Document ID: EPA-HQ-OPP-2009-0737-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-06-23T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

CHEMICAL SAFETY

AND POLLUTION PREVENTION

MEMORANDUM  

Date:		May 3, 2010 

Subject:	Thiamethoxam: Occupational and Residential Exposure/Risk
Assessment for Proposed Section 3 Registration for Seed Treatment Use on
Bulb Onions.  

		PC Code: 060109			DP Barcode: D372848

                        MRID No.:  NA			Registration No.:  100-1294
Cruiser 70 WS 

		Petition No.:  NA			Regulatory Action: Section 3 Registration

                        Assessment Type: ORE		Reregistration Case No.: 
NA

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

                        Decision No.:  415289		40 CFR:  180.565

	

TO:		Venus Eagle, RM 01

		Insecticide-Rodenticide Branch 

		Registration Division (7505P)

FROM:	Shih-Chi Wang, Biologist

		Risk Assessment Branch 2

		Health Effects Division (7509P)

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

		Risk Assessment Branch 2

		Health Effects Division (7509P)

CONCLUSIONS

HED has evaluated the proposed seed treatment use of thiamethoxam on
bulb onions.  With the exception of the multiple activities scenario,
using HED’s standard assumptions for the amount of seed treated per
day (5,500 & 300 lbs treated/day for film-coated and pelletized seed
treatments, respectively), the potential occupational exposures/risks
resulting from the proposed use do not exceed HED’s level of concern. 

The margin of exposure (MOE) of 59 estimated for the multiple activities
scenario with film-coated seed is below HED’s level of concern of an
MOE of 100; however, this is a conservative estimate for the following
reasons.  First, it was based on the use of a single layer plus gloves
as personal protection.  If dust mask and coveralls (currently required
on the label) are added, the exposure for multiple activities workers
may be not of concern.  In addition, the MOE of 59 for the multiple
activities scenario is based on the unit exposure value for liquid
products, but the product being evaluated for the proposed use of
thiamethoxam is a wettable powder packaged in water soluble packets (an
engineering control measure which can provide more than 50% reduction in
exposures).  Therefore, HED does not consider the MOE of 59 to be of
concern.   

If the Registration Division considers it appropriate, additional label
language can be added to minimize the chance that the LOC of 100 is
exceeded for multiple activities workers.  In this case, the label
should indicate that the maximum amount of CRUISER® 70WS Insecticide
that can be used to treat bulb onion seed in a seed treatment facility
is 260 lbs per production line per 8-hour work shift (based on the MOE
calculated for treating 3,000 lbs seed per day;   MOE for multiple
activities worker = 110).  This requires that a worker perform tasks
associated with seed treatment only on one production line per 8-hour
shift and the worker works no more than one 8-hour shift per 24 hour
period.

	Table of Contents

 TOC \f 

1.0  Executive Summary	3

2.0  Hazard Characterization	5

Acute Toxicity of Thiamethoxam 	6

Toxicological PODs Selected by the HED for Thiamethoxam 	6

3.0  Proposed Use Pattern	7

4.0  Residential (Non-Occupational) Exposure 	7

5.0  Occupational Exposure	8

            5.1  Handlers 	8

5.2  Secondary Seed Handlers 	11

              

 

6.0  Review of Human Research 	12

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 registration to the CRUISER®
70WS Insecticide (packaged in water soluble bags) for both pelletized &
film-coated seed treatment uses on bulb onions.  Thiamethoxam is to be
applied only in 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 (indoor crack and crevice and
outdoor turf) scenarios, the proposed seed treatment use on bulb onions
does not result in additional residential exposure and risk. 
Residential exposures and risks were previously summarized 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 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.  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 NOAEL of 1.2 mg/kg/day
(point of departure for all durations) and reproductive effects
(endpoints) for inhalation risk assessment that were used in the dermal
assessment.   Since an oral study was selected for both dermal and
inhalation risk assessments, 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 in conjunction with the proposed use, which is limited to
occupational workers (handlers and postapplication).  For the purpose of
conducting an aggregate assessment, refer to the most recent residential
exposure and risk assessment (M. Collantes, November 24, 2009, D371303)
for a summary of scenarios, exposures and risks.  All handlers and
post-application scenarios 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 use on bulb onions for seed
treatment 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 & Policy # 14:
Amount of Seed Treated or Planted Per Day (March 2, 2004).  The one
exception is the substitution of the loader/operator exposure estimates
with the unit exposures given for the water soluble packets formulation
in the Pesticide Handlers Exposure Database (PHED).  This substitution
was made because the product being evaluated is a water soluble bag, and
not a liquid.  

