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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF 

CHEMICAL SAFETY

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: December 3, 2010

Subject: Thiamethoxam: Occupational and Residential Exposure/Risk Assessment for 

Proposed Section 3 Registration for Seed Treatment Uses on Peanut and Alfalfa.

PC Code: 060109 DP Barcode: D373377; D376089

 MRID No.: 48020202 Registration No.: 100-936; 100941

Petition No.: 9F7657; 0F7707 Regulatory Action: Section 3 Registration

 Assessment Type: ORE Reregistration Case No.: NA

 TXR No.: NA CAS No.: 152719-23-4 

 Decision No.: 424517; 430284 40 CFR: 180.565

FROM: Shih-Chi Wang, Biologist

Risk Assessment Branch 2

Health Effects Division (7509P)

THRU: Richard Loranger, Ph.D., Branch Senior Scientist

Margarita Collantes, M.S. Biologist

Risk Assessment Branch 2

Health Effects Division (7509P)

TO: Kable Davis/Venus Eagle, RM 01

Insecticide-Rodenticide Branch 

Registration Division (7505P)

CONCLUSIONS

The registrant, Syngenta, has requested a label amendment to add treatment of alfalfa and peanut 

seeds using both open and closed commercial seed treating systems to the existing Cruiser® 5FS 

label. The registrant also submitted a request for a new product registration for Cruiser® PD 

Insecticide for seed treatment of peanuts in open and closed commercial seed treatment facilities

HED has evaluated the proposed seed treatment uses of thiamethoxam on peanut and alfalfa. The 

potential occupational exposures/risks resulting from the proposed uses do not exceed HED’s

level of concern provided the appropriate personal protective equipment (PPE) (i.e., gloves,

coveralls and a PF10 respirator) are used while treating peanuts with Cruiser PD in open seed 

treatment facilities. HED recommends that the Registration Division ensure that the appropriate 

respirator is required on the final Cruiser PD label.
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Table of Contents

1.0 Executive Summary..................................................................................................................3

2.0 Hazard Characterization............................................................................................................5

3.0 Proposed Use Pattern ................................................................................................................7

4.0 Residential (Non-Occupational) Exposure ..............................................................................8

5.0 Occupational Exposure .............................................................................................................9

 5.1 Handlers .......................................................................................................................9

5.2 Secondary Seed Handlers ...........................................................................................16

 

6.0 Review of Human Research ...................................................................................................17
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I. EXECUTIVE SUMMARY

Thiamethoxam is a systemic insecticide belonging to the neonicotinoid class of chemistry. It is 

used to treat various agricultural crops, turf grass, sod farms, golf course, residential lawns, indoor 

cracks and crevices, ornamental plants grown in greenhouses, and Christmas trees. The registrant, 

Syngenta, has requested a label amendment to add treatment of alfalfa and peanut seeds using 

both open and closed commercial seed treating systems to the existing Cruiser® 5FS label. The 

registrant also submitted a request for a new product registration for Cruiser® PD Insecticide for 

seed treatment of peanuts in open and closed commercial seed treatment facilities. Based on 

proposed label information, occupational exposure is expected to occur for short- and 

intermediate-term durations.

Although there are existing residential uses (indoor crack and crevice and outdoor turf), the 

proposed seed treatment uses on peanut and alfalfa do not result in additional residential exposure 

and risk. Residential exposures and risks assessed previously were summarized in this document 

for the purpose of conducting an aggregate exposure and risk assessment.

Hazard Characterization

Thiamethoxam is classified as Toxicity Category III for acute oral toxicity and Category IV for

acute dermal, inhalation toxicity and eye irritation. Thiamethoxam is not a dermal sensitizer. 

Although points of departure and endpoints for risk assessment were selected for children’s 

dermal and incidental oral exposures, these are not discussed herein, since only adult occupational 

workers are expected to be exposed for this particular use based on the proposed seed treatment

label.

The adult dermal NOAEL of 1.2 mg/kg/day (point of departure for all durations) is based on 

sperm abnormalities and testicular effects observed after in utero and post-natal exposure at 

LOAELs of 1.8 and 3 mg/kg/day in 2 rat reproduction toxicity studies. Since the dermal endpoint 

is based on an oral study a dermal absorption factor of 5% was used to estimate exposure.

Although a 21-day dermal toxicity study in rats is available, HED selected the endpoint and dose 

(NOAEL) from the reproduction toxicity study because the reproductive parameters were not 

evaluated in the dermal toxicity study, and therefore use of the dermal toxicity study for endpoint 

selection would not be protective of potential reproductive effects.

A route-specific inhalation toxicity study has not been submitted for thiamethoxam. Therefore, 

HED selected the same reproductive effect/endpoint (NOAEL of 1.2 mg/kg/day (point of 

departure for all durations) for inhalation risk assessment that was used in the dermal assessment.

An oral study was selected for both dermal and inhalation risk assessments. Therefore, 

corresponding dermal and inhalation absorption factors were used for route-to-route extrapolation.

For both dermal and inhalation risk assessments, a 60 kg body weight (for females) was used to 

calculate exposure since reproductive endpoints were selected for risk assessment.

