Indoxacarb Human Health Risk Assessment DP No. D416367

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: November 25, 2013

SUBJECT: 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. 

PC Code: 067710 DP Barcode: D416367

Decision No.: 464583 Registration No.: 352-579 and 352-638

Petition No.: 2E8029 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical

Aggregate 

Case No.: NA

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

MRID No.: NA 40 CFR: §180.564

FROM: Danette Drew, Chemist

Ideliz Negrón-Encarnación, Ph.D., Chemist

Ana Rivera-Lupiáñez, Chemist

William Irwin, Ph.D., Toxicologist

 Risk Assessment Branch V/VII

Health Effects Division (7509P)

THROUGH: Michael Metzger, Branch Chief

Risk Assessment Branch V/VII

Health Effects Division (7509P)

TO: Laura Nollen, Risk Manager

Barbara Madden, Risk Manager

Risk Integration, Minor Use & Emergency Response Branch

Registration Division (7505P)
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1.0 Executive Summary............................................................................................................. 4

2.0 HED Recommendations....................................................................................................... 7

2.1 Data Deficiencies ............................................................................................................. 7

2.2 Tolerance Considerations................................................................................................. 8

2.2.1 Enforcement Analytical Method .................................................................................. 8

2.2.2 Recommended Tolerances............................................................................................ 8

2.2.3 Revisions to Petitioned-For Tolerances........................................................................ 9

2.2.4 International Harmonization......................................................................................... 9

2.3 Label Recommendations................................................................................................ 10

2.3.1 Recommendations from Residue Reviews................................................................. 10

2.3.2 Recommendations from Occupational Assessment ................................................... 10

2.3.3 Recommendations from Residential Assessment....................................................... 10

3.0 Introduction........................................................................................................................ 10

3.1 Chemical Identity ........................................................................................................... 10

3.2 Physical/Chemical Characteristics................................................................................. 11

3.3 Pesticide Use Pattern...................................................................................................... 12

3.4 Anticipated Exposure Pathways..................................................................................... 13

3.5 Consideration of Environmental Justice ....................................................................... 13

4.0 Hazard Characterization and Dose-Response Assessment................................................ 14

4.1 Summary of Toxicological Effects ................................................................................ 14

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)....................................... 16

4.2.1 Completeness of the Toxicology Database ................................................................ 16

4.2.2 Evidence of Neurotoxicity.......................................................................................... 16

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal............. 17

4.2.4 Residual Uncertainty in the Exposure Database......................................................... 17

4.3 Toxicity Endpoint and Point of Departure Selections.................................................... 17

5.0 Dietary Exposure and Risk Assessment ............................................................................ 21

5.1 Residues of Concern Summary and Rationale............................................................... 21

5.2 Food Residue Profile...................................................................................................... 22

5.3 Water Residue Profile .................................................................................................... 23

5.4 Dietary Risk Assessment................................................................................................ 24

5.4.1 Description of Residue Data Used in Dietary Assessment......................................... 24

5.4.2 Percent Crop Treated Used in Dietary Assessment.................................................... 24

5.4.3 Acute Dietary Risk Assessment.................................................................................... 25

5.4.4 Chronic Dietary Risk Assessment .............................................................................. 25

5.4.5 Summary Table........................................................................................................... 25

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ..................................... 26

6.1 Residential Handler Exposure........................................................................................ 26

6.2 Residential Post-Application Exposure.......................................................................... 29

6.3 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 34

6.4 Residential Bystander Post-application Inhalation Exposure ........................................ 37

6.5 Spray Drift...................................................................................................................... 37

7.0 Aggregate Exposure/Risk Characterization....................................................................... 38

7.1 Acute Aggregate Risk .................................................................................................... 38

7.2 Short- and Intermediate-Term Aggregate Risk............................................................... 38

7.3 Long-Term (Chronic) Aggregate Risk........................................................................... 39
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7.4 Cancer Aggregate Risk................................................................................................... 40

8.0 Cumulative Exposure/Risk Characterization....................................................................... 40

9.0 Occupational Exposure/Risk Characterization .................................................................... 40

9.1 Short- and Intermediate- Term Handler Risk................................................................. 42

9.2 Short- and Intermediate-Term Post-Application Risk ................................................... 45

9.2.1 Dermal Post-Application Risk.................................................................................... 46

9.2.2 Inhalation Post-Application Risk................................................................................ 46

10.0 References.......................................................................................................................... 47

Appendix A. Toxicology Profile and Executive Summaries....................................................... 48

Appendix B. Physical/Chemical Properties................................................................................. 55

Appendix C. Review of Human Research ................................................................................... 56
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1.0 Executive Summary

The Registration Division (RD) requested that the Health Effects Division (HED) conduct a

human health risk assessment to support an IR-4 petition (PP#2E8029) for the proposed foliar 

uses of the insecticide indoxacarb on the following agricultural crops: 1) new uses on dry beans

and succulent beans and 2) expanded crop group uses on small fruit vine climbing subgroup 13-

07F (except kiwifruit) and low-growing berry subgroup 13-07H (except strawberry). 

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, 

is an oxadiazine class insecticide active ingredient (ai). It is registered for use in both 

agricultural and residential sites. Permanent tolerances are established under 40 CFR 180.564(a) 

for the combined residues of indoxacarb and its R-enantiomer on a number of plant as well as 

livestock commodities (tolerances on poultry commodities also include several indoxacarb 

metabolites). The primary residues of toxicological concern for risk assessment are indoxacarb 

(S-enantiomer) and its R-enantiomer; various metabolites and degradates are also included as 

residues of concern in milk, poultry commodities and drinking water. This assessment takes into 

account the proposed crop uses and previously registered uses on other crops and in residential 

sites.

Indoxacarb is formulated as granular; impregnated materials; water dispersible granules; 

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

products are frequently formulated as a mixture of the insecticidally active S-enantiomer and the 

insecticidally inactive R-enantiomer. The percent active ingredient and application rates listed 

on indoxacarb product labels only reflect the S-enantiomer; labels do not reflect the amount of

R-enantiomer in the mixtures. Adjustments are made in this assessment to add in the percent of 

R-enantiomer in product mixtures so that the total amount of indoxacarb applied (both S- and Renantiomers) is considered. The term ‘indoxacarb’ generally refers to the S-enantiomer (also 

called DPX-KN128 or KN128) but may also refer to a mixture. Mixtures may appear as 1) 

isomer enriched DPX-MP062 (also referred to as MP062) which is a mixture containing the Senantiomer and its R-enantiomer at approximately a 75:25 ratio, or 2) racemic mixture DPXJW062 (also referred to as JW062) which is a mixture of the enantiomers at a 50:50 ratio. The 

R-enantiomer is also referred to as IN-KN127 or KN127. 

The database for indoxacarb is complete and is sufficient for characterizing toxicity. Toxicology

studies have been performed using either MP062 or JW062 (S-enantiomer and R-enantiomer 

mixtures) or the KN128 (S-enantiomer only). 

The toxicity profiles for KN128, MP062 and JW062 in rats, mice and dogs with both subchronic 

and chronic oral exposures were qualitatively similar. The endpoints that most frequently

defined the lowest-observed-adverse-effect-level (LOAEL) were non-specific, and included 

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

compounds also affected the hematopoietic system by decreasing the red blood cell count, 

hemoglobin and hematocrit in rats, dogs and mice. 
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There was no evidence of reproductive effects in the 2-generation reproduction study in rats. 

There was no evidence of susceptibility from either in utero or neonatal exposure to both rat and 

rabbit young or in the developmental neurotoxicity study in rats. Neurotoxicity was seen in 

animal studies in rats and mice but at doses much higher than those selected for points of 

departure (which are based on changes in body weight, food consumption and changes in 

hematology) for the current risk assessment. There is no evidence of teratogenicity, 

mutagenicity, or carcinogenicity in the indoxacarb studies.

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 post-natal 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.

The only new toxicity information received since the last indoxacarb risk assessments (D351087, 

5/18/09, Indoxacarb. Health Effects Division (HED) Human Health Risk Assessment for 

Bushberry Crop Subgroup 13-07B and Beets (Garden) and D365306, 5/26/09, Indoxacarb. 

Addendum to the Health Effects Division (HED) Human Health Risk Assessment for Bushberry 

Crop Subgroup 13-07B and Beets (Garden)) is the immunotoxicity study, which did not indicate 

immunotoxic potential for indoxacarb. The toxicity endpoints have not changed with the 

exception of the addition of a long-term oral endpoint to cover residential uses of that duration 

and a revision to the dermal toxicity endpoint. The long-term oral endpoint and point of 

departure are the same as those selected for short- and intermediate –term durations. A reevaluation of the available dermal toxicity studies, including rat in vivo, and rat and human in 

vitro studies, has been performed. Based on this evaluation, it has been determined that a 

quantitative dermal assessment is not required for indoxacarb, since the calculated human dermal 

LOAEL exceeds the limit dose of 1000 mg/kg/day and dermal toxicity is therefore not expected 

in humans.

Acute and chronic dietary (combined food and drinking water) assessments were performed for 

indoxacarb using partially refined assumptions such as residues from field trail data and, where 

available, percent crop treated estimates and processing factors. Estimated drinking water 

concentrations were derived from modeling procedures. The resulting acute and chronic dietary

exposures are below HED’s level of concern for the general U.S. population and all population 

subgroups (aPAD or cPAD <100%). 

No new residential uses are being requested with this petition; however, there are existing 

residential uses (ornamental lawns and turf/golf courses, and spot-on applications for the control 

of fleas and ticks on domestic animals) that have been previously assessed and are assessed 

herein to reflect updates to HED’s 2012 Residential SOPs1, policy changes for body weight 

assumptions, and a re-evaluation of the dermal toxicity of indoxacarb. In addition, there are 

existing residential uses (insect control treatments of household premises; Arilon Insecticide 20% 

ai, EPA Reg. No. 100-1501 and Aperion Insecticide 14.5% ai ,EPA Reg. No. 352-770) which do 

not appear to have been previously assessed and are assessed herein.

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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Indoxacarb RTU bait stations and gels products are formulated at very low application rates and 

are designed to be self-contained; therefore, handler contact is expected to be negligible and 

post-application exposures are not expected. Exposure and risk for these uses were not 

quantified. Inhalation assessments are not performed for applying pet spot-on treatments as 

inhalation exposure is not expected from these uses. Dermal exposures are expected to be 

negligible when applying spot-on products; in addition, indoxacarb does not have a dermal 

toxicity endpoint for humans. Therefore, a quantitative handler assessment is not performed for 

the indoxacarb pet spot-on treatments.

Residential adult handler scenarios assessed include turf applications and indoor spray

applications (inhalation only). Residential post-application scenarios assessed include 1) 

children’s exposure (inhalation and non-dietary oral) to treated pets, treated turf and spraytreated indoor surfaces and 2) adult exposure to spray-treated indoor surfaces (inhalation only).

Most indoxacarb residential handler (adult) and post-application (adult and children) exposure 

scenarios result in risk estimates below HED’s level of concern. However, for spot-directed 

treatments of the indoor directed spray, incidental oral (hand-to-mouth) exposure estimates alone 

for children exceed HED’s level of concern. For crack and crevice treatment only scenario of 

the indoor directed spray, the combined inhalation and incidental oral risk estimates for children 

are not of concern. 

Based on the existing and newly proposed uses of indoxacarb, exposures can occur both from 

dietary sources (food and water) and in residential settings. Acute, short-term, intermediate-term 

and long-term (chronic) aggregate (combined food, water and residential exposure) assessments 

were performed for indoxacarb. The scenarios resulting in the highest exposures are selected as 

protective scenarios for the aggregate assessments. There are no acute, short-term, intermediateterm, or long-term (chronic) aggregate risk estimates of concern for adult (handler or postapplication) or child (post-application) exposure to indoxacarb as a result of current and 

proposed uses. Note: the aggregate assessment for indoor surface directed spray assumed 

only crack and crevice treatment. The residential post-application (hand-to-mouth) 

exposure to the spot-directed sprays resulted in risks of concern for children and was not 

used in the aggregate assessment. At this time, labels for the indoor surface directed sprays 

do not limit the use to only crack and crevice.

A quantitative dermal risk assessment is not required for indoxacarb. All occupational handler 

scenarios assessed associated with the proposed uses result in inhalation MOEs that do not 

exceed HED's level of concern (MOEs ≥ 100) for short- and intermediate-term exposure 

durations at label specified personal protective equipment (PPE). Further, there were no risks of 

concern identified for post-application exposure to indoxacarb associated with these new uses.

No additional (PPE) is required. The label restricted entry interval (REI) of 12 hours is 

appropriate and in compliance Worker Protection Standard requirements. 

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898 (see Section 3.5 

of this document). For information regarding human studies, see Appendix C.
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2.0 HED Recommendations

Assuming spot-directed spray treatments are removed from residential product labels (i.e. use 

limited to crack and crevice only), HED has no objection to registration and associated 

tolerances for the use of indoxacarb on dry beans, succulent beans, small fruit vine climbing 

subgroup 13-07F (except kiwifruit) and low growing berry subgroup 13-07H (except 

strawberry). Additional requirements are outlined in Section 2.1 below. The specific tolerance 

recommendations are discussed in Section 2.2, and label modifications are discussed in Section 

2.3.

2.1 Data Deficiencies

Residue Chemistry

860.1200 Directions for Use

The proposed label directions are adequate for evaluating the residue data for the proposed new 

uses. However, the labels should be revised to clarify discrepancies or add specificity (see 

Section 2.3.1 of this document).

860.1550 Proposed Tolerances

A revised Section F should be submitted according to Table 2.2.2. 

860.1650 Submittal of Analytical Reference Standards 

An analytical standard for the insecticide indoxacarb is currently available in the EPA National 

Pesticide Standards Repository. However, the indoxacarb standard has an expiration date of 

4/2013. A reference standard should be sent to the Analytical Chemistry Laboratory located in 

Fort Meade to the attention of either Theresa Cole or Thuy Nguyen at the following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

Please note that mail will be returned if the entire extended zip code is not used when addressing 

correspondence to the Repository. 

Toxicology and Hazard

None.

Occupational and Residential Exposure

None.
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2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

A number of adequate methods are available for enforcing indoxacarb tolerances on plant 

commodities. These protocols are all common moiety methods which measure both indoxacarb 

and its R-enantiomer as a single component.

The primary protocol for the tolerance enforcement of plant commodities is DuPont method 

AMR 2712-93 which is an HPLC/UV procedure. It has been validated by the Agency and 

forwarded to the FDA for inclusion in PAM Vol. II (D267339, S. J. Levy, 10/12/2000). 

For the confirmation of residues in plant commodities, DuPont method AMR 3493-95 

Supplement No. 4 is a GC/MSD procedure is also available. This method has also been 

validated by the Agency and forwarded to the FDA accordingly (D282821, S. J. Levy, 

05/09/2002). Residues are quantified using the m/z 527 ion, and confirmatory analyses utilize 

the 218, 321 and 527 ions. 

 

Another HPLC/UV procedure developed by the registrant, DuPont-11978, is also available for 

tolerance enforcement analyses (D313518, S. J. Levy, 02/18/2005). This protocol works by 

uniquely combining the extraction procedure of method AMR-3493-95 with the cleanup and 

determination techniques developed in method AMR 2712-93. 

2.2.2 Recommended Tolerances

HED recommends that 40 CFR 180.564 be amended by establishing or removing tolerances for 

the plant commodities as listed in the Table 2.2.2. Tolerances for livestock commodities and 

rotational crops are not needed to support the proposed uses of indoxacarb. The tolerances for 

indoxacarb in plant commodities are defined as follows: Tolerances are established for residues 

of indoxacarb, including its metabolites and degradates, in or on the commodities in the table 

below. Compliance with the tolerance levels specified below is to be determined by measuring 

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

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

carboxylate, and its R-enantiomer, (R)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-

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

carboxylate, in or on the commodity.
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Table 2.2.2. Tolerance Summary for Indoxacarb.

