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 Trea tment Uses on Legume Vegetables, Cereal Grains (except Rice and Wild Rice) and Rape seed.

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 ' MargaritaCollantes

, Biol ogist

## '/!!Ctt~ 

# (:**~** Risk Assessment Branch II

Health Effec t s Division (7509 P)

Alexandra LaMay

# ({**~** [ Kelly O'Rourke**~~** ;,**~** · 

### 'C**~~~'-** Matthew Crowley

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

and

C hristina Swartz, Chief 

# C

Risk Assessment Branch II

Health Effects Di vision (7509P)

TO: Dominic Schuler / Tony Kish, RM 22 Fungicide Branch Registration Di vision (7505P)

Introduction

Th e Registration Division (RD) requested that the Health Effects Di vision (HE D ) 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 chemica l-specific

data

, include the Standard Operating Procedure s (SOPs) for Seed Treatment (Policy 14)

, Amount

Page 1 of16of 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 b y the Exposure Science Advisory Commi ttee (ExpoSAC) on April4, 2013.

Page 2 of16Page 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 Estim ates

................................ ................................ ........ 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

............................. 16Page 4 of 16

1.0 Executive Summary

The Registration Division (RD) r equested 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 f o r legume vege tables, cereal grains (except rice and wild rice)

, and rapeseed

. T he 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 import ed 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 cro ps. The active ingredient, ethaboxam, provides protection against the Oomycete class of fungi including Pythium spp, Phytophthora spp and Aphanomyces spp. c ausing 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. Th ere 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 ( NOA E L ) 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 short

and intermediate

- term inhalation risk assessment. The NOAEL of 16 .3 mg/kg/day and the

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

a bsorption data are not available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure.

E thaboxam 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 ) result ing from ethaboxam exposure s

.

HED recommends that the 10 X Food Quality Protection Act ( FQPA ) Safety Factor (for the protection of infants and childre n) be reduced to 1 X

. 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

inte rspecies (10X) and intraspecies (10X) uncertainty factors.

Occupational Handler Exposure and Risk Estimates Occupational handler dermal and i nhalation risk estimates are not of concern (LOC = MOE > 100) for all proposed uses assessed. The label

- required PPE on the proposed label s tates 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

co nservative 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 che mical 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 treat er ) MOEs ranged from 14 ,000 for dermal exposure resulting from multiple activities while treating legume vegetable s eeds to 41 0, 000 for inhalation exposure resulting from treating canola ( rapeseed )

. Since the short

- and intermediate

- term endpo int s 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 a n 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

N o quantitative post

- application assessment is required for exposure to treated seeds that have already been planted

. The refore, the labeling properly state s 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 1 5.1 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. Descr iptions of data sources, as well as guidance on their use, can be found at http://www.epa.gov/pesticides/science/handler

- exposure

data.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

ethabox a m 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. Ethabox a m is not an eye irritant o r 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 LD 50 Males and females > 5,000 mg/kg

LD 50 Combined > 5,000 mg/kg IV

870.1200 Acute

- dermal 48535632 LD 50 Males and females > 5,000 mg/kg IV

870.1300 Acute

- inhalation 48535633 LC 50 Males and females> 4.89 mg/L IV

870.2400 Acute

- eye

irritation

- rabbit 48535634 No corneal involvement or iritis observed. No positive conju n ctival 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 NegativePage 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 NO A EL 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, t he 13

- week f eeding study in the rat was selected for the short

- and 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.

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 stud y , there

are no residual uncertainties with regard to p re

- 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 effe cts observed in the study is low based on the following: the offspring effects observed

in the stud y are well characterized and clear NOAELs/LOAELs have been identified in the stud y for the effects of concern

. Additionally, the P O Ds 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 10 X F QPA Safety Factor (for the protection of infants and children) be reduced to 1 X

. In addition, no other uncertainty factors are needed to account for missing data. T he LOC for dermal and inhalation risk assessments is a MOE of 100, based on

the combined i nterspecies (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 UF A = 10 X

UF H = 10 X Occupational

LOC for

MOE = 100 28

- D ay D ermal T oxicity

– 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] UF A = 10 X

UF H = 10 X Occupational

LOC for

MOE = 100 13

- W eek Oral Toxicity

– Rat LOAEL

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

t esticular/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 ad verse 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). LOC = level of concern. MOE = margin of

exposure.

Der mal Absorption

Since the short

- and intermediate

- term dermal POD w as based on a route

- specific toxicity stud y ,

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

data are not available, toxicity by the inhalati on 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 t he 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 propo sed label requires applicators and other handlers to wearPage 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 Rate 1
(lb ai/ lb seed) *

Legume Vegetables (Crop Group 6)

V

- 10208 3.2 FS

Fungicide / Liquid

(59639

- 185) Commercial and

On

- Farm 0.00 01 5

(0.6 fl oz/cwt seed)

Cereal Grains

– Crop Group 15

( barley

, buckwheat, millet, pearl, proso, oats, rye, teosinte, triticale, wheat) 0.0 00065 (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 20APage 10 of 16

Mixing, loading, applying liquid formulations for commercial ly and on

- farm treat ed

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.) w as addressed.

