

(1-30 days); 

Intermediate

-Term (1-6 

months) 

NOAEL = 

16.3 

mg/kg/day

[inhalation 

toxicity 

assumed to be 

equivalent to 

oral toxicity]

UFA = 10X

UFH = 10X

Occupational 

LOC for 

MOE = 100 

13-Week Oral Toxicity – Rat LOAEL 

(mg/kg/day): 49.7/58.0 mg/kg/day, based on 

testicular/epididymal effects in males 

(abnormal spermatids in the testes, and 

abnormal spermatogenic cells in the 

epididymides), lung effects (increased lung 

weights, congestion, and alveolar septal 

congestion and focal alveolar hemorrhage).

Cancer (oral, 

dermal, 

inhalation)

Classification: “Suggestive Evidence of Carcinogenicity, based on increased incidence of Leydig 

Cell tumors in males.

Point of Departure (POD) = A data point or an estimated point that is derived 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. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). LOC = level of concern. MOE = margin of 

exposure.

Dermal Absorption

Since the short- and intermediate-term dermal POD was based on a route-specific toxicity study, 

a dermal absorption factor was not necessary to estimate exposure. Since inhalation absorption 

data are not available, toxicity by the inhalation route is considered to be equivalent to the 

estimated toxicity by the oral route of exposure.

Body Weight

The standard body weight for the general population (80 kg) was used for all exposure scenarios 

covered in this risk assessment since the endpoints selected were not developmental and/or fetal 

effects.

4.0 Use Profile 

Valent is proposing a new use for V-10208 3.2 FS as a seed treatment for various crops for 

commercial and on-farm use. Although the proposed product is for on-farm use the label for the 

FS formulation specifies that seed should be treated using mechanical, slurry, or mist-type seed 

treating equipment and not applied in hopper or planter boxes at planting. The end-use product 

contains 3.2 lbs. ethaboxam per gallon, or 0.025 lb ai per fluid ounce. The Personal Protective 

Equipment (PPE) statement on the proposed label requires applicators and other handlers to wear
Page 9 of 16

the following: long-sleeved shirt and long pants, socks, shoes, and chemical-resistant gloves. 

The proposed use directions are summarized in Table 4.1.

1

Rate = Maximum application rates specified on proposed labels.

*Maximum Application Rate (lb ai/lb seed) = (fl oz/cwt x 3.2 lb ai/gal x 1 gal/128 fl. oz)/100 cwt 

5.0 Residential Exposure and Risk Estimates

There are currently no registered or proposed residential uses of ethaboxam. 

5.1 Spray Drift and Residential Bystander Post-Application Inhalation Exposure

A quantitative post-application exposure assessment is not required since there is no application 

of pesticide to the fields (seeds are previously treated in seed treatment facilities). Therefore,

exposure is expected to be negligible. 

6.0 Occupational Exposure and Risk Estimates

6.1 Occupational Handler Exposure/Risk Estimates

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. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

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

following scenarios:

Table 4.1. Summary of Directions for Use of Ethaboxam For Seed Treatment

Crop/ Use Site Product/ Formulation

(EPA Reg. No.)

Treatment Type Maximum Application Rate1

(lb ai/ lb seed)*

Legume Vegetables (Crop 

Group 6)

V-10208 3.2 FS 

Fungicide/Liquid

(59639-185)

Commercial and 

On-Farm

0.00015

(0.6 fl oz/cwt seed)

Cereal Grains –

Crop Group 15

(barley, buckwheat, millet, 

pearl, proso, oats, rye, 

teosinte, triticale, wheat)

0.000065

(0.26 fl oz/cwt seed)

Corn – Crop Group 15 

(sweet, field and popcorn;

sorghum, grain (milo)) 0.000075

(0.3 fl oz/cwt seed) Rapeseed, Canola Crop 

Group 20A
Page 10 of 16

Mixing, loading, applying liquid formulations for commercially and on-farm treated

seeds;

Multiple activities, and

Planting treated seed.

Typically, for large-scale commercial seed treatments, workers perform only those specific 

individual tasks listed above; however, it is assumed that workers also may perform multiple 

activities throughout the day. As a result a “multiple activities” scenario (i.e. where one worker 

performs all seed treatment tasks such as loading/applying, sewing, bagging, cleaning, 

calibration, repair, forklift driver, etc.) was addressed.