With the exception of the multiple activities scenario using HED’s
standard assumption regarding the amount of seed treated per day (5,500
lbs treated/day, MOE=59), the potential occupational exposures/risks
resulting from the proposed use do not exceed the HED level of concern
(MOEs range from 300 to 7,400).  The MOE of 59 for the multiple
activities scenario is a very conservative estimate because it was based
on single layer plus gloves protection.  If dust mask and coveralls are
added, as currently required on the label, the exposure for multiple
task workers may be not of concern.  In addition, the MOE of 59 for the
multiple activities scenario is based on the unit exposure for liquid
product, and the product being evaluated here is a wettable powder
packaged in water soluble packets (an engineering control measure which
can provide more than 50% reduction in exposures); therefore this MOE is
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 190 to 310.  

Review of Human Research

This risk assessment relies in part on data from studies in which adult
human subjects were intentionally exposed to a pesticide or other
chemical.  These studies, which comprise the Pesticide Handlers Exposure
Database (PHED) have been determined to require a review of their
ethical conduct, and have received that review; and were considered
appropriate for use in risk assessments.

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.  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 NOAEL of 1.2 mg/kg/day
(point of departure for all durations) and reproductive effects
(endpoints) for inhalation risk assessment that were used in the dermal
assessment.   Since an oral study was selected for both dermal and
inhalation risk assessments, 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 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	Level of Concern for
Risk Assessment	Study and Toxicological Effects

Dermal (all durations) (Adults)

	Oral study NOAEL= 1.2

 mg/kg/day

(dermal absorption rate = 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 rate = 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.   

UF = Uncertainty Factor

LOC = Level of Concern

3.0	PROPOSED USE PATTERN

The proposed use pattern for thiamethoxam (packaged in water soluble
bags, thiamethoxam 70.0%) as a seed treatment for bulb onions is
summarized in Table 3.

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

	Bulb Onions	Cruiser 70WS

-water soluble bags	Seed Treatment: commercial-

pelleted & film-coated

seed treatment	NA	0.06	NA	NA

1 Maximum number of applications allowed on label.

2 Rate = Maximum application rates specified on proposed labels (0.20 mg
per seed, 136,000 seeds per pound).  This number of       seeds per
pound represents the middle of the range specified in Exp SAC SOP 15
(120,000 to 154,640 seeds per pound).

3 PHI = Pre-harvest Interval

4 NA= Not Applicable

RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE/RISK PATHWAY

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.

HED assumes that inhalation exposures are minimal following outdoor
applications of an active ingredient, due to the large volume of air
exchange.  A separate inhalation post-application risk assessment was
not conducted since post-application inhalation exposure is expected to
be much lower than the inhalation exposure associated with pesticide
applications.  Therefore, a handlers’ inhalation exposure and risk
assessment is protective of post-application exposure and risk.  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.  

A revised combined residential assessment based on indoor crack and
crevice use was performed in the July 2009 thiamethoxam residential
assessment (M. Collantes, July 2009, D359462).   HED combined all
non-dietary sources of post-application exposure to obtain an estimate
of potential combined residential exposure.  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.  A
summary of the combined residential exposures is provided in Table 4.

Spray drift is always a potential source of exposure to residents nearby
to spraying operations.  This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for
thiamethoxam.  The Agency has been working with the Spray Drift Task
Force, EPA Regional Offices and State Lead Agencies for pesticide
regulation and other parties to develop the best spray drift management
practices.  The Agency is now requiring interim mitigation measures for
aerial applications that must be placed on product labels/labeling.  The
Agency has completed its evaluation of the new database submitted by the
Spray Drift Task Force, a membership of U.S. pesticide registrants, and
is developing a policy on how to appropriately apply the data and the
AgDRIFT computer model to its risk assessments for pesticides applied by
air, orchard airblast and ground hydraulic methods.  After the policy is
in place, the Agency may impose further refinements in spray drift
management practices to reduce off-target drift and risks associated
with aerial as well as other application types where appropriate.