Commodity Established/Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Comments (correct 

commodity definition)

Bean, dry, seed 0.07 0.2

Pea, southern, seed 0.1 Remove

Bean, succulent 0.64 0.9

Bean, forage 37 50 Cowpea, forage

Cowpea, hay -- 100

Small fruit vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

2.0 2

Low growing berry, except 

strawberry, subgroup 13-07H

0.9 1

Cranberry 0.90 Remove

Grape 2.0 Remove

2.2.3 Revisions to Petitioned-For Tolerances

The registrant-proposed tolerances for indoxacarb are different from those recommended by the 

HED. The recommended tolerances were derived by using the Organization for the Economical 

Cooperation and Development (OECD) calculation procedures while the registrant used the 

North America Free Trade Agreement (NAFTA) calculation procedures. In addition, the 

tolerance for indoxacarb on dry beans covers the southern pea variety (cowpea) which already 

has a tolerance established in the CFR. Since the forage and hay of cowpea are the only 

significant feedstuff associated with dry beans, the correct commodity definition would be 

cowpea, forage instead of bean, forage. HED is recommending a tolerance be established for 

residues of indoxacarb on cowpea hay; a tolerance for cowpea hay was not proposed. In order to 

harmonize with the Codex maximum residue level (MRL) for cowpea (see discussion in 2.2.4 

below), the tolerance for dry bean obtained by the OECD calculation procedures (0.06 ppm) will 

be increased to 0.2 ppm. The registrant should submit a revised Section F in which the proposed 

tolerances are the same as those recommended by the HED.

2.2.4 International Harmonization

U.S. tolerances are recommended for dry beans, succulent beans, small fruit vine climbing 

subgroup 13-07F, and low growing berry subgroup 13-07H based on residues of indoxacarb and 

its R-enantiomer. Maximum residue limits (MRLs) have not been established by Canada or 

Mexico. However, Codex has established MRLs for grapes (2 ppm), dry grapes (5.0 ppm), 

cranberries (1ppm), dry chick-pea (0.2 ppm), dry mung bean (0.2 ppm), and dry cowpea (0.1 

ppm) based on measurement of indoxacarb and its R-enantiomer. The U.S. tolerances for raisins 

(5.0 ppm) and cranberries (1 ppm) are harmonized with the corresponding Codex MRLs. The 

U.S. tolerance for grapes (subgroup 13-07F) obtained with the OECD calculator (3 ppm) is 

higher than the Codex MRL for grapes (2 ppm). The U.S. crop field trial data for grapes show 

that the highest residue is 1.74 ppm, and the registrant proposed a tolerance level of 2.0 ppm. 

HED recommends establishment of a grape tolerance level of 2 ppm in order to harmonize with 

Codex. The tolerance level for dry bean (0.06 ppm) obtained by the OECD calculation 
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procedures will be increased to 0.2 ppm in order to harmonize with the Codex MRLs for dry

chick pea and dry mung bean. 

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

The following label recommendations are needed to clarify discrepancies or add specificity:

 Under the application instructions (page 3 of Avaunt®label) include dry bean in the 

sentence “For bushberry, cranberry, dry bean, pome and stone fruit the minimum

interval between treatments is 7 days.” 

 Under the tabulated instructions (page 6 of Avaunt®label and page 5 of Steward®EC 

label) for dry bean and/or succulent bean edit the sentence “Make a uniform application 

in approximately 20-100 gallons of water per acre” to specify the volume for ground 

and/or aerial applications.

2.3.2 Recommendations from Occupational Assessment

None.

2.3.3 Recommendations from Residential Assessment

The assessment for indoxacarb indoor surfaces directed sprays resulted in post-application risk 

estimates of concern for children for spot-directed treatment scenarios; however, when the 

surfaces directed spray treatments were assumed to be limited to crack and crevice only, risk 

estimates were not of concern. HED recommends amending the EPA Reg. No. 100-1501 label 

to restrict indoor residential uses to only crack and crevice treatments limiting applications to 

areas not accessible to young children; any spot, perimeter, or baseboard treatments should be 

restricted on the label.

3.0 Introduction

3.1 Chemical Identity
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Table 3.1 Indoxacarb Nomenclature.

Compound

Common name Indoxacarb

Company experimental name DPX-KN128

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

(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine4a(3H)-carboxylate

CAS name methyl (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-

(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine4a(3H)-carboxylate

CAS registry number 173584-44-6

End-use product (EP) 30% WDG (DuPont Avaunt®Insecticide; EPA Reg. No. 352-597) and 16% 

Emusifiable Concentrate (Steward® EC Insecticide; EPA Reg. No. 352-638)

Compound

Common name R-enantiomer of indoxacarb

Company name IN-KN127 (pesticidally inactive)

3.2 Physical/Chemical Characteristics

Indoxacarb has a very low vapor pressure of 1.9x10-10 mm Hg at 25 oC; volatilization is not 

expected to be a significant route of dissipation for this pesticide. The octanol water partition 

coefficient (Kow = 44000) suggests that it is lipophilic. Indoxacarb is slightly soluble in water 

(0.8 mg/L at pH 7). 

Indoxacarb is stable to aqueous photolysis and hydrolysis. Aerobic aquatic, aerobic soil, and 

anaerobic aquatic metabolism of indoxacarb results in half-lives of 71 days, 267 days, and 577 

days, respectively.

See Appendix B for a table of physicochemical properties of indoxacarb.

O

N

N

O O

CH3

Cl N

O

O

O

O

CF3

CH3

O

N

N

O O

CH3

Cl N

O

O

O

CH3

O

CF3
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3.3 Pesticide Use Pattern

IR-4 has submitted field trial data in support of a petition proposing tolerances for the use of 

Avaunt® WDG and Steward®EC on dried beans and Avaunt® WDG on succulent beans. In 

addition, crop subgroup tolerances and registration of Avaunt® WDG for use on small fruit vine 

climbing subgroup (except kiwifruit) 13-07F, and low growing berry subgroup (except 

strawberry) 13-07H are proposed based on established tolerances for grapes and cranberries. 

The proposed new uses are summarized below in Table 3.3. Refer to section 2.3 for 

recommended modifications to the proposed labels.

Table 3.3 Summary of Directions for Use of Indoxacarb.

Applic. Timing, Type, 

and Equip. 1

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations 2

Bean, succulent

Broadcast foliar 

applications when 

insects reach economic 

thresholds; ground or 

air equipment

30% WDG

[352-597] 0.11 NS 0.44 3

A minimum 7-day RTI is 

specified. Make a uniform 

application of approximately

20-100 gal/A.

Bean, dry

Broadcast foliar 

applications when 

insects reach economic 

thresholds; ground or 

air equipment

30% WDG

[352-597]

and 

16% EC

[352-638]

0.11 NS 0.44 7

A minimum 7-day RTI is 

specified. Make a uniform 

application of approximately

20-100 gal/A.

Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F

Broadcast foliar 

applications when 

insects reach economic 

thresholds; ground or 

air equipment

30% WDG

[352-597] 0.11 NS 0.22 7

A minimum 21-day RTI is 

specified. Apply in a 

minimum of 10 gal/A and 50

gal/A for aerial and ground 

applications, respectively.

Low growing berry, except strawberry, subgroup 13-07H

Broadcast foliar 

applications when 

insects reach economic 

thresholds; ground or 

air equipment

30% WDG

[352-597] 0.11 NS 0.44 30

A minimum 7-day RTI is 

specified. Apply in a 

minimum of 5 gal/A and 10

gal/A for aerial and ground 

applications, respectively.

1 Do not apply through any type of irrigation system, expect for application to cranberry, mint, potato, and sweet corn, and as

allowed on supplemental labels.

2 Applications may include the use of an adjuvant. Rotational crop restrictions: (1) 30%WDG: Crops with labeled uses and 

alfalfa, cotton, peanuts and soybeans may be planted immediately following harvest of a treated crop. Do not plant any food or 

feed crops not registered for use with indoxacarb for 30 days after last use. (2) 16% EC: Crops that are on this label and all 

brassica leafy vegetables, cucurbit vegetables, fruiting vegetables, leafy green vegetables, leafy petiole vegetables, pome fruit 

and stone fruit, plus sweet corn, cranberry, grape, mint, southern pea and the tuberous and corm vegetables found in crop 

subgroup 1C (arracacha, arrowroot, Chinese artichoke, edible canna (Queensland arrowroot), bitter and sweet cassava, 

chayote(root), chufa, dasheen (taro), ginger, leren, potato, sweet potato, tanier (cocoyam), tumeric, yam bean (jicama, manoic 

pea) and true yam) may be planted immediately following harvest. Do not plant for food or feed any other crops not registered

for use with indoxacarb for 30 days after last use.
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3.4 Anticipated Exposure Pathways

Indoxacarb is registered for use on numerous agricultural crops as well as on pets, turf and inside 

homes. Exposure to indoxacarb may occur from ingestion of residues in/on foods and in 

drinking water, and via the dermal and inhalation routes for adults using indoxacarb products in 

occupational and residential settings. In addition, both adults and children may be exposed 

dermally or via inhalation in post-application scenarios on golf courses, lawns, and in homes; 

children may also be exposed orally in post-application scenarios on pets, lawns and in homes. 

There is a potential for post-application dermal or inhalation exposure for workers re-entering 

treated fields. 

Risk assessments have been previously conducted for indoxacarb (2009, D351087 and 

D365306). The toxicity endpoints and points of departure have not changed with the exception 

of the addition of a long-term oral point of departure to cover residential uses of that duration 

and a revision to the dermal toxicity endpoint. A re-evaluation of the dermal toxicity studies, 

including rat in vivo, and rat and human in vitro studies, has been performed. Based on this 

evaluation, it has been determined that a quantitative dermal assessment is not required for 

indoxacarb, since the calculated human dermal LOAEL exceeds the limit dose of 1000 

mg/kg/day and dermal toxicity is therefore not expected in humans. In addition, residential 

SOPs have since been revised (2012) and there are registered residential use products for which 

assessments have not been previously performed. This risk assessment considers the 

aforementioned relevant exposure pathways based on all of the existing and proposed new uses 

of indoxacarb.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption,

and activities in and around the home that involve pesticide use in a residential setting.

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and/or the CDC under the National Health and 

Nutrition Examination Survey/What We Eat in America (NHANES/WWEIA), and are used in 

pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and 

categorized by subgroups based on age, season of the year, ethnic group, and region of the 

country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary
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patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

The only new toxicity information received since the last risk assessment (2009; D351087 and 

D365306) is the immunotoxicity study, which was negative at doses up to 23 mg/kg/day. The 

toxicity endpoints have not changed with the exception of the addition of a long-term oral 

endpoint to cover residential uses of that duration and a revision to the dermal toxicity endpoint. 

The long-term oral endpoint and point of departure is the same as that selected for short- and 

intermediate –term durations. A re-evaluation of the dermal toxicity studies, including rat in 

vivo, and rat and human in vitro studies, has been performed. Based on this evaluation, it has 

been determined that a quantitative dermal assessment is not required for indoxacarb, since the 

calculated human dermal LOAEL exceeds the limit dose of 1000 mg/kg/day and dermal toxicity

is therefore not expected in humans.

4.1 Summary of Toxicological Effects

Indoxacarb products contain the enantiomeric compounds indoxacarb (S-enantiomer; DPXKN128) and its R-enantiomer (IN-KN127). DPX-MP062 (also referred to as MP062) is a 

mixture containing the S-enantiomer and its R-enantiomer at approximately a 75:25 ratio. DPXJW062 (also referred to as JW062) is the racemic mixture of the enantiomers. Many of the 

toxicity studies were conducted with JW062 (50:50). HED’s Hazard Identification Assessment 

Review Committee (HIARC; HED Doc No. 013528) determined that it is appropriate to use data 

from DPX-JW062 (50:50) to satisfy the requirements for dietary subchronic, chronic, 

oncogenicity and reproductive studies. Based on previous conclusions by the HIARC, HED also 

accepted the same rationale for bridging the data from DPX-JW062 and DPX-MP062 to register 

DPX-KN128 formulations (S-enantiomer only; no R-enantiomer).

The toxicity profiles for KN128, MP062 and JW062 in rats, mice and dogs with both subchronic 

and chronic oral exposures were qualitatively similar. Dermal subchronic exposure in the rat 

also resulted in a similar profile. The toxic signs occurred at similar doses and with a similar 

magnitude of response, with females generally being more sensitive than males. The endpoints 

that most frequently defined the lowest-observed-adverse-effect-level (LOAEL) were nonspecific, and included decreases in body weight, weight gain, food consumption and food 

efficiency. These compounds also affected the hematopoietic system by decreasing the red 

blood cell count, hemoglobin and hematocrit in rats, dogs and mice. It was frequently 

accompanied by an increase in reticulocytes in all three species and an increase in Heinz bodies 

(dogs and mice only). None of these signs of toxicity appeared to get worse over time. In one 

subchronic rat study, the parameters appeared to return to normal levels following a four-week 

recovery period. High doses in the rats and mice also sometimes caused mortality.

Neurotoxicity was observed in rats and mice but at higher doses (>100 mg/kg/day) than the 

hematologic effects (3.3 mg/kg/day) on which the risk assessments are based. Neurotoxicity

was characterized by one or more of the following symptoms in both male and female rats and 

mice: weakness, head tilting, and abnormal gait or mobility with inability to stand, ataxia. There 
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was possible evidence of lung damage in the acute inhalation studies with both MP062 and 

JW062. Subchronic (28 days) inhalation toxicity on indoxacarb in rats was characterized by

increased spleen weights, increased pigmentation and hematopoiesis in the spleen, and 

hematological changes.

There was no evidence of carcinogenicity in either the rat or mouse in acceptable studies 

(JW062). JW062 was not mutagenic in a complete battery of mutagenicity studies. There was 

also no evidence of mutagenicity with either KN128, or MP062. Therefore, KN128, MP062 

were classified as “not likely” to be carcinogenic in humans by all relevant routes of exposure.

In rats, both JW062 and MP062 were rapidly absorbed and eliminated following oral 

administration. The metabolite profile for DPX-JW062 was dose dependent and varied 

quantitatively between males and females. Differences in metabolite profiles were also observed 

for the different label positions. Fat tissue contained the greatest level of radioactivity and, for 

both compounds, was greater in female rats. Both MP062 and JW062 were extensively

metabolized and the metabolites were eliminated in the urine, feces, and bile. All of the biliary

metabolites appear to undergo further biotransformation in the gut. 

A quantitative dermal assessment is not required for indoxacarb, since the calculated human 

dermal LOAEL exceeds the limit dose of 1000 mg/kg/day. The rat 28-day dermal study had a 

wide dose spacing at the lowest two doses (i.e. 50 mg/kg/day and 500 mg/kg/day), thus the rat 

NOAEL value of 50 mg/kg/day may be well below the no-effect dose in both rats and humans. 

The rat in vivo dermal absorption was 4.91%, with results from an acceptable guideline study. In 

comparison, the ratio of the LOAELs from the rat developmental study and the rat 28-day dermal 

study of similar durations estimates the rat dermal absorption to be a much lower value of 0.8% 

(i.e. 100 x 4 mkd/500 mkd), with the rat dermal absorption typically multiple times higher than 

humans. Based on the in vitro dermal absorption data for human skin and rat skin, the rat dermal 

absorption was 17.5X higher than human dermal absorption, thus the calculated indoxacarb 

internal dose would be much higher in rats than humans. Specifically for indoxacarb, the rat in 

vitro absorption was 15.2% and human in vitro absorption was 0.87%. Therefore, the dermal 

triple pack data was utilized to refine the dermal POD from the rat sub-chronic dermal study. 

Using the NOAEL value of 50 mg/kg/day from the route-specific 28-day dermal study in rats 

and the 17.5x ratio of human skin to rat skin absorption, the equivalent human dermal NOAEL is 

875 mg/kg/day for indoxacarb (mixed isomers, 50 mkd x 15.2%/0.87%). The corresponding 

human dermal LOAEL value is calculated to be 8750 mg/kg/day, thus a dermal assessment is not 

required for indoxacarb. Additionally, utilizing the 4.91% rat dermal absorption and the 

rat:human dermal absorption ratio of 17.5X, the human equivalent dermal absorption is 

estimated to be very low, at 0.28%, using the parallelogram method.

The toxicological database for indoxacarb is complete and adequate for dose response 

assessment and susceptibility determinations. The immunotoxicity study in mice did not indicate 

toxicity to the immune system at doses up to 23 mg/kg/day. In the 28-day inhalation study (rats) 

increased spleen weights, pigmentation and hematopoiesis in the spleen, and hematological 

changes were observed at the highest dose tested (75.6 mg/kg/day). Increased spleen weights 

were also observed in the 28-day dermal rat study (500 mg/kg/day). The increase in spleen 

weights are not considered immunological in origin but can be considered a result of the 
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hemolytic effects, which is the mode of action of indoxacarb. Indoxacarb is currently regulated 

based on a NOAEL of 2.0 mg/kg/day for chronic dietary exposure (protective of hemolytic 

effects) and 12 mg/kg/day for acute dietary exposure.

