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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL 

SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

DATE: 08/27/2013

SUBJECT: Indoxacarb: Residential Exposure and Aggregate Human-Health Risk 

Assessment for Proposed Amendment for Indoor Uses of Arilon (EPA reg. 

No 100-1501) Label.

PC Code: 067710 DP Barcode: D413735

Decision No.: 481544 Registration No.: EPA Reg. No. 100-1501

Petition No.: Regulatory Action: Label Amendment/Section 3

Risk Assessment Type Single Chemical

Aggregate

Case No.: NA

TXR No.: NA CAS No.: 173584-44-6

MRID Nos.: NA 40 CFR: §180.564

 

FROM: Ana Rivera-Lupiáñez, Chemist

Risk Assessment Branch V

Health Effects Division (7509P)

THROUGH: Danette Drew, Chemist 

Kelly Lowe, Environmental Scientist

Michael Metzger, Branch Chief

Risk Assessment Branch V

Health Effects Division (7509P)

TO: Jennifer Urbanski/John Hebert, Risk Manager

Registration Division (7505P)
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1.0 EXECUTIVE SUMMARY

Indoxacarb, (S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-

(trifluoromethoxy)phenyl] amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-

carboxylate, a reduced risk pesticide, is an oxadiazine class insecticide active ingredient 

(ai). It is formulated as granular, impregnated materials, water dispersible granules, 

emulsifiable, flowable, soluble concentrates, and solution-ready-to-use. Indoxacarb 

formulations can be used by homeowners and by commercial applicators in agricultural 

and non-agricultural use sites.

The last Human-Health Risk Assessment for indoxacarb (5/2/13, D402099, D. Drew, et 

al, Indoxacarb. Human Health Risk Assessment for the Proposed New Use on Dry Beans, 

Succulent Beans, Small Fruit Vine Climbing Subgroup (except kiwifruit) 13-07F and Low 

Growing Berry Subgroup (except strawberry) 13-07H; (PP#2E8029)) identified postapplication risk estimates of concern for children (hand-to-mouth oral exposure) as a 

result of spot-directed treatment scenarios to indoor surfaces. The Health Effects Division 

(HED) recommended amending the EPA Reg. No. 100-1501 label to withdraw indoor 

spot treatments, and restrict indoor residential uses to only crack and crevice treatments 

limiting applications to areas not accessible to young children. The registrant had been 

notified of this and responded by submitting an amended label which, rather than restrict 

the use to crack and crevice only, reduced the maximum spray volume allowed to be 

applied for indoor spot treatments. The Registration Division (RD) requested that HED

determine if this labeling language is acceptable. The residential exposure and risk 

estimates were also revised, as was the aggregate (residential plus dietary) assessment,

for the amended indoor use.

Proposed Use Profile

Indoxacarb products are frequently formulated as a mixture of the insecticidally active Senantiomer and the insecticidally inactive R-enantiomer. The percentage of active 

ingredient and application rates listed on the product labels only reflect the S-enantiomer 

and not the R-enantiomer. Adjustments are made in this assessment to add in the percent 

of R-enantiomer in product mixtures so that the total amount of indoxacarb (both S- and 

R- enantiomers) applied is accounted for as both are residues of toxicological concern. 

Arilon Insecticide 20% ai (EPA Reg. No. 100-1501, a water-soluble packaging (WSP) 

formulation of indoxacarb (75:25 ratio of S- and R-enantiomers), is registered for insect 

control on households and domestic dwellings. The product registrant, Syngenta Crop 

Protection LLC, has submitted a proposed label amendment to the indoor surface use 

directions for crack and crevice and spot directed spray applications.

The original indoor application (i.e., crack and crevice and spot directed spray treatment) 

allowed for a maximum application rate of 0.66 oz product (dry) per gallon of water (i.e., 

0.011 lb ai total isomer /gal) with a maximum application volume of 4 gallons diluted 

product per 1000 sq ft (equivalent to a maximum application rate of 0.00004 lb ai total 

isomer/ft2). The amended label proposes to limit the maximum volume of product used 

for indoor applications to 1 gallon diluted product per 1000 sq ft, equivalent to a 

maximum application rate of 0.00001 lb ai total isomer/ft2.
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Hazard Profile 

The toxicology database for indoxacarb is complete and is sufficient for characterizing 

hazard. The indoxacarb endpoints that most frequently defined the lowest-observedadverse-effect-level (LOAEL) in laboratory animals were non-specific, and included 

decreases in body weight, weight gain, food consumption and food efficiency. 

