Page 1 of 18 UNI TED STATES ENVIRONMENTALPROTECTI ON AGENCY

WASHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION MEMORANDUM Date: December 3 , 20 10 Subject: Thiamethoxam : Occupational and Residential Exposure/Risk Assessment for

Proposed Section 3 Registration for Seed Treatment Use s on Peanut and Alfalfa
. PC Code: 0 60109 DP Barcode: D3 7 3377 ; D376089 MRID No.: 48020202 Registration No.: 100
- 936 ; 100941 Petition No.: 9F7657 ; 0 F7707 Regula tory Action: Section 3 Registration Assessment Type: ORE Reregistration Case No.: NA TXR No.: NA CAS No.: 152719
- 23
- 4 Decision No. : 4 24517 ; 430284 40 CFR: 180.565 FROM: Shih
- Chi Wang, Biologist

Risk Assessment Branch 2 Health Effects Division (7509P) THRU : Richard L oranger, Ph.D., Branch Senior Scientist

Margarita Collantes, M.S. Biologist Risk Assessment Branch 2 Health Effects Division (7509P) TO : Kable Dav is/Venus Eagle, RM 01

In secticide
- Rodenticide Branch Registration Division (7505P) CONCLUSIONS The registrant, Sy

ngenta, has requested a label amendment to add treatment of alfalfa and peanut seeds using both open and closed commercial seed treating sy stems to the existing Cruiser® 5FS label. The registrant also submitted a request for a new product registration for Cruiser® PD In secticide for seed treatment of peanuts in open and closed commercial seed treatment facilities HED has evaluated the proposed seed treatment use s of thiamethoxam on p eanut and alfalfa
. T he potential occupational exposures/risks resulting from the proposed use s 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.Page 2 of 18 Table of Contents
1.0 Executive Summary
................................ ................................ ................................ .................. 3 2.0 Hazard Characterization
................................ ................................ ................................ ............ 5 3.0 Pro posed Use Pattern
................................ ................................ ................................ ................ 7 4.0 Residential (Non
- Occupational ) Exposure
................................ ................................ .............. 8 5.0 Occupational Exposure
................................ ................................ ................................ ............. 9 5.1 Handlers
................................ ................................ ................................ ....................... 9 5.2 Secondary

Seed Handlers
................................ ................................ ........................... 1 6 6.0 Review of Human Research
................................ ................................ ................................ ... 1 7Page 3 of 18

I. EXECUTIVE SUMMARY Thiamethoxam is a sy stemic insecticide belonging to the neonicotinoid class of chemistry . It is used to treat various agricultural crops, turf grass, sod farms, gol f course, residential lawns, indoor crack s and crevice s , ornamental plants grown in greenhouses, and Christmas trees. The registrant, Sy ngenta, has requested a label amendment to add treatment of alfalfa and peanut s eeds using both open and closed commerc ial 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 peanut s 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 use s on peanut and alfalfa do not result in additional residential exposure and risk. R esidential exposure s and risks assessed previously w ere summarized in this document for the purpose of conducting an aggregate exposure and risk assessment. Hazard Characterizatio n Thiam ethoxam is classified as Toxicity Category I II 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 wer e 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 i s based on an oral study

a dermal absorption factor of 5% was used to estimate exposure. A lthough 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 derma l 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 s ) of 10x for interspecies extrapolation and 10x for intraspecies varia

bility (total UF of 100x) were used. Therefore, for all occupatio nal and residential exposure scenarios, the level of concern (LOC) is a margin of exposure (MOE) of 100.Page 4 of 18

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 no t performed at this time in conjunction with the proposed use s . The proposed uses are limited to occupational worke rs (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 an d 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/p lanting data fr om 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. Si nce the treater (loader/ operator) unit exposure values from Policy 14 are based on liquid formulations, the loader/ operator exposure for Cruiser® PD was estimate d using surrogate unit exposure values for a w ettable powder formulation in the P esticide Han dlers Exposure Database (P HED )
. 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. Inassessing the multiple activity scenario for commercially treating 718,000 lbs of alfalfa seed using an open system , handler exposure resu lted in a MOE of 59 at baseline with addition of gloves. T he addition of a PF 5 dust m i s t 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 = 1 7 0)
. Howev er, 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 3 8 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 aPage 5 of 18

single layer of clothing plus gloves , with MOEs rang ing from 760 to 2,500 and were not of concern . R eview 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 I II 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 abs orption factor of 5% was used to estimate exposure. A lthough 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 se lected 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. Th erefore, 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 10xPage 6 of 18

for intraspecies varia

bility (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
- genotoxi c 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 requi red
. 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 ( D 371303)
. N o 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 c oncern (LOC) of 100 for MOEs for both residential and occupational exposure assessments.

