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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: December 7, 2010 

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

Proposed Section 3 Registration for Use in Food/Feed Handling Establishments. 

 PC Code: 060109 DP Barcode: D382248 

 Decision No.: 436785 Registration No.: 100-1036 

 Petition No.: 0F7734 Regulatory Action: Section 3 Registration 

 Risk Assessment Type: ORE Reregistration Case No.: NA 

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

 MRID No.: NA 40 CFR: 180.565 

 

FROM: Shih-Chi Wang, Biologist 

 Risk Assessment Branch 2 

 Health Effects Division (7509P) 

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

 Margarita Collantes, Biologist 

Risk Assessment Branch 2 

 Health Effects Division (7509P) 

TO: Kable Davis/Venus Eagle, RM 01 

 Insecticide-Rodenticide Branch 

 Registration Division (7505P) 

CONCLUSIONS 

HED has evaluated the proposed expansion of the use of thiamethoxam in food/feed handling 

areas. The potential occupational exposures/risks resulting from the proposed use do not exceed 

HED’s level of concern with the exception of use of the foam formulation. The handler scenario 

using a foam application resulted in an MOE of 160 with the use of additional PPE (gloves, 

coveralls and PF5 dust mist respirator). The current label does not require use of coveralls and 

respirators. HED recommends that if this use is to remain on the label, that the Registration 

Division ensure that the correct PPE be included in the final registered label. 
Page 2 of 13 

 

Table of Contents 

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

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

2.1 Hazard Profile ...............................................................................................................5 

2.2 FQPA and Uncertainty Factor Considerations .............................................................6 

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

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

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

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

5.2 Post-Application ........................................................................................................12

 

6.0 Review of Human Research ...................................................................................................12
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I. EXECUTIVE SUMMARY 

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

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

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

registrant, Syngenta, has requested an amendment to the registration of Optigard® Flex Liquid 

Insecticide (EPA Reg. No. 100-1306) and a tolerance petition for thiamethoxam associated with 

the use of thiamethoxam in food/feed handling areas of food/feed handling establishments. 

Previously, the label directions precluded the potential for residues in food/feed, but the relevant 

restrictions are now proposed to be removed. The proposed application is intended to be made 

by or under the supervision of commercial applicators. Based on the proposed label information, 

occupational exposure is expected to occur for short- and intermediate-term durations. 

Hazard Characterization: 

The oral no observed adverse effect level (NOAEL) of 8.23 mg/kg/day is the point of departure 

(POD) for all incidental oral durations and is based on effects seen in the kidney, liver, testis, 

ovary and hematopoietic system in a 90-day oral study in the dog. The adult dermal NOAEL of 

1.2 mg/kg/day is the POD for all durations and is based on sperm abnormalities and testicular 

effects observed after in utero and post-natal exposure in the rat reproduction studies. Although a 

21-day dermal toxicity study in rats is available, the Health Effects Division (HED) selected a 

reproductive NOAEL because the reproductive parameters are not evaluated in the dermal 

toxicity study and thus, the consequences of these effects cannot be ascertained for the dermal 

route of exposure. Since the adult dermal endpoint was based on an oral study, a 5 percent 

dermal absorption factor was used to estimate dermal exposure for all durations. The infants and 

children’s (1-6 years) dermal NOAEL of 60 mg/kg/day is the POD for all durations and is based 

on liver effects seen in a 28-day dermal toxicity study in rats. The inhalation NOAEL of 1.2 

mg/kg/day is the POD for all durations and is based on the same study used for the adult dermal 

NOAEL. Other than acute toxicity, no inhalation studies are available; therefore, the oral 

reproductive endpoint is selected for inhalation exposure. Inhalation toxicity is assumed to be 

equivalent to oral toxicity. 

Since the dermal and inhalation toxicological endpoints of concern are based on a reproductive 

study, the body weight of an adult female (60 kg) is used to estimate dermal and inhalation dose 

in the assessment. Resulting dermal and inhalation risk estimates were combined into total risk 

estimates because the same endpoint was chosen to evaluate both routes of exposure. 

Cancer Assessments: 

Thiamethoxam is classified as “not likely” to be a human carcinogen 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. 

Food Quality Protection Act (FQPA) and Uncertainty Factors (UF): 

Based upon the hazard data and the methods used to estimate exposure, it is recommended that 

the 10X FQPA SF for the protection of infants and children be reduced to 1X. For all exposure 

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

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

 

Residential Exposure: 

There are no new residential exposure scenarios associated with this food handling use. 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 handlers 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 Handler and Postapplication Exposures: 

No chemical-specific handler exposure data were submitted in support of the proposed labels. 