KN128 and MP062 appear to be of similar acute oral toxicity with an acute oral toxicity category

II, while JW062 appears less toxic acutely (acute oral toxicity category IV). MP062 and JW062 

had low acute inhalation toxicity. MP062 and JW062 had moderate to low ocular irritant 

properties, while KN128 was practically non-irritating to the rabbit’s eyes. By the dermal route, 

KN128, MP062 and JW062 demonstrate low toxicity. By the maximization test, KN128 and 

MP062 were considered dermal sensitizers, while JW062 was not a sensitizer.

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

The following factors supporting reduction of the FQPA safety factor (SF) to 1X: 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; 4) the acute 

neurotoxicity, subchronic neurotoxicity, and developmental neurotoxicity studies are available 

and all endpoints used in this risk assessment are protective of neurotoxic effects; and 5) 

exposures estimates will not underestimate actual exposures.

4.2.1 Completeness of the Toxicology Database

The toxicity database for indoxacarb is complete. There was no evidence of reproductive effects 

in the 2-generation reproduction study in rats. Teratogenicity was not observed in rats or rabbits. 

There was no evidence of susceptibility from either in utero or neonatal exposure to both rat and 

rabbit young or in the developmental neurotoxicity study in rats. 

HED has confidence that the risk assessment conducted with a reduced FQPA safety factor (1X) 

will provide a reasonable certainty of no harm to the safety of infants and children.

4.2.2 Evidence of Neurotoxicity

Neurotoxicity was observed in rats and mice but at higher doses (>100 mg/kg/day) than the 

hematologic effects (3.3 mg/kg/day) on which EPA’s risk assessments are based. Neurotoxicity

was characterized by one or more of the following symptoms in both male and female rats and 

mice: weakness, head tilting, and abnormal gait or mobility with inability to stand, ataxia. 

Acute and subchronic neurotoxicity screening batteries were performed using MP062 in rats. 

Neurotoxicity was characterized by clinical signs (depression, abnormal gait, head shake, 

salivation) and functional-observation battery (FOB) (circling behavior, incoordination, slow 

righting reflex, decreased forelimb grip strength, decreased foot splay, decreased motor activity). 

However, there was no evidence of neurohistopathology in any study. There was no evidence of 

increased sensitivity of offspring in the developmental neurotoxicity study using KN128. 

Clinical observations, motor activity, acoustic startle habituation, and learning and memory

testing were all comparable between the control and treated groups. Mean brain weight, gross 
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and microscopic examinations and morphometric measurements of the brain were also 

comparable between the controls and treated groups.

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There was no evidence of susceptibility from either in utero or neonatal exposure to both rat and 

rabbit young with either MP062 or JW062. There was no evidence of increased susceptibility in 

the young in the developmental neurotoxicity study in rats with KN128. There was no evidence 

of reproductive effects in the 2-generation reproduction study in rats (JW062). No evidence of 

teratogenicity was observed in rats and rabbits with MP062 or JW062 nor evidence of 

teratogenicity in rats treated with KN128. 

4.2.4 Residual Uncertainty in the Exposure Database

The database for indoxacarb is extensive and is sufficient for characterizing toxicity and hazard. 

There are no outstanding toxicity or exposure data and the FQPA safety factor is reduced to 1X. 

HED used partially refined assumptions in the dietary exposure assessment, including the use of 

percent crop treated and field trial residue values. Upper-bound estimates of potential exposure 

through drinking water were used. In addition, the residential exposure assessment was 

conducted such that residential exposure and risk will not be underestimated. The aggregate 

exposure and risk estimates presented in this assessment will not underestimate actual exposure 

and risk expected based on the current and proposed use patterns.

4.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes since the last risk assessment to the prior dose-response assessment, 

endpoint selection or cancer classification, except for the addition of the long-term incidental 

oral category for to residential uses of that duration and the re-evaluation of the dermal toxicity

endpoint. The long-term incidental oral point of departure is the same as that selected for the 

short- and intermediate-term incidental oral durations. A re-evaluation of the dermal toxicity

studies, including rat in vivo, and rat and human in vitro studies, has been performed. Based on 

this evaluation, it has been determined that a quantitative dermal assessment is not required for 

indoxacarb, since the calculated human dermal LOAEL exceeds the limit dose of 1000 

mg/kg/day and dermal toxicity is therefore not expected in humans. The endpoint selections for 

indoxacarb are listed in Table 4.3.1.

Acute Dietary Endpoint: An acute reference dose (aRfD) of 0.12 mg/kg was established for the 

general U.S. population (including infants and children). It was based on an acute oral 

neurotoxicity study in the rat. A NOAEL of 12 mg/kg was based on decreased body weight, 

body-weight gain, and food consumption in females observed at the LOAEL of 50 mg/kg. The 

NOAEL is based on a 7% body weight decrease (in females only on day 8, but no significant 

differences were noted for days 1, 2 or 15). Currently, a 10% decrease in adult body weight is the 

threshold for an adverse effect, thus this study NOAEL is considered to be very conservative. 

The standard 100 UF was applied to account for interspecies extrapolation and intraspecies 
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variation. A FQPA SF of 1x is applicable for acute dietary risk assessment. Thus, the acute 

population-adjusted dose (aPAD) is equivalent to the aRfD of 0.12 mg/kg. An endpoint of 

concern attributable to a single dose for females 13-49 was not identified in the database.

Chronic Dietary Endpoint: The chronic RfD (cRfD) of 0.02 mg/kg/day was based on the: 1) rat 

90-day subchronic toxicity study; 2) rat subchronic neurotoxicity study; and 3) rat chronic/ 

carcinogenicity study. The selected NOAEL was 2.0 mg/kg/day. The LOAELs for the three cocritical studies were: 1) 3.8 mg/kg/day; 2) 3.3 mg/kg/day; and; 3) 3.6 mg/kg/day. These were 

based on decreased body weight, alopecia, body-weight gain, food consumption and food 

efficiency in females. In addition, study #3 also had decreased hematocrit, hemoglobin and red 

blood cells only at 6 months in females. Using a weight-of-evidence approach, the NOAEL for 

use in establishing the cRfD was 2.0 mg/kg/day). This NOAEL was also supported by the 

developmental neurotoxicity study in which the systemic toxicity NOAEL was 1.5 mg/kg/day. 

The standard 100 UF was applied to account for interspecies extrapolation and intraspecies 

variation. A FQPA SF of 1x is applicable for chronic dietary risk assessment. Thus, the chronic 

population-adjusted dose (cPAD) is equivalent to the cRfD of 0.02 mg/kg.

Short-, Intermediate-, and Long-Term Incidental Oral: The short, intermediate and long-term 

endpoints were selected from the studies mentioned in the chronic dietary endpoint (see above), 

using the NOAEL of 2 mg/kg. A margin of exposure (MOE) of 100 is considered adequate for 

incidental oral exposure risk assessment.

Short-, Intermediate-, and Long-Term Dermal Endpoints: A quantitative dermal assessment is 

not required for indoxacarb, since the calculated human dermal LOAEL exceeds the limit dose 

of 1000 mg/kg/day. The rat 28-day dermal study had a wide dose spacing at the lowest two doses 

(i.e. 50 mg/kg/day and 500 mg/kg/day), thus the rat NOAEL value of 50 mg/kg/day may be well 

below the no-effect dose in both rats and humans. The rat in vivo dermal absorption was 4.91%, 

with results from an acceptable guideline study. In comparison, the ratio of the LOAELs from 

the rat developmental study and the rat 28-day dermal study of similar durations estimates the rat 

dermal absorption to be a much lower value of 0.8% (i.e. 100 x 4 mkd/500 mkd), with the rat 

dermal absorption typically multiple times higher than humans. Based on the in vitro dermal 

absorption data for human skin and rat skin, the rat dermal absorption was 17.5X higher than 

human dermal absorption, thus the calculated indoxacarb internal dose would be much higher in 

rats than humans. Specifically for indoxacarb, the rat in vitro absorption was 15.2% and human 

in vitro absorption was 0.87%. Therefore, the dermal triple pack data was utilized to refine the 

dermal POD from the rat sub-chronic dermal study. Using the NOAEL value of 50 mg/kg/day

from the route-specific 28-day dermal study in rats and the 17.5x ratio of human skin to rat skin 

absorption, the equivalent human dermal NOAEL is 875 mg/kg/day for indoxacarb (mixed 

isomers, 50 mkd x 15.2%/0.87%). The corresponding human dermal LOAEL values is calculated 

to be 8750 mg/kg/day, thus a dermal assessment is not required for indoxacarb. Additionally, 

utilizing the 4.91% rat dermal absorption and the rat:human dermal absorption ratio of 17.5X, 

the human equivalent dermal absorption is estimated to be very low, at 0.28%, using the 

parallelogram method.

Short- , Intermediate- and Long-Term Inhalation Endpoints: The short-, intermediate-, and 

long-term inhalation endpoints were selected from a 28-day inhalation toxicity study in rats with 
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MP062. The NOAEL of 23 μg/L/day (equivalent to 6 mg/kg/day) was based on increased spleen 

weights, pigmentation and hematopoiesis in the spleen, hematological changes and mortality

(females) seen at the LOAEL of 290 μg/L/day (equivalent to 75.69 mg/kg/day). The effects do 

not seem to be progressing as study duration increases from subchronic to chronic since the 

NOAELs of oral subchronic and chronic studies are similar. Therefore, use of the 28-day

inhalation study is also appropriate for the long-term exposure scenario. MOEs of 100 are 

considered adequate for inhalation exposure risk assessment.

Carcinogenicity: Indoxacarb is classified as “not likely” to be carcinogenic to humans via 

relevant routes of exposure. Therefore, a quantitative cancer risk assessment is not required.

Table 4.3.1 Points of Departure and Toxicological Endpoints Selected for INDOXACARB for 

Various Exposure Scenarios.

Exposure

Scenario

Dose for Use in Risk 

Assessment,

UF

FQPA SF* and 

Level of Concern 

for Risk 

Assessment

Study and Toxicological 

Effects

Acute Dietary

females 13-49 years 

of age

An endpoint of concern specific to females 13-49 and attributable to a single dose was 

not identified in the toxicity study data base, thus an acute RfD was not established.

Acute Dietary

general population

including infants and 

children

NOAEL= 12 mg/kg

UF = 100

Acute RfD = 0.12 mg/kg

UFA= 10x

UFH=10x

FQPA SF = 1x

aPAD = 

= 0.12 mg/kg

Acute oral rat neurotoxicity 

study.

LOAEL = 50 mg/kg based 

on decreased body weight 

and body-weight gain in 

females (MP062).

Chronic Dietary

all populations

NOAEL= 2.0 mg/kg/day

UF = 100

Chronic RfD = 0.02 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 1x 

cPAD = 

= 0.02 mg/kg/day

Weight of evidence approach 

was used from four studies: 

1) Subchronic toxicity studyrat (MP062).

2) Subchronic neurotoxicity 

study - rat (MP062).

3) Chronic/carcinogenicity 

study - rat (JW062).

4) Two generation rat 

reproduction study (JW062).

LOAEL = 3.3 mg/kg/day 

based on decreased body 

weight, body-weight gain, 

food consumption and food 

efficiency; decreased 

hematocrit, hemoglobin and 

red blood cells only at 6 

months.

Short-Term

Incidental Oral

(1 to 30 days)

Oral NOAEL= 2.0 mg/kg/day UFA= 10x

UFH=10x

FQPA SF = 1x

Residential LOC for 

MOE = 100

Weight of evidence approach 

was used from four studies: 

1) Subchronic toxicity studyrat (MP062).

2) Subchronic neurotoxicity 

study - rat (MP062).
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Occupational LOC 

for MOE = 100

3) Chronic/carcinogenicity 

study - rat (JW062).

4) Two generation rat 

reproduction study (JW062).

LOAEL = 3.3 mg/kg/day 

based on decreased body 

weight, body-weight gain, 

food consumption and food 

efficiency; decreased 

hematocrit, hemoglobin and 

red blood cells only at 6 

months.

Intermediate-Term

Incidental Oral (1- 6 

months)

Oral NOAEL= 2.0 mg/kg/day UFA= 10x

UFH=10x

FQPA SF = 1x 

Residential LOC for 

MOE = 100

Occupational LOC 

for MOE = 100

Weight of evidence approach 

was used from four studies:

1) Subchronic toxicity studyrat (MP062).

2) Subchronic neurotoxicity 

study - rat (MP062).

3) Chronic/carcinogenicity 

study - rat (JW062).

4) Two generation rat 

reproduction study (JW062).

LOAEL = 3.3 mg/kg/day 

based on decreased body 

weight, body-weight gain,

food consumption and food 

efficiency; decreased 

hematocrit, hemoglobin and 

red blood cells only at 6 

months.

Long-Term

Incidental Oral (1- 6 

months)

Oral NOAEL= 2.0 mg/kg/day UFA= 10x

UFH=10x

FQPA SF = 1x 

Residential LOC for 

MOE = 100

Occupational LOC 

for MOE = 100

Weight of evidence approach 

was used from four studies:

1) Subchronic toxicity studyrat (MP062).

2) Subchronic neurotoxicity 

study - rat (MP062).

3) Chronic/carcinogenicity 

study - rat (JW062).

4) Two generation rat 

reproduction study (JW062).

LOAEL = 3.3 mg/kg/day 

based on decreased body 

weight, body-weight gain, 

food consumption and food 

efficiency; decreased 

hematocrit, hemoglobin and 

red blood cells only at 6 

months.

Short-Term Dermal 

(1 to 30 days)

Intermediate-Term

Dermal (1 - 6

months)

A quantitative dermal assessment is not required for indoxacarb, since the calculated 

human dermal LOAEL exceeds the limit dose of 1000 mg/kg/day.
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Long-Term Dermal 

(> 6 Months)

Short-Term

Inhalation (1 to 30 

days)

Intermediate-Term

Inhalation (1 - 6 

months)

Long-Term

Inhalation (> 6 

Months)

Inhalation NOAEL= 23 

μg/L/day (6 mg/kg/day)

UFA= 10x

UFH=10x

FQPA SF = 1x 

Residential LOC for 

MOE = 100

Occupational LOC 

for MOE = 100

28-day rat inhalation toxicity 

study (MP062). The LOAEL 

of 290 μg/L/day (75.69 

mg/kg/day). is based on 

increased spleen weights, 

pigmentation and 

hematopoiesis in the spleen, 

hematological changes and 

mortality (females). 

Cancer (oral, dermal,

inhalation)

“Not likely” to be carcinogenic to humans since no evidence of carcinogenicity in 

either the rat or mouse studies, and no evidence of mutagenicity.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to 

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL 

= no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk 

assessment. UFDB = to account for the absence of key data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD 

= population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

N/A = not applicable.

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The residues of concern for dietary risk assessment and the tolerance expression are summarized 

in Table 5.1. 

Table 5.1 Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression1

Matrix Residues included in Risk 

Assessment

Residues included in Tolerance 

Expression

Plants

Primary Crop Indoxacarb2

and its R-enantiomer3Indoxacarb and its R-enantiomer

Rotational Crop Indoxacarb and its R-enantiomer Indoxacarb and its R-enantiomer

Livestock

Ruminant

Indoxacarb and its R-enantiomer

(for all)

Metabolite IN-MP819 (for milk 

only)

Indoxacarb and its R-enantiomer

Poultry

Indoxacarb, its R-enantiomer, and 

the metabolites IN-JT333, INJU873, IN-KB687, IN-KG433, 

IN-KT319, 5-HO-IN-JT333, and 

Metabolite F

Indoxacarb, its R-enantiomer, and 

the metabolites IN-JT333, INJU873, IN-KB687, IN-KG433, and 

IN-KT319
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Table 5.1 Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression1

Matrix Residues included in Risk 

Assessment

Residues included in Tolerance 

Expression

Drinking Water

Indoxacarb, and the degradation 

products IN-JT333, IN-KG4333, 

IN- KT413, and IN-ML437-0H

1 Adapted from: S. Levy, D325479, 03/09/2007; and D402100, Christopher M. Koper, 11/06/2012.

2

“Indoxacarb” in this table refers to the S-enantiomer (KN-128)

3 R-enantiomer of indoxacarb (KN-127)

5.2 Food Residue Profile

The dry bean and snap bean field trials submitted with this petition are adequate to support the 

proposed new uses on dry bean and succulent bean. A sufficient number of trials were 

conducted on each crop at 1x the maximum proposed rate in the appropriate geographic regions

with the proper representative raw agricultural commodities (RACs) being collected for analysis. 