Table 1 . Acute Toxicity Profile of Thiam ethoxam . Guideline No. Study Type MRID(s) Results Toxicity Category 870.1100 Acute oral [rat] 44703314 LD 50 : 1563 mg/kg III 870.1200 Acute dermal [rabbit] 44703316 LD 50 = 13.3 g/kg IV 870.1300 Acute inhalation [rat] 44703317 LC 50 > 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 ir ritation 44703319 PIS = 0 IV 870.2600 Skin sensitization 44710401 Is not a sensitizer using method of Magnusson and Kligman N/APage 7 of 18

Abbreviations: UF = uncertainty factor, UF A = extrapolation from animal to human (intersp ecies), UF H = 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 leve l, MOE = margin of exposure, LOC = level of concern.
3.0 PROPOSED USE PATTERN The p roposed use pattern for thiamethoxam [Cruiser® 5FS In secticide ( 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, chemical
resistant gloves, and s hoes 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 In secticide 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 Thiom ethoxam Occupational Handler Risk Assessm ents. Exposure/ Scen ario Point of

Departure Uncertainty Factors

(UF) Level of Concern for Risk Assessm ent Study and Toxicological Effects Dermal (all durations) (Adults) Oral study

NOAEL= 1.2 mg/kg/day ( D ermal A bsorption Factor = 5%) UF A= 10x

UF H = 10x LOC = an MOE of 10 0 (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 determi ned (females) mg/kg/day based on sperm abnormalities in F1 males. Inhalation (all durations) Oral study

NOAEL= 1.2 mg/kg/day ( I nhalation A bsorption Factor = 100% of oral absorption) UF A= 10x

UF H = 10x LOC = an MOE of 100 (occupational) 2 - Generation re production

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 Hum ans” 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.Page 8 of 18 mask, quarter or half mask respirator). Table 3. Propos ed Use Pattern for Thiam ethoxam . Crop Seed Product,

Form ulation Treatm ent Type Applications Per Season 1 Maxim um Application Rate 2 (lb ai/lb seed) PHI 3 (days) Per Application Per Season Peanut Cruiser ® 5FS

Reg. No. 100
- 941 Op en and Closed

Commercial Seed Treatment NA 0.00054 NA NA

Cruiser PD Reg. No. 100
- RGAL NA 0.00054 NA NA
Alfalfa Cruiser ® 5FS
Reg. No. 100
- 941 C om mercial (open and closed systems) Seed Treatment NA 0. 00046 NA NA

1 Maximum number of applications allo wed on label. 2 Rate = Maximum application rates specified on proposed labels ( Peanut: 0.2 9 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 postap plication). 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, D359 207 ). 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 cond ucted. A ll 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 th e 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 a nd 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.Page 9 of 18

Table 4. Combined Residential Exposure and Risk Estim ates fromthe Indoor Crack and Crevice Use . Post - application Scenarios Daily Dose (m g/kg/day) 1 MOE 2 Combined MOE 3 Short - term Adult Dermal

– indoor surface 0.0027 8 430 430 Toddler Dermal
- indoor surface 0.08 750 610 Hand
- to - Mouth 0.00267 3100 Interm ediate - term Adult Dermal
- indoor surface 0. 0 027 8 430 430 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/MOE Dermal) + (1/MOE Hand
- to - Mouth)]
5.0. OCCUPATIONAL EXPOSURE Sy ngenta 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 o pen 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 activit ies
. 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: Derm al 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:Page 10 of 18 Rate (App lication 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 ( D ermal A

bsorption F actor) = Factor to account for dermal absorption ( 5 %) w hen POD is sele cted from an oral study. IAF (Inhalation Absorption Factor) = Factor to account for inhalation absorption (100%) w hen 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 powd er 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).