For all exposure scenarios, uncertainty factors (UFs) of 10x for interspecies extrapolation and 10x 

for intraspecies variability (total UF of 100x) were used. Therefore, for all occupational and 

residential exposure scenarios, the level of concern (LOC) is a margin of exposure (MOE) of 100.
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That is, MOEs less than 100 represent risks of concern.

Cancer Assessments: 

Thiamethoxam is classified as “Not Likely to be Carcinogenic to Humans” based on 

convincing evidence that a non-genotoxic mode of action for liver tumors was established in the 

mouse and that the carcinogenic effects are a result of a mode of action dependent on sufficient 

amounts of a hepatotoxic metabolite produced persistently. Quantification of cancer risk is not

required.

Residential Exposure:

A residential (non-occupational) exposure/risk assessment was not performed at this time in 

conjunction with the proposed uses. The proposed uses are limited to occupational workers 

(handlers and postapplication). A summary of previous residential turf and crack and crevice 

exposure assessments is provided strictly for the purpose of conducting an aggregate assessment 

in the associated human health risk assessment. All handler and post-application scenarios in 

previous assessments resulted in MOEs greater than 100 and are not of concern. All combined 

residential post-application scenarios resulted in MOEs greater than 100 and are not of concern. 

Occupational Exposure:

The handler assessments for the proposed seed treatment uses were based on the unit exposure 

data from the Science Advisory Council for Exposure (Exposure SAC) Policy #14: Standard 

Operating Procedures (SOP) for Seed Treatment (May 1, 2003) and on the treating/planting data 

from the Exposure SAC Policy #15: Amount of Seed Treated or Planted Per Day (March 2, 2004).

Handlers scenarios resulting in MOEs greater than 100 are not of concern. 

The Cruiser® PD is intended for use as a dry application on peanuts. Since the treater (loader/ 

operator) unit exposure values from Policy 14 are based on liquid formulations, the 

loader/operator exposure for Cruiser® PD was estimated using surrogate unit exposure values for 

a wettable powder formulation in the Pesticide Handlers Exposure Database (PHED). The treater 

scenario resulted in a MOE of 100 with the use of additional PPE (i.e. gloves, coveralls and a 

PF10 respirator). Currently the label only requires a dust mask (quarter or half mask) respirator. 

HED recommends that the Registration Division ensure that the appropriate respirator is required 

on the final Cruiser® PD label.

In assessing the multiple activity scenario for commercially treating 718,000 lbs of alfalfa seed

using an open system, handler exposure resulted in a MOE of 59 at baseline with addition of 

gloves. The addition of a PF 5 dust mist respirator to current label PPE [i.e., gloves and coveralls]

was required for multiple activity workers scenario to reach an MOE greater than 100 (MOE = 

170). However, the Cruiser® 5FS label contains a restriction for commercial open system seed 

treatment facilities that limits the amount of product handled per day to no more than 38 gallons 

product/worker/8-hr day which is equivalent to treating 413,043 lbs of seed a day. Therefore, 

HED also assessed treatment of 413,043 lbs of alfalfa seed at baseline with addition of gloves 

which resulted in a MOE of 100 and was not of concern. 

Risks for all other commercial open and closed system scenarios were not of concern. All MOEs 

for secondary seed handlers (i.e., those who plant treated seed) are greater than 100 assuming a 
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single layer of clothing plus gloves, with MOEs ranging from 760 to 2,500 and were not of 

concern. 

Review of Human Research

This exposure/risk assessment relies in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED). EPA has 

reviewed all the studies in these multi-pesticide generic exposure databases, and on the basis of 

available evidence has found them to have been neither fundamentally unethical nor significantly

deficient relative to standards of ethical research conduct prevailing when they were conducted. 

There is no regulatory barrier to continued reliance on these studies, and all applicable 

requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) 

have been satisfied.

2.0. HAZARD CHARACTERIZATION

2.1 Hazard Profile

The database for acute toxicity for thiamethoxam is complete and is summarized below in Table 

1. Thiamethoxam is classified as Toxicity Category III for acute oral toxicity and Category IV for

acute dermal, inhalation toxicity and eye irritation. Thiamethoxam is not a dermal sensitizer. 

Although points of departure and endpoints for risk assessment were selected for children’s 

dermal and incidental oral exposures, these are not discussed herein, since only adult occupational 

workers are expected to be exposed based on the proposed label for seed treatment use.

The adult dermal NOAEL of 1.2 mg/kg/day (point of departure for all durations) is based on 

sperm abnormalities and testicular effects observed after in utero and post-natal exposure at 

LOAELs of 1.8 and 3 mg/kg/day in 2 rat reproduction toxicity studies. Since the dermal endpoint 

is based on an oral study a dermal absorption factor of 5% was used to estimate exposure. 

Although a 21-day dermal toxicity study in rats is available, HED selected the endpoint and dose 

(NOAEL) from the reproduction toxicity study because the reproductive parameters were not 

evaluated in the dermal toxicity study, and therefore use of the dermal toxicity study for endpoint 

selection would not be protective of potential reproductive effects.