Indoxacarb also affected the hematopoietic system in animals by decreasing the red blood 

cell count, hemoglobin and hematocrit. 

The FQPA safety factor (SF) for indoxacarb is reduced to 1X based on the following: 1) 

the hazard and exposure databases are complete; 2) there are no concerns for pre- and/or 

postnatal toxicity; 3) there are no residual uncertainties with regard to pre- and/or postnatal toxicity; and 4) the acute neurotoxicity (ACN), subchronic neurotoxicity (SCN) and 

developmental neurotoxicity (DNT) studies are available and all endpoints used in this 

risk assessment are protective of any neurotoxic effects.

See the 5/2013 risk assessment (D402099) for the complete details regarding the hazard 

characterization and selection of toxicity endpoints and points of departure for

indoxacarb.

Residential Exposure/Risk

The residential exposure and risk estimates were revised for the amended indoor use label 

since they will impact the aggregate (residential plus dietary exposures) assessment for 

indoxacarb. Dermal exposures resulting from residential uses are not quantitatively

assessed as a dermal toxicity endpoint is not identified for indoxacarb. Only inhalation 

(adult and children) and incidental oral (children) exposures are assessed. The handler 

and post-application exposures for this residential use are expected to be short-term in 

duration. 

Residential handler (adults) risk estimates result in inhalation MOEs that do not exceed 

HED's level of concern (i.e., MOEs ≥ 100) from the Arilon indoor application exposure 

scenarios. All adult and children post-application risk estimates from the Arilon indoor 

surface directed sprays scenarios (crack and crevice and spot treatments) do not exceed 

HED’s level of concern (MOEs are ≥ 100) at the proposed reduced maximum volume 

rate of 1 gallon diluted product per 1000 sq ft.

Aggregate Risk

The short- term aggregate (residential plus dietary food and water) risk estimates for 

adults and children are below HED’s level of concern when considering the postapplication exposure to indoor spray treated surfaces assuming a reduced volume 

application rate of 1 gallon diluted product per 1000 sq. ft.

2.0 RISK ASSESSMENT CONCLUSIONS AND RECOMMENDATIONS
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2.1 Summary of Risk Estimates

The residential handler scenarios assessed resulted in inhalation MOEs that do not exceed 

HED's level of concern (i.e., MOEs ≥ 100 for short-term exposure durations). All adult 

and children inhalation and incidental oral post-application short-term risk estimates from

indoor surface directed sprays scenarios (crack and crevice and spot treatments) resulted 

in MOEs that do not exceed HED's level of concern (i.e., MOEs ≥ 100) at the proposed 

reduced maximum volume rate of 1 gallon diluted product per 1000 sq ft. The short- term 

aggregate (residential plus dietary food and water) risk estimates for adults and children 

are below HED’s level of concern when considering residential exposures from indoor 

surface directed sprays (spot treatments) assuming a reduced volume application rate of 1 

gallon diluted product per 1000 sq. ft. 

2.2 Label Recommendations from Residential Assessment

HED recommends amending the “Application Directions” section of the Arilon label 

(EPA Reg. No. 100-1501) to list the maximum spray volume allowed (i.e., 1 gallon 

diluted product per 1000 sq ft) for all indoor application scenarios.

3.0 RESIDENTIAL EXPOSURE AND RISK ESTIMATES

Both residential handler and post-application exposures have been previously assessed 

for the indoor uses of indoxacarb (05/01/2013, D464583, A. Rivera-Lupianez). The 

residential exposures for the proposed amendment to the Arilon indoor use label are 

reassessed below. 

Dermal exposures resulting from residential uses are not quantitatively assessed as a 

dermal toxicity endpoint is not identified for indoxacarb. Only inhalation and incidental 

oral exposures are assessed for the indoor residential uses of indoxacarb. The handler and 

post-application exposures for this residential use are expected to be short-term in 

duration. The risk estimates from residential exposures will impact the human health 

aggregate risk assessment for indoxacarb.