Therefore, the handler assessment for the proposed use was based on surrogate unit exposure 

data from the Pesticide Handlers Exposure Database (PHED) Version 1.1 (HED Science 

Advisory Council for Exposure, SOP Number .007, January 1999). 

Exposure scenarios resulting in MOEs greater than 100 are not of concern to HED. All but one 

exposure scenario resulted in a combined MOE ranging from 280 to 8,300 for occupational 

handlers with use of personal protective equipment (PPE) mitigation (baseline attire plus 

chemical-resistant gloves), which are already required on the label. The handler scenario using a 

foam application to treat cracks and crevices resulted in an MOE of 160 with the use of 

additional PPE (gloves, coveralls and PF5 dust mist respirator). Current label does not require 

use of coverall and respirators. Without such PPE, the MOE is only 56. HED recommends 

that if this use is to remain on the label, the Registration Division ensure that the correct 

PPE be included in the final registered label. Commercial applicators are not expected to 

return to treatment sites; therefore, a quantitative postapplication exposure assessment was not 

performed for commercial applicators. 

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. 
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2.0. HAZARD CHARACTERIZATION 

2.1 Hazard Profile 

Toxicological endpoints and doses for thiamethoxam risk assessment were summarized in detail 

in the last comprehensive aggregate risk assessment (D. McNeilly, 5/3/2010, D373596). The 

database for acute toxicity for thiamethoxam is complete and is summarized in Table 1. A 

summary of the toxicological doses and endpoints for risk assessment is provided in Table 2. 

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

acute dermal toxicity, acute inhalation toxicity, skin irritation, and eye irritation. Thiamethoxam 

is not a dermal sensitizer. 

 

For incidental oral exposure the oral NOAEL of 8.23 mg/kg/day (point of departure for all 

durations) is based on slightly prolonged prothrombin times and decreased plasma albumin and 

A/G ratio (both sexes); decreased calcium levels and ovary weights and delayed maturation in 

the ovaries; decreased cholesterol and phospholipid levels, testis weights, spermatogenesis, and 

spermatic giant cells in testes from a 90-day oral study in the dog. The LOAEL ranged from 32 

mg/kg/day in males to 33.9 in females. 

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 in the 

rat reproduction studies. Since the adult dermal endpoint was based on an oral study, a 5 percent 

dermal absorption factor was used to estimate dermal exposure for all durations. Although a 21-

day dermal toxicity study in rats is available, HED selected a reproductive NOAEL because the 

reproductive parameters are not evaluated in the dermal toxicity study and thus the consequences 

of these effects cannot be ascertained for the dermal route of exposure. 

The infants and children’s (1-6 years) dermal NOAEL of 60 mg/kg/day (point of departure for 

all durations) is based on increased plasma glucose, triglyceride levels, and alkaline phosphatase 

activity and inflammatory cell infiltration in the liver and necrosis of single hepatocytes in 

females from a 28-day dermal toxicity study in rats. The LOAEL is 250 mg/kg/day (females). 

For inhalation exposure assessment, the inhalation 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 in the rat reproduction studies. Since no data are available to indicate 

how much exposure will induce the effects, the effects are considered to be appropriate for all 

exposure durations. Other than acute toxicity, no inhalation studies are available. Therefore, the 

reproductive endpoint from an oral study is selected for inhalation exposure. 

On April 27, 2005 the Cancer Assessment Review Committee of HED met to re-evaluate the 

carcinogenic potential of thiamethoxam. In accordance with the EPA’s Final Guidelines for 

Carcinogen Risk Assessment, the CARC 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. 
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2.2 FQPA and Uncertainty Factor Considerations 

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

the 10X FQPA SF for the protection of infants and children be reduced to 1X. There is no 

quantitative or qualitative evidence of increased susceptibility of rat or rabbit fetuses to in utero 

exposure to thiamethoxam in the developmental toxicity studies. The developmental NOAELs 

are either higher than or equal to the maternal NOAELs. The Developmental Neurotoxicity 

(DNT) workgroup concluded there was no evidence of increased susceptibility in the DNT study 

in rats, based on evaluation of additional brain morphometric data for the low- and mid-dose 

pups (January 17, 2007 meeting). Although there is evidence of increased quantitative 

susceptibility for male pups of both two generation reproductive studies, NOAELs and LOAELs 

were established in these studies, and the Agency selected the NOAEL for testicular effects in F1 

pups as the basis for risk assessment. The Agency has confidence that the NOAEL selected for 

risk assessment is protective of the most sensitive effect for each population of concern. 