Occupational Handler Exposure Data, and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational 

handler (seed treatment and planting) risk assessments. Each assumption and factor is detailed 

below on an individual basis.

Application Rate 

The maximum application rates listed on the proposed label provided by the Registration 

Division was used for all exposure assessments. The maximum rate is 0.00015 lb ai/lb seed for 

legume vegetable seeds, 0.000065 lb ai/lb seed for cereal grains (barley, buckwheat, millet, pearl, 

proso, oats, rye, teosinte, triticale, wheat) and 0.000075 lb ai/lb seed for corn (sweet, field and 

popcorn); sorghum, grain (milo); rapeseed (canola).

Unit Exposures:

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

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

HED Exposure SAC Policy 14: SOPs for Seed Treatment. Some of these data are proprietary 

(e.g., Agricultural Handler Exposure Task Force (AHETF) data), and subject to the data 

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

exposure that are used in this assessment, known as “unit exposures”, are outlined in the SOP 14. 

The registrant has not submitted a chemical-specific exposure study in support of this action. 

Amount Handled: 

The AHETF is currently conducting surveys for use in seed treatment exposure assessment, 

providing daily seed treatment throughput data along with information on seed treating 

equipment and worker activities. The HED Interim Guidance (SOP 15.1) Amount of 

Commercial Seed Treated per Day provides updated additional information regarding these 

throughput data which will ultimately be incorporated into a final revised Seed Treatment SOP 

15. Since the AHETF surveys only include information for the five major field crops (canola, 

corn, rice, soybean and wheat), throughput values for non-surveyed crops are assigned based on 

a combination of “best professional judgement;” similarity of seed size to that of the surveyed 

crops; and general knowledge of each crop and its production. The amount of seed treated per 

day at a commercial facility is summarized below for each crop:

281,250 lbs of legume vegetables (succulent or dried) for short-term exposure (no survey 
Page 11 of 16

data available; based on daily soybean throughput values) 

360,000 lbs of small cereal grains (barley, buckwheat, oats, rye, triticale, wheat) for 

short-term exposure (no survey data available; based on daily wheat throughput values) 

339,500 lbs of field corn for short-term exposure 

125,000 lbs of rapeseed subgroup of oilseed group for short- term exposure (no survey 

data available; based on daily canola throughput values)

Amount of Seed Planted Per Day:

The amount of seed planted per day is based on information provided in the HED Reviewer’s 

Aid to Calculating Occupational Exposures from Activities Related to Agricultural Seed 

Treatment (November 29, 2012) and the BEAD Acres Planted per Day and Seeding Rates of 

Crops Grown in the United States, Appendix B, Table B-1:

10,640 lbs of legume vegetable (surrogate – soybeans) seeds planted per acre

[(200,000 seed/A × 1 lb seed/ 1,500 seeds) × 80 A (legumes) = 10,640]

37,500 lbs of cereal grains (surrogate – wheat) planted per acre

[(1,500,000 seed/A × 1 lb seed/ 8,000 seeds) × 200 A = 37,500]

6,000 lbs of field corn planted per acre

[(40,250 seed/A × 1 lb seed/ 1,361 seeds) × 200 A = 6,000]

1645 lbs of canola seed planted per acre

[(740,520 seed/A × 1 lb seed/ 90,000 seeds) × 200 A =1645]

Note: Although soybeans served as a surrogate for legumes and are considered a high 

acreage crop which therefore assumes that 200 acres will be planted, legumes are considered 

a typical acreage crop. Therefore 80 acres were used to refine the amount of legume seeds 

planted per day in place of 200 acres.

Exposure Duration:

Treatment of the proposed seeds is expected to result in short- and intermediate-term exposure. 

The AHETF survey reports that corn commercial facilities operate 240 days per year (50th

percentile; range 150 to 270 days), canola commercial facilities operate 180 days per year (50th

percentile: range 90 to 210 days) and 39% of soybean is treated downstream for a duration of 49 

days (50th percentile; range 4 to 150 days), while soybean commercial facilities operate 210 days 

per year (50th percentile; range 1 to 270 days). While these durations would be considered to 

potentially exceed the typical intermediate-term duration used in HED’s occupational 

assessments, HED had no information to indicate that the same chemical is used consecutively 

for a long-term duration. Therefore, chronic occupational handler exposure for seed treatment 

was not assessed. Furthermore, the dermal and inhalation unit exposure values specified in 

Policy 14 are based on open-pour systems, whereas the majority of the seed treatment facilities 

with large throughputs are equipped with fully or partially automated closed mixing and loading 

systems. Therefore, HED concluded that a chronic exposure assessment for ethaboxam seed 

treatment would result in overly conservative estimates of exposure. 