Samples were analyzed using adequate analytical methods; total indoxacarb (both S- and Renantiomer) was measured. Sample storage durations are supported by the available storage 

stability data. The current plant-back restrictions on the label remain adequate. Processing

studies are not required for these RACs.

The tolerance for dry beans covers the southern pea variety, cowpea. Cowpea is the only dry 

bean crop considered for livestock feeding (cowpea seed, forage and hay). Residue data have 

been submitted and a tolerance has been proposed for residues of indoxacarb on dry bean 

(cowpea) forage. However, residue data for cowpea hay have not been submitted nor has a 

tolerance been proposed. HED is recommending establishment of a tolerance for indoxacarb on 

cowpea hay of 100 ppm. The recommended hay tolerance is derived from the highest forage 

residue to which a drying factor has been applied. Specifically, the 32 ppm residue is multiplied 

by the ratio of maximum percent dry matter for hay and forage (32 *86/30=92). This results in a 

very conservative tolerance level for indoxacarb on cowpea hay which was considered in dietary

burden calculations. Cowpea (forage and hay) are fed to dairy cattle. 

For snap beans (with pods), the total combined residues of indoxacarb (KN128 and KN127)

ranged from 0.04 ppm to 0.59 ppm. Residues in whole snap bean plants/foliage were found 

between 1.3 ppm and 32 ppm. For dry bean seeds, total residues ranged from <0.01 ppm to 

0.069 ppm. Adequate residue decline data was generated with snap beans and dry beans 

indicating that residues of indoxacarb decline fairly rapidly after treatment. 

Residue data for cranberries and grapes was previously evaluated and considered acceptable. 

The data for cranberries is adequate to support the tolerance for low growing berry subgroup 13-

07H. The use pattern of the grape field trial correspond to the same single application rate and 

PHI of the proposed use pattern for small fruit vine climbing subgroup 13-07F but a higher 

maximum seasonal application rate (0.44 lb ai/A instead of 0.22 lb ai/A) and shorter RTI (5-days 

instead of 21-days). Since the single application rate and PHI are similar and higher residues 
Indoxacarb Human Health Risk Assessment DP No. D416367

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than the proposed tolerance would not be expected, it is recommended to use available residue 

data without applying a scaling factor to adjust the residue level. The existing cranberry and 

grape residue data are considered adequate to recommend tolerances for the corresponding crop 

subgroups.

5.3 Water Residue Profile

EFED performed a Tier II drinking water assessment (DWA) which utilized modeling to 

estimate the surface water and groundwater concentrations of indoxacarb in drinking water 

source water (pre-treatment) resulting from use on vulnerable sites (D402100, 11/6/13, Tier II 

Drinking Water Assessment for the New Use Registration of Indoxacarb on Dry Beans, Snap 

Beans, Small Fruit Vine Climbing Subgroup 13-07F and Low-Growing Berry Subgroup 13-

07H). No monitoring data were available for indoxacarb at the time of this assessment. Based 

on the Metabolism Assessment Review Committee (MARC) recommendations, a Total Toxic 

Residue (TTR) approach was used for the parent indoxacarb and the degradation products with 

toxicological concern (IN-JT333, IN-KG4333, IN- KT413, IN-ML437-0H) for the drinking 

water assessment. 

The recommended estimated drinking water concentrations (EDWCs) for the human health risk 

assessment are based on highest predicted value for surface water and groundwater (Table 5.3), 

which are based on two applications of 0.11 lbs. a.i./acre/season on cranberry and four 

applications of 0.11 lbs. a.i./acre on beans and berries respectively. For acute and chronic dietary

risk assessments, respectively, the 1-in -10 year peak (59.26 ppb) and the 1-in -10 year annual 

average (18.48 ppb) indoxacarb residues of concern in surface water from the Provisional 

Cranberry Model (PCM) were used.

Table 5.3 Recommended Estimated Drinking Water Concentrations (EDWCs)1for Surface Water 

and Ground Water –Indoxacarb and Degradation Products

Drinking 

Water 

Source

Model

Scenario Method2

Maximum 

Application Rate

(interval between 

applications)

1-in-10 

year 

acute 

(μg/L)

1-in-10 

year 

chronic 

(μg/L)

30- year 

average 

(μg/L)

Surface 

Water

Provisional Cranberry Model

Cranberry PCM 2 app @ 0.11 lb a.i./acre 59.26 18.48 18.48

Ground 

Water

SCI-GROW

(Beans, Berries) -- 4 app @ 0.11 lb a.i./acre 0.33 0.33 0.33

1 For surface water (PRZM/EXAMS), EDWC values adjusted with a Percent Cropped Area (PCA) factor of 0.87. 

For ground water (SCI-GROW), no PCA adjustment was utilized. 

2 PCM = The Provisional Cranberry Model (PCM) is a provisional refinement to the Tier I Rice Model (v1.0, May 8, 

2007). Refinements include the addition of simple degradation processes in dry and flooded conditions and a water 

depth of twelve inches, rather than the water depth of four inches used in the rice model. These modifications allow 

estimation of screening-level peak and annual mean EDWCs of residues of concern that may occur in untreated 

surface water used as drinking water following use on cranberries.
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5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Refined acute probabilistic and chronic dietary (food plus drinking water) exposure assessments 

were conducted for the existing and proposed food uses of indoxacarb (I. Negrón-Encarnación, 

5/1/13, D408983, Indoxacarb Acute and Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessment for the Section 3 Registration Action on Dry Beans, Succulent 

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

Subgroup (except strawberry) 13-07H). A cancer dietary exposure assessment was not 

conducted for indoxacarb because indoxacarb has been classified as “not likely to be 

carcinogenic.” The dietary assessments were conducted using the Dietary Exposure Evaluation 

Model software with the Food Commodity Intake Database (DEEM-FCID) Version 3.16, which 

uses food consumption data from the U.S. Department of Agriculture’s National Health and 

Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA) from 2003 to 

2008. Anticipated residues (ARs) for all registered and proposed food commodities were based 

on field trial data (FTD), and for some crops tolerance level residues were used. Residue 

estimates for many current uses were further refined using percent crop treated (%CT) data. 

Available processing data for indoxacarb were used to refine ARs for apples/pears (juice), potato 

(dry, chips), cotton (oil), tomato (paste and puree), peanut (oil), soybean (oil), grapes (raisin and 

juice), prunes (dried), and mint (oil), and other commodities where translation was applicable. 

DEEM-FCID (ver. 7.81) default processing factors (PFs) were assumed for all other processed 

commodities.

EDWCs were provided by EFED (C. Koper, D402100, 11/06/12) and incorporated directly into 

the DEEM-FCID analyses. Both the acute and chronic analyses were conducted using 

estimated surface water residues generated using the Provisional Cranberry Model.

For acute and chronic assessments, HED is concerned when dietary risk exceeds 100% of the 

aPAD and cPAD, respectively. The DEEM-FCIDTM analyses estimate the dietary exposure of 

the U.S. population and various population subgroups: all infants (<1 year old), children 1-2, 

children 3-5, children 6-12, youth 13-19, females 13-49, adults 20-49, and adults 50+ years. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

The following maximum percent crop treated estimates (BEAD Screening Level Usage Analysis 

(SLUA), 10/12/12) were used in the acute dietary risk assessment for the following crops that are 

currently registered for indoxacarb: apples: 10%; broccoli: 70%, cabbage: 35%; cauliflower: 

60%; cherries: 2.5%; lettuce: 40%; peaches: 2.5%; peanuts: 10%; pears: 2.5%; potatoes: 2.5%; 

soybeans: 2.5%; spinach: 5%; sweet corn: 10%; tomatoes: 40%. The following average percent 

crop treated BEAD estimates were used in the chronic dietary risk assessments for the following 

crops that are currently registered for indoxacarb: apples: 5%; broccoli: 50%, cabbage: 25%; 

cauliflower: 40%; celery: 5%; cherries: 1%; grapes: 1%; lettuce: 10%; peaches: 2.5%; peanuts: 

2.5%; pears: 1%; potatoes: 1%; soybeans: 1%; spinach: 2.5%; sweet corn: 2.5%; tomatoes: 20%. 

For all other crop commodities, including the proposed uses (dry bean, succulent bean and small 
Indoxacarb Human Health Risk Assessment DP No. D416367

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fruit vine climbing subgroup (except kiwifruit) 13-07F and low growing berry subgroup (except 

strawberry) 13-07H), 100% of the crop treated was assumed.

5.4.3 Acute Dietary Risk Assessment

Estimated acute dietary exposure, using fairly refined assumptions, to indoxacarb from food and 

drinking water is below HED’s level of concern for all population subgroups. Combined dietary

exposure from food and drinking water at the 99.9th percentile of exposure is estimated to be 

0.033 mg/kg/day for the overall U.S. population, equivalent to 27% of the aPAD. The 

population subgroup with the highest estimated acute dietary exposure to indoxacarb is all 

infants, with an estimated exposure at the 99.9th percentile of 0.058 mg/kg/day, equivalent to 

49% of the aPAD.

Results of the dietary assessments can be found in Table 5.4.5 below.

5.4.4 Chronic Dietary Risk Assessment

Estimated chronic dietary exposure, using fairly refined assumptions, to indoxacarb from food 

and drinking water is below HED’s level of concern for all population subgroups. Combined 

dietary exposure from food and drinking water is estimated to be 0.0011 mg/kg/day for the 

overall U.S. population, equivalent to 5.7% of the cPAD. The population subgroup with the 

highest estimated chronic dietary exposure to indoxacarb is children, 1 to 2 years old, with an 

estimated exposure of 0.0024 mg/kg/day, equivalent to 12% of the cPAD.

Results of the dietary assessments can be found in Table 5.4.5 below.

5.4.5 Summary Table

Table 5.4.5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Indoxacarb

Population Subgroup

Acute Dietary

(99.9 Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population 0.032762 27 0.001133 5.7

All Infants (<1 year old)* 0.058294 49 0.001772 8.9

N/A N/A

Children 1-2 years old* 0.054158 45 0.002381 12

Children 3-5 years old 0.046841 39 0.001818 9.1

Children 6-12 years old 0.035434 30 0.001105 5.5

Youth 13-19 years old 0.025623 21 0.000743 3.7

Adults 20-49 years old 0.025109 21 0.001036 5.2

Adults 50+ years old 0.030965 26 0.001165 5.8

Females 13-49 years old 0.026456 22 0.001037 5.2

*The subpopulation(s) with the highest risk estimates are highlight in bold print.
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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

No new residential uses and no occupational uses at residential sites are being requested with this 

petition; however, there are existing residential uses (turf and spot-on pet applications) that have 

been previously assessed and are assessed herein to reflect updates to HED’s 2012 Residential 

SOPs2, policy changes for body weight assumptions, and a re-evaluation of the dermal toxicity of 

indoxacarb. In addition, there are existing residential uses (insect control treatments of 

household premises; Arilon Insecticide 20% ai, EPA Reg. No. 100-1501 and Aperion Insecticide 

14.5% ai, EPA Reg. No. 352-770) which do not appear to have been previously assessed and are 

assessed herein. These existing uses may potentially result in handler and post-application 

inhalation and dermal exposures for adults and post-application dermal, inhalation, and oral 

exposures to children. The risk estimates from residential exposures will impact the human 

health aggregate risk assessment for indoxacarb. Note that dermal exposures resulting from 

residential uses are not quantitatively assessed as a dermal toxicity endpoint is not identified for 

indoxacarb. Only the inhalation and incidental oral exposures are assessed for the residential uses 

of indoxacarb.

6.1 Residential Handler Exposure

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. Residential handler exposure is expected to 

be short-term in duration. Intermediate-term exposures are not likely because of the intermittent 

nature of applications by homeowners. The indoxacarb handler assessment considers short-term 

inhalation exposures only since a dermal toxicity endpoint is not identified.

The anticipated use patterns and current labeling indicate that exposure to pesticide handlers is 

likely during the residential uses of indoxacarb products. Indoxacarb use patterns and current 

labeling indicate several likely residential handler exposure scenarios: 

(1) Placements of ready- to-use (RTU) bait stations.

(2) Spot-on applications of gels (crack and crevices) for household insect control (indoor

treatments).

(3) Spot-on treatments for the control of fleas and ticks on dogs and cats.

(4) Broadcast, perimeter and ant mound treatment on ornamentals, trees, and lawns/turf 

utilizing granular and liquid formulations (outdoor treatments). 

(5) Indoor spray applications with granular and liquid formulations for insect control on

households/domestic dwellings (crack and crevice and spot directed treatments).

 

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Indoxacarb RTU bait stations and gels products are formulated for very low application rates 

(e.g., 6.6 x 10-7lb ai/spot to 5.2 x10-5lb ai/placement) and are designed to be self-contained; 

therefore, handler contact is expected to be negligible and exposure/risk for these uses were not

quantitatively assessed. The spot-on product for the control of fleas and ticks on dogs and cats is 

designed to be self-contained as it is applied directly from the tube to the pet with the tip of the 

applicator used to part the pet’s hair. Therefore, handler exposure is expected to be minimal for 

this type of applications. Inhalation assessments are not performed for applying pet spot-on 

treatments, as inhalation exposure is not expected from these uses. Therefore, a handler 

assessment is not performed for the indoxacarb pet spot-on treatments.

Indoxacarb liquid and granular formulations (e.g., Provaunt 1.25 SC and Advion G), are 

registered for use in residential lawns, recreational areas and golf courses. Additionally, a dry

flowable formulation (Provaunt Insecticide DF) is registered for use in residential lawns and 

recreational areas. Even though the labels states that these products are “intended to be applied 

by professional commercial operators (PCO) only”, this label restriction is not considered 

sufficient to preclude use by homeowners; therefore, these uses were assessed. 

Other granular products intended for residential treatments on ornamentals, trees, and lawns such 

as Chemsico Insect Bait (EPA Reg. No. 9688-217), and ant mound treatment product, Tomcat 

Ant Killer (EPA Reg. No. 12455-107), are also formulated at very low application rates 

(maximum application rate of 8 x 10 -8 lb ai/ft2). MOE estimates for these uses will be well 

above a million, and; therefore, were not quantified.

Two indoxacarb formulations: Arilon Insecticide 20% ai (EPA Reg. No. 100-1501) and Aperion

Insecticide 14.5% ai (EPA Reg. No. 352-770), were identified for use in households and 

domestic dwellings. Even though the labels state that both products are “intended to be applied 

by PCOs only”, this restriction is not considered sufficient to preclude use by

homeowner/residential applicators; therefore, these uses were assessed. Although outdoor 

treatments are also permitted, only the indoor uses were assessed since the outdoor applications 

are expected to result in lower risk/exposure estimates than the indoor spray applications and the 

turf uses assessed.

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

existing indoxacarb uses is based on the following scenarios: 

(1) Mixing/loading/applying granular formulation for insect control on lawns/turf.

(2) Mixing/loading/applying liquid flowable formulation for insect control on lawns/turf.

(3) Mixing/loading/applying water-soluble packaging formulation for indoor spray

applications with manually-pressurized hand wand (crack and crevice and spot directed 

treatments) for insect control in households/domestic dwellings.

(4) Mixing/loading/applying liquid flowable formulation for indoor spray applications with 

manually-pressurized hand wand (crack and crevice) for insect control on

households/domestic dwellings.

Residential Handler Exposure Data and Assumptions
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A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments. These assumptions and factors, including application rate, body

weights, unit exposure, etc. are detailed in D411342 (A. Rivera-Lupianez, 5/1/13, Indoxacarb

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 

Low-Growing Berry Subgroup 13-07H) and the 2012 Residential SOPs3.