The Agency’s level of concern (LOC) for risks (i.e., target level for Margins of Exposure) is 

defined by the uncertainty factors that are applied to the assessment. The Agency applies a 

factor of 10X to account for interspecies extrapolation to humans from the animal test species 

and another factor of 10X to account for intra-species variability. With the reduction of the 

FQPA safety factor to 1X, the total uncertainty factor that has been applied for thiamethoxam 

risk assessment is 100 for short- and intermediate-term dermal and inhalation exposures. 

Table 1. Acute Toxicity Profile of Thiamethoxam.

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

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

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

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

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

PIS = 0 at 24 hr 

Minimally irritating 

IV 

870.2500 Acute dermal irritation 44703319 PIS = 0 IV 

870.2600 Skin sensitization 44710401 Is not a sensitizer using 

method of Magnusson and 

Kligman 

N/A 
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3.0 PROPOSED USE PATTERN 

The registrant, Syngenta, proposes to amend the current Optigard® Flex Liquid Insecticide (EPA 

Reg. No. 100-1306) label for use in food/feed handling areas and establishments. 

Table 2. Toxicological Doses and Endpoints for Thiamethoxam Residential Non-dietary and Occupational 

Assessments. 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty 

Factors 

Level of Concern 

for Risk 

Assessment 

Study and Toxicological Effects 

Incidental Oral 

(all durations) 

NOAEL= 8.23 

mg/kg/day 

UFA= 10x 

UFH= 10x 

SFFQPA=1 

LOC = an MOE of 

100 (residential) 

90-day Dog Study 

LOAEL= 32 (males) 33.9 (females) 

mg/kg/day based on slightly prolonged 

prothrombin times and decreased 

plasma albumin and A/G ratio (both 

sexes); decreased calcium levels and 

ovary weights and delayed maturation in 

the ovaries (females); decreased 

cholesterol and phospholipid levels, 

testis weights, spermatogenesis, and 

spermatic giant cells in testes (males).

Dermal (all 

durations) 

(infants/ 

children 1-6 yrs) 

Dermal Study 

NOAEL=60 

mg/kg/day 

UFA= 10x 

UFH= 10x 

SFFQPA=1 

LOC = an MOE of 

100 (residential) 

Rat 28-Day Dermal Toxicity Study 

LOAEL = 250 (females) mg/kg/day 

based on increased plasma glucose, 

triglyceride levels, and alkaline 

phosphatase activity and inflammatory 

cell infiltration in the liver and necrosis 

of single hepatocytes in females.

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. 
Page 8 of 13 

The proposed use pattern for thiamethoxam for the end-use product Optigard® Flex Liquid 

Insecticide (liquid, thiamethoxam 21.6%) is summarized in Table 3. 

TABLE 3: Proposed Use Patterns for Thiamethoxam 

Proposed 

Use 

Product, 

Formulation Treatment Type Applications 

Per Season 1 Max Application Rate2

(lb ai/Gal of Sol) 

Control of Insects 

in Food/Feed 

Handling Areas 

Optigard® 

Flex Liquid 

Insecticide 

(21.6% ai) 

Reg No: 

 100-1306 

(2 lb ai/gal) 

Commercial: 

crack and crevice spray, 

low pressure spot spray, 

surface spray, structural 

void application 

applying as a liquid 

spray or foam 

application 

NA3

 0.0084 lb ai/gal 

(0.1% liquid spray solution, 

0.54 fl oz product./gal) or 

*0.0423 lb ai/gal (0.1% foam 

solution, 2.71 fl oz 

product/gallon) 

1

 Maximum number of applications allowed on label. 2

 Rate = Maximum application rates specified on proposed label. 2* Appl. Rate of foam = 2.7 fl oz prod. x 2 lb ai/gal x 1 gal/128 fl oz = 0.0423 lb ai/gal 

 Foaming agent is than added to increase volume (not product) 5X = 0.0423/0.0834 (factor to convert lb/gal to %) = 0.05% 

 0.05%/5 = 0.1% foam solution 

3

 NA= Not Applicable. 

The proposed application is intended to be made by or under the supervision of commercial 

applicators. According to the proposed label, applicators and other handlers must wear: (1) longsleeved shirt and long pants, (2) chemical-resistant gloves, and (3) shoes plus socks. 

4.0 RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE 

The Optigard® Flex Liquid label specifies that use of product in all indoor permitted sites, 

including food handling establishments, must be restricted to areas which eliminate exposure to 

food handling surfaces and areas that are not easily accessible to occupants (i.e., structural voids, 

cracks and crevices, corners or out of the way places such as under and behind kitchen 

appliances, under sinks, crawl spaces, attics, unfinished basements, baseboards, windows and 

door frames). Since the label stipulates that treatment areas are situated away from eating areas 

and other areas where children may come in contact with treated surfaces (i.e., not in or around 

room where children are playing or eating), a quantitative residential exposure assessment is not 

required for this action. Furthermore, the registered label also indicates that product is to be 

applied under the supervision of commercial applicators. 