A route-specific inhalation toxicity study has not been submitted for thiamethoxam. Therefore, 

HED selected the same reproductive effect/endpoint (NOAEL of 1.2 mg/kg/day (point of 

departure for all durations) for inhalation risk assessment that was used in the dermal assessment 

An oral study was selected for both dermal and inhalation risk assessments. Therefore, 

corresponding dermal and inhalation absorption factors were used for route-to-route extrapolation. 

For both dermal and inhalation risk assessments, a 60 kg body weight (for females) was used to 

calculate exposure since reproductive endpoints were selected for risk assessment.

For all exposure scenarios, uncertainty factors (UF) of 10x for interspecies extrapolation and 10x 
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for intraspecies variability (total UF of 100x) were used. Therefore, for all occupational and 

residential exposure scenarios, the level of concern (LOC) is a margin of exposure (MOE) of 100.

That is, MOEs less than 100 represent risks of concern.

HED’s CARC has classified Thiamethoxam as “Not Likely to be Carcinogenic to Humans” 

based on convincing evidence that a non-genotoxic mode of action for liver tumors was 

established in the mouse and that the carcinogenic effects are a result of a mode of action 

dependent on sufficient amounts of a hepatotoxic metabolite produced persistently. 

Quantification of cancer risk is not required.

A summary of the toxicological doses and points of departure is provided in Table 2.

2.2 FQPA and Uncertainty Factor Considerations

Based upon the hazard data and the methods used to estimate exposure, HED previously

recommended the 10X FQPA SF for the protection of infants and children be reduced to 1X. The 

complete discussion of the rationale for reducing the FQPA SF to 1X is provided in the

11/24/2009 risk assessment (D371303). No additional uncertainty factors were considered 

necessary to account for missing data, for severity of toxic effects, or for the lack of a NOAEL. 

Therefore, the standard 10X uncertainty factors to account for intraspecies variability and 

interspecies extrapolation (for a total of 100X) serve as the basis for the level of concern (LOC) of 

100 for MOEs for both residential and occupational exposure assessments.

Table 1. Acute Toxicity Profile of Thiamethoxam.

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [rat] 44703314 LD50: 1563 mg/kg III

870.1200 Acute dermal [rabbit] 44703316 LD50 = 13.3 g/kg IV

870.1300 Acute inhalation [rat] 44703317 LC50 > 3.72 mg/L IV

870.2400 Acute eye irritation [rabbit] 44703318 PIS = 10 at 1 hr

PIS = 0 at 24 hr

Minimally irritating

IV

870.2500 Acute dermal irritation 44703319 PIS = 0 IV

870.2600 Skin sensitization 44710401 Is not a sensitizer using 

method of Magnusson and 

Kligman

N/A
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Abbreviations: UF = uncertainty factor, UFA = extrapolation from animal to human (interspecies), UFH = potential 

variation in sensitivity among members of the human population (intraspecies), DAF = dermal absorption factor, IAF 

= inhalation absorption factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect 

level, MOE = margin of exposure, LOC = level of concern.

3.0 PROPOSED USE PATTERN

The proposed use pattern for thiamethoxam [Cruiser®5FS Insecticide (thiamethoxam 47.6% a.i.) 

& Cruiser® PD Insecticide (thiamethoxam 70.0% a.i.)] as a seed treatment for peanut and alfalfa 

seeds is summarized in Table 3.

The personal protective equipment (PPE) requirements proposed on the Cruiser® Insecticide 

labels are:

 Applicators and other handlers must wear: long-sleeved shirt & long pants, chemicalresistant gloves, and shoes plus socks. 

 Multiple task workers must wear: chemical-resistant gloves, chemical-resistant 

coveralls over long sleeved shirt and long pants, and shoes plus socks.

 

The personal protective equipment (PPE) requirements proposed on the Cruiser® PD Insecticide 

label are:

 Applicators and other handlers must wear: coveralls over long sleeved shirt & long 

pants, chemical-resistant gloves, shoes plus socks, and a respirator (i.e., single use dust 

Table 2. Toxicological Doses and Endpoints for Thiomethoxam Occupational Handler Risk Assessments.

Exposure/

Scenario

Point of 

Departure

Uncertainty Factors

(UF)

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal (all 

durations) 

(Adults)

Oral study 

NOAEL= 1.2

mg/kg/day

(Dermal 

Absorption 

Factor = 5%)

UFA= 10x

UFH= 10x

LOC = an MOE of 

100 (occupational)

2-Generation reproduction study 

(MRID 44718707)

LOAEL = 1.8 mg/kg/day based on 

increased incidence and severity of 

tubular atrophy in testes of F1 

generation males.

2-Generation reproduction study 

(46402904) 

LOAEL = 3 (males), not determined 

(females) mg/kg/day based on sperm 

abnormalities in F1 males.

Inhalation (all 

durations)

Oral study 

NOAEL= 1.2 

mg/kg/day

(Inhalation 

Absorption 

Factor = 100% 

of oral 

absorption)

UFA= 10x

UFH= 10x

LOC = an MOE of 

100 (occupational)

2-Generation reproduction 

study(MRID 44718707)

LOAEL = 1.8 mg/kg/day based on 

increased incidence and severity of 

tubular atrophy in testes of F1 

generation males.

