Document ID: EPA-HQ-OPP-2010-0324-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-08-17T04:00Z

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.

	Table of Contents

 TOC \f 

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

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. 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 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 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.

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

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.   

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, chemical-resistant 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 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 ® 5FS-

Reg. 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.

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.  

 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)]

  SEQ CHAPTER \h \r 1 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:

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)

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).

                

 

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/Operator- Cruiser®	

0.023	

0.00034	

single layer, glove

Commercial Loader/Operator- Cruiser® 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/Stack-Tyvek	

0.00027	

0.000064	

Tyvek coverall, glove 

Bagger/Sewer/Stack-Cotton	

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

≥ 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.

(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).



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.

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

Treater-Loader/Applicator (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/Stacker (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.

5.2  Secondary Seed Handlers  tc \l2 "5.2.2  Post-application  

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
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         SEQ CHAPTER \h \r 1 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.

	

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.

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