However, HED previously performed a crack and crevice residential exposure assessment for 

this same exact product, previously known as OptigardTM ZT (Registration number 100-1170) 

containing 21.6% of the active ingredient thiamethoxam (M. Collantes, July 2009, D359207). A 

residential exposure assessment for the use thiamethoxam on turf was also previously performed 

(M. Collantes; March 2007; D332064). 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. 
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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 for Thiamethoxam 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 the M. Collantes memo, D359462. 

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

 Child Dermal MOE = NOAEL (60 mg/kg/day)/Dermal Dose 

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

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

5.0. OCCUPATIONAL EXPOSURE 

Syngenta has requested an amendment to the current registered Optigard® Flex Liquid 

Insecticide (EPA Reg. No. 100-1306) product label. This proposed label amendment is to allow 

the use of thiamethoxam in food/feed handling areas or establishments. The proposed use is 

intended to be applied by or under the supervision of commercial applicators as a liquid spray or 

foam. The product is to be applied to cracks and crevices, spots, surfaces, and structural voids 

using low pressure handwand, backpack and other hand-held equipment. 

5.1 Handlers 

Exposure Scenarios

The following scenarios were assessed for the proposed use: 

• Mixing/Loading/Applying liquid spray using low-pressure equipment for surface 

treatment 

• Mixing/Loading/Applying foam spray using low-pressure equipment for surface treatment 

• Mixing/Loading/Applying wettable powder formulation as surrogate for liquid 

formulation using low-pressure equipment for crack and crevice treatment 

• Mixing/Loading/Applying wettable powder formulation as surrogate for foam formulation 
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using low-pressure equipment for crack and crevice treatment 

Equations/Calculations

The following equations were used to calculate handler exposure and risk: 

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

BW (kg) 

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

 BW (kg) 

Where: 

Rate (Application Rate) = Maximum application rate on product label (lb ai/gal) 

UE (Unit Exposure) = Exposure value derived from PHED (mg/lb ai handled) 

DA (dermal absorption factor) = Factor to account for dermal absorption (5%) 

Amount Treated = Maximum number of gallons treated per day (gal/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) 

Application Rate

The maximum application rate listed on the proposed labels provided by the Registration Division 

was used for all exposure assessments. The maximum rate is 0.0084 lb ai /gallon of liquid spray 

solution (0.1% ai spray solution; 0.54 fl oz product / gallon) or 0.0423 lb ai/gal of foam solution 

(0.1% ai foam solution; 2.71 fl oz product/gallon) 

Gallons or the Amount Treated

Based on HED’s Exposure Science Advisory Council (Expo SAC) minutes (11/18/10), the 

following application capacity was assumed for commercial applicators treating food handling 

establishments: 

• 20 gallons/day for mixer/loader/applicator using low-pressure handwand 

Body Weight 

The average adult female body weight (60 kg) was used for estimating dermal and inhalation 

exposure. The endpoint selected for risk assessment was based on testicular effects in male pups 

(F1 generation) observed 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 is used in order to be 

protective of effects. 

Absorption Factors:

A dermal absorption factor of 5% was used in estimating short- and intermediate-term dermal 

doses, since the dermal point of departure was based on an oral study. 
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Since no inhalation absorption data are available, toxicity by the inhalation route is considered to 

be equivalent to the estimated toxicity by the oral route of exposure. 

Exposure Frequency

No data on the number of exposure days per year was provided. For this risk assessment, it was 

assumed that handlers would be exposed for less than 6 months per year (i.e., short- and 

intermediate-term exposures). Long-term exposures are not expected and were not assessed. 

Unit Exposures

Chemical-specific data for assessing exposure during pesticide handling activities (typical 

mixing/loading and applying) were not submitted to the Agency in support of this Section 3 

application. It is HED policy to use surrogate data from the Pesticide Handlers Exposure 

Database (PHED) Version 1.1 to assess handler exposures for regulatory actions when chemicalspecific data are not available (HED Science Advisory Council for Exposure, SOP Number .007, 

January 1999). 

Although the proposed product is formulated as a liquid, handler exposure resulting from 

treatment of cracks and crevices was assessed using surrogate PHED unit exposures for mixing/ 

loading and applying a wettable powder formulation using low pressure equipment. Unit 

exposure values for this scenario were based on actual crack and crevice application. HED 

believes these unit exposures most accurately represent anticipated exposure. The unit exposures 

for mixing/loading and applying a liquid formulation using low pressure equipment were based 

on broadcast treatment of poultry and green houses and were used to assess surface spray 

scenarios. 