2-Generation reproduction study 

(46402904) 

LOAEL = 3 (males), not determined 

(females) mg/kg/day based on sperm 

abnormalities in F1 males.

Cancer (oral, 

dermal, 

inhalation)

“Not Likely to be Carcinogenic to Humans” based on convincing evidence that a non-genotoxic mode of 

action for liver tumors was established in the mouse and that the carcinogenic effects are a result of a mode 

of action dependent on sufficient amounts of a hepatotoxic metabolite produced persistently. Quantification 

of cancer risk is not required. 
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mask, quarter or half mask respirator).

Table 3. Proposed Use Pattern for Thiamethoxam.

Crop 

Seed Product, 

Formulation Treatment Type

Applications 

Per Season 1

Maximum Application Rate2

(lb ai/lb seed)

PHI3

(days)

Per 

Application Per Season

Peanut

Cruiser ® 5FS

Reg. No. 

100-941

Open and Closed 

Commercial 

Seed Treatment

NA 0.00054 NA NA

Cruiser PD

Reg. No. 

100-RGAL

NA 0.00054 NA NA

Alfalfa Cruiser ® 5FSReg. No.

100-941

Commercial

(open and closed 

systems) Seed 

Treatment

NA 0.00046 NA NA

1 Maximum number of applications allowed on label.

2 Rate = Maximum application rates specified on proposed labels (Peanut: 0.29 mg a.i. per seed, 850 seeds per pound; Alfalfa: 

 0.001 mg a.i. per seed, 210,000 seeds per pound ). 

3

PHI = Pre-harvest Interval.

4 NA= Not Applicable.

4.0 RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE/RISK PATHWAY

A residential (non-occupational) exposure/risk assessment was not performed at this time in 

conjunction with the proposed uses. The proposed uses are limited to occupational workers 

(handlers and postapplication).

Residential exposure assessments were previously performed for the use thiamethoxam on turf 

(M. Collantes; March 2007; D332064) and indoor crack and crevice applications (M. Collantes, 

July 2009, D359207). The product labels indicate that thiamethoxam is applied by commercial 

applicators only. Therefore, a quantitative assessment for handler exposure was performed for 

commercial applicators only. However, residential post-application exposure assessments for 

adults and toddlers were conducted. All post-application dermal and oral scenarios associated 

with turf and indoor crack and crevice uses resulted in MOEs greater than 100 and are not of 

concern. 

For the purpose of future thiamethoxam human health risk assessments, a summary of the 

combined residential assessment based on indoor crack and crevice use is provided in Table 4

below (M. Collantes, July 2009, D359462). All combined post-application scenarios resulted in 

MOEs greater than 100 and were not of concern. These exposures and risks were greater than 

exposure/risk from the use on lawns. Therefore, the indoor exposures should be used in an 

aggregate assessment in order to be protective. 
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Table 4. Combined Residential Exposure and Risk Estimates from the Indoor Crack and

Crevice Use.

Post-application

Scenarios

Daily Dose

(mg/kg/day) 1

MOE 2 Combined

MOE 3

Short-term

Adult Dermal – indoor surface 0.00278 430 430

Toddler Dermal - indoor 

surface

0.08 750

610

Hand-to-Mouth 0.00267 3100

Intermediate-term

Adult Dermal - indoor surface 0.00278 430 430

Toddler Dermal - indoor 

surface

0.08 750

680

Hand-to-Mouth 0.001267 6500

1. Daily Dose = see Tables 4.2.2.2 and 4.2.2.3 in M. Collantes memo, D359462.

2. Adult Dermal MOE = NOAEL (1.2 mg/kg/day) Child Dermal MOE = NOAEL (60 mg/kg/day)

 Dermal Dose Dermal Dose

 Hand-to-Mouth MOE = NOAEL (8.23 mg/kg/day)

Oral Dose

3. Toddler Combined MOE = 1/ [(1/MOEDermal) + (1/MOEHand-to-Mouth)]

5.0. OCCUPATIONAL EXPOSURE

Syngenta has requested a label amendment to add open and closed system treatment of alfalfa and 

peanut seeds in commercial seed treatment facilities to the existing Cruiser® 5FS label. The 

registrant also submitted a request for a new product registration for Cruiser® PD Insecticide for 

seed treatment of peanuts using open and closed treating systems in commercial seed treatment 

facilities. Based on proposed label information, occupational exposure is expected to occur for 

short- and intermediate-term durations. HED generally relied on the seed treatment policies and 

standard assumptions to evaluate occupational exposure.

5.1 Handlers 

Based on the proposed use pattern, pesticide handlers will be exposed to thiamethoxam when they

perform seed treatment activities.

Equations/Calculations

HED uses standard equations when estimating handler exposure during seed treatments. 