The inhalation exposure and risk estimates are presented for the residential scenarios that led to 

the highest exposure (i.e., backpack and manually pressurized hand wand applications of liquid 

sprays on turf, belly grinder application of granules on turf, and manually pressurized hand wand 

applications for indoor spray treatments). Residential handler exposure scenarios for the

indoxacarb S-enantiomer and its R-enantiomer 75:25 ratio mixture (KN128/KN127) formulation 

are summarized as follows:

KN128/KN127 (75:25 isomeric mixture):

1. Lawn/Turf: Provaunt 1.25 SC 14.5% ai (EPA Reg. No. 352-637); a liquid formulation

for use on turf (residential lawns, recreational areas, and golf courses).

2. Lawn/Turf: Advion G 0.22% ai (EPA Reg. No. 100-1483); a granular formulation for use 

on turf (residential lawns, recreational areas, and golf courses).

3. Lawn/Turf: Provaunt Insecticide DF (EPA Reg. No 100-1487); a dry flowable 

formulation for use on turf (residential lawns, recreational areas, and golf courses).

4. Indoor Spray (Crack and Crevice and Spot Treatment): Arilon Insecticide 20% ai (EPA 

Reg. No. 100-1501); a water-soluble packaging formulation for use on

households/domestic dwellings.

5. Indoor Spray (Crack and Crevice): Aperion Insecticide 14.5% ai (EPA Reg. No. 352-

770); a liquid formulation for use on households/domestic dwellings.

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

KN128/KN127 (75:25 Isomeric Mixture) Exposure Scenarios- Lawn/Turf and Indoor Crack and 

Crevice/Spot-Directed Treatments:

The residential handler exposure assessment for turf (lawn) and indoor (crack and crevice and 

spot-directed) applications resulted in short-term inhalation MOEs that do not exceed HED's 

level of concern (i.e., MOEs ≥ 100). Table 6.1.1 presents a summary of the residential handler 

scenarios assessed.

Table 6.1.1. Residential Handler Short -Term Exposure and Risk Estimates for Indoxacarb: KN128/KN127 (75:25 

Isomeric Mixture)

Exposure Scenario Level of 

Concern

Inhalation Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

Area 

Treated or 

Amount 

Handled 

Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

 

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Table 6.1.1. Residential Handler Short -Term Exposure and Risk Estimates for Indoxacarb: KN128/KN127 (75:25 

Isomeric Mixture)

Exposure Scenario Level of 

Concern

Inhalation Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

Area 

Treated or 

Amount 

Handled 

Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

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

Lawns/Turf

Provaunt Insecticide DF -Dry Flowable Formulations – EPA Reg. No. 100-1487 (Former: EPA Reg. No. 352-716)

Mannually Pressurized Hand 

Wand/

Backpack

100 1.1 0.0065 lb ai/gal 5 gal 0.00045 13,000

Provaunt 1.25 SC-Liquid Formulations - EPA Reg. No. 352-637

Backpack

(liquid) 100 0.14

0.0065 lb ai/gal 5 gal

0.000057 105,000

Manually Pressurized Hand 

Wand

(liquid) 100 0.018 7.3 x 10-6

825,000

Advion G- Granular Formulations- EPA Reg. No. 100-1483 (Former: EPA Reg. No. 352-651)

Belly grinder

(granules) 100 0.039 0.000013 lb ai/ft2

1,200 ft27.6 x 10-6785,000

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

Arilon Insecticide 20% ai - EPA Reg. No. 100-1501 (Former: EPA Reg. No. 352-776)

Manually Pressurized Hand 

Wand (water dispersible 

packets) 100 1.1

0.011 lb ai/gal

(0.00004 lb ai/ft2)

0.5 gal 0.000076 80,000

Aperion Insecticide 14.5% ai - EPA Reg. No. 352-770

Manually Pressurized Hand 

Wand

(liquid) 100 1.1

0.010 lb ai/gal

(0.00004 lb ai/ft2)

0.5 gal 0.00006 86,000

1. Based on registered label (EPA Reg. No.). Application rates = maximum application rates from labels (EPA Reg. No.: 352-

637, 100-1487, 100-1483, 100-1501, 100-1498, and 352-770). The application rate for all mixture formulations 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.

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

3. 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 (kg).

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

6.2 Residential Post-Application Exposure

There is the potential for post-application exposure for individuals exposed as a result of being in 

an environment, such as on a lawn or floor or petting an animal, that has been previously treated 

with indoxacarb. Residential post-application exposures (e.g., exposures from treated lawns and 

indoor environments), are generally considered to be intermittent and short-term in duration. 

However, because of the preventative nature of pet products and the potential for extended usage 

in more temperate parts of the country, the residential post-application exposures to treated pets 
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may be short-, intermediate-, or long-term in duration. The post-application assessment 

considers inhalation and oral exposures only since a dermal toxicity endpoint is not identified for 

indoxacarb. The toxicological endpoints and points of departure are the same for each route of 

exposure regardless of duration.

The quantitative exposure/risk assessment for residential post-application exposures is based on 

the following scenarios: 

(1) Treated pets (dogs and cats): children 1 to < 2 years old (incidental oral);

(2) Treated turf: children 1 to < 2 years old (incidental oral);

(3) Crack and crevice indoor and spot-directed spray applications: inhalation (adults and 

young children 1 to <2 years old), and incidental oral (young children 1 to <2 years old) 

exposures.

It should be noted that post-application exposures (incidental oral) from treated golf courses 

were not quantified since youth old enough to play golf are not expected to exhibit significant 

hand-to-mouth behavior. Furthermore, the residential lawn assessment provides the highest 

estimate of potential exposure from turf applications and is protective of any exposures to

indoxacarb turf treatment scenarios.

The lifestages selected for each post-application scenario are based on an analysis provided as an 

Appendix in the 2012 Residential SOPs4. These lifestages are not the only lifestages that could 

be potentially exposed for these post-application scenarios; however, the assessment of these 

lifestages is health protective for the exposures and risk estimates for any other potentially 

exposed lifestages.

Two indoxacarb formulations: Arilon Insecticide 20% ai (EPA Reg. No. 100-1501) and Aperion

Insecticide 14.5% ai (EPA Reg. No. 352-770), were identified for insect control in households 

and domestic dwellings. Even though outdoor treatments are also permitted; outdoor 

applications are expected to result in lower risk/exposure estimates than indoor spray treatments 

or turf uses. Therefore, only the indoor uses that would potentially lead to the highest postapplication exposures were assessed (i.e., exposure from contact with carpet and hard surfaces 

resulting from surface directed spray applications). It should be noted that even though neither 

of these labels have been previously assessed, only the Arilon formulation was assessed for postapplication exposures. The Aperion Insecticide formulation, a termiticide, was not assessed for 

post-application exposure since the label use pattern limits indoor uses to “localized spot 

treatments” such as crawlspaces, basements or attics and post-application exposures are not 

likely. Furthermore, the assessment of the Arilon formulation, which is applied at a higher 

application rate than the Aperion formulation, is assumed to provide a conservative surrogate 

assessment for the Aperion uses. 

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. Two chemical specific animal petting studies 

 

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(MRIDs 47834502 and MRID 48010801) were used to estimate transferable residues for the 

incidental oral exposure for children for the treated pet scenario. A chemical specific 

(indoxacarb) turf transferable residue (TTR) study (MRID 4679820) was used to estimate 

incidental oral exposure for children for the turf (liquid formulations) scenarios. A default TTR 

was used for the turf granular formulation scenario since the available chemical specific study 

was only for the liquid formulation. The assumptions and factors, as well as those regarding 

application rate and timing, body weights, etc., are detailed in D411342, 5/1/13, and the 2012 

Residential SOPs5.

Combining Exposure and Risk Estimates

Since inhalation and incidental oral exposure routes share a common toxicological endpoint (i.e.,

hematological changes), risk estimates have been combined for those routes. Incidental oral 

ingestion (i.e., hand-to-mouth, object-to-mouth, and soil ingestion (where appropriate)) for a 

given residential scenario should be considered inter-related and it is likely that they occur 

interspersed amongst each other across time. Combining all of these incidental oral exposure 

estimates with the inhalation exposure would be overly-conservative because of the conservative 

nature of each individual incidental oral assessment. Therefore, the post-application exposure 

scenarios that were combined for children 1 < 2 years old are the inhalation and hand-to-mouth 

(the highest incidental oral exposure assessment) for the indoor surfaces directed spray

applications. This combination is considered protective of children’s exposure to indoxacarb 

from residential uses.

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

For the purpose of presentation of post-application exposure and risk estimates, the exposure 

scenarios for the KN128 (S-enantiomer only) formulation and the KN128/KN127 (75:25 S-and 

R- enantiomer mixture) formulations have been separated. 

KN128 (S-enantiomer only):

1. Treated Pets: Actyvil Liquid RTU Formulation for spot-on treatments on cats (EPA Reg. 

No. 773-93) and dogs (EPA Reg. No 773-94).

KN128/KN127 (75:25 S- and R- isomeric mixture):

1. Lawn/Turf: Provaunt 1.25 SC 14.5% ai (EPA Reg. No. 352-637); a liquid formulation

for use on turf (residential lawns, recreational areas, and golf courses).

2. Lawn/Turf: Advion G 0.22% ai (EPA Reg. No. 100-1483); a granular formulation for use 

on turf (residential lawns, recreational areas, and golf courses).

3. Lawn/Turf: Provaunt Insecticide DF (EPA Reg. No 100-1487); a dry flowable 

formulation for use on turf (residential lawns, recreational areas, and golf courses).

4. Indoor Spray (Crack and Crevice and Spot-Directed Treatments): Arilon Insecticide 20% 

ai (EPA Reg. No. 100-1501); a water-soluble packaging formulation for use on

households/domestic dwellings.

KN128 Exposure Scenarios

Treated Pets Scenarios

 

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A summary of the children short-, intermediate- and long-term (ST/IT/LT) exposure and risk 

estimates from treated pet (cat and dog) scenarios are shown in Table 6.2.1. Incidental oral 

(hand to mouth) risk estimates for children for the indoxacarb pet spot-on liquid formulations do 

not exceed HED’s level of concern (MOEs ≥ 100).

Table 6.2.1. Residential Post-application ST/IT/LT (Non-Cancer) Exposure and 

Risk Estimates for Indoxacarb: KN128 formulation

Lifestage

Post-application Exposure 

Scenario

Application 

Rate a

Dose b,c

(mg/kg/day)

MOEs d Combined 

Route of MOEs 

Exposure Use Site

Liquid Spot-on Treatments Formulations (Companion Pets)

Child 1 to < 2

years old Oral (HTM)

Cats 115 (mg ai/pet) 0.0012 1,600

NA

Dogs 900 (mg ai/pet) 0.0024 830

a Based on application rates (AR) from labels that led to highest dermal exposure: Actyvil Liquid RTU Formulation for spot-on 

treatments on cats (EPA Reg. No. 773-93) and dogs (EPA Reg. No 773-94) 

b. Fraction Application Rate (Far) = Peaked amount of indoxacarb removed as a fraction of dose applied from MRIDs: 48135325 

and 48010801; Far = 0.0255 (dogs); 0.0124 (cats).

c. Hand-to-Mouth Dose (mg/kg/day) = [(Hand Residue Loading (mg/cm2) × Fraction of Hand Mouthed × Surface Area of 1 

Hand (150 cm2) × Exposure Time (1.5 hrs/day) × # of Replenishment Intervals/hr (4 int/hr) × (1-((1-Saliva Extraction Factor 

(0.5))^(Number of Hand-to-Mouth Events per Hour (13.9 events/hr) ) ÷ ( # of Replenishment Intervals/hr))] / Body Weight 

(11 kg child 1 < 2 years old)]

d. Oral MOE = NOAEL (2 mg/kg/day; KN128)/ Oral Dose (mg/kg/day)

KN128/KN127 (75:25 Isomeric Mixture) Exposure Scenarios

Turf Scenarios

A summary of the children short-term post-application exposure and risk estimates from the turf 

scenarios is shown in Table 6.2.2. Children’s short-term incidental oral risk estimates (for both 

liquid and granular formulations) do not exceed HED’s level of concern (MOEs ≥ 100). 

Indoor Surfaces Directed Spray Scenarios (Crack and Crevice and Spot-Directed Treatments)

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

from the indoor spray uses of indoxacarb is shown in Table 6.2.2. All adult and children 

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

incidental oral risk estimates for crack and crevice treatments do not exceed HED’s level of 

concern (MOEs ≥ 100). However, for spot-directed treatments, oral (hand-to-mouth) exposure 

estimates alone for children 1 to < 2 years old exceed HED’s level of concern (MOE = 32). For 

crack and crevice only scenarios the combined inhalation and incidental oral risk estimates for 

children 1 to < 2 years old are not of concern (MOEs ≥ 100).
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Table 6.2.2. Residential Post-application ST (Non-Cancer) Exposure and Risk Estimates for 

Indoxacarb: KN128/KN127 (75:25 Isomeric Mixture).

Lifestage

Post-application Exposure 

Scenario

Application 

Rate a, b

(lb ai/A)

Dose c, d, 

(mg/kg/day)

MOEs e, f, g, 

h,

Combined 

Routes

(X 

indicates 

included 

in 

Combined 

MOE)

Combined 

MOEs i Route of 

Exposure Use Site

Lawn/Turf Scenarios

Provaunt 1.25 SC-Liquid Formulations and Provaunt Insecticide DF -Dry Flowable Formulations

Child 1 < 2 

year old Oral 

Hand-to-Mouth 0.22 lb ai/A

(0.29 lb ai 

total 

isomer/A)

0.0042 480

Object-to-Mouth 0.0001 20,000 NA

Soil Ingestion 9.9 x 10-6 200,000

Advion G- Granular Formulations 

Child 1 < 2 

year old Oral 

Hand-to-Mouth

0.44 lb ai/A

(0.586 lb ai 

total 

isomer/A)

0.0009 2,300

NA

Object-to-Mouth 0.00005 40,000

Soil Ingestion 2 x 10-5 100,000

Episodic Granular 

Ingestion 0.060 200

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

Arilon Insecticide 20% ai 

Adult Inhalation Surface directed 

sprays

0.00004 lb ai 

total isomer 

/ft2

2.2x 10-82.6 x 108 NA

Child 1 < 2 

years old

Oral

Hand-to-Mouth 

from carpets (crack 

and crevice 

treatment)

0.0126 160 X

160

Hand-to-Mouth 

from carpets (spot 

directed 

Treatment)

0.0632 32

Object-to- Mouth 

from carpets (crack 

and crevice 

treatment)

0.002 1000

Object-to- Mouth 

from carpets (spot 

directed 

Treatment)

0.008 250

Inhalation Surface directed 

sprays

9.6x 10-8

6.2x 107 X

a. Based on application rates (AR) from labels that led to highest dermal exposure: 

 AR = maximum application rates from labels (EPA Reg. No.: 352-637, 100-1483, 100-1501 and 352-770). The application 

rate for all mixture formulations 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.
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b. Turf Transferable Residue (TTR) – The highest average value (0.023 μg/cm2) from NY, NC and CA site study (MRID 

46798201) was used for the Provaunt 1.25 SC and Provaunt Insecticide DF formulations assessment. The TTR value was

adjusted to 0.031 μg/cm2to account for 4 parts of total (S- and R-) indoxacarb for every 3 parts of S-indoxacarb. A default 

predicted Day 0 TTR value (0.013 μg/cm2) was used for Advion G.

c. Turf Scenarios Dose Equations

 Hand-to-Mouth Dose (mg/kg/day) = [(Hand Residue Loading (mg/cm2) × Fraction of Hand Mouthed × Surface

 Area of 1 Hand (150 cm2) × Exposure Time (1.5 hrs/day) × # of Replenishment Intervals/hr (4 int/hr) × (1-((1-Saliva

 Extraction Factor (0.5))^(Number of Hand-to-Mouth Events per Hour (13.9 events/hr) ÷ ( # of Replenishment 

 Intervals/hr))] / Body Weight (11 kg child 1 < 2 years old)]

 

 Object-to-Mouth Dose (mg/kg/day) = object residue loading (μg/cm2) × unit conversion factor (0.001 mg/μg) ×

 object surface area mouthed / event (10 cm2/event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 

 int/hr) × (1-((1- saliva extraction factor (0.50))^(# Object-to-Mouth Events/hr (8.8 events/hr) ÷ # replenishment 

 intervals/hr)) ÷ body weight (11 kg).