 Lo ading/Applying W ettable Powder for Seed Treatment (Scenario 1
- Cruiser PD
- peanuts only ) Handler exposure resulting from treatment of peanut and alfalfa s eeds using Cruiser® 5FS and Cruiser PD in open systems is based on the following exposure scenarios in accordance with HED’s Seed Treatment Standard Operatin g Procedures (SOP) #14:

 Lo ading/Applying Li quid for Commercial Seed Treatment (Scenario 2
- Cruise r® 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 sy stems is based on the following exposure scenarios in accordance with Sy ngenta’s proprietary

seed treatment study , Helix® 289 FS (Novartis Crop Protection Canada In c, J. Purdy . and D. Houghton; August 22, 2000; MRID 452000
- 02; DP 273566) :

 Lo ading/Applying Liquid for Close d
- Sy stem Seed Treatment (Scenario 6 )  Bagging/Sewing/Stacking Bags (Ty vek) after Seed Treatment (Scenario 7 )  Bagging/Sewing/Stacking Bags (Cotton) after Seed Treatment (Scenario 8 )  Forklif

t Operators (Scenario 9 )  Cleaner (Scenario 1 0 )Page 11 of 18

Application Rate The maximum application rate listed on the proposed label w as used for all exposure assessments. The maximum rate for treating peanut seeds is 0. 00 0 54 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 , w as based on the data shown in the Science Advisory Council for Exposure (Exposure SAC) Policy

#15 o r in HED’s previous documents
. The f o llowing treating capacit ies were used to assess seed treatment handlers :

 120 , 0 00 lbs/day

for treatment of peanut seeds (HED standard assumption) ;  718,000 lbs/day for treatment of alfalfa seeds (HED standard assumpti on)  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 se ed 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 wh ich results in 2,3 3 6,956 lbs of alfalfa seed a day

(215 gal/day

* 5 lb ai/gal)/0.00046 lb ai/lb seed = 2,3 3 6,956 lbs of alfalfa seed). (MRID 48020202) Body Weight The average adult female weight of 60 kg was used for estimating dermal and inhalation exp osure 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 fema le 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 wou ld be exposed for less than 6 months per year (i.e. , short
- /intermediate
- term duration s ). 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: Stan dard Operating Procedures (SOP) for Seed Treatment (May

1, 2003). The Cruiser® PD loader/operator exposure was estimated using the unit exposure given for the w ettable powder formulation in the Pesticide Handlers Exposure Database (PHED). The unit expos ures used for assessing closed system s 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).Page 12 of 18 Table 5. Unit Exposure Values fromExposure SAC Policy #14 (Open System) . Scenario Derm al (m g/lb ai) Inhalation (m g/lb ai) PPE Level Commerical Loader/Operator
Cruiser® 0.023 0.00034 single layer, glove

Commercial Loader/Operator
Cruiser® PD (Wettable Powder
- PHED) 0. 1 7

0.13 0.0 43 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 we re based on surrogate w ettable powder scenario from PHED. Table 6. Unit Exposure Values from Helix® 289FS study (Closed System) . Scenario Derm al (m g/lb ai) Inhalation (m g /lb ai) PPE Level Loader/Operator 0.0 011 0.000 11 coverall , glove Bagger/ Sewer

/Stack
Ty vek 0.00 027 0.00 0 0 64 Ty vek coverall , glove Bagger /Sewer/Stack
Cotton 0.00 037 0.000 0 6 4 Cotton coverall, glove Forklif t Operator 0.000145 0.00001 coverall, glov e 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 treatme nt 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 (MO Es ≥ 100) with the exception of the following two scenario s . (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/op erator 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. , gl oves, 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 sy stem resulted in a MOE of 59 at baseline and addition of gloves
. Inassessing 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. W ith the addition of a PF 5 dust m ist 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 = 1 7 0) 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 handle d 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 o f 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 a lfalfa 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. Thiam ethoxamNon - Cancer Risk for Com me rcial Seed - Treatm ent Handlers - Open System . Exposure Scenario (Scenario #) Mitigation

Level Dermal

Unit Exposure (mg/lb ai) Inh alation

Unit Exposure (mg/lb ai) Seed

Species Application Rate

(lb ai per lb seed) Amount Treated a

(lb seed trt per day) Daily Dermal Dose b (mg/kg/day) Daily Inhalation Dose c (mg/kg/day) Combined Daily Dose d (mg/kg/day) MOE e
Loader/Applicator Loading/Applying Wettable Powder (PHED) (1) Doublee

