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

Date:

S ubject: February 28, 2013 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

Sedaxane: Occupational and R esidentia l Ex posure/Risk Assessment of Sedaxane

for Seed Treatment Uses on Rapeseed

, Sorghum, crop group 6a (except soybeans), Com and Potato seed piece.

PC Code: 129223 DP Barcode: 408790

Decision No.: 469252 Registration No.: 100-1374

Petition No.: Regulatory Action: Section 3 Registration

Risk Assessment Type: ORE Case No. :
TXRNo.:NA CAS No.: 874967-67-6

MRIDNo.:NA 40 CFR:

REV IEWER:

Expo SAC :

THROUG H : 

### Seyed Tadayon

,

# Chemis~ Risk Assessment Branch V

Health Effects Division (7509P)

Kelly O ' Rourke

, Bi ologist, Ex po SAC Reviewer

## ~ .w1 

## <Q**~-<-.** Shalu Shelat, Industrial Hygieni st, Ex po SAC

### Re**iewer ~~** 

Mike Metzger, Chief

# I g 

# oy

Risk Assessmen t Branch V**~** ,.. He alth Effects Division (75 9 ) · ,

TO: William Donovan, PhD, Ri sk Assessor

Risk Assessment Branch V

Health Effec ts Division (7509P)

Introduction

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

assessment for proposed uses of sedaxane. Sy n genta Crop Protection

, LLC proposed the US registration of the new uses of sedaxane for treating rapeseed, sorghum, Crop group 6a (except soybeans), com see d and potato seed piece treatment. 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 (SO P s) for Seed Treatment ( Policy 14), Amount of Seed Treated or Planted per Da y (Policy 15) and Interim Guidance

" Amount of Commercial Seed Treated Per Day " (Policy 15.1)

. Thi s assessment uses the AHETF

surveys (Ol/ 12 / 2012) which were conducted in the United States and Canada. The main objective

Pag e 1 of 19of this survey was to collect seed treatment throughput data for updating EPA l-IED 's Science Advisory

Council for Exposure

, Standard Operating Procedure Number 15, entitled Am ou nt of Seed Treated or Plant ed

per Day. Specifically

, survey data were collected to update daily seed treatment throughput data and to

cha ract e rize seed treating equipme nt and worker activ i t i es for five seed types -c anola, corn, ric e, soybean, and wheat. The AHETF surveys replace s maxim u m equ ipm e n t capacity referenced in, SOP 15.

Note: This memorandum was reviewed by the Exposure Science Advisory Committee (Ex poSAC ) on 02 / 2 1 / 2013 20 1 3.

Page 

### 2 ofl9

### Page 3 of 19 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4

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 Us e Profile

................................ ................................ ................................ ........................... 8

5.0 Residential Exposure and Risk Estimates

................................ ................................ ............ 8

5.1 Spray Drift

................................ ................................ ................................ ........................ 8

5.2 Residential By stander Post

- Application Inhalation Exposure

................................ ......... 8

6.0 Occupational Exposure and Risk Estimates

................................ ................................ ........ 8

6.1 Occupational Handler Exposure/Risk Estimates

................................ .............................. 9

6.2 Occupational Post

- application Exposure/Risk Estimates

................................ .............. 16

6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

...................... 16

6.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

.......................... 16 Appendix A. Summary of Occupational Non

- cancer and cancer Algorithms

............................. 18

### Page 4 of 19

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, sedaxane . Syngenta Crop Protection LLC is proposing new uses on rapeseed, sorghum, crop group 6a (except soybeans), corn seed and seed piece potato. Sedaxane is a broad spectrum fungicide that is particularly effective against all patho genic strains of rhizoctonia (soilborn) along with a number of bunts and smuts (seed born).