 

Mitigation Approaches

There are three basic risk mitigation approaches considered appropriate for reducing occupational 

exposure. These include administrative controls, use of personal protective equipment (PPE), and 

the use of engineering controls. Occupational handler exposure assessments were completed by 

HED using exposure estimates at baseline and with PPE mitigation. There are currently no 

engineering controls appropriate for the exposure scenarios represented in this assessment 

The baseline clothing level for occupational exposure scenarios is an individual wearing long 

pants, a long-sleeved shirt, shoes, socks, no chemical-resistant gloves, and no respirator. The first 

level of mitigation generally applied is PPE, which may include addition of chemical resistantgloves, an additional layer of clothing, and/or a respirator. 

Handlers’ Exposure and Risk

Exposure scenarios resulting in MOEs greater than 100 are not of concern to HED. All but one 

exposure scenario resulted in a combined MOE ranging from 280 to 8,300 for occupational 

handlers with use of personal protective equipment (PPE) mitigation (baseline attire plus 

chemical-resistant gloves), which are already required on the label. The handler scenario using a 

foam application to treat cracks and crevices resulted in an MOE of 160 with the use of additional 

PPE (gloves, coveralls and PF5 dust mist respirator). Current label does not require use of 

coverall and respirators. Without such PPE, the MOE is only 56. HED recommends that if this 

use is to remain on the label, the Registration Division ensure that the correct PPE be 

included in the final registered label. Exposures/risks for occupational handlers are presented 

in Table 5. 
Page 12 of 13 

Characterization of Risk

The label does not specify amount of area treated for the various exposure scenarios (i.e., crack 

and crevice, spot and surface sprays). Furthermore the label only provides one application rate 

for all three exposure scenarios. Therefore, HED used a standard assumption of 20 gallons per 

day to define the amount of material applied by commercial applicators in food and feed handling 

establishments. 

5.2 Postapplication

Commercial applicators are not expected to return to treatment sites; therefore, a quantitative 

postapplication assessment of handler exposure was not performed. 

6.0 REVIEW OF HUMAN RESEARCH 

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

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

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

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

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

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

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

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

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

have been satisfied. 
Page 13 of 13 

Table 5. Handler Exposure and Risk for Thiamethoxam Use in Food/Feed Handling Establishments.Product & Formulation 

Method of Application 

Mitigation Dermal Unit 

Exposurea(mg/lb ai) 

Inhalation Unit Exposurea(μg/lb ai) 

Application Rate b(lb ai/Gal)

Amount Treated c(Gal/day)

Dermal Dosed (mg/kg/day) 

Inhalation Dose e(mg/kg/day) 

Mixer/Loader/ Applicator

Optigard ® Flex Insecticide (21.6% ai) 

LowPressure Spray – liquid/foam 

Baseline + gloves 

0.43 (liquid surface spray) 

30 

(liquid surface 

spray) 

0.0084 

(liquid) 20 

0.00006 0.000084 

0.0423 

(foam) 

0.00030 0.000423 

LowPressure Spray – Wettable Powder/foam 

Baseline + gloves 

8.6 (WP crack and crevice) 

1,100 

(WP crack and 

crevice) 

0.0084 

(liquid) 

0.0012 0.0030 

Baseline + gloves 

8.6 (WP crack and crevice) 

1,100 

(WP crack and 

crevice) 

0.0423 

(foam) 

0.006 0.015 

Baseline + gloves, coveralls and PF5 dust mist respirator 

6.22 (WP crack and crevice) 

220 

(WP crack and 

crevice) 

0.004385 0.0031 

a. Unit Exposures based on PHED Version 1.1.

b. Application Rate is based on proposed label for thiamethoxam product - Optigard® Flex Liquid Insecticide c. Science Advisory Council for Exposure (11/18/10)d. Dermal Dose (mg/kg/day) = [Rate (lb ai/Gal) x UE (mg /lb ai ) x 5% DAF x Amount Treated (Gal/day)]/ BW (60 kg) e. Inhalation Dose (mg/kg/day) = [Rate (lb ai/Gal) x UE (mg /lb ai ) x Amount Treated (Gal/day)] / BW (60 kg) f. Combined Daily Dose (mg/kg/day) = Dermal Dose (mg/kg/day) + Inhalation Dose (mg/kg/day) g. Total MOE = [NOAEL (1.2 mg/kg/day)]/ Combined Daily Dose (mg/kg/day) 

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