Since the same short- and intermediate-term endpoint was selected for dermal exposure and 

inhalation exposure, a quantitative assessment was only performed for short-term durations. 

Short-term risk estimates are expected to be protective of intermediate-term exposure.
Page 12 of 16

Combining Exposures/Risk Estimates:

Short-term dermal and inhalation exposure estimates were not combined since they did not have 

the same toxicological effects. 

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

Occupational handler dermal and inhalation risk estimates are not of concern (LOC = MOE > 

100) for all proposed uses assessed. Short-term dermal and inhalation handler (seed treatment)

MOEs ranged from 14,000 for dermal exposure resulting from multiple activities while treating 

legume vegetables to 410,000 for inhalation exposure resulting from treating canola (rapeseed). 

The planter exposure estimates ranged from a dermal MOE of 39,000 for cereal grain seeds to an 

inhalation MOE of 7,800,000 for canola seeds. A summary of dermal and inhalation risk 

estimates for occupational handlers (treaters and planters) can be found in Tables 6.1, and 6.2. 

All exposure estimates for seed treaters and planters were assessed using baseline clothing and 

gloves (no respirator). HED notes that for loader/planter scenarios, the dermal unit exposures 

reflect the use of gloves for occupational workers loading the seed into the hopper, but not while 

driving the tractor during planting; this is considered to reflect typical agricultural practices.

Downstream (Soybeans) and On-farm Assessment

HED assumes that the commercial seed treatment risk assessment is protective of downstream 

seed treatment risk assessment. Thus, a separate risk assessment is not required for handlers in 

downstream facilities. Likewise, commercial seed treatment risk assessments are protective of 

on-farm seed treatment because the equipment is similar but the on-farm throughput is 

significantly less. The proposed product label specifies that seed should be treated using 

mechanical, slurry, or mist-type seed treating equipment and not applied in hopper or planter 

boxes at planting for on-farm use.
Page 13 of 16

Table 6.1. Short-and Intermediate-term Occupational Seed-Treatment Handlers Exposure and Risk Estimates for Ethaboxam

Use Site PPE

Dermal Unit 

Exposure a 

(mg/lb ai)

Inhalation 

Unit 

Exposurea 

(mg/lb ai)

Application 

Rate b

(lb ai/ lb seed)

Amount 

Treatedc

(lb seed/ 

day)

Dermal

Dose d

(mg/kg/day)

Daily

Inhalation

Dosee

(mg/kg/day)

Dermal 

MOEf Inhalation 

MOEg

Loader/Applicator

Legume 

Vegetables 

(surrogate –

soybeans) Single 

Layer, 

Gloves 0.023 0.00034

0.00015 281,250 0.012

0.000179 25,000 91,000

Cereal Grains 

(surrogate –

wheat) 0.000065 360,000 0.0067 0.000099 45,000 160,000

Field Corn

0.000075

339,500 0.0073 0.00010 41,000 150,000

Canola and 

Rapeseed 125,000 0.0027 0.000039 110,000 410,000

Multiple Activities

Legume 

Vegetables 

(surrogate –

soybeans)

Single 

Layer, 

Gloves 0.042 0.0016

0.00015 281,250 0.022 0.00084 14,000 19,000

Cereal Grains 

(surrogate –

wheat) 0.000065 360,000 0.012 0.000468 24,000 35,000

Field Corn

0.000075

339,500 0.0133 0.00050 22,000 32,000

Canola and 

Rapeseed 125,000 0.0049 0.000187 61,000 87,000

a Unit Exposures are based on Policy 14: Standard Operating Procedures for Seed Treatment.

b Application Rate is based on Proposed Label for V-10208 3.2 FS (EPA Reg No. 59639-185.

c. Amount of Seed Treated is based on information provided in the HED Interim Guidance SOP 15.1: Amount of Commercial Seed Treated Per Day (November 14, 2012).

d. Dermal Dose (mg/kg/day) = (unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × daily amounts treated ÷ body weight (80 kg).

e. Inhalation Dose (mg/kg/day) = (unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × daily amounts treated ÷ body weight (80 kg).