Occupational Handler Exposure Data, and Assumptions A series of assumptions and exposure fa ctors 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 0.00 01 5 lb ai/lb seed for legume vegetable s eeds

, 0.000065 lb ai/lb seed for cereal grains (barley

, buckwheat, millet, pearl, proso, oats, rye, teosint e, triticale, wheat) and 0.000075 lb ai/lb seed for corn (sweet, field and

popco r n ); 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 thes e 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,

pro viding 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

thro ughput 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) , t hroughput 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 i s summarized below for each crop :

281,250 lbs of legume vegetables (succulent or dried) for s hort

- term exposure (no surveyPage 11 of 16

data available ; based on daily soybean throughput values )
360,000 lbs of small cereal grains (barley, b u ckwheat, oats, rye, triticale, wheat) fo r 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 dail y 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 :

1 0,640 lbs of legume vegetable (surrogate

– soybeans) seeds planted per acre [(2 0 0,000 seed/A × 1 lb seed/ 1,500 seeds) × 80 A (legumes) = 10,640 ]

3 7 ,5 0 0 lbs of cereal grains (surrogate

– wheat) planted per acre [( 1,5 0 0 ,000 seed/A × 1 lb seed/ 8,000 seeds) × 200 A = 3 7 ,5 0 0 ]
6,00 0 lbs of field corn planted per acre [( 4 0, 25 0 seed/A × 1 lb seed/ 1,361 seeds) × 200 A = 6,0 00 ]

1 6 4 5 lbs of canola seed planted per acre [( 74 0, 52 0 seed/A × 1 lb seed/ 90,000 seeds) × 20 0 A = 1645 ]

Note: A lthough soybeans served as a surrogate for legumes and are considered a high acreage crop which therefore assume s 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.

T he AHETF survey reports that corn commercial facilities operate 240 days per year (50 th
percentile; range 150 to 270 days), canola commercial facilities opera te 180 days per year (50 th
percentile: range 90 to 210 days) and 39% of soybean is treated downstream for a duration of 49 days (50 th percentile; range 4 to 150 days) , while soybean commercial facilities operate 210 days per year (50 th 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 indicat e that the same chemical is used consecutively for a long

- term du ration . 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 fa cilities 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 exp osure.

Since the same s hort

- 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 d ermal 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 i nhalation risk estimates are not of concern ( LOC = MOE >

100 ) for all proposed uses assessed. Short

- term dermal and inhalation handler (seed treatment) MOEs range d from 1 4 ,000 for der mal exposure resulting from multiple activities while treating legume vegetables to 41 0, 000 for inhalation exposure resulting from treating canola ( rapeseed )

. The planter exposure estimates ranged from a dermal MOE of 39 ,00 0 for cereal grain seeds to a n inhalation MOE of 7,8 00,000 for canola seed s

. A summary of dermal and inhalation risk estimates for occupational handlers (treaters and planters ) can be found in Table s 6.1

, and 6.2

. All exposure estimates for seed treaters and planters were assessed usi ng 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 ( S oybeans) 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 a ssessment 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. T he 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 Exposure a (mg/lb ai) Application

Rate b
(lb ai/ lb seed) Amount

Treated c (lb seed/ day) Dermal

Dose d
(mg/kg/day) Daily

Inhalation

Dose e (mg/kg/day) Dermal

MOE f Inhalation

MOE g

Loader/Applicator
Legume Vegetables (surrogate

– soybeans) Single

Layer,

Gloves 0.023 0.00034 0.00015 281,250 0.0 1 2 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 Treat ed Per Day (November 14, 2012).

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

e. Inhalation Dose (mg/kg/d ay ) = (unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × daily amounts treated ÷ body wei ght (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 Exposure a (mg/lb ai) Inhalation

Unit Exposure a (mg/lb ai) Application

Rate b
(lb ai lb seed) Amount

Planted c Dermal

Dose d
(mg/kg/day) Dermal

MOE e Inhalation

Dose f
(mg/kg/day) Inhalation

MOE g

Legume Vegetables (surrogate

– soybeans) S ingle

L ayer, G loves

0.25 0.0034 0.00015 10,640 0.00 5 6 0,000 0.0006 9 2 4 0,000

Cereal

Grains (surrogate

– wheat) 0.000065 3 7,50 0 0.00 7 6 39 ,000 0.000 1 0 1 6 0,000

Field Corn

0.000075 6,000 0.00 14 21 0,000 0.000019 85 0,000

Canola and Rapeseed 1645 0.000 39 78 0,000 0.000002 7

, 8 00,000

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 i s 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 Agri cultural Seed Treatment (November 29, 2012) and th e BEAD Acres Planted per Day and Seeding Rates of Crops Grown in the United States, Appendix B, Table B

- 1

. d. D ermal D ose (mg/kg/d ay ) = (unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × daily amounts treated / body weight (80 kg).

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

f Short

- term Dermal MOE = NOAEL (30 0 mg/kg/day) / d ermal dose (mg/kg/day)

. g. Short

- term Inhalation MOE = NOAEL ( 16 .3 mg/kg/day) / inhalation dose (mg/kg/day)

.Page 15 of 16

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 re

entry exposure). The potential for dermal and inhalation post

- appl ication exposures following the planting of ethaboxam

- treated seeds is unlikely because s ustained 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 re quired 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 s eeds that have already been planted

. The labeling properly state s the exception to the Agricultural Use Requirements restricted entry interval (REI) of 12 hours.Page 16 of 16

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 ( mg ai / lb of seed ) * AR (lb ai /

100 lbs of seed ) * AT (A mount of s eed treated /day) * 1E

- 3 mg/μg

W here :

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 see d ) , 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)

W here: 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 chemi cal 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)

W here:

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

PO D = 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

.