The product, Vibrance TM 

### Fungicide, is a suspension concentrate formulation containing 45 % active ingredient sedaxane (4 .3 lbs a.i. per gallon). Th ere are no prop osed 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 did not show systemic toxicity at the limit dose of 1000 mg/kg/day. For

short

- and intermediate

- term occupational exposure scenarios involving inhalation exposure, the NOAEL of 30 mg/kg/day was selected from the rat acute neurotoxicity study

. The chronic rat study was selected for the end point in the long

- term inhalation scenario since its duration best matches the exposure interval and it is the most protective POD in the sedaxane toxicity data base (NOAEL=11 mg/kg/day). No non

- cancer dermal hazard was identified for sedaxane. The

risk as sessments were based on the most sensitive endpoints in the toxicity database, and the NOAELs selected for risk assessment are considered protective of potential developmental

, neurotoxic, and immunotoxic effects for infants and children. Further, highly conservative exposure estimates were incorporated into the risk assessment; therefore, reduction of the 10x Food Quality Protection Act (FQPA) safety factor to 1x is considered appropriate.

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

the CARC classified s edaxane as “Likely to be Carcinogenic to Humans”. This classification is based on the presence of liver and thyroid tumors in male rats, uteri ne tumors in female rats and liver tumors in male mice. Uterine tumors were also seen in a chemical structurally related to

s edaxane. There is no mutagenic concern for s edaxane. A linear low

- dose extrapolation model (Q1*) was used for quantification of c ancer risk to humans. Q1*= 4.64x10 - 3 

### (mg/kg

- day) - 1



### Combining Exposures/Risk Estimates

For non

- cancer risk assessment dermal route of exposure does not need to be combined with

another route of exposure or included in the aggregate risk assessment because there is no dermal

hazard. For cancer risk assessment dermal route of exposure was combined with inhalation route of exposure.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates Occupational handler i nhalation risk estimates for treaters and planters are not of concern (MOEs > 100) for all proposed uses assessed. The label

- required PPE on the proposed label is that all handlers must wear long

- sleeved shirt and long pants, chemical

- resistant gloves, and socks and

shoes. Inha lation MOEs range from 1 1 ,000 to 4,400,000

.

### Page 5 of 19

Summary of Occupational Handler Cancer Exposure and Risk Estimates The results of the occupational c ancer risk indicate that the values range from 8 E

- 10 to 1 E

- 07 at
the baseline for baggers and sewers and che mical resistance glove for loader/ treaters

, multiple

activities and planters

.

Summary of Occupational Post

- Application Exposure and Risk Estimates Based on the Agency's current practices, a quantitative post

- application inhalation exposure

assessment is not needed for sedaxane at this time. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative post

- application inhalation exposure

assessment for sedaxane

.

The potential for dermal and inhalation post

- application exposures following the planting of

sedaxane

- 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 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

.

Restricted Entry Interval Sedaxane is classified as toxicity category IV for acute oral and dermal toxicity, and category IV for acute inhalation toxicity, acute eye irri tation, and acute dermal irritation. It is not a skin

sensitizer.

The labeling properly state s the exception to the Agricultural Use Requirements restricted entry interval (REI) of 12 hours : " Exception: Once the seeds are planted in the soil, the Work er Protection Standard, under certain circumstances, allows workers to enter the treated area

without restriction if there will be no worker contact with the soil subsurface or treated seed. PPE required for early entry to treated areas that is permitted under the Worker Protection Standard and that involves contact with anything that has been treated, such as plants, soil, or water, is: long

- sleeved shirt and long pants and chemical

- resistant gloves.

Human Studies Review This risk assessment relies in p art 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 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. Descript ions 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 19

2.0 S UMMARY OF 

### C ONCLUSIONS AND 

### D ATA 

### R EQUIREMENTS



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

uses of sedaxane . There are no data gaps in the exposure database . A quantification of dermal

risk is n ot required for sedaxane

.

2.1 Summary of Risk Estimates

Occupational exposure scenarios assessed resulted in MOEs that do not exceed HED's level of

concern ( i.e., short

- term

, intermediate

- term and long

- term MOEs ≥ 100 ) for sedaxane inhalation exposures, at level specified PPE ( e.g., gloves, eye protection, and no respirator). The results of

t he occupational c ancer risk indicate that the values range from 8 .0 E

- 10 to 1 E

- 07 at the baseline and chemical resistance glove for loader/treaters

, multiple activities and planters

.

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 is no residential assessment.

2.4 Data Deficiencies and Requirements

There are no data deficiencies or data requirements for the pro posed uses of sedaxane.