Layer, Gloves & PF 10 Respirator 0.13 0.0043 Peanut 0.00054 120,000 0.007 0 2 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 71 8,000 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 provid ed 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 D ermal D ose (mg/kg/d) = [ Unit D ermal E xposure (mg/lb ai) * D ermal Absorption Factor (0.0 5 ) * A pplication R ate (lb ai/lb seed) * D aily Amounts T reated ] / B ody W eight ( 6 0 kg). c Daily Inhalation D ose (mg/kg/d) = [Unit E xposure (mg/lb ai) * A pplication. R ate (lb ai/lb seed) * D aily Amounts T reated ] / B ody W eight ( 6 0 kg). d Combined D aily D ose (mg/kg/d) = Daily D ermal D ose (mg/kg/d ay ) + Daily Inhalation D ose (mg/kg/d ay )
. e MOE = NOAEL ( 1
. 2 mg/kg/d) / C ombined D aily D ose. UF = 100.Page 15 of 18

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

Treated a (lb seed trt per day) Daily

Dermal Dose b (mg/kg/day) Dai ly

Inhalation Dose c (mg/kg/day) Combined

Daily Dose d (mg/kg/day) MOE e
Loader/Applicator Treater
Loader/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 t acker ( 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 0.0001 45 0.00001 Alfalfa 0.00046 718,000 0.0000399 0.000055 0.0000949 13,000 Cleaner Cleaner (1 0 ) 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 t he information provided by the Registrant through Registration Division. b Daily D ermal D ose (mg/kg/d) = [ Unit D ermal E xposure (mg/lb ai) * D ermal Absorption Factor (0.0 5 ) * A pplication R ate (lb ai/lb seed) * D aily Amounts T reated/ B ody W eight ( 6 0 kg). c Daily Inhalation D ose (mg/kg/d) = [Unit E xposure (mg/lb ai) * A pplication R ate (lb ai/lb seed) * D aily Amounts T reated ] / B ody W eight ( 6 0 kg). d Combined D aily D ose (mg/kg/d) = Daily D ermal D ose (mg/kg/d ay ) + Daily Inhalation D ose (mg/kg/d ay )
. e MOE = NOAEL ( 1
. 2 mg/kg/d) / C ombined D aily D ose. UF = 100.Page 16 of 18

5.2 Secondary Seed Handlers Scenario and Unit Exposure The exposure scenario for secondary seed handlers from treat ed seeds consists of the farmer purchasi ng bags of treated seed s , placing the seed s in the hopper, and planting seed s in fields. The e xposure associated with handling treat ed seeds was calculated using unit exposures given in the HED Exposure Science Advisory Council (ExpoSAC) Policy #14 (May

1 , 2003)
. Assumptions and Factors

· Unit E xposure is based on HED Exposure SAC Policy #14 ( D ermal Unit E xposure = 0.25 mg/lb ai; Inhalation Unit E xposure = 0.0034 mg/lb ai)

· Amount of seed planted per day (lb seed/day

) is based on the data shown in H ED Exposure SAC Policy # 15 ( 11,000 lb/day for peanut and 4,000 lb/day for alfalfa)

· Exposure F requency = 60 day s/year and 8 hour/day exposure

· Body W eight = 6 0 kg

· Dermal Absorption Factor (DA F ) = 5 %, Inhalation Absorption Factor (IAF) = 100% Equations an d Calculations Daily Derm al 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) Combin ed Daily Dose Dose (m g/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 MOE s 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 hi gh
- 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 eff

ects of the active ingredient. The thiamethoxam technical material is classified asPage 17 of 18

Category I II for acute oral and Category IV for acute dermal and eye irritation. T hiamethoxam is not a dermal sensitizer. Acute toxicity categories I II 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 any thing 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 cov ered by the REI . Therefore, a 12
- hour REIon 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

e xposed 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 re viewed 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 pre vailing 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 . Th iam ethoxamNon - 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

Planted a (lb s eed pnted/day) Daily

Dermal Dose b (mg/kg/day) Daily

Inhalation Dose c (mg/kg/day) Combined

Daily Dose d (mg/kg/day) MOE e

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 D ermal D ose (mg/kg/d) = [ Unit D ermal E xposure (mg/lb ai) * D ermal Absorption Factor (0.0 5 ) * A pplication R ate (lb ai/lb seed) * D aily Amounts T reated ] / B ody W eight ( 6 0 kg). c Daily Inhalation D ose (mg/kg/d) = [Unit E xposure (mg/lb ai) * A pplication R ate (lb ai/lb seed) * D aily Amounts T reated ] / B ody W eight ( 6 0 kg). d Combined D aily D ose (mg/kg/d) = Daily D ermal D ose (mg/kg/d ay ) + Daily Inhalation D ose (mg/kg/d ay )
. e MOE = NOAEL ( 1
. 2 mg/kg/d) / C ombined D aily D ose. UF = 100. CC: RAB2 RF, D. McNeilly , S. Wang