Exposure is based on the application rate and the amount of seed treated per day. The following 

equations were used to calculate handler exposure and risk:

Dermal Dose (mg/kg/day) = Rate (lb ai/lb seed) x UE (mg/lb ai) x DA x Amount Treated (lb/day)

BW (kg)

Inhalation Dose (mg/kg/day) = Rate (lb ai/lb seed) x UE (mg/lb ai) x IAF x Amount Treated (lb/day)

 BW (kg)

Where:
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Rate (Application Rate) = Maximum application rate on product label (lb ai/lb seed)

UE (Unit Exposure) = Exposure value derived from Exposure SAC Policy #14; May 

1, 2003

DA (Dermal Absorption Factor) = Factor to account for dermal absorption (5%) when POD is 

selected from an oral study.

IAF (Inhalation Absorption Factor) = Factor to account for inhalation absorption (100%) when POD 

is selected from an oral study.

Amount Treated = Maximum number of pounds (of seeds) treated per day 

 (lb/day)

BW = Body weight (60 kg)

Combined Daily Dose (mg/kg/day) = Dermal Dose (mg/kg/day) + Inhalation Dose (mg/kg/day)

Total MOE = NOAEL (1.2 mg/kg/day) 

 Combined Daily Dose (mg/kg/day)

Exposure Scenarios

The proposed label states that Cruiser® PD is a wettable powder formulation developed for dry

application to peanut seeds. Since the treater (loader/ operator) unit exposure values from Policy

14 are based on liquid formulations, the loader/operator exposure for Cruiser® PD was estimated 

using surrogate unit exposure values for a wettable powder formulation in the Pesticide Handlers 

Exposure Database (PHED). 

 Loading/Applying Wettable Powder for Seed Treatment (Scenario 1- Cruiser PD -peanuts 

only)

Handler exposure resulting from treatment of peanut and alfalfa seeds using Cruiser® 5FS and 

Cruiser PD in open systems is based on the following exposure scenarios in accordance with 

HED’s Seed Treatment Standard Operating Procedures (SOP) #14:

 Loading/Applying Liquid for Commercial Seed Treatment (Scenario 2 - Cruiser® 5FS) 

 Sewing Bags after Seed Treatment (Scenario 3)

 Bagging Seeds after Seed Treatment (Scenario 4)

 Multiple Activities for Commercial Seed Treatment (Scenario 5)

Handler exposure resulting from treatment of peanut and alfalfa seeds using Cruiser® 5FS and 

Cruiser PD in closed systems is based on the following exposure scenarios in accordance with 

Syngenta’s proprietary seed treatment study, Helix® 289 FS (Novartis Crop Protection Canada 

Inc, J. Purdy. and D. Houghton; August 22, 2000; MRID 452000-02; DP 273566):

 Loading/Applying Liquid for Closed-System Seed Treatment (Scenario 6) 

 Bagging/Sewing/Stacking Bags (Tyvek) after Seed Treatment (Scenario 7)

 Bagging/Sewing/Stacking Bags (Cotton) after Seed Treatment (Scenario 8)

 Forklift Operators (Scenario 9)

 Cleaner (Scenario 10)
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Application Rate

The maximum application rate listed on the proposed label was used for all exposure assessments. 

The maximum rate for treating peanut seeds is 0.00054 lb ai/lb seed, and the maximum rate for 

treating alfalfa seeds is 0.00046 lb ai/lb seed.

Treating Capacity

The treating capacity, which is the amount of seed treated per day in a commercial seed treatment 

facility, was based on the data shown in the Science Advisory Council for Exposure (Exposure 

SAC) Policy #15 or in HED’s previous documents. The following treating capacities were used

to assess seed treatment handlers:

 120,000 lbs/day for treatment of peanut seeds (HED standard assumption);

 718,000 lbs/day for treatment of alfalfa seeds (HED standard assumption)

 The proposed Cruiser ® 5FS label contains a restriction for commercial open system seed 

treatment facilities that limits the amount of product handled per day to no more than 38 

gallons product/worker/8-hr day which results in 413,043 lbs of alfalfa seed a day (38 

gal/day * 5 lb ai/gal)/0.00046 lb ai/lb seed = 413,043 lbs of alfalfa seed). For commercial 

closed system seed treatment facilities the label limits the amount of product handled per 

day to no more than 215 gallons product/worker/8-hr day which results in 2,336,956 lbs of 

alfalfa seed a day (215 gal/day * 5 lb ai/gal)/0.00046 lb ai/lb seed = 2,336,956 lbs of 

alfalfa seed). (MRID 48020202)

Body Weight

The average adult female weight of 60 kg was used for estimating dermal and inhalation exposure 

since the endpoint selected for risk assessment was based on testicular effects in male pups (F1

generation) seen in two different 2-generation reproductive studies in the rat. Since these effects 

could have been due to in utero exposure, the female body weight of 60 kg is used in order to be 

protective of these effects.

Exposure Frequency/Duration

No data on the number of exposure days per year was provided. Due to the seasonal nature of 

seed treatment operation, it was assumed that handlers would be exposed for less than 6 months 

per year (i.e., short-/intermediate-term durations). 

Unit Exposures

The unit exposures used for assessing seed treatment risks were based on the exposure data 

(Table 5) obtained from the Exposure SAC Policy #14: Standard Operating Procedures (SOP) for 

Seed Treatment (May 1, 2003). The Cruiser® PD loader/operator exposure was estimated using 

the unit exposure given for the wettable powder formulation in the Pesticide Handlers Exposure 

Database (PHED). The unit exposures used for assessing closed systems in large commercial 

seed treatment facilities were based on the exposure data (Table 6) obtained from the Helix® 

289FS study (Purdy, J. and Houghton, D. 8/22/2000, MRID No. 45200002).