 Soil Ingestion Dose (mg/kg/day) = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 

 g/μg) ÷ body weight (11 kg).

 Episodic Granular Ingestion Dose (mg/kg/day) = [(ingestion rate of dry pesticide formulation (g/day) * fraction of ai 

 in dry formulation (unitless) * weight unit conversion factor (1,000 mg/g)] ÷ body weight (11 kg).

d. 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)]

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

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

h. Episodic Granular Ingestion MOE = NOAEL (12 mg/kg/day;) / Episodic Granular Ingestion Dose (mg/kg/day)

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

6.3 Residential Risk Estimates for Use in Aggregate Assessment

Tables 6.3.1 and 6.3.2 show residential risk estimates that can be used in the aggregate 

assessment for indoxacarb. The scenarios and lifestages resulting in the highest residential 

exposures are selected for use in the aggregate assessment and are considered protective of other 

scenario exposures (those risk estimates in bold in the tables are included in the aggregate 

assessments). 

For indoxacarb, there are potential residential exposures from indoor applications, outdoor/lawn 

applications and pet applications. Each of these scenarios are assessed using high-end, 
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conservative assumptions (e.g., maximum application rate, high-end area treated or amount 

handled, no dissipation of residue over the exposure duration, etc). Because each scenario 

reflects the use of high-end inputs, the individual residential scenarios are not combined for use 

in the aggregate; rather, the scenario resulting in the highest exposure is aggregated with 

food/water to be protective of all possible residential scenarios. Multiple residential scenarios 

are also not combined in many cases because available survey data indicate that the probability

of multiple residential products (e.g., a pet care product and an indoor product), containing the 

same active ingredient, being used on the same day is very low.

Exposure from the pet spot-on use is assumed to occur over short-, intermediate-, and long-term 

durations. As is the case for all the residential exposure scenarios, the long-term exposure 

assessment for the pet uses are conducted using high-end, conservative inputs (e.g., maximum 

application rates, day-0 residue values, no dissipation of residues over time) resulting in a very

conservative long-term exposure/risk estimate that would not be appropriate to include in the 

short- term aggregate assessment as “background” exposure.

Based on the potential residential scenarios for indoxacarb and the considerations noted above, 

the following is a list of the recommended residential scenarios for the indoxacarb aggregate 

assessments: 

 The short -term residential exposure for use in the adult aggregate assessment reflects 

residential handler inhalation exposures from mixer/loader/applicator scenarios for dry

flowable formulations treatments on turf via manually pressurized hand wand or 

backpack.

 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 crack and crevice treatments with surface directed sprays. The 

incidental oral (hand-to-mouth) risk estimate for the indoor spot-directed treatments was 

of concern by itself and is not included in the aggregate.

 The intermediate- and long -term residential exposure for use in the child (1<2 years old) 

aggregate assessment reflects post-application incidental oral (hand-to-mouth) exposures 

from treated pets.
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Table 6.3.1. Residential Exposures for the Indoxacarb Aggregate Assessment (KN128; Pet Treatment).

Lifestage

Residential Handler Residential Post-application 

Dose (mg/kg/day) MOE Dose (mg/kg/day MOE

Dermal Inhalation Total Dermal Inhalation Total Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Short–Term (Pet Treatment) 

Adult N/A N/A N/A N/A N/A N/A N/A N/A N/A

Child 1<2 N/A N/A N/A 0.0024 0.0024 N/A N/A 830 830

Intermediate- or Long-Term (Pet Treatment) 

Adult N/A N/A N/A N/A N/A N/A N/A N/A N/A

Child 1<2 N/A N/A 0.0024 0.0024 N/A N/A 830 830

N/A= not applicable

Table 6.3.2. Residential Exposures for the Indoxacarb Aggregate Assessment (KN128/127; Turf or Indoor Use)

Lifestage

Residential Handler (Turf) Residential Post-application (Indoor Use)

Dose (mg/kg/day) MOE Dose (mg/kg/day) MOE

Dermal Inhalation Total Dermal Inhalation Total Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Short-Term Term (Turf or Indoor)

Adult N/A 0.00045 0.00045 N/A 13,000 13,000 N/A 2.2 x 10-

8 N/A 2.2 x 10-8 N/A 2.7 x 10 8 N/A 2.0 x 10 8

Child 1<2 N/A N/A 9.6 x 10-

8

.0126 0.0126 N/A 6.2 x 10 7160 160

N/A= not applicable

1. Turf Use Scenario

2. Indoor Environment Scenario
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6.4 Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for indoxacarb at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV). However, volatilization of pesticides may be a 

source of post-application inhalation exposure to individuals nearby pesticide applications. The 

Agency sought expert advice and input on issues related to volatilization of pesticides from its 

Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are developed, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for indoxacarb.

6.5 Spray Drift

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 indoxacarb. 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 (see the Agency’s Spray Drift website for more information6). 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 with specific products with significant risk estimates associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not 

performed as a result of indoxacarb drift from neighboring treated agricultural fields, an 

inhalation exposure assessment was performed for flaggers and there were no risk estimates of 

concern. This exposure scenario is representative of high-end inhalation (drift) exposure and may

be considered protective of indoxacarb outdoor agricultural and commercial post-application 

inhalation exposure scenarios. 

Furthermore, residential turf uses were quantitatively assessed as part of this risk assessment; 

risk estimates addressed in the residential turf assessment provide a worst case estimate of 

potential exposure from spray drift. It is noted that the 0.44 lb ai/acre application rate for turf 

was modeled to estimate post-application residential exposure of children. As this rate is equal 

 

6 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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to or higher than agricultural application rates for indoxacarb, this scenario is protective of any 

exposure of children via spray drift from agricultural indoxacarb applications.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

Based on the existing and newly proposed uses of indoxacarb, exposures can occur both from 

dietary sources (food and water) and in residential settings. Uses of indoxacarb that may result 

in residential exposures include indoor treatments, spot-treatment of companion animals, and turf

(lawn uses and golf courses).

The aggregate risk assessments are intended to be representative of exposures that are likely to 

co-occur. The scenarios expected to result in the highest exposures are used as representative 

scenarios for the aggregate assessment and are considered protective of other scenarios. The 

lifestages selected for the aggregate assessments represent the population subgroups expected to 

be the most highly exposed for each scenario. For more information on the exposure scenarios 

selected for aggregate assessment, see Section 6.3 above.

7.1 Acute Aggregate Risk

Typically, HED does not consider residential exposures when assessing acute aggregate risk 

unless such exposures can be characterized as a series of single-day exposures, which is not the 

case for indoxacarb. Therefore, acute aggregate risk estimates for indoxacarb are equivalent to 

the acute dietary (food and drinking water) risk estimates (Section 5.4) and are below HED’s 

level of concern.

7.2 Short- Term Aggregate Risk

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

(food and drinking water) exposure plus the highest short- term residential exposures for adults 

and children (Table 7.2.1 below). The short-term aggregate assessment for adults includes 

residential exposure from mixing, loading and applying indoxacarb to turf. The short-term 

aggregate risk estimate for adults is below HED’s level of concern. The short- term aggregate 

assessment for children includes post-application exposure from indoor spray-treated surfaces. 

The short-term aggregate risk estimate for children is below HED’s level of concern. Note that 

the indoor spray-treated aggregate assessment assumes only crack and crevice treatment since 

the spot-treated directed sprays exposure estimate was of concern by itself for children.
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Table 7.2.1 Short-Term Aggregate Risk Calculations 

Population

Short- Term Scenario

LOC for 

Aggregate 

Risk1

Dietary

MOE2

MOE Oral 

Residential 

Exposure3

MOE 

Inhalation 

Residential 

Exposure4

Aggregate MOE (food, 

water, and residential)5

Adult 100 1800 NA 13,000 1600

Child (1<2 

yrs) 100 840 160 6.2 x 107

130

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

2 MOE dietary = [(short- -term oral NOAEL)/(chronic dietary exposure)]. Oral NOAEL= 2 mg/kg/day. Chronic 

dietary exposure value from Table 5.4.5 

3 MOE oral = [(short- -term oral NOAEL)/(hand-to-mouth residential exposure)]. Oral NOAEL= 2 mg/kg/day. 

Oral exposure value from Table 6.3.2 (indoor use) 

4MOE inhalation = [(short-term oral NOAEL)/(inhalation exposure). Oral NOAEL= 2 mg/kg/day .Inhalation 

exposure value from Table 6.3.2 (turf or indoor use)

5MOE Aggregate = 1/[(1/MOE dietary) + (1/MOE oral) + (1/MOE inhalation)]

7.3 Intermediate-/Long-Term (Chronic) Aggregate Risk

The intermediate-/long-term (or chronic) aggregate risk for indoxacarb includes contribution 

from dietary (food and drinking water) exposure plus the intermediate-/long-term postapplication exposure to treated pets. The intermediate-/long-term aggregate risk estimate for 

children post-application exposure to treated pets is below HED’s level of concern (Table 7.3). 

For adults, since there is no expectation of inhalation or non-dietary oral exposures to treated 

pets, the intermediate-/long-term aggregate risk assessment for indoxacarb is equivalent to 

chronic dietary risk assessment conducted in Section 5.4 of this document and is below HED’s 

level of concern.

Table 7.3 Intermediate-/Long- Term Aggregate Risk Calculations 

 Post-Application Treated Pets (KN128 )

Population

Long-Term Scenario

LOC for 

Aggregate 

Risk1

Dietary

MOE2

MOE Oral 

Residential 

Exposure3

MOE 

Inhalation 

Residential 

Exposure4

Aggregate MOE (food, 

water, and residential)5

Child (1<2 

yrs) 100 840 830 NA 420

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

2 MOE dietary = [(long-term oral NOAEL)/(chronic dietary exposure)]. Oral NOAEL= 2 mg/kg/day. Chronic 

dietary exposure value from Table 5.4.5 

3 MOE oral = [(long-term oral NOAEL)/(hand-to-mouth residential exposure)]. Oral NOAEL= 2 mg/kg/day. 

Residential exposure value from Table 6.3.1 

4 Not applicable. Inhalation exposures not expected.

5MOE Aggregate = 1/[(1/MOE dietary) + (1/MOE oral) + (1/MOE inhalation)]
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7.4 Cancer Aggregate Risk

Indoxacarb is classified as “Not Likely to be Carcinogenic to Humans;” therefore, cancer risk is

not a concern and cancer risks are not quantified.

8.0 Cumulative Exposure/Risk Characterization

EPA does not have, at this time, available data to determine whether indoxacarb, an oxadiazine 

class insecticide, has a common mechanism of toxicity with other substances. Unlike other 

pesticides for which EPA has followed a cumulative risk approach based on a common 

mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to 

indoxacarb and any other substances and indoxacarb does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that indoxacarb has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

The insecticide indoxacarb 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 to be used in 

agricultural and non-agricultural use sites 

IR-4 has proposed a Section 3 registration (Petition# 2E8029) for proposed foliar uses of the 

active ingredient indoxacarb on the following agricultural crops: 1) new uses on dry beans and 

succulent beans and 2) expanded crop group uses on small fruit vine climbing subgroup 13-07F 

and low-growing berry subgroup 13-07H. Occupational assessments are performed for the new 

uses on dry beans and succulent beans. Existing grape and cranberry uses were reassessed in this 

document to reflect updates to the Agricultural Reentry Task Force (ARTF) database regarding 

transfer coefficients (TC) data since both crops are included in the new subgroups. The end-use 

products included in this IR-4 petition are Avaunt® 30% WDG (EPA Reg. No. 352-597) and 

StewardTM EC (EPA Reg. No. 352-638). 

The Avaunt®formulation contains an isometric mixture of 75% indoxacarb (insecticidally active 

S-enantiomer; DPX-KN128) and 25% of the R-enantiomer (insecticidally inactive; IN-KN127). 

The percentage of active ingredient indicated on the Avaunt® label and the labeled use rates for 

each crop are based only on the amount of S-indoxacarb (KN128) and do not reflect the amount 

of the toxicologically significant R- enantiomer (KN127). Therefore, to determine combined 

exposures to both for risk assessment the maximum proposed label rate of application is adjusted 
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to account for the 25% isomer not reflected on the label (i.e., lb total indoxacarb applied = 

application rate * 4/3). The Steward product contains only the S-enantiomer (KN128); therefore, 

the proposed label rate does not need to be adjusted.

Avaunt®insecticide, a WDG formulation containing 30% of insecticidally active ingredient (Sindoxacarb) is proposed for foliar uses on dry beans, succulent beans, small fruit vine climbing 

subgroup 13-07F, and low-growing berry subgroup 13-07H at a maximum single application rate 

of 0.11 lb ai/acre or 0.147 lb total (S- and R-) indoxacarb per acre (0.11 *4/3= 0.147). In

addition, Steward®EC insecticide, an emulsifiable concentrate containing 15.84% of S -

indoxacarb (and no R-indoxacarb) is proposed for uses on dry beans at a maximum single 

application rate of 0.11 lb ai/acre. 

The proposed maximum seasonal application rate for dry and succulent beans and the lowgrowing berry subgroup is 0.44 lb ai/acre (4 applications at 0.11 lb ai/acre are permitted). For 

the small fruit vine climbing subgroup, the proposed maximum seasonal application rate is of 

0.22 lb ai./acre (2 applications at 0.11 lb ai/acre are permitted). Aerial, airblast, ground foliar 

spray applications, and chemigation techniques (cranberry only) are the proposed application 

methods. According to the proposed label, pre-harvest intervals (PHIs) range from 3 to 30 days. 

The REI specified on the labels is 12 hours. The proposed labels require applicators and other 

handlers to wear a long-sleeved shirt and long pants and shoes plus socks, plus chemicalresistant gloves. The proposed uses and application rates are further described in Table 9.0. 

Table 9.0 Summary of Directions for Use of Indoxacarb.

Applic. Timing, 

Type, and 

Equip.

Formulation 

[EPA Reg. No.]

Applic. 

Rate (lb 

ai/A) *

Max. 

No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

PHI 

(days)

Use Directions and 

Limitations

Beans, Dried 

Broadcast foliar 

applications

Air, Ground 

(groundboom)

DuPont TM 

Steward® EC

15.84% ai EC

(EPA Reg. No. 

352-638)

0.11 NS 0.44 7

Retreatment interval (RTI) 

is 7 days

Broadcast foliar 

applications

Air, Ground 

(groundboom) 

DuPont TM 

Avaunt®

30% ai WDG

(EPA Reg. No. 

352-597)

0.11 

(adjusted 

to 0.147)

NS

0.44

(adjusted to 

0.586)

7

Retreatment interval (RTI) 

is 7 days

Beans, Succulent

Broadcast foliar 

applications

Air, Ground 

(groundboom)

DuPont TM 

Avaunt®

30% ai WDG

(EPA Reg. No. 

352-597)

0.11 

(adjusted 

to 0.147)

NS

0.44

(adjusted to 

0.586)

3

Retreatment interval (RTI) 

is 7 days

Small Fruit Vine Climbing Subgroup 13-07F

Broadcast foliar 

applications

Air, Ground 

DuPont TM 

Avaunt®

30% ai WDG

0.11 

(adjusted 

to 0.147)

NS

0.22

(adjusted to 

0.293)

7

Retreatment interval (RTI) 

is 21 days
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* Based on proposed application rates for DuPont TM Steward® EC (EPA Reg. No. 352-638) and DuPont TM Avaunt®

(EPA Reg. No. 352-597) . DuPont TM Avaunt®contains an isometric mixture of 75% indoxacarb (insecticidally 

active S-enantiomer; DPX-KN128) and 25% of the R-enantiomer (insecticidally inactive; IN-KN127). The 

percentage of active ingredient indicated on the Avaunt® label and the labeled use rates for each crop are based only 

on the amount of indoxacarb (KN128). Therefore, the maximum proposed label rate of application must be adjusted 

to account for the 25 % isomer not reflected as “ai” (i.e., lb total indoxacarb = application rate * 4/3).

9.1 Short- and Intermediate- Term Handler Risk

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

application process. HED believes that there are distinct job functions or tasks related to 

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

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler inhalation (short-term and intermediate- term) 

exposure is expected from the proposed uses of indoxacarb on dry beans, succulent beans and the 

uses on small fruit vine climbing subgroup 13-07F and low-growing berry subgroup 13-07H . 