 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	0.0027	430	430

Toddler Dermal - indoor surface	0.08	750	

610

Hand-to-Mouth	0.00267	3100

	Intermediate-term

Adult Dermal - indoor surface	0.027	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

	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

This assessment only covers commercial handlers (loader/applicator,
sewer, bagger, and multiple activities worker).  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
lb. Treated (lb/day)

BW (kg)

Inhalation Dose (mg/kg/day)	=	 Rate (lb ai/lb seed) x UE (mg/lb ai) x
lb. 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.

lb. 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)

MOE	                                                         =          
 NOAEL (1.2 mg/kg/day)              

                                                                        
             Combined Daily Dose (mg/kg/day)

Exposure Scenarios

There are four handler scenarios that are typically assessed by HED and
are expected to result in the highest exposure for the proposed use:

Loading (Open)/Applying Water Soluble Bags for Seed Treatment (Scenario
1) 

Sewing Bags after Seed Treatment (Scenario 2)

Bagging Seeds after Seed Treatment (Scenario 3)

Multiple Activities Worker for Seed Treatment (Scenario 4)

Application Rate

The maximum application rate listed on the proposed label provided by
the Registration Division was used for all exposure assessments.  The
maximum rate for treating bulb onion seeds is 0.06 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:

5,500  lbs/day for film-coated treatment of vegetable seeds (HED
standard assumption);

300 lbs/day for pelletized seed treatment (as used in previous
assessment; M. Collantes, 11/12/08, D 354886) 

Body Weight

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

Because the endpoint selected for risk assessment was based on
testicular effects in male pups (F1generation) seen in two different
2-generation reproductive studies in the rat.   Because these effects
could have been due to in utero exposure, the female body weight 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 one exception is the substitution of the loader/operator exposure
estimates recommended in Policy #14 with the unit exposures given for
loader/applicator for the water soluble packets formulation in the PHED
(because the product being evaluated is water soluble bags, not liquid).

                Table 5.  Unit Exposure Values from Exposure SAC Policy
#14.

  

Scenario	

Dermal (mg/lb ai)	

Inhalation (mg/lb ai)	

PPE Level

Loader/Operator	

0.0098	

0.00024	

single layer, glove

Sewer	

0.0062	

0.00023	

single layer, no glove 

Bagger	

0.0091	

0.00016	

single layer, no glove

Multiple Activities	

0.042	

0.0016	

single layer, glove

                 The unit exposures for loader/operator are substituted
with those for water soluble packets in the PHED. 

Handlers’ Exposure and Risk

With the exception of the multiple activities scenario using HED’s
standard assumption regarding the amount of seed treated per day (5,500
lbs treated/day, MOE=59), the potential occupational exposures/risks
resulting from the proposed use do not exceed the HED level of concern
(MOEs range from 300 to 7,400).  

According to the label, loader/applicator must wear personal protective
equipment (PPE) consisting of a single layer of clothing plus
chemical-resistant gloves and dust mask; workers conducting sewer and
bagger activities must wear a single layer of clothing plus
chemical-resistant gloves.  The multiple task workers must wear (1) a
single layer of clothing, (2) chemical-resistant gloves, (3) dust mask,
and (4) chemical-resistant coveralls.  Thus, the MOE of 59 for the
multiple activities scenario is a very conservative estimate because it
was based on single layer plus gloves protection.  If dust mask and
coveralls are added to the single layer plus gloves protection, the
exposure for multiple task workers may not be of concern.  

In addition, the MOE of 59 for the multiple activities scenario is based
on the unit of exposure for liquid product, and the product being
evaluated here is a wettable powder packaged in water soluble packets;
the use of water soluble packaging is considered to be an engineering
control measure which can provide more than 50% reduction in exposure,
because the unit exposure is approximately 2X lower than the unit
exposure for a liquid (see below).  Since a significant portion of the
exposure in the multiple activities scenario is likely a result of
mixer/loader exposure, the MOE of 59 is not of concern in light of the
use of water soluble packaging    

Note:  The significance of using water soluble packets in exposure
reduction:

●   PHED unit exposure for mixing/loading liquid product 

      = 0.023 + 0.0012 = 0.0242 mg/lb ai handled

●   PHED unit exposure for mixing/loading water soluble packet product

      = 0.0098 + 0.00024 = 0.01004 mg/lb ai handled       

A summary of the exposures and risks for handlers is presented in Table
6.