3 .0 Hazard Characterization

Acute Toxicity

Sedaxane is classified as toxicity category IV for acute oral and dermal toxicity, and category IV for acute inhalation toxicity, acute eye irritation, and acute dermal irritation. It is not a skin

sensitizer.

Table 3.1.1. Acute Toxicity Profile

– Sedaxane Tec hnical

Guideline

No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral

- rat 47473366 LD 50 > 5 000 mg/kg (both sexes) IV

870.1200 Acute dermal

- rabbit 47473367 LD 50 > 5 000 mg/kg (both sexes) IV

870.1300 Acute inhalation

- rat 47473368 LC 50 > 5.244 mg/L (both sexes) IV

870.2400 Acute eye irritation

- rabbit 47473370 Minimally irritating IV

870.2500 Acute dermal irritation

- rabbit 47473369 Non

- irritant IV

870.2600 Skin sensitization

- guinea pig 47473371 Not a sensitizer N/A

### Page 7 of 19

Toxicological PODs Used for Risk Assessment

ToxSAC memo; Sedaxane

- Summary of Toxicology Science Advisory Council (ToxSAC) Meeting of December 1,

201 1 ; Jessica Kidwell; January 24, 2012



### Short

- and Intermediate

- Term Incidental Ora l Endpoint : This endpoint was not established since there are no residential uses being proposed which would raise the concern for incidental

oral exposure of children.

Short

- (1

- 30 days), Intermediate

- (1

- 6 months) and Long

- Term Dermal Endpoints: An acceptable/guid eline dermal toxicity study is available. The 28

- day dermal study had no systemic effects at the limit dose of 1000 mg/kg/day

.

Short

- (1

- 30 days) and Intermediate

- (1

- 6 months) Term Inhalation Endpoints: The NOAEL of

30 mg/kg/day is based on clinical si gns of reduced activity, decreased rearing, initial inactivity, piloerection, ruffled fur and recumbency, decreased body weight, body weight gains and food consumption in males at the LOAEL of 250 mg/kg.

Table 3.1.2 Summary of Toxicological Doses and End points for Sedaxane for Use in Human Health Risk

Assessments Exposure/

Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Dermal, All

Durations Not applicable as the 28

- day dermal study had no systemic effects at the limit dose of 1000

mg/kg/day.

Incidental Oral, All

Durations Not applicable as there are no residential uses of sedaxane.

Inhalation

, Short

- Term Term (1

- 30 days )

and

Intermediate

Term (1

- 6

months ) NOAEL=30

mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x LOC for MOE

= 100 ACN Study

NOAEL=30 mg/kg LOAEL = 250 mg/kg bw , based on reduced activity, decreased rearing, initial inactivity, piloerection, ruffled fur and recumbency, decreased body weight, body wei ght gains and food consumption (♂); plus weakened condition, swaying gait, decreased activity, reduced muscle tone and decreased locomotor activity & rearing (♀). The weakened condition, swaying gait and decreased activity were observed on days 2

- 7, while the other effects were on day 1.
Inhalation, Long

- Term (>6 months) Long

- term exposure is not expected for the proposed use patterns.

Cancer (oral, dermal, inhalation) Classification: “Likely to be Carcinogenic to Humans” based on significant tumor increases in two

adequate rodent carcinogenicity studies. Q 1 *= 4.64x10 - 3 (mg/kg/day) - 1

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 ob served adverse effect level.

### Page 8 of 19

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). FQPA SF = FQPA Safety Factor.



### Inhalation absorption

Since no inhalation absorption data are 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

1 Rate = Maximum application rates specified on proposed labels.



### 5.0 Residential Exposure and Risk Estimates

There are no proposed residential uses of sedaxane at this time.

5

. 1 Spray Drift

Not applicable for seed treatment uses.