3.1 Residential Handler Exposure/Risk Estimates

HED uses the term “handlers” to describe those individuals who are involved in the 

pesticide application process. HED believes that there are distinct tasks related to 

applications and that exposures can vary depending on the specifics of each task. 

Residential handlers are addressed somewhat differently by HED as homeowners are 

assumed to complete all elements of an application without use of any protective 

equipment.

The quantitative exposure/risk assessment developed for residential handlers for the 

indoxacarb indoor use is based on the following scenario: 

(1) Mixing/loading/applying water-soluble packaging formulation for indoor spray
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applications with manually-pressurized hand wand (crack and crevice and spot 

directed treatments) for insect control on households/domestic dwellings.

Residential Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the 

residential post-application risk assessment for indoxacarb. Each assumption and factor is 

detailed in the previous occupational and residential assessment (D464583).

Application Rate:

0.011 lb ai total isomer/gal for indoor spray applications of water-soluble packaging 

formulation.

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

The residential handler scenarios assessed resulted in inhalation MOEs that do not exceed 

HED's level of concern (i.e., MOEs ≥ 100 for short-term exposure durations). Table 3.1

presents a summary of the residential handler scenario assessed.

Table 3.1. Residential Handler Short -Term Exposure and Risk Estimates for Indoxacarb 

Indoor Surface Treatments of Arilon 20% (KN128/KN127:75:25 Isomeric Mixture). 

Exposure Scenario Level of 

Concern

Inhalation Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Ratea

Area Treated 

or Amount 

Handled 

Dailyb

Inhalation

Dose 

(mg/kg/day)c MOEd

Mixer/Loader/Applicator (M/L/A)

Crack and Crevice and Spot-Directed Treatments (Indoor Environments)

Arilon Insecticide 20% ai - EPA Reg. No. 100-1501 

Manually 

Pressurized Hand 

Wand (water 

dispersible packets)

100 1.1

0.011 lb ai/gal

(0.00001 lb ai/ft2)

0.5 gal 0.000076 80,000

a..Based on registered label (EPA Reg. No.100-1501). Application rates = maximum application rates from label (EPA 

Reg. No.: 100-1501). The application rates have been adjusted by a 4/3 factor to account for 4 parts of total (S- and 

R-) indoxacarb for every 3 parts of S- indoxacarb.

b..Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

c. Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or 

Amount Handled (A/day or gallons/day) ÷ Body Weight (80 kg).

d. Inhalation MOE = Inhalation NOAEL (6 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

3.2 Residential Post-application Exposure/Risk Estimates from Indoor Surfaces 

Directed Spray Scenarios (Crack and Crevice and Spot Treatments)

Post-application exposure can result from pesticide residue transfer to the skin of 

individuals who contact previously treated indoor surfaces (e.g., carpets, floors, furniture, 

and other surfaces) during standard activities and/or who inhale pesticide vapors that emit 

from treated surfaces after application. Such exposure is assumed to occur for adults and 

small children. An assessment has been conducted for inhalation (adults and children 1 

to < 2 years), and incidental oral (children 1 to < 2 years) exposures from the proposed 

amended indoor use of indoxacarb. These lifestages are not the only lifestages that could 

be potentially exposed for these post-application scenarios; however, the assessment of 
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these lifestages is health protective for the exposures and risk estimates for any other 

potentially exposed lifestages.

Residential Post-application Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the 

residential post-application risk assessment for indoxacarb. Each assumption and factor is 

detailed in the previous occupational and residential assessment (D464583).

Application Rate:

0.011 lb ai total isomer/gal and maximum spray volume allowed of 1 gallon diluted 

product per 1000 sq ft equivalent to 0.00001 lb ai total isomer /ft2.

Summary of Residential Post-application Non-Cancer Exposure and Risk Estimates

A summary of the adult and children short-term exposure and risk estimates from the 

proposed indoor surfaces directed spray scenarios is shown in Table 3.2. All adult and 

children inhalation risk estimates do not exceed HED’s level of concern (MOEs ≥ 100). 