If the Registration Division considers it appropriate, additional label
language can be added to minimize the chance that the LOC of 100 is
exceeded for multiple activities workers.  In this case, the label
should indicate that the maximum amount of CRUISER® 70WS Insecticide
that can be used to treat bulb onion seed in a seed treatment facility
is 260 lbs per production line per 8-hour work shift (based on the MOE
calculated for treating 3,000 lbs seed per day; MOE for multiple
activities worker = 110).  This requires that a worker perform tasks
associated with seed treatment only on one production line per 8-hour
shift and the worker works no more than one 8-hour shift per 24 hour
period.

The handler exposure estimates in this assessment are based on a central
tendency estimate of unit exposure and an upper-percentile assumption
for the application rate, and are assumed to be representative of
high-end exposures.  The uncertainties associated with this assessment
stem from the assumptions regarding that amount of chemical handled and
the amount of seed treated per day.  The estimated exposures are
believed to be reasonable high-end estimates based on observations from
field studies and professional judgment.

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 (400 lb/day) or based on the amount
provided by Syngenta (240 lb/day) (provided thru an e-mail from Patrick
McCain of Syngenta to Julie Chao, 1/19/2010)..

Exposure frequency = 60 days/year and 8 hour/day exposure

Body weight  = 60 kg

Dermal absorption (DA) = 5%, inhalation absorption = 100%

Equations and Calculations

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

Body Weight (kg)

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

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 (190 or 310).  A summary of the exposure/risk values is
presented in Table 7.

    

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 risk assessment relies in part on data from studies in which adult
human subjects were         intentionally exposed to a pesticide or
other chemical.  These studies, which comprise the Pesticide Handlers
Exposure Database (PHED) have been determined to require a review of
their ethical conduct, and have received that review. The studies in
PHED were considered appropriate (or ethically conducted) for use in
risk assessments.

Table 6.  Thiamethoxam Non-Cancer Risk for Seed-Treatment 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 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

Water soluble bags  for Seed Treatment (1)	Single Layer, Gloves	0.0098
0.00024	Onion (bulb)	0.06	5,500	0.002695	0.00132	0.004015	300

300	0.00015	0.000072	0.000222	5,400

Sewer

Sewing Bags after Seed treatment (2)	Single Layer, 

No Gloves	0.0062	0.00023	Onion (bulb)	0.06	5,500	0.001705	0.001265
0.00297	400

300	0.000093	0.000069	0.000162	7,400

Bagger

Bagging Seeds after Seed treatment (3)	Single Layer, 

No Gloves	0.0091	0.00016	Onion (bulb)	0.06	5,500	0.002503	0.00088
0.003383	360

300	0.000136	0.000048	0.000184	6,500

Multiple Activities Worker

Multiple Activities for Seed treatment (4)	Single Layer, Gloves	0.042
0.0016	Onion (bulb)	0.06	5,500	0.01155	0.0088	0.02035	59

300	0.000631	0.00048	0.001111	1,100

a	Daily amounts treated values are based on exposure SAC Policy #15 or
the information provided by the Registrant through Registration
Division.  5,500 for film-coated treatment, 

                  300 for pelletizing treatment. 

b	Daily dermal dose (mg/kg/d) =  [unit dermal exposure (mg/lb ai) *
dermal absorption (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/d) + Daily
inhalation dose (mg/kg/d).

e	MOE = NOAEL (1.2  mg/kg/d) / combined daily dose.  UF = 100.



Table 7.  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	Onion (bulb)	0.06	400	0.005	0.00136	0.00636	190

240	0.003	0.000816	0.003816	310

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 (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/d) + Daily
inhalation dose (mg/kg/d).

e	MOE = NOAEL (1.2 mg/kg/d) / combined daily dose.  UF = 100.			

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

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