5

. 2 Residential Bystander Post

- Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for sedaxane at this time primarily because of t he low acute inhalation toxicity ( Toxicity Category I V ) and low vapor pressure ( 1.7x10 - 7 

### Pa 25 oC )

. A postapplication inhalation exposure assessment is not required as exposure is expected to be negligible. Seed treatment assessments provide quantitative inhalation exposure assessments for seed treaters and secondary handlers (i.e.planters). It is expected that these e xposure estimates would be protective of most postapplication inhalation exposure scenarios

6.0 Occupational Exposure and Risk Estimates Table 4 .1. 1. Summary of Directions for Use of Sedaxane

Type of Seed Product, Formulation Treatment Type Maximum Application Rate 1

(lb ai/100 lb seed)

Corn , rapeseed, sorghum crop group 6a(except soybeans) Vibrance TM /Liquid Commercial

Seed treatment 0.005

Corn (Sm u t treatment ) 0.04

Potato 0.00 25

### Page 9 of 19

6.1 Occupational Handler Exposure/Risk Estimates

Occupational seed treatment primary handlers may experience short

- and intermediate

- term
exposure to sedaxane while performing seed treatment activities in commercial settings. In addition, individuals may experience short

- and intermediate

- term exposure while planting

sedaxane

- treated seeds. Long

- term exposure is not e xpected for the proposed use patterns. The registrant has not submitted a chemical

- specific exposure study in support of this action . In

the absence of chemical

- specific data, HED relies on the most scientifically reliable surrogate data currently available from various sources such as Exposure SAC Policy No s . 14 , 15 and 15 .1 ( Interim Guidance “Amount of Commercial Seed Treated Per Da y ” ) to evaluate handler

exposures. For assessing commercial seed treatment and seed planting activities, unit exposure

data were taken from HED Expo SAC Policy 14: SOPs for Seed Treatment

. The amount of active ingredient handled depends on the applicatio n rate (lb ai/lb seed) and the pounds of seed treated in a day (or the pounds of seed that can be planted in a day)

.

Potato Seed Piece Treatment

Large scale (commercial) potato seed piece treatment typically involves the following procedures. Seed potatoes are handled with some type of front end loader to dump them into a machine that cuts them into “seed pieces”. The pieces emerge on a conveyer where an individual(s) sorts and culls the pieces. Pieces too large are cut again by hand and diseased or damaged pieces are culled. The seed pieces proc essed by conveyer through the spray treatment machine as described above. There is no applicator in a typical sense of an individual using any type of sprayer to apply the material. It is applied in an automated fashion in a covered device. Finally, treated seed is again mechanically loaded in bulk to potato seed planters. Planters are

similar in con cept to other types of machines that plant seeds. Potato planters are basically large open bins filled with seed pieces.

The risk assessment for liquid seed piece treatment to potatoes (using data from MRID 47054702) is presented in Table 6

. 1.1. The results of the occupational handler exposure and risk

assessment s indicate that inhalation risks are not of concern ( MOEs ≥ 100) at baseline exposure

.

Corn S eed T reatment for Head Smut

Sedaxane is effective against seed and seedling blight or damping off caused by certain pathogens including Rhizoctonia sp and Sphacelotheca reiliana (head smut). For effective control of head smut in corn plants, the recommended sedaxane use rate is 0.04 lb ai /100 lb of

seed. The highest rate should be used when disea se pressure is expected to be severe.

Treating Seed

P otential occupational exposure scenarios from the use of sedaxane as a commercial seed

treatment include: Mixing, loading, applying liquid formulations; Bagging treated seed; Sewing bags; and

### Page 10 of 19

Multiple activities

.

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.

Planting Treated Seed

P otential occupational exposure scenarios from the use of sedaxane as a commercial seed

treatment include p lanting treated seed.

Exposure Data, Factors, and Assumptions

The following are exposure factors and assumptions used to calculate exposure and risk in the occupational assessment for commercial seed treatment sce narios.

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate

The maximum application rates listed on the proposed labels provided by the Registration Division was used for all exposure assessments. The maximum rate is 0.00 25 lb ai/100 lbs is for potato seed piece treatment

, 0.04 lb ai/100 lbs of seed on corn for the treatment of sm u t and 0.005 lb ai/100 lbs of seed on rapeseed, sorghum and crop group 6a (except soybeans)

.

Amount of Seed Treated Per Day (Primary Handler)

Interim Guidance (SOP 15.1), used for the amount of seed treated (November 12, 2012) in a

commercial seed treatment facilities.

