UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: 

Subject: 

February 28, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Sedaxane: Occupational and Residential Exposure/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: 

REVIEWER: 

Expo SAC: 

THROUGH: 

Seyed Tadayon, Chemis~ Risk Assessment Branch V 

Health Effects Division (7509P) 

Kelly O'Rourke, Biologist, Expo SAC Reviewer ~ .w1 <Q ~-<-. Shalu Shelat, Industrial Hygienist, Expo SAC Re iewer~~ 

Mike Metzger, Chief I g oy Risk Assessment Branch V ~ ,.. 

Health Effects Division (75 9 ) · , 

TO: William Donovan, PhD, Risk Assessor 

Risk Assessment Branch V 

Health Effects Division (7509P) 

Introduction 

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

assessment for proposed uses of sedaxane. Syngenta Crop Protection, LLC proposed the US 

registration of the new uses of sedaxane for treating rapeseed, sorghum, Crop group 6a (except 

soybeans), com seed 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 (SOPs) for Seed Treatment 

(Policy 14), Amount of Seed Treated or Planted per Day (Policy 15) and Interim Guidance 

"Amount of Commercial Seed Treated Per Day" (Policy 15.1). This assessment uses the AHETF 

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

Page 1 of 19 
of 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 Amount of Seed Treated or Planted 

per Day. Specifically, survey data were collected to update daily seed treatment throughput data and to 

characterize seed treating equipment and worker activities for five seed types-canola, corn, rice, 

soybean, and wheat. The AHETF surveys replaces maximum equipment capacity referenced in, SOP 15. 

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

(ExpoSAC) on 02/21/2013 2013. 

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

5.0 Residential Exposure and Risk Estimates............................................................................ 8

5.1 Spray Drift........................................................................................................................ 8

5.2 Residential Bystander 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 

pathogenic 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). There are no 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 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 endpoint 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 assessments 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 sedaxane as “Likely to be Carcinogenic to Humans”. This classification is 

based on the presence of liver and thyroid tumors in male rats, uterine tumors in female rats and 

liver tumors in male mice. Uterine tumors were also seen in a chemical structurally related to 

sedaxane. There is no mutagenic concern for sedaxane. A linear low-dose extrapolation model 

(Q1*) was used for quantification of cancer 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 inhalation 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. Inhalation MOEs range from 11,000 to 4,400,000.
Page 5 of 19

Summary of Occupational Handler Cancer Exposure and Risk Estimates

The results of the occupational cancer risk indicate that the values range from 8E-10 to 1E-07 at

the baseline for baggers and sewers and chemical 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 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.

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 irritation, and acute dermal irritation. It is not a skin 

sensitizer. 

The labeling properly states 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 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 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 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-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
Page 6 of 19

2.0 SUMMARY OF CONCLUSIONS AND DATA REQUIREMENTS

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 not 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 

the occupational cancer risk indicate that the values range from 8.0E-10 to 1E-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 proposed 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 Technical

Guideline 

No.

Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral - rat 47473366 LD50 > 5000 mg/kg (both sexes) IV

870.1200 Acute dermal - rabbit 47473367 LD50 > 5000 mg/kg (both sexes) IV

870.1300 Acute inhalation - rat 47473368 LC50 > 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, 

2011; Jessica Kidwell; January 24, 2012

Short- and Intermediate-Term Incidental Oral 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/guideline 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 signs 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 Endpoints 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 

IntermediateTerm (1-6 

months)

NOAEL=30 

mg/kg/day

UFA= 10x

UFH= 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 weight 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. Q1*= 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 observed adverse effect level. 
Page 8 of 19

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). 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 the low acute 

inhalation toxicity (Toxicity Category IV) and low vapor pressure (1.7x10-7Pa 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 exposure 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 Rate1

(lb ai/100 lb seed)

Corn, rapeseed, sorghum 

crop group 6a(except 

soybeans)

VibranceTM /Liquid Commercial

Seed treatment

0.005

Corn (Smut treatment) 0.04

Potato 0.0025
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 expected 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 Nos. 14, 15 and 15.1

(Interim Guidance “Amount of Commercial Seed Treated Per Day” ) 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 application 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 processed 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 concept 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 

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

Corn Seed Treatment 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/100lb of 

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

Treating Seed 

Potential 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.) was addressed.