 
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Table 5. Unit Exposure Values from Exposure SAC Policy #14 (Open System).

 

Scenario Dermal (mg/lb ai) Inhalation (mg/lb ai) PPE Level

Commerical 

Loader/OperatorCruiser®

0.023 0.00034 single layer, glove

Commercial 

Loader/OperatorCruiser® PD

(Wettable Powder -

PHED)

0.17

0.13

0.043 single layer, glove

double layer, gloves

Sewer 0.0062 0.00023 single layer, no glove 

Bagger 0.0091 0.00016 single layer, no glove

Commercial 

Multiple Activities

0.042 0.0016 single layer, glove

 The unit exposures for loader/operator-Cruiser® PD were based on surrogate wettable powder scenario from PHED. 

 

Table 6. Unit Exposure Values from Helix® 289FS study (Closed System).

 

Scenario Dermal (mg/lb ai) Inhalation (mg/lb ai) PPE Level

Loader/Operator 0.0011 0.00011 coverall, glove

Bagger/Sewer/StackTyvek 0.00027 0.000064 Tyvek coverall, glove 

Bagger/Sewer/StackCotton 0.00037 0.000064 Cotton coverall, glove

Forklift Operator 0.000145 0.00001 coverall, glove

Cleaner 0.00921 0.00115 coverall, glove

 Helix® 289FS study : Purdy, J. and Houghton, D. 8/22/2000, MRID No. 45200002.

Handlers’ Exposure and Risk

The exposures and risks for handlers using open and closed loading systems for seed treatment 

facilities are summarized in Tables 7 and 8. The occupational exposures/risks resulting from the 

proposed uses of Cruiser® 5FS and Cruiser PD for treatment of peanut and alfalfa seed using 

open and closed systems do not exceed HED’s level of concern (MOEs ≥ 100) with the exception 

of the following two scenarios.

(1 ) The Cruiser® PD is intended for use as a dry application on peanuts. Since the treater 

(loader/ operator) unit exposure values from Policy 14 are based on liquid formulations, the 

loader/operator exposure for Cruiser® PD was estimated using surrogate unit exposure values for 

a wettable powder formulation in the Pesticide Handlers Exposure Database (PHED). The treater 

scenario resulted in a MOE of 100 with the use of additional PPE (i.e., gloves, coveralls and a 

PF10 respirator). Currently the label only requires use of a dust mask (quarter or half mask) 

respirator. HED recommends that the Registration Division ensure that the appropriate 

respirator is required on the final Cruiser PD label.
Page 13 of 18

(2) The multiple activity scenario for commercially treating 718,000 lbs of alfalfa seed using an 

open system resulted in a MOE of 59 at baseline and addition of gloves. In assessing the multiple 

activity scenario for commercially treating 718,000 lbs of alfalfa seed using an open system, 

handler exposure resulted in a MOE was 59 at baseline with the addition of gloves. With the 

addition of a PF 5 dust mist respirator to current label personal protective equipment (PPE) [ie. 

gloves and coveralls] the multiple activity workers scenario resulted in a MOE greater than 100 

(MOE = 170) which is not of concern. However, the Cruiser® 5FS label contains a restriction for 

commercial open system seed treatment facilities that limits the amount of product handled per 

day to no more than 38 gallons product/worker/8-hr day which results in 413,043 lbs of seed a 

day. Therefore, HED also assessed treatment of 413,043 lbs of alfalfa seed at baseline with

addition of gloves which resulted in a MOE of 100 and was not of concern.

The exposures/risks resulting from the use of Cruiser® Insecticide in commercial closed peanut

seed treatment facility were not quantitatively calculated because they are no greater than those 

resulting from the use of Cruiser® Insecticide on alfalfa because exposures/risks resulting from 

the peanut use are approximately 20% of those resulting from the alfalfa use (Dose= Rate x UE x

DA (or IA) x Amount Treated / BW; when UE, DA, IA, BW are fixed, Exposure from peanut :

Exposure from alfalfa = 0.00054 x 120,000 : 0.00046 x 718,000 = 0.1962 : 1).
Page 14 of 18

Table 7. Thiamethoxam Non-Cancer Risk for Commercial Seed-Treatment Handlers-Open System.