Amount Handled: The amount of seed treated per day at a commercial facility is summarized below for each crop

Corn seed tr eatment (Short

- term) 339,500lbs

Corn seed treatment (Intermediate

- term) 240,000lbs Rapeseed all durations 125,000 lbs Sorghum seed treatment (Short

- term) 360

, 000 lbs , s orghum seed treatment (Intermediate

term) 180 ,000lbs Crop group 6a (except soybeans)seed treatment (Short

- term) 281,250 lbs

### Page 11 of 19

Crop group 6a(except soybeans) seed treatment (Intermediate

- term) 2 00 ,000lbs Potato seed piece treatment (short

- term) 800,000 lbs Potato seed piece treatment (Intermediate

- term) 400,000 lbs

Planting rate for Potato Seed Pi eces

– 800,000 lbs, Planting rate for c orn

– 3000 lbs Planting rate for sorghum

– 800 lbs Planting rate for rapeseed

– 320 lbs Planting rate for peas

– 16000 lbs Planting rate for beans

– 4960 lbs

Body Weight

The standard bod

y 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.

Absorption factors

Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure. The conservative assumption is that the dermal absorption of sedaxane is 8.0% using dilutions

similar to the end

- use product s. A comparison of the NOAELs from the rat dermal study with the rat developmental study of similar duration, supports that the dermal absorption is less than 10% ( i.e., NOAELs >1000 and 100 mg/kg/day, respectively).

Exposure Duration

HED classifies ex posures from 1 to 30 days as short

- term

, exposures 30 days to six months as

intermediate

- term and exposure over 6 months as long

- term . Exposure duration is determined by many things, including the exposed population and the cultural practices

. For most a gricultural uses, it is reasonable to believe that occupational handlers will not apply the same chemical every day for more than a one

- month time frame; however, there may be a large treatment
facilities who may apply a product over a period of weeks (e.g ., completing multiple applications for multiple clients within a region).

Margin of Exposure : Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoi nt to the daily dose of concern. The daily dermal and inhalation dose received by occupational

handlers were compared to the appropriate POD ( i.e. NOAEL) to assess the risk to occupational handlers for each exposure route.

Estimates of inhalation exposure were calculated. Results are presented for “baseline,” defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respirator. The product label dir ects mixers, loaders, applicators and

### Page 12 of 19

other handlers to wear long

- sleeved shirt and long pants, chemical

- resistant gloves, socks and

shoes.

Combining Exposures/Risk Estimates:

Dermal and inhalation risk estimates were not combined in this assessment, sinc e no dermal hazard was identified; therefore no dermal quantitative risk assessment is required

.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates Occupational handler i nhalation risk estimates are not of concern (MOEs > LOC) for al l proposed uses assessed. The label

- required PPE on the proposed label is that all handlers must wear long

- sleeved shirt and long pants, chemical

- resistant gloves, and socks and shoes. Inhalation MOEs range from 1 1 ,000 to 4

, 4 00 ,000

. A summary of inhalat ion risk estimates for occupational handlers can be found in Table s 6.1.1 and 6.1.2

.

Occupational Handler Cancer Exposure and Risk Estimate Equations

Lifetime Average Daily Dose (LADD): To estimate the carcinogenic risk from absorbed average daily dose, the values were amortized over the working lifetime of occupational handlers. Current use patterns indicate that application can occur numerous times during a year.

Based on use scenari o and use patterns, it is anticipated that a commercial seed treater would apply sedaxane to corn seed 180 days per year ( Agricultural Handler Exposure Task Force (AHETF) January 13, 2012) and 90 days for rapeseed, sorghum, and crop group 6a seed types.

Al so that planting the proposed treated seed types lasts 3 0 days ( USDA, National Agricultural Statistics Service, 2010 )

. Finally, a 35

- year career and a 7 8

- year lifespan were used to complete

the cancer risk assessment

. A summary of cancer risk estimates for occupational handlers can be

found in Tables 6.1.3 and 6.1.4

.