Planting Treated Seed 

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

treatment include planting 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 scenarios. 

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 0.0025 lb ai/100 lbs is for 

potato seed piece treatment, 0.04 lb ai/100 lbs of seed on corn for the treatment of smut 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 treatment(Short-term) 339,500lbs

Corn seed treatment (Intermediate-term) 240,000lbs

Rapeseed all durations 125,000 lbs

Sorghum seed treatment(Short-term) 360,000lbs, sorghum seed treatment (Intermediateterm) 180,000lbs

Crop group 6a (except soybeans)seed treatment(Short-term) 281,250lbs
Page 11 of 19

Crop group 6a(except soybeans) seed treatment (Intermediate-term) 200,000lbs

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

Potato seed piece treatment (Intermediate-term) 400,000 lbs

Planting rate for Potato Seed Pieces – 800,000 lbs,

Planting rate for corn – 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 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.

 

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 products. 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 exposures 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 agricultural 

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 endpoint 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 directs 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, since 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 inhalation risk estimates are not of concern (MOEs > LOC) 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. 

Inhalation MOEs range from 11,000 to 4,400,000. A summary of inhalation risk estimates for 

occupational handlers can be found in Tables 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 scenario 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.

Also that planting the proposed treated seed types lasts 30 days (USDA, National Agricultural 

Statistics Service, 2010). Finally, a 35-year career and a 78-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

Table 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 

Treateda

(lb seed 

treated per 

day)

Daily

Inhalation

Dose 

(mg/kg/day)b

Short 

- Term 

Inhalation 

MOEc 

Commercial: Loader/Applicator

Loading/Applying

Liquids for

Seed Treatment

SL, G 0.023 0.00034 Corn (smut 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 (smut 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 (smut 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 (smut 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 

Planteda

Daily

Inhalation

Doseb(mg/kg/day)

Short- -Term 

Inhalation MOEc 

Seed Planters

Planting Treated Seed Corn 0.04 3,000 0.000051 590,000

Potato seed pieces 0.0025 800,000 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 LADDc

(mg/kg/day)

Commercial Cancer Riskd

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

Corn 2.30E-04 4.25E-05 2.73E-04 6.03E-05 3E-07

Sorghum 2.07E-04 3.83E-05 2.45E-04 2.71E-05 1E-07

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 3E-08

Beans and peas 6.20E-05 2.88E-05 9.08E-05 1.00E-05 5E-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 4E-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 LADDc

(mg/kg/day)

Commercial Cancer Riskd

Beans and peas 9.10E-05 2.00E-05 1.11E-04 1.23E-05 6E-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 3E-07

Rapeseed 2.63E-04 1.25E-04 3.88E-04 4.29E-05 2E-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 4E-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/78yrs)

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 ADDb

(mg/kg/day)

Planters / LADDc

(mg/kg/day)

Planters

Cancer Risk d

Corn 5.1E-05 3.0E-04 3.51E-05 1.29E-06 6E-09

Potato 2.5E-03 4.25E-04 5.85E-03 2.16E-04 1E-08

Sorghum 1.00E-05 1.70E-06 1.17E-05 4.32E-07 2E-09

Rapeseed 4.00E-06 6.80E-07 4.68E-06 1.73E-07 8E-10

Beans 6.20E-05 1.05E-05 2.34E-04 8.63E-06 4E-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 weight (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 [(30 days/yr)/ (365 days/yr)] x (35 yrs/78yrs)

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

the planting of sedaxane-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

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 IV) and the low vapor pressure (1.7x10-7Pa 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 resuspension 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 December 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 

inhalation 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 in 

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 Dermal Exposure/Risk Estimates

The potential for dermal and inhalation post-application exposures following the planting of 

sedaxane-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). 
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 states 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 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. 
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 (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.

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 Percent (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 (78

years).

Cancer risk estimates: Estimated cancer risk calculations were completed by multiplying the 

LADD values by the Q1* for sedaxane (Q1* = 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 lifetime (mg/kg/day); and

Q1* = Quantitative dose response factor used for linear, 

low-dose response cancer risk calculations 

(mg/kg/day)-1.

Estimated Cancer Risk = LADD x Q1*

=RiskC~Cancer~Risk~~=~~LADD~~x~~Q1

*