Exposure 

Scenario 

(Scenario #)

Mitigation 

Level

Dermal 

Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Seed 

Species

Application Rate

(lb ai per lb seed)

Amount Treateda

(lb seed trt per day)

Daily

Dermal

Dose b(mg/kg/day)

Daily

Inhalation

Dosec(mg/kg/day)

Combined Daily 

Dosed 

(mg/kg/day)

MOEe 

Loader/Applicator

Loading/Applying

Wettable Powder 

(PHED) (1)

Doublee 

Layer, Gloves 

& PF 10 

Respirator

0.13 0.0043 Peanut 0.00054 120,000 0.00702 0.00464 0.0116 100

Loading/Applying

Liquids for Seed 

Treatment (2)

Single Layer, 

Gloves 0.023 0.00034

Peanut 0.00054 120,000 0.001242 0.0003672 0.001609 750

Alfalfa 0.00046 718,000 0.006325 0.00187 0.008195 150

Sewer

Sewing Bags after 

Seed treatment (3)

Single Layer, 

No Gloves 0.0062 0.00023

Peanut 0.00054 120,000 0.000335 0.000248 0.000583 2,100

Alfalfa 0.00046 718,000 0.001705 0.001265 0.00297 400

Bagger

Bagging Seeds 

after Seed 

treatment (4)

Single Layer, 

No Gloves 0.0091 0.00016

Peanut 0.00054 120,000 0.000491 0.000173 0.000664 1,800

Alfalfa 0.00046 718,000 0.002503 0.00088 0.003383 360

Multiple Activities Worker

Multiple Activities 

for Seed treatment 

(5)

Single Layer, 

Gloves 0.042 0.0016 Peanut 0.00054 120,000 0.002268 0.001728 0.003996 300

Alfalfa 0.00046

718,000

0.01155 0.0088 0.02035 59

Double layer, 

Gloves

0.019

0.0016

0.005229

0.0088 0.0140 85

Double layer, 

Gloves, & 

Dust Mist 

Respirator

0.00032 0.00176 0.00699 170

Single Layer, 

Gloves 0.042 0.0016 413043 * 0.00665 0.0050 0.01171 100

a Daily amounts treated values are based on exposure SAC Policy #15 or the information provided by the Registrant through Registration Division (413043 lb seed treated per day is the daily seed treated value in 

accordance with label restriction for open loading system). 

b Daily Dermal Dose (mg/kg/d) = [Unit Dermal Exposure (mg/lb ai) * Dermal Absorption Factor (0.05) * Application Rate (lb ai/lb seed) * Daily Amounts Treated] / Body Weight (60 kg).

c Daily Inhalation Dose (mg/kg/d) = [Unit Exposure (mg/lb ai) * Application. Rate (lb ai/lb seed) * Daily Amounts Treated]/ Body Weight (60 kg).

d Combined Daily Dose (mg/kg/d) = Daily Dermal Dose (mg/kg/day) + Daily Inhalation Dose (mg/kg/day).

e MOE = NOAEL (1.2 mg/kg/d) / Combined Daily Dose. UF = 100.
Page 15 of 18

Table 8. Thiamethoxam Non-Cancer Risk for Commercial Seed-Treatment Handlers-Closed System.

Exposure 

Scenario 

(Scenario #)

Mitigation 

Level

Dermal 

Unit 

Exposure 

(mg/lb ai)

Inhalation Unit 

Exposure 

(mg/lb ai)

Seed 

Species

Application Rate

(lb ai per lb seed)

Amount 

Treateda

(lb seed trt 

per day)

Daily

Dermal

Dose b

(mg/kg/day)

Daily

Inhalation

Dosec

(mg/kg/day)

Combined 

Daily Dosed 

(mg/kg/day)

MOEe 

Loader/Applicator

TreaterLoader/Applicat

or (6)

Coveralls, 

Gloves 0.0011 0.00011 Alfalfa 0.00046 718,000 0.0003027 0.0006055 0.0009082 1,300

Bagger/Sewer/Stacker

Bagger/Sewer/S

tacker (7) + (8)

Coveralls, 

Gloves

0.00027 0.000064 Alfalfa 0.00046 718,000 0.0000743 0.0003552 0.0004295 2,800

0.00037 0.000064 Alfalfa 0.00046 718,000 0.0001018 0.0003552 0.000457 2,600

Forklift Operator

Forklife 

Operator (9)

Coveralls, 

Gloves 0.000145 0.00001 Alfalfa 0.00046 718,000 0.0000399 0.000055 0.0000949 13,000

Cleaner

Cleaner (10)

Coveralls, 

Gloves 0.00921 0.00115 Alfalfa 0.00046 718,000 0.002535 0.00633 0.008865 140

a Daily amounts treated values are based on exposure SAC Policy #15 or the information provided by the Registrant through Registration Division. 

b Daily Dermal Dose (mg/kg/d) = [Unit Dermal Exposure (mg/lb ai) * Dermal Absorption Factor (0.05) * Application Rate (lb ai/lb seed) * Daily Amounts Treated/ Body Weight (60 kg).

c Daily Inhalation Dose (mg/kg/d) = [Unit Exposure (mg/lb ai) * Application Rate (lb ai/lb seed) * Daily Amounts Treated] / Body Weight (60 kg).

d Combined Daily Dose (mg/kg/d) = Daily Dermal Dose (mg/kg/day) + Daily Inhalation Dose (mg/kg/day).

e MOE = NOAEL (1.2 mg/kg/d) / Combined Daily Dose. UF = 100.
Page 16 of 18

5.2 Secondary Seed Handlers

Scenario and Unit Exposure

The exposure scenario for secondary seed handlers from treated seeds consists of the farmer 

purchasing bags of treated seeds, placing the seeds in the hopper, and planting seeds in fields. 