Dermal exposure to handlers is not quantitatively assessed as a toxic endpoint is not identified 

for dermal exposure to indoxacarb. The quantitative exposure/risk assessment developed for 

occupational handlers is based on the following scenarios: 

1) Mixing/loading liquids for aerial and groundboom applications;

2) Mixing/loading water dispersible granules for aerial, chemigation, airblast, and groundboom

applications,

3) Applying Sprays via aerial equipment, airblast and groundboom equipment;

4) Mixing/loading/applying water dispersible granules via mechanically pressurized 

handgun;and, 

5) Flagging for aerial spray applications.

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data, used as surrogate data in the absence of chemical-specific data, include 

PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) 

database, or other registrant-submitted occupational exposure studies. Some of these data are 

(groundboom, 

airblast)

(EPA Reg. No. 

352-597)

Low-Growing Berry Subgroup 13-07H

Broadcast foliar 

applications

Air, Ground 

(groundboom), 

Chemigation 

(cranberry only),

Mechanically 

pressured handgun

DuPont TM 

Avaunt®

30% ai WDG

(EPA Reg. No. 

352-597)

0.11 

(adjusted 

to 0.147)

NS

0.22 to 0.44

(0.293 to 

0.586 

depending on 

pest)

30

Broadcast applications may 

need supplemental spot 

treatment in localized areas 

of heavy insect pressure
Indoxacarb Human Health Risk Assessment DP No. D416367

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proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The 

standard values recommended for use in predicting handler exposure that are used in this 

assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit 

Exposure Surrogate Reference Table7”, which, along with additional information on HED policy

on use of surrogate data, including descriptions of the various sources, can be found at the 

Agency website8. 

Estimates of inhalation exposure were calculated at “baseline” level of personal protective 

equipment (PPE). “Baseline” is defined as a single layer of clothing consisting of a long sleeved 

shirt, long pants, shoes plus socks, no protective gloves, and no respirator. The proposed labels 

require applicators and other handlers to wear a long-sleeved shirt and long pants and shoes plus 

socks, plus chemical-resistant gloves.

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

risk assessments. See D411342, 5/1/13, complete details regarding body weight assumptions, 

absorption, unit exposures, area treated, exposure durations, and the associated calculations.

Summary of Occupational Handler Short-Term and Intermediate-Term (Non-Cancer) Exposure 

and Risk Estimates

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for human 

flaggers where appropriate, agricultural aviation has changed dramatically over the past two 

decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will continue to monitor all available information sources to 

best assess and characterize the exposure potential for human flaggers in agricultural aerial 

applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

Table 9.1 presents a summary of the short- and intermediate -term occupational handler 

exposures and risks. All occupational handler scenarios assessed result in inhalation MOEs that 

do not exceed HED's level of concern (MOEs ≥ 100) for short and intermediate-term exposure 

durations at label specified PPE (i.e ., no respirator ). 

 

7 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

8 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
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Table 9.1 Occupational Handler ST and IT (Non-Cancer) Exposure and Risk Estimates for 

Indoxacarb.

Exposure Scenario Crop or Target

Inhalation 

Unit Exposure 

(μg/lb ai)1 Maximum

Application 

Rate2

(lb ai/A)

Area Treated 

or Amount 

Handled Daily 

(acres)3

Inhalation

Mitigation 

Level

(Baseline, no 

respirator)

Dose 

(mg/kg/day)4 MOE5

Mixer/Loader

Mixing/Loading Water 

Dispersible granules 

(WDG) for Aerial 

Applications

Fruit, small vine 

climbing- Subgroup 13-07F 

Bean (snap), 8.96 0.147 350 0.00576 1000

Low-Growing 

Berry Subgroup

13-07H

Mixing/Loading Water 

Dispersible granules 

(WDG) for Aerial 

Applications

Bean (dry) 8.96 0.147 1,200 0.0198 300

Mixing/Loading Water 

Dispersible granules 

(WDG) for Airblast 

Applications

Fruit, small vine 

climbing- Subgroup 13-07F 8.96 0.147 40 0.00065 9,000

Mixing/Loading Water 

Dispersible granules 

(WDG) for Chemigation 

Applications

Fruit, small vine 

climbing- Subgroup 13-07F

(cranberry0

8.96 0.147 350 0.00576 1,000

Mixing/Loading Water 

Dispersible granules 

(WDG) for Groundboom 

Applications

Bean (snap),

8.96 0.147 80 0.00131 4,600

Low-Growing 

Berry Subgroup

13-07H

Mixing/Loading Water 

Dispersible granules 

(WDG) for Groundboom 

Applications

Bean (dry)

Bean (dry)

8.96

0.147 200 0.00329 1,800

Mixing/Loading Liquid 

Flowables for Aerial 

Applications

0.219 0.11 1,200 0.0003 16,000

Mixing/Loading Liquid 

Flowables for Groundboom 

Applications

0.219 0.11 200 0.00006 98,000

Applicator

Applying Sprays via 

Airblast Equipment (Open 

Cab)

Fruit, small vine 

climbing- Subgroup 13-07F 

4.71

0.147 40 0.00034 17,300

Applying Sprays via 

Groundboom Equipment 

Bean (snap),

Low-Growing 0.32 0.147 80 0.00005 120,000

Berry Subgroup

13-07H
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Table 9.1 Occupational Handler ST and IT (Non-Cancer) Exposure and Risk Estimates for 

Indoxacarb.

Exposure Scenario Crop or Target

Inhalation 

Unit Exposure 

(μg/lb ai)1 Maximum

Application 

Rate2

(lb ai/A)

Area Treated 

or Amount 

Handled Daily 

(acres)3

Inhalation

Mitigation 

Level

(Baseline, no 

respirator)

Dose 

(mg/kg/day)4 MOE5

Applying Sprays via 

Groundboom Equipment Bean (dry) 0.34

0.147

200

0.00012 48,000

0.11 0.00009 64,000

Flagger

Flagging for Aerial Spray 

Applications 

Bean (snap), LowGrowing Berry 

Subgroup

13-07H, and Fruit, 

small vine 

climbing- Subgroup 13-07F, 

0.35 0.147

350

0.00022 27,000

Flagging for aerial spray 

applications Bean (dry)

0.35 0.147 0.00016 27,000

0.35 0.11 0.0001 36,000

Mixer/Loader/Applicator

Applying Water Dispersible 

Granules Via Mechanically 

Pressurized Handgun 

Fruit, small vine 

climbing- Subgroup 13-07F

Bean (snap), 3.9 0.147 1000 gallons 0.00716 840

Low-Growing 

Berry Subgroup

13-07H

1. Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” September 2012]); Level of mitigation: Baseline, 

PPE, Eng. Controls.

2. Based on registered or proposed labels: DuPont TM Avaunt®30% ai WDG (EPA Reg. No. 352-597) and DuPont TM Steward® EC 15.84% ai EC 

(EPA Reg. No. 352-638). The application rate used to calculate MOEs for Avaunt applications has been adjusted by a 4/3 factor to account for 

4 parts of total indoxacarb for every 3 parts of S-indoxacarb.

3. Exposure Science Advisory Council Policy #9.1.

4. Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated 

or Amount Handled Daily (A or gal/day) ÷ BW (kg).

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

Occupational Handler Cancer Exposure and Risk Equations

Cancer risk estimates are not provided for indoxacarb since it is classified as not likely

carcinogenic to humans.

9.2 Short- and Intermediate-Term Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.
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Dermal and inhalation exposures to indoxacarb may occur for post-application workers. A 

quantitative dermal assessment is not performed since a dermal toxicity endpoint is not identified 

for indoxacarb. A quantitative occupational post-application inhalation exposure assessment was 

not performed for indoxacarb; however, an inhalation exposure assessment was performed for 

occupational/commercial handlers, which is likely to result in higher exposure than would occur 

post-application. Therefore, these handler inhalation exposure estimates would be protective of 

occupational post-application inhalation exposure scenarios.

9.2.1 Dermal Post-Application Risk

Occupational Post-Application Dermal Exposure Data and Assumptions

Short- and intermediate-term dermal post-application risk estimates were not quantified, since 

the calculated human dermal LOAEL exceeds the limit dose of 1000 mg/kg/day and dermal 

toxicity to indoxacarb is not expected. 

Restricted Entry Interval

The REI specified on the proposed label is 12 hours and is based on the acute toxicity of 

Indoxacarb. Indoxacarb is classified as Toxicity Category IV via the dermal route and Toxicity

Category IV for skin irritation potential. It is not a skin sensitizer. Under 40 CFR 156.208 (c) (2) 

(iii), ai’s classified as Acute III or IV for acute dermal, eye irritation and primary skin irrigation 

are assigned a 12-hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim 

REI of 12 hours is adequate to protect agricultural workers from post-application exposures to 

indoxacarb.

 

9.2.2 Inhalation Post-Application Risk

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for indoxacarb at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), and low vapor pressure (2.5 x 10-8). However, there 

are multiple potential sources of post-application inhalation exposure to individuals performing 

post-application activities in previously treated fields. These potential sources include 

volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. 

The Agency sought expert advice and input on issues related to volatilization of pesticides from 

its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 20109. The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the ARTF and may, as appropriate, develop policies and procedures, to 

identify the need for and, subsequently, the way to incorporate occupational post-application 

inhalation exposure into the Agency's risk assessments. If new policies or procedures are put 

into place, the Agency may revisit the need for a quantitative occupational post-application 

inhalation exposure assessment for indoxacarb.

 

9 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Indoxacarb Human Health Risk Assessment DP No. D416367

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Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

10.0 References

A.Rivera-Lupianez, 5/1/13, D411342, Indoxacarb: 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 Low-Growing Berry Subgroup 13-07H. 

I. Negrón-Encarnación, 5/1/13, D408983, Indoxacarb Acute and Chronic Aggregate Dietary

(Food and Drinking Water) Exposure and Risk Assessment for the Section 3 Registration Action

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

and Low Growing Berry Subgroup (except strawberry) 13-07H. 

I. Negrón-Encarnación, 5/2/13, D408982, Indoxacarb. Petition for the Establishment of

Permanent Tolerances and Registration for Use on Dry Bean, Snap Bean, Small Fruit Vine 

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

strawberry) 13-07H. Summary of Analytical Chemistry and Residue Data.

C. Koper, 11/06/12, D402100, Tier II Drinking Water Assessment for the New Use Registration 

of Indoxacarb on Dry Beans, Snap Beans, Small Fruit Vine Climbing Subgroup 13-07F and 

Low-Growing Berry Subgroup 13-07H.

D. Drew, 5/26/09, D365306, Indoxacarb. Addendum to the Health Effects Division (HED) 

Human Health Risk Assessment for Bushberry Crop Subgroup 13-07B and Beets (Garden). 

D. Drew, 5/18/09, D351087, Indoxacarb. Health Effects Division (HED) Human Health Risk 

Assessment for Bushberry Crop Subgroup 13-07B and Beets (Garden). 

HIARC Report on Indoxacarb, HED Doc No. 013528 (June 24, 1999)
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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for indoxacarb are in Table 1. Use of the new guideline numbers does not 

imply that the new (1998) guideline protocols were used.

Table A.1 Toxicology Requirements for Indoxacarb 

Guideline Number and Toxicity Study Required Satisfied

870.1100 Acute Oral Toxicity......................................................

870.1200 Acute Dermal Toxicity.................................................

870.1300 Acute Inhalation Toxicity.............................................

870.2400 Primary Eye Irritation ..................................................

870.2500 Primary Dermal Irritation.............................................

870.2600 Dermal Sensitization ....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Sub-chronic (Rodent)...........................................

870.3150 Oral Sub-chronic (Non-Rodent)...................................

870.3200 21-Day Dermal.............................................................

870.3250 90-Day Dermal.............................................................

870.3465 90/28-Day Inhalation ...................................................

yes

yes

yes

CR

CR

yes

yes

yes

--

yes

870.3700 Developmental Toxicity (Rodent)...............................

870.3700 Developmental Toxicity (Non-rodent).........................

870.3800 Reproduction................................................................

yes

yes

yes

yes

yes

yes

870.4100 Chronic Toxicity (Rodent) ...........................................

870.4100 Chronic Toxicity (Non-rodent) ....................................

870.4200 Oncogenicity (Rat).......................................................

870.4200 Oncogenicity (Mouse)..................................................

870.4300 Chronic/Oncogenicity ..................................................

yes

no

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity: Gene Mutation - bacterial .....................

870.5300 Mutagenicity: Gene Mutation - mammalian ................

870.5375 Mutagenicity: Structural Chromosomal Aberrations ...

870.5395 Mutagenicity: Cytogenetics

870.5500 Mutagenicity: Other Genotoxic Effects .......................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.6100 Acute Delayed Neurotoxicity (Hen).............................

870.6100 90-Day Neurotoxicity (Hen) ........................................

870.6200 Acute Neurotoxicity Screening Battery (Rat) ..............

870.6200 90-Day Neurotoxicity. Screening Battery (Rat)...........

870.6300 Developmental Neurotoxicity ......................................

no

no

yes

yes

CR

-

-

yes

yes

yes

870.7485 General Metabolism.....................................................

870.7600 Dermal Penetration.......................................................

870.7800 Immunotoxicity.......................................................................

yes

no

yes

yes

yes

yes
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A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Data on Indoxacarb (DPX-KN128)

Guideline No./Study Type MRID # Results Toxicity 

Category

870.1100 Acute oral toxicity 44477115 LD50 = 179 (F) and 

843 (M) mg/kg (rat) II

870.1200 Acute dermal toxicity 46240001 LD50 > 5000 mg/kg 

(rat) IV

870.1300 Acute inhalation toxicity N/A N/A IV

870.2400 Primary eye irritation 46240002 Not a eye irritant 

(rabbit) IV

870.2500 Primary dermal irritant 46240003 Not a dermal irritant 

(rabbit) IV

870.2600 Skin sensitization 46240004 Is a dermal sensitizer 

(Guinea Pig) NA

Table A.2.2 Acute Toxicity Data on DPX-MP062 Technical (94.5%;)

 80% DPX KN128, 20% IN KN127

Study

Type

MRID # Results Toxicity 

Category

870.1100 Acute oral 

toxicity

44477113 LD50 = 

1730mg/kg males

268 mg/kg females

<1000 mg/kg combined (rat)

II

870.1200 Acute dermal 

toxicity 44477118 LD50 >5000mg/kg (limit test) (rat)

IV

870.1300 Acute inhalation 

toxicity

70%MUP

44477120

LC50 > 5.5 mg/L males, 

females and combined

IV

870.2400 Primary eye 

irritation 44477122 Moderate eye irritant (rabbit) III

870.2500 Primary dermal 

irritant

44477125 Not a dermal irritant (rabbit) IV

870.2600 Skin 

sensitization

44477126 Magnusson-Kligman 

Maximization test, Is a dermal 

sensitizer (Guinea Pig)

NA

Table A.2.3 Acute Toxicity Data on DPX-JW062 (50% DPX KN128,50% IN KN127)

Guideline No./ Study Type MRID No. Results Toxicity 

Category

870.1100 Acute oral toxicity 44701601 LD50 > 5000 mg/kg (males, 

females, combined) (in corn oil)

IV
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870.1200 Acute dermal toxicity 44477119 LD50 > 2000 mg/kg (males, 

females, combined) (rabbit)

III

870.1300 Acute inhalation toxicity 44477121 LC50 > 5.4 mg/L males

LC50 = 4.2 mg/L females (rat)

IV

870.2400 Primary eye irritation 44701602 Slight eye irritant (rabbit) IV

870.2500 Primary dermal irritation 44701603 Slight dermal irritation (rabbit) IV

870.2600 Skin sensitization 44701604 Is not a dermal sensitizer 

Magnusson-Kligman 

Maximization test, (Guinea Pig)

NA

Table A.2.4 Sub-Chronic, Chronic, and Other Toxicity Data on Indoxacarb (DPX-KN128)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

870.3700a

Prenatal 

developmental in 

rodents - rat

46240005(2004)

Acceptable/guideline

0, 0.5, 1.0, 2.0, or 3.5 

mg/kg/day

Maternal NOAEL = 2.0 mg/kg/day

LOAEL = 3.5 mg/kg/day, based on decrease in maternal 

overall body-weight gain and adjusted body-weight gain.

Developmental NOAEL = 2.0 mg/kg/day

LOAEL = 3.5 mg/kg/day, based on decreased mean fetal 

weight.