### Page 13 of 19

T able 6.1.1 Non

- Cancer Risk for Seed

- Treatment Handlers

Exposure

Scenario (Scenario #) PPE Dermal

Unit Exposure (mg/lb ai) Inhalation

Unit Exposure (mg/lb ai) Seed Type Application

Rate (lb ai per 100 lb seed) Amount

Treated a (lb seed

tr eated per day) Daily

Inhalation

Dose (mg/kg/day) b Short

- Term

Inhalation

MOE c

Commercial: Loader/Applicator
Loading/Applying Liquids for

Seed Treatment SL, G 0.023 0.00034 Corn (sm u t treatment) 0.04 339,500 (ST) 0.00058 52,000

Sorghum(AHETF Wheat Data) 0.005 360,000 (ST) 0.000077 390,000

Rapeseed (AHETF Canola data) 125,000(ST) 0.000027 1,100,000

Peas and Bean (AHETF Soybeans Data) 281,250(ST) 0.00006 500,000

Commercial: Sewer Sewing Seeds after

Seed treatment SL,

no G 0.0062 0.00023 Corn (sm u t treatment) 0.04 339,500 (ST) 0.00039 77,000

Sorghum (AHETF Wheat Data) 0.005 360,000 (ST) 0.000052 580,000

Rapeseed ( AHETF Canola data) 125,000(ST) 0.000018 1,700,000

Peas and Bean ( AHETF Soybeans Data) 281,250(ST) 0.00004 740,000

Commercial: Bagger Bagging Seeds

after Seed

treatment SL,

no G 0.0091 0.00016 Corn (sm u t treatment) 0.04 339,500 (ST) 0.00027 110,000

Sorghum (AHETF Wheat Data) 0.005 360,000 (ST) 0.000036 830,000

Rapeseed (AHETF Canola data) 125,000(ST) 0.000013 2,400,000

Peas and Bean ( AHETF Soybeans Data) 281,250(ST) 0.000028 1,100,000

Multiple Activities Worker Multiple Activities

for Seed treatment SL,G 0.042 0.0016 Corn (sm u t treatment) 0.04 339,500 (ST) 0.0027 11,000

Sorghum (AHETF Wheat Data) 0.005 360,000 (ST) 0.00036 83,000

Rapeseed ( AHETF Canola data) 125,000(ST) 0.000125 240,000

Peas and Bean ( AHETF Soybeans Data) 281,250(ST) 0.00028 780,000

Potato Seed Piece Treatment

Multiple Activities for Treating Potato

seed Piece SL,

no G 0.127 0.0064 Potato seed Pieces 0.0025 800,000(ST) 0.0016 19,000

a Daily amounts treated values are based on the information on Expo SAC policy 15.1

b Daily inhalation dose (mg/kg/d) = (unit exposure (mg/lb ai) * application. rate (lb ai/lb seed) * daily amounts treated / body weight (80 kg).

c Short

- and intermediate

- term inhalation MOE = NOAEL (30 mg/kg/day) / daily inhalation dermal dose.

### Page 14 of 19

Table 6

. 1.2 Non

- Cancer Risk for Handler

- Seed Planters
Exposure Scenario (Scenario #) Mitigation

Level Inhalation Unit

Exposure (mg/lb ai) Seed Type Application Rate (lb ai per 100lb seed) Amount

Planted a Daily

Inhalation

Dose b (mg/kg/day) Short

- - Term

Inhalation MOE c

Seed Planters

Planting Treated Seed Corn 0.04 3 ,000 0.0000 51 590 ,000

Potato seed piece s 0.0 025 8 00,000 0.00085 35,000

Sorghum 0.005 800 0.0000017 1,800,000

Rapeseed 0.005 320 0.00000068 4,400,000

Peas 0.005 16000 0.000034 880,000

Bean 0.005 4960 0.000011 2,800,000

a Daily amounts treated values are based on the information on Expo SAC policy 15. 1

b Daily inhalation dose (mg/kg/d) = (unit exposure (mg/lb ai) * application. rate (lb ai/lb seed) * daily amounts treated / body weight (80 kg).

c Short

- term and intermediate

- term inhalation MOE = NOAEL (30 mg/kg/d) / daily inhalation dose.



