Page 1 of 13 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 in cluded 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 ................................................................................................

... 12Page 3 of 13 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 gr own in greenhouses, and Christmas trees. The registrant, Syngenta, has requested an amendmen t 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 toxi city 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 expos ure. 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 m ode 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 intraspeciesPage 4 of 13 variation (total UF of 100x) were used. Theref ore, 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 require d 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, th e 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.Page 5 of 13 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 inhalati on 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 i nhalation 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 classifi ed thiamethoxam as “Not Likely to be Carcinogenic to Humans” based on convincing ev idence 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 6 of 13 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 LD 50 : 1563 mg/kg III

870.1200 Acute dermal [rabbit] 44703316 LD 50 = 13.3 g/kg IV

870.1300 Acute inhalation [rat] 44703317 LC 50 > 3.72 mg/L IV

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

PIS = 0 at 24 hr

Minimally irritating IV

870.2500 Acute dermal irritation 44703319 PIS = 0 IV

870.2600 Skin sensitization 44710401 Is not a sensitizer using method of Magnusson and Kligman N/APage 7 of 13 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 Thia methoxam 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 UF A = 10x

UF H = 10x

SF FQPA =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, sp ermatogenesis, and spermatic giant cells in testes (males).
Dermal (all durations) (infants/
children 1-6 yrs) Dermal Study

NOAEL=60 mg/kg/day UF A = 10x

UF H = 10x

SF FQPA =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%) UF A = 10x

UF H = 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) UF A = 10x

UF H = 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 establishe d in the mouse and that the carcinoge nic effects are a result of a mode of action dependent on sufficient amounts of a hepatot oxic 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 Rate 2

(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 NA 3 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 appli cations allowed on label.

2 Rate = Maximum application rate s 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 commercialapplicators. 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 tr eatment 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.Page 9 of 13 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. Therefor e, the indoor exposures should be used in an aggregate assessment in order to be protective.

Table 4. Combined Residential Exposure a nd 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/MOE Dermal ) + (1/MOE Hand-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 usi ng 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 formul ation as surrogate for foam formulationPage 10 of 13 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 app lication 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 propos ed 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 produc t / 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.Page 11 of 13 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 e xposures 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 us ing 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 formula tion 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 chem ical-resistant gloves, and no respirator. The firstlevel 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 resu lted 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 Registrati on 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 13Table 5. Handler Exposure and Risk for Thiamethoxam Use in Food/FeedHandling Establishments.Product &FormulationMethod ofApplicationMitigationDermal UnitExposurea(mg/lb ai)InhalationUnitExposurea(μg/lb ai)ApplicationRateb(lb ai/Gal)AmountTreatedc(Gal/day)Dermal Dosed(mg/kg/day)InhalationDosee(mg/kg/day)CombinedDaily Dosef(mg/kg/day)Total MOEgMixer/Loader/ ApplicatorOptigard ®FlexInsecticide(21.6% ai)LowPressureSpray –liquid/foamBaseline +gloves0.43(liquid surfacespray)30(liquid surfacespray)0.0084(liquid)200.00006 0.000084 0.000144 83000.0423(foam)0.00030 0.000423 0.000726 1700LowPressureSpray –WettablePowder/foamBaseline +gloves8.6(WP crackand crevice)1,100(WP crack andcrevice)0.0084(liquid)0.0012 0.0030 0.00428 280Baseline +gloves8.6(WP crackand crevice)1,100(WP crack andcrevice)0.0423(foam)0.006 0.015 0.021556Baseline +gloves,coveralls andPF5 dust mistrespirator6.22(WP crackand crevice)220(WP crack andcrevice)0.004385 0.0031 0.00748 160a. Unit Exposures based on PHED Version 1.1.b. Application Rate is based on proposed label for thiamethoxam product - Optigard® Flex Liquid Insecticidec. 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) = DermalDose (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