f Short- term Dermal MOE = NOAEL (300 mg/kg/day) ÷ dermal dose (mg/kg/day).

g. Short-term Inhalation MOE = NOAEL (16.3 mg/kg/day) ÷ inhalation dose (mg/kg/day).
Page 14 of 16

Table 6.2 Short- and Intermediate-term Handler-Seed Planters Exposure and Risk Estimates for Ethaboxam

Use Site Mitigation 

Level

Dermal

Unit 

Exposurea 

(mg/lb ai)

Inhalation 

Unit 

Exposurea 

(mg/lb ai)

Application 

Rateb

(lb ai lb 

seed)

Amount 

Plantedc

Dermal

Dosed

(mg/kg/day)

Dermal 

MOEe Inhalation

Dosef

(mg/kg/day)

Inhalation 

MOEg 

Legume 

Vegetables 

(surrogate –

soybeans)

Single 

Layer,

Gloves

0.25 0.0034

0.00015 10,640 0.005 60,000 0.00069 240,000

Cereal 

Grains 

(surrogate –

wheat)

0.000065 37,500

0.0076 39,000 0.00010 160,000

Field Corn

0.000075

6,000 0.0014 210,000 0.000019 850,000

Canola and 

Rapeseed

1645 0.00039 780,000 0.000002 7,800,000

a Unit Exposures are based on Policy 14: Standard Operating Procedures for Seed Treatment. Note: the dermal unit exposure reflects handlers’ exposure resulting from 

loading treated seed into hopper while using gloves, but reflects the driver operating the tractor without gloves, and this is considered appropriate based on typical 

agricultural practices.

b Application Rate is based on Proposed Label for V-10208 3.2 FS (EPA Reg No. 59639-185).

c. Amount planted is based on information provided in the HED Reviewer’s Aid to Calculating Occupational Exposures from Activities Related to Agricultural Seed 

Treatment (November 29, 2012) and the BEAD Acres Planted per Day and Seeding Rates of Crops Grown in the United States, Appendix B, Table B-1.

d. Dermal Dose (mg/kg/day) = (unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × daily amounts treated / body weight (80 kg).

e. Inhalation Dose (mg/kg/day) = (unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × daily amounts treated / body weight (80 kg).

f Short- term Dermal MOE = NOAEL (300 mg/kg/day) / dermal dose (mg/kg/day).

g. Short-term Inhalation MOE = NOAEL (16.3 mg/kg/day) /inhalation dose (mg/kg/day).
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6.2 Occupational Post-application Exposure/Risk Estimates

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). The potential for dermal and inhalation post-application exposures following 

the planting of ethaboxam-treated seeds is unlikely because sustained levels of contact with 

treated seed after it has been placed in the soil or other planting media would not be expected 

because no routine cultural practice required for the production of agricultural commodities 

involves such an activity as defined in the no/low contact criteria in the Worker Protection 

Standard (WPS). Therefore, no quantitative post-application assessment is required for exposure 

to treated seeds that have already been planted. The labeling properly states the exception to the 

Agricultural Use Requirements restricted entry interval (REI) of 12 hours.
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Appendix A. Summary of Occupational Non-cancer and cancer Algorithms

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations

Potential daily exposures for occupational handlers were calculated using the following 

formulas:

Daily Exposure (mg ai /day) = UE (mgai / lb of seed) * AR (lb ai /100 lbs of seed) * AT (Amount of seed treated

/day) * 1E-3 mg/μg

Where :

Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption,

UE = Unit Exposure (μg ai / lb ai),

AR = maximum application rate according to proposed label (lb ai /100lbs of seed), and

AT = daily amount treated (lbs/day).

The daily doses were calculated using the following formula:

Average Daily Dose (mg ai/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)]

Body Weight (kg)

Where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg

pesticide active ingredient/kg body weight/day),

Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption,

Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as

the skin and lungs (%), and

Body Weight = Body weight determined to represent the population of interest in a risk 

assessment (kg).

MOE = POD (typically a NOAEL in mg/kg/day) 

ADD (mg/kg/day)

Where:

MOE = Margin of Exposure: value used by HED to represent risk or risk estimates (unitless),

POD = Point of Departure,

NOAEL = No Observed Adverse Effect Level (mg/kg/day): Dose level in a toxicity study, where no 

observed adverse effects occurred in the study, and

ADD = Average Daily Dose (mg/kg/day): the absorbed dose received from exposure to a 

pesticide in a given scenario.