Gene Mutation

870.5100

46240006 (2004) 

Acceptable/guideline strains TA98, TA100, TA1535 and TA1537 of S. 

typhimurium and strain WP2(uvrA) of E. coli were negative 

for mutagenic activity both with and without S9 activation 

for the concentration range 2.5-5000 μg/plate

Gene Mutation

870.5300

46240007 (2003)

Acceptable/guideline

negative for mutagenic activity for the following 

concentration range 5-50 μg/mL (±S9)

Cytogenetics 

870.5375

46240008 (2003)

Acceptable/guideline

no evidence of chromosomal aberrations induced by the test 

article over background for the following concentration 

ranges: 1.25-100 μg/mL (+S9)

870.6300

Developmental 

neurotoxicity - rat

46749002 (2006)

46749003 (2006)

Acceptable/non-guideline

0, 0.5, 1.0, 1.5, or 3.0 

mg/kg/day

Maternal systemic/neurotoxicity NOAEL = 1.5 mg/kg/day

LOAEL = 3.0 mg/kg/day, based on the adverse clinical signs 

observed, decreased body-weight gain and food 

consumption and mortality.

Offspring systemic/neurotoxicity NOAEL= 1.5 mg/kg/day

LOAEL = 3.0 mg/kg/day, based on an increased incidence 

of stillbirths, decreased mean pup body weight at birth and 

increased pup mortality during PND 1-4 in males and 

females, and increase in number of learning trials to reach 

criterion and increased latency in males.

870.7800

Immunotoxicity

48478002 (2011)

Acceptable/guideline

Immunotoxicity NOAEL=23 mg/kg/day HDT 

Systemic NOAEL=23 mg/kg/day HDT

Systemic LOAEL was not established (>23 mg/kg/day).
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Table A.2.5 Sub-Chronic, Chronic, and Other Toxicity Data on Indoxacarb (DPX-MP062)

80% DPX KN128, 20% IN KN127

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100

90-Day oral 

toxicity rodents

44477129 (1997)

Acceptable/guideline

M: 0, 10, 50, 100, 200 

ppm

M: 0, 0.6, 3.1, 6.0, 15 

mg/kg/day

F: 0, 10, 25, 50, 100 

ppm, F: 0, 0.76, 2.1, 

3.8, 8.9 mg/kg/day

NOAEL = 3.1 (M), 2.1 (F) mg/kg/day

LOAEL = 6.0 (M), 3.8 (F) mg/kg/day based on 

decreased body weight, body-weight gain, food 

consumption and food efficiency.

870.3200

28-Day dermal 

toxicity

44477134 (1997)

acceptable (guideline)

0, 50, 500, 1000, 2000 

mg/kg/day

NOAEL = 2000 mg/kg/day

LOAEL = >2000 mg/kg/day in rats.

870.3200

28-Day dermal 

toxicity

44983901 (1999)

acceptable/guideline

0, 50, 500, 1000, 2000 

mg/kg/day

NOAEL = 50 mg/kg/day

LOAEL = 500 mg/kg/day based on decreased body 

weights, body-weight gains, food consumption, and 

food efficiency in F, and changes in hematology 

parameters (incr. reticulocytes), the spleen (incr. abs. 

and rel. weight–M only, gross discoloration), clinical 

signs of toxicity in both sexes in rats.

[Based on the in vitro dermal absorption data from rat 

skin and human skin (i.e. 15.2% and 0.87%, 

respectively), the human equivalent NOAEL is 875 

mg/kg/day (i.e. 50 x 15.2%/0.87%). Thus, the 

calculated human dermal LOAEL of 8750 mg/kg/day 

exceeds the dermal limit dose of 1000 mg/kg/day. See 

MRIDs 45911401, 45911402, 45911403]

870.3465

28-Day inhalation 

toxicity

45870001 (2003)

Acceptable/nonguideline

0, 4.6, 23, 290 

μg/L/day

NOAEL = 23 μg/L/day

LOAEL = 290 μg/L/day (75.69 mg/kg/day), based on 

increased absolute and relative spleen weights, 

pigmentation and hematopoiesis in the spleen, and 

hematological changes.

870.3700a

Prenatal 

developmental in 

rodents - rat

44477138, 44477142 

(1997)

Acceptable (guideline)

0.0, 0.5, 1.0, 2.0, or 4.0 

mg/kg/day (in PEG)

Maternal NOAEL = 2.0 mg/kg/day

LOAEL = 4.0 mg/kg/day based on decreased mean 

body weights, body-weight gains, food consumption.

Developmental NOAEL = 2.0 mg/kg/day

LOAEL = 4.0 mg/kg/day based on decreased fetal 

weights.

Gene Mutation

870.5100

44477149 (1997)

acceptable/guideline

Negative: strains TA97a, TA98, TA100 and TA1535 

of S. typhimurium and strain WP2(uvrA) of E. coli

were negative for mutagenic activity both with and 
Indoxacarb Human Health Risk Assessment DP No. D416367

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Table A.2.5 Sub-Chronic, Chronic, and Other Toxicity Data on Indoxacarb (DPX-MP062)

80% DPX KN128, 20% IN KN127

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

without S9 activation for the concentration range 10-

5000 μg/plate

Gene Mutation

870.5300

44477147 (1997)

acceptable/guideline

Negative: negative for mutagenic activitity for the 

following concentration ranges: 3.1-250 μg/mL (-S9); 

3.1-250 μg/mL (+S9)

Cytogenetics 

870.5375

44477146 (1996)

acceptable/guideline

Negative: no evidence of chromosomal aberrations 

induced by the test article over background for the 

following concentration ranges: 15.7-1000 μg/mL 

(+S9)

Cytogenetics 

870.5395

44477148 (1997)

acceptable/guideline

Negative: no evidence of mutagenicity for the 

following dose ranges: 3000-4000 mg/kg - males; 

1000-2000 mg/kg - females

Other Effects 

870.5550

44477151 (1997)

acceptable/guideline

Negative: no evidence of mutagenic activity at the 

following concentration range: 1.56-200 μg/mL; 

cytotoxicity was seen at concentrations of >100 μg/mL

870.6200a

Acute 

neurotoxicity 

screening battery

44477127 (1997)

acceptable/guideline

M: 0, 25, 100, 200 

mg/kg

F: 0, 12.5, 50, 100 

mg/kg

NOAEL = 100 mg/kg (M), 12.5 mg/kg (F)

LOAEL = 200 mg/kg (M) based on decreased bodyweight gain, decreased food consumption, decreased 

forelimb grip strength, and decreased foot splay. 50 

mg/kg (M) based on decreased body weight and bodyweight gain

870.6200b

Subchronic 

neurotoxicity 

screening battery

44477135 (1997)

acceptable/guideline

M: 0, 10, 100, 200 ppm 

0.57, 5.6, 12 mg/kg/d, 

F: 0, 10, 50, 100 ppm

0.68, 3.3, 6.1 mg/kg/d

NOAEL =0.57 (M), 0.68 (F) mg/kg/day

LOAEL = 5.6 (M), 3.3 (F) mg/kg/day based on 

decreased body weight and alopecia.

870.7600

Dermal 

penetration

(Triple pack 

study)

45911401 (2002) 

45911402 (2002)

45911403 (2002)

Acceptable/guideline

0, 13.3, 2000 μg/cm2 

for 6 hours

Dermal absorption ranged from 0.41% to 0.94% 

following 6 hours exposure in rats. Following a 162 

hours post dosing, the absorption in rats ranged from 

0.88% to 4.91% depending upon the dose/dilution. 

The in vitro dermal absorption for rat skin was 15.2%

and the in vitro dermal absorption in human skin was 

0.87%, or 17.5X lower. The equivalent dermal 

absorption in humans was calculated to be 0.28%.

Table A.2.6 Sub-Chronic, Chronic, and Other Toxicity Data on Indoxacarb (DPX-JW062)

(50% DPX KN128, 50% IN KN127)

Guideline No./ MRID No. (year)/ Results
Indoxacarb Human Health Risk Assessment DP No. D416367

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Study Type Classification/Doses

870.3700a

Prenatal 

developmental in 

rodents - rat

44477140, 44477143 

(1997)

acceptable/guideline

0, 10, 100, 500, 1000 

mg/kg/day (in methyl 

cellulose)

Maternal NOAEL = 10 mg/kg/day

LOAEL = 100 mg/kg/day based on mortality, clinical signs, 

and decreased mean body weights, body-weight gains, and 

food consumption.

Developmental NOAEL = 10 mg/kg/day

LOAEL = 100 mg/kg/day based on decreased numbers of 

live fetuses/litter.

870.3700a

Prenatal 

developmental in 

rodents - rat

44477139 (1997)

acceptable/guideline

0, 20, 40, 80, or 120 ppm

1.11, 2.2, 4.1, 5.7 

mg/kg/day (rounded to 2 

sig. fig.)

Maternal NOAEL = 1.1 mg/kg/day

LOAEL = 2.2 mg/kg/day based on decreased mean body

weights, body-weight gains, food consumption, and food 

efficiency.

Developmental NOAEL = 1.1 mg/kg/day

LOAEL = 4.1 mg/kg/day based on decreased fetal body 

weights.

870.3700b

Prenatal 

developmental in 

nonrodents - rabbit

44477141 (1995)

acceptable/guideline

0, 250, 500, or 1000 

mg/kg/day in methyl 

cellulose

Maternal NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day based on slight decreases in 

maternal body-weight gain and food consumption.

Developmental NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day based on decreased fetal bodyweights and reduced ossification of the sternebrae.

870.3800

Reproduction and 

fertility effects

44477144 (1997)

acceptable/guideline

0, 20, 60, 100 ppm

M: 0, 1.3, 3.9, 6.4 

mg/kg/d

F: 0, 1.5, 4.4, 6.9 mg/kg/d

Parental/Systemic NOAEL = 1.5 mg/kg/day

LOAEL = 4.4 mg/kg/day based on decreased body weights, 

body-weight gains, and food consumption of F0 females, and 

incr. spleen weights in the F0 and F1 females.

Reproductive NOAEL = 6.4 mg/kg/day

LOAEL > 6.4 mg/kg/day.

Offspring NOAEL = 1.5 mg/kg/day

LOAEL = 4.4 mg/kg/day based on decrease in the body 

weights of the F1 pups during lactation.

870.4100a

Chronic toxicity 

rodents - rat

44477145 (1997)

acceptable/guideline

0, 20, 40, 60, 125, 250 

ppm

M: 0, 0.80, 1.6, 2.4, 5.0, 

10 mg/kg/day

F: 0, 10, 20, 40, 60, 125 

ppm

0, 0.55, 1.0, 2.1, 3.6, 7.8 

mg/kg/day

NOAEL = 5 (M), 2.1 (F) mg/kg/day

LOAEL = 10 (M), 3.6 (F) mg/kg/day based on decreased 

body weight, body-weight gain, and food consumption and 

food efficiency; decreased HCT, HGB and RBC at 6 months 

in F only.

No evidence of carcinogenic potential.

870.4100b

Chronic toxicity 

dogs

44477136 (1997)

acceptable/guideline

0, 40, 80, 640, 280 ppm

M: 0, 1.1, 2.3, 18, 34 

mg/kg/day

F: 0, 1.3, 2.4, 19, 36 

mg/kg/day

NOAEL = 2.3 (M), 2.4 (F) mg/kg/day

LOAEL = 18 (M), 19 (F) mg/kg/day based on decreased 

HCT, HGB and RBC; incr. Heinz bodies and reticulocytes 

and assoc. secondary microscopic changes in the liver, 

kidneys, spleen, and bone marrow; incr. abs. and rel. liver 

weights.

870.4200

Carcinogenicity rats

see 870.4100a see 870.4100a

No evidence of carcinogenicity.
Indoxacarb Human Health Risk Assessment DP No. D416367

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870.4300

Carcinogenicity 

mice

44477137 (1997)

0, 20, 100, 200/150/125 

ppm

M: 2.6, 14, 22 mg/kg/day

F: 4.0, 20, 31 mg/kg/day

(rounded to 2 sig. fig.)

NOAEL = 2.6 (M), 4.0 (F) mg/kg/day

LOAEL = 14 (M), 20 (F) mg/kg/day based on decreased 

body weight, body-weight gain, and food efficiency and 

clinical signs indicative of neurotoxicity.

No evidence of carcinogenicity.

Gene Mutation

870.5100

44701606 (1995)

acceptable/guideline

Negative: strains TA97a, TA98, TA100 and TA1535 of S. 

typhimurium and strain WP2(uvrA) of E. coli were negative 

for mutagenic activity both with and without S9 activation 

for the concentration range 10-5000 μg/plate.

Gene Mutation

870.5300

44701607 (1995)

acceptable/guideline

Negative for mutagenic activity for the following 

concentration ranges: Negative;100-1000 μg/mL (-S9); 100-

1000 μg/mL (+S9), precipitate >1000 μg/mL

Cytogenetics 

870.5375

44701608 (1995)

acceptable/guideline

Negative: No evidence of chromosomal aberrations induced 

by the test article over background for the following 

concentration ranges: 19-300 μg/mL (-S9), 19-150 μg/mL 

(+S9); partial insoluble & cytotoxicity > 150 μg/mL

Cytogenetics 

870.5395

44701610 (1995) Negative: No evidence of mutagenicity at 2500 or 5000 

mg/kg

Other Effects 

870.5550

44701609 (1995)

acceptable/guideline

Negative: No evidence of mutagenic activity at the 

following concentration range: 0.1-50 μg/mL, cytotoxicity 

observed at >50 μg/mL

870.6200a

Acute neurotoxicity 

screening battery

44477128 (1996)

acceptable/guideline

0, 500, 1000, 2000 mg/kg

NOAEL >= 2000 mg/kg (M)

= < 500 mg/kg (F)

LOAEL > 2000 mg/kg (M)

< 500 mg/kg (F) based on clinical signs, decreased 

body-weight gains and food consumption, and FOB 

effects

870.7485

Metabolism and 

pharmacokinetic

44477152, 44477153 

(1997)

acceptable/guideline

Both indoxacarb and JW062 were extensively metabolized 

and the metabolites were eliminated in urine, feces, and bile. 

The metabolite profile for JW062 was dose dependent and 

varied quantitatively between males and females. 

Differences in metabolite profiles were also observed for the 

different label positions (indanone and 

trifluoromethoxyphenyl rings). All biliary metabolites 

undergo further biotransformation in the gut. The proposed 

metabolic pathway for both indoxacarb and JW062 has 

multiple metabolites bearing one of the two ring structures.
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Appendix B. Physical/Chemical Properties

1 EFED memo D402100, 11/6/12

Table B.1 Physicochemical Properties of Indoxacarb

Parameter Value Reference

Melting point/range 140-141oC DP# D244253, S. Levy, 

1/19/2000 pH 5.32 at 25oC

Density 1.34 at 20oC

Water solubility 15.4 ± 2.3 ppb in pH 5 buffer

800 ppb at pH 7 (20◦C)1

Solvent solubility 1.72 g/L in n-heptane; 14.5 g/L in 1-

octanol; 103 g/L in methanol; 117 g/L in 

o-xylene; 139 g/L in acetonitrile; 160 

g/L in ethyl acetate; and >250 g/kg in 

methylene chloride, acetone, and 

dimethyl-formamide

Vapor pressure (25°C) 2.5 x 10-8Pa (1.9x10-10 mmHg)

Dissociation constant, pKa Does not dissociate at pHs of 2.42-11.36

Octanol/water partition coefficient, 

Log(KOW)

4.65 at pH 5

UV/visible absorption spectrum Molar absorptivities at three maxima 

were affected by pH, but not over 

wavelengths of environmental 

significance.
Indoxacarb Human Health Risk Assessment DP No. D416367

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Appendix C. 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 data, which include studies from 

Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler 

Exposure Task Force (AHETF) database; the ARTF database; and the Outdoor Residential 

Exposure Task Force (ORETF) database, are (1) subject to ethics review pursuant to 40 CFR 26, 

(2) have received that review, and (3) are compliant with applicable ethics requirements. For 

certain studies, the ethics review may have included review by the Human Studies Review 

Board. Descriptions of data sources, as well as guidance on their use, can be found at the 

Agency website10. 

 

10 http://www.epa.gov/pesticides/science/handler-exposure-data.html and

http://www.epa.gov/opp00001/science/residential-exposure-sop.html