### Table 6.1.3 Primary Handler Cancer Risk for Sedaxane

Crop Dermal Dose a

(mg/kg/day) Inhalation Dose a

(mg/kg/day) Combined

ADD b
(mg/kg/day) Commerical LADD c

(mg/kg/day) Commercial Cancer Risk d

Commercial : Mixer/Loader/Treater (G, No respirator)

Corn 2.30E

- 04 4.25E

- 05 2.73E

- 04 6.03E

- 05 3 E

- 07

Sorghum 2.07E

- 04 3.8 3 E

- 05 2.45E

- 04 2.71 E

- 05 1 E

- 0 7

Rapeseed 1.44E

- 04 2.66E

- 05 1.70E

- 04 1.88E

- 05 8E

- 07

Beans 2.30E

- 04 4.25E

- 05 2.73E

- 04 3.02E

- 05 1E

- 07

Peas 2.30E

- 04 4.25E

- 05 2.73E

- 04

Commercial :Sewer (Baseline)

Corn 6.20E

- 05 2.88E

- 05 9.08E

- 05 2.01E

- 05 9E

- 08 Sorghum 5.58E

- 05 2.59E

- 05 8.17E

- 05 9.04E

- 06 4E

- 08 Rapeseed 3.88E

- 05 1.80E

- 05 5.67E

- 05 6.28E

- 06 3 E

- 08 Beans and peas 6.20E

- 05 2.88E

- 05 9.08E

- 05 1.00E

- 05 5 E

- 08 Commercial :Bagger (Baseline)

Corn 9.10E

- 05 2.00E

- 05 1.11E

- 04 2.46E

- 05 1E

- 07 Sorghum 8.19E

- 05 1.8E

- 05 9.99E

- 05 1.11E

- 05 5E

- 08 Rapeseed 5.69E

- 05 1.25E

- 05 6.94E

- 05 7.68E

- 06 4 E

- 08

### Page 15 of 19

Table 6.1.3 Primary Handler Cancer Risk for Sedaxane

Crop Dermal Dose a

(mg/kg/day) Inhalation Dose a

(mg/kg/day) Combined

ADD b
(mg/kg/day) Commerical LADD c

(mg/kg/day) Commercial Cancer Risk d

Beans and peas 9.10E

- 05 2.00E

- 05 1.11E

- 04 1.23E

- 05 6 E

- 08 Multiple Activities (G, no respirator)

Corn 4.20E

- 04 2.00E

- 05 6.20E

- 04 1.37e

- 04 6E

- 07 Sorghum 3.78E

- 04 1.80E

- 04 5.58E

- 04 6.17E

- 05 3 E

- 07 Rapeseed 2.63E

- 04 1.25E

- 04 3.88E

- 04 4.29E

- 05 2 E

- 07 Beans and peas 4.20E

- 04 2.00E

- 04 6.20E

- 04 6.86E

- 05 3E

- 07

Seed Piece Treatment (Baseline)

Potato 1.27E

- 03 8.0E

- 04 2.07E

- 03 7.65E

- 05 4 E

- 07

a. Unit exposure (mg ai/lb of seed) x Application Rate (0.00005lb ai/lb of seed) x the amount of seed planted/day (lbs) // body weight (80kg) b. ADD (mg/kg/day) = [Dermal Dose (mg/kg/day) x 8%DA]+ Inhalation Dose (mg/kg/day) c. LADD (mg/kg/day) = ADD x [( 180 days (corn) 90 days ( all other crops ) /yr Commercial)/ (365 days/yr)] x (35 yrs/7 8 yrs) d Cancer Risk = LADD x Q* ( 4.64 x 10

- 3 mg/kg/day)

- 1

Table 6.1.4: Planter Cancer Risk for Sedoxane Crop Dermal Dose a (mg/kg/day) (glove) Inhalation Dose a (mg/kg/day) No respirator Planters ADD b
(mg/kg/day) Planters / LADD c (mg/kg/day) Planters