The exposure associated with handling treated seeds was calculated using unit exposures given in

the HED Exposure Science Advisory Council (ExpoSAC) Policy #14 (May 1, 2003).

Assumptions and Factors

· Unit Exposure is based on HED Exposure SAC Policy #14 (Dermal Unit Exposure = 0.25 mg/lb ai; 

Inhalation Unit Exposure = 0.0034 mg/lb ai) 

· Amount of seed planted per day (lb seed/day) is based on the data shown in HED Exposure SAC 

Policy # 15 (11,000 lb/day for peanut and 4,000 lb/day for alfalfa)

· Exposure Frequency = 60 days/year and 8 hour/day exposure

· Body Weight = 60 kg

· Dermal Absorption Factor (DAF) = 5%, Inhalation Absorption Factor (IAF) = 100%

Equations and Calculations

Daily Dermal Dose = Dermal UE x Amount of Seed Planted/day x Application Rate x DAF

Body Weight (kg)

Daily Inhalation Dose = Inhalation UE x Amount of Seed Planted/day x Application Rate x IAF

Body Weight (kg)

 Combined Daily Dose Dose (mg/kg/day) = Daily Dermal Dose + Daily Inhalation Dose

MOE = NOAEL (1.2 mg/kg/day) 

 Combined Daily Dose (mg/kg/day)

Secondary Seed Handler’s Exposure and Risk

All MOEs for secondary seed handlers are greater than 100 and do not exceed HED’s level of 

concern at the single layer plus gloves level of mitigation (760 to 2,500). A summary of the

exposure/risk values is presented in Table 9.

 

The secondary seed handler’s exposure estimates in this assessment are based on a central 

tendency estimate of unit exposure, upper-percentile assumptions for the application rate, and a 

conservative estimate of exposure frequency; and are assumed to be representative of high-end 

exposures. The uncertainties associated with this assessment stem from the use of surrogate 

exposure data (e.g., differences in use scenario and data confidence) and assumptions regarding 

that amount of chemical handled. The estimated exposures are believed to be reasonable high-end 

estimates based on observations from field studies and professional judgment.

Restricted Entry Interval

The restricted entry interval (REI) is based on the acute dermal toxicity, eye irritation and skin 

irritation effects of the active ingredient. The thiamethoxam technical material is classified as 
Page 17 of 18

Category III for acute oral and Category IV for acute dermal and eye irritation. Thiamethoxam is 

not a dermal sensitizer. Acute toxicity categories III and IV chemicals require a 12-hour REI. 

The Worker Protection Standard (WPS) allows workers to enter treated areas without restriction if 

there will be no contact with anything that has been treated with the pesticide. For purposes of 

seed treatment, once the seeds are planted, workers can enter during the REI, provided they do not 

contact the soil/media subsurface that contains the treated seeds. Certain tasks may involve 

contact with the soil subsurface (e.g. repair of certain irrigation equipment) and they are covered 

by the REI. Therefore, a 12-hour REI on the proposed label is required. 

6.0 REVIEW OF HUMAN RESEARCH

This exposure/risk assessment relies in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED). EPA has 

reviewed all the studies in these multi-pesticide generic exposure databases, and on the basis of 

available evidence has found them to have been neither fundamentally unethical nor significantly

deficient relative to standards of ethical research conduct prevailing when they were conducted. 

There is no regulatory barrier to continued reliance on these studies, and all applicable 

requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) 

have been satisfied.
Page 18 of 18

Table 9. Thiamethoxam Non-Cancer Risk for Secondary Seed Handlers.

Exposure Scenario 

(Scenario #)

Mitigation 

Level

Dermal 

Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Seed Species Application 

Rate

(lb ai per lb 

seed)

Amount 

Planteda

(lb seed 

pnted/day)

Daily

Dermal

Dose b

(mg/kg/day)

Daily

Inhalation

Dosec

(mg/kg/day)

Combined 

Daily Dosed

(mg/kg/day)

MOEe 

Secondary Seed Handlers

Secondary Seed 

Handlers: planting 

seeds in the field

Single 

Layer, 

Gloves

0.25 0.00342

Peanut 0.00054 11,000 0.001238 0.000337 0.001575 760

Alfalfa 0.00046 4,000 0.0003833 0.0001042 0.0004875 2,500

a Daily amounts planted values are based on exposure SAC Policy #15 or the information provided by the Registrant through Registration Division.

b Daily Dermal Dose (mg/kg/d) = [Unit Dermal Exposure (mg/lb ai) * Dermal Absorption Factor (0.05) * Application Rate (lb ai/lb seed) * Daily Amounts Treated] / Body Weight (60 kg).

c Daily Inhalation Dose (mg/kg/d) = [Unit Exposure (mg/lb ai) * Application Rate (lb ai/lb seed) * Daily Amounts Treated] / Body Weight (60 kg).

d Combined Daily Dose (mg/kg/d) = Daily Dermal Dose (mg/kg/day) + Daily Inhalation Dose (mg/kg/day).

e MOE = NOAEL (1.2 mg/kg/d) / Combined Daily Dose. UF = 100.

CC: RAB2 RF, D. McNeilly, S. Wang