All children oral non-dietary ingestion risk estimates for indoor treatments do not exceed 

HED’s level of concern (MOEs ≥ 100). Combined inhalation and oral non-dietary

ingestion risk estimates for children are not of concern to the Agency at the proposed 

reduced maximum volume rate of 1 gallon diluted product per 1000 sq ft.

Table 3.2. Residential Post-application ST (Non-Cancer) Exposure and Risk Estimates for 

Indoxacarb Indoor Surface Treatments of Arilon 20% (KN128/KN127:75:25 Isomeric Mixture).

Lifestage

Post-application Exposure 

Scenario

Application

Rate a,

(lb ai/ft2)

Dose b, 

(mg/kg/day) MOEs c

Combined 

Routes

(X 

indicates 

included in 

Combined 

MOE)

Combined 

MOEs d Route of 

Exposure

Use Site

Crack and Crevice and Spot Directed Treatments (Indoor Surface Directed Sprays Scenario)

Arilon Insecticide 20% ai- EPA Reg. No. 100-1501

Adult Inhalation Surface directed 

sprays

0.00001 lb ai 

total isomer 

/ft2

(0.011 lb 

ai/gal)

2.5x 10-82.4 x 108 NA

Child 1 < 2 

years old Oral

Hand-to-Mouth 

from carpets 

(crack and 

crevice 

treatment)

0.0032 630

130

Hand-to-Mouth 

from carpets 

(spot directed 

Treatment)

0.0158 130 X

Object-toMouth from 

carpets (crack 

and crevice 

0.0004 4,800
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Table 3.2. Residential Post-application ST (Non-Cancer) Exposure and Risk Estimates for 

Indoxacarb Indoor Surface Treatments of Arilon 20% (KN128/KN127:75:25 Isomeric Mixture).

Lifestage

Post-application Exposure 

Scenario

Application

Rate a,

(lb ai/ft2)

Dose b, 

(mg/kg/day) MOEs c

Combined 

Routes

(X 

indicates 

included in 

Combined 

MOE)

Combined 

MOEs d Route of 

Exposure Use Site

Crack and Crevice and Spot Directed Treatments (Indoor Surface Directed Sprays Scenario)

Arilon Insecticide 20% ai- EPA Reg. No. 100-1501

treatment)

Object-toMouth from 

carpets (spot 

directed 

Treatment)

0.0021 950

Inhalation Surface directed 

sprays

1.1x 10-75.7x 107 X

Note: Assumes both spot treatment and crack and crevice directions are amended to reduce the maximum volume of 

product used to 1 gallon diluted product per 1000 sq. ft.

a. Based on maximum application rates from proposed amended label (EPA Reg. No.: 100-1501). The application rate

 have been adjusted by a 4/3 factor to account for 4 parts of total (S- and R-) indoxacarb for every 3 parts of S

indoxacarb.

b. Crack and Crevice and Spot Directed Treatment Scenarios Dose Equations

 Hand-to-Mouth Dose (mg/kg/day) = [(Fraction of ai on Hands (0.15) x Dermal Exposure (0.14)) ÷ (2 x Surface Area

 of 1 hand (150 cm2) ) × Fraction of Hand Mouthed (0.13) × Exposure Time per Day (carpet, 4; hard surfaces, 2 

 hours hrs/day) × # of Replenishment Intervals per Hour (4 int/hr) × (1-((1-Saliva Extraction Factor (0.5)) ^ (Number 

 of Hand-to-Mouth Events per Hour (20 events/hr) ÷ ( # of Replenishment Intervals per Hour (4)))] / Body 

 Weight (child, 11 kg)]

 Object-to-Mouth Dose (mg/kg/day) = [(Deposited Residue (1.0 μg/cm2) x Fraction of Residue Transferred to an

Object(carpet, 0.06; hard surface, 0.08)) × Unit Conversion Factor (0.001 mg/μg) × Object Surface Area Mouthed

(10 cm2/event) × Exposure Time (carpet, 4; hard surface, 2 hrs/day) × # Replenishment Intervals per Hour (4 int/hr) 

× (1-((1- Saliva Extraction Factor (0.50)) ^ (# Object-to-Mouth Events per Hour (14 events/hr) ÷ # Replenishment 

Intervals per Hour (4/ hr))) ÷ Body Weight (child, 11 kg)]