Cancer Risk d

Corn 5.1E

- 05 3.0E

- 04 3.51E

- 05 1.29E

- 06 6 E

- 09

Potato 2.5E

- 03 4.25E

- 04 5.85E

- 03 2.16E

- 04 1 E

- 0 8

Sorghum 1.00E

- 05 1.70E

- 06 1.17E

- 05 4.32E

- 07 2 E

- 09

Rapeseed 4.00E

- 06 6.80E

- 07 4.68E

- 06 1.73E

- 07 8 E

- 10

Beans 6.20E

- 05 1.05E

- 05 2.34E

- 04 8.63E

- 06 4 E

- 08

Peas 2.00E

- 04 3.40E

- 05 7.25E

- 05 2.68E

- 06 1E

- 08

a. Unit exposure (mg ai/lb of seed) x Application Rate (0.00005lb ai/lb of seed) x the amount of seed planted/day (lbs) / body w eight (80kg)

b. ADD (mg/kg/day) = [Dermal Dose (mg/kg/day) x 8%DA]+ Inhalation Dose (mg/kg/day) c. Planter LADD (mg/kg/day) = ADD x [( 3 0 days/yr)/ (365 days/yr)] x (35 yrs/7 8 yrs) d Planter Cancer Risk = LADD x Q* ( 4.64 x 10

- 3 mg/kg/day)

- 1

### Page 16 of 19

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 exposu re). The potential for dermal and inhalation post

- application exposures following the planting of sedaxane

- 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 n ot 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

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

6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for sedaxane at this time primarily because of the low acute

inhalation toxicity (Toxicity Category I V ) and the low vapor pressure ( 1. 7x10 - 7 

### Pa 25 oC ).

However , there are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and r esuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in D ecember 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post

- application

i nhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for sedaxane

.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result i n higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

6

. 2 .2 Occupational Post

- application Derm al Exposure/Risk Estimates

The potential for dermal and inhalation post

- application exposures following the planting of

sedaxane

- 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 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)

.

### Page 17 of 19

Therefore, no quantitative post

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

.

The labeling properly state s the exception to the Agricultural Use Requirements restricted entry interval (REI) of 12 hours : " Exception: Once the seeds are planted in the soil, the Worker Protection Standard, under certain circumstances, allows workers to enter the treated area

without restriction if there will be no worker contact with the soil subsurface or treated seed. PPE required fo r early entry to treated areas that is permitted under the Worker Protection Standard and that involves contact with anything that has been treated, such as plants, soil, or water, is: long

- sleeved shirt and long pants and chemical

- resistant gloves.

### Page 18 of 19

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 seed 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 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)

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 chemical that crosses a biological boundary such as the skin and lungs (%) , and Body Weight = Body weight determined to represent the popu lation 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

.



### Occupational Handler Cancer Exposure and Risk Estimate Equations

LADD values were calculated using the following equation:

where: LADD = ADD x Exposure Frequency x Exposure Duration

365 Days per Year Lifetime

### Page 19 of 19

Lifetime Average Daily Dose = the amount as absorbed dose received from exposure to a pesticide or degradate in a given scenario over a lifetime (mg/ kg/day, also referred to as LADD); Average Daily Dose = the amount as absorbed dose received from exposure to a pesticide or degradate in a given scenario on a daily basis (mg/kg/day, also referred to as ADD); Dermal Absorption Factor = 8 Percen t (MRID #47474632) Exposure Frequency = the annual frequency of exposure to an individual ( 180 days/year for corn seed treatment, 90 day /year

for all other seed types and 30 days /year for planting all seed types .); Exposure Duration = the amount of a lifetime that an individual is exposed (35 years for occupational); and

Lifetime = the average life expectancy of an individual (7 8 years).

Cancer risk estimates: Estimated cancer risk calculations were completed by multiplying the LADD values by the Q 1 * 

### for sedaxane ( Q 1 * 

### = 4.6 x 10 - 3 

### (mg/kg/day) - 1 

### ). Cancer risk estimates were calculated using the following equation:

Estimated Cancer Risk =Probability of excess cancer cases over a lifetime (unitless); Lifetime Average Daily Dose = the amount as absorbed dose received from exposure to a pesticide or degradate in a given

scenario over a li fetime (mg/kg/day); and Q 1 

### * = Quantitative dose response factor used for linear,

low

- dose response cancer risk calculations (mg/kg/day) - 1



### . Estimated Cancer Risk = LADD x Q1*

=RiskC~Can cer~Risk~~=~~LADD~~x~~Q1

*