 Inhalation Daily Dose (mg/kg/day) = [(Inhalation Rate (0.64, adult; 0.33 child m3/hr) x Mass of Active Ingredient 

Applied (298 mg ai)) ÷ (Air Exchanges per Hour (0.45/hr) x Volume of Room (33 m3)) ÷ [1 – ((Air Exchanges per 

Hour (0.45/hr) x e ^ (-First Order Decay Rate (2.1 x 10-5) x Exposure Time (hr))) – (First Order Decay Rate (2.1 x 

10-5) x e ^ (-Air Exchanges per Hour (0.45/hr) x Exposure Time (hr))) ÷ (Air Exchanges per Hour (0.45/hr) – First 

Order Decay Rate (2.1 x 10-5))] ÷ Body Weight (child, 11 kg)]

c. MOEs: Inhalation MOE = Inhalation NOAEL (6 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

 Oral MOE = NOAEL (2 mg/kg/day) / Oral Dose (mg/kg/day)

d. Combined MOE = 1 ÷ [(1/incidental oral MOE) + (1/ Inhalation MOE)], where applicable.

3.3 Short-Term Aggregate Assessment

The short- term aggregate risk for indoxacarb includes background contribution from 

dietary (food and drinking water) exposure plus the short- and/or intermediate-term postapplication exposure to spray-treated indoor areas. The scenarios used in the aggregate 

assessment for indoxacarb are detailed below:
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 The short -term residential exposure for use in the adult aggregate assessment 

reflects residential handler inhalation from indoor treatments with surface directed 

sprays (spot treatments). 

 The short -term residential exposure for use in the child (1<2 years) aggregate 

assessment reflects combined post-application inhalation and incidental oral 

(hand-to-mouth) exposures from indoor treatments with surface directed sprays 

(spot treatments). 

The short- term aggregate (residential plus dietary) risk estimates for adults and children 

are below HED’s level of concern when considering residential exposures from indoor 

surface directed sprays (spot treatments) assuming a reduced spray volume application 

rate of 1 gallon diluted product per 1000 sq. ft (Table 3.3).

Table 3.3. Short-Term Aggregate Risk Calculations

Residential (Indoor Spray) plus Dietary (Food and Water) Exposures

Population

Short- Term Scenario

LOC for 

Aggregate 

Riska

Dietary

MOEb

MOE Oral 

Residential 

Exposurec

MOE 

Inhalation 

Residential 

Exposured

Aggregate MOE (food, 

water, and residential)e

Adult 100 1,800 NA 80,000 1,800

Child (1<2 yrs) 100 840 130 5.7 x 107110

a LOC=100 (10x inter- and 10x intra- species uncertainty factors)

b MOE dietary = [(short- or intermediate-term oral NOAEL)/(chronic dietary exposure)]. Oral NOAEL= 

2.0 mg/kg/day. Chronic dietary exposure value from D402099, 05/02/2013; Table 5.4.5. 

c MOE oral = [(short- or intermediate-term oral NOAEL)/(hand-to-mouth residential exposure)]. Oral 

NOAEL= 2 mg/kg/day. 

d MOE inhalation = [(short- or intermediate-term inhalation NOAEL)/ (high end inhalation residential 

exposure)]. Inhalation NOAEL= 6.0 mg/kg/day. Adult residential handler exposure value from Table 3.1

and child residential exposure value from Table 3.2.

eMOE Aggregate = 1/[(1/MOE dietary) + (1/MOE oral) + (1/MOE inhalation)]

4.0 REFERENCES

Rivera-Lupiáñez A., D464583, 05/01/2013. Indoxacarb: Revised Occupational and 

Residential Risk Assessment to Support Request for Section 3 Registrations on Bean (dry), 

Bean (snap), Bean (forage), and Small Fruit Vine Climbing Subgroup 13-07F and LowGrowing Berry Subgroup 13-07H.

Drew D. et al; D402099, 05/02/2013. Indoxacarb: Human Health Risk Assessment for 

the Proposed New Use on Dry Beans, Succulent Beans, Small Fruit Vine Climbing 

Subgroup (except kiwifruit) 13-07F and Low Growing Berry Subgroup (except 

